2024 ESC Guidelines for the management of peripheral arterial and aortic diseases: Developed by the task force on the management of peripheral arterial and aortic diseases of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), and the European Society of Vascular Medicine (ESVM)

Classes of recommendations

Table 2

Levels of evidence

The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. Their declarations of interest were reviewed according to the ESC declaration of interest rules which can be found on the ESC website (http://www.escardio.org/guidelines) and have been compiled in a report published in a supplementary document with the guidelines. Funding for the development of ESC Guidelines is derived entirely from the ESC with no involvement of the healthcare industry.

The ESC Clinical Practice Guidelines (CPG) Committee supervises and co-ordinates the preparation of new guidelines and is responsible for the approval process. In addition to review by the CPG Committee, ESC Guidelines undergo multiple rounds of double-blind peer review by external experts, including members from across the whole of the ESC region, all National Cardiac Societies of the ESC and from relevant ESC Subspecialty Communities. After appropriate revisions, the guidelines are signed off by all the experts in the task force. The finalized document is signed off by the CPG Committee for publication in the European Heart Journal.

ESC Guidelines are based on analyses of published evidence, chiefly on clinical trials and meta-analyses of trials, but potentially including other types of studies. Evidence tables summarizing key information from relevant studies are generated early in the guideline development process to facilitate the formulation of recommendations, to enhance comprehension of recommendations after publication, and reinforce transparency in the guidelines development process. The tables are published in their own section of ESC Guidelines and reference specific recommendation tables.

Off-label use of medication may be presented in this guideline if a sufficient level of evidence shows that it can be considered medically appropriate for a given condition. However, the final decisions concerning an individual patient must be made by the responsible health professional giving special consideration to:

The specific situation of the patient. Unless otherwise provided for by national regulations, off-label use of medication should be limited to situations where it is in the patient’s interest with regard to the quality, safety, and efficacy of care, and only after the patient has been informed and has provided consent.
Country-specific health regulations, indications by governmental drug regulatory agencies, and the ethical rules to which health professionals are subject, where applicable.

2. Introduction

Peripheral arterial and aortic diseases (PAAD) are highly prevalent and significantly increase cardiovascular (CV) mortality and morbidity in the general population,^1,2 consequently, intensive preventive strategies are needed. However, patients with PAAD are generally underdiagnosed and undertreated^3,4 compared with patients with coronary artery disease (CAD).⁵ Common risk factors in PAAD often coexist, requiring a multidisciplinary approach for effective management.⁵ Early diagnosis is crucial for better outcomes. These guidelines address PAAD, updating and merging the 2017 peripheral arterial diseases and 2014 aortic diseases guidelines. The focus is primarily on atherosclerotic arterial diseases, but they also address some non-atherosclerotic genetic conditions. While not exhaustive, these 2024 guidelines offer guidance on diagnosis, surveillance, and treatment. A number of new and revised recommendations are summarized in Tables 3 and 4, respectively. Readers should consider non-atherosclerotic conditions and refer to specific documents.^6–9

A general approach to PAAD is provided in the central illustration (Figure 1).

Figure 1

Central illustration: from diagnosis to treatment, a holistic multidisciplinary peripheral arterial and aortic diseases approach.

CV, cardiovascular; CVRFs, cardiovascular risk factors; MACE, major adverse cardiac event; MALE, major adverse limb event; PAAD, peripheral arterial and aortic diseases; QoL, quality of life.

In the management of PAAD, the following aspects must be highlighted:

Shared decision-making to involve patients, explore treatment options, assess patient values, and reach decisions collaboratively.
Multidisciplinary approach (Figure 1) in expert and high-volume PAAD centres for complex patients or procedures. These centres provide diverse services, including diagnosis, treatment planning, minimally invasive procedures, open surgery, post-operative and outpatient care, and ideally, research and innovation. They should provide continuous clinical service (24/7) and have access to digital imaging. These guidelines recognize variations in healthcare systems, population sizes, and needs, impacting the definition of ‘high volume’ in PAAD care across countries.

3. What is new

Table 3

New recommendations

Table 4

Revised recommendations

4. Epidemiology and risk factors

4.1. Epidemiology

Peripheral arterial disease (PAD) is prevalent worldwide and affects 113 million people aged 40 and older, of which 42.6% are in countries with a low-to-middle sociodemographic index. Global prevalence is 1.52%, increases with age (14.91% in those aged 80–84 years), and is higher in females than in males (18.03% vs. 10.56%, in the same age group).^10–13

PAD prevalence rose by 72% from 1990 to 2019, considering a 45% growth rate in the world population.^10,11,14 The overall global age-standardized prevalence is about 1470 per 100 000 persons (Figure 2).¹⁴

Figure 2

Estimated specific prevalence of peripheral arterial disease, by sex, in people aged 40 years and older.

Adapted from¹² under the terms of the Open access Creative Commons CC-BY license.

Ischaemic cerebral disease, mainly linked to carotid stenosis (65% of cases), has a prevalence of 77.19 million, marking a 95% increase from 1990 to 2019.¹⁵

The overall prevalence of aortic disease including aneurysm and dissections is estimated at around 1% to 3% in the general population, with up to 10% prevalence in older age groups. European studies show a decrease in abdominal aortic aneurysm (AAA) prevalence in screened men >65 years of age, at 1.3%–3.3%,^16,17 contrasting with the United States of America’s 5% found in screened male smokers.^16,17 Globally, in 2019, there were 172 000 aortic aneurysm-related deaths (82.1% increase from 1990).¹⁰

4.2. Risk factors

Main PAAD risk factors are summarized in Figure 3. Traditional risk factors in tools like Framingham, Reynolds, Atherosclerotic Cardiovascular Disease (ASCVD) risk estimator Plus (United States of America), SCORE2 (Systematic Coronary Risk Evaluation 2, age 40–69 years), SCORE2-Diabetes (Systematic Coronary Risk Evaluation 2 - diabetes), and SCORE2-OP (Systematic Coronary Risk Evaluation 2–Older Persons) (Europe)¹⁸ also contribute to PAAD’s pathophysiology and development. More details are available in Supplementary data online, Section 1.1, and the 2021 ESC Guidelines on CV disease prevention in clinical practice.¹⁹

Figure 3

Main risk factors associated with atherosclerosis in peripheral arterial and aortic diseases.

PAAD, peripheral arterial and aortic diseases.

Low-density lipoprotein cholesterol (LDL-C) is a pivotal factor in atherosclerosis,¹⁹ with diabetes and tobacco exposure significantly amplifying PAD risk by 2–4 times each.²⁰ Both men and women face a similar risk of PAD, but women have distinct risk factors (Figure 3).²¹ Hypertension and male sex are major risk factors for AAA, whereas diabetes mellitus lowers its incidence by 25%.^22–24 Thoracic aortic aneurysm (TAA) or dissection share atherosclerotic risk factors, yet monogenic or polygenic diseases like Marfan syndrome (MFS), more prevalent in younger individuals, also contribute.^24,25 Inflammation as a risk factor can be observed in PAAD²⁶ and the potential for inflammation to be a modifiable risk factor is indicated by research related to colchicine and the effects demonstrated by canakinumab (a monoclonal antibody that reduces inflammation by inhibiting interleukin-1 beta).^27,28

5. Evaluation of peripheral arteries and aorta

To be consistent with existing literature, the term PAD is used to refer to lower-extremity atherosclerotic arterial disease.

5.1. Clinical history and examination, and laboratory assessment, in patients with peripheral arterial and aortic diseases

Clinical evaluation encompassing history (including family history), review of symptoms, and physical examination are the first steps in diagnosing and assessing patients with PAAD. Pulse palpation, femoral, carotid, and abdominal bruit auscultation, heart auscultation, and observation of the legs and feet need to be part of the vascular examination.

Clinical signs, beyond aiding diagnosis, offer prognostic insights. Carotid bruits double the risk of myocardial infarction (MI) and CV death,^29,30 while a brachial systolic blood pressure (SBP) difference of more than 15 mmHg raises CV death risk by 50%.³¹ Hence, bilateral arm blood pressure (BP) measurement is recommended.³² Lab assessments should include lipid profile (including lipoprotein[a] at least once in a lifetime),³³ fasting glycaemia, glycated haemoglobin (HbA1c), renal function, blood count, coagulation studies, liver function, electrolytes, and inflammatory markers (C-reactive protein [CRP] and erythrocyte sedimentation rate). Additional evaluations, like thyroid function tests, are advised as needed.

5.2. Functional and quality of life assessment in patients with peripheral arterial and aortic diseases

Patients with PAD have decreased walking performance and self-reported physical and mental health-related quality of life (HRQoL).^34–40 Muscle strength and balance are also impaired,^41–45 leading to a faster decline in functional (physical functioning) performance in both symptomatic and asymptomatic patients.^46,47 Depression is associated with greater impairment in functional performance.^48,49 Impaired functional status is related to decreased self-reported HRQoL,^50,51 and predicts further mobility loss and CV mortality.^52,53 Very poor HRQoL has been found in patients with chronic limb-threatening ischaemia (CLTI).⁵⁴

Different questionnaires are available assessing different facets (functional, mental, and social status) of patient-reported outcome measures (PROMs).^34–36,38 The Short-form 36-item health questionnaire (SF-36) (including physical- and mental health-related items) is the most used generic questionnaire in PAD.^35,36,38 The Edinburgh Claudication Questionnaire is a modified version of the initially developed Rose questionnaire and has a sensitivity of 91% and a specificity of 99% in comparison with a physician-based diagnosis.^55,56 The Walking Impairment Questionnaire (WIQ), the Walking Estimated Limitation Calculated by History (WELCH), and the Vascular quality of life (VascuQoL) questionnaire are the most used PAD-specific questionnaires.^34–36,38

Treadmill testing, using standardized criteria, is the gold standard to assess walking performance.^37,57–62 Patients are asked to walk until maximal pain levels, defining the maximal walking distance (MWD). Patients are also asked to indicate the point at which pain begins, defining the pain-free walking distance (PFWD). Constant-load protocols have poorer reliability than graded protocols.^60–64 Additionally, the six-minute walk test (6MWT) should be performed to assess functional walking performance.^62,65 For muscular lower-limb strength assessment,⁶⁶ isokinetic dynamometry has good test–retest reliability.⁶⁷ Alternatively, the Short physical performance battery (SPPB) test should be used.^62,64,68,69 The SPPB has good test–retest reliability.⁶⁴

Few data exist on HRQoL, functional assessment, and exercise capacity in patients with aortic diseases.^70,71 Those with acute aortic dissection (AAD), as well as patients who had aortic valve or thoracic aortic surgery, may present with depression and anxiety, leading to mental health issues^72,73 that can also be assessed with the SF-36 questionnaire or the hospital anxiety and depression score (HADS).⁷² Patients with MFS have reduced HRQoL and a significant decline over time in physical HRQoL.^74,75 Assessing HRQoL in aortic disease patients is crucial for understanding well-being, disease impact, and treatment effects. This involves PROMs, including surveys, symptom assessment, functional evaluation, psychological well-being (HADS), social and occupational function, and medication/treatment side effects. It also covers healthcare utilization and patient satisfaction, informing care and enhancing aortic disease management.

Recommendation Table 1

Recommendations for clinical and laboratory, and for functional and quality of life, assessment in patients with peripheral arterial and aortic disease (see also Evidence Table 1)

5.3. Vascular examination of peripheral arteries

The ankle-brachial index (ABI)^78,79 is a low-cost, easy, and largely used tool, used both at rest or after exercise^80–84 for PAD diagnosis and surveillance (Figure 4). Both oscillometric and Doppler methods have shown good concordance.⁷⁸

Figure 4

Haemodynamic assessment of peripheral arterial disease.

ABI, ankle–brachial index; CLTI, chronic limb-threatening ischaemia; PAD, peripheral arterial disease; TBI, toe–brachial index; TcPO₂, transcutaneous oxygen pressure.

Resting ABI has a 68%–84% sensitivity and an 84%–99% specificity for PAD diagnosis (Figure 4).⁷⁹ An ABI ≤0.90 confirms PAD diagnosis.^79,85–87 For values >1.40, the term ‘non-compressible arteries’ should be used.

Ankle–brachial index >1.40, seen in arterial stiffness (diabetes, severe kidney failure, or advanced age), correlates with increased CV events and mortality risk.^88,89 For ABI >1.40, assessing resting toe–brachial index (TBI) is recommended.^79,90–95

Toe–brachial index addresses medium-calibre artery rigidity⁹⁶ measuring pressure on the hallux, second, or third toe using laser Doppler probe or plethysmography.^97,98 Sensitivity and specificity for PAD diagnosis range from 45% to 100% and 17% to 100%, respectively.⁹¹ The usual pathological threshold for TBI is ≤0.70 (Figure 4).⁹⁹

Used within the Framingham risk score, ABI enables the upgrading of risk estimation in ‘low-risk’ women and men,^77,88 it allows CV risk assessment in diverse ethnic groups independently of risk factors,^77,89 and is inexpensive and minimally time-consuming.¹⁰⁰ Trained physicians have better reproducibility than inexperienced ones.^101,102

In patients with exertional limb pain relieved by rest and a resting ABI >0.90, exercise testing with post-exercise ABI measurements or exercise oximetry has been proposed to diagnose lower-limb arterial stenoses.^103–105

The post-exercise ABI is determined 1 min after the cessation of a standardized treadmill exercise.¹⁰⁶ The physician measures bilateral ankle BP, starting with the symptomatic leg, using the ankle artery used for the reference resting ABI measurement. Brachial SBP should simultaneously be measured to enable calculation of the post-exercise ABI.¹⁰⁴

Discrepancies in PAD diagnosis exist between exercise criteria, such as a fall in absolute ankle BP >30 mmHg or a drop of >20% in the post-exercise ABI.¹⁰⁴ Recent studies identified numerous false positives in a healthy population when using a post-exercise ABI drop of >20% as the diagnostic threshold, as commonly proposed.¹⁰³

Measurement of transcutaneous oxygen pressure (TcPO₂) is a means of evaluating tissue viability and is proposed as a diagnostic criterion of CLTI (Figure 4).¹⁰⁷ TcPO₂ is affected by local and general factors such as skin thickness, probe temperature, inflammation, and oedema,^108,109 resulting in misleading values.

Resting TcPO₂ >30 mmHg is a favourable indicator of wound healing;^110–112 however, resting TcPO₂ <10 mmHg is associated with bad prognosis for wound healing and amputation in CLTI patients treated with bone marrow-derived stem cells.¹⁰⁷ When performed at successive levels on an ischaemic limb, TcPO₂ measurement may help to determine amputation level.^113–115

Exercise transcutaneous oximetry has also been proposed.^116,117 This seems of interest to detect proximal (buttock) claudication¹⁰⁵ or unsuspected exercise-induced hypoxaemia¹¹⁸ in patients with intermittent claudication (IC).¹¹⁷

5.3.1. Duplex ultrasound

Duplex ultrasound (DUS) is a first step in the vascular work-up for PAD screening and diagnosis, allowing a dynamic, non-invasive, radiation- and contrast-free examination. It localizes vascular lesions and quantifies their extent and severity through velocity criteria.^119–121 In combination with ABI or TBI, DUS permits determining the haemodynamic relevance of arterial lesions^122,123 and estimation of ABI.¹²⁴ DUS has a sensitivity of 88% and specificity of 95% for >50% stenosis detection.¹²⁵ Post-exercise DUS can reveal borderline arterial lesions if initial findings are inconclusive.^122,126,127

Duplex ultrasound distinguishes atherosclerotic (even subclinical disease) from non-atherosclerotic lesions, but its reliability relies on the sonographer’s expertise.¹²² Cross-sectional imaging is advisable for revascularization planning. ABI and DUS are recommended for PAD patient follow-up post-revascularization.¹²⁸

More recent techniques, such as flow imaging, 3D echography, ultrafast ultrasound, and shear wave elastography, as well as the use of contrast-enhanced ultrasound (CEUS), could further improve DUS performance.¹²⁹

5.3.2. Digital subtraction angiography, computed tomography angiography, and magnetic resonance angiography

Detailed information about these techniques can be found in the Supplementary data online, Section 1.2 (Table S1). Digital subtraction angiography (DSA) remains mostly limited to revascularization procedures. Computed tomography angiography (CTA) offers better spatial resolution than magnetic resonance angiography (MRA) and better calcification visualization; however, it can also overestimate stenosis severity due to the blooming effect. MRA allows arterial wall and lumen assessment as well as tissue and organ perfusion distal to or surrounding the explored arterial territory.

Recommendation Table 2

Recommendations for diagnostic tests in patients with peripheral arterial disease

5.4. Evaluation of the aorta

The aorta can be divided into different anatomical regions (from proximal to distal) for reporting purposes. The main anatomical aortic regions are the aortic root, ascending aorta, aortic arch, descending thoracic aorta (DTA), abdominal aorta (AA), infrarenal aorta, and the iliac arteries (Figure 5).^134,135

Figure 5

Anatomy and aortic segments and upper normal values for aortic dimensions.

Numbers represent the 11 aortic segments based on the Society for Vascular Surgery/Society of Thoracic Surgeons (SVS/STS) classification for surgical and endovascular purposes.¹³⁶ Z-scores can be calculated for aortic root and ascending aorta. Calculation of z-scores can be performed following these links: https://www.marfan.fr/accueil/z-score-calculus/ or https://marfan.org/dx/z-score-adults.

5.4.1. Aortic measurements

The main imaging techniques used for aortic evaluation are illustrated in Table 5.

Table 5

Main aortic imaging techniques

	TTE/DUS	TOE	CCT	CMR
Availability	++++	+++	++	+
Cost	+	++	+++	++++
Time requirement	+	+++	+++	++++
Radiation	0	0	+++	0
Spatial resolution	1 mm	1 mm	0.6 mm	1–2 mm
Temporal resolution	20 msec	20 msec	80 msec	30 msec
Nephrotoxicity	0	0	+++	+
Accuracy	++	++++	++++	++++
Serial examination	++++	++	++	++++
Aortic wall visualization	++	+++	++++	++++
Aortic valve function	+++	++++	+	++++
RV/LV function	+++	+++	+++^a	++++
Aortic root assessment	+++	+++	++++	++++
Aortic arch assessment	++	+++	++++	++++
Thoracic aorta assessment	+	++	++++	++++
Abdominal aorta assessment	+++	-	++++	++++

	TTE/DUS	TOE	CCT	CMR
Availability	++++	+++	++	+
Cost	+	++	+++	++++
Time requirement	+	+++	+++	++++
Radiation	0	0	+++	0
Spatial resolution	1 mm	1 mm	0.6 mm	1–2 mm
Temporal resolution	20 msec	20 msec	80 msec	30 msec
Nephrotoxicity	0	0	+++	+
Accuracy	++	++++	++++	++++
Serial examination	++++	++	++	++++
Aortic wall visualization	++	+++	++++	++++
Aortic valve function	+++	++++	+	++++
RV/LV function	+++	+++	+++^a	++++
Aortic root assessment	+++	+++	++++	++++
Aortic arch assessment	++	+++	++++	++++
Thoracic aorta assessment	+	++	++++	++++
Abdominal aorta assessment	+++	-	++++	++++

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic resonance; LV, left ventricle; RV right ventricle; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography.

^aCCT can be used to evaluate left and right ventricular function only if retrospective gating is used.

Table 5

Main aortic imaging techniques

	TTE/DUS	TOE	CCT	CMR
Availability	++++	+++	++	+
Cost	+	++	+++	++++
Time requirement	+	+++	+++	++++
Radiation	0	0	+++	0
Spatial resolution	1 mm	1 mm	0.6 mm	1–2 mm
Temporal resolution	20 msec	20 msec	80 msec	30 msec
Nephrotoxicity	0	0	+++	+
Accuracy	++	++++	++++	++++
Serial examination	++++	++	++	++++
Aortic wall visualization	++	+++	++++	++++
Aortic valve function	+++	++++	+	++++
RV/LV function	+++	+++	+++^a	++++
Aortic root assessment	+++	+++	++++	++++
Aortic arch assessment	++	+++	++++	++++
Thoracic aorta assessment	+	++	++++	++++
Abdominal aorta assessment	+++	-	++++	++++

	TTE/DUS	TOE	CCT	CMR
Availability	++++	+++	++	+
Cost	+	++	+++	++++
Time requirement	+	+++	+++	++++
Radiation	0	0	+++	0
Spatial resolution	1 mm	1 mm	0.6 mm	1–2 mm
Temporal resolution	20 msec	20 msec	80 msec	30 msec
Nephrotoxicity	0	0	+++	+
Accuracy	++	++++	++++	++++
Serial examination	++++	++	++	++++
Aortic wall visualization	++	+++	++++	++++
Aortic valve function	+++	++++	+	++++
RV/LV function	+++	+++	+++^a	++++
Aortic root assessment	+++	+++	++++	++++
Aortic arch assessment	++	+++	++++	++++
Thoracic aorta assessment	+	++	++++	++++
Abdominal aorta assessment	+++	-	++++	++++

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic resonance; LV, left ventricle; RV right ventricle; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography.

^aCCT can be used to evaluate left and right ventricular function only if retrospective gating is used.

Evaluating aortic dilation and progression depends on standardized measurements. In echocardiography, aortic diameters should be measured using the leading-to-leading edge method during end-diastole (as systole sees about a 2 mm aortic expansion) in all segments (Figure 6).^137,138

Figure 6

Conventional measurements of the aorta at different levels by echocardiography or duplex ultrasound (A, B, C), cardiovascular computed tomography or cardiovascular magnetic resonance (D, E, F).

(A) Echocardiographic measurements of the aortic root and ascending aorta using the leading-to-leading edge methodology. (B) The outer-to-outer convention in the abdominal aorta in cases with aortic wall disease in a longitudinal view. This method can be used in a non-circular section as an alternative. (C) The outer-to-outer antero-posterior diameter of the abdominal aorta in a cross-sectional view. Evaluation of the aortic root using the cusp-to-cusp diameter (D) and the cusp-to-commissure convention (E); (F) measurement of the ascending aorta and the descending aorta with the double-oblique technique. AoR, aortic root; ASC, proximal ascending aorta.

Most studies supporting prophylactic surgery have used this approach. Furthermore, better agreement exists between echo’s leading-to-leading edge and cardiovascular computed tomography (CCT)/cardiovascular magnetic resonance (CMR)’s inner-to-inner edge during end-diastole.^137,139,140 However, when the aortic wall thickens (e.g. atheroma, thrombus, intramural haematoma [IMH], or aortitis) or in cases of aortic dissection (AD), also report the outer-to-outer diameter (Figure 6).

Given the high incidence of atherosclerotic plaques/thrombi in the AA, the outer-to-outer convention should be preferred (also presenting the best agreement with CCT and CMR) (Figure 6).^141,142

Regarding CCT and CMR, measurements must be performed using the inner-to-inner edge method (Figure 6) in end-diastole (fewer motion artefacts).^137,143,144

The aortic root is measured in the parasternal long axis by transthoracic echocardiography (TTE),^{137,139,140,145} since the short axis underestimates the diameter due to possible plane obliquity. By CMR or CCT, the cusp-to-cusp diameter best correlates with echocardiography (Figure 6). A diameter difference >5 mm (among root diameters within the same imaging modality) indicates root asymmetry, frequent in bicuspid aortic valve (BAV) or genetic aortopathies, which is important to be determined since it generates underestimations.¹⁴⁶ While 3D echocardiography is a potential surveillance alternative in these cases (especially if CMR/CCT is limited for serial follow-up), validation studies are lacking.¹⁴⁷

In end-diastole, measure the ascending aorta by moving the transducer 1–2 intercostal spaces up in the parasternal long axis. Echocardiography provides information on aortic arch or DTA enlargement, but diagnostic certainty (precise measurement of the diameters) is lacking. CCT or CMR uses the double-oblique technique to measure aortic diameters, reporting antero-posterior and perpendicular dimensions for accurate assessment.¹⁴⁸ It is recommended to report aortic measurements by specific segments based on anatomical landmarks and to relate the largest diameter to a nearby anatomical structure for reference.

Changes in aortic diameter require a ≥3 mm increase in echocardiography, which should be confirmed with CCT/CMR and compared with baseline measurements. For accurate assessment, stick to the same imaging technique, centre, methodology, and side-by-side comparisons.^137,140

5.4.2. Normal aortic values

When evaluating aortic dimensions and clinical relevance, consider factors like aortic region, anthropometric measurements, patient history, and underlying medical conditions. Factors influencing aortic and peripheral artery size in the normal population include age, sex, ethnicity, body surface area (BSA), and, particularly, height.¹⁴⁹

Body surface area is the most used method to normalize aortic dimensions based on an individual’s body size, thus an ascending thoracic aorta >22 mm/m² or a DTA >16 mm/m² is considered aortic dilatation.^150–152 However, extremes of low or high body weight pose limitations. In such cases, surgical thresholds may involve indexing aortic diameter by height (an aorta height index >32.1 mm/m is associated with a 12% yearly risk of aortic adverse events [AAE]),¹⁵³ aortic cross-sectional area to patient height (a ratio ≥10 cm²/m implies reduced long-term survival),¹⁵⁴ or aortic length (from the aortic annulus to the innominate artery, considering a length >11 cm a threshold for surgery).¹⁵⁵

To correlate measured diameter with the expected one based on age, sex, and body surface, use nomograms or z-score calculation formulas, especially in heritable thoracic aortic disease (HTAD). Supplementary data online, Figure S1 and Table S2, presents nomograms developed for echocardiography, applicable also to CCT and CMR.^156,157 Calculation of z-scores can be performed following these links: https://www.marfan.fr/accueil/z-score-calculus/ or https://marfan.org/dx/z-score-adults/; reference values used for their estimation may vary depending on age and other factors. However, z-scores are limited by the fact that not all ethnic groups are equally represented (mostly white) and over- or underweight can lead to an over- or underestimation.¹⁵⁸

Moreover, with ageing and loss of elastic properties, the aorta tends to enlarge. Aortic growth in adults is about 0.9 mm per 10 years in males and 0.7 mm per 10 years in females, which may be influenced by BP, physical activity, and genetic factors.

Recommendation Table 3

Recommendations for imaging of the aorta (see also Evidence Table 2)

5.4.3. Chest X-ray and electrocardiogram

Chest X-ray obtained for other indications in asymptomatic patients or in cases of acute aortic syndrome (AAS) suspicion may detect abnormalities of aortic size/contour that need to be confirmed by another imaging technique. It presents limited sensitivity (64%) and specificity (86%) in the diagnosis of aortic diseases;¹⁶² thus, a normal chest X-ray may not rule out the diagnosis of AAS.^162–164 On the contrary, chest X-ray may identify other causes of chest pain (e.g. pleural effusion or pneumothorax).

Electrocardiogram (ECG) might be useful to rule out other causes of chest pain (e.g. MI) or AAS complications (coronary occlusion/dissection) but it is not useful for AAS diagnosis.

5.4.4. Echocardiography

It is considered the first-line imaging technique in the evaluation of aortic disease, assessing all echocardiographic windows and the aortic valve. It provides key anatomic information (i.e. dilatation, atherosclerotic lesions, or dissection) for the ascending aorta, arch, and AA; however, it is not useful to assess the exact diameters of the aortic arch and DTA (requiring confirmation with CCT/CMR). Also, the distal ascending aorta and proximal arch (blind spot) are inadequately visualized due to left mainstem bronchus interposition.

Transthoracic echocardiography can identify AAS complications (e.g. aortic regurgitation, tamponade, or wall motion abnormalities), but its diagnostic accuracy for AAS is limited (sensitivity: 78%–100% for type A, 31%–55% for type B). Contrast enhancement improves diagnosis.¹⁶⁵ Transoesophageal echocardiography (TOE) is highly accurate (sensitivity: up to 99%, specificity: 89% for AAS), except with absolute contraindications like oesophageal issues, bleeding, recent gastro-oesophageal surgery, or respiratory distress. TOE is convenient for bedside and intraoperative use but less suitable for long-term surveillance, which requires evaluation with CCT/CMR.

Recommendation Table 4

Recommendations for thoracic aortic measurements

5.4.5. Duplex ultrasound imaging of the abdominal aorta

After scanning both transversally and longitudinally, the antero-posterior (AP) diameter in a cross-sectional view of the AA should be measured. Ensure the DUS beam is perpendicular to the AA axis, forming a circular vessel section. If the AA is sinuous or dilated, achieving equal AP and transverse diameters may be challenging. In such instances, calculate the mean ellipse diameter or measure the AA diameter in a clear longitudinal view with a perpendicular diameter (Figure 6).¹²² The outer-to-outer (Figure 6) method is the one recommended by the American Institute of Ultrasound in Medicine, the American College of Cardiology/American Heart Association (ACC/AHA), and the European Society of Cardiology (ESC), since it is more reliable in cases of atherosclerotic plaque or intravascular thrombus and best correlates with CCT and CMR. However, the most effective methodology is under debate and further studies are needed to determine the best convention.¹⁶⁹

Normal diameters of the AA are reported in Figure 5 and Supplementary data online, Section 1.3.

5.4.6. Cardiovascular computed tomography

Cardiovascular computed tomography, due to its quick acquisition, wide availability, high reproducibility, and suitability for emergency departments, is the primary imaging method for aortic disease diagnosis, prognosis, and therapy planning (sensitivity 100%, specificity 98% for AAS).^170–172 ‘Double or triple rule-out’ protocols concurrently assess the aorta, pulmonary, and coronary arteries.^173,174

Electrocardiogram triggering is crucial to prevent motion artefacts (especially in the aortic root and ascending aorta), which can distort measurements or resemble dissection flaps, facilitating coronary artery assessment. The standard protocol comprises non-enhanced scans (for calcification, IMH, or surgical material), contrast-enhanced CCT angiography, and a late scan (to visualize contrast leakage or aortic wall late enhancement suggestive of inflammation or infection).¹⁷⁵

Iodinated contrast agents carry potential allergic reactions and post-contrast acute kidney injury (PC-AKI) risks.¹⁷⁶ In these cases, opt for contrast-free CCT for accurate aortic diameter measurement (also for CMR-intolerant patients). Moreover, excessive radiation caution is crucial, particularly in young females, when performing CCT for monitoring chronic aortic diseases.¹⁷⁷

5.4.7. Cardiovascular magnetic resonance

Cardiovascular magnetic resonance comprehensively evaluates the aorta, including shape, diameter, tissue characteristics (inflammation, infection, atheroma, bleeding),¹⁷⁸ lesion extent, side branches, adjacent structures, and mural thrombus. It assesses ventricular and valve function, quantifies flow, and employs cine steady-state free precession (SSFP) or ECG-gated angio-CMR for the aortic root, while non-gated sequences suffice for the rest. Recently, 4D flow sequences¹⁷⁹ have been developed to evaluate complex intravascular flows,^180,181 complex flow parameters (wall shear stress, pulse wave velocity, or kinetic energy), or flow quantification at different levels in one unique acquisition (useful in AD or congenital diseases).^182,183

Cardiovascular magnetic resonance obviates ionizing radiation and iodinated contrast (3D contrast CMR), making it ideal for young patients, women, and pregnancy. Caution is warranted, especially with non-macrocyclic gadolinium, for estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² (Supplementary data online, Section 1.2). CMR is increasingly used in patients with intracardiac devices (pacemakers/implantable cardioverter defibrillators, CMR- and non-CMR-compatible devices) with proper monitoring, but not for those with cochlear implants or intracranial clips.^184,185

In the acute setting, CMR use is limited because of low availability, difficulties in monitoring unstable patients, and longer acquisition times.^166,186

5.4.8. Positron emission tomography

Positron emission tomography (PET) usually uses ¹⁸F-fluorodeoxyglucose (FDG), allowing non-invasive assessments of metabolic activity (inflammation/infection) and treatment response.^187,188 Although different tracers have been tested to identify calcification, fibrosis and/or thrombus formation, most PET studies have focused on vasculitis.

The relationship between FDG-PET images and AAA progression is controversial. However, fluorine-18–sodium fluoride (¹⁸F–NaF) PET-computed tomography (PET-CT), a marker of active vascular calcification and high-risk plaques, has shown a correlation between increased tracer uptake, AAA growth, and CV events.¹⁸⁹

PET-CT has shown better diagnostic accuracy in identifying lesions and detecting graft infection or infectious aortic diseases.^190–193 High radiation exposure, high costs, and limited availability are the main limitations of PET.

5.4.9. Intravascular ultrasound

Intravascular ultrasound (IVUS) provides high-resolution imaging for artery and vein diseases, aiding complex aortic disease management by distinguishing true and false lumens and guiding stent placement. It is operator-dependent, costly, and less accessible, but seems to provide better measurements for acute aortic syndromes.¹⁹⁴

5.4.10. Digital subtraction aortography

Non-invasive imaging modalities have replaced DSA in first-line diagnostic testing, both in suspected AAS or known chronic AD; however, DSA might be useful if findings in non-invasive techniques are ambiguous or incomplete. It is primarily used for the percutaneous treatment of CAD, aortic visceral branches, or for monitoring thoracic endovascular aortic aneurysm repair (TEVAR/EVAR) implantation.

6. Screening for carotid, peripheral arterial, and aortic diseases

6.1. Screening for carotid and peripheral arterial diseases

6.1.1. Lower-extremity peripheral arterial disease

Due to elevated CV risk in chronic PAD, early diagnosis, prevention, and robust cardiovascular risk factor (CVRF) control are essential, even in asymptomatic cases. ‘Intermediary CV risk’ individuals may be reclassified as ‘high or very high risk’, prompting adapted prevention. ABI is the preferred first-line test for asymptomatic individuals aged ≥65 years,^14,195 especially women.¹⁹⁶ Screening might also be beneficial at a younger age in case of CVRFs, but data are still lacking. Clinical examination, functional status, and walking capacity assessment are recommended to detect ‘masked PAD’.⁷⁷

In diabetes, early PAD (and foot neuropathy) diagnosis is crucial. Effective CVRF management and treatment can prevent CV disease, foot wounds, and amputation.¹⁹⁷ In patients with diabetes and normal resting ABI, TBI measurement should be considered.

The prevalence of popliteal aneurysms (PAs) is high in patients with AAA and subaneurysmal aortic dilatation, warranting screening. PAs are correlated with iliac and femoral artery diameters.⁷⁶ In patients needing transfemoral access, screening for iliofemoral artery disease may be considered.¹⁹⁸

6.1.2. Carotid artery stenosis

Due to the low prevalence of ≥70% asymptomatic carotid artery stenosis (CS) in the general population (0%–3.1%), widespread screening is not recommended since it does not reduce stroke risk and might lead to inappropriate stress and invasive procedures.^199,200 Conversely, screening for significant CS in a highly selected population might be cost-effective, especially if prevalence is ≥20% (Table 6).²⁰¹ When the degree of asymptomatic CS is ≥70%, the 5 year ipsilateral stroke risk is significantly increased (14.6%) and revascularization may be beneficial.²⁰² Selective screening aims to prevent CV events, rather than identifying candidates for an intervention.²⁰³

Table 6

High-risk populations for carotid artery stenosis

Population	Prevalence of carotid stenosis (%)
>60 years + CVRFs (hypertension, CAD, current smoking, first-degree family history of stroke)²¹⁰	Two CVRFs: 14% Three CVRFs: 16% Four CVRFs: 67%
Hypertension + cardiac disease²¹¹	22%
HD²¹²	In HD patients, prevalence of carotid stenosis is high, and is associated with high peri-operative and long-term stroke or death rates Carotid stenosis is a predictor of death in patients with long-term dialysis and aged ≥70 years at time of surgery Lower risk if previous renal transplant.
PAD²¹³	23.2%
Severe CAD (before CABG)	Almost 20%²¹⁴ Carotid bruit and T2DM: increased predictive value²¹⁵ Carotid stenosis = risk factors for peri-operative stroke.²¹⁵
Carotid bruit²¹⁶	31%
Previous neck irradiation²¹⁷	21.7% (70%–99% stenosis)

Population	Prevalence of carotid stenosis (%)
>60 years + CVRFs (hypertension, CAD, current smoking, first-degree family history of stroke)²¹⁰	Two CVRFs: 14% Three CVRFs: 16% Four CVRFs: 67%
Hypertension + cardiac disease²¹¹	22%
HD²¹²	In HD patients, prevalence of carotid stenosis is high, and is associated with high peri-operative and long-term stroke or death rates Carotid stenosis is a predictor of death in patients with long-term dialysis and aged ≥70 years at time of surgery Lower risk if previous renal transplant.
PAD²¹³	23.2%
Severe CAD (before CABG)	Almost 20%²¹⁴ Carotid bruit and T2DM: increased predictive value²¹⁵ Carotid stenosis = risk factors for peri-operative stroke.²¹⁵
Carotid bruit²¹⁶	31%
Previous neck irradiation²¹⁷	21.7% (70%–99% stenosis)

CABG, coronary artery bypass grafting; CAD, coronary artery disease; CVRFs, cardiovascular risk factors; HD, haemodialysis; PAD, peripheral arterial disease; T2DM, type 2 diabetes mellitus.

Table 6

High-risk populations for carotid artery stenosis

Population	Prevalence of carotid stenosis (%)
>60 years + CVRFs (hypertension, CAD, current smoking, first-degree family history of stroke)²¹⁰	Two CVRFs: 14% Three CVRFs: 16% Four CVRFs: 67%
Hypertension + cardiac disease²¹¹	22%
HD²¹²	In HD patients, prevalence of carotid stenosis is high, and is associated with high peri-operative and long-term stroke or death rates Carotid stenosis is a predictor of death in patients with long-term dialysis and aged ≥70 years at time of surgery Lower risk if previous renal transplant.
PAD²¹³	23.2%
Severe CAD (before CABG)	Almost 20%²¹⁴ Carotid bruit and T2DM: increased predictive value²¹⁵ Carotid stenosis = risk factors for peri-operative stroke.²¹⁵
Carotid bruit²¹⁶	31%
Previous neck irradiation²¹⁷	21.7% (70%–99% stenosis)

Population	Prevalence of carotid stenosis (%)
>60 years + CVRFs (hypertension, CAD, current smoking, first-degree family history of stroke)²¹⁰	Two CVRFs: 14% Three CVRFs: 16% Four CVRFs: 67%
Hypertension + cardiac disease²¹¹	22%
HD²¹²	In HD patients, prevalence of carotid stenosis is high, and is associated with high peri-operative and long-term stroke or death rates Carotid stenosis is a predictor of death in patients with long-term dialysis and aged ≥70 years at time of surgery Lower risk if previous renal transplant.
PAD²¹³	23.2%
Severe CAD (before CABG)	Almost 20%²¹⁴ Carotid bruit and T2DM: increased predictive value²¹⁵ Carotid stenosis = risk factors for peri-operative stroke.²¹⁵
Carotid bruit²¹⁶	31%
Previous neck irradiation²¹⁷	21.7% (70%–99% stenosis)

CABG, coronary artery bypass grafting; CAD, coronary artery disease; CVRFs, cardiovascular risk factors; HD, haemodialysis; PAD, peripheral arterial disease; T2DM, type 2 diabetes mellitus.

6.1.3. Multisite artery disease

Multisite artery disease (MAD) is defined as the presence of atherosclerosis in two or more vascular beds.²⁰⁴ This is a common condition in patients with atherosclerotic diseases. Although associated with worse clinical outcomes, screening for asymptomatic disease in additional vascular sites did not seem to improve outcomes.⁷⁷ More recently, screening for coronary calcifications (coronary artery calcium [CAC] score) and screening for carotid and femoral plaques have been shown to be of potential assistance in CV risk reclassification of ‘presumed moderate-risk patients’ into a higher-risk category, leading to more aggressive prevention strategies.^205–209

Recommendation Table 5

Recommendations for peripheral arterial disease screening (see also Evidence Table 3)

6.2. Screening for aortic diseases

6.2.1. Screening for abdominal aortic aneurysm

Abdominal aortic aneurysm screening by DUS is effective in reducing rupture-related mortality in populations with high AAA prevalence (especially male smokers aged ≥65 years).^221–224 However, no such effect has been found in a single large study in which AAA prevalence was low (current or former smoking women aged 65–74 years, or with a history of CAD).²²⁵

Screening for AAA by non-contrast computed tomography (CT) was not found to be effective over 5 years in males aged 65–74 years in a Danish trial.²²⁶ Longer-term follow-up is planned, and as the technique involves ionizing radiation, no recommendation is made in relation to CT at present.

Screening may be considered in populations at intermediate risk, such as men aged >75 years, or women aged >75 years who are hypertensive, smokers, or both, since almost all women in a contemporary population-based study who had ruptured AAA and were aged >75 years were either smokers or hypertensive.^227,228

Screening for AAA is recommended in first-degree relatives (FDRs) of patients with AAA (especially siblings), as they are at increased risk of AAA when >50 years of age.²²⁹ The risk associated with family history is uncertain, but a population-based study estimated a relative risk of around 2.²³⁰ Screening should be repeated periodically if initial assessment is reassuring and performed at a relatively young age.²³¹

Opportunistic screening (during TTE) identified AAA in about 2% of subjects, thus it may be considered in high-prevalence populations (males ≥65 or women ≥75 years of age).²³² Additionally, opportunistic screening detects AAA in patients with symptomatic/asymptomatic PAD (with a 12% cumulative incidence in symptomatic PAD), making it worthwhile in this population.²³³

Recommendation Table 6

Recommendations for abdominal aortic aneurysm screening

6.2.2. Screening for thoracic aortic aneurysm

Screening for TAA is described in detail in Section 10.1 and Section 10.2.

7. Optimal medical treatment

Optimal medical treatment (OMT), including lifestyle measures and pharmacological treatment, is recommended for all patients with PAAD (Figure 7).

Figure 7

Cardiovascular risk modification and healthy lifestyle interventions and targets in patients with peripheral arterial and aortic diseases.

ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blocker; BMI, body mass index; LDL, low-density lipoprotein; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; HbA1c, glycated haemoglobin.

7.1. Lifestyle, exercise, patient education

Apart from genetic-related TAA, hypertension and ASCVD are the main causative factors for PAAD. As lifestyle factors are strongly related to ASCVD,¹¹ patients with PAAD should strive to maintain a healthy lifestyle. The 2021 ESC Guidelines on cardiovascular prevention¹⁹ give comprehensive guidance on risk factors for ASCVD and their treatment.

7.1.1. Diet

A Mediterranean diet rich in legumes, dietary fibre, nuts, fruits, and vegetables proves crucial and efficacious for primary and CV prevention in PAAD.²³⁸ It has demonstrated notable reductions in cholesterol and BP,^239–247 and holds potential protective benefits against PAAD development.^248,249 In a large cohort with 17.5 years of follow-up, adherence to a Mediterranean diet was associated with reduced AAA risk in current and ex-smokers.^249,250 Malnutrition and metabolic disorders can complicate post-invasive procedure recovery and nutritional support may improve nutritional status and HRQoL.²⁵¹

7.1.2. Physical activity

Few patients with chronic symptomatic PAD meet the physical activity guidelines²⁵² for reducing the risk of major adverse cardiac events (MACE).^253,254 Better ambulation, HRQoL, and vascular outcomes have been observed in patients meeting the physical activity time-intensity guidelines.^19,255 Regular physical activity is also relevant in patients with aortic diseases^{70,71,256–259} and lowers resting heart rate and BP, thus decreasing the risk of aortic complications.^256,259 Few data exist on the practice of exercise and sports in patients with aortic diseases.^{70,71,256–259} Recommendations should be individualized and based on risk stratification.⁷¹

7.1.3. Smoking

Patients with PAAD who smoke should strongly be advised to quit (see Supplementary data online, Section 1.1.5). Complete smoking cessation and avoiding second-hand smoke or environmental particle air pollution are crucial in patients with PAAD to reduce the risk of death, AD, acute mesenteric ischaemia (AMI), AAA, and PAD.^{119,260–267} Smokers should be offered structural follow-up support, including nicotine replacement therapy, varenicline, and bupropion, individually or in combination.^19,268,269 Smoking avoidance also includes cannabis, associated with premature ASCVD.²⁶⁶

Vaping and e-cigarette use has surged in the past decade, viewed by some as a healthier option than smoked tobacco, though long-term health effects remain unknown.²⁷⁰ E-cigarettes may be considered as an aid to quit tobacco smoking, as a recent Cochrane review found that they increase quit rates as compared with nicotine replacement therapy,²⁷¹ but their use has been associated with adverse effects on CV, respiratory, immunological, and periodontal health compared with non-users, but with a milder impact than smoked cigarettes.^272–274 However, their use should be brief and preferably not concurrent with traditional cigarettes.^271,275

The main limitation of the evidence base remains imprecision due to the small number of randomized controlled trials (RCTs), often with low event rates and follow-up limited to 2 years.

7.1.4. Patient education

While detailed explanations of CVRFs might not always inspire lifestyle changes,²⁷⁶ providing plain language and visual aids is essential for patient understanding.²⁷⁷ Structured programmes, incorporating psychological and behavioural aspects, are pivotal in fostering desired changes.²⁷⁶ Engaging patients’ families, friends, and support networks significantly contributes to perpetuating these changes (particularly in self-care),²⁷⁶ and increases treatment compliance and self-efficacy, reducing hospitalization risk and enriching patient HRQoL.^278,279 When caregivers disconnect from healthcare professionals, they should be recognised to receive better support systems.^280,281 Psychosocial interventions are crucial to navigating complexities with resilience.²⁸²

Advocating active involvement, education, clear communication, and shared decision-making is key for achieving optimal patient outcomes.^276–283

7.1.5. Risk scoring models in secondary prevention

Recent ESC CV prevention guidelines discuss risk models for developing vascular disease in healthy individuals and ASCVD patients.¹⁹ Several registries enabling risk prediction in ASCVD have been developed: REACH (The REduction of Atherothrombosis for Continued Health)²⁸⁴ and SMART (Secondary Manifestation of ARTerial disease)²⁸⁵ which use clinical parameters such as medical history, SBP, and common biomarkers. Addition of carotid ultrasound did not improve the model.²⁸⁶ A new algorithm combining the SMART and REACH models²⁸⁷ enables calculation of lifetime risk and treatment effects. The SMART model has recently been updated and validated^288,289 with the SMART-2 algorithm. These tools are available online as clinical risk calculators (see www.u-preveotnt.com) and smartphone apps on the ESC website (https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Risk-assessment/SMART-Risk-Score).

Recommendation Table 7

Recommendations for lifestyle, physical activity, and patient education (see also Evidence Table 4)

7.2. Principles of pharmacological medical therapy

7.2.1. Antithrombotic therapy

Antithrombotic therapy is crucial for patients with symptomatic PAAD at high CV risk. While trials are fewer than in CAD, recent evidence should guide practice. In the absence of specific indications for chronic oral anticoagulation (OAC) in concomitant CV disease, a single antiplatelet agent is the primary long-term treatment for patients with symptomatic PAAD. Combining it with another antiplatelet agent or low-dose anticoagulants depends on the patient’s ischaemic and bleeding risk, as well as therapeutic paths (e.g. endovascular therapy). Recent guidelines²⁹⁹ propose a tool for bleeding risk assessment in PAD patients (OAC³ PAD score).

Antithrombotic strategy is detailed in Sections 8 and 9 for each arterial territory.

7.2.2. Antihypertensive therapy

New 2024 ESC Guidelines on hypertension are currently published and should be reviewed for further details.³⁰⁰ Patients with hypertension and PAAD are considered to have target organ damage and are at high CV risk.³⁰⁰

Different meta-analyses showed that systolic BP treatments reduce CV risk in all ages up to 85 years down to a level of 120–129 mmHg.^301,302 There is no need to increase the BP target in healthy patients up to the age of 85 years.^303,304 To reduce cardiovascular disease (CVD) risk, it is recommended that treated SBP values in most adults be targeted to 120–129 mmHg, provided the treatment is well tolerated. However, in cases where BP-lowering treatment is poorly tolerated and achieving an SBP of 120–129 mmHg is not possible, it is recommended to target an SBP level that is ‘as low as reasonably achievable’ (ALARA principle).^301,302,305 To avoid overtreatment, out-of-office BP measurements may be helpful when pursuing this target.

If on-treatment SBP is on target, but diastolic blood pressure (DBP) is ≥80 mmHg, intensified treatment may be considered to further reduce the CV risk.³⁰⁶

Because the CVD benefit of an on-treatment BP target of 120–129 mmHg may not generalize to some groups, setting personalized and more lenient BP targets (e.g. <140/90 mmHg) has to be considered in patients with pre-treatment orthostatic hypotension, age ≥85 years, clinically significant frailty at any age, or a limited lifespan (<3 years).³⁰¹

Patients with both PAAD and hypertension face a high or very high CV risk. Antihypertensive medications such as diuretics, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) are all appropriate options for managing hypertension in PAAD. These agents can be used as monotherapy or in various combinations (excluding ARBs+ACEIs), considering individual patients’ conditions. It is often necessary to implement combination therapy, preferably in the form of a single pill, to effectively achieve the recommended treatment goals. However, ACEIs or ARBs should be considered as first-line antihypertensive therapy to reduce CV events.^{300,307–312}

Regardless of BP levels and in the absence of contraindications, ACEIs/ARBs may be considered in all patients with PAD to reduce cardiovascular events.^312,313 A meta-analysis suggests that antihypertensive treatment may improve mean walking distance in patients with PAD.³¹⁰

Beta-blockers can be prescribed, if necessary, to patients with intermittent claudication, since they do not worsen walking capacity or limb events.³¹⁴ There is some evidence suggesting a higher amputation rate³¹⁵ or increased rate of re-intervention³¹⁶ in patients with CLTI treated with ACEIs, although in one smaller study no effect on limb-related outcomes was observed.³¹⁷ Thus, they remain a treatment option in hypertensive patients with PAD, especially in those with concomitant CAD.³¹⁸ BBs were not associated with worsened clinical outcomes in a retrospective study³¹⁹ on CLTI patients, but it seems prudent to avoid excessively low heart rates in these patients.

7.2.2.1. Renovascular hypertension

Angiotensin-converting enzyme inhibitors and ARBs effectively manage unilateral renal artery stenosis (RAS) by blocking the renin–angiotensin system, potentially reducing renal capillary perfusion pressure.^320–322 This transiently lowers glomerular filtration rate (GFR) and raises serum creatinine. For bilateral RAS, regular follow-up assessments of renal function and kidney perfusion are advised.

Angiotensin-converting enzyme inhibitors and ARBs additionally (combined with hydrochlorothiazide and/or CCBs if needed) contribute to CV risk reduction in patients with atherosclerotic disease and reduced eGFR.^307,323,324

Recommendation Table 8

Recommendations for antihypertensive therapy in patients with peripheral and aortic disease

7.2.3. Lipid-lowering therapy

Patients with symptomatic PAAD are at very high CV risk but are usually inadequately managed compared with patients with CAD.^{5,247,326–332} Both LDL-C reduction by ≥50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended to obtain a reduction in CV death, MI, and stroke, and to improve walking distance.^{242,333–336}

7.2.3.1. Statins

Statins demonstrate mortality and CV event reduction in RCTs for PAD, CS, and severe aortic arch plaques.^243–245 Even in advanced disease stages, they are linked to lower MACE and mortality.²⁴⁶

Statins significantly improve CV outcomes in patients with PAD, reducing major adverse limb events (MALE).^{244,327–329,337,338} Meta-analyses show enhanced walking distances.^244,338,339

For CS, statin pre-treatment lowers recurrent stroke risk post-transient ischaemic attack (TIA).^19,340–343 While lacking RCTs in renovascular or visceral artery disease, statins benefit cardiorenal events and post-RAS stenting prognosis.^344–346

Mixed evidence suggests statins may mitigate AAA and TAA growth.^347–352 However, since most patients with AAA or TAA present with associated CVRFs, liberal use of lipid-lowering treatment¹⁹ should be considered, using an individualized approach with shared decision-making and considering residual CV risk.³⁵³ Pre-operative statin use links to increased 5 year survival after TEVAR.¹⁹

Statin use was associated with a mean AAA growth rate reduction and a lower rupture risk.^{347–349,352,354}

Some evidence suggests that statins may reduce TAA growth rate and risk of rupture.^350,351,355

No benefit on AAA or TAA growth rate was shown with fenofibrate therapy.^356,357

7.2.3.2. Ezetimibe

Ezetimibe combined with statins benefits selected patients with PAAD, particularly when the target LDL-C level is not met.³³⁵ In an IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) subanalysis, involving acute coronary syndrome (ACS) patients with PAD, ezetimibe consistently reduced CV risk, especially in high-risk subgroups.^247,331

7.2.3.3. Proprotein convertase subtilisin/kexin type 9 inhibitors

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, in addition to statins, reduce CV events in symptomatic atherosclerotic disease patients with LDL-C ≥1.8 mmol/L.³³⁶ Adding them to statins further reduces MACE and MALE risk in patients with PAD and improves walking distance;³³³ however, their potential in TAA/AAA is an emerging area of research.²⁴⁷

Inclisiran, administered semi-annually, has proved a notable 26% MACE risk reduction in a pooled phase III analysis,³⁵⁸ but its role in PAAD is not firmly established and ongoing RCTs including PAD participants (e.g. ClinicalTrials.gov NCT05030428) aim to provide insights.

7.2.3.4. Bempedoic acid

Bempedoic acid, acting upstream of statins in cholesterol metabolism, has been shown to reduce cholesterol levels by 17%–28%^359,360 and demonstrated a decrease in the incidence of MACE in statin-intolerant PAD patients.³⁶¹ However, its impact on aortic diseases and AAA still requires further research.

7.2.3.5. Hypertriglyceridaemia

Beyond LDL-C, evidence shows insulin resistance, elevated triglycerides, and remnant lipoproteins are associated with ASCVD, particularly in PAD.^362–365 However, in a meta-analysis and an RCT, fibrates showed no benefit over placebo in reducing MACE in patients with PAD for a composite outcome of non-fatal stroke, non-fatal MI, and vascular death.³⁶⁶ Fibrates showed no benefit over placebo in reducing coronary and cerebrovascular events in patients with PAD in an RCT.³⁶⁷ While the relationship between triglycerides and aortic diseases is complex and not fully understood, some evidence suggests that triglyceride levels may contribute to the development and progression of aortic diseases.

In contrast, icosapent ethyl (IPE) demonstrated a reduction in mortality and morbidity among individuals with hypertriglyceridaemia in the Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial (REDUCE-IT).³⁶⁸ Its impact on patients with PAAD is unexplored,³⁶⁹ although a small pilot RCT suggested an improved ABI in hyperglycaemic haemodialysis patients.³⁷⁰

Recommendation Table 9

Recommendations for lipid-lowering therapy in patients with peripheral arterial and aortic diseases

7.2.4. Diabetes and pre-diabetes conditions

Screening for diabetes or pre-diabetes is recommended in PAAD. Recent ESC Guidelines on diabetes and CVD³⁷⁴ provide detailed diagnostic criteria and underscore the importance of diagnosing diabetes in ASCVD patients and vice versa. Both Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus imply significantly increased risk of PAD, carotid stenosis, and polyvascular disease, depending on disease duration and the status of other CVRFs. Diabetes is present in 30% of patients with IC and 50%–70% of those with CLTI.^375,376 Although the prevalence of PAD in patients with diabetes is 20%–30%, only half of them are symptomatic because of peripheral neuropathy with decreased pain sensitivity.³⁷⁷ As already detailed in Section 4, diabetes implies reduced risk of TAA, AAA, or aortic dissection. However, patients with T2DM and PAAD are in the very high-risk group for stroke, MI, and CV death,³⁷⁴ and for T1DM, an online risk prediction tool has recently been developed.^377–380

For non-pregnant PAAD patients, aiming for an HbA1c level of <53 mmol/mol (7%) to avoid significant hypoglycaemia is appropriate. Consider a higher threshold (<69 mmol/mol [8.5%]) for limited life expectancy or when treatment risks outweigh benefits.³⁷⁴

In PAAD, it is recommended to aim for tight glycaemic control, preferably with agents with proven CV benefits such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), adding metformin and other glucose-lowering agents as necessary.^{374,381–384}

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) investigated subcutaneous GLP-1RAs liraglutide (≤1.8 mg/day) and semaglutide (0.5 or 1.0 mg/week), respectively, vs. placebo in T2DM patients with high CV risk. Overall, 12.7% of patients in LEADER and 14.0% in SUSTAIN-6 presented with PAD at baseline. Although non-statistically significant due to a lack of power, the effects on MACE showed a consistently beneficial trend in PAD: liraglutide (hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.58–1.01) and semaglutide (HR, 0.61; 95% CI, 0.33–1.13).³⁸¹

The (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) investigated the SGLT2i empagliflozin (10 mg or 25 mg per day) vs. placebo in patients with T2DM and high CV risk. Overall, 20.8% of patients presented with PAD at baseline. In these patients, empagliflozin reduced CV death (HR, 0.57; 95% CI, 0.37–0.88) and all-cause mortality (HR, 0.62; 95% CI, 0.44–0.88), and there was a non-significant reduction in limb amputation: 5.5% with empagliflozin vs. 6.3% with placebo (HR, 0.84; 95% CI, 0.54–1.32).³⁸² In the Canagliflozin Cardiovascular Assessment Study (CANVAS)³⁸⁵ investigating canagliflozin, there was an increased risk of amputation, but this was not confirmed in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial investigating canagliflozin in patients with T2DM and chronic kidney disease (CKD).³⁸⁶ Still, the use of other SLGT2is seems reasonable in PAD patients.

Patients with carotid stenosis were included in trials testing GLP-1RA and SGLT2i, but no analysis on this subpopulation was performed. A meta-analysis of eight trials investigating GLP-1RAs vs. placebo in patients with T2DM reported a reduction in all strokes (HR, 0.84; 95% CI, 0.75–0.93).³⁸⁷ Among patients with T2DM and prior history of MI or non-fatal stroke, GLP-1RAs reduced the incidence of recurrent MACE (HR, 0.86; 95% CI, 0.8–0.92).³⁸⁸ SGLT2is do not appear to reduce stroke in patients with T2DM, but patients with a stroke history experienced similar cardiorenal benefits as the rest of the population.³⁸⁹

Before the era of GLP-1RAs and SGLT2is, different studies (United Kingdom Prospective Diabetes Study [UKPDS] 34³⁹⁰ and Hyperinsulinaemia: the Outcomes of its Metabolic Effects [HOME] trials³⁹¹) showed that metformin reduced the risk of MALE and MACE in patients with PAD.^391,392 But a recent study with GLP-1RA dulaglutide found the same risk reduction in MACE between patients with and without baseline metformin, calling into question its add-on value.^384,393 However, there are studies suggesting that metformin may reduce AAA growth (see Section 9.2.4).

Recommendation Table 10

Recommendations for the medical management of patients with peripheral arterial and aortic diseases and diabetes

7.2.5. Other pharmacological therapy

Increased attention is focused on inflammation in ASCVD,⁴¹³ supported by the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS),⁴¹⁴ which showed that canakinumab, a monoclonal antibody targeting interleukin (IL)-1β, reduced MACE in high-risk patients with previous MI and increased high-sensitivity (hs)-CRP. Data for patients with PAAD are not reported. Furthermore, low-dose colchicine (0.5 mg/day) has been shown to reduce MACE among those with stable atherosclerosis after recent MI.⁴¹⁵ However, the effect of colchicine and other anti-inflammatory drugs in PAAD remains unproven.⁴¹⁶

8. Peripheral arterial disease

8.1. Lower-extremity peripheral arterial disease

8.1.1. Peripheral arterial disease syndromes

8.1.1.1. Clinical presentation and diagnosis

Atheromatous lower-extremity PAD is a chronic disease with different clinical manifestations. PAD may be symptomatic or asymptomatic and may or may not be associated with limb wounds. Wound healing and amputation risk may be affected by the concomitant presence of PAD, diabetes, and/or infection;⁴¹⁷ therefore, amputation risk assessment should be systematically performed using the Wound, Ischaemia, and foot Infection (WIfI) classification.

PAD presents as:

Asymptomatic PAD: suspected by lower-limb pulse abolition or imaging studies performed for other purposes and detected by pathological ABI or TBI.^418,419 These patients do not present with IC or atypical effort-related symptoms. However, attention should be paid to those with wounds, with masked effort-related symptoms due to reduced walking capacity (for reasons other than PAD), or reduced pain sensitivity. ‘Masked PAD’ is defined as PAD without provoked leg pain because of reduced walking capacity for other reasons or reduced pain sensitivity.⁴²⁰
Symptomatic (effort-related) PAD: patients with pathological ABI or TBI, presenting with IC, atypical effort-related symptoms, or chronic lower-limb wounds (diabetic foot or non-healing ulceration/gangrene ≥2 weeks) without critically reduced limb perfusion.^417,421 In these patients, IC is characterized by exertional muscle pain and dysfunction in the supply area of the obstructed arterial segment, which is relieved at rest.⁴²² Some patients may present with atypical symptoms or with ‘masked PAD’.^420,423 In women, the prevalence of IC is lower than in men, while atypical symptoms are more common.⁴²⁴
CLTI represents the more severe chronic PAD presentation and underlies poor limb outcomes without intervention. In addition to common signs of chronic PAD, patients with CLTI present with a critical haemodynamic status (ankle pressure <50 mmHg, toe pressure [TP] <30 mmHg, or TcPO₂ <30 mmHg) responsible for ischaemic rest pain, non-healing chronic (>2 weeks of duration) ulceration, or foot gangrene.^425,426

PAD syndromes can be categorized according to their clinical presentation (Table 7).

Table 7

Peripheral arterial disease categorized according to clinical presentation

Clinical characteristics of PAD	Rutherford classification		Fontaine classification
Clinical characteristics of PAD	Category	Signs and symptoms	Stage	Signs and symptoms
Asymptomatic PAD	0	Asymptomatic	I	Asymptomatic
Symptomatic (effort-related) PAD	1	Mild claudication	IIa	Non-disabling intermittent claudication
	2	Moderate claudication	IIb	Disabling intermittent claudication
	3	Severe claudication
Chronic limb-threatening Ischaemia	4	Ischaemic rest pain	III	Ischaemic rest pain
	5	Minor tissue loss	IV	Ischaemic ulceration or gangrene
	6	Major tissue loss

Clinical characteristics of PAD	Rutherford classification		Fontaine classification
Clinical characteristics of PAD	Category	Signs and symptoms	Stage	Signs and symptoms
Asymptomatic PAD	0	Asymptomatic	I	Asymptomatic
Symptomatic (effort-related) PAD	1	Mild claudication	IIa	Non-disabling intermittent claudication
	2	Moderate claudication	IIb	Disabling intermittent claudication
	3	Severe claudication
Chronic limb-threatening Ischaemia	4	Ischaemic rest pain	III	Ischaemic rest pain
	5	Minor tissue loss	IV	Ischaemic ulceration or gangrene
	6	Major tissue loss

PAD, peripheral arterial disease.

Table 7

Peripheral arterial disease categorized according to clinical presentation

Clinical characteristics of PAD	Rutherford classification		Fontaine classification
Clinical characteristics of PAD	Category	Signs and symptoms	Stage	Signs and symptoms
Asymptomatic PAD	0	Asymptomatic	I	Asymptomatic
Symptomatic (effort-related) PAD	1	Mild claudication	IIa	Non-disabling intermittent claudication
	2	Moderate claudication	IIb	Disabling intermittent claudication
	3	Severe claudication
Chronic limb-threatening Ischaemia	4	Ischaemic rest pain	III	Ischaemic rest pain
	5	Minor tissue loss	IV	Ischaemic ulceration or gangrene
	6	Major tissue loss

Clinical characteristics of PAD	Rutherford classification		Fontaine classification
Clinical characteristics of PAD	Category	Signs and symptoms	Stage	Signs and symptoms
Asymptomatic PAD	0	Asymptomatic	I	Asymptomatic
Symptomatic (effort-related) PAD	1	Mild claudication	IIa	Non-disabling intermittent claudication
	2	Moderate claudication	IIb	Disabling intermittent claudication
	3	Severe claudication
Chronic limb-threatening Ischaemia	4	Ischaemic rest pain	III	Ischaemic rest pain
	5	Minor tissue loss	IV	Ischaemic ulceration or gangrene
	6	Major tissue loss

PAD, peripheral arterial disease.

The 5 year cumulative incidence of clinical deterioration from asymptomatic PAD to IC is 7%, and 21% from IC to CLTI.⁴²⁷ All patients with PAD are at high risk of MACE, cerebrovascular disease, and MALE (Figure 8).^428–430 The 5 year cumulative incidence of CV mortality is 9% in asymptomatic PAD and 13% in symptomatic patients. In comparison with symptomatic PAD, CLTI further increases all-cause mortality risk (relative risk [RR] 2.26) and the risk of MACE (RR 1.73).⁴³¹ Health insurance data reveal a major amputation rate of 9% in patients with CLTI and 1% in patients with IC, while considerably higher amputation rates were reported in trials and registries data focusing on patients with CLTI.^432–435 Among patients with PAD, development of MALE is associated with poor prognosis, with a three-fold increase in death and a 200-fold increase in subsequent lower-extremity amputation.⁴²⁹

Figure 8

Cardiovascular risk in patients with peripheral arterial disease.

CV, cardiovascular; MACE, major adverse cardiac event; MALE, major adverse limb event; PAD, peripheral arterial disease.

Prevention of MALE is crucial, and the risk of MACE/MALE increases with the increased number of arterial beds involved.

Diagnostic tests

Vascular assessment: ABI, TBI, TcPO₂ measurements (refer to Section 5.3)

Ankle–brachial index is the proposed initial non-invasive diagnostic test to confirm lower-limb decreased perfusion status^90,436,437 and needs to be reported separately for each leg (see Recommendation Table 2). An ABI ≤0.90 confirms PAD diagnosis.^90,436,437 In cases of an ABI >0.90 and clinical suspicion of PAD, post-exercise ABI measurements should be considered, along with imaging studies (preferably by treadmill). A post-exercise ABI decrease of >20% may serve as a PAD diagnostic criterion.^438,439

In cases of abnormally high ABI values (ABI >1.4; see Recommendation Table 2) and patients with CLTI and diabetes⁴⁴⁰ (see Recommendation Table 11), TP measurements, the calculation of TBI and TcPO₂, as well as pulse volume recordings or analysis of distal arterial Doppler waveforms, should be considered,^{90,91,132,133,441} and ABI can be estimated from distal Doppler waveforms independent of diabetes and media sclerosis.¹²⁴

Apart from the assessment of limb perfusion, ABI serves as a surrogate marker for CV and all-cause mortality.^88,442,443 A diagnostic PAD algorithm is depicted in Figure 9.

Figure 9

Diagnostic algorithm for peripheral arterial disease.

6MWT, six-minute walk test; ABI, ankle–brachial index; AP, ankle pressure; DUS, duplex ultrasound; PAD, peripheral arterial disease; SPPB, short physical performance battery; TcPO₂, transcutaneous oxygen pressure; TP, toe pressure; WIfI, Wound, Ischaemia, and foot Infection classification.

Walking impairment questionnaires, assessment of functional and walking capacity

Determining walking impairment, capacity, and functional status in all patients with PAD is mandatory (refer to Section 5.2).

Assessment of amputation risk

In patients with PAD and chronic lower-limb wounds (diabetic foot ulcer, non-healing lower-limb ulceration, or gangrene of ≥2 weeks of duration), even without haemodynamic parameters of critical limb perfusion, the additional presence of comorbidities such as diabetes and/or wound infection may contribute to an increased risk of amputation. The WIfI classification system takes the patients’ limb perfusion, wound size, and the extent of foot infection into account to determine the amputation risk (Table 8).^{417,444–446}

Table 8

Assessment of the risk of amputation: the Wound, Ischaemia, and foot Infection classification

Imaging methods

Duplex ultrasound is recommended as the first-line imaging method for PAD screening and diagnosis. CTA and/or MRA are recommended as adjuvant imaging. For details refer to Supplementary data online, Section 1.4.

Recommendation Table 11

Recommendations for diagnostic tests in patients with peripheral arterial disease and diabetes, renal failure, and wounds

Recommendation Table 12

Recommendations for imaging in patients with peripheral arterial disease

8.1.1.2. Medical treatment

Patients with PAD should receive comprehensive OMT, including supervised exercise training and lifestyle modification (Figures 10–12). A personalized programme of guidelines-guided pharmacotherapy to reduce MACE and MALE should be prescribed and tightly followed.

Figure 10

Optimal medical treatment in patients with peripheral arterial disease.

CV, cardiovascular.

Figure 11

Treatment algorithm in peripheral arterial disease without wounds.

CLTI, chronic limb-threatening ischaemia; PAD, peripheral arterial disease.

Figure 12

Treatment algorithm in peripheral arterial disease with wounds.

CLTI, chronic limb-threatening ischaemia; PAD, peripheral arterial disease.

Patients with PAD are less likely to receive OMT than patients with CAD.^450–452 For general lifestyle and pharmacological therapy see Section 7.

Exercise therapy

A consensus document on exercise and PAD has been published recently.⁶² Symptomatic patients should be medically screened before any supervised exercise training (SET) programme initiation.^37,62 In patients with symptomatic PAD, SET is safe and improves treadmill PFWD, MWD, functional walking as measured by six-minute walking distance (6MWD), HRQoL, and cardiorespiratory fitness (Figure 13).^{294,453–463} Exercise has not been found to improve ABI.^457,458 Ideally, SET should be co-ordinated by vascular physicians, and training sessions supervised by clinical exercise physiologists or physiotherapists.⁶² In Europe, SET is usually underused.^464,465

Figure 13

Exercise training characteristics and benefits in patients with peripheral arterial disease.

CVR, cardiovascular risk.

When SET is not available, home-based exercise training (HBET) should be proposed (Figure 13), although it is inferior with regard to improving walking performance.^466–469 HBET is safe and its inferiority is reduced if monitoring is implemented.^469,470 Compared with no exercise, HBET improves walking performance.⁴⁷¹ SET training frequency should be at least three times per week, for 30–60 min, and the programme last for at least 12 weeks.^{37,58,59,454,472,473} Patients should exercise to moderate-severe claudication pain to improve walking performance.^{37,294,453,454,456–458,474} However, prescribing high-pain exercise may hinder programme uptake and adherence. Additionally, it has been reported that improvements in walking performance may be obtained with less severe claudication pain.^455,460 Therefore, a flexible approach is recommended, considering the patient’s needs and preferences.⁶² Alternative training modalities, such as strength training, arm cranking, cycling, and combinations of different modes, have proven effective in improving walking performance compared with traditional walking training, with limited evidence for HRQoL.⁴⁷⁵ However, this evidence is low due to small sample size and risk of bias.⁴⁷⁵ Vigorous intensity exercise training (77%–95% of maximal heart rate or 14–17 on the rate of perceived exertion on Borg’s scale) has been shown to induce the best walking and cardiorespiratory fitness improvements.^294,457 Training programmes should begin at low-to-moderate intensity, gradually advancing to vigorous exercise if well tolerated.⁶² This approach assesses patient response and minimizes complications.^37,62

Data on the efficacy of exercise therapy in women compared with men are scarce. Women may respond less well than men,^476,477 although discrepancies among studies exist.^478–481

SET combined with endovascular revascularization significantly improves walking performance, HRQoL, and reduces future revascularization.^482,483

An exercise therapy algorithm in PAD has been recently described.⁶²

Recommendation Table 13

Recommendations for exercise therapy in patients with peripheral arterial disease (see also Evidence Table 5)

Pharmacological treatment

Antithrombotic therapy

Asymptomatic PAD

Although patients with PAD are at very high CV risk,^404,484 a trial evaluating the effect of antiplatelet agents in asymptomatic patients with an ABI ≤0.95 did not show an effect on MACE or revascularization.⁴⁸⁵ Another trial on patients with an ABI ≤0.99 and diabetes also failed to show any difference in MACE or amputation.⁴⁸⁶ However, these data were not powered to analyse subgroups and do not rule out the possibility that aspirin could provide a benefit in subjects at increased risk of CV events. In a randomized trial evaluating aspirin in the prevention of cancer and CVD in patients with diabetes without known arterial disease, MACE occurred in a significantly lower percentage of participants in the aspirin group than in the placebo group, with more major bleeding events in the aspirin group.⁴⁸⁷ The effect of antithrombotics in patients with higher-risk PAD (i.e. ABI <0.90 and other CV risk factors) has not been evaluated in randomized trials. Antithrombotic therapy should not be systematically administered in patients with asymptomatic PAD.

Symptomatic PAD

In patients with symptomatic PAD, antithrombotic therapy improves CV prognosis.^488–492 Clopidogrel may have a modest advantage over aspirin (Figure 14).^493,494 In the Examining Use of tiCagreLor In peripheral artery Disease (EUCLID) trial, single antiplatelet therapy (SAPT) with ticagrelor showed no superior benefit in the reduction of MACE or major bleeding compared with clopidogrel.^495–497

Figure 14

Long-term antithrombotic therapy in patients with symptomatic peripheral arterial disease.

b.i.d., twice daily; OAC, oral anticoagulant; PAD, peripheral arterial disease; ASA, aspirin ^aHigh-risk limb presentation: previous amputation, chronic limb-threatening ischaemia, previous revascularization, high-risk comorbidities: heart failure, diabetes, vascular disease in two or more vascular beds, moderate kidney dysfunction; eGFR <60 mL/min/1.73 m².

Dual antithrombotic therapy with aspirin and vascular-dose rivaroxaban (2.5 mg b.i.d.) in patients with PAD is more effective than aspirin alone, reducing MACE, MALE, and preventing acute limb ischaemia (ALI), but with increased major bleeding risk.^{429,430,498,499} Patients with high-risk limb presentation (CLTI, previous amputation, or revascularization) or high-risk comorbidities (heart failure [HF], diabetes, or polyvascular disease [PVD]) benefit the most.⁴⁹⁸

After endovascular therapy, dual antiplatelet therapy (DAPT) for 1–3 months is supported by rare randomized studies.^500,501 DAPT is not associated with reduced CV mortality or MACE,⁵⁰¹ but seems to improve patency without increasing bleeding (Figure 15).^502–504 The combination of aspirin 100 mg and vascular-dose rivaroxaban (2.5 mg b.i.d.), started post-revascularization, showed a moderate but significantly lower incidence of MALE and MACE compared with aspirin alone,^490,505 without an increase in thrombolysis in myocardial infarction (TIMI) major bleedings, but with an increase in International Society on Thrombosis and Haemostasis (ISTH) major bleedings, especially when clopidogrel was given for >1 month.⁵⁰⁶

Figure 15

Patients with chronic symptomatic PAD after endovascular revascularization.

b.i.d., twice daily; DAPT, dual antiplatelet therapy; OAC, oral anticoagulant; PAD, peripheral arterial disease; ASA, aspirin; SAPT, single antiplatelet therapy

^aHigh bleeding risk: dialysis or a renal impairment glomerular filtration rate <15 mL/min/1.73 m², acute coronary syndrome <30 days, history of intracranial haemorrhage, stroke or TIA, active or clinically significant bleeding.

Patients with CLTI are at high risk of MACE and MALE.^429,431,507 Among CLTI patients, there is no robust evidence favouring a specific antithrombotic strategy for vein graft maintenance. DAPT with clopidogrel and aspirin is not superior to aspirin alone in below-the-knee (BTK) bypass grafts.^508–510 Vitamin K antagonists (VKAs) may be considered for high-risk conduits with low bleeding risk.⁵⁰⁹

Dual antiplatelet therapy could confer benefit for prosthetic conduit (occlusion, revascularization, amputation, or death), without increasing major bleeding.⁵¹⁰ VKAs with an international normalized ratio (INR) of 3–4.5 are slightly beneficial in venous conduits, but with a 1.9-fold and 1.3-fold increase in major and fatal bleedings, respectively.⁵⁰⁹ A study suggested that VKAs could be associated with prolonged patency of at-risk prosthetic grafts due to poor run-off.⁵¹¹

In patients with another indication for OAC (such as atrial fibrillation [AF] or mechanic valve replacement) and PAD, anticoagulation is warranted.⁵¹² Additional SAPT post-endovascular therapy should be brief.

Recommendation Table 14

Recommendations for antithrombotic therapy in patients with peripheral arterial disease (see also Evidence Table 6)

Pharmacotherapy to decrease walking impairment

Verapamil,⁵¹⁶ statins,^517,518 antiplatelet agents, and prostanoids (prostaglandins I₂ and E₁)⁵¹⁹ can alleviate walking impairment in patients with symptomatic PAD. However, drugs like cilostazol, naftidrofuryl, pentoxifylline, buflomedil, carnitine, and propionyl-L-carnitine are suggested to increase walking distance in patients with IC without impacting CV health.^339,520 Their objective benefit is generally limited, ranging from mild to moderate, with considerable variability.³³⁹ The additional benefit of these drugs alongside antithrombotics, antihypertensives, and statins remains unknown.

Cilostazol, a phosphodiesterase type III inhibitor, improved MWD compared with placebo and pentoxifylline.^520–522 In a Cochrane analysis, 100 mg twice daily increased MWD by 76%,⁵²¹ while another review reported a 25% average improvement.⁵²⁰ Cilostazol also has antiplatelet effects, requiring cautious combination with other anticoagulant and antiplatelet treatments.⁵²² Notably, it increases bleeding complications.⁵²³

Naftidrofuryl oxalate, tested for IC,⁵²⁴ demonstrated a 74% average increase in MWD and improved HRQoL.^524,525 In a systematic review, the average MWD improvement was 60% compared with placebo.⁵²⁰ However, inconsistent results for other medications, such as prostanoids, pentoxifylline, L-arginine, buflomedil, or Gingko biloba, preclude their recommendation for patients with IC.^519,526,527

Aorto-iliac lesion revascularization

Aorto-iliac lesions can be treated by either an endovascular or a surgical approach according to the lesion morphology and patient risk. Long-term patency with a low risk of complications can be achieved by balloon angioplasty with or without stenting in external iliac arteries or primary stenting in common iliac arteries.⁵²⁸ A meta-analysis evaluated outcomes of open surgery vs. an endovascular approach in aorto-iliac lesions (TASC II C-D) and found that short-term morbidity and mortality favours the endovascular approach, but early and mid-term primary patency favours open surgery; however, secondary patency is comparable in all groups.

Femoro-popliteal lesion revascularization

If revascularization is indicated, endovascular therapy should be the first choice even for complex lesions, especially in surgical high-risk patients.^{119,529–531}

Endovascular therapy faces the challenge of sustaining long-term patency and durability in the femoro-popliteal region, particularly post-stent placement in a highly mobile artery. Drug-eluting balloons have improved long-term patency in complex patient cohorts and lesions.⁵³² With regard to paclitaxel-coated devices, a meta-analysis caused a decline in their usage, especially as the United States Food and Drug Administration (FDA) reacted and restricted their use.⁵³³ Consequently, data from large national databases were evaluated and the mortality signal could not be confirmed. The FDA revised its position, and drug-eluting treatment is now deemed to be a safe and efficient treatment strategy for femoro-popliteal lesions.^534–538

An open surgical approach in femoro-popliteal lesions should be considered when an autologous vein (e.g. great saphenous vein [GSV]) is available and the patient shows low surgical risk, and in complex lesions after an interdisciplinary team discussion.

Below-the-knee artery revascularization

In patients with severe IC in whom endovascular femoro-popliteal treatment is performed, BTK arteries can be treated in the same intervention if there is substantially impaired outflow.⁵³⁹

Recommendation Table 15

Recommendations for interventional treatment of asymptomatic and symptomatic peripheral arterial disease (general)

Recommendation Table 16

Recommendations for interventional treatment of patients with symptomatic peripheral arterial disease (per arterial bed)

8.1.1.3. Follow-up

Asymptomatic and symptomatic PAD are at increased risk of leg symptom worsening⁴²⁷ and of CV mortality and morbidity.^419,431,551 Follow-up post-revascularization is crucial to ensure perfusion improvement, address CVRFs, optimize pharmacological treatment adherence, identify disease progression, and evaluate mental health and functional capacity. Experienced vascular care physicians should conduct follow-up, although specific protocols are currently undefined.^128,552 Data on asymptomatic PAD follow-up are limited.⁵⁵³ For symptomatic PAD or post-intervention, annual follow-up are advised, including ABI/TBI measurement and DUS for new or worsening symptoms.

Recommendation Table 17

Recommendations in patients with peripheral arterial disease: follow-up of patients with peripheral arterial disease

8.1.2. Chronic limb-threatening ischaemia

8.1.2.1. Clinical presentation and diagnosis

Chronic limb-thretening ischaemia describes chronic lower-limb hypoperfusion responsible for ischaemic rest pain, or non-healing ulceration or gangrene (typically in distal segments).^555,556 Ischaemic rest pain primarily affects the patient’s forefoot and aggravates in a supine position, while lowering of the affected leg eases ischaemic symptoms.

Definition

Chronic limb-thretening ischaemia should be considered in the presence of one of the following lower-limb clinical signs or symptoms:

Ischaemic rest pain
Non-healing lower-limb wound of ≥2 weeks’ duration
Lower-limb gangrene

The following haemodynamic criteria may be used to guide diagnosis in patients with suspicion of CLTI:

Ankle pressure <50 mmHg
TP <30 mmHg
TcPO₂ <30 mmHg

Initial assessment and risk of amputation

For patients with CLTI, initial diagnostic steps involve clinical examination and limb perfusion assessment through haemodynamic measurements. Regarding haemodynamic assessment in CLTI, standard ABI may be normal or falsely elevated due to non-compressible arteries related to medial sclerosis (common in diabetes or CKD),⁵⁵⁷ which can be overcome by estimation of ABI based on Doppler waveforms.¹²⁴ Therefore, standard ankle pressure alone may not be reliable in estimating limb loss risk.^441,558 In addition, a large proportion of patients with ulcers may have below-the-ankle lesions.⁴⁴⁰ In patients with CLTI, TP, TBI, or TcPO₂ should additionally be obtained.^90,441,559

Particularly in patients with CLTI, the WIfI classification system should be applied. In addition to patients’ limb perfusion, the WIfI classification considers the wound size and the extent of foot infection to determine the individual risk of amputation.^{417,444–446}

Imaging

In all patients with CLTI, comprehensive vascular imaging is mandatory to evaluate revascularization options. CLTI commonly affects more than one arterial segment of the lower limbs, involving infra-popliteal arteries (BTK and below-the-ankle arteries) in most cases. While non-invasive imaging (DUS, CTA, MRA) provides reliable results for above-the-knee arteries, imaging of BTK arteries, especially below the ankle, may be hampered by severe calcification.^448,560,561 Therefore, in CLTI additional DSA with dedicated views of the foot should be considered for the assessment of BTK arteries.⁵⁶⁰ Even in patients who are not candidates for revascularization, DSA should be obtained to prevent unnecessary amputation or to minimize amputation extent.^560,562

Mortality risk assessment

All-cause mortality and event rates of MI are more than two-fold higher in CLTI patients than in unselected patients with an ABI ≤0.90.⁴³¹

In CLTI patients undergoing revascularization, the post-revascularization period is particularly associated with an increased risk of MALE and MACE.⁵⁶³ The management of patients with CLTI should therefore include an individual peri-procedural risk assessment. Referring to the peri-procedural risk patients can be categorized as average procedural risk (peri-procedural mortality <5% and 2 year survival >50%) or high procedural risk (peri-procedural mortality ≥5% and 2 year survival ≤50%).^564,565

Besides revascularization, it also needs to be considered that lower-limb amputation is associated with 30 day mortality rates of up to 22%.⁵⁶⁶

Recommendation Table 18

Recommendations for the management of chronic limb-threatening ischaemia

8.1.2.2. Medical treatment

Chronic limb-thretening ischaemia is associated with a high risk of ischaemic events,^429,431 thus management of patients with CLTI must include OMT.

In addition, rest pain, optimal wound care, and infection control should be managed. A vascular team, including at least a vascular physician, a vascular surgeon, and a radiologist, should be involved to prevent amputation.⁵⁶⁸ Lower-limb exercise training is contraindicated until ulcers are healed and aggressive offloading should be ensured to allow healing. Depending on infection extent, oral antibiotics may suffice, however, if extensive with systemic signs of inflammation, admission for intravenous (i.v.) antibiotic administration may be required.^569,570

Good-quality evidence on the advantages of one type of wound dressing over others is lacking, while in selected patients individualized treatments with antimicrobial dressing,⁵⁷¹ silver dressing,⁵⁷² collagen dressing,⁵⁷³ honey- or iodine-based dressings,⁵⁷⁴ platelet-rich plasma, or negative pressure therapy^575,576 may accelerate wound healing, shorten hospital stay, and prevent amputations. If deep-seated infection is suspected, X-ray or MRA are required to diagnose osteomyelitis, in which case a longer course of antibiotics may be necessary.⁵⁷⁷ Antibiotics for osteomyelitis treatment may be empirical, however, they should be adapted according to (preferably tissue) cultures.^578–581

Ulcers require assessment of venous aetiology and potential for endovenous therapy, while mixed ulcers require compression therapy after revascularization.⁵⁸²

Recommendation Table 19

Recommendations for medical treatment in patients with chronic limb-threatening ischaemia (see also Evidence Table 7)

8.1.2.3. Interventional treatment

Revascularization

In CLTI, revascularization should be attempted to rapidly restore an inline direct blood flow to the foot.^585–588 Three RCTs compared endovascular therapy with open surgery in infra-inguinal arteries. In the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial, no significant difference was found regarding mortality or amputation-free survival at 2 years.⁵⁸⁹ However, surgery was associated with a significantly reduced risk of amputation, death, or both after 2 years.^564,589 In the Best Endovascular versus Best Surgical Therapy for Patients with Critical Limb Ischemia (BEST-CLI) trial (median follow-up of 2.7 years), the incidence of MALE or death was lower in patients in which one segment of the GSV was available for surgical revascularization than in patients who underwent endovascular revascularization. In the same trial, outcomes of patients for whom an alternative bypass conduit was needed for surgical revascularization were similar to those of patients who underwent endovascular revascularization.⁵⁶⁷

In the BASIL-2 trial, which included patients requiring infra-popliteal, with or without additional further proximal infra-inguinal, revascularization procedures, endovascular revascularization was associated with better amputation-free survival than surgical revascularization, which was primarily due to fewer deaths in this group.⁵⁹⁰ It is important to consider⁵⁹¹ both revascularization options individually in each patient, considering the complexity of the diseased anatomical region.

Multilevel disease

Patients with CLTI commonly present with multilevel disease.⁵⁹² Especially for complex lesions, comprehensive patient assessment, including the individual patient’s clinical presentation, the lesion morphology, and the peri-procedural risk, needs to be undertaken by a multidisciplinary vascular team to weigh the risks against the benefits of the respective methods of revascularization (endovascular vs. surgical).^{590,593–596} A structured approach is essential to achieve rapid and durable restoration of an inline flow to the foot. When possible, the angiosome concept can be considered, targeting the most affected ischaemic area.⁵⁹⁷ When CLTI leaves no viable revascularization options, transcatheter arterialization of deep veins may be considered.⁵⁹⁸

Aorto-iliac disease

An endovascular approach is the first choice, commonly employing bare metal or covered stents.^599–603 Surgery is reserved for extensive obstructions and lesions treated unsuccessfully with an endovascular procedure.⁶⁰⁴ Hybrid revascularization should be considered in occlusion of the common femoral artery or profunda femoris artery requiring endarterectomy, in addition to inflow and/or outflow disease amenable to endovascular therapy. Hybrid procedures should be encouraged in a one-step modality.⁶⁰⁵

Femoro-popliteal disease

Chronic limb-threatening ischaemia is unlikely to be related to isolated superficial femoral artery lesions; femoro-popliteal involvement in combination with aorto-iliac or infra-popliteal disease is frequently found. In 40% of cases, inflow treatment of femoro-popliteal disease is necessary.⁶⁰⁶ The revascularization strategy should be selected according to lesion complexity.⁴²² If endovascular therapy is chosen, landing zones for potential bypass grafts should be preserved. When bypass surgery is decided, the bypass should be as short as possible, using the saphenous veins.⁵⁶⁷

Infra-popliteal disease

Extended infra-popliteal disease is mainly seen in patients with diabetes^607–610 and CKD,^611,612 often being associated with superficial femoral artery lesions. In short infra-popliteal lesions, endovascular therapy is the first choice.⁵⁹³ Drug-eluting balloons⁶⁰⁷ and bare metal stent implantation⁶¹³ have shown no superiority over plain balloon angioplasty, although drug-eluting stents may be used for relatively short proximal lesions.^614–616

Spinal cord stimulation

Spinal cord stimulation (SCS) may be considered in treating patients with CLTI and no viable revascularization options. SCS offers modest pain relief and an 11% reduction in amputation rate compared with conservative management at 1 year. No effect was seen in ulcer healing and benefits should be weighed against the high cost and possible complications.⁶¹⁷ Recent technological advances in neuromodulation may improve the treatment value of this modality.⁶¹⁸

Amputation

Minor amputation, usually up to the forefoot, is often needed for necrotic tissue removal with minor impact on patient mobility. Pre-amputation revascularization enhances wound healing. In cases of extensive necrosis or infectious gangrene, primary major amputation without revascularization may be preferable to avoid complications. Secondary amputation is indicated when revascularization fails, re-intervention is not possible, or limb deterioration persists despite a patent graft and optimal management. BTK amputation allows better mobility with a prosthesis. For bedridden patients, above-the-knee amputation may be the preferred choice.

Recommendation Table 20

Recommendations for interventional treatment of chronic limb-threatening ischaemia

8.1.2.4. Follow-up

In patients with CLTI, the incidence of CV events is increased.^619,620 Follow-up should focus on general clinical CV condition, prevention of revascularization failure, wound healing, and contralateral limb status. After revascularization, at least an annual appointment with a vascular physician expert in CLTI management is warranted. Due to the lack of evidence, recommendations are largely based on consensus and expert opinions.¹²⁸

First-year incidence of vein graft stenosis is 20%;⁶²¹ however, if uneventful for 12 months, late issues are scarce.⁶²² Clinical examination, ABI (or TBI) measurement, and DUS should be performed within 4–6 weeks and thereafter at 3, 6, 12, and 24 months after bypass surgery.¹²⁸

After endovascular treatment, restenosis and occlusion ranges from 5% in the pelvic region to >50% in the infra-popliteal arteries.^623,624 Unlike after surgery, no plateau phase is seen, and the failure rate is constant for at least 5 years. Surveillance includes clinical assessment looking for recurrent symptoms or signs, ABI measurement, and DUS based on the first check-up: if normal, DUS is recommended if symptoms reappear; if abnormal, initial DUS, re-intervention, or closer DUS follow-up on a case-by-case basis are recommended.¹²⁸ Post-procedural ankle duplex-based estimated ABI of <0.90 predicts suboptimal wound healing, clinically driven target lesion revascularization (cdTLR), and MALE.⁶²⁵

After revascularization, closer follow-up and wound care are recommended until healing. Thereafter, annual appointments with vascular physicians with expertise in CLTI management should be scheduled to check for symptoms, foot condition, ABI, and CVRFs, including availability for TP and TcPO₂ if needed. Recurrence of symptoms may also be due to the progression of atherosclerotic disease above or below the bypass or angioplasty site.⁴²⁷

Recommendation Table 21

Recommendations for follow-up in patients with chronic limb-threatening ischaemia

8.1.3. Acute limb ischaemia

8.1.3.1. Clinical presentation and diagnosis

Acute limb ischaemia is caused by an abrupt decrease in arterial limb perfusion. Potential causes are PAD progression, cardiac/aortic embolization, AD, graft thrombosis, aneurysm thrombosis, popliteal artery entrapment syndrome, trauma, phlegmasia cerulea dolens, ergotism, hypercoagulable states, and iatrogenic complications related to vascular procedures. ALI is a medical emergency and timely recognition is crucial to successful treatment.^629–632 Patients should be rapidly evaluated by a vascular specialist⁶³³ or rapidly transferred to a facility with such resources.

The time constraint is due to the period that skeletal muscle and nerves will tolerate ischaemia—roughly 4–6 h.⁶³⁴ Lower-extremity symptoms can include both pain and loss of function. The longer and the stronger these symptoms are, the less likely the possibility of limb salvage.

Clinical examination

The emergency level and the choice of therapeutic strategy depend on the clinical presentation, mainly according to neurological deficits. Clinical assessment must include symptom duration as well as sensory and motor deficit severity to distinguish a threatened from a non-viable extremity. Neurological deficits (sensory loss or especially motor deficit) are signs of limb threat and require emergency imaging and revascularization.⁶³⁵ Severe sensory deficit and paralysis suggest the limb may be unsalvageable. Clinical ALI categories are presented in Table 9.

Table 9

Clinical categories of acute limb ischaemia

Grade	Category	Sensory loss	Motor deficit	Arterial Doppler signal	Venous Doppler signal	Capillary refill	Biomarkers	Prognosis
I	Viable	None	None	Yes	Yes	Yes	Not elevated	No immediate threat
IIA	Marginally threatened	None or minimal (toes)	None	No	Yes			Salvageable if promptly treated
IIB	Immediately threatened	More than toes	Mild-moderate	No	Yes			Salvageable if promptly revascularized
III	Irreversible	Profound, anaesthetic	Profound paralysis (rigor)	No	No	No	Massively elevated	Major tissue loss, permanent nerve damage inevitable

Grade	Category	Sensory loss	Motor deficit	Arterial Doppler signal	Venous Doppler signal	Capillary refill	Biomarkers	Prognosis
I	Viable	None	None	Yes	Yes	Yes	Not elevated	No immediate threat
IIA	Marginally threatened	None or minimal (toes)	None	No	Yes			Salvageable if promptly treated
IIB	Immediately threatened	More than toes	Mild-moderate	No	Yes			Salvageable if promptly revascularized
III	Irreversible	Profound, anaesthetic	Profound paralysis (rigor)	No	No	No	Massively elevated	Major tissue loss, permanent nerve damage inevitable

Adapted with permission from.⁶⁴¹

Table 9

Clinical categories of acute limb ischaemia

Grade	Category	Sensory loss	Motor deficit	Arterial Doppler signal	Venous Doppler signal	Capillary refill	Biomarkers	Prognosis
I	Viable	None	None	Yes	Yes	Yes	Not elevated	No immediate threat
IIA	Marginally threatened	None or minimal (toes)	None	No	Yes			Salvageable if promptly treated
IIB	Immediately threatened	More than toes	Mild-moderate	No	Yes			Salvageable if promptly revascularized
III	Irreversible	Profound, anaesthetic	Profound paralysis (rigor)	No	No	No	Massively elevated	Major tissue loss, permanent nerve damage inevitable

Grade	Category	Sensory loss	Motor deficit	Arterial Doppler signal	Venous Doppler signal	Capillary refill	Biomarkers	Prognosis
I	Viable	None	None	Yes	Yes	Yes	Not elevated	No immediate threat
IIA	Marginally threatened	None or minimal (toes)	None	No	Yes			Salvageable if promptly treated
IIB	Immediately threatened	More than toes	Mild-moderate	No	Yes			Salvageable if promptly revascularized
III	Irreversible	Profound, anaesthetic	Profound paralysis (rigor)	No	No	No	Massively elevated	Major tissue loss, permanent nerve damage inevitable

Adapted with permission from.⁶⁴¹

Imaging and functional tests

The imaging method depends on availability and aims to diagnose clot presence and assess haemodynamic severity. DSA, CTA, DUS, and contrast-enhanced (CE)-MRA are options based on local expertise, availability, and preference.⁶³⁶ DUS helps determine treatment urgency when assessing neurological deficit is challenging. Loss of arterial signal suggests limb threat, while a present signal may indicate the limb is not immediately threatened, allowing for ABI measurement. The absence of both arterial and venous Doppler signals, coupled with extensive motor deficit, suggests the limb may be irreversibly damaged (non-salvageable).⁶³⁷ In addition, biomarkers of muscle damage such as creatinine kinase (CK) or myoglobin may be useful as high levels indicate rhabdomyolysis, risk of amputation,⁶³⁸ kidney failure, and mortality.⁶³⁹ In limb ischaemia, CK and myoglobin elevations may be lower in chronic cases, possibly due to ischaemic pre-conditioning and collateral development.⁶⁴⁰

8.1.3.2. Medical treatment

Upon clinical diagnosis, initiate analgesia, anticoagulation, and i.v. fluids. Addressing acidosis and hyperkalaemia may be necessary. Administer i.v. unfractionated heparin (bolus 5000 IU or 70–100 IU per kg body weight, followed by continuous infusion with dose adjustment based on patient response, monitored by activated clotting time or activated partial thromboplastin time) or subcutaneous low molecular weight heparin (e.g. enoxaparin 1 mg per kg twice daily) to prevent further embolization and thrombus propagation.

8.1.3.3. Surgical and interventional treatment

For a salvageable limb, urgent revascularization is essential. Diagnostic imaging, if it will not delay treatment, is recommended to guide therapy. If the limb is deemed unsalvageable, primary amputation or comfort care is indicated.

Different revascularization modalities can be applied, including percutaneous catheter-directed thrombolytic therapy, percutaneous mechanical thrombus extraction or thrombo-aspiration (with or without thrombolytic therapy), or surgical thrombectomy, bypass, and/or arterial repair.⁶⁴² Moreover, these modalities can be combined, with the strategy determined by factors such as neurological deficit, ischaemia duration, localization, size, aetiology, comorbidities, type of conduit (artery or graft), and therapy-related risks and outcomes. Current endovascular approaches to ALI boast high technical success rates.⁶²⁶ To reduce morbidity and mortality, an endovascular-first approach is often preferred, especially in patients with severe comorbidities. Thrombus extraction, thrombo-aspiration, and surgical thrombectomy are indicated in cases of neurological deficit, while catheter-directed thrombolytic therapy is more appropriate in less severe cases without neurological deficit. Modern catheter-based thrombectomy (CDT) is associated with 12-month amputation rates of <10% in Rutherford IIB.⁶⁴³ A meta-analysis showed that although CDT in the treatment of not immediately threatening ALI showed high angiographic success, the long-term outcomes were relatively poor, with low patency and a substantial risk of major amputation.⁶⁴⁴ Systemic thrombolysis has no role in the treatment of patients with ALI.

A meta-analysis showed that CDT and surgery have similar limb salvage rates.⁶⁴⁵ Recent analyses indicate benefits of endovascular approaches in terms of mortality at similar amputation rates.^646,647

A comparison of percutaneous thrombectomy vs. ultrasound-accelerated thrombolysis for the initial management of ALI showed no difference in terms of amputation, bleeding, clinical success, and adverse events, with primary patency at 30 days of 82% and 71%, respectively.^629,648,649

After thrombus removal, in cases of pre-existing arterial lesions, these should be treated by endovascular therapy or open surgery. If surgical treatment is required, it should be ideally performed in a hybrid room with capacity to allow sufficient completion angiographic imaging and initiation of local lysis if any remaining clot is visualized. Lower-extremity four-compartment fasciotomies should be performed in patients with long-lasting ischaemia to prevent post-reperfusion compartment syndrome.⁶³⁷ The management of ALI is summarized in Figure 16.

Figure 16

Management of acute limb ischaemia.

ALI, acute limb ischaemia; CTA, computed tomography angiography; DSA, digital subtraction angiography; DUS, duplex ultrasound; MRA, magnetic resonance angiography. ^aShould not delay treatment.

8.1.3.4. Follow-up

After revascularization or amputation, haemodynamic success should be established, aetiology of ALI investigated, and OMT ensured. Statins improve outcomes after revascularization.^552,630 Since ALI is frequently caused by thrombo-embolism, Holter-ECG, echocardiogram, and aortic imaging are useful to allow initiation of appropriate therapy, in particular anticoagulation.⁶⁵⁰ Additionally, consider other prothrombotic syndromes, such as antiphospholipid syndromes and vasculitis, if clinically suspected. While there is only sparse evidence, the inclusion of PAD patients after revascularization into structured follow-up may improve their functional outcomes.⁶²⁷

Recommendation Table 22

Recommendations for the management of patients presenting with acute limb ischaemia (see also Evidence Table 8)

8.2. Extracranial carotid and vertebral artery disease

8.2.1. Clinical presentation and diagnosis

8.2.1.1. Clinical presentation

Atherosclerotic CS represents one of the major causes of acute ischaemic stroke (20%).⁶⁵⁷

CS may be revealed by a cervical bruit, but also by a TIA or stroke.

8.2.1.2. Diagnosis

Atherosclerotic lesions are primarily located in specific arterial segments, including the carotid bifurcation, siphon, M1 segment of the middle cerebral artery, brachiocephalic trunk, subclavian artery, first and fourth segments of the vertebral artery, or first segment of the basilar artery. Carotid plaques (CP), originating in the intima, offer a better representation of the atherosclerotic process than carotid intima-media thickness (cIMT). CP may be diffuse or focal (protuberant). According to the Mannheim carotid plaque consensus, a CP is defined as a focal structure encroaching into the arterial lumen by ≥0.5 mm or ≥50% of the surrounding vessel.⁶⁵⁸ The American Society of Echocardiography (ASE) recently proposed a definition that includes any focal thickening considered atherosclerotic in origin and encroaching into the lumen of any carotid artery segment (protuberant-type plaque) or, in the case of diffuse vessel wall atherosclerosis, when cIMT measures ≥1.5 mm in any carotid artery segment.⁶⁵⁹ Plaques can progress to CS, defined as ≥50% narrowing of the extracranial internal carotid artery (ICA), with stenosis severity estimated using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method or its non-invasive equivalent assessed by DUS (Figure 17).^122,660 Other methods are described in the Supplementary data online, Section 1.5. The European Carotid Surgery Trial (ECST) and the area methods overestimate the severity of the CS and are not recommended.⁷⁷

Figure 17

North American Symptomatic Carotid Endarterectomy Trial/European Carotid Surgery Trial methods.

ECST, European Carotid Surgery Trial; NASCET, North American Symptomatic Carotid Endarterectomy trial.

Carotid DUS is safe, accurate, and reliable if performed by a skilled vascular specialist. It is the first-line imaging modality for screening, diagnosis, and surveillance of extracranial carotid arteries.⁷⁷ The degree of stenosis is mostly based on Doppler analysis of blood flow in the common carotid artery (CCA), ICA, and external carotid artery (Table 10).^661,662 Vertebral and subclavian arteries must also be checked. In some cases, indirect signs of severe stenosis have to be evaluated by transcranial and/or ophthalmic artery Doppler. Severe arterial calcification can decrease DUS accuracy.¹²²

Table 10

Peak systolic velocity criteria for grading internal carotid artery stenosis

% stenosis	Reference	50%–69% (moderate stenosis)	≥70% (severe stenosis)
PSV threshold	SRUCC⁶⁶² ------------------------- Gornik et al.⁶⁶¹	125–230 cm/s ------------------------- ≥180 cm/s or ≥125 cm/s + PSV ICA/CCA ≥2	>230 cm/s ------------------------- Overestimation with SRUCC criteria but no consensus

% stenosis	Reference	50%–69% (moderate stenosis)	≥70% (severe stenosis)
PSV threshold	SRUCC⁶⁶² ------------------------- Gornik et al.⁶⁶¹	125–230 cm/s ------------------------- ≥180 cm/s or ≥125 cm/s + PSV ICA/CCA ≥2	>230 cm/s ------------------------- Overestimation with SRUCC criteria but no consensus

CCA, common carotid artery; ICA, internal carotid artery; PSV, peak systolic velocity; SRUCC, Society of Radiologists in Ultrasound.

Table 10

Peak systolic velocity criteria for grading internal carotid artery stenosis

% stenosis	Reference	50%–69% (moderate stenosis)	≥70% (severe stenosis)
PSV threshold	SRUCC⁶⁶² ------------------------- Gornik et al.⁶⁶¹	125–230 cm/s ------------------------- ≥180 cm/s or ≥125 cm/s + PSV ICA/CCA ≥2	>230 cm/s ------------------------- Overestimation with SRUCC criteria but no consensus

% stenosis	Reference	50%–69% (moderate stenosis)	≥70% (severe stenosis)
PSV threshold	SRUCC⁶⁶² ------------------------- Gornik et al.⁶⁶¹	125–230 cm/s ------------------------- ≥180 cm/s or ≥125 cm/s + PSV ICA/CCA ≥2	>230 cm/s ------------------------- Overestimation with SRUCC criteria but no consensus

CCA, common carotid artery; ICA, internal carotid artery; PSV, peak systolic velocity; SRUCC, Society of Radiologists in Ultrasound.

Recommendation Table 23

Recommendations for carotid artery stenosis assessment

8.2.2. Asymptomatic carotid artery stenosis

8.2.2.1. Medical treatment

Optimal medical treatment is based on CVRF correction through lifestyle intervention and pharmacological treatment, with the goal of reducing cerebrovascular and global CV events.¹⁹ Concerning hypertension, similar target values as those presented in the general section are recommended for patients with asymptomatic CS.

Lipid-lowering therapy

See Section 7.

Antihypertensive therapy

See Section 7.

Glucose-lowering therapy

See Section 7.

Antithrombotic therapy

The clinical benefit of antithrombotic treatment in patients with asymptomatic CS remains unproven.⁶⁶⁴ The only RCT (the Asymptomatic Cervical Bruit Study [ACB]) addressing the issue enrolled only 188 patients per arm, and failed to show superiority of aspirin vs. placebo in reducing TIA, stroke, MI, or death.⁶⁶⁵ In observational studies, SAPT (mainly low-dose aspirin) was associated with reduced risk of MACE, although data were conflicting for moderate stenosis (i.e. 50%–75%);⁶⁶⁴ DAPT, combining aspirin and clopidogrel, has no benefit over SAPT.^496,497

The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial reported a non-significant decrease in MACE in patients with either history of carotid revascularization or asymptomatic patients with >50% CS and CVRFs allocated to dual antithrombotic therapy (aspirin 100 mg o.d. and rivaroxaban 2.5 mg b.i.d.) vs. aspirin alone or rivaroxaban 5 mg b.i.d. alone. However, specific data on asymptomatic CS were not reported.

Since these patients present a two times higher risk of MI,³⁰ lifelong low-dose aspirin should be considered in asymptomatic CS patients at increased risk for CV events (i.e. diabetic patients) and low bleeding risk⁴⁹⁷ to reduce stroke and CV risk.^{19,299,488,666}

Recommendation Table 24

Recommendations for antithrombotic treatment in patients with carotid stenosis

8.2.2.2. Interventional treatment

Open surgery vs. medical therapy

The rationale for carotid endarterectomy (CEA) in asymptomatic CS stems from two trials that were published some time ago. The Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial 1 (ACST-1) compared CEA with medical therapy in asymptomatic patients with 60%–99% CS.^672–674 In ACAS, 5 year rates of ipsilateral stroke/death under CEA vs. medical therapy were 5.1% vs. 11.0%. ACST-1 reported 5 year rates of any stroke of 6.4% vs. 11.8%, respectively. In a combined analysis of both trials, CEA conferred less benefit in women at 5 years.⁶⁷⁵ At 10 years, however, ACST-1⁶⁷⁴ reported that females benefit following CEA (absolute risk reduction [ARR] 5.8%) to the same extent as men (ARR 5.5%).

Medical treatment has advanced following the recruitment of patients in these trials.^672–676 A 60%–70% decline in annual stroke rates was also observed in medically treated patients in both trials over 1995 to 2010.⁶⁷⁶ This reduction was attributed to better medical treatment and lower smoking incidence. The Stent Protected Angioplasty versus Carotid Endarterectomy study (SPACE-2) compared OMT alone against OMT plus CEA/carotid artery stenting (CAS) in asymptomatic patients with CS ≥70% according to ECST criteria. Due to slow recruitment, the study was underpowered. The 1 year rate of the major secondary endpoint was 2.5% after CEA, 3.0% after CAS, and 0.9% after OMT.⁶⁷⁷ Incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2.5% with CEA plus OMT, 4.4% with CAS plus OMT, and 3.1% with OMT alone. Results from the Carotid Revascularization Endartectomy vs. Stenting Trial 2 (CREST-2) are awaited to clarify whether intervention is beneficial in the treatment of asymptomatic CS compared with modern OMT.

The ARR in stroke favouring surgery over OMT was only 4.6% at 10 years in ACST-1, indicating that 95% of asymptomatic patients ultimately underwent unnecessary interventions.^674,678

A recent meta-analysis confirmed the role of modern OMT in reducing major stroke, combined stroke, and mortality in asymptomatic patients, suggesting that OMT has the potential to reduce the requirement for surgical intervention in patients with asymptomatic carotis stenosis.⁶⁷⁹

In conclusion, for invasive treatment of asymptomatic carotid stenosis, the overall risk reduction is low compared with OMT. Current data are not available to assess subgroups that may still benefit from intervention. However, there is a need to target revascularization in a subgroup of patients with clinical and/or imaging features that increase the risk for stroke on OMT (Table 11).^678,680

Table 11

High-risk features associated with increased risk of stroke in patients with asymptomatic internal carotid artery stenosis on optimal medical treatment

Clinical^a

Contralateral TIA/stroke^681,682

Cerebral imaging

Ipsilateral silent infarction^683–685

Ultrasound/CT imaging

Stenosis progression (>20%)^340,684,685
Spontaneous embolization on transcranial Doppler (HITS)^341,686
Impaired cerebral vascular reserve^687,688
Large plaques^689,690
Echolucent plaques^136,691
Increased juxta-luminal black (hypoechogenic) area^689,690

MRA^b

Intraplaque haemorrhage^692,693
Lipid-rich necrotic core^694,695

CT, computed tomography; HITS, high-intensity transient signal; MRA, magnetic resonance angiography; TIA, transient ischaemic attack.

^aAge is not a predictor of poorer outcome.

^bMore than 40 mm² on digital analysis.

Importantly, ACST-1 found no evidence that age >75 years at baseline was associated with any ipsilateral stroke reduction at 5–10 years.^{676–678,696} Neither the ACAS nor ACST-1 studies found any evidence that stenosis severity or contralateral occlusion increased late stroke risk.^672,674,697 In a recent meta-analysis, increasing stenosis was associated with late ipsilateral stroke only in the presence of concomitant high-risk features.⁶⁹⁸ The general algorithm of CS management is presented in Figure 18.⁵⁵²

Figure 18

Algorithm of carotid artery stenosis management.

CAS, carotid artery stenting; CEA, carotid endarterectomy; CTA, computed tomography angiography; MRA, magnetic resonance angiography; OMT, optimal medical treatment; TCAR, transcarotid artery revascularization; TIA, transient ischaemic attack. ^aAssess presence of high-risk features according to Table 11. If surgery/revascularization is considered, assess the overall risk related to surgery according to Table 12.

Carotid revascularization: surgery vs. stenting

In a recent meta-analysis update on RCTs in asymptomatic patients comparing CEA vs. CAS, including altogether 7092 patients, CAS was associated with significantly higher rates of 30 day ‘any’ stroke and 30 day death/any stroke, while CEA was associated with significantly higher rates of 30 day MI. No significant differences were seen in 30 day death, 30 day disabling stroke, 30 day death/disabling stroke, or 30 day death/any stroke/MI when CAS was compared with CEA.⁶⁹⁹ In the largest RCT, ACST-2, post-operative death and major stroke were similar (1.0%) between groups.^700,701

No significant difference was found in the 5 and 10 year incidence of ipsilateral stroke and any stroke between CEA and CAS.^696,702,703 The 5 year non-procedural stroke rate in ACST-2 was 2.5% in each group for fatal/disabling stroke, and 5.3% with CAS vs. 4.5% with CEA for any stroke.^700,701

The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial randomized symptomatic and asymptomatic patients deemed ‘high-risk for surgery’ to either CEA or CAS (using embolic protection devices).⁷⁰⁴ Overall, 71% of SAPPHIRE patients were asymptomatic, and in these patients the 30 day rate of death/stroke after CAS was 5.8% vs. 6.1% after CEA⁷⁰⁴—both beyond the recommended 3%. If these procedural risk levels reflect contemporary practice, most ‘high-risk for surgery’ asymptomatic patients would be better treated medically.

A small sample size RCT has provided evidence that the use of a double-layer mesh stent can reduce the occurrence of peri-procedural diffusion-weighted imaging (DWI)-detected ischaemic lesion after carotid stents, when compared with conventional stents. At 1 year follow-up the use of a double-layer mesh stent was associated with a significant reduction in the composite endpoint of MACE and in-stent restenosis or occlusion. The clinical benefit of these findings has to be proven.^705,706

Transcarotid artery revascularization (TCAR) has been introduced recently. Although no RCTs are available, large registry-based analyses report a 99.7% technical success rate and low 30 day complication rates (<3% in 30 day stroke/death and <1% MI).⁶⁸¹

In a large-scale registry the 1 year rate of stroke or death was 6.4% for TCAR, 5.2% for CEA, and 9.7% for transfemoral carotid artery stenting (TFCAS).⁷⁰⁷

Properly conducted RCTs comparing TCAR with CEA in asymptomatic patients are required to establish the true place of TCAR in carotid revascularization.⁷⁰⁸

Recommendation Table 25

Recommendations for interventional treatment in patients with asymptomatic carotid artery stenosis

8.2.3. Symptomatic carotid artery stenosis

8.2.3.1. Medical treatment

Lipid-lowering therapy

See Section 7.

Antihypertensive therapy

See Section 7.

Glucose-lowering therapy

See Section 7.

Antithrombotic therapy

Symptomatic CS is associated with a high risk of early recurrence of cerebrovascular ischaemic events.^{667–669,683} DAPT with low-dose aspirin and clopidogrel is recommended for all patients with symptomatic CS for at least 3 months.⁶⁶⁹ Those undergoing surgical revascularization can stop clopidogrel after surgery.⁷¹¹ Those undergoing endovascular revascularization should continue DAPT with clopidogrel and low-dose aspirin for 4 weeks after the procedure.^{488,666,711,712} In patients with stroke related to extracranial arterial disease, aspirin was more effective than VKAs in reducing recurrencies.^687,713 Subgroup analysis from the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial suggested a lower rate of MACE in patients receiving ticagrelor vs. aspirin;⁶⁸⁹ however, this analysis was underpowered to make any conclusions regarding the benefit of ticagrelor.

A combination of aspirin and clopidogrel in the early phase of symptomatic carotid stenosis reduces asymptomatic cerebral embolization and stroke.^692,694,714 It also reduces stroke recurrence after a minor stroke/TIA.^667,668

Recently, the Acute Stroke or Transient Ischaemic Attack Treated with Ticagrelor and acetylsalicylic acid for Prevention of Stroke and Death (THALES) trial showed a 17% reduction in the risk of death or stroke when using ticagrelor and aspirin vs. aspirin alone in patients with minor stroke or high-risk TIA;⁷¹⁵ however, bleeding events occurred more frequently in the ticagrelor plus aspirin group.^700,716 Of note, COMPASS data cannot be applied to symptomatic carotid stenosis since these patients were excluded because of intracranial bleeding risk.⁴⁹⁹

Recommendation Table 26

Recommendations for evaluation and medical treatment in patients with symptomatic carotid artery stenosis

8.2.3.2. Interventional treatment

Open surgery

Optimal medical treatment is recommended for all symptomatic patients with CS. In recently symptomatic patients with <50% stenosis, CEA (plus OMT) did not prevent stroke. However, surgery reduced stroke risk in patients with moderate (50%–69%) and severe (70%–99%) stenosis. The benefit from surgery increased with increasing severity of stenosis, except for ‘near-occlusion’ lesions (95%–99% stenosis with distal ICA collapse or a narrow calibre lumen with ‘trickle flow’).^{660,717–720}

Some features are associated with a higher increase of stroke in symptomatic patients (50%–99% stenosis) medically treated: age (>75 years), symptoms within 14 days, male sex, hemispheric (vs. retinal) symptoms, cortical (vs. lacunar) stroke, increasing comorbidities, irregular stenosis, stenosis severity, contralateral occlusion, tandem intracranial stenosis, and failure to recruit intracranial collaterals.⁷²¹

Large-scale registries suggest that CEA can be performed safely in the first 7 days after TIA/minor stroke.^722–724 However, not all patients benefit from urgent revascularization, and controversy exists over the safety of performing CEA within the first 48 h after symptom onset due to an increased risk of haemorrhagic transformation. Higher-risk patients include those with acute carotid occlusion, a persisting major neurological deficit, an area of middle cerebral artery infarction exceeding one-third, evidence of pre-existing parenchymal haemorrhage, and signs of impaired consciousness.^724,725

The choice to perform carotid revascularization within 48 h from symptom onset is still debatable.⁷²⁶

Endovascular therapy vs. open surgery

Contemporary RCTs comparing CEA with CAS in symptomatic patients reported a significantly higher risk of 30 day ‘any stroke’ and ‘death/stroke’ following CAS. This is mainly due to higher rates of minor stroke, which were non-disabling and resolved within 6 months.^711,727

However, the occurrence of a peri-operative stroke is associated with three-fold poorer long-term survival,⁷²⁷ similar to a post-procedural MI (which was more frequent after CEA).⁷²⁸

In CAS patients, the risk increased in those aged >60 years, especially for those aged >80 years, who are four times more likely to experience a procedural stroke/death. When comparing CAS with CEA, the age-related effect became apparent in patients aged 60–65 years, and CEA is superior to CAS in patients aged >70 years.^729,730

Elderly CAS patients may experience more peri-operative strokes, mainly minor ipsilateral strokes, possibly due to a higher burden of aortic arch disease. In these cases, operator/institution experience may play a role in determining peri-procedural outcomes. CAS is associated with significantly lower risks for MI, transient cranial nerve injury, and haematoma.^731,732

Beyond the 30 day peri-operative period, long-term data suggest that outcomes after CAS are similar to those with CEA.^703,733 The predicted magnitude of 30 day risk (according to clinical/anatomical characteristics and operator/centre experience) will thus largely determine whether CEA or CAS is preferable in individual patients.

Post-hoc trial analysis revealed enhanced benefits of CEA when performed within 2 weeks of the ischaemic event,⁷³⁴ with reduced complications compared with CAS performed within 1 week of stroke/TIA. The Carotid Stenosis Trialists’ Collaboration found a higher stroke/death rate (8.3% with CAS vs. 1.3% with CEA) for CAS in patients treated within 1 week of the last symptomatic event.⁷³⁵ These findings support a preference for early CEA in symptomatic patients. However, these trials, initiated over 30 years ago, lack evaluation of current OMT. Initially designed as an alternative for high surgical risk (HSR) patients,^704,736 carotid stenting’s efficacy needs consideration in contemporary practice (Table 12).⁷³⁵

Table 12

High-risk peri-operative features for carotid endarterectomy

Clinical
Congestive heart failure (NYHA functional class III/IV)
Unstable angina (CCS III/IV)
CAD with LM or >1 vessel with 70% stenosis
Recent MI (<30 days)
Planned open heart surgery (<30 days)
LVEF <30%
Severe pulmonary disease
Severe renal disease

Clinical
Congestive heart failure (NYHA functional class III/IV)
Unstable angina (CCS III/IV)
CAD with LM or >1 vessel with 70% stenosis
Recent MI (<30 days)
Planned open heart surgery (<30 days)
LVEF <30%
Severe pulmonary disease
Severe renal disease

Anatomical
Surgically inaccessible lesions At or above C2 Below the clavicle
Ipsilateral neck irradiation
Spinal immobility of the neck
Contralateral carotid artery occlusion (increases risk for stroke)
Contralateral laryngeal palsy
Tracheostomy

Anatomical
Surgically inaccessible lesions At or above C2 Below the clavicle
Ipsilateral neck irradiation
Spinal immobility of the neck
Contralateral carotid artery occlusion (increases risk for stroke)
Contralateral laryngeal palsy
Tracheostomy

CAD, coronary artery disease; CCS, Canadian Cardiovascular Society; LM, left main; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association.

Table 12

High-risk peri-operative features for carotid endarterectomy

Clinical
Congestive heart failure (NYHA functional class III/IV)
Unstable angina (CCS III/IV)
CAD with LM or >1 vessel with 70% stenosis
Recent MI (<30 days)
Planned open heart surgery (<30 days)
LVEF <30%
Severe pulmonary disease
Severe renal disease

Clinical
Congestive heart failure (NYHA functional class III/IV)
Unstable angina (CCS III/IV)
CAD with LM or >1 vessel with 70% stenosis
Recent MI (<30 days)
Planned open heart surgery (<30 days)
LVEF <30%
Severe pulmonary disease
Severe renal disease

Anatomical
Surgically inaccessible lesions At or above C2 Below the clavicle
Ipsilateral neck irradiation
Spinal immobility of the neck
Contralateral carotid artery occlusion (increases risk for stroke)
Contralateral laryngeal palsy
Tracheostomy

Anatomical
Surgically inaccessible lesions At or above C2 Below the clavicle
Ipsilateral neck irradiation
Spinal immobility of the neck
Contralateral carotid artery occlusion (increases risk for stroke)
Contralateral laryngeal palsy
Tracheostomy

CAD, coronary artery disease; CCS, Canadian Cardiovascular Society; LM, left main; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association.

In conclusion, CEA is still the treatment choice for patients with symptomatic carotid stenosis. However, in patients eligible for carotid revascularization but deemed high surgical risk by a multidiscliplinary team, CAS may be preferred over CEA—the patient must be a suitable candidate for CAS, and the complication rate should not surpass 6%.

At present, TCAR results have been analysed in registries only. In these studies, in-hospital stroke/death has been significantly lower after TCAR compared with transfemoral CAS.^707,737 Similar to the previous results established for CEA, symptomatic patients undergoing TCAR demonstrate similar outcomes if the procedure is performed >48 h after the neurological event.⁷³⁸ However, TCAR has not yet been evaluated in RCTs and has not been compared with CEA or OMT.

Vertebral arteries

The evidence on the use of lifestyle modifications and medical therapy in cases of symptomatic vertebral artery stenosis is lacking, but their use is reasonable given the overall CV risk in these patients.

Evidence on the use of preventive strategies and antithrombotic agents is lacking, but their use is reasonable in the presence of other CVRFs.

Surgery on extracranial vertebral stenosis (with transposition to CCA, trans-subclavian vertebral endarterectomy, distal venous bypass) can be performed with low stroke/death rates in experienced centres.^739,740 However, with limited expertise in complex vertebral artery reconstructions, open surgery has been mostly replaced by endovascular interventions.

In a combined analysis of the the Vertebral Artery Ischaemia Stenting Trial (VIST), the Vertebral Artery Stenting Trial (VAST), and the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial,⁷⁴¹ no clear benefit was shown for extracranial vertebral artery stenting.

Randomized controlled trials have not assessed surgical techniques like vertebral artery endarterectomy or transposition. While case series exist, they often lack a control group following a consistent medical treatment protocol.⁷⁴² As a result, the effectiveness of these procedures remains uncertain.

Recommendation Table 27

Recommendations for interventions in patients with symptomatic carotid artery stenosis

8.2.3.3. Follow-up

Peri-operative and post-procedural medical management after carotid revascularization should include OMT. Post-operative hypertension is a risk factor for stroke and TIAs, wound bleeding, and intracranial haemorrhage.⁷⁴³ Therefore, proper pharmacological BP control is important in optimizing outcomes.⁷⁴⁴

Fluctuations of hypertension and hypotension are not uncommon and should be treated promptly.^744,745

An intensive lipid-lowering therapy (ILT) aiming at >50% LDL-C reduction and LDL-C <1.4 mmol/L (55 mg/dL) is also recommended.¹⁹

Antiplatelet therapy should be tailored according to type of intervention. In CEA, the reduction in peri-procedural and long-term ischaemic events under low-dose aspirin has been demonstrated.^746,747 After carotid stenting, DAPT (aspirin and clopidogrel) is recommended, while optimal duration is debated.⁷⁴⁸ In the peri-operative period after CAS, DAPT should be prescribed and continued for at least 30 days post-procedure.^77,749,750 Ticagrelor, when included in DAPT following CAS/TCAR, presents a drawback due to its elevated bleeding risk compared with clopidogrel.^751–753

Duplex ultrasound is the first-line technique to evaluate patients after CEA or CAS. CTA and MRA are alternative methods for determining restenosis.^749,754

After CEA or CAS, DUS is recommended at baseline (<3 months) and annually thereafter until the patient is stable (i.e. until no restenosis is observed in two consecutive annual scans). Regular surveillance (e.g. every 2 years) can be performed based on the stenosis of the contralateral ICA, risk profile, and patient’s life expectancy.^749,754

For patients combining multiple CVRFs after the procedure, DUS may be beneficial every 6 months until a stable clinical pattern is established, and annually thereafter.^749,754

Early surveillance, especially within 1–3 months and particularly in cases where intraoperative completion imaging is absent (e.g. after CEA), aids in detecting technical errors and setting a baseline for future comparisons.

Follow-up enables the identification of ipsilateral carotid restenosis and contralateral disease progression, offering a chance for timely intervention to minimize the risk of stroke. Nevertheless, this concept is facing growing challenges due to a reduced and selective role for intervention in asymptomatic patients. A surveillance protocol holds significance when anticipated outcomes are expected to cost-effectively influence a medical or interventional treatment plan.^749,754

Recommendation Table 28

Recommendations for follow-up in patients with carotid artery stenosis

8.3. Other arterial locations

8.3.1. Subclavian artery disease

8.3.1.1. Clinical presentation and diagnosis

Atherosclerotic upper-limb artery disease (UEAD) is most frequently located in the subclavian artery.^755,756 Digital ischaemia is most frequently caused by non-atherosclerotic aetiologies, including thrombo-embolism, systemic sclerosis, idiopathic, thromboangiitis obliterans, iatrogenic, or cancer.⁷⁵⁷ Isolated subclavian stenosis (SS) is often asymptomatic and may be suspected because of an absolute inter-arm SBP difference >10–15 mmHg.⁷⁵⁸ In the Multi-Ethnic Study of Atherosclerosis (MESA), prevalence of asymptomatic SS was approximately 4.5% (male: 5.1%, female: 3.9%) in adults and more frequent in patients with PAD (11.4%).⁷⁵⁹ In patients attending CV clinics, a >25 mmHg SBP difference doubles prevalence and independently predicts mortality.^32,758 As obstructive disease progresses, particularly affecting vertebral vessels, the risk of ischaemia or steal symptoms significantly rises. Visual disturbances, syncope, ataxia, vertigo, dysphasia, dysarthria, and facial sensory deficits during arm movements may indicate subclavian steal syndrome, correlating with inter-arm BP difference.⁷⁶⁰ Brachiocephalic occlusive disease can lead to stroke or TIA in carotid and vertebral territories, manifesting as exercise-induced fatigue, pain, and arm claudication. Severe cases, especially with distal disease, may result in rest pain and digital ischaemia with necrosis.

Duplex ultrasound assessment of subclavian arteries enables the detection of SS via intrastenotic high-velocity flows (50% stenosis: peak systolic velocity [PSV] ≥230 cm/s, PSV ratio [PSVr] ≥2.2; 70% stenosis PSV ≥340 cm/s and PSVr ≥3.0) or monophasic post-stenotic waveforms.⁷⁶¹ The majority of patients (>90%) with at least 50% proximal SS have either intermittent or continuous flow reversal in the vertebral artery, though not all will be symptomatic.^760,762 When subclavian steal syndrome is suspected, flow reversal should be assessed in the ipsilateral extracranial vertebral artery by hyperaemia testing and if available transcranial Doppler.⁷⁶² Severe stenosis or occlusion of the right brachiocephalic trunk is associated with reduced flow velocities in the ipsilateral subclavian artery and the CCA. Abnormal or doubtful DUS should lead to anatomic imaging (CTA/MRA).⁷⁶³ CTA is excellent for supra-aortic lesions and can provide extravascular information, especially when thoracic outlet syndrome is a differential diagnosis. MRA provides both functional and morphological information useful to distinguish antegrade from retrograde perfusion and to estimate stenosis severity.⁷⁶⁴ DSA is performed if endovascular therapy is indicated. PET is useful for the diagnosis of arteritis but not for assessment of atherosclerotic lesions in clinical practice.

8.3.1.2. Treatment strategy (medical and interventional)

Optimal medical treatment is recommended in all patients with symptomatic UEAD to reduce CV risk.³² Revascularization is indicated in symptomatic patients with TIA/stroke, coronary subclavian steal syndrome, ipsilateral haemodialysis access dysfunction, or impaired HRQoL. Revascularization should be considered in asymptomatic patients with planned coronary artery bypass grafting (CABG) using the internal mammary artery and those with ipsilateral haemodialysis access, as well as asymptomatic patients with significant bilateral SS/occlusion for adequate BP surveillance. For revascularization, both endovascular and surgical procedures are available. There are no RCTs comparing endovascular vs. open repair but individual studies, including the Danish Vascular Registry, indicate similar long-term symptom resolution but higher general complication rates and hospital length of stay for open surgery.⁷⁶⁵ The risk of severe complications, including vertebrobasilar stroke, is low with both approaches. The post-procedural stroke rate is reported at 1.3% for endovascular therapy⁷⁶⁵ and 0.9%–2.4% after open surgery.^765–767

Percutaneous angioplasty for subclavian arterial stenosis is often used with stenting. There is no conclusive evidence to determine whether stenting is more effective than balloon angioplasty.⁷⁶⁸ Similar results were reported for endovascular therapy of the innominate artery.⁷⁶⁹ In heavily calcified ostial lesions, balloon-expandable stents give more radial force than nitinol stents. An endovascular approach is often the default strategy. However, in selected patients with low operative risk, with subclavian artery occlusion or after endovascular therapy failure, surgical subclavian–carotid transposition is safe with excellent long-term patency results (5 year patency 96%).⁷⁶⁶ Carotid–subclavian bypass surgery with a prosthetic graft showed long-term benefit with low operative mortality and morbidity, especially in patients with extensive disease or re-occlusion after stenting (5 year patency 97%).⁷⁷⁰ Other options are extrathoracic extra-anatomic bypass procedures (axillo-axillary, carotid–axillary, or carotid–carotid bypass);^771,772 however, axillo-axillary bypasses may occlude at 1 year in 14% of cases.⁷⁷³ The transthoracic approach is an option in patients with multivessel disease involving the aortic arch and several supra-aortic vessels.⁷⁶⁷

While critical hand ischaemia owing to below-the-elbow atherosclerotic occlusive disease is relatively uncommon, interventions are associated with a high rate of success, major amputations are rare, and many can be treated non-operatively.⁷⁵⁶ In appropriately selected patients, both endovascular and open interventions have a high rate of success.^755,756

In symptomatic patients with contraindications for endovascular therapy or open surgery, prostanoid infusion or thoracic sympathectomy may be considered.⁷⁷⁴

8.3.1.3. Follow-up

Patients with UEAD should be followed up to ensure optimal CV prevention. Tighter follow-up is required in symptomatic patients to re-assess indication for revascularization as a large proportion of symptoms resolve spontaneously.⁷⁷⁵ After revascularization, patients should be followed up to allow early detection and treatment of impending late procedural failure.

Recommendation Table 29

Recommendations for the management of subclavian artery stenosis (see also Evidence Table 9)

8.3.2. Renal artery disease

8.3.2.1. Clinical presentation and diagnosis

Epidemiology

In >90% of cases, RAS is caused by atherosclerosis and typically involves the ostial renal arterial segment (Table 13).⁷⁸² Above 65 years of age, overall prevalence of ≥60% RAS is 6.8%, with a higher prevalence in men (9.1%) than in women (5.5%).⁷⁸³ In patients with PAD, RAS prevalence ranges between 7% and 42%, influenced by diagnostic criteria.⁷⁸⁴

Table 13

Clinical signs suggestive of renal artery disease

Hypertension onset before 30 years of age

Severe hypertension after the age of 55 years, when associated with CKD or heart failure

Hypertension and abdominal bruit

Rapid and persistent worsening of previously controlled hypertension

Resistant hypertension

Three antihypertensive drugs including a diuretic agent
or
≥4 antihypertensive drugs
and
Other secondary form unlikely

Hypertensive crisis (i.e. acute renal failure, acute heart failure, hypertensive encephalopathy, or grade 3–4 retinopathy)

New azotaemia or worsening of renal function after treatment with RAAS blockers

Unexplained atrophic kidney or discrepancy in kidney size, or unexplained renal failure

Flash pulmonary oedema

CKD, chronic kidney disease; RAAS, renin–angiotensin–aldosterone system.

Clinical presentation

Clinical presentation comprises renovascular hypertension, renal function impairment and eventually, flash pulmonary oedema (Table 13). RAS reduces the filtration capacity of the affected kidney, which activates the renin–angiotensin–aldosterone pathway, potentially resulting in renovascular hypertension.^782,785 In unilateral RAS, the functioning contralateral kidney may increase sodium excretion to prevent sodium retention and volume overload. In high-grade bilateral RAS or in unilateral RAS without a functioning second kidney, the risk of cardiorenal deterioration is higher than in unilateral disease.⁷⁸⁶

Diagnosis of renal artery disease

First diagnostic steps include laboratory tests to examine renal function, analysis of office and out-of-office BP recordings (ambulatory BP monitoring or home BP monitoring, as recommended by [upcoming] ESC/European Society of Hypertension [ESH] Guidelines for arterial hypertension), and non-invasive haemodynamic assessment of renal arteries by DUS.⁷⁸⁷

Renal artery PSV >200 cm/s measured by DUS allows the diagnosis of a >50% RAS (sensitivity 95%, specificity 90%).⁷⁸⁸ A renal-aortic peak flow velocity ratio (RAR = renal artery PSV/aortic PSV) >3.5 has 84%–91% sensitivity and 95%–97% specificity for the detection of ≥60% RAS.⁷⁸⁹ A side-to-side difference of the intrarenal resistance index ≥0.5 between both kidneys may serve as an additional haemodynamic criterion for haemodynamically relevant RAS.^787,790 Other DUS criteria (acceleration time, acceleration index) have lower diagnostic accuracy.⁷⁹¹

Sensitivity and specificity of contrast-enhanced MRA in the diagnosis of RAS is 88% and 100%, respectively;⁷⁸⁹ however, MRA overestimates the degree of RAS by 26%–32%.⁷⁸⁹ The advantages of MRA are the possibility of assessing renal parenchymal blood flow and freedom from radiation and iodinated contrast agents.

Spiral multidetector CTA allows renal artery diameter measurements and provides information on vessel wall calcification and mural plaques. RAS diagnosis by CTA presents 64%–100% sensitivity and 92%–98% specificity.⁷⁸⁹ CTA drawbacks include radiation exposure, the need for contrast media in patients with impaired renal function, and limited haemodynamic assessment of RAS.

Catheter angiography is the gold standard for diagnosing RAS, enabling additional haemodynamic measures (Figure 19).⁷⁹² Considering the potential risks of invasive procedures, DUS and other non-invasive modalities (CTA or MRA) should precede catheter angiography and invasive haemodynamic measurements (Figure 19).

Figure 19

Diagnostic and treatment algorithm for renal artery stenosis.

CTA, computed tomography angiography; MRA, magnetic resonance angiography; OMT, optimal medical treatment; Pd/Pa, distal coronary pressure to aortic pressure ratio; PSV, peak systolic velocity; RAR, renal-aortic peak flow velocity ratio; RAS, renal artery stenosis.

^asee table below

^aKidney viability in RAS

Signs of viability

Signs of non-viability

Renal size

>8 cm

<7 cm

Renal cortex

Distinct cortex (>0.5 cm)

Loss of corticomedullar differentiation

Proteinuria

Albumin-creatinine ratio <20 mg/mmol

Albumin-creatinine ratio >30 mg/mmol

Renal resistance index

<0.8

>0.8

^bRapidly progressive, treatment-resistant arterial hypertension; rapidly declining renal function; flash pulmonary oedema; solitary kidney.

^cResting mean pressure gradient >10 mmHg; systolic hyperaemic pressure gradient >20 mmHg; renal PdPa ≤ 0.9 (or 0.8).

Renal scintigraphy, plasma renin measurements before and after ACEI provocation, and venous renin measurements are not considered for RAS evaluation.

Prognosis

Atherosclerotic RAS progresses with respect to the degree of stenosis, while total renal artery occlusions occur less frequently.⁷⁹³ The presence of significant RAS is a strong predictor for mortality⁷⁹⁴ and renovascular disease is an important risk factor for the development of end-stage renal disease (ESRD).⁷⁹⁵ The risk of RAS-related ESRD is higher in men than in women and increases with age.⁷⁹⁵

8.3.2.2. Treatment strategy (medical and interventional)

Medical therapy

Optimal medical treatment is recommended in RAS patients.⁷⁸⁵ Data on antithrombotic therapy in patients with atherosclerotic RAS are scarce and retrospective.⁷⁹⁶ However, the use of an antiplatelet agent is reasonable in atherosclerotic RAS.

No prospective study has specifically examined antithrombotic therapy post-RAS stenting, and information from existing RAS stenting trials is limited.⁷⁹⁷ Following the antithrombotic treatment approach in non-coronary arterial beds, it is suggested to use DAPT for at least 1 month after RAS stent implantation.⁶⁶⁶

Revascularization

Revascularization in atherosclerotic RAS

Prospective RCTs comparing endovascular revascularization with OMT in atherosclerotic RAS favoured renal artery stenting over balloon angioplasty.⁷⁹²

However, renal artery stenting showed no superiority over OMT in reducing BP, CV events, renal events, or mortality in unilateral atherosclerotic RAS.^788,798,799 A trial suggested a potential benefit of renal artery angioplasty for BP in bilateral RAS, but subsequent RCTs did not confirm this.^800–802 Data on the benefit of renal artery stenting in sparing antihypertensive drugs are inconsistent.^{324,800,801,803,804}

In specific circumstances or RAS aetiologies, revascularization should be considered (Figure 19). Open surgical renal artery revascularization appears comparable to endovascular treatment regarding BP and renal function.^805,806 Thus, open surgery can be an alternative approach in cases with a revascularization indication and complex anatomy or failed endovascular repair.

8.3.2.3. Follow-up

Following the diagnosis of significant RAS and the implementation of OMT and/or renal artery revascularization, regular follow-up exams are crucial. Monitoring should encompass laboratory tests to assess renal function, analysis of office and out-of-office BP recordings (ambulatory or home BP monitoring per upcoming ESC/ESH Guidelines for arterial hypertension), and renal artery DUS. DUS, comprising renal PSV, RAR, side-to-side difference of the resistance index, and kidney size, is the preferred imaging modality during follow-up.⁷⁸⁷

In conservatively managed RAS patients, follow-up assessment should re-evaluate potential indications for renal artery revascularization (Figure 19).

After renal artery stenting, the initial follow-up is recommended at 1 month and subsequently every 12 months or when new signs or symptoms arise.⁸⁰⁷ Re-intervention may be considered for in-stent restenosis ≥60% detected by DUS, recurrent signs and symptoms (diastolic BP >90 mmHg on >3 antihypertensive drugs, or a >20% increase in serum creatinine).^787,808

Recommendation Table 30

Recommendations for diagnostic strategies for renal artery disease

Recommendation Table 31

Recommendations for treatment strategies for renal artery disease (see also Evidence Table 10)

8.3.3. Visceral artery disease

8.3.3.1. Acute mesenteric ischaemia

Acute mesenteric ischaemia can be caused by arterial embolism or thrombosis in situ, non-occlusive mesenteric ischaemia (usually due to superior mesenteric artery [SMA] vasoconstriction), and venous thrombosis. In recent decades, embolism decreased from 46% to 35%, while arterial thrombosis increased from 20% to 35%.^815–817 Acute thrombo-embolic occlusion most frequently affects the SMA. Due to extensive collaterals, it infrequently leads to intestinal infarction.

Clinical presentation and diagnosis

Clinical examination

Early diagnosis of AMI is based on high clinical suspicion. Embolic AMI typically manifests as sudden onset intense abdominal pain, accompanied by minimal physical findings, bowel emptying (vomiting, diarrhoea), and a common embolic source (primarily AF).^818–820 Emboli may also lodge in other locations, aiding diagnosis. Acute arterial thrombosis tends to occur in areas with pre-existing atherosclerotic disease, resulting in a less dramatic clinical presentation. Patients may have previous symptoms of chronic mesenteric ischaemia (CMI) or other atherosclerotic manifestations.⁸²¹

Laboratory tests are unreliable for the diagnosis of AMI, although elevated levels of l-lactate, leucocytosis, and D-dimer (DD) may exist.^822–825

Imaging

Computed tomography angiography is the gold standard for diagnosis,^826,827 allowing the detection of thrombi and/or emboli in the SMA trunk or its branches together with the recognition of intestinal ischaemic signs. A plain abdominal X-ray lacks specificity. A normal result does not rule out the diagnosis.⁸²⁸

Treatment strategy

Most patients require immediate revascularization to survive. There are no RCTs comparing surgical vs. endovascular intervention in AMI. Two meta-analyses found endovascular revascularization to be superior to surgical intervention in terms of in-hospital mortality and rates of bowel resection.^829,830 An open surgical approach is most appropriate in centres where endovascular interventions are less available and in patients with peritonitis.⁸³¹ Retrograde open mesenteric stenting (ROMS) is an alternative that offers shorter operative time; the SMA is punctured in the open abdomen, followed by stenting.⁸³²

Follow-up

Most patients treated for AMI require lifelong anticoagulant/antiplatelet therapy to prevent recurrence. Patients undergoing revascularization should have surveillance with CTA or DUS within 6 months,⁸³³ as recurrent AMI after mesenteric revascularization accounts for 6%–8% of late deaths.⁸³⁴ Current Society for Vascular Surgery (SVS) Guidelines recommend DUS at 1, 6, and 12 months after the intervention, and then annually thereafter.⁷⁵⁴

8.3.3.2. Chronic mesenteric artery disease

Occlusive CMI is mostly caused by atherosclerosis and more frequently affects females (65%–72%).^835,836 Symptoms typically manifest when at least two mesenteric vessels are involved due to extensive collaterals. Prevalence of asymptomatic coeliac artery and/or SMA stenosis is 3% in patients under 65 years of age and 18% in those aged >65.⁸³⁷ However, inadequate anastomoses can result in symptomatic ischaemia even with a single-vessel atherosclerotic occlusion.^838,839

Clinical presentation and diagnosis

Clinical examination

Like AMI, early diagnosis of CMI relies on clinical suspicion. Classic symptoms include post-prandial abdominal pain, weight loss, and gastrointestinal disturbances like diarrhoea or constipation. Patients may develop food aversion to avoid pain, but their appetite remains unaffected, distinguishing them from individuals with malignancies. An abdominal examination might reveal a bruit.

Lactate, lactate dehydrogenase, and/or leucocyte count are unhelpful in CMI diagnosis.^840,841 Functional testing (tonometry, visible light spectroscopy) is applicable in patients with symptomatic mesenteric stenosis and single-vessel disease.⁸⁴²

Imaging

Duplex ultrasound is valuable due to its low costs, absence of the need for contrast agents, and no radiation. However, skilled investigators in specialized centres are required for the examination. Despite suggested diagnostic criteria, consensus is lacking.^843,844 Anatomical mapping for treatment planning typically involves CTA or MRA, ^845,846 with DSA reserved only for therapeutic purposes (Figure 20).

Figure 20

Algorithm of chronic mesenteric ischaemia management.

CA, coeliac artery; CMI, chronic mesenteric ischaemia; CTA, computed tomography angiography; MALS, median arcuate ligament syndrome; NOMI, non-occlusive mesenteric ischaemia; SMA, superior mesenteric artery.

Treatment strategy

Optimal medical treatment is the basis of CMI management. Prophylactic revascularization is not recommended for asymptomatic CMI. In symptomatic cases, a meta-analysis favoured endovascular over open surgery due to fewer complications and a trend towards lower 30 day mortality.⁸³⁵ However, open surgery showed superior long-term results, with fewer symptom recurrences and higher 1 and 5 year primary patency rates in two additional meta-analyses.^847,848 Despite the growing use of endovascular therapy, open surgery remains indicated after failed endovascular therapy without the option for repeat intervention, and in cases with extensive occlusions, calcifications, or technical challenges.

Follow-up

Following CMI revascularization, lifelong medical treatment, including lifestyle changes and OMT for atherosclerosis, is recommended. SVS guidelines propose mesenteric DUS surveillance for recurrent stenosis. A potential follow-up schedule involves controls within 1 month post-procedure, biannually for the first 2 years, and annually thereafter.⁸⁴⁹

Recommendation Table 32

Recommendations in patients with visceral artery stenosis

9. Aorta

9.1. Atheromatous disease of the aorta

9.1.1. General concepts

Atheromatous disease of the aorta has an estimated incidence of 40%–51.3%, being complicated in 7.6% of cases.^850–853 Earlier stages of atherosclerosis, presenting as plaque inflammation, can be present in 48% of asymptomatic individuals.⁸⁵⁰ Atherosclerotic plaque classification is based on plaque thickness and the presence of ulceration or mobile components (Table 14).^159,171,854 This classification is crucial because severe or complex atherosclerotic plaques in the aortic arch or ascending aorta are strongly linked to cerebrovascular events (odds ratio [OR] 4–9.1 for plaques ≥4 mm).^855–860 Additionally, the annual incidence of stroke recurrence remains high (up to 16%) despite antiplatelet or anticoagulant therapy.^855,861

Table 14

Grading of atherosclerotic aortic plaques

Grade	Severity (atheroma thickness)	Description
1	Normal	Intimal thickness <2 mm
2	Mild	Intimal thickening of 2 to <3 mm
3	Moderate	Atheroma ≥3 to <4 mm (no mobile/ulcerated components)
4	Severe	Atheroma ≥4 mm (no mobile/ulcerated components)
5	Complex	Grade 2, 3, or 4 atheroma plus mobile/ulcerated components

Grade	Severity (atheroma thickness)	Description
1	Normal	Intimal thickness <2 mm
2	Mild	Intimal thickening of 2 to <3 mm
3	Moderate	Atheroma ≥3 to <4 mm (no mobile/ulcerated components)
4	Severe	Atheroma ≥4 mm (no mobile/ulcerated components)
5	Complex	Grade 2, 3, or 4 atheroma plus mobile/ulcerated components

Table 14

Grading of atherosclerotic aortic plaques

Grade	Severity (atheroma thickness)	Description
1	Normal	Intimal thickness <2 mm
2	Mild	Intimal thickening of 2 to <3 mm
3	Moderate	Atheroma ≥3 to <4 mm (no mobile/ulcerated components)
4	Severe	Atheroma ≥4 mm (no mobile/ulcerated components)
5	Complex	Grade 2, 3, or 4 atheroma plus mobile/ulcerated components

Grade	Severity (atheroma thickness)	Description
1	Normal	Intimal thickness <2 mm
2	Mild	Intimal thickening of 2 to <3 mm
3	Moderate	Atheroma ≥3 to <4 mm (no mobile/ulcerated components)
4	Severe	Atheroma ≥4 mm (no mobile/ulcerated components)
5	Complex	Grade 2, 3, or 4 atheroma plus mobile/ulcerated components

9.1.2. Treatment

9.1.2.1. Primary prevention

Asymptomatic non-severe/non-complex aortic plaques (Table 14) should not mandate antiplatelet therapy. Nonetheless, in severe/complex plaques, statins should be indicated to decrease plaque progression or CV events,⁸⁶² and SAPT with clopidogrel or low-dose aspirin should be considered after risk/benefit evaluation.^{493,666,861,863} However, in this scenario, anticoagulation⁸⁶¹ or DAPT (low-dose aspirin and clopidogrel) are not indicated.^666,863 Floating aortic thrombi and complex mobile plaques are rare, with limited large-scale trials on their management. Guidance relies on case reports, observational studies, and expert opinions, yet there is evidence favouring anticoagulation, particularly for symptomatic cases.⁸⁶⁴

9.1.2.2. Secondary prevention

Secondary prevention with antiplatelet therapy after an embolic event is recommended to prevent recurrences.^666,865,866 While the value of DAPT vs. SAPT remains uncertain, recent studies indicate that prolonged DAPT raises bleeding risk without added antithrombotic benefits.^667,863,867 Treatment duration is unclear and must strike a balance between early benefit (notably within 7 days post-emboli) and steady bleeding risk. Statins (LDL target below 1.4 mmol/L [55 mg/dL]) prove effective in preventing strokes regardless of the aetiology.^862,865,868 Additionally, a healthy lifestyle is crucial for improving CV health and reducing complications.

Recommendation Table 33

Recommendations for primary and secondary prevention in aortic atheromatous plaques

9.2. Aortic aneurysms

9.2.1. General concepts

9.2.1.1. Definitions

Aortic dilatation, the second most frequent aortic disease after atherosclerosis, is defined as an aortic diameter >2 standard deviations of the predicted mean diameter depending on age, sex, and body size (z-score >2). However, in clinical practice, aortic root dilatation can be suspected in male adults when aortic diameter is >40 mm and in females at >36 mm,^138,149,869 or with an indexed diameter/BSA (aortic size index [ASI]) >22 mm/m². In extreme BSA and age values, use of z-scores is recommended (see Section 5.4 for their calculation).

Arterial aneurysm is defined as a diameter >1.5 times (>50%) larger than the predicted one. This definition, as well as the use of z-scores, introduces the need for normal values and correction for age, sex, and body size. However, correcting for BSA can lead to underestimation in overweight patients,⁸⁷⁰ therefore a correction for height (aortic height index [AHI]) is becoming more popular.¹⁵³ In terms of clinical risk, both ASI and AHI have been shown to improve risk stratification for AAE.^153,871 Since in many cases of aortic dilatation the surgical indication is established before achieving this aneurysmal diameter, we strongly recommend the use of significant aortic dilation specifying the diameter or the indexed diameter value rather than the term ‘aneurysm’.

Thoracic aortic aneurysms (TAAs) are more prevalent in men than in women (ratio 4:1);⁸⁷² however, the growth rate is greater in women (0.96 ± 1.00 mm per year) than in men (0.45 ± 0.58 mm per year), and thus the risk of AAE.⁸⁷³

Aneurysms can be fusiform or saccular based on morphology. Saccular aneurysms relate to infection, penetrating atherosclerotic ulcer (PAU), trauma, or inflammatory diseases, while fusiform aneurysms connect with degenerative and connective tissue conditions. Although evidence about their natural course is limited, saccular aneurysms are considered more malignant in terms of AAE. Based on location, aortic aneurysms are classified into TAA and abdominal aortic aneurysm (AAA) (Figure 21). They differ in treating specialists, causes, age at onset, risk factors, and complications. However, this binary classification is artificial due to the prevalence of thoracoabdominal aortic aneurysms (TAAA) and tandem lesions (20%–30% of AAA patients also have TAA),^874,875 emphasizing the importance of comprehensive aortic and vascular assessments at diagnosis. When detecting an aortic aneurysm at any site, it is advisable to conduct a thorough evaluation of the entire aorta initially and during subsequent follow-ups. Specifically, when diagnosing a TAA, it is crucial to assess the aortic valve, particularly in cases of BAV. Data on peripheral aneurysms in TAA, particularly in femoro-popliteal segments, is less clear compared with AAA. However, cerebral aneurysms, notably prevalent in women and those with HTAD, warrant thorough screening, particularly in symptomatic cases.^876–878

Figure 21

Thoracic and abdominal aortic aneurysms: aetiology, screening and diagnostic methods.

AAA, abdominal aortic aneurysm; BAV, bicuspid aortic valve; CCT, cardiovascular computed tomography; CEUS, contrast-enhanced Doppler ultrasound; CMR, cardiovascular magnetic resonance; DUS, Doppler ultrasound; HTAD, heritable thoracic aortic disease; TAA, thoracic aortic aneurysm; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography.

Recommendation Table 34

Recommendations for initial evaluation of thoracic aortic aneurysm and abdominal aortic aneurysm

9.2.2. Thoracic aortic aneurysms

9.2.2.1. Aetiology, risk factors, and natural history

Thoracic aortic aneurysms occur in 5–10/100 000 person-years,⁸⁸⁴ with an approximate predominance of root and/or ascending aorta of ∼60%, arch of ∼10%, and descending aorta of ∼30%.^885,886

Hypertension is the main risk factor (80%); however, genetics may be involved in 20% of cases.⁸⁸⁷ The decision to refer patients for genetic evaluation should consider age, family history, and presence of syndromic features,^25,888 as reported in more detail in Section 10.1.

9.2.2.2. Ascending thoracic aorta and arch aneurysms

Aortic root aneurysms (including sinuses of Valsalva: annulo-aortic ectasia). They can be idiopathic, associated with HTAD (syndromic/non-syndromic), or found in 20%–30% of BAV patients (see Section 10).^879,880 Patients are usually younger (30–50 years of age), with aortic regurgitation, and with a 1:1 sex ratio.
Supra-coronary aortic aneurysms (above sinuses of Valsalva). Caused by atherosclerosis in relation to hypertension affecting older patients (59–69 years) and males (ratio 3:1),⁸⁸⁰ or related to medial degeneration (isolated or associated with aortic valve disease, including BAV) (see Section 10). Primary bacterial infection or syphilis are uncommon. Arteritis is rare, but Takayasu’s and giant cell arteritis can lead to aneurysm formation.
Aortic arch aneurysms. Often accompanying adjacent ascending or descending aorta aneurysms, aortic arch aneurysms present surgical challenges due to potential neurological and CV risks. They are typically linked to atherosclerosis, with cystic medial degeneration primarily affecting ascending aorta-related arch aneurysms. Deceleration injuries or coarctation may extend into the aortic arch.⁸⁸⁹

Thoracic aortic aneurysm patients are usually asymptomatic, diagnosed incidentally during unrelated imaging or screenings. Symptoms such as chest pain, aortic regurgitation, and compression-related issues may occur.⁸⁹⁰ Patients with aortic root involvement (as seen in HTAD) are more prone to suffer from AAE.^891,892

Thoracic aortic aneurysm growth rate is variable, associated with aetiology, location, and baseline aortic diameter.^893–895 Degenerative TAAs grow faster in women than men and are associated with a three-fold higher risk of AAE.^24,873,896 When the aorta reaches 57.5 mm in size, reported yearly rates of rupture, dissection, and death are 3.6%, 3.7%, and 10.8%, respectively.^897–899

9.2.2.3. Descending thoracic aorta and thoracoabdominal aorta aneurysms

They can involve different parts of the DTA and may extend to the AA: TAAA. TAAAs are divided into five groups⁹⁰⁰ according to the modified TAAA classification scheme (Figure 22), which is crucial for risk stratification. By classifying aneurysm extent, surgeons can anticipate procedure complexity, select suitable techniques, and reduce risks during surgical planning.

Classification of thoracoabdominal900 and abdominal aortic aneurysms.

Figure 22

Classification of thoracoabdominal⁹⁰⁰ and abdominal aortic aneurysms.

AAA, abdominal aortic aneurysm; IMA, inferior mesenteric artery; SMA, superior mesenteric artery.

Most DTA aneurysms and TAAA are degenerative with calcification, although other causes include trauma, infection, inflammation, or genetic factors^901,902 (Figure 21). Patients with HTAD rarely develop thoracoabdominal aortic aneurysms without dissection. Mean age at diagnosis is 59–69, with a male predominance of 2–4:1. Aneurysm growth rate is 1.9–3.4 mm per year,^902,903 but tends to increase notably with diameters over 50 mm or post-proximal aorta surgery in patients with MFS. In this population, debate continues as to whether this reflects a more vulnerable aorta associated to the genetic disease or haemodynamic changes post-surgery.

For untreated DTA aneurysm patients, 5 year survival is about 54%, with aortic rupture as the leading cause of death.⁹⁰⁴ Rupture risk factors include HTAD, a diameter over 50 mm, hypertension, smoking, chronic obstructive pulmonary disease (COPD), symptoms, chronic aortic dissection, and age. A significant rise in AAE risk occurs at a 60 mm diameter. Although dissection can occur in smaller aortas, the individual risk is low.⁸⁹⁹ High-risk features for rupture are represented in Figure 23.

Figure 23

Risk factors for thoracic and abdominal aneurysm rupture.

AAA, abdominal aortic aneurysm; COPD, chronic obstructive pulmonary disease; DTAA, descending thoracic aorta aneurysm; PAU, penetrating atherosclerotic ulcer; TAAA, thoracoabdominal aortic aneurysm.^905–908

9.2.2.4. Surveillance

Patients with TAA who do not meet surgical criteria require chronic follow-up that includes clinical evaluation and imaging techniques. The best imaging modality depends on aneurysm location: TTE, CCT, or CMR when affecting the aortic root and the ascending aorta; CMR and CCT when involving the distal ascending aorta, the aortic arch, or the DTA.^159,171 Follow-up should be conducted with the same imaging technique and in the same centre.⁹⁰⁹ If a TAA is only moderate in size and remains relatively stable over time, CMR rather than CCT is reasonable to minimize radiation exposure.^172,910 Follow-up for aortic aneurysms associated with HTAD is described in Section 10.1.3.2.

Figure 24 proposes a follow-up algorithm for patients with TAA. In cases of aortic root or proximal ascending aorta dilatation, after initial diagnosis by TTE the basal diameter and extension must be confirmed by CMR or CCT. If there is agreement between techniques, TTE can be used for follow-up; however, if there is a difference of ≥3 mm, surveillance must be performed by CMR or CCT. After the initial diagnosis, imaging is required at 6–12 months, depending on aetiology and baseline diameter (Figure 24); see Sections 5.4.2 and 9.2.1 about indexed values of aortic dimensions, to ensure stability.^159,911 Subsequently, imaging can be performed annually if there is no expansion/extension or customized according to the underlying condition. If the aorta shows rapid expansion (≥3 mm per year) or approaches the surgery/endovascular repair threshold, a closer evaluation is recommended every 6 months. In contrast, stability in aortic diameters over years could lengthen these intervals (especially in non-genetic aneurysms and those <45 mm). In cases of dilatation of aortic arch or DTA, diameters obtained by TTE are deemed less precise and need confirmation by CMR or CCT. In those types of aneurysms, follow-up frequency will depend on the baseline diameter and aetiology and will follow the same criteria established in the algorithm in Figure 24 for the 40–49 mm range. However, for the 50–55 mm range, the aorta should be re-imaged every 6 months until the threshold for intervention is reached (see Sections 9.2.5.3 and 9.2.5.4).

Figure 24

Surveillance of patients with non-heritable thoracic aortic disease and abdominal aortic aneurysms.

AAA, abdominal aortic aneurysm, BAV, bicuspid aortic valve; CCT, cardiovascular computed tomography; HTAD, heritable thoracic aortic disease; CMR, cardiovascular magnetic resonance; TAV, tricuspid aortic valve; TTE, transthoracic echocardiography. ^a36–44 mm in women. ^bFor TAV and BAV: age <50 years; height <1.69 m; ascending length >11 cm; uncontrolled hypertension; and, for BAV: coarctation; family history of acute aortic events.

Recommendation Table 35

Recommendation for the surveillance of patients with thoracic aortic aneurysms (non-heritable thoracic aortic disease)

9.2.3. Abdominal aortic aneurysms

9.2.3.1. General concepts

An AAA is defined as a focal dilation at least 1.5 times its normal diameter, generally ≥30 mm. Most AAAs are fusiform, and many are lined with laminated thrombi.⁹¹⁶ Their prevalence increases with age, with a 4:1 male/female ratio.⁸⁷² They are commonly classified based on their relation to renal arteries (Figure 22) because of the complexity of surgical treatment. AAA extends to the common iliac arteries in 25% of cases and in up to 20% of patients is associated with peripheral femoral and/or popliteal artery aneurysm.^876–878

9.2.3.2. Aetiology, risk factors, and natural history

Smoking, age, male sex, and familial history of aneurysmal disease are major risk factors,^917–921 whereas diabetes is associated with a decreased risk^922,923 and slower growth rate⁹²⁴ (Figure 21, see also Section 5). Other aetiologies include inflammation (5%–10% of all AAA),⁹²⁵ genetic disorders, and infection. The mean growth rate is around 3 mm per year (1–6 mm)^906,926 and depends on sac diameter, presence of genetic disorders, continuous smoking, metabolism (presence of inflammation), and aortic wall calcification.^927–929 Risk of rupture rises exponentially depending on diameter, being higher in women.^930,931

AAAs are asymptomatic in two-thirds of cases and if they become symptomatic, rupture is the main manifestation. They often represent incidental imaging findings, as the sensitivity of clinical examination—especially palpation of an abdominal mass—is generally poor. Symptoms may include acute abdominal or back pain, and in some cases, hypovolaemic shock. However, contained rupture may present with atypical low flank or abdominal pain (see Figure 23 for high-risk factors and radiological signs or AAA rupture).^932–935 Independently of risk of rupture, patients with AAA have impaired survival: the 5 year mortality rate is higher (×4 in women, ×2 in men) despite AAA repair, likely due to the presence of cardiovascular disease in other areas.⁹³⁶

9.2.3.3. Surveillance

Those with an aortic diameter <25 mm present low risk of developing large AAA in 10 years, whereas a diameter of 25–29 mm deserves reassessment after 4 years.^937,938 DUS is the standard imaging technique for surveillance; however, CCT provides superior visualization of the AA and its branches, especially for pre-operative planning. CMR is reasonable in selected patients (young and female) when a long follow-up is considered, to avoid radiation.

A meta-analysis advises follow-up intervals for AAAs based on size: 3 years for 30–39 mm, 1 year for 40–44 mm, and 6 months for 45–54 mm in men, with <1% rupture risk.⁹³⁸ Women have similar growth rates but a four-fold higher rupture risk.⁹³⁸ A proposed follow-up algorithm is displayed in Figure 24. Consider shorter intervals for rapid growth (≥10 mm per year or ≥5 mm per 6 months), in which case repair may be considered.

Recommendation Table 36

Recommendations for surveillance of patients with abdominal aortic aneurysm

9.2.4. Optimal medical treatment of aortic aneurysms

In patients with aortic aneurysms, the role of antithrombotic therapy is uncertain. In complicated aortic atherosclerotic plaques, concomitant CAD is common (OR 2.99) and SAPT should be considered (see Section 9.1). In patients with AAA, results of observational studies are conflicting in relation to aneurysm growth. Low-dose aspirin is not associated with a higher risk of AAA rupture but could worsen prognosis in cases of rupture.⁹⁴⁴ In an RCT of patients with AAA (35–44 mm), ticagrelor did not reduce growth rate.⁹⁴⁵

Optimal medical treatment for aortic aneurysms aims to lower CV morbidity, slow growth rate, delay surgery, reduce peri-operative risk, and prevent AAE. Aneurysm patients face elevated CV risk due to common CVRFs, and the 10 year CV event mortality risk (heart attacks or strokes) is 15 times higher than AAE risk, even after repair.^882,883 According to the SMART risk score algorithm, optimal implementation of risk management guidelines would reduce the 10 year risk of MACE from 43% to 14% in patients with AAA.⁹³⁶ Thus, lifestyle modification, exercise, smoking cessation, and treatment of risk factors are crucial (see Section 7).

Risk factors and possible drug treatment to reduce AAA growth and/or the risk of rupture have been thoroughly discussed in a recent review paper.⁹⁴⁶ Their meta-analysis suggested a possible effect of ACEIs (but not ARBs) on the risk of rupture, whereas another meta-analysis⁹⁴⁷ did not indicate an effect of ACEIs on AAA growth. A reduction of AAA growth by statins is indicated in a recent meta-analysis.³⁵² Furthermore, reduced AAA growth by the antidiabetic drug metformin has been suggested in several meta-analyses^352,948,949 and there are several ongoing RCTs to explore this. For BP, follow general hypertension guidelines. Aim for BP below 140/90 mmHg, with a target of 120/80 mmHg, if tolerated.^300,302,305 Data on the specific positive effects of beta-blockers and ARBs in TAA and AAA are limited (mostly derived from MFS populations). However, it is reasonable to use BBs and/or ARBs as first-line antihypertensive drugs in TAA and AAA.

Consider moderate/high-intensity statins in TAA patients but skip for those with low CV risk and non-atherosclerotic (HTAD). In AAA, consider statins to reduce aneurysm risks, including growth, rupture, and peri-operative mortality.^330,347,348 Low-dose aspirin is debated but may be reasonable given elevated CV risk factors in TAA and AAA patients.^666,950 Additionally, apply all CVD secondary prevention measures to these patients (see Section 7).

Some evidence suggests that fluoroquinolones could be associated with an increased risk for aneurysm progression and dissection,^951–956 but conflicting analyses do not support this association. The cautious use of fluoroquinolones should not be discouraged when there is a clinical indication, even considering concerns regarding aortic aneurysm and dissection (AA/AD). Note that AA/AD risk (both thoracic and abdominal) may increase due to infection itself, regardless of the antibiotic chosen. Infectious disease specialists discourage routine fluoroquinolone use as a first-line antibiotic if equally effective alternatives exist. Hence, do not withhold this therapy in aortic disease cases when clinically necessary. All medical and lifestyle recommendations are summarized in Figure 7.

Recommendation Table 37

Recommendations for medical treatment in patients with thoracic aorta or abdominal aortic aneurysms

9.2.5. Surgical management of aortic aneurysms

9.2.5.1. Surgical treatment of aortic root and ascending aorta

In isolated dilatation of the ascending tubular (supra-coronary) aorta, a supra-commissural tubular graft is inserted with the distal anastomosis just before the aortic arch. For aneurysms extending proximally below the sinotubular junction (STJ) with involvement of aortic sinuses, the surgical approach depends on the aortic annulus and valve condition. If the aortic valve cusps are pliable, experienced centres may recommend aortic valve-sparing techniques,^961–965 such as David’s procedure (reimplantation) or the Yacoub technique (remodelling).^{890,966–968} Otherwise, composite replacement of the aortic root and valve with the Bentall procedure is indicated.

Pre-operative evaluation⁸⁹⁰ and initial follow-up of patients is defined in Figure 25. Patients with a bioprosthetic valve should be monitored by TTE annually. However, in patients with mechanical prosthesis or native aortic valve, clinical evaluation and TTE should be performed as soon as possible if new heart symptoms develop.⁹⁶⁹ SAPT with low-dose aspirin (75–100 mg per day) should be considered for the first 3 months after conservative aortic valve surgery if there are no indications for OAC. Lifelong OAC with a VKA is recommended for all patients with a Bentall mechanical prosthesis.^970,971 However, in patients with no baseline indications for OAC, low-dose aspirin (75–100 mg/day) or OAC using a VKA should be considered for the first 3 months after Bentall surgery with a bioprosthesis.^972,973

Figure 25

Peri-operative algorithm for the management of patients with surgically treated aortic root and ascending aortic aneurysm.

AR, aortic regurgitation; CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic resonance; STJ, sinotubular junction; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography.

Although many risk factors associated with AAE have been described (such as elongation, angulation, and unfavourable biomechanics), aortic diameter is still the main determinant of aortic complications and death.^974–976 AAE rates decreased with prophylactic aortic surgery over a decade,⁹⁷⁷ and additionally, surgical risk for ascending aortic/aortic root surgery dropped significantly.^978–980 Now, experienced cardiac surgery centres report <1% mortality with elective surgery.^980,981

Most acute type A aortic dissections (acute TAAD) occur at diameters below 55 mm. However, the risk exceeds 1% between 50 and 54 mm,⁹⁸² with a critical point at 52–53 mm.^153,981,983 Pre-dissection aortic diameter at the tubular level is 25%–30% smaller than post-dissection. Over 60% of non-MFS, non-BAV acute TAAD patients have a non-dilated ascending aorta before dissection.^984,985 Additionally, the ‘root phenotype’ has been reported to be more malignant than those with ascending phenotype, with higher velocity of progression and AAE risk.^{154,891,892,986}

Novel parameters, like ascending aortic length (AAL) and the ascending-arch angle, correlate with acute TAAD risk.^155,976 AAL ≥13 cm links to nearly five-fold higher yearly AAE rates compared with AAL <9 cm, with a threshold of >11 cm as a risk indicator.¹⁵⁵ Indexing aortic diameters to anthropometric parameters has been suggested and a proportional increase in the risk of AAE has been retrospectively demonstrated for increasing diameter indexed to BSA,⁹⁰⁴ diameter indexed to patient height,¹⁵³ or cross-sectional area indexed to patient height.¹⁵⁴ However, these diameter-based indexing methods share the same limitations in risk prediction as the absolute diameter in the general population,^984,985 whereas they can be advantageous in patients with small body size.^153,154 These additional risk factors (beyond the diameter) are summarized in Figure 23.

Recommendation Table 38

Recommendations for surgery in aortic root and ascending aorta dilatation associated with tricuspid aortic valve (see also Evidence Table 11)

9.2.5.2. Surgical treatment of aortic arch aneurysms

Surgery for arch aneurysms is challenging, primarily due to risks like hypothermic circulatory arrest and the need for brain protection, resulting in higher mortality and stroke rates. Isolated aortic arch surgery is appropriate for asymptomatic degenerative aortic arch aneurysms ≥55 mm in diameter or symptoms or signs of local compression. Hemi-arch or total arch replacement are frequently required in patients who have an indication for surgery on an adjacent aneurysm of the ascending aorta. In specific cases, supra-aortic vessel transposition via off-pump debranching followed by TEVAR of the arch can be an alternative to traditional surgery, particularly when avoiding hypothermic circulatory arrest is a concern.^992–996 When the disease involves the proximal descending aorta or future need for treatment of the descending aorta is anticipated, the frozen elephant trunk (FET) technique is a good option.⁹⁹⁷ Assessment of patency and morphology of the circle of Willis is recommended when treatment involves the aortic arch.^998,999

Recommendation Table 39

Recommendations for surgery in aortic arch aneurysms

9.2.5.3. Surgical treatment of the thoracic descending aorta

General considerations

At 60 mm diameter, a DTA aneurysm has a 10% annual rupture risk, justifying intervention at ≥55 mm.^902,1002 Intervention at a diameter <55 mm may not bring any further survival benefit except for women,^904,1003 patients with connective tissue disorders,⁹⁰⁴ or rapid growth (≥10 mm per year or ≥5 mm every 6 months),¹⁰⁰⁴ (for high-risk factors see Figure 23). This threshold may be increased in high surgical risk patients.¹⁰⁰⁵ It is advisable to centralize complex procedures in centres with expertise in aortic diseases and a multidisciplinary team for effective patient management.

Open repair

Thoracic endovascular aortic aneurysm repair is recommended as first-choice intervention for DTA aneurysms,^1006–1010 thus open repair is limited to patients with unsuitable anatomy for TEVAR¹⁰¹¹ or connective tissue disorders.¹⁰¹² The early mortality benefit of TEVAR seems to decrease after 1 year, and thereafter long-term survival (10 years) seems better with open repair.¹⁰¹³ Therefore, open repair is advisable for young, healthy patients with unsuitable TEVAR anatomy and prolonged life expectancy, particularly when symptoms from aneurysm rupture or compression arise.

However, open repair involves significant post-operative risks, necessitating thorough pre-operative evaluations for cardiac, pulmonary, renal function, carotid, and peripheral arterial diseases. Risks include stroke, mesenteric and renal ischaemia due to clamping duration,^1014,1015 and paraplegia tied to the extent of aneurysmal disease.^1016,1017 Outside experienced centres, outcomes have shown minimal improvement in recent years, with mortality rates around 10% and spinal cord ischaemia rates at 11%–15%.^1016,1018

Endovascular repair

Comparative studies favour TEVAR over open repair, showing lower mortality (6%) and morbidity.^{1006,1019,1020} However, TEVAR’s survival advantage is balanced by an increased risk of follow-up re-intervention. It reduces spinal cord injury risk (3%).^1021–1024 Left subclavian artery (LSA) coverage during TEVAR for proximal sealing is required in up to 50% of cases.¹⁰²⁵ This is associated with an increased risk of cerebrovascular events, spinal cord ischaemia (SCI), and upper-limb ischaemia,^1026,1027 justifying previous surgical or concomitant endovascular (with branched or fenestrated grafts) revascularization of the LSA in an elective setting.^{1026,1028,1029} In cases of inadequate distal zone sealing, safe coverage of the coeliac artery has been proposed when sufficient collateral circulation exists,^1030,1031 but results are controversial.¹⁰³²

9.2.5.4. Surgical treatment of thoracoabdominal aorta aneurysms

General considerations

Since AAEs increase when TAAA diameter exceeds 60 mm,^{902,1002,1033} and there are more technical surgical challenges in TAAA repair (compared with DTA aneurysm or AAA), TAAA repair, in low-moderate surgical risk patients, is proposed if the aortic diameter is ≥60 mm. However, surgical repair should be considered at diameters ≥55 mm if patients present with high-risk features (Figure 24) or are at very low risk and under the care of experienced surgeons in a multidisciplinary aorta team.^{1004,1033,1034} HTAD, distal location, chronic dissection, and BAV⁹⁰³ are associated with rapid growth rate and will require closer follow-up.

Open repair

Open TAAA repair is a complex aortic procedure. Post-operative mortality risk increases with left ventricular (LV) dysfunction, renal insufficiency, and advanced age.^1035–1037 Since organs and tissues distal to the aortic clamp will suffer from prolonged ischaemia, extracorporeal circulation is mandatory to reduce complications,^1011,1038 especially SCI (2.5%–15%).^{1011,1039–1044} The mortality rate after open TAAA repair varies between 6% and 8% in high-volume centres^{1006,1011,1039} vs. 30% in less experienced centres,^1045,1046 raising the recommendation to perform these complex procedures only in specialized institutions.

Endovascular repair

Endovascular repair is a promising alternative for treating challenging aortic anatomy like juxta-renal AAA (Figure 22).^1047,1048 The use of fenestrated and branched endografts has shown excellent results, allowing perfusion of visceral vessels.^1049–1053 While direct comparison studies with open TAAA repair are lacking,¹⁰⁵⁴ the increasing adoption of endovascular procedures is notable, especially for high-risk patients, with low post-operative mortality rates (<10%).^{1051,1052,1055–1058} A recent meta-analysis confirms these excellent outcomes, endorsing endovascular repair for TAAA.¹⁰⁵⁹ The incidence of post-operative SCI (around 5%) is similar between endovascular and open repair.^{1052,1057,1060,1061} Thus, at mid-term follow-up, endovascular repair is durable with acceptable secondary re-intervention rates, which remain one of the major limitations.^{1052,1057,1058,1060,1061} Factors favouring endovascular vs. open repair in TAAA are presented in Table 15.

Table 15

Overview of factors favouring open vs. endovascular repair in thoracoabdominal aortic aneurysm

Characteristic	Favours open repair	Favours endovascular repair
Biological age and life expectancy	Younger age Considerable life expectancy with acceptable quality of life	Older age Limited life expectancy
Anatomical considerations	If aortic and branch anatomy preclude endovascular approach Poor vascular access	Suitable proximal and distal landing zones Favourable visceral and renal configuration Vascular access obtainable
Pathological	Chronic dissection	Acute dissection
Background/causal factor	Hereditary aortic disease	Degenerative aortic disease
Cardiopulmonary condition	Good cardiopulmonary reserve	Poor cardiopulmonary reserve
Fitness	No significant comorbidities Successful rehabilitation likely	Severe organ impairment (renal, kidney, pulmonary) Obesity Limited mobility, unlikely to rehabilitate successfully
Urgency	Elective repair Emergency repair without a viable endovascular solution	Elective repair Emergency repair with time for custom-made graft or suitable for standard grafts

Characteristic	Favours open repair	Favours endovascular repair
Biological age and life expectancy	Younger age Considerable life expectancy with acceptable quality of life	Older age Limited life expectancy
Anatomical considerations	If aortic and branch anatomy preclude endovascular approach Poor vascular access	Suitable proximal and distal landing zones Favourable visceral and renal configuration Vascular access obtainable
Pathological	Chronic dissection	Acute dissection
Background/causal factor	Hereditary aortic disease	Degenerative aortic disease
Cardiopulmonary condition	Good cardiopulmonary reserve	Poor cardiopulmonary reserve
Fitness	No significant comorbidities Successful rehabilitation likely	Severe organ impairment (renal, kidney, pulmonary) Obesity Limited mobility, unlikely to rehabilitate successfully
Urgency	Elective repair Emergency repair without a viable endovascular solution	Elective repair Emergency repair with time for custom-made graft or suitable for standard grafts

Adapted from Ouzounian et al. with permission.¹⁰⁶²

Table 15

Overview of factors favouring open vs. endovascular repair in thoracoabdominal aortic aneurysm

Characteristic	Favours open repair	Favours endovascular repair
Biological age and life expectancy	Younger age Considerable life expectancy with acceptable quality of life	Older age Limited life expectancy
Anatomical considerations	If aortic and branch anatomy preclude endovascular approach Poor vascular access	Suitable proximal and distal landing zones Favourable visceral and renal configuration Vascular access obtainable
Pathological	Chronic dissection	Acute dissection
Background/causal factor	Hereditary aortic disease	Degenerative aortic disease
Cardiopulmonary condition	Good cardiopulmonary reserve	Poor cardiopulmonary reserve
Fitness	No significant comorbidities Successful rehabilitation likely	Severe organ impairment (renal, kidney, pulmonary) Obesity Limited mobility, unlikely to rehabilitate successfully
Urgency	Elective repair Emergency repair without a viable endovascular solution	Elective repair Emergency repair with time for custom-made graft or suitable for standard grafts

Characteristic	Favours open repair	Favours endovascular repair
Biological age and life expectancy	Younger age Considerable life expectancy with acceptable quality of life	Older age Limited life expectancy
Anatomical considerations	If aortic and branch anatomy preclude endovascular approach Poor vascular access	Suitable proximal and distal landing zones Favourable visceral and renal configuration Vascular access obtainable
Pathological	Chronic dissection	Acute dissection
Background/causal factor	Hereditary aortic disease	Degenerative aortic disease
Cardiopulmonary condition	Good cardiopulmonary reserve	Poor cardiopulmonary reserve
Fitness	No significant comorbidities Successful rehabilitation likely	Severe organ impairment (renal, kidney, pulmonary) Obesity Limited mobility, unlikely to rehabilitate successfully
Urgency	Elective repair Emergency repair without a viable endovascular solution	Elective repair Emergency repair with time for custom-made graft or suitable for standard grafts

Adapted from Ouzounian et al. with permission.¹⁰⁶²

Recommendation Table 40

Recommendations for the management of patients presenting with descending thoracic aortic and thoracoabdominal aortic aneurysms

9.2.5.5. Surgical treatment of abdominal aorta aneurysms

General considerations

Rupture remains the most feared AAA complication, and is associated with the maximum diameter,¹⁰⁶³ as well as other risk factors (Figure 23). Different studies^1064–1071 (including the United Kingdom Small Aneurysm Trial [UKSAT] and American Aneurysm Detection and Management [ADAM] trial) reported no benefits from open or endovascular interventions (despite lower peri-operative complication rates) in asymptomatic AAA patients with a maximal diameter <55 mm in men and <50 mm in women. Evidence that women are more likely to rupture under surveillance and at a smaller aortic diameter justified a lower (50 mm) threshold. Another interesting method to quantify the risk of rupture based on body size, which seems a better predictor in women, has been proposed.¹⁰⁷² However, in the absence of recent studies, thresholds for intervention have not changed in recent years. Considering the complexity of patient management, it is advisable to centralize complex procedures in centres with a high level of expertise in aortic diseases and a multidisciplinary team.

Pre-operative cardiovascular evaluation and choice of treatment

Coronary artery disease is the leading cause of early mortality after AAA repair,^937,1073 and is associated with a 5%–10% rate of peri-operative CV complications such as death, MI, or stroke.^1074,1075 Since endovascular repair is associated with lower mortality (<1%) and CV complications,^1076–1079 the need for pre-operative cardiac work-up will depend on procedure risk, symptoms, and patient-specific CVRFs (see Sections 4 and 12, and the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery).¹⁰⁸⁰ Coronary revascularization before elective aortic surgery in patients with stable cardiac symptoms cannot be recommended, since there is evidence that this strategy does not improve outcomes or reduce the 30 day MI rate.^1080,1081

A complete vascular evaluation (that includes not only the AA but also the entire aorta: ascending, arch, and descending aorta) is mandatory to determine the best strategy in AAA management, CCT being, by consensus, the optimal pre-operative imaging modality.^1082,1083 When CCT is contraindicated, consider CMR, though calcification assessment is challenging. Pre-operative planning should determine EVAR feasibility by sizing the aorto-iliac system, yet adherence to device-specific instructions remains uncertain.^1084–1090 DUS assessment of the femoro-popliteal segment is advocated since femoro-popliteal aneurysms are commonly associated with AAA.^1091,1092 Additionally, the technique of choice should be discussed between the treating physician and the patient based on the patient’s life expectancy and preferences, operator and hospital volumes, and surveillance compliance.^{910,1093–1097} Elective AAA repair is not recommended in frail patients or those with life expectancy <2 years.^1098,1099 The individual decision-making process in AAA patients is displayed in Figure 26.

Figure 26

Algorithm for individual decision-making process in the treatment of patients with abdominal aortic aneurysm.

(A) Illustration of open repair (graft). (B) Illustration of endovascular treatment (EVAR). AAA, abdominal aortic aneurysm; EVAR, endovascular aortic aneurysm repair.

Different studies have demonstrated a significant short-term survival benefit for EVAR, but with similar long-term outcomes compared with open repair (up to 15 years)^1100–1103 also reported in females.¹¹⁰⁴ However, loss of early benefit is associated with an increased rate of late complications occurring after 8 years, especially late ruptures.¹⁰⁷⁹ These trials used earlier-generation EVAR devices, so the durability of the latest-generation devices remains uncertain. Recent data, however, suggest a reduced risk of late complications and fewer re-interventions.^1105–1108

Open abdominal aorta aneurysm repair

Open AAA repair through mid-line laparotomy (with <30 min clamping time) with a Dacron graft has been the preferred choice for years, despite notable CV morbidity^{1078,1100,1109–1113} and a 2%–5% mortality rate.^{1110,1111,1113,1114} In ruptured AAA, open repair results are worse than those of elective surgery, with an unchanged complication rate of around 48%.¹¹¹⁵ Thus, endovascular repair is recommended to reduce peri-operative morbidity and mortality.^1116–1118

Open AAA repair raises incisional hernia risk, particularly in obese patients, suggesting prophylactic mesh use in high-risk cases.^1119–1121

Endovascular abdominal aorta aneurysm repair

Endovascular abdominal aorta aneurysm repair reduces peri-operative mortality to <1%, although it implies higher risk of re-intervention in the long term.^1122–1124 Current devices offer features like active fixation, repositioning ability, low-profile design, and polymer-filled rings for improved sealing.^{1106,1125–1128} New devices demonstrate similar long-term outcomes with reduced re-intervention risk,¹⁰⁹⁰ expanding treatment possibilities to 60%–70% of infrarenal AAA cases.^1129,1130

In cases of juxta- or para-renal AAA (Figure 22), both open and endovascular treatment can be proposed in high-volume centres, with similar short- and long-term results. The choice between open surgical repair and endovascular repair depends on various factors, including the patient’s anatomy, overall health, and the extent of the aneurysm (see Table 15). In cases of complex endovascular treatment, a fenestrated or branch stent endograft should be considered.^1096,1131

A percutaneous femoral approach is suitable since it provides quicker access, reduced invasiveness, and allows local anaesthesia. Some evidence supports the use of ultrasound-guided percutaneous access for EVAR due to a lower rate of access-related complications and a shorter operation time.^1132–1135

As patients treated by EVAR are more prone to late complications (endoleaks, migration, or rupture) and re-interventions, lifelong surveillance is currently mandatory.^{1096,1136–1140}

Recommendation Table 41

Recommendations for the management of patients presenting with abdominal aortic aneurysm

9.2.6. Endoleaks

Endoleaks are defined as the persistence of blood flow outside the graft but inside the aneurysm sac, preventing complete thrombosis (Figure 27). They are the most common complication, with an incidence up to one-third of either early or late procedures (those appearing after 1 year).¹¹⁴⁵ Chronic anticoagulation constitutes a risk factor for re-intervention, late conversion surgery, or mortality.¹¹⁴⁶ Endoleaks exposing the aneurysm sac to systemic pressure and expansion will require re-intervention to prevent rupture.

Figure 27

Algorithm for follow-up after thoracic endovascular aortic aneurysm repair, and management of endoleaks and their classification.

CEUS, contrast-enhanced ultrasound; CCT, cardiovascular computed tomography; DUS, duplex ultrasound; TEVAR, thoracic endovascular aortic aneurysm repair; EVAR: Endovascular aortic repair. ^aIn cases of TEVAR, CCT is the preferred imaging technique since DUS/CEUS does not permit the correct evaluation of the thoracic aorta. In cases of renal failure, non-contrast CCT is a good alternative to monitor aneurysm sac growing and is associated to DUS/CEUS for EVAR monitoring. Endoleaks are classified into five types: Type Ia, proximal attachment site endoleak; Type Ib, distal attachment site endoleak; Type II, backfilling of the aneurysm sac through branch vessels of the aorta; Type III, graft defect or component misalignment; Type IV, leakage through the graft wall attributable to endograft porosity; and Type V; caused by ‘endotension’, possibly resulting from aortic pressure transmitted through the graft/thrombus to the aneurysm sac. Adapted from Rokosh et al. with permission.¹¹⁴⁷

Five types of endoleaks have been described, as detailed in Figure 27. Type I and type III require correction with a new (endovascular) procedure. Type II is present in about 25% of patients but may seal spontaneously in approximately 50% of cases. Risk factors for type II endoleaks include patent collaterals, presence of accessory arteries, and anticoagulation. In cases of significant sac expansion (≥10 mm), re-intervention should be considered, preferably by vessel or sac embolization. Type IV, attributed to device porosity, is rare with modern devices and no intervention is needed. Type V induces sac expansion without any visible endoleak. Treatment may be considered for significant sac growth (≥10 mm) and consists of stent graft relining or definitive endograft explant and open surgical repair.

Cardiovascular computed tomography with(out) contrast, and DUS and/or CEUS, are the main imaging modalities for TEVAR/EVAR follow-up. Imaging within the first 30 days is recommended to assess treatment success and/or complications. For TEVAR, contrast-enhanced CCT is the preferred imaging technique for follow-up and should be performed regularly (shorter or longer intervals are based on the expansion rate). In renally impaired patients, combined follow-up using DUS and non-contrast enhanced CCT is a suitable alternative (see follow-up algorithm, Figure 27). For EVAR, CCT and DUS/CEUS are recommended at 1 month following repair. Thereafter, surveillance should be based on the risk of late complications and includes DUS and/or CEUS (Figure 27).

Recommendation Table 42

Recommendations for the management of patients presenting with endoleaks

9.2.7. Long-term follow-up after aortic repair

Long-term success in the management of aortic aneurysms depends also on strict post-treatment surveillance, for both secondary prevention of the aortic disease and early identification of post-repair complications.

In endovascularly treated patients, surveillance aims to detect endoleaks, aneurysmal sac dilatation, and graft structural failure or migration.¹¹⁵⁰ Surgical treatments, while carrying higher operative risks, often yield more durable results with rarer late complications mostly related to laparotomy.¹¹⁵¹

After intervention on the thoracic aorta, TTE, TOE, CCT, and CMR are used for follow-up, CCT being the most used and available method for both endovascular and surgical treatments.^1150–1152 After intervention on the AA, CCT, CMR, and DUS/CEUS are used. DUS/CEUS can detect the most common drawbacks of EVAR, except for graft structural issues. For chronic and periodic monitoring, the use of CMR, especially in young women, should be considered (to reduce radiation exposure). However, the choice between these modalities should consider patient factors, potential artefacts, and local imaging expertise and availability. Both for the thoracic and abdominal aorta, due to the lack of studies systematically comparing different surveillance time intervals, recommendations are mostly based on consensus or evidence from single-centre observational studies.^70,1153

9.2.7.1. Follow-up after thoracic aortic aneurysm treatment

Complications after ascending aorta graft replacement, though rare, include pseudo-aneurysms and graft infections. Pseudo-aneurysms, occurring in roughly 5% of cases, are most common within the first 2 post-operative years, linked to aortic dissection surgery, HTAD, and synthetic glues.¹¹⁵⁴ CMR studies systematically following peri-anastomotic haematomas have reported higher rates (15%).¹¹⁵⁵ Graft infections can occur in 0.5%–6% of surgical patients with high morbidity and mortality rates, requiring rapid diagnosis. Treatment typically involves surgery and antibiotics, tailored to factors like overall health, infection severity, and underlying conditions.¹¹⁵⁶ Residual aortic disease progression depends on the underlying condition, such as HTAD, and requires individualized surveillance.

After TEVAR for DTA aneurysm, late complications are higher than with surgery (up to 38%), leading to re-operation in 24% of cases.¹¹⁵⁰ However, over 80% of TEVAR complications arise within the initial post-operative years.¹¹⁵⁷ Notably, FET results in fewer stent graft-related complications: 2% stent-induced intimal tear, 3% endoleak, and 7% need for additional TEVAR.¹¹⁵⁸

After surgical treatment of TAAs, the protocol is a first CCT scan at discharge or 1 month, then another in the first post-operative year (at 6, 9, or 12 months), followed by a 2 year scan, and if no issues arise, scans every 5 years thereafter (Figure 25).^1062,1159 Stricter lifelong surveillance is recommended after TEVAR: after first imaging at 1 month, yearly controls are recommended for at least the first 5 post-operative years, then less frequently if no complications are detected (Figure 27).

Cardiovascular risk profile modification, cardiac rehabilitation, and lifestyle adjustments are an integral part of post-aneurysm repair follow-up (Figure 7).²⁴

9.2.7.2. Follow-up after abdominal aortic aneurysm treatment

Evidence for follow-up after AAA is more robust than after TAA repair.^70,1096 Post-surgery, anastomotic or para-anastomotic complications are rare (2%–4%).¹¹⁶⁰ In contrast, EVAR has higher complication rates (16%–30%), necessitating lifelong surveillance.^1079,1150 EVAR’s survival advantage over surgery diminishes after 8 years, with higher aneurysm-related mortality risk for EVAR.¹⁰⁷⁹ However, most failures are detectable early, and complications seldom occur later in patients with normal early controls.^1161,1162 CCT effectively detects early EVAR abnormalities,¹¹⁶³ but DUS/CEUS surveillance proves accurate, reducing the need for radiation and nephrotoxic agents, and lowering costs (Figure 27).^1164–1167

Interestingly, a meta-analysis found low compliance of patients to post-operative surveillance without differences in all-cause mortality, aneurysm-related mortality, and re-intervention between compliant and non-compliant patients.¹¹⁶⁸ Altogether, the above-mentioned evidence supports stratified methods of surveillance,¹⁰⁹⁶ with identification of high-risk situations (e.g. older patients, inadequate sealing, type II endoleaks, no early post-procedural shrinkage of the aneurysmal sac) for which more frequent evaluation should be planned.^{1161,1169,1170}

Follow-up of OMT is highly important in AAA patients (Figure 7).²⁴ Statin use after AAA repair (surgical or EVAR) is associated with decreased short- and long-term mortality.¹¹⁷¹ In addition, surveillance for aneurysm development in other arterial locations is recommended.

Recommendation Table 43

Recommendations for follow-up after treatment of aortic aneurysms (see also Evidence Table 12)

9.3. Acute thoracic aortic syndromes

9.3.1. General concepts

Acute aortic syndromes are life-threatening emergencies, including classic AAD, IMH, PAU, aortic pseudo-aneurysm, and traumatic aortic injuries (TAI). They involve aortic wall damage and share a dynamic, overlapping pathophysiology, clinical presentation, and diagnostic and therapeutic approaches.^{24,172,174,910} AAS may also be iatrogenic following open or endovascular/percutaneous procedures, or cardiac surgery.¹¹⁷²

To guide AAS management, several anatomical classifications have been developed, the Stanford and the DeBakey systems being the most widely used. The Stanford system classifies AAS according to whether the ascending aorta is involved (type A or DeBakey type I and type II) or not (type B or DeBakey type IIIa and type IIIb) regardless of the site of origin of the intimal tear.^{172,174,910,1173} This classification considers not only anatomical and treatment aspects, but also prognostic implications, since patients with DeBakey type II AAS will probably be left without structural aortic wall lesions after surgery (Figure 28).

Figure 28

Anatomical and temporal classification of acute aortic syndrome.

AAS, acute aortic syndrome.

Furthermore, if time elapsed from symptom onset to diagnosis is considered, AAS can be divided into hyperacute (<24 h), acute (1–14 days), subacute (15–90 days), and chronic (>90 days) (Figure 28).^1174–1176

A new classification considers the intimal tear’s entry site and dissection extension (Figure 29).¹³⁶ Subscript P describes the proximal involved aorta, and subscript D indicates the distal zone. This classification guides treatment decisions for sealing the entry tear. AADs limited to the aortic arch or originating as retrograde dissections from the descending aorta that extend into the arch and stop before the ascending aorta are termed as non-A non-B AD.^1177–1179

Figure 29

Aortic dissection classification system based on the 2020 Society for Vascular Surgery/Society of Thoracic Surgeons Reporting Standards and the European update of the Stanford classification—Type Entry Malperfusion classification.

A, type A aortic dissection; B, type B aortic dissection; non-A, non-B, aortic dissection limited to the aortic arch or retrograde dissection extending into the arch (but not in the ascending aorta). Upper panel: Classification of AAD considering the intimal tear’s entry site and dissection extension. Subscript P describes the proximal involved aorta, and subscript D indicates the distal zone. Lower panel: The TEM classification is the European update of the Stanford classification combining information about the Type of dissection (T), the Entry site (E), and the presence of Malperfusion (M). Also refer to Supplementary data online, Section 1.6. Society for Vascular Surgery/Society of Thoracic Surgeons (SVS/STS). Reproduced with permission from.^136,1180

Recently, a European update of the Stanford classification—Type Entry Malperfusion (TEM) classification—has been proposed.¹¹⁸⁰ This combines information about the type of dissection, its extent, and the presence of complications (malperfusion), thus providing greater prognostic insights (Figure 29). This classification is recommended by the European Association for Cardio-Thoracic Surgery. The TEM and other classifications are described in the Supplementary data online, Section 1.6.

9.3.1.1. Epidemiology and risk factors

Classic AAD (comprising 80%–90% of AAS; incidence of 2.6–3.5 cases per 100 000 person-years)^24,1181 is characterized by the presence of an intimal flap separating the true from the false lumen (FL).^24,172,910

Acute aortic dissection occurs mostly in males (∼65%) and in the seventh decade of life (∼63 years).^1175,1182 Multiple risk factors often coexist directly linked to factors like wall stress (with systemic hypertension being the most common) and/or aortic media abnormalities, including syndromic and non-syndromic genetic diseases. HTAD, BAV, prior aortic surgery, and larger aortic dimensions are more frequent among young patients (<40 years).^24,1182,1183 Systemic hypertension and cocaine abuse are more common among African-American than among white patients.^1184,1185 Of note, the incidence of iatrogenic AD during cardiac catheterization is very low (around 0.01%–0.02%) and during cardiac surgery is 0.06%–0.23%, with favourable in-hospital and long-term prognosis.^1186,1187

Sex differences

A specific female sex phenotype appears to be evident in acute TAAD. At admission, acute TAAD female patients are usually older but have lower body mass index (BMI), BSA, and creatinine plasma levels. They present less frequently with active smoking, BAV, and previous cardiac surgery,¹¹⁸⁸ but diabetes mellitus is more common in women than in men. In-hospital surgical mortality does not differ between sexes, although 10 year survival appears to be higher in men. Among only medically treated acute TAAD patients, prohibitive high in-hospital mortality has been equally registered for both sexes (men 58.6% vs. women 53.8%).¹¹⁸⁸ However, further studies are needed to explore AAD sex differences to design appropriate diagnostic and therapeutic interventions and preventive strategies.¹¹⁸⁹

Pregnancy increases the risk of AAS, more often in the last trimester (50%) or post-partum (33%).¹¹⁹⁰

Chronobiology

Acute aortic dissection presents chronobiological patterns, with a higher incidence in morning hours (peak between 8 am and 9 am) and winter (peak in January in the Northern Hemisphere).^24,1175

Outcomes

For acute TAAD, in-hospital mortality has decreased from 31% to 22% due to better surgical outcomes; for acute type B aortic dissection (acute TBAD), in-hospital mortality has remained stable over the years (14%).^1175,1182 Including deaths before admission, 30 day mortality for AAD ranges from 23% to 55.8% in Western Europe.¹¹⁸¹

Non-A, non-B dissection patients tend to be younger (median age 59 years) and have a lower mortality than acute TAAD patients.^1180,1191 The 30 day mortality in patients medically treated is around 14%,¹¹⁷⁹ and 4.4% for those successfully treated surgically.¹¹⁷⁷

9.3.1.2. Clinical presentation

Acute TAAD typically presents with sudden, severe chest/back pain, often described as ‘sharp’, alongside a history of arterial hypertension. However, around 6.4% of patients do not experience pain.^{1182,1192,1193} Hypotension and shock are frequent. Unique clinical features specific to acute TAAD include pericardial effusion, aortic regurgitation, and coronary artery involvement leading to ACS (particularly the right coronary artery).¹¹⁹⁴ Stroke may occur when supra-aortic branches are involved. Additional complications encompass paraplegia (resulting from spinal ischaemia), acute kidney injury, intestinal ischaemia, or limb ischaemia. Isolated abdominal aortic dissection occurs in about 1.3% of acute TBAD cases when the intimal flap originates below or at the renal arteries.¹¹⁹⁵

A complete clinical evaluation is mandatory, consisting of a central neurological evaluation, heart and lung auscultation (aortic diastolic murmur, pericardial rubbing, etc.), abdominal palpation (tenderness, etc.), and assessment of peripheral pulsations as well as mobility and sensibility in upper and lower limbs. SBP differences (pulse deficit) should be sought.

9.3.1.3. Diagnostic work-up

Early diagnosis is still a major pitfall in managing AAD patients, therefore, a diagnostic multiparametric algorithm is proposed (Figure 30). It combines the aortic dissection detection-risk score (ADD-RS) with D-dimer (DD) and has been validated with an excellent capacity to rule out AAS.^1196–1200

Figure 30

Multiparametric diagnostic work-up of acute aortic syndrome.

AAS, acute aortic syndrome; ADD-RS, aortic dissection detection-risk score; CCT, cardiovascular computed tomography; ECG, electrocardiogram; POCUS, point-of-care ultrasound; STEMI, ST elevation myocardial infarction; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography; +, findings compatible with AAS. ^aIn haemodynamically unstable patients: consider TTE and/or TOE as first-line imaging technique depending on local expertise and availability.

In patients presenting with chest pain, a routine chest radiography and ECG are recommended to exclude other aetiologies; however, the absence of these findings should not delay further investigations.¹⁶³ Laboratory tests should be obtained, but awaiting results should not delay imaging if there is a high probability of AAD. The most common finding is an increase in DD level, which is the case in several other conditions such as pulmonary embolism or infections. When DD levels are below 500 ng/mL, AAD is unlikely.^172,1201

A focused TTE at the emergency department, if available, is recommended^1202,1203 to assess pericardial effusion, wall motion abnormalities, aortic regurgitation, and aortic diameters. Sometimes a dissection flap can be visualized, especially when using contrast.¹⁶⁵

When AAD is suspected, ECG-gated CCT from neck to pelvis is the preferred imaging technique, with 100% sensitivity and 98% specificity, and should be performed as soon as possible to confirm diagnosis, localize entry tear, extension (type A vs. type B), and malperfusion.^{170,172,1182,1204} When ACS or pulmonary embolism are still in the differential diagnosis, a triple rule-out ECG-gated CCT scan protocol can be performed be performed to avoid motion artefacts mimicking acute TAAD.^{170,1205,1206} However, this strategy is associated with higher contrast and radiation doses, might be less accurate for AAS, and does not reduce the need for additional imaging tests.^170,1207 If CCT is not available or in haemodynamically unstable patients, TOE can confirm diagnosis. TOE is especially useful pre-, intra, and post-operatively to monitor changes in the anatomical AAD configuration or surgical complications. CMR could be a valuable alternative for CCT, however, it is less available, requires a longer examination time, relies on patient collaboration, and consequently, is less frequently used in the acute setting. CCT, CMR, and TOE all provide good diagnostic accuracy^172,1204 (See Supplementary data online, Table S4).

Recommendation Table 44

Recommendations for diagnostic work-up of acute aortic syndromes

9.3.1.4. Therapeutic intervention in acute aortic dissection

Initial treatment

Acute aortic syndrome care should be centralized in experienced centres and managed by aorta teams.¹²¹¹ The cornerstone in AAS is initial reduction of the pulse pressure by lowering SBP below 120 mmHg and heart rhythm ≤60 beats per minute (b.p.m.). The aim is to decrease aortic wall stress to avoid further extension of dissection with possible rupture or malperfusion.^{174,1212–1216} Intravenous beta blockade (labetalol as a first choice due to its alpha- and beta-blocking properties) is generally accepted as the best option. Also, esmolol, an ultra-short-acting beta-blocker, can be titrated quickly and easily, making it particularly useful in the acute setting. If contraindicated, i.v. non-dihydropyridine CCBs could be used for heart rate control. If the BP target is not reached after initiating beta-blockers, i.v. vasodilators such as nitrates or dihydropyridine CCBs (e.g. nicardipine) can be administered concomitantly with rate-controlling agents first to avoid reflex tachycardia. In cases of malperfusion, higher BP could be tolerated to optimize perfusion to the threatened region. Early placement of an arterial line to monitor BP invasively is mandatory and admission to an intensive care unit is advisable (including ECG and urine output monitoring).^{1205,1217,1218} Antihypertensive treatment can be gradually switched to oral therapy once BP and heart rate targets are reached and the patient has normal gastrointestinal transit. Adequate pain control is necessary to help reach these haemodynamic goals. Intravenous morphine can be cautiously titrated to induce pain relief (Figure 31).

Figure 31

Medical management of acute aortic syndrome.

BP, blood pressure; b.p.m: beats per minute.

In-hospital mortality, reaching 60%, correlates with AAS type, location, patient comorbidities, and treatment. Risk rises with complications like pericardial tamponade, coronary involvement, or malperfusion. Figure 32 describes the main signs and symptoms of complications and the mortality rate associated with them.^1219–1223

Figure 32

Complications in acute aortic syndromes, clinical evidence associated with malperfusion syndrome, and in-hospital mortality associated with these complications.

Recommendation Table 45

Recommendation for medical treatment in acute aortic syndromes

Interventional treatment in acute TAAD and acute TBAD is described in the next sections and summarized in Figure 33.

Figure 33

Interventional treatment algorithm in acute aortic dissection.

AAD, acute aortic dissection; Ao, aorta; CCT, cardiovascular computed tomography; OMT, optimal medical treatment; TEVAR, thoracic endovascular aortic repair. ^aOn serial imaging in the acute phase during the hospital stay. ^bOngoing hypertension despite more than three classes of antihypertensive drugs. ^cDefined as the presence of adequate proximal and distal landing zones for the prosthesis and adequate iliac/femoral vessels for vascular access. ^dBetween 14 and 90 days after dissection onset.^{172,1226–1231}

Type A aortic dissection interventional treatment

Immediate surgical repair is recommended for acute TAAD, however, a high mortality rate (∼50% and 1%–2% per hour) within the first 48 h is described if managed medically only.¹²³² Despite advances in surgical and anaesthetic techniques, there is still a high risk of peri-operative mortality (17%–25%) and neurological complications (18%).¹²³³ In recent reports from the International Registry of Acute Aortic Dissection (IRAD), medically managed patients had a 23.7% mortality rate (0.5% per hour) compared with 4.4% (0.09% per hour) for those undergoing surgery.¹²³⁴ Analyses of pre- and post-July 2007 IRAD data showed no difference in 48 h mortality for medically treated patients, but surgical mortality decreased (from 5.5% to 3.9%).¹²³⁴ As surgical techniques have improved, data have shown improved post-operative survival rates.¹²³⁵ The use of the GERAADA (German Registry of Acute Aortic Dissection Type A) score¹²³⁶ should be considered in patients undergoing surgery to determine 30 day mortality (https://www.dgthg.de/de/GERAADA_Score).

Surgical intervention surpasses conservative therapy in long-term follow-up,¹²³⁷ even for challenging cases. Thus, all acute TAAD patients should receive surgical treatment; however, cardiogenic shock secondary to pericardial tamponade, malperfusion of coronary arteries, mesenteric circulation, lower extremities, kidneys, or brain, and/or coma are major predictors for post-operative mortality (Figure 32).^1234,1238 Among octogenarians, in-hospital mortality was lower after surgery than with conservative treatment (37.9% vs. 55.2%), but with a non-significant difference due to small sample size.¹²³⁹ While some have reported excellent surgical and quality of life (QoL) outcomes in elderly patients,¹²³⁹ others found a higher rate of post-operative neurological complications.¹²⁴⁰ Based on the current evidence, age per se should not be considered an exclusion criterion for surgery.

For optimal repair of acute TAAD regarding long-term outcomes, including risk of late death and late re-operation, the following points need to be addressed. First, in most cases of aortic regurgitation associated with acute TAAD, the aortic valve is essentially normal and can be preserved.^1241–1243 Alternatively, valve replacement can be performed in cases of pre-existent structural valve disease. The decision whether to replace the aortic root is based on the presence of tears in the sinuses, extensive dissection of sinuses/coronary ostia, or significant dilatation of the root. The risk of late dilatation of the aortic sinuses when spared should be considered.^1242,1244 Additionally, the distal extent of aortic repair is a topic of debate. Ascending aortic replacement or hemi-arch replacement alone is technically easier and effectively closes the entry site but leaves a large part of the diseased aorta untreated. In acute TAAD with visceral or renal malperfusion, the primary entry tear is often in the descending aorta. Consider extended therapies like FET repair for these patients, offering a complete repair with a low chance of late re-intervention despite increased technical complexity.^1245–1247

For potential cardiac arrest from pericardial tamponade, consider an emergency pericardial puncture as a temporary life-saving measure before transferring to the operating room.^1248,1249

Recommendation Table 46

Recommendations for intervention in type A acute aortic dissection

The frozen elephant trunk technique

The FET technique addresses complex aortic and aortic arch issues in a single operation,^1260–1263 creating a secure landing zone for future interventions. Recent advances involve ‘proximalization’—placing the FET in the aortic arch’s zone 0 or 1, treating proximal arch aortic issues, and enhancing the landing zone for downstream procedures—which surpasses the standard elephant trunk technique.^1264,1265

Recommendation Table 47

Recommendations for aortic repair strategies in type A acute aortic dissection

Malperfusion in type A aortic dissection

In acute TAAD with malperfusion, operative mortality correlates with the number of affected organs. Around 30% of patients develop malperfusion syndrome due to elevated pressure in the FL caused by substantial proximal inflow and insufficient distal outflow, leading to visceral organ and limb ischaemia.¹¹⁷⁵ The intimal flap may extend into peripheral arteries, causing a static ‘stenosis-like’ blockage. Malperfusion typically combines dynamic and static obstructions, necessitating surgical and hybrid interventions for affected patients (Figure 34).

Figure 34

Mechanisms and clinical management of aortic branch obstruction in acute aortic dissection.

CPR, cardiopulmonary resuscitation; F, false lumen; FET, frozen elephant trunk; OR, operating room; T, true lumen; TOE, transoesophageal echocardiography; TEVAR/EVAR, thoracic endovascular aortic aneurysm repair. ^aDevelops only in retrograde type A dissection.

Mesenteric malperfusion, a life-threatening complication with a mortality rate of 65%–95%, leads to diverse treatment approaches. Some centres prefer early direct reperfusion before aortic surgery, while others favour conventional central aortic repair.¹²⁷⁵ The IRAD registry highlights the superiority of a surgical and hybrid approach over medical or endovascular therapy alone. Central aortic repair effectively restores perfusion, showing promising results for renal malperfusion, extremity malperfusion, uncomplicated mesenteric malperfusion, or combinations.

Cerebral malperfusion, equally grave, triggers treatment debates necessitating a multidisciplinary strategy. Evidence supports surgical intervention, reducing mortality rates to 25%–27%, compared with 76% with medical management alone.^1255,1276 Close monitoring and rapid intervention are essential to achieve optimal outcomes and minimize the risk of permanent neurological damage. A recommended algorithm for malperfusion management is displayed in Figure 34.

Recommendation Table 48

Recommendations for the management of malperfusion in the setting of acute aortic dissection

Endovascular treatment in type A aortic dissection

Endovascular therapy alone has been attempted in highly selected cases and the concept of a single endovascular valve-carrying conduit was suggested recently but has not yet been validated.^1281,1282

Treatment in non-A non-B aortic dissection

Conservative management leads to high mortality (malperfusion, aortic rupture); thus, surgery or endovascular therapy is favoured within 14 days of symptom onset. For complicated non-A non-B aortic dissection with an arch tear, consider FET repair, though if feasible, stent-graft implantation for primary tear coverage is an alternative.^1179,1283

Acute type B aortic dissection interventional treatment

Acute TBAD presents without complications (uncomplicated) in around 50% of cases.¹²⁵⁰ Complicated acute TBAD includes aortic rupture, malperfusion-related issues, rapid aortic expansion, paraplegia/paraparesis, aortic haematoma, refractory pain, and hypertension despite optimal therapy, which associates with an approximately 50% mortality risk with conservative treatment.^{1193,1250,1284,1285}

Open surgery used to be the sole option for complicated acute TBAD but carried a mortality rate of 25%–50%. Consequently, medical management, now considered the standard for uncomplicated cases, significantly reduces mortality. Goals include lowering SBP and heart rate with BBs (see Section 9.3.1.4.1). However, adherence is the main limitation of chronic medical treatment, with a rate below 50%.^1286,1287 Compliance increases with previous aortic surgery, severity of hypertension, and understanding of the disease process. Thus, surveillance and disease awareness are imperative for these patients.

Endovascular therapy for complicated acute TBAD is now the first-line treatment, provided there is favourable anatomy, due to positive short- and long-term outcomes.^1288–1294 Open surgery is reserved for unsuitable cases, and fenestration could be considered as an ultima ratio. In selected instances, correcting side branch compression before proximal sealing may be considered.¹³⁶

In recent years, the ADSORB (Acute Dissection Stentgraft OR Best Medical Treatment) and INSTEAD-XL (Investigation of Stent Grafts in Aortic Dissection with extended length of follow-up) trials^{1219,1226,1295} have reported that early intervention for uncomplicated acute and subacute TBAD is beneficial compared with medical management, and there is important debate on whether to treat patients with uncomplicated acute TBAD to improve their life expectancy.^1296–1298 Intervention is considered early within 90 days after onset of symptoms and may be safer when performed in the subacute phase (>14 days after onset of symptoms), but data are scarce.^1298–1300 The Society of Thoracic Surgeons/American Association for Thoracic Surgery (STS/AATS) 2022 guidelines¹²⁹⁴ state that prophylactic TEVAR may be considered also in patients with suitable anatomy and high-risk features (Figure 33) to reduce late aortic-related adverse events. However, this matter is not entirely settled, and the Improving outcomes in vascular disease—aortic dissection (IMPROVE-AD trial) is currently underway. This trial aims to evaluate clinical outcomes in patients with subacute (from 48 h to 6 weeks) uncomplicated type B aortic dissection (uTBAD), comparing upfront TEVAR plus medical therapy against medical therapy with surveillance for deterioration.

Aortic characteristics change over time, and endovascular treatment in the chronic phase offers limited potential for aortic remodelling. Identifying specific characteristics at the time of acute TBAD diagnosis that predict a complicated course has been attempted. Independent predictors of TBAD outcomes include a primary entry tear >10 mm located at the inner aortic curvature,¹³⁰¹ initial aortic diameter >40 mm,^1301,1302 initial FL diameter >20 mm,¹³⁰¹ number/size of fenestrations between the true lumen and FL,¹³⁰³ stent graft-induced new entry tear,^1304,1305 and partial FL thrombosis.^1306,1307 These parameters are summarized in a new system for the categorization of AD, DISSECT (Duration from onset of symptoms, Intimal tear location, Size of the aorta based on maximum trans-aortic diameter, Segmental Extent, Clinical complications related to the dissection, Thrombosis of the FL),¹³⁰⁸ which serves as a guide to support a therapeutic decision (Figure 33).¹³⁰⁸ A recent meta-analysis found TEVAR to be superior to best medical therapy in uncomplicated acute TBAD. Early outcomes were similar, but TEVAR was associated with fewer long-term events and better aortic remodelling.^{1297,1298,1309} Thus, in stable TBAD with suitable anatomy and high-risk features, pre-emptive TEVAR to improve the late outcome should be considered.

Accurate endograft sizing is vital for TEVAR success, as errors may lead to complications. Disease-specific factors, such as acute thoracic aortic syndromes, pose challenges due to fluctuations in aorta diameter from haemorrhagic shock and resuscitation. Sizing decisions must account for these changes. Measuring the thoracic aorta based on admission CCT may be imprecise, even with proper centreline measurements. Real-time imaging, especially IVUS, enhances accuracy, particularly in hypovolaemic cases. However, further research is required to clarify the role of intraoperative imaging methods (e.g. IVUS, TOE, 3D CCT) in endograft sizing and long-term outcomes for optimal patient care.¹⁹⁴

Recommendation Table 49

Recommendations for the management of patients presenting with acute type B aortic dissection

Chronic type B aortic dissection interventional treatment

Type B aortic dissection is considered as chronic 3 months after the onset of symptoms, but it also includes residual type B dissection after repair of TAAD. Aortic complications, especially aneurysmal degeneration, will occur in up to 50% of these patients.^1302,1313 Therefore, in chronic TBAD, indications for treatment include the onset of new aortic symptoms such as rapid expansion, malperfusion, or rupture.¹³¹⁴ In asymptomatic patients, aneurysmal dilatation is the most important risk factor for rupture, reaching 20% when the diameter exceeds 55 mm.^1302,1315 Risk of rupture increases with diameter; it has been reported a risk of 15.3% and 18.8% between 50–55 mm and 54–56 mm, respectively, thus suggesting 50–55 mm as a threshold for elective surgery.¹³¹⁶ However, smaller diameters should be considered in patients with HTAD. According to several studies, mortality in the chronic phase is high (40%–70%) and it is mainly related to patients’ comorbidities, such as heart disease and stroke.

Open repair

Despite the lack of data comparing open repair vs. TEVAR in chronic TBAD, open surgery remains the first-line treatment in low-risk patients or those with HTAD. The STS/AATS guidelines¹²⁹⁴ state that open repair should be considered in chronic TBAD patients with indication for intervention, unless comorbidities are prohibitive or anatomy is not suitable for TEVAR. The surgical technique for chronic TBAD is like those for degenerative aneurysms, but repair is more complex due to the dissection flap.¹³¹⁷ Surgical mortality rates between 6% and 11% and SCI rates between 3% and 11% have been reported.^1317–1321 Patients treated in low-volume centres present higher mortality rates (up to 20%), which reinforces the recommendation for centralization in experienced centres.

Endovascular repair

Thoracic endovascular aortic aneurysm repair (TEVAR) is the preferred treatment for eligible chronic TBAD patients, offering low early mortality (<5%), with stroke and SCI rates below 3%. It is also suitable for high-risk patients who are not candidates for open repair. The primary goal is to close the entry tear, induce FL thrombosis, and promote aortic remodelling to mitigate growth and rupture risk.^1322,1323 A systematic review showed 90% immediate technical success and 86% complete FL thrombosis. However, FL thrombosis usually occurs above the coeliac trunk, necessitating lifelong distal FL surveillance.¹³²⁴ Coverage of the LSA is often necessary and should be associated with revascularization. In a recent meta-analysis¹³²⁵ comparing TEVAR to open repair in chronic TBAD, TEVAR showed lower early mortality, stroke rates, SCI, and respiratory complications but a higher re-intervention rate. Long-term survival rates were similar, but open repair offered greater durability.¹³²⁶

Adequate distal sealing poses a challenge due to the dissection extending to the iliac artery, with additional re-entries, allowing retrograde flow into the thoracic aneurysm. In chronic TBAD patients with AA enlargement, insufficient distal landing, or large re-entry tears, TEVAR alone is discouraged. Instead, a comprehensive repair involving the visceral aorta, infra-renal aorta, and iliac artery is needed. Recent studies have shown favourable results using custom or improvized fenestrated/branched endografts with careful patient selection.^{1062,1327–1329} A multidisciplinary team-based approach in experienced centres is necessary for good outcomes.¹³³⁰

Recommendation Table 50

Recommendations for the management of patients presenting with chronic type B aortic dissection

Management during pregnancy

Management of AD during pregnancy requires a multidisciplinary team and specialized centres. Initial care should consider general medical recommendations (as previously described), using drugs with the lowest teratogenic impact.

In cases of type A dissection, if the foetus is viable, caesarean delivery will be performed before aortic repair. If the foetus is not viable, surgery will be done with the foetus in place.^1335,1336 In uncomplicated type B dissections, strict control of the pregnant patient and foetus with conservative medical management is recommended.^1224,1335 Although limited to selected cases, successful TEVAR has been described in complicated TBAD.¹²²⁷ More information is detailed in the 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy.¹³³⁷

9.3.2. Intramural haematoma

Intramural haematoma, constituting 5%–25% of AAS cases, involves vasa vasorum haemorrhage within the aortic media, with or without intimal disruption (ID).^70,172,1338 Most cases (60%–70%) involve the DTA (ascending aorta ∼30%, aortic arch ∼10%).^70,172,1192 Although it usually occurs at an older age than AAD, risk factors and symptoms are similar;^{70,172,1192,1338} however, aortic regurgitation, malperfusion syndrome, and pulse deficits are less frequent in type A IMH than in TAAD.^70,172

9.3.2.1. Diagnostic work-up

Diagnostic IMH work-up should be similar to that proposed for AAS (Figure 30), but with different morphological features in the imaging techniques.

CCT and CMR (followed by TOE) are the leading techniques for diagnosis.^{70,159,171–173} Unenhanced followed by contrast-enhanced CCT represents the most used tool in the acute setting (hyperintense signal of aortic wall before contrast administration).^70,171,172 The IMH diagnostic hallmark consists of crescentic or circular aortic wall thickening in the absence of an intimal flap or aortic wall enhancement following contrast administration.^70,171,172 CMR is an excellent imaging technique to detect small IMHs and for the differentiation of IMH (hyperenhanced images in T1-weighted images) from atherosclerotic thickening of the aorta, thrombus, or thrombosed dissection.¹⁷² TTE yields low sensitivity (<40% for IMH cut-off limit of 5 mm).¹⁷¹

9.3.2.2. Clinical outcomes

Intramural haematoma may evolve into AAD (12% of patients), saccular (8%) or fusiform aneurysm (22%), and/or ID (54%).^{1192,1339–1342} Partial or total regression is reported in 34% of patients.^70,1192,1343 Outcomes are comparable to those in AAD. In-hospital mortality for type A IMH is 26.6% (surgical 24.1% and medical 40.0%). In this regard, higher mortality for IMH involving the aortic valvular complex has been observed.¹¹⁷⁵ In-hospital mortality for type B IMH is 4.4% but worsens once surgery is indicated (surgical 20.0% vs. medical 3.8%).^1175,1344

9.3.2.3. Geographical variations

Reports from South Korea and Japan reveal notable disparities with Western nations in IMH incidence (28.9% vs. 5.7% of overall AAD as reported by IRAD), treatment strategies, and outcomes. In Eastern regions, the majority (80.8%) of type A IMH patients received medical treatment, resulting in significantly improved clinical outcomes (in-hospital mortality 6.6% [5.9% for medical and 9.4% for surgical]).¹³⁴⁵ These results may be partially explained by the detection of early-stage IMH (mild, uncomplicated cases) at primary centres.^1345–1347

9.3.2.4. Management

Current IMH therapeutic interventions are similar to AAD, with the first step consisting mainly of pain and BP control regardless of the anatomopathological features (Figure 31).

Type A intramural haematoma

As in AAD, type A IMH involves the ascending aorta. Surgery (emergency or urgent depending on clinical status) is recommended. In selected patients with increased operative risk (i.e. multiple comorbidities) and uncomplicated type A IMH without high-risk imaging features (Table 16) a ‘wait-and-see strategy’ in a reference/experienced centre may be reasonable.^{70,172,1348,1349}

Table 16

High-risk features of intramural haematoma type A and B

Ascending aorta involvement

Difficult BP control

Persistent/recurrent pain despite aggressive BP control

Maximum aortic diameter:

Type A: >45–50 mm
Type B: >47–50 mm

Progression to aortic dissection

Focal intimal disruption with ulcer-like projection

Haematoma thickness >10 mm (type A) or >13 mm (type B)

Enlarging haematoma thickness

Enlarging aortic diameter

Pericardial effusion at admission (type A)

Recurrent pleural effusion

Detection of organ malperfusion

BP, blood pressure.

Adapted with permission from.¹⁷²

Type B intramural haematoma

In type B IMH, the disease is in the descending aorta, distal to the left subclavian artery. For uncomplicated type B IMH, initial management involves medical treatment and thorough clinical and imaging monitoring.^70,172 If uncomplicated type B IMH presents high-risk imaging characteristics (see Table 16), the multidisciplinary team should consider endovascular repair as an option. In contrast, complicated type B IMH warrants consideration of TEVAR.^1350,1351 However, in unfavourable anatomy, open surgery remains an alternative.

ID has been described in 54% of type B IMH cases.^{1192,1339–1342} Approximately 28% of them are tiny intimal disruptions (≤3 mm) that are not related to AAEs. However, 14% of them evolve into focal intimal disruptions (FID) (>3 mm), with prognostic implications; thus, all patients with ID require close follow-up with imaging techniques. In the acute phase, FID has a poor prognosis owing to the high risk of aortic rupture and should be treated early and invasively, especially large FID (≥10 mm length and ≥5 mm depth).^1342,1352 However, in the chronic phase, most FIDs evolve with slow aortic dilatation and without complications, and they can be managed with medical treatment and close imaging surveillance.¹³⁵²

Recommendation Table 51

Recommendations for the management of intramural haematoma

9.3.3. Penetrating atherosclerotic ulcer

Penetrating atherosclerotic ulcer (2%–7% of all AAS cases) is characterized by localized ulceration of an aortic atherosclerotic plaque penetrating through the internal elastic lamina into the media, frequently associated with IMH and diffuse atherosclerosis.^{70,172,174,910,1338,1343}

Often, multiple PAUs are present, ranging from 5 to 25 mm in diameter and 4 to 30 mm in depth.^{70,172,174,1338} They occur mostly in the middle and lower DTA, with the aortic arch and AA less involved. The ascending aorta is rarely affected,^{70,172,910,1192} but when this occurs, especially complicated with IMH, the risk of rupture is 33%–75% and progression to dissection is associated with a high mortality rate.

Most patients are older males, smokers, aged >65, with multiple comorbidities like systemic hypertension, CAD, COPD, renal insufficiency, and concurrent abdominal aneurysm.^{24,172,910,1357}

Symptoms are like those in AAD and may manifest in older age after a long asymptomatic phase (often PAU is diagnosed as an incidental finding during an imaging examination).^{24,172,910,1357} It should be highlighted that symptom onset may indicate PAU expansion (tunica adventitia involvement); thus, urgent imaging (CCT or CMR) and appropriate therapeutic intervention are needed to prevent aortic rupture.^{70,171,172,174}

9.3.3.1. Diagnosis

Diagnostic work-up is described in Figure 30. CCT represents the technique of choice for diagnosis. TOE and CMR represent possible valid alternatives considering availability and local expertise.^{70,159,171–173} Of note, ¹⁸FDG-PET-CT is a promising technique since it can detect increased glucose uptake in PAUs as a marker of increased metabolic activity and inflammation, which has been associated with major adverse events.^1358,1359 This information may be used to guide treatment decisions, such as the selection of patients who may benefit from endovascular or surgical intervention.¹³⁶⁰

9.3.3.2. Treatment

Medical treatment as described for AD is recommended (Figure 31). Management of incidental cases is not clearly defined.¹⁷⁴ Small series suggest that isolated, asymptomatic, small PAUs may be safely managed conservatively with regular surveillance.^1361,1362

Surgery is recommended in type A PAU with the option of a ‘wait-and-see strategy’ in highly selected high-risk patients with no high-risk features (Figure 35). However, in uncomplicated type B PAU, medical treatment along with careful clinical and imaging surveillance is recommended.^174,1350 When intervention is needed, endovascular treatment (early and 3 year aortic mortality 7.2% and 10.4%, respectively)¹³⁵⁰ should be preferred to open surgery (early and 3 year aortic mortality of 15.9% and 25.0%, respectively).^174,1350 In cases of uncomplicated PAU with high-risk imaging features^1363–1365 (Figure 35), endovascular treatment should also be considered. The natural history of PAU of the abdominal aorta (AA) with associated IMH is less known. In a review of PAU of the AA, endovascular stenting was the preferred treatment of choice (62%), followed by open surgical repair (35%) and conservative therapy (3%).¹³⁶⁶

Figure 35

High-risk features in penetrating atherosclerotic ulcer and management of patients with type B penetrating atherosclerotic ulcer.

IMH, intramural haematoma; PAU, penetrating atherosclerotic ulcer; TEVAR, thoracic endovascular aortic repair. (A) Maximum PAU width. (B) Maximum PAU depth; (C) Maximal aortic diameter at the site of the PAU.⁹¹⁰

Recommendation Table 52

Recommendations for the management of penetrating atherosclerotic ulcer

9.3.4. Aortic pseudo-aneurysm

Aortic pseudo-aneurysms, or false aneurysms, result from aortic wall disruption, typically caused by factors like trauma,¹³⁶⁸ surgery, or infections. They are often symptomless, detected incidentally during post-aortic procedure imaging. Symptoms may include chest pain, compression, and if untreated, they can lead to fatal rupture or other severe complications.^1369,1370

Pseudo-aneurysm repair seems always indicated regardless of size or position to prevent progression and rupture. Nevertheless, in some circumstances and under close follow-up, patients could be monitored by CCT, CMR, or TOE and intervention could be postponed unless size expansion, symptoms, or compression of surrounding structures occur.¹³⁷¹ Pseudo-aneurysms could be treated by open surgery or endovascular treatment (occluders, stent grafts, or coils). There is no randomized study comparing open surgery vs. TEVAR; however, treatment of choice is commonly based on anatomical features, clinical presentation, and the patient’s comorbidities and decided by a multidisciplinary team in specialized centres.^1045,1371

9.3.5. Traumatic aortic injury

Traumatic aortic injury (TAI), commonly from high-speed motor accidents or falls, involves partial or complete aorta transection. It results from rapid deceleration causing torsion and shearing forces, often affecting relatively immobile aorta segments like the aortic isthmus (90%), aortic root (5%), or diaphragmatic hiatus (5%).^24,70,172

Traumatic aortic injury is classified based on the degree of lesion in the aortic wall (Figure 36): grade I (intimal tear), grade II (IMH), grade III (pseudo-aneurysm), and grade IV (aortic rupture). In the Crash Injury Study, 130/613 deaths (21%) were associated with TAI (mortality associated with aortic rupture 91%; at-scene survival 9%).¹³⁷²

Figure 36

Classification and treatment of traumatic aortic injuries.

Med, medical; OR, open surgery repair; TEVAR, thoracic endovascular aortic repair; Tx, treatment.

9.3.5.1. Diagnosis and therapeutic interventions

Due to non-specific symptoms and signs (often obscured by concomitant multiple organ injury) a timely diagnosis relies on a high level of clinical suspicion.^70,172 CCT (accuracy close to 100%) represents the technique of choice, acting as a ‘one-stop shop’ to rapidly assess the entire skeletal system and internal organs.^70,171,172 TOE may be an alternative, although limited by availability, local expertise, and potentially a patient’s multiple traumas.^24,70,172 Therapeutic interventions are dependent on the extent of aorta lesion and patient clinical status as assessed by a multidisciplinary team. Generally, aggressive fluid administration should be avoided because it may exacerbate bleeding, coagulopathy, and hypertension. To reduce risk of rupture, mean BP should not exceed 80 mmHg.¹⁷² Minimal aortic injury (grades 1 and 2) may be managed medically along with strict clinical and imaging surveillance; moderate aortic injury (grade 3) with semi-elective repair (within 24–72 h) to allow patient stabilization (though in some patients urgent repair is needed);^24,1373 and severe aortic injury (grade 4) with immediate repair.¹³⁷⁴ If there is progression of the IMH (grade 2), semi-elective repair (within 24–72 h) may be considered. TEVAR is preferred (if feasible) to open surgery (in-hospital mortality 7.9% vs. 20% and 1 year mortality 8.7% vs. 17%). In semi-elective repair, if the LSA needs to be covered, prior LSA revascularization before TEVAR is suggested to reduce the risk of paraplegia ^{172,1373,1374}

9.3.5.2. Long-term surveillance in traumatic aortic injury

In addition to clinical assessment, CCT is the imaging choice for follow-up.^70,171,172 Cumulative exposure to radiation and iodinated contrast medium remains the major limitation in young patients, especially in women. A combination of a chest X-ray and CMR (if no graft artefacts) would be a valid alternative.^24,171,172

Recommendation Table 53

Recommendations for traumatic aortic injury

9.3.6. Iatrogenic aortic injuries

Iatrogenic aortic lesions are those associated with invasive procedures (cardiac surgery, most commonly dissection type A, or coronary angiography, with a similar proportion of type A and B dissections) (see Section 9.3.2.1). Incidence is low and ADs are the most common lesions. Main risk factors are advanced age, presence of CVRFs, atherosclerosis, aortic aneurysms, or PAD (Figure 37). Patients with iatrogenic AAS are often painless with correspondingly less chest or back pain.¹³⁷⁵

Figure 37

Aetiology, risk factors, and classification of iatrogenic aortic injuries.

PAD, peripheral arterial disease. Dunning classification of iatrogenic aortic dissection:¹³⁷⁷: type 1, dissection limited to the sinuses of Valsalva; type 2, dissection of the ascending aorta outside the sinuses but < 40 mm from the aortic annulus. type 3, dissection > 40 mm from the annulus.

While historically associated with high mortality,¹³⁷⁵ recent registries like the German GERAADA indicate a mortality rate similar to that for spontaneous dissections.¹¹⁸⁶

Clinical management is based on the underlying lesion (AAD, IMH) and location; however, conservative management has been described with good results in type A iatrogenic dissection if the coronary flow is preserved and the dissection is small.¹³⁷⁶ Iatrogenic lesion classification is depicted in Figure 37.¹³⁷⁷ Although scarce, data support a conservative approach based on evolution in type 1 and 2 lesions (Dunning classification), and surgery in type 3.¹³⁷⁷ In cases of coronary involvement, stent implantation sealing the flap may be proposed.^1376,1377

9.3.7. Long-term follow-up of acute aortic syndrome

Imaging modalities and time intervals for surveillance vary according to lesion location (ascending/descending aorta), type of treatment (medical, endovascular, surgical), and underlying disease (HTAD).^70,1062,1153 Compared with the chronic disease setting, follow-up of AAS patients is characterized by a higher risk of complications and need for re-operation.¹³⁷⁸ Patients receiving TEVAR for AAS involving the descending aorta are more prone (27%–49%) to requiring a second intervention than patients undergoing surgical repair.^1379,1380 However, need for re-intervention at follow-up (after initial treatment of AAD) seems to have a significant impact on survival for TAAD¹³⁸¹ but not for TBAD.¹³⁸⁰

9.3.7.1. Follow-up after invasive treatment

Following surgery for AAS, imaging surveillance will focus on persistence/obliteration of the FL, anastomotic dehiscence, progressive dilatation of residual native aorta (with or without residual dissection), or graft infection. CCT is the most used modality, but in patients requiring frequent examinations CMR can be considered to reduce radiation.

Compared with outcomes of open surgery for aortic aneurysms, time to re-intervention in patients developing complications is significantly shorter,¹¹⁵⁹ also due to the faster average growth of the dissected aorta (about 1 mm per year).⁷⁰ Considering the reported incidence rates (around 10%) of complications requiring re-operation, it is reasonable to follow patients every 6 months in the first year (including an early—within 1 month—echocardiography to follow native or prosthetic aortic valve function), then yearly up to the third post-operative year and then every 2–3 years if there are no complications (Figure 38).^1153,1159

Figure 38

Algorithm for follow-up after acute aortic syndrome.

AAS, acute aortic syndrome; AD, aortic dissection; CMR, cardiovascular magnetic resonance; CCT, cardiovascular computed tomography IMH, intramural haematoma; PAU, penetrating atherosclerotic ulcer.

TEVAR implies a higher risk for late re-interventions,^1159,1378 and a sequence of imaging intervals at 1, 6, 12, 24, 36, 48, and 60 months is recommended if no abnormality is detected (shorter intervals should be considered in high-risk patients). Thereafter, controls can be performed every 2–3 years. Compared with the time points after surgery, an adjunctive early control at 1 month is necessary to exclude asymptomatic retrograde type A dissection induced by TEVAR (70% of cases occurring within 30 post-operative days).¹³⁸²

Besides imaging surveillance, clinical follow-up is aimed at achieving strict BP control, limiting the burden of CVRFs, and providing patients with counselling for lifestyle modifications and prescriptions for sport activity.²⁴ There is evidence that statin treatment may improve survival in AAS patients under medical treatment, whereas BBs may improve survival in surgically treated patients.¹³³³

9.3.7.2. Follow-up under medical treatment (chronic type B aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer)

Around 70% of TBAD patients survive the hyperacute phase. If there is no malperfusion, uncontrolled hypertension, or impending rupture, initiate anti-impulse therapy alongside surveillance.

Chronic aortic dilatation, reaching 55 mm, is the leading cause (about 40%) of intervention, while acute complications necessitating immediate treatment are rare.^1301,1383 Imaging controls should be performed at least at 1, 6, and 12 months after discharge and yearly thereafter; however, one additional earlier scan, e.g. within 3 months, may reveal important changes occurring in the subacute phase, when the dissected aorta remains successfully amenable to early TEVAR.¹³⁸³ During surveillance, late complications may be predicted by imaging features, including the number and location of the entry tear(s), and dimensions of the FL, total (true + false) lumen, or entry tear.¹³⁸³ This might help in risk stratification to modulate the stringency of surveillance in the individual patient (Figure 33).¹²¹³

Type B IMH and PAU are usually conservatively treated with antihypertensive therapy and watchful monitoring. Most of the medically treated IMHs have a favourable course, whereas PAUs are less predictable in terms of risk of acute TBAD or rupture.¹³⁵⁰ Therefore, for IMH the same surveillance criteria as for medically treated uncomplicated TBAD can be employed; for PAU more frequent controls are advisable, i.e. one every 6 months instead of every year. Selectively, in asymptomatic patients with 2 year growth-rate stabilization and no high-risk features, intervals between controls can be longer (every 1–2 years) (Figures 35 and 38).^70,1384

Recommendation Table 54

Recommendations for follow-up after treatment of acute aortic syndrome

10. Genetic and congenital diseases of the aorta

10.1. Genetic and chromosomal diseases

This section discusses genetic and congenital aortic diseases. Aortic root and ascending aortic disease is commonly linked to congenital or hereditary factors, while descending aortic problems, especially in the AA, often result from atherosclerosis.¹³⁸⁵ Unless noted otherwise, recommendations provided herein are intended for adults.

Genetic diseases affecting the thoracic aorta are grouped under the broader term of HTAD. HTAD comprises a clinically and genetically heterogeneous group of disorders sharing the common denominator of aneurysm or dissection of the thoracic aorta. Familial forms (thoracic aortic disease [TAD] affecting ≥2 individuals in one family) or confirmed genetic entities (familial or sporadic) as well as syndromes conferring a risk for TAD fall under the definition of HTAD.⁷⁰ Due to the rarity of these conditions, robust evidence for many scenarios, such as intervention thresholds, surgical methods, open surgery vs. endovascular approaches, and pregnancy planning, is lacking. Thus, a multidisciplinary and individualized approach is advisable.^70,1386,1387

Recommendation Table 55

Recommendations for the management of patients with heritable thoracic aortic disease

Clinically, HTADs can manifest as either syndromic or non-syndromic entities. The genes identified to date may underly both entities and predominantly show autosomal dominant inheritance patterns. While TAD is the primary feature in HTAD, extra-aortic features (skeletal/ocular) may be key to diagnosing certain syndromic cases. In some cases, the presence of extra-aortic manifestations may aid in risk stratification and hence in defining optimal management.^1388–1390 The main clinical and genetic data on syndromic and non-syndromic HTADs are summarized in the Supplementary data online, Table S5.

Numerous underlying gene defects have been discovered in both syndromic and non-syndromic cases, leading to the constitution of three major molecular groups: genes encoding components of: (i) the extracellular matrix; (ii) the transforming growth factor-beta (TGF-ß) signalling pathway; and (iii) the smooth muscle cell contractile apparatus. Clinical and CV outcomes vary between these groups and will help pave the way to precision medicine in HTAD.¹³⁹¹ Extensive clinical and imaging studies in HTAD revealed arterial vasculature involvement beyond the thoracic aorta. Patients may develop aneurysms and/or dissections beyond the aorta in diseases such as MFS, Loeys–Dietz or vascular Ehlers–Danlos syndrome (vEDS),^{1390,1392,1393} or can be prone to occlusive vascular disease in the setting of alpha-actin gene (ACTA2) variants.¹³⁹⁴ Large clinical variability is observed within families carrying an identical variant and instances of incomplete penetrance (a ‘skipped generation’) are observed. All HTAD entities display cystic medial degeneration, hindering precise diagnosis using pathology.

Both genetic testing and imaging (mainly by TTE, but also consider CMR or CCT if the aortic root/ascending aorta are not properly visualized) in patients and family members are important in the diagnosis of HTAD. In those patients in whom no genetic cause is identified, but in whom there is a high suspicion of an underlying genetic defect, genetic re-evaluation needs to be considered after 3–5 years. Genetic testing should always be accompanied with appropriate counselling. Furthermore, appropriate assessment of HRQoL and psychological support should be offered to patients and families.¹³⁹⁵ Indications for genetic testing and aortic screening in HTAD are illustrated in the algorithm in Figure 39.

Figure 39

Algorithm for genetic and imaging screening in patients with thoracic aortic disease.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic resonance; FDR, first-degree relative; HTAD, heritable thoracic aortic disease; HTN, arterial hypertension; TAD, thoracic aortic disease; TTE, transthoracic echocardiography; VUS, variant of uncertain significance. ^amainly by TTE, but also consider CMR or CCT if the aortic root/ascending aorta are not properly visualized.

Although isolated AAA is less frequently associated with a genetic basis, patients with high-risk features (syndromic features, early onset of disease, absence of CVRFs, and/or family history of TAD or AAA) should be evaluated in centres with experience in HTAD to evaluate the need for genetic testing and specific surveillance, including active clinical screening in family members.

Recommendation Table 56

Recommendations for genetic testing and aortic screening in aortic disease

10.1.1. Turner syndrome

10.1.1.1. Diagnosis, clinical presentation, and natural history

Turner syndrome (TS), resulting from partial or complete monosomy of the X-chromosome, affects 1 in 2500 live-born females.

About 50% of patients experience CV issues like ascending aortic dilatation, BAV, aortic coarctation, elongated aortic arch, and partial abnormal pulmonary venous return.^1417–1419 All women present with generalized arteriopathy and TS itself is an independent risk factor for thoracic aortic dilatation. AD risk (type A in 85% and type B in 15%) is elevated in this population,^1420–1422 although recent studies indicate that this risk may be lower with proper treatment guidelines.^1423–1426 Risk factors include aortic dilatation, BAV, coarctation, and arterial hypertension. Defining aortic dilatation in TS requires adjustment for anthropometric parameters and aortic growth data for dissection risk estimation.¹⁴²⁷ Z-scores used in the general population are equivalent to Turner-specific z-scores.¹⁴²⁸

Imaging surveillance

In newly diagnosed TS, TTE and CMR are recommended at baseline for the evaluation of congenital heart defects and aortic anatomy/diameters. For women aged 15 years and older with TS, adjusting for their smaller body size is essential when assessing aortic dimensions. Utilize metrics like the ascending aortic size index (ASI), aortic height index (AHI), or aortic z-scores to gauge aortic dilation and dissection risk. Further follow-up is dictated by baseline aortic diameters, age, and risk factors (Figure 40).

Figure 40

Algorithm for surveillance in women (≥15 years) with Turner syndrome.

AHI, aortic height index (ratio of aortic diameter [mm] to height [m]); ASI, aortic size index (ratio of aortic diameter [mm] to BSA [m²]); BAV, bicuspid aortic valve; BSA, body surface area; CCT, Cardiovascular Computed Tomography; CMR, cardiovascular magnetic resonance; CoA, coarctation of the aorta; HTN, arterial hypertension; TTE, transthoracic echocardiography. ^aHTN: arterial hypertension, not under control despite more than three classes of antihypertensive drugs. ^bCMR (preferably) or CCT if inadequate visualization of the ascending aorta.

Recommendation Table 57

Recommendations for imaging in women with Turner syndrome

10.1.1.2. Medical treatment

In the absence of clinical trials, a pragmatic approach in a shared-decision model is adopted regarding TS medical treatment. Adoption of the strategy for inhibition of aortic growth with BBs and/or ARBs as in MFS may be considered. Hypertension should be treated according to general guidelines.³⁰⁰

Hormonal treatment with growth hormone (in childhood), sex (oestrogen and/or progesterone), and thyroid hormones needs to be discussed in a multidisciplinary team with the paediatrician and endocrinologist.^1430–1434

10.1.1.3. Surgery of aortic aneurysms

Aortic aneurysm surgery in TS should be informed, individualized, and consider factors beyond aortic diameter (indexed). These include BAV, coarctation, uncontrolled hypertension (despite more than three classes of antihypertensive drugs), rapid aortic growth (≥3 mm per year) and planned pregnancy.

Recommendation Table 58

Recommendations for aortic surgery in women with Turner syndrome

10.1.1.4. Pregnancy and physical exercise

Turner syndrome often involves fertility challenges, but assisted reproductive therapy has increased pregnancy rates. However, pregnancy in TS can elevate the risk of AD, particularly with additional risk factors (Figure 40). Recent studies suggest improved pregnancy outcomes due to better guideline adherence.^1435,1436 Prophylactic aortic root surgery in women with TS contemplating pregnancy is recommended when the ASI reaches 25 mm/m².¹³³⁷ These decisions should be made by an expert team in a shared-decision process.

Physical exercise has a beneficial impact on CVD risk and HRQoL in TS.¹⁴³⁷ Structural congenital heart defects and aortic diameters (ASI, AHI and z-score) (Figure 40) need to be considered in the recommendations on the level of sports practice.¹⁴¹⁸

10.1.2. Vascular Ehlers–Danlos syndrome

10.1.2.1. Diagnosis, clinical presentation, and natural history

Vascular Ehlers–Danlos syndrome is a rare (prevalence of 1/50 000 to 1/200 000) autosomal dominant disease caused by pathogenic variants in the COL3A1 gene, which encodes the pro-alpha1 chains of type III procollagen. The most common COL3A1 variants provoke a disruption in the assembly of type III collagen fibrils, causing an important loss of mechanical strength of arteries and other hollow organs, especially the bowel and uterus.¹⁴³⁸ Identification of a causal COL3A1 variant is a requirement for the diagnosis of vEDS.¹⁴³⁹

vEDS is the most severe form of Ehlers–Danlos syndrome because of its clinical life-threatening vascular complications, making early identification and a thorough family inquiry particularly crucial.

Clinical complications may start during adolescence and repeat at unpredictable time intervals. The most common complications involve medium-sized arteries: dissections, aneurysms, arterial ruptures, and arteriovenous fistulas. AD (both type A and B) occurs in up to 10% of patients.¹⁴⁴⁰

Prognosis depends on the type of COL3A1 variant, with null variants (no gene product or absence of function) showing a better outcome.¹⁴⁴¹ The rate of recurrence of organic complications in patients with vEDS is 1.6 events per 5 year period. Life expectancy is reduced to an average of 51 years.¹⁴⁴²

10.1.2.2. Surveillance and imaging

Management of vEDS is complex and requires a multidisciplinary approach. Recommendations include: lifestyle modification to minimize injury and risk of vessel/organ rupture, identification of a care team, individualized emergency care plans, maintaining BP in the normal range, aggressive hypertension treatment, and annual surveillance of the vascular tree by DUS, CCT (low radiation alternatives), or CMR (if feasible).¹⁴³⁹ A recent survey among European expert centres indicated that arterial monitoring is standard clinical practice and that frequency of follow-up should be adapted individually.¹⁴⁴³ The prognosis improves when patients are properly managed.¹⁴⁴¹

10.1.2.3. Medical treatment

Medical management is based on optimal BP control. Celiprolol, a BB with vasodilatory properties, has been shown to reduce vascular morbidity in two retrospective studies^1441,1444 and one randomized, open-label trial.¹⁴⁴⁵ There is no consensus about the age at which to start treatment, but starting after 10 years of age is considered reasonable by many experts.

Recommendation Table 59

Recommendations for medical treatment in patients with vascular Ehlers–Danlos syndrome (see also Evidence Table 13)

10.1.2.4. Surgical treatment

Acute, unexplained pain requires urgent imaging to exclude arterial rupture. Acute arterial complications usually require hospitalization and a conservative approach in most cases. Interventional vascular or intestinal procedures are limited to vital risk. Procedures requiring organ inflation should be avoided or performed with extreme caution. There are no clear recommendations regarding aortic/arterial diameters at which to intervene in patients with vEDS. Thus, decisions need to be made on a case-by-case basis.

10.1.2.5. Pregnancy

Pregnancy in vEDS incurs a risk of (fatal) arterial and uterine complications. Pregnancy does not appear to affect overall mortality compared with nulliparous vEDS women.¹⁴⁴⁶ However, patients need to be engaged in a shared-decision process, informed by vascular status and underlying variant type.

10.1.3. Marfan syndrome

10.1.3.1. Diagnosis, clinical presentation, and natural history

Marfan syndrome, the most common syndromic HTAD condition (prevalence of 1/5000–1/10 000), arises from pathogenic fibrillin-1 gene (FBN1) variants. Beyond the CV system, multiple organ systems are often affected, including the eyes and skeleton. Diagnosis relies on recognizing clinical features in line with the revised Ghent nosology, which includes genetic testing.¹⁴⁴⁷

Aortic aneurysm and dissection involving the aortic root are a hallmark of the disease. Less commonly, the descending thoracic and abdominal aorta may be involved. With increasing survival and age in MFS, the prevalence of TBAD seems to be increasing, exceeding type A dissection rates in recent reports.^1448,1449 TBAD will often occur at diameters below surgical thresholds. Previous aortic root replacement, mitral valve surgery, and a longer life span are associated with TBAD. Additional CV features include mitral valve prolapse, extra-aortic arterial involvement, myocardial dysfunction, and arrhythmias.^{1393,1450–1452} Thanks to improved diagnosis in earlier stages, proper management including surveillance, medical treatment, and timely prophylactic aortic surgery, life expectancy in MFS patients is now approaching that of the general population.^1416,1453

The major determinant of TAAD is the aortic root diameter, with increased risk of rupture when it exceeds 50 mm.¹⁴⁵⁴ Other risk factors include family history of AAS at low diameter, aortic root growth rate (annualized growth rate ≥3 mm or more in adults), pregnancy, and hypertension (hypertension persisting notwithstanding three or more antihypertensive medications prescribed by a physician with experience in hypertension treatment). Increasing evidence for variant-based differences in aortic risk is emerging and may be considered.^1413,1416

10.1.3.2. Imaging surveillance

Transthoracic echocardiography is the appropriate imaging modality for initial evaluation and follow-up of the aortic root in most patients and allows evaluation of the distal segments of the aorta in many. Also, TTE is useful for assessing mitral and aortic valve regurgitation, mitral valve prolapse with/out annular disjunction, and LV dysfunction. In some cases (especially when pectus abnormalities are present) TTE windows may be suboptimal, and CMR (preferably)/CCT may be preferred. Periodical evaluation of the global aorta and peripheral arteries with CMR/CCT and DUS (every 3–5 years based on the patient’s evolution) is indicated since they also present a higher incidence of peripheral aneurysms,¹⁴⁵⁵ which are associated with more aggressive forms of the disease.¹³⁹³ CMR is preferred over CCT to avoid radiation exposure; however, its use should be adapted to local availability/expertise. Additionally, CMR allows evaluation of biomechanical and haemodynamic parameters that can be useful in risk stratification.^{181,1456,1457} Given its superior spatial resolution, CCT may be recommended for pre-operative planning and in cases of measurement inconsistency. Imaging of intracerebral vessels is indicated in cases of symptoms and/or clinical manifestations of aneurysms/rupture. Recommendations for imaging surveillance are illustrated in Figure 41 and should be adjusted to the individual patient, taking the history and presence of abnormalities during preceding studies into account.

Figure 41

Algorithm for imaging surveillance in patients with syndromic and non-syndromic heritable thoracic aortic disease.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic resonance; DUS, duplex ultrasound; HTAD, heritable thoracic aortic disease; SMC, smoth muscle cell; TTE, transthoracic echocardiography. ^aPre-surgical CCT. ^bSee respective tables of recommendations for aortic surgery in Marfan (Table 62) and Loeys-Dietz syndrome (Table 66).

Recommendation Table 60

Recommendations for vascular imaging in Marfan syndrome

10.1.3.3. Medical treatment

Medical treatment is described in Recommendation Table 61. Some caution may be warranted with the use of CCBs: these have shown an increased aortic risk in a mouse model and in retrospective case control studies,¹⁴⁶⁰ and alternatives are preferred for hypertension treatment.

Recommendation Table 61

Recommendations for medical treatment in Marfan syndrome (see also Evidence Table 14)

10.1.3.4. Aortic surgery

Open surgery is preferred over endovascular procedures in patients with MFS. Endovascular procedures may be considered in selected cases in emergency settings and/or in centres with a high level of expertise.¹⁴⁶⁵ The thresholds for aortic root surgery need to take additional risk factors, as well as the expertise of the team, into account.¹⁴⁶⁶

Recommendation Table 62

Recommendations for aortic surgery in Marfan syndrome

10.1.3.5. Pregnancy and physical exercise

In pregnant MFS women, the risk of AD increases up to eight times relative to the general population.¹⁴⁷⁰ The risk for TAAD is determined by the aortic diameter, but type B dissections tend to occur even more commonly and may occur without prior dilatation.^1470,1471 Patients should be aware of the persisting risk of TBAD after aortic root replacement.¹⁴⁷¹ Women unaware of the diagnosis are at the highest risk of dissection.^1470–1472

The Registry Of Pregnancy And Cardiac disease (ROPAC) indicates that women managed according to guidelines are at low risk of pregnancy-related complications and major effects of BBs on foetal growth were not shown, although this needs to be carefully monitored.^{70,1337,1435,1471,1472}

Recommendation Table 63

Recommendations for pregnancy in women with Marfan syndrome

Exercise is potentially associated with an increased risk of aortic dilatation and AAD. It is recommended to individualize physical activity in MFS based on aortic diameter, family history of dissection or sudden death, and pre-existing fitness status.⁷¹ Although competitive sports are contraindicated, moderate aerobic exercise is recommended with a level of intensity based on aortic diameters.⁷¹

Two studies^1481,1482 showed that mild-moderate dynamic exercise improved aortic wall structure and function and reduced aortic growth rate in MFS mouse models. Recent data in MFS children and young adults indicate that adhering to daily physical exercise (10 000 steps a day) had a beneficial effect on aortic root growth.¹⁴⁸³ Although a limited number of clinical studies have evaluated physical activity rehabilitation programmes, two studies^1484,1485 evidenced that physical activity, up to a moderate specific intensity, may be recommended. Thus, although physical activity poses a dilemma, individualized adapted programmes are most likely successful in encouraging exercise in MFS.

Recommendation Table 64

Recommendations for physical exercise in patients with Marfan syndrome

10.1.4. Other syndromic and non-syndromic heritable thoracic aortic diseases and/or arterial disorders

Main clinical and genetic data of known syndromic and non-syndromic HTAD entities are summarized in the Supplementary data online, Table S5. The two most prevalent diseases for each entity include Loeys–Dietz syndrome and ACTA2-related HTAD, respectively. Given the rarity of these entities, specific recommendations regarding surveillance and treatment are lacking and largely adopted from the recommendations for MFS. Some disease-specific recommendations are mentioned below.

10.1.4.1. Loeys–Dietz syndrome

Diagnosis, clinical presentation, and natural evolution

The spectrum of clinical presentations in Loeys–Dietz syndrome is very wide. Some patients fulfil criteria for MFS,¹⁴⁴⁷ while some features such as bifid uvula and hypertelorism are very specific to the disease. Clinical manifestations are listed in the Supplementary data online, Table S5. There is a tendency for AD and rupture at lower vessel dimensions than is typically seen in other similar conditions.^1390,1487 Pathogenic variants in six genes (TGFBR1 and TGFBR2, TGFB2 and TGFB3, SMAD2 and SMAD3), all encoding components of the TGF-ß signalling pathway, cause Loeys–Dietz syndrome. Differences in clinical manifestations and aortic outcome according to the underlying gene and the extent of extra-aortic features have been reported and need to be considered in surveillance and defining thresholds for surgery.^{1388,1390,1391}

Surveillance in Loeys–Dietz syndrome is described in Recommendation Table 65 and Figure 41. Although the indication for surgery must be considered according to the underlying genetic defect and the presence of risk factors (Recommendation Table 66 and Figure 42), a 45 mm aortic diameter threshold should be considered (≥40 mm in cases of associated high-risk features).

Figure 42

Suggested thresholds for prophylactic aortic root/ascending replacement in Loeys–Dietz syndrome.

From a¹³⁸⁸, b¹³⁹¹, c¹⁴⁹², d¹⁴⁹¹, e¹⁴⁹⁰, f¹⁴⁸⁹, g¹⁴⁹³, h¹⁴⁹⁴, i¹⁴⁹⁵.

Recommendation Table 65

Recommendations for imaging follow-up in Loeys–Dietz syndrome

Recommendation Table 66

Recommendations for aortic root surgery in Loeys–Dietz syndrome

10.1.4.2. ACTA2-related heritable thoracic aortic disease

Pathogenic variants in the ACTA2 gene, encoding for smooth muscle-specific alpha-actin (a critical component of the vascular smooth muscle cell contractile apparatus), lead to aortic aneurysms and dissections in non-syndromic patients.¹⁴⁹⁶ Patients primarily present with type A or B aortic dissection, and with aneurysms that involve the root and/or ascending aorta. A subset of pathogenic variants predisposes to occlusive vascular diseases.¹⁴⁹⁷ Surveillance is summarized in Recommendation Table 67 and Figure 41. TAAD may occur at aortic diameters <45 mm, and consideration of surgery at diameters <45 mm should be informed by the presence of additional clinical and genetic risk factors.¹⁴¹⁰ Genetic and imaging cascade screening of first-degree family members is an essential element of care, as treatable disease may otherwise be missed in family members—with fatal consequences.

Recommendation Table 67

Recommendations for imaging and surgery in ACTA2-related heritable thoracic aortic disease (see also Evidence Table 11)

10.2. Aortic disease associated with bicuspid aortic valves

Bicuspid aortic valves, the most common congenital heart defect (0.5%–2% of live births), besides being a risk factor for aortic valve disease, is associated with a peculiar form of aortopathy, characterized by morphological and clinical heterogeneity (bicuspid valvulo-aortopathy). Its inheritance is high, with autosomal dominant transmission of BAV in a minority of cases, but no single-gene model clearly explaining BAV inheritance.^1500–1502 Several genes, generally implicated in embryogenesis and cell differentiation, have been associated with BAV/BAV-related aortopathy, but each of them explained <5% of cases.^1503–1507 Therefore, genetic testing is not indicated for isolated BAV disease, but reserved for patients with syndromic features, family history of aortic disease, or aneurysms/dissections of medium-sized arteries other than the thoracic aorta, and may be considered in patients with the root phenotype.^{1389,1508,1509}

We recommend adopting a new international consensus nomenclature and classification, established by a panel of experts, to replace the previous various concurrent nomenclatures used¹⁵¹⁰ (Figure 43). Aneurysm prevalence reaches 40% in clinical series and 0.85 per 100 patient-years in population studies. AAEs are rare, but 8- to 10-fold more frequent than in the general population.^1001,1511 The longest available follow-up of BAV subjects was recently reported,¹⁵¹² showing a total lifetime morbidity burden as high as 86%, a predominant part of which was driven by valve-related complications (aortic stenosis, endocarditis, HF).

Figure 43

Bicuspid aortic valve, valvulo-aortopathy nomenclature.

Modified from Michelena et al.¹⁵¹⁰ A, anterior; BAV, bicuspid aortic valve; L, lateral; P, posterior. Although preferential associations exist, each of the three valve types—‘fused BAV’, ‘2-sinus BAV’, and ‘partial-fusion BAV’—can be variably associated with dilatation predominantly located at the sinuses of Valsalva (‘root phenotype’, 15%–20%) or at the tubular (supra-coronary) tract (‘ascending phenotype’, 70%–75%). A minor proportion of patients present with equal dilatation of the sinusal and tubular segments or ascending dilatation extending into the proximal arch (‘extended phenotype’, 5%–10%).

When a BAV is first detected, a complete study of the thoracic aorta is necessary; vice versa, in every patient with ascending aortic dilatation, valve morphology should be ascertained.^70,969 When TTE detects BAV-associated aortic dilatation, CCT or CMR is recommended to confirm measurements, exclude coarctation, and record baseline diameters at different levels for subsequent periodic assessments.^137,1001 Surveillance by TTE becomes necessary when the maximum diameter exceeds 40 mm. In mixed tricuspid aortic valve (TAV) and BAV series, AAEs occurred in 2/10 000 patient-years with a diameter >40 mm (vs. 0.1–0.3/10 000 patient-years in the general population)⁸⁹⁴ (Figure 43). Considering average aortic diameter growth of 0.2–0.6 mm per year,^893,1513 once fast progression is excluded, follow-up can be scheduled every 2–3 years (according to risk profile). In 5%–15% of cases, BAV patients have at least one FDR with either BAV or ascending aortic dilatation; root phenotype and aortic regurgitation in the proband predict ascending dilatation in FDRs.¹⁵¹⁴ FDR screening is considered cost-effective, but the age at which relatives should undergo TTE remains to be determined.^1515,1516

A diameter exceeding 55 mm at any level mandates surgery.^70,969,1001 However, the historically known relation between diameter and acute complications has been recently reappraised. Both in large mixed¹⁵³ and purely BAV series,⁹⁸¹ an ascending diameter of about 52 mm already marked an AAE risk increase from ∼1% to 4%–5%. Additionally, early post-operative mortality for elective surgery of the proximal aorta ranges today between 0.25% and 2%.^980,981 Therefore, aortic surgery in low surgical risk (<3%) patients with an ascending diameter >52 mm implies a lower risk than observed in the natural history of the disease. For aortic root dilatation in BAV patients, the ‘hinge point’ was at 50 mm;⁹⁸¹ this phenotype is associated with faster growth rate,⁸⁹³ higher risk of events following isolated aortic valve replacement,¹⁵¹⁷ worse survival if not operated,¹⁵¹⁸ and higher risk of acute TAAD.^976,1519

Surgery should be considered when the diameter is ≥50 mm in selected ascending phenotype patients (Figures 23, 24 and 43).^70,1001 Among those factors, family history of AAEs, poorly controlled hypertension, aortic coarctation, and rapid (≥3 mm per year) diameter growth should be noted. Surgery at >50 mm may also be considered in a shared decision with the patient, taking lifestyle and psychological factors into consideration,^70,1001 since 50 mm should correspond to an approximately 10-fold increase in the risk of AAEs.⁸⁹⁴ In a study of patients with aortic diameter ≥40 mm, those with diameters of 50 mm faced a 1% risk of AAEs within 5 years, compared with 0.1% for those with 40 mm diameters, explaining the 10-fold difference; however, this study did not exclusively involve BAV patients.⁸⁹⁴ Another recent study¹⁵²⁰ specifically focused on BAV patients found a 0.4% incidence of AAEs per patient-year for diameters above 50 mm, in contrast to the general BAV population’s 0.03% incidence.¹⁵²¹ Previous guidelines also suggested aortic repair for a cross-sectional area-to-height ratio (CSA/h) >10 cm²/m;⁷⁰ nevertheless, more recently, it has been suggested that the CSA/h threshold for the ascending tract in BAV should be 13 cm²/m.⁹⁸¹ For the average height of male and female Europeans (1.8 m and 1.67 m, respectively), a CSA/h of 10 cm²/m would correspond to a diameter of 48 mm or 46 mm, respectively, whereas 13 cm²/m means 54 mm or 53 mm. It is reasonable to refer to the 13 cm²/m CSA/h cut-off for ascending aortic repair, especially in individuals ≤1.69 m in height (since 13 cm²/m corresponds to ≤52 mm diameter). Recently, besides dilatation, aortic elongation is also considered a risk factor,⁹⁷⁴ and a curvilinear length >11.5 cm at the vessel’s centreline increases the yearly risk of AAEs.¹⁵⁵ Age is another factor to consider: at 50 years, a 40 mm ascending aorta corresponds to the upper normal limit for patients with large body size,¹⁴⁹ and therefore the same diameter at a higher age could imply a lower risk of AAEs.

Recommendation Table 68

Recommendations for bicuspid aortic valve-associated aortopathy management

10.3. Coarctation of the aorta and aortic arch variants

10.3.1. Coarctation of the aorta

This topic is extensively discussed in the ESC 2020 Guidelines for the management of adult congenital heart disease.¹⁴⁶⁸ Coarctation of the aorta (CoA) manifests as a discrete stenosis or a hypoplastic segment typically located at the insertion of the ductus arteriosus. More distal locations are known as mid-aortic syndrome and require dedicated management.¹⁵²⁴ Associated lesions include BAV (up to 50%–85%), intracerebral aneurysms (10%), and ascending aortic aneurysms.^1525,1526 CoA may be associated with syndromes such as TS. Research indicates that up to 12.6% of females diagnosed with CoA also have TS, and coarctation is observed in 7%–18% of patients with TS.^{1417,1468,1527}

10.3.1.1. Diagnostic work-up

Mild cases of CoA may only become evident in adulthood. Symptoms reflect pre-stenotic hypertension (e.g. headache, nosebleeds) and post-stenotic hypoperfusion (e.g. abdominal angina and claudication). The natural course is largely driven by hypertension-related complications, including HF, intracranial haemorrhage, premature coronary/cerebral artery disease, and aortic rupture/dissection.¹⁵²⁸ Presently, there is no evidence supporting screening for intracerebral aneurysms in asymptomatic patients.

A systolic non-invasive gradient between upper and lower extremities, an abnormal ABI, or an invasive peak-to-peak gradient ≥20 mmHg indicates significant CoA. In the presence of collaterals or decreased LV function, gradients or ABI may underestimate severity. A diastolic tail in the DTA or abdominal diastolic antegrade flow by TTE is suggestive of significant narrowing. Criteria to consider significant CoA are listed in Figure 44. TTE is also useful to detect LV hypertrophy, which is a marker of disease. CMR and CCT are the preferred imaging techniques, depicting the narrowing as well as the surrounding anatomy, necessary for interventional decision-making.

Figure 44

Criteria for significant coarctation/re-coarctation of the aorta and management algorithm.

BP, blood pressure; CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic resonance; CoA, coarctation of the aorta; DUS, duplex ultrasound; HTN, hypertension; TTE, transthoracic echocardiography. ^aDiagnosis of hypertension may require confirmation with ambulatory BP measurement and should also be considered in cases of exercise-induced hypertension and/or left ventricular hypertrophy on TTE.

10.3.1.2. Treatment and follow-up

In native CoA and re-coarctation (Figure 44) covered stenting is the first-choice treatment. Interposition of a tube graft is the preferred surgical therapy if stenting is less suitable.¹⁵²⁹ Hypertension remains an important complication, even after successful treatment, and is more common when the initial repair is performed in adulthood.¹⁵²⁸ Right arm 24 h ambulatory BP measurement or exercise tests better detect hypertension.^1530,1531

All CoA patients require lifelong follow-up.¹⁵³² Imaging of the aorta with CMR/CCT every 3–5 years, adjusted to previous imaging findings and type of intervention, is required to document post-repair or post-interventional complications (such as re-coarctation). Patch repairs are at particular risk of repair-site para-anastomotic aneurysms or pseudo-aneurysms, the latter possibly occurring following interposition grafts as well.¹⁵³³

Recommendation Table 69

Recommendations for evaluation and medical treatment of patients with coarctation of the aorta

10.3.2. Aortic arch anatomic variants

A type I arch, where the three great vessels directly arise from the aorta, is the most common form, occurring in about 70% of the population. The type II (bovine) arch is the most frequent variant: type II-A (9% of the population) has the left common carotid artery arising from the innominate artery, and type II-B (13% of the population) has both the innominate and left common carotid arteries originating from a common point on the aortic arch.^1538,1539 Limited data suggest that a bovine arch is associated with a higher risk of aortic dilation and aortic events/complications.^1540,1541 These variations are important to report as they can impact specific medical procedures and diagnostic interpretations.

10.3.3. Aberrant subclavian artery and Kommerell’s diverticulum

The most common variant is the aberrant right subclavian artery, where the right subclavian artery arises as the last branch of the aortic arch, usually after the left subclavian artery, and often passes behind the oesophagus through the mediastinum, potentially causing dysphagia lusoria, respiratory symptoms, or recurrent laryngeal nerve palsy. The less common variant, the aberrant left subclavian artery, is typically associated with congenital heart defects, such as a right aortic arch. However, in adulthood, both variations are often incidental findings.¹⁵⁴²

Kommerell’s diverticulum is a remnant of the fourth dorsal aortic arch due to incomplete regression, found in 20%–60% of those with an aberrant subclavian artery.¹⁵⁴³ Surgical intervention is advised for a diverticulum orifice >30 mm or combined diverticulum and adjacent descending aorta diameter >50 mm, or both.¹⁵⁴⁴ Successful repair has been described using open, endovascular, or hybrid approaches depending on anatomy, comorbidities, and expertise.¹⁵⁴³

11. Polyvascular peripheral arterial disease and peripheral arterial disease in patients with cardiac diseases

11.1. Polyvascular disease

Polyvascular disease is defined as the simultaneous presence of clinically relevant obstructive atherosclerotic lesions in at least two major arterial territories.

11.1.1. Epidemiology and prognosis

Approximately 1 in 4–6 patients with atherosclerosis have PVD (Figure 45).^620,1545 According to the REACH registry, patients with PAD were most likely both to have PVD at baseline and to develop PVD over the observational period.^1546,1547

Figure 45

Reported rate ranges of other localizations of atherosclerosis in patients with a specific arterial disease.

The graph reports the rates of concomitant arterial diseases in patients presenting an arterial disease in one territory (e.g. in patients with CAD, 5%–9% of cases have concomitant carotid stenosis >70%). Adapted from 2017 ESC Guidelines on PAD.^{77,493,784,1549,1551–1556} ABI, ankle–brachial index; CAD, coronary artery disease; PAD, peripheral arterial disease; RAS, renal artery stenosis.

PVD independently increases major CV event risk, roughly doubling it compared with single arterial bed symptoms.^1547–1549 Event rates rise with the number of affected arterial beds.^1546,1550

11.1.2. Screening for atherosclerosis in other arterial territories

Screening for PVD in atherosclerotic patients relies on medical history, clinical exam, and ABI measurement. If suspected, start with non-invasive DUS, followed by CTA/MRA if needed.¹⁵⁵⁷ Assessing concurrent atherosclerosis in other vascular regions is detailed in Table 17.

Table 17

Need for assessment of associated atherosclerotic disease in additional vascular territories in symptomatic patients with coronary artery disease, peripheral arterial disease, or carotid stenosis

	Leading disease
Assessment in other vascular territories	CAD	PAD	Carotid stenosis
CAD		May be helpful to optimize medical treatment⁴³¹ and to be considered in patients scheduled for open vascular surgery with poor functional capacity or significant risk factors or symptoms. ¹⁰⁸⁰	Consider in patients scheduled for carotid endarterectomy and suspected CAD.¹⁵⁵⁸
PAD	Potential benefits in identifying high-risk patients and guiding treatment decisions.^{429,1559–1561}
Carotid stenosis	Useful in patients undergoing elective CABG.^1555,1562

	Leading disease
Assessment in other vascular territories	CAD	PAD	Carotid stenosis
CAD		May be helpful to optimize medical treatment⁴³¹ and to be considered in patients scheduled for open vascular surgery with poor functional capacity or significant risk factors or symptoms. ¹⁰⁸⁰	Consider in patients scheduled for carotid endarterectomy and suspected CAD.¹⁵⁵⁸
PAD	Potential benefits in identifying high-risk patients and guiding treatment decisions.^{429,1559–1561}
Carotid stenosis	Useful in patients undergoing elective CABG.^1555,1562

CABG, coronary artery bypass grafting; CAD, coronary artery disease; PAD, peripheral arterial disease.

Table 17

Need for assessment of associated atherosclerotic disease in additional vascular territories in symptomatic patients with coronary artery disease, peripheral arterial disease, or carotid stenosis

	Leading disease
Assessment in other vascular territories	CAD	PAD	Carotid stenosis
CAD		May be helpful to optimize medical treatment⁴³¹ and to be considered in patients scheduled for open vascular surgery with poor functional capacity or significant risk factors or symptoms. ¹⁰⁸⁰	Consider in patients scheduled for carotid endarterectomy and suspected CAD.¹⁵⁵⁸
PAD	Potential benefits in identifying high-risk patients and guiding treatment decisions.^{429,1559–1561}
Carotid stenosis	Useful in patients undergoing elective CABG.^1555,1562

	Leading disease
Assessment in other vascular territories	CAD	PAD	Carotid stenosis
CAD		May be helpful to optimize medical treatment⁴³¹ and to be considered in patients scheduled for open vascular surgery with poor functional capacity or significant risk factors or symptoms. ¹⁰⁸⁰	Consider in patients scheduled for carotid endarterectomy and suspected CAD.¹⁵⁵⁸
PAD	Potential benefits in identifying high-risk patients and guiding treatment decisions.^{429,1559–1561}
Carotid stenosis	Useful in patients undergoing elective CABG.^1555,1562

CABG, coronary artery bypass grafting; CAD, coronary artery disease; PAD, peripheral arterial disease.

11.1.2.1. Screening for coronary artery disease in patients with symptomatic peripheral arterial disease

The morbidity and mortality of patients with PAD is high due to CV complications. Given high CAD event rates in patients with PAD, CAD screening may be helpful to optimize medical treatment and is not intended to increase the rate of coronary interventions.⁴³¹ Evaluation can be performed by stress testing or CCT; however, there is no evidence that systematic screening for CAD in stable PAD improves outcomes. Coronary angiography is less suitable due to invasiveness. In patients requiring lower-limb revascularization, CAD management should be based on the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.¹⁰⁸⁰

11.1.2.2. Screening for peripheral arterial disease in patients with coronary artery disease

In high-risk CAD patients with three-vessel disease or recent ACS, systematic screening for multisite atherosclerotic disease through ABI and DUS of carotids, lower-extremity, and renal arteries did not improve outcomes.¹⁵⁶³ However, a subgroup analysis of the COMPASS trial suggests potential benefits when adding vascular-dose rivaroxaban to aspirin in stable patients with CAD and PAD, raising the question of whether identifying PAD in stable CAD patients could be advantageous.^429,1559 In patients undergoing CABG, the presence of concomitant PAD is associated with a three-fold risk of subsequent CV events after CABG.^1560,1561 The GSV should be spared whenever possible, since the success of peripheral arterial revascularization in complex lesions is strongly associated with the availability of sufficient autologous venous segments.^567,1564

11.1.2.3. Screening for coronary artery disease in patients with carotid stenosis

Due to the high prevalence of CAD among patients scheduled for elective CEA,^1565,1566 pre-operative CAD screening, including coronary angiography, may be considered in suspected patients.¹⁵⁵⁸ CAD requires prioritization of revascularization according to the patient’s clinical status and the severity of carotid disease and CAD. Coronary revascularization should generally be performed first; the exception is recently symptomatic patients with unstable neurological symptoms in whom carotid revascularization should be prioritized.⁶⁸⁰

11.1.2.4. Screening for carotid stenosis in patients with coronary artery disease

Carotid artery stenosis screening may be useful in patients undergoing elective CABG. Ischaemic stroke after CABG is multifactorial,¹⁵⁶⁷ but also depends on the degree of carotid disease.¹⁵⁵⁶ Two studies suggest that limiting DUS to patients with at least one risk factor (age >65 years, history of cerebrovascular disease, presence of a carotid bruit, multivessel CAD or PAD) identifies most patients with significant (≥70%) CS.^1555,1562 Nevertheless, addition of CEA to CABG is unlikely to provide significant stroke reduction. In a study in patients with CAD with >80% CS undergoing staged or synchronous carotid procedures (two-thirds were neurologically asymptomatic and 73% had unilateral asymptomatic carotid stenosis), in-hospital stroke rates and 30 day mortality were similar in patients treated with CABG + CEA and in those treated with isolated CABG.¹⁵⁶⁸ Another study suggests that selective use of DUS should be considered before CABG in patients with a history of neurological events or PAD.¹⁵⁶⁹

11.1.3. Management of patients with polyvascular disease

Polyvascular disease requires proactive management of all modifiable risk factors through lifestyle changes and drug therapy. Scientific evidence suggests the benefit of intensified antithrombotic therapy, with no increase in risk of bleeding.¹⁵⁷⁰ ILT offers comparable benefits for PVD patients and those with single arterial territory disease. However, the benefits of ILT in patients with PVD are not dependent on baseline LDL-C.¹⁵⁷¹

Revascularization should be reserved for symptomatic arterial territories, using the least invasive strategy in a multidisciplinary vascular team approach.

11.2. Peripheral arterial disease and heart failure

Left ventricular (LV) dysfunction is observed in 20%–30% of PAD patients,^1572,1573 mostly associated with CAD.¹⁵⁷⁴ High aortic stiffness can increase LV afterload and impair coronary blood flow, resulting in hypertension, LV hypertrophy, LV diastolic dysfunction, and HF.^1575,1576 Skeletal muscle involvement and deconditioning due to PAD may aggravate HF severity.^1577,1578

Peripheral arterial disease and HF are independently associated with poor outcomes and those with concomitant HF have a 30% higher risk of MACE and 40% higher risk of all-cause mortality.¹⁵⁷⁴ Evaluation of LV function in patients with PAD may be useful for better CV risk stratification and comprehensive management of their CV disease.¹⁵⁷⁹ This is of particular importance when an intermediate- or high-risk vascular intervention is planned. Expectedly, the presence of PAD in patients with HF is also associated with poor outcomes.^1580–1584 These patients represent a high-risk group in which intense risk-factor modification strategies and optimization of HF therapy are warranted.

11.3. Peripheral arterial disease and AF

The prevalence of AF among patients with PAD is around 12%.^1585–1590 A meta-analysis revealed that in patients with AF and PAD, risk of all-cause mortality, CV mortality, and MACE is 40%, over 60%, and over 70% higher, respectively compared with patients with AF without PAD.¹⁵⁹¹ PAD is included in the CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥75 [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74 and sex category [female]) risk score, which underlies the prognostic importance of PAD in patients with AF.¹⁵⁹²

11.4. Peripheral arterial disease and aortic stenosis

Peripheral arterial disease frequently accompanies symptomatic aortic stenosis, especially among patients not eligible for surgical aortic valve replacement (20%–30%).^{198,1593–1595} In these patients, pre-procedural CCT/CTA or CMR¹⁵⁹⁶ of the aorta and major peripheral arteries is mandatory to evaluate the access site for transcatheter aortic valve implantation (TAVI) and plan a closure strategy for the access site. Patients with PAD have increased risk of all-cause mortality and vascular complications after TAVI,¹⁹⁸ thus, screening for PAD in these patients may be helpful.

Recommendation Table 70

Recommendations for screening and management of polyvascular disease and peripheral arterial disease with cardiac diseases (see also Evidence Table 15)

12. Key messages

Peripheral arterial and aortic diseases are highly prevalent, often asymptomatic, and linked to increased morbidity and mortality. Early diagnosis is crucial for better outcomes and management requires a multidisciplinary team. CVRF control is crucial to prevent progression and complications. Despite the benefit of medical therapy, lifestyle changes, healthy diet, abstinence from smoking, exercise/rehabilitation, and education are essential for effective management. Patient empowerment is essential to improve adherence and close/regular monitoring is essential to improve prognosis. Use of web- or app-based calculators for estimation of CV risk in the secondary prevention of ASCVD may aid patient motivation for lifestyle changes and adherence to medication.

Peripheral arteries

Atherosclerotic lower-extremity PAD is a chronic disease needing lifelong follow-up.

Assessment of walking impairment, functional status, and amputation risk is crucial in PAD management.

Ankle–brachial index should be the initial diagnostic test for screening and diagnosing PAD, and serves as a surrogate marker for CV and all-cause mortality. DUS is the first-line imaging method to confirm PAD lesions.

Supervised exercise training or, if not available, HBET, improves walking and functional performances, and reduces CV risk. Exercise training remains underused and increased awareness is warranted.

In asymptomatic PAD patient revascularization is not recommended. In symptomatic PAD patient need for interventional treatment, following a period of optimal medical treatment and exercise, should be discussed in a multidisciplinary setting.

Chronic limb-threatening ischaemia increases the risk of CV events, needs early diagnosis, rapid referral to a multidisciplinary vascular team, and revascularization for limb salvage.

Acute limb ischaemia warrants rapid clinical assessment by a vascular team and urgent revascularization.

Duplex ultrasound is the first-line diagnostic modality for carotid stenosis. Routine revascularization is not recommended if asymptomatic. In symptomatic patients multidisciplinary assessment is recommended.

Atherosclerotic UEAD is most frequently located in the subclavian artery and may be suspected because of an absolute inter-arm SBP difference >10–15 mmHg. DUS is first-line imaging and routine revascularization is not recommended.

The key to early diagnosis of acute and chronic mesenteric ischaemia is a high level of clinical suspicion—laboratory tests are unreliable for the diagnosis. Acute SMA occlusion requires immediate revascularization.

Aorta

Aortic aneurysms are managed based on size, location, and growth rate. Small aneurysms are monitored regularly (Guidelines provide disease-specific follow-up algorithms), while larger ones may require surgical/endovascular repair to prevent rupture.

In aortic root aneurysms, aortic replacement may be considered at >52 mm in low-risk patients and at experienced centres.

Aortic diameter is the primary risk factor for aortic events. However, evidence supports diameter indexation (especially in extreme BSA populations) and the use of aortic length (>11 cm), the AHI (>32.1 mm/m), growth rate (≥3 mm per year for ascending aorta and arch or >5 mm per 6 months in the thoracoabdominall aorta), and age/sex for risk assessment.

Multidisciplinary collaboration, hybrid operating rooms, and advanced stent technology have increased the adoption of hybrid approaches and endovascular therapies for different thoracoabdominal aortic diseases.

Acute aortic syndrome management involves medical treatment in critical care units and selective surgical intervention based on location and complications. The main problem in these conditions continues to be a delay in diagnosing patients or transferring them to an aortic centre. Improved diagnostic algorithms and reduced surgical complications have lowered mortality rates. Surgical/endovascular treatment in the subacute phase is advised for high-risk patients with type B aortic syndrome.

Suspected genetic aortic conditions require evaluation at experienced centres to assess both the patient and their FDRs for genetic studies. Genetic aortic conditions should be considered based on family history, syndromic features, age <60 years, and no CVRFs (Guidelines offer a screening algorithm for thoracic aorta disease). A comprehensive evaluation of the entire aorta and other vascular territories is recommended in HTAD. Recent advances in genetics are enabling personalized and patient-centred assessment. This includes using different aortic diameter thresholds to indicate surgery and implementing diverse surveillance algorithms.

13. Gaps in evidence

There are several areas where robust evidence is still lacking and which deserve to be addressed in future clinical research.

Epidemiology and risk factors in PAAD:
- Improve PAAD risk definition.
- Provide contemporary data on PAAD prevalence in Europe.
- Inflammation biomarkers, metabolomics, and proteomics may have prognostic value in PAAD.
Evaluation of peripheral arteries and aorta:
- Follow-up algorithms can assist PAAD patient management but have limitations and evidence on cost-effectiveness is needed.
- The best methodology for aortic measurements remains to be elucidated.
Screening for carotid, peripheral arterial, and aortic diseases:
- Screening in specific populations: research is needed to understand the nuances of screening in particular populations and whether modifications to current guidelines are necessary.
- Patient outcomes and benefits of screening: impact of screening on patient outcome should be assessed.
OMT and PAAD:
- Research needed on QoL and workability.
- Research needed for optimal preventive strategies.
- Exercise therapy and rehabilitation for PAAD should be more accessible and employed.
- Anti-inflammatory therapy should be investigated.
- Antithrombotic therapies in specific risk groups of PAAD and patients undergoing revascularization should be addressed.
Aortic aneurysms:
- Discovering novel individualized risk stratification parameters beyond well-established markers.
- Assessing the safety of fluoroquinolone use in patients with aortic aneurysm.
Acute aortic syndromes:
- Assess the management of pregnancy-related AAS.
- Identify diagnostic biomarkers other than D-dimer.
- Management in uncomplicated TBAD and IMH should be assessed.
Genetic aortic diseases:
- Need to refine risk estimation in AD, particularly in HTAD, especially the risk of type B aortic dissection.
- There is insufficient evidence to support the efficacy of any medication in reducing the risk of AD.
Sex differences in PAAD:
- Investigate sex and age differences.
- Assess the optimal parameter or indexed parameter to guide intervention decisions in women with aortic and PAD diseases.

14. Sex differences

Sex differences have been evaluated and discussed in the specific sections.

15. ‘What to do’ and ‘What not to do’ messages from the guidelines

Table 18 ‘What to do’ and 'What not to do’. ‘What to do and What not to do’ lists all Class I and Class III recommendations from the text.

Table 18

10.1016/j.ahj.2014.05.011

‘What to do’ and ‘What not to do’

16. Evidence tables

Evidence tables are available on the European Heart Journal website.

17. Data availability statement

No new data were generated or analysed in support of this research.

18. Author information

Author/task force Member Affiliations: Gisela Teixido-Tura, Cardiovascular Imaging section and Aortic diseases Unit (VASCERN), Department of Cardiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Vall d′Hebron Institut de Recerca (VHIR), Barcelona, Spain, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Stefano Lanzi, Department of Angiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland; Vinko Boc, Department of Vascular Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia; Eduardo Bossone, Department of Public Health, University of Naples “Federico II”, Naples, Italy, Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy; Marianne Brodmann, Division of Angiology, Medical University Graz, Graz, Austria; Alessandra Bura-Rivière, Vascular Medicine Department, Toulouse University Hospital, Toulouse, France, Faculty of Medicine, University Toulouse 3, Toulouse, France; Julie De Backer, Cardiology and Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Sebastien Deglise, Department of Vascular Surgery, University Hospital Lausanne (CHUV), Lausanne, Switzerland; Alessandro Della Corte, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy, Unit of Cardiac Surgery, Monaldi Hospital, Naples, Italy; Christian Heiss, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, United Kingdom, Vascular Medicine Department, Surrey and Sussex Healthcare NHS Trust, Redhill, United Kingdom; Marta Kałużna-Oleksy, 1st Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland; Donata Kurpas, Division of Research Methodology, Department of Nursing, Faculty of Nursing and Midwifery, Wroclaw Medical University, Poland; Carmel M. McEniery, Medicine, University of Cambridge, Cambridge, United Kingdom; Tristan Mirault, Vascular Medicine Department, Université Paris Cité, Paris, France, Vascular Medicine Department, Assistance Publique Hôpitaux de Paris-APHP, Hôpital Européen Georges-Pompidou, Paris, PARCC U970 team 5 Innate and Adaptative Immunity in Vascular Diseases, INSERM, Paris, France; Agnes A. Pasquet, Department of Cardiovascular Diseases, Cliniques Universitaires Saint Luc, Brussels, Belgium, IREC/CARD, UCLouvain, Brussels, Belgium; Alex Pitcher, The Heart Centre, Oxford University NHS Foundation Trust, Oxford, United Kingdom; Hannah A.I. Schaubroeck, Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium; Oliver Schlager, Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria; Per Anton Sirnes, Cardiology Practice, Kardiokonsult, Son, Norway, Cardiology section, Volvat Medical Centre, Moss, Norway; Muriel G. Sprynger, Cardiology, University Hospital of Liège, Liège, Belgium; Eugenio Stabile, Division of Cardiology, Health Science Department, Università della Basilicata, Potenza, Italy; Françoise Steinbach (France), ESC Patient Forum, Sophia Antipolis, France; Matthias Thielmann, Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Roland R.J. van Kimmenade, Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands; and Maarit Venermo, Department of Vascular Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

19. Appendix

ESC Scientific Document Group

Includes Document Reviewers and ESC National Cardiac Societies.

Document Reviewers:

Alessia Gimelli (CPG Review Co-ordinator) (Italy), Jean-Baptiste Ricco (CPG Review Co-ordinator) (France), Elena Arbelo (Spain), Christian-Alexander Behrendt (Germany), Michael Böhm (Germany), Michael A. Borger (Germany), Margarita Brida (Croatia), Sergio Buccheri (Sweden), Gill Louise Buchanan (United Kingdom), Christina Christersson (Sweden), Gert J. de Borst (Netherlands), Marco De Carlo (Italy), Roman Gottardi (Austria), Lydia Hanna (United Kingdom), Lynne Hinterbuchner (Austria), Borja Ibanez (Spain), Ignatios Ikonomidis (Greece), Stefan James (Sweden), Thomas Kahan (Sweden), Klaus Kallenbach² (Luxemburg), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Juraj Madaric¹ (Slovakia), Blandine Maurel (France), John William McEvoy (Ireland), Gil Meltzer (Israel), Borislava Mihaylova (United Kingdom), Richard Mindham (United Kingdom), Ioana Mozos (Romania), Jens Cosedis Nielsen (Denmark), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Barbara Rantner (Germany), Bianca Rocca (Italy), Xavier Rossello (Spain), Jean Paul Schmid (Switzerland), Daniel Staub (Switzerland), Sabine Steiner (Germany), Isabella Sudano (Switzerland), Martin Teraa (Netherlands), Ilonca Vaartjes (Netherlands), Rafael Vidal-Perez (Spain), Christiaan Vrints (Belgium), and Katja Zeppenfeld (Netherlands).

ESC National Cardiac Societies actively involved in the review process of the 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases:

Algeria: Algerian Society of Cardiology, Mohammed El Amine Bouzid; Armenia: Armenian Cardiologists Association, Arsen A. Tsaturyan; Austria: Austrian Society of Cardiology, Georg Delle Karth; Azerbaijan: Azerbaijan Society of Cardiology, Fuad Samadov; Belgium: Belgian Society of Cardiology, Antoine Bondue; Bosnia and Herzegovina: Association of Cardiologists of Bosnia and Herzegovina, Alden Begić; Bulgaria: Bulgarian Society of Cardiology, Ivo Petrov; Croatia: Croatian Cardiac Society, Majda Vrkic Kirhmajer; Cyprus: Cyprus Society of Cardiology, Georgios P. Georghiou; Czechia: Czech Society of Cardiology, Pavel Procházka; Denmark: Danish Society of Cardiology, Torsten B. Rasmussen; Egypt: Egyptian Society of Cardiology, Yasser A. Sadek; Estonia: Estonian Society of Cardiology, Jaagup Truusalu; Finland: Finnish Cardiac Society, Petri Saari; France: French Society of Cardiology, Guillaume Jondeau; Germany: German Cardiac Society, Christiane Tiefenbacher; Greece: Hellenic Society of Cardiology, Kimon Stamatelopoulos; Hungary: Hungarian Society of Cardiology, Endre Kolossváry; Iceland: Icelandic Society of Cardiology, Elín Hanna Laxdal; Ireland: Irish Cardiac Society, Monica Monaghan; Israel: Israel Heart Society, Jonathan Koslowsky; Italy: Italian Federation of Cardiology, Ciro Indolfi; Kazakhstan: Association of Cardiologists of Kazakhstan, Nursultan Kospanov; Kosovo (Republic of): Kosovo Society of Cardiology, Pranvera Ibrahimi; Kyrgyzstan: Kyrgyz Society of Cardiology, Olga Lunegova; Latvia: Latvian Society of Cardiology, Ainars Rudzitis; Lithuania: Lithuanian Society of Cardiology, Andrius Berūkštis; Luxembourg: Luxembourg Society of Cardiology, Katja Lottermoser; Malta: Maltese Cardiac Society, Maryanne Caruana; Morocco: Moroccan Society of Cardiology, Raissuni Zainab; North Macedonia: National Society of Cardiology of North Macedonia, Marijan Bosevski; Norway: Norwegian Society of Cardiology, Stein Samstad; Portugal: Portuguese Society of Cardiology, Ana Teresa Timoteo; Romania: Romanian Society of Cardiology, Ovidiu Dragomir Chioncel; San Marino: San Marino Society of Cardiology, Pier Camillo Pavesi; Slovakia: Slovak Society of Cardiology, Maria Rasiova; Slovenia: Slovenian Society of Cardiology, Borut Jug; Spain: Spanish Society of Cardiology, Ariana González Gomez; Sweden: Swedish Society of Cardiology, Stefan James; Switzerland: Swiss Society of Cardiology, Marc Righini; Tunisia: Tunisian Society of Cardiology and Cardio-Vascular Surgery, Amine Tarmiz; Turkey: Turkish Society of Cardiology, Eralp Tutar; and Ukraine: Ukrainian Association of Cardiology, Maksym Sokolov.

ESC Clinical Practice Guidelines (CPG) Committee: Eva Prescott (Chairperson) (Denmark), Stefan James (Co-Chairperson) (Sweden), Elena Arbelo (Spain), Colin Baigent (United Kingdom), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Borja Ibanez (Spain), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), John William McEvoy (Ireland), Borislava Mihaylova (United Kingdom), Richard Mindham (United Kingdom), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Ilonca Vaartjes (Netherlands), Christiaan Vrints (Belgium), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands).

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