The purpose of this EHRA survey was to examine the current clinical practice of screening and risk evaluation for sudden cardiac death in ischaemic and non-ischaemic cardiomyopathy with a focus on selection of candidates for implantable cardioverter-defibrillator (ICD) therapy, timing of ICD implantation, and use of non-invasive and invasive diagnostic tests across Europe. A systematic screening programme for sudden cardiac death existed in 19 out of 31 centres (61.3%). Implantation of ICDs according to the inclusion criteria of MADIT-II and SCD-HeFT trials was reported in 30 and 29% of centres, respectively, followed by MADIT-CRT (18%), COMPANION (16%), and combined MADIT and MUSTT (7%) indications. In patients with severe renal impairment, ICD implantation for primary prevention of sudden death was always avoided in 8 centres (33.3%), was not used only if creatinine level was >2.5 mg/dL in 10 centres (32.2%), and in patients with permanent dialysis in 8 centres (33.3%). Signal-averaged electrocardiography and heart rate variability were never considered as risk stratification tools in 23 centres (74.2%). Implantation of a loop recorder was performed in patients with borderline indications for ICD therapy in 6 centres (19.4%), for research purposes in 5 (16.1%), and was never performed in 20 (64.5%) centres.
In conclusion, the majority of participating European centres have a screening programme for sudden cardiac death and the selection of candidates for ICD therapy was mainly based on the clinical risk stratification and not on non-invasive and invasive diagnostic tests or implantable loop recorder use.
Strategies to reduce sudden cardiac death (SCD) in ischaemic and non-ischaemic cardiomyopathy must focus on better identification of risk factors and diverse pathogeneses of SCD.1–3 An ideal risk stratification strategy would identify those patients who will experience SCD due to reversible ventricular tachyarrhythmias within a specified time period. This European Heart Rhythm Association (EHRA) survey included several questions on the strategy and clinical tools for identification of appropriate candidates for life-saving therapy such as implantable cardioverter-defibrillator (ICD).
Responses were received from 31 partners of the EHRA Research Network. There was a wide geographic distribution of respondents, with responses received from 15 countries (7 centres in Italy, 5 in the UK, 3 in Germany, 2 in the Netherlands, and 2 in Denmark). The majority of centres declared a medium (100–199) or high (400 or more) volume of catheter ablations, a high (200–399) or very high (200 or more) number of ICD implantations, and a high (200–399) or very high (400 or more) number of pacemaker implantations in the last calendar year.
A screening programme for patients with high risk of SCD due to ischaemic and non-ischaemic cardiomyopathy was implemented in 19 (61.3%) of 31 centres. Specifically, a multidisciplinary dedicated programme was present in 9 (33.3%) centres, a screening programme for SCD risk stratification within heart failure clinics in 6 (22.2%), or pacemaker and ICD clinics in 4 (14.8%).
A high number (>70) of patients treated in the year 2012 with their first ICD for primary prevention of SCD was reported in 10 centres (37%) with large referral areas, followed by 7 (25.9%) centres which treated 50 to 69 patients, and 7 centres which treated 20 to 49 patients for this indication. The remaining 7 (10.8%) of the centres treated less than 20 patients.
Implantation of ICDs in MADIT-II (Multicenter Automatic Defibrillator Implantation Trial)4 and SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)5 types of patients was reported by 30 and 29% of the collaborating centres, followed by the MADIT-Cardiac Resynchronization Therapy (CRT)6 type (18%), COMPANION (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure)7 type (16%), and combined MADIT8 and MUSTT (Multicenter UnSustained Tachycardia Trial)9 types (7%). In patients fulfilling MADIT-II inclusion criteria, ICD implantation was considered at least 3 months after myocardial infarction in 22 centres (71%) and 6 months after myocardial infarction in 3 (9.7%) (Figure 1A). No specific limitations for ICD implantation in relation to time elapsed since myocardial infarction were reported by six (19.3%) centres.
In patients satisfying MADIT-II inclusion criteria, a selection of appropriate ICD candidates on the basis of a clinical risk stratification [New York Heart Association (NYHA) class ≥II, history of atrial fibrillation, QRS duration >120 ms, >70 years, and urea levels >26 mg/dL] was considered in all patients in 4 centres (14.8%), some patients in 19 centres (70.4%), and never in 8 (29.6%) of the centres.
Regarding the timing of ICD implantation in patients with SCD-HeFT inclusion criteria, 15 centres (55.6%) considered ICD implantation only after 3 months of optimal medical therapy for heart failure, 9 centres (33.3%) considered it after 6 months of optimal drug therapy, and 3 centres (11.1%) at first clinical evaluation (Figure 1B). Four centres reported no particular duration of medical therapy before ICD implantation.
In patients with severe kidney disease, ICD implantation for primary prevention of SCD was always avoided in 8 (33.3%) centres, only if creatinine levels were >2.5 mg/dL in 10 (32.2%) of the centres, and in patients with permanent dialysis in 8 (33.3%). When selecting ICD therapy for primary prevention, no age limit was reported by 15 (48.4%) of the centres, a <80 years limit by 7 (22.6%), and a <75 years limit in 5 (16.1%). No data were available for the remaining 4 centres.
In patients with previous myocardial infarction and a left ventricular ejection fraction (LVEF) between 30% and 40% programmed electrical stimulation in order to identify candidates for ICD therapy was never performed in 16 (51.6%) of the centres, only in patients with LVEF between 35 and 40% in 7 (25.9%), in the presence of non-sustained ventricular tachycardia during Holter monitoring in 7 (25.9%), and in all cases in only 1 centre (3.7%).
In patients with ischaemic and non-ischaemic cardiomyopathy, risk stratification based on signal-averaged electrocardiography and heart rate variability was never considered in 23 (74.2%) centres, and only in combination with other clinical and laboratory risk factors in 8 (25.8%). In patients with coronary artery disease, ICD therapy on the basis of T-wave alternans and/or baroreceptor sensitivity was considered for a research purpose in only 4 centres (12.9%), while the remaining 27 centres (87.1%) never considered this model of non-invasive stratification. Repeating the non-invasive test for risk stratification for SCD was considered in selected cases in 10 (32.3%) of the centres, at regular time intervals in 5 (16.1%), in the presence of clinical deterioration in 5 (16.1%), and never in the remaining 11 (35.5%) of the centres.
On the basis of the CARISMA (Cardiac Arrhythmias and RIsk Stratification After Acute Myocardial InfArction)10 results, a loop recorder for SCD risk stratification was used in patients with borderline indications for ICD therapy in 6 (19.4%) centres, for a research purpose in 5 (16.1%), and never in the remaining 20 (64.5%) of the centres.
The main findings of this survey of 31 European centres are summarized below.
Screening programme for SCD
The majority of collaborating centres have a multidisciplinary dedicated programme for screening for SCD or concentrates the risk stratification activity in the heart failure or device clinics. This reflects the importance of combining a set of multiple variables from the patient's history and clinical characteristics with selected invasive or non-invasive risk stratification tools to predict the outcome and to select appropriate therapy.1,2 This is particularly important for the accurate identification of patients who can benefit from ICD therapy or from other therapies to reduce the risk of non-arrhythmic death.11–13 No data are available on the relationship between the application of a risk stratification strategy and the subsequent number of ICD implantations.
In patients who underwent ICD implantation for primary prevention of SCD, the inclusion criteria were evenly distributed among the MADIT II4 and SCD-HeFT5 types of patients, followed by MADIT-CRT6 and COMPANION7 types of patients. Similar observations were reported in the IRIDE (Italian Registry of prophylactic Implantation of Defibrillators) study which compared clinical characteristics and outcome in patients undergoing prophylactic ICD implantation in ‘real-life’ practice.14
Timing of implantable cardioverter-defibrillator implantation
In 2012, more than 50 first ICD implantations for primary prevention of SCD were reported in 63% of centres (Figure 1). In patients with MADIT II characteristics, ICD implantation was considered at least 3 or 6 months after myocardial infarction in the majority of centres. However, despite the fact that multiple studies have shown that risk of SCD is greater immediately after myocardial infarction, there is a temporal paradox between the estimation of SCD risk and the benefits of ICD in this patient population.15,16 Major trials failed to demonstrate any significant improvement in survival with ICD implantation early after myocardial infarction compared with optimal medical therapy.17,18 However, analysis from the SCD-HeFT trial16 has shown that a very simply, conservatively programmed ICD has proven valuable early in the post-myocardial infarction period (>40 days). In patients with SCD-HeFT characteristics, ICD implantation was employed in the majority of centres at least after 3 or 6 months of optimal medical therapy. This trend reflects the ‘real world’ observations19,20 and the guideline recommendations that a trial of medical therapy before an ICD should be used in patients with new-onset systolic heart failure.12
Clinical risk stratification of implantable cardioverter-defibrillator candidates
A selection of ICD therapy on the basis of the main clinical characteristics, ECG aspects, and laboratory tests was considered in the majority of centres suggesting that it is important to account for overall mortality risk from cardiovascular causes. In recent sub-analysis of the MADIT II study, patients at intermediate risk had the greatest benefit from an ICD (60% mortality reduction), whereas patients at low risk showed no benefit.11 No upper age limit was used in half the centres, in consistency with recent observational studies that have shown a significant reduction in mortality in the elderly patients. This supports the extrapolation of ICD guidelines on to elderly patients without clinically severe heart failure.21 The presence of renal failure has been considered an important limitation to ICD therapy in the majority of centres. It is well known that despite ICD therapy, patients with severe renal impairment still manifest a three-fold increase in overall mortality. In addition, subgroup analysis from MADIT II showed that patients with advanced renal disease did not demonstrate a mortality benefit from ICD implantation.22,23
Non-invasive and invasive tests for indication to implantable cardioverter-defibrillator therapy
This EP survey showed that in clinical practice <20% of the centres based the selection of candidates for ICD therapy on signal-averaged electrocardiography, heart rate variability, T-wave alternans, and/or baroreceptor sensitivity analysis. Very few centres considered non-invasive tests research purposes. This trend reflects the contradictory results of previous observational studies evaluating the prognostic value of several non-invasive tests that cannot be recommended as independent risk-stratifying tools.1,2 A programmed electrical stimulation to select ICD candidates was performed in 25.9% of the centres when LVEF was between 35 and 40% or only if non-sustained ventricular tachycardia was present. The major limitation of invasive electrophysiologic testing is its low negative predicting value.1,9 In clinical practice, an invasive study may be useful for patient with LVEF between 35 and 40% and a high-risk clinical profile. For these patients a positive test indicates high risk for SCD and warrants ICD implantation.9
Loop recorders for sudden cardiac death risk stratification
In this survey, implantation of loop recorders in order to improve risk stratification for SCD was performed only in patients with borderline indications to ICD (19.4%) or for scientific purposes (16.1%). In CARISMA study, which evaluated 312 post-myocardial infarction patients with reduced LVEF (≤40%) who received an implantable loop recorder, sustained ventricular tachycardia or ventricular fibrillation was documented at the time of death in 8% of cases during a 2-year follow-up.10 Such arrhythmias accounted for half the recorded events at the time of death, while bradyarrhythmias and electromechanical dissociation appeared dominant in non-SCD and non-cardiac death.
The ‘Screening and risk evaluation for SCD in ischaemic and non-ischaemic cardiomyopathy’ survey demonstrates that most participating European centres have a screening evaluation programme for SCD and the selection of ICD candidates was mainly based on clinical risk stratification. Non-invasive and invasive diagnostic tests or implantable loop recorders were considered in only a minority of cases or for research purpose.
The production of this EP wire document is under the responsibility of the Scientific Initiative Committee of the European Heart Rhythm Association: Carina Blomström-Lundqvist (chairman), Philippe Mabo, Maria Grazia Bongiorni, Nikolaos Dagres, Dan Dobreanu, Thorsten Lewalter, Gregory YH Lip, Antonio Madrid, Germanas Marinskis, Laurent Pison, Alessandro Proclemer, and Jesper Hastrup Svendsen. We acknowledge the EHRA Research Network centres participating in this EP wire. A list of the Research Network can be found on EHRA website.
Conflict of interest: none declared.