Abstract

Recently, debate has erupted about the clinical significance of cardiovascular shunts. Several major health problems such as stroke and migraine have been associated with patent foramen ovale (PFO) with right-to-left shunt (RLS). The nature of the relationship between these syndromes and PFO is not clearly understood. Technical advances have led to more therapeutic options including device closure of PFO, hence prevention of such a PFO-related stroke has become feasible. Therefore, optimal diagnosis of PFO has become of greater clinical importance. Contrast echocardiography with non-transpulmonary contrast agents has been the cornerstone in diagnosis of PFO with RLS for over four decades. Despite being a relatively invasive procedure, transesophageal echocardiography (TEE) is considered the gold standard for detection of RLS. Several other echocardiographic techniques such as transthoracic echocardiography (TTE) with second harmonic imaging and transcranial Doppler ultrasonography (TCD) have shown increased sensitivity and specificity compared to TEE for the detection of PFO with RLS. Moreover, improvement of skills and techniques used for detection of these shunts has led to greater detection of small and large sized RLS in the echocardiographic laboratory. This review gives and overview of the echocardiographic techniques, contrast agents and manoeuvres used for detection of the major cardiovascular shunts and their clinical relevance to major health problems.

Introduction

Although the clinical significance of cardiovascular shunts in relation to cerebrovascular accidents is still controversial, 1–4 detection and assessment of these shunts have become a routine diagnostic procedure in many echocardiographic laboratories especially in centers with an active cerebrovascular stroke unit. In the literature to-date, both the rate of shunt detection and the clinical interpretation of the shunts found have varied considerably. In some studies 5 a patent foramen ovale (PFO) with right-to-left-shunt (RLS) has been detected in about 10% of a cerebral stroke population, while others have reported an incidence of >50%. 6 This might be explained by differences in the patient population included, type of cerebral infarction (all cerebral infarction included or only cortical infarction which, is more likely to be caused by embolization than lacunar infarction), age of the patients, comorbidity (particularly hypertension and diabetes), and also by the skills and techniques used for detection of these shunts in the echocardiographic laboratories.

Since the first report in 1968 by Gramiak, 7 contrast echocardiography has become an indispensable tool for cardiovascular imaging. The primarily used aircontained contrast agents such as agitated saline were not able to pass the pulmonary circulation; in the normal circulation no contrast agent would appear in the left side of the heart, which implied that it was useless for the analysis of left-sided cardiac morphology. This property, however, forms the basis for visualization of right-to-left shunts (RLSs): if contrast appears in the left side of the heart, there must be a shunt. Currently, a variety of echocardiographic techniques are available for visualization of cardiac shunts, such as transthoracic (TTE) and transesophageal (TEE) echocardiography and transcranial Doppler ultrasonography (TCD). In this article, the value of contrast echocardiography for detection of shunts and its clinical implications are discussed. Emphasis will be on the four most common shunt types: PFO, atrial septal defect (ASD), ventricular septal defect (VSD) and pulmonary arterio-venous malformations (PAVMs).

Principles of contrast echocardiography

Microbubble generation

The established theory is that the contrast effect is based on microbubbles that are already present in the solution. However, the intensity of the contrast effect can be enhanced by rapid injection of contrast (see later). 8

Echogenicity

The contrast effect of microbubbles depends on the difference in density at the interface between gas-contained microbubbles and the surrounding tissue, which is known as acoustic impedance. The higher the acoustic impedance, the more echogenic the interface, since gas is 100 000 times less dense than blood, gas-contained microbubbles are excellent contrast agents. 9

Echo-contrast agents

The most commonly used contrast agent for the detection of shunts is agitated saline. However, several solutions (see Table 1 ) have the potential to be used for detection of shunts.

Table 1

Echo-contrast agents commonly used for shunt detection

Agents Recommended dose (ml) 
Saline/blood/air 9ml 0.9% saline/1ml blood+0.1ml air 
Dextrose 5% water 10 
D-galactose microparticle solution (Echovist ® )  5–10 
Urea-linked gelatin (Haemaccel ® ) a 10 
Oxypolygelatine (Gelifundol ® ) 22 10 
Agents Recommended dose (ml) 
Saline/blood/air 9ml 0.9% saline/1ml blood+0.1ml air 
Dextrose 5% water 10 
D-galactose microparticle solution (Echovist ® )  5–10 
Urea-linked gelatin (Haemaccel ® ) a 10 
Oxypolygelatine (Gelifundol ® ) 22 10 
a

Main agent in our echo-lab used for shunt detection.

Echocardiographic techniques

Several echocardiographic techniques can be used for detection of shunts (including TTE, TEE and TCD), because of superior resolution TEE is the most commonly used technique for detection of shunts especially in the current era if PFO closure is considered. 10,11 However, a good Valsalva manoeuvre (see later) is often more difficult to obtain from a patient during TEE study, especially if he/or she is heavily sedated than can do a patient during TTE study. The most relevant contrast studies that compared two or more of the echocardiographic techniques for the detection of shunts are summarized in Table 2 .

Table 2

Contrast echocardiography for detection of right-to-left shunts (transesophageal echocardiography used as gold standard)

Authors Year Patients Echocardiographic technique Contrast agent Patients with RLS at TEE Sensitivity Specificity 
Di Tullio 70 1993 49 TCD Saline 19 68 100 
Job 71 1994 137 TCD  Gelifundol ® 64 89 92 
Klötzsch 72 1994 111 TCD  Echovist ® 50 91 94 
Devuyst 73 1997 37 TCD Saline 24 100 100 
Hamann 17 1998 44 TCD  Echovist ® 22 75 100 
Stendel 11 2000 92 TCD  Echovist ® 24 92 97 
Droste 74 2000 64 TCD  Echovist ® 20 100 65 
Di Tullio 70 1993 49 TTE-FI Saline 19 47 100 
Kuhl 75 1999 111 TTE-FI  Gelifundol ® 51 62 100 
TTE-HI  Gelifundol ® 51 92 100 
Stendel 11 2000 92 TTE-FI  Echovist ® 24 42 83 
Ha 16 2000 136 TTE-FI Saline 40 22 100 
TTE-HI Saline 40 63 100 
Van Camp 76 2000 109 TTE-FI Saline 24 46 100 
TTE-HI Saline 24 100 100 
Daniels 77 2004 256 TTE-HI Saline 53 91 97 
Authors Year Patients Echocardiographic technique Contrast agent Patients with RLS at TEE Sensitivity Specificity 
Di Tullio 70 1993 49 TCD Saline 19 68 100 
Job 71 1994 137 TCD  Gelifundol ® 64 89 92 
Klötzsch 72 1994 111 TCD  Echovist ® 50 91 94 
Devuyst 73 1997 37 TCD Saline 24 100 100 
Hamann 17 1998 44 TCD  Echovist ® 22 75 100 
Stendel 11 2000 92 TCD  Echovist ® 24 92 97 
Droste 74 2000 64 TCD  Echovist ® 20 100 65 
Di Tullio 70 1993 49 TTE-FI Saline 19 47 100 
Kuhl 75 1999 111 TTE-FI  Gelifundol ® 51 62 100 
TTE-HI  Gelifundol ® 51 92 100 
Stendel 11 2000 92 TTE-FI  Echovist ® 24 42 83 
Ha 16 2000 136 TTE-FI Saline 40 22 100 
TTE-HI Saline 40 63 100 
Van Camp 76 2000 109 TTE-FI Saline 24 46 100 
TTE-HI Saline 24 100 100 
Daniels 77 2004 256 TTE-HI Saline 53 91 97 

FI=fundamental imaging, HI=harmonic imaging, TCD=transcranial Doppler ultrasonography, TTE=transthoracic echocardiography.

Preparation and safety of contrast agents

A 20-Gauge or more cannula is placed in either an antecubital or femoral vein and 0.9% saline with blood from the patient is agitated between two 10ml syringes connected to a three-way stopcock. A range of 5–20ml saline/blood mixed with 0.2–1ml air has been used. Alternatively, 5–10ml Echovist ® , a galactose-based contrast agent, can be used. All non-transpulmonary agents are safe when injection of large microbubbles is prevented. 12

Provocative tests

The majority of RLSs cannot be seen during conventional TEE and TCD. 13,14 Therefore, provocative manoeuvres such as Valsalva or coughing are used to disclose transient RLSs. Coughing or releasing a sustained Valsalva manoeuvre results in increased filling of the right atrium and therefore a right-to-left atrial pressure gradient develops with opening of the foramen ovale ( Fig. 1 ). 15 Abdominal compression may be used instead if the patient is deeply sedated during TEE, however it seems not sensitive as a good Valsalva manoeuvre. Kronik et al. 13 were the first to demonstrate the effect of the Valsalva manoeuvre for the detection of RLSs. Later on, Lynch et al. 14 demonstrated that in healthy volunteers the detection of PFO increased from 5% to 18% using the Valsalva manoeuvre. Likewise, a 3–4 times increase in sensitivity for shunt detection was shown for TEE. 16

Figure 1

Mechanism of unrevealing right-to-left shunt by Valsalva manoeuvre, an arrow with head up means increase and head down is decrease, number of arrows represent how much is the change. Abbreviations: LA=left atrium, RA=right atrium, P LA =left atrial pressure, P RA =right atrial pressure and VR=venous return.

Figure 1

Mechanism of unrevealing right-to-left shunt by Valsalva manoeuvre, an arrow with head up means increase and head down is decrease, number of arrows represent how much is the change. Abbreviations: LA=left atrium, RA=right atrium, P LA =left atrial pressure, P RA =right atrial pressure and VR=venous return.

Femoral versus antecubital vein

In some reports 17–19 it was shown that the sensitivity of TCD for detection of PFO was markedly increased when a femoral vein is used for contrast injection rather than a antecubital vein. This is probably explained by different inflow patterns into the right atrium: inferior vena caval flow is directed to the atrial septum, whereas superior vena caval flow is directed to the tricuspid valve. Practical disadvantages are the more vascular complications such as arterio-venous fistula when the femoral vein is used; this explains why this is hardly used in clinical practice.

Diagnosis of intra-cardiac shunts by contrast echocardiography

Normally, right atrial cardiac pressure is lower than the left atrial pressure. However, during isovolumic contraction and early ventricular diastole transient periods with a positive right-to-left atrial pressure gradient can occur with opening of the foramen ovale. 20 This fact explains why the use of colour-Doppler echocardiography is mainly applicable for detection of left-to-right shunts (LRSs) but not for transient RLSs.

Positive contrast effect

Since contrast microbubbles with a diameter≥9μm do not pass the pulmonary capillary circulation, any appearance of intravenously injected microbubbles in the left side of the heart is considered positive for an RLS. However, timing of contrast appearance in the left atrium and in particular the exact amount of contrast to define a positive test is still controversial. 21

A negative contrast effect

A negative contrast effect is a sharply delineated washout phenomenon appearing on the right atrial side of the inter-atrial septum in continuity with the contrast-free left atrium and indicates inter-atrial LRS. 22 A negative contrast effect is consistent with ASD, with a considerably wide range in sensitivity. 22 However, with the current use of colour-Doppler imaging the use of contrast for detection of ASD is less important. More importantly, in our practice we use the contrast after closure of ASD to detect any residual shunt after closure (see later). Pitfalls of the positive and negative contrast effects are summarized in Table 3 .

Table 3

Pitfalls of contrast echocardiography for shunt detection

False test results Possible mechanism and solution 
False positive contrast effect 
Valsalva effect  Stagnation of blood in the pulmonary veins during strain phase of Valsalva, upon release a rouleaux formation from stagnant blood flowing into left atrium. 78 Repeat the Valsalva manoeuvre without contrast.  
Large Eustachian valve  A fibro-muscular crescentic fold located at the junction of right atrium and inferior vena cava that can be mistaken for inter-atrial septum. Injected contrast into antecubital vein is streamed along the fold to the right ventricle directly. Use femoral venous injection. 17,18 
False negative contrast effect 
Inadequate contrast injection Inadequate opacification of right atrium. Increase the dose or optimize machine settings. 
Inadequate Valsalva manoeuvre Failure of the Valsalva manoeuvre to increase the right atrial pressure above left atrial pressure. Either the patient ineffectively performs Valsalva manoeuvre or due to a persistently elevated left atrial pressure. The left-sided cardiac pathology is probably seen clearly by echocardiography. RLSs could not be excluded. 
Large Eustachian valve As mentioned before. 
False test results Possible mechanism and solution 
False positive contrast effect 
Valsalva effect  Stagnation of blood in the pulmonary veins during strain phase of Valsalva, upon release a rouleaux formation from stagnant blood flowing into left atrium. 78 Repeat the Valsalva manoeuvre without contrast.  
Large Eustachian valve  A fibro-muscular crescentic fold located at the junction of right atrium and inferior vena cava that can be mistaken for inter-atrial septum. Injected contrast into antecubital vein is streamed along the fold to the right ventricle directly. Use femoral venous injection. 17,18 
False negative contrast effect 
Inadequate contrast injection Inadequate opacification of right atrium. Increase the dose or optimize machine settings. 
Inadequate Valsalva manoeuvre Failure of the Valsalva manoeuvre to increase the right atrial pressure above left atrial pressure. Either the patient ineffectively performs Valsalva manoeuvre or due to a persistently elevated left atrial pressure. The left-sided cardiac pathology is probably seen clearly by echocardiography. RLSs could not be excluded. 
Large Eustachian valve As mentioned before. 

Semi-quantification of shunt

The principle of semi-quantification is based on counting the number of microbubbles crossing from the right to the left atrium within the first three cardiac cycles from right-sided contrast opacification. However, there is no uniform definition in the literature about the number of microbubbles that should appear in the left atrium; either 1, 23 3 2,24 or 5 25 microbubbles was considered positive for PFO. Small, moderate, and large PFOs may be defined as less than 10, more than 10, and full opacification of the left atrium with microbubbles, respectively. 26 With TCD a “curtain” or “shower” pattern (indicating a large RLS) may be associated with the highest risk of cryptogenic stroke. 27 The number of microbubbles passing the PFO is often dependent on the quality of the Valsalva manoeuvre. In case of absent (no microbubbles) or small (few microbubbles) appeared in the left atrium, the study should be repeated using optimal Valsalva manoeuvres at least once. With varying results in one patient, the largest number of microbubbles decides the size of shunt. RLSs of different sizes are shown in Fig. 2 .

Figure 2

Transoesophageal echocardiography using Haemaccel ® (contrast agent), showing: (A) small-sized (less than 10 microbubbles), (B) small-to-moderate (more than 10 microbubbles), and (C) large right-to-left shunt. Abbreviations: AO=aorta, LA=left atrium, MB=microbubbles, PFO=patent foramen ovale and RA=right atrium.

Figure 2

Transoesophageal echocardiography using Haemaccel ® (contrast agent), showing: (A) small-sized (less than 10 microbubbles), (B) small-to-moderate (more than 10 microbubbles), and (C) large right-to-left shunt. Abbreviations: AO=aorta, LA=left atrium, MB=microbubbles, PFO=patent foramen ovale and RA=right atrium.

Patent foramen ovale

General overview

Persistent PFO is associated with stroke, decompression sickness (DCS), and other disorders related to paradoxical embolism ( Table 4 ). However, it is still not clear whether this association is causal, due to predisposition, or have an innocent coincidence. Most evidence for a causal relation exists for young patients with cryptogenic stroke. 1,28 Also, PFO may induce hypoxemia that predispose to the platypnea–orthodeoxia syndrome (see later). 29 In the USA of the 700 000 non-hemorrhagic strokes per year 80% are ischemic and 20% are cryptogenic. 30 PFO and/or ASA with or without PFO are present in approximately half of the patients with cryptogenic stroke and in approximately a quarter of healthy individuals. 30 In a meta-analysis by Overell et al. 31 cryptogenic stroke and transient ischemic attacks were significantly associated with PFO and/or ASA. In contrast, in a recently published population-based prospective study from the Mayo Clinic 4 only ASA, but not PFO, was an independent predictor of stroke or transient ischemic attacks, confirming other negative studies. However, essential differences in the Mayo Clinic study should be taken into account when interpretation of the results is applied; the relatively higher age (mean 66.9±13.3 years) of the studied population, other risk factors (hypertension and diabetes mellitus) for stroke are often present. Moreover, it should be noticed that in all (negative and positive) PFO studies conclusions are based on a relatively low number of events. A summary of the results of some important studies is seen in Tables 5 and 6 .

Table 4

Conditions associated with PFO and inter-atrial septal abnormalities

Cryptogenic stroke 
Transient ischemic attacks 
Migraine 
Peripheral ischemia 
Platypnea–orthodeoxia syndrome 
Decompression sickness of the divers 
Un-explained dementia 79 
Un-explained syncope 
“Economy-class” stroke syndrome 80 
Obstructive sleep apnea 81 
Post-total knee arthroplasty cerebral microembolism 82 
Cryptogenic stroke 
Transient ischemic attacks 
Migraine 
Peripheral ischemia 
Platypnea–orthodeoxia syndrome 
Decompression sickness of the divers 
Un-explained dementia 79 
Un-explained syncope 
“Economy-class” stroke syndrome 80 
Obstructive sleep apnea 81 
Post-total knee arthroplasty cerebral microembolism 82 
Table 5

Relationship between PFO and stroke or transient ischemic attack from prospective studies (incidence of stroke or transient ischemic attack among patients with PFO)

Author Year Follow-up (yrs) Echo Patients Stroke or TIA  Event rate (%)
 
      PFO PFO+ASA No PFO 
Negative studies 
Homma 26 2002 TEE 630  203 (34%) a 14 16 15 
Meissner 3 2006 TEE 585  41 (7%) b 19 
Positive studies 
Mas 2 2001 TEE 581  24 (4%) a 15 
Author Year Follow-up (yrs) Echo Patients Stroke or TIA  Event rate (%)
 
      PFO PFO+ASA No PFO 
Negative studies 
Homma 26 2002 TEE 630  203 (34%) a 14 16 15 
Meissner 3 2006 TEE 585  41 (7%) b 19 
Positive studies 
Mas 2 2001 TEE 581  24 (4%) a 15 

a=recurrent; b=new-onset; ASA=atrial septal aneurysm; PFO=patent foramen ovale; TEE=transesophageal echocardiography; TIA=transient ischemic attack. All hazard ratios were non-significant.

Table 6

Observational and cross-sectional studies (prevalence of PFO among patients with stroke)

Author Year Echo Patients  Cryptogenic stroke
 
Non-cryptogenic stroke
 
Control
 
     PFO/stroke ( n )   PFO/stroke ( n )   PFO/controls ( n )  
Negative studies 
Hausmann 83 1992 TEE 238 16/74 22 10/48 21 25/116 22 
Jones 84 1994 TEE 422 14/71 20 21/149 14 31/202 15 
Fisher 85 1995 TEE 1000 39/391 10 NA NA 391/609 
Positive studies 
Lechat 1 1988 TTE 160 14/26 54 4/19 21 10/100 10 
Webster 86 1988 TTE 80 20/40 50 NA NA 6/40 15 
De Belder 5 1992 TEE 198 9/35 26 10/69 14 3/94 
De Tullio 87 1992 TEE 146 22/45 48 4/101 NA NA 
Cabanes 6 1993 TEE 150 56/100 56 NA NA 9/50 18 
Job 71 1994 TCD 137 27/41 66 11/33 33 27/63 43 
Van Camp 88 1994 TEE 57 6/29 21 NA NA 0/28 
Author Year Echo Patients  Cryptogenic stroke
 
Non-cryptogenic stroke
 
Control
 
     PFO/stroke ( n )   PFO/stroke ( n )   PFO/controls ( n )  
Negative studies 
Hausmann 83 1992 TEE 238 16/74 22 10/48 21 25/116 22 
Jones 84 1994 TEE 422 14/71 20 21/149 14 31/202 15 
Fisher 85 1995 TEE 1000 39/391 10 NA NA 391/609 
Positive studies 
Lechat 1 1988 TTE 160 14/26 54 4/19 21 10/100 10 
Webster 86 1988 TTE 80 20/40 50 NA NA 6/40 15 
De Belder 5 1992 TEE 198 9/35 26 10/69 14 3/94 
De Tullio 87 1992 TEE 146 22/45 48 4/101 NA NA 
Cabanes 6 1993 TEE 150 56/100 56 NA NA 9/50 18 
Job 71 1994 TCD 137 27/41 66 11/33 33 27/63 43 
Van Camp 88 1994 TEE 57 6/29 21 NA NA 0/28 

Abbreviations as in Table 2 . NA=Not applicable.

PFO and recurrence of cerebrovascular complications

The annual stroke recurrence rate in patients with cryptogenic stroke and PFO with or without ASA varies widely from 1.5% to 14%, depending on the study population. Mas et al. 2 reported a cumulative 4-year recurrence rate of 14% among patients with PFO and ASA. It is still controversial whether PFO and/or ASA are associated with an increased risk of stroke recurrence. In a meta-analysis of 10 studies of PFO device closure and 6 studies of medical therapy for PFO, overall, the 1-year rate of recurrent neurological thromboembolism with transcatheter intervention was 0%–4.9% compared to 3.8%–12.0% on medical management 32 ( Table 7 ).

Table 7

Recurrence of neurological complications in patients with patent foramen ovale

Author Year Follow-up (yrs) Patients  PFO closure
 
Medical therapy
 
    Patients Recurrence rate Patients  Recurrence rate
 
       Aspirin Warfarin 
Khairy 32 2003 >1 2250 1355  0–4.9 a 895  3.8–12 a  3.8–12 a 
Windecker 89 2004 2.4 308 150 8.5 158 28.3 13.3 
Schuchlenz 90 2005 2.6 280 167 0.6 113 13.0 5.6 
Author Year Follow-up (yrs) Patients  PFO closure
 
Medical therapy
 
    Patients Recurrence rate Patients  Recurrence rate
 
       Aspirin Warfarin 
Khairy 32 2003 >1 2250 1355  0–4.9 a 895  3.8–12 a  3.8–12 a 
Windecker 89 2004 2.4 308 150 8.5 158 28.3 13.3 
Schuchlenz 90 2005 2.6 280 167 0.6 113 13.0 5.6 
a

Range of studies included in the meta-analysis by Khairy et al.

When does PFO need treatment?

In the recently published AHA/ACC/AAN guideline for the management of stroke it is recommended that any patient, who suffered ischemic stroke or a transient ischemic attack with a PFO, may receive antiplatelets or warfarin therapy to minimize stroke recurrence (Class IIa, level of Evidence C) while device or surgical closure of PFO is not supported (Class IIb, level of Evidence C). 30 Ongoing research in this field will provide definite answers in the near future. Our practice is that only patients <55 years who suffer stroke or transient ischemic attack are screened for the presence of PFO. If a PFO is diagnosed with an RLS and there is no other risk factor present, patients are informed about the therapeutic choices, medical treatment or device closure with advantages and disadvantages of both management regimens. If both a PFO and an ASA are present, we recommend PFO device closure because of the huge recurrence rate of stroke under medical treatment alone. If a patient with a PFO but without other risk factors had a recurrent stroke despite medical treatment, we advise device closure. If other risk factors are not present we advice medical treatment.

PFO and migraine

Recent evidence supports an association between PFO and migraine headache, particularly if combined with aura. In a series of case-controlled studies 33–36 approximately half of migraine patients had a PFO. However, compared to controls the prevalence of PFO was only increased in migraine patients with aura (54% vs. 17%). 33 PFOs in migraineurs are moderately large but rather less than that associated with stroke patients. 35 The nature of the relation between PFO and migraine is still poorly understood. Autosomal dominant inheritance, 37 small venous thrombus or platelets aggregate, or vaso-active substances 38 entering the cerebral circulation through the PFO are possible mechanisms. In several PFO closure device studies a significant reduction in the frequency of migraine was described, particularly in patients with aura ( Table 8 ). 39–42 However, in a double-blinded, prospective placebo and sham procedure controlled study, the results were not as convincing as in retrospective studies. Other trials are currently in progress. 36

Table 8

Improvement of migraine after PFO closure

   Migraine
 
Migraine with aura
 
Migraine without aura
 
  Patients Patients Patients 
Wilmshurst 41 2000 18/21 86 15/16 94 3/5 60 
Morandi 40 2003 15/17 88 NA NA NA NA 
Schwerzmann 91 2004 35/43 81 26/33 79 9/10 90 
Azarbal 42 2005 24/30 80 16/20 80 8/10 80 
Reisman 92 2005 35/50 70 NA NA NA NA 
Composite  127/161 79 57/69 83 20/25 80 
   Migraine
 
Migraine with aura
 
Migraine without aura
 
  Patients Patients Patients 
Wilmshurst 41 2000 18/21 86 15/16 94 3/5 60 
Morandi 40 2003 15/17 88 NA NA NA NA 
Schwerzmann 91 2004 35/43 81 26/33 79 9/10 90 
Azarbal 42 2005 24/30 80 16/20 80 8/10 80 
Reisman 92 2005 35/50 70 NA NA NA NA 
Composite  127/161 79 57/69 83 20/25 80 

PFO and DCS

Nitrogen is an inert gas normally stored throughout the human body such as tissues and fluids, in physical solution. When the body is exposed to decreased pressures, such as during a scuba ascent through water, the nitrogen dissolved in the body comes out of the solution. These nitrogen bubbles are mostly trapped in the lung capillaries because of their larger size than the tiny diameter of the capillaries. Once trapped, the bubbles break up and the nitrogen gas is exhaled. A PFO allows bubbles to pass from right-to-left circulation, bypassing the screening effects of the pulmonary circulation. However, about 30% of divers have a PFO and the prevalence of serious DCS is very low (1%) 43 ; a causative role for DCS of PFO is outsized entity and therefore, routine screening of divers for PFO is not recommended. Moreover, in the analysis of diving incidents with serious DCS with high spinal cord and cerebral affection, a PFO with a RLS was present much more often than in a control population of divers without DCS. 44,45 This suggests that a PFO with the possibility of intra-cardiac RLS may play a role, albeit small, in DCS. Because of a possible elevated risk for DCS for patients with a PFO, it might be advisable to screen scuba professional divers who will make significantly more dives than amateur/sport/recreational divers for the presence of a PFO with RLS. 46 If a PFO with RLS is present they should be advised to stop diving or at least change diving habits, minimising the amount of nitrogen load on the tissue. 46 Theoretically, percutaneous PFO closure by a device could be efficacious in lowering the risk of DCS in divers, but this hypothesis has not been properly tested yet.

PFO and the platypnea–orthodeoxia syndrome

Platypnea–orthodeoxia is an uncommon syndrome of dyspnea (platypnea) and hypoxemia (orthodeoxia) induced by upright posture, which is subsequently relieved by recumbence. Traditionally, this condition has been reported in association with pulmonary, hepatic and cardiac diseases. The occurrence of the syndrome mandates anatomical and functional abnormalities. 47 The anatomical abnormality is an RLS either intra-cardiac (PFO, ASD, fenestrated ASA) or extra-cardiac such as PAVM. Mechanisms explaining postural hypoxemia are RLSs resulting from either elevation of right atrial pressure or redirection of the inferior vena cava flow towards the atrial septum 48 due to the presence of an associated persistent Eustachian valve. The definitive treatment in such cases is closure of the defect. 49 It should be noted that a PFO with RLS could be only seen in upright position in such patients.

Pulmonary arterio-venous malformations

PAVMs represent a direct communication between one or more pulmonary arteries and one or more pulmonary veins and often associated with hereditary hemorrhagic teleangiectasia (Osler–Weber–Rendu syndrome). 50,51 PAVMs are commonly (>70%) single sacks ranging from 1 to >10cm in diameter, with a single feeding artery and a single draining vein. 52 The main complications of PAVMs are thought to relate to the RLS of thrombotic particles with eventually stroke and/or brain abscess, which may occur in up to one half of patients if left untreated. 53,54 Several diagnostic techniques were investigated for screening of PAVMS including contrast echocardiography, oxygen shunt test (oxygen saturation after breathing 100% oxygen), pulmonary angiography, computed tomography and magnetic resonance imaging. 55 In comparison to other techniques such as pulmonary angiography 56,57 and oxygen shunt test 58 contrast echocardiography was the most sensitive but least specific non-invasive technique for detection of PAVMs. 54,56,57 However, it should be noticed that radioisotope evaluation of PAVMs in a non-comparative study resulted in a similar sensitivity to contrast echocardiography but had a higher specificity. 59 Appearance of microbubbles in the left atrium after 3 beats from opacification of the right atrium is suggestive of PAVMs. 60 However, microbubbles appearing earlier do not exclude PAVMs, and may be caused by a combined inter-atrial RLS plus PAVMs or PAVMs connecting to a lower pulmonary vein. 61 Thus, a comprehensive TEE examination of the lower pulmonary veins during contrast echocardiography is important to exclude PAVM. The 3-cardiac cycle conventional rule of differentiating extra-cardiac from intra-cardiac RLSs through a PFO by noting the appearance of contrast echoes in the left atrium 3 or more beats after first appearance in the right atrium has been found to be unreliable. 62 Treatment is recommended for all PAVMs with single feeding vessels of ≥3mm, in order to reduce the risk of paradoxical embolization, however, if multiple feeding vessels are present it may be difficult or impossible to treat. 63

Atrial septal defects

ASDs are the most common congenital heart abnormalities in adults after bicuspid aortic valve. The most common anatomical types are ostium primum, secundum and sinus venosus defects. The use of contrast echocardiography for the diagnosis of ASD is limited; the combination of 2D (TTE and TEE) and Doppler techniques (especially colour-Doppler) almost always leads to the diagnosis. In case of doubt or incomplete diagnosis contrast echocardiography can be useful. Contrast echocardiography is very useful and is used very often for the assessment of residual shunt after device closure of an ASD. 64–66 Because of the high echogenicity of the closure device, the ultrasound wave reflections make the conventional echocardiographic techniques (including Doppler) unreliable. A residual LRS can be seen as a negative contrast effect in contrast-filled right atrium. Residual RLSs can be seen as bubbles passing the inter-atrial septum to the left atrium which mandates the use of optimal Valsalva manoeuvre. 64

Ventricular septal defect

A VSD may be an isolated single congenital defect, part of a complex congenital cardiac anomaly or acquired after an acute myocardial infarction. It may be situated in the membranous or muscular part of the septum. In the past contrast echocardiography has been used successfully in clinical practice for the detection of VSD. 67 Since the introduction of colour-Doppler the use of contrast for detection of VSD is almost not seen in clinical practice. However, contrast could be used for the detection of residual shunt after VSD closure. At the Thoraxcenter, both colour flow mapping and contrast echocardiography are performed after VSD closure before closure of the chest for the immediate exclusion of residual shunting. 68,69

Conclusion

Contrast echocardiography is a safe, simple, non-invasive, feasible and reproducible imaging technique with a proven accuracy for the detection of cardiovascular shunts.

References

1
Lechat
P.
Mas
J.L.
Lascault
G.
Loron
P.
Theard
M.
Klimczac
M.
, et al.  . 
Prevalence of patent foramen ovale in patients with stroke
N Engl J Med
 , 
1988
, vol. 
318
 (pg. 
1148
-
1152
)
2
Mas
J.L.
Arquizan
C.
Lamy
C.
Zuber
M.
Cabanes
L.
Derumeaux
G.
, et al.  . 
Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both
N Engl J Med
 , 
2001
, vol. 
345
 (pg. 
1740
-
1746
)
3
Meissner
I.
Khandheria
B.K.
Heit
J.A.
Petty
G.W.
Sheps
S.G.
Schwartz
G.L.
, et al.  . 
Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study
J Am Coll Cardiol
 , 
2006
, vol. 
47
 (pg. 
440
-
445
)
4
Petty
G.W.
Khandheria
B.K.
Meissner
I.
Whisnant
J.P.
Rocca
W.A.
Christianson
T.J.
, et al.  . 
Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events
Mayo Clin Proc
 , 
2006
, vol. 
81
 (pg. 
602
-
608
)
5
de Belder
M.A.
Tourikis
L.
Leech
G.
Camm
A.J.
Risk of patent foramen ovale for thromboembolic events in all age groups
Am J Cardiol
 , 
1992
, vol. 
69
 (pg. 
1316
-
1320
)
6
Cabanes
L.
Mas
J.L.
Cohen
A.
Amarenco
P.
Cabanes
P.A.
Oubary
P.
, et al.  . 
Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography
Stroke
 , 
1993
, vol. 
24
 (pg. 
1865
-
1873
)
7
Gramiak
R.
Shah
P.M.
Kramer
D.H.
Ultrasound cardiography: contrast studies in anatomy and function
Radiology
 , 
1969
, vol. 
92
 (pg. 
939
-
948
)
8
Meltzer
R.S.
Tickner
E.G.
Sahines
T.P.
Popp
R.L.
The source of ultrasound contrast effect
J Clin Ultrasound
 , 
1980
, vol. 
8
 (pg. 
121
-
127
)
9
Forsberg
F.
Basude
R.
Liu
J.B.
Alessandro
J.
Shi
W.T.
Rawool
N.M.
, et al.  . 
Effect of filling gases on the backscatter from contrast microbubbles: theory and in vivo measurements
Ultrasound Med Biol
 , 
1999
, vol. 
25
 (pg. 
1203
-
1211
)
10
Schneider
B.
Zienkiewicz
T.
Jansen
V.
Hofmann
T.
Noltenius
H.
Meinertz
T.
Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings
Am J Cardiol
 , 
1996
, vol. 
77
 (pg. 
1202
-
1209
)
11
Stendel
R.
Gramm
H.J.
Schroder
K.
Lober
C.
Brock
M.
Transcranial Doppler ultrasonography as a screening technique for detection of a patent foramen ovale before surgery in the sitting position
Anesthesiology
 , 
2000
, vol. 
93
 (pg. 
971
-
975
)
12
Bommer
W.J.
Shah
P.M.
Allen
H.
Meltzer
R.
Kisslo
J.
The safety of contrast echocardiography: report of the Committee on Contrast Echocardiography for the American Society of Echocardiography
J Am Coll Cardiol
 , 
1984
, vol. 
3
 (pg. 
6
-
13
)
13
Kronik
G.
Slany
J.
Moesslacher
H.
Contrast M-mode echocardiography in diagnosis of atrial septal defect in acyanotic patients
Circulation
 , 
1979
, vol. 
59
 (pg. 
372
-
378
)
14
Lynch
J.J.
Schuchard
G.H.
Gross
C.M.
Wann
L.S.
Prevalence of right-to-left atrial shunting in a healthy population: detection by Valsalva maneuver contrast echocardiography
Am J Cardiol
 , 
1984
, vol. 
53
 (pg. 
1478
-
1480
)
15
Meier
B.
Lock
J.E.
Contemporary management of patent foramen ovale
Circulation
 , 
2003
, vol. 
107
 (pg. 
5
-
9
)
16
Ha
J.W.
Shin
M.S.
Kang
S.
Pyun
W.B.
Jang
K.J.
Byun
K.H.
, et al.  . 
Enhanced detection of right-to-left shunt through patent foramen ovale by transthoracic contrast echocardiography using harmonic imaging
Am J Cardiol
 , 
2001
, vol. 
87
 (pg. 
669
-
671
[A11]
17
Hamann
G.F.
Schatzer-Klotz
D.
Frohlig
G.
Strittmatter
M.
Jost
V.
Berg
G.
, et al.  . 
Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale
Neurology
 , 
1998
, vol. 
50
 (pg. 
1423
-
1428
)
18
Gin
K.G.
Huckell
V.F.
Pollick
C.
Femoral vein delivery of contrast medium enhances transthoracic echocardiographic detection of patent foramen ovale
J Am Coll Cardiol
 , 
1993
, vol. 
22
 (pg. 
1994
-
2000
)
19
Lindeboom
J.E.
van Deudekom
M.J.
Visser
C.A.
Traditional contrast echocardiography may fail to demonstrate a patent foramen ovale: negative contrast in the right atrium may be a clue
Eur J Echocardiogr
 , 
2005
, vol. 
6
 (pg. 
75
-
78
)
20
Levin
A.R.
Spach
M.S.
Boineau
J.P.
Canent
R.V.
Jr.
Capp
M.P.
Jewett
P.H.
Atrial pressure-flow dynamics in atrial septal defects (secundum type)
Circulation
 , 
1968
, vol. 
37
 (pg. 
476
-
488
)
21
Woods
T.D.
Patel
A.
A critical review of patent foramen ovale detection using saline contrast echocardiography: when bubbles lie
J Am Soc Echocardiogr
 , 
2006
, vol. 
19
 (pg. 
215
-
222
)
22
Konstantinides
S.
Kasper
W.
Geibel
A.
Hofmann
T.
Koster
W.
Just
H.
Detection of left-to-right shunt in atrial septal defect by negative contrast echocardiography: a comparison of transthoracic and transesophageal approach
Am Heart J
 , 
1993
, vol. 
126
 (pg. 
909
-
917
)
23
Homma
S.
Di Tullio
M.R.
Sacco
R.L.
Mihalatos
D.
Li Mandri
G.
Mohr
J.P.
Characteristics of patent foramen ovale associated with cryptogenic stroke. A biplane transesophageal echocardiographic study
Stroke
 , 
1994
, vol. 
25
 (pg. 
582
-
586
)
24
Martin
F.
Sanchez
P.L.
Doherty
E.
Colon-Hernandez
P.J.
Delgado
G.
Inglessis
I.
, et al.  . 
Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism
Circulation
 , 
2002
, vol. 
106
 (pg. 
1121
-
1126
)
25
Hausmann
D.
Mugge
A.
Daniel
W.G.
Identification of patent foramen ovale permitting paradoxic embolism
J Am Coll Cardiol
 , 
1995
, vol. 
26
 (pg. 
1030
-
1038
)
26
Homma
S.
Sacco
R.L.
Di Tullio
M.R.
Sciacca
R.R.
Mohr
J.P.
Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study
Circulation
 , 
2002
, vol. 
105
 (pg. 
2625
-
2631
)
27
Serena
J.
Segura
T.
Perez-Ayuso
M.J.
Bassaganyas
J.
Molins
A.
Davalos
A.
The need to quantify right-to-left shunt in acute ischemic stroke: a case-control study
Stroke
 , 
1998
, vol. 
29
 (pg. 
1322
-
1328
)
28
De Castro
S.
Cartoni
D.
Fiorelli
M.
Rasura
M.
Anzini
A.
Zanette
E.M.
, et al.  . 
Morphological and functional characteristics of patent foramen ovale and their embolic implications
Stroke
 , 
2000
, vol. 
31
 (pg. 
2407
-
2413
)
29
Zanchetta
M.
Rigatelli
G.
Ho
S.Y.
A mystery featuring right-to-left shunting despite normal intracardiac pressure
Chest
 , 
2005
, vol. 
128
 (pg. 
998
-
1002
)
30
Sacco
R.L.
Adams
R.
Albers
G.
Alberts
M.J.
Benavente
O.
Furie
K.
, et al.  . 
Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline
Circulation
 , 
2006
, vol. 
113
 (pg. 
e409
-
e449
)
31
Overell
J.R.
Bone
I.
Lees
K.R.
Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies
Neurology
 , 
2000
, vol. 
55
 (pg. 
1172
-
1179
)
32
Khairy
P.
O'Donnell
C.P.
Landzberg
M.J.
Transcatheter closure versus medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: a systematic review
Ann Intern Med
 , 
2003
, vol. 
139
 (pg. 
753
-
760
)
33
Anzola
G.P.
Magoni
M.
Guindani
M.
Rozzini
L.
Dalla Volta
G.
Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study
Neurology
 , 
1999
, vol. 
52
 (pg. 
1622
-
1625
)
34
Wilmshurst
P.
Nightingale
S.
Relationship between migraine and cardiac and pulmonary right-to-left shunts
Clin Sci (Lond)
 , 
2001
, vol. 
100
 (pg. 
215
-
220
)
35
Schwerzmann
M.
Nedeltchev
K.
Lagger
F.
Mattle
H.P.
Windecker
S.
Meier
B.
, et al.  . 
Prevalence and size of directly detected patent foramen ovale in migraine with aura
Neurology
 , 
2005
, vol. 
65
 (pg. 
1415
-
1418
)
36
Dowson
A.J.
Wilmshurst
P.
Muir
K.W.
Mullen
M.
Nightingale
S.
a prospective, multicenter, randomized, double blind, placebo-controlled trial to evaluate the efficacy of patent foramen ovale closure with the STARFlex septal repair implant to prevent refractory migraine headaches: the MIST trial: S61.002
Neurology
 , 
2006
, vol. 
67
 pg. 
185
 
37
Wilmshurst
P.T.
Pearson
M.J.
Nightingale
S.
Walsh
K.P.
Morrison
W.L.
Inheritance of persistent foramen ovale and atrial septal defects and the relation to familial migraine with aura
Heart
 , 
2004
, vol. 
90
 (pg. 
1315
-
1320
)
38
Schwedt
T.J.
Dodick
D.W.
Patent foramen ovale and migraine – bringing closure to the subject
Headache
 , 
2006
, vol. 
46
 (pg. 
663
-
671
)
39
Post
M.C.
Thijs
V.
Herroelen
L.
Budts
W.I.
Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine
Neurology
 , 
2004
, vol. 
62
 (pg. 
1439
-
1440
)
40
Morandi
E.
Anzola
G.P.
Angeli
S.
Melzi
G.
Onorato
E.
Transcatheter closure of patent foramen ovale: a new migraine treatment?
J Interv Cardiol
 , 
2003
, vol. 
16
 (pg. 
39
-
42
)
41
Wilmshurst
P.T.
Nightingale
S.
Walsh
K.P.
Morrison
W.L.
Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons
Lancet
 , 
2000
, vol. 
356
 (pg. 
1648
-
1651
)
42
Azarbal
B.
Tobis
J.
Suh
W.
Chan
V.
Dao
C.
Gaster
R.
Association of interatrial shunts and migraine headaches: impact of transcatheter closure
J Am Coll Cardiol
 , 
2005
, vol. 
45
 (pg. 
489
-
492
)
43
Hagberg
M.
Ornhagen
H.
Incidence and risk factors for symptoms of decompression sickness among male and female dive masters and instructors – a retrospective cohort study
Undersea Hyperb Med
 , 
2003
, vol. 
30
 (pg. 
93
-
102
)
44
Torti
S.R.
Billinger
M.
Schwerzmann
M.
Vogel
R.
Zbinden
R.
Windecker
S.
, et al.  . 
Risk of decompression illness among 230 divers in relation to the presence and size of patent foramen ovale
Eur Heart J
 , 
2004
, vol. 
25
 (pg. 
1014
-
1020
)
45
Cartoni
D.
De Castro
S.
Valente
G.
Costanzo
C.
Pelliccia
A.
Beni
S.
, et al.  . 
Identification of professional scuba divers with patent foramen ovale at risk for decompression illness
Am J Cardiol
 , 
2004
, vol. 
94
 (pg. 
270
-
273
)
46
Schwerzmann
M.
Seiler
C.
Recreational scuba diving, patent foramen ovale and their associated risks
Swiss Med Wkly
 , 
2001
, vol. 
131
 (pg. 
365
-
374
)
47
Cheng
T.O.
Mechanisms of platypnea–orthodeoxia: what causes water to flow uphill?
Circulation
 , 
2002
, vol. 
105
 pg. 
e47
 
48
Cheng
T.O.
Reversible orthodeoxia
Ann Intern Med
 , 
1992
, vol. 
116
 pg. 
875
 
49
Cheng
T.O.
Transcatheter closure of patent foramen ovale: a definitive treatment for platypnea–orthodeoxia
Catheter Cardiovasc Interv
 , 
2000
, vol. 
51
 pg. 
120
 
50
Dines
D.E.
Arms
R.A.
Bernatz
P.E.
Gomes
M.R.
Pulmonary arteriovenous fistulas
Mayo Clin Proc
 , 
1974
, vol. 
49
 (pg. 
460
-
465
)
51
Giordano
P.
Nigro
A.
Lenato
G.M.
Guanti
G.
Suppressa
P.
Lastella
P.
, et al.  . 
Screening for children from families with Rendu–Osler–Weber disease: from geneticist to clinician
J Thromb Haemost
 , 
2006
, vol. 
4
 (pg. 
1237
-
1245
)
52
White
R.I.
Jr.
Mitchell
S.E.
Barth
K.H.
Kaufman
S.L.
Kadir
S.
Chang
R.
, et al.  . 
Angioarchitecture of pulmonary arteriovenous malformations: an important consideration before embolotherapy
AJR Am J Roentgenol
 , 
1983
, vol. 
140
 (pg. 
681
-
686
)
53
White
R.I.
Jr.
Pollak
J.S.
Wirth
J.A.
Pulmonary arteriovenous malformations: diagnosis and transcatheter embolotherapy
J Vasc Interv Radiol
 , 
1996
, vol. 
7
 (pg. 
787
-
804
)
54
Gossage
J.R.
Kanj
G.
Pulmonary arteriovenous malformations. A state of the art review
Am J Respir Crit Care Med
 , 
1998
, vol. 
158
 (pg. 
643
-
661
)
55
Fink
C.
Eichhorn
J.
Kiessling
F.
Bock
M.
Delorme
S.
[Time-resolved multiphasic 3D MR angiography in the diagnosis of the pulmonary vascular system in children]
Rofo
 , 
2003
, vol. 
175
 (pg. 
929
-
935
)
56
Nanthakumar
K.
Graham
A.T.
Robinson
T.I.
Grande
P.
Pugash
R.A.
Clarke
J.A.
, et al.  . 
Contrast echocardiography for detection of pulmonary arteriovenous malformations
Am Heart J
 , 
2001
, vol. 
141
 (pg. 
243
-
246
)
57
Feinstein
J.A.
Moore
P.
Rosenthal
D.N.
Puchalski
M.
Brook
M.M.
Comparison of contrast echocardiography versus cardiac catheterization for detection of pulmonary arteriovenous malformations
Am J Cardiol
 , 
2002
, vol. 
89
 (pg. 
281
-
285
)
58
Lee
W.L.
Graham
A.F.
Pugash
R.A.
Hutchison
S.J.
Grande
P.
Hyland
R.H.
, et al.  . 
Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations
Chest
 , 
2003
, vol. 
123
 (pg. 
351
-
358
)
59
Thompson
R.L.
Cattaneo
S.M.
Barnes
J.
Recurrent brain abscess: manifestation of pulmonary arteriovenous fistula and hereditary hemorrhagic telangiectasia
Chest
 , 
1977
, vol. 
72
 (pg. 
654
-
655
)
60
Gossage
J.R.
The role of echocardiography in screening for pulmonary arteriovenous malformations
Chest
 , 
2003
, vol. 
123
 (pg. 
320
-
322
)
61
Ahmed
S.
Nanda
N.C.
Nekkanti
R.
Yousif
A.M.
Contrast transesophageal echocardiographic detection of a pulmonary arteriovenous malformation draining into left lower pulmonary vein
Echocardiography
 , 
2003
, vol. 
20
 (pg. 
391
-
394
)
62
Naqvi
T.Z.
Nagai
T.
Atar
S.
Siegel
R.J.
Early appearance of echo-contrast simulating an intracardiac shunt in a patient with liver cirrhosis and intrapulmonary shunting
J Am Soc Echocardiogr
 , 
2002
, vol. 
15
 (pg. 
379
-
381
)
63
De Cillis
E.
Burdi
N.
Bortone
A.S.
D'Agostino
D.
Fiore
T.
Ettorre
G.C.
, et al.  . 
Endovascular treatment of pulmonary and cerebral arteriovenous malformations in patients affected by hereditary haemorrhagic teleangiectasia
Curr Pharm Des
 , 
2006
, vol. 
12
 (pg. 
1243
-
1248
)
64
Schneider
B.
Bauer
R.
Is surgical closure of patent foramen ovale the gold standard for treating interatrial shunts? An echocardiographic follow-up study
J Am Soc Echocardiogr
 , 
2005
, vol. 
18
 (pg. 
1385
-
1391
)
65
Bartz
P.J.
Cetta
F.
Cabalka
A.K.
Reeder
G.S.
Squarcia
U.
Agnetti
A.
, et al.  . 
Paradoxical emboli in children and young adults: role of atrial septal defect and patent foramen ovale device closure
Mayo Clin Proc
 , 
2006
, vol. 
81
 (pg. 
615
-
618
)
66
Herrmann
H.C.
Silvestry
F.E.
Glaser
R.
See
V.
Kasner
S.
Bradbury
D.
, et al.  . 
Percutaneous patent foramen ovale and atrial septal defect closure in adults: results and device comparison in 100 consecutive implants at a single center
Catheter Cardiovasc Interv
 , 
2005
, vol. 
64
 (pg. 
197
-
203
)
67
Funabashi
T.
Yoshida
H.
Nakaya
S.
Maeda
T.
Taniguchi
N.
Echocardiographic visualization of ventricular septal defect in infants and assessment of hemodynamic status using a contrast technique. Comparison of M-mode and two-dimensional imaging
Circulation
 , 
1981
, vol. 
64
 (pg. 
1025
-
1031
)
68
Gussenhoven
E.J.
van Herwerden
L.A.
van Suylen
R.J.
Ansing
T.
Witsenburg
M.
Elzenga
N.
, et al.  . 
Recognition of residual ventricular septal defect by intraoperative contrast echocardiography
Eur Heart J
 , 
1989
, vol. 
10
 (pg. 
801
-
805
)
69
Stumper
O.
Fraser
A.G.
Elzenga
N.
Van Daele
M.
Frohn-Mulder
I.
Van Herwerden
L.A.
, et al.  . 
Assessment of ventricular septal defect closure by intraoperative epicardial ultrasound
J Am Coll Cardiol
 , 
1990
, vol. 
16
 (pg. 
1672
-
1679
)
70
Di Tullio
M.
Sacco
R.L.
Massaro
A.
Venketasubramanian
N.
Sherman
D.
Hoffmann
M.
, et al.  . 
Transcranial Doppler with contrast injection for the detection of patent foramen ovale in stroke patients
Int J Card Imaging
 , 
1993
, vol. 
9
 (pg. 
1
-
5
)
71
Job
F.P.
Ringelstein
E.B.
Grafen
Y.
Flachskampf
F.A.
Doherty
C.
Stockmanns
A.
, et al.  . 
Comparison of transcranial contrast Doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients
Am J Cardiol
 , 
1994
, vol. 
74
 (pg. 
381
-
384
)
72
Klötzsch
C.
Janssen
G.
Berlit
P.
Transesophageal echocardiography and contrast-TCD in the detection of a patent foramen ovale: experiences with 111 patients
Neurology
 , 
1994
, vol. 
44
 (pg. 
1603
-
1606
)
73
Devuyst
G.
Despland
P.A.
Bogousslavsky
J.
Jeanrenaud
X.
Complementarity of contrast transcranial Doppler and contrast transesophageal echocardiography for the detection of patent foramen ovale in stroke patients
Eur Neurol
 , 
1997
, vol. 
38
 (pg. 
21
-
25
)
74
Droste
D.W.
Silling
K.
Stypmann
J.
Grude
M.
Kemeny
V.
Wichter
T.
, et al.  . 
Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts: time window and threshold in microbubble numbers
Stroke
 , 
2000
, vol. 
31
 (pg. 
1640
-
1645
)
75
Kuhl
H.P.
Hoffmann
R.
Merx
M.W.
Franke
A.
Klotzsch
C.
Lepper
W.
, et al.  . 
Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events
J Am Coll Cardiol
 , 
1999
, vol. 
34
 (pg. 
1823
-
1830
)
76
Van Camp
G.
Franken
P.
Melis
P.
Cosyns
B.
Schoors
D.
Vanoverschelde
J.L.
Comparison of transthoracic echocardiography with second harmonic imaging with transesophageal echocardiography in the detection of right to left shunts
Am J Cardiol
 , 
2000
, vol. 
86
 (pg. 
1284
-
1287
A9
77
Daniels
C.
Weytjens
C.
Cosyns
B.
Schoors
D.
De Sutter
J.
Paelinck
B.
, et al.  . 
Second harmonic transthoracic echocardiography: the new reference screening method for the detection of patent foramen ovale
Eur J Echocardiogr
 , 
2004
, vol. 
5
 (pg. 
449
-
452
)
78
Van Camp
G.
Cosyns
B.
Vandenbossche
J.L.
Non-smoke spontaneous contrast in left atrium intensified by respiratory manoeuvres: a new transoesophageal echocardiographic observation
Br Heart J
 , 
1994
, vol. 
72
 (pg. 
446
-
451
)
79
Angeli
S.
Carrera
P.
Del Sette
M.
Assini
A.
Grandis
M.
Biancolini
D.
, et al.  . 
Very high prevalence of right-to-left shunt on transcranial Doppler in an Italian family with cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy
Eur Neurol
 , 
2001
, vol. 
46
 (pg. 
198
-
201
)
80
Isayev
Y.
Chan
R.K.
Pullicino
P.M.
“Economy class” stroke syndrome?
Neurology
 , 
2002
, vol. 
58
 (pg. 
960
-
961
)
81
Agnoletti
G.
Iserin
L.
Lafont
A.
Sidi
D.
Desnos
M.
Obstructive sleep apnoea and patent foramen ovale: successful treatment of symptoms by percutaneous foramen ovale closure
J Interv Cardiol
 , 
2005
, vol. 
18
 (pg. 
393
-
395
)
82
Sulek
C.A.
Davies
L.K.
Enneking
F.K.
Gearen
P.A.
Lobato
E.B.
Cerebral microembolism diagnosed by transcranial Doppler during total knee arthroplasty: correlation with transesophageal echocardiography
Anesthesiology
 , 
1999
, vol. 
91
 (pg. 
672
-
676
)
83
Hausmann
D.
Mugge
A.
Becht
I.
Daniel
W.G.
Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events
Am J Cardiol
 , 
1992
, vol. 
70
 (pg. 
668
-
672
)
84
Jones
E.F.
Calafiore
P.
Donnan
G.A.
Tonkin
A.M.
Evidence that patent foramen ovale is not a risk factor for cerebral ischemia in the elderly
Am J Cardiol
 , 
1994
, vol. 
74
 (pg. 
596
-
599
)
85
Fisher
D.C.
Fisher
E.A.
Budd
J.H.
Rosen
S.E.
Goldman
M.E.
The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study
Chest
 , 
1995
, vol. 
107
 (pg. 
1504
-
1509
)
86
Webster
M.W.
Chancellor
A.M.
Smith
H.J.
Swift
D.L.
Sharpe
D.N.
Bass
N.M.
, et al.  . 
Patent foramen ovale in young stroke patients
Lancet
 , 
1988
, vol. 
2
 (pg. 
11
-
12
)
87
Di Tullio
M.
Sacco
R.L.
Gopal
A.
Mohr
J.P.
Homma
S.
Patent foramen ovale as a risk factor for cryptogenic stroke
Ann Intern Med
 , 
1992
, vol. 
117
 (pg. 
461
-
465
)
88
Van Camp
G.
Schulze
D.
Cosyns
B.
Vandenbossche
J.L.
Relation between patent foramen ovale and unexplained stroke
Am J Cardiol
 , 
1993
, vol. 
71
 (pg. 
596
-
598
)
89
Windecker
S.
Wahl
A.
Nedeltchev
K.
Arnold
M.
Schwerzmann
M.
Seiler
C.
, et al.  . 
Comparison of medical treatment with percutaneous closure of patent foramen ovale in patients with cryptogenic stroke
J Am Coll Cardiol
 , 
2004
, vol. 
44
 (pg. 
750
-
758
)
90
Schuchlenz
H.W.
Weihs
W.
Berghold
A.
Lechner
A.
Schmidt
R.
Secondary prevention after cryptogenic cerebrovascular events in patients with patent foramen ovale
Int J Cardiol
 , 
2005
, vol. 
101
 (pg. 
77
-
82
)
91
Schwerzmann
M.
Wiher
S.
Nedeltchev
K.
Mattle
H.P.
Wahl
A.
Seiler
C.
, et al.  . 
Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks
Neurology
 , 
2004
, vol. 
62
 (pg. 
1399
-
1401
)
92
Reisman
M.
Christofferson
R.D.
Jesurum
J.
Olsen
J.V.
Spencer
M.P.
Krabill
K.A.
, et al.  . 
Migraine headache relief after transcatheter closure of patent foramen ovale
J Am Coll Cardiol
 , 
2005
, vol. 
45
 (pg. 
493
-
495
)

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