Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events

doi:10.1016/0002-9149(92)90210-P

The American Journal of Cardiology

Volume 70, Issue 6, 1 September 1992, Pages 668-672

https://doi.org/10.1016/0002-9149(92)90210-P Get rights and content

Abstract

This study compares the value of transthoracic (TTE) and transesophageal (TEE) color Doppler and contrast echocardiography for detecting a patent foramen ovale (PFO). A total of 238 patients were studied: 74 patients with a history of otherwise unexplained ischemic stroke, transient cerebral ischemic attacks or peripheral embolic events (group A), 48 with a history of similar episodes explained by other cardiac abnormalities (group B), and 116 with no embolic events (group C). A PFO was detected by contrast TEE in 50 of 238 patients (21%) compared with 45 patients (19%) by color Doppler TTE. In a subgroup of 198 patients, TEE results could be compared with TTE findings. No patient had a PFO identified by color Doppler TTE. Contrast TTE detected a PFO in 15 patients (8%) compared with contrast TEE which demonstrated a PFO in 44 of 198 patients (22%) (p < 0.001). Prevalence of PFO by TEE was 22, 21 and 22% in groups A, B and C, respectively. A PFO was present in 50% of patients aged <40 years and otherwise unexplained ischemic stroke; this percentage was higher (p < 0.05) than corresponding values found in all other groups. Thus, contrast and color Doppler TEE are significantly superior to TTE for detecting PFO. The prevalence of PFO is significantly increased in young adults with otherwise unexplained ischemic stroke.

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Cited by (307)

Diagnostic Accuracy of Transthoracic Echocardiography With Contrast for Detection of Right-to-Left Shunt: A Systematic Review and Meta-analysis
2022, Canadian Journal of Cardiology
Citation Excerpt :
The area under the hierarchical summary receiver operator characteristic curve was 0.83 (Fig. 3). The specificity of TTE for detection of RLS with colour flow Doppler in the absence of contrast use ranged from 0 to 35%.14,15,17,19,24,27,34 A total of 27 studies were published in the year 2000 or after (Fig. 4A).7,19-44
The clinical utility of transthoracic echocardiography with contrast (TTE-C) for detection of right-to-left shunt (RLS) remains unknown. In this meta-analysis we evaluated the accuracy of TTE-C for RLS diagnosis compared with transesophageal echocardiography (TEE) as the reference standard.
A systematic review and meta-analysis was performed using a search of MEDLINE, EMBASE, PubMed, and Cochrane library databases. Studies that were included provided data to assess sensitivity and specificity of TTE-C compared with TEE for RLS detection.
A total of 35 studies, involving 4209 patients, were analyzed. The average patient age was 49.1 ± 11.2 years and 53.9% were male. For RLS detection in the entire cohort, TTE-C sensitivity was 73% (95% confidence interval [CI], 66%-80%) and specificity was 94% (95% CI, 92%-96%). The sensitivity of TTE-C was 80% (95% CI, 74%-86%) in studies published in 2000 or later compared with 51% (95% CI, 36%-65%) in those published before 2000. In studies that used harmonic imaging, TTE-C sensitivity was 82% (95% CI, 77%-87%) and specificity was 95% (95% CI, 93%-97%). Among those with patent foramen ovale closure indications, TTE-C sensitivity was 74% (95% CI, 59%-89%) and specificity was 98% (95% CI, 95%-100%). In patients in whom RLS was diagnosed using a guideline-suggested 3 cardiac cycle cutoff, TTE-C sensitivity was 75% (95% CI, 66%-83%) and specificity was 94% (95% CI, 92%-97%). Provocative manoeuvres increased sensitivity by approximately 40%.
TTE-C offers excellent specificity and moderate sensitivity for RLS diagnosis compared with TEE, and it might therefore serve as an initial screening modality for selected patients with a high likelihood of having RLS and for indications for treatment.
L’utilité clinique de l’échocardiographie transthoracique avec contraste (ETT-C) dans la détection du shunt gauche-droit demeure inconnue. Dans cette méta-analyse, nous avons évalué l’exactitude du diagnostic par ETT-C du shunt gauche-droit comparativement à l’échocardiographie transoesophagienne (ETO), l’outil diagnostique de référence.
Un examen systématique et une méta-analyse ont été réalisés à partir des bases de données MEDLINE, EMBASE, PubMed et Cochrane Library. Les études incluses fournissaient des données permettant d’évaluer la sensibilité et la spécificité de l’ETT-C comparativement à l’ETO pour la détection du shunt gauche-droit.
Au total, 35 études menées auprès de 4 209 patients ont été analysées. L’âge moyen des patients était de 49,1 ± 11,2 ans, et 53,9 % des patients étaient des hommes. Pour la détection du shunt gauche-droit dans toute la cohorte, la sensibilité de l’ETT-C était de 73 % (intervalle de confiance [IC] à 95 % : de 66 à 80 %) et la spécificité était de 94 % (IC à 95 % : de 92 à 96 %). La sensibilité de l’ETT-C était de 80 % (IC à 95 % : de 74 à 86 %) pour les études publiées en 2000 ou après, et de 51 % (IC à 95 % : de 36 à 65 %) dans les études publiées avant 2000. Dans les études utilisant l’imagerie harmonique, la sensibilité de l’ETT-C était de 82 % (IC à 95 % : de 77 à 87 %) et la spécificité, de 95 % (IC à 95 % : de 93 à 97 %). Chez les patients pour qui la fermeture de la persistance du foramen ovale était indiquée, la sensibilité de l’ETT-C était de 74 % (IC à 95 % : de 59 à 89 %) et la spécificité de 98 % (IC à 95 % : de 95 à 100 %). Chez les patients dont le shunt gauche-droit a été diagnostiqué à l’aide de trois moments précis du cycle cardiaque, conformément aux lignes directrices, la sensibilité de l’ETT-C était de 75 % (IC à 95 % : de 66 à 83 %) et la spécificité, de 94 % (IC à 95 % : de 92 à 97 %). Les manœuvres de provocation augmentaient la sensibilité d’environ 40 %.
L’ETT-C a une excellente spécificité et une sensibilité modérée dans le diagnostic du shunt gauche-droit comparativement à l’ETO. Il pourrait donc servir d’outil de dépistage initial pour certains patients chez qui un shunt gauche-droit est très probable et chez qui le traitement est indiqué.
Cardiac Diseases
2021, Stroke: Pathophysiology, Diagnosis, and Management
Stroke due to cardiac embolism is commonly of sudden onset, is more prone to hemorrhagic transformation, and is associated with higher mortality than other stroke subtypes. The etiologic workup for stroke due to a cardiogenic source is crucial in determining appropriate secondary prevention. Anticoagulation is the mainstay of therapy for patients with cardioembolic stroke secondary to atrial fibrillation, absent any contraindications. Some cardioembolic sources, including infective endocarditis and some intracardiac tumors, present a contraindication to treatment with anticoagulation.
Ischaemic Stroke and the Echocardiographic “Bubble Study”: Are We Screening the Right Patients?
2019, Heart Lung and Circulation
Patent foramen ovale (PFO) is a potential mechanism for paradoxical embolism in cryptogenic ischaemic stroke or transient ischaemic attack (TIA). PFO is typically demonstrated with agitated saline (“bubble study”, BS) during echocardiography. We hypothesised that the BS is frequently requested in patients that have a readily identifiable cause of stroke, that any PFO detected is likely incidental, and its detection often does not alter management.
This was a retrospective observational study of patients with recent ischaemic stroke/TIA referred for a BS. Patient demographics, stroke risk factors, vascular/cerebral imaging results and transoesophageal echocardiogram (TOE) reports were recorded. A “modified” Risk of Paradoxical Embolism (RoPE) score was calculated. Change in management was defined as antiplatelet/anticoagulant therapy alteration or referral for PFO closure. Bubble Study complications were recorded.
Among 715 patients with ischaemic stroke/TIA referred for a BS, 8.7% had atrial fibrillation and 9.2% had carotid stenosis ≥70%. At least three stroke risk factors were present in 39.3% and only 47.1% of patients screened had a “modified” RoPE score of >5. A PFO was detected in 248 patients of whom only 31% (77/248) had a subsequent change in management. Of BS performed, 1/924 patients (0.1%) suffered a TIA as a complication.
The echocardiographic BS is frequently performed in patients that have a readily identifiable cause of stroke and whose PFO unlikely relates to the stroke/TIA. Bubble Study findings resulted in a change in management in the minority. The procedure is safe but the complication rate warrants informed consent.
Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling stroke at older ages: a population-based study, systematic review, and meta-analysis
2018, The Lancet Neurology
Percutaneous closure of patent foramen ovale (PFO) has been shown to be superior to medical treatment alone for prevention of recurrent stroke after cryptogenic transient ischaemic attack or non-disabling stroke in patients aged 60 years or younger. The justification for trials in older patients with transient ischaemic attack or stroke depends on whether PFO is shown to be associated with cryptogenic events at older ages, for which existing evidence is conflicting, and on the population burden of PFO-associated events. Therefore, we did a population-based screening study using contrast-enhanced transcranial Doppler (bubble-TCD) to detect probable PFO as indicated by a right-to-left shunt (RLS); we also did a systematic review and meta-analysis to compare our results with previous studies.
In this population-based study, nested in the Oxford Vascular Study (OXVASC), we established the prevalence of any RLS, and of large RLS (>20 microbubbles), in consecutive patients attending a rapid-access transient ischaemic attack and stroke clinic, or at 1-month follow-up after stroke unit admission, with transient ischaemic attack or non-disabling ischaemic stroke, comparing cryptogenic events with those of known cause (according to Trial of Org 10172 in Acute Stroke Treatment [TOAST] criteria). We stratified participants by age, and extrapolated data to the UK population. We also did a systematic review of published studies of PFO prevalence (using transthoracic or transoesophageal echocardiography or bubble-TCD) according to stroke subtype, which included older patients and reported age-specific results, and determined by meta-analysis (including the OXVASC data) the pooled odds ratio (95% CI) of finding PFO of any size in cryptogenic events compared with events of known cause, stratified by screening modality (transthoracic or transoesophageal echocardiography or bubble-TCD). The study protocol is registered with PROSPERO, number CRD42018087074.
Among 572 consecutive patients with transient ischaemic attack or non-disabling stroke between Sept 1, 2014, and Oct 9, 2017 (439 [77%] patients aged >60 years, mean age 70·0 years [SD 13·7]), bubble-TCD was feasible in 523 patients (91%) of whom 397 were aged older than 60 years. Compared with those with transient ischaemic attack or stroke of known cause, patients with cryptogenic events had a higher prevalence of RLS overall (odds ratio [OR] 1·93, 95% CI 1·32–2·82; p=0·001), and in those aged older than 60 years (2·06, 1·32–3·23; p=0·001). When we pooled the OXVASC data with that from two previous smaller studies of bubble-TCD in patients aged 50 years or older, we found an association between RLS and cryptogenic events (OR 2·35, 95% CI 1·42–3·90; p=0·0009; p_{heterogeneity}=0·15), which was consistent with the equivalent estimate from transoesophageal echocardiography studies (2·20, 1·15–4·22; p=0·02; p_{heterogeneity}=0·02). No data on large RLS in patients with TOAST-defined cryptogenic events compared with other events were available from previous studies, but we found no evidence that the association was diminished in such cases. Of 41 patients with large RLS and cryptogenic transient ischaemic attack or non-disabling stroke in our study, 25 (61%) were aged older than 60 years, which extrapolates to 5951 patients per year in the UK (data from mid-2016).
Bubble-TCD was feasible in most older patients with transient ischaemic attack or non-disabling stroke, the association of RLS with cryptogenic events remained at older ages, and the population burden of PFO-associated events is substantial. Randomised trials of PFO closure at older ages are required and should be feasible.
National Institute for Health Research, Oxford Biomedical Research Centre, Wellcome Trust, and Wolfson Foundation.
Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial
2018, Journal of the American College of Cardiology
Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates.
This study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography.
Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction–defined major bleeding during 2 years of follow-up.
From September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction–defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1).
PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)
Treatment options for recurrent thromboembolism in patients with cryptogenic cerebrovascular events: Medical therapy versus device closure or surgical repair of patent foramen ovale
2018, Cardiovascular Thrombus: From Pathology and Clinical Presentations to Imaging, Pharmacotherapy and Interventions
Patent foramen ovale (PFO) is a cardiac anatomic structure frequently found in the general population, with an estimated prevalence of 25%–30%. PFO has been linked to increased risk for thromboembolism, including ischemic systemic and cerebrovascular events. The risk stems from the potential of paradoxical embolization of thrombi originating from the venous system through the anatomic patency onto the left-heart circulation. In fact, PFO has been found in up to 40%–50% of adult patients with stroke of unknown origin (cryptogenic) using transesophageal echocardiography and serves as an independent predictor of cryptogenic stroke. To decrease the risk of recurrent cerebrovascular events in this population, multiple treatment strategies, including medical therapy, device closure, and surgical repair, have been initiated and studied. Although data on the medical management of cryptogenic stroke in the setting of PFO are limited, the available evidence supports the notion that both aspirin (81–325 mg/day) and warfarin (international normalized ratio goal 2–3) decrease the risk of recurrent cryptogenic stroke in patients with PFO, with the latter potentially achieving lower recurrence rates. However, the preferred therapy, the ideal antiplatelet dosing, the duration of therapy, and the benefit of newer antiplatelet agents (P2Y12 inhibitors) are still unknown. Current guidelines denote that there is insufficient evidence to establish whether anticoagulation is superior or equivalent to aspirin. Nevertheless, the guidelines recommend at least antiplatelet therapy for patients with PFO and prior ischemic cerebrovascular events.
A large body of literature supports the application of percutaneous devices for closure of PFO, as it decreases the incidence of recurrent stroke in patients with cryptogenic stroke. Two PFO closure devices, the Amplatzer PFO occluder and the GORE Cardioform, have shown a 45% and 76% risk reduction, respectively, in randomized controlled trials, compared with medical therapy alone. The Amplatzer PFO occluder is already US Food and Drug Administration approved for this indication (since 2016) and the GORE Cardioform closure device is expected to receive approval by the end of 2017. Accordingly, the guidelines stand to change in the near future to include PFO device closure in addition to standard medical therapy for the management of patients with cryptogenic stroke. Surgical closure of PFO appears to be a safe approach; nevertheless, conflicting data exist regarding the efficacy of elimination of an interatrial shunt, and a valid concern for recurrent cerebrovascular events remains. As no direct comparison is currently available between the three main management approaches, there are no clear advantages of surgery over medical therapy or over percutaneous device closure. Accordingly, a surgical approach should be considered as the last therapeutic option, limited to select patients who sustained cryptogenic stroke with a high risk of recurrent events in whom both device closure and medical therapy have failed or are contraindicated.

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Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events

Abstract

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Soc Echo

Am J Cardiol

Am J Cardiol

Lancet

Lancet

J Am Coll Cardiol