Patent Foramen Ovale Closure For Secondary Prevention Research Articles

Venous thrombo-embolic events as the probable cause of arterial ischemic event in patients with patent foramen ovale

Abstract Introduction The origin of the emboli involved in patent foramen ovale (PFO)-related embolic events remains mostly unknown. Purpose To evaluate the venous thrombo-embolic (VTE) origin of patients with PFO-related embolic event. Methods Patients planned for PFO closure for secondary prevention of PFO-related arterial embolic event had a systematic venous thrombo-embolic (VTE) risk evaluation that included : an extensive questionnaire on past history of VTE events, clinical situations at high risk of VTE including complicated hemorrhoids, prior saphenectomy or venous sclerosis, varicocele, intrapelvic tumor, pregnancy, surgery or prolonged travel or presence of hyperthrombotic state (i.e., thrombophilia, active cancer or covid) and an abdominopelvic magnetic resonance venography (MRV) evaluation to identify any intrapelvic venous disease. Results From July 2020 to May 2023, 366 consecutive patients (Median age 51 [42-58] years, 42.9% female) were prospectively included. A past medical VTE events, a high risk VTE situation, a hyperthrombotic state and a pelvic venous abnormality on MRV were present in 8.5% (95%CI 6.0-11.8), 22.7% (95%CI 18.7-27.2), 7.1% (95%CI 4.9-10.2), and 36.3% (95%CI 31.6-41.4), respectively, and 58.5% (95%CI 53.4-63.4) of the patients presented at least one of the previous conditions. MRV identified various undiagnosed pelvic venous abnormalities with 20.0% of pelvic varices, 9.8% of May-Thurner-Cockett and 7.4% of Nutcracker phenomenons (Figure 1). Imaging abnormalities were more frequent among younger patients (aOR 1.02 95%CI:1.00-1.04) and women (aOR 1.94 ; 95%CI:1.25-3.02). Conclusion A majority of patients undergoing PFO closure for secondary prevention have a potential VTE source of paradoxical emboli suggesting that VTE events is the probable cause of arterial ischemic event in these patients.

Incidence, determinants, and impact of in-hospital complications during percutaneous patent foramen ovale closure

Abstract Introduction The incidence, types, determinants, and clinical impact of in-hospital complications after contemporary patent foramen ovale (PFO) percutaneous closure is unclear. Purpose To describe the incidence, types, determinants, and clinical impact of in-hospital complications after percutaneous PFO closure. Methods This study included consecutive patients undergoing PFO percutaneous closure for any indication in 18 centers in France and Italy from the ongoing AIR-FORCE registry. Periprocedural complications were collected, including death, bleeding, myocardial infarction (MI), supraventricular arrhythmia, pericardial effusion or tamponade, cardiac perforation, device embolization, intracardiac thrombus, venous thrombosis, atrioventricular block, brachial paraesthesia, oesophageal hematoma, and veno-arterial fistula. Determinants of periprocedural complications were evaluated using a logistic multivariate model. The clinical impact of periprocedural complications on cardiovascular events after discharge measured by the composite endpoint of death, stroke, transient ischemic attack, MI atrial arrhythmia, pulmonary embolism, deep veinous thrombosis, BARC ≥2 bleeding, or percutaneous or surgical re-intervention on the PFO) at longest follow-up was evaluated using a Cox model adjusted on age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, and shunt severity prior to closure. Results We analyzed a total of 2,799 patients undergoing PFO closure with median age 50.7 [41.7-58.6] years and 57.9% male. A total of 109 (3.9% 95%CI 3.2%-4.7%) patients presented at least one in-hospital complication, the most frequent being supraventricular arrhythmia in 39 (1.4% 95%CI 1.0-1.9%) patients and BARC bleeding type ≥2 in 26 (0.9% 95%CI 0.6-1.4%) patients. Determinants of in-hospital complications were older age (per on year aOR 1.02 95%CI 1.01-1.04), diabetes mellitus (aOR 2.58 95%CI 1.36-4.89) and PFO closure for secondary prevention of an arterial embolic event (aOR 2.12 95%CI 1.18-3.82). With a median follow-up of 1.1 [0.3-3.1] years, the occurrence of an in-hospital complication was associated with an increased risk of cardiovascular events after discharge (aHR 1.90 95%CI 1.26-2.89) (Figure 1). Conclusions Although relatively rare, the occurrence of in-hospital complication during PFO percutaneous closure is associated with an increased risk of cardiovascular events in the year following the procedure.

Stroke recurrence after transcatheter PFO closure in patients with cryptogenic stroke.

Patent foramen ovale (PFO) closure is recommended for secondary prevention of cryptogenic stroke. However, data on long-term results are limited. We aimed to evaluate safety and efficacy of transcatheter PFO closure and predict neurologic recurrence. Data from patients undergoing PFO closure between 2010 and 2015 was collected to assess the combined endpoint of transient ischemic attack (TIA), stroke, or death from stroke at short- and long-term follow-up. 330 patients were included, mean age was 49 (±12) years and 55.5% were male. Before PFO closure, 86% experienced a stroke and 19% multiple neurological events. Procedure-related complications occurred in 2.4% of patients. Over a median follow-up of 10 years, the combined endpoint occurred in 3.6%, with a recurrence rate of 0.38 per 100 patient-years. Freedom from the combined endpoint at 5 and 10 years was 97.5% and 96.2%, respectively. New-onset atrial fibrillation was detected in 3%. The Risk of Paradoxical Embolism (RoPE) score (adjHR: 0.68; p=0.032), the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system (adjHR: 0.37; p=0.042), and a history of prior neurological events (adjHR: 9.94; p<0.001) were independent predictors of future recurrent neurologic events. Age, sex, and cardiovascular risk factors did not influence outcomes. In this real-world cohort, transcatheter PFO closure was associated with low long-term recurrence of neurologic events, especially cryptogenic strokes. The RoPE score, the PASCAL score and history of previous neurological events were predictive of recurrent events. This study supports the safety and efficacy of PFO closure for secondary prevention of cryptogenic strokes, and underscores the importance of patient selection.

P466 PREDICTORS OF RECURRENT CEREBRAL ISCHEMIA AFTER PATENT FORAMEN OVALE CLOSURE: A SINGLE CENTER EXPERIENCE WITH A LONG–TERM FOLLOW–UP

Abstract Aims Transcatheter patent foramen ovale (PFO) closure has been shown to lower recurrent stroke in patients with cryptogenic stroke (CS) or transient ischemic attack (TIA) with an indication for closure. However, the incidence of recurrent stroke is not negligible and underlying pathogenic mechanisms remain largely unknown. We sought to evaluate the prevalence of recurrent CS/TIA and to assess its predictors after transcatheter PFO closure. Methods We enrolled consecutive patients who underwent PFO closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2006 and 2021. For each subject, CS/TIA index event was diagnosed after exclusion of alternative etiologies, PFO features were characterized by transesophageal echocardiography (TEE), the Risk of Paradoxical Embolism (ROPE) score was retrospectively assessed and the presence of migraine was investigated. Clinical follow–up was scheduled with outpatient visits at 3 – 12 months and yearly thereafter device implantation; the primary outcome was the recurrence of any ischemic neurological event. Results We enrolled a total of 169 patients with mean Risk of Paradoxical Embolism (ROPE) score at hospital admission of 6.4 ± 1.5. The primary indication for PFO closure was previous CS (94 [55.6%] subjects), followed by TIA (75 [44.4%]). Among patients with complete outcome data (n= 154), after a median follow–up of 112 months, recurrent cerebral ischemia occurred in 13 [8.4%], with an annualized rate of 0.92/100 patients. The presence of obesity [OR 5.268, p = 0.018], ROPE score &amp;lt; 7 [OR 5.991, p = 0.035] and migraine [OR = 5.932 p = 0.012] were independent positive predictors of recurrent stroke/TIA after PFO closure. Conclusion In our study, recurrent cerebral events after PFO closure were not negligible, with an annualized rate of 0.92/100 patients, consistent with prior research. Multiple heterogeneous predictors were identified: the presence of obesity, ROPE score &amp;lt; 7 and migraine were independent positive predictors of recurrent stroke/TIA after PFO closure

215 PREDICTORS OF RECURRENT CEREBRAL ISCHEMIA AFTER PATENT FORAMEN OVALE CLOSURE: A SINGLE CENTER OBSERVATIONAL STUDY

Abstract Background Transcatheter patent foramen ovale (PFO) closure is an effective therapy in patients with cryptogenic stroke (CS) or transient ischemic attack (TIA) and evidence of PFO. However, the incidence of recurrent cerebral ischemia is not negligible and underlying pathogenic mechanisms remain largely unknown. We sought to evaluate the magnitude of the problem and to assess predictors of recurrent stroke/TIA after transcatheter PFO closure. Methods We enrolled non-randomized consecutive patients who underwent PFO closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2004 and 2021. Clinical, echocardiographic and procedure-related features were collected for each patient. The incidence of recurrent ischemic neurological events was assessed at follow-up. Results We enrolled a total of 154 patients. The primary indication for PFO closure was previous stroke (85 [55.2%] subjects) and a third of patients (51 [33.1%]) suffered from migraine, 22 [14.3%] with and 29 [18.8%] without aura. Moreover, mean Risk of Paradoxycal Embolism (ROPE) score at hospital admission was 6.4 ± 1.5. After a median follow-up of 112 months, the incidence of recurrent cerebral ischemia occurred in 13 [8.4%] patients, with an annualized rate of 0.92/100 patients. The presence of migraine, obesity and ROPE &amp;lt; 7 were independent positive predictors of recurrent stroke/TIA. Conclusion The presence of obesity, a familiar history of CVD, ROPE &amp;lt; 7 and migraine were independent positive predictors of recurrent ischemic neurological events after PFO closure.

Outcomes Following Patent Foramen Ovale Percutaneous Closure According to the Delay From Last Ischemic Event.

Randomised controlled trials evaluating percutaneous closure of patent foramen ovale (PFO) have included only patients with a recent embolic event. We aimed to evaluate outcomes after percutaneous PFO closure according to the delay from the last embolic episode. This international ambispective cohort included consecutive patients from 2 centres in France and Canada undergoing PFO closure for secondary prevention of a paradoxical embolic event. The primary end point was the composite of stroke or transient ischemic attack (TIA). A logistic regression model was used to evaluate determinants of late PFO closure procedures. A total of 1179 patients (mean age 49 ± 12.7 years; 44.4% female) underwent PFO closure from 2001 to 2021. The median delay from last embolic event to procedure was 6.0 (interquartile range 3.4-11.2) months. The determinants of late PFO closure procedure were the centre (France vs Canada; adjusted odds ratio [aOR] 1.65, 95% confidence interval [CI] 1.25-2.19), year of procedure (since 2018 vs before 2018; aOR 1.43, 95% CI 1.08-1.90), female sex (aOR 1.63, 95% CI 1.28-2.07), and lower risk of paradoxical embolism score (aOR 1.10, 95% CI 1.03-1.19). After a median follow-up of 2.61 (1.13-7.25) years, the incidence rate of first stroke or TIA did not differ between early and late PFO procedures, with 0.51 vs 0.29 events per 100 patient-years, respectively (incidence rate ratio 1.74, 95% CI 0.66-5.08; P= 0.24), and the timing of PFO closure was not associated with the occurrence of stroke or TIA in univariate analysis (hazard ratio 0.54, 95% CI 0.22-1.34) for late vs early closure). This analysis provides indirect evidence that the delay from the last ischemic event does not affect outcomes after PFO closure for secondary prevention.

Reverse takotsubo cardiomyopathy caused by patent foramen ovale-related cryptogenic stroke: a case report.

BackgroundReverse takotsubo cardiomyopathy (rTTC) is recognized as an atypical type of TTC. It has been suggested that neurological events are typical trigger of rTTC, especially in young individuals.Case summaryIn this case report, we describe a 16-year-girl who presented with neurological deficits due to embolic stroke and acute heart failure. Transthoracic echocardiography on admission revealed a severely reduced left ventricular (LV) function with akinesis of basal to mid LV, but normal contraction in apex. Coronary computed tomography angiography confirmed unobstructed coronary arteries. Two weeks later, her LV wall motion and ejection fraction were completely normalized. Transthoracic echocardiography and transoesophageal echocardiography demonstrated no evidence of intracardiac thrombus but showed a patent foramen ovale (PFO) with large shunt. After thorough work-up and brain–heart team discussion, we concluded that the patient developed rTTC due to cryptogenic stroke related with her PFO. She underwent percutaneous PFO closure for secondary prevention with good clinical course.DiscussionReverse TTC is a rare condition. It should be considered in stroke patients with acute heart failure. Quick diagnosis and management with brain–heart team is crucial for better prognosis.

STEMI and CVA in Hypercoagulable State with Ostium Secundum Defect.

Atrial septal defect (ASD) is a risk factor for multiple vascular thrombotic events, which can occur either sequentially or simultaneously. In this report we present a case of ST-elevation myocardial infarction (STEMI) and cerebrovascular accident (CVA). The severity of adverse cardiovascular or cerebrovascular events can be increased by the presence of specific type of ASD, such as a patent foramen ovale (PFO) or osteum secundum defect. This case report discusses a unique presentation of a 48-year old male on warfarin therapy for a history of cerebral venous thrombosis (CVT) who subsequently presented with simultaneous STEMI with CVA, and who was incidentally found to have an ostium secundum defect on echocardiography. He was emergently taken for cardiac catheterization, which revealed significant proximal LAD occlusion. There has been a long standing debate within the international scientific communities regarding the therapeutic benefit of PFO closure for long-term secondary prevention of recurrence CVA. We discuss the different points of view regarding PFO closure for secondary prevention of CVA with a review of the literature on this rather controversial topic.

Device Closure of Patent Foramen Ovale for Cryptogenic Stroke: Patient Selection and Outcomes According to New Randomized Trials.

This review summarizes the most recent randomized clinical trials that studied the role of device-mediated patent foramen ovale (PFO) closure in patients after an ischemic stroke presumed to have been caused by a paradoxical embolism. Three major randomized trials published in 2017 studied the strategy of using PFO closure for secondary prevention in patients between the ages of 18 and 60 who presented with an index stroke having characteristics of an embolic mechanism. All patients had a PFO that potentially could have enabled paradoxical embolism and other causes of stroke were excluded by a thorough neurologic and cardiac evaluation. Patients were randomized to PFO closure versus medical therapy alone using a variety of guideline-recommended medications. After multiple years of follow-up, all three trials showed superiority in the device arm versus the medical arm with a relative risk reduction of recurrent stroke from 46 to 100% and an absolute recurrent stroke reduction from 0.49 to 1.32% per year. Complications related to the procedure and the device were infrequent and mostly transient. These results have transformed the care of these patients, lead to FDA approval of two PFO closure devices, and started the process of updating guidelines. Patient selection is critically important since the presence of a PFO may be incidental. Therefore, both a neurologist and a cardiologist, who can also perform this procedure safely and effectively, should complete the initial evaluation and discuss their findings and recommendations with the patient as part of a shared decision-making process. There are remaining questions regarding how these trial results relate to older patients, patients with overt venothrombotic disease, and those with thrombophilia.

SCAI expert consensus statement on operator and institutional requirements for PFO closure for secondary prevention of paradoxical embolic stroke: The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists.

Until recently, evidence to support Patent Foramen Ovale (PFO) closure for secondary prevention of recurrent stroke has been controversial. Publication of high-quality evidence from randomized clinical trials and the subsequent FDA approval of two devices for percutaneous PFO closure is expected to increase the volume of PFO closure procedures not only in the United States but worldwide. As this technology is disseminated broadly to the public, ensuring the safe and efficacious performance of PFO closure is essential to mitigate risk and avoid unnecessary procedures. This document, prepared by a multi-disciplinary writing group convened by the Society for Cardiovascular Angiography and Interventions and including representatives from the American Academy of Neurology, makes recommendations for institutional infrastructure and individual skills necessary to initiate and maintain an active PFO/stroke program, with emphasis on shared decision making and patient-centered care.

Meta-analysis of Randomized Controlled Trials on Patent Foramen Ovale Closure Versus Medical Therapy for Secondary Prevention of Cryptogenic Stroke

The optimal management of patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) remains controversial. We conducted a meta-analysis to assess the effect of PFO closure for secondary prevention of stroke on patients with CS. We searched the literature for randomized control trials assessing the recurrence of stroke after PFO closure compared with medical therapy (antiplatelet and/or anticoagulation). Five randomized control trials with a total of 3,440 patients were included. The mean age was 45.2 ± 9.7 years and follow-up duration ranged from 2.0 to 5.9 years. PFO closure significantly reduced the risk of stroke compared with the medical therapy (2.8% vs 5.8%; relative risk [RR] 0.48, confidence interval [CI] 0.27 to 0.87, p = 0.01, I2 = 56%). The number needed to treat for stroke prevention was 10.5. PFO closure was associated with an increased risk of atrial fibrillation compared with medical therapy (4.2% vs 0.7%; RR 4.55, CI 2.16 to 9.6, p = 0.0001, I2 = 25%). There was no significant difference in all-cause mortality (RR 1.33, CI 0.56 to 3.16, p = 0.52, I2 = 0%), as well as no difference in bleeding risk between the 2 groups (RR 0.94, CI 0.49 to 1.83, p = 0.86, I2 = 29%). In conclusion, our meta-analysis demonstrates that PFO closure is associated with significantly lower risk of recurrent stroke in patients with PFO and CS compared with medical therapy. However, atrial fibrillation was more common among closure patients.

Cryptogenic Stroke and PatentForamenOvale.

Nearly one-half of patients with cryptogenic stroke have a patent foramen ovale (PFO). The dilemma of whether to close these PFOs percutaneously, in an effort to reduce the risk of recurrent paradoxical embolism, has been a matter of ongoing debate for more than a decade. Early randomized clinical trials failed to demonstrate a significant benefit of percutaneous PFO closure for secondary prevention of cryptogenic stroke in an intention-to-treat analysis. The long-term follow-up data from the RESPECT trial and 2 new randomized trials (CLOSE and REDUCE) have clarified these findings. They showed thatwith good patient selection, transcatheter PFO closure significantly reduces the risk of recurrent stroke compared withmedical therapy in patients with cryptogenic stroke, with no increased risk of serious adverse events or influence onmajor bleeding.

Closure of patent foramen ovale for secondary prevention of cerebrovascular events

Stroke is the most debilitating cardiovascular event. It has a variety of causes that may be present simultaneously. In young or otherwise healthy people a patent foramen ovale (PFO) is increasingly searched for. In stroke of the elderly atherosclerosis and atrial fi brillation are in the foreground but the PFO should not be ignored. The risk of a PFO related stroke over time is controversial and so is its prevention by PFO closure. Percutaneous PFO closure is a minimally invasive procedure which can be performed with high success and low morbidity. We review the rationale for PFO closure for secondary prevention of embolic events.

Recurrent events after percutaneous closure of patent foramen ovale

To determine the incidence of symptomatic recurrent embolic events after patent foramen ovale (PFO) closure and potential causes for these events. It is well-known that cerebral or other embolic events may occur after PFO closure. This is a retrospective analysis of consecutive patients who underwent PFO closure for secondary prevention of embolic events at a single institution. 1,930 patients (mean age of 50 ± 13.3 years) underwent transcatheter PFO closure. Complete closure occurred in 92%. The annual recurrence rate of embolic events before PFO closure was 22.4% (785 events in 3,497 patient-years). During follow-up (mean 39 months), 63 recurrent events were documented: 25 strokes, 36 transient ischemic attacks (TIAs), and 2 peripheral embolic events. The overall annual recurrence rate after the procedure was 1% per year (63 events in 6,211 patient-years). The majority of events occurred in patients without residual shunts (54/63). There was no significant association between the presence of a residual shunt and recurrent events [hazard ratio (HR) 1.7; 95% confidence interval (CI) 0.8-3.6, P = 0.16]. The most common cause for recurrent events was atherosclerosis. Nine out of 63 events were considered likely or possible paradoxical embolism due to residual shunt [stroke (2), TIA (5), and peripheral embolism (2)]. After PFO closure, the annual rate of events potentially related to paradoxical embolism was 0.14% (9 events in 6,211 patient-years). The incidence of symptomatic embolic events after PFO closure is low. Most recurrent events are related to coexistent conditions associated with thromboembolic risk rather than residual shunts.

Transcatheter Closure of Patent Foramen Ovale in Chinese Patients With Paradoxical Embolism - Immediate Results and Long-Term Follow-up -

The aim of the present study was to assess immediate and long-term clinical outcome of Chinese patent foramen ovale (PFO) patients with paradoxical embolism who underwent transcatheter PFO closure. One hundred and ninety-two patients underwent transcatheter PFO closure for secondary prevention of thromboembolic events (TE). During the procedure, 7 patients had frequent atrial premature beats or transient atrial tachycardia in implantation and 1 patient had a transitory ST-elevation in leads II, III and aV(F). These complications converted spontaneously after a few minutes. No cases of procedure-related death or TE were observed during hospitalization. Minor adverse events, including chest discomfort (11%), palpitations (25%) and dyspnea (1%) were reported within 1 month of the procedure. These symptoms had disappeared in most patients by 6-month follow-up. One patient had a new occurrence of migraine at 27 months after the implantation. Within a median follow-up of 49 ± 8 months, no residual shunt of the atrial level was identified and correct positioning of the device was confirmed on transthoracic echocardiography in all patients. No death related to any cause or recurrent TE were recorded. Transcatheter PFO closure is a minimally invasive procedure with a high success rate, low complication rate and an excellent long-term outcome, and appears to be a wise approach for secondary prevention of recurrent embolic events in symptomatic patients.

Antiphospholipid antibodies are common in patients referred for percutaneous patent foramen ovale closure.

Very little is known about any interaction between patent foramen ovale (PFO) and various hypercoagulable disorders that have been associated with cryptogenic stroke. Percutaneous PFO closure for secondary prevention of paradoxical thromboembolization is receiving increasing attention. Hypercoagulability may affect the potential risks and expected benefits of percutaneous PFO closure. Consecutive patients undergoing percutaneous PFO closure at a single center were screened for the presence of antiphospholipid antibodies, elevated lipoprotein(a), hyperhomocysteinemia, and dysfibrinogenemia. Sixteen of 34 patients (47%) with complete arterial hypercoagulability screening had laboratory evidence of arterial hypercoagulability. Thirteen of these patients (38%) had antiphospholipid antibodies. Antiphospholipid antibodies appear to be common in patients referred for percutaneous PFO closure for secondary prevention of systemic thromboembolic events. Thorough testing based on established recommendations is warranted. Further studies are needed regarding the interaction between PFO and various hypercoagulable disorders that have been associated with cryptogenic stroke.