Predictors of recurrent cerebral ischemia after patent foramen ovale closure: A single center observational study.

OBJECTIVES: Transcatheter patent foramen ovale closure lowers recurrent stroke in patients with cryptogenic stroke or transient ischemic attack with an indication for closure. However, the incidence of recurrent stroke is not negligible and underlying pathophysiology remains largely unknown. We sought to evaluate the prevalence of recurrent ischemic neurological events and to assess its predictors after transcatheter patent foramen ovale closure. METHODS: We enrolled consecutive patients who underwent patent foramen ovale closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2006 and 2021. Clinical 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 169 patients with mean Risk of Paradoxical Embolism score at hospital admission of 6.4 ± 1.5. The primary indication was previous cryptogenic stroke (94 [55.6 %] subjects), followed by transient ischemic attack (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], Risk of Paradoxical Embolism score < 7 [OR 5.991, p = 0.035] and migraine [OR = 5.932 p = 0.012] were independent positive predictors of recurrent stroke/ transient ischemic attack after patent foramen ovale closure. CONCLUSIONS: The presence of obesity, Risk of Paradoxical Embolism score < 7 and migraine were independent positive predictors of recurrent ischemic neurological events after patent foramen ovale closure.

Detecting Patent Foramen Ovale after Cryptogenic Stroke - A Single Center Experience in Taiwan.

Background: Cryptogenic strokes related to a patent foramen ovale (PFO) in young patients have been reported. Percutaneous transcatheter occlusion is considered a safe and effective method for achieving PFO closure. Here, we present our experience of PFO closure in a series of young patients diagnosed with cryptogenic stroke. Methods: This was a retrospective study of 62 patients who were younger than 60 years of age and previously diagnosed with cryptogenic stroke. They underwent cardiac catheterization for the diagnosis of PFO and/or device closure. Bubble and echocardiography studies, the patients' characteristics, complications, and recurrence of stroke were recorded. The Risk of Paradoxical Embolism (RoPE) score index was also calculated. Results: Patients with a bubble study grade greater than grade I were likely to have PFO (odds ratio: 22.2 [95% confidence interval: 1.2-412.3]). The mean RoPE score in the PFO closure group was 7.18. Two patients (3.9%) developed atrial fibrillation during the procedure. Ischemic stroke recurred in two patients (3.3%). Conclusions: Combining a bubble study with transcranial Doppler ultrasound or transthoracic echocardiography may increase the validity of PFO diagnosis. Because of the low recurrence rate of stroke and low complication rate, it is important to identify PFO patients with a bubble study grade greater than grade I. Closure of PFO may be a good strategy for preventing recurrent stroke among such patients.

Carotid Atherosclerosis and Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

BACKGROUND: Carotid atherosclerosis and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. AIM: To investigate the relation between carotid atherosclerosis and likely pathogenic PFO in patients with ESUS. We hypothesized that ipsilateral carotid atherosclerotic plaques are less prevalent in ESUS with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO. METHODS: The presence of PFO was assessed with transthoracic echocardiography with microbubble test and, when deemed necessary, through trans-oesophageal echocardiography. The presence of PFO was considered as likely incidental if the RoPE (Risk of Paradoxical Embolism) score was 0-6 and likely pathogenic if 7-10. RESULTS: Among 374 ESUS patients (median age: 61years, 40.4% women), there were 63 (49.6%) with likely incidental PFO, 64 (50.4%) with likely pathogenic PFO and 165 (44.1%) with ipsilateral carotid atherosclerosis. The prevalence of ipsilateral carotid atherosclerosis was lower in patients with likely pathogenic PFO (7.8%) compared to patients with likely incidental PFO (46.0%) or patients without PFO (53.0%) (p<0.001). After adjustment for multiple confounders, the prevalence of ipsilateral carotid atherosclerosis remained lower in patients with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO (adjusted OR=0.32, 95%CI:0.104-0.994, p=0.049). CONCLUSIONS: The presence of carotid atherosclerosis is inversely related to the presence of likely pathogenic PFO in patients with ESUS.

Correlations between serum homocysteine levels and RoPE score in patients with patent foramen ovale.

The pathophysiological relationship between elevated serum homocysteine (Hcy) levels and patent foramen ovale (PFO) has not yet been completely clarified. In the present study, we assess the correlation between serum homocysteine levels and the RoPE score in PFO patients. We retrospectively reviewed clinical and instrumental data of 244 subjects referred to a single tertiary center for PFO evaluation and/or treatment between January 2010 and January 2018,stratified as closure and control group, respectively. Patients in the closure group had an higher serum Hcy levels compared to the control group (28.5 ± 8.5 vs 10.2 ± 6.6 µg/dL, p < 0.0001). A significant direct correlation was observed between serum Hcy levels and the RoPE Score in the entire population. A positive significant correlation continued to exist also in the closure and control groups (r = 0.472, p < 0.0001 and r = 0.378, p < 0.0001, respectively). A receiver operating characteristics curve identified the optimal cutoff value of homocysteinemia as a predictor of RoPE score > 7 in the closure group (AUC 0.90, 95% CI 0.81-0.94, p < 0.0001) when 19.5 µg/dL. Multivariate logistic regression analysis demonstrated that an Hcy serum level ≥ 19.5 µg/dL predict an RoPE score > 7 (OR 3.21, 95% CI 2.82-3.26, p < 0.0001) in closed patients independently from the presence of permanent right-to-left (RLS) (OR 2.28, 95% CI 2.01-2.43, p = 0.001) and atrial septal aneurysm (ASA) (OR 3.04, 95% CI 2.64-3.51, p < 0.0001). Serum homocysteine levels in PFO patients are positively correlated with the RoPE score. Moreover, a homocysteinemia ≥ 19.5 µg/dL predicts an RoPE score > 7 independently from the presence of a permanent RLS and a concomitant ASA.

Ischaemic Stroke and the Echocardiographic "Bubble Study": Are We Screening the Right Patients?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Transcatheter PFO closure for cryptogenic stroke: current approaches and future considerations.

Patent Foramen Ovale (PFO) is a common congenital atrial septal defect present in 20%-35% of the general population. Although generally considered a benign anatomic variant, a PFO may facilitate passage of a thrombus from the venous to arterial circulation, thereby resulting in cryptogenic stroke or systemic embolization. A PFO is detected in nearly one half of patients presenting with cryptogenic stroke and often considered the most likely etiology when other causes have been excluded. In this review, we discuss the contemporary role of transcatheter closure of PFO in the treatment of cryptogenic stroke, including devices currently available for commercial use in the United States (Amplatzer PFOTM Occluder and GoreTM Cardioform Septal Occluder) and a novel suture-mediated device (NobleStitchTM EL) under clinical investigation. To provide the best care for cryptogenic stroke patients, practitioners should be familiar with the indications for PFO closure and corresponding treatment options.

The Modified Risk of Paradoxical Embolism Score Is Associated with Patent Foramen Ovale in Patients with Ischemic Stroke: A Nationwide US Analysis.

BACKGROUND: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. METHODS: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of the modified RoPE score in identifying the presence of a PFO in patients with acute ischemic stroke (AIS). RESULTS: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without a PFO (median 63 years vs. 71 years, p < 0.001) and fewer were female (46.1% vs. 49.7%, p < 0.001). The patients with PFO had greater mean modified RoPE scores (4.0 vs. 3.3, p < 0.001). The area under the curve for the RoPE score in predicting PFOs was 0.625 (95%CI 0.620-0.629). The best diagnostic power of the RoPE score was achieved with a cut-off point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut-off point of ≥5 increased the specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFOs was deep vein thrombosis (OR 3.97, 95%CI 3.76-4.20). CONCLUSIONS: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

Prevalence of patent foramen ovale in the Greek population is high and impacts on the interpretation of the risk of paradoxical embolism (RoPE) score.

BACKGROUND: The risk of paradoxical embolism (RoPE) score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFOAF), based on PFO prevalence in patients with cryptogenic stroke (CS) compared with that in the general population. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely. METHODS: Since PFO prevalence in Greece remains unknown, we evaluated it and we calculated PFOAF stratified by RoPE score in a cohort of patients with CS ⩽55 years old. PFO was detected according to the international consensus transcranial Doppler (TCD) criteria in 124 healthy subjects (H), in 102 patients with CS, and in 56 patients with stroke of known cause (nonCS). Each subject underwent unilateral middle cerebral artery recording after infusion of agitated saline, at rest, and after a controlled Valsalva maneuver. We characterized PFO as large (>20 microbubbles or curtain), moderate (11-20), and small (⩽10). RESULTS: PFO was detected in 42.7% of H, 49% of CS, and 25% of nonCS (p = 0.013). Large PFOs were numerically higher in CS [28.4% (29/102)] compared with H [19.3% (24/124); p = 0.1] and to nonCS [7.1% (4/56), p = 0.04]. The median RoPE score in patients with CS and PFO was seven. Even patients with very high RoPE score (9-10) had moderate PFOAF (57%). For any individual stratum up to RopE score 8, PFOAF was <33%. CONCLUSIONS: PFO prevalence in the Greek population is much higher than the widely accepted 25%. PFO may be the cause of stroke in one out of nine Greek patients with CS. Among Greek CS patients who harbor a PFO, the latter is causal in one out of five. The established RoPE score cutoff of ⩾7 for having a probable PFO-associated stroke may overestimate the probability in patients deriving from populations with high PFO prevalence.

Cryptogenic Stroke and Patent Foramen Ovale Risk Assessment.

Stroke is a devastating condition. It is the fifth leading cause of death in the United States, and a leading cause of serious long-term disability. Stroke occurs at any age. Younger patients tend to have strokes of undetermined cause, termed cryptogenic. Herein, the authors describe the classification of stroke cause; the risk of recurrent cryptogenic stroke with patent foramen ovale (PFO); a risk assessment model to stratify incidental versus a pathogenic PFO in patients presenting with stroke; and patient selection for device occluder therapy in the context of the long-term follow-up of the RESPECT randomized clinical trial.