BACKGROUND:There is an association between cryptogenic stroke and patent foramen ovale (PFO). The optimal treatment strategy for secondary prevention remains unclear. The purpose of this study was to analyze aggregate data examining the safety and efficacy of transcatheter device closure versus standard medical therapy in patients with PFO and cryptogenic stroke.METHODS:A search of published data identified 3 randomized clinical trials for inclusion. The primary outcome was a composite end-point of death, stroke and transient-ischemic attack (TIA). Pre-defined subgroup analysis was performed with respect to baseline characteristics including age, sex, atrial septal aneurysm and shunt size. Data was synthesized using a random effects model and results presented as hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS:A cohort of 2,303 patients with a history of cryptogenic stroke and PFO were randomized to device closure (n=1150) and medical therapy (n=1153). Mean follow-up was 2.5years. Transcatheter closure was not superior to medical therapy in the secondary prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI: 0.43 to 1.01 / p=0.056). However, the results were statistically significant using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98 / p=0.043). Males had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96 / p=0.038).CONCLUSIONS:In this meta-analysis, using intention-to-treat analysis, transcatheter device closure of PFO was not superior to standard medical therapy in the secondary prevention of cryptogenic stroke. Transcatheter closure was superior using per-protocol analysis.

Background: The ideal treatment strategy for patients with cryptogenic stroke and patent foramen ovale (PFO) is not yet clear. Previous randomized controlled trials (RCTs) comparing transcatheter PFO closure with medical therapy in patients with cryptogenic stroke to prevent recurrent ischemic stroke showed mixed results. This meta-analysis aims to compare rates of recurrent stroke, transient ischemic attack (TIA) and all-cause mortality with PFO closure and medical therapy vs. medical therapy alone. Methods: PubMed and the Cochrane Center Register of Controlled Trials were searched for studies published through June 2018, comparing PFO closure plus medical therapy versus medical therapy alone. Six RCTs (n = 3750) comparing PFO closure with medical therapy were included in the analysis. End points were recurrent stroke, TIA and all-cause mortality. The odds ratios (OR) with 95% confidence interval (CI) were computed and p < 0.05 was considered as a level of significance. Results: A total of 1889 patients were assigned to PFO closure plus medical therapy and 1861 patients were assigned to medical therapy only. Risk of recurrent stroke was significantly lower in the PFO closure plus medical therapy group compared to medical therapy alone. (OR 0.47, 95% CI 0.33–0.67, p < 0.0001). Rate of TIA was similar between the two groups (OR 0.76, 95% CI 0.52–1.14), p = 0.18). There was no difference in all-cause mortality between two groups (OR 0.73, CI 0.33–1.58, p = 0.42). Patients undergoing PFO closure were more likely to develop transient atrial fibrillation than medical therapy alone (OR: 5.85; CI: 3.06–11.18, p ≤0.0001) whereas the risk of bleeding was similar between the groups (OR: 0.93; CI: 0.55–1.57, p = 0.78). Conclusions: The results of this meta-analysis suggest that transcatheter closure of PFO plus medical therapy is superior to medical therapy alone for the prevention of recurrent cryptogenic stroke. However, PFO closure in these patients has not been shown to reduce the risk of recurrent TIA or all-cause mortality. There is a higher rate of transient atrial fibrillation post PFO closure device placement, the long-term effects of which have yet to be studied.

The role of patent foramen ovale (PFO) in stroke was debated for decades. Randomized clinical trials (RCTs) have shown fewer recurrent events after PFO closure in patients with cryptogenic stroke (CS). However, in clinical practice, treating stroke patients with coexisting PFO raises some questions. This brief review summarizes current knowledge and challenges in handling stroke patients with PFO and identifies issues for future research. The rationale for PFO closure was initially based on the concept of paradoxical embolism from deep vein thrombosis (DVT). However, RCTs did not consider such details, limiting their impact from a pathophysiological perspective. Only a few studies explored the coexistence of PFO and DVT in CS with varying results. Consequently, the PFO itself might play a role as a prothrombotic structure. Transesophageal echocardiography thus appears most appropriate for PFO detection, while a large shunt size or an associated atrial septum aneurysm qualify for a high-risk PFO. For drug-based treatment alone, studies did not find a definite superiority of oral anticoagulation over antiplatelet therapy. Remarkably, drug-based treatment in addition to PFO closure was not standardized in RCTs. The available literature rarely considers patients with transient ischemic attack (TIA), over 60 years of age, and competing etiologies like atrial fibrillation. In summary, RCTs suggest efficacy for closure of high-risk PFO only in a small subgroup of stroke patients. However, research is also needed to reevaluate the pathophysiological concept of PFO-related stroke and establish strategies for older and TIA patients and those with competing risk factors or low-risk PFO.

Background: Stroke is a leading cause of significant physical, cognitive, and psychiatric morbidity. One risk factor for stroke is paradoxical embolization through a patent foramen ovale (PFO). In cardiac clinical practice, power M-mode Transcranial Doppler (TCD) evaluation is the gold standard for diagnosis of PFO, or right-to-left cardiac shunt (RLS). Brain micro-embolization due to diagnostic bubble contrast echocardiography may cause neurological symptoms in patients with PFO. However, the neurocognitive effects of TCD have not been studied. Objective: The purpose of this study was to evaluate cognitive outcomes in patients who undergo routine diagnostic bubble contrast TCD. The aims of the study were (1) to determine if cognitive function declines pre- to post-TCD evaluation and, (2) to assess the relationship between cognitive function and severity of the RLS measured using the Spencer Grading System. Methods: One hundred and four participants referred to Sorensen Cardiovascular Group for diagnosis of RLS were evaluated for changes in cognitive functioning at three time points. A dual baseline (pre-test and baseline test) was administered to mitigate practice effects between the first and second administrations. All pre and post-TCD comparisons were analyzed using the baseline test and post-TCD test, controlling for the effects of practice, if present. Results: Practice effects were observed for the working memory task, with significant improvement in working memory scores occurring between the first (pre-test) and second (baseline) administrations. The main effect for shunt group (no shunt vs. moderate-to-severe shunt) and the shunt group by time interactions were not significant for processing speed, attention, or working memory, adjusting for practice effects, age, and education. Migraine did not predict group status for mood or shunt variables. Conclusion: Cardiac patients with both small and large RLS did not experience a decline in processing speed, attention, or working memory ability following TCD, suggesting that TCD-induced microemboli do not result in immediate cognitive deficits in these domains. These findings support the use of TCD for routine evaluation of PFO, even in patients with severe RLS, although findings are limited to young (30s), medically healthy, predominately Caucasian individuals assessed immediately following TCD. Results do not exclude the possibility of cognitive impairment at follow-up, on other cognitive tests, or in other cognitive domains.