Patent Foramen Ovale Closure Group Research Articles

Long-term clinical outcomes for patients with uncrossable patent foramen ovale.

Patent foramen ovale (PFO) closure is performed in selected patients with cryptogenic stroke to prevent recurrence. The prognosis of patients with uncrossable PFO after failed guidewire or catheter passage during the procedure remains unknown. We compared the long-term prognosis between uncrossable PFO and successful PFO closure in patients with high-grade PFO shunts. We analyzed patients who underwent PFO closure for stroke or transient ischemic attack (TIA) prevention at Gachon University Gil Medical Center between April 2010 and March 2022. The primary outcome was a composite of recurrent stroke or TIA. Secondary outcomes included stroke, TIA, all-cause death, and a composite of stroke, TIA, and all-cause death. Of 286 patients, 245 were included in the analysis after excluding those with transseptal puncture technique usage or concurrent atrial septal defect. Among them, 82 had uncrossable PFO, and 163 underwent successful PFO closure. Large shunts were more prevalent in the PFO closure group compared to the uncrossable PFO group (62.0% vs. 34.1%, P < 0.001), and resting shunts were also more common in the PFO closure group (17.8% vs. 2.4%, P < 0.001). Stroke or TIA occurred in 2 patients (2.4%) in the uncrossable PFO group and 8 patients (4.9%) in the PFO closure group (hazard ratio, 1.44; 95% confidence interval, 0.30-6.81; P = 0.647). Additionally, no disparities in the occurrence of stroke or TIA were found in subgroups divided by baseline characteristics, RoPE score, or shunt grade. Clinical outcomes for patients with uncrossable PFO seem similar to those with successful PFO closure.

1049 PREVALENCE OF ATRIAL FIBRILLATION AND FEASIBILITY OF PULMONARY VEIN ISOLATION AFTER PATENT FORAMEN OVALE CLOSURE

Abstract Background Data about prevalence and the risk of atrial fibrillation, stroke, and need for pulmonary vein isolation (PVI) after device closure of a patent foramen ovale (PFO) are still lacking. We aim to investigate the prevalence and the risk of atrial fibrillation after PFO closure and the feasibility of PVI in a PFO closure cohort compared to contemporary PVI without PFO closure. Methods retrospective observational study of consecutive patients undergoing PFO closure enrolled from February 2013 to September 2020. Patients were divided into 3 groups: i) patients without AF before and after the procedure (n=132), ii) patients with paroxysmal AF prior to the procedure (n=21), iii) patients with documented AF after the procedure (n=13). All patients with AF occurrence were treated with adequate anticoagulation therapy according to the current ESC Guidelines. We compared the procedural data of these patients to a matched contemporary cohort without previous PFO closure undergoing PVI in our center. AF and stroke prevalence and PVI feasibility after PFO closure were assessed at follow up. Results one-hundred and sixty-six consecutive PFO closure patients were enrolled; the mean age was 54 ± 13 years. Median follow-up was 3.5 + 2.5 years. During the study period, 21 patients had AF before or after the PFO closure (group 2) and 13 (7.8%) new onset AF (group 3). Stroke after the PFO closure occurred in 8 patients (4.8%), of which 4 in the group with new onset AF (30% of the group 3). Among the 34 patients with AF, 10 patients (6%) underwent a PVI. Compared to a contemporary matched PVI cohort, total procedural times and fluoroscopy times were significantly higher in the patients with previous PFO closure (108±15 vs 75±29, p=0.002 and 3±1.5 vs 8±7, p&amp;lt;0.001). Similar rate of AF relapses (p=0.198) was observed between the two groups, with a trend for higher rate of complication (pericardial effusion) for the cohort with previous PFO closure (p=0.06). Conclusion This study shows that a more accurate screening and treatment of AF is needed in patients with cryptogenic stroke despite the presence of a PFO, possibly a bystander. In our study, 30% of patients with new onset AF after PFO closure, experienced a further stroke after the procedure. In case of AF, the indication for PVI should be considered prior to the PFO closure since it turns out to be more difficult in terms of procedural and fluoroscopy times and risks of complications after PFO closure.

Cryptogenic ischemic cerebral vascular disease with patent foramen ovale: analysis of the long-term efficacy of treatments and prognostic factors

Objective: To evaluate the long-term efficacy of treatments on cryptogenic ischemic cerebral vascular disease (CICVD) with patent foramen ovale (PFO) and analyze prognostic factors, so as to provide the references for the treatment and secondary prevention of PFO related cerebral vascular disease. Methods: Consecutive patients with CICVD and PFO related right-to-left shunting confirmed by transesophageal echocardiography or transcranial doppler bubble test, who admitted to the Department of Neurology in Xuanwu Hospital from May 1, 2012 to December 31 2021 were enrolled. All the patients underwent hypercoagulability screening, and the degree of hypercoagulability was evaluated by a scoring scale. Each PFO was classified as either high-risk or low-risk according to its anatomic features. Patients were divided into the drug treatment group (including antiplatelet and anticoagulation therapies) and transcatheter PFO closure group. After follow-up, the recurrence of cerebral ischemic events were compared between the two groups by Kaplan-Meier method, the prognostic factors were analyzed by multifactorial Cox's regression model. Results: A total of 117 patients were recruited, 10 patients were lost to follow-up, and 107 patients were included in the final analysis, consisting of 66 males and 41 females, with age ranging from 14 to 67 years and the follow-up period of 1 229 (45, 3 508) d. The recurrence rate of cerebral ischemic events was 6% (4/66) and 7% (3/41) for the drug treatment group (66 cases) and closure group (41 cases), respectively, and residual shunting was detected in all patients with recurrent events in the closure group. Cumulative hazard curve indicated that there was no significant difference of recurrence risk of cerebral ischemic events between the two groups (cumulative recurrence rate: 17.9% in the closure group vs 7.1% in the drug treatment group, χ2=0.368, P=0.544), and the insignificance persisted even in subgroup analysis of CICVD patients with either high-risk (χ2=0.685, P=0.408) or low-risk PFO (χ2=0.072, P=0.789). Cox's regression model indicated that hypercoagulability related factor score was an independent predictor of recurrent cerebral ischemic events (HR=2.079, 95%CI 1.069-4.045, P=0.031) after adjusting for high-risk PFO, PFO closure and other confounding factors. Moreover, a rising trend of cumulative recurrence rate was observed as the score got higher (P=0.046). Conclusions: For CICVD patients with either high-risk or low-risk PFO, the significant value of drug treatment as the first-line therapy for PFO related CICVD should not be ignored, which awaits further discussion. The abnormality of hypercoagulability related factors might increase the recurrent risk of cerebral ischemic events, which calls for more attention and should be screened and treated with corresponding medication.

Abstract 9538: Impact of Device Closure on Heart Failure Progression in Patients With Patent Foramen Ovale

Background: Patent foramen ovale (PFO) can unload left atrial pressure via interatrial shunt. We evaluated whether device occlusion of PFO is associated with subsequent risk of heart failure (HF). Methods: We enrolled 4,804 consecutive patients (median age: 68 years, 62.4% male) who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF. The independent association of PFO closure with HF was evaluated using the Cox regression hazard model after multivariate adjustment for demographics, clinical risk factors, and echocardiographic parameters. Additional subgroup analysis was performed according to the presence structural heart disease defined as left ventricular (LV) ejection fraction &lt; 55%, left atrial (LA) size &gt; 35ml or LA volume ≥ 40ml/m 2 , LV mass index ≥ 115g/m 2 , E/e' ≥ 15, or presence of atrial fibrillation. Results: In total, PFO was observed in 981 (20.4%) patients, where 161 (16.4%) of them underwent device closure. Patients with PFO showed a lower risk of HF than those without (2.6 vs. 4.0%, adjusted hazard ratio [HR]: 0.65, 95% confidence interval [CI] 0.45-0.94, p=0.021). PFO closure group showed a significantly higher risk of HF than no closure group (5.5 vs. 1.2%, adjusted HR: 5.59, 95% CI 4.26-7.34, p&lt;0.001) (Figure). In subgroup analysis, PFO closure was significantly associated with HF risk in patients with underlying structural heart disease (9.6 vs. 3.9%, adjusted HR: 2.55, 95% CI 1.95-3.33, p&lt;0.001), demonstrating an increasing trend in proportion to the number of structural abnormalities. However, PFO closure showed no significant association with HF risk in patients without structural heart disease (1.7 vs. 1.5%, adjusted HR: 1.22, 95% CI 0.99-1.50, p=0.054). Conclusion: PFO closure may increase the risk of HF. Therefore, careful patient selection is needed, especially among those with underlying structural heart disease.

Prevalence of atrial fibrillation and feasibility of pulmonary vein isolation after patent foramen ovale closure

Abstract Background Data about prevalence and the risk of atrial fibrillation, stroke, and need for pulmonary vein isolation (PVI) after device closure of a patent foramen ovale (PFO) are still lacking. We aim to investigate the prevalence and the risk of atrial fibrillation after PFO closure and the feasibility of PVI in a PFO closure cohort compared to contemporary PVI without PFO closure. Methods Retrospective observational study of consecutive patients undergoing PFO closure enrolled from February 2013 to September 2020. Patients were divided into 3 groups: i) patients without AF before and after the procedure (n=132), ii) patients with paroxysmal AF prior to the procedure (n=21), iii) patients with documented AF after the procedure (n=13). All patients with AF occurrence were treated with adequate anticoagulation therapy according to the current ESC Guidelines. We compared the procedural data of these patients to a matched contemporary cohort without previous PFO closure undergoing PVI in our center. AF and stroke prevalence and PVI feasibility after PFO closure were assessed at follow up. Results One-hundred and sixty-six consecutive PFO closure patients were enrolled; the mean age was 54±13 years. Median follow-up was 3.5±2.5 years. During the study period, 21 patients had AF before or after the PFO closure (group 2) and 13 (7.8%) new onset AF (group 3). Stroke after the PFO closure occurred in 8 patients (4.8%), of which 4 in the group with new onset AF (30% of the group 3). Among the 34 patients with AF, 10 patients (6%) underwent a PVI. Compared to a contemporary matched PVI cohort, total procedural times and fluoroscopy times were significantly higher in the patients with previous PFO closure (108±15 vs 75±29, p=0.002 and 3±1.5 vs 8±7, p&amp;lt;0.001). Similar rate of AF relapses (p=0.198) was observed between the two groups, with a trend for higher rate of complication (pericardial effusion) for the cohort with previous PFO closure (p=0.06). Conclusion This study shows that a more accurate screening and treatment of AF is needed in patients with cryptogenic stroke despite the presence of a PFO, possibly a bystander. In our study, 30% of patients with new onset AF after PFO closure, experienced a further stroke after the procedure. In case of AF, the indication for PVI should be considered prior to the PFO closure since it turns out to be more difficult in terms of procedural and fluoroscopy times and risks of complications after PFO closure. Funding Acknowledgement Type of funding sources: Public Institution(s).

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

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. 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. 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%). 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.

The Efficacy of Percutaneous Patent Foramen Ovale Closure on Migraine: a Meta-Analysis of Randomized Controlled Trials and Observational Studies

Objectives Whether patent foramen ovale (PFO) closure is effective on migraine is controversial. This article was aimed at assessing the efficacy of PFO closure on migraine based on randomized controlled trials (RCTs) and observational studies. Methods We searched PubMed, Embase, and Cochrane databases up to October 2020 evaluating PFO closure versus control in patients with migraine, then conducted a meta-analysis of all RCTs and observational studies, respectively. The main outcomes were (1) respond rate: complete cessation of migraine; (2) reduction in the frequency of migraine attacks per month; and (3) reduction in migraine days per month. Results Seven studies (3 RCTs and 4 observational studies), containing 887 migraine patients, were identified. (1) The respond rate of PFO closure on migraine was significantly higher than control group both in RCT subgroup and observational studies subgroup (OR 3.86, 95% CI 1.35-11.04, P = 0.01 in RCTs; OR 8.28, 95% CI 2.31-29.67, P = 0.001 in observational studies). (2) Reduction in frequency of migraine attacks was higher in PFO closure group compared with control group in the RCT subgroup analysis (mean difference (MD) = 0.57, 95% CI 0.23-0.90, P = 0.0009). (3) Reduction in migraine days was also higher in PFO closure group compared with control group in the RCT subgroup analysis (MD = 1.33, 95% CI 0.35-2.31, P = 0.008). Conclusions PFO closure might be suitable for migraine patients, especially for migraine with aura, by cessation of migraine headaches or reducing migraine attacks and migraine days.

Transcatheter Patent Foramen Ovale Closure Is Effective in Alleviating Migraine in a 5-Year Follow-Up.

Background: The association between patent foramen ovale (PFO) and migraine has been reported. However, whether transcatheter PFO closure is effective in alleviating migraine remains controversial. The objective of this study was to investigate the efficacy of PFO closure in alleviating migraine in a 5-year follow-up.Methods: Migraineurs with PFO from 2013 to 2015 were included and divided into PFO closure group and non-PFO closure group according to their therapy. Contrast-enhanced transcranial Doppler (c-TCD) was performed to evaluate the degree of the right-to-left shunt (RLS), and headache impact test (HIT-6) questionnaire was administered to assess the disability of migraine at 1- and 5-year follow-up.Results: Of 192 patients, 91 patients underwent PFO closure, and 101 patients refused. The HIT-6 scores of patients in the PFO closure group were significantly lower than those of the non-PFO closure group at both 1- and 5-year follow-up. These results were more pronounced in patients younger than 45 years. Furthermore, in patients with large RLS, the HIT-6 scores of patients in the PFO closure group were significantly lower at both 1- and 5-year follow-up compared with those of the non-PFO closure group. However, in patients with moderate RLS, this difference was significant only at 5-year follow-up.Conclusions: PFO closure is effective in alleviating migraine in the long term. This effect is more obvious when patients are younger than 45 years and RLS is large.

Superior vena cava-right atrium junction flow-pattern post-transcatheter closure of patent foramen ovale.

The patent foramen ovale (PFO) occluder is a bulky metallic device. Its impact on the normal blood flow at the superior vena cava-right atrial (SVC-RA) junction is not clear. We examined SVC-RA junction flow-pattern using pulsed-wave (PW) ultrasound Doppler in 21 patients (4 male, aged 52.7±9years) who underwent PFO device closure 4-120months previously, in comparison with 21 age- and sex-matched controls (4 male, aged 51±8.5years) with structurally normal hearts. Mean systolic flow velocity at the SVC-RA junction was 60±11cm/s in the PFO closure group and 64±17cm/s in the control group (P=0.27). Mean diastolic blood flow velocity at the SVC-RA junction in those groups was 30±8 and 35±9cm/s, respectively (P=0.1).The mean systolic wave duration was 439±52ms in the PFO closure group and 422±67ms in the control group (P=0.4). The mean diastolic wave duration was 320±75 and 277±88ms, respectively (P=0.12). The study results show that transcatheter PFO closure does not affect the normal blood flow at the SVC-RA junction.

Are we there yet with patent foramen ovale closure for secondary prevention in cryptogenic stroke? A systematic review and meta-analysis of randomized trials.

Background:We performed a meta-analysis to evaluate the benefit of patent foramen ovale closure in stroke prevention.Methods:We searched Medline/PubMed, EMBASE, Web of Science and Cochrane central database for randomized control trials assessing the incidence of recurrent stroke after patent foramen ovale closure when compared to medical therapy. Pooled odds ratio and 95% confidence intervals were calculated using a random effects model. The heterogeneity among studies was tested using the χ2 test and inconsistency was quantified using the I2 statistic.Results:Our search strategy yielded 71 articles. We included five studies with a total of 3440 patients. Median age in the device group was 45 (43, 5.5) years and in the medical group was 45 (44.5, 46) years; 52% were male, 27.7% of patients had an atrial septal aneurysm, 25% had hypertension, and 20.5% had diabetes mellitus. The median follow-up time was 44 (34.5–50) months. The pooled odds ratio of recurrent stroke, transient ischemic attack and composite end point of stroke + transient ischemic attack + peripheral embolism in the patent foramen ovale closure versus medical therapy group were 0.4 (95% confidence interval 0.25–0.63, I2 = 57.5%), 0.93 (95% confidence interval 0.61–1.42, I2 = 0%), and 0.6 (95% confidence interval 0.44–0.82, I2 = 0%), respectively. The incidence of atrial fibrillation was found to be significantly higher in the patent foramen ovale closure group with odds ratio of 6 (95% confidence interval 3.13–11.4, I2 = 33.5%). On subgroup analysis, patent foramen ovale closure appeared to benefit males and patients with a large shunt. Number needed to treat to prevent one recurrent stroke with patent foramen ovale closure is 42. Number needed to harm to cause one atrial fibrillation with patent foramen ovale closure is 39.Conclusion:This meta-analysis of randomized trials concludes that percutaneous patent foramen ovale closure is effective in recurrent stroke prevention especially in males and in those with a large shunt.

Percutaneous Closure of Patent Foramen Ovale in Patients with Cryptogenic Stroke - An Updated Comprehensive Meta-Analysis.

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. 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. 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). 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.

Closure versus Medical Therapy for Patent Foramen Ovale in Patients with Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials

BackgroundDebate continues about whether percutaneous closure of patent foramen ovale (PFO) is a better strategy for the treatment of patients with cryptogenic stroke in comparison with medical therapy alone. We performed an updated meta-analysis of 6 randomized controlled trials (RCTs) to assess the effectiveness and safety of percutaneous closure of PFO as secondary prevention for patients with previous cryptogenic stroke compared to medical therapy. Materials and MethodsMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and Internet-based resources were retrieved in March 2018 for eligible RCTs. The primary effectiveness outcome was recurrent strokes. ResultsSix studies meeting our selection criteria were identified. Among 3560 participants, 1889 patients were assigned to PFO closure and 1671 patients to medical therapy. There were no significant differences among the baseline characteristics. The pooled incidence of recurrent strokes was 1.96% in the PFO closure group and 4.60% in the medical therapy group (Relative risk [RR] .39, 95% confidence interval [CI] .18-.82, P = .01). Newly detected atrial fibrillation occurred in 77 of 1844 (4.18%) patients in the PFO closure group and in 12 of 1667 (.72%) patients in the medical therapy group (RR 4.56, 95% CI 2.21-9.41, P <.0001). There was no difference in terms of serious adverse events, total mortality or bleeding between 2 groups. ConclusionsOur updated meta-analysis suggests that in patients with PFO and cryptogenic stroke, the rate of recurrent stroke is significantly reduced with percutaneous closure of PFO compared to the medical therapy.

TCT-822 Patent Foramen Ovale (PFO) closure compared to medical therapy for prevention of stroke recurrence in cryptogenic stroke population: Systematic Review and Meta-Analysis

Background Closure of a Patent Foramen Ovale(PFO), may play a role in reducing the risk of recurrent strokes in the cryptogenic stroke population. With recent new evidence published, we aimed to conduct a review of currently available randomised controlled trials(RCT) in order to evaluate the utility of percutaneous device closure of PFO compared to medical therapy in prevention of recurrent strokes. Our aim was to compare the incidence of recurrent stroke between the 2 approaches and also to compare the incidence of transient ischaemic attacks(TIA) and major bleeding between the 2 approaches. Methods A comprehensive search of major databases was performed. We included comparative RCTs, where outcomes of percutaneous PFO closure with medical therapy were available in patients with cryptogenic stroke and a PFO. Results Six studies were included with total of 3560 patients. Incidence of recurrent stroke was significantly less in the PFO closure group compared to medical therapy (2.86% vs. 5.09%, OR 0.49, 95% CI 0.35 – 0.70, p < 0.0001). Incidence of TIA was not significantly different in both PFO closure group compared to medical therapy (2.75% vs. 3.83%, OR 0.79, 95% CI 0.54 – 1.15, p = 0.22). Major bleeding was shown to not be significantly different in PFO closure group compared to medical therapy (1.64% vs. 1.76%, OR 0.90, 95% CI 0.54 – 1.49, p = 0.68) either. Sub group analysis of patients with ASA, comparing PFO closure group to medical therapy showed significant benefit in terms of stroke prevention in the PFO closure group (3.02% vs. 7.99%, OR 0.39, 95% CI 0.21 – 0.72, p = 0.002). Sub group analysis of large intra-atrial shunt similarly showed significant benefit in terms of stroke prevention in the PFO closure group (1.43% vs. 5.40%, OR 0.26, 95% CI 0.13 – 0.51, p < 0.0001). Download : Download high-res image (119KB)Download : Download full-size image Conclusion When combining all trials published so far, our analysis demonstrates a net beneficial effect of PFO closure overall. Our study also highlights the need of a dedicated RCT to explore PFO closure compared to oral anticoagulation to reduce the likelihood of bias in the future.

Patent foramen ovale closure versus medical therapy for cryptogenic stroke: An updated meta-analysis

BackgroundThe efficacy of patent foramen ovale (PFO) closure for secondary stroke prevention in cryptogenic stroke (CS) patients with PFO is uncertain. This meta-analysis aims to assess whether PFO closure is superior to medical therapy. MethodsPooled estimates were calculated using Revman 5.3. The two primary endpoints were stroke and transient ischemic attack (TIA). Secondary outcomes included all-cause mortality, new-onset atrial fibrillation or flutter, major bleeding and any adverse event. ResultsFive randomized controlled trials were included. A total of 3440 patients were randomized to either PFO closure (n = 1829) or medical therapy group (n = 1611) and followed for average 2.0–5.9 years. PFO closure reduced the incidence of recurrent stroke in CS patients with PFO compared to medical therapy (Risk ratio (RR) 0.42, 95% confidence intervals (CI) 0.20–0.91, P = 0.03; hazard ratio (HR) 0.34, 95% CI 0.15–0.78, p = 0.01). There were no significant differences between the two groups in TIA (RR 0.78, 95% CI 0.53–1.15, P = 0.21; HR 0.73, 95% CI 0.49–1.09, p = 0.12), all-cause mortality (RR 0.76, 95% CI 0.35–1.63, P = 0.48), major bleeding (RR 0.96, 95% CI 0.42–2.20, P = 0.93) and any adverse event (RR 1.06, 95% CI 0.95–1.18, P = 0.29). Higher risk of new-onset atrial fibrillation or flutter was found in closure group (RR 4.69, 95% CI 2.17–10.12, P < 0.0001). ConclusionsPFO closure combined with medical therapy showed superiority over medical therapy alone for stroke prevention in carefully selected CS patients with PFO, but increased the risk of atrial fibrillation or flutter.

Transcatheter Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke: A Meta-Analysis of Randomized Controlled Trials

Background: Patent foramen ovale (PFO) with atrial septal aneurysm is suggested as an important potential source for cryptogenic strokes. Percutaneous PFO closure to reduce the recurrence of stroke compared to medical therapy has been intensely debated. The aim of this study is to assess whether PFO closure in patients with cryptogenic stroke is safe and effective compared with medical therapy. Method: A search of PubMed, Medline, and Cochrane Central Register from January 2000 through September 2017 for randomized controlled trails (RCT), which compared PFO closure to medical therapy in patients with cryptogenic stroke was conducted. We used the items “PFO or patent foramen ovale”, “paradoxical embolism”, “PFO closure” and “stroke”. Data were pooled for the primary outcome measure using the random-effects model as pooled rate ratio (RR). The primary outcome was reduction in recurrent strokes. Result: Among 282 studies, 5 were selected. Our analysis included 3,440 patients (mean age 45 years, 55% men, mean follow-up 2.9 years), 1,829 in the PFO closure group and 1,611 in the medical therapy group. The I² heterogeneity test was found to be 48%. A random effects model combining the results of the included studies demonstrated a statistically significant risk reduction in risk of recurrent stroke in the PFO closure group when compared with medical therapy (RR 0.42; 95% CI 0.20–0.91, p = 0.03). Conclusion: Pooled data from 5 large RCTs showed that PFO closure in patients with cryptogenic stroke is safe and effective intervention for prevention of stroke recurrence compared with medical therapy.

Percutaneous Closure of Patent Foramen Ovale in Patients With Migraine: The PREMIUM Trial

BackgroundMigraine is a prevalent and disabling disorder. Patent foramen ovale (PFO) has been associated with migraine, but its role in the disorder remains poorly understood. ObjectivesThis study examined the efficacy of percutaneous PFO closure as a therapy for migraine with or without aura. MethodsThe PREMIUM (Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management) was a double-blind study investigating migraine characteristics over 1 year in subjects randomized to medical therapy with a sham procedure (right heart catheterization) versus medical therapy and PFO closure with the Amplatzer PFO Occluder device (St. Jude Medical, St. Paul, Minnesota). Subjects had 6 to 14 days of migraine per month, had failed at least 3 migraine preventive medications, and had significant right-to-left shunt defined by transcranial Doppler. Primary endpoints were responder rate defined as 50% reduction in migraine attacks and adverse events. Secondary endpoints included reduction in migraine days and efficacy in patients with versus without aura. ResultsOf 1,653 subjects consented, 230 were enrolled. There was no difference in responder rate in the PFO closure (45 of 117) versus control (33 of 103) groups. One serious adverse event (transient atrial fibrillation) occurred in 205 subjects who underwent PFO closure. Subjects in the PFO closure group had a significantly greater reduction in headache days (–3.4 vs. –2.0 days/month, p = 0.025). Complete migraine remission for 1 year occurred in 10 patients (8.5%) in the treatment group versus 1 (1%) in the control group (p = 0.01). ConclusionsPFO closure did not meet the primary endpoint of reduction in responder rate in patients with frequent migraine. (Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management [PREMIUM]; NCT00355056)

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke

BackgroundWhether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown.MethodsIn a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory.ResultsWe enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group.ConclusionsAmong adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.)

Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke

BackgroundThe efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions.MethodsIn this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on imaging.ResultsWe enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.62; P=0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet-only group (18 patients [4.7%] vs. 19 patients [10.7%]; relative risk, 0.44; 95% CI, 0.24 to 0.81; P=0.02), but the incidence of silent brain infarction did not differ significantly between the study groups (P=0.75). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P=0.22). Serious device-related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure.ConclusionsAmong patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894.)

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BackgroundTrials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy.MethodsIn a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3.ResultsA total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone.ConclusionsAmong patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289.)

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