Recurrence Risk in Patients with Cryptogenic Stroke, Patent Foramen Ovale, and Thrombophilia: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 119 (11) ◽  
pp. 1839-1848 ◽  
Author(s):  
Claus V. B. Hviid ◽  
Claus Ziegler Simonsen ◽  
Anne-Mette Hvas

Objective A patent foramen ovale (PFO) is frequently associated with cryptogenic stroke in the young. Endovascular closure is superior to antithrombotic treatment in prevention of recurrence, but in the presence of a concomitant thrombophilia, the best preventive strategy is unknown. This review investigates if thrombophilia increases the risk of recurrence in patients with cryptogenic stroke and PFO and attempts to evaluate the best antithrombotic strategy after PFO closure in these patients. Methods Medline, Embase, and Web of Science were searched until April 2018. Study quality was assessed by the National Heart, Lung and Blood Institute Quality assessment tool. Odds ratio (OR) and hazard ratio for recurrence were pooled in a random effect model stratified by secondary preventive strategy. Results Eleven studies were included. Inherited or acquired thrombophilia was associated with an increased risk of recurrence (OR = 2.41, 95% confidence interval [CI]: 1.44–4.06). Looking only at patients treated with PFO closure, the risk of recurrence just lost significance (OR = 2.07, 95% CI: 0.95–4.48). The antithrombotic treatment after PFO closure was heterogeneous and recurrent events occurred in patients with both inherited and acquired thrombophilia treated by antiplatelet as well as anticoagulant therapy. Conclusion Thrombophilia is associated with an increased risk of recurrence in patients with PFO and cryptogenic stroke, which may persist after PFO closure. This suggests a need for antithrombotic therapy after PFO closure. Study heterogeneity precludes strong conclusions on antithrombotic treatment, but life-long antiplatelet therapy to patients without preexisting indication for anticoagulant therapy seems reasonable.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F Leclercq ◽  
X Odorico ◽  
C Arquizan ◽  
J C Macia ◽  
B Lattuca ◽  
...  

Abstract Background An increased risk of new-onset atrial fibrillation (AF) after patent foramen ovale (PFO) closure was observed in randomized trials. However, systematic screening of AF was not performed in these studies. Purpose We aimed to evaluate incidence of AF in patients undergoing percutaneous PFO closure with serial 24-hours ambulatory electrocardiogram (AECG) monitoring during a 6-months follow-up. Methods All consecutive patients undergoing PFO closure for cryptogenic stroke or decompression sickness (DSC) were prospectively included in 2 centers. AF was defined as an irregular rhythm without discernible P waves lasting at least 30 seconds on 24-hours AECG performed at day 0, 1 month and 6-months follow-up. Primary endpoint was incidence of AF within the study period. Secondary endpoints evaluated clinical outcomes (hospitalization for cardiovascular causes, new stroke or bleeding) within 6-months follow-up. Results Between February 2018 and March 2019, a total of 62 patients underwent PFO closure: 59 (95.2%) for cryptogenic stroke and 3 (4.8%) for DSC. In the overall population, 40 were male (64.5%) and the mean age was 48±9.5 years. An atrial septal aneurysm was present in 37 patients (64.9%). The PFO device mean size was 26±5.0 mm. After a mean follow-up of 33.3±12.2 weeks, new-onset AF occurred in 3 patients (4.8%), all within 1-month after closure and paroxysmal. While symptomatic ectopic atrial heart beats occurred in one fourth of patients, all AF episodes asymptomatic. Two patients (3.2%) required oral anticoagulant therapy according to CHA2DS2-VASc score. No adverse outcomes occurred. Age (RR 1.26 [0.98; 1.61] p=0.3), male sex (p=0.6) and device (p=1.0) were not associated with occurrence of AF but all patients with AF were men and received an Amplatzer device. Conclusion Incidence of AF, evaluated with serial systematic 24-hours AECG during a 6-months follow-up after PFO closure, was relatively low (<5%). Always paroxysmal, AF always occurred within one month after the procedure and was not associated with adverse outcomes. FUNDunding Acknowledgement Type of funding sources: None.


2021 ◽  
Vol 51 (1) ◽  
pp. 63-67
Author(s):  
Björn Edvinsson ◽  
◽  
Ulf Thilén ◽  
Niels Erik Nielsen ◽  
Christina Christersson ◽  
...  

Introduction: Interatrial communication is associated with an increased risk of decompression sickness (DCS) in scuba diving. It has been proposed that there would be a decreased risk of DCS after closure of the interatrial communication, i.e., persistent (patent) foramen ovale (PFO). However, the clinical evidence supporting this is limited. Methods: Medical records were reviewed to identify Swedish scuba divers with a history of DCS and catheter closure of an interatrial communication. Thereafter, phone interviews were conducted with questions regarding diving and DCS. All Swedish divers who had had catheter-based PFO-closure because of DCS were followed up, assessing post-closure diving habits and recurrent DCS. Results: Nine divers, all with a PFO, were included. Eight were diving post-closure. These divers had performed 6,835 dives (median 410, range 140–2,200) before closure, and 4,708 dives (median 413, range 11–2,000) after closure. Seven cases with mild and 10 with serious DCS symptoms were reported before the PFO closure. One diver with a small residual shunt suffered serious DCS post-closure; however, that dive was performed with a provocative diving profile. Conclusion: Divers with PFO and DCS continue to dive after PFO closure and this seems to be fairly safe. Our study suggests a conservative diving profile when there is a residual shunt after PFO closure, to prevent recurrent DCS events.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yangyang Han ◽  
Xiquan Zhang ◽  
Fengwei Zhang

Abstract Background Percutaneous closure of patent foramen ovale (PFO) is routinely performed using plain fluoroscopy in the catheter room. This method results in inevitable radiation damage, adverse effects of contrast agents on kidneys, and high cost. We performed PFO closure with a simplified and economical transesophageal echocardiography (TEE)-only guided approach in the operating room. This study aimed to investigate the feasibility, safety, and effectiveness of the percutaneous closure of PFO by only using TEE. Methods We reviewed the medical records of patients who underwent percutaneous PFO closure at our center from December 2013 to December 2017. A total of 132 patients with PFO and cryptogenic strokes underwent PFO closure by using cardi-O-fix PFO device under TEE guidance. The participants comprised 64 and 68 male and female patients, respectively. The mean age and body weight of the patients were 39.40 ± 13.22 years old (12–68 years old) and 65.42 ± 9.70 kg (40–95 kg), respectively. All patients only received aspirin (3–5 mg/kg body weight, oral administration) for 6 months. Contrast-enhanced transthoracic echocardiography (c-TTE) with Valsalva maneuver was performed during follow-up, and questionnaire surveys were obtained at 3, 6, and 12 months after the procedure. Results All (100%) patients were successfully closed. Follow-ups were conducted for 13 months to 48 months, with an average of 27 months. No severe complications were found during the follow-up period. Paroxysmal atrial fibrillation occurred in 4 patients within 3 months after the procedure. No recurrent stroke or death occurred in all patients during the follow-up period. Transient ischemic attack occurred in one patient 6 months after the procedure. Ten (7.6%) patients had a right-to-left shunt, as demonstrated by c-TTE at 12 months of follow-up. Among the 57 patients suffering from migraine, significant relief or resolution was reported by 42 (73.7%) patients. Conclusion TEE-only guided PFO closure was a safe, feasible, and effective method that did not require the use of X-rays and contrast agents.


Stroke ◽  
2021 ◽  
Vol 52 (5) ◽  
pp. 1653-1661
Author(s):  
Jessie Ze-Jun Chen ◽  
Vincent N. Thijs

Background and Purpose: Multiple studies evaluated whether patent foramen ovale (PFO) closure reduces the risk of ischemic stroke. One commonly reported complication of PFO closure is the development of atrial fibrillation (AF), which is itself a powerful stroke risk factor that requires specific management. This study aims to evaluate the frequency of AF in patients post-percutaneous closure of PFO and the clinical factors that predict AF detection. Methods: Studies were identified by systematically searching EMBASE and MEDLINE databases on July 11, 2019. Meta-analysis of proportions was performed, assuming a random-effects model. Results: A total of 6 randomized controlled trials and 26 observational studies were included, comprising 3737 and 9126 patients, respectively. After PFO closure, the rate of AF development was 3.7 patients per 100 patient-years of follow-up (95% CI, 2.6–4.9). The risk of AF development is concentrated in the first 45 days post-procedure (27.2 patients per 100 patient-years [95% CI, 20.1–34.81], compared with 1.3 patients per 100 patient-years [95% CI, 0.3–2.7]) after 45 days. Meta-regression by age suggested that studies with older patients reported higher rate of AF ( P =0.001). In medically treated patients, the rate of AF development was 0.1 per 100 patient-years of follow-up (95% CI, 0.0–0.4). Closure of PFO is associated with increased risk of AF compared with medical management (odds ratio, 5.3 [95% CI, 2.5–11.41]; P <0.001). Conclusions: AF is more common in PFO patients who had percutaneous closure compared with those who were medically treated. The risk of AF was higher in the first 45 days post-closure and in studies that included patients with increased age.


2018 ◽  
Vol 13 (3) ◽  
pp. 240-242 ◽  
Author(s):  
Jean-Louis Mas ◽  
Gilles Chatellier

Contrasting with three randomized trials that failed to show any superiority of patent foramen ovale closure over antithrombotic therapy, two trials recently reported lower rates of stroke recurrence among patients assigned to patent foramen ovale closure than among those assigned to antiplatelet therapy. In addition, one of the initially negative trials concluded in favor of patent foramen ovale closure after an extended follow-up period. A better selection of patients, the use of reference treatment groups that included patients who received antiplatelet therapy alone (rather than antiplatelet drugs or oral anticoagulants, according to physician preference), and a longer follow-up of patients, may explain the divergent findings across studies. Procedural complications were reported in 1.5% to 5.9% of the patients, none of which led to permanent disability or death. Patent foramen ovale closure was associated with an increased risk of new-onset atrial fibrillation in several studies and of venous thromboembolism in one study.


2021 ◽  
Vol 6 (1) ◽  
pp. 2
Author(s):  
Agnete Teivāne ◽  
Kristaps Jurjāns ◽  
Ainārs Rudzītis ◽  
Krista Lazdovska ◽  
Artūrs Balodis ◽  
...  

Background and Objectives: According to guidelines, patent foramen ovale (PFO) closure is recommended for secondary stroke prevention in patients with cryptogenic stroke. Paradoxial embolism from PFO-mediated right to left shunt has been described as the mechanism of stroke in these cases. The aim of the study was to determine whether PFO closure can be associated with improvement of complaints (headaches, fatigue, heart palpitations, dizziness, and visual impairment) and determine its long-term effectiveness on recurrent stroke risk reduction. Materials and Methods: A total of 103 patients were enrolled in a retrospective study and followed-up by phone up to five years after PFO closure. Standardized survey was conducted about their well-being, recurrent cerebrovascular events, and the use of prescribed medication. Patients were also followed up for residual shunts 24 h, 30 days, 1 year, and 2 years after PFO. The pathogenic ischemic stroke subtypes are determined using CCS (Causative Classification System for Ischemic Stroke). Results: Male patients accounted for 43.7% (n = 45). The mean age was—44.4 ± 13 (18–75). The most probable cause for cryptogenic stroke for 53.4% (n = 55) of patients with possible cardio-aortic embolism was PFO. Residual shunts were mostly observed in patients with Amplatzer occluder—87.5% (n = 14). There was correlation between residual shunt and increased risk of transient ischemic attack recurrence (p = 0.067). Five-years after PFO closure recurrent cerebrovascular events were reported in only 5.1% (n = 5) of patients, this difference is statistically relevant (p < 0.001). Out of 51 patients presented with complaints before PFO closure, 25.5% (n = 13) did not present with any complaints after PFO closure. Conclusions: PFO can be considered a possible risk factor for cryptogenic stroke. PFO closure is effective in reducing recurrent cerebrovascular events. Residual shunt after PFO closure increases the risk of transient ischemic attack recurrence. Amplatzer occluder device is associated with a higher risk for residual shunts after PFO closure. PFO closure can be associated with improvement of complaints.


2021 ◽  
Vol 42 (3) ◽  
Author(s):  
Dhanang Ali Yafi ◽  
Azmi Azmi

A patent foramen ovale (PFO) is a common disorder that affects between 20-34% of the adult population. This condition is a benign finding for most people. However, In some the PFO can open widely and enabling paradoxical embolism to transit from venous to arterial circulation, which is associated with stroke and systemic embolization. There are still unclear to date regarding the effectiveness of pharmacological anticoagulant therapy, defined as antithrombin or antiplatelet therapy, which has proven to be more beneficial for patients with PFO and cryptogenic stroke. In addition, surgical and transcutaneous PFO closure has been proposed for secondary prevention of stroke in patients with cryptogenic stroke with PFO. Both catheter-based and surgical modes of closure have been shown to reduce the incidence of subsequent embolism substantially. This review will discuss the evidence regarding the relationship between PFO and cryptogenic stroke and decision making for management strategies.


2018 ◽  
Vol 34 (S1) ◽  
pp. 112-113
Author(s):  
Jeonghoon Ahn ◽  
Eung Ju Kim ◽  
Kyungmi Oh ◽  
Justin Seung-Ho Yoo ◽  
Maria Koullick

Introduction:Patent foramen ovale (PFO) is an open hole between the right and left upper chambers of the heart. It may increase the risk of stroke, so closure of the hole is considered a secondary prevention in patients who have experienced cryptogenic stroke. Recent evidence has been published on the effectiveness of PFO closure, including a publicly funded prospective study on the effectiveness of PFO closure for preventing recurrent stroke or transient ischemic attack in selected Korean patients who have experienced cryptogenic stroke. The objective of this study was to examine the cost-effectiveness of PFO closure using this recent evidence.Methods:Available clinical data from the aforementioned Korean prospective study and other recent multicenter trials funded by public bodies were used. The cost data were obtained from the current Korean National Health Insurance fee schedule. Utility data were extracted from local research on stroke patients. A cost-effectiveness analysis, based on a 20-year Markov model, was conducted using these data to compare PFO closure plus antiplatelet therapy with oral anticoagulants alone.Results:The initial analysis showed that PFO plus antiplatelet therapy costs KRW 7.13 million (USD 6,547) more than oral anticoagulants alone but has a higher utility of 1.3 quality-adjusted life-years (QALYs) per patient, which corresponds to an incremental cost-effectiveness ratio (ICER) of KRW 5.6 million (USD 5,142) per QALY. The implicit Korean ICER threshold is KRW 25 million (USD 22,955) for non-cancer drugs, so it seems that PFO plus antiplatelet therapy is cost effective in the Korean setting.Conclusions:Since this study used some transition probabilities from foreign sources, the results may not be completely transferable to the Korean setting. However, this is the best available evidence so far in Korea for the economic evaluation of the PFO closure procedure. Therefore, use of PFO closure in carefully selected patients with a history of cryptogenic stroke may benefit the public payer in Korea.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Stephen B Wilton ◽  
Mohammed A Almekhlafi ◽  
Doreen M Rabi ◽  
William A Ghali ◽  
Diane L Lorenzetti ◽  
...  

In patients with a patent foramen ovale (PFO) and a prior cryptogenic ischemic stroke or transient ischemic attack (TIA), the risk of recurrent events is unclear. To conduct a systematic review and meta-analysis of studies assessing the risk of recurrent cerebrovascular events in patients with cryptogenic cerebral ischemia and PFO. MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) databases were searched to identify studies in any language. Searches were supplemented by scanning bibliographies of key articles. Studies reporting original data on recurrent cerebrovascular events in patients with prior cryptogenic stroke or TIA and PFO, with or without a non-PFO comparison group, were included. Uncontrolled case series evaluating device or surgical closure of PFO were excluded. Two authors independently extracted the data from included studies and evaluated study quality. For studies with a non-PFO comparison group, relative risks were pooled using a fixed effects model after confirming homogeneity of results. For all studies, the pooled absolute rate of recurrent events was calculated using a random effects model due to heterogeneity of results. Fifteen studies published between 1994 and 2007, following 2377 patients over a mean of 37 months were included. In the four studies with a non-PFO comparison group, the pooled relative risk of recurrent stroke or TIA associated with the presence of a PFO was 1.1 (95% CI 0.8 to 1.5), while for recurrent ischemic stroke the pooled relative risk associated with the presence of a PFO was 0.8 (95% CI 0.5 to 1.3). The pooled absolute rate of recurrent ischemic stroke or TIA in patients with PFO was 4.0 events per 100 person-years (95% CI 3.0 to 5.1) while the rate of recurrent ischemic stroke was 1.6 events per 100 person years (95% CI 1.1 to 2.1). No clinical or imaging features are reliably associated with increased risk of recurrent events. In medically treated patients with prior cryptogenic stroke, available evidence does not support an increased risk of recurrent ischemic events in those with vs. without a PFO. Routine PFO closure in these patients may not be warranted, outside of ongoing clinical trials.


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