The PROOF Trial - Prospective, Open-label, Multicenter, Non-randomized Investigation on Percutaneous Patent Foramen Ovale (PFO) Closure Using the Occlutech PFO Occluder to Prevent Recurrence of Stroke in Patients With Cryptogenic Stroke and High Risk PFO

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.

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Cryptogenic Stroke and High-Risk Patent Foramen Ovale

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2018.02.046 ◽

2018 ◽

Vol 71 (20) ◽

pp. 2335-2342 ◽

Cited By ~ 146

Author(s):

Pil Hyung Lee ◽

Jae-Kwan Song ◽

Jong S. Kim ◽

Ran Heo ◽

Sahmin Lee ◽

...

Keyword(s):

High Risk ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Foramen Ovale

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Five Year Follow-Up of Cryptogenic Stroke Patients Following Patent Foramen Ovale Closure

Medical Sciences Forum ◽

10.3390/iecmd2021-10313 ◽

2021 ◽

Vol 6 (1) ◽

pp. 2

Author(s):

Agnete Teivāne ◽

Kristaps Jurjāns ◽

Ainārs Rudzītis ◽

Krista Lazdovska ◽

Artūrs Balodis ◽

...

Keyword(s):

Ischemic Stroke ◽

Transient Ischemic Attack ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Foramen Ovale ◽

Residual Shunt ◽

Amplatzer Occluder ◽

Cerebrovascular Events ◽

Ischemic Attack ◽

Pfo Closure

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.

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Endovascular closure of patent foramen ovale: a critical appraisal of published trials

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190120 ◽

2019 ◽

Vol 77 (10) ◽

pp. 731-740

Author(s):

Charles ANDRÉ

Keyword(s):

Patent Foramen Ovale ◽

Therapeutic Option ◽

Cryptogenic Stroke ◽

Young Patients ◽

Foramen Ovale ◽

Open Label ◽

Number Of Patients ◽

Numbers Needed To Treat ◽

Atrial Septum Aneurysm ◽

Incomplete Occlusion

ABSTRACT The treatment of cryptogenic stroke patients with a patent foramen ovale (PFO) is controversial. A critical review of these studies is presented. Methods A description of all trials comparing medical and endovascular treatment with closing devices is given. Additional pertinent studies are discussed to help construct a rational basis for treatment decisions. Results Initial negative trials evaluating PFO closure were followed by positive studies published in 2017 and 2018. All trials evaluated young patients (up to 60 years). Methodological problems are present in all trials including their open label construction. Most positive trials developed strategies to increase the percentage of patients with interatrial septal aneurysms or hypermobility and large right-to-left shunts. Even in these positive trials, large numbers of patients need to be treated to avoid one stroke. Atrial fibrillation occurred in 2-6% and other adverse effects related to the procedure and to the devices occurred in a substantial number of patients. Incomplete occlusion of the PFO is also frequent. Anticoagulant treatment has not been adequately studied as a therapeutic option. Conclusion Young patients with cryptogenic strokes seem to benefit from endovascular closure of a PFO in the presence of a large right-to-left shunt or an associated atrial septum aneurysm. For most other patients, a highly-individualized decision must be made, taking into account the low risk of recurrence in patients with a cryptogenic stroke attributable to a PFO, the high numbers needed to treat and the risks related to the procedure.

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Patent Foramen Ovale and Cryptogenic Stroke: Challenges in Diagnosis and Management

Indonesian Journal of Cardiology ◽

10.30701/ijc.1144 ◽

2021 ◽

Vol 42 (3) ◽

Author(s):

Dhanang Ali Yafi ◽

Azmi Azmi

Keyword(s):

Patent Foramen Ovale ◽

Adult Population ◽

Management Strategies ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Foramen Ovale ◽

Arterial Circulation ◽

Systemic Embolization ◽

The Relationship ◽

Pfo Closure

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.

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Importance of Contrast Transthoracic Echocardiography for Evaluating Large Right-to-Left Shunt in Patent Foramen Ovale Associated with Cryptogenic Stroke

10.21203/rs.3.rs-760835/v1 ◽

2021 ◽

Author(s):

Yoichi Takaya ◽

Rie Nakayama ◽

Teiji Akagi ◽

Fumi Yokohama ◽

Takashi Miki ◽

...

Keyword(s):

High Risk ◽

Transesophageal Echocardiography ◽

Transthoracic Echocardiography ◽

Patent Foramen Ovale ◽

Transcatheter Closure ◽

Cryptogenic Stroke ◽

Effective Therapy ◽

Foramen Ovale

Abstract Transcatheter closure of patent foramen ovale (PFO) is an effective therapy for preventing cryptogenic stroke (CS). The identification of high-risk PFO, which is more likely to be linked to CS, is essential. This study aimed to assess the accuracy of contrast transthoracic echocardiography (TTE) for evaluating large right-to-left (RL) shunt. We enrolled 119 patients with or without CS who were confirmed to have PFO. The severity of RL shunt evaluated by contrast TTE and transesophageal echocardiography (TEE) was classified as follows: small (<10 microbubbles), moderate (10–20 microbubbles), and large (>20 microbubbles). With contrast TTE, large RL shunt was observed in 94 (79%) of 119 patients, including 66 of 74 with CS and 28 of 45 without CS. With contrast TEE, large RL shunt was observed in 33 (28%) patients, including 26 with CS and 7 without CS. Contrast TTE showed large RL shunt more frequently than contrast TEE (p < 0.01). Large RL shunt evaluated by contrast TTE had a sensitivity of 89% and an accuracy of 70% for the association with CS, whereas large RL shunt evaluated by contrast TEE had a sensitivity of 35% and an accuracy of 56%. Accuracy was significantly greater in contrast TTE than in contrast TEE (p = 0.02). In conclusion, contrast TTE identified large RL shunt more frequently. Large RL shunt evaluated by contrast TTE provided greater accuracy for the association with CS. Our findings suggest that contrast TTE is valuable for evaluating large RL shunt as high-risk PFO.

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

Thrombosis and Haemostasis ◽

10.1055/s-0039-1693739 ◽

2019 ◽

Vol 119 (11) ◽

pp. 1839-1848 ◽

Cited By ~ 4

Author(s):

Claus V. B. Hviid ◽

Claus Ziegler Simonsen ◽

Anne-Mette Hvas

Keyword(s):

Anticoagulant Therapy ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Preventive Strategy ◽

Foramen Ovale ◽

Antithrombotic Treatment ◽

Risk Of Recurrence ◽

Increased Risk ◽

Acquired Thrombophilia ◽

Pfo Closure

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.

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PP122 A Quick Cost-Effectiveness Analysis Of Patent Foramen Ovale Closure In Korean Patients With Cryptogenic Stroke

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462318002581 ◽

2018 ◽

Vol 34 (S1) ◽

pp. 112-113

Author(s):

Jeonghoon Ahn ◽

Eung Ju Kim ◽

Kyungmi Oh ◽

Justin Seung-Ho Yoo ◽

Maria Koullick

Keyword(s):

Cost Effectiveness ◽

Prospective Study ◽

Antiplatelet Therapy ◽

Patent Foramen Ovale ◽

Oral Anticoagulants ◽

Cryptogenic Stroke ◽

Foramen Ovale ◽

Effectiveness Analysis ◽

The Cost ◽

Pfo Closure

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.

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Closing the Patent Foramen Ovale with Amplatzer Devices

European Cardiology Review ◽

10.15420/ecr.2009.5.1.71 ◽

2009 ◽

Vol 5 (1) ◽

pp. 71

Author(s):

Bernhard Meier ◽

Keyword(s):

Medical Treatment ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

University Hospital ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

Residual Shunt ◽

Catheter Closure ◽

Pfo Closure

The relative risk of a thromboembolic event is four-fold higher in the 25–35% of adults with a patent foramen ovale (PFO) and 33-fold higher in patients who also have an atrial septal aneurysm. The American PICSS trial showed a yearly incidence of stroke or death after an initial event of 5% with warfarin and 9% with acetylsalicylic acid. The presence of a PFO more than doubles the mortality rate in patients with clinically relevant pulmonary embolism. The risk of a PFO increases with age. Proof of effectiveness in migraine alleviation is likely to be achievable in a couple of years – much quicker than in prevention of paradoxical embolism. Percutaneous closure of PFO has been performed with various devices at the University Hospital Bern in Switzerland since April 1994, with over 1,000 patients treated. At the last available transoesophageal echocardiogram, a significant residual shunt persisted in 4% with Amplatzer devices and 17% with other devices. During follow-up, a recurrent embolic event was observed in 1.6% of patients per year – less than would be expected under medical treatment. Several randomised multicentre trials comparing catheter closure with medical treatment have been started. The PC and CLOSURE trials are in the follow-up phase; results cannot be expected before 2010, and they may well be ‘falsely’ neutral because the follow-up is rather short for the low-risk patients randomised. In a matched control study on patients with cryptogenic stroke and a PFO, 158 patients were treated medically and 150 concomitant patients underwent percutaneous PFO closure. At four years, PFO closure resulted in a trend towards risk reduction of death, stroke or transient ischaemic attack (TIA) (9 versus 24%; p=0.08) compared with medical treatment. The calculated occurrence of patients with cryptogenic strokes associated with a PFO amounts to somewhere between 100 and 300 per year and per million population, corresponding to more than 10% of yearly coronary angioplasty cases. Coronary and peripheral paradoxical emboli without prior exclusion of competing causes plus the presumed associations between PFO and migraine or decompression illness in divers open additional vast fields of potential indications for catheter closure. Finally, the linearly decreasing prevalence of a PFO with age suggests a weeding out of PFO carriers (unless spontaneous closure is assumed). A PFO represents a lethal threat that increases with age. It can be closed percutaneously in 15 minutes virtually free of complications. The patient can resume unrestricted physical activities a few hours after the intervention.

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