Introduction
Patent foramen ovale (PFO) is a common anatomical variation present in approximately 25% of the adult population. While often benign, it serves as a potential conduit for paradoxical embolism, where a venous thrombus bypasses the pulmonary circulation to enter the systemic arterial system, leading to cryptogenic stroke or transient ischemic attack (TIA). Transcatheter closure of the PFO has emerged as a definitive therapy to prevent recurrent ischemic events. However, while short-to-medium-term data are robust, very long-term outcome data—spanning two decades—have remained scarce until recently. Understanding the 20-year trajectory is essential for clinicians to counsel patients on the lifelong safety and efficacy of the device and the necessity of concurrent medical therapy.
Patient Information and Study Design
This report details the findings of a single-center cohort study conducted at a tertiary university hospital. The study population comprised 130 consecutive patients who underwent transcatheter PFO closure between 2001 and 2006. The mean (SD) age of the participants at the time of the procedure was 46 (14) years, representing a relatively young cohort often seen in cryptogenic stroke cases. The gender distribution was nearly equal, with 67 women (51.5%) and 63 men (48.5%). All patients had a history of PFO-associated embolism, manifested as cryptogenic stroke, TIA, or peripheral embolism, prior to the intervention.
Diagnosis
The primary diagnosis for inclusion was PFO-associated paradoxical embolism. This diagnosis was established through a rigorous workup to exclude other potential causes of stroke. Key diagnostic criteria included:
- Confirmed PFO: Demonstrated via transesophageal echocardiography (TEE) or transthoracic echocardiography (TTE) with bubble study, showing right-to-left shunting.
- Ischemic Event: Clinical and imaging evidence (MRI or CT) of stroke or TIA without an identifiable source such as carotid stenosis or atrial fibrillation.
- Paradoxical Embolism: Suspected based on the absence of traditional cardiovascular risk factors and the presence of a PFO, often quantified by the Risk of Paradoxical Embolism (RoPE) score.
Differential Diagnosis
Before attributing an ischemic event to a PFO, several other etiologies must be ruled out to ensure the patient will benefit from closure:
- Large Artery Atherosclerosis: Ruled out via carotid ultrasound or CT angiography.
- Small Vessel Disease (Lacunar Infarction): Ruled out based on neuroimaging patterns.
- Cardioembolism: Specifically atrial fibrillation (AF), ruled out via extended ECG monitoring or Holter monitoring.
- Hypercoagulable States: While not a reason to rule out PFO closure, thrombophilia screening was performed, as it significantly impacts recurrence risk.
Treatment and Management
All 130 patients underwent technically successful transcatheter PFO closure. The procedures involved the deployment of an occluder device (typically a double-disk system) via femoral venous access. Post-procedure management included:
- Echocardiographic Follow-up: Performed within 1 to 6 months post-procedure to ensure proper device positioning and the absence of significant residual shunt.
- Antithrombotic Regimen: Initially, patients were placed on various regimens, including antiplatelet therapy (aspirin or clopidogrel) or anticoagulation, depending on individual risk profiles and contemporaneous clinical guidelines.
- Long-term Monitoring: Patients were followed prospectively in the early stages, with retrospective long-term data collected via medical records and telephone interviews at the 20-year mark.
Outcome and Prognosis
The 20-year follow-up data provided a comprehensive look at the “lifelong” efficacy of the procedure:
- Survival: At 20 years, 20 patients (15.3%) had died. Notably, the majority of deaths (12.2%) were due to non-cardiovascular causes, suggesting the procedure does not introduce long-term life-threatening cardiac complications.
- Ischemic Recurrence: Recurrent events were remarkably infrequent. Only 1 stroke occurred (an incidence rate of 0.04 per 100 patients per year) and 6 TIAs were reported (0.25 per 100 patients per year). This confirms the sustained efficacy of the closure device in preventing paradoxical embolism.
- Antithrombotic Discontinuation: Approximately 20.5% of patients eventually discontinued antithrombotic treatment. Interestingly, none of these patients experienced an ischemic event during the follow-up period.
- Bleeding Complications: Bleeding was the primary adverse finding, occurring in 17 patients (13%). Major bleeding occurred in 9 cases (6.9%). These events were significantly more common in women (19.4% vs 6.3%) and were exclusively found in patients who remained on long-term antithrombotic therapy.
Discussion
This 20-year follow-up study reinforces transcatheter PFO closure as a safe and highly effective intervention for the prevention of recurrent stroke. The recurrence rate of less than 1% over two decades is a testament to the procedure’s durability. However, the study brings to light several critical nuances in long-term management.
First, the correlation between recurrent ischemic events and thrombophilia (33% in the recurrence group vs 4.8% in the non-recurrence group) suggests that patients with known hypercoagulable states may require more aggressive or tailored medical management even after successful PFO closure. Second, the findings regarding bleeding events are provocative. The fact that bleeding occurred exclusively in those on long-term antithrombotics—and that those who stopped therapy had zero ischemic events—raises important questions about the necessity of lifelong antiplatelet therapy after the device has successfully endothelialized.
The higher incidence of bleeding in women also warrants further investigation into gender-specific dosing or duration of therapy. Clinicians should consider a more personalized approach to post-closure care, potentially tapering or discontinuing antithrombotic therapy in low-risk patients once complete PFO occlusion is confirmed and sufficient time has passed for device healing.
References
- Vidal-Calés P, Houde C, Battistolo Q, et al. Twenty-Year Follow-Up After Patent Foramen Ovale Closure in Patients With Paradoxical Embolism. JAMA Cardiol. 2026 Feb 25:e260020. doi: 10.1001/jamacardio.2026.0020.
- Schuchlenz HW, Weihs W, Horner S, et al. The association between the presence of a patent foramen ovale and cryptogenic stroke. Multidisciplinary approach to a common problem. Z Kardiol. 2005.
- Kent DM, Saver JL, Kasner SE, et al. Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke. JAMA. 2021.