Patent foramen ovale (PFO) is present in approximately one quarter of adults and is usually clinically silent.1 In a subset of patients with otherwise unexplained ischemic stroke – particularly younger individuals with an embolic event, a PFO is a plausible mechanism. Randomized trials have shown that transcatheter PFO closure, compared with medical therapy alone, reduces recurrent stroke in carefully selected patients, especially when high-risk anatomical features are present.2–5 However, closure is not without trade-offs, including periprocedural complications and an increased risk of atrial fibrillation, typically early after the procedure and often transient.2–5 Accordingly, the central challenge has shifted from technical feasibility to precision in patient selection and long-term net clinical benefit, a principle reinforced by European Society of Cardiology (ESC) guidance and European interdisciplinary position papers.6–8

Conde et al.2 present a well-executed single-center experience with percutaneous PFO closure in young adults with cryptogenic stroke, offering valuable insight into contemporary real-world practice. While randomized trials have established the benefit of closure in carefully selected younger patients,2–5 this study highlights a critical and evolving challenge in the field: refining who should undergo closure as referrals and potential indications extend beyond the original trial populations.

A key strength of the authors’ work lies in their disciplined selection strategy. Only 51.6% of evaluated patients proceeded to closure, guided by a multidisciplinary Cardiology-Neurology framework that incorporated neuroimaging review, exclusion of alternative stroke etiologies, and structured risk stratification using RoPE and PASCAL classifications.9,10 This approach aligns closely with pooled randomized trial data showing that the magnitude of benefit from PFO closure depends strongly on the likelihood that the PFO is causally related to the index stroke.10 By predominantly selecting patients categorized as PASCAL “probable” or “possible,” the authors mirror populations in whom randomized trials have demonstrated the greatest reduction in recurrent ischemic events.2,9,10

The consistently excellent procedural outcomes – 100% technical success, no major complications, and complete closure at follow-up – reinforce the safety of PFO closure when performed in experienced centers.2–5 Yet these results also underscore an important point: procedural success alone should not drive the expansion of indications. As the authors acknowledge, the central unresolved issue is not how safely PFOs can be closed, but rather in whom closure confers durable clinical benefit.8

This question is particularly pressing in older patients (>60 years). Randomized trials largely excluded this group2–5 and observational evidence suggests that, as age increases, competing stroke mechanisms – atrial fibrillation, atherosclerosis, and small-vessel disease – become more prevalent, thereby diminishing the causal role of PFO.7,10,11 European position papers recognize the limited evidence base in this age group, supporting highly selective, individualized decision-making and highlighting the need for dedicated trials or high-quality prospective registries.6–8

Other subgroups increasingly referred for PFO closure, such as patients with migraine, professional divers and platypnea–orthodeoxia syndrome cases, also warrant careful consideration. The European position paper specifically addresses these non-stroke scenarios, recommending restraint and individualized assessment given the uncertainty of durable patient-centered benefit and the predominance of non-randomized evidence in several indications.8

In this evolving landscape, the present study is an important reminder that rigorous multidisciplinary evaluation remains essential as indications for PFO closure expand. The authors’ conservative approach aligns with European recommendations that emphasize avoiding indiscriminate expansion beyond evidence-based criteria, thereby minimizing exposure to harm and preserving the credibility of an intervention that is highly effective when appropriately applied.6–8

Ultimately, no algorithm, score, or guideline can substitute for individualized clinical judgment. Even in the presence of favorable anatomy or high-risk scores, the decision to proceed with closure should remain case-based, integrating neurological phenotype, competing stroke mechanisms, age, comorbidities, and procedural risk.6,10 Equally important is meaningful patient involvement. Patients should be counseled not only on potential benefits, but also on persisting uncertainties, particularly in older individuals and in non-stroke indications such as migraine or decompression illness.7,8 Shared decision-making is therefore a clinical and ethical necessity, ensuring that enthusiasm for a technically safe procedure does not outpace evidence of durable patient-centered benefit.