LAUSR

Patent foramen ovale (PFO) has been the subject of great interest and controversy, and has captivated the attention of specialists across multiple disciplines. The last 10 years (Round 1) have focused on assessing the relationship between PFOs and cryptogenic strokes in ambulatory patients with a history of stroke or transient ischaemic attack (TIA). The major morbidity and mortality associated with stroke, the availability of percutaneous closure technology, and the high prevalence of PFOs in the general population prompted a flurry of investigations in the field. However, the large body of evidence that emerged from case control series, institutional registries, and the first three PFO randomized clinical trials (RCTs) often led to conflicting conclusions, discordant societal guidelines, and different practice patterns. Invasive cardiologists, among others, embraced the concept of device closure for secondary stroke prevention at least in younger patients (<65 years), while neurologists remained doubtful of the cause–effect relationship and favoured medical treatment as a first-line therapy in most patients. Nonetheless, the last 2 years witnessed two tipping points for PFO closure. First, in October 2016, the Food and Drug Administration (FDA) approved the AMPLATZER PFO Occluder (St. Jude, Minneapolis, MN, USA), although the panel vote reflected unsettled debates, with an overwhelming majority approving the safety of the device (15–1) but only a slight majority approving of the device’s efficacy (9–7). Secondly, three RCTs were published in September 2017, the results of which unequivocally suggested the superiority of device closure over medical therapy for secondary stroke prevention. The FDA approval, along with these emerging positive data, led to an increasing utilization of PFO device closure, but also to a growing interest in multidisciplinary collaboration and additional investigations to identify the optimal candidates for the procedure. What did we learn from Round 1 of PFO closure for stroke prevention? (i) There is now compelling evidence that PFOs can be blamed for ‘some’ cryptogenic strokes, at least in a certain subset of patients. (ii) Anatomic features of PFOs vary significantly and the magnitude of benefit of PFO closure appears to be highest in patients with high-risk PFO anatomical features (e.g. those with large right to left shunt, or with significant septal aneurysm). (iii) Controversies remain regarding the optimal use of PFO closure devices, partially due to the strikingly high prevalence of PFOs, the relative infrequent incidence of strokes/TIAs that are felt to be cryptogenic, and the nonnegligible risk of incident atrial fibrillation following PFO device closure. We now move to Round 2 where the emerging science aims to confirm the findings of the RCTs, to ascertain the pathological impact of PFO in various clinical settings, and to guide optimal patient selection for device closure or medical therapy. In this issue of the European Heart Journal, Friedrich et al. bring to the forefront the topic of PFO-attributable ischaemic strokes in patients undergoing noncardiac surgery (Take home figure). The study cohort is derived from a retrospective institutional registry of 182 393 patients who were undergoing non-cardiac surgery with general anaesthesia at three hospitals in the USA between 2007 and 2015. The first analysis of this database compared peri-operative (30-day) ischaemic stroke rates between patients with and those without a diagnosis of PFO, and found that the estimated risks of stroke were 5.9/1000 patients with PFO and 2.2/1000 patients without PFO [adjusted odds ratio (aOR) 2.66; 95% confidence interval (CI) 1.96–3.63; P <0.001]. These findings provided a unique ‘proof-of-concept’ of the cause–effect relationship between PFO and strokes in a different cohort of patients from those who have been studied in RCTs and large registries. In the current study, the authors extended their previous 30-day analysis to (i) compare the long-term risk of ischaemic stroke after surgery between patients with and without a PFO and (ii) assess the impact of antithrombotic therapy on the incidence of post-operative stroke in patients with a PFO. The presence of a PFO was associated with a significant increase in post-operative acute ischaemic stroke at 1 year; 54 (4.7%) in patients with a PFO vs. 1588 (1.1%) in patients without a PFO (aOR 2.01; 95% CI 1.51–2.69; P < 0.001). This