Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke.

INTRODUCTION: Patent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. METHODS: Consecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. RESULTS: Our cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). CONCLUSIONS: In this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

Association of Shunt Size and Long-Term Clinical Outcomes in Patients with Cryptogenic Ischemic Stroke and Patent Foramen Ovale on Medical Management.

INTRODUCTION: Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. METHODS: Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. RESULTS: The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]. CONCLUSIONS: In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Potential Embolic Sources in Embolic Stroke of Undetermined Source Patients with Patent Foramen Ovale.

INTRODUCTION: A patent foramen ovale (PFO) may coexist with other potential embolic sources (PESs) in patients with embolic stroke of undetermined source (ESUS), leading to difficulty in attributing the stroke to either the PFO or other PESs. We aimed to investigate the prevalence and predictors of concomitant PESs in ESUS patients with PFOs. METHODS: A retrospective cohort study was conducted in a tertiary stroke centre. Consecutive patients with ESUS and a concomitant PFO admitted between 2012 and 2021 were included in the study. Baseline characteristics and investigations as a part of stroke workup including echocardiographic and neuroimaging data were collected. PESs were adjudicated by 2 independent neurologists after reviewing the relevant workup. RESULTS: Out of 1,487 ESUS patients, a total of 309 patients who had a concomitant PFO with mean age of 48.8 ± 13.2 years were identified during the study period. The median Risk of Paradoxical Embolism (RoPE) score for the study cohort was 6 (IQR 5-7.5). Of the 309 patients, 154 (49.8%) only had PFO, 105 (34.0%) patients had 1 other PES, 34 (11.0%) had 2 PES, and 16 (5.2%) had 3 or more PES. The most common PESs were atrial cardiopathy (23.9%), left ventricular dysfunction (22.0%), and cardiac valve disease (12.9%). The presence of additional PESs was associated with age ≥60 years (p < 0.001), RoPE score ≤6 (p ≤0.001), and the presence of comorbidities including diabetes mellitus (p = 0.004), hypertension (p≤ 0.001), and ischaemic heart disease (p = 0.011). CONCLUSION: A large proportion of ESUS patients with PFOs had concomitant PESs. The presence of concomitant PESs was associated with older age and a lower RoPE score. Further, large cohort studies are warranted to investigate the significance of the PES and their overlap with PFOs in ESUS.