Epidemiology of Patent Foramen Ovale in General Population and in Stroke Patients: A Narrative Review

Abstract

Introduction: Percutaneous closure of patent foramen ovale (PFO) in selected patients with cryptogenic cerebrovascular ischemic events (CEs) decreases the risk of recurrent stroke; however, optimal patient selection criteria are still under investigation. Candidates for PFO closure are usually selected from the pool of CE patients with a high risk of Paradoxical Embolism (RoPE) score. The RoPE score calculates the probability that PFO is causally related to stroke, based on PFO prevalence in patients with CE compared with that in healthy subjects. The latter has been set at 25% based on the average of autopsy and transesophageal echocardiography (TEE) studies. Methods: We conducted a comprehensive review of studies investigating PFO prevalence in general population and in patients with CE and non-CE using autopsy, TEE, transcranial Doppler (TCD) or transthoracic echocardiography (TTE). Studies were excluded if they (1) reported data from referred subjects with underlying cerebrovascular disease or (2) did not specify etiologically the events. Results: In healthy/control subjects, PFO prevalence was 24.2% (1,872/7,747) in autopsy studies, 23.7% (325/1,369) in TEE, 31.3% (111/355) in TCD, and 14.7% (186/1,267) in TTE studies. All diagnostic modalities included PFO prevalence was higher in CE compared with healthy/control population [odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.5-3.8] and compared with non-CE (OR = 2.3, 95% CI = 2.0-2.6). In patients with CE, PFO prevalence in the young compared to the old was higher when the diagnostic modality was TEE (48.9 vs. 27.3%, p < 0.0001, OR = 2.6 with 95% CI = 2.0-3.3) or TCD (58.1 vs. 41%, OR = 1.9, 95% CI = 1.6-2.5), but not TTE (53.3 vs. 37.5%, p = 0.16). Regarding non-CE, PFO prevalence in the young compared to the old was higher when the diagnostic modality was TEE (20 vs. 12.9%, OR = 1.7, 95% CI = 1.0-2.8) but not TTE (10.4 vs. 7.8%, p = 0.75) or TCD (22.8 vs. 20.1%, p = 0.56). Conclusions: Given the limitations of autopsy and TEE studies, there is good reason not to take a fixed 25% PFO prevalence for granted. The estimation of degree of causality may be underestimated or overestimated in populations with PFO prevalence significantly lower or higher than the established. Given the high sensitivity, non-invasive nature, low cost, and repeatability of TCD, future large-scale TCD-based studies should investigate potential heterogeneity in PFO prevalence in different healthy racial/ethnic populations.

Systemic thromboemboli in patients with Covid-19 may result from paradoxical embolization

“…Patients with COVID-19 pneumonia will almost certainly have some intra-pulmonary shunt [10][11][12]. Previous studies have reported that the prevalence of intra-pulmonary shunt is higher in patients with cryptogenic stroke (22%) than in matched controls (10%) [13].…”

“…However, discussion of paradoxical embolization, a well-recognised cause of stroke and systemic embolization [9,10,12], was conspicuously absent from their scoping review. We therefore suspect that this phenomenon is being overlooked during the current pandemic.…”

“…The most common inter-atrial defect is patent foramen ovale (PFO). The prevalence of PFO is significantly higher in patients with a history of ischaemic stroke (prevalence 50%) [12] than in the general population (prevalence 20-30%) [12]. Indeed, prevention of recurrence after a PFO-related stroke is currently the only indication for PFO closure that is supported by randomised controlled trials [10,12].…”

“…This may be counterproductive. Despite the absence of specific data in patients with COVID-19; prevention of recurrence of PFO-related stroke and treatment of hypoxia due to RTL inter-atrial shunt are well recognised indications for PFO closure [10,12]. Patients with shunt may be at high risk of complications from COVID-19 [9,10].…”

The Role of Echocardiography Screening at the Stroke Unit

“…In young patients with cryptogenic stroke and a high Risk of Paradoxical Embolism (RoPE) score the presence of a PFO must be evaluated (24). TTE may detects certain normal anatomic variations of cardiac structures that may favor the formation of thrombi (25). The aneurysm of the interatrial septum, defined as >11 mm to >15 mm septum protrusion, is frequently associated with larger PFO (>4 mm size) and increases the risk of further stroke (26,27).…”