Unexplained Hypoxemia Following Acute Ischemic Stroke: Unmasking Platypnea-Orthodeoxia Syndrome in the Setting of a Patent Foramen Ovale

Introduction

Patent foramen ovale (PFO) is implicated in cryptogenic stroke and, less commonly, refractory hypoxemia via right-to-left shunting. Though often asymptomatic, PFO may rarely present with Platypnea-Orthodeoxia Syndrome (POS)—positional hypoxemia that worsens upright and resolves supine. Diagnosis is often delayed, particularly in acute care where common causes of hypoxia dominate the differential. This case highlights the importance of recognizing POS in a post-stroke patient with a PFO and recurrent unexplained hypoxemia.

Case Presentation

A 72-year-old male with hypertension, hyperlipidemia, prediabetes, and prior CVA without residual deficits presented with acute expressive aphasia. Imaging confirmed acute left MCA ischemia with probable thrombus in the proximal left M2 branch; he received tenecteplase. Echocardiography showed EF 50–55%, mild mitral and tricuspid regurgitation, and a PFO, with TEE confirming a significant right-to-left interatrial shunt. Based on a RoPE score estimating only 38% probability of PFO-related stroke, cardiology favored paroxysmal atrial fibrillation and recommended long-term monitoring prior to closure.

The course was complicated by recurrent desaturation to 88%, requiring high-flow nasal cannula and BiPAP, with one episode necessitating ICU transfer for hypoxic respiratory failure requiring vasopressors. Extensive workup (serial radiographs, D-dimer, lower extremity duplex, CT chest, procalcitonin) identified no definitive cardiopulmonary or infectious etiology. The turning point came when pulmonology identified a positional pattern to oxygen requirements consistent with POS (sitting 91%, supine 98%). Right heart catheterization confirmed normal pulmonary pressures, and continuous telemetry showed no atrial fibrillation, diminishing the initial leading differential. PFO closure on hospital day 21 was uncomplicated, promptly stabilizing room-air oxygenation to 94–97%. The patient was started on DAPT and transferred to a skilled nursing facility.

Discussion

This case illustrates the diagnostic challenge of POS in a hospitalized post-stroke patient, where evaluation appropriately focused on common causes of hypoxia, delaying recognition of the positional component. It parallels prior stroke-associated POS reports in which older patients with post-stroke dyspnea and a PFO improved after percutaneous closure—treating both the shunt and a stroke risk factor. POS requires both an anatomic defect (shunt) and a functional/positional component, explaining why a "hemodynamically insignificant" shunt can cause profound positional hypoxemia despite normal right heart pressures. Before attributing hypoxemia to a PFO, mimics such as hepatopulmonary syndrome, pulmonary AVMs, and V/Q mismatch must be excluded. Key points: (1) consider POS for unexplained hypoxemia when a PFO is known, even if the shunt appears insignificant; (2) the positional nature of desaturation is easily obscured in acutely ill patients with limited mobility; and (3) rapid resolution after closure serves as both diagnostic confirmation and definitive therapy. Contemporary series report a median symptom-to-diagnosis delay near 13 weeks and marked oxygenation improvement after closure. However, POS patients carry higher long-term mortality—largely non-cardiovascular—suggesting POS may mark broader underlying illness rather than an isolated curable lesion.