CASE PRESENTATION: We describe a case of a 44-year-old female COPD, Systolic Heart Failure, and Asthma presenting with sudden onset hypoxemic respiratory failure requiring emergent endotracheal intubation. On arrival, hypoxemia persisted with oxygen saturations 69-73% despite maximal supplemental oxygen and airway pressure release ventilation with a positive end expiratory pressure of 20. The admission vital signs included a blood pressure of 90/54, pulse 87, and temperature of 100.3 degrees F. The cardiopulmonary examination encompassed a sedated female with bilateral rhonchi without wheezing/rales and s1/s2 without additional mummers. The rest of the examination was unremarkable. A computed tomography angiogram revealed a submissive PE to the left lower lobe anterobasal and medial-basal segments with diffuse ground glass opacities throughout the lungs due to infarction. Given her refractory hypoxia and hypotension requiring norepinephrine, a bedside echocardiogram was performed and revealed evidence of right ventricular failure and transesophageal echocardiogram demonstrated a PFO (9mm) with right to left intra-cardiac shunting. Initiating Inhaled NO (INO), epoprostenol, and milrinone facilitated shunt reversal by reducing the PVR. Ultimately, the patient was extubated and discharged with closure of the PFO.