Case Presentation: A 56-year-old male with WHO Group I/III pulmonary hypertension (PH), Gold Stage III COPD, and right ventricular failure presented with several weeks of gradually worsening dyspnea. One month prior, he was hospitalized for an acute exacerbation of PH and was discharged on an increased dose of ambrisentan after excluding intra-atrial shunting. On the current presentation, exam was significant for an oxygen saturation of 82% on his baseline oxygen of 4 L/min via nasal cannula. He required high flow oxygen with high FiO2 to improve his saturation. Cardiopulmonary exam revealed clear lungs, jugular venous distension, and trace peripheral edema. Chest radiograph revealed no infiltrates or effusions. Infectious evaluation was negative.Acute decompensated heart failure was suspected based largely on his JVD. However, despite several days of aggressive diuresis, he had no improvement in his dyspnea or oxygenation, making low cardiac output an unlikely etiology. Taken together with normal imaging and lack of any evidence supporting alternative etiologies, he was deemed to have intravascular shunting to emphysematous areas of the lung related to aggressive vasodilation in the setting of his recently increased ambrisentan dose. Ambrisentan was held, resulting in improvement of his symptoms and return to his baseline oxygen requirement, thus confirming the diagnosis.
Discussion: Hospitalists frequently serve as primary inpatient physicians for patients with PH and therefore must understand its pathophysiology and complications. The differential diagnosis for acute hypoxemic respiratory failure in PH includes ventilation (V) to perfusion (Q) mismatch, reduced diffusion capacity, intracardiac shunting, and low cardiac output. Pulmonary vasodilators are used to reduce pulmonary vascular resistance and improve cardiopulmonary function. Hypoxic pulmonary vasoconstriction is a homeostatic mechanism in which pulmonary arteries constrict in response to alveolar hypoxia to maximize V/Q matching (1). In the setting of underlying lung disease, vasodilator therapy can counter this mechanism and result in increased perfusion to diseased areas of the lung, resulting in worsened V/Q mismatch and subsequent hypoxemia. Multiple studies have demonstrated worsened systemic oxygenation and functional capacity with vasodilator therapy due to this proposed mechanism (2,3). Resolution of the hypoxemia after discontinuation of vasodilators confirms this etiology. Similar decline precipitated by vasodilators can occur with pulmonary veno-occlusive disease (PVOD), a rare subtype of PH caused by diseased post-capillary lung vasculature (4). In PVOD, vasodilation results in pulmonary edema due to increased intravascular hydrostatic pressure in the setting of pulmonary venous occlusion. Recent inconsistent evaluation and lack of evidence of significant pulmonary edema makes PVOD very unlikely in this case.
Conclusions: Vasodilator therapy in PH patients with underlying COPD carries a risk of precipitating hypoxemia due to worsened V/Q mismatch. Hospitalists must recognize this as a potential etiology in such patients, as reduction of vasodilator therapy is necessary to improve oxygenation.