View Abstract

A6994 - Onset of Hereditary Pulmonary Arterial Hypertension Provoked by High Altitude
Author Block: K. M. Moffitt1, J. C. Robinson2; 1Department of Medicine, Providence St. Vincent Medical Center, Portland, OR, United States, 2Pulmonary Vascular Institute, The Oregon Clinic, Portland, OR, United States.
Introduction:
Hereditable pulmonary arterial hypertension (HPAH) has been associated with mutations in several different genes. Penetrance of these mutations is variable with average onset at 36 years of age. Here, we report a case of a 69-year-old woman with likely HPAH that developed only after moving to high altitude, suggesting high altitude as a potential trigger of HPAH.
Case Report:
A 69-year-old woman presented to her local emergency department complaining of dyspnea. On presentation she was found to have volume overload due to new onset right heart failure and was admitted for diuresis. The patient underwent echocardiogram, followed by right heart catheterization which showed findings consistent with severe pulmonary arterial hypertension (PAH) with RV dysfunction. Importantly, the patient resided for the past 18 months at an altitude of 9500 feet, and had just returned home from a two-week trip at sea level. Further, the patient’s family history was notable for a daughter who died at age 18 years from what was thought to be idiopathic PAH. Her history and diagnostic evaluation were otherwise negative for toxin exposure, left heart disease, primary lung disease, thrombosis, and connective tissue disease, thus she was given a diagnosis of WHO Group I HPAH. The patient was started on tadalafil, ambrisentan, and supplemental home oxygen and subsequently moved to sea level. She continues showing signs of significant functional improvement, though echocardiographic evidence for PAH persists.
Discussion:
HPAH is associated most commonly with mutations in bone morphogenetic protein receptor 2 (BMPR2), which (via incompletely understood mechanisms) plays a role in pulmonary vascular remodeling. However, BMPR2 and other identified mutations display incomplete penetrance and variable expressivity, suggesting the importance of modifying factors in the development of disease. Chronic hypoxia caused by high altitude leads to a cascade of physiologic changes beginning with pulmonary vasoconstriction and ultimately involving endothelial remodeling of pulmonary vasculature. It is known that existing pulmonary hypertension and rapid ascent are risk factors for developing altitude related lung disease. For our patient with underlying undiagnosed pulmonary vascular disease, travel to sea level followed by rapid ascent may have resulted in added vasoconstriction, leading to acute right heart failure.
This case demonstrates the potential influence of high altitude as a modifying factor for development of HPAH. With further investigation into genetic and environmental factors involved in HPAH, earlier diagnosis and prevention of disease development may lead to improved patient outcomes with regard to morbidity and mortality.