Right ventricular and pulmonary vascular reserve in asymptomatic BMPR2 mutation carriers

Abstract

BACKGROUND: Non-invasive estimates have suggested that asymptomatic BMPR2 mutation cat-tiers may have an abnormal pulmonary vascular response to exercise and hypoxia. However, this has not been assessed with "gold standard" invasive measures. METHODS: Eight controls and 8 asymptomatic BMPR2 mutation carriers underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording during bicycle exercise in normoxia, hypoxia and after sildenafil administration. Abnormal pulmonary vascular reserve was defined as an increase in mean pulmonary artery pressure relative to cardiac output (P/Q slope) >3 nun Hg/liter/min. RESULTS: During normoxic exercise, BMPR2 mutation carriers had a similar P/Q slope when compared with healthy subjects. Only 1 of 8 BMPR2 mutation carriers had a P/Q slope >3 mm Hg/liter/min. During exercise in hypoxia, 3 of 8 BMPR2 mutation carriers had P/Q slopes >3 nun Hg/liter/min compared with none of the controls. Sildenafil decreased the P/Q slope both in controls and BMPR2 mutation carriers. The exercise-induced increase in right ventricular ejection fraction was similar between groups. None of the BMPR2 mutation carriers developed pulmonary arterial hypertension within 2 (range 1.3 to 2.8) years. CONCLUSIONS: The presence of a BMPR2 mutation, per se, is not associated with an abnormal pulmonary vascular and right ventricular functional response to exercise in asymptomatic individuals. Longer follow-up will be required to determine whether a P/Q slope of >3 mm Hg/liter/min during exercise in normoxia or hypoxia is a sign of pre-clinical disease expression. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.