Right ventricular and pulmonary vascular reserve in asymptomatic BMPR2 mutation carriers.

Abstract

BACKGROUND:

Non-invasive estimates have suggested that asymptomatic BMPR2 mutation carriers 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 mm 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 mm 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.

• Authors: Guido Claessen, Andre La Gerche, Thibault Petit, Hilde Gillijns, Jan Bogaert, Mathias Claeys, Steven Dymarkowski, Piet Claus, Marion Delcroix, Hein Heidbuchel
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 36 Issue 2 Pg. 148-156 (Feb 2017) ISSN: 1557-3117 [Electronic] United States
• PMID: 27475894 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Sildenafil Citrate
• BMPR2 protein, human
• Bone Morphogenetic Protein Receptors, Type II

Topics

• Adult
• Blood Gas Analysis
• Bone Morphogenetic Protein Receptors, Type II (genetics)
• Cardiac Output (physiology)
• Case-Control Studies
• Exercise Test (methods)
• Female
• Heterozygote
• Humans
• Hypertension, Pulmonary (diagnosis, genetics)
• Magnetic Resonance Imaging, Cine (methods)
• Male
• Middle Aged
• Mutation
• Pulmonary Circulation (drug effects, physiology)
• Reference Values
• Retrospective Studies
• Severity of Illness Index
• Sildenafil Citrate (administration & dosage)
• Ventricular Function, Right (physiology)