Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

Author:

Hsu Steven1,Houston Brian A.1,Tampakakis Emmanouil1,Bacher Anita C.1,Rhodes Parker S.1,Mathai Stephen C.1,Damico Rachel L.1,Kolb Todd M.1,Hummers Laura K.1,Shah Ami A.1,McMahan Zsuzsanna1,Corona-Villalobos Celia P.1,Zimmerman Stefan L.1,Wigley Fredrick M.1,Hassoun Paul M.1,Kass David A.1,Tedford Ryan J.1

Affiliation:

1. From Divisions of Cardiology (S.H., B.A.H., E.T., A.C.B., P.S.R., D.A.K., R.J.T.), Pulmonary and Critical Care (S.C.M., R.L.D., T.M.K., P.M.H.), and Rheumatology (L.K.H., A.A.S., Z.M., F.M.W.), Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD; and Departments of Radiology (C.P.C.-V., S.L.Z.) and Biomedical Engineering (D.A.K.), Johns Hopkins Medical Institutions, Baltimore, MD.

Abstract

Background— Right ventricular (RV) functional reserve affects functional capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis than idiopathic PAH (IPAH), even though many measures of resting RV function and pulmonary vascular load are similar. We therefore tested the hypothesis that RV functional reserve is depressed in SSc-PAH patients. Methods and Results— RV pressure-volume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental atrial pacing or supine bicycle ergometry. Systolic and lusitropic function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH. The recirculation fraction, which indexes intracellular calcium recycling, was also depressed in SSc-PAH (0.32±0.05 versus 0.50±0.05; P =0.039). At matched exercise (25 W), SSc-PAH patients did not augment contractility (end-systolic elastance) whereas IPAH did ( P <0.001). RV afterload assessed by effective arterial elastance rose similarly in both groups; thus, ventricular-vascular coupling declined in SSc-PAH. Both end-systolic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas chamber dilation was absent in IPAH (+37±10% versus +1±8%, P =0.004, and +19±4% versus –1±6%, P <0.001, respectively). Exercise-associated RV dilation also strongly correlated with resting ventricular-vascular coupling in a larger cohort. Conclusions— RV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling. During exercise, this results in ventricular-pulmonary vascular uncoupling and acute RV dilation. RV dilation during exercise can predict adverse ventricular-vascular coupling in PAH patients.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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