Impaired Right Ventricular–Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction

Author:

Hussain Imad1,Mohammed Selma F.1,Forfia Paul R.1,Lewis Gregory D.1,Borlaug Barry A.1,Gallup Dianne S.1,Redfield Margaret M.1

Affiliation:

1. From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).

Abstract

Background— Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV–pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV–PA coupling may be uniquely sensitive to sildenafil. Methods and Results— In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV–PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO 2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO 2 slope were unchanged with sildenafil. There was no interaction between RV–PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO 2 in patients with pulmonary hypertension and RVD. Conclusions— HFpEF patients with RVD and impaired RV–PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV–PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00763867.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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