TY - JOUR
T1 - Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure with Preserved Ejection Fraction
AU - Borlaug, Barry A.
AU - Lewis, Gregory D.
AU - McNulty, Steven E.
AU - Semigran, Marc J.
AU - Lewinter, Martin
AU - Chen, Horng
AU - Lin, Grace
AU - Deswal, Anita
AU - Margulies, Kenneth B.
AU - Redfield, Margaret M.
N1 - Publisher Copyright:
© 2015 American Heart Association, Inc.
PY - 2015/5/4
Y1 - 2015/5/4
N2 - Background-Early studies showed beneficial effects of phosphodiesterase 5 inhibitors on cardiovascular function in heart failure (HF) patients, but the RELAX trial observed no improvement in exercise capacity with sildenafil treatment in subjects with HF and preserved ejection fraction. Methods and Results-A subgroup of participants in the RELAX trial (n=48) underwent comprehensive noninvasive cardiovascular assessment before and after treatment with sildenafil or placebo in a prospective ancillary study. Left ventricular contractility was assessed by peak power index and stroke work index. Systemic arterial load was assessed by arterial elastance (Ea) and right ventricular afterload by pulmonary artery systolic pressure. Endothelial function was assessed by reactive hyperemia index after upper arm cuff occlusion. Compared with placebo (n=25), sildenafil (n=23) decreased Ea (-0.29±0.28 mm Hg/mL versus +0.02±0.29, P=0.008) and tended to improve reactive hyperemia index (+0.30±0.45 versus-0.17±0.30, P=0.054). In contrast, left ventricular contractility was reduced by 11% to 16% with sildenafil compared with placebo (ΔPWR/EDV-52±70 versus +0±40 mm Hg/s, P=0.006; ΔSW/EDV +0.3±5.8 versus-6.0±5.1 mm Hg, P=0.04). Sildenafil had no effect on pulmonary artery systolic pressure. Conclusions-In subjects with HF and preserved ejection fraction, sildenafil displayed opposing effects on ventricular and vascular function. We speculate that beneficial effects of phosphodiesterase 5 inhibitors in the systemic vasculature and endothelium were insufficient to improve clinical status or that the deleterious effects on left ventricular function offset any salutary vascular effects, contributing to the absence of benefit observed with sildenafil in subjects with HF and preserved ejection fraction in the RELAX trial. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
AB - Background-Early studies showed beneficial effects of phosphodiesterase 5 inhibitors on cardiovascular function in heart failure (HF) patients, but the RELAX trial observed no improvement in exercise capacity with sildenafil treatment in subjects with HF and preserved ejection fraction. Methods and Results-A subgroup of participants in the RELAX trial (n=48) underwent comprehensive noninvasive cardiovascular assessment before and after treatment with sildenafil or placebo in a prospective ancillary study. Left ventricular contractility was assessed by peak power index and stroke work index. Systemic arterial load was assessed by arterial elastance (Ea) and right ventricular afterload by pulmonary artery systolic pressure. Endothelial function was assessed by reactive hyperemia index after upper arm cuff occlusion. Compared with placebo (n=25), sildenafil (n=23) decreased Ea (-0.29±0.28 mm Hg/mL versus +0.02±0.29, P=0.008) and tended to improve reactive hyperemia index (+0.30±0.45 versus-0.17±0.30, P=0.054). In contrast, left ventricular contractility was reduced by 11% to 16% with sildenafil compared with placebo (ΔPWR/EDV-52±70 versus +0±40 mm Hg/s, P=0.006; ΔSW/EDV +0.3±5.8 versus-6.0±5.1 mm Hg, P=0.04). Sildenafil had no effect on pulmonary artery systolic pressure. Conclusions-In subjects with HF and preserved ejection fraction, sildenafil displayed opposing effects on ventricular and vascular function. We speculate that beneficial effects of phosphodiesterase 5 inhibitors in the systemic vasculature and endothelium were insufficient to improve clinical status or that the deleterious effects on left ventricular function offset any salutary vascular effects, contributing to the absence of benefit observed with sildenafil in subjects with HF and preserved ejection fraction in the RELAX trial. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
KW - diastolic heart failure
KW - heart failure
KW - vascular function
KW - ventricular function
UR - http://www.scopus.com/inward/record.url?scp=84942936387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942936387&partnerID=8YFLogxK
U2 - 10.1161/CIRCHEARTFAILURE.114.001915
DO - 10.1161/CIRCHEARTFAILURE.114.001915
M3 - Article
C2 - 25782985
AN - SCOPUS:84942936387
SN - 1941-3289
VL - 8
SP - 533
EP - 541
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 3
ER -