Sildenafil did not improve right ventricular function, peak oxygen consumption, or ventilatory efficiency compared with placebo at 24 weeks in HFpEF patients with right ventricular dysfunction.
RCT
Does sildenafil improve right ventricular function, exercise capacity, or ventilatory efficiency in HFpEF patients with right ventricular dysfunction and impaired RV-pulmonary arterial coupling?
Sildenafil does not improve right ventricular function, exercise capacity, or ventilatory efficiency in patients with HFpEF complicated by right ventricular dysfunction and impaired RV-pulmonary arterial coupling.
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/VCO2 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/CO2 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/VCO2 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.
Hussain et al. (2016) conducted an RCT in Heart failure with preserved ejection fraction (HFpEF). Sildenafil vs. Placebo was evaluated on Right ventricular function (TAPSE), peak oxygen consumption, and ventilatory efficiency. Sildenafil did not improve right ventricular function, peak oxygen consumption, or ventilatory efficiency compared with placebo at 24 weeks in HFpEF patients with right ventricular dysfunction.