Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study

Abstract

Background Heart failure with preserved ejection fraction (HFpEF) is frequently complicated by pulmonary hypertension (PH). A pulmonary vascular contribution could be considered as a substantial therapeutic target in HFpEF and PH and combined pre- and postcapillary PH (Cpc-PH). Methods We enrolled 50 patients with HFpEF and Cpc-PH who were determined by echocardiography to have pulmonary artery systolic pressure (PASP) > 40 mmHg, pulmonary vascular resistance > 3 Wood units, and/or transpulmonary gradient > 15 mmHg. Results The patients were assigned to the phosphodiesterase 5 (PDE5) inhibitor sildenafil group (25 mg TID for 3 months followed by 50 mg TID for 3 months; n = 30) or the control group (n = 20). In the sildenafil group after 6 months, the 6-min walk distance increased by 50 m (95% CI, 36 to 64 m); substantial improvement in NYHA functional class and exercise capacity during diastolic stress test were revealed; decreases in early mitral inflow to mitral annulus relaxation velocities ratio by 2.4 (95% CI, − 3.3 to − 1.4) and PASP by 17.0 mmHg (95% CI, 20.4 to 13.5) were observed; right ventricular systolic function (M-mode tricuspid annular plane systolic excursion) increased by 0.42 cm (95% CI, 0.32 to 0.52 cm; P < 0.01 for all). No changes occurred in the control group. Conclusions In a subset of patients with HFpEF and Cpc-PH assessed by echocardiography, PDE5 inhibition was associated with an improvement in exercise capacity, pulmonary haemodynamic parameters, and right ventricular function. The role of sildenafil needs to be considered in randomized trials in selected patients with HFpEF with invasively confirmed Cpc-PH. Trial registration Russian National Information System of Research, Development and Technology Data of Civilian Usage (NIS, https://rosrid.ru), registration number 01201257849. Registered 20 April 2012. This manuscript adheres to the CONSORT guidelines.

Prevalence and haemodynamic profiles of pulmonary hypertension in cardiac amyloidosis

“…However, despite these reasonable concerns, several recent pharmaceutical and interventional trials targeting the pulmonary vasculature have shown benefit in CPCPH. [22][23][24][25] Whether targeted PH therapies may similarly benefit appropriately phenotyped patients with CA with CPCPH is currently unknown.…”

Unloading the right to fill the left: vasodilation to treat hypotension: a case report

“…7 Similarly, Belyavskiy et al . 8 showed improvement in exercise capacity, pulmonary hemodynamics, and RV function in patients with HFpEF and combined pre- and post-capillary PH who were treated with sildenafil in a randomized open-label pilot study.…”

Chronic Sildenafil Therapy in the ZSF1 Obese Rat Model of Metabolic Syndrome and Heart Failure With Preserved Ejection Fraction

“…8 Indeed, recently Guazzi’s positive results were corroborated in an independent sample of HFpEF patients with pulmonary hypertension. 17 Furthermore, in the RELAX trial the effects on exercise capacity were hampered by an abnormally high proportion of patients with chronotropic incompetence and an inferior dose and duration of therapy. More recently, the potential role of mitochondrial dysfunction and endoplasmic reticulum stress caused by sildenafil 18 and pharmacogenomics of liver metabolizing enzymes 19 were pointed out as other possible explanations.…”