Abstract
BackgroundHeart 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).MethodsWe 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.ResultsThe 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.ConclusionsIn 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 registrationRussian 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.
Highlights
Heart failure with preserved ejection fraction (HFpEF) is frequently complicated by pulmonary hypertension (PH)
We aimed to investigate the effect of chronic phosphodiesterase 5 (PDE5) inhibition with sildenafil on exercise capacity, right ventricle (RV) function, and pulmonary haemodynamic parameters in patients with HFpEF and combined pre- and postcapillary PH (Cpc-PH) determined by echocardiography
We enrolled 50 patients with stable heart failure of New York Heart Association (NYHA) functional class II-III with preserved left ventricular (LV) ejection fraction (> 50%) and Cpc-PH determined by echocardiography as high LV-filling pressures (LV diastolic dysfunction grade II/III) [15] and pulmonary artery systolic pressure (PASP) > 40 mmHg
Summary
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). With increased severity and duration of LA pressure overload pulmonary vascular disease (PVD) can develop by an increase in pulmonary arterial tone and/or intrinsic arterial remodeling. These progressive pathologic alterations of the pulmonary arterial vasculature manifest by a rise in the pulmonary vascular resistance (PVR) and the condition is defined as combined pre- and postcapillary pulmonary hypertension (Cpc-PH) [6, 7]. Patients with Cpc-PH are younger than patients with Ipc-PH, despite similar comorbidities and prevalence, severity, and chronicity of left heart disease, and display genes and biological pathways in the lung known to contribute to “pulmonary arterial hypertension” pathophysiology [10]
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