The effects of phosphodiesterase 5 inhibition on hemodynamics, functional status and survival in advanced heart failure and pulmonary hypertension: A case–control study

Background The goal was to examine the hemodynamic and clinical effects of long-term therapy with PDE5 inhibitor sildenafil (SILD) in patients with advanced, pre-transplant heart failure (HF) and severe pulmonary hypertension (PH), in comparison to a similar control group (CON). Methods In this non-randomized, retrospective case–control study, 32 middle-aged patients (81% males) with advanced systolic HF (80%≥NYHA III, 56% ischemic) and severe pre-capillary PH (transpulmonary pressure gradient>15mm Hg) were studied before and after initiation of SILD (dose 73±25mg/day) and were compared to 15 CON patients, matched for key clinical characteristics (including PH severity, age and co-morbidities), not exposed to SILD. Changes at 3months and the long-term outcome were compared between groups. Results SILD significantly reduced pulmonary vascular resistance (−32% vs. baseline), transpulmonary gradient (−25%) and increased cardiac output (+15%) compared to controls, without affecting systemic or ventricular filling pressures. SILD-treated subjects experienced an improvement in NYHA class and had a steady body weight which contrasted with significant weight loss in the CON group (by −4.8%, absolutely by 4.3±6kg). During follow-up (median 349days from baseline), 60% of patients underwent heart transplantation. Two patients in CON group had severe post-transplant failure of the right ventricle, none in SILD group. Overall pre- and peritransplant survival (censored 30days after transplantation) was significantly better in SILD than CON group (93.7 vs 60%, p=0.0048). Conclusions In patients with advanced HF and severe PH, SILD therapy has beneficial effects on hemodynamics, clinical status, cardiac cachexia, and contributes to improved peri-transplant survival.