Hemodynamic Benefits of Chronic Sildenafil Therapy in Advanced Heart Failure (HF): A Multi-Center Experience

Abstract

Purpose Type II pulmonary hypertension (PH) is frequent in advanced HF patients. Initially passive, secondary to elevated left side filling pressures, PH can evolve to a reactive profile involving the pulmonary arterial vasculature, defined at right heart catheterization (RHC). When reactive PH remains fixed despite an aggressive reversibility protocol, heart transplantation is contraindicated. This study reports the experience of two cardiac transplant centres of open-label 3-months (3M) sildenafil (S) therapy, a selective phosphodiesterase inhibitor (PDE-5), in HF patients with PH, focusing on pulmonary hemodynamics at rest. Methods and Materials We conducted a retrospective review of HF patients evaluated for cardiac transplantation who received sildenafil therapy because of severe PH despite optimal medical therapy. We compared hemodynamic findings, including trans-pulmonary gradient (TPG), cardiac index (CI) and pulmonary vascular resistance(PVR) at baseline and after 3M of S. Results 37 advanced HF patients (NYHA III-IV, 86% male) with a mean age of 50±12 years and depressed LVEF (23±5%), received S for severe PH (mPAP 41±11mmHg). Compared to baseline, RHC resting values at 3M showed 19% increase in CI (1.6, 1.4–1.9 to 1.9, 1.6–2.6 l/min/m2, p=0.002) and 23% decrease in PVR (4.6, 3.2-6.0 to 3.2, 2.4–5.4 WU, p=0.01), without TPG change (−12%, 16 to 13 mmHg, p=0.09). sPAP, dPAP and PCWP were also unchanged. Amongst the patients with reactive PH at baseline (32/37), six evolved toward a passive PH profile at 3M and 14/18 of the fixed PH patients, had a reversible profile at 3M. Conclusions In advanced HF patients with type II PH, 3M of sildenafil therapy increased CI and decreased PVR on resting RHC. An aggressive reversibility protocol was able to modify reactive or fixed PH to a passive profile, leading to potential transplant candidacy for these patients. These results suggest a strong implication of NO and PDE pathway in severePH secondary to HF.