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(Circulation. 2007;116:1555-1562.)
© 2007 American Heart Association, Inc.

Heart Failure

Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension

Gregory D. Lewis, MD; Ravi Shah, MD; Khurram Shahzad, MD; Janice M. Camuso, RN; Paul P. Pappagianopoulos, MEd; Judy Hung, MD; Ahmed Tawakol, MD; Robert E. Gerszten, MD; David M. Systrom, MD; Kenneth D. Bloch, MD; Marc J. Semigran, MD

From the Cardiology Division (G.D.L., R.S., K.S., J.M.C., J.H., A.T., R.E.G., K.D.B., M.J.S.) and Pulmonary and Critical Care Unit (P.P.P., D.M.S.), Department of Medicine, and the Department of Anesthesia and Critical Care (K.D.B.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Marc J. Semigran, Heart Failure and Cardiac Transplantation Unit, Massachusetts General Hospital, Bigelow 800, Fruit St, Boston, MA 02114. E-mail msemigran{at}partners.org

Received May 21, 2007; accepted July 31, 2007.

Background— Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH.

Methods and Results— Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak O₂ from baseline, the primary end point, was greater in the sildenafil group (1.8±0.7 mL · kg^–1 · min^–1) than in the placebo group (–0.27 mL · kg^–1 · min^–1; P=0.02). Sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise (P<0.05 versus placebo for both) without altering pulmonary capillary wedge or mean arterial pressure, heart rate, or systemic vascular resistance. The ability of sildenafil treatment to augment peak O₂ correlated directly with baseline resting pulmonary vascular resistance (r=0.74, P=0.002) and indirectly with baseline resting right ventricular ejection fraction (r=–0.64, P=0.01). Sildenafil treatment also was associated with improvement in 6-minute walk distance (29 m versus placebo; P=0.047) and Minnesota Living With Heart Failure score (–14 versus placebo; P=0.01). Subjects in the sildenafil group experienced fewer hospitalizations for HF and a higher incidence of headache than those in the placebo group without incurring excess serious adverse events.

Conclusions— Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH.

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