Open AccessSildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension
Author(s) -
Gregory D. Lewis,
Ravi Shah,
Khurram Shahzad,
Janice Camuso,
Paul P. Pappagianopoulos,
Judy Hung,
Ahmed Tawakol,
Robert E. Gerszten,
David M. Systrom,
Kenneth D. Bloch,
Marc J. Semigran
Publication year - 2007
Publication title -
circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.795
H-Index - 607
eISSN - 1524-4539
pISSN - 0009-7322
DOI - 10.1161/circulationaha.107.716373
Subject(s) - sildenafil , medicine , vascular resistance , placebo , pulmonary hypertension , heart failure , cardiology , pulmonary wedge pressure , ejection fraction , heart rate , clinical endpoint , blood pressure , anesthesia , randomized controlled trial , alternative medicine , pathology
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 V̇o 2 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 V̇o 2 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.