Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension

• Published in: Circulation (New York, N.Y.) Vol. 116; no. 14; pp. 1555 - 1562
• Main Authors: LEWIS, Gregory D, SHAH, Ravi, SEMIGRAN, Marc J, SHAHZAD, Khurram, CAMUSO, Janice M, PAPPAGIANOPOULOS, Paul P, HUNG, Judy, TAWAKOL, Ahmed, GERSZTEN, Robert E, SYSTROM, David M, BLOCH, Kenneth D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 02.10.2007
• Subjects: Aged; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Cardiovascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Exercise; Female; Follow-Up Studies; Heart Failure - complications; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart Rate - drug effects; Humans; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Male; Medical sciences; Middle Aged; Motor Activity; Pharmacology. Drug treatments; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - adverse effects; Piperazines - administration & dosage; Piperazines - adverse effects; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Pulmonary Wedge Pressure - drug effects; Purines - administration & dosage; Purines - adverse effects; Quality of Life; Sildenafil Citrate; Sulfones - administration & dosage; Sulfones - adverse effects; Systole; Treatment Outcome; Vascular Resistance - drug effects; Vasodilator agents. Cerebral vasodilators; Physical exercise; Human; Heart failure; Vasodilator agent; 3',5'-Cyclic-GMP phosphodiesterase; Respiratory disease; Enzyme; Enzyme inhibitor; hypertension, pulmonary; Cardiovascular disease; exercise; Esterases; Phosphoric diester hydrolases; Pulmonary hypertension; Quality of life; Heart disease; Hydrolases; Sildenafil
• DOI: 10.1161/CIRCULATIONAHA.107.716373
• ISSN: 0009-7322

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. 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 VO2 from baseline, the primary end point, was greater in the sildenafil group (1.8+/-0.7 mL x kg(-1) x min(-1)) than in the placebo group (-0.27 mL x kg(-1) x 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 VO2 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. Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH.