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


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 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.


CONCLUSIONS
Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH.
Lewis
Gregory D
GD
Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Shah
Ravi
R
Shahzad
Khurram
K
Camuso
Janice M
JM
Pappagianopoulos
Paul P
PP
Hung
Judy
J
Tawakol
Ahmed
A
Gerszten
Robert E
RE
Systrom
David M
DM
Bloch
Kenneth D
KD
Semigran
Marc J
MJ
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D013599:Systole; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects