| Abstract | 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 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. |
| Authors | Gregory D Lewis, Ravi Shah, Khurram Shahzad, Janice M Camuso, Paul P Pappagianopoulos, Judy Hung, Ahmed Tawakol, Robert E Gerszten, David M Systrom, Kenneth D Bloch, Marc J Semigran
(Affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.)
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| Journal | Circulation
(Circulation)
Vol. 116
Issue 14
Pg. 1555-62
(Oct 2 2007)
ISSN: 1524-4539 United States |
| PMID | 17785618
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Phosphodiesterase Inhibitors
- Piperazines
- Purines
- Sulfones
- sildenafil
- Cyclic Nucleotide Phosphodiesterases, Type 5
|
| Topics |
- Aged
- Blood Pressure
(drug effects)
- Cyclic Nucleotide Phosphodiesterases, Type 5
(antagonists & inhibitors)
- Exercise
- Female
- Follow-Up Studies
- Heart Failure
(complications, drug therapy, physiopathology)
- Heart Rate
(drug effects)
- Humans
- Hypertension, Pulmonary
(diagnosis, drug therapy, etiology)
- Male
- Middle Aged
- Motor Activity
- Phosphodiesterase Inhibitors
(administration & dosage, adverse effects)
- Piperazines
(administration & dosage, adverse effects)
- Pulmonary Wedge Pressure
(drug effects)
- Purines
(administration & dosage, adverse effects)
- Quality of Life
- Sulfones
(administration & dosage, adverse effects)
- Systole
- Treatment Outcome
- Vascular Resistance
(drug effects)
|
