Effect of sildenafil on cardiac performance in patients with heart failure.
Sildenafil is rarely used in patients with heart failure despite a high prevalence of erectile dysfunction, and the theoretic possibility that by increasing nitric oxide availability, it may improve left ventricular (LV) load and performance. This study aimed to determine the peak effects of sildenafil on LV load and performance in patients with heart failure caused by systolic LV dysfunction. Twenty patients with controlled LV failure and ejection fractions <35% received sildenafil 50 mg or a matching placebo when not receiving regular medication for > or =12 hours, in a randomized, placebo-controlled, double-blind, 2-way crossover fashion. Cardiac output was measured by Doppler echocardiography. The aortic pressure waveform was determined using generalized transfer function from radial artery applanation tonometry. Aortic and femoral arterial stiffness was determined as carotid-femoral and femoral-pedal pulse-wave velocity (PWV); wave reflection was measured as an augmentation index (AIx). Cardiac index increased significantly (by 0.37 L/min.m(2), p <0.0001), with the peak effect 60 minutes after sildenafil administration. Compared with the baseline value, total systemic resistance showed a reduction of 479 dynes.s.cm(-5) (p <0.0001). Aortic and lower limb PWV decreased significantly (by 0.89 and 1.14 m/s, respectively, p <0.0001 for both), as did AIx (by 3.6% absolute, p <0.0001); these remained significant after adjustment for mean pressure and heart rate changes. In conclusion, sildenafil improves cardiac performance because of a decrease in LV load, which is caused by decreases in peripheral resistance, in aortic and large artery stiffness, and in wave reflection from peripheral sites. This can explain the increase in cardiac output and in exercise capacity with sildenafil in patients with heart failure.
Hirata
Kozo
K
St. Vincent's Clinic, University of New South Wales, Sydney, Australia.
Adji
Audrey
A
Vlachopoulos
Charalambos
C
O'Rourke
Michael F
MF
D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000000981:diagnostic imaging / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects; D013450:Sulfones; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate