PDE5-Inhibition With Sildenafil in Chronic Heart Failure
PDE5-Inhibition With Sildenafil in Chronic Heart Failure
To test the hypothesis that long-term PDE5-inhibition by overexpressing the nitric oxide
 pathway is beneficial in chronic heart failure patients.

 Double-blind and placebo-controlled trial. Primary end-points: quality of life and exercise
 performance
In chronic heart failure (CHF), endothelial function (EF) deterioration and muscle
 underperfusion elicit ergoreflex exercise oversignaling, hyperventilation and breathlessness.
 PDE5 inhibition, by improving EF, might be beneficial. We tested this hypothesis in a
 long-term therapeutic trial. CHF patients were randomly assigned to placebo (23 cases, group
 1) or sildenafil (23 cases, group 2) in addition to their current antifailure therapy, for 6
 months. In group 2 and not in group 1, assessments at 3 and 6 months showed the following
 changes: reduction of systolic pulmonary artery pressure (-25.2 and -29.0 %), ergoreflex
 effect on ventilation (-66.6 and -72.5%), ventilation to CO2 production slope (VE/VCO2, -14.0
 and -16.0%) and breathlessness (-29.6 and -27.1%); increase of brachial artery flow-mediated
 dilatation (FMD, +57.6 and +67.0%), peak exercise O2 uptake (peak VO2, +25.0 and +26.3%) and
 ratio of VO2 to work rate changes (VO2WR, +20.7 and +22.0%). These changes were
 significant at p<0.01. In group 2 and not in group 1, a significant correlation was found, at
 3 and 6 months, between changes in FMD and those in ergoreflex VE. Changes in ergoreflex
 correlated with those in peak VO2 and VE/VCO2 slope. No remarkable side effects were noted,
 but flushing in 3 patients.

 In CHF, benefits of sildenafil are sustained and consist of improvement in EF, modulation in
 ergoreflex signaling, attenuation in exercise hyperventilation and breathlessness, increase
 in aerobic efficiency and exercise performance. Thus, sildenafil can affect peripheral
 mechanisms of breathlessness and may be viewed as an effective and safe adjunct to the
 therapeutic armamentarium of CHF.
Inclusion Criteria:

 -  Eligibility criteria were: consent to participate in the study after detailed
 information about procedures, possible clinical benefits and risks; ability to
 complete a maximal exercise test; forced expiratory volume in 1 sec/forced vital
 capacity ratio>70%; left ventricular ejection fraction  45%, determined by
 echocardiography.

 Exclusion Criteria:

 -  Patients were not recruited if they had systolic blood pressure > 140 and <110 mmHg,
 diabetes mellitus, therapy with nitrate preparations, history of sildenafil
 intolerance, significant lung or valvular diseases, neuromuscular disorders,
 exercise-induced myocardial ischemia, atrial fibrillation (6), claudication,
 peripheral vascular disease.