Abstract 13384: PDE5-Inhibition with Sildenafil Reverses Exercise Oscillatory Breathing in Chronic Heart Failure: a 1-Year Cardiopulmonary Exercise Testing Placebo-Controlled Study.
Introduction: Exercise oscillatory breathing (EOB) is a ventilatory abnormality occurring in approximately 20% of heart failure (HF) patients, which carries a very unfavourable prognosis. Phosphodiesterase 5 (PDE5) is highly expressed in the pulmonary microcirculation andits inhibition significantly augments endothelial nitric oxide signaling due to an increase in cellular cGMP.
Hypothesis: We hypothesize that the favourable effects of PDE5-inhibition on endothelial arterial function will ameliorate EOB in patients with HF.
Methods: 32 stable HF patients, presenting with EOB at cardiopulmonary exercise testing (CPX) evaluation, were randomly assigned to placebo (n=16) or sildenafil at the dose of 50 mg three times a day (n=16) in addition to their current drug treatment for 1 year, with assessments (at 6 months and 1 year) of gas exchange CPX-derived variables and pulmonary hemodynamic response to drug treatment.
Results: In the 95% of HF patients randomized to sildenafil, we observed a disappearance of EOB at both 6 months and 1 year (p<0.01; see single case in figure). This observation was accompanied by an improvement in functional performance (peak VO2 ml · min-1 · kg-1; from 12.9. to 16.8 and 17.4; p<0.01) and exercise ventilation efficiency (ventilation to CO2 production slope; from 42.4 to 34.1 and 32.0; p<0.01). Chronic treatment with PDE5 inhibition significantly decreased pulmonary systolic pressure (PASP) and pulmonary vascular resistances compared with placebo (p<0.01 for each comparison). Placebo did not alter any of the aforementioned variables.
Conclusions: Our findings confirm that in HF, sildenafil therapy improves functional capacity and ventilation efficiency and provide evidence that prognostic ventilatory abnormalities are an additional target of benefits related to chronic PDE5 inhibition.
- © 2010 by American Heart Association, Inc.