Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure

Marco Guazzi, Michele Samaja, Ross Arena, Marco Vicenzi, Maurizio D. Guazzi

Research output: Contribution to journalArticle

Abstract

Objectives: This study sought to test the functional exercise capacity and endothelial function in a cohort of chronic heart failure (CHF) patients treated with chronic type 5 phosphodiesterase (PDE5) inhibitor. Background: In CHF, endothelial dysfunction is involved in muscle underperfusion, ergoreflex oversignaling, and exercise ventilation inefficiency. Inhibition of PDE5 by improving endothelial dysfunction might be beneficial. Methods: Stable CHF patients were randomly assigned to placebo (23 patients) or sildenafil at the dose of 50 mg twice per day (23 patients) in addition to their current drug treatment for 6 months, with assessments (at 3 and 6 months) of endothelial function by brachial artery flow-mediated dilatation (FMD), cardiopulmonary exercise testing, and ergoreflex response. Results: In the sildenafil group only, at 3 and 6 months we observed reduction of systolic pulmonary artery pressure (from 33.7 to 25.2 mm Hg and 23.9 mm Hg), ergoreflex effect on ventilation (from 6.9 to 2.3 l·min-1 and 1.9 l·min-1), ventilation to CO2 production slope (VE/Vco2, from 35.5 to 32.1 and 29.8), and breathlessness (score) (from 23.6 to 16.6 and 17.2), and an increase of FMD (from 8.5% to 13.4% and 14.2%), peak Vo2 (from 14.8 to 18.5 ml·min-1·kg-1 and 18.7 ml·min-1·kg-1), and ratio of Vo2 to work rate changes (from 7.7 to 9.3 and 10.1). All changes were significant at p <0.01. In the sildenafil group, a significant correlation was found at 3 and 6 months between changes in FMD and those in ergoreflex. Changes in ergoreflex correlated with those in peak Vo2 and VE/Vco2 slope. No adverse effects were noted except for flushing in 3 patients. Conclusions: In CHF, improvement in exercise ventilation and aerobic efficiency with sildenafil is sustained and is significantly related with an endothelium-mediated attenuation of exercising muscle oversignaling. Chronic sildenafil seems to be a remedy based on CHF pathophysiology and devoid of remarkable adverse effects.

Original languageEnglish
Pages (from-to)2136-2144
Number of pages9
JournalJournal of the American College of Cardiology
Volume50
Issue number22
DOIs
Publication statusPublished - Nov 27 2007

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Heart Failure
Ventilation
Dilatation
Exercise
Therapeutics
Phosphodiesterase 5 Inhibitors
Muscles
Phosphodiesterase Inhibitors
Brachial Artery
Exercise Test
Dyspnea
Pulmonary Artery
Endothelium
Placebos
Sildenafil Citrate
Pressure
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure. / Guazzi, Marco; Samaja, Michele; Arena, Ross; Vicenzi, Marco; Guazzi, Maurizio D.

In: Journal of the American College of Cardiology, Vol. 50, No. 22, 27.11.2007, p. 2136-2144.

Research output: Contribution to journalArticle

Guazzi, Marco ; Samaja, Michele ; Arena, Ross ; Vicenzi, Marco ; Guazzi, Maurizio D. / Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure. In: Journal of the American College of Cardiology. 2007 ; Vol. 50, No. 22. pp. 2136-2144.
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abstract = "Objectives: This study sought to test the functional exercise capacity and endothelial function in a cohort of chronic heart failure (CHF) patients treated with chronic type 5 phosphodiesterase (PDE5) inhibitor. Background: In CHF, endothelial dysfunction is involved in muscle underperfusion, ergoreflex oversignaling, and exercise ventilation inefficiency. Inhibition of PDE5 by improving endothelial dysfunction might be beneficial. Methods: Stable CHF patients were randomly assigned to placebo (23 patients) or sildenafil at the dose of 50 mg twice per day (23 patients) in addition to their current drug treatment for 6 months, with assessments (at 3 and 6 months) of endothelial function by brachial artery flow-mediated dilatation (FMD), cardiopulmonary exercise testing, and ergoreflex response. Results: In the sildenafil group only, at 3 and 6 months we observed reduction of systolic pulmonary artery pressure (from 33.7 to 25.2 mm Hg and 23.9 mm Hg), ergoreflex effect on ventilation (from 6.9 to 2.3 l·min-1 and 1.9 l·min-1), ventilation to CO2 production slope (VE/Vco2, from 35.5 to 32.1 and 29.8), and breathlessness (score) (from 23.6 to 16.6 and 17.2), and an increase of FMD (from 8.5{\%} to 13.4{\%} and 14.2{\%}), peak Vo2 (from 14.8 to 18.5 ml·min-1·kg-1 and 18.7 ml·min-1·kg-1), and ratio of Vo2 to work rate changes (from 7.7 to 9.3 and 10.1). All changes were significant at p <0.01. In the sildenafil group, a significant correlation was found at 3 and 6 months between changes in FMD and those in ergoreflex. Changes in ergoreflex correlated with those in peak Vo2 and VE/Vco2 slope. No adverse effects were noted except for flushing in 3 patients. Conclusions: In CHF, improvement in exercise ventilation and aerobic efficiency with sildenafil is sustained and is significantly related with an endothelium-mediated attenuation of exercising muscle oversignaling. Chronic sildenafil seems to be a remedy based on CHF pathophysiology and devoid of remarkable adverse effects.",
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N2 - Objectives: This study sought to test the functional exercise capacity and endothelial function in a cohort of chronic heart failure (CHF) patients treated with chronic type 5 phosphodiesterase (PDE5) inhibitor. Background: In CHF, endothelial dysfunction is involved in muscle underperfusion, ergoreflex oversignaling, and exercise ventilation inefficiency. Inhibition of PDE5 by improving endothelial dysfunction might be beneficial. Methods: Stable CHF patients were randomly assigned to placebo (23 patients) or sildenafil at the dose of 50 mg twice per day (23 patients) in addition to their current drug treatment for 6 months, with assessments (at 3 and 6 months) of endothelial function by brachial artery flow-mediated dilatation (FMD), cardiopulmonary exercise testing, and ergoreflex response. Results: In the sildenafil group only, at 3 and 6 months we observed reduction of systolic pulmonary artery pressure (from 33.7 to 25.2 mm Hg and 23.9 mm Hg), ergoreflex effect on ventilation (from 6.9 to 2.3 l·min-1 and 1.9 l·min-1), ventilation to CO2 production slope (VE/Vco2, from 35.5 to 32.1 and 29.8), and breathlessness (score) (from 23.6 to 16.6 and 17.2), and an increase of FMD (from 8.5% to 13.4% and 14.2%), peak Vo2 (from 14.8 to 18.5 ml·min-1·kg-1 and 18.7 ml·min-1·kg-1), and ratio of Vo2 to work rate changes (from 7.7 to 9.3 and 10.1). All changes were significant at p <0.01. In the sildenafil group, a significant correlation was found at 3 and 6 months between changes in FMD and those in ergoreflex. Changes in ergoreflex correlated with those in peak Vo2 and VE/Vco2 slope. No adverse effects were noted except for flushing in 3 patients. Conclusions: In CHF, improvement in exercise ventilation and aerobic efficiency with sildenafil is sustained and is significantly related with an endothelium-mediated attenuation of exercising muscle oversignaling. Chronic sildenafil seems to be a remedy based on CHF pathophysiology and devoid of remarkable adverse effects.

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