Document Detail


Long-term use of sildenafil in the therapeutic management of heart failure.
MedLine Citation:
PMID:  18036451     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 x min(-1) and 1.9 l x min(-1)), ventilation to CO2 production slope (V(E)/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 x min(-1) x kg(-1) and 18.7 ml x min(-1) x 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 V(E)/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.
Authors:
Marco Guazzi; Michele Samaja; Ross Arena; Marco Vicenzi; Maurizio D Guazzi
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2007-11-13
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  50     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-26     Completed Date:  2008-01-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2136-44     Citation Subset:  AIM; IM    
Affiliation:
Cardiopulmonary Unit, Cardiology Division, University of Milan, San Paolo Hospital, Milan, Italy. marco.guazzi@unimi.it
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MeSH Terms
Descriptor/Qualifier:
Aged
Brachial Artery / physiology*
Chronic Disease
Endothelium, Vascular / drug effects
Exercise Test
Heart Failure / drug therapy*
Humans
Male
Middle Aged
Phosphodiesterase Inhibitors / administration & dosage*
Piperazines / administration & dosage*
Purines / administration & dosage
Regional Blood Flow
Sulfones / administration & dosage*
Treatment Outcome
Vasodilation / drug effects*
Chemical
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 139755-83-2/sildenafil
Comments/Corrections
Comment In:
J Am Coll Cardiol. 2007 Nov 27;50(22):2145-7   [PMID:  18036452 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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