Document Detail


Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure.
MedLine Citation:
PMID:  15277317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. METHODS AND RESULTS: Thirty medically treated ambulatory hypertensive patients (19 women, age 62+/-6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A <1, E deceleration time >250 m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31+/-5 kg/m2) with reduced treadmill exercise capacity (6.7+/-2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133+/-17/80+/-7 mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57+/-0.46 s(-1) versus 6-months: -1.91+/-0.36 s(-1), P<0.01), peak systolic strain (-20.3+/-5.0% versus -26.9+/-4.3%, P<0.001), and CVIB (7.4+/-1.7 dB versus 8.6+/-1.7 dB, P=0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P=0.05, P=0.02, and P=0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P=0.04) and a trend to reduced left atrial area (P=0.09). CONCLUSIONS: Aldosterone antagonism improves myocardial function in hypertensive heart disease.
Authors:
Philip M Mottram; Brian Haluska; Rodel Leano; Diane Cowley; Michael Stowasser; Thomas H Marwick
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2004-07-26
Journal Detail:
Title:  Circulation     Volume:  110     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-03     Completed Date:  2005-02-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  558-65     Citation Subset:  AIM; IM    
Affiliation:
University of Queensland, Brisbane, Australia.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aldosterone Antagonists / pharmacology*,  therapeutic use
Aorta / drug effects,  physiopathology
Compliance
Diastole
Dyspnea / etiology
Exercise Test
Exercise Tolerance / drug effects
Female
Heart Atria / drug effects,  pathology
Heart Failure / drug therapy*,  etiology,  physiopathology,  ultrasonography
Heart Ventricles / drug effects,  pathology
Humans
Hypertension / complications,  drug therapy*,  physiopathology
Male
Middle Aged
Myocardial Contraction / drug effects*
Organ Size / drug effects
Spironolactone / pharmacology*,  therapeutic use
Treatment Outcome
Vascular Resistance / drug effects
Ventricular Dysfunction, Left / drug therapy*,  etiology,  ultrasonography
Chemical
Reg. No./Substance:
0/Aldosterone Antagonists; 52-01-7/Spironolactone

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


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