Published online before print July 26, 2004, doi: 10.1161/01.CIR.0000138680.89536.A9
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(Circulation. 2004;110:558-565.)
© 2004 American Heart Association, Inc.
Original Articles |
Effect of Aldosterone Antagonism on Myocardial Dysfunction in Hypertensive Patients With Diastolic Heart Failure
From the University of Queensland, Brisbane, Australia.
Correspondence to Prof TH Marwick, University of Queensland Department of Medicine, Princess Alexandra Hospital, Ipswich Road, Brisbane, Q4102, Australia. E-mail tmarwick{at}soms.uq.edu.au
Received April 22, 2004; revision received June 2, 2004; accepted June 4, 2004.
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 >250m/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±7mm 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±1.7dB 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.
Key Words: hypertension • diastole • systole • myocardial contraction
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