Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure.
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.


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.
Mottram
Philip M
PM
University of Queensland, Brisbane, Australia.
Haluska
Brian
B
Leano
Rodel
R
Cowley
Diane
D
Stowasser
Michael
M
Marwick
Thomas H
TH
D000368:Aged; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D003187:Compliance; D003971:Diastole; D004417:Dyspnea / Q000209:etiology; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014463:Ultrasonography; D014655:Vascular Resistance / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone