Publication Detail

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Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure.

George Suzuki; Hideaki Morita; Takayuki Mishima; Victor G Sharov; Anastassia Todor; Elaine J Tanhehco; Amy E Rudolph; Ellen G McMahon; Sidney Goldstein; Hani N Sabbah (Profiled Author: Hani N Sabbah)

Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart & Vascular Institute, Detroit, Mich, USA.
Circulation 2002;106(23):2967-72.

BACKGROUND: In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS AND RESULTS: HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62+/-4 versus 68+/-4 mL, P<0.001, and 38+/-3 versus 47+/-3 mL, P<0.001, respectively), and EF decreased significantly (38+/-1% versus 31+/-2%, P<0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis. CONCLUSIONS: Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.

1 Originating Grant

• 1.

  Sabbah, Hani N

  PROGRESSION OF HEART FAILURE

  1 April 1994 - 31 December 2003

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

  Total Funding: $ 2,329,997

Scientific Context

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