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CLINICAL RESEARCH: HEART FAILURE

Aldosterone Receptor Antagonism Induces Reverse Remodeling When Added to Angiotensin Receptor Blockade in Chronic Heart Failure

Anna K.Y. Chan, MB, MRCP^_*, John E. Sanderson, MD, FRCP, FACC^_*,_*, Tian Wang, PhD^_*, Wynnie Lam, FRCR, Gabriel Yip, MD^_*, Mei Wang, MD, PhD^_*, Yat-Yin Lam, MB, MRCP^_*, Yan Zhang, PhD^_*, Leata Yeung, RN, MPhil^_*, Eugene B. Wu, MD^_*, Wilson W.M. Chan, MD^_*, John T.H. Wong, MB, MRCP^_*, Nina So, FRCR and Cheuk-Man Yu, MD, FRCP^_*

^_* Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Manuscript received January 24, 2007; revised manuscript received March 9, 2007, accepted March 12, 2007.

^_* Reprint requests and correspondence: Prof. John E. Sanderson, Department of Cardiovascular Medicine, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. (Email: j.e.sanderson{at}bham.ac.uk).

Objectives: The objective of this study was to determine if adding spironolactone to an angiotensin II receptor blocker improves left ventricular (LV) function, mass, and volumes in chronic heart failure.

Background: Add-on spironolactone therapy substantially improves clinical outcomes among patients with severe heart failure (HF) on standard therapy. However, the value of combining spironolactone with an angiotensin II receptor blocker on LV reverse remodeling in mild-to-moderate systolic HF is unclear.

Methods: Fifty-one systolic HF patients with left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive 1-year treatment of candesartan and spironolactone (combination group) or candesartan and placebo (control group). Reverse remodeling was assessed by serial cardiac magnetic resonance imaging and echocardiographic tissue Doppler imaging (TDI).

Results: There were significant improvements in LVEF (35 ± 3% vs. 26 ± 2%, p < 0.01) and reduction of LV end-diastolic volume index (121 ± 16 ml/m² vs. 155 ± 14 ml/m², p = 0.001), end-systolic volume index (88 ± 17 ml/m² vs. 120 ± 15 ml/m², p < 0.0005), and LV mass index (81 ± 6 g/m² vs. 93 ± 6 g/m², p = 0.002) in the combination group at 1 year. In addition, there was significant increase in peak basal systolic velocity and strain by TDI, decrease in index of filling pressure, and increase in cyclic variation integrated backscatter. In the control group, there were no significant changes in all these parameters after 1 year.

Conclusions: The addition of spironolactone to candesartan has significant beneficial effects on LV reverse remodeling in patients with mild-to-moderate chronic systolic HF.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ARB = angiotensin II receptor blocker   CMR = cardiac magnetic resonance imaging   CVIB = cyclic variation of integrated backscatter   HF = heart failure   LV = left ventricle/ventricular   LVEDVI = left ventricular end-diastolic volume index   LVEF = left ventricular ejection fraction   LVESVI = left ventricular end-systolic volume index   TDI = tissue Doppler imaging

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