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on September 6, 2005

Circulation. 2005
Published online before print September 6, 2005, doi: 10.1161/CIRCULATIONAHA.105.538272
A more recent version of this article appeared on September 13, 2005
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Submitted on January 24, 2005
Revised on June 16, 2005
Accepted on June 20, 2005

Left Ventricular Reverse Remodeling but Not Clinical Improvement Predicts Long-Term Survival After Cardiac Resynchronization Therapy

Cheuk-Man Yu MD, FRCP*, Gabe B. Bleeker MD, Jeffrey Wing-Hong Fung MRCP, FHKAM, Martin J. Schalij MD, PhD, Qing Zhang BM, MM, Ernst E. van der Wall MD, PhD, Yat-Sun Chan MRCP, FHKAM, Shun-Ling Kong BN, MN, and Jeroen J. Bax MD, PhD

From the Division of Cardiology (C.-M.Y., J.W.-H.F., Q.Z., Y.-S.C., S.-L.K.), Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, and the Department of Cardiology (G.B.B., M.J.S., E.E.v.d.W., J.J.B.), Leiden University Medical Center, Leiden, the Netherlands.

* To whom correspondence should be addressed. E-mail: cmyu{at}cuhk.edu.hk.

Background--In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study.

Methods and Results--Patients (n=141) with advanced heart failure (mean±SD age, 64±11 years; 73% men) who received CRT were followed up for a mean (±SD) of 695±491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of ≥9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank {chi}2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank {chi}2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank {chi}2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause ({beta}=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular ({beta}=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event.

Conclusions--A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.


Key words: pacing • prognosis • heart failure • echocardiography • mortality


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