Cardiac Resynchronization Therapy
Predictors of Super-Response to
Cardiac Resynchronization Therapy and
Associated Improvement in Clinical Outcome
The MADIT-CRT (Multicenter Automatic Deﬁbrillator
Implantation Trial With Cardiac Resynchronization Therapy) Study
Jonathan C. Hsu, MD,* Scott D. Solomon, MD,† Mikhail Bourgoun, MD,† Scott McNitt, MS,‡
Ilan Goldenberg, MD,‡ Helmut Klein, MD,‡ Arthur J. Moss, MD,‡ Elyse Foster, MD,*
on behalf of the MADIT-CRT Executive Committee
San Francisco, California; Boston, Massachusetts; and Rochester, New York
The authors investigated predictors of left ventricular ejection fraction (LVEF) super-response to cardiac resyn-
chronization therapy with deﬁbrillator (CRT-D) and whether super-response translated into improved event-free
survival in patients with mildly symptomatic heart failure (HF).
Few data exist on predictors of super-response to CRT-D and associated morbidity and mortality in mildly symp-
tomatic HF populations.
Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months (n ϭ 752). Super-
response was deﬁned by the top quartile of LVEF change. Best-subset regression analysis identiﬁed predictors of
LVEF super-response. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to
investigate associations of response category with development of nonfatal HF event or all-cause death.
All 191 super-responders experienced an LVEF increase of Ն14.5% (mean LVEF increase 17.5 Ϯ 2.7%). Six pre-
dictors were associated with LVEF super-response to CRT-D therapy: female sex (odds ratio [OR]: 1.96;
p ϭ 0.001), no prior myocardial infarction (OR: 1.80; p ϭ 0.005), QRS duration Ն150 ms (OR: 1.79; p ϭ 0.007),
left bundle branch block (OR: 2.05; p ϭ 0.006), body mass index Ͻ30 kg/m
(OR: 1.51; p ϭ 0.035), and
smaller baseline left atrial volume index (OR: 1.47; p Ͻ 0.001). Cumulative probability of HF or all-cause death
at 2 years was 4% in super-responders, 11% in responders, and 26% in hypo-responders (log-rank p Ͻ 0.001
overall). In multivariate analysis, hyporesponse was associated with increased risk of HF or all-cause death, com-
pared with super-response (hazard ratio: 5.25; 95% conﬁdence interval: 2.01 to 13.74; p ϭ 0.001).
Six baseline factors predicted LVEF super-response in CRT-D–treated patients with mild HF. Super-response was
associated with reduced risk of subsequent cardiac events. (Multicenter Automatic Deﬁbrillator Implantation
Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271) (J Am Coll Cardiol 2012;59:
2366–73) © 2012 by the American College of Cardiology Foundation
Biventricular pacing with cardiac resynchronization therapy
(CRT) and CRT with deﬁbrillator (CRT-D) have been
shown to improve heart failure (HF) morbidity, quality of
life, and survival in those with reduced left ventricular
ejection fraction (LVEF), advanced HF symptoms, and
increased QRS duration (1,2). Despite the overall improve-
ment demonstrated in randomized controlled trials, up to
30% of patients do not exhibit improvements in New York
See page 2374
From the *Division of Cardiology, Department of Medicine, University of California–
San Francisco, San Francisco, California; the †Cardiovascular Division, Brigham and
Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and the ‡Depart-
ment of Medicine, University of Rochester Medical Center, Rochester, New York.
The MADIT-CRT study was supported by a research grant from Boston Scientiﬁc
Corporation to the University of Rochester School of Medicine and Dentistry, Rochester,
New York. The current study was not funded by Boston Scientiﬁc Corporation. Dr. Solomon
has received research support and consulting fees from Boston Scientiﬁc. Dr. Klein has
received research support from Boston Scientiﬁc. Dr. Moss has received research support and
lecture honoraria from Boston Scientiﬁc. Dr. Foster has received research support from Boston
Scientiﬁc, Abbott Vascular Structural Heart, and EBR Systems Inc. All other authors have
reported that they have no relationships to disclose relevant to the contents of this paper.
Manuscript received September 16, 2011; revised manuscript received December 14,
2011, accepted January 2, 2012.
Journal of the American College of Cardiology Vol. 59, No. 25, 2012
© 2012 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2012.01.065