Clinical Research
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

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Objectives

The authors investigated predictors of left ventricular ejection fraction (LVEF) super-response to cardiac resynchronization therapy with defibrillator (CRT-D) and whether super-response translated into improved event-free survival in patients with mildly symptomatic heart failure (HF).

Background

Few data exist on predictors of super-response to CRT-D and associated morbidity and mortality in mildly symptomatic HF populations.

Methods

Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months (n = 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.

Results

All 191 super-responders experienced an LVEF increase of ≥14.5% (mean LVEF increase 17.5 ± 2.7%). Six predictors were associated with LVEF super-response to CRT-D therapy: female sex (odds ratio [OR]: 1.96; p = 0.001), no prior myocardial infarction (OR: 1.80; p = 0.005), QRS duration ≥150 ms (OR: 1.79; p = 0.007), left bundle branch block (OR: 2.05; p = 0.006), body mass index <30 kg/m2 (OR: 1.51; p = 0.035), and smaller baseline left atrial volume index (OR: 1.47; p < 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 < 0.001 overall). In multivariate analysis, hyporesponse was associated with increased risk of HF or all-cause death, compared with super-response (hazard ratio: 5.25; 95% confidence interval: 2.01 to 13.74; p = 0.001).

Conclusions

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)

Key Words

cardiac resynchronization therapy
heart failure
pacing
super-response

Abbreviations and Acronyms

BMI
body mass index
CRT
cardiac resynchronization therapy
CRT-D
cardiac resynchronization therapy with defibrillator
HF
heart failure
ICD
implantable cardioverter-defibrillator
LA
left atrial
LAVI
left atrial volume index
LBBB
left bundle branch block
LV
left ventricular
LVEF
left ventricular ejection fraction
NYHA
New York Heart Association

Cited by (0)

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.