The Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

Study Questions:

What is the relationship between left ventricular ejection fraction (LVEF) and clinical outcomes of patients with mild heart failure (HF) enrolled in the MADIT-CRT study, with a specific focus on the subset of patients with more preserved LVEF enrolled in the trial?


In the MADIT-CRT study, the echocardiography core laboratory assessed baseline LVEF independent of the enrolling centers and identified a range of LVEFs, including those >30% (i.e., beyond the eligibility criteria). Echocardiographic response with cardiac resynchronization therapy (CRT), defined as percent change in LV end-diastolic volume (LVEDV), was analyzed in three prespecified LVEF groups: >30%, 26%-30%, and ≤25%. The primary endpoint was HF or death, and the secondary endpoint included all-cause mortality.


LVEF was evaluated in 1,809 study patients. There were 696 (38%) patients with LVEF >30% (in the range of 30.1%-45.3%); 914 patients (50.5%) with LVEF 26%-30%; and 199 patients with LVEF ≤25% (11%). The mean reduction in LVEDV with CRT-D therapy at the 1-year follow-up was directly related to increasing LVEF (LVEF >30%: 22.3%; LVEF 26%-30%: 20.1%; and LVEF ≤25%: 18.7% reduction, respectively [p = 0.001]). CRT-D treatment similarly reduced the risk of HF/death in patients with LVEF >30% (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.39-0.82; p = 0.003), LVEF 26%-30% (HR, 0.67; 95% CI, 0.50-0.90; p = 0.007), and LVEF ≤25% (HR, 0.57; 95% CI, 0.35-0.95; p = 0.03; all p values for LVEF-by-treatment interactions >0.1).


The authors concluded that in the MADIT-CRT study, the clinical benefit of CRT was evident regardless of baseline LVEF, including those with LVEF >30%.


This subgroup analysis of the MADIT-CRT study suggests that the clinical benefit of CRT-D was maintained across all LVEF groups, and the echocardiographic response to CRT-D was even more pronounced among patients with higher LVEFs, including those with LVEF >30%. These findings would appear to suggest that mildly symptomatic HF patients with LVEF >30% might also be potential candidates for CRT-D. Given the limitations of this study, including post-hoc analysis, exclusion of incomplete data sets or images with poor quality and lack of power due to small sample size, the study findings need to be prospectively tested and validated prior to application in clinical practice.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Heart Diseases, Incidence, Defibrillators, Follow-Up Studies, Cardiac Pacing, Artificial, Cardiology, Heart Failure, Stroke Volume, Ventricular Function, Echocardiography, Cardiac Resynchronization Therapy

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