Predictors of Response to Cardiac Resynchronization Therapy in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)

Study Questions:

What are predictors of a favorable response to cardiac resynchronization therapy (CRT)?


This was a secondary analysis of the MADIT-CRT trial, which compared benefits of CRT with defibrillator therapy (CRT-D, n = 718) versus defibrillator (ICD) therapy alone in patients with a left ventricular (LV) ejection fraction ≤30%, QRS ≥130 ms, and New York Heart Association (NYHA) class I-II heart failure (HF). A response to CRT was defined as a ≥10% reduction in LV end-diastolic volume (LVEDV) or 15% reduction in end-systolic volume (ESV). Study aims were to identify baseline factors associated with a favorable echocardiographic response after CRT implant. Then, a CRT response score was created and applied to both CRT-D and ICD-only groups for outcome analysis. The primary outcome of interest was first HF event or death.


Factors associated with a favorable CRT response included female sex, nonischemic cardiomyopathy, QRS ≥150 ms, a left bundle branch block (LBBB), prior HF hospitalization, baseline LVEDV ≥125 ml/m2, and baseline left atrial volume <40 ml/m2. A CRT “response score” was derived from these variables (range 0-14) and patients in both CRT-D and ICD groups were then categorized into quartiles based on scores. Patients with higher response scores were younger, more likely to have a nonischemic etiology for cardiomyopathy, to be on an aldosterone antagonist, and to be of NYHA class II status. There were 397 (20%) primary events. CRT-D therapy was not superior to ICD therapy in reducing events in patients in the lowest “response score” quartile. However, compared with ICD therapy alone, CRT-D was associated with 33%, 36%, and 69% fewer events in patients in the second, third, and fourth “response quartile” (p < 0.04).


The authors concluded that a combination of factors associated with reverse remodeling can be used to predict response to CRT.


Identifying responders to CRT remains a challenge, and this analysis helps further elucidate who may benefit from CRT-D therapy. This analysis supports others demonstrating the importance of a QRS ≥150 ms, a left bundle branch morphology, and smaller LV volumes prior to implant. However, important to risk stratification is a model that is easy to use, is accurate, and validates. Positive and negative predictive values or an area under a receiver operating characteristic curve would assist in determining accuracy. Validation may be a challenge in a model that has seven components, relies on echocardiographic measurements that may have substantial inter- and intra-observer variability, converts continuous measures to categorical predictors, and employs variables likely to correlate (QRS duration and LBBB). If it does validate, it would be highly useful. The response score would suggest that patients in the lowest response score quartile (value <4) would have scant benefit from the addition of CRT, whereas those in the highest quartile (value ≥9) are very likely to gain benefit. The middle quartiles are less clearly ‘teased out.’

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

Keywords: Defibrillators, Heart Atria, Heart Conduction System, Mineralocorticoid Receptor Antagonists, Observer Variation, New York, Cardiac Resynchronization Therapy, Heart Diseases, Cardiac Pacing, Artificial, Cardiomyopathies, Ventricular Remodeling, Heart Failure, Bundle-Branch Block, Ventricular Function, ROC Curve, Echocardiography

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