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

Study Questions:

Is a super-response to cardiac resynchronization therapy (CRT) associated with improved outcome in patients with mild heart failure (HF)?


This is a secondary analysis from the MADIT-CRT study, which randomized patients with a left ventricular ejection fraction (LVEF) ≤30%, QRS ≥130 ms, and New York Heart Association (NYHA) class I/II heart failure (HF) (nonischemic cardiomyopathy had to be class II) in sinus rhythm to CRT-implantable cardioverter-defibrillator (ICD) versus ICD. This substudy examined 752 patients undergoing CRT who had echocardiograms at baseline and 12 months after CRT implant. Patients were categorized as super-responders (top study cohort quartile EF difference at 12 months [≥14.5% EF increase]), responders, or hyporesponders (lowest quartile of EF increase (<7.9% EF increase) to CRT. The primary outcome of interest was all-cause mortality or nonfatal HF event.


There were 191 super-responders, 371 responders, and 190 hyporesponders. Super-responders were more often female, had a lower body mass index, a QRS ≥150 ms, or a left bundle branch block morphology on electrocardiogram, and smaller left atrial volumes on echo. The primary outcome occurred in 70 patients over a median follow-up of 15.2 months. At 2 years, the probability of death/HF event was 4%, 11%, and 26% in super-responders, responders, and hyporesponders, respectively (p < 0.001). Hyporesponders and responders had an adjusted 5.3 [2.0-13.7] and 2.2 [0.86-5.8] higher risk of mortality/HF event, respectively, compared with super-responders.


The authors concluded that super-response is associated with a lower risk of cardiac events.


While this study was meant to focus on CRT super-responders and predictors thereof, the most striking result was the very poor outcome in patients with ‘mild HF’ (class I/II) and nonresponse to CRT. The event curve for hyporesponders diverged early (at 6 months) and steeply from responders and super-responders. Hyporesponders had astonishing 10% and 26% probabilities of death/HF events at 6 months and 2 years, respectively. This suggests that even mildly symptomatic patients with HF who poorly respond to CRT warrant close follow-up. In contrast, outcomes were not significantly different between responders and super-responders. The survival curves suggest that patients with a super-response to CRT may have better outcome than responders in the long-term (beyond 1.5 years), but long-term follow-up studies are warranted.

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: Myocardial Infarction, Follow-Up Studies, Ventricular Function, Left, Methotrexate, Electrocardiography, New York, Dexamethasone, Cardiac Resynchronization Therapy, Body Mass Index, Cardiac Pacing, Artificial, Flavins, Cardiomyopathies, Heart Failure, Bundle-Branch Block, Stroke Volume, Luciferases, Death, Sudden, Cardiac, Defibrillators, Implantable, Echocardiography

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