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

Abstract

on behalf of the MADIT-CRT Executive CommitteeBackground-We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device. Methods and Results-The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score. Cox proportional hazards regression analysis was used to evaluate the CRT-D versus defibrillator-only reduction in the risk of heart failure or death by the response score. Seven factors were identified as associated with echocardiographic response to CRT-D and made up the response score (female sex, nonischemic origin, left bundle-branch block, QRS Ն150 milliseconds, prior hospitalization for heart failure, left ventricular end-diastolic volume Ն125 mL/m 2 , and left atrial volume Ͻ40 mL/m 2 ). Multivariate analysis showed a 13% (PϽ0.001) increase in the clinical benefit of CRT-D per 1-point increment in the response score (range, 0 -14) and a significant direct correlation between risk reduction associated with CRT-D and response score quartiles: Patients in the first quartile did not derive a significant reduction in the risk of heart failure or death with CRT-D (hazard ratioϭ0.87; Pϭ0.52); patients in the second and third quartiles derived 33% (Pϭ0.04) and 36% (Pϭ0.03) risk reductions, respectively; and patients in the upper quartile experienced a 69% (PϽ0.001) risk reduction (P for trendϭ0.005). Conclusion-Combined assessment of factors associated with reverse remodeling can be used for improved selection of patients for cardiac resynchronization therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Predictors of response to cardiac resynchronization therapy: A prospective cohort study

“…Other investigators also did not find gender or etiology, adjusted to LV volumes, to be independent predictors. 8 On the other hand, sub-analyses of randomized clinical trials have suggested that CRT has greater beneficial effects on LV function and/or prognosis in females 6,9,10,19 and in nonischemic etiology. 7,11 Of our patients, 34% were in atrial fibrillation, the most common arrhythmia in HF and associated with worse prognosis.…”

“…3,9,10 Park et al demonstrated that baseline LV volume was a predictor of echocardiographic CRT response. 8 Rickard et al 3 showed that the smaller the LV size, the greater the improvement in LVEF and all-cause mortality after CRT.…”

Clinical trials of antiarrhythmic therapies and optimizing health care resource deployment: the need for a paradigm shift

“…In a recent report on the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, we noted a general effect of well-defined baseline variables, such as coronary or pulmonary disease and heart failure, that limited beneficial outcomes with all interventions tested [6]. Similar situations exist in trials employing implantable cardioverterdefibrillators (ICDs) for sudden death prophylaxis in patients with renal dysfunction and class IV heart failure [4,8]. Other baseline variables influence outcomes only with specific interventions, for example, amiodarone use in atrial fibrillation patients with preexisting or treated thyroid disease or high energy shocks in patients with impaired left ventricular function and comorbidities [6,7].…”

“…Prophylaxis of sudden death events in clinical practice using implantable defibrillator devices in high-risk patients resulted in unused device therapy in a very large proportion of all recipients [3]. These non-uniform outcomes are also seen in cardiac resynchronization therapy and ablation of an increasingly broad spectrum of the AF population [4,5].…”

Heart Failure in Women

“…A recent substudy of the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) population found 7 different patient characteristics that were most predictive of this positive response, with female gender conferring a greater degree of reverse remodeling and better outcomes with resynchronization therapy. 51 Menopause and Hormone Replacement Therapy After menopause, a woman's risk of HF rises exponentially. The loss of endogenous estrogen plays an important role in this increased risk.…”