Predicting the Response to CRT-D Therapy

Abstract & Commentary

By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco does research for Medtronic, is a consultant for Medtronic, Novartis, and St. Jude, and is a speaker for Boston Scientific.

Source: Goldenberg I, et al, on behalf of the MADIT-CRT Executive Committee. Predictors of response to cardiac resynchronization therapy in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT). Circulation 2011;124:1527-1536.

This paper gives the results of a substudy from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) trial. The hypothesis for this substudy was that echocardiographic signs of favorable reverse remodeling would be associated with certain clinical factors that might therefore be used to predict clinical response to cardiac resynchronization therapy (CRT). MADIT-CRT was a large, randomized trial which enrolled patients with class I and class II heart failure, an indication for an implantable cardioverter defibrillator (ICD), a left ventricular ejection fraction ≤ 0.30, and a QRS duration > 130 msec. Patients were randomized to receive either an ICD only or resynchronization therapy ICD (CRT-D). The previously published main trial results showed a reduction in the combined endpoint of heart failure admission and mortality in the CRT-D therapy group.

In MADIT-CRT, an echocardiographic response was monitored by serial assessment in the left ventricular end diastolic and systolic volumes (LVEDV and LVESV) at enrollment and at 1 year. Only patients with technically adequate paired echocardiograms are included in this report. The endpoint for a clinical response was first heart failure event or death during follow-up. The authors sought to identify factors associated with a favorable echocardiographic response, defined either as a 10% or 15% reduction in LVEDV or LVESV, respectively. Once factors associated with favorable echocardiographic response were identified, these factors were weighted and a response prediction score was then calculated.

Regression analysis of response in the CRT-D arm of MADIT-CRT identified seven factors associated with a favorable echocardiographic response to CRT-D therapy. The factors were: female gender, nonischemic cardiomyopathy, QRS duration ≥ 150 msec, left bundle branch block, prior heart failure hospitalization, baseline LVEDV > 125 mL/m2, and baseline left atrial volume < 40 mL/m2. These factors were associated with favorable echocardiographic responses in both LVEDV and LVESV. The relative effect in the regression model for each of the influential covariates was assigned a numeric value. Prior heart failure hospitalization was assigned a value of 1 point. Female gender, nonischemic cardiomyopathy, left bundle branch block, QRS duration ≥ 150 msec, and LVEDV were assigned a value of 2 points, and left atrial volume < 40 mL/m2 a value of 3 points. Using this system, the response score might range from 0 to 14. The entire study population was then categorized into quartiles based on the distribution of the response scores. The lowest quartile had scores from 0 to 4, the next two quartiles had scores of 5 or 6 and 7 or 8. The highest quartile had a response score of 9 to 14. Response score quartiles showed a direct correlation between reduction in cardiac volumes in the CRT-D group. In contrast, when the same scoring system was applied to the ICD only arm of the trial, similar reductions in cardiac volumes were not seen. The response score also predicted clinical events. In the lowest response score quartile, there was no significant reduction in the risk of heart failure, hospitalization, or death compared to ICD only therapy. In the second and third response score quartiles, CRT-D therapy was associated with 33% and 35% risk reductions. In the highest response score quartile, CRT-D was associated with a 69% reduction in the risk of heart failure or death. If response score was expressed as a continuous measure, the benefit of CRT-D therapy for reducing heart failure or death was increased by 13% for each 1 point increment in the response score. CRT response scores also predicted total mortality.

The authors conclude that baseline factors can predict favorable echocardiographic responses and this is associated with improved clinical response to CRT therapy. The degree of clinical response to CRT-D therapy can be estimated using a scoring system based on clinically available parameters.

Commentary

ICD therapy may prolong life by preventing arrhythmic deaths, but it should not improve symptoms in patients with heart failure. CRT can improve symptoms and quality of life, and the addition of CRT to standard pacemakers and ICDs has been a major advance in device therapy. However, CRT devices are more costly, have shorter battery lives, and are associated with an increased rate of device-related complications. Selecting patients who are most likely to benefit from CRT is therefore particularly important in patients such as those in MADIT-CRT who have less severe heart failure symptoms at the time of implant. The system described here is relatively simple and can be used to stratify patients in whom the likely benefit of CRT will outweigh the disadvantages.