Finding Pieces of the Puzzle of Nonresponse to Cardiac Resynchronization Therapy

Abstract

Cardiac resynchronization therapy (CRT) is an exciting advance for heart failure patients. As a result of a wealth of evidence from randomized clinical trials, guidelines for selecting patients for CRT have been established, including New York Heart Association functional class III or IV on optimal medical therapy, QRS width ≥120 ms, and ejection fraction ≤35%.1,2 The landmark Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial published in 2002 reported a 67% improvement in the group randomized to CRT using a clinical composite score in which patients were judged to be improved, unchanged, or worsened.1 Interestingly, the very recent Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial, designed to assess strategies for atrioventricular (AV) and interventricular (VV) interval optimization, reported a 67.5% improvement after CRT using the same clinical composite score.3 Despite tremendous advances in knowledge and experience with CRT, the proportion of patients considered clinical nonresponders has remained at one third over the last 8 years. Puzzling questions remain: Why are there nonresponders to CRT? Can we improve on current patient selection for CRT to reduce nonresponders? The important article by Delgado et al4 in this issue finds some pieces of the puzzle of nonresponse by focusing on a large series of patients with ischemic heart failure. They reported that mortality and heart failure hospitalizations after CRT in patients with routine indications are associated with dyssynchrony, left ventricular (LV) lead position, and estimates of regional scar. It is worthwhile to consider these factors individually, in combination, and in context of other variables that may influence response to CRT (the Figure). Figure. The puzzle of nonresponse to CRT. Article see p 70 There is an abundance of data to support dyssynchrony as the major pathological derangement associated with mechanical inefficiency and deleterious biological effects that …