Clinical Investigation
Congestive Heart Failure
Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure: Results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials

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Background

Based on current patient selection criteria, a significant proportion of recipients of cardiac resynchronization therapy (CRT) do not respond to treatment. The purpose of this analysis is to identify predictors and characterize the timing of response to CRT in patients with advanced heart failure.

Methods

Patients randomized to receive CRT in the MIRACLE and MIRACLE-ICD trials, designed to assess the benefit of CRT compared with standard medical therapy in patients with advanced heart failure, left ventricular ejection fraction <0.35, and QRS ≥130 milliseconds, were included for this analysis. Patients with an improvement of ≥1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up were considered responders and those who had no change or worse NYHA class or died were classified as nonresponders. Responders were subdivided into early (within 1-3 months) and late (6 months).

Results

One hundred forty-three (64%) of 224 and 190 (61%) of 313 patients in the MIRACLE and MIRACLE-ICD trials, respectively, responded to therapy, with 81 (57%) of 143 and 100 (53%) of 190 responding early. Several but differing factors predicted CRT response and timing in the two trials with a high sensitivity (89%-90%) but, owing to a low specificity (31%-49%), a modest predictive accuracy (66%-75%).

Conclusions

Based on improvement of ≥1 NYHA class, less than two thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to CRT, with just more than half responding within the first month. Several factors predicted CRT response and timing, but given their modest predictive accuracy, comparable for both studies, additional methods for selecting candidates most likely to benefit from CRT are needed.

Section snippets

Patients and study protocol

Included in this analysis were patients randomized to receive CRT as part of two multicenter, prospective trials (MIRACLE and MIRACLE-ICD) designed to assess the benefit of CRT compared with standard medical therapy in patients with moderate-to-severe (NYHA class III and IV) HF, LVEF ≤0.35, and QRS ≥130 milliseconds. The two studies shared similar inclusion criteria5, 16 except for indications for ICD therapy in the MIRACLE-ICD trial. After baseline assessment and randomization, patients were

Responders and nonresponders

Of the 224 patients in the MIRACLE trial, 143 (64%) responded and 81 (36%) did not respond to CRT. Nonresponders consisted of 65 (80%) patients who had no change in NYHA class from baseline to 6 months, 4 (5%) with a worse NYHA class (a change from NYHA class III to IV), and 12 (15%) who died before the 6-month follow-up visit. For MIRACLE-ICD patients, 190 (61%) responded and 123 (39%) did not respond to CRT. Nonresponders included 86 (70%) patients with no change in NYHA class, 8 (6.5%) with

Main findings

This analysis shows that (1) only about two thirds of patients enrolled in MIRACLE and MIRACLE-ICD trials have an improvement of ≥1 NYHA class, with just more than half showing early response (by 1 and 3 months) and that (2) several factors predict response and its timing, with high sensitivity (∼90%) but, owing to very low specificity (∼45%), a modest predictive accuracy (∼70%). The results are remarkably similar for patients enrolled in the two trials, although the predictive factors for

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