Systolic Stretch Characterizes the Electromechanical Substrate Responsive to Cardiac Resynchronization Therapy

Objectives: In this study, the authors tested the hypotheses that the systolic stretch index (SSI) developed by computer modeling and applied using echocardiographic strain imaging may characterize the electromechanical substrate predictive of outcome following cardiac resynchronization therapy (CRT). They included patients with QRS width 120 to 149 ms or non-left bundle branch block (LBBB), where clinical uncertainty for CRT exists. They further tested the hypothesis that global longitudinal strain (GLS) has additional prognostic value. Background: Response to CRT is variable. Guidelines favor patient selection by electrocardiographic LBBB with QRS width ≥150 ms. Methods: The authors studied 442 patients enrolled in the Adaptive CRT 94-site randomized trial with New York Heart Association functional class III–IV heart failure, ejection fraction ≤35%, and QRS ≥120 ms. A novel computer program semiautomatically calculated the SSI from strain curves as the sum of posterolateral prestretch percent before aortic valve opening and the septal rebound stretch percent during ejection. The primary endpoint was hospitalization for heart failure (HF) or death, and the secondary endpoint was death over 2 years after CRT. Results: In all patients, high longitudinal SSI (≥ group median of 3.1%) was significantly associated with freedom from the primary endpoint of HF hospitalization or death (hazard ratio [HR] for low SSI: 2.17; 95% confidence interval [CI]: 1.45 to 3.24, p < 0.001) and secondary endpoint of death (HR for low SSI: 4.06; 95% CI: 1.95 to 8.45, p < 0.001). Among the 203 patients with QRS 120 to 149 ms or non-LBBB, those with high longitudinal SSI (≥ group median of 2.6%) had significantly fewer HF hospitalizations or deaths (HR for low SSI: 2.08; 95% CI: 1.27 to 3.41, p = 0.004) and longer survival (HR for low SSI: 5.08; 95% CI: 1.94 to 13.31, p < 0.001), similar to patients with LBBB ≥150 ms. SSI by circumferential strain had similar associations with clinical outcomes, and GLS was additive to SSI in predicting clinical events (p = 0.001). Conclusions: Systolic stretch by strain imaging characterized the myocardial substrate associated with favorable CRT response, including in the important patient subgroup with QRS width 120 to 149 ms or non-LBBB. GLS had additive prognostic value.