Title: Multicenter Study Using Strain Delay Index for Predicting Response to Cardiac Resynchronization

Therapy (MUSIC study). Abstract Aims: Strain delay index (SDI) allows quantification of the wasted contraction or gain of myocardial contractility expected after cardiac resynchronization therapy (CRT). The present multicenter prospective study aimed to assess the accuracy of the SDI in predicting responses to CRT in real life patients that include wide and narrow (<130ms) QRS complexes. Methods and Results: Implantation of a CRT device was performed in 235 heart failure patients and echocardiography data were analyzable in 80% (n=189) of patients (age 65±12 years, LVEF=26±8%, 63 ischaemic, 51 with narrow QRS complexes). Mechanical dyssynchrony before CRT was quantified by the 12-segment standard deviation of peak longitudinal strain by speckle tracking (12SD-ε), and SDI, defined as the sum of difference between end-systolic and peak-ε across the 16 segments. Response to CRT was defined as an end-systolic volume reduction (ESVR) at 6 months >15%. After CRT, ESVR>15% was observed in 60% (n=114/189) of patients, and was greater in non-ischaemic (68% vs. 44%, p=0.003) and wide QRS patients (65% vs. 49%, p=0.04). Correlation between 12SD-ε and ESVR was poor (r=0.18, p=0.01). In contrast, SDI correlated with reverse remodelling (r=0.61, p<0.0001 for all) in both wide and narrow QRS patients and ischaemic and non ischaemic patients. Decrease in SDI after CRT was greater in responders and correlated with ESVR. Finally, SDI>25% identified responders to CRT (positive and negative predictive value of 80% and 84%, respectively) with 6% inter-observer variability. Conclusion: The present multicenter study suggests that SDI may identify responders to CRT in ischaemic and non-ischaemic patients.