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Aims: Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT., Methods and Results: RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, -1.4% to 10.6%; P < 0.001 for non-inferiority margin -10.0%) (Table 2). At an overall mean follow-up of 548 ± 190 days SonR was associated with a 35% risk reduction in HF hospitalization (hazard ratio, 0.65; 95% CI, 0.46-0.92; log-rank P = 0.01)., Conclusion: Automatic AV and VV optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT., Clinicaltrials.gov Number: NCT01534234., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)