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The identification of responders remains challenging in cardiac resynchronization therapy (CRT). In this study we assessed the role of myocardial contractile reserve (CR) during dobutamine stress echocardiography (DSE) and resting severe diastolic dysfunction for identifying responders to CRT.Sixty-nine patients (59% with ischaemic aetiology, ejection fraction: 26 ± 5%) referred for CRT underwent high-dose DSE. Contractile reserve was evaluated using a pressure–volume relationship, defined as systolic cuff pressure/end-systolic volume index difference between rest and peak DSE. We defined severe diastolic dysfunction as the presence of restrictive patterns and/or E/E′ > 15. We divided the patients into four groups as follows: presence (CR+) or absence (CR−) of myocardial CR and presence (Diast+) or absence (Diast−) of severe diastolic dysfunction. Patients with CR+ Diast− showed higher percentage of clinical responders (91 vs. 46%, P= 0.002) and echocardiographic responders (90 vs. 25%, P= 0.001) to CRT, compared with patients with CR− Diast+. By log-rank analysis, event-free survival was significantly poorer in patients with CR− Diast+ (log rank = 18.36, P= 0.0004).Heart failure patients with severe diastolic dysfunction and absence of myocardial CR during DSE had a poorer clinical and echocardiographic response to CRT. The associated evaluations of diastolic function and CR had an additive value in the identification of responders to CRT.