Abstract Background Cardiac resynchronization therapy (CRT) has an additive therapeutic influence on left ventricular (LV) function in heart failure (HF) patients, but the underlying mechanisms through which it works are not completely explained. Our aim was to further elucidate the role of this intervention via rotational mechanics using 2D speckle tracking echocardiography (2D-STE). Methods We investigated 46 patients (65 ± 9 years) who received CRT. All enrolled patients were assessed on admission by 2D-STE and 6 min walk test (6m WT) and followed in the outpatient device clinic by 2D-STE (at one week and 6 months post-implantation) and 6m WT (at 6 months post-implantation). On their first appointment all biventricular systems were optimized by atrioventricular delay optimization and by changing the temporal activation of ventricular electrodes aiming to reach the highest effective LV stroke volume (eff SV) across all activation options. A new 2D-STE based index (twist integral – TI) targeting to assess the rotational mechanics of the whole cardiac cycle was also measured to further explain the CRT response. For the calculation of LV TI of the full cardiac cycle, serial isochronal apical and basal rotation measurements (in degrees) were exported to a worksheet Excel file and the final algebraic summation was calculated by the formula: Twist Integral = (systolic twist integral – diastolic twist integral) Σ twisti= twist1+twist2+...+twistn (table 1). Results Twenty-two (48%) patients with dilated cardiomyopathy as the predominant aetiology of HF were responders at 6-month follow-up. The commonest selected mode that was related with the greatest LV performance response was the simultaneous activation of the 2 ventricular leads (39%). The strongest predictor of CRT response was the improvement of eff SV between admission and first appointment at clinic, followed by the improvement of TI, the non-existence of CAD, and the improvement of peak systolic twist (table 2). Conclusions Additional CRT optimization via changing the temporal activation of ventricular electrodes is beneficial for LV performance in HF patients. Rotational mechanics essentially explain the beneficial CRT contribution to these patients.