Background Three-dimensional (3D) speckle tracking imaging (STI) allows the simultaneous assessment of left ventricular (LV) strain and volume. We aim to explore the value of LV strain–volume loops in predicting response to cardiac resynchronization therapy (CRT). Methods Forty heart failure (HF) patients scheduled for CRT and twenty healthy individuals were enrolled. All subjects received a 3D echocardiography and 3D STI analysis to acquire LV global and segmental principal strain (PS) and volume simultaneously. Values were plotted in a Cartesian system to construct PS–volume loop which was assessed using the two characteristics of the linear fitting curve: the slope and the coefficient of determination (R 2 -S/D coupling). Results HF patients at baseline showed significantly lower slope and R 2 -S/D coupling of all PS–volume loops than healthy subjects. As for as comparing Segmental PS–Global volume loop at baseline, Midseptal R 2 -S/D coupling was lower and Midlateral slope was higher in CRT responders than in non-responders. For each individual, the abnormal segmental heterogeneity of Midseptal slope and R 2 -S/D coupling were lower than Midlateral was observed only in responders. At follow-up, significant improvements of the Midseptal slope and R 2 -S/D coupling were observed in responders. Midseptal R 2 -S/D coupling at baseline was an independent predictor of CRT response and the cut-off value of 0.55 was recommended with sensitivity of 89% and specificity of 77%. Conclusions Analysis of strain–volume loops could provide unique information for predicting response to CRT. Assessment of septal myocardial wasted work at baseline is helpful to improve patient selection for CRT.

The mechanism of cardiac resynchronization therapy ( CRT ) remains unclear. In this study, mitochondria calcium uniporter ( MCU ), dynamin‐related protein‐1 ( DNM 1L/Drp1) and their relationship with autophagy in heart failure ( HF ) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF , CRT ). Animals received left bundle branch ( LBB ) ablation followed by either 8‐week rapid atrial pacing or 4‐week rapid atrial pacing and 4‐week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes ( DEG s) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT . Cells were divided into three groups (control, angiotensin‐ II and angiotensin‐ II + stretching). MCU , DNM 1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down‐regulating MCU and up‐regulating DNM 1L/Drp1. Cell stretching reversed the angiotensin‐ II induced changes of MCU and DNM 1L/Drp1 and partly restored autophagy. CRT 's mechanical effects down‐regulated MCU , up‐regulated DNM 1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin‐ II ‐induced cellular enlargement.