Synchronous ventricular electrical activation is a prerequisite for adequate left ventricular (LV) systolic function. Conduction abnormalities such as left bundle branch block, and ventricular pacing lead to a dyssynchronous electrical activation sequence, which may have deleterious consequences. The present review attempts to connect the various processes involved in the development of ‘dyssynchronopathy’, and its correction by cardiac resynchronization therapy (CRT). Abnormal electrical impulse conduction leads to abnormal contraction, characterized by regional differences in timing as well as shortening patterns and amount of external work performed. Early activated regions may show ‘wasted work’, which leads to inefficient action of the entire left ventricle. Moreover, both the development of heart failure (HF) in general and the regional differences in mechanical load lead to structural, electrical, and contractile remodelling processes. These have been demonstrated at the level of the myocardium (asymmetric hypertrophy, fibrosis, prolongation of activation and reduction in repolarization forces, decrease in LV ejection fraction), cell (gap junctional remodelling, derangement of the T-tubular structure), and molecule (under or overexpression of ion channels and contractile proteins subtypes and abnormal calcium handling). The myocardial adaptations to dyssynchrony are ‘maladaptive’. This also explains why CRT, unlike most pharmacological treatments, continues to increase its therapeutic effect over time. Finally, better understanding of all processes involved in dyssynchrony and CRT may also lead to new pharmacological agents for treating HF and to novel pacing strategies.

Premature beats originating in clinically concealed areas of local early repolarization promote ventricular arrhythmias and sudden cardiac arrest.

To investigate the relationship between vectorcardiography (VCG) and myocardial scar on cardiac magnetic resonance (CMR) imaging, and whether combining these metrics may improve cardiac resynchronization therapy (CRT) response prediction. Thirty-three CRT patients were included. QRSarea, Tarea and QRSTarea were derived from the ECG-synthesized VCG. CMR parameters reflecting focal scar core (Scar2SD, Gray2SD) and diffuse fibrosis (pre-T1, extracellular volume [ECV]) were assessed. CRT response was defined as ≥15% reduction in left ventricular end-systolic volume after six months' follow-up. VCG QRSarea, Tarea and QRSTarea inversely correlated with focal scar (R = -0.44--0.58 for Scar2SD, p ≤ 0.010), but not with diffuse fibrosis. Scar2SD, Gray2SD and QRSarea predicted CRT response with AUCs of 0.692 (p = 0.063), 0.759 (p = 0.012) and 0.737 (p = 0.022) respectively. A combined ROC-derived threshold for Scar2SD and QRSarea resulted in 92% CRT response rate for patients with large QRSarea and small Scar2SD or Gray2SD. QRSarea is inversely associated with focal scar on CMR. Incremental predictive value for CRT response is achieved by a combined CMR-QRSarea analysis.