A novel ECG marker to distinguish proximal left bundle branch block from intraventricular conduction delay in candidates for cardiac resynchronization therapy

Background Distinguishing proximal left bundle branch block (LBBB) from intraventricular conduction delay (IVCD) is essential for cardiac resynchronization therapy (CRT) candidate selection, but remains challenging using standard 12-lead ECG. Calculation of negative-derivative activation times (NDAT) enables non-invasive assessment of epicardial ventricular activation from conventional ECG signal. We hypothesised that NDAT may provide a practical marker for differentiating proximal LBBB from IVCD. Purpose To assess the ability of NDAT to differentiate proximal LBBB from IVCD in CRT candidates and compare its performance with Strauss criteria. Methods Consecutive CRT candidates with non-RBBB morphology and QRS ≥130 ms from the multicentre UHF-BLOCK trial were included. Invasive electrophysiological study with left ventricular (LV) septal activation mapping was performed to classify conduction disorder as proximal LBBB or IVCD. NDATs were measured as the interval from the QRS onset to the steepest negative downslope of the QRS complex in leads V1-V8 during spontaneous rhythms (Figure 1A). The presence of LBBB according to the Strauss criteria on standard 12-lead ECG was assessed by an independent investigator. Results Among 125 patients (84 male; LVEF 28 [23–34]%; QRS 167±18 ms), invasive LV septal mapping identified proximal LBBB in 84 (67%) and IVCD in 41 (33%) cases. Patients with proximal LBBB presented with longer QRS duration than those with IVCD (175±16 vs 153±12 ms; P<0.001). Strauss criteria differentiated proximal LBBB from IVCD with an AUC of 0.67, sensitivity of 98%, and specificity of 37%. A specific activation pattern was observed in patients with proximal LBBB and IVCD: NDATs in right ventricular and septal leads (V1–V3) were similar, while NDATs in leads associated with LV lateral wall activation (V5–V8) were more prolonged in patients with proximal LBBB than with IVCD (Figure 1B). Receiver operating characteristic (ROC) analysis showed that NDAT in leads V5, V6, V7, and V8 all outperformed Strauss criteria for differentiating proximal LBBB from IVCD, with AUCs of 0.78, 0.93, 0.91, and 0.90 (P=0.03 for V5 and P<0.001 for V6–V8 vs. Strauss criteria), optimal cutoffs of 89, 110, 116, and 122 ms, with sensitivity/specificity (se/sp) of 74/83%, 83/98%, 89/90%, and 88/85%, respectively. (Figure 1C). Conclusion NDAT in leads V5-V8 differentiates proximal LBBB from IVCD more accurately than the Strauss criteria and provides a clinically available tool to improve the results of cardiac resynchronization therapy.