Targeted left ventricular lead placement in biventricular pacing for heart failure: a national, multicentre, double-blind, randomised controlled trial in Denmark.

BACKGROUND: Left ventricular lead position is a key determinant of optimal biventricular pacing for heart failure. Observational data indicate better outcomes in patients with late myocardial activation at the left ventricular lead site. We aimed to test whether targeting the left ventricular lead at site of latest electrical activation improves outcomes. METHODS: In this national, randomised, controlled, double-blinded, superiority trial we included patients from all five Danish university centres performing device implantation who had heart failure and wide QRS on guideline-directed medication, eligible for biventricular pacing. We randomly assigned (1:1) patients to either the intervention group, with left ventricular lead placement at the latest electrically activated site within the coronary sinus branches, or to control group, with left ventricular lead placement in a posterolateral non-apical branch. Primary outcome was a composite of time to death or first unplanned heart failure hospitalisation. We used block randomisation and masked patients and all study personnel (except operating room personnel) to treatment allocation. The primary outcome was a composite of time to death or first unplanned hospitalisation for heart failure. Analysis followed a modified intention-to-treat approach. Safety was assessed in all correctly assigned patients. The trial is registered at ClinicalTrials.gov (NCT03280862) and is complete. FINDINGS: From March 20, 2018, to June 3, 2024, we included 1001 patients (255 females and 746 males); 499 were randomly assigned to the intervention group and 502 to the control group. One incorrectly enrolled patient was excluded, leaving 1000 patients for the modified intention-to-treat analysis. Electrical activation at left ventricular lead was a mean of 9 milliseconds (95% CI 5-13) later in the intervention group. Follow-up was completed on Feb 27, 2026, after a median 45·8 months (IQR 28·5-65·7). The primary endpoint occurred in 139 (28%) of 499 patients in the intervention group and 128 (26%) of 501 in control group (hazard ratio 1·10 [95% CI 0·86-1·39]; p=0·45). Overall complication risk was similar between groups (71 [14%] patients in the intervention group vs 64 [13%] in the control group), but lead-related complications were more frequent in the intervention group. One procedure-related death occurred in the intervention group. INTERPRETATION: In patients with heart failure and prolonged QRS, targeted left ventricular lead placement at the site of latest electrical activation did not reduce the composite endpoint of death or unplanned hospitalisation for heart failure compared with conventional lead placement in a posterolateral, non-apical position. FUNDING: Novo Nordisk Foundation, Danish Heart Foundation, Danish Pacemaker and ICD Registry, and Independent Research Fund Denmark.