Aiming a pacing lead at the heart's slowest spot did not help patients

Cardiac resynchronisation therapy is a pacemaker strategy for people whose heart failure comes with a conduction problem: the two ventricles beat out of step, and carefully timed pacing brings them back together. It works for most patients — but up to a third get no benefit from it [s2].

The obvious explanation is placement. If the left ventricular lead sits somewhere that already activates on time, pacing there achieves little; put it where activation is latest and the resynchronising effect should be greatest. Observational data have pointed that way for years [s2]. DANISH-CRT, published in The Lancet and presented at ESC Congress 2026 on 31 August, is the first large randomised test of the idea [s1] [s2].

It did not work.

What the trial did

DANISH-CRT was an investigator-initiated, national, double-blind, randomised superiority trial conducted at all five Danish university centres that perform these implants [s1] [s2]. Patients with heart failure and a wide QRS complex on guideline-directed medication, referred for biventricular pacing, were randomly assigned 1:1 [s1].

The intervention group had the left ventricular lead placed at the site of latest electrical activation within the coronary sinus branches. The control group had it placed conventionally, in a posterolateral, non-apical branch [s1].

Patients and all study personnel except the operating room team were masked to allocation [s1] — a meaningful design feature for a trial whose secondary endpoints include quality of life and functional status.

The primary outcome was a composite of time to death or first unplanned hospitalisation for heart failure [s1].

What happened

Between 20 March 2018 and 3 June 2024, 1,001 patients were included, of whom 255 were female and 746 male; 499 were assigned to the intervention and 502 to control, with one incorrectly enrolled patient excluded, leaving 1,000 in the modified intention-to-treat analysis [s1].

The targeting worked, in the narrow technical sense. Electrical activation at the left ventricular lead was a mean of 9 milliseconds later in the intervention group (95% CI 5 to 13) [s1].

Follow-up completed on 27 February 2026, after a median of 45.8 months (IQR 28.5 to 65.7) [s1]. The primary endpoint occurred in 139 of 499 patients (28%) in the intervention group and 128 of 501 (26%) in the control group, a hazard ratio of 1.10 (95% CI 0.86 to 1.39, p=0.45) [s1]. The ESC's own summary reports the same comparison as 27.9% against 25.5% [s2].

Overall complication risk was similar — 71 patients (14%) in the intervention group against 64 (13%) in the control group — but lead-related complications were more frequent with targeting, and one procedure-related death occurred in the intervention group [s1].

Secondary endpoints followed the primary. The ESC reports consistently similar findings across structural changes to the left ventricle, quality of life, functional status and physical capacity, and across subgroup analyses of the primary endpoint [s2].

Why 9 milliseconds is the number to hold onto

The trial achieved a mean difference of 9 milliseconds in activation timing at the lead site (95% CI 5 to 13) [s1]. That is a real, statistically distinguishable difference — and it is small.

This is the interpretive fork. One reading is that the hypothesis is wrong: latest-activation targeting does not translate into better outcomes. The other is that the hypothesis was under-tested, because a 9-millisecond shift may not be enough anatomical difference to produce a physiological one, given that lead placement is constrained by wherever the coronary sinus branches happen to run.

DANISH-CRT cannot separate those two readings, and neither can any single trial with this design. What it can say is that a strategy of routine electrical mapping to guide placement — the practical question a clinician faces — did not improve outcomes over conventional placement, and carried more lead-related complications [s1] [s2].

That is how the investigators put it: the findings do not support routine electrical mapping to target left ventricular lead placement in contemporary practice [s2].

Limits

The trial ran in one country, at five academic centres, from 2018 to 2024 [s1]. Device technology and background heart failure therapy both changed over that period.

Analysis followed a modified intention-to-treat approach, with safety assessed in all correctly assigned patients [s1]. And a hazard ratio of 1.10 with a confidence interval of 0.86 to 1.39 is a null result rather than a demonstration of harm — the data are compatible with a modest benefit from targeting as well as a modest disadvantage [s1].

The trial was funded by the Novo Nordisk Foundation, the Danish Heart Foundation, the Danish Pacemaker and ICD Registry, and Independent Research Fund Denmark, and registered as NCT03280862 [s1].

What to watch

The investigators say they will continue analysing the data to identify which patient subgroups benefited most from resynchronisation therapy itself [s2]. That is the more useful question the trial is positioned to address: not where to put the lead, but who should get the device.

This article describes trial results. It is not advice about any treatment, and nothing here should be used to make decisions about care.

Sources

• Targeted left ventricular lead placement in biventricular pacing for heart failure: a national, multicentre, double-blind, randomised controlled trial in Denmark, The Lancet, 31 August 2026
• Targeted lead placement is no better than standard placement in cardiac resynchronisation therapy, European Society of Cardiology, 31 August 2026