Giving multipoint pacing a try for CRT nonresponders may reduce HF hospitalizations or death

Multipoint pacing (MPP) is associated with a significant reduction in heart failure (HF) hospitalizations or death in patients who do not respond to cardiac resynchronization therapy (CRT) using standard biventricular pacing (BiVP), according to a secondary analysis of the MORE-CRT MPP trial presented at EHRA 2025.

At a mean follow-up of 5 months, the incidence of HF hospitalizations or all-cause mortality was 6.6 percent in patients randomized to have their CRT devices programmed to MPP vs 10.4 percent in those continuing BiVP, corresponding to a relative risk (RR) reduction of 36 percent for the composite endpoint (p=0.0107).

In a time-to-event analysis that visualizes the treatment differences over time, the estimated incidence of HF hospitalizations or deaths at 8 months was 11.5 percent in MPP patients vs 18.2 percent in BiVP patients (log-rank p=0.0121). [EHRA 2025, Late-breaking science session 1]

“When you look at the Kaplan-Meier curves, you may appreciate that we have a difference very early in favour of MPP as compared to BiVP, with a risk reduction of 37 percent for the combined endpoint,” said Professor Christophe Leclercq from the Rennes University Hospital, France, at a late-breaking science session.

Regardless of BiVP percentage

MORE-CRT MPP was a prospective, randomized, multicentre trial (n=1,677) with a primary endpoint of nonresponder-to-responder conversion rate 6 months after activating MPP or continuing with BiVP. [Europace 2023;25:euad294] HF hospitalizations and death from any cause were prespecified secondary endpoints of the study. [Europace 2025;doi:10.1093/europace/euaf070]

When dissecting the composite endpoint in the current analysis, the improved clinical prognosis with MPP was driven by a lower incidence of HF hospitalizations (5.4 percent vs 8.9 percent; RR reduction, 39 percent; p=0.0154). All-cause deaths also occurred at a lower rate with MPP, but not significantly (1.9 percent vs 2.9 percent; p>0.05).

From multivariable analysis, randomization to MPP instead of BiVP was independently associated with a reduced risk of composite endpoint events (odds ratio, 0.59, 95 percent confidence interval, 0.39–0.89; p=0.0116).

The other parameters that exhibited an independent association with the composite endpoint were renal disease status (p=0.0006), left ventricular (LV) ejection fraction (p=0.0056), and left bundle branch block (p=0.0144). The BiVP percentage during the 6 months before randomization (>97 percent vs ≤97 percent) was not a predictor in either univariable or multivariable analysis.

“Contrary to a previous analysis, MPP vs BiVP had a significant benefit, whereas the extent of BiVP did not,” said discussant Professor Cecilia Linde from the Karolinska Institute, Stockholm, Sweden. “MPP vs BiVP reduced the composite endpoint irrespective of the extent of BiVP, and the results give a positive signal that MPP may enhance CRT response.”

CRT “nonresponse”

Randomized patients in MORE-CRT MPP were nonresponders to CRT, as defined by <15 percent reduction in LV end-systolic volume from implant to 6 months, despite having received BiVP for the duration of that time.

“The assessment of CRT response in the MORE-CRT MPP data could have been underpowered to show MPP value due to some patients not being treated with BiVP for long enough, possibly because of atrial tachyarrhythmias or other conditions,” said Leclercq and colleagues in a simultaneously published manuscript, hypothesizing why MPP did not improve the responder rate but improved clinical prognosis.

Indeed, a 2021 joint position statement from three European Society of Cardiology associations has discouraged the term “response to CRT” due to its arbitrary and dichotomous definitions, advocating instead for the concept of “disease modification by CRT”. [Europace 2021;23:1324-1342]