Predictors of the efficacy of AV-optimised His bundle pacing in patients with a prolonged PR interval: a stratified analysis of the HOPE-HF clinical trial

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Foundation. Main funding source(s): British Heart Foundation. BACKGROUND: HOPE-HF was a randomised, placebo-controlled, cross-over trial of AV-optimised His bundle pacing in patients with heart failure (LVEF ≤40%), a PR interval (≥200ms) and without left bundle branch block.1,2. In this analysis we studied the impact of baseline PR interval and acute blood pressure change at the optimal AV-delay on the placebo-controlled effect of His bundle pacing on the trial endpoints of peak VO2 (primary) and patient symptoms (using the Minnesota Living with Heart Failure Questionnaire). METHODS AND RESULTS: 167 patients were successfully implanted and randomised to 6 month blocks of pacing and placebo. We performed a non-invasive, high-precision protocol to calculate the optimal AV delay and associated acute blood-pressure response at randomisation. To test the impact of the baseline PR interval and acute BP response on the placebo-controlled effect of AV-optimised His bundle pacing on endpoints we compared Bayesian ordinal regression models and the relative explained variance (REV) of variables in the model. There was weak evidence that His-bundle pacing improved peak VO2 across all patients (OR 1.31, 95% CrI 0.86 to 2.01, Pr(OR > 1)=89%). The baseline PR interval had little impact on this benefit (REV 0%), and the blood pressure response was more likely (88% vs 12%) to be predictive. However, there was strong evidence that overall AV-optimised His-bundle pacing improved patient symptoms as compared to placebo (OR 1.58, 95% CrI 1.04 to 2.40, Pr(OR>1)=98%). Again, the baseline PR interval had little impact on this benefit (REV 0%) and the blood pressure response was much more likely (97% vs 3%) to be predictive. Higher acute BP increments led to greater placebo-controlled improvements in MLWHF at 6-months. CONCLUSION: An individual’s acute BP response with AV-optimised His-pacing is a powerful predictor of their placebo-controlled improvement in symptoms (MLWHF) at 6-months. This can form the basis of patient selection for future studies and clinical practice. [Figure: see text]