Calcium-mediated force-interval relationship drives post-extrasystolic potentiation in premature ventricular complexes: a computational study.

Authors

Sjoerd Vossen, Nick van Osta, Guilherme Pedro Carvalho Lourenço, Sérgio Matoso Laranjo, Joost Lumens

Published in

Biomechanics and modeling in mechanobiology. Volume 25. Issue 5. Aug 30, 2026. Epub Aug 30, 2026.

Abstract

Premature ventricular complexes (PVCs) are common cardiac arrhythmias that can lead to cardiomyopathy when frequent. Post-extrasystolic potentiation (PESP), which is the transient increase in contractility following a PVC, may serve as a predictive marker for heart failure risk; yet, the underlying calcium-mediated mechanisms and their relative contribution compared to loading conditions remain poorly understood. We integrated a mechanochemical model coupling intracellular calcium dynamics to sarcomere mechanics within the CircAdapt closed-loop cardiovascular framework. A novel calcium source model incorporating the force-interval relationship was calibrated using experimental canine data. We simulated single PVCs across varying coupling intervals and systematically investigated the contributions of calcium dynamics versus loading conditions to PESP, quantified as changes in systolic blood pressure (∆SBP), maximum rate of left ventricular pressure rise (∆max(dP_Lv/dt)), and left ventricular ejection fraction (∆LVEF). The calcium-based force-interval relationship reproduced experimental mechanical restitution curves with high accuracy (RMSE 9.59 ± 0.08%). Shorter coupling intervals reduced premature beat contractility while enhancing PESP in subsequent beats. Systematic variation of preload, afterload, and intrinsic contractility revealed that calcium dynamics reproduce the observed PESP patterns, with loading conditions as modulators. Notably, ∆max(dP_Lv/dt) and ∆SBP responded differently, with ∆SBP exhibiting complex non-monotonic behavior. The model qualitatively reproduced pressure-volume patterns from a single clinical quadrigeminy case. This study demonstrates that a calcium-based force-interval formulation reproduces the qualitative features of PESP within this framework, with preload and afterload modulating the pattern of beat-to-beat pressure response. The divergent behavior among contractility metrics emphasizes the need for multimetric assessment. This framework enables distinguishing intrinsic myocardial dysfunction from extrinsic loading effects, facilitating patient-specific risk stratification in PVC-induced cardiomyopathy.

PMID:
42669085
Bibliographic data and abstract were imported from PubMed on 31 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.