Journal Article Epublish
PubMed: 42669085 DOI: 10.1007/s10237-026-02119-w
Calcium-mediated force-interval relationship drives post-extrasystolic potentiation in premature ventricular complexes: a computational study.
Biomech Model Mechanobiol 25(5)
Authors: Sjoerd Vossen, Nick van Osta, Guilherme Pedro Carvalho Lourenço, Sérgio Matoso Laranjo, Joost Lumens
Affiliations
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
- Pediatric Cardiology Department, Hospital de Santa Marta, Unidade Local de Saúde de S. José, 1150-199, Lisbon, Portugal.
- Comprehensive Health Research Center, NOVA Medical School, NMS, Faculdade de Ciências Médicas, FCM, Universidade NOVA de Lisboa, 1169-056, Lisbon, Portugal.
- Medtech, AI, RWE and Digital Health Knowledge Center, NOVA Medical School, NMS, Faculdade de Ciências Médicas, FCM, Universidade NOVA de Lisboa, 1169-056, Lisbon, Portugal.
- Digital Data Design Institute at Nova SBE and NOVA Medical School (D^3 Institute), Campus de Carcavelos, Rua da Holanda, 1, 2775-405, Carcavelos, Portugal.
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.
MeSH
Calcium, Cardiomyopathies