Linking cross-bridge cycling kinetics to response to cardiac resynchronization therapy: a multiscale modelling study

Lauren J. Dupuis, Theo Arts, Frits W. Prinzen, Tammo Delhaas, Joost Lumens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Aims Cardiac resynchronization therapy (CRT) is currently the most widely used treatment for heart failure patients with left bundle branch block (LBBB). In recent years, the presence of septal rebound stretch (SRS) has been found to be a positive indicator for CRT response although the mechanism is unknown.

Methods and results In an attempt to understand the relation between cellular mechanics and global pump function in CRT patients, we utilize the CircAdapt closed-loop cardiovascular system model in combination with the MechChem model of cardiac sarcomere contraction. Left bundle branch block has been simulated with increasing delay in left ventricular free wall and septal wall activation. In addition to the electrical dyssynchrony, myocardial mechanical function was diminished by decreasing the cross-bridge cycling rate. Our results have shown that a decrease in the cross-bridge cycling rate in addition to LBBB resulted in a decrease in SRS with a concomitant decreased response to resynchronization.

Conclusions The results of our multiscale modelling study suggest that, while greater SRS during systole clearly indicates electrical dyssynchrony, it also predicts mechanical viability and healthy cross-bridge cycling rates in the myocardium. Hence, SRS positively indicates response to CRT.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalEP Europace
Publication statusPublished - Nov 2018
Event9th Theo Rossi di Montelera (TRM) Forum on Computer Simulation and Experimental Assessment of Cardiac Function: From Model to Clinical Outcome - Ctr Computat Med Cardiol, Lugano, SWITZERLAND, Lugano, Switzerland
Duration: 4 Dec 20175 Dec 2017


  • CircAdapt
  • MechChem
  • Cardiac resynchronization therapy
  • Left bundle branch block
  • Heart failure
  • WORK

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