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

Abstract

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.

• Authors: Lauren J Dupuis, Theo Arts, Frits W Prinzen, Tammo Delhaas, Joost Lumens
• Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) Vol. 20 Issue suppl_3 Pg. iii87-iii93 (Nov 01 2018) ISSN: 1532-2092 [Electronic] England
• PMID: 30476050 (Publication Type: Journal Article)

Topics

• Action Potentials
• Bundle of His (physiopathology)
• Bundle-Branch Block (diagnosis, physiopathology, therapy)
• Cardiac Resynchronization Therapy
• Computer Simulation
• Heart Failure (diagnosis, physiopathology, therapy)
• Heart Rate
• Heart Ventricles (physiopathology)
• Humans
• Kinetics
• Models, Cardiovascular
• Myocardial Contraction
• Treatment Outcome
• Ventricular Function, Left