Mechano-electrical coupling as framework for understanding functional remodeling during LBBB and CRT

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Cardiac Electrophysiology

Background:

• Left bundle-branch block (LBBB) leads to progressive cardiac dysfunction, a phenomenon not fully understood.
• Adverse cardiac events typically trigger compensatory adaptations, unlike the sustained deterioration seen in LBBB.
• The role of mechano-electrical coupling (MEC) in long-term cardiac remodeling following LBBB and cardiac resynchronization therapy (CRT) requires investigation.

Purpose of the Study:

• To investigate if mechano-electrical coupling (MEC) can explain the long-term cardiac remodeling observed in patients with LBBB.
• To explore the potential of MEC in understanding the effects of cardiac resynchronization therapy (CRT) on cardiac function.
• To utilize an integrative modeling approach to link local cardiac mechanics and electrophysiology to global cardiovascular function.

Main Methods:

• Developed an integrative computational model of the left ventricle, incorporating mechanically and electrically coupled myocardial segments.
• Integrated mechano-electrical coupling (MEC) by adapting L-type Ca(2+) current to minimize dispersion of local external work.
• Simulated the effects of sustained left bundle-branch block (LBBB) and subsequent cardiac resynchronization therapy (CRT) on cardiac mechanics and electrophysiology.

Main Results:

• Left bundle-branch block (LBBB) initially decreased left-ventricular stroke work and increased end-diastolic volume.
• During sustained LBBB, MEC reduced mechanical workload and repolarization dispersion but led to further decreases in stroke work and increases in end-diastolic volume due to reduced contractility in late-activated regions.
• Cardiac resynchronization therapy (CRT) increased stroke work despite wider mechanical workload dispersion, and sustained CRT with MEC reduced end-diastolic volume by minimizing workload and repolarization dispersion.

Conclusions:

• Mechano-electrical coupling (MEC) provides a framework for understanding progressive cardiac dysfunction in left bundle-branch block (LBBB).
• MEC helps explain the long-term remodeling effects of both LBBB and cardiac resynchronization therapy (CRT).
• The study highlights the complex interplay between mechanical and electrical forces in cardiac adaptation and maladaptation.