Left Atrial Function in Patients with Titin Cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Biomedical Engineering

Background:

• Titin truncating variants (TTNtv) are the primary genetic cause of dilated cardiomyopathy (DCM).
• Previous studies linked TTNtv to atrial fibrillation, but the impact on left atrial (LA) function in DCM patients remained unclear.

Purpose of the Study:

• To compare LA function in DCM patients with and without TTNtv.
• To investigate the influence of left ventricular (LV) function on LA function using computational modeling.

Main Methods:

• Analysis of 377 DCM patients from the Maastricht DCM registry, including genetic testing and cardiovascular magnetic resonance (CMR).
• Utilized the CircAdapt computational model to simulate LV and LA myocardial hemodynamic substrates.
• Compared LA volume and strain parameters between TTNtv-positive and TTNtv-negative DCM groups.

Main Results:

• Patients with TTNtv (n=42) showed significantly larger LA volume index (60 mLm⁻² vs 51 mLm⁻²) and reduced LA reservoir strain (24% vs 28%) and LA booster strain (9% vs 14%) compared to those without genetic variants (n=335).
• Computational modeling indicated that while LV dysfunction partially explained LA dysfunction in TTNtv patients, intrinsic LV and LA dysfunction were present in both groups.

Conclusions:

• DCM patients with TTNtv experience more pronounced LA dysfunction than those without genetic variants.
• Both intrinsic LV and LA dysfunction contribute to the pathophysiology of DCM, irrespective of TTNtv status.