Left Atrial Function in Patients with Titin Cardiomyopathy.

BACKGROUND: Truncating titin variants (TTNtv) are the most prevalent genetic etiology of dilated cardiomyopathy (DCM). While TTNtv has been associated with atrial fibrillation, it remains unknown whether and how left atrial (LA) function differs between DCM patients with and without TTNtv. We aimed to determine and compare LA function in DCM patients with and without TTNtv and to evaluate whether and how left ventricular (LV) function affects the LA using computational modeling.

METHODS & RESULTS: DCM patients from the Maastricht DCM registry that underwent genetic testing and cardiovascular magnetic resonance (CMR) imaging were included in the current study. Subsequent computational modeling (CircAdapt model) was performed to identify potential LV and LA myocardial hemodynamic substrates.

RESULTS: In total, 377 DCM patients (N=42 with TTNtv; N=335 without a genetic variant) were included (median age 55 years, IQR [46-62], 62% men). TTNtv patients had a larger LA-volume, and reduced LA-strain compared to patients without a genetic variant (LA-volume index 60mLm-2 [49;83] vs 51mLm-2 [42;64];LA reservoir strain 24%[10;29] vs 28%[20;34];LA-booster strain 9%[4;14] vs 14%[10;17], respectively; all P<0.01). Computational modeling suggests that while the observed LV-dysfunction partially explains the observed LA-dysfunction in the TTNtv patients, both intrinsic LV- and LA-dysfunction are present in patients with and without a TTNtv.

CONCLUSION: DCM patients with TTNtv have more severe LA dysfunction compared to patients without a genetic variant. Insights from computational modeling suggest that both intrinsic LV and LA dysfunction are present in DCM patients with and without TTNtv.