Genotype-Driven Pathogenesis of Atrial Fibrillation in Hypertrophic Cardiomyopathy: The Case of Different TNNT2 Mutations

• DOI: 10.3389/fphys.2022.864547
• Publication Date: 2022-04-19T06:14:45Z
• Authors: Josè Manuel Pioner; Giulia Vitale; Francesca Gentile; Beatrice Scellini; Nicoletta Piroddi; Elisabetta Cerbai; Iacopo Olivotto; Jil Tardiff; Raffaele Coppini; Chiara Tesi; Corrado Poggesi; Cecilia Ferrantini
• Keywords: Myofilament; Pathogenesis

Atrial dilation and atrial fibrillation (AF) are common in Hypertrophic CardioMyopathy (HCM) patients associated with a worsening of prognosis. The pathogenesis myopathy HCM remains poorly investigated no specific association genotype has been identified. By re-analysis our cohort thin-filament (Coppini et al. 2014) AF was identified 10% sporadic mutations the cardiac Troponin T gene ( TNNT2 ), while occurrence much higher (25–75%) carrying “hot-spot” mutations. To determine molecular basis arrhythmia occurrence, two mouse models expressing human variants (a one, R92Q, “sporadic” E163R) were selected according to different pathophysiological pathways previously demonstrated ventricular tissue. Echocardiography studies showed significant left both models, but more pronounced R92Q. In E163R trabeculae, line what observed preparations, energy cost tension generation markedly increased. However, changes twitch amplitude kinetics observed, there arrhythmic propensity. R92Q instead, displayed normal ATP consumption increased myofilament calcium sensitivity, as preparations. This reduced inotropic reserve slower contractions and, importantly, an spontaneous beats triggered that represent intrinsic arrhythmogenic mechanism promoting AF. depends on mutation-driven pathomechanism (i.e., sensitivity rather than cost) may influence individual response treatment.