Truncating Variants in TTN are Associated With Primary Atrial Myopathy.

Area of Science:

• Cardiology
• Genetics
• Echocardiography

Background:

• Truncating TTN variants (TTNtv) are a primary genetic cause of dilated cardiomyopathy (DCM) and are linked to atrial fibrillation (AF).
• In DCM, AF typically results from left atrial (LA) remodeling due to left ventricular systolic dysfunction.
• The association between TTNtv and primary LA dysfunction, independent of left ventricular systolic dysfunction, is not well understood.

Purpose of the Study:

• To investigate atrial function in TTNtv carriers using strain echocardiography across the left ventricular ejection fraction (LVEF) spectrum.
• To determine the relationship between TTNtv, atrial function, and atrial fibrillation (AF).
• To explore whether TTNtv are associated with primary LA dysfunction independent of left ventricular systolic dysfunction.

Main Methods:

• Retrospective, multicenter study evaluating atrial function via strain echocardiography in TTNtv carriers.
• Comparison of TTNtv carriers with preserved LVEF (≥50%) to healthy controls.
• Comparison of TTNtv carriers with reduced LVEF (<50%) to patients with idiopathic, variant-negative DCM (iDCM).

Main Results:

• Reduced LA strain parameters were observed in TTNtv carriers with preserved LVEF compared to controls.
• In TTNtv carriers with reduced LVEF, only LA contractile strain was significantly reduced compared to iDCM.
• LA contractile strain correlated with LVEF only when LVEF was <50%; atrial dysfunction worsened in parallel with declining LVEF.
• AF incidence was higher in TTNtv carriers, particularly those with reduced LVEF.

Conclusions:

• Early LA myopathy, detectable by strain imaging, is present in TTNtv carriers even with preserved LVEF, suggesting an independent phenotypic marker.
• Atrial dysfunction progresses in parallel with declining LVEF in TTNtv carriers.
• Increased AF frequency in TTNtv carriers highlights the potential utility of LA strain for AF risk stratification.