Clinical Characteristics and Outcomes in Patients With Atrial Fibrillation and Pathogenic TTN Variants

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• TTN gene encodes titin, a sarcomeric protein.
• Pathogenic rare variants in TTN are frequently found in patients with atrial fibrillation (AF) and positive genetic testing.

Purpose of the Study:

• To characterize patients with AF and pathogenic TTN variants.
• To compare outcomes of TTN-variant positive AF patients with genotype-negative AF patients.

Main Methods:

• AF patients underwent genetic sequencing for cardiomyopathy and arrhythmia genes.
• TTN(+) AF cases with pathogenic or likely pathogenic variants were matched 1:2 with control subjects.
• Phenotyping involved retrospective chart review.

Main Results:

• Low QRS complex voltage was more common in TTN(+) AF cases (18% vs. 5%).
• Persistent AF (44% vs. 30%) and multiple cardioversions (61% vs. 37%) were more frequent in TTN(+) AF cases.
• Over median 8.3 years, 11% developed sustained ventricular arrhythmias, 44% developed LV systolic dysfunction, and 47% met a combined endpoint.

Conclusions:

• TTN(+) AF patients experience more persistent AF and cardioversions.
• Approximately 50% of TTN(+) AF patients develop LV systolic dysfunction and/or malignant ventricular arrhythmias.
• Specialized diagnostic evaluation and management are crucial for TTN(+) AF patients.