Zain M Virk, Majd A El-Harasis, Zachary T Yoneda, Katherine C Anderson, Lili Sun, Joseph A Quintana, Brittany S Murphy, James L Laws, Giovanni E Davogustto, Matthew J O'Neill, Bibin T Varghese, Diane M Crawford, Hollie L Williams, Mahsima Shabani, Cassady J Pelphrey, Dakota D Grauherr, Kelsey Tomasek, Yan Ru Su, Megan C Lancaster, Quinn S Wells, Jeffrey M Dendy, Pablo Saavedra, Juan C Estrada, Travis D Richardson, Sharon T Shen, Arvindh N Kanagasundram, Jay A Montgomery, Christopher R Ellis, George H Crossley, Harikrishna Tandri, Prince J Kannankeril, Steven A Lubitz, William G Stevenson, Fei Ye, Patrick T Ellinor, Lynne W Stevenson, Dan M Roden, M Benjamin Shoemaker
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引用次数: 0
Abstract
Background: TTN encodes a sarcomeric protein called titin. Pathogenic rare variants in TTN are the most common finding in patients with atrial fibrillation (AF) and positive genetic testing.
Objectives: This study sought to define the characteristics and outcomes in patients with AF and pathogenic TTN variants compared with genotype-negative patients with AF.
Methods: Patients who presented initially with AF were enrolled in an AF registry. Retrospectively they underwent research sequencing for cardiomyopathy and arrhythmia genes. TTN(+) AF cases were defined as participants with pathogenic or likely pathogenic (P/LP) rare variants located in exons with high cardiac expression. They were matched 1:2 with control subjects with no P/LP variants. Phenotyping used retrospective manual chart review.
Results: Among 2794 participants; 57 (2.0%) TTN(+) AF cases were identified and matched with 114 control subjects. Low QRS complex voltage was present more often in TTN(+) AF cases (18% vs 5%; P < 0.01), with no difference in PR, QRS interval, or QTc. More TTN(+) AF cases had persistent AF at enrollment (44% vs 30%; P = 0.028) and had undergone multiple cardioversions (61% vs. 37%; P < 0.01). By end of follow-up (median 8.3 years; Q1, Q3: 4.5, 13.7 years), 11% of TTN(+) AF cases developed sustained ventricular tachycardia/ventricular fibrillation, 44% left ventricular (LV) systolic dysfunction (LV ejection fraction <50%), and 47% met a combined endpoint of sustained ventricular tachycardia/ventricular fibrillation or LV systolic dysfunction.
Conclusions: TTN(+) AF patients undergo more cardioversions and have more persistent forms of AF. Approximately 50% develop LV systolic dysfunction and/or malignant ventricular arrhythmias. These results highlight the need for diagnostic evaluation and management in TTN(+) patients beyond the usual care for AF.
期刊介绍:
JACC: Clinical Electrophysiology is one of a family of specialist journals launched by the renowned Journal of the American College of Cardiology (JACC). It encompasses all aspects of the epidemiology, pathogenesis, diagnosis and treatment of cardiac arrhythmias. Submissions of original research and state-of-the-art reviews from cardiology, cardiovascular surgery, neurology, outcomes research, and related fields are encouraged. Experimental and preclinical work that directly relates to diagnostic or therapeutic interventions are also encouraged. In general, case reports will not be considered for publication.