Phenotype and Clinical Outcomes of Titin Cardiomyopathy

Tayal, Upasana, Newsome, Simon, Buchan, Rachel, Whiffin, Nicola, Halliday, Brian, Lota, Amrit, Roberts, Angharad, Baksi, A John, Voges, Inga, Midwinter, Will, Wilk, Alijca, Govind, Risha, Walsh, Roddy, Daubeney, Piers, Jarman, Julian W E, Baruah, Resham, Frenneaux, Michael, Barton, Paul J, Pennell, Dudley, Ware, James S, Prasad, Sanjay K and Cook, Stuart A (2017) Phenotype and Clinical Outcomes of Titin Cardiomyopathy. Journal of the American College of Cardiology, 70 (18). pp. 2264-2274. ISSN 0735-1097

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BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. METHODS: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. RESULTS: Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/- groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.

Item Type: Article
Additional Information: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Uncontrolled Keywords: adolescent,adult,aged,aged, 80 and over,diagnostic imaging,child,cohort studies,genetics,female,follow-up studies,humans,male,middle aged,phenotype,prospective studies,single-blind method,treatment outcome,young adult
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Depositing User: LivePure Connector
Date Deposited: 15 Mar 2019 11:30
Last Modified: 12 May 2023 21:30
DOI: 10.1016/j.jacc.2017.08.063

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