Phenotype and Clinical Outcomes of Titin Cardiomyopathy

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Title: Phenotype and Clinical Outcomes of Titin Cardiomyopathy
Authors: Tayal, U
Newsome, S
Buchan, R
Whiffin, N
Halliday, B
Lota, A
Roberts, A
Baksi, AJ
Voges, I
Midwinter, W
Wilk, A
Govind, R
Walsh, R
Daubeney, P
Jarman, JWE
Baruah, R
Frenneaux, M
Barton, PJ
Pennell, D
Ware, JS
Prasad, SK
Cook, SA
Item Type: Journal Article
Abstract: 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.
Issue Date: 23-Oct-2017
Date of Acceptance: 30-Aug-2017
URI: http://hdl.handle.net/10044/1/50547
DOI: https://dx.doi.org/10.1016/j.jacc.2017.08.063
ISSN: 0735-1097
Publisher: Elsevier
Start Page: 2264
End Page: 2274
Journal / Book Title: Journal of the American College of Cardiology
Volume: 70
Issue: 18
Copyright Statement: © 2017 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY LICENSE ( http://creativecommons.org/licenses/by/4.0/ ) .
Sponsor/Funder: British Heart Foundation
Fondation Leducq
British Heart Foundation
Royal Brompton & Harefield NHS Foundation Trust
Wellcome Trust
Royal Brompton & Harefield NHS Foundation Trust
Department of Health
Wellcome Trust
Royal Brompton & Harefield NHS Foundation Trust
Medical Research Council
Funder's Grant Number: SP/10/10/28431
11 CVD-01
FS/13/13/29819
6178/39020
HICF-R6-373
RBHT6179
HICF-R6-373
107469/Z/15/Z
N/A
MR/M003191/1
Keywords: 1102 Cardiovascular Medicine And Haematology
1117 Public Health And Health Services
Cardiovascular System & Hematology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute



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