Phenotype and Clinical Outcomes of Titin Cardiomyopathy

Upasana Tayal; Simon Newsome; Rachel Buchan; Nicola Whiffin; Brian Halliday; Amrit Lota; Angharad Roberts; A John Baksi; Inga Voges; Will Midwinter; Alijca Wilk; Risha Govind; Roddy Walsh; Piers Daubeney; Julian W E Jarman; Resham Baruah; Michael Frenneaux; Paul J Barton; Dudley Pennell; James S Ware; Sanjay K Prasad; Stuart A Cook

doi:10.1016/j.jacc.2017.08.063

Phenotype and Clinical Outcomes of Titin Cardiomyopathy

Upasana Tayal, Simon Newsome, Rachel Buchan, Nicola Whiffin, Brian Halliday, Amrit Lota, Angharad Roberts, A John Baksi, Inga Voges, Will Midwinter, Alijca Wilk, Risha Govind, Roddy Walsh, Piers Daubeney, Julian W E Jarman, Resham Baruah, Michael Frenneaux, Paul J Barton, Dudley Pennell, James S WareSanjay K Prasad, Stuart A Cook

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	2264-2274
Number of pages	11
Journal	Journal of the American College of Cardiology
Volume	70
Issue number	18
Early online date	23 Oct 2017
DOIs	https://doi.org/10.1016/j.jacc.2017.08.063
Publication status	Published - 31 Oct 2017

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Cardiomyopathy, Dilated/diagnostic imaging
Child
Cohort Studies
Connectin/genetics
Female
Follow-Up Studies
Humans
Male
Middle Aged
Phenotype
Prospective Studies
Single-Blind Method
Treatment Outcome
Young Adult

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Cite this

Tayal, U., Newsome, S., Buchan, R., Whiffin, N., Halliday, B., Lota, A., Roberts, A., Baksi, A. J., Voges, I., Midwinter, W., Wilk, A., Govind, R., Walsh, R., Daubeney, P., Jarman, J. W. E., Baruah, R., Frenneaux, M., Barton, P. J., Pennell, D., ... Cook, S. A. (2017). Phenotype and Clinical Outcomes of Titin Cardiomyopathy. Journal of the American College of Cardiology, 70(18), 2264-2274. https://doi.org/10.1016/j.jacc.2017.08.063

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 ; Cook, Stuart A. / Phenotype and Clinical Outcomes of Titin Cardiomyopathy. In: Journal of the American College of Cardiology. 2017 ; Vol. 70, No. 18. pp. 2264-2274.

@article{49b4ad35d66e49c887751b98a2add474,

title = "Phenotype and Clinical Outcomes of Titin Cardiomyopathy",

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.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Cardiomyopathy, Dilated/diagnostic imaging, Child, Cohort Studies, Connectin/genetics, Female, Follow-Up Studies, Humans, Male, Middle Aged, Phenotype, Prospective Studies, Single-Blind Method, Treatment Outcome, Young Adult",

author = "Upasana Tayal and Simon Newsome and Rachel Buchan and Nicola Whiffin and Brian Halliday and Amrit Lota and Angharad Roberts and Baksi, {A John} and Inga Voges and Will Midwinter and Alijca Wilk and Risha Govind and Roddy Walsh and Piers Daubeney and Jarman, {Julian W E} and Resham Baruah and Michael Frenneaux and Barton, {Paul J} and Dudley Pennell and Ware, {James S} and Prasad, {Sanjay K} and Cook, {Stuart A}",

year = "2017",

month = oct,

day = "31",

doi = "10.1016/j.jacc.2017.08.063",

language = "English",

volume = "70",

pages = "2264--2274",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "18",

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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 2017, 'Phenotype and Clinical Outcomes of Titin Cardiomyopathy', Journal of the American College of Cardiology, vol. 70, no. 18, pp. 2264-2274. https://doi.org/10.1016/j.jacc.2017.08.063

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; Cook, Stuart A.

In: Journal of the American College of Cardiology, Vol. 70, No. 18, 31.10.2017, p. 2264-2274.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Phenotype and Clinical Outcomes of Titin Cardiomyopathy

AU - Tayal, Upasana

AU - Newsome, Simon

AU - Buchan, Rachel

AU - Whiffin, Nicola

AU - Halliday, Brian

AU - Lota, Amrit

AU - Roberts, Angharad

AU - Baksi, A John

AU - Voges, Inga

AU - Midwinter, Will

AU - Wilk, Alijca

AU - Govind, Risha

AU - Walsh, Roddy

AU - Daubeney, Piers

AU - Jarman, Julian W E

AU - Baruah, Resham

AU - Frenneaux, Michael

AU - Barton, Paul J

AU - Pennell, Dudley

AU - Ware, James S

AU - Prasad, Sanjay K

AU - Cook, Stuart A

PY - 2017/10/31

Y1 - 2017/10/31

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Cardiomyopathy, Dilated/diagnostic imaging

KW - Child

KW - Cohort Studies

KW - Connectin/genetics

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Prospective Studies

KW - Single-Blind Method

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1016/j.jacc.2017.08.063

DO - 10.1016/j.jacc.2017.08.063

M3 - Article

C2 - 29073955

VL - 70

SP - 2264

EP - 2274

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 18

ER -