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

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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 languageEnglish
Pages (from-to)2264-2274
Number of pages11
JournalJournal of the American College of Cardiology
Volume70
Issue number18
Early online date23 Oct 2017
DOIs
Publication statusPublished - 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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