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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