Author + information
- Received June 17, 2017
- Revision received August 4, 2017
- Accepted August 30, 2017
- Published online October 23, 2017.
- Upasana Tayal, BMBCha,b,
- Simon Newsome, MScc,
- Rachel Buchan, MSca,b,
- Nicola Whiffin, PhDa,b,d,
- Brian Halliday, MBChB, MRCPa,b,
- Amrit Lota, BMBCha,b,
- Angharad Roberts, MBBS, PhDb,
- A. John Baksi, PhDa,b,
- Inga Voges, MDb,
- Will Midwinter, BScb,
- Alijca Wilk, BScb,
- Risha Govind, MScb,
- Roddy Walsh, MSca,b,
- Piers Daubeney, DMb,
- Julian W.E. Jarman, MBBS, MD(Res)b,
- Resham Baruah, MBBS, BSc, PhDb,
- Michael Frenneaux, MDa,b,
- Paul J. Barton, PhDa,b,
- Dudley Pennell, MDb,
- James S. Ware, PhDa,b,d,
- Sanjay K. Prasad, MDa,b and
- Stuart A. Cook, PhDa,b,d,e,f,∗ ()
- aNational Heart Lung Institute, Imperial College London, London, United Kingdom
- bCardiovascular Research Centre, Royal Brompton Hospital, London, United Kingdom
- cDepartment of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
- dMedical Research Council London Institute of Medical Sciences, Imperial College London, London, United Kingdom
- eNational Heart Centre, Singapore
- fDuke-NUS Medical School, Singapore
- ↵∗Address for correspondence:
Dr. Stuart A. Cook, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609.
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.
This project was supported by the Medical Research Council UK, the Alexander Janson’s Foundation, Rosetrees Trust, the Wellcome Trust, the National Institute for Health Research Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, the British Heart Foundation, and the Health Innovation Challenge Fund (HICF-R6-373) funding from the Wellcome Trust and Department of Health, United Kingdom. This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The views expressed in this work are those of the authors and not necessarily those of the Department of Health or Wellcome Trust. Dr. Pennell has received research funding from Siemens; has served as a consultant to Bayer; and is a director of and shareholder in CVIS. Dr. Prasad has received honoraria for talks from Bayer Schering. Dr. Cook has served as a consultant for Illumina; and is a shareholder in Enleofen Bio. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Prasad and Cook contributed equally to this work and are joint senior authors.
- Received June 17, 2017.
- Revision received August 4, 2017.
- Accepted August 30, 2017.
- 2017 The Authors