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Original research article
Characterisation of circulating biomarkers before and after cardiac resynchronisation therapy and their role in predicting CRT response: the COVERT-HF study
  1. Christopher J McAloon1,2,
  2. Temo Barwari3,
  3. Jimiao Hu2,
  4. Thomas Hamborg2,
  5. Alan Nevill4,
  6. Samantha Hyndman1,
  7. Valerie Ansell1,
  8. Anntoniette Musa1,
  9. Julie Jones1,
  10. Julie Goodby1,
  11. Prithwish Banerjee1,2,5,
  12. Paul O’Hare1,2,
  13. Manuel Mayr3,
  14. Harpal Randeva1,2 and
  15. Faizel Osman1,2
  1. 1 Department of Cardiology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK
  2. 2 Warwick Medical School, University of Warwick , Coventry, UK
  3. 3 King's British Heart Foundation Centre, King's College London, London, UK
  4. 4 Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton, UK
  5. 5 Faculty of Health and Life Sciences, University of Coventry, Coventry, UK
  1. Correspondence to Professor Faizel Osman; faizel.osman{at}uhcw.nhs.uk

Abstract

Aims Cardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome.

Methods A prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6  weeks and 6  months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6  min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486).

Results A total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5  ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6  m, MLHFQ=46.4±21.3  and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3  and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response.

Conclusion No specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study.

Trial registration number NCT02541773.

  • heart failure
  • cardiac resynchronization therapy
  • non-response
  • vascular biomarkers
  • micro-RNAs

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All authors contributed to the planning, conduct and reporting of the work described in the article. FO is responsible for the overall content as guarantor.

  • Funding We would like to thank the Research, Development and Innovation department at University Hospitals Coventry and Warwickshire for their support with the study.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval South Birmingham Regional Ethics committee (13/WM/0355).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data statement No additional data are available.

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