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Heart failure and cardiomyopathies
Original research article
Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy
  1. Jennifer E Ho1,
  2. Ling Shi2,
  3. Sharlene M Day3,
  4. Steven D Colan4,
  5. Mark W Russell3,
  6. Jeffrey A Towbin5,
  7. Mark V Sherrid6,
  8. Charles E Canter7,
  9. John Lynn Jefferies5,
  10. Anne Murphy8,
  11. Matthew Taylor9,
  12. Luisa Mestroni9,
  13. Allison L Cirino10,
  14. Lynn A Sleeper2,
  15. Peter Jarolim11,
  16. Begoña Lopez12,
  17. Arantxa Gonzalez12,
  18. Javier Diez12,13,
  19. E John Orav14 and
  20. Carolyn Y Ho1
  21. for the HCMNet Investigators
  1. 1Division of Cardiology, Department of Medicine, Cardiovascular Research Center, Massachusetts General Hospital, Ann Arbor, Michigan, USA
  2. 2New England Research Institutes, Watertown, Massachusetts, USA
  3. 3Departments of Internal Medicine and Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
  4. 4Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts, USA
  5. 5The Heart Institute and Pediatric Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
  6. 6Division of Cardiology, Department of Medicine, New York University Langone Medical Center, New York, New York, USA
  7. 7Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, USA
  8. 8Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  9. 9Department of Medicine, University of Colorado Denver CU-Cardiovascular Institute, Aurora, Colorado, USA
  10. 10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  11. 11Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
  12. 12Program of Cardiovascular Diseases, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
  13. 13Department for Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Pamplona, Spain
  14. 14Department of Biostatistics, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Jennifer E Ho; jho1{at}partners.org

Abstract

Objective Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH−) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH− individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM.

Methods We studied 76 individuals with overt HCM, 50 G+/LVH− individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured.

Results Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH− subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH− individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function.

Conclusion Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH− individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.

  • hypertrophic cardiomyopathy
  • echocardiography
  • biomarker

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 and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2017-000615

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    Footnotes

    • Contributors All authors have contributed to this investigation as follows: study concept and proposal (JEH, EJO, CYH), data acquisition (SMD, SDC, MWR, JAT, MVS, CEC, JLJ, AM, MT, LM, ALC, LAS, PJ, BL, AG, JD, CYH), data analysis (JEH, LS, EJO, CYH), drafting of manuscript (JEH, LS, CYH) and critical revisions of the manuscript (all authors).

    • Funding This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health (K23-HL116780 to JEH, 1P20HL101408 to CYH).

    • Competing interests PJ has received research support from Abbott Laboratories, Amgen, AstraZeneca LP, Beckman Coulter, Daiichi Sankyo, GlaxoSmithKline, Merck & Co, Roche Diagnostics Corporation, Takeda Global Research and Development Center, and Waters Technologies Corporation.

    • Ethics approval The study protocol was approved by the appropriate individual institutional review boards.

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

    • Data sharing statement There are no additional data available for this paper.