Distinct Subgroups in Hypertrophic Cardiomyopathy in the NHLBI HCM Registry

Stefan Neubauer, Paul Kolm, Carolyn Y. Ho, Raymond Y. Kwong, Milind Y. Desai, Sarahfaye F. Dolman, Evan Appelbaum, Patrice Desvigne-Nickens, John P. DiMarco, Matthias G. Friedrich, Nancy Geller, Andrew R. Harper, Petr Jarolim, Michael Jerosch-Herold, Dong-Yun Kim, Martin S. Maron, Jeanette Schulz-Menger, Stefan K. Piechnik, Kate Thomson, Cheng ZhangHugh Watkins, William S. Weintraub, Christopher M. Kramer*, HCMR Investigators

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)

Abstract

Background
The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute–funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.

Objectives
The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.

Methods
Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.

Results
A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation–positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.

Conclusions
The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers.
Original languageEnglish
Pages (from-to)2333-2345
Number of pages13
JournalJournal of the American College of Cardiology
Volume74
Issue number19
Early online date4 Nov 2019
DOIs
Publication statusPublished - 12 Nov 2019

Bibliographical note

Acknowledgments
The authors acknowledge the technical assistance of Michael Bowman, PhD, Shapour Jalilzadeh, PhD, and image analysis skills of Kathleen Cheng, BA, Sebastian Estrada, BA, Hannah King, BA, and Evan Yang.

Funding by the National Heart, Lung, and Blood Institute grant U01HL117006-01A1 (to Drs. Kramer and Neubauer) and the Oxford NIHR Biomedical Research Centre (to Drs. Neubauer and Watkins). Dr. Neubauer has been a consultant for Pfizer and Cytokinetics; and has received research grants from Boehringer Ingelheim. Dr. Ho has been a consultant for and received research support from MyoKardia. Dr. Kwong has received research support from Siemens Healthineers, Bayer AG, and MyoKardia. Dr. DiMarco has been a consultant to Novartis, Celgene, and Daiichi-Sankyo. Dr. Friedrich has been a board member, shareholder, and consultant for Circle Cardiovascular Imaging. Dr. Jarolim has received research support from Abbott Laboratories, AstraZeneca, LP, Daiichi-Sankyo, GlaxoSmithKline, Merck and Co., Roche Diagnostics Corporation, Takeda Global Research and Development Center, and Waters Technologies Corporation; and has received consulting fees from Roche Diagnostics Corporation. Dr. Maron has been a consultant to iRhythm, Celltrion, and Cytokinetics; and has received research support from iRhythm. Dr. Schulz-Menger has been a consultant for Bayer; and has received research grants from Bayer, Siemens Healthineers, and Circle Cardiovascular Imaging. Dr. Piechnik has patent authorship rights for a U.S. patent held by Siemens Healthcare and managed by Oxford University Innovations. Dr. Watkins has been a consultant for Cytokinetics. Dr. Weintraub has been a consultant for Amarin, Janssen, AstraZeneca, and SC Pharma; and has received research grants from Amarin. Dr. Kramer has been a consultant for Cytokinetics; and has received research grants from Biotelemetry and MyoKardia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper.

Keywords

  • biomarkers
  • cardiac magnetic resonance
  • fibrosis
  • hypertrophic cardiomyopathy
  • late gadolinium enhancement

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