Large Registries

1385422 - The Hypertrophic Cardiomyopathy Registry (HCMR) study - Update on event accrual and ancillary studies

Friday, January 27, 2023

2:40 PM – 2:55 PM

Location: Silver Pearl 3

Presenting Author(s)

Stefan Neubauer, MD, FSCMR

Professor of Cardiovascular Medicine
University of Oxford
Oxford, England, United Kingdom

Primary Author(s)

Stefan Neubauer, MD, FSCMR

Professor of Cardiovascular Medicine
University of Oxford
Oxford, England, United Kingdom

Co-Author(s)

LA

Lisa Anderson

Cardiology Consultant
St. Georges, UK, United Kingdom
Colin Berry, MD, PhD

Professor of Cardiology
University of Glasgow
Glasgow, Scotland, United Kingdom
WB

William Bradlow

Cardiology Consultant
Birmingham University Hospitals, United Kingdom
Chiara Bucciarelli-Ducci, MD, PhD

Consultant Cardiologist
Royal Brompton & Harefield NHS Foundation Trust
London , England, United Kingdom
Amedeo Chiribiri, MD PhD FHEA FSCMR

Professor of Cardiovascular Imaging; Consultant Cardiologist
King's College London
London, England, United Kingdom
Andrew M. Crean, MD, MPH, FSCMR

Cardiology Consultant
Liverpool Heart and Chest Hospital
Ottawa, Ontario, United Kingdom
Dana Dawson, MD, PhD

Professor
University of Aberdeen
Aberdeen, Scotland, United Kingdom
Milind Desai, MD

Professor of Cardiovascular Medicine
Cleveland Clinic
Cleveland, Ohio, United States
AF

Andrew Flett, MD

Consultant Cardiologist
University Hospital Southampton
Southampton, England, United Kingdom
Matthias G. Friedrich, MD, FSCMR

Senior Author
Research Institute of the McGill University Health Center
Montreal, Quebec, Canada
SH

Stephen Heitner, MD

Vice President, Clinical Research & Therapeutic Area Lead, Cardiovascular
Cytokinetics
Oregon Health Sciences University
Portland, OR, United States
DJ

Daniel Jacoby, MD

Senior Medical Director
Cytokinetics
Madison, Connecticut, United States
HK

Han Kim, MD

Associate Professor of Medicine
Duke University
Durham, North Carolina, United States
Raymond Y. Kwong, MD, MPH, FSCMR

Director of Cardiac Magnetic Resonance Imaging
Brigham and Women's Hospital
Boston, Massachusetts, United States
MM

Masliza Mahmod, MD, PhD

Associate Professor
Oxford Centre for Magnetic Resonance Research, England, United Kingdom
HM

Heiko Mahrholdt, MD

Leitender Arzt für Bildgebung in der Kardiologie
Robert-Bosch-Krankenhaus Stuttgart, Germany
MM

Martin Maron, MD

Director, Hypertrophic Cardiomyopathy Center
Tufts Medical Center
Boston, Massachusetts, United States
Gerry P. McCann, MD

NIHR research professor
University of Leicester
Leicester, England, United Kingdom
MM

Michelle Michels, MD, PhD

Cardiologist
Erasmus MC, Netherlands
SM

Saidi A. Mohiddin, MD, PhD

Consultant Cardiologist in Inherited and Acquired Heart Muscle Disease and in CMR
Barts Heart Centre at St Bartholomew's Hospital, England, United Kingdom
FM

F. Pierre Mongeon, MD

Chief, Division of non-invasive cardiology
Montreal Heart Institute, Quebec, Canada
DN

David E. Newby, MD, PhD, BA

Professor
University of Edinburgh, Scotland, United Kingdom
Sven Plein, MD, PhD

Professor
University of Leeds
Leeds, England, United Kingdom
SP

Sanjay Prasad, MD, PhD, FSCMR

Professor
Royal Brompton Hospital and Imperial College London, London, England, United Kingdom
Michael Salerno, MD, PhD, MSc

Professor
Stanford University, California, United States
Jeanette Schulz-Menger, MD

Professor
Charité – Universitätsmedizin Berlin, ECRC, MDC, Helios Klinikum Berlin Buch, DZHK, Berlin, Germany
Berlin, Berlin, Germany
Av

Albert C. van Rossum, MD, PhD

MD
Amsterdam University Medical Centers- Location VUmc, Netherlands
HW

Hugh Watkins, MD, PhD

Professor of Cardiovascular Medicine
University of Oxford, England, United Kingdom
Jonathan W. Weinsaft, MD

Professor of Medicine
Weill Cornell Medical College
New York, New York, United States
WW

William Weintraub, MD

Director, Population Health Research
Medstar Georgetown University Hospital, District of Columbia, United States
James White, MD

Professor of Cardiology
Stephenson Cardiac Imaging Centre
Calgary, Alberta, Canada
TH

The HCMR Investigators

Group authorship
Multiple, United Kingdom
Christopher M. Kramer, MD

Chief
University of Virginia Health System
Charlottesville, Virginia, United States

Disclosure(s):

Stefan Neubauer, MD, FSCMR: No relevant disclosure to display

Chiara Bucciarelli-Ducci, MD, PhD: No relevant disclosure to display

Amedeo Chiribiri, MD PhD FHEA FSCMR: No relevant disclosure to display

Han Kim, MD: No financial relationships to disclose

Sven Plein, MD, PhD: No financial relationships to disclose

Michael Salerno, MD, PhD, MSc: No relevant disclosure to display

Jeanette Schulz-Menger, MD: No relevant disclosure to display

Jonathan W. Weinsaft, MD: No relevant disclosure to display

Background: Hypertrophic Cardiomyopathy (HCM) is the most common inherited cardiac condition and the #1 cause of sudden death in the young. Current HCM risk prediction algorithms are imperfect, with underestimation leading to avoidable deaths and overestimation to unnecessary ICD implantation. Current HCM guidelines assign either no role (European) or a secondary role (American) to cardiac magnetic resonance (CMR) in HCM risk prediction. The Hypertrophic Cardiomyopathy Registry (HCMR – www.hcmregistry.org), a prospective registry funded by the NHLBI, is asking whether CMR measures add independent predictive utility in HCM.

Methods:

2,750 HCM patients were recruited in 44 sites across Europe and North America between April 2014 and April 2017. The primary goal is to improve risk prediction for important adverse clinical outcomes in HCM by integrating CMR imaging, biomarker, and genetic data with standard clinical and echocardiographic findings. Primary outcomes are cardiac death (SCD and HF death), stroke death, aborted SCD (incl. ICD discharge) and need for heart transplantation or LVAD implantation; secondary outcomes are all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization, atrial fibrillation and non-fatal stroke. The CMR protocol included cine imaging, LGE, and pre-and post-contrast T1 mapping.

Results:

As of 11/2022, mean patient follow up is 5.72 years (13,741 patient years). Outcomes are shown in Table 1. With 72 primary outcomes currently, we expect to reach 100, preferred for risk prediction modelling, within 12-24 months. As expected, secondary outcomes, primarily AF requiring treatment (n=234), are much more frequent. Baseline data show that patients fall into two groups: Sarcomere mutation +, more likely showing reverse septal curvature morphology, more LGE and interstitial fibrosis and less LVOT obstruction; and sarcomere mutation -, more likely with isolated basal septal morphology, less LGE and interstitial fibrosis and more LVOT obstruction.

11 manuscripts have been published to date (details given in Table 2). Ancillary study highlights include, among others: Common variants and modifiable risk factors have clinically actionable roles in HCM (Nature Genetics 2021); Virtual native enhancement detects patchy fibrosis in HCM similar to LGE without need for Gadolinium Contrast (Circulation 2021); Predictors of atrial fibrillation endpoints (JACC Clin EP 2021); 3D strain analysis in HCM (JACC CV Imaging in press).

Proposals for ancillary studies can be submitted to the ancillary studies committee for consideration. A follow-up grant to fund a repeat CMR is being prepared, to assess phenotype change over time.

Conclusion:

HCMR is the largest HCM registry to date that includes detailed clinical, genetic, biomarker and CMR data. It is expected to guide risk stratification once sufficient primary outcomes have accrued. In addition, it provides a unique resource to probe the pathophysiology of HCM and identify new therapeutic targets.