HCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy
HCMR
1 other identifier
observational
2,750
6 countries
44
Brief Summary
Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease and the most frequent cause of sudden cardiac death (SCD) in the young. It is characterized by unexplained left ventricular hypertrophy (LVH), diffuse and patchy fibrosis, and myofibrillar disarray. While the majority of patients remain asymptomatic, prognosis is poor in a subset who present with SCD or progress to heart failure (HF). Current methods to predict risk of these adverse events and to target therapy are limited. Current medical therapy does not protect against SCD, nor does it prevent development of HF. Therefore, the identification of novel risk markers would help develop therapeutic targets aimed at altering the phenotypic expression to impact the natural history, especially SCD and HF. Cardiovascular magnetic resonance (CMR) is emerging as a powerful tool for diagnosis and risk stratification in HCM including assessment of LV mass and pattern of hypertrophy. Late gadolinium enhancement by CMR is a marker of focal myocardial fibrosis which is thought to underlie the arrhythmogenic substrate as well as promote development of HF. The investigators hypothesize that HCM patients with a higher primary outcome event rate can be identified by novel CMR findings. The majority of cases of HCM are autosomal dominant and about 60% are caused by mutations in genes encoding cardiac sarcomeric proteins. However, the relationship between genetic mutation, disease phenotype, and clinical outcomes remains poorly understood. The investigators hypothesize that HCM patients with sarcomeric HCM mutations will have a higher primary outcome event rate and more marked myocardial pathology on CMR than those without. Furthermore, there may be a link between sarcomeric mutations and fibrosis, as mutation carriers with overt HCM as well as those without hypertrophy have elevated markers of collagen turnover. The investigators therefore hypothesize that serum biomarkers of collagen metabolism in HCM will predict outcomes. Thus, the Specific Aim is to develop a predictive model of cardiovascular outcomes in HCM by: 1) using exploratory data mining methods to identify demographic, clinical, and novel CMR, genetic and biomarker variables associated with the outcomes and 2) develop a score from the predictive model that can be used to assess risk given a patient's combination of risk factors, thus establishing the evidence base to enable clinical trial design to reduce morbidity and mortality in HCM in a cost-effective manner.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Apr 2014
Longer than P75 for all trials
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 31, 2013
CompletedFirst Posted
Study publicly available on registry
August 5, 2013
CompletedStudy Start
First participant enrolled
April 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2025
CompletedDecember 13, 2024
December 1, 2024
11.2 years
July 31, 2013
December 12, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Cardiac death
Sudden cardiac death and heart failure death
5 years
Aborted sudden cardiac death
Includes appropriate ICD firing (sustained ventricular tachycardia, rate\>200bpm, or ventricular fibrillation)
5 years
Heart transplantation
5 years
left ventricular assist device placement
5 years
Secondary Outcomes (5)
All-cause mortality
5 years
Ventricular tachyarrhythmias
5 years
Hospitalization for heart failure
5 years
Atrial fibrillation
5 years
Stroke
5 years
Study Arms (1)
Hypertrophic cardiomyopathy
None - this is an observational study. Patients with hypertrophic cardiomyopathy will be observed for up to 5 years after index cardiac magnetic resonance imaging and blood draw for genetics and biomarkers
Interventions
None - this is an observational study
Eligibility Criteria
Hypertrophic cardiomyopathy clinics Cardiology clinics Genetic clinics Hypertrophic Cardiomyopathy Association
You may qualify if:
- Patients aged 18-65 with an established diagnosis of HCM defined as unexplained LVH defined as any segment ≥15mm thick, without a predisposing cause.
- Signed informed consent
You may not qualify if:
- Prior septal myectomy or alcohol septal ablation
- Prior myocardial infarction
- Incessant ventricular arrhythmias
- Inability to lie flat,
- Contraindication to CMR including pacemakers, defibrillators, intraocular metal, certain types of intracranial aneurysm clips, severe claustrophobia,
- Stage IV/V chronic kidney disease with glomerular filtration rate \<30 ml/min,
- Diabetes mellitus with end organ damage
- Pregnant female
- Inability to provide informed consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Virginialead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- Oxford University Hospitals NHS Trustcollaborator
Study Sites (44)
Yale University
New Haven, Connecticut, 06520, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Johns Hopkins University
Baltimore, Maryland, 21287-0409, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University of Michigan Health System
Ann Arbor, Michigan, 48109-56444, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
NYU Medical Center
New York, New York, 10016, United States
St. Luke's Roosevelt University Hospital of Columbia University
New York, New York, 10019, United States
Weill Cornell - New York Presbyterian
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
Philadelphia, Pennsylvania, 19104, United States
Methodist DeBakey Cardiology Associates
Houston, Texas, 77030, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
University of Calgary
Calgary, Alberta, T2N 2T9, Canada
Toronto General Research Institute (TGRI), Toronto General Hospital
Toronto, Ontario, M5G 2C4, Canada
Montreal Heart Institute (Institut de Cardiologie de Montreal)
Montreal, Quebec, H1T 1C8, Canada
McGill University Health Center
Montreal, Quebec, QC H3G 1B3, Canada
Quebec Heart Insititute
Québec, G1V 4G5, Canada
Charite - Universitatsmedizin Berlin
Berlin, 13125, Germany
Universitats Klinikum Heidelberg
Heidelberg, D-69120, Germany
Robert-Bosch-Krankenhaus GmbH
Stuttgart, 70376, Germany
Universita di Bologna
Bologna, 40138, Italy
Careggi University Hospital
Florence, 50134, Italy
San Raffaele University Hospital
Milan, 20132, Italy
Sapienza University
Rome, 00185, Italy
VU University Medical Center
Amsterdam, 1081 HV, Netherlands
Erasmus MC
Rotterdam, 3015 CE, Netherlands
University of Aberdeen, School of Medicine and Dentistry
Aberdeen, Scotland, AB25 2ZD, United Kingdom
University of Glasgow (BHF Glasgow Cardiovascular Research Centre)
Glasgow, Scotland, G12 8TA, United Kingdom
University Hospitals Birmingham (Queen Elizabeth Hospital)
Birmingham, B15 2TH, United Kingdom
Bristol Heart Institute
Bristol, BS2 8HW, United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SB, United Kingdom
University of Leeds
Leeds, LS2 9JT, United Kingdom
Glenfield Hospital Leicester
Leicester, LE3 9QP, United Kingdom
London Chest Hospital
London, E2 9JX, United Kingdom
King's College London (St. Thomas' Hospital)
London, SE1 7EH, United Kingdom
St. George's Healthcare NHS Trust
London, SW17 0RE, United Kingdom
Royal Brompton Hospital
London, SW3 6NP, United Kingdom
Oxford University
Oxford, OX3 9DU, United Kingdom
University of Southhamptom
Southampton, SO16 6YD, United Kingdom
Related Publications (2)
Antiochos P, Ge Y, Jerosch-Herold M, David LP, Heydari B, Kolm P, Kim DY, van der Geest RJ, Watkins H, Desai MY, Ho CY, Dolman SF, Desvigne-Nickens P, Maron MS, Schulz-Menger J, Piechnik SK, Appelbaum E, Weintraub WS, Neubauer S, Kramer CM, Kwong RY. Myocardial Entropy and Risk Predictors in Hypertrophic Cardiomyopathy: An Analysis From the NHLBI HCM Registry. Circ Cardiovasc Imaging. 2025 Nov;18(11):e018031. doi: 10.1161/CIRCIMAGING.125.018031. Epub 2025 Sep 24.
PMID: 40988612DERIVEDKramer CM, Appelbaum E, Desai MY, Desvigne-Nickens P, DiMarco JP, Friedrich MG, Geller N, Heckler S, Ho CY, Jerosch-Herold M, Ivey EA, Keleti J, Kim DY, Kolm P, Kwong RY, Maron MS, Schulz-Menger J, Piechnik S, Watkins H, Weintraub WS, Wu P, Neubauer S. Hypertrophic Cardiomyopathy Registry: The rationale and design of an international, observational study of hypertrophic cardiomyopathy. Am Heart J. 2015 Aug;170(2):223-30. doi: 10.1016/j.ahj.2015.05.013. Epub 2015 May 22.
PMID: 26299218DERIVED
Biospecimen
Blood samples for genetic analysis and biomarkers will be obtained and retained.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher M Kramer, MD
University of Virginia Health System
- PRINCIPAL INVESTIGATOR
Stefan Neubauer, MD
University of Oxford
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Time Perspective
- PROSPECTIVE
- Target Duration
- 5 Years
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Ruth C. Heede Professor of Cardiology, Professor of Radiology
Study Record Dates
First Submitted
July 31, 2013
First Posted
August 5, 2013
Study Start
April 1, 2014
Primary Completion
June 1, 2025
Study Completion
June 1, 2025
Last Updated
December 13, 2024
Record last verified: 2024-12