ClinicalTrials.gov
ClinicalTrials.gov Menu

HCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy (HCMR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01915615
Recruitment Status : Active, not recruiting
First Posted : August 5, 2013
Last Update Posted : October 11, 2018
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Oxford University Hospitals NHS Trust
Information provided by (Responsible Party):
Christopher Kramer, University of Virginia

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.

Condition or disease Intervention/treatment
Hypertrophic Cardiomyopathy Other: None - this is an observational study

  Show Detailed Description

Study Type : Observational [Patient Registry]
Estimated Enrollment : 2750 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: HCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy
Study Start Date : April 2014
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022


Group/Cohort Intervention/treatment
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

Other: None - this is an observational study
None - this is an observational study




Primary Outcome Measures :
  1. Cardiac death [ Time Frame: 5 years ]
    Sudden cardiac death and heart failure death

  2. Aborted sudden cardiac death [ Time Frame: 5 years ]
    Includes appropriate ICD firing (sustained ventricular tachycardia, rate>200bpm, or ventricular fibrillation)

  3. Heart transplantation [ Time Frame: 5 years ]
  4. left ventricular assist device placement [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: 5 years ]
  2. Ventricular tachyarrhythmias [ Time Frame: 5 years ]
    Ventricular fibrillation or sustained ventricular tachycardia

  3. Hospitalization for heart failure [ Time Frame: 5 years ]
  4. Atrial fibrillation [ Time Frame: 5 years ]
  5. Stroke [ Time Frame: 5 years ]

Biospecimen Retention:   Samples With DNA
Blood samples for genetic analysis and biomarkers will be obtained and retained.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Hypertrophic cardiomyopathy clinics Cardiology clinics Genetic clinics Hypertrophic Cardiomyopathy Association
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01915615


  Hide Study Locations
Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-0409
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109-56444
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
NYU Medical Center
New York, New York, United States, 10016
St. Luke's Roosevelt University Hospital of Columbia University
New York, New York, United States, 10019
Weill Cornell - New York Presbyterian
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Methodist DeBakey Cardiology Associates
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 2T9
Canada, Ontario
Toronto General Research Institute (TGRI), Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
Montreal Heart Institute (Institut de Cardiologie de Montreal)
Montreal, Quebec, Canada, H1T 1C8
McGill University Health Center
Montreal, Quebec, Canada, QC H3G 1B3
Canada
Quebec Heart Insititute
Quebec, Canada, G1V 4G5
Germany
Charite - Universitatsmedizin Berlin
Berlin, Germany, 13125
Universitats Klinikum Heidelberg
Heidelberg, Germany, D-69120
Robert-Bosch-Krankenhaus GmbH
Stuttgart, Germany, 70376
Italy
Universita di Bologna
Bologna, Italy, 40138
Careggi University Hospital
Florence, Italy, 50134
San Raffaele University Hospital
Milan, Italy, 20132
Sapienza University
Rome, Italy, 00185
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Erasmus MC
Rotterdam, Netherlands, 3015 CE
United Kingdom
University of Aberdeen, School of Medicine and Dentistry
Aberdeen, Scotland, United Kingdom, AB25 2ZD
University of Glasgow (BHF Glasgow Cardiovascular Research Centre)
Glasgow, Scotland, United Kingdom, G12 8TA
University Hospitals Birmingham (Queen Elizabeth Hospital)
Birmingham, United Kingdom, B15 2TH
Bristol Heart Institute
Bristol, United Kingdom, BS2 8HW
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom, EH16 4SB
University of Leeds
Leeds, United Kingdom, LS2 9JT
Glenfield Hospital Leicester
Leicester, United Kingdom, LE3 9QP
London Chest Hospital
London, United Kingdom, E2 9JX
King's College London (St. Thomas' Hospital)
London, United Kingdom, SE1 7EH
St. George's Healthcare NHS Trust
London, United Kingdom, SW17 0RE
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Oxford University
Oxford, United Kingdom, OX3 9DU
University of Southhamptom
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
University of Virginia
National Heart, Lung, and Blood Institute (NHLBI)
Oxford University Hospitals NHS Trust
Investigators
Principal Investigator: Christopher M Kramer, MD University of Virginia Health System
Principal Investigator: Stefan Neubauer, MD University of Oxford

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Christopher Kramer, Ruth C. Heede Professor of Cardiology, Professor of Radiology, University of Virginia
ClinicalTrials.gov Identifier: NCT01915615     History of Changes
Other Study ID Numbers: U01HL117006-01A1 ( U.S. NIH Grant/Contract )
U01HL117006-01A1 ( U.S. NIH Grant/Contract )
First Posted: August 5, 2013    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018

Keywords provided by Christopher Kramer, University of Virginia:
Hypertrophic cardiomyopathy
Cardiac magnetic resonance imaging
CMR
Genetics
Biomarkers
Late gadolinium enhancement
T1 mapping

Additional relevant MeSH terms:
Cardiomyopathies
Hypertrophy
Cardiomyopathy, Hypertrophic
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases