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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01915615
First Posted: August 5, 2013
Last Update Posted: April 12, 2017
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.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Oxford University Hospitals NHS Trust
Information provided by (Responsible Party):
Christopher M. Kramer MD, University of Virginia
  Purpose
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 Intervention
Hypertrophic Cardiomyopathy Other: None - this is an observational study

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: HCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by Christopher M. Kramer MD, University of Virginia:

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

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

  • Heart transplantation [ Time Frame: 5 years ]
  • left ventricular assist device placement [ Time Frame: 5 years ]

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

  • Hospitalization for heart failure [ Time Frame: 5 years ]
  • Atrial fibrillation [ Time Frame: 5 years ]
  • Stroke [ Time Frame: 5 years ]

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

Estimated Enrollment: 2750
Study Start Date: April 2014
Estimated Study Completion Date: April 2022
Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

  Show Detailed Description

  Eligibility

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)
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
  Contacts and Locations
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


  Show 44 Study Locations
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
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Christopher M. Kramer MD, 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 )
First Submitted: July 31, 2013
First Posted: August 5, 2013
Last Update Posted: April 12, 2017
Last Verified: April 2017

Keywords provided by Christopher M. Kramer MD, 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


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