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HCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy

This study is currently recruiting participants.
Verified April 2014 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Virginia
ClinicalTrials.gov Identifier:
NCT01915615
First received: July 31, 2013
Last updated: April 8, 2014
Last verified: April 2014
  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 University of Virginia:

Primary Outcome Measures:
  • Cardiac death [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Sudden cardiac death and heart failure death

  • Aborted sudden cardiac death [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Includes appropriate ICD firing (sustained ventricular tachycardia, rate>200bpm, or ventricular fibrillation)

  • Heart transplantation [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • left ventricular assist device placement [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All-cause mortality [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Ventricular tachyarrhythmias [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Ventricular fibrillation or sustained ventricular tachycardia

  • Hospitalization for heart failure [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Atrial fibrillation [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Stroke [ Time Frame: 5 years ] [ Designated as safety issue: No ]

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: November 2018
Estimated Primary Completion Date: November 2018 (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
Other Name: None - this is an observational study

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01915615

Contacts
Contact: Christopher M Kramer, MD 4342430736 ckramer@virginia.edu
Contact: Stefan Neubauer, MD 44 1865 221088 stefan.neubauer@cardiov.ox.ac.uk

  Show 38 Study Locations
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Christopher M Kramer, MD University of Virginia Health System
Principal Investigator: Stefan Neubauer, MD Oxford University
  More Information

No publications provided

Responsible Party: University of Virginia
ClinicalTrials.gov Identifier: NCT01915615     History of Changes
Other Study ID Numbers: U01HL117006-01A1, U01HL117006-01A1
Study First Received: July 31, 2013
Last Updated: April 8, 2014
Health Authority: United States: Data and Safety and Monitoring Board

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

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

ClinicalTrials.gov processed this record on April 16, 2014