Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers)

Cardiac Biomarkers in Pediatric Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle. It is rare, but it can be serious. Cardiomyopathy in children can result in death, disability, heart transplantation or serious heart rhythm disorders. Natural substances in the blood called cardiac biomarkers can be measured in the laboratory and could be a less invasive way (compared to echocardiograms or MRIs) to detect heart dysfunction in children with cardiomyopathy. Little is known about how useful and valid cardiac biomarkers are in the diagnosis and determination of the symptoms in children with cardiomyopathy. The long-term goal of this project is to study how helpful measuring cardiac biomarkers in children with cardiomyopathy is to their doctors in managing the care of these patients as well as improving their overall health. Measures of these cardiac biomarkers could help doctors in determining how best to care for a child with cardiomyopathy, including when to consider heart transplantation as a treatment option.

Study Overview

• Status: Unknown
• Conditions: Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy

Detailed Description

Pediatric cardiomyopathy is a heterogeneous disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. Highly sensitive and specific cardiac biomarkers or panels of biomarkers, representing different pathologic mechanisms or pathways, are the least invasive (a particularly important consideration in children) and most-cost-effective approach to the early detection of cardiac dysfunction. The long-term goal of this project is to identify such biomarkers in children with cardiomyopathy. These findings could represent a major advance in determining the most appropriate evidence-based clinical care for these children, including when to consider heart transplantation.

The specific aims of this study are:

1. To determine the ability of established and novel cardiac biomarkers to predict short- and long-term outcomes in children with newly diagnosed (incident) dilated cardiomyopathy (DCM)
2. To assess the clinical utility of cardiac biomarkers of collagen metabolism in determining the presence of myocardial fibrosis, as established by cardiac MRI (cMRI), and left ventricular (LV) diastolic dysfunction, as established by echocardiography in both newly diagnosed and existing cases of idiopathic and familial hypertrophic cardiomyopathy (HCM) in children.
3. To determine whether longitudinal changes in cardiac biomarkers are associated with worsening heart failure (HF) class in clinically stable children with dilated or hypertrophic cardiomyopathy. This study will determine the importance of serological biomarkers, in conjunction with cardiac imaging, in the early identification of heart disease before cardiac remodeling and functional impairment have become irreversible in a pediatric population.

This is a 5-year prospective study of up to 480 children with either primary dilated or hypertrophic cardiomyopathy. The study will have three components: 1) clinical data collection by chart review, 2) biospecimen collection and testing, and 3) centralized review and measurement of echocardiograms and cMRIs.

• Study Type: Observational
• Enrollment (Actual): 288

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital, University of Alberta
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore
    • New York, New York, United States, 10032
      • Children's Hospital of New York, Columbia Presbyterian Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UMPC
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 20 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric cases of dilated and hypertrophic cardiomyopathy will be recruited at 11 pediatric cardiology centers in the US and Canada.

Description

Inclusion Criteria:

• Patient is alive and has not received a transplant prior to enrollment in the study.
• Under age 21 years at age of enrollment
• For Group 1 (incident DCM), a case of DCM presenting to a study site within 2 years of the original cardiomyopathy diagnosis
• Group 2 (incident/recent HCM), a new or existing diagnosis of idiopathic or familial HCM with a cMRI within 12 months of diagnosis
• Group 3 (prevalent HCM or DCM), any child with a diagnosis of DCM or idiopathic, familial, or HCM due to a known disease-causing mutation who has survived transplant-free at least 12 months from the date of original cardiomyopathy diagnosis
• For all 3 groups, diagnosis of cardiomyopathy must be confirmed by Echocardiographic or cMRI criteria

Exclusion Criteria:

A patient is not eligible for enrollment if one or more of the following conditions are met at the time of presentation with cardiomyopathy:

• Any cardiomyopathy diagnosis other than DCM or idiopathic HCM, familial HCM or HCM due to a known disease-causing gene
• Endocrine disease known to cause heart muscle disease (including infants of diabetic mothers)
• History of rheumatic fever
• Toxic exposures known to cause heart muscle disease (anthracyclines, mediastinal radiation, iron overload or heavy metal exposure)
• HIV infection or born to an HIV positive mother
• Kawasaki disease
• Congenital heart defects unassociated with malformation syndromes (e.g., valvular heart disease or congenital coronary artery malformations)
• Immunologic disease
• Invasive cardiothoracic procedures or major surgery during the preceding month, except those specifically related to cardiomyopathy including left ventricular assist device (LVAD), extracorporeal membrane oxygenator (ECMO), and automatic implantable cardioverter defibrillator (AICD) placement
• Uremia, active or chronic
• Abnormal ventricular size or function that can be attributed to intense physical training or chronic anemia
• Chronic arrhythmia, unless there are studies documenting inclusion criteria prior to the onset of arrhythmia (except a patient with chronic arrhythmia, subsequently ablated, whose cardiomyopathy persists after two months is not to be excluded)
• Malignancy
• Systemic Hypertension
• Pulmonary parenchymal or vascular disease (e.g., cystic fibrosis, cor pulmonale, or pulmonary hypertension)
• Ischemic coronary vascular disease
• Association with drugs (e.g., growth hormone, corticosteroids, cocaine) or other diseases known to cause hypertrophy

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Incident DCM; A case of dilated cardiomyopathy that presents to the study site for the first time.
Incident/Recent HCM; A new or existing diagnosis of idiopathic or familial hypertrophic cardiomyopathy, diagnosed within the past 2 months and with a cMRI within 2 months of diagnosis.
Prevalent HCM or DCM; Any child with a diagnosis of dilated cardiomyopathy or idiopathic or familial hypertrophic cardiomyopathy who has survived transplant-free at least 24 months from the date of cardiomyopathy diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to Death	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to heart transplant	2 years
Worsening heart failure	2 years

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: Children's Hospital of Philadelphia; Washington University School of Medicine; Columbia University; University of Pittsburgh; Children's Hospital Colorado; Boston Children's Hospital; Montefiore Medical Center; Ann & Robert H Lurie Children's Hospital of Chicago; HealthCore-NERI; Children's Hospital Medical Center, Cincinnati; Primary Children's Hospital; Stollery Children's Hospital; Monroe Carell Jr. Children's Hospital at Vanderbilt; Le Bonheur Children's Hospital

Publications and helpful links

General Publications

• Everitt MD, Wilkinson JD, Shi L, Towbin JA, Colan SD, Kantor PF, Canter CE, Webber SA, Hsu DT, Pahl E, Addonizio LJ, Dodd DA, Jefferies JL, Rossano JW, Feingold B, Ware SM, Lee TM, Godown J, Simpson KE, Sleeper LA, Czachor JD, Razoky H, Hill A, Westphal J, Molina KM, Lipshultz SE; Pediatric Cardiomyopathy Registry Investigators. Cardiac Biomarkers in Pediatric Cardiomyopathy: Study Design and Recruitment Results from the Pediatric Cardiomyopathy Registry. Prog Pediatr Cardiol. 2019 Jun;53:1-10. doi: 10.1016/j.ppedcard.2019.02.004. Epub 2019 Mar 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2013
• Primary Completion (ACTUAL): January 1, 2017
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: June 6, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (ESTIMATE): June 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 14, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Aortic Valve Disease; Heart Valve Diseases; Cardiomegaly; Laminopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 1R01HL109090-01A1 (NIH)