Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers)

Summary: 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.

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.

Eligibility: 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

Relevance to patient case: not relevant