Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)

Learn more about:
Related Clinical Trial
Evaluation of the CIRCULATE Catheter for Transcoronary Administration of Pharmacologic and Cell-based Agents Intraventricular Stasis In Cardiovascular Disease Dilated Cardiomyopathy-Cardiac Magnetic Resonance (DCM-CMR) Ancillary Study A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease CorCinch-HF Repair System in Patients Who Present With Symptomatic Non-Ischemic or Ischemic Dilated Cardiomyopathy Early Administration of Ivabradine in Children With Heart Failure Metabolomics and Microbiomics in Cardiovascular Diseases Mannheim TORCH-Plus is a Registry for Patients With Cardiomyopathies and Serves as Source for Cardiovascular Research Studies Risk Stratification in Children and Adolescents With Primary Cardiomyopathy Pediatric Cardiomyopathy Mutation Analysis German Centre for Cardiovascular Research Cardiomyopathy Register Hemodynamic Evaluation of Preload Responsiveness in Children by Using PiCCO An Integrative-“Omics” Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China Metabolomic Study of All-age Cardiomyopathy Coronary Artery Disease and Coronary Microvascular Disease in Cardiomyopathies Registry The Genetics of Cardiomyopathy and Heart Failure Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in Europe Randomized Trial of Interventions to Improve Warfarin Adherence Testing Strategies to Improving Warfarin Adherence Prospective Study Looking at Quality of Life Measures in Non-ischaemic Cardiomyopathy After Mitral Valve Repair Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study The Cardiovascular Genetic and Therapeutic Implications of Muscular Dystrophy A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy Role of Endothelial Function, Muscular Fitness and Metabolism in Functional Activity in Patients With Chronic Heart Failure (CHF) Echo Assessment of Intraventricular Dyssynchrony Brain Function and Perfusion in Patients With Heart Failure Molecular and Imaging Studies of Cardiovascular Health and Disease Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES) Optimizing Left Ventricular Lead To Improve Cardiac Output Using Ripple Mapping to Guide Substrate Ablation of Scar Related Ventricular Tachycardia. Long-term Evaluation of Patients Receiving Bone Marrow-derived Cell Administration for Heart Disease Study Evaluating the Safety, Tolerability and Preliminary Pharmacokinetics and Pharmacodynamics of MYK-491 Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure ACC – Atrial Contribution to CRT Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril Non-Invasive Evaluation of Myocardial Stiffness by Elastography in Pediatric Cardiology (Elasto-Pédiatrie) Manganese-Enhanced Magnetic Resonance Imaging of the Myocardium Efficacy of Implantable Cardioverter Defibrillator in Patients With Non-ischemic Systolic Heart Failure on Mortality Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) Arrhythmia Prediction Trial Exome Sequencing Study in Cardiomyopathy to Identify New Risk Variants A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491 Exercise Stress MRI to Evaluate Aortic Function (Compliance, Distensibility, Pulse Wave Velocity) and Left Ventricular Function : Validation in Healthy Volunteers and in Selected Patients. A Pilot Study. Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy Observational Trial of Cardiotoxicity in Patients Undergoing Chemotherapy. A Pivotal Trial to Establish the Efficacy and Safety of Algisyl in Patients With Moderate to Severe Heart Failure Effect of Rosuvastatin on Left Ventricular Remodeling Intraventricular Stasis in Non Ischemic Dilated Myocardiopathy Assessment of Right Ventricular Function in Advanced Heart Failure An Open Label Rollover Trial for Patients Randomized to the Control Group of Study LSH-10-001 Optimized Biventricular Pacing Allograft Recipients BiPAP for Cardiomyopathy With Central Sleep Apnea Relationship Between Abnormalities of Desmin Cytoskeleton, Mitochondrial Activity and Expression of Ubiquitin in Aspect of Pathogenesis of Heart Failure and Prognosis Effect of Aldosterone on Energy Starvation in Heart Failure Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside Therapy With Verapamil or Carvedilol in Chronic Heart Failure Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart Training Study to Evaluate the Benefit of Exercise for Patients With Chronic Heart Failure Danish ICD Study in Patients With Dilated Cardiomyopathy Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy DCM Precision Medicine Study A Randomized, Controlled Study to Evaluate Algisyl-LVR™ as a Method of Left Ventricular Augmentation for Heart Failure The Genetics of Dilated Cardiomyopathy: A Quebec-Based Study Potential Role of Water-soluble Ubiquinol in Complementary Therapy for Pediatric Dilated Cardiomyopathy A Trial of Autologous Bone Marrow Derived Stem Cells in Paediatric Heart Failure Resynchronization Therapy in Young Patients With and Without CHD Withdrawal of Medication in Recovered DCM Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM The Influence of Atorvastatin on the Parameters of Inflammation and the Function of Left Ventricle Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery PUFAs and Left Ventricular Function in Heart Failure 18F-deoxyglucose (FDG) PET-CMD Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy (REMEDIUM) Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy Autologous Transplantation of Bone Marrow Mononuclear Stem-Cells by Mini-Thoracotomy Combination of Olmesartan Effect on Myocardial Viability of Patients With Dilated Cardiomyopathy Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea Pathophysiology of Dilated Cardiomyopathy Multicenter Exploratory Study of Accelerometry in Dilated Cardiomyopathy Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy Autologous Transplantation of Bone Marrow Mononuclear Stem-Cells for Dilated Cardiomyopathy Clinical and Genetic Examinations of Dilated Cardiomyopathy Simvastatin Therapy in Patients With Dilated Cardiomyopathy. Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy Respiratory Muscles Training in Patients With Dilated Cardiomyopathy Myocardial Metabolism in Patients With Dilated Cardiomyopathy Intracoronary Autologous Mesenchymal Stem Cells Implantation in Patients With Ischemic Dilated Cardiomyopathy Orodispersible Minitablets of Enalapril in Children With Heart Failure Due to Dilated Cardiomyopathy Multicenter Study of Immunoadsorption in Dilated Cardiomyopathy Cell Therapy In Dilated Cardiomyopathy Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure. Nesiritide – Dilated Cardiomyopathy A Study of Impact of Anemia on Morbidity and Mortality in Children With Dilated Cardiomyopathy Defining the Role of Insulin Resistance in ‘Idiopathic’ Dilated Cardiomyopathy Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM) Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy Intramuscular Injection of Mesenchymal Stem Cell for Treatment of Children With Idiopathic Dilated Cardiomyopathy Honey in Idiopathic Dilated Cardiomyopathy A Clinical Study of Immunoadsorption Therapy for Dilated Cardiomyopathy

Brief Title

Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)

Official Title

Genotype-Phenotype Associations in Pediatric Cardiomyopathy

Brief Summary

      Cardiomyopathy in children is a serious disease which can result in death, disability, heart
      transplantation or serious heart rhythm disorders. Doctors know little about the causes of
      cardiomyopathy but would like to learn more. In fact, up to 50-75% of cases in children have
      no known cause. For this reason, the purpose of this study is to identify genes that cause
      cardiomyopathy or that influence how people with cardiomyopathy do over time. These findings
      could improve disease prevention, surveillance, early management, and prognosis.

Detailed Description

      Pediatric cardiomyopathy is a heterogeneous genetic disease with high morbidity and mortality
      in which children often present with fulminant disease leading to death or transplant. The
      long-term goal of this project is to identify the genetic basis of cardiomyopathy and to
      correlate these findings with clinical phenotypes for risk stratification. These findings
      could improve disease prevention, surveillance, early management, and prognosis.

      The specific aims of this study are:

        1. To identify the disease-causing and disease-associated genetic variants underlying
           pediatric cardiomyopathy in a carefully phenotyped cohort.

        2. To identify genotype-phenotype correlations that allow for risk stratification and
           improve management and therapy.

      Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of up to
      700 pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic
      (hypertrophic or restrictive cardiomyopathy) dysfunction. The biological parent(s) of
      enrolled participants will also be approached about participating and providing a blood
      sample for genetic testing. In addition to the parent(s), the participants siblings and other
      relatives may also be approached regarding enrollment, based on the pedigree and family

      This study will significantly increase our understanding of pediatric cardiomyopathy by
      defining the prevalence of mutations in genes known to cause cardiomyopathy as well as
      identifying novel disease-causing genes in the pediatric population. Genetic association
      tests will identify variants that modify disease. Novel bioinformatics and systems biology
      applications for interpretation of exome level genetic information will contribute
      fundamental knowledge and technical innovation to the translation of genomic data to clinical
      utility. These aims will provide critical genetic architecture data, identify variants with
      large effects, and enable genotype-phenotype correlations necessary for advancing management
      and therapy.

      The Study will have two components: 1) clinical data collection by chart review and family
      interview, and 2) biospecimen collection and genetic testing.

Study Type


Primary Outcome

Time to death

Secondary Outcome

 Time to transplant


Dilated Cardiomyopathy

Study Arms / Comparison Groups

 Pediatric cardiomyopathy
Description:  Diagnosis of primary or idiopathic dilated, hypertrophic or restrictive cardiomyopathy. Diagnosis must have been made before the age of 18 and must be confirmed by established echocardiographic criteria or cardiac MRI (cMRI) at the time of diagnosis.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

April 2013

Completion Date

March 31, 2018

Primary Completion Date

February 2017

Eligibility Criteria

        Inclusion Criteria:

          -  Patient is alive. (except samples from deceased relatives who have consented for
             testing).Patients who are status-post heart transplant are eligible if pre-transplant
             longitudinal data are available.

          -  Under age 18 years at the time of diagnosis of either primary or idiopathic dilated,
             hypertropic, or restrictive cardiomyopathy.

          -  A diagnosis of cardiomyopathy which, at the time of diagnosis, was confirmed by
             echocardiographic criteria or cardiac MRI

        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:

          -  Arrhythmogenic right ventricular dysplasia

          -  Neuromuscular disease (defined by specific conditions)

          -  Endocrine disease known to cause heart muscle disease (including infants of diabetic

          -  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

          -  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 known to cause hypertrophy (e.g., growth hormone,
             corticosteroids, cocaine)

          -  Genetic syndrome or chromosomal abnormality known to be associated with cardiomyopathy




N/A - N/A

Accepts Healthy Volunteers



Steven E Lipshultz, MD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party

Principal Investigator

Study Sponsor

Wayne State University



Study Sponsor

Steven E Lipshultz, MD, Principal Investigator, Wayne State University

Verification Date

April 2018