Precision Medicine for Dilated Cardiomyopathy in European and African Ancestry

The DCM Precision Medicine Study is a multi-site consortium-based cross-sectional study of families with an embedded open-label randomized controlled trial. The aims of the study are to test the hypothesis that dilated cardiomyopathy (DCM) has a substantial genetic basis and to evaluate the effectiveness of a family communication intervention in improving the uptake of preventive screening and surveillance in at-risk first-degree relatives. The Study goal was to recruit 1,300 individuals (600 non-Hispanic African ancestry, 600 non-Hispanic European ancestry, and 100 Hispanic; 50% female) meeting rigorous diagnostic criteria for idiopathic DCM (probands) and 2,600 of their relatives. The probands were inpatients or outpatients identified by heart failure and cardiac transplant cardiovascular physicians and clinical research personnel in heart failure/heart transplant programs at sites in the DCM Consortium. The DCM phenotype was selected for this study because of its prevalence and its prior inclusion in the development of virtually all pharmacotherapy for non-ischemic heart failure from reduced ejection fraction. Study procedures included obtaining family history, cardiac history, medical record review, surveys, and blood sample collection. Exome data from 1219 idiopathic DCM probands and 127 idiopathic DCM relatives are included in dbGaP.]]>
Inclusion Criteria: Meeting criteria for DCM: Left ventricular ejection fraction <50% Left ventricular enlargement (A left ventricular end-diastolic dimension > 95%ile population standard based on gender and height) Detectable causes of cardiomyopathy, except genetic, excluded beyond a reasonable doubt at the time of DCM diagnosis (that is, meeting clinical criteria for idiopathic DCM) Any age (including children) Non-Hispanic and Hispanic ethnicity All races (PI pre-approval required for recruitment beyond pre-specified recruitment targets) Ability to communicate in English (except Spanish language at sites approved to recruit individuals of Hispanic ethnicity) Willingness to participate in a family-based study (patient willing to work with a clinical site and/or OSU to facilitate the recruitment and enrollment of family members to the study) Exclusion Criteria: Coronary artery disease (CAD) causing ischemic cardiomyopathy (> 50% narrowing, any major epicardial coronary artery) Primary valvular disease Adriamycin or other cardiotoxic drug exposure Other forms of cardiomyopathy: Hypertrophic, Restrictive, or Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Congenital heart disease Other detectable causes of dilated cardiomyopathy, including sarcoid and hemochromatosis Other active multi-system disease that may cause DCM (e.g., active connective tissue disease) Severe and untreated or untreatable hypertension (systolic blood pressures routinely greater than 180 mm Hg and/or diastolic blood pressures greater than 120 mm Hg, and if resistant to multidrug treatment) However, conventional risk factors for DCM, including obesity, routinely treated hypertension, alcohol use, pregnancy or the peri-partum period, or left ventricular noncompaction, will NOT be considered exclusion criteria ]]>
September 1, 2019 – European ancestry (EA) proband enrolled closed. March 15, 2020 – African ancestry (AA) and Hispanic ethnicity (HE) closed due to COVID-19. April 1, 2021 – Family member enrollment closed. ]]>