Dilated cardiomyopathy of unknown cause (DCM) is a major public health problem affecting more than a million people in the U.S. Most DCM is now known to have an underlying genetic basis. First-degree relatives (FDRs) of an individual with DCM are considered to be genetically at risk, particularly if they carry variants classified as pathogenic (P), likely pathogenic (LP) or uncertain significance (VUS) in DCM genes. Practice guidelines recommend that these FDRs undergo serial imaging because prompt intervention may avert advanced disease. While tissue damage is already well underway when DCM is manifest, myocardial tissue changes, termed "pre-DCM" herein, are known to precede adverse changes in myocardial structure and function. The investigators central hypothesis states that cardiac magnetic resonance (CMR) imaging may detect pre-DCM in individuals with increased genetic risk by identifying myocardial tissue changes prior to myocardial structural and functional changes. CMR measures of myocardial tissue characteristics, including late gadolinium enhancement and myocardial T1 mapping, have been histopathologically validated and have established diagnostic and prognostic value in DCM. Thus, the investigators specific hypotheses state that adverse CMR-based myocardial tissue characteristics will be associated with (1) A higher burden (number) of relevant variants (P, LP, VUS) in established DCM genes; and (2) Subsequent adverse changes in measures of cardiac structure and function. The investigators propose to leverage the DCM Precision Medicine Study, a multisite DCM Consortium study now with 1230 DCM patients (probands), balanced for race and sex, and their FDRs, most with no history of DCM. FDRs are cascade tested for relevant variants (P, LP, VUS) in DCM genes identified in probands. The investigators aim to (1) Estimate the associations between CMR-based myocardial tissue characteristics and the number (burden) of the proband's variants in DCM genes in at-risk FDRs. In 650 FDRs of probands with LP/P variants and/or VUSs, CMR scans will be completed at 9 participating DCM Consortium sites. The association between CMR-based myocardial tissue characteristics and the number of the proband's variants of each class (LP/P, VUS) carried by an at-risk FDR in a particular age group will be evaluated, adjusting for biologically relevant covariates. The investigators will also (2) Estimate the association between CMR-based myocardial tissue characteristics and subsequent changes in measures of cardiac structure and function in FDRs with normal baseline left-ventricular size and function. FDRs examined in Aim 1 will receive a second CMR exam 2.5 years after their baseline exam. The investigators will estimate the covariate-adjusted associations between baseline myocardial tissue characteristics and subsequent changes in CMR-derived measures of cardiac structure and function in groups defined by the most deleterious of the proband's variants carried (none, VUS, or LP/P). This study will validate a CMR-derived "pre-DCM" phenotype for FDRs who carry P or LP variants (established risk), and also provide preliminary evidence that some VUSs are biologically relevant.
