Precision medicine for dilated cardiomyopathy - novel assessment of cardiac mechanics via speckle tracking echocardiography to identify early phenotypes

Project: Research project

Project Details


Idiopathic dilated cardiomyopathy (DCM)—a morbid and lethal condition affecting >1 million in the US and the leading indication for heart transplantation—is often diagnosed late only after significant left ventricular (LV) dilation and LV systolic dysfunction have occurred.[ref PMID 23900355] Historically, by definition the cause of idiopathic DCM was unknown, but recent preliminary data [ref PMID 20215591] suggests that most of DCM, whether familial or non-familial, may be genetically mediated.[ref PMID 29237686] This hypothesis is now being tested in the DCM Precision Medicine study, [ref PMID 29237686] the parent study of this ancillary application, which includes family-based enrollment of DCM patients (probands) and their first-degree relatives (FDRs). All probands will undergo genetic analysis to identify pathogenic or likely pathogenic (P, LP) variants, or variants of uncertain significance (VUS) in relevant DCM genes. Cascade Sanger sequencing will then be conducted in at-risk family members to determine if they carry these variants. Clinical cardiac screening will also be conducted for at-risk family members, which includes a limited, screening echocardiogram (echo), an ECG, and a cardiovascular-directed history and exam. While a limited echo study is highly cost effective for this NIH-funded study, it only evaluates LV dimension and identifies overt LV systolic dysfunction, measured as a reduction in LV ejection fraction (LVEF). Precision medicine offers enormous opportunity to detect early DCM and to intervene with treatment to avert late phase disease (Box 1), with surveillance imaging guided by genetic information in at-risk family members. Family members shown to carry relevant variants can have periodic imaging by echocardiography, and when LV dysfunction is detected, therapy can be initiated to prevent disease progression. This ancillary study proposes to remedy important limitations of the current parent study design, as family members receive only a limited screening echocardiogram that is able to exclude only LV enlargement or decreased LVEF. While such data are sufficient to test the parent study hypotheses, this minimal exam is insufficient to detect abnormalities in cardiac mechanics that precede overt systolic dysfunction. We also note that myocardial function is only evaluated at rest without a physiologic stressor.
Effective start/end date8/1/196/30/23


  • Ohio State University (GR116057/SPC-1000003925/R01HL149423 AMD1)
  • National Heart, Lung, and Blood Institute (GR116057/SPC-1000003925/R01HL149423 AMD1)


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