Microstructural disease and hypoperfusion in dilated cardiomyopathy underpin midwall septal fibrosis

Figures

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  Fig. 1. The microstructural abnormalities in DCM with MSF can be detected using cardiac DTI. Panel A: Expected cardiac DTI metrics in normal myocardium and DCM. A diffusion imaging tensor is represented pictorially in the top panel: isotropic diffusion is depicted as a sphere, and anisotropic diffusion is depicted as an ellipsoid. λ denotes the eigenvalue (the magnitude of diffusion), and E denotes the eigenvector (the direction of diffusion). In normal myocardium, water diffusion exhibits an anisotropic pattern, diffusing preferentially along the long axis of densely organized cardiomyocytes. In contrast, DCM is associated with an isotropic diffusion pattern in areas of fibrosis or myocardial disarray. MD is the mean of λ1, λ2, and λ3 and measured in units of square millimeters per second. MD measures the overall magnitude of diffusion and represents myocyte packing, with increased values reflecting looser cell packing, e.g. interstitial fibrosis, as water has more freedom to diffuse. FA is a scalar value which measures restrictiveness to water diffusion. In normal tissue, cell membranes act as barriers and restrict water diffusion. Therefore, FA is expected to be high in voxels with…

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  Fig. 2. Study overview and clinical characterization of DCM cohort and controls. A) CONSORT flow diagram of study design. B) Representative mid-ventricular short-axis CMR images of control, DCM without mid-wall septal fibrosis (MSF–) and DCM with mid-wall septal fibrosis (MSF+) from the study cohort. C) Box and whisker plots for global LV features in DCM cohort, stratified by MSF status (MSF+ red; MSF– orange) and controls (green). D) Bullseye plot of percentage of LGE within each myocardial segment in MSF+, MSF– and controls. Darker colors indicate larger values. E) Bullseye plot of -log10p-values for between group comparisons of LGE percentage in myocardial segments, with darker colors indicating smaller p-values. Statistically significant segments (p-value<0.05) are bordered in a thick edge. DCM dilated cardiomyopathy, CMR cardiovascular magnetic resonances, MSF midwall septal fibrosis, LV left ventricular, LGE late gadolinium enhancement

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  Fig. 3. Microstructural characterization of the DCM cohort by cDTI. A) Violin and box and whisker plots for global and septal DTI parameters in DCM, stratified by MSF status (MSF+ red; MSF– orange) and all controls (green). The p-value represents the comparison between the MSF+/- group and their control group. B) Violin and box and whisker plots for global and septal DTI parameters in DCM, stratified by LV systolic function (severely reduced, LV ejection fraction [LVEF] <40% [darkest blue]; mildly reduced, LVEF 41%–49%; and preserved, LVEF >50% [lightest blue]). C) Bullseye plot of mean E2A and MD values in myocardial segments in MSF+, MSF–and controls, with darker colors indicating larger values. D) Bullseye plot of -log10p-values for between group comparisons of E2A and MD values in myocardial segments, with darker colors indicating smaller p-values. Statistically significant segments (p-value<0.05) are bordered in a thick edge. E) Correlation heat map between mean global DTI parameters in all participants (left) and those with DCM (right). Asterix indicates significant correlations (p-value<0.05). F) Correlation heat maps of global LV features with mean global DTI parameters in all…

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  Fig. 4. Microvascular characterization of DCM cohort by resting myocardial blood flow. A) Violin and box and whisker plots for global and septal resting myocardial blood flow in MSF+ (red), MSF– (orange) and all controls (green). The p-value represents the comparison between the MSF+/- group and their controls. B) Bullseye plot of absolute resting myocardial blood flow in myocardial segments in MSF+, MSF–and controls, with darker colors indicating larger values. C) Bullseye plot of -log10p-values for between group comparisons of myocardial blood flow in myocardial segments, with darker colors indicating smaller p-values. Statistically significant segments (p-value<0.05) are bordered in a thick edge. D) Violin and box and whisker plots for global and septal myocardial blood flow in DCM, stratified by LV systolic function (severely reduced, LVEF <40% [darkest blue]; mildly reduced, LVEF 41–49%; and preserved, LVEF >50% [lightest blue]). DCM dilated cardiomyopathy, MSF midwall septal fibrosis, LVEF left ventricular ejection fraction