Abstract
Abstract Background Changes in myocardial microstructure that underlie post-myocardial infarction (MI) left ventricular (LV) remodelling may contribute to progressive deterioration in cardiac function and increased risk of adverse clinical events. Diffusion Tensor Cardiovascular Magnetic Resonance (DT-CMR) derived parameters provide in vivo measures of helix angle (HA) and sheetlet angle (SA), which allow non-invasive characterization of microstructural dynamics associated with cardiac contraction. Purpose To evaluate the relationship between DT-CMR metrics of myocardial microstructure with the development of adverse LV remodelling and to determine the relationship between DT-CMR and strain post- MI. Methods We performed a longitudinal pre-clinical CMR study whereby DT-CMR, cine imaging and strain were acquired pre-MI and 3 days and 16 weeks post- MI in a pig model. HA (E1A), SA (E2A), and sheetlet angle mobility (ΔE2A = E2Asystole– E2Adiastole), as well as circumferential (Ecc) and radial (Err) strain were calculated at each timepoint and related to change in left ventricular end-diastolic volume (ΔLVEDV) and change in left ventricular end-systolic volume (ΔLVESV) between 3 days post-MI and 16 weeks post-MI. The translational value of this preclinical study was further assessed in six patients with chronic MI. Results ΔE2A over the whole LV (global ΔE2A) at 3 days post-MI correlated significantly with ΔLVEDV (R2=0.89, p=0.0013, Fig.1A;) and ΔLVESV (R2=0.81, p=0.0055, Fig.1B). Global Ecc at 3 days post-MI also correlated with both ΔLVEDV (R2=0.75, p=0.012, Fig.1C) and ΔLVESV (R2=0.71, p=0.018, Fig.1D). Global Err at 3 days post-MI did not show significant correlation with either ΔLVEDV (R2=0.32, p=0.19, Fig.1E) or ΔLVESV (R2=0.35, p=0.17, Fig.1F). Global ΔE2A correlated strongly with global Ecc 3 days post-MI (R2=0.9, p=0.00099, Fig.1G) but less strongly with global Err 3 days post-MI (R2=0.57, p=0.049, Fig.1H). Global ΔE2A at the chronic stage correlated significantly with ejection Fraction (EF), in both clinical (R2=0.87, p=0.007) and preclinical data (R2=0.87, p=0.0024). Global ΔE2A correlated well with LVEDV (clinical: R2=0.72, p=0.033; preclinical: R2=0.8, p=0.0066) and LVESV (clinical: R2=0.78, p=0.020; preclinical: R2=0.89, p=0.0013). In vivo E1A maps at 16 weeks post-MI and ex vivo DT-CMR demonstrated reduced right-handed helix angles in the endocardium of the infarct region. Conclusion ΔE2A measured at 3 day post-reperfused MI is strongly correlated with the development of increased end-systolic and end-diastolic volumes, and may therefore serve as a novel CMR early predictor of adverse LV remodelling after reperfused MI. Strong correlations between ΔE2A, LV volumes and EF in a small cohort of stable patients with remodelled hearts after chronic MI confirm the feasibility of performing these measurements in patients and the plausibility of further evaluation of ΔE2A as a predictor of adverse remodelling after reperfused MI. Sheetlet mobility predicts volume change Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Institutes of Health by the Division of Intramural Research (NHLBI, NIH, DHHS); British Heart Foundation
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