Extracellular vesiclinvestigation of post-myocardial infarction left ventricular remodelling by diffusion tensor cardiovascular magnetic resonance
File(s)
Author(s)
Rajakulasingam, Ramyah
Type
Thesis
Abstract
Background: Dynamic changes in myocardial microstructure may determine adverse left ventricular (LV) remodelling and altered cardiac function after acute ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) provides novel insights into these complex microstructural dynamics, including cyclical changes in laminar microstructures termed sheetlets (E2A), which reorient from diastole (E2ADIA) to systole (E2ASYS) during myocardial thickening, the helical arrangement of cardiomyocytes and markers of myocardial integrity (mean diffusivity [MD] and fractional anisotropy [FA]). This research investigated whether altered microstructural dynamics in diastole and systole, assessed using biphasic DT-CMR a) predict adverse LV remodelling; b) associate with myocardial injury and contractile dysfunction.
Methods: Biphasic DT-CMR was performed in STEMI patients at 3-5 days (n=70) and 4 months (n=66) following reperfusion, and healthy volunteers (HVOLs) (n=22). Results: In the acute infarct zone, E2ADIA was raised and E2ASYS reduced, resulting in impaired E2A mobility (∆E2A). On multivariable analysis, acute global ∆E2A (odds ratio 0.72; 95% CI: 0.58 – 0.90; p=0.004) and acute global proportion of cardiomyocytes with left-handed orientation in systole (odds ratio 1.35; 95% CI: 1.08 – 1.70; p=0.009) independently predicted adverse LV remodelling. Acute global ∆E2A had the highest predictive power on ROC analysis. Microstructural alterations were more pronounced with increasing MI size and led to reduced strain and LV ejection fraction. DT-CMR biomarkers of tissue integrity enabled detection of MI with good-excellent sensitivity and specificity and correlated with biochemical measures of myocardial injury, including cardiac myosin-binding protein C (cMyC).
Conclusion: Biphasic DT-CMR detects aberrant microstructural dynamics in acute STEMI in both cardiac phases, including a unique pattern of sheetlet dynamics. Biphasic DT-CMR allows detection of MI and prediction of adverse LV remodelling using novel biomarkers, including sheetlet mobility, via a single contrast-free modality...
Methods: Biphasic DT-CMR was performed in STEMI patients at 3-5 days (n=70) and 4 months (n=66) following reperfusion, and healthy volunteers (HVOLs) (n=22). Results: In the acute infarct zone, E2ADIA was raised and E2ASYS reduced, resulting in impaired E2A mobility (∆E2A). On multivariable analysis, acute global ∆E2A (odds ratio 0.72; 95% CI: 0.58 – 0.90; p=0.004) and acute global proportion of cardiomyocytes with left-handed orientation in systole (odds ratio 1.35; 95% CI: 1.08 – 1.70; p=0.009) independently predicted adverse LV remodelling. Acute global ∆E2A had the highest predictive power on ROC analysis. Microstructural alterations were more pronounced with increasing MI size and led to reduced strain and LV ejection fraction. DT-CMR biomarkers of tissue integrity enabled detection of MI with good-excellent sensitivity and specificity and correlated with biochemical measures of myocardial injury, including cardiac myosin-binding protein C (cMyC).
Conclusion: Biphasic DT-CMR detects aberrant microstructural dynamics in acute STEMI in both cardiac phases, including a unique pattern of sheetlet dynamics. Biphasic DT-CMR allows detection of MI and prediction of adverse LV remodelling using novel biomarkers, including sheetlet mobility, via a single contrast-free modality...
Version
Open Access
Date Issued
2023-12-17
Date Awarded
2024-04-01
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
de Silva, Ranil
Pennell, Dudley
Nielles-Vallespin, Sonia
Khalique, Zohya
Dalby, Miles
Sponsor
British Heart Foundation
Grant Number
FS/19/22/34334
RG/19/1/34160
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)