Extracellular Volume-Guided Late Gadolinium Enhancement Analysis for Non-Ischemic Cardiomyopathy: The Women’s Interagency HIV Study.

Abstract

BACKGROUND: Quantification of non-ischemic myocardial scar remains a challenge due to the patchy diffuse nature of fibrosis. Extracellular volume (ECV) to guide late gadolinium enhancement (LGE) analysis may achieve a robust scar assessment.METHODS: Three cohorts of 80 non-ischemic-training, 20 non-ischemic-validation, and 10 ischemic-validation were prospectively enrolled and underwent 3.0 Tesla cardiac MRI. An ECV cutoff to differentiate LGE scar from non-scar was identified in the training cohort from the receiver-operating characteristic (ROC) curve analysis, by comparing the ECV value against the visually-determined presence/absence of the LGE scar at the highest signal intensity (SI) area of the mid-left ventricle (LV) LGE. Based on the ECV cutoff, an LGE semi-automatic threshold of n-times of standard-deviation (n-SD) above the remote-myocardium SI was optimized in the individual cases ensuring correspondence between LGE and ECV images. The inter-method agreement of scar amount in comparison with manual (for non-ischemic) or full-width half-maximum (FWHM, for ischemic) was assessed. Intra- and inter-observer reproducibility were investigated in a randomly chosen subset of 40 non-ischemic and 10 ischemic cases. RESULTS: The non-ischemic groups were all female with the HIV positive rate of 73.8% (training) and 80% (validation). The ischemic group was all male with reduced LV function. An ECV cutoff of 31.5% achieved optimum performance (sensitivity: 90%, specificity:86.7% in training; sensitivity: 100%, specificity: 81.8% in validation dataset). The identified n-SD threshold varied widely (range 3SD to 18SD), and was independent of scar amount (β= -0.01, p=0.92). In the non-ischemic cohorts, results suggested that the manual LGE assessment overestimated scar (%) in comparison to ECV-guided analysis (training: 4.5 [3.2 – 6.4] vs. 0.92 [0.1 – 2.1]; validation: 2.5 [1.2 – 3.7] vs. 0.2 [0 – 1.6]; P<0.01 for both). Intra- and inter-observer analyses of global scar (%) showed higher reproducibility in ECV-guided than manual analysis with CCC=0.94 and 0.78 vs. CCC=0.86 and 0.73, respectively (P<0.01 for all). In ischemic validation, the ECV-guided LGE analysis showed a comparable scar amount and reproducibility with the FWHM. CONCLUSIONS: ECV-guided LGE analysis is a robust scar quantification method for a non-ischemic cohort. Trial-Registration: ClinicalTrials.gov; NCT00000797, retrospectively-registered 2 November 1999; NCT02501811, registered 15 July 2015.