Extracellular volume-guided late gadolinium enhancement analysis for non-ischemic cardiomyopathy: The Women’s Interagency HIV Study

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 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 3 SD–18 SD), 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 versus 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.