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Extracellular Volume Associates With Outcomes More Strongly Than Native or Post-Contrast Myocardial T1

Treibel, TA; Fridman, Y; Bering, P; Sayeed, A; Maanja, M; Frojdh, F; Niklasson, L; ... Schelbert, EB; + view all (2020) Extracellular Volume Associates With Outcomes More Strongly Than Native or Post-Contrast Myocardial T1. JACC: Cardiovascular Imaging , 13 (1) pp. 44-54. 10.1016/j.jcmg.2019.03.017. Green open access

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Abstract

OBJECTIVES: Because risk stratification data represents a key domain of biomarker validation, we compared associations between outcomes and various cardiovascular magnetic resonance (CMR) metrics quantifying myocardial fibrosis (MF) in noninfarcted myocardium: extracellular volume fraction (ECV), native T1, post-contrast T1, and partition coefficient. // BACKGROUND: MF associates with vulnerability to adverse events (e.g., mortality and hospitalization for heart failure [HHF]), but investigators still debate its optimal measurement; most histological validation data show strongest ECV correlations with MF. // METHODS: We enrolled 1,714 consecutive patients without amyloidosis or hypertrophic cardiomyopathy from a single CMR referral center serving an integrated healthcare network. We measured T1 (MOdified Look-Locker Inversion recovery [MOLLI]) in nonenhanced myocardium, averaged from 2 short-axis slices (basal and mid) before and 15 to 20 min after a gadolinium contrast bolus. We compared chi-square test values from CMR MF measures in univariable and multivariable Cox regression models. We assessed "dose-response" relationships in Kaplan-Meier curves using log-rank statistics for quartile strata. We also computed net reclassification improvement (NRI) and integrated discrimination improvement (IDI for Cox models with ECV vs. native T1). // RESULTS: Over a median of 5.6 years, 374 events occurred after CMR (162 HHF events and 279 deaths, 67 with both). ECV yielded the best separation of Kaplan-Meier curves and the highest log-rank statistics. In univariable and multivariable models, ECV associated most strongly with outcomes, demonstrating the highest chi-square test values. Native T1 or post-contrast T1 did not associate with outcomes in the multivariable model. ECV provided added prognostic value to models with native T1, for example, in multivariable models IDI = 0.0037 (95% confidence interval [CI]: 0.0009 to 0.0071), p = 0.02; NRI = 0.151 (95% CI: 0.022 to 0.292), p = 0.04. // CONCLUSIONS: Analogous to histological previously published validation data, ECV myocardial fibrosis measures exhibited more robust associations with outcomes than other surrogate CMR MF measures. Superior risk stratification by ECV supports claims that ECV optimally measures MF in noninfarcted myocardium.

Type: Article
Title: Extracellular Volume Associates With Outcomes More Strongly Than Native or Post-Contrast Myocardial T1
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jcmg.2019.03.017
Publisher version: https://doi.org/10.1016/j.jcmg.2019.03.017
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: T1 mapping, cardiovascular magnetic resonance, extracellular matrix, extracellular volume fraction, myocardial fibrosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10077729
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