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

Abstract

Since 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 measurements; most histologic validation data show strongest ECV correlations with MF. Methods: We enrolled 1714 consecutive patients without amyloidosis or hypertrophic cardiomyopathy from a single CMR referral center serving an integrated healthcare network. We measured T1 (MOLLI) in noninfarcted myocardium, averaged from 2 short axis slices (basal and mid) before and 15-20 minutes after a gadolinium contrast bolus. We compared chi square (χ 2) 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 best separation of Kaplan-Meier curves and highest log-ranks statistics. In univariable and multivariable models, ECV associated most strongly with outcomes, demonstrating the highest χ 2 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, e.g., in multivariable models IDI=0.

Secreted Frizzled-Related Protein 2 and Extracellular Volume Fraction in Patients with Heart Failure

“…Recently, Treibel et al enrolled 1,714 consecutive patients without amyloidosis or hypertrophic cardiomyopathy from a single CMR referral center. Over a median follow-up of 5.6 years, ECV fraction exhibited more robust associations with outcomes than other surrogate CMR measures of myocardial fibrosis [4]. Furthermore, Roy et al reported that, among HFpEF patients, high ECV fraction was associated with an increased risk of all-cause death and HF hospitalization in short-term follow-up [6].…”

“…Myocardial fibrosis is a key pathological process in HF [3]. It predicts risk and represents a potential therapeutic target, and its measurement holds promise for future precision medicine [4]. Although myocardial biopsy is the gold standard for evaluating myocardial fibrosis, it is an invasive procedure with a high risk of complication.…”

Diffusely Increased Myocardial Extracellular Volume With or Without Focal Late Gadolinium Enhancement

“…These patients represent a non-negligible part of all patients and an increased ECV, measured in myocardium that is free from focal LGE. Such ECV measurements have been found to be associated with adverse events including elevated mortality, and hospitalisation for cardiac reasons (27)(28)(29)(30)(31)57). These patients are important to identify at an early stage to provide the best possible treatment in order to mitigate adverse outcomes.…”

Cardiac magnetic resonance imaging: the future is bright

“…Although a number of metrics exist in CMR for measuring myocardial fibrosis, only limited data for stratification purposes are available 11 . Treibel et al .…”

“…Treibel et al . evaluated the relationship between clinical outcomes and various indices such as ECV, native T1, post-contrast T1, and the partition coefficient in 1714 consecutive patients without amyloidosis or hypertrophic cardiomyopathy 11 . The authors showed ECV demonstrating highest log-rank statistics and best separation of Kaplan–Meier curves.…”