Among myriad changes occurring during the apparent evolution of HFpEF where elevated BNP is prevalent, MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF might precede clinical HFpEF diagnosis. Regardless, MF was associated with disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating MF represent therapeutic targets in HFpEF warrants further evaluation.
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.
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