Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality

Abstract

Background Extracellular matrix (ECM) expansion may be a fundamental feature of adverse myocardial remodeling, appears to be treatable, and its measurement may improve risk stratification. Yet, the relationship between mortality and ECM is not clear due to difficulties with its measurement. To assess its relationship with outcomes, we used novel, validated cardiovascular magnetic resonance (CMR) techniques to quantify the full spectrum of ECM expansion not readily detectable by conventional CMR. Methods and Results We recruited 793 consecutive patients at the time of CMR without amyloidosis or hypertrophic cardiomyopathy as well as 9 healthy volunteers (ages 20–50). We measured the extracellular volume fraction (ECV) to quantify the extracellular matrix expansion in myocardium without myocardial infarction (MI). ECV employs gadolinium contrast (Gd) as an extracellular space marker based on T1 measures of blood and myocardium pre-/post-Gd and hematocrit measurement. In volunteers, ECV ranged from 21.7–26.2%, but in patients, it ranged from 21.0–45.8%, indicating considerable burden. There were 39 deaths over a median follow-up of 0.8 years (IQR 0.5–1.2 years), and 43 individuals who experienced the composite endpoint of death/cardiac transplant/left ventricular assist device (LVAD) implantation. In Cox regression models, ECV related to all-cause mortality and the composite endpoint (HR 1.55; 95% CI 1.27–1.88 and HR 1.48; 95% CI 1.23–1.78, respectively, for every 3% increase in ECV), adjusting for age, left ventricular ejection fraction, and MI size. Conclusions ECV measures of extracellular matrix expansion may predict mortality as well as other composite endpoints (death/cardiac transplant/LVAD).

T1, T2 Mapping and Extracellular Volume Fraction (ECV): Application, Value and Further Perspectives in Myocardial Inflammation and Cardiomyopathies

“…Even a connection between elevated ECV and mortality prediction was reported. In a study with 793 patients suffering from ischemic heart disease, ECV showed potential in the prediction of short-term mortality [15]. T2 mapping, however, enables the identification of myocardial edema in acute infarction and inflammatory disease [16].…”

Cardiac Magnetic Resonance Imaging for the Investigation of Cardiovascular Disorders. Part 2: Emerging Applications

“…14 An association between ECV, short-term death, and other adverse clinical outcomes also has been recently shown 9 ; this association appears to be stronger with ECV than with LGE. 7 On the basis of this association, the use of ECV as a biomarker for risk stratification has been proposed.…”

“…Consequently, it can be said that ECV attempts to divide the myocardium into its cellular and interstitial components, with estimates expressed as volume fractions. 7 Extracellular volume maps are generated by quantifying the native and postcontrast T1 values on co-registered images while adjusting for the hematocrit, 9 in order to account for the effects of changes in body composition, renal function, and hematocrit due to the underlying disease process.…”

“…Given the pathophysiologic signif icance of myocardial ECM, ECV measures might be of prognostic signif icance equivalent to left ventricular (LV) ejection fraction. 7,9,10 Extracellular matrix is a modifiable target in several disease processes-so T1 mapping might find wide applicability in disease characterization, monitoring, outcome prediction, and therapeutics. 12 Quantitative T1 measurement using equilibrium contrast (EQ)-CMR has also shown strong correlation to histology for quantification of diffuse myocardial fibrosis in patients with aortic stenosis or HOCM.…”

Correlation of Electrocardiogram and Regional Cardiac Magnetic Resonance Imaging Findings in ST‐Elevation Myocardial Infarction: A Literature Review

“…47 Alterations in these compartments occurring from different physiologic and pathophysiologic biologic processes leading to fibrotic changes can be more easily detected with ECV than with LGE. 51 This is true especially with the changes resulting from pathologies other than MI, where the differences between the normal and affected myocardium are less distinct. 47,[51][52][53] Therefore, the more widespread clinical use of these tissue characterization techniques requires further exploration.…”