Comparative assessment of extracellular volume metrics in predicting adverse outcomes in patients with transthyretin amyloid cardiomyopathy

Abstract Introduction The indexed total extracellular volume of the myocardium (iECV) has recently been proposed to be superior in predicting adverse outcome in severe aortic stenosis as compared to conventional extracellular volume (ECV). So far, no study has assessed the comparative predictive performance of both measures in transthyretin amyloid cardiomyopathy (ATTR-CM). Aim We aimed to assess and compare the predictive performance of conventional ECV against iECV in determining adverse outcomes in patients with ATTR-CM. Methods From 2012 to 2023, patients with ATTR-CM undergoing contrast cardiac magnetic resonance (CMR) imaging prior to any specific treatment were enrolled. Both, conventional ECV and iECV were quantified on CMR alongside left ventricular volumetrics and late gadolinium enhancement. Adverse outcome was defined as a composite endpoint of hospitalization for heart failure and/or death. Results Analysis of 178 patients with ATTR-CM (82% males, mean age 77±8 years) revealed a mean conventional ECV of 47±13% and a mean iECV of 46±21 mL/m2, with a median follow-up of 2.5 years (IQR: 1.00-4.08 years). Conventional ECV was significantly associated with the composite endpoint (HR=1.03, 95%CI=1.01–1.05, p=0.006), outperforming iECV (HR=1.01, 95%CI=1.00–1.02, p=0.010). On multivariate analysis, adjusted for age, sex and left ventricular function, conventional ECV remained associated with the composite endpoint (p=0.002), while iECV demonstrated a slightly less significant association (p=0.003). Kaplan-Meier analysis, stratified by conventional ECV tertiles, revealed that patients in the highest tertile (ECV ≥53%) demonstrated the highest event rate (p = 0.043 by log rank test, see Figure 1A), in contrast to iECV (p=NS, Figure 1B). Conclusions High conventional ECV, among CMR fibrosis markers, is linked to heart failure hospitalizations and death in ATTR-CM, demonstrating superior prognostic value compared to iECV. Conventional ECV measurements may offer enhanced risk stratification for patients with ATTR-CM.