A compartment-based myocardial density approach helps to solve the native T1 vs. ECV paradox in cardiac amyloidosis

Abstract

Cardiovascular magnetic resonance (CMR) plays an important clinical role for diagnosis and therapy monitoring of cardiac amyloidosis (CA). Previous data suggested a lower native T1 value in spite of a higher LV mass and higher extracellular volume fraction (ECV) value in wild-type transthyretin amyloidosis (ATTRwt) compared to light-chain amyloidosis (AL)—resulting in the still unsolved “native T1 vs. ECV paradox” in CA. The purpose of this study was to address this paradox. The present study comprised N = 90 patients with ATTRwt and N = 30 patients with AL who underwent multi-parametric CMR studies prior to any specific treatment. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as T2-mapping and pre-/post-contrast T1-mapping allowing to measure myocardial ECV. Left ventricular ejection fraction (LV-EF), left ventricular mass index (LVMi) and left ventricular wall thickness (LVWT) were significantly higher in ATTRwt in comparison to AL. Indexed ECV (ECVi) was also higher in ATTRwt (p = 0.041 for global and p = 0.001 for basal septal). In contrast, native T1- [1094 ms (1069–1127 ms) in ATTRwt vs. 1,122 ms (1076–1160 ms) in AL group, p = 0.040] and T2-values [57 ms (55–60 ms) vs. 60 ms (57–64 ms); p = 0.001] were higher in AL. Considering particularities in myocardial density, “total extracellular mass” (TECM) was substantially higher in ATTRwt whereas “total intracellular mass” (TICM) was rather similar between ATTRwt and AL. Consequently, the “ratio TICM/TECM” was lower in ATTRwt compared to AL (0.58 vs. 0.83; p = 0.007). Our data confirm the presence of a “native T1 vs. ECV paradox” with lower native T1 values in spite of higher myocardial mass and ECV in ATTRwt compared to AL. Importantly, this observation can be explained by particularities regarding myocardial density that result in a lower TICM/TECM “ratio” in case of ATTRwt compared to AL—since native T1 is determined by this ratio.