Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy

Abstract

Objectives: The goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis.

Background: Cardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltration alone in the remission phase.

Methods: Prospectively enrolled subjects with cardiac AL amyloidosis (21 remission AL amyloidosis; age: 63.4 ± 7.3 years; 47.6% male; and 48 active AL amyloidosis; age: 62.5 ± 7.4 years; 60.4% male) underwent contrast-enhanced cardiac magnetic resonance with T1 and T2 mapping and measurement of extracellular volume (ECV). By definition, serum free light-chain levels were normal for at least 1 year following successful AL therapy in the remission group and abnormal in the active group.

Results: Myocardial ECV was similarly expanded in the remission and active AL amyloidosis groups (0.488 ± 0.082 vs 0.519 ± 0.083, respectively; P = 0.15). However, myocardial T2 relaxation times (47.7 ± 3.2 ms vs 45.5 ± 3.0 ms; P = 0.008) as well as native T1 times (1,368 ms [IQR: 1,290-1,422 ms] vs 1,264 ms [IQR: 1,203-1,380 ms]; P = 0.024) were significantly higher in the remission compared to the active AL amyloidosis group.

Conclusions: Myocardial ECV is substantially expanded in the active AL and remission AL cardiac amyloidosis groups, but native T1 values were higher, suggesting a different myocardial composition. There is no evidence of myocardial edema in active AL cardiac amyloidosis. Future phenotyping studies of AL cardiac amyloidosis need to consider complementary myocardial markers that define the interstitial milieu in addition to changes in extracellular volume. (Molecular Imaging of Primary Amyloid Cardiomyopathy; NCT02641145).

Keywords: AL; CMR; active AL amyloidosis; cardiac amyloidosis; light-chain amyloidosis; myocardial composition; remission.

Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the National Institutes of Health (to Dr Dorbala: R01 HL 130563, R01 HL 150342, AHA16 CSA 2888 0004, and K24 HL157648 AHA19SRG34950011; to Dr Falk: HL 130563; to Dr Liao: AHA16 CSA 2888 0004 and AHA19SRG34950011; to Dr Ruberg: HL 130563 and R01 HL 093148) (NCT02641145). Dr Cuddy has received an investigator-initiated research grant from Pfizer. Dr Singh has received a research grant from American Society of Nuclear Cardiology/Pfizer. Dr Ruberg has received consulting fees from Pfizer, GlaxoSmithKline, and Caleum Biosciences and research support from Eidos Therapeutics. Dr Sanchorawala has received research support from Takeda, Celgene, Janssen, and Prothena and has served on the Scientific Advisory Board for Caleum Biosciences. Dr Landau has received consulting fees from Celgene, Takeda, Janssen, Prothena, Pfizer, and Juno and research support from Amgen, Spectrum, and Takeda. Dr Maurer has received consulting income and his institution has received clinical trial funding from Pfizer, Eidos, Prothena, Akcea, and Alnylam. Dr Yee has received consulting fees from Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda. Dr Di Carli has received research grants from Spectrum Dynamics and Gilead and consulting fees from Sanofi and GE. Dr Falk has received consulting fees from Ionis Pharmaceuticals, Alnylam Pharmaceuticals, and Caelum Biosciences and research funding from GlaxoSmithKline and Akcea. Dr Dorbala has received consulting fees from Pfizer and GE Health Care; and her institution has received investigator-initiated grants from Pfizer, GE Healthcare, and Attralus. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Native T1 Values in the Study Cohort

Median native myocardial T1 in active and remission AL cardiac amyloidosis groups, with individual values overlaid. AL = light-chain.

FIGURE 2. Extracellular Volume and Indexed Extracellular Volume in the Study Cohort

The (A) extracellular volume and (B) adjusted extracellular volume in active and remission groups with AL cardiac amyloidosis, with individual values overlaid. (One subject from the remission group was not included in the indexed extracellular volume analysis, as mentioned in text.) AL = light-chain; iECV = indexed extracellular volume.

FIGURE 3. T2 Relaxation Times in the Study Cohort

Median myocardial T2 in the active and remission AL cardiac amyloidosis groups, with individual values overlaid. AL = light-chain.

FIGURE 4. Correlation of the Difference in Free Light Chain Levels to Native T1 and Native T2

Correlations of the difference in free light chain levels to (A) native T1 and (B) native T2.

CENTRAL ILLUSTRATION. Myocardial Composition in Cardiac Light-Chain Amyloidosis

In the remission and active light-chain cardiac amyloidosis groups, the native T1 and extracellular volume are elevated, with normal T2 values. The mean values for each group are in parentheses; the native T1 and T2 were significantly higher in the treated group in this cohort (*P < 0.05), and there was no significant difference in the extracellular volume.