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Clinical Trial
. 2024 Nov;17(11):1271-1286.
doi: 10.1016/j.jcmg.2024.05.004. Epub 2024 Jul 10.

Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis

Olivier F Clerc  1 , Sarah A M Cuddy  1 , Michael Jerosch-Herold  2 , Dominik C Benz  1 , Ethan Katznelson  2 , Jocelyn Canseco Neri  1 , Alexandra Taylor  1 , Marie Foley Kijewski  3 , Giada Bianchi  4 , Frederick L Ruberg  5 , Marcelo F Di Carli  6 , Ronglih Liao  7 , Raymond Y Kwong  2 , Rodney H Falk  8 , Sharmila Dorbala  9
Affiliations
Clinical Trial

Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis

Olivier F Clerc et al. JACC Cardiovasc Imaging. 2024 Nov.

Abstract

Background: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor outcomes.

Objectives: The authors' objectives were to detect early myocardial alterations, to analyze longitudinal changes with therapy, and to predict major adverse cardiac events (MACE) in participants with AL amyloidosis using cardiac magnetic resonance imaging (MRI).

Methods: Recently diagnosed participants were prospectively enrolled. AL amyloidosis with and without cardiomyopathy (AL-CMP, AL-non-CMP) were defined based on abnormal cardiac biomarkers and wall thickness. MRI was performed at baseline, 6 months in all participants, and 12 months in participants with AL-CMP. MACE were defined as all-cause death, heart failure hospitalization, and cardiac transplantation. Mayo stage was based on troponin T, N-terminal pro-B-type natriuretic peptide, and difference in free light chains.

Results: This study included 80 participants (median age 62 years, 58% men). Extracellular volume (ECV) was abnormal (>32%) in all participants with AL-CMP and in 47% of those with AL-non-CMP. ECV tended to increase at 6 months (median +2%; AL-CMP P = 0.120; AL-non-CMP P = 0.018) and returned to baseline values at 12 months in participants with AL-CMP. Global longitudinal strain (GLS) improved at 6 months (median -0.6%; P = 0.048) and 12 months (median -1.2%; P < 0.001) in participants with AL-CMP. ECV and GLS were strongly associated with MACE (P < 0.001) and improved the prognostic value when added to Mayo stage (P ≤ 0.002). No participant with ECV ≤32% had MACE, while 74% of those with ECV >48% had MACE.

Conclusions: In patients with systemic AL amyloidosis, ECV detects subclinical myocardial alterations. With therapy, ECV tends to increase at 6 months and returns to values unchanged from baseline at 12 months, whereas GLS improves at 6 and 12 months in participants with AL-CMP. ECV and GLS offer additional prognostic performance over Mayo stage. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).

Keywords: T1 mapping; cardiac magnetic resonance imaging; extracellular volume; global longitudinal strain; light-chain (AL) amyloidosis; myocardial characterization.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by National Institutes of Health. Dr Dorbala was supported by grants R01 HL 130563, K24 HL 157648, AHA16 CSA 2888 0004, and AHA19SRG34950011. Dr Falk was supported by grant R01 HL 130563. Dr Liao was supported by grants AHA16 CSA 2888 0004 and AHA19SRG34950011. Dr Ruberg was supported by grants R01 HL 130563 and R01 HL 093148. Dr Cuddy was supported by grants NIH 1K23HL166686-01 and AHA 23CDA857664NIH. Dr Bianchi was partially supported by a grant K08 CA245100. Dr Clerc has received a research fellowship from the International Society of Amyloidosis and Pfizer. Dr Cuddy has received an investigator-initiated research grant from Pfizer, as well as consulting fees from BridgeBio, Ionis, Astra Zeneca and Novo Nordisk. Dr Bianchi has received consulting fees from Prothena. Dr Ruberg has received consulting fees from AstraZeneca and Attralus; and has received research support from Pfizer, Alnylam, Anumana, and Ionis/Akcea. Dr DiCarli has received a research grant from Spectrum Dynamics and Gilead; and has received consulting fees from Sanofi and General Electric. Dr Kwong has received grant funding from Alynlam Pharmaceuticals. Dr Falk has received consulting fees from Ionis Pharmaceuticals, Alnylam Pharmaceuticals, and Caelum Biosciences; and has received research funding from GlaxoSmithKline and Akcea. Dr Dorbala has received consulting fees from Pfizer, GE Healthcare, and Novo Nordisk; and has received investigator-initiated grants from Pfizer, GE Healthcare, Attralus, Siemens, and Phillips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Baseline Myocardial Characteristics, Cardiac Structure and Function
P-values were calculated using Wilcoxon rank-sum test. Extracellular volume was increased (>32%) in all AL-CMP and in 47% of AL-non-CMP, suggesting high sensitivity for subclinical cardiomyopathy, while other metrics were rarely abnormal in AL-non-CMP. AL-CMP/AL-non-CMP: Light-chain amyloidosis with/without cardiomyopathy. MRI: Magnetic resonance imaging.
Figure 2.
Figure 2.. Changes in Myocardial Characteristics over Time
This figure displays left ventricular native T1 and ECV maps of a participant with AL-CMP. Native T1 was normal at baseline, and increased over time. ECV was elevated at baseline, increased at 6 months, and decreased at 12 months. AL-CMP: Light-chain amyloidosis with cardiomyopathy. ECV: Extracellular volume.
Figure 3.
Figure 3.. Longitudinal Analysis of Myocardial Characteristics
The first row presents spaghetti plots of longitudinal data for participants with follow-up MRI, and the average trends from mixed-effects regressions (coefficients and p-values shown). For ECV in AL-CMP, a curved trend over time using time and time2 showed the best fit. The second and third rows display waterfall plots of individual changes from baseline to 6-month and 12-month visits. For ECV, most participants showed an increase at 6 months, then a decrease at 12 months. For GLS, most participants exhibited an decrease at both visits. AL-CMP/AL-non-CMP: Light-chain amyloidosis with/without cardiomyopathy. ECV: Extracellular volume. GLS: Global longitudinal strain. LV: Left ventricular. MRI: Magnetic resonance imaging.
Figure 4.
Figure 4.. Outcome Analysis for MACE
Normal levels were defined using reference values (ECV ≤32% and GLS ≤−13%), while high levels were determined using log-rank statistic maximization for MACE (ECV >48% and GLS >−12%). For Kaplan-Meier analyses (first row), p-values were calculated using the log-rank test, and for event rates (second row), using an exact test with Poisson distribution, adjusted for multiple testing by the Benjamini-Hochberg procedure. In Kaplan-Meier analyses, pairwise log-rank tests between levels for ECV and GLS showed significant differences for normal vs. high level and intermediate vs. high level. ECV: Extracellular volume. GLS: Global longitudinal strain. LV: Left ventricular. MACE: Major adverse cardiac events (all-cause death, heart failure hospitalization, or cardiac transplantation).
Central Illustration
Central Illustration
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References

    1. Falk RH, Alexander KM, Liao R, Dorbala S. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol. 2016;68:1323–1341. - PubMed
    1. Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2-evidence base and standardized methods of imaging. J Nucl Cardiol. 2019;26:2065–2123. - PubMed
    1. Bianchi G, Zhang Y, Comenzo RL. AL Amyloidosis: Current Chemotherapy and Immune Therapy Treatment Strategies: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2021;3:467–487. - PMC - PubMed
    1. Fontana M, Pica S, Reant P, et al. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation. 2015;132:1570–1579. - PMC - PubMed
    1. Banypersad SM, Fontana M, Maestrini V, et al. T1 mapping and survival in systemic light-chain amyloidosis. Eur Heart J. 2015;36:244–251. - PMC - PubMed

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