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. 2024 Dec;12(12):1994-2006.
doi: 10.1016/j.jchf.2024.07.007. Epub 2024 Sep 4.

Functional Status and Quality of Life in Light-Chain Amyloidosis: Advanced Imaging, Longitudinal Changes, and Outcomes

Olivier F Clerc  1 , Shilpa Vijayakumar  2 , Sarah A M Cuddy  1 , Giada Bianchi  3 , Jocelyn Canseco Neri  1 , Alexandra Taylor  1 , Dominik C Benz  1 , Yesh Datar  1 , Marie Foley Kijewski  4 , Andrew J Yee  5 , Frederick L Ruberg  6 , Ronglih Liao  7 , Rodney H Falk  8 , Vaishali Sanchorawala  6 , Sharmila Dorbala  9
Affiliations

Functional Status and Quality of Life in Light-Chain Amyloidosis: Advanced Imaging, Longitudinal Changes, and Outcomes

Olivier F Clerc et al. JACC Heart Fail. 2024 Dec.

Abstract

Background: In light-chain (AL) amyloidosis, whether functional status and heart failure-related quality of life (HF-QOL) correlate with cardiomyopathy severity, improve with therapy, and are associated with major adverse cardiac events (MACE) beyond validated scores is not well-known.

Objectives: The authors aimed to: 1) correlate functional status and HF-QOL with cardiomyopathy severity; 2) analyze their longitudinal changes; and 3) assess their independent associations with MACE.

Methods: This study included 106 participants with AL amyloidosis, with 81% having AL cardiomyopathy. Functional status was evaluated using the NYHA functional class, the Karnofsky scale, and the 6-minute walk distance (6MWD), and HF-QOL using the MLWHFQ (Minnesota Living with Heart Failure Questionnaire). Cardiomyopathy severity was assessed by cardiac 18F-florbetapir positron emission tomography/computed tomography, cardiac magnetic resonance, echocardiography, and serum cardiac biomarkers. MACE were defined as all-cause death, heart failure hospitalization, or cardiac transplantation.

Results: NYHA functional class, Karnofsky scale, 6MWD, and MLWHFQ were impaired substantially in participants with recently diagnosed AL cardiomyopathy (P < 0.001), and correlated with all markers of cardiomyopathy severity (P ≤ 0.010). NYHA functional class, 6MWD, and MLWHFQ improved at 12 months in participants with cardiomyopathy (P ≤ 0.013). All measures of functional status and HF-QOL were associated with MACE (P ≤ 0.017), independent of Mayo stage for 6MWD and MLWHFQ (P ≤ 0.006).

Conclusions: Functional status and HF-QOL were associated with AL cardiomyopathy severity, improved on therapy within 12 months, and were associated with MACE, independently of Mayo stage for 6MWD and MLWHFQ. They may be validated further in addition to prognostic scores and as surrogate outcomes for future studies.

Keywords: Light-chain (AL) amyloidosis; cardiomyopathy; functional status; heart failure–related quality of life; longitudinal changes; major adverse cardiac outcomes.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the National Institutes of Health (NIH) (NCT02641145). Dr Clerc has received a research fellowship from the International Society of Amyloidosis and Pfizer. Dr Vijayakumar has received a research fellowship from the Amyloidosis Foundation. Dr Cuddy is supported by NIH 1K23HL166686-01 and AHA 23CDA857664; has received an investigator-initiated research grant from Pfizer; and has received consulting fees from Ionis Pharmaceuticals, AstraZeneca, BridgeBio, and Novo Nordisk. Dr Bianchi was partially supported by a grant K08 CA245100; and has received consulting fees from Prothena. Dr Benz has received investigator-initiated funding from AstraZeneca; and has received consulting fees from Pfizer and travel support from Philips Research and Pfizer. Dr Yee has received consulting fees from AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, Regeneron, Sanofi, and Takeda. Dr Ruberg is supported by NIH R01 HL 130563; has received consulting fees from Pfizer, AstraZeneca, and Attralus; and has received research support to his institution from Pfizer, Alnylam, Anumana, and Ionis/Akcea. Dr Liao is supported by NIH AHA16 CSA 2888 0004 and AHA19SRG34950011. Dr Falk is supported by NIH R01 HL 130563; has received consulting fees from Ionis Pharmaceuticals, Alnylam Pharmaceuticals, and Caelum Biosciences; and has received research funding from GlaxoSmithKline and Akcea. Dr Sanchorawala has received research support from Takeda, Celgene, Janssen, and Prothena; and is a scientific advisory board member for Caleum Biosciences. Dr Dorbala is supported by NIH R01 HL 130563, K24 HL 157648, AHA16 CSA 2888 0004, and AHA19SRG34950011; has received consulting fees from Pfizer, GE Health Care, AstraZeneca, and Novo Nordisk; and has received investigator-initiated grant from Pfizer, GE Healthcare, Attralus, Siemens, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Functional Status and HF-QOL of Life at Baseline and at Follow-up Visits
Medians of each variable were converted to percentages of chart radius with better values further away from the center. Hence, a larger surface represents better functional status and HF-QOL. AL-CMP/AL-non-CMP: Recently-diagnosed light-chain amyloidosis with/without cardiomyopathy. AL-res-CMP: Light-chain amyloidosis with hematologic response for >12 months and cardiomyopathy. HF-QOL: Heart-failure-related quality of life. MLWHFQ: Minnesota living with heart failure questionnaire. NYHA: New York Heart Association.
Figure 2.
Figure 2.. Outcome Analysis Based on Functional Status and HF-QOL
Kaplan-Meier analysis and the log-rank test for trend were performed for MACE by levels of functional status and HF-QOL. HF-QOL: Heart-failure-related quality of life. MACE: Major adverse cardiac events. MLWHFQ: Minnesota living with heart failure questionnaire. NYHA: New York Heart Association.
Figure 3.
Figure 3.. Outcome Analysis Based on Functional Status and HF-QOL Adjusted for Mayo Stage
In Cox regression, the 6-minute walk distance and the MLWHFQ total score remained significantly associated with MACE after adjustment for Mayo stage 2004. HF-QOL: Heart-failure-related quality of life. MACE: Major adverse cardiac events. MLWHFQ: Minnesota living with heart failure questionnaire.
See this image and copyright information in PMC

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;68:1323–41. - PubMed
    1. Dispenzieri A, Gertz MA, Kyle RA et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol 2004;22:3751–7. - PubMed
    1. Bayliss M, McCausland KL, Guthrie SD, White MK. The burden of amyloid light chain amyloidosis on health-related quality of life. Orphanet J Rare Dis 2017;12:15. - PMC - PubMed
    1. Yates JW, Chalmer B, McKegney FP. Evaluation of patients with advanced cancer using the Karnofsky performance status. Cancer 1980;45:2220–4. - PubMed
    1. Cosiano MF, Tobin R, Mentz RJ, Greene SJ. Physical Functioning in Heart Failure With Preserved Ejection Fraction. J Card Fail 2021;27:1002–1016. - PubMed