Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus

doi:10.1016/j.jacadv.2025.101784

Review

. 2025 Jun;4(6 Pt 1):101784.

doi: 10.1016/j.jacadv.2025.101784. Epub 2025 May 14.

Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia; The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia; University of New South Wales Sydney, Sydney, NSW, Australia.
² Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA; Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
³ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Program for the Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
⁵ Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
⁶ Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA; Division of Cardiovascular Medicine, Department of Internal Medicine, VA Ann Arbor Health System, Ann Arbor, Michigan, USA.
⁷ Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia; The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia; University of New South Wales Sydney, Sydney, NSW, Australia.
⁸ Cardiac Amyloidosis Program, Department of Cardiology, Columbia University Irving Medical, New York City, New York, USA.
⁹ Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia; The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.
¹⁰ Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
¹¹ New England Geriatric Research, Education, and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts, USA; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA; Division of Aging, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹² Amyloidosis Center, Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
¹³ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Cardiovascular Center on Aging, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA. Electronic address: Abdulla.Damluji@jhu.edu.

PMID: 40373524
PMCID: PMC12144467
DOI: 10.1016/j.jacadv.2025.101784

Review

Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus

Nicole K Bart et al. JACC Adv. 2025 Jun.

. 2025 Jun;4(6 Pt 1):101784.

doi: 10.1016/j.jacadv.2025.101784. Epub 2025 May 14.

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia; The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia; University of New South Wales Sydney, Sydney, NSW, Australia.
² Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA; Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
³ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Program for the Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
⁵ Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
⁶ Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA; Division of Cardiovascular Medicine, Department of Internal Medicine, VA Ann Arbor Health System, Ann Arbor, Michigan, USA.
⁷ Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia; The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia; University of New South Wales Sydney, Sydney, NSW, Australia.
⁸ Cardiac Amyloidosis Program, Department of Cardiology, Columbia University Irving Medical, New York City, New York, USA.
⁹ Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia; The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.
¹⁰ Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
¹¹ New England Geriatric Research, Education, and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts, USA; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA; Division of Aging, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹² Amyloidosis Center, Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
¹³ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Cardiovascular Center on Aging, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA. Electronic address: Abdulla.Damluji@jhu.edu.

PMID: 40373524
PMCID: PMC12144467
DOI: 10.1016/j.jacadv.2025.101784

Abstract

Amyloidosis, which is caused by misfolded proteins that form amyloid fibrils, is predominantly diagnosed in older adults. Although previously considered a rare disease, increased awareness and noninvasive diagnostic methods have resulted in a rise in diagnoses. As a multisystem disease that affects multiple organ systems (cardiac, gastrointestinal, renal, and neurological), there is significant overlap with both geriatric conditions and common conditions in heart failure. Frailty is recognized as a distinct biological syndrome of declines across multiple physiological systems, which prevents maintenance of homeostasis and limits the ability to respond to stressors. Frailty was initially characterized as physical frailty alone; however, it is increasingly recognized that it is multidimensional with components including nutrition, cognitive, psychological, and social. Frailty in cardiovascular disease has become an important risk factor, indicator for disease severity, and can help guide decisions around intervention. In certain patients, frailty may be reversible. Given the lack of consensus definitions, tools, and implementation of frailty in both clinical and research settings in the field of amyloidosis, we convened a group of experts from cardiology, geriatric cardiology, geriatrics, hematology, and allied health to form this state-of-the-art review. There are many points of intersectionality between amyloidosis, aging, and frailty which herald a need for multidisciplinary care. This review document aims to provide guidance in how to understand and address frailty in older patients with a specific focus on cardiac amyloidosis.

Keywords: aging; amyloidosis; frailty; geriatric syndromes; inflammation; multimorbidity; multisystem dysregulation; older adults.

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Conflict of interest statement

Funding support and author disclosures Dr Bart has received research funding from Pfizer; speaking fees from Pfizer; and advisory board fees from Bridge Bio, Novo Nordisk, and Bristol Myers Squibb. Dr Cuddy has received grant support from NIH1K23HL166686-01 and AHA23CDA857664; site support for Helios-B (Alnylam), Cardio-TTRansform (Ionis, Astra Zeneca), and DepleTTR (Alexion); and personal fees from Pfizer, Bridgebio, Ionis, AstraZeneca, Alexion, and Novo-Nordisk. Dr Griffin has received grant support from Pfizer; and personal fees from Pfizer and BridgeBio. Dr Maurer has received grant support from NIHR01HL139671 and AG081582 and grants from Alnylam, BridgeBio, Intellia, and Ionis; and personal fees from Alnylam, Novo-Nordisk, Roche, Prothena Astra Zeneca, Akcea, and Intellia. Dr Nanne has received current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute (PCORI), and the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342). Dr Sanchorawala has received research support (to institution) from Celgene, Millennium-Takeda, Janssen, Prothena, Sorrento, Karyopharm, Oncopeptide, and Caelum–Alexion; has served as a consultant for Pfizer, Janssen, Attralus, GateBio, Abbvie, and BridgeBio; has served on the Scientific advisory board for Proclara, Caelum, Abbview, Janssen, Regeneron, Protego, Pharmatrace, Telix, Prothena, AstraZeneca, and Nexcella. Dr Damluji has received research funding from the Pepper Scholars Program of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center funded by the National Institute on AgingP30-AG021334; has mentored patient-oriented research career development award from the National Heart, Lung, and Blood Institute K23-HL153771, the NIH National Institute of AgingR01-AG078153, and the Patient-Centered Outcomes Research Institute (PCORI). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**Central Illustration**
Multisystem Involvement in Amyloidosis Including Cardiac, Gastrointestinal, Neurological, and Skeletal Muscle ATTRwt = wild-type transthyretin; GI = gastrointestinal; HF = heart failure.

**Figure 1**
Representation of Specific Interventions for Frailty and Amyloidosis That Have “Double Impact” by Resulting in Improvements in Both

**Figure 2**
Flowchart of Key Recommendations GAD-7 = Generalized Anxiety Disorder Instrument; MMSE = Mini-Mental State Examination; NT-proBNP = N-terminal pro–B-type natriuretic peptide.

See this image and copyright information in PMC

References

1. Peng Y., Zhong G.C., Zhou X., Guan L., Zhou L. Frailty and risks of all-cause and cause-specific death in community-dwelling adults: a systematic review and meta-analysis. BMC Geriatr. 2022;22(1):725. - PMC - PubMed
1. Morley J.E. The new geriatric giants. Clin Geriatr Med. 2017;33(3):xi–xii. - PubMed
1. Denfeld Q.E., Jha S.R., Fung E., et al. Assessing and managing frailty in advanced heart failure: an International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2024;43(1):1–27. - PubMed
1. Bart N.K., Powell A., Macdonald P.S. The role of frailty in advanced HF and cardiac transplantation. Front Cardiovasc Med. 2023;10 - PMC - PubMed
1. Damluji A.A., Cohen M.G. The influence of frailty on cardiovascular disease: the time for a “Frailty Academic Research Consortium” is now! Circ Cardiovasc Interv. 2022;15(1) - PMC - PubMed

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[1] Peng Y., Zhong G.C., Zhou X., Guan L., Zhou L. Frailty and risks of all-cause and cause-specific death in community-dwelling adults: a systematic review and meta-analysis. BMC Geriatr. 2022;22(1):725. - PMC - PubMed

[2] Peng Y., Zhong G.C., Zhou X., Guan L., Zhou L. Frailty and risks of all-cause and cause-specific death in community-dwelling adults: a systematic review and meta-analysis. BMC Geriatr. 2022;22(1):725. - PMC - PubMed

[3] Morley J.E. The new geriatric giants. Clin Geriatr Med. 2017;33(3):xi–xii. - PubMed

[4] Morley J.E. The new geriatric giants. Clin Geriatr Med. 2017;33(3):xi–xii. - PubMed

[5] Denfeld Q.E., Jha S.R., Fung E., et al. Assessing and managing frailty in advanced heart failure: an International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2024;43(1):1–27. - PubMed

[6] Denfeld Q.E., Jha S.R., Fung E., et al. Assessing and managing frailty in advanced heart failure: an International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2024;43(1):1–27. - PubMed

[7] Bart N.K., Powell A., Macdonald P.S. The role of frailty in advanced HF and cardiac transplantation. Front Cardiovasc Med. 2023;10 - PMC - PubMed

[8] Bart N.K., Powell A., Macdonald P.S. The role of frailty in advanced HF and cardiac transplantation. Front Cardiovasc Med. 2023;10 - PMC - PubMed

[9] Damluji A.A., Cohen M.G. The influence of frailty on cardiovascular disease: the time for a “Frailty Academic Research Consortium” is now! Circ Cardiovasc Interv. 2022;15(1) - PMC - PubMed

[10] Damluji A.A., Cohen M.G. The influence of frailty on cardiovascular disease: the time for a “Frailty Academic Research Consortium” is now! Circ Cardiovasc Interv. 2022;15(1) - PMC - PubMed

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Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus

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Cardiac Amyloidosis in Older Adults With a Focus on Frailty: JACC: Advances Expert Consensus

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