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Observational Study
. 2025 Sep;18(9):e012777.
doi: 10.1161/CIRCHEARTFAILURE.125.012777. Epub 2025 Jul 2.

Prognostic Value of Malnutrition, Frailty, and Physical Performance in Transthyretin Cardiac Amyloidosis: Insights From a Prospective Multicenter Cohort Study

Carlo Fumagalli  1   2 , Mattia Zampieri  2 , Roberto Presta  3 , Greta Pini  2 , Giulia Vetere  4 , Alessia Argirò  2 , Simone Longhi  5 , Giacomo Tini  6 , Beatrice Musumeci  6 , Giuseppe Limongelli  7 , Giuseppe Palmiero  7 , Federica Verrillo  7 , Matteo Beltrami  2 , Mario Bo  3 , Gaetano De Ferrari  3 , Lorenzo Tofani  8 , Celestino Sardu  1 , Raffaele Marfella  1 , Niccolò Marchionni  9 , Federico Perfetto  3 , Iacopo Olivotto  9 , Stefano Fumagalli  9 , Mathew S Maurer  10 , Marianna Fontana  11 , Andrea Ungar  9 , Francesco Cappelli  2   9
Affiliations
Observational Study

Prognostic Value of Malnutrition, Frailty, and Physical Performance in Transthyretin Cardiac Amyloidosis: Insights From a Prospective Multicenter Cohort Study

Carlo Fumagalli et al. Circ Heart Fail. 2025 Sep.

Abstract

Background: The prevalence of transthyretin cardiac amyloidosis among older adults (often octogenarians) is increasing. We aimed to determine whether age and geriatric syndromes bear any impact on the management and outcomes in transthyretin cardiac amyloidosis and assess the risk of ageism.

Methods: In a prospective, multicenter cohort study, 256 patients diagnosed with transthyretin cardiac amyloidosis from March 2021 to March 2024 underwent comprehensive geriatric assessment (CGA). The study evaluated the prevalence and clinical associations of CGAs across different disease stages (National Amyloidosis Centre stage). Key CGA domains included disability, malnutrition, depression, frailty, Short Physical Performance Battery, and cumulative deficits (sum of the single CGA items). Associations of these measures with disease-modifying therapy and overall mortality were analyzed.

Results: Median age was 82 years (men: n=223 [87%]; variant: n=19 [7.4%]); 129 (50.3%) patients received disease modifiers. Those ≥85 years had significantly lower odds of receiving disease-modifying therapy even after adjusting for disability, frailty, and cumulative deficits. Over 1.9 (interquartile range, 1.0-2.3) years, 45 (17.6%) patients died. After adjustment for National Amyloidosis Centre stage, diuretics and disease modifiers, CGA domains of disability, malnutrition, Short Physical Performance Battery, frailty, and number of deficits, but not age, were significantly associated with mortality. Assessment of CGA domains improved National Amyloidosis Centre prognostic accuracy.

Conclusions: In a national prospective cohort of patients with transthyretin cardiac amyloidosis, older age was associated with lower prescription of disease modifiers, even among individuals with a low burden of geriatric syndromes. However, when adjusted for geriatric domains, age was not associated with survival, indicating potential ageism. Because some geriatric syndromes may be modifiable, a CGA could enhance risk stratification, reduce age-related bias, and improve outcomes.

Keywords: amyloidosis; frailty; malnutrition; octogenarians; prognosis.

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Conflict of interest statement

Dr Maurer is supported by grants from the National Institutes of Health (R01HL139671 and R01AG081582-01); grants and personal fees from Alnylam, Pfizer, Eidos, Prothena, and Ionis; and personal fees from AstraZeneca, Akcea, Intellia, and Novo Nordisk. Dr Fontana is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447). Dr Marfella is supported by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (scientific research programs of high national interest; No. 2020LM8WNW). Dr Longhi is supported by the Italian Ministry of Health, RC-2024-2789983 project, and the European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart. Dr Olivotto is supported by grants for Respect, StratifyHF, and SmashHCM and has received grants from Bayer, MyoKardia Inc, which is a wholly owned subsidiary of Bristol Myers Squibb, Sanofi Genzyme, and Shire, which is now part of Takeda; personal fees from Bayer, Sanofi Genzyme, and Shire/Takeda; and payments as a consultant from MyoKardia Inc. Dr Perfetto has received honoraria for advisory board participation from Pfizer, Alnylam, and Akcea. Dr Ungar is supported by Piano Nazionale di Ripresa e Resilienza grants. F. Cappelli has received consultant fees from Pfizer, Alnylam, AstraZeneca, BridgeBio, Daiichi Sankyo, and NovoNordisk. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Prevalence of comprehensive geriatric assessment items by year at enrollment. CFS indicates Clinical Frailty Scale; NAC, National Amyloidosis Centre; and SPPB, Short Physical Performance Battery. Years have been divided as follows: year 1, March 2021–April 2022; year 2, April 2022–March 2023; and year 3, April 2023–March 2024.
Figure 2.
Figure 2.
Survival analysis of patients diagnosed with transthyretin cardiac amyloidosis referred to a comprehensive geriatric assessment according to the presence or absence of disease-modifying therapy. CFS indicates Clinical Frailty Scale; and SPPB, Short Physical Performance Battery.
See this image and copyright information in PMC

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