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Multicenter Study
. 2025 Nov 4;11(7):1015-1022.
doi: 10.1093/ehjqcco/qcaf024.

Change in prevalence of ATTR variants in Italy: results from a national survey

Carlo Fumagalli  1   2 , Simone Longhi  3   4 , Alberto Aimo  5   6 , Alessia Argirò  2 , Alessandro Barilaro  7 , Elena Biagini  3   4 , Giulia Biagioni  2 , Marco Ceccanti  8 , Alberto Cipriani  9 , Cristina Chimenti  10 , Laura De Michieli  9 , Gianluca Di Bella  11 , Michele Emdin  5   6 , Francesca Graziani  12 , Pietro Guaraldi  13 , Massimo Imazio  14 , Giuseppe Limongelli  15 , Carla Lofiego  16 , Marco Luigetti  17   18 , Stefania Marazia  19 , Filomena My  20 , Francesco Musca  21 , Paolo Ossola  21 , Giovanni Palladini  22   23 , Stefano Perlini  23   24 , Aldostefano Porcari  25   26 , Roberta Mussinelli  22   23 , Beatrice Musumeci  27 , Giuseppe Palmiero  15 , Federico Perfetto  2 , Massimo Russo  11 , Giacomo Tini  27 , Giuseppe Vergaro  5   6 , Fabio Vagnarelli  16 , Federica Verrillo  15 , Guerino Giuseppe Varrà  25 , Maria Ausilia Sciarrone  18 , Gianfranco Sinagra  25 , Marco Merlo  24 , Laura Obici  23 , Francesco Cappelli  2
Affiliations
Multicenter Study

Change in prevalence of ATTR variants in Italy: results from a national survey

Carlo Fumagalli et al. Eur Heart J Qual Care Clin Outcomes. .

Abstract

Aims: Hereditary transthyretin amyloidosis (ATTRv) is a rare, heterogeneous, inherited disorder caused by over 130 gene mutations. Its prevalence was estimated to 4.33/million in 2020 in Italy. Whether growing disease awareness and improved diagnostics may have increased national diagnoses in the last 4 years is unresolved.

Methods and results: All alive ATTRv diagnoses from 2004 to 2024 from 16 Italian referral centres were retrospectively assessed and included in the analysis. As of March 2024, 373 ATTRv patients were in active follow-up, with an overall national prevalence increased from 2020 previous survey up to 6.33/million. The most prevalent mutations were Ile68Leu (25.1%), Phe64Leu (21.9%), Val30Met (19.3%), Glu89Gln (10.7%), and Val122Ile (6.7%). Ile68Leu, Val122Ile, and Val30Met were more common in Northern and Central Italy, while Glu89Gln and Phe64Leu were prevalent in Southern Italy. Cardiovascular phenotype was the most common (35.6%), followed by neuropathic (33.2%) and mixed phenotypes (31.2%). Referral to disease-specific therapy mirrored the change in epidemiology.

Conclusion: ATTRv prevalence in Italy has increased by 50% in a 4 years' time frame, with a shift towards milder disease stages and more mixed phenotypes. These changes may reflect improved disease awareness, enhanced genetic screening, and comprehensive care in specialized centres.

Keywords: Epidemiology; Genotype; Screening; Transthyretin cardiac amyloidosis.

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Conflict of interest statement

Conflict of interest: A.B. received financial grants (honoraria and speaking) from Alnylam, and travel grants from Alnylam, Sanofi Genzyme. F.C. received advisory board honoraria from Pfizer, Alnylam, Astra Zeneca, Amicus, Novonordisk, Bridgebio, Daiichi Sankyo. Bayer. F.G. has received research grant from Takeda; funding from: Takeda, Sanofi, Alnylam, Amicus Therapeutics and Chiesi; advisory board/speaker fees from Amicus Therapeutics, Sanofi Genzyme, Takeda, Shire and Alnylam and travel support from Pfizer, Takeda and Amicus. G.P. received advisory board honoraria from Pfizer, Life Molecular Science, Protego. G.T. has received consultant honoraria from Alnylam. M.L. received financial grants (honoraria and speaking) from Ackea, Alnylam, AstraZeneca, Sobi, and Pfizer and travel grants from Ackea, Alnylam, AstraZeneca, Sobi, Pfizer, Kedrion, and Grifols. S.L. received fees at meetings and Advisory Boards for Pfizer and Alnylam. P.G. has been advisory board member of Alnylam and Sobi; received speaker fees and honoraria from Akcea Therapeutics, Alnylam, Chiesi and Theravance Biopharma.

Publication types

Supplementary concepts