Prevalence of transthyretin-related amyloidosis in Tuscany: Data from the regional population-based registry

doi:10.1016/j.ijcard.2023.03.063

International Journal of Cardiology

Volume 382, 1 July 2023, Pages 87-90

https://doi.org/10.1016/j.ijcard.2023.03.063 Get rights and content

Highlights

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The exact prevalence transthyretin amyloidosis (ATTR) is still largely unknown.
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Available data so far are mostly drawn from insurance claims or registries.
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Prevalence of ATTRwt and ATTRv is 90.3 and 9.5 per million based on data from a Tuscany registry of rare diseases.
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ATTR is increasingly being recognized and is less uncommon than previously believed.

Abstract

The limited available data regarding the prevalence of transthyretin amyloidosis, both for wild-type (ATTRwt) and hereditary form (ATTRv), is inferred from highly selected patients and subsequent extrapolations that limit the comprehension of the clinical disease impact. The Tuscan healthcare system in 2006 developed a web-based rare disease registry, to monitor and profile patients affected by rare diseases.

Clinicians belonging to regional validated healthcare data centres can register patients at the diagnosis, with a rigorous approach and distinguishing the types of amyloidosis, i.e., ATTRwt versus ATTRv. Thanks to this data collection method, available from July 2006 and extended with electronic therapy plans related to a diagnosis since May 2017, we analysed prevalence and incidence of ATTR and its subtypes. On November 30th 2022, ATTRwt prevalence in Tuscany is 90.3 per 1,000,000 persons and ATTRv prevalence is 9.5 per 1,000,000 persons, whereas the annual incidence ranges from 14.4 to 26.7 per 1,000,000 persons and from 0.8 to 2.7 per 1,000,000 persons, respectively. The male gender is predominant in both forms. All except one patient showed evidence of cardiomyopathy. This epidemiological data requires attention, not only to increase the effort for the clinical management and earlier diagnosis, but also to underline the need for the disease-specific treatments.

Section snippets

Methods

Since July 2006 the Tuscan health care system has developed a web-based rare disease registry, to monitor and profile patients affected by rare diseases (https://malattierare.toscana.it/dati-statistici/registro-toscano-malattie-rare/), for all rare diseases (RDs) in Italian ministerial decree attachments since 2001 until 2017, including amyloidosis; the registry is managed by FTGM (Fondazione Toscana Gabriele Monasterio for medical and public health research in Pisa). This web-based

Results

From July 2006 to November 2022, 367 alive patients with ATTR had been registered in Tuscany, including 332 with ATTRwt and 35 patients with ATTRv. This translates into an estimated prevalence of 90.3 per 1,000,000 for ATTRwt and 9.5 per 1,000,000 for ATTRv. The annual incidence ranged from 14.4 to 26.7 per 1,000,000 for ATTRwt and from 0.8 to 2.7 per 1,000,000 for ATTRv. Mean age at diagnosis of the 367 patients was 74 years. Two-thirds of patients with ATTRwt were in the 80–99 year age-range,

Discussion

The prevalence of ATTRwt and ATTRv in Tuscany is 90.3 and 9.5 per million respectively, with an annual incidence ranging from 14.4 to 26.7 and from 0.8 to 2.7 per million respectively, an increasing trend in diagnoses during the recent years. This data likely results from a greater awareness in the clinical community, an organized regional network with 2 Referral Centres in Florence and Pisa, favouring early and comprehensive diagnostic process, allowing rapid ATTR diagnoses, as well as an

Disclosures

Iacopo Olivotto: Advisory board and research grants from: Bristol Myers Squibb, Cytokinetics, Boston Scientific, Sanofi Genzyme, Amicus, Menarini International, Bayer, Tenaya, Rocket Pharma.

Francesco Cappelli: Advisory board and research grants from Pfizer, Alnylam, Novonordisk.

Federico Perfetto: Advisory board and research grants from Pfizer, Alnylam, Akcea Federico.

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There are more references available in the full text version of this article.

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Defining the epidemiology of systemic and cardiac amyloidosis (CA) is a contemporary challenge. The present study aimed to estimate incidence and time trends in amyloidosis-related hospitalizations (AH) in Veneto Region (5 million inhabitants, Northeastern Italy).
International Classification of Diseases (ICD-9) codes were used to identify AH in Veneto from 2010 to 2020. AH were defined as any hospitalization with a discharge summary reporting an ICD-9 code for systemic amyloidosis. Hospitalization for CA was defined as records with ICD-9 code for systemic amyloidosis and ICD-9 code for heart failure,cardiomyopathy or arrhythmia. Hospital/outpatient encounters for carpal tunnel syndrome (CTS) surgeries also were extracted. AH incidence was estimated using a buffer of 5 years.
In the time range 2015–2020, the incidence rate of AH was 23.5 cases per 10⁶ (95% confidence interval, CI, 21.8; 25.3), mainly affecting patients>65 years (76.2%) and males (63.5%), with a progressively increasing trend (percent annual increase 17%, 95% CI 12; 22%). The 10 year prevalence of AH in 2020 was 124.5 per 10⁶ (95% CI 114.9; 134.8). In 2020, annual hospitalized prevalent cases of CA were about 70% of all cases (159/228), mainly patients >65 years and males. Among patients with multiple CTS surgeries, a subsequent code for cardiac disease was found in 913 after a median of 3.9 years, more frequently in men than in women (463/6.526 7.1% versus 450/11.406 3.9%).
In Veneto, we recorded a significantly increasing trend in the incidence of AH, with concordant increasing prevalence estimates.
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Identification and management of gastrointestinal manifestations of hereditary transthyretin amyloidosis: Recommendations from an Italian group of experts
2023, Digestive and Liver Disease
Gastrointestinal manifestations are common across all hereditary transthyretin amyloidosis (ATTRv) genotypes. However, they are poorly specific, and their recognition as part of ATTRv is difficult, resulting in misdiagnosis with more common conditions. Moreover, delays in diagnosis occur because of fragmented knowledge, a shortage of centers of excellence and specialists dedicated to ATTRv management, and the scarce involvement of gastroenterologists in multidisciplinary teams. A group of Italian gastroenterologists with experience in the management of ATTRv took part in a project aimed at assessing the awareness of ATTRv among the community of Italian gastroenterologists through an online survey and providing education about practical aspects of ATTRv management. Survey results reported low participation, and very few patients with ATTRv were cared for by gastroenterologists. This highlights the need for greater attention to rare diseases in gastroenterology and emphasizes increasing awareness of ATTRv and diagnostic suspicion. Based on the experts' recommendations, a diagnosis of ATTRv should be suspected when at least one of the 'red flags' is detected. Subsequently, it is suggested to promptly ask for genetic testing and exclude a serum and urinary monoclonal protein, even before the detection of amyloid in biopsy samples, particularly in non-endemic areas.
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Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy
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¹: These authors equally contributed to this work.

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Short communicationPrevalence of transthyretin-related amyloidosis in Tuscany: Data from the regional population-based registry

Highlights

Abstract

Section snippets

Methods

Results

Discussion

Disclosures

J. Am. Coll. Cardiol.

Mayo Clin. Proc.

Int. J. Cardiol.

ATTRv amyloidosis Italian Registry: clinical and epidemiological data

Amyloid.

Incidence of light chain amyloidosis in Florence metropolitan area, Italy: a population-based study

Amyloid.

Global epidemiology of amyloid light-chain amyloidosis

Orphanet J. Rare Dis.

Short communication
Prevalence of transthyretin-related amyloidosis in Tuscany: Data from the regional population-based registry