Abbreviations
ATTR-CM, Transthyretin amyloid cardiomyopathy
ATTRv, Variant transthyretin amyloidosis; hereditary transthyretin amyloidosis
ATTRwt, Wild-type transthyretin amyloidosis
TTR, Transthyretin
Cardiac amyloidosis is a disorder characterized by the accumulation of abnormal proteins in the myocardium, resulting in heart failure and poor clinical outcomes.1 In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has gained increasing recognition due to the emergence of novel treatment options. ATTR-CM is a progressive and life-threatening disease. There are two types of ATTR-CM, a hereditary form (ATTRv) and a wild-type form (ATTRwt). Its prevalence is higher than previously estimated by recent prevalence studies,2 but limited cases have been identified in Taiwan, and it is believed that many patients remain undiagnosed or have passed away before receiving a proper diagnosis. In addition, the genetic mutation of transthyretin (TTR) is highly regional and the specific type of ATTRv, Ala97Ser, which is the most common type of TTR mutation in Taiwan.3 This genetic mutation is less discussed in previous studies.4 The Taiwan Society of Cardiology has recently published an expert consensus on the diagnosis and treatment of cardiac amyloidosis to increase the awareness of this disease, initiating diagnostic work-up and further management.5
The clinical presentation of patients with ATTR-CM is characterized by the cardiac and extra-cardiac (mainly neurological) disorders, which can vary in severity and may not be present in the early stages of the disease. To aid clinicians in identifying potential cases, this expert consensus outlines major and minor red-flag signs of ATTR-CM and provides the usefully mnemonics to assist with recognizing the multisystem and variable clinical presentations associated with this condition. After identification of potential cases, a comprehensive diagnostic work-up involving multidisciplinary specialists, including cardiologists, neurologists, radiologists, nuclear radiologists, and pathologists, is necessary. This expert consensus provides a diagnostic algorithm that is appropriate for the work-up of cardiac amyloidosis in patients with clinical suspicion. The diagnostic algorithm emphasizes the significance of precise interpretation of 99mTc-pyrophosphate scans,6 light chain analysis, the clinical implications of cardiac magnetic resonance, and the optimal timing for biopsy. The use of this algorithm can help prevent unnecessary invasive biopsies and is particularly practical in the clinical setting.
There are growing evidences of these novel treatment option on slowing down the progression of amyloid disposition and improving clinical outcomes.7 However, the treatment option remained limited in cardiac amyloidosis in Taiwan. Until today, the tafamidis is the only available Food and Drug Administration (FDA) approved treatment for ATTR-CM in Taiwan. In ATTR-ACT study, tafamidis was associated with a decrease the all-cause mortality and cardiovascular-related hospitalizations in ATTR-CM patients.4 The most common type of ATTRv in Taiwan is Ala97Ser, the tafamidis can stabilize these variant and further improved outcomes.8,9 Interestingly, the tafamidis can also decreases 99mTc-Pyrophosphate uptake in patients with hereditary Ala97Ser ATTR-CM.10 In recent years, numerous novel treatment options with varying mechanisms have emerged, increasing the prospects for aiding these patients. For asymptomatic patients carrying the TTR gene mutation, establishing a follow-up plan is crucial. According to this consensus recommendations, at least annual follow-up, especially for those with genotypes carrying the risk of early onset symptoms and those nearing the predicted age of disease onset, is necessary. Nevertheless, additional studies are necessary to support this recommendation. In conclusion, cardiac amyloidosis is an important disease that is frequently underdiagnosed. This consensus can assist clinicians in identifying and diagnosing the disease, as well as comprehending the treatment options and follow-up plans for affected patients.
DECLARATION OF CONFLICT OF INTEREST
All the authors declare no conflict of interest.
REFERENCES
- 1.Ruberg FL, Grogan M, Hanna M, et al. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73:2872–2891. doi: 10.1016/j.jacc.2019.04.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Damy T, Costes B, Hagege AA, et al. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness. Eur Heart J. 2016;37:1826–1834. doi: 10.1093/eurheartj/ehv583. [DOI] [PubMed] [Google Scholar]
- 3.Lai HJ, Huang KC, Liang YC, et al. Cardiac manifestations and prognostic implications of hereditary transthyretin amyloidosis associated with transthyretin Ala97Ser. J Formos Med Assoc. 2020;119:693–700. doi: 10.1016/j.jfma.2019.08.027. [DOI] [PubMed] [Google Scholar]
- 4.Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007–1016. doi: 10.1056/NEJMoa1805689. [DOI] [PubMed] [Google Scholar]
- 5.Wang CC, Chang WT, Lin YH, et al. 2023 expert consensus of the Taiwan Society of Cardiology on the diagnosis and treatment of cardiac amyloidosis. Acta Cardiol Sin. 2023;39:511–543. doi: 10.6515/ACS.202307_39(4).20230610A. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Huang YH, Lin YH, Yen RF, et al. 2021 advocacy statements for the role of (99m)Tc-pyrophosphate scintigraphy in the diagnosis of transthyretin cardiac amyloidosis: a report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China. Acta Cardiol Sin. 2021;37:221–231. doi: 10.6515/ACS.202105_37(3).20210420A. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kittleson MM, Maurer MS, Ambardekar AV, et al. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2020;142:e7–e22. doi: 10.1161/CIR.0000000000000792. [DOI] [PubMed] [Google Scholar]
- 8.Wu YA, Tsai CH, Su MY, et al. Reverse cardiac remodelling and dysfunction in A97S transthyretin cardiac amyloidosis after tafamidis treatment. ESC Heart Fail. 2022;9:4335–4339. doi: 10.1002/ehf2.14165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Tsai CH, Yu AL, Wu YK, et al. Efficacy of tafamidis in patients with Ala97Ser hereditary transthyretin cardiac amyloidosis: a six-month follow-up study. Acta Cardiol Sin. 2023;39:619–627. doi: 10.6515/ACS.202307_39(4).20221116A. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Yu AL, Chen YC, Tsai CH, et al. Tafamidis treatment decreases (99m)Tc-pyrophosphate uptake in patients with hereditary Ala97Ser transthyretin amyloid cardiomyopathy. JACC Cardiovasc Imaging. 2023;16:866–867. doi: 10.1016/j.jcmg.2022.12.016. [DOI] [PubMed] [Google Scholar]