An article by cardiologists Dr. Grogan and Dr. Scott Wright, published in Mayo Clinic Proceedings in 2023, describes a simple screening regimen that is particularly important for the main risk group for wild-type transthyretin cardiomyopathy – men over 60 and women over 70 – as rapid diagnosis and initiation of treatment has been shown to have a favorable prognosis.
“Cardiac amyloidosis concerns us much more in everyday clinical practice than it used to,” says Prof. Dr. Stephan Achenbach, Clinic Director, Medicine 2, University Hospital Erlangen [1]. The most common forms of amyloidosis with cardiac involvement are AL amyloidosis and transthyretin (TTR) amyloidosis. In recent years, there has been an increase in the number of detected cases of amyloidosis in parallel with advances in diagnosis and treatment [2]. Nowadays, international specialist societies recommend that patients who show a thickening of the left ventricular myocardium of ≥12 mm on echocardiography should undergo further investigations [2].
Is a biopsy indicated or not?
The speaker summarized the most important points of the pragmatic clarification algorithm published by Dr. Grogan and Dr. Scott Wright in 2023 [1,3]. If cardiac amyloidosis is suspected on the basis of clinical symptoms and echocardiography, the following two diagnostic measures are decisive (Table 1) :
- Skeletal scintigraphy
- Determination of light chains in serum
TTR amyloidosis is reliably detected by skeletal scintigraphy and AL amyloidosis may be associated with monoclonal gammopathy. If the scintigraphy is positive and the findings regarding light chains are negative, the diagnosis of TTR amyloidosis can be made, the speaker said, adding: “A biopsy is no longer required in this situation” [1]. If the scintigraphy is negative but the findings on light chains are positive, the whole thing looks a little more complicated. This is because the patient could simply have a monoclonal gammopathy without AL amyloidosis. A biopsy is therefore indicated in this situation. If both scintigraphy and light chains are positive, the diagnosis may be AL amyloidosis, which is revealed by scintigraphy, or TTR amyloidosis with an independent monclonal gammopathy. A biopsy therefore also makes sense in these cases, explained Prof. Achenbach [1]. If both tests are negative, it is highly unlikely to be cardiac amyloidosis.
Long-term data is now available for Tafamidis
Inotersen, patisiran and tafamidis are currently available for the treatment of TTR amyloidosis, with tafamidis (Vindaqel®) currently being the only drug specifically approved for the indication TTR-CM (wild-type and hereditary form) [4]. In the multicenter phase III ATTR-ACT (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) study, which included 441 patients from 13 countries, tafamidis led to a significant reduction in the decline in functional capacity (measured by the 6-minute walk test) and quality of life (KCCQ-OS score**) compared to placebo [5,6]. In addition, the relative frequency of cardiovascular-related hospitalizations and all-cause mortality was significantly lower in the verum group compared to the placebo group. Most of the subjects included in the study were older patients with wild-type TTR-CM, but there were also some younger patients with a hereditary form of TTR-CM, reported Prof. Achenbach [1]. The mean age of the test subjects was 74 years.
** KCCQ-OS-Score = Kansas City Cardiomyopathy Questionnaire-Overall Summary
An analysis of the ATTR-ACT long-term extension study published in 2022 showed that a reduction in mortality was also detectable in the treatment arm after 58 months and that those patients who received early tafamidis therapy survived longer, which underlines the importance of early therapy, the speaker summarized [1,7].
Congress: DGK Cardio Update
Literature:
- “Cardiac imaging, cardiomyopathies, storage diseases”, Prof. Dr. med. Stephan Achenbach, DGK Cardio Update, 23-24.02.2024, Mainz.
- “Care of patients with cardiac amyloidosis”, consensus paper of the German Society of Cardiology, 2023, https://leitlinien.dgk.org/files/2023_konsensuspapier_versorgung_amyloidosepatienten.pdf,(last accessed 02.05.2024)
- Grogan M, Wright RS: Decreasing Door-to-Diagnosis Time in Cardiac Amyloidosis: A Simple “One-Stop Shop” Approach. Mayo Clin Proc 2023; 98(1): 7-10. www.mayoclinicproceedings.org/article/S0025-6196(22)00657-7/fulltext.
- Swissmedic: Medicinal product information, www.swissmedicinfo.ch,(last accessed 02.05.2024)
- Maurer MS, et al: ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2018; 379(11): 1007-1016.
- “European Commission Approves VYNDAQEL®, the First Treatment in the EU for Transthyretin Amyloid Cardiomyopathy (ATTR-CM)”, Pfizer, February 18, 2020.
- Elliott P, et al: Long term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Fail 2022; 15: e008193.
HAUSARZT PRAXIS 2024; 19(5): 18 (published on 25.5.24, ahead of print)
