Cardiac amyloidosis — structured written assessment

SAQ 1 (10 marks)

Practice scenario. A 78-year-old man has heart failure with preserved ejection fraction. His echocardiogram shows increased LV wall thickness, and his ECG shows QRS voltage that is low relative to that thickness. He had bilateral carpal tunnel surgery, and his NT-proBNP is high for the severity of his heart failure.^[1]

1. Name the three red flags in this scenario that appear in ESC 2026 Table 20, say for which form each is marked, and state when ESC 2026 says cardiac amyloidosis should be suspected. (2)^[1]
2. Which initial tests does ESC 2026 recommend for him, with class and level? Give the matching 2022 AHA/ACC/HFSA rows with COR and LOE. (2)^[1][14]
3. Describe the four grades of myocardial uptake on bone scintigraphy. (2)^[3]
4. State the ESC 2021 position statement criteria for diagnosing ATTR cardiac amyloidosis without histology. (2)^[3]
5. His scan shows Grade 3 uptake and all three monoclonal protein tests are normal. What is the next test, and does his age change that? (2)^[3][2]

Model answers — SAQ 1

1. Low or decreased QRS voltage relative to LV thickness and disproportionally elevated NT-proBNP relative to HF severity are marked for both TTR and AL; bilateral carpal tunnel syndrome is marked for TTR only (1 mark).^[1] ESC 2026: cardiac amyloidosis should be suspected in patients with HF and increased LV wall thickness in the presence of specific red flags, particularly in patients aged over 65 years, which fits him (1 mark).^[1]
2. ESC 2026 (patients with established HF): initial diagnostic testing with serum and urine immunofixation, serum free light chains assay and DPD/PYP/HMDP bone scintigraphy is recommended in HF with a suspicion of cardiac amyloidosis (Class I, Level B) (1 mark).^[1] 2022 AHA/ACC/HFSA: screening for serum and urine monoclonal light chains with serum and urine immunofixation electrophoresis and serum free light chains when cardiac amyloidosis is clinically suspected (COR 1, LOE B-NR), and bone scintigraphy to confirm transthyretin cardiac amyloidosis in high clinical suspicion without monoclonal light chains (COR 1, LOE B-NR) (1 mark).^[14]
3. Grade 0: no myocardial uptake and normal bone uptake; Grade 1: myocardial uptake lower than bone (1 mark).^[3] Grade 2: myocardial uptake similar to bone; Grade 3: myocardial uptake greater than bone with reduced or absent bone uptake (1 mark).^[3]
4. Typical echocardiographic or CMR findings with Grade 2 or 3 myocardial uptake on PYP, DPD or HMDP scintigraphy (1 mark).^[3] A clonal dyscrasia excluded by all of serum free light chain assay, serum immunofixation and urine immunofixation; non-invasive criteria are accepted only for ATTR (1 mark).^[3]
5. ATTR cardiac amyloidosis can be diagnosed with Grade 2 or 3 uptake and negative protein tests, and the next step is genetic testing to separate ATTRv from ATTRwt (ESC 2021 position statement) (1 mark).^[3] Age does not change it: ESC 2023 says TTR genetic testing is recommended in all ATTR-CM patients regardless of age, as 5% of ATTR-CM patients aged 70 years or more (and 10% of women) have ATTRv; the 2024 ANZ consensus statement says all patients with confirmed ATTR-CA should have genetic testing (1 mark).^[2][13]

SAQ 2 (10 marks)

Practice scenario. A 76-year-old man has wild-type ATTR cardiac amyloidosis with heart failure in NYHA class II. He has just been found to have atrial fibrillation. He lives in Australia.^[1][5]

1. What disease-specific treatment does ESC 2026 recommend, with class and level, and which earlier ESC rows did it replace? (2)^[1]
2. What do the 2022 AHA/ACC/HFSA recommendation row and value statement say about tafamidis? (2)^[14]
3. Compare the ESC 2024 and 2022 AHA/ACC/HFSA rows on anticoagulation for his AF. (2)^[5][14]
4. Give two ESC 2026 statements on supportive heart failure drugs in cardiac amyloidosis. (2)^[1]
5. What did the 2024 Australia–New Zealand consensus statement say about access to ATTR drugs in Australia and New Zealand? (2)^[13]

Model answers — SAQ 2

1. ESC 2026: a TTR silencer (vutrisiran) or stabiliser (tafamidis or acoramidis) is recommended in variant or wild-type ATTR cardiac amyloidosis with NYHA classes I–III, to reduce progression of symptoms and the risk of cardiovascular hospitalisation and all-cause death (Class I, Level A) (1 mark).^[1] It replaced the 2021 ESC rows recommending tafamidis in genetic-testing-proven hereditary TTR-CA and in wild-type TTR-CA with NYHA class I or II symptoms (Class I, Level B) (1 mark).^[1]
2. Recommendation row: in select patients with wild-type or variant transthyretin cardiac amyloidosis and NYHA class I to III HF symptoms, tafamidis is indicated to reduce cardiovascular morbidity and mortality (COR 1, LOE B-R) (1 mark).^[14] Value statement: at 2020 list prices, tafamidis provides low economic value (more than 180 000 US dollars per QALY gained) (low value, B-NR) (1 mark).^[14]
3. ESC 2024 AF: oral anticoagulation is recommended in all patients with AF and cardiac amyloidosis, regardless of CHA2DS2-VA score, to prevent ischaemic stroke and thromboembolism (Class I, Level B) (1 mark).^[5] 2022 AHA/ACC/HFSA: in cardiac amyloidosis with AF, anticoagulation is reasonable to reduce the risk of stroke regardless of the CHA2DS2-VASc score (COR 2a, LOE C-LD); both apply regardless of score, but with different strength (1 mark).^[14]
4. ESC 2026 says evidence for foundational medical therapy in cardiac amyloidosis is still scarce and limited to post-hoc analyses of trials or retrospective studies; within that, any two of: diuretics remain central for congestion but must be used cautiously within a narrow euvolaemic window; evidence supports the safety and benefit of SGLT2 inhibitors (1 mark each).^[1] An MRA might also be useful; beta-blockers and ACE inhibitors, ARNI or ARB require caution, individualised decisions and close monitoring; digoxin is generally discouraged because of a high risk of toxicity (1 mark each).^[1]
5. Tafamidis had received a positive Pharmaceutical Benefits Advisory Committee recommendation and would soon be available for ATTR-CA in NYHA class 1 and 2, with prescribing limited to cardiologists and amyloidosis specialists in Australia, but would not be readily available in New Zealand (1 mark).^[13] Diflunisal was available through the Special Access Scheme at all Australian Amyloidosis Network centres, and acoramidis and TTR synthesis suppressors were not yet available in Australia or New Zealand (1 mark).^[13]