Cardiac amyloidosis — viva

Stem

Practice viva. The examiner asks about an older patient with heart failure and a thick, non-dilated left ventricle, and works through what cardiac amyloidosis is, how to reach a diagnosis, how to treat ATTR and AL, and where ESC, AHA/ACC and ANZ advice differ.

Branch A — What is it?

Examiner: Define cardiac amyloidosis and tell me which types matter.^[3]

Strong answer:

• The ESC 2021 position statement defines it as extracellular deposition of misfolded proteins in the heart, with the pathognomonic histological property of green birefringence under cross-polarised light after Congo red staining.^[3]
• More than 30 proteins can aggregate as amyloid in vivo, but only nine accumulate in the myocardium to cause significant cardiac disease.^[3]
• More than 98% of diagnosed cardiac amyloidosis is AL or ATTR, the latter hereditary (ATTRv) or acquired (ATTRwt).^[3]
• ESC 2026 says wild-type disease accounts for more than 90% of transthyretin amyloidosis.^[1]

Follow-up: Why does the distinction between AL and ATTR matter so much?^[2][1]

• ESC 2023: AL cardiac amyloidosis is associated with more rapid progression of heart failure and a worse prognosis than ATTR.^[2]
• ESC 2026: a timely, definitive diagnosis should be obtained, as outcomes depend largely on early initiation of therapy, particularly in AL.^[1]
• The 2024 ANZ consensus statement gives an approximate untreated life expectancy of 4 years for ATTR amyloidosis, but as little as 3 months for advanced cardiac AL amyloidosis.^[13]

Branch B — Getting to the diagnosis

Examiner: How do you test a patient in whom you suspect it?^[1][3]

Strong answer:

• ESC 2026: in HF with a suspicion of cardiac amyloidosis, initial testing with serum and urine immunofixation, a serum free light chain assay and DPD/PYP/HMDP bone scintigraphy is recommended (Class I, Level B).^[1]
• The ESC 2021 position statement builds its algorithm on scintigraphy coupled to SPIE, UPIE and serum free light chain quantification.^[3]
• The combination of SPIE, UPIE and serum free light chains has a sensitivity of 99% for the abnormal pro-amyloidotic precursor in AL amyloidosis (ESC 2021 position statement).^[3]
• The 2024 ANZ consensus statement also recommends simultaneous screening with bone scintigraphy and blood and urine testing for a monoclonal protein.^[13]

Follow-up: The scan shows Grade 3 uptake, but the free light chain ratio is abnormal. What now?^[3]

• ESC 2021 position statement: ATTR with concomitant MGUS (or another FLC-producing haematological disorder), AL amyloidosis, or both together are possible; diagnosis requires histology with amyloid typing, usually via endomyocardial biopsy.^[3]
• If any of SPIE, UPIE or the serum free light chain assay is abnormal, bone scintigraphy should not be used to establish the diagnosis of transthyretin amyloidosis.^[3]
• The 2022 AHA/ACC/HFSA guideline adds that PYP scans may be positive even in AL amyloidosis, so scintigraphy alone cannot distinguish ATTR-CM from AL-CM.^[4]

Branch C — Treating ATTR

Examiner: The diagnosis is wild-type ATTR with NYHA class II symptoms. What do you offer?^[1]

Strong answer:

• 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]
• 2022 AHA/ACC/HFSA: in select patients with wild-type or variant ATTR cardiac amyloidosis and NYHA class I to III symptoms, tafamidis is indicated to reduce cardiovascular morbidity and mortality (COR 1, LOE B-R).^[14]
• ESC 2026 notes that none of the studies compared TTR silencers with stabilisers, or monotherapy with combination therapy, head to head.^[1]

Follow-up: Summarise the evidence behind those drugs.^[9][10][11]

• ATTR-ACT: tafamidis lowered all-cause mortality (29.5% vs 42.9%; hazard ratio 0.70, 95% CI 0.51 to 0.96) and cardiovascular-related hospitalisations (0.48 vs 0.70 per year) over 30 months.^[9]
• ATTRibute-CM randomised 632 patients; in the efficacy population (eGFR at least 30 mL/min/1.73 m2) the four-step primary hierarchical analysis favoured acoramidis (win ratio 1.8, 95% CI 1.4 to 2.2).^[10]
• HELIOS-B: vutrisiran lowered the risk of death from any cause and recurrent cardiovascular events (hazard ratio 0.72 overall, 95% CI 0.56 to 0.93).^[11]
• ESC 2026 notes that patisiran reduced functional decline in APOLLO-B but that no morbidity and mortality data are available.^[1]

Branch D — Heart failure care, AF and devices

Examiner: What changes in his supportive care?^[1]

Strong answer:

• ESC 2026: patients with cardiac amyloidosis may poorly tolerate standard HF therapies because of restrictive physiology, autonomic dysfunction, AV conduction disturbance and kidney impairment.^[1]
• ESC 2026: diuretics remain central for congestion but must be used cautiously within a narrow euvolaemic window, and digoxin is generally discouraged because of a high risk of toxicity.^[1]
• ESC 2024 AF: if he has AF, oral anticoagulation is recommended regardless of CHA2DS2-VA score, to prevent ischaemic stroke and thromboembolism (Class I, Level B); the 2022 AHA/ACC/HFSA row calls anticoagulation reasonable to reduce the risk of stroke regardless of CHA2DS2-VASc score (COR 2a, LOE C-LD).^[5][14]

Follow-up: Does he need a defibrillator or a pacemaker?^[2][7]

• ESC 2023: available data do not support ICD use for primary prevention in cardiac amyloidosis.^[2]
• ESC 2022: an ICD should be considered in light-chain or transthyretin cardiac amyloidosis with haemodynamically not-tolerated VT (Class IIa, Level C).^[6]
• ESC 2026 HF also has a general secondary-prevention row for patients with HF that does not name amyloidosis: an ICD is recommended after recovery from a ventricular arrhythmia causing haemodynamic instability, with expected survival of more than 1 year with good functional status, no reversible cause, and not within 48 h of a myocardial infarction, to reduce the risk of sudden death and all-cause death (Class I, Level A).^[1]
• ESC 2021 pacing: conventional indications should be used for pacing in cardiac amyloid; ESC 2023 adds that the clinical threshold for a pacemaker should be low.^[7][2]

Branch E — AL amyloidosis and regional practice

Examiner: A different patient has AL cardiac amyloidosis. Who treats it, and what would an Australian centre do differently?^[1][13]

Strong answer:

• ESC 2026: treatment includes chemotherapy or autologous stem cell transplantation, managed by a multidisciplinary team of oncohaematology specialists and cardiologists, in specialised centres whenever possible.^[1]
• 2022 AHA/ACC/HFSA: patients with AL amyloidosis with cardiac involvement should promptly be referred to haematology-oncology for timely treatment.^[4]
• 2024 ANZ consensus statement: where a monoclonal protein is detected and AL amyloidosis is suspected, urgent haematology referral for work-up including bone marrow biopsy is recommended.^[13]
• The ANZ statement says specialised Australian Amyloidosis Network centres are limited in number and location, but their pathways triage urgent referrals.^[13]