Cardiac Amyloidosis

Cardiac amyloidosis is extracellular deposition of misfolded protein fibrils in the myocardium, causing restrictive cardiomyopathy.

AL (light chain) amyloidosis: clonal plasma cell disorder; cardiac involvement in about 50%; median survival untreated 6 months with advanced cardiac disease.

ATTR amyloidosis: wild type (age related, men over 65, underdiagnosed cause of heart failure with preserved ejection fraction) or hereditary variant (V122I in 3 to 4% of Black Americans, V30M, T60A).

Rare causes: AA amyloid, apolipoprotein and atrial natriuretic peptide amyloid.

Complications: heart failure, conduction disease, atrial fibrillation, intracardiac thrombus, aortic stenosis (frequent in ATTRwt), orthostatic hypotension.

• Progressive dyspnoea, oedema, fatigue, syncope; heart failure with preserved ejection fraction with intolerance to antihypertensives.
• Low voltage ECG despite thick walls, pseudoinfarct pattern.
• Extracardiac clues: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture (ATTR), peripheral and autonomic neuropathy, macroglossia, periorbital purpura, nephrotic syndrome, hepatomegaly (AL).

• Echocardiography: increased wall thickness (over 12 mm), granular sparkling, biatrial dilatation, apical sparing of longitudinal strain, small pericardial effusion.
• Cardiac MRI: diffuse subendocardial late gadolinium enhancement, elevated extracellular volume.
• Step one: exclude AL with serum free light chains, serum and urine immunofixation. If monoclonal protein present, tissue biopsy (fat pad, bone marrow, endomyocardial) with mass spectrometry typing.
• If no monoclonal protein: technetium pyrophosphate (PYP), DPD or HMDP scintigraphy with Perugini grade 2 or 3 uptake confirms ATTR.
• Genetic testing (TTR sequencing) in all ATTR to distinguish hereditary.
• Staging AL: Mayo staging with NT proBNP and troponin.

ATTR cardiomyopathy

• Tafamidis 61 mg (meglumine 80 mg) daily reduces mortality and hospitalisation (ATTR ACT).
• Acoramidis 712 mg twice daily (stabiliser, improved outcomes).
• Silencers: vutrisiran 25 mg SC every 3 months, patisiran 0.3 mg/kg IV every 3 weeks (neuropathy), eplontersen 45 mg monthly.
• Liver transplantation in selected hereditary V30M neuropathy.

AL amyloidosis

Urgent haematology: daratumumab with cyclophosphamide, bortezomib and dexamethasone (dara CyBorD), followed by autologous stem cell transplant in selected patients. Response measured by free light chains and NT proBNP.

Supportive

• Diuretics (furosemide 40 to 160 mg, torsemide, spironolactone) titrated carefully; avoid hypovolaemia.
• Avoid digoxin, nondihydropyridine calcium channel blockers, and generally beta blockers, ACE inhibitors and ARBs.
• Anticoagulation for atrial fibrillation (apixaban 5 mg twice daily) regardless of score; rhythm control with amiodarone; pacemaker for conduction disease.
• ICD only in selected secondary prevention cases.
• Midodrine 5 to 10 mg for orthostatic hypotension.
• Transcatheter aortic valve implantation in co existing severe aortic stenosis.
• Heart transplantation for suitable AL and ATTR patients.