Medically reviewed by Dr Nabila Laskar, Consultant Cardiologist (GMC 7040901). Cardiac amyloidosis is a condition where abnormal proteins called amyloid fibrils deposit in the heart muscle, causing it to stiffen and thicken. Long considered rare and untreatable, it is now recognised as more common than previously thought and, in certain forms, can be treated effectively with targeted therapy if identified at the right stage.
The two main forms relevant to adult cardiology are light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis. AL amyloidosis is caused by abnormal immunoglobulin light chains produced by a plasma cell disorder, is relatively fast progressing, and is managed in close collaboration with haematology. ATTR amyloidosis arises from misfolding of the transthyretin protein, either from an inherited genetic variant (hereditary ATTR) or from the wild-type form that occurs with ageing. Wild-type ATTR amyloidosis predominantly affects older men and is thought to be significantly underdiagnosed, particularly in those presenting with heart failure with preserved ejection fraction or severe aortic stenosis.
Cardiac amyloidosis presents with heart failure symptoms: progressive breathlessness, fatigue, reduced exercise tolerance, and ankle swelling. Certain features suggest amyloidosis rather than other causes of heart failure: a history of carpal tunnel syndrome (bilateral or recurrent) and spinal stenosis are now recognised red flags for ATTR amyloidosis, as amyloid deposits in soft tissue commonly precede overt cardiac involvement. Orthostatic hypotension, peripheral neuropathy, and spontaneous biceps tendon rupture are additional features that should raise suspicion.
Echocardiography typically shows increased wall thickness with a characteristic granular, sparkling appearance of the myocardium, reduced longitudinal strain on deformation imaging, and often preserved ejection fraction with impaired filling (diastolic dysfunction). Cardiac MRI with gadolinium contrast shows the characteristic diffuse subendocardial or transmural late gadolinium enhancement pattern. Bone scintigraphy (DPD or pyrophosphate scan) is highly sensitive and specific for ATTR amyloidosis and can provide non-invasive confirmation. Tissue biopsy may be required in certain cases.
ATTR amyloidosis is now treatable with tafamidis, a transthyretin stabiliser shown to reduce cardiovascular mortality and hospitalisation in patients with symptomatic ATTR cardiac amyloidosis. RNA silencing therapies are also available for hereditary ATTR with neuropathy. The effectiveness of these treatments underscores why early diagnosis is important. AL amyloidosis is managed primarily through treating the underlying plasma cell disorder.
One form, hereditary ATTR amyloidosis, is caused by genetic variants in the TTR gene and is inherited. Wild-type ATTR amyloidosis occurs with ageing and is not inherited. AL amyloidosis is not hereditary.
Wild-type ATTR predominantly affects men over 65. It is significantly underdiagnosed in patients presenting with heart failure with preserved ejection fraction, severe aortic stenosis, or a history of bilateral carpal tunnel syndrome.
ATTR amyloidosis cannot currently be cured, but disease progression can be significantly slowed with tafamidis when started at an appropriate stage. AL amyloidosis can achieve remission if the underlying plasma cell disorder responds to treatment.
It is less rare than previously believed. Improved diagnostic awareness and non-invasive testing have revealed that wild-type ATTR amyloidosis is a meaningful cause of heart failure in older adults that was historically attributed to other causes.