Table 1.

Major Etiologies of Cardiac Amyloidosis

Features	Light Chain Cardiac Amyloidosis (AL-CA)	Transthyretin Cardiac Amyloidosis
		Wild type (ATTRwt-CA)	Variant / Hereditary Transthyretin (ATTRv-CA)
Age at diagnosis	5th to 9th decade	7th to 10th decade	3rd to 8th decade
Sex distribution	Roughly equal male:female	Very significant male predominance	Male predominance
Precursor protein	Light-chain	Transthyretin	Transthyretin
Genetic etiology	None	None	Autosomal dominant inheritance
Genetic modifier to therapeutic efficacy	t(11,14) presence – poor response to bortezomib but responsive to venetoclax	None	None
Extracardiac involvement	Nerves, kidney, liver, gastrointestinal tract, skin, tongue/soft tissue	Carpal tunnel, lumbar spine, gastrointestinal tract	Nerves,
Clinical Manifestations	Multi-systemic disease with cardiac and renal involvement (60–70%); liver (15%) and peripheral / autonomic neuropathy (10%)	Predominant cardiac phenotype with a restrictive cardiomyopathy, atrial and ventricular arrhythmias and HFpEF	Depends on variant. Val122Ile predominately cardiac, Thr60Ala mixed and Val30Met predominately neuropathic
Prognosis after diagnosis	Depends on stage. Median survival 4–6 months with advanced heart failure	Depends on stage. Median survival 2–6 years in the absence of treatment	Depends on mutation and stage. Median survival 3–12 years

AL-CA, immunoglobulin light-chain cardiac amyloidosis; ATTRwt, wild-type transthyretin amyloidosis; ATTRv, variant (hereditary, familial) transthyretin amyloidosis; CA, cardiac amyloidosis; HFpEF, heart failure with a preserved ejection fraction.