transthyretin cardiac amyloidosis; amyloid transthyretin cardiomyopathy (ATTR-CM)

Epidemiology

• occurs primarily in men > 60 years of age
• may be > 10% in elderly men with preserved LVEF
• hereditary cardiac amyloidosis with Val122Ile mutation in transthyretin gene present in 3.5% of blacks

Pathology

• occurs when misfolded transthyretin protein accumulates as amyloid fibrils in the heart, leading to heart failure & cardiac arrhythmias
• in hereditary cardiac amyloidosis with Val122Ile mutation in transthyretin gene, end-organ damage other than cardiac is uncommon

Genetics

• can be inherited as an autosomal dominant trait
• hereditary cardiac amyloidosis due to Val122Ile mutation in the transthyretin gene
• deposition of wild-type transthyretin protein can occur

Laboratory

• also see cardiac amyloidosis
• biopsy
  • aspiration of abdominal fat pad (first line)
  • myocardial biopsy (last resort)
• amyloid amyloid typing
  • Val122Ile mutation in transthyretin gene is most common variant in hereditary cardiac amyloidosis*

* MGUS may co-occur with transthyretin cardiac amyloidosis

Diagnostic procedures

• electrocardiography
• echocardiography
• see cardiac amyloidosis

Radiology

• cardiac technetium-99m pyrophosphate scintigraphy diagnostic

Complications

• disease interaction(s) of sleep apnea with transthyretin cardiac amyloidosis

Differential diagnosis

• AL amyloidosis

Management

• tafamidis meglumine (Vyndaqel)
• subcutaneous inotersen (Tegsedi) 300 mg weekly
• subcutaneous eplontersen (Wainua) 45 mg every 4 weeks (FDA-approved)
• prior to tafamidis, treatment has been supportive
• liver transplantation for severe disease

More general terms

• transthyretin amyloidosis; ATTR amyloidosis
• cardiac amyloidosis