cardiac amyloidosis

Last edited 05/2021 and last reviewed 09/2021

Although the heart may be involved in all forms of amyloidosis, cardiac amylodosis is most commonly a result of immunocyte disease (and resultant AL fibril deposition). Clinical cardiac abnormality is also associated with deposition of AA fibrils in familial Mediterrranean fever.

It is often an incidental post-mortem finding in an elderly patient (>50% of those over 70 yrs have cardiac amyloid). Deposits are usually widely spaced but when they occur subendocardially there is a risk of conducting tissue damage and arrhythmias.

Cardiac amyloidosis is a cause of restrictive cardiomyopathy.

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Cardiovascular involvement of amyloidosis is present in 90% of cases, which is frequently associated with the primary form of the disease (AL amyloidosis).

• clinical manifestations are represented by heart failure due to restrictive myocardiopathy and electrical impulse conduction abnormalities, which are clinically remarkable in up to 50% of the cases

The prognosis of patients with systemic amyloidosis (AL amyloidosis) is directly associated with the presence of cardiac involvement, such that survival does not usually exceed 4 months after the onset of heart failure signs and symptoms (1)

Transthyretin amyloid (aTTR) cardiomyopathy

• results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium
  • can be inherited as an autosomal dominant trait caused by pathogenic variants in the transthyretin gene TTR (ATTRv)
  • or
  • by the deposition of ATTRwt (wild-type transthyretin protein), previously called senile cardiac amyloidosis
• survival is much better for TTR amyloid compared to AL amyloidosis
• targets for disease-modifying therapies in cardiac amyloidosis include TTR silencing, TTR stabilization, and TTR disruption

Reference:

• Morais GCP et al. Cardiac amyloidosis: a challenging diagnosis.Autops Case Rep. 2014 Oct-Dec; 4(4): 9-17
• Cavusoglu Y et al. Cardiac amyloidosis: Recent advances in the diagnosis and therapy.Turk Kardiyol Dern Ars. 2019; 47(2): 1-34 | DOI: 10.5543/tkda.2019.28035
• Kittleson MM et al. Cardiac Amyloidosis: Evolving Diagnosis and Management - A Scientific Statement From the American Heart Association.Circulation. 2020;142:e7-e22. DOI: 10.1161/CIR.0000000000000792