Cardiac amyloidosis: pathogenesis, clinical context, diagnosis and management options

Amyloidosis covers a group of disorders that can manifest in virtually any organ system in the body and is thought to be secondary to misfolding of extracellular proteins with subsequent deposition in tissues. The precursor protein that is produced in excess defines the specific amyloid type. This requires histopathological confirmation using Congo-red dye with its characteristic demonstration of green birefringence under cross-polarized light. There are three main types of amyloidosis associated with cardiac involvement: light-chain (AL), familial or senile (ATTR), and secondary (AA) amyloidosis. The frequency of cardiac involvement and prognosis varies among each type. Amyloid cardiomyopathy commonly manifests as heart failure and the presenting features are usually dyspnoea, oedema, angina, pre-syncope and syncope. The diagnosis of cardiac amyloidosis is very hard and can easily be misdiagnosed. Although the imaging studies (such as echocardiography and cardiovascular magnetic resonance) may guide the diagnosis, tissue biopsy is needed for confirmation. Management of cardiac amyloidosis initially is to treat the underlying heart failure. Pacemaker implantation is usually required in patients with any conduction abnormalities. Transplantation is the next step with worsening heart failure. However, the aim of any treatment in amyloidosis, irrespective of type, is to prevent further deposition of amyloid while managing concurrent symptoms. In this manuscript, we will discuss the pathogenesis of cardiac amyloidosis, diagnostic methods and management options.