Amyloid Cardiomyopathy: Disease on the Rise.

Abstract

Amyloidoses represent a group of human degenerative diseases characterized by the deposition of aggregates of abnormally folded proteins in single or multi-organs. Whereas neurological amyloidoses, such as Alzheimer and Parkinson disease, have received the greatest recognition, there also exists many systemic amyloidoses that affect many target organs, including the heart. Cardiac amyloidosis is primarily associated with the systemic production and release of many amyloidogenic proteins, notably immunoglobulin light chain or transthyretin (TTR). AL (light chain amyloidosis) is the result of a clonal plasma cell dyscrasia and production of amyloidgenic light chain proteins. TTR amyloidosis may result from normal wild-type amyloidogenic TTR protein as seen in the elderly (known as senile systemic amyloidosis or ATTRwt) or from mutations in the TTR protein (ATTRm) as in familial amyloid cardiomyopathy.1,2 Cardiac deposition of amyloidogenic proteins often results in an aggressive form of heart disease with resulting cardiac failure that is largely resistant to many common heart failure therapies. Although once thought to be a rare disease, cardiac amyloidosis is more recently acknowledged to be much more common. For instance, AL amyloidosis, the most frequent cause of systemic amyloidosis in the developed world, has an incidence similar to that of Hodgkin lymphoma or chronic myelogenous leukemia and was widely underdiagnosed because of its ambiguous presentation and rapid mortality. Similarly, autopsy studies have identified significant cardiac deposition of wild-type TTR deposition in over 25% of individuals >80 years of age.3 Physician education, along with now widely accessible assays for diagnosis and monitoring (such as the Freelite serum-free LC assay), and improved cardiac imaging have contributed to the increase in diagnosis. In addition to ultrasound echocardiography and late gadolinium enhancement by cardiac magnetic resonance imaging,4 newer imaging modalities with 99mTc-pyrophosphate4,5 and florbetapir6 have improved detection, monitoring …