Cardiac Amyloidosis: Heterogenous Pathogenic Backgrounds

Abstract

Cardiac amyloidosis is a fatal disorder which develops on the basis of the different pathologic conditions in systemic amyloidosis: the most common underlying disease is immunoglobulin light chain-derived primary amyloidosis and the next is transthyretin-related hereditary amyloidosis; the latter disorder, typically represented by familial amyloid polyneuropathy, was long regarded as an endemic disease. However, this disorder has now been shown to involve a highly variable clinical picture due to a large number of transthyretin gene mutations, and many patients with diverse ancestors suffer from severe cardiac amyloidosis. Additionally, senile systemic amyloidosis is now noted as a cause of cardiac dysfunction in elderly individuals. Echocardiogram and myocardial technetium-99m-pyrophosphate scintigraphy can provide characteristic findings. Immunohistochemistry on tissue amyloid, biochemical analysis of serum and urine proteins, and DNA sequencing are usually employed to determine the disease-related amyloid fibril protein.Although systemic amyloidosis has become treatable, the prognosis of each patient who received up-to-date and effective, but nevertheless stressful, therapy depends on the severity of cardiac involvement by amyloid deposition.

Amyloid in endomyocardial biopsies

“…While some TTR variants predominantly cause familial amyloidotic polyneuropathy (FAP), there are also mutations that result in a cardiomyopathy in nearly 100% of the cases such as p.Val30Met, p.Thr60Ala, p.Ile84Ser and p.Val122Ile [6,9,18]. In our series, the p.Val30Met substitution was found in two patients, which is in agreement with earlier studies describing it as one of the most common mutations [7,34]. Furthermore, this variant is known to nearly always involve the heart [9].…”

“…The heart is affected in approximately 50% of immunoglobulin light chain-derived AL amyloidosis cases [5]. As this is a very aggressive form, affected individuals have a mean survival of 1.08 years after diagnosis [6,7]. Cardiac involvement is less frequent in transthyretinderived ATTR amyloidosis, and the prognosis is often more favorable because of a slower progression rate and a lack of toxic effects on the heart [8].…”

Ten Years of Experience with Liver Transplantation for Familial Amyloid Polyneuropathy in Japan: Outcomes of Living Donor Liver Transplantations

“…Autopsy revealed heavy deposition of amyloid on the myocardium in these two patients (22). Serious cardiac involvement by amyloid is known to be one cardinal feature in FAP patients with non-Val30Met TTR type (16,23), and this severe phenotype of cardiac amyloidosis has been suggested to be responsible for the poor post-transplant prognosis in these FAP patients. Recently, it was noted that after transplantation rapid deterioration of cardiac function with further thickening of the ventricular wall occurred in some FAP patients, although polyneuropathy and autonomic dysfunction were stabilized or slightly improved.…”

Unusual Case of Cardiac Amyloidosis Preceded by a Twenty-year History of Dilated Cardiomyopathy and Heart Failure

“…It has previously been reported that 41 of 1,278 patients (3.2%) with DCM have underlying amyloidosis (14). Nevertheless, case reports of DCM secondary to amyloidosis are rare (9,(15)(16)(17). The predominant deposition of amyloid in vessel walls causes microvascular stenosis or occlusion and is considered to be one of the primary mechanisms for the development of DCM in amyloidosis patients (18,19).…”