Clinical and pathological studies of cardiac amyloidosis in transthyretin type familial amyloid polyneuropathy

Abstract

To clarify the clinicopathological features of cardiac amyloidosis in transthyretin (TTR) familial amyloid polyneuropathy (FAP), 169 patients were divided into three groups. Group I consisted of 113 patients with ATTR Val30Met who originated from an endemic focus, II consisted of 36 patients with ATTR Val30Met in nonendemic areas, and III consisted of 20 patients who had non-Val30Met ATTRs with 15 differernt gene mutations.

The median age of onset in Group I was 34 years. On our initial examination, only one 65-year-old female patient was found to be suffering from congestive heart failure. During the follow-up of 65 patients, 7 developed congestive heart failure, the average duration of their illness being 8.7 years. In Group II, the median age of onset was 53 years and 6 of the 36 patients were diagnosed as having cardiac amyloidosis in the course of this disease. In 20 autopsied patients with ATTR Val30Met, congestive heart failure was clinically seen in 6 of the 20 and all 6 showed considerably increased cardiac weight (500g or more). In Group III patients with non-Val30Met ATTRs, the median age of onset was 51.5 years and 14 of the 20 patients had cardiac amyloidosis with congestive heart failure on admission or soon after a definite diagnosis. Cardiac amyloidosis occurs in the classical form of FAP with ATTR Val30Met, especially in older patients, and is also a common clinical manvestation in FAP patients with non-Va l30Met ATTRs. In the pathogenesis of cardiac amyloidosis in A TTR FAP, aging seems to play an important role.

Key Words:

• familial amyloid polyneuropathy
• cardiac amyloidosis
• amyloid
• cardiomyopathy