Transthyretin Amyloidosis: The Heart and beyond
Qiang Xie, Xuchen Zhang, Jenny Libien. SUNY Downstate Medical Center, Brooklyn, NY; The Mount Sinai Medical Center, New York, NY
Background: The most common mutation leading to cardiac amyloidosis in the US is the V122I mutation, present in 3-4% of African-Americans. We studied the distribution of TTR amyloid deposition in autopsy material from our predominantly African-American patient population in order to better characterize the pathology associated with the V122I mutation. Since an association of wild-type TTR deposition in systemic senile amyloidosis (SSA) and myocardial infarction has been reported in a Finnish population, we also assessed whether any myocardial infarcts were present.
Design: Cases of TTR cardiac amyloidosis and age-matched controls were identified from 2007-2010 autopsy records. The presence of amyloid deposition in tissues was examined by H&E, Congo Red, and TTR immunohistochemistry. Apoptosis was measured by TUNEL staining.
Results: Four cases of TTR cardiac amyloidosis (average age 82.8 years; range 80 to 87 years) were identified. TTR gene sequencing identified mutant TTR (V122I) in three cases and wild-type (WT) TTR in one case. No myocardial infarcts were identified in cases or controls, however, there was an increase in apoptosis in the myocardium in the TTR cases compared to controls. Cardiac amyloidosis was in a patchy and diffuse distribution in the sub-endocardium, sub-epicardium, and myocardium in all the cases and in pericardial adipose tissue in two of three V122I cases. Amyloid was not present in the major coronary arteries but was found in smaller epicardial vessels in all of the cases. In addition to the heart, amyloid deposition was present variably in blood vessels of multiple tissues including adrenal gland, appendix, bladder, colon, esophagus, gallbladder, kidney, liver, lung, pancreas, prostate, spleen, stomach, thyroid, tongue, adipose, pancreas and kidney. Interstitial deposition of amyloid was also seen in the adrenal gland (1 V122I), bladder (1 V122I), gallbladder, esophagus (1 V122I case), colon (2 V122I), liver (1 WT and 1 V122I case), prostate (1 V122I case), kidney (1 WT and 2 V122I), and spleen (1 V122I case).
Conclusions: Although the heart was the most severely affected organ, TTR amyloid deposition extended beyond the heart in all four cases with the distribution varying among the individual cases. Frequent involvement of coronary arteries with amyloid has been reported in cases of AL amyloidosis, however, no TTR amyloid deposits were seen in the major coronary arteries in the four cases studied. Unlike SSA amyloidosis in the Finnish population, no myocardial infarcts were identified.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 4, Wednesday Morning