Cardiac Amyloid Load as a Biomarker in Amyloidosis
What is the utility of amyloid load for predicting prognosis and treatment response in cardiac amyloidosis?
This was a single-center retrospective analysis of 216 patients with histologically confirmed cardiac amyloidosis. Endomyocardial biopsies were immunohistochemically stained for amyloid, and digital images were exported for analysis. Amyloid load was calculated by measuring the ratio of immunohistochemically stained to nonstained pixels. Electrocardiographic, echocardiographic, and standard blood test data, as well as chemotherapy treatment data, were collected.
A total of 107 patients had light-chain (AL) amyloidosis and 109 patients had transthyretin (ATTR) amyloidosis (76 wild-type ATTR [wt-ATTR] and 33 mutant ATTR [mt-ATTR]). No correlation was found between biopsy site (right vs. left ventricle) and amyloid type. There was a higher prevalence of males with wt-ATTR. The median amyloid load was 30.5% (interquartile range, 18.3%-42.1%), and amyloid load was higher in ATTR compared to AL amyloidosis (28.3% [AL] vs. 35% [mt-ATTR] and 34.0% [wt-ATTR]). AL amyloidosis patients with amyloid load <20% and >40% had worse survival than those patients with amyloid load of 20-40% (median survival 12.5 [3.5-21.4] months vs. 6.7 [0-15.1] months vs. 24.5 [0.6-48.4] months, respectively). AL amyloid patients who responded to chemotherapy with amyloid load <20% showed a significant improvement in overall survival compared to chemotherapy responders and nonresponders whose amyloid load was 20-40% or >40%. Multivariate Cox regression showed that New York Heart Association (NYHA) class, estimated glomerular filtration rate, chemotherapy response, and amyloid load were independent predictors of survival in AL amyloidosis. For ATTR amyloidosis, multivariate Cox regression analysis showed only NYHA class to be an independent predictor of patient survival.
In AL amyloidosis, amyloid load may be a novel marker of patient survival, suggesting that patients with low AL amyloid load (<20%) have improved survival with chemotherapy. In contrast, chemotherapy in later stage AL amyloid with higher amyloid load (>20%) may not affect survival, even in patients who are chemotherapy responders.
There are distinct differences between AL and ATTR cardiac amyloidosis, possibly related to the toxic effects of light-chain deposition causing cardiomyocyte apoptosis. This study showed that amyloid load is an independent predictor of survival in AL, but not ATTR amyloidosis patients. It appears that chemotherapy is effective in AL amyloidosis patients with low amyloid load, but less so in patients with higher amyloid load. Further studies are needed to determine whether amyloid load in AL amyloidosis patients can predict effectively which patients will respond to chemotherapy.
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