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Cardiac Amyloid Load: A Prognostic and Predictive Biomarker in Patients With Light-Chain Amyloidosis
Arnt V Kristen1, Eva Brokbals1, Fabian Aus dem Siepen1
1Department of Cardiology, Angiology, and Respiratory Medicine, University of Heidelberg, Heidelberg, Germany.
Insights
In amyloid light-chain (AL) amyloidosis, higher amyloid load predicts mortality. Chemotherapy improves survival, especially in patients with less than 20% amyloid load who respond to treatment. Early identification is key.
Area of Science:
- Cardiology
- Oncology
- Pathology
Background:
- Cardiac amyloid load's impact on mortality in amyloid light-chain (AL) cardiac amyloidosis remains unquantified.
- This study addresses the gap by comparing histological amyloid load with established clinical mortality predictors.
Purpose of the Study:
- To retrospectively analyze the correlation between histological cardiac amyloid load and mortality in patients with AL amyloidosis.
- To identify independent predictors of mortality in AL amyloidosis and transthyretin amyloidosis (ATTR).
Main Methods:
- Retrospective analysis of 216 patients with histologically confirmed cardiac amyloidosis.
- Assessment included electrocardiography, echocardiography, laboratory testing, and histological amyloid load quantification.
- Multivariate and Cox regression analyses were used to identify predictors of survival.
Main Results:
- Chemotherapy significantly improved overall survival in AL amyloidosis (16.2 months vs. 1.4 months).
- Amyloid load, NYHA functional class, and response to chemotherapy were independent predictors of mortality in AL amyloidosis.
- NYHA functional class (III vs. II) was the sole independent predictor of survival in ATTR amyloidosis.
Conclusions:
- Early identification of AL amyloidosis is crucial for effective treatment.
- In advanced AL amyloidosis with extensive amyloid load, chemotherapy may not significantly alter outcomes.
- Amyloid load is a significant prognostic factor in AL amyloidosis.
Background:
Cardiac amyloid load has not been analyzed for its effect on mortality in patients with amyloid light-chain (AL) cardiac amyloidosis.
Objectives:
This study retrospectively compared histological amyloid load with common clinical predictors of mortality.
Methods:
This study assessed 216 patients with histologically confirmed cardiac amyloidosis at a single center with electrocardiography, echocardiography, and laboratory testing.
Results:
AL amyloid deposits were usually distributed in a reticular/pericellular pattern, whereas transthyretin amyloid (ATTR) more commonly showed patchy deposits. Median amyloid load was 30.5%; no amyloid load was above 70%. During follow-up (median 19.1 months), 112 patients died. Chemotherapy had a significant effect on overall survival in AL amyloidosis (16.2 months vs. 1.4 months; p = 0.003). Patients with <20% AL amyloid load who responded to chemotherapy showed significantly better survival than nonresponders. According to univariate analysis, predictors of survival in AL amyloidosis included sex, Karnofsky index, New York Heart Association (NYHA) functional class, diastolic blood pressure, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, mineralocorticoid receptor antagonists, low voltage, ineligibility for chemotherapy, response to chemotherapy, and amyloid load. Independent predictors of mortality by multivariate analysis included NYHA functional class (III vs. II), estimated glomerular filtration rate, responders to chemotherapy, and amyloid load. In ATTR amyloidosis, survival correlated with NYHA functional class, diastolic blood pressure, and use of diuretic agents. Following Cox regression analysis, NYHA functional class (III vs. II; p < 0.05) remained the only independent predictor of patient survival in ATTR amyloidosis.
Conclusions:
Early identification of subjects with AL amyloid is essential given that in late-stage disease with extensive amyloid load, our data suggested that outcomes are not affected by administration of chemotherapy.
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