To compare the major biomolecular mechanisms underlying cardiac injury in transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, emphasizing the differences in their upstream drivers and the contributions of soluble toxic intermediates, which is crucial for developing targeted therapies.
Key Findings:
Cardiac amyloidosis is characterized by progressive ventricular wall thickening, impaired diastolic filling, and arrhythmias.
ATTR and AL amyloidosis share a common phenotype but differ in their underlying mechanisms and contributions to myocardial injury, including the roles of proteostasis failure and immune-inflammatory activation.
Soluble toxic intermediates play a significant role in cardiac injury, alongside extracellular fibril deposition.
Immune-inflammatory activation and proteostasis failure are critical in shaping disease progression and clinical heterogeneity.
Interpretation:
A more precise understanding of the interconnected pathways in cardiac amyloidosis may improve early diagnosis, risk stratification, and the development of targeted therapies.
Limitations:
The review focuses primarily on biomolecular mechanisms and may not cover all clinical aspects of cardiac amyloidosis, particularly diagnostic and management strategies.
Emerging therapeutic strategies are discussed but not exhaustively evaluated, limiting the practical application of the findings.
Conclusion:
An integrated mechanistic framework is essential for understanding disease progression and guiding future research in cardiac amyloidosis.
