Current and future circulating biomarkers for cardiac amyloidosis

Area of Science:

• Cardiology
• Biochemistry
• Pathophysiology

Background:

• Cardiac amyloidosis (CA) involves myocardial protein infiltration, stemming from misfolded protein aggregation into amyloid fibers.
• The disease's complex pathophysiology, including oligomer metastasis, makes early clinical detection difficult, limiting therapeutic windows.
• Current diagnostic and prognostic tools for CA lack a stage-specific framework.

Purpose of the Study:

• To propose a novel classification of cardiac amyloidosis biomarkers.
• To categorize biomarkers based on their utility across different disease time stages (early, intermediate, late).
• To enhance the understanding and management of cardiac amyloidosis through a staged biomarker approach.

Main Methods:

• Review and categorization of existing cardiac amyloidosis biomarkers.
• Classification of biomarkers into early (detection), intermediate (mechanisms), and late (prognosis/response) stages.
• Analysis of biomarker applicability across various CA subtypes and disease progression.

Main Results:

• Early markers (e.g., free light chains, serum amyloid A) aid in initial disease detection.
• Intermediate markers (e.g., sST-2, MR-proADM, vWF) provide insights into myocardial damage mechanisms.
• Late-stage markers (e.g., troponins, natriuretic peptides) assist in prognosis and evaluating treatment response.

Conclusions:

• A time-stage-based biomarker classification offers a structured approach to managing cardiac amyloidosis.
• This framework supports earlier detection, mechanistic understanding, and tailored therapeutic strategies.
• Future research should focus on upstream biomarkers targeting protein folding defects to further expand the therapeutic window.