Early Detection of Concealed Cardiac Amyloidosis Using AI-ECG and CT-Derived Extracellular Volume in Patients With Atrial Fibrillation

Early Detection of Concealed Cardiac Amyloidosis Using AI-ECG and CT-Derived Extracellular Volume in Patients With Atrial Fibrillation

This study investigates the clinical efficacy of a non-invasive screening protocol using AI-ECG and CT-ECV analysis for cardiac amyloidosis. The study targets on atrial fibrillation(AF) patients with "red-flag" indicators.

Participants are randomized 1:1 into either an early screening or usual care group.

• Early screening group : AI- ECG and/or CT-ECV analysis + AF treatment
• Usual care group : AF treatment Both groups followed for 2 years to compare CA detection rates and clinical outcomes.

This study is a prospective randomized trial designed to evaluate the clinical utility of non-invasive early screening for cardiac amyloidosis (CA) using AI-ECG and CT-ECV in patients with atrial fibrillation (AF). The study primarily targets patients presenting with "red-flag" signs, such as heart failure symptoms, ECG findings of low voltage or pseudo-infarction, Troponin T > 0.03 ng/L, NT-proBNP > 332 pg/mL, LV wall thickness > 12 mm, a history of carpal tunnel syndrome or spinal canal stenosis, or proteinuria (e.g., UACR ≥ 300 mg/g, 24-hour proteinuria ≥ 0.5-1.0 g/day, or nephrotic-range proteinuria > 3.5 g/day).

The objective is to assess whether early screening improves the detection rate of CA and whether such early detection and subsequent treatment can improve clinical outcomes for patients. Subjects who meet the inclusion and exclusion criteria and provide informed consent will be randomly assigned to either the Early Screening Group or the Usual Care Group in a 1:1 ratio for comparative analysis. Participants will be allocated using stratified block randomization (allocation ratio 1:1) with a computer-generated random number sequence. Stratification variables, including age (age ≥ 75 vs. < 75 years) and sex.

Upon enrollment, all patients will undergo a baseline evaluation encompassing demographic information, medical history, and medication status, along with blood tests (e.g., NT-proBNP, troponin, creatinine). Additionally, AI-ECG analysis using standard 12-lead ECG or ECV analysis using cardiac CT will be performed. For AI-ECG analysis, the Mayo Clinic AI-ECG algorithm will be utilized; raw ECG data will be transmitted, and results will be received only for those patients who have provided specific consent. Patients who test positive in the AI-ECG analysis or cardiac CT-ECV analysis will undergo further diagnostic workup, including SPEP, UPEP, IFE, Free Light Chain Assay, and 99mTc-DPD scintigraphy. For those who test positive in these subsequent evaluations, definitive diagnosis will be attempted through endomyocardial biopsy or genetic testing.

Inclusion Criteria:

• Adults aged 19 or older who have provided voluntary written informed consent.
• Patients with a history of AF (paroxysmal or persistent) and one or more red-flag symptoms/signs.
• Patients who can undergo at least one of the following: AI-ECG analysis or CT-ECV analysis.

Exclusion Criteria:

• Patients previously diagnosed with cardiac amyloidosis (AL or ATTR).
• Patients with severe heart failure (NYHA class IV) or terminal illness with a life expectancy of less than 1 year.
• Patients deemed inappropriate for participation by the investigator.