A Pathophysiology-Oriented Imaging Phenotype Framework for Nonobstructive Coronary Artery Disease

Area of Science:

• Cardiology
• Medical Imaging
• Pathophysiology

Background:

• Nonobstructive coronary artery disease (NOCAD) is a complex condition with varied underlying mechanisms, despite no flow-limiting blockages.
• Current diagnostic approaches may not fully capture the prognostic implications of NOCAD's heterogeneity.

Purpose of the Study:

• To develop and validate a rule-based imaging phenotype framework for NOCAD using multiparametric coronary computed tomography angiography (CCTA).
• To integrate functional, structural, and inflammatory data to categorize NOCAD patients and assess prognostic significance.

Main Methods:

• Retrospective analysis of 485 NOCAD patients.
• Assessment of CT-derived fractional flow reserve (CT-FFR), plaque burden, high-risk plaque features, and perivascular fat attenuation index (FAI).
• Categorization into function-, structure-, inflammation-dominant, or low-risk phenotypes based on hierarchical rules and percentile thresholds.

Main Results:

• During a median 36-month follow-up, 11.5% of patients experienced major adverse cardiovascular events (MACE).
• Function dominance was linked to the highest MACE risk (HR 4.054), followed by structure dominance (HR 3.129).
• Isolated inflammation dominance did not show a significant independent association with MACE.

Conclusions:

• A phenotype-oriented interpretation of CCTA metrics can reflect distinct biological pathways in coronary pathology.
• The developed framework highlights a graded prognostic association across functional and structural abnormalities in NOCAD.
• This approach supports improved risk stratification for patients with nonobstructive coronary artery disease.