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A Pathophysiology-Oriented Imaging Phenotype Framework for Nonobstructive Coronary Artery Disease
Hongqun Du1, Wenyue Chen1, Hao Tian1
1Department of Medical Imaging, Affiliated Hospital of Jiangnan University, No. 1000 Hefeng Road, Wuxi 214122, China.
Insights
Nonobstructive coronary artery disease (NOCAD) has diverse causes. A new imaging phenotype framework shows functional and structural dominance predict major adverse cardiovascular events, guiding risk stratification.
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.
Abstract:
Nonobstructive coronary artery disease (NOCAD) is increasingly recognized as a heterogeneous condition characterized by diverse pathophysiological mechanisms despite the absence of flow-limiting stenosis. We sought to establish a rule-based dominant imaging phenotype framework integrating functional, structural, and inflammatory dimensions derived from multiparametric coronary computed tomography angiography (CCTA). In this retrospective cohort of 485 patients with NOCAD, CT-derived fractional flow reserve (CT-FFR), quantitative plaque burden and high-risk plaque features, and perivascular fat attenuation index (FAI) were assessed. Using predefined percentile thresholds and hierarchical rules, patients were categorized into function-, structure-, inflammation-dominant, or low-risk phenotypes. During a median follow-up of 36 months, 56 patients (11.5%) experienced major adverse cardiovascular events (MACE). After multivariable adjustment, function dominance was associated with the highest risk (hazard ratio [HR] 4.054, 95% confidence interval [CI] 1.984-8.281; p < 0.001), followed by structure dominance (HR 3.129, 95% CI 1.410-6.944; p = 0.005), whereas isolated inflammation dominance did not show a statistically significant independent association with events, with wide confidence intervals indicating limited precision. These findings suggest a graded pattern of prognostic associations across functional and structural abnormalities in NOCAD and support a phenotype-oriented interpretation of CCTA metrics reflecting distinct biological axes of coronary pathology.
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