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Plaque Progression and Rupture in Obstructive Coronary Artery Disease: A Review of Current Imaging Modalities
Francesco Antonio Veneziano1, Nino Cocco2, Francesco Gentile3
1Division of Cardiology, South Padova General Hospitals, 35043 Monselice, Italy.
Insights
This review highlights how advanced imaging techniques can identify vulnerable atherosclerotic plaques, shifting focus from stenosis to plaque instability for better prevention of acute coronary syndromes.
Area of Science:
- Cardiovascular Medicine
- Medical Imaging
- Immunology
Background:
- Obstructive coronary artery disease (CAD) management faces residual risk due to unresolved vascular inflammation and plaque instability, despite optimal lipid-lowering therapies.
- Acute coronary syndromes are precipitated by vulnerable plaque rupture, not necessarily the most stenotic lesions.
- Understanding the mechanisms of plaque progression and rupture is crucial for improving patient outcomes.
Purpose of the Study:
- To review the mechanistic pathways of atherosclerotic plaque progression and rupture.
- To examine how various in vivo imaging modalities characterize these processes and track disease activity.
- To discuss therapeutic implications of plaque imaging for risk stratification and personalized prevention strategies.
Main Methods:
- Review of mechanistic pathways from endothelial dysfunction and lipoprotein oxidation to immune responses and biomechanical forces.
- Integration of in vivo imaging phenotypes, including intravascular ultrasound (IVUS), optical coherence tomography (OCT), near-infrared spectroscopy (NIRS), coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and positron emission tomography (PET).
- Discussion of emerging therapeutic strategies targeting inflammation, immune pathways, and cap stability.
Main Results:
- Imaging techniques like IVUS, OCT, NIRS, CCTA, CMR, and PET can characterize vulnerable plaque features and enable longitudinal tracking of disease.
- These modalities provide insights into endothelial dysfunction, lipoprotein retention, inflammation, efferocytosis failure, and biomechanical cap stress.
- Plaque imaging aids in identifying unstable lesions that pose a higher risk of rupture and infarction.
Conclusions:
- Advanced imaging of atherosclerotic plaque offers a paradigm shift from stenosis-based revascularization to vulnerability-centered prevention.
- Improved identification of vulnerable plaque features can refine risk stratification and guide therapy.
- Serial imaging and biomarkers can support risk-adapted treatment strategies beyond lipid-lowering to modulate inflammation and enhance plaque stability.
Abstract:
Atherosclerotic plaque progression and rupture are the chief determinants of acute coronary syndromes and long-term outcomes in obstructive coronary artery disease (CAD). Residual risk persists despite intensive low-density lipoprotein-lowering and contemporary secondary prevention, because vascular inflammation and microstructural frailty often remain unresolved. At the bedside, the lesion that precipitates infarction is seldom the tightest but rather the most unstable. This review integrates the mechanistic chain, from endothelial dysfunction and retention/oxidation of apolipoprotein B lipoproteins to maladaptive innate and adaptive immunity, failed efferocytosis with necrotic core expansion, and biomechanical forces that thin and fatigue the fibrous cap, with their corresponding in vivo imaging phenotypes. Thus, this study aimed to examine how intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), alongside coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and positron emission tomography (PET), characterize these processes and enable longitudinal tracking of disease activity. Moreover, we briefly discuss emerging therapeutic implications of plaque imaging, focusing on how improved identification of vulnerable plaque features may inform risk stratification. Finally, we evaluate therapies that extend beyond lipid-lowering to modulate inflammatory and immune pathways, reinforce cap stability, and support a risk-adapted, trajectory-based pathway in which serial imaging and biomarkers guide treatment intensity. Together, these advances support a shift in clinical practice from stenosis-centered revascularization to imaging-guided, vulnerability-centered prevention.
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