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Functional coronary vascular disease: endotype-based classification, diagnosis, and targeted management
Omar El Khatib1, Ashraf Al Azzoni2, Ronney Shantouf2
1Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.
Insights
Patients with angina and non-obstructive coronary arteries (ANOCA) experience chest pain due to underlying coronary abnormalities. Precise, endotype-guided management is crucial for symptom control and preventing adverse cardiovascular events.
Area of Science:
- Cardiology
- Vascular Biology
- Diagnostic Imaging
Background:
- Angina and exertional dyspnea are common in coronary artery disease (CAD), often linked to obstructive epicardial lesions.
- A significant group presents with angina despite non-obstructive coronary arteries (<50%), termed ANOCA, which can progress to ischemia (INOCA) or myocardial infarction (MINOCA).
- The pathophysiology of ANOCA/INOCA is complex and often underappreciated, leading to imprecise management strategies.
Purpose of the Study:
- To elucidate the heterogeneous pathophysiology of ANOCA and INOCA.
- To outline current diagnostic approaches for endotype characterization.
- To emphasize the importance of personalized, endotype-guided management strategies.
Main Methods:
- Non-invasive testing including ECG, laboratory studies, echocardiography, and coronary CT.
- Invasive functional testing for detailed endotype characterization.
- Review of current literature on ANOCA and INOCA pathophysiology and management.
Main Results:
- ANOCA/INOCA involve diverse functional and structural coronary abnormalities, including endothelial dysfunction and microvascular dysfunction.
- Disrupted nitric oxide, adenosine, and prostacyclin signaling contribute to ischemia despite normal epicardial arteries.
- Stepwise diagnostic evaluation is essential for identifying specific endotypes.
Conclusions:
- Personalized, endotype-guided strategies are vital for managing ANOCA and INOCA.
- Integrated pharmacologic therapies (e.g., calcium channel blockers, ranolazine) and non-pharmacologic interventions (lifestyle modification, risk reduction) are key.
- Optimizing symptom control, preventing disease progression, and reducing major adverse cardiovascular events require tailored treatment approaches.
Background:
Angina and exertional dyspnea are hallmark manifestations of coronary artery disease (CAD), traditionally linked to obstructive epicardial lesions. However, a substantial subset of patients experience angina despite angiographically non-obstructive coronary arteries (<50%), termed angina with non-obstructive coronary arteries (ANOCA). ANOCA may progress to ischemia with non-obstructive coronary arteries (INOCA), myocardial infarction with non-obstructive coronary arteries (MINOCA), and ischemic cardiomyopathy. Despite advances in diagnostic modalities, the underlying pathophysiology remains underappreciated, and management often lacks precision.
Pathophysiology:
ANOCA and INOCA encompass heterogeneous functional and structural coronary abnormalities, including endothelial dysfunction, impaired vasodilation, and inappropriate vasoconstriction of epicardial or microvascular vessels. Epicardial arteries serve primarily as conduits, whereas the microcirculation regulates coronary flow, mediating myocardial perfusion through nitric oxide, adenosine, and prostacyclin signalling. Disruption of these mechanisms precipitates ischemia despite normal epicardial anatomy, defining distinct endotypes with diagnostic and therapeutic relevance.
Diagnosis And Management:
Evaluation involves stepwise assessment from non-invasive testing, including ECG, laboratory studies, echocardiography, and coronary computed tomography, to invasive functional testing for endotype characterization. Management should integrate endotype-specific pharmacologic therapies such as calcium channel blockers, nitrates, ranolazine, ACE inhibitors, and beta-blockers with non-pharmacologic interventions including lifestyle modification and overall cardiovascular risk reduction.
Conclusion:
Personalized, endotype-guided strategies targeting both pathophysiology and modifiable risk factors are essential to optimize symptom control, prevent disease progression, and reduce major adverse cardiovascular events in patients with ANOCA and INOCA.
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