Overview
This lecture covers Syndrome X (now known as microvascular angina), its pathophysiology, diagnosis, and management, emphasizing its prevalence, heterogeneity, and clinical significance, particularly in women without obstructive coronary artery disease.
Introduction to Syndrome X
- Syndrome X describes patients, primarily women, with angina symptoms and normal coronary arteries.
- First described in 1973, it was initially considered benign or psychosomatic.
- Later studies, like the WISE study, showed increased risk of adverse cardiovascular outcomes, including heart failure and stroke.
Pathophysiology and Coronary Anatomy
- Syndrome X involves dysfunction in the coronary microcirculation (small arteries <100 microns).
- Key mechanisms: impaired vasodilation or increased vasoconstriction due to endothelial dysfunction.
- Nitric oxide and endothelin-1 are major regulators of vascular tone; their dysregulation leads to ischemia.
Evaluation of Microvascular Function
- Gold standard: invasive coronary angiogram with functional testing (acetylcholine for endothelial function, adenosine for microvascular function).
- Non-invasive options: cardiac PET (assesses myocardial blood flow reserve), cardiac MRI, or Doppler echocardiography (technically challenging and less reliable).
- Stress tests are poorly predictive for microvascular dysfunction.
Clinical Implications and Outcomes
- Even in patients under 40 or without risk factors, symptomatic women with normal coronaries have worse outcomes than asymptomatic peers.
- Coronary microvascular dysfunction is associated with increased major cardiovascular events.
- Syndrome X is not benign; clinical vigilance is needed.
Management Strategies
- Treatment is individualized; not all therapies work for every patient.
- Beta-blockers (especially nebivolol, carvedilol) and ACE inhibitors can improve symptoms and microvascular function.
- Calcium channel blockers may help in vasospastic cases; nitrates have inconsistent evidence.
- Newer therapies (e.g., SGLT2 inhibitors, PCSK9 inhibitors, endothelin receptor antagonists) show promise.
- Outcomes data is limited; improvement in symptoms is more evident than reduction in events.
Diagnostic and Treatment Algorithm
- Rule out obstructive CAD first.
- If microvascular dysfunction is confirmed, tailor therapy based on physiology (beta-blockers for reduced flow reserve, CCBs for spasm, lifestyle modifications).
- Non-cardiac chest pain should be considered only if comprehensive testing is negative.
Key Terms & Definitions
- Syndrome X — Angina with normal coronary arteries, now called microvascular angina.
- Coronary microcirculation — Small coronary arteries and arterioles responsible for regulating myocardial blood flow.
- Endothelial dysfunction — Impaired endothelial regulation of vascular tone, leading to ischemia.
- Coronary flow reserve (CFR) — Ratio of maximum to baseline coronary blood flow; reduced in microvascular disease.
- IMR (Index of Microvascular Resistance) — Measure of resistance in microcirculation; higher values indicate dysfunction.
- WISE Study — A major study highlighting risks associated with microvascular angina.
Action Items / Next Steps
- Review assigned readings on WISE study and microvascular angina.
- Prepare for discussion on non-invasive diagnostic tools for ischemia.
- Apply learning to evaluate chest pain in women and consider microvascular causes.