1. Mechanism and Management of Coronary Microvascular Angina Dingcheng Xiang, MD, Ph.D Cardiovascular Department Liuhuaqiao Hosptial Guangzhou, China 广州军区广州总医院心血管内科向定成

2. Definition Cardiac Syndrome X (1973, Kemp) Microvascular Angina (1986, Cannon) –Effort chest pain –Evidence of myocardial ischemia –No significant coronary artery stenosis

3. Mechanisms of Microvascular Angina Microvascular dysfunction Microvascular dysfunction – –Decreased reservation of arteriole dilation – –Arteriole spasm Myocardiac ischemia Myocardiac ischemia Effort angina Effort angina

4. Mechanisms of Microvascular Dysfunction Endothelial dysfunction Arteriole atherosclerosis Inflammation Autonomic nerves dysfunction

5. Mechanisms of Microvascular Dysfunction Endothelial dysfunction Arteriole atherosclerosis Inflammation Autonomic nerves dysfunction

6. Microvascular endothelial dysfunction (evidence 1) Coronary sinusPeripheral Venous ET1 ↑ and/or NO  Microvascular spasm Blood sample MVA patients

7. Microvascular endothelial dysfunction (evidence 2) Microvascular angina Patients Flow-Mediated-Dilation  Systemic endothelial dysfunction

8. Microvascular endothelial dysfunction (evidence 3) Ergonovine/Acetylcholine Test Coronary flow resistance ↑ (Myocardial perfusion  ) No epicardiac artery spasm Microvascular angina Patients

9. Mechanisms of Microvascular Dysfunction Endothelial dysfunction Arteriole atherosclerosis Inflammation Autonomic nerves dysfunction

10. Arteriole Atherosclerosis Lacking in direct evidence –Limitation of angiographic resolution –No autopsy data: benign prognosis –No available animal model

11. Arteriole Atherosclerosis Indirect evidence –Angio/IVUS: mild stenosis in ischemia-related coronary arteries –Future PCI candidate vessel –Spotted scar in ischemia-related area –Accompanied by atherosclerotic risk factors –Anti-atherosclerosis therapy improved angina Am J Cardiol. 2006 Jun 15;97(12):1727-31

12. Mechanisms of Microvascular Dysfunction Endothelial dysfunction Arteriole atherosclerosis Inflammation Autonomic nerves dysfunction

13. Inflammation Increased inflammatory factors level during episode of angina –CRP –Interleukins Decreased during silence Future Cardiol. 2006 Jan;2(1):63-73

14. Mechanisms of Microvascular Dysfunction Endothelial dysfunction Arteriole atherosclerosis Inflammation Autonomic nerves dysfunction

15. spinal cord stimulation Reduced episode angina episode of angina Cardiac sympathetic nerves Autogenic training Sympathetic/para activity Menopause. 2009 Jan-Feb;16(1):60-5 J Nucl Cardiol. 2008 Nov-Dec;15(6):804-10

16. Mechanisms of Coronary Microvascular Dysfunction Endothelial dysfunction Arteriole atherosclerosis Inflammation Autonomic nerves dysfunction

17. Diagnosis of coronary microvascular angina Typic episodic effort chest pain Evidence of myocardial ischemia –ST  during chest pain –Positive stress test ( ECG/ECT/UCG) No significant coronary angiographic stenosis Negative ergonovine/acetylcholine test

18. Management of coronary microvascular angina Combined therapy –Life-style modification –Relieving chest pain –Preventing episode of chest pain –Improving endothelial function

19. Management of coronary microvascular angina Combined therapy –Life-style modification –Relieving chest pain –Preventing episode of chest pain –Improving endothelial function

20. Life-style modification Same risk factors of CHD Same life-style modification

21. Management of coronary microvascular angina Combined therapy –Life-style modification –Relieving chest pain –Preventing episode of chest pain –Improving endothelial function

22. Relieving chest pain Discontinue inducement Nitrates Spinal cord stimulation –Refractory chest pain Am J Med. 2006 Jul;119(7):560-6 J Nucl Cardiol. 2008 Nov-Dec;15(6):804-10

23. Management of coronary microvascular angina Combined therapy –Life-style modification –Relieving chest pain –Preventing episode of chest pain –Improving endothelial function

24. Preventing episode of angina Nitrates +  -blockers  reduce 80% of episodes  -blockers –Not as effective as in stenotic effort angina –nebivolol better than atenolol Am J Med. 2006 Jul;119(7):560-6

25. Preventing episode of angina CCBs: Controversial Nicorandil Aminophylline or adenosine precursor –Effective but side-effect

26. Preventing episode of angina External counterpulsation –Reducing 87% of chest pain –Mechanism increasing myocardial perfusion Improving endothelial function Autogenic training Int J Cardiol. 2009 Jun 26;135(2):256-7 Menopause. 2009 Jan-Feb;16(1):60-5

27. Management of coronary microvascular angina Combined therapy –Life-style modification –Relieving chest pain –Preventing episode of chest pain –Improving endothelial function

28. Improving endothelial function Statins –Simvastatin & Xuezhikang –Decrease IL6,CRP,ET1 –Improve exercise-induced ischemia Cardiology. 2008;110(1):39-44 Int J Cardiol. 2007 Oct 31;122(1):82-4

29. Improving endothelial function ACEI –Hypertension & microvascular angina –Enalapril: decrease blood pressure & improve endothelial function –Reduced episode of chest pain Am J Cardiol, 1995, 76: 31D

30. Improving endothelial function ARB –Irbesartan vs placebo:24 patients with 3w –No statistical improvement in ischemia and exercise tolerance Heart. 2007 February; 93(2): 253–254.

31. Summary of management Life-style modification Nitrates+  -blockers+CCBs+ nicorandil StatinsAspirin ACEI/ARB: hypertension ? Refractory: EEP or spinal cord stimulation

32. Prognosis Depends on the left ventricular function Majority undergoes benign prognosis but poor life quality.

33. Conclusions Since initial report over 4 decades ago, microvascular angina continues to be a common occurrence for cardiologists. Despite considerable efforts over 4 decades, the syndrome remains controversial with regard to mechanism and management.