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

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

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

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

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

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

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

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

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

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

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 Jun 15;97(12):

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

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

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

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

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

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

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

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

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

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

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

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

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 Jul;119(7):560-6

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

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

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

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

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

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

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

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

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.