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.

Mechanism and Management of Mechanism and Management of Coronary Microvascular Angina Coronary Microvascular Angina

Dingcheng Xiang, MD, Ph.DDingcheng Xiang, MD, Ph.DCardiovascular DepartmentCardiovascular DepartmentLiuhuaqiao HosptialLiuhuaqiao HosptialGuangzhou, ChinaGuangzhou, China

广州军区广州总医院心血管内科广州军区广州总医院心血管内科向定成向定成

DefinitionDefinition

Cardiac Syndrome X (1973, Kemp)Cardiac Syndrome X (1973, Kemp)

Microvascular Angina (1986, Cannon) Microvascular Angina (1986, Cannon) – Effort chest painEffort chest pain

– Evidence of myocardial ischemiaEvidence of myocardial ischemia

– No significant coronary artery stenosisNo significant coronary artery stenosis

Mechanisms of Microvascular AnginaMechanisms of Microvascular Angina

Microvascular dysfunctionMicrovascular dysfunction– Decreased reservation of arteriole dilation– Arteriole spasm

Myocardiac ischemiaMyocardiac ischemia

Effort anginaEffort angina

Mechanisms of Microvascular Mechanisms of Microvascular DysfunctionDysfunction

Endothelial dysfunctionEndothelial dysfunction

Arteriole atherosclerosisArteriole atherosclerosis

InflammationInflammation

Autonomic nerves dysfunctionAutonomic nerves dysfunction






Microvascular endothelial Microvascular endothelial dysfunction (evidence 1)dysfunction (evidence 1)

Coronary sinus Peripheral Venous

ET1 ↑ and/or NO

Microvascular spasm

Blood sample

MVA patients


Microvascular angina Patients

Flow-Mediated-Dilation

Systemic endothelial dysfunction


Ergonovine/Acetylcholine Test

Coronary flow resistance ↑(Myocardial perfusion )

No epicardiac artery spasm

Microvascular angina Patients






Arteriole AtherosclerosisArteriole Atherosclerosis

Lacking in direct evidence Lacking in direct evidence – Limitation of angiographic resolutionLimitation of angiographic resolution

– No autopsy data: benign prognosisNo autopsy data: benign prognosis

– No available animal modelNo available animal model

Arteriole AtherosclerosisArteriole Atherosclerosis

Indirect evidenceIndirect evidence– Angio/IVUS: mild stenosis in ischemia-related Angio/IVUS: mild stenosis in ischemia-related

coronary arteriescoronary arteries– Future PCI candidate vesselFuture PCI candidate vessel– Spotted scar in ischemia-related areaSpotted scar in ischemia-related area– Accompanied by atherosclerotic risk factorsAccompanied by atherosclerotic risk factors– Anti-atherosclerosis therapy improved angina Anti-atherosclerosis therapy improved angina

Am J Cardiol. 2006 Jun 15;97(12):1727-31







Increased inflammatory factors level Increased inflammatory factors level during episode of anginaduring episode of angina– CRPCRP– InterleukinsInterleukins

Decreased during silenceDecreased during silence

Future Cardiol. 2006 Jan;2(1):63-73







spinal cord spinal cord

stimulationstimulation

Reduced Reduced episodeepisode of anginaangina

Cardiac sympathetic nerves

Autogenic training

Sympathetic/paraactivity

Menopause. 2009 Jan-Feb;16(1):60-5

J Nucl Cardiol. 2008 Nov-Dec;15(6):804-10

Mechanisms of Coronary Mechanisms of Coronary Microvascular DysfunctionMicrovascular Dysfunction





Diagnosis of coronary Diagnosis of coronary microvascular anginamicrovascular angina

Typic episodic effort chest painTypic episodic effort chest pain

Evidence of myocardial ischemiaEvidence of myocardial ischemia– ST ST during chest pain during chest pain– Positive stress test ( ECG/ECT/UCG)Positive stress test ( ECG/ECT/UCG)

No significant coronary angiographic No significant coronary angiographic stenosisstenosis

Negative ergonovine/acetylcholine testNegative ergonovine/acetylcholine test

Management of coronary Management of coronary microvascular anginamicrovascular angina

Combined therapyCombined therapy–Life-style modificationLife-style modification

–Relieving chest painRelieving chest pain

–Preventing episode of chest painPreventing episode of chest pain

–Improving endothelial functionImproving endothelial function






Life-style modificationLife-style modification

Same risk factors of CHDSame risk factors of CHD

Same life-style modificationSame life-style modification






Relieving chest painRelieving chest pain

Discontinue inducementDiscontinue inducement

NitratesNitrates

Spinal cord stimulationSpinal cord stimulation– Refractory chest painRefractory chest pain

Am J Med. 2006 Jul;119(7):560-6

J Nucl Cardiol. 2008 Nov-Dec;15(6):804-10






Preventing episode of anginaPreventing episode of angina

Nitrates + Nitrates + -blockers -blockers reduce 80% of reduce 80% of episodesepisodes

-blockers-blockers– Not as effective as in stenotic effort anginaNot as effective as in stenotic effort angina– nebivolol better than atenololnebivolol better than atenolol

Am J Med. 2006 Jul;119(7):560-6


CCBs: ControversialCCBs: Controversial

NicorandilNicorandil

Aminophylline or adenosine precursorAminophylline or adenosine precursor– Effective but side-effectEffective but side-effect


External counterpulsationExternal counterpulsation– Reducing 87% of chest painReducing 87% of chest pain– MechanismMechanism

increasing myocardial perfusion increasing myocardial perfusion

Improving endothelial functionImproving endothelial function

Autogenic trainingAutogenic training

Int J Cardiol. 2009 Jun 26;135(2):256-7

Menopause. 2009 Jan-Feb;16(1):60-5







StatinsStatins–Simvastatin & XuezhikangSimvastatin & Xuezhikang

–Decrease IL6,CRP,ET1Decrease IL6,CRP,ET1

–Improve exercise-induced ischemia Improve exercise-induced ischemia

Cardiology. 2008;110(1):39-44

Int J Cardiol. 2007 Oct 31;122(1):82-4


ACEIACEI– Hypertension & microvascular anginaHypertension & microvascular angina– Enalapril: decrease blood pressure & improve Enalapril: decrease blood pressure & improve

endothelial functionendothelial function– Reduced episode of chest pain Reduced episode of chest pain

Am J Cardiol, 1995, 76: 31D


ARBARB– Irbesartan vs placebo:24 patients with 3wIrbesartan vs placebo:24 patients with 3w– No statistical improvement in ischemia and No statistical improvement in ischemia and

exercise toleranceexercise tolerance

Heart. 2007 February; 93(2): 253–254.

Summary of managementSummary of management

Life-style modificationLife-style modification

Nitrates+Nitrates+-blockers+CCBs+ nicorandil-blockers+CCBs+ nicorandil

StatinsStatins

AspirinAspirin

ACEI/ARB: hypertension ?ACEI/ARB: hypertension ?

Refractory: EEP or spinal cord stimulationRefractory: EEP or spinal cord stimulation

PrognosisPrognosis

Depends on the left ventricular functionDepends on the left ventricular function

Majority undergoes benign prognosis but Majority undergoes benign prognosis but poor life quality.poor life quality.

ConclusionsConclusions

Since initial report over 4 decades ago, Since initial report over 4 decades ago, microvascular angina continues to be a microvascular angina continues to be a common occurrence for cardiologists. common occurrence for cardiologists.

Despite considerable efforts over 4 Despite considerable efforts over 4 decades, the syndrome remains decades, the syndrome remains controversial with regard to mechanism controversial with regard to mechanism and management. and management.

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.

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