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Learning objectives
Microvascular angina: Definition and pathogenic mechanisms
Understand the importance of MVA in the context of ischaemic heart disease
Clinical presentation and diagnosis
The rationale for therapeutic intervention
Prognostic implications and management
Angina Pectoris
Angustio = tightness
Pectus = chest (lat
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The Coronary Microcirculation
A dynamic network of blood vessels <300µm in diameter
Highly adapted to ensure the efficient exchange of nutrients & metabolites between blood
and tissue
Vessels change their caliber in response to neurohormonal stimuli, metabolic demand &
mechanical signals
Metabolic changes, temperature changes and PH value determines the diameter of the
micro vessels
Ischaemia causes Ca2+ overload
Heart becomes stiff and micro vessels become compressed
Coronary Micro vessels
Spasm of these can lead to myocardial ischaemia
Markedly increased resistance to coronary blood flow at the site of the coronary
microvasculature can trigger angina pectoris associated with ECG shifts, myocardial
perfusion defects and LV dysfunction in patients who otherwise have patent epicardial
coronary arteries
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Coronary artery spasm and microvascular dysfunction are the underlying mechanisms in
these cases

Distal embolisation of thrombus or plaque material
Occlusion
Open up artery and the heart usually recovers
Some people don't due to debris from original
thrombus, inflammation and vasoconstriction of micro
vessels

Cardiac Syndrome X
Typical exertion/rest chest pain
Major cause is oestrogen deficiency
Ischaemic ECG changes
ST-segment depression but normal arteries
Normal coronary arteriograms
These patients have myocardial ischaemia (~30%) due to an abnormal dilatory response
of the coronary microvessels, often associated with endothelial dysfunction

Could not identify
ischaemia -->

Burden to individual
Cardiologists can send patients home as their arteries look 'normal'
Impaired quality of life
Psychosocial morbidity
Financial hardship
Prognosis: Impaired survival (?)

Coronary Flow reserve
Physiologically, Myocardial Blood Flow increases several-fold in response to an increased
myocardial oxygen demand
CFRis reduced due to stenosis
In the absence of coronary stenoses, CFR reflects microvascular function
Ischaemia - obstruction to blood flow in coronary tree

Myocardial Blood Flow

CFR = ratio of hyperaemic
MBF to basal MBF

Flow deficit
Normal
Ischaemia

Pt with impaired CFR

Rest

*Functional is the
most common

Disorganised muscle
in vessel wall -->

↑Myocardial O2 demand

The Endothelium
In health: Balanced release of endothelium derived factors (NO, ET-1, A-II, Prostacyclin,
TM, PAF, vWF, PAI-1)
Damage to endothelium means loss of vascular protection

Coronary Microvascular Dysfunction is often caused by endothelial dysfunction (reduced
NO and ET-1 release)
Risk factors and causes:
Diabetes, Obesity, Hypertension, Smoking
Chronic inflammation
Oxidative stress
Oestrogen deficiency

ET-1 - vasoconstriction
NFkB - Transcription factor

Enzyme which produces NO becomes so dysfunctional it actually produces oxidative
stress (free radicals)

Diffuse Epicardial Coronary Vasoconstriction in CSX
ACH

Typical angina pectoris

Nitro

Angina pectoris resolved

Microvascular Spasm in Patients With Cardiac Syndrome X
ACH

Typical anginal chest pain and
ECG ischaemic ST segment shifts

Nitro

Chest pain and ECG ischaemic ST
segment shifts resolved after GTN

Ach should dilate arteries of normal endothelium
Spasm of abnormal endothelium (no occlusion)
Studies have reported the co-existence of microvascular vasoconstriction and epicardial
coronary artery spasm within patients
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min-1
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Basal

Adenosine

Patients

Relationship between duration of Rheumatic Disease and CFR

Longer the patients had the inflammatory disease - the worse the angina
Coronary microvascular abnormalities play an important role in the pathogenesis of
ischaemic heart disease
Microvascular dysfunction is thus an important therapeutic target
Microvascular patients would benefit from :
Beta-blockers
Statins - decrease inflammation
ACEi
Calcium channel blockers

Beneficial Effects of Anti-Inflammatory/Anti-Oxidant Interventions in Cardiac Syndrome X
ACEIs improve microvascular dysfunction and ETT responses
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Ramipril & Atorvastatin treatment improve endothelial function (reduced oxidative stress)
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8 mmol/l (High LDL (should be 2-3))
FMD: 1
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8 (should be 4

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