Myocardial ischemia refers to the result of a mismatch between myocardial oxygen supply and demand as a consequence of the cessation of blood flow resulting in reversible injury or myocardial cell death if prolonged and associated with a loss of contractile function.
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Epidemiology
The total prevalence of ischemic heart disease in the US is 6.7% for adults >20 years old and is more common in males than in females. Globally it is the leading cause of death and global mortality rates range from below 150/100,000 in most of the world up to 280/100,000 in Eastern Europe and Central Asia 1,2.
Risk factors
Attributes, characteristics or exposures that increase the likelihood of developing myocardial ischemia are coronary artery disease (CAD) and all its associated risk factors 3-6:
male sex
family history
increased age
tobacco smoking
Beyond that coronary artery anomalies and certain cardiomyopathies might carry an increased risk for myocardial ischemia.
Associations
Clinical conditions associated with myocardial ischemia include the following:
stable/unstable angina
Clinical presentation
Patients usually present with angina and/or dyspnea, new-onset heart failure or left ventricular dysfunction 3-6.
Typical angina is traditionally classified as follows 3:
tightness or discomfort of the anterior chest, neck, jaw, shoulder or arm
worse on physical exertion
and alleviated by rest or nitrates within about 5 minutes
Atypical angina is defined by two of the above features and non-anginal thoracic pain by one.
Unstable angina can present at rest for a longer period (>20 min) as new-onset angina or with progressively worsening symptoms.
Acute ischemic events have a wide range of presentations from typical symptoms to electrophysiologic and/or hemodynamic instability with potential cardiac arrest to mechanical complications like mitral valve insufficiency 4.
Initial clinical workup of ischemia includes ECG and biochemical biomarkers of cardiomyocyte injury especially in the setting of an acute situation.
Complications
The main complication of prolonged myocardial ischemia is myocardial infarction and all of its complications including 7:
tachyarrhythmia/bradyarrhythmia
Pathology
A mismatch in myocardial-oxygen supply and demand characterized by alterations in oxygen delivery and consumption of the myocardium leads to immediate changes on a molecular and cellular level, usually affecting the myocardium of the respective vascular territory 7.
A model referring to a temporal sequence of pathophysiological events described in the setting of myocardial ischemia is the ischemic cascade 9-11:
metabolic changes: conversion from aerobic to anaerobic metabolism
inducible perfusion changes
diastolic dysfunction
systolic dysfunction including regional wall motion abnormalities
ECG changes indicating ischemia
Etiology
Major causes of myocardial ischemia include 3-6:
coronary plaque disruption or erosion with thrombus formation
coronary artery disease/coronary artery stenosis
coronary artery dissection or aortic dissection with the involvement of coronaries
supply-demand mismatch of other causes (tachyarrhythmia/bradyarrhythmia, anemia, hypotension, shock, severe hypertension, hypertrophic cardiomyopathy, etc.)
Location
Myocardial ischemia in the setting of vascular compromise is usually confined to the correspondent vascular territory and typically affects primarily the subendocardium progressing towards the epicardium.
Radiographic features
The choice of imaging modalities in suspected myocardial ischemia depends on presenting symptoms and their temporal course, the clinical likelihood of obstructive coronary artery disease, patient comorbidities as well as clinical parameters like ECG, myocardial necrosis markers and others.
Imaging modalities can depict different pathophysiological events within the ischemic cascade such as altered glucose metabolism or perfusion, diastolic and systolic dysfunction including regional wall motion abnormalities and can help in risk stratification.
Echocardiography
Echocardiography will offer valuable information about cardiac function. The first ischemic sign which might be detected echocardiographically is diastolic dysfunction and later in the course systolic dysfunction. Other signs include 3,6:
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regional wall motion abnormalities under stress and/or rest in the affected vascular territory
decreased systolic thickening (<40%)
early systolic lengthening
post systolic thickening
tardokinesis
adjacent hyperkinesia
Also, echocardiography will help in the detection of concurrent heart disease or the exclusion of cardiac differential diagnosis.
Stress echocardiography is a non-invasive functional imaging method based on the inotropic reserve of the myocardium and is well established by a sequential application of dobutamine and possibly atropine.
CT
Coronary CTA
A CT coronary angiogram can be used for the diagnosis or exclusion of coronary artery disease in symptomatic patients in the setting of a low to intermediate pretest probability 3,4. It can also help in the characterization of coronary plaques. CT-based fractional flow reserve (CT-FFR) can help in the assessment of haemodynamically relevant stenosis.
CT perfusion
CT perfusion can show hypodense first-pass perfusion defects in the affected vascular territory indicating myocardial ischemia.
Coronary angiography
Invasive coronary angiography (ICA) is the modality of choice in the clinical setting of acute coronary syndrome and/or severe symptoms refractory to medical therapy and a high pretest probability of coronary artery disease (CAD). It will accurately visualize luminal arterial compromise and can be utilized for primary percutaneous coronary intervention (PCI) with angioplasty and/or stenting in the same setting 3.
Invasive functional testing should accompany invasive coronary angiography due to the frequent mismatch between angiographic and hemodynamic severity of coronary stenosis. The assessment of the fractional flow reserve (FFR) is still considered the gold standard in the evaluation of hemodynamic-relevant stenosis, which is the ratio of the maximal flow in the affected artery distal to the stenosis compared to the proximal flow of that artery.
Intravascular imaging as intravascular ultrasound (IVUS) or optical coherence tomography (OCT) can be used in the workup of plaque rupture, ulceration as well as coronary artery dissection 12,13.
Provocative spasm testing can be performed to confirm coronary vasospasm. However, the procedure should not be conducted in an acute coronary syndrome or an acute stage of a myocardial infarction 12.
MRI
Cardiac MRI is a non-invasive functional imaging method, which allows the evaluation of myocardial perfusion and viability for the assessment of myocardial ischemia.
A basic myocardial ischemia protocol includes the assessment of cardiac function, regional wall motion abnormalities and perfusion during stress and rests ideally in conjunction with a myocardial viability assessment with late gadolinium enhancement. The latter might indicate myocardial necrosis in the setting of acute myocardial infarction or show myocardial scar tissue from a previous infarct to which alterations in wall motion and perfusion should be compared 11.
In the setting of an MRI in an acute coronary syndrome (where stress testing is contraindicated) additional T2 weighted imaging should be obtained for the assessment of myocardial edema to assess the acute ischemic event and the area at risk 11.
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cine imaging
regional wall motion abnormalities under stress and/or rest in the affected vascular territory
post-systolic thickening
perfusion imaging: decreased or delayed uptake during the first-pass perfusion at vasodilator stress and/or at rest
T2/STIR black blood: hyperintensity indicates myocardial edema and thus advanced ischemic injury
IRGE/PSIR: subendocardial late gadolinium enhancement indicates myocardial necrosis or myocardial scar from previous myocardial infarction
Nuclear medicine
There are several non-invasive functional imaging methods for myocardial ischemia testing 3,6.
SPECT
Can be done as a Technetium-99m MIBI SPECT or Technetium-99m tetrofosmin SPECT scan for stress and resting scan. On perfusion scintigraphy, a decrease in regional flow would typically result in a cold defect area. There may be an associated regional wall motion abnormality or decrease in left ventricular ejection fraction.
PET-CT/PET-MRI
The myocardium utilizes fatty acids under normal circumstances and glucose during ischemia which results in an increased uptake of FDG of the ischemic myocardium compared to the normal cells.
Radiology report
The radiological report depends mostly on the examination but usually includes a description of the following features. Localization is done according to the cardiac segmentation model:
regional wall-motion abnormalities
perfusion defects during stress and rest
MRI
In addition to the above-mentioned features the MRI report should include the description of the following:
and the relation of those parameters to each other
Treatment and prognosis
Treatment of myocardial ischemia varies with the clinical presentation, underlying cause, cardiac risk profile and the presence of other comorbidities 3-6.
Percutaneous coronary intervention (PCI) with revascularization and potentially stent placement with adjunctive antiplatelet therapy plays the central role in the management of the two most common causes namely haemodynamically relevant coronary artery stenosis and atherosclerotic plaque rupture with thrombus formation 3-6.
Adequate pharmacological therapy with anti-ischemic medications as beta-blockers, the immediate relief of anginal symptoms with nitroglycerin as well as the prevention of further cardiac events with antiplatelet therapy, lipid-lowering drugs and angiotensin-converting enzyme (ACE) inhibitors forms a further mainstay in the management 3-6.
The third part of the management consists of lifestyle modifications and the control of risk factors 3-6.
Management of other causes of myocardial ischemia includes the following 3-6,11:
microvascular dysfunction: beta-blockers, ACE inhibitors, statins, lifestyle modifications
coronary vasospasm: calcium antagonists, nitrates, Rho-kinase inhibitors
coronary artery dissection: conservative treatment with antiplatelet therapy and beta-blockers
coronary embolism: PFO closure device, antiplatelet therapy, anticoagulation
oxygen supply-demand mismatch situations: reversal of the underlying cause
The overall prognosis depends on many factors including exact etiology, the presence, amount and control of underlying risk factors, previous cardiac events and other comorbidities.
Differential diagnosis
Conditions that can mimic the presentation and/or appearance of myocardial ischemia include 3,4:
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cardiac disorders
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vascular disorders
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pulmonary disorders
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gastrointestinal disorders
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musculoskeletal disorders
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