Myocardial ischemia
Myocardial ischemia refers to the result of a mismatch in myocardial oxygen supply and demand as a consequence of the cessation of blood flow resulting in reversible injury or myocardial cell death if prolonged associated with a loss of contractile function.
Epidemiology
The total prevalence of ischemic heart disease in the US has been 6.7% for adults above the age of 20 years and is more common in males than in females. Globally it is the leading cause of death and global mortality rates range from below 150/100000 in most of the world up to 280/100000 in eastern Europe and central Asia .
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 (male sex, family history, age, dyslipidemia, diabetes, hypertension smoking and others) .
Associations
Clinical conditions associated with myocardial ischemia include the following:
- stable/unstable angina
- myocardial infarction
- ischemic cardiomyopathy
Clinical presentation
Patients usually present with angina and/or dyspnea, new-onset heart failure or left ventricular dysfunction .
Typical angina is traditionally classified as :
- 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 presentation from typical symptoms to electrophysiologic and/or hemodynamic instability with potential cardiac arrest to mechanical complications like mitral valve insufficiency .
Initial clinical workup of ischemia obviously 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 :
- tachyarrhythmia/bradyarrhythmia
- heart failure
- mitral insufficiency
- death
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 .
A model referring to a temporal sequence of pathophysiological events described in the setting of myocardial ischemia is the ischemic cascade :
- metabolic changes: conversion from aerobic to anaerobic metabolism
- inducible perfusion changes
- diastolic dysfunction
- systolic dysfunction including regional wall motion abnormalities
- ECG changes indicating ischemia
- angina
Etiology
Major causes of myocardial ischemia include :
- coronary plaque disruption or erosion with thrombus formation
- coronary artery disease/coronary artery stenosis
- coronary artery spasms
- coronary embolism
- coronary microvascular dysfunction
- 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
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 in regard to cardiac function. The first ischemic sign which might be detected echocardiographically is diastolic dysfunction and later in the course systolic dysfunction. Other signs include :
- 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 in 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
CT 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 . It can also help in the characterization of coronary plaques. CT-based fractional flow reserve (CT-FFR) can help in the assessment of hemodynamic 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 an 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 .
Invasive functional testing should accompany invasive coronary angiography due to frequent mismatch between angiographic and hemodynamic severity of coronary stenosis. The assessment of the fractional flow reserve (FFR) is still considered the current 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 .
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 .
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 to .
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 .
- cine imaging
- regional wall motion abnormalities under stress and/or rest in the affected vascular territory
- tardokinesis
- 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 indicating myocardial edema and thus advanced ischemic injury
- late gadolinium enhancement
- indicates myocardial necrosis or myocardial scar tissue from previous myocardial infarction
Nuclear medicine
There are several non-invasive functional imaging methods for myocardial ischemia testing .
SPECT
Can be done as technetium-99m MIBI SPECT or technetium-99m tetrofosmin SPECT scan for stress and resting scan.
PET-CT/PET-MRI
The myocardium utilizes fatty acids under normal circumstances and glucose during ischemia with 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 17 segment 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:
- myocardial edema
- signs of myocardial necrosis/myocardial scar tissue
- and the relation of those parameters to each other
Treatment and prognosis
Obviously, treatment of myocardial ischemia varies with the clinical presentation, underlying cause, cardiac risk profile and the presence of other comorbidities .
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 causes namely haemodynamically relevant coronary artery stenosis and atherosclerotic plaque rupture with thrombus formation .
Adequate pharmacological therapy with anti-ischemic medications as beta-blockers, the immediate relieve 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 .
The third part of the management consists of lifestyle modifications and the control of risk factors .
Management of other causes of myocardial ischemia include the following :
- 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 which can mimic the presentation and/or appearance of myocardial ischemia include :
- cardiac disorders
- vascular disorders
- pulmonary disorders
- gastrointestinal disorders
- musculoskeletal disorders