Coronary artery disease: Pathology review

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Case study0:00–1:30

In an urban emergency department, 3 people came in for chest pain. The first is Anish, a 54 year old man with a known history of hypertension, hyperlipidemia, and 25-pack year smoking.
He’s complaining of shortness of breath, and squeezing, retrosternal chest pain that radiates to his neck, jaw and left arm.
He’s been having these episodes but they only come after riding his bicycle for at least 20 minutes, and is relieved once he rests.
Investigations reveal a normal ECG and normal troponin levels. Next, is Erica, a 66-year old woman with a history of diabetes mellitus who complains of sudden-onset shortness of breath, fatigue and dizziness, but no chest pain.
An ECG reveals ST-segment depression, and troponin levels are elevated. Finally, There’s Tyrion, a 45-year old man, with a known history of hypertension, diabetes, and hyperlipidemia.
He complains of epigastric abdominal pain at rest, shortness of breath, sweating and lightheadedness for the past 30 minutes.
His blood pressure is 80/60, and his heart is 45 beats per minute. An ECG reveals ST-segment elevation in leads II, III and aVF.
All three have coronary artery disease which is defined as an imbalance between myocardial oxygen demand and supply from the coronary arteries.

Pathology1:30–4:54

Reduced oxygen supply to the heart is defined myocardial ischemia, which results in a severely reduced ability of the heart muscle ability to contract.
If this is prolonged, it can go on to cause myocardial infarction, otherwise known as heart attack, which refers to death of heart muscle.
Now, coronary artery disease is usually caused by atherosclerosis of the coronary arteries. Risk factors for atherosclerosis can be divided into non-modifiable ones, which include age, with men greater than 45 years and women greater than 55 years being at risk, and family history of coronary artery disease, and modifiable ones, like lipid abnormalities including elevated LDL or low HDL levels, as well as hypertension, diabetes mellitus and smoking.
Coronary artery disease can present in many ways, including stable angina, Prinzmetal angina, acute coronary syndrome - which includes unstable angina, non-ST-segment elevation myocardial infarction, or NSTEMI, ST-segment elevation myocardial infarction, or STEMI, chronic ischemic heart disease, and sudden cardiac death.
Now, aside from atherosclerosis, there are other less common causes of coronary artery disease, such as coronary artery embolus vasculitis and vasospasm.
In a coronary embolism, pieces of a clot from another site break off and can travel into a coronary artery, occluding it.
Risk factors for a coronary embolism include atrial fibrillation, infective endocarditis, a left atrial or ventricular thrombus or in individuals undergoing cardiac catheterization.
As for vasculitis, coronary artery disease in young children should prompt you to consider Kawasaki disease, a medium-vessel vasculitis that classically causes a coronary artery aneurysm.
Also, other vasculitides like polyarteritis nodosa can also cause coronary artery disease. Now, coronary artery vasospasm, meaning the smooth muscles around the arteries constrict extremely tightly, may also reduce blood flow and result in coronary artery disease.
Then, another cause of coronary artery disease is aortic valve stenosis. See, the right and left main coronary arteries branch off the base of the aorta, and so in aortic stenosis, not enough blood gets through the aorta and into the coronaries, resulting in myocardial ischemia.
Also, any cause of concentric ventricular hypertrophy, such as aortic valve stenosis, hypertension, or hypertrophic cardiomyopathy may result in coronary artery disease, because you essentially have more heart muscle to supply.
Now let’s take a look at the presentations of coronary artery disease, starting with stable angina! This occurs secondary to myocardial ischemia, caused by a fixed atherosclerotic plaque occluding more than 75 percent of the coronary artery lumen.

Stable angina4:54–9:17

What you must remember here is that this results in reversible cell injury. An infarction, on the other hand, is when there’s irreversible cell injury or cell death.Now, stable angina manifests as a deep, poorly localized, squeezing, crushing or suffocating retrosternal pain that may radiate to the arm, jaw or neck.
Lots of adjectives. It’s often accompanied by other symptoms, such as shortness of breath, nausea, vomiting, diaphoresis, fatigue or dizziness.
A high yield fact is that this chest pain is reproducible during any activity that increases myocardial oxygen demand, such as physical exertion or emotional stress, and is relieved within 5 minutes by rest or sublingual nitroglycerin.
The term “stable” refers to the atherosclerotic plaque itself, which hasn’t ruptured yet and is structurally stable. Now, sometimes in stable angina, an atherosclerotic plaque can cause near-total occlusion of the coronary artery, yet individuals may not develop infarction.
The reason is because athersclerotic plaques grow slowly, giving time for the heart to develop collateral circulation that supplies the hypoperfused area.
The ECG in stable angina is typically normal at rest, but may become abnormal on stress testing, which measures the heart's ability to respond to external stress in a controlled clinical environment.
The stress response is induced by exercise or by stimulation with medications, like dipyridamole. Now, when a vasodilating medication like dipyridamole is given to an individual with stable angina, coronary steal syndrome may occur.
That’s because it causes vasodilation of all coronary arteries, except the ones which are obstructed - because beyond the obstruction, the coronary artery is already maximally dilated.
The end result is that blood is diverted, or stolen, away from the ischemic myocardium to non-ischemic areas, which further worsens the ischemia.
This shows in the ECG as an ST-segment depression.However, a high yield fact is that cardiac biomarkers like troponin levels are always normal because there’s ischemia, but no infarction.
A variant of angina is called well... variant angina, or Prinzmetal angina.
Here, there’s no atherosclerotic plaque occluding the lumen, instead the coronary artery undergoes vasospasm, narrowing the lumen.
Individuals typically develop angina at rest, and triggers include smoking, cocaine, alcohol, and triptans. For example, the exam may tell you about an individual with a history of migraines, and triptans like sumatriptan are one of the treatment options for migraine.
Due to transmural ischemia, a 24-hour ECG called a Holter monitor classically shows transient elevation of the ST-segment, but troponin levels are normal, because once again, there is no infarction.
To help with the diagnosis, low doses of vasoconstrictive medication called ergonovine are given to provoke vasospasm which results in transient ST-segment elevation.
Treatment includes calcium channel blockers and nitroglycerin, which relax the vascular smooth muscle, and cessation of the trigger.Okay, in stable angina, the atherosclerotic plaque was fixed and not disrupted.
But when the atherosclerotic plaques are disturbed, we get the next three disorders: unstable angina, NSTEMI and STEMI. These three are huddled together under the umbrella of acute coronary syndrome, or ACS.
An acute coronary syndrome typically manifests as sudden, new-onset angina, or an increase in the severity of an existing stable angina.

Acute Coronary Syndrome9:17–13:22

This may be an increase in the frequency or intensity of episodes, when they can be triggered by less exertion than before, or when symptoms occur at rest.
Sometimes, though, there are atypical presentations. Older people, females, and individuals with diabetes can present without chest pain.
Instead, they come with vague symptoms like shortness of breath, fatigue, and dizziness. Now, plaques are made of a fibrous cap and a necrotic lipid core and the composition of the plaque determines the risk of rupture.
The high yield concept here is that a thin fibrous cap and a rich lipid core mean that the plaque is at high risk of rupture.
When a plaque ruptures, the underlying collagen is exposed, and in response, platelets quickly aggregate, forming a thrombus.
Okay in unstable angina, the atherosclerotic plaque ruptures and causes near-total but incomplete occlusion of the coronary artery.
The ECG shows ST-segment depression or T-wave inversion, but troponin levels are normal, because there is no myocyte necrosis.
But if the troponin levels are elevated, then we now call it NSTEMI, which signifies an infarction beneath the endocardium, also called a subendocardial infarct.
The infarct happens here because the coronary vessels run along the epicardium, the outer one-third of the heart wall. So this is the farthest area from the blood supply.
Now, the reason we call it NSTEMI is because on ECG, a subendocardial infarct manifests with changes like ST-depression or T-wave inversion, however it never shows ST-segment elevation.
If there’s ST segment elevation, then it’s a STEMI, which happens when the thrombus occludes 100 percent of the lumen. The ST-segment elevation signifies an acute transmural infarction, meaning it involves the whole wall.
Troponin levels are also elevated in a STEMI, but it’s the ST-segment elevation on an ECG that immediately clinches the diagnosis.
The reason why we’re talking about troponin, of which there are two types, troponin I and T, is that, together with CK-MB, which is a combination of creatine kinase enzymes M and B, they make up what’s known as the key cardiac biomarkers.
So, when there’s been irreversible damage to heart cells, their membranes become damaged and these proteins and enzymes inside escape, and can enter the bloodstream.
Both troponin I and T levels can be elevated in the blood within 2-4 hours after infarction, and usually peak around 48 hours, but stay elevated for 7-10 days.
CK-MB starts to rise 2-4 hours after infarction, peaks around 24 hours, and returns to normal after 48 hours. Since CK-MB returns to normal more quickly, it can be useful to diagnose reinfarction, a second infarction that happens after 48 hours but before troponin levels go back to normal.
Bare in mind though that unlike troponins, CK-MB is not specific for cardiac injury and it may also be elevated in cases of skeletal muscle damage elsewhere in the body, like trauma, heavy exertion, and myopathy.Now for your exam, you might be asked to locate the infarct and the vessel involved based on the on the ECG.
This can be done by locating which leads had the ST elevation: V1 and V2 involvement is an anteroseptal MI, which means the left anterior descending artery, or LAD is involved.

Infarct location13:22–14:50

V3, V4 involvement is an anteroapical MI, which means the distal part of the LAD is involved. V5, V6 involvement is an anterolateral MI, which involves the LAD or left circumflex artery.
Lateral MI involves leads I and aVL, and the left circumflex is occluded. Inferior MI involves leads II, III and aVF with the right coronary artery being the culprit.
Inferior wall myocardial infarctions are very high yield because they can also present as epigastric abdominal pain instead of chest pain.
RCA occlusion can also cause right ventricular infarction, but right sided leads would have to be obtained to see that. Finally, whenever there is ST depression with tall R-waves in V1 to V3, then a posterior MI involving the posterior descending artery is a possibility.
Therefore, posterior leads V7-V9 must be obtained in such a scenario. Okay, exams love to ask about the pathological manifestations and complications of a myocardial infarction based on the time elapsed.
Therefore, let’s take a look at a timeline illustrating this. In the first 24 hours, the heart looks grossly normal.
On light microscopy, after 4 hours, coagulative necrosis begins, and the necrotic myocardial cells hypercontract, giving them a wavy appearance.

Pathology timeline14:50–20:55

During this period, arrhythmias can occur because the infarction disrupts the electrical flow through the myocardium. Premature ventricular arrhythmias or PVCs are the most common arrhythmia, but these are benign.
On the other hand, ventricular arrhythmias like ventricular tachycardia or fibrillation are the most common cause of sudden cardiac death, which is death within 1 hour of symptom onset.
A common way the exam might try to confuse you, is by telling you that the individual is an athlete, which makes you inclined to choose hypertrophic cardiomyopathy.
However, ventricular arrhythmias due to coronary artery disease are a more common cause of death in athletes over 35 years old, whereas hypertrophic cardiomyopathy is more common in those under 35 years old.
Other complications include heart failure and cardiogenic shock, which are the most common cause of death from MI in the hospital.
In case of right coronary artery occlusion, the infarcted right ventricle dilates, pushing the interventricular septum onto the left ventricular cavity, causing decreased left ventricular filling, which results in a decreased stroke volume and hypotension.
You can differentiate between right and left ventricular failure clinically, because in a right ventricular failure, the lungs are clear on auscultation, and there is elevation of jugular venous pressure.
It’s important to look for a right ventricular MI because veno-dilating medications like nitroglycerin are contraindicated in these cases, as they further decrease the preload, worsening the hypotension.
1 to 3 days after the infarction, the affected area appears grossly red. On light microscopy, there’s extensive coagulative necrosis, and a large amount of neutrophils have infiltrated causing acute inflammation.
That inflammation can spread towards pericardium, causing postinfarction fibrinous pericarditis. This presents with a low-grade fever, and sharp, pleuritic chest pain, meaning it increases with inspiration.
Okay, 3 to 14 days after the infarction, macrophages come over to clean up the necrotic mess, and soft, yellow granulation tissue begins to develop to repair the infarcted tissue.
This soft granulation tissue is quite weak, so there’s a risk of interventricular septum or ventricular free wall rupture.
Interventricular septum rupture typically presents at around 3 to 5 days as a left-to-right ventricular septal defect, which presents as a new holosystolic murmur at the left sternal border, and increased oxygen saturation in the right ventricle.
Ventricular free wall rupture classically occurs in anterior wall STEMIs, and presents at around 5 to 14 days. As a result, large amounts of blood leak into the pericardial cavity, causing a pericardial tamponade.
Sometimes, the rupture is contained by the adherent pericardium, producing a balloon-like sack of blood called a ventricular pseudoaneurysm.
This pocket of blood is static, and stasis promotes clotting, producing what’s called a mural thrombus. Bits of this thrombus can embolize to the systemic circulation, resulting in peripheral complications like a stroke.
Okay, if someone had previously had an old MI, or they have ventricular hypertrophy because of something like hypertension, then this actually protects them against wall rupture, due to the fibrosis and a thick wall, respectively.
A rare instance in which a pathology protects from another pathology. Another complication is rupture of the papillary muscles, small muscles that anchor to the atrioventricular valves by the chordae tendineae.
This usually occurs 2 to 7 days post-infarction. Normally, the anterolateral papillary muscle receives a dual blood supply from both the LAD and the left circumflex artery.
The posteromedial papillary muscle, however, is solely supplied by the posterior descending artery, so it’s more at risk of rupture, and this can cause acute-onset mitral regurgitation and pulmonary edema.
Alright, now 2 weeks to a couple of months post-MI, macrophages invade the tissue, and the healing process begins with the formation of granulation tissue, which is a type of scar tissue that’s yellow and soft, along with some new blood vessels, in a process called neovascularization.
This scar tissue may cause the ventricular wall to bulge out, forming a true ventricular aneurysm. The affected segment is made of scar tissue, so it doesn't contract.
Therefore, there is a risk of developing heart failure, as well as a mural thrombus due to stasis of blood flow in that area.
But unlike a pseudoaneurysm, the ventricular wall is now strong, so there’s no risk of rupture. Another complication during this period is Dressler syndrome, a fibrinous pericarditis that occurs secondary to formation of autoantibodies that target serosal surfaces like the pericardium.
Now, as for treatment, unstable angina and NSTEMI are managed with a combination of antiplatelet and anticoagulation therapies to prevent further thrombosis or embolism from an ulcerated plaque.
After that, some patients may also need immediate coronary angiography and revascularization, which is also called reperfusion therapy, to restore coronary perfusion.
STEMI is managed with emergency reperfusion therapy, either with percutaneous coronary intervention or PCI, where a tiny catheter is used to place a stent in the coronary artery to physically open up a blood vessel or fibrinolytic therapy, which uses medications to break down fibrin in blood clots.

Treatment 20:55–23:26

Then, after reperfusion therapy, patients are given a combination of antiplatelet and anticoagulation therapies.Alright, so reperfusion therapy focuses on re-establishing blood flow to the dying heart heart cells.
Remember that within 60 seconds after the onset of total ischemia, we have myocardial cell injury and contractility loss.
However, for about 30 minutes, this remains reversible,which is known as myocardial stunning. So, if we manage to re-establish blood flow within the first 30 minutes following blockage, these myocardial cells can be salvaged and contractility will be gradually returning to normal over the next several hours to days.
However, after about 30 minutes, ischemic injury becomes irreversible, so, no matter what we do, these cells will be destroyed and removed.
Now an important complication of re-establishing perfusion, or reperfusion therapy, is reperfusion injury, where tissue is damaged by returning blood flow.
And, this is thought to happen because of a couple mechanisms. First, blood flowing back to cells brings this influx of calcium, and since calcium leads to muscle contraction, the irreversibly damaged cells contract, and since they’ve been irreversibly damaged, they get stuck like that and can’t relax.
This shows up on histology as this characteristic contraction band necrosis. Also though, blood brings along oxygen, which, paradoxically, can actually lead to more cellular damage.
The conditions in an ischemic heart seem to cause an increased conversion of the returning oxygen to reactive oxygen species, which go on to damage more heart cells.Okay, to review.
Coronary artery disease is usually an atherosclerotic disease of the coronary arteries and includes a variety of presentations including stable angina and acute coronary syndrome.
Stable angina occurs secondary to a stable athersclerotic plaque occluding at least 75% of the coronary artery, and presents with exertional chest pain relieved by rest and nitroglycerin.
ECG and troponin levels are normal. ACS occurs when the athersclerotic plaque is disrupted, resulting in thrombosis.
ACS includes unstable angina, NSTEMI and STEMI. Unstable angina presents as new-onset angina or a change in the pattern of symptoms.

Review23:26–24:41

ECG shows ST-segment depression or T-wave changes, but troponin levels are normal. NSTEMI is similar to unstable angina, but troponin levels are elevated.
STEMI shows ST-segment elevation, Q-waves, and elevated troponin levels. Prinzmetal angina is not due to atherosclerotic disease but is caused by coronary vasospasm, and causes transient ST-segment elevation with normal troponin levels.
Okay, back to our cases. Anish has multiple risk factors for atherosclerosis, including hypertension, hyperlipidemia and smoking.
He’s presenting with stable angina, because his angina only comes when riding his bicycle, and is relieved during rest. Erica has two risk factors for a silent MI: she’s an elderly lady with diabetes mellitus.
Her type of MI is NSTEMI, because there is no ST-segment elevation on the ECG, and troponin levels are elevated. Tyrion came in with epigastric pain, and considering his risk factors and associated symptoms, this is a potential presentation of inferior MI.
This was confirmed as the ECG showed STEMI in leads II, III and aVF. Fortunately, the MI was caught early, and he’s being treated with percutaneous coronary intervention.

Summary24:41–25:37

is Angelina only comes when riding his bicycle and is relieved during rest. Erica has to risk factors for a silent Mi.
She's an elderly lady with diabetes mellitus type of Mi is nstemi because there is no st-segment elevation on the ECG. And troponin levels are elevated.
Syrian came in with epigastric pain and considering his risk factors and Associated symptoms. This is a potential presentation of inferior Mi.
This was confirmed as to eat PG showed stemi and leads to three and avf. Fortunately, the m i was caught early and he's being treated with percutaneous coronary intervention.
Coronary artery disease: Pathology Review: Video | Osmosis