Ischemic heart disease: Pathology review

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Case study0:00–1:30

I 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 a 25-year history of regular tobacco use.
He's reporting 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 are 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 describes 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 Tirion, a 45-year-old man with a known history of hypertension, diabetes, and hyperlipidemia.
He reports epigastric abdominal pain at rest, shortness of breath, sweating, and lightheadedness for the past 30 minutes.
His BP is 80/60, and his heart beat is 45 BPM. An ECG reveals ST segment elevation and leads 23, and AVF.
All three have ischemic heart 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 muscle is called myocardial ischemia, which results in a severely reduced ability of the heart muscle 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 the most common cause of ischemic heart disease is atherosclerosis of the coronary arteries, which is referred to as coronary artery disease.
Risk factors for atherosclerosis can be divided into two main groups non-modifiable risk factors include age, with biological males greater than 45 years and biological females greater than 55 years being at risk, and family history of coronary artery disease.
On the other hand, modifiable risk factors include lipid abnormalities such as elevated LDL or low HDL levels, as well as hypertension, diabetes mellitus, and smoking.
Ischemic heart disease can present in many ways including stable angina, Princemetal angina, acute coronary syndrome, which includes unstable angina, non-ST segment elevation myocardial infarction, or N stimia, and ST segment elevation myocardial infarction, or STII, chronic ischemic heart disease, and sudden cardiac death.
Now aside from atherosclerosis, there are other less common causes of ischemic heart 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 coronary embolism include atrial fibrillation, infective endocarditis, a left atrial or ventricular thrombus, or an individual's 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 vasculotides 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 ischemic heart disease.
Then another cause of ischemic heart 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 ischemic heart 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 70% of the coronary artery lumen.
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.

Stable angina4:54–9:17

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 atherosclerotic plaques grow slowly, giving time for the heart to develop collateral circulation.
That supplies the hypo perfused 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 dipyridol. Now when a vasodilating medication like dipyridamole is given to an individual with stable angina, coronary steel 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 vasospastic angina or prince metal angina. Here there is no atherosclerotic plaque including the lumen.
Instead, the coronary artery undergoes vasospasm, narrowing the lumen. Individuals typically develop angina at rest, and triggers include smoking, cocaine, alcohol, and tryptans.
For example, the exam may tell you about an individual with a history of migraines, and tryptans, 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 medications can be 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.
OK. 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, in stimmi, and stimmi.
These three are huddled together under the umbrella of acute coronary syndrome, or ACS. An acute coronary syndrome typically manifests as a sudden new onset angina or an increase in the severity of an existing stable angina.
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, biological 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.

Acute Coronary Syndrome9:17–13:22

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.
OK, 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 instimmy, 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 in stimmy 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 stimmi, which happens when the thrombus occludes 100% 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 stimmi, but it's the ST segment elevation on an ECG that immediately clinches the diagnosis.
The reason we're talking about troponin, of which there are two types, troponin I and T, is that this enzyme is a specific cardiac biomarker.
So when there's been irreversible damage to heart cells, their membranes become damaged and the troponin inside escapes and can enter the bloodstream.
Both troponin I and T levels can be elevated in the blood within 2 to 4 hours after infarction. And usually peak around 48 hours but stay elevated for 7 to 10 days.
Now for your exam you might be asked to locate the infarct and the vessel involved based on the ECG. This can be done by locating which leads have the ST elevation.
V1 and V2 involvement is an anteroseptal MI, which means that the left anterior descending artery or LAD is involved. 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 1 and AVL, and the left circumflex is occluded.
Inferior MI involves leads 23, 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 through V9 must be obtained in such a scenario. OK, exams love to ask about the pathological manifestations and complications of a myocardial infarction based on the time elapsed.

Infarct location13:22–14:50

Therefore, let's take a look at a timeline illustrating this. In the 1st 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.
During this period, arrhythmias can occur because the infarction disrupts the electrical flow through the myocardium. Premature ventricular contractions, 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 one 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 the 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.

Pathology timeline14:50–20:55

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 an elevation of jugular venous pressure.
It's important to look for a right ventricular MI because venodilating 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 is extensive coagulative necrosis, and a large amount of neutrophils have infiltrated, causing acute inflammation.
That inflammation can spread towards pericardium, causing post-infarction fibrinous pericarditis. This presents with a low grade fever and sharp pleuritic chest pain, meaning it increases with inspiration.
OK, 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 intraventricular 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.
Additionally, as oxygen-rich blood is shunted from the high pressure left ventricle to the lower pressure right ventricle, the oxygen saturation in the right ventricle increases.
Ventricular free wall rupture classically occurs in anterior wall stems 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.
OK, if someone had previously had an old MI or they have ventricular hypertrophy because of something like hypertension, 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 corda tendina.
This usually occurs 2 to 7 days post infarction. Normally the anterior lateral papillary muscle receives a dual blood supply from both the LAD and the left circumflex artery.
The posterior medial 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 NSTI are managed with a combination of antiplatelet and anticoagulation therapies to prevent further thrombosis or embolism from a ruptured plaque.
After that, some patients may also need immediate coronary angiography and revascularization, which is also called reperfusion therapy to restore coronary perfusion.
Stimia 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 open up a blood vessel or fibrinolytic therapy which uses medications to break down fibrin in blood clots.
Then after reperfusion therapy, patients are given antiplatelet therapy and occasionally anticoagulation therapy as well.
All right, so reperfusion therapy focuses on reestablishing blood flow to the dying 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 reestablish blood flow within the 1st 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.

Treatment 20:55–23:26

Now an important complication of reestablishing perfusion or reperfusion therapy is reperfusion injury where the 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.
Alright, as a quick recap, ischemic heart disease is usually due to coronary artery disease or atherosclerosis of the coronary arteries.
It includes a variety of presentations, including stable angina and acute coronary syndrome. Stable angina occurs secondary to a stable atherosclerotic plaque occluding at least 70% of the coronary artery and presents with exertional chest pain relieved by rest and nitroglycerin.
ECG and troponin levels are normal. ACS usually occurs when the atherosclerotic plaque is disrupted, resulting in thrombosis.
ACS includes unstable angina, in stimmi, and stimmi. Unstable angina presents as new onset angina or a change in the pattern of symptoms.
ECG shows ST segment depression or T wave changes, but troponin levels are normal. NSTI also can have ST segment depression or T wave changes on ECG.
But here troponin levels are elevated. STIMI has ST segment elevation on ECG and elevated troponin levels.
Prince metal angina is not due to atherosclerotic disease, but it's caused by coronary vasospasm and causes transient ST segment elevation on ECG with normal troponin levels.
OK, back to our cases. Anish has multiple risk factors for atherosclerosis, including hypertension, hyperlipidemia, and tobacco use.
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.

Review23:26–24:41

She's an elderly lady with diabetes mellitus. Her type of MI is NSTI 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 stimmi in leads 23, and AVF. Fortunately, the MI was caught early, and he's being treated with percutaneous coronary intervention.

Summary24:41–24:07

Coronary artery disease: Pathology Review: Video | Osmosis