Topics B2-7. Cardio 2: MI, SCD, Angina, Ischemic Heart Disease, Endocarditis, Valvular Heart Disease, Cardiomyopathies, Myocarditis

Question 1

Note: Topic A5 includes myocardial infarction as well as B2, so will repeat some questions but not everything. I will ask more detailed questions and use the book more for these cards, since the other one I kept it too simple and this is really important

Answer 1

OK, mark this card 5 and hopefully it won’t come back

Question 2

How does ischemic heart disease rank as far as cause of death in developed countries?

How many people who have heart attacks normally die from them?

Answer 2

1 cause of death in developed countries

1/3 of people with MI die from it, and half of those before they get to the hospital

Question 3

What is the major underlying cause of MI in the vast majority of cases?

Answer 3

Coronary atherosclerosis (“fixed coronary”) that are then involved in thrombogenesis.

Fixed coronary + dynamic changes like rupture of plaque -> AMI.

Question 4

How do plaques rupture and cause thrombosis?

answer has some general review of formation of thrombus too

Answer 4

A plaque is disrupted (usually at its “shoulder”) by mechanical forces or intraplaque hemorrhage
-> subendothelial collagen and necrotic plaque contents get into the blood
-> platelets adhere and aggregate, releasing Thromboxane A2, ADP, and serotonin, causing further platelet aggregation and vasospasm
-> Coagulation cascade is actvated by tissue factor/VIIa and thrombus develops with fibrin network
Thrombus grows to completely occlude the lumen

Question 5

What is a “transmural” versus “subendocardial” myocardial infarction?

What is the “wavefront theory?”

Answer 5

Transmural: traverses the entire ventricular wall from endocardium to the epicardium

Subendocardial infarction: limited to the interior 1/3 of the wall (of the left ventricle because RV infarcts are very very rare)

Wavefront: Myocardial infarctions always start in the subendocardial area, then progress to the transmural area step-by-step as a “wave-front.” Fast treatment limits extent of necrosis.

Question 6

What are the 3 reasons behind the Wave-Front Theory?

Answer 6

1. Coronaries run in the subepicardium, and the endocardium only gets the distal branches
2. Myocardial fibers twist like a spiral, and subendocardium works harder (more sensitive to O2 deprivation)
3. Ventricle has higher pressure, which compresses the subendocardium more than subepicardium

Question 7

Which gender is more prone to myocardial infarctions, but how does this change over time?

Answer 7

Men are more susceptible with MIs, but women lose the protective effects of estrogen after menopause, and so their risk of MI is also high when they are elderly.

Ischemic heart disease is still the leading cause of death in elderly women. Plus, if they smoke or have other factors that increase their risk, the estrogen benefit is less important.

Question 8

7 notable time periods that mark MI progression via how the tissue changes (patient symptoms and EKG are not relevant here)
it’s a lot but going to write these as simply as possible to pack in key details, it’s better to be able to link them together

Answer 8

1. 0-30 min: no real morph changes, reversible
2. 30min-4hrs: only change is dilated cells. Diaphorase rxn may be used to detect infarct in lab
3. 4-12 hours: begin coagulation necrosis, usually not grossly apparent yet
4. 12-24 hrs: full-blown MI w/ firm, pale (or dark mottled) area. Preciptated proteins in histo
5. 1-2 days: degeneration, hyperemic red ring around pale necrotic area. Macrophages infiltrate, soften tissue
6. 3-12 days: capillarization of tissue, early scar formation with fibroblast infiltration. Risk of myocardial rupture
7. 12-20 days: scar tissue replaces necrotic area. white, “egg-shell” color.

Question 9

What is the functional consequence of acute ischemia? Why does it occur?

How long does it take for reversible changes to occur?

Answer 9

Functional consequence is rapid loss of contractility, within ~1 min of ischemia onset

Loss of myocardial blood supply -> impaired aerobic glycolysis and anaerobic glycolysis causes lactic acid buildup

Reversible ultrastructural changes include myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling occur but may not be visible before 30 minutes. After 30-40 minutes, starts to get irreversible.

Question 10

When is the ideal time for reperfusion therapy in myocardial infarction? Why?
(4 specific effects are listed)

Answer 10

3-6 hours after infarction. Effects:

1. Free radicals are produced after reperfusion, damaging myocytes
2. Myocyte hypercontracture: ischemia caused high intracellular calcium levels, impaired calcium cycling and sarcolemma damage. Reperfusion causes uncontrolled contraction because they lack ATP to undergo relaxation. Can also kill myocytes
3. Leukocytes aggregate + platelets and complement are activated, injuring tissue and the microvasculature
4. Vascular injury/leakiness can cause bleeding into necrotic area (major risk)

Question 11

Ways to perform reperfusion therapy?

Answer 11

1. Thrombolysis, for example by tPA
2. Angioplasty: balloon catheter opens the coronary artery, usually followed by a stent placement to ensure it stays open
3. Coronary arterial bypass graft (CABG)

Question 12

Which artery is most commonly occluded in an MI? What about the other two?

Answer 12

Most common: LAD (40-50%). Infarcts the anterior wall, septum, and much of apex.

RCA: 30-40% of infarcts. Affects right ventricle, but usually RV can compensate without infarction. LV can instead be affected on posterior septum etc, depends on left vs right dominance of the heart

LCX: 15-20% of infarcts. Affects lateral left ventricle

Question 13

What 3 clinical signs and symptoms are heart attacks based on?

Answer 13

1. Chest Pain: crushing pain. Patient typically quiet and sweating. Pain may radiate to the left shoulder, arm, or neck. Posterior infarcts may cause abdominal pain. Pain is not relieved by nitroglycerin (like with angina pectoris). However, may still have painless AMI (especially with diabetes).
2. ECG: transmural necrosis marked by ST elevation. Other signs: T-en-dome, T wave inversion
3. Enzyme alteration: most used are Troponin T and I, creatine kinase, maybe also lactate dehydrogenase. Leak from myocardium when the cells undergo necrosis.

Question 14

What are 5 consequences of myocardial infarction? (from lecture.. there are more in book)

Answer 14

1. Pump failure / heart failure: can cause hypotension, pulmonary edema, cardiogenic shock
2. Arrythmias: conducting system impaired
3. Myocardial rupture: usually 5-6 days after due to inflammatory cells digesting tissue. May cause hemiparcardium, cardiac tamponade
4. Aneurysm: soft infarct tissue bulges from pressure
5. Chronic ischemic heart disease: heart failure in long run, hypertrophy

Question 15

What happens to non-infarcted zones in a survived myocardial infarction?

Answer 15

Non-infarcted zones undergo compensatory hypertrophy and dilation.

This + scarring/thinning from infarcted zone = “ventricular remodeling”

Question 16

People who undergo Sudden Cardiac Death are categorized into 2 groups, what are they?

Answer 16

1. All those sudden cardiac deaths relating to AMI. Severe atherosclerosis is present. Accounts for 80-90% of cases.
2. Any other cause besides AMI, also don’t have significant atherosclerosis. Maybe 10-20% of cases.

Question 17

What are the 4 non-myocardial infarction causes of sudden cardiac death?

Answer 17

1. Congenital heart malformations. May have been undetected, then they could die while exercising
2. Any developmental problem of the conductive system: causes arrhythmias again often after exercising. This is the most common one, and it’s a reasoning for AEDs in many gyms.
3. Myocarditis: may be related to viral/bacterial infections, flu, etc (later topic, B5)
4. Cardiomyopathies: hereditary disorders of myocardium (later topic, B7)

Question 18

How occluded is a coronary artery to be considered “fixed?”

What percentage is called the “critical stenosis?”

Answer 18

> 70% of the artery is covered by plaque. If it’s less than 70%, then they usually will be asymptomatic

> 90% occlusion is “critical stenosis” - have chest pain even at rest (unstable angina)

Question 19

What is ischemic heart disease (NOT chronic)

What are 4 diseases covered by this blanket term?

Answer 19

Discrepancy between blood supply and myocardium that makes ischemia

Covers: AMI, Angina Pectoralis, Chronic Ischemic Heart Disease, and Sudden Cardiac Death

Question 20

What is Angina Pectoris?

What are the 3 types? (just the name, will elaborate in other cards)

Answer 20

Intermittent chest pain caused by transient, reversible ischemia. Pain may be due to bradykinin/ adenosine released by ischemia.

1. Stable/ “Typical”
2. Prinzmetal / “Variant”
3. Unstable / “Crescendo”

Question 21

What is stable / typical angina pectoris?

How does it appear on EKG?

What medication is regularly used to treat it?

Answer 21

Patient has no symptoms at rest, but on physical exertion or emotional stress they have crushing and radiating chest pain similar to MI. Strong sign that patient has fixed coronary >70%.

Appears as ST depression on EKG

Medication: normally nitroglycerin is given to cause coronary vasodilation. They should also rest, and then get some sort of angioplastic surgery like stent placement before they have a MI.

Question 22

What is Prinzmetal / variant angina pectoris?

What medication is used to treat it?

Answer 22

Chest pain occurs at rest, but it’s because of a functional malformation that causes vasospasm. May or may not have atherosclerosis.

Usually it’s well-treated with nitroglycerine

Question 23

What is Unstable / crescendo angina pectoris?

Answer 23

Chest pain that is increasing in frequency, lasting longer, generally getting worse. They have a fixed plaque, maybe have self-resolving thrombus or microinfarcts.

It’s a very bad sign, developing >90% occlusion. Needs intervention soon.

Question 24

What is chronic ischemic heart disease?

What are 3 causes?

Answer 24

Progressive heart failure secondary to ischemic myocardial damage.

1. History of MI and compensatory mechanisms begin to fail
2. Atherosclerosis: many coronaries with plaques that don’t make ischemia in one area, but more a “global shortage” of blood supply - distributed ischemia with small infarcts
3. Hypertension: causes hypertrophy, limit is 500-600g weight and then start to get small necroses throughout, coronaries can’t handle the size

Question 25

Ischemic heart disease that occurs after MI: why does it occur?
How does it look macroscopically?

Answer 25

Infarcted area loses its contractile force, and so other muscle hypertrophies to compensate. However, atherosclerosis means it can’t get enough O2.

Results in “spotty fibrosis”

Question 26

What are 3 clinical risks with ischemic heart disease?

Answer 26

1. Severe progressive heart failure
2. New episodes of angina or infarction
3. Arrhythmias

Question 27

What bacterial infection is related to Rheumatic Fever? More specifically, what causes it?

What type of acquired stenosis is it essentially the only cause for?

Answer 27

Bacteria: Streptococcus pyogenes (group A β-hemolytic strep). But rheumatic fever itself is not caused by the bacteria, but rather a cross-reactivity of antigens (namely M protein) that is present on both the bacteria and myocardium/ cardiac valves. Only ~ 3% of people with S. pyogenes infection develop RF.

Essentially the only acquired cause of mitral stenosis (causes deforming, fibrotic mitral stenosis)

Question 28

With Rheumatic Valvular Disease, what special substance becomes deposited in the leaflets?

Answer 28

Verruca: “verrucous endocarditis” with immune complexes, coagulated fibrin, and necrotic cell debris

Rarely, may cause microemboli

Question 29

What 2 special things that are named after some dudes appear histologically in the myocardium during Rheumatic Fever?
(the naming is particularly annoying here)

Answer 29

Anitschkow cells: plump activated macrophages. Have abundant cytoplasm and central nuclei with chromatin condensed to form a wavy ribbon (so they’re also called “caterpillar cells”). Can fuse together to form multinucleated “Aschoff cells”

Aschoff bodies: granulomatosus myocardial inflammatory lesions / nodules. Contain lymphocytes, plasma cells, and the Anitschkow cells

Question 30

What is the type III hypersensitive reaction part of rheumatic fever?

Answer 30

Immune complexes deposit in kidney glomeruli, causing activation of complement, attracting neutrophils and macrophages, triggering inflammation. This leads to glomerulonephritis

Question 31

How do the valves and endocardium heal after a bout of rheumatic fever, in a way that forms “chronic rheumatic fever disease?”

Answer 31

They become fibrotic and deformed, leading to mitral stenosis or insufficiency. May have “fish mouth stenosis” where mitral valve looks like a fish mouth.

This deformity predisposes it to infective endocarditis (this time with bacteria being directly involved, and not immune complexes)

Question 32

What is the 5-point mnemonic to remember the MAJOR effects of rheumatic fever?

Answer 32

J♡NES
J: Joints: non-specific synovitis, migratory polyarthritis, normally large joints like shoulder
♡: causes endocarditis, myocarditis, and pericarditis (altogether PANcarditis)
N: subQ nodules (Rheumatoid nodules)
E: Erythema marginatum
S: Sydenham’s chorea: ataxic movements of limbs and face

Question 33

For diagnosis of rheumatic fever based on symptoms, the patient should have how many of the J♡NES criteria (the MAJOR criteria) and how many of the MINOR criteria?

What are the minor criteria?

Answer 33

Only 1 J♡NES criteria
2 or more minor criteria

Minor criteria are more broad: fever, arthralgia, elevated acute phase proteins

Question 34

What are 2 examples of endocarditis that are NOT related to infection?

Answer 34

1. Nonbacterial Thrombotic Endocarditis: aka Marantic Endocarditis. Occurs during terminal phases of cancer. Fibrin and platelets activated and thrombosis develops on valves.
2. Libman-Sacks Endocarditis: related to SLE, talked about there. Also has verruca like RF. Immunological rxn on edge of valves, develops into vegetations.

Question 35

How is verruca different than the vegetations of infective endocarditis?

Answer 35

Verruca are small, contain Ig complexes, undergo fibrinoid necrosis

Infected vegetations: bulky, huge, contain bacteria or fungi + inflammatory cells and necrotic tissues

Question 36

What is the difference between acute and subacute endocarditis?

Answer 36

Acute endocarditis: more fulminant microbe causes it, like S. aureus. Often this is part of sepsis. These dangerous organisms are capable of attaching to normal, undamaged endocardium. High mortality

Subacute endocarditis: “Lenta” type - less fulminant, slower process, low virulence bacteria like S. viridans. Attack previously damaged heart valves. Better prognosis.

Question 37

Heart problems that are predisposing factors to infective endocarditis:
(5 are listed, definitely need a few but prob not all are essential)

Answer 37

1. Rheumatoid heart disease
2. Congenital heart disease: esp. VSD which causes jet stream damage
3. Mitral Prolapse
4. Calcifying Aortic Stenosis
5. Prosthetic Valves

Of course immunocompromisation is also a problem, plus drug abuse, diabetes, cancer, etc.

Question 38

What are some ways that bacteria or fungi might enter the circulation and end up causing infective endocarditis?
(4 are listed)

Answer 38

1. Small injuries from everyday things like brushing teeth causing bleeding, oral flora like S. viridans are important
2. Mucous membranes of GI, then get into portal circulation..
3. Fungal infections in the feet (or elsewhere)
4. IV drug use

Question 39

What are 3 possible fates of the vegetations in infective endocarditis?

Answer 39

1. Fragmentation -> thrombus formation or metastatic abscesses, can infect the brain for example
2. Perforate the valvular structure
3. Ring abscess: as the valve moves, it hits the endocardium of LV and bacteria attach to the muscular or endocardial area and form a ring-shaped abscess

Question 40

What are the most common symptoms and signs of infective endocarditis?
(4 are listed)

Answer 40

1. Fever, flu-like symptoms
2. Malaise, weakness
3. Cardiac murmur
4. Hemoculture positive (have bacteremia)

(May see splenomegaly in subacute. May also have microemboli, glomerulonephritis, or general signs of sepsis)

Question 41

Valves can be defective in what 2 key ways (hint: they cause murmurs, and they’re basically the only 2 things that can wrong with valves and other valve-like things, such as doors or windows)

Answer 41

1. Stenosis: valve fails to open completely, obstructing forward flow. Usually due to chronic process like scarring or calcification.
2. Insufficiency: valve fails to close properly, causing regurgitation. Can be the result of diseased valve cusps or their supporting structures like papillary muscles

However, both of these can occur together. Defects can be congenital or acquired.

Question 42

5 Categories / Types of Valvular Disease:

3 of them were already topics

Answer 42

1. Degenerative: Calcifying Aortic Stenosis, Myxomatous Mitral Valve
2. Carcinoid Heart Disease: related to cancer
3. Rheumatic Valvular Disease
4. Non-Infective Vegetations
5. Infective Endocarditis

Question 43

What is the most common cause of aortic stenosis? What are the health risks?

Answer 43

Calcifying Aortic Stenosis: part of age-related arteriosclerosis and wear-and-tear. Normally asymptomatic. Causes left ventricular hypertrophy, and when poorly compensated maybe syncope, CHF, and angina.

Question 44

What is the morphology of calcifying aortic stenosis?

Answer 44

Heaped-up calcified masses on the outflow side of the aortic cusps. Calcifications protrude into the Valsalva sinuses and impede valve opening.

Question 45

What is the problem in Myxomatous Mitral Valve? How common is it?

Answer 45

“Floppy Valve Syndrome” - because the chordae tendinae are too long, one or both leaflets prolapse into the left atrium during systole, allowing regurgitation. Prevalence ~ 1-2%.

In histo: thinning of the “fibrosa” layer of the valve, and the structural integrity depends on this layer. The middle “spongiosa” layer is expanded due to myxomatous (mucoid) deposits

Question 46

The primary form of Myxomatous Mitral Valve is called what? What is one congenital disease that can cause it as a primary feature?

How does it occur secondarily?

Answer 46

Primary form: Mitral Valve Prolapse. The etiology is usually unknown, but it is common in Marfan syndrome due to fibrillin-1 mutations, also other collagen diseases.

Secondary: injury to valve myofibroblasts causes myxomatous change

Question 47

What are the risks of Myxomatous Mitral Valve?

3 are listed

Answer 47

Usually asymptomatic, but may have:

1. Thickening of valves because they rub against each other. May make them vulnerable to infective endocarditis
2. Thrombosis and embolism risk due to a static region of blood under the valves
3. May have arrhythmias or sudden cardiac death

Question 48

What normally causes the carcinoid heart disease form of valvular disease? Which valve is affected?

Answer 48

Carcinoid tumors like those of the GI that produce vasoactive amines (serotonin, bradykinin, kallikrein).

These vasoactive amines are normally neutralized by the liver, but liver metastases may produce them and then they get into IVC then the right side of the heart, where they affect the Tricuspid Valve to make it thicker, stiffer, deformed and stenotic. This is because those compounds cause smooth muscle and endothelium to proliferate.

Question 49

What are primary vs secondary cardiomyopathies?

Answer 49

Primary: disease process is confined to the myocardium. This is what to focus on in this topic.

Secondary: Myocardial disease is part of a larger disease, like atherosclerosis, etc

Question 50

What are the 4 different cardiomyopathies? (primary cardiomyopathy)
1 of them is more newly described

Answer 50

1. Dilated Cardiomyopathy(DCM): most common one
2. Hypertrophic Cardiomyopathy (HCM)
3. Restrictive Cardiomyopathy
4. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): the new one

Question 51

What are the heart features of Dilated Cardiomyopathy? (6 are listed, I don’t think you need all)

Answer 51

-Progressive cardiac dilation of all 4 chambers
-Reduced contractile function, low EF (less than 25%)
-Hypertrophy: may weigh up to 800-1000g
-Ischemia: due to hypertrophy
-Mitral insufficiency
-Mural thrombosis
Note that it usually has progressed to end-stage by the time it is diagnosed

Question 52

5 things that have been shown to increase the risk of Dilated Cardiomyopathy (DCM)?

Answer 52

1. Genetic causes: dystrophin mutations in particular
2. Alcoholism: acetaldehyde + thiamine deficiency
3. Chemotherapy
4. Viral infections: coxsackie virus B
5. Pregnancy: peripartum. May be from volume overload and hypertension. Can recover after delivery.

Question 53

How old are people who normally develop dilated cardiomyopathy?
What are the symptoms they usually show?
How long do they usually live after diagnosis?

Answer 53

Between 20 and 50 years old.
Usually show slowly-progressing CHF, dyspnea, fatigability,
50% die within 2 years of diagnosis, others usually within 5 years. Need a heart transplant.

Question 54

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): what is the fundamental problem? What is believed to be the cause of the disease?

Answer 54

Fundamental problem: right ventricle is severely thinned due to fat infiltration and fibrosis. Develops right side heart failure and arrhythmia, may have sudden cardiac death.

Cause: Matolcsy said it could be sporadic or familiar, Robbins says it’s autosomal dominant and has mutations in genes that code for desmosomal junctional proteins

Question 55

Hypertrophic Cardiomyopathy (HCM): what is the morphology of the heart?

• What is the fundamental problem that results?
• What is normally the cause?

Answer 55

Morphology: heart is thick-walled, heavy, and hypercontractile. “banana shaped lumen” on cross-section because of subaortic stenosis

Problem: Heart does not relax, and so has poor diastolic filling and thus reduced stroke volume. Additionally, muscle fibers have disorganized arrangement and do not contract in sync.

Cause: usually genetic disorder of myosin heavy chain, sometimes troponin

Question 56

Hypertrophic Cardiomyopathy (HCM):

• What are the clinical features?
• How do people usually die from it?

Answer 56

Clinical features: related to reduced cardiac output and increased pulmonary pressure. Exertional dyspnea, systolic murmur, myocardial ischemia from hypertrophic heart, arrhythmias.

Most common cause of death is arrhythmia, often the cause of death in young athletes who have sudden cardiac death

Question 57

What is Restrictive Cardiomyopathy?

Answer 57

Decrease in ventricular compliance (ventricles are stiff, firm) but it’s not very hypertrophic like HCM. May see biatrial dilation.

There are 4 causes to know, will be on the next card

Question 58

What are the 4 causes of Restrictive Cardiomyopathy?

Answer 58

1. Amyloidosis: either from systemic amyloidosis or cardiac-specific amyloidosis related to transthyretin
2. Loeffler’s Endomyocarditis: eosinophilic granulocytes release major basic protein, which is toxic for endocardium and myocardium, causing fibrosis
3. Bush Tea Fibrosis: some places in Africa drink a tea that has toxins that cause myocardial fibrosis (Robbins says link to diet and helminths too)
4. Irradiation

Question 59

What are 2 major divisions for Myocarditis?

(btw myocarditis is just inflammation of myocardium, not specific, but not due to ischemia or hypertension or some other secondary cause)

Answer 59

1. Infective: viruses (Coxsackie A and B, flu, cytomegalovirus), protozoa (Chagas, Toxoplasmosis), bacteria (Lyme disease) all related
2. Noninfective: autoimmune reactions like SLE, drug hypersensitivity etc

Question 60

What is the morphology of acute vs chronic myocarditis?

Answer 60

Acute: appears normal or dilated

Chronic: myocardium is flabby, mottled with pale and hemorrhagic areas. Mural thrombi may be present.

Chronic myocarditis may progress to DCM (Dilated Cardiomyopathy)

Question 61

What is hypersensitivity myocarditis?

What is Chagas myocarditis?

Answer 61

Hypersensitivity myocarditis: infiltration of lymphocytes, a lot of eosinophils, and macrophages (may see Giant Cell Myocarditis too if they start fusing in more severe reaction)

Chagas myocarditis: the Chagas protozoa (mostly in South America) infects myocardium and so you have neutrophil, macrophage, lymphocyte infiltrate, maybe eosinophils.

Question 62

What are the clinical features of myocarditis? (runs a spectrum from mild to severe)

Answer 62

Mild: Can be asymptomatic and heal completely
Moderate: fatigue, palpitations, fever, pain, dyspnea
Severe: all the moderate ones + heart failure, arrhythmia, sudden death