Chapter 11: Ischemic Heart Disease

Question 1

What is Ischemic heart disease (IHD)?

Answer 1

Ischemic heart disease (IHD) is a broad term encompassing several closely related syndromes caused by myocardial ischemia—an imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements

Question 2

What is IHD, in 90% of the cases, a consequence of?

Answer 2

Reduced coronary blood flow secondary to obstructive atherosclerotic vascular disease

Question 3

Are coronary artery disease (CAD) and ischemic heart disease (IHD) synonyms?

Answer 3

Yes, unless otherwise specified

Question 4

The manifestations of IHD are a direct consequence of the insufficient blood supply to the heart. The clinical presentation may include one or more of the following cardiac syndromes: (name four)

Answer 4

• Angina pectoris • Myocardial infarction (MI) • Chronic IHD with CHF (congestive heart failure) • Sudden cardiac death (SCD)

Question 5

What is angina pectoris? (in relation to IHD)

Answer 5

(literally, “chest pain”). Ischemia induces pain but is insufficient to cause myocyte death. Angina can be stable (occurring predictably at certain levels of exertion), can be caused by vessel spasm (Prinzmetal angina), or can be unstable (occurring with progressively less exertion or even at rest).

Question 6

What is myocardial infarction (MI)?

Answer 6

This occurs when the severity or duration of ischemia is sufficient to cause cardiomyocyte death.

Question 7

What is chronic IHD with CHF?

Answer 7

This progressive cardiac decompensation, which occurs after acute MI or secondary to accumulated small ischemic insults, eventually precipitates mechanical pump failure.

Question 8

What causes sudden cardiac death?

Answer 8

This can occur as a consequence of tissue damage from MI, but most commonly results from a lethal arrhythmia without myocyte necrosis

Question 9

Which of the 4 manifestations of IHD are also classified as acute coronary syndrome?

Answer 9

unstable angina, MI, and SCD (MI = myocardial infarction) (SCD = sudden cardiac death)

Question 10

IHD is a consequence of inadequate coronary perfusion relative to myocardial demand, usually as a consequence of a preexisting (“fixed”) … occlusion of the coronary arteries and new, superimposed thrombosis and/ or vasospasm

Answer 10

atherosclerotic

Question 11

True/false: Fixed obstructions that occlude less than 70% of a coronary vessel lumen typically are asymptomatic

Answer 11

True, even with exertion.

Question 12

How is a lesion that occludes more than 70% of a vessel lumen called?

Answer 12

Critical stenosis (patient has stable angina)

Question 13

What does a fixed stenosis of more than 90% cause?

Answer 13

Unstable angina (even at rest)

Question 14

What elements contribute to the development and consequences of coronary atherosclerosis?

Answer 14

• Inflammation plays an essential role at all stages of atherosclerosis • Thrombosis associated with an eroded or ruptured plaque triggers the acute coronary syndromes • Vasoconstriction

Question 15

Explain how inflammation plays a role in atherosclerosis

Answer 15

Interaction EC and leukocytes -> T-cell and macrophage recruitment and activation -> SMC accumulation and proliferation -> matrix production, superimposed on an atheromatous core of lipid, cholesterol, calcification and necrotic debris -> destabilization of atherosclerotic plaque through macrophage metalloproteinase secretion

Question 16

In most patients, unstable angina, infarction, and sudden cardiac death occur because of …

Answer 16

abrupt plaque change followed by thrombosis

Question 17

What are possible events after a plaque disruption?

Answer 17

• healing -> severe fixed coronary obstruction (IHD)
• Mural thrombus with variable obstruction/emboli (unstable angina/acute subendocardial myocardial infarction / sudden death)
• Occlusive thrombus (acute transmural myocardial infarction / sudden death)

Question 18

Factors that trigger plaque erosion include …, likely attributable to some combination of inflammatory and toxic exposures.

Answer 18

Endothelial injury and apoptosis

Question 19

Acute plaque rupture, on the other hand (of plaque erosion), involves factors that influence plaque susceptibility to disruption by …

Answer 19

Mechanical stress (These include intrinsic aspects of plaque composition and structure and extrinsic factors, such as blood pressure and platelet reactivity)

Question 20

Plaques that contain large atheromatous cores or have thin overlying fibrous caps are more likely to … and are therefore termed …

Answer 20

Rupture, vulnerable respectively

Question 21

What is angina pectoris?

Answer 21

Angina pectoris is an intermittent chest pain caused by transient, reversible myocardial ischemia. The pain is a consequence of the ischemia-induced release of adenosine, bradykinin, and other molecules that stimulate autonomic nerves

Question 22

Which three variants of angina pectoris are recognized?

Answer 22

• Typical or stable angina • Prinzmetal or variant angina • Unstable angina (also called crescendo angina) (i did not include what they mean since they’re not discussed in the lecture, it’s on page 411)

Question 23

What is myocardial infarction (MI)?

Answer 23

Myocardial infarction (MI), also commonly referred to as “heart attack,” is necrosis of the heart muscle resulting from ischemia

Question 24

What is the major underlying cause of IHD?

Answer 24

Atherosclerosis

Question 25

What is the major underlying cause of MIs?

Answer 25

Acute thrombosis in coronary arteries (disruption or erosion of preexisting atherosclerotic plaque serves as the nidus for thrombus generation, vascular occlusion, and subsequent infarction of the perfused myocardium)

Question 26

In 10% of MIs transmural infarction occurs. What is a transmural infarction?

Answer 26

An infarction of the full thickness of the myocardium

Question 27

How does transmural infarction occur?

Answer 27

In the absence of occlusive atherosclerotic vascular disease; such infarcts are mostly ascribed to coronary artery vasospasm or to embolization from mural thrombi (e.g., in the setting of atrial fibrillation) or from valve vegetations

Question 28

In what part of the heart can an infarct occur where thrombi or emboli are absent? How, if not because of atherosclerosis?

Answer 28

innermost (subendocardial) myocardium. during a prolonged period of increased demand (tachycardia/hypertension) -> ischemic necrosis of endomyocardium

Question 29

Ischemia without detectable atherosclerosis or thromboembolic disease can be caused by disorders of small intramyocardial arterioles, including … (3 answers), as in sickle cell disease.

Answer 29

vasculitis, amyloid deposition, or stasis

Question 30

Explain the process/steps of a typical MI? (4 steps)

Answer 30

1. An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to the blood. 2. Platelets adhere, aggregate, and are activated, releasing thromboxane A2, adenosine diphosphate (ADP), and serotonin—causing further platelet aggregation and vasospasm. 3. Activation of coagulation by exposure of tissue factor and other mechanisms adds to the growing thrombus. 4. Within minutes, the thrombus can evolve to completely occlude the coronary artery lumen.

Question 31

In the early stages of MI, what are some functional/ultrastructural changes that are seen? (you don’t have to learn them all!)

Answer 31

• Aerobic metabolism ceases -> drop in ATP and accumulation of potentially noxious metabolites - Functional: rapid loss of contractility - Ultrastructural: myofibrillar relaxation, glycogen depletion, cellular and mitochondrial swelling

Question 32

Are the early stages of an MI reversible? (e.g. ATP drop, loss contractility, myofibrillar relaxation, glycogen depretion, cellular swelling..)

Answer 32

Yes

Question 33

How many minutes of ischemia do there has to be in order for irreversibel damage to occur?

Answer 33

20-40 minutes of prolonged ischemia and coagulative necrosis of myocytes

Question 34

Even if reperfusion is timely, dysfunction for a number of days can be seen due to persistent abnormalities in cellular biochemistry that result in noncontractile state. How is this state called?

Answer 34

Stunned myocardium

Question 35

MI also contributes to arrhythmias, how?

Answer 35

probably by causing electrical instability (irritability) of ischemic regions of the heart

Question 36

In which region is irreversible injury first found? Why?

Answer 36

Subendocardial zone (this region is especially susceptible to ischemia because it is the last area to receive blood delivered by the epicardial vessels, and also because it is exposed to relatively high intramural pressures, which act to impede the inflow of blood)

Question 37

With prolonged ischemia, a wavefront of cell death moves through other regions of the myocardium, how?

Answer 37

driven by progressive tissue edema and myocardial-derived reactive oxygen species and inflammatory mediators

Question 38

The location, size, and morphologic features of an acute myocardial infarct depend on multiple factors, which?

Answer 38

• Size and distribution of the involved vessel (see figure for illustration)
• Rate of development and duration of the occlusion
• Metabolic demands of the myocardium (affected, for example, by blood pressure and heart rate)
• Extent of collateral supply

Question 39

it’s important to understand an infarct can present in different ways, but you don’t have to learn all the types

Answer 39

for insight see fig 11.9

Question 40

Based on the size of the involved vessel and the degree of collateral circulation, myocardial infarcts may take one of the following patterns, name the 3.

Answer 40

• Transmural infarctions • Subendocardial infarctions • Microscopic infarcts

Question 41

We have already discussed the 3 different types of infarctions, but for overview purposes, what are they/do they present with?

Answer 41

• Transmural infarctions involve the full thickness of the ventricle and are caused by epicardial vessel occlusion through a combination of chronic atherosclerosis and acute thrombosis
• Subendocardial infarctions are MIs limited to the inner third of the myocardium. The subendocardial region is most vulnerable to hypoperfusion and hypoxia. Thus, in the setting of severe coronary artery disease, transient decreases in oxygen delivery (as from hypotension, anemia, or pneumonia) or increases in oxygen demand (as with tachycardia or hypertension) can cause subendocardial ischemic injury. This pattern also can occur when an occlusive thrombus lyses before a full-thickness infarction can develop.
• Microscopic infarcts occur in the setting of small-vessel occlusions and may not show any diagnostic ECG changes. These can occur in the setting of vasculitis, embolization of valve vegetations or mural thrombi, or vessel spasm due to elevated catecholamines, as may occur in extreme emotional stress, with certain tumors (e.g., pheochromocytoma), or as a consequence of cocaine use.

Question 42

How is reperfusion of MI achieved?

Answer 42

By thrombolysis, angioplasty or coronary arterial bypass graft

Question 43

Look at the next figure

Answer 43

You obv don’t have to know this, but it is good for illustration :)

Question 44

What are factors that contribute to reperfusion injury?

Answer 44

• Mitochondrial dysfunction • Myocyte hypercontracture • Free radicals • Leukocyte aggregation • Platelet and complement activation

Question 45

What are the symptoms a patient with MI has?

Answer 45

Severe, crushing substernal chest pain (or pressure) that can radiate to the neck, jaw, epigastrium, or left arm

Question 46

How can you distinguish MI from angina pectoris?

Answer 46

MI lasts several minutes-hours

Question 47

The laboratory evaluation of MI is based on measuring blood levels of macromolecules that leak out of injured myocardial cells through damaged cell membranes. What are these moleculres?

Answer 47

Myoglobin, cardiac troponins T and I (TnT, TnI), creatine kinase (CK), lactate dehydrogenase. (don’t think you have to learn this, but included it anyway)

Question 48

There are many complications to an acute MI, what are complicaties that 3/4th of patients unfortunately experience?

Answer 48

• Contractile dysfunction (common) • Papillary muscle dysfunction (common) • Right ventricular infarction (rare) • Myocardial rupture (rare) • Arrhythmias (common) • Pericarditis (in transmural) • Chamber dilation • Mural thrombus • Ventricular aneurysm • Progressive heart failure (please don’t learn by heart, you should be able to recognize though!)

Question 49

What is chronic IHD?

Answer 49

Chronic IHD, also called ischemic cardiomyopathy, is progressive heart failure secondary to ischemic myocardial damage

Question 50

Does chronic IHD occur after a MI?

Answer 50

Often not (there is no known previous MI), but sometimes it can occur when compensatory mechanisms (e.g. hypertrophy) of residual myocardium begin to fail

Question 51

What are the symptoms/clinical appearances/prognosis of chronic IHD?

Answer 51

The heart failure of chronic IHD is typically severe and is occasionally punctuated by new episodes of angina or infarction. Arrhythmias, CHF, and intercurrent MI account for most of the associated morbidity and mortality.

Question 52

Is the left or right ventricle dilated and hypertrophic in chronic IHD?

Answer 52

left

Question 53

True/false: cardiac stem cell therapy cannot be used as a treatment because cardiac myocytes are post-mitotic

Answer 53

False, they are post-mitotic, but there has been found a small population of bone marrow-derived precurors that (very slowly) show self-renewal and proliferation (and this could be used, but unfortunately in vivo results have not shown much :()