Chapter 11: Ischemic Heart Disease Flashcards
What is Ischemic heart disease (IHD)?
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
What is IHD, in 90% of the cases, a consequence of?
Reduced coronary blood flow secondary to obstructive atherosclerotic vascular disease
Are coronary artery disease (CAD) and ischemic heart disease (IHD) synonyms?
Yes, unless otherwise specified
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)
• Angina pectoris • Myocardial infarction (MI) • Chronic IHD with CHF (congestive heart failure) • Sudden cardiac death (SCD)
What is angina pectoris? (in relation to IHD)
(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).
What is myocardial infarction (MI)?
This occurs when the severity or duration of ischemia is sufficient to cause cardiomyocyte death.
What is chronic IHD with CHF?
This progressive cardiac decompensation, which occurs after acute MI or secondary to accumulated small ischemic insults, eventually precipitates mechanical pump failure.
What causes sudden cardiac death?
This can occur as a consequence of tissue damage from MI, but most commonly results from a lethal arrhythmia without myocyte necrosis
Which of the 4 manifestations of IHD are also classified as acute coronary syndrome?
unstable angina, MI, and SCD (MI = myocardial infarction) (SCD = sudden cardiac death)
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
atherosclerotic
True/false: Fixed obstructions that occlude less than 70% of a coronary vessel lumen typically are asymptomatic
True, even with exertion.
How is a lesion that occludes more than 70% of a vessel lumen called?
Critical stenosis (patient has stable angina)
What does a fixed stenosis of more than 90% cause?
Unstable angina (even at rest)
What elements contribute to the development and consequences of coronary atherosclerosis?
• Inflammation plays an essential role at all stages of atherosclerosis • Thrombosis associated with an eroded or ruptured plaque triggers the acute coronary syndromes • Vasoconstriction
Explain how inflammation plays a role in atherosclerosis
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
In most patients, unstable angina, infarction, and sudden cardiac death occur because of …
abrupt plaque change followed by thrombosis
What are possible events after a plaque disruption?
- 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)
Factors that trigger plaque erosion include …, likely attributable to some combination of inflammatory and toxic exposures.
Endothelial injury and apoptosis
Acute plaque rupture, on the other hand (of plaque erosion), involves factors that influence plaque susceptibility to disruption by …
Mechanical stress (These include intrinsic aspects of plaque composition and structure and extrinsic factors, such as blood pressure and platelet reactivity)
Plaques that contain large atheromatous cores or have thin overlying fibrous caps are more likely to … and are therefore termed …
Rupture, vulnerable respectively
What is angina pectoris?
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
Which three variants of angina pectoris are recognized?
• 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)
What is myocardial infarction (MI)?
Myocardial infarction (MI), also commonly referred to as “heart attack,” is necrosis of the heart muscle resulting from ischemia
What is the major underlying cause of IHD?
Atherosclerosis
What is the major underlying cause of MIs?
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)
In 10% of MIs transmural infarction occurs. What is a transmural infarction?
An infarction of the full thickness of the myocardium
How does transmural infarction occur?
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
In what part of the heart can an infarct occur where thrombi or emboli are absent? How, if not because of atherosclerosis?
innermost (subendocardial) myocardium. during a prolonged period of increased demand (tachycardia/hypertension) -> ischemic necrosis of endomyocardium
Ischemia without detectable atherosclerosis or thromboembolic disease can be caused by disorders of small intramyocardial arterioles, including … (3 answers), as in sickle cell disease.
vasculitis, amyloid deposition, or stasis
Explain the process/steps of a typical MI? (4 steps)
- 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.
In the early stages of MI, what are some functional/ultrastructural changes that are seen? (you don’t have to learn them all!)
- 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
Are the early stages of an MI reversible? (e.g. ATP drop, loss contractility, myofibrillar relaxation, glycogen depretion, cellular swelling..)
Yes
How many minutes of ischemia do there has to be in order for irreversibel damage to occur?
20-40 minutes of prolonged ischemia and coagulative necrosis of myocytes
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?
Stunned myocardium
MI also contributes to arrhythmias, how?
probably by causing electrical instability (irritability) of ischemic regions of the heart
In which region is irreversible injury first found? Why?
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)
With prolonged ischemia, a wavefront of cell death moves through other regions of the myocardium, how?
driven by progressive tissue edema and myocardial-derived reactive oxygen species and inflammatory mediators
The location, size, and morphologic features of an acute myocardial infarct depend on multiple factors, which?
- 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
it’s important to understand an infarct can present in different ways, but you don’t have to learn all the types
for insight see fig 11.9
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.
• Transmural infarctions • Subendocardial infarctions • Microscopic infarcts
We have already discussed the 3 different types of infarctions, but for overview purposes, what are they/do they present with?
- 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.
How is reperfusion of MI achieved?
By thrombolysis, angioplasty or coronary arterial bypass graft
Look at the next figure
You obv don’t have to know this, but it is good for illustration :)
What are factors that contribute to reperfusion injury?
• Mitochondrial dysfunction • Myocyte hypercontracture • Free radicals • Leukocyte aggregation • Platelet and complement activation
What are the symptoms a patient with MI has?
Severe, crushing substernal chest pain (or pressure) that can radiate to the neck, jaw, epigastrium, or left arm
How can you distinguish MI from angina pectoris?
MI lasts several minutes-hours
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?
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)
There are many complications to an acute MI, what are complicaties that 3/4th of patients unfortunately experience?
• 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!)
What is chronic IHD?
Chronic IHD, also called ischemic cardiomyopathy, is progressive heart failure secondary to ischemic myocardial damage
Does chronic IHD occur after a MI?
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
What are the symptoms/clinical appearances/prognosis of chronic IHD?
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.
Is the left or right ventricle dilated and hypertrophic in chronic IHD?
left
True/false: cardiac stem cell therapy cannot be used as a treatment because cardiac myocytes are post-mitotic
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 :()
