Goldman

Question 1

What is ischemic heart disease caused by?

Answer 1

obstruction or stenosis of one or more of the epicardial coronary arteries by atheromatous plaque

Question 2

What is angina pectoris caused by?

Answer 2

generally a consequence of a supply-demand imbalance: an activity increases cardiac workload or “demand,” thereby resulting in an increase in heart rate, blood pressure, and contractility, leading to an increase in left ventricular (LV) wall tension; but stenotic coronary arteries are unable to augment antegrade flow or “supply” adequately in response to this increase in demand.

Such an imbalance classically results in chest discomfort

Question 3

What is angina pectoris?

Answer 3

discomfort in the chest or adjacent areas caused by myocardial ischemia.

Question 4

How is angina pectoris graded?

Answer 4

The Canadian Cardiovascular Society (CCS) angina grading scale is a widely used four-point ordinal scale that classifies angina pectoris from mild (class I: angina occurring only during strenuous or prolonged physical activity) to severe (class IV: inability to perform any activity without angina, or angina at rest) and includes the full spectrum of angina from chronic stable to unstable

Question 5

For classification purposes, subjects with stable ischemic heart disease generally exhibit CCS class I-II symptoms, which are typically provoked by exertion.

Answer 5

Other grading systems include a specific activity scale, which is based on the metabolic cost of specific activities, and an anginal score, which integrates the clinical features and tempo of angina with electrocardiographic changes and offers independent prognostic information beyond that provided by age, gender, ventricular function, and coronary anatomy.

Question 6

Incidence of angina pectoris?

Answer 6

Among individuals aged 45 years and older, the incidence of stable angina pectoris is about 500K per year, of whom about 65% are men

Question 7

When does ischemia arise?

Answer 7

which rapidly develops when a mismatch arises between myocardial oxygen needs and myocardial oxygen supply

Question 8

How does ischemia manifest clinically?

Answer 8

variable ranging from no symptoms (e.g., silent myocardial ischemia) to angina as a precursor to unstable angina, myocardial infarction (MI), or sudden cardiac death

Question 9

Two major pathogenetic mechanisms may result in myocardial ischemia and angina in the chronic setting

Answer 9

so-called demand angina, which is caused by an increase in myocardial oxygen requirements and workload; and supply angina, which is caused by diminished oxygen delivery to myocardial tissue.

Question 10

Demand angina is a consequence of the increased myocardial oxygen requirements that occur with what things commonly?

Answer 10

increased physical activity, emotion, or stress.

In a patient with chronic, restricted oxygen delivery due to atherosclerotic narrowing of a coronary artery, this increased demand may precipitate angina.

Question 11

Other extracardiac precipitants of angina include the excessive metabolic demands imposed by

Answer 11

• fever,
• thyrotoxicosis,
• severe anemia from blood loss,
• tachycardia from any cause
• hypoglycemia, and
• pain.

Question 12

The pathophysiologic basis for angina and ischemia in patients with stable ischemic heart disease has important implications for the selection of anti-ischemic agents.

Answer 12

The greater the contribution from increased myocardial oxygen requirements to the imbalance between supply and demand, the greater the likelihood that agents that reduce heart rate and wall tension, such as β-blockers or non-dihydropyridine calcium antagonists, will provide clinical benefit, whereas nitrates and calcium antagonists with more potent vasodilatory properties (particularly the dihydropyridines) will be more beneficial to alleviate angina and ischemia mediated by coronary vasoconstriction.

Question 13

What is the most common cause of ischemic heart disease?

Answer 13

atherosclerotic narrowing of the coronary arteries resulting in flow-limiting obstruction to epicardial blood flow

Question 14

What are some nonatherosclerotic causes of obstructive coronary artery disease?

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Answer 14

• congenital abnormalities of the coronary arteries,
• vasospasm,
• myocardial bridging,
• coronary arteritis in association with systemic vasculitides, and
• radiation-induced coronary disease.

Question 15

How can radiation cause obstructive disease?

Answer 15

Radiation therapy for thoracic or mediastinal malignant neoplasms, particularly breast cancer and Hodgkin lymphoma, can cause long-term coronary microangiopathy and macroangiopathy.

There is a four- to seven-fold increase in clinically significant, high-grade coronary artery stenosis of the mid and distal left anterior descending coronary artery in women with irradiated left-sided breast cancer compared with those treated with radiation for right-sided breast cancer.

Question 16

How else might myocardial ischemia and angina pectoris occur?

Answer 16

in the absence of obstructive coronary artery disease, as in the case of aortic valve disease, hypertrophic cardiomyopathy, and dilated cardiomyopathy.

Question 17

What is acute coronary syndrome?

Answer 17

used to describe the continuum of myocardial ischemia (unstable angina pectoris) or infarction (with or without concomitant ST segment elevation)

Question 18

What is unstable angina?

Answer 18

The patient with unstable angina has cardiac chest pain that is new, worsening (i.e., more severe, prolonged, or frequent than previous episodes of angina), or occurring at rest, without serologic evidence of myocyte necrosis—that is, no elevation of serum concentrations of troponin or the MB isoenzyme of creatine kinase (CK-MB) and no ST elevation

Question 19

What is a non-ST segment elevation MI ?

Answer 19

The patient with cardiac chest pain WITH serologic evidence of myonecrosis but without ST segment elevation

Question 20

T or F. Both unstable angina and non-ST segment elevation MI are termed non-ST segment elevation ACS

Answer 20

T. aka NSTE ACS. Because unstable angina and non–ST segment elevation MI are characterized by the absence of ST segment elevation

Question 21

What is an ST segment elevation MI (STEMI)?

Answer 21

If the involved coronary artery is totally occluded by fresh thrombus, the patient with acute-onset cardiac chest pain, serologic evidence of myonecrosis, and persistent (>20 minutes) ST segment elevation as revealed from an ECG is said to have an ST segment elevation MI

Question 22

What is a primary ACS?

Answer 22

is precipitated by rupture of a coronary arterial atherosclerotic plaque, with subsequent platelet aggregation and thrombus formation, leading in turn to diminished blood flow in the involved artery

Question 23

What is a secondary ACS?

Answer 23

caused by a transient or sustained marked imbalance between myocardial oxygen supply and demand

Question 24

Causes of secondary ACS?

Answer 24

Substantial reductions in oxygen supply, for example, can be caused by severe systemic arterial hypotension, anemia, or hypoxemia; dramatic increases in oxygen demand can be caused by tachycardia, severe systemic arterial hypertension, or thyrotoxicosis.

treat the underlying cause

Question 25

What is the precipitating event in almost all subjects with NSTE ACS?

Answer 25

coronary arterial atherosclerotic plaque rupture or erosion, with subsequent platelet aggregation and thrombus formation, leading to subtotal occlusion of the involved artery.

In an occasional patient, total thrombotic occlusion of the artery leads to NSTE ACS rather than to ST segment elevation MI when extensive collateral blood supply perfuses the region of myocardium that is distal to the occluded artery.

Question 26

Other causes of NSTE ACS?

Answer 26

• Rarely, intense vasospasm of a segment of an epicardial coronary artery, due to focal endothelial dysfunction (i.e., Prinzmetal’s angina)
• drug ingestion (caused, for example, by cocaine, chemotherapeutic agents, or one of the serotonin receptor agonist “triptans”), causes a transient or sustained compromise of coronary arterial blood flow, with resultant NSTE ACS.
• Spontaneous coronary arterial dissection, which occurs most often in peripartum women and patients with vasculitis, may result in NSTE ACS.

Question 27

What factors help erode the fibrous cap of a coronary arterial atherosclerotic plaque to precipitate NSTE ACS?

Answer 27

Local and systemic inflammation, mechanical features, and anatomic changes contribute to the transformation of a stable atherosclerotic plaque to a so-called vulnerable plaque, the rupture of which triggers platelet adherence, activation, and aggregation, with subsequent thrombus formation.

Question 28

What stimulates this inflammatory response?

Answer 28

The deposition of oxidized LDL in the coronary arterial wall stimulates an inflammatory response, which results in the accumulation of macrophages and T lymphocytes at the plaque border.

Question 29

What do the inflammatory cells do?

Answer 29

These inflammatory cells secrete cytokines (e.g., tissue necrosis factor, interleukin-1, interferon-γ), which inhibit collagen synthesis and deposition, as well as enzymes (e.g., matrix metalloproteinases and cathepsins), which promote collagen and elastin degradation, thereby rendering the overlying fibrous cap vulnerable to rupture.

Question 30

Which individuals have a predisposition for ACS development?

Answer 30

chronic gingivitis, rheumatoid arthritis, and chronic or acute infection.

all involve systemic inflammation

Question 31

The mechanical characteristics and location of coronary arterial plaques appear to influence their stability. Explain.

Answer 31

Obviously, thin fibrous caps are more likely to erode or to rupture than are thick ones.

Sites of low shear stress, such as vessel bifurcations, have reduced production of endothelial vasodilator substances (i.e., nitric oxide and prostacyclin), accelerated accumulation of lipids and inflammatory cells, increased degradation of the extracellular matrix, and thinning of the fibrous cap, all of which contribute to plaque instability.

Question 32

How else do plaques very commonly destabilize?

Answer 32

Neovascularization that is the result of angiogenic peptides contributes to the growth of atheroma and to leukocyte trafficking, plaque hemorrhage, and destabilization

Question 33

What happens when a plaque ruptures?

Answer 33

circulating platelets adhere to the exposed subendothelial proteins, after which they are activated and form a clot (thrombus)

Question 34

What do elevated levels of troponin or CK-MB suggest?

Answer 34

myonecrosis of some kind

Question 35

When coronary flow is occluded, electrocardiographic ST segment elevation occurs, resulting in STEMI. Partial occlusion, occlusion in the presence of collateral circulation, and distal coronary embolization result in unstable angina or non–ST segment elevation MI

Answer 35

When coronary flow is occluded, electrocardiographic ST segment elevation occurs, resulting in STEMI. Partial occlusion, occlusion in the presence of collateral circulation, and distal coronary embolization result in unstable angina or non–ST segment elevation MI

Question 36

How long can myocytes live without oxygen?

Answer 36

myocardial cell death begins within 15 minutes of occlusion and proceeds rapidly in a wave front from endocardium to epicardium

Question 37

What are some conditions other than atherosclerosis that can cause acute MI?

Answer 37

• coronary emboli
• thrombotic coronary artery disease
• coronary vasospasm or vasculitis
• trauma
• coronary ostial occlusion
• etc.

Question 38

Thrombotic coronary artery disease can arise secondary to what things?

Answer 38

• oral contraceptives
• sickle cell
• hemoglobinopathies
• TTP, DIC
• any hypercoaguable state

Question 39

Risk factors for coronary artery disease and subsequent MI?

Answer 39

-estimated to be 40% genetic, with the balance being environmental.

A large international collaborative meta-analysis identified or validated 23 common genetic susceptibility loci for coronary artery disease, many unrelated to traditional risk factors, but these loci account for only 10% of genetic variance.

Question 40

What can protect someone with coronary artery disease from MI?

Answer 40

Among patients with coronary artery disease, only a variant in the glycosyltransferase gene associated with the ABO blood group O phenotype has been shown to protect against MI.