Lecture 10: Ischemic Heart Disease

Coronary circulation supplies the heart with __ (2) to maintain adequate function.

oxygen & nutrients

Coronary circulation must adapt to __ in the systemic metabolic needs.

rapid fluctuations

Imbalance between myocardial oxygen demand and supply leads to: (3)

• myocardial ischemia and contractile dysfunction

• cardiac arrhythmia

• myocardial infarction and possibly death

What are the 2 main coronary arteries?

right coronary artery & left coronary artery (which includes left anterior descending artery & circumflex artery)

Following a coronary artery occlusion, __ may occur beneath the __ surface & spread within the __.

necrosis; endothelial; myocardial tissue

What is ischemia?

myocardial oxygen demand in excess of supply (demand is larger than supply)

What is infarction?

continued ischemia leading to muscle damage

Myocardial O2 __ depends on heart rate, contractility, and wall tension.

consumption

Myocardial O2 consumption demand increases with factors that increase: (3)

• rate

• ionotropic stimuli (ca and catecholamines)

• elevated aortic pressure

Myocardial O2 supply depends on: (2)

• coronary arterial and capillary inflow

• O2 transport and delivery

  • needs adequate inspired O2 (amount of oxygen in blood is normal) and normal hemoglobin (to allow for effective oxygen transport)

Coronary arterial and capillary inflow usually has [high/low] resistance unless __. The resistance is regulated by several factors, some dependent on __.

low; occluded; endothelial cells

Vascular endothelium has important __ functions that promote __.

homeostatic; vasodilation

How do vascular endothelium promote homeostasis? (2)

1. sense mechanical forces and regulating vascular tone

2. production of many other vasoactive substances (pro and anti-proliferative, pro and anti-thrombotic, and angiogenic factors)

How does vascular endothelium regulate vascular tone?

• vasodilators: endothelium-derived relaxing factor (EDRF), nitric oxide (NO), and prostacyclin

• vasoconstrictors: endothelin 1 (ET-1), angiotensin II, thromboxane A2

__ inhibits recruitment and differentiation of inflammatory cells by inhibiting __. This is a __ effect in the setting of ischemia.

NO; inflammatory cytokines; protective (prevents excessive inflammatory response that can damage tissues during a time with limited blood supply)

What are the predisposing risk factors for ischemic heart disease? (3)

1. age: inc risk as inc age

2. sex: males > females, but more risk for females after menopause

3. family history

What are risk modulating behaviors for IHD? (behaviors that will increase risk) (5)

1. smoking

2. atherogenic diet

3. alcohol intake

4. lifestyle: physical activity

5. personality type: hard to measure but data appears real

What are some metabolic factors that increase risk of IHD? (7)

1. HTN

2. diabetes

3. obesity

4. metabolic syndrome

5. dyslipidemia

6. iron overload

7. homocysteine excess

Metabolic syndrome includes __ resistance and impaired __.

insulin; glucose tolerance

The best predictor of atherosclerotic heart disease is total __ ratio.

cholesterol to HDL (ideal is 3.5 or lower)

__ has antifibrinolytic properties. Elevation is strongly correlated with __.

lipoprotein (a); heart disease

__ is protective, while __ is damaging

HDL; LDL

__ occurs as a result of impaired plasma lipid control and is typically characterized by abnormal levels of lipoproteins.

Dyslipidemia

__ facilitates LDL oxidation.

iron overload

__ causes a direct toxic effect on endothelial cells, interference with clotting factors, and promotion of oxidation of LDL.

homocysteine excess

__ can correct homocysteine excess.

folic acid

Inflammation is emerging as an important __ for IHD.

risk factor

__ is a marker of systemic inflammation.

C-reactive protein (CRP)

CRP is produced by the __ and cells within the __.

liver; atheroma

CRP is strongly correlated with the risk of: (4)

• MI

• stroke

• peripheral arterial disease

• sudden cardiac death

__ can also be a risk factor for IHD, but the effect is weak.

plasma fibrinogen

Label each of the following with inc/dec to determine how each would be a risk factor for IHD.

• total cholesterol

• LDL

• lipoprotein a

• homocysteine

• CRP

• fibrinogen

• HDL

all inc except dec for HDL will put a person at higher risk for IHD

__ are used to determine and diagnose a patient’s risk of coronary heart disease.

risk charts

What does this risk chart study show?

color- where risk is

highest risk = man who is smoker over the age of 70, high systolic pressure & high blood cholesterol

lowest risk = young man <30 y/o, nonsmoker, good BP, even with high BP if cholesterol is managed —> risk is same

• if cholesterol high, but BP is good —> risk stays low

when women age, risk becomes similar to men

__ consists of an atheroma plaque and thrombosis. It is involved in most cases of infarction.

Atherosclerosis

Plaque rupture and hemorrhage into vessel wall precipitates many cases of __, even with coronary artery lumen __ of less than 70%.

infarction; narrowing

meaning can occur even if coronary artery is not significantly narrowed by the build-up plaque (which causes stiffness and narrowing of the vessel)

__ is a significant cause of ischemia characterized by normal coronary arteries. Usually it doesn’t lead to infarction unless:

spasm; significant atherosclerotic lesion

What is an example of spasm?

prinzmetal’s angina

• spasms in (normal) coronary arteries that temporarily restrict blood flow to heart muscle —> reduced oxygen —> pain/angina

__ caused by leutic, collagen, or immune-mediated diseases can lead to cardiac ischemia.

arteritis

__ to coronary arteries can cause cardiac ischemia.

emboli

Infective endocarditis can cause __

emboli to coronary arteries

What occurs when atheroma is initiated?

1. extracellular lipid accumulation and oxidation: usually occurs when diet is high in cholesterol or saturated fat

2. leukocyte recruitment via expression of adhesion molecules

3. foam cell formation: via endothelial and smooth muscle cell chemokine release —> recruit monocytes that differentiate into foam cells

During innate and adaptive inflammation in atherogenesis, there is release of __ by foam cells and __ activation.

proinflammatory cytokines; T cell

proinflammatory cytokine release is not Ag (antigen) dependent, but T cell activation needs Ags as infectious agents

How do smooth muscle cells respond during atheroma evolution?

• migrate to intima layer in response to signals from inflammatory cells and growth factors —> contribute to plaque formation

• proliferate in the intima & form ECM —> fibrous cap that stabilizes the plaque

• can undergo apoptosis/cell death —> increases risk of plaque rupture and triggers thrombosis

In a developing atheroma, there is deposition of __ in the arterial extracellular matrix, which contributes to the outward growth of the __.

fibrillar collagen; intima

**this makes atheroma irreversible in size

During atheroma evolution, plaque __ contribute to plaque __.

neovessels; growth

bc more fibrillar collagen deposition means needs more blood supply

• demonstrates that this is a continuously growing living tissue

Atheroma can become __ to become a fixed, dense plaque on the blood vessel.

mineralized

In arterial stenosis, gradual occlusion and flow limitation occurs, characterizing __ ischemic disease or __.

chronic; angina

can be stable bc occurs very gradually, severity increases as plaque formation increases

A disruption of the plaque or rupture and thrombosis characterizes an __ ischemic disease or __.

acute; acute coronary syndrome (MI/heart attack)

What types of chest pain are consistent with chronic or acute ischemia?

pressure, squeezing, burning (elephant sitting on chest)

less common = sharp and stabbing

Label what type of angina/ischemia might be indicated for the following presentations of chest pain:

• chest pain present with exercise, emotional stress, large meals relieved with rest

• chest pain prolonged at rest

• chest pain frequent at early AM

• new and acute chest pain (no chest pain before)

• stable angina

• unstable angina

• atypical/prinzmetal’s angina

• myocardial infarction/MI/heart attack

Pain radiating to left shoulder, jaw, and left arm are consistent for

ischemia

Chest pain is presented for the following durations. Label each as stable angina, unstable angina, or MI.

• brief (2-10 min)

• long pain but <20 min

• prolonged pain of 30+ min

• stable angina

• unstable angina

• MI

What are some symptoms associated with acute ischemia? (4)

• nausea

• vomiting

• cold sweat

• SOB

Coronary vasodilators relieve __.

angina

In __ ischemia, no symptoms are present. This occurs commonly and mortality is as high as __.

silent; when patients present with pain

How does the heart sound in ischemic patients?

usually very distant, gallop rhythms, occasional murmurs

How do the lungs present in ischemic disease?

may be signs of rales/congestive heart failure (congestion in lungs)

How does the patient appear when they have ischemic disease?

pale and in distress

Taking patient’s __ is the most important element of diagnostic work up of acute vs chronic ischemia.

history

When diagnosing IHD with an ECG, it must be taken both __ and __.

at rest; during exercise

How are early/late (serious) ischemias reflected in an ECG reading?

• evidence of myocardial/early ischemia —> ST and T wave abnormalities

• evidence of loss of electrically functional cardiac tissue = serious ischemia —> Q wave abnormality

What are limitations of using ECG to diagnose IHD?

• when combined with exercise for ischemia work up, sensitivity (identifies disease correctly) of ECG is only about 65% while specificity (identifies who does not have correctly) about 90% → better for ruling out ischemia

• when diagnosing an infarction, changes in infarction may take days to develop following the event

How do ECG readings change with acute MI evolution?

A&B) show normal QRS

1. T wave becomes broader and peaks (C)

2. ST elevation (D)

3. waves become bigger, ST elevation is maximal, and eventually T wave inversion begins (E&F)

4. T waves evolve as ST returns to baseline (F)

5. becomes normal, except Q wave dips a lot —> persistance of Q wave abnormality (G)

What markers/enzymes in plasma indicate ischemia?

• troponin I (TpI) and troponin T (TnT)

• creatine kinase (CK) MB isoenzyme

• lactate dehydrogenase (LDH)

these enzymes are released from damaged cells when infarction occurs

• troponin & CK are present in a lot of cells: have higher concentration at onset

• LDH increases slowly after onset and then decreases

How does nuclear cardiology diagnose ischemia?

myocardial perfusion diminishes with ischemia

How do echocardiograms diagnose ischemia?

abnormal wall motion from ischemia or infarction

How do coronary angiographies diagnose ischemia?

demonstrates vessel obstruction

What is the most commonly used nuclear cardiology test?

SPECT scan

How does a SPECT Scan work?

radioactive tracers/radioisotopes injected via IV and images are obtained with heart at rest or after exercise. because radioisotope concentration in myocardium depends on perfusion rate, the test shows ischemia

What 2 radioisotopes are used in SPECT scans? What are the differences between them? How do they help with diagnosis?

• technetium-99m: emits high photon energy and has short half life

• thallium-201: emits lower photon energy and has longer half life

can provide more detailed images to show severity of ischemia

What three views can be viewed in a SPECT scan? What do the colors mean?

• short axis: anterior, inferior, lateral, septal walls

• vertical long-axis: anterior and inferior walls and apex

• horizontal long axis: septum, apex, and lateral walls

colors: yellow = more perfused, blue/purple = less perfused

How does this SPECT Scan show abnormalities?

theres areas of less perfusion, seen by cooler colors, that are in the middle of continuous yellow/more perfused areas

How does a PET scan work?

isotope tracers are tagged to a glucose analog with a positron-emitting Fluorine-18 molecule. glucose is taken up for metabolic function, so can track metabolic function and tissue viability.

How do SPECT and PET scans compare?

SPECT: shows reduced perfusion areas and highly perfused areas

PET: shows quantative measurement of myocardial perfusion and metabolism (bc tracks through glucose = which is taken up for metabolic fxn)

What does this PET scan show?

5 years later, decrease of color bc of less metabolic activity, especially at apical area and inferior segment of myocardium

How does coronary angiography work?

• maps blood vessels in coronary system

• receives dye that goes through systemic vessel —> shows interruptions

Ambulatory EKG / Holter can be useful for screening __ ischemia.

silent ischemia

What diagnostic tests are useful to evaluate risk of ischemia?

measurement of lipids and CRP (c-reactive protein)

What are some preventive approaches to IHD? (6)

• control BP

• stop smoking

• dietary changes

• exercise

• aspirin —> prevents clotting

• lipid lowering agents

What would medications prescribed for IHD target?

• decrease oxygen demand of myocardium or workforce of myocardium

• increase oxygen delivery to heart muscle or increase blood flow to heart = vasodilators

If a patient has already had a thrombotic event already, what can be done immediately?

chew on aspirin to reduce progression to heart attack and symptoms

What are 4 invasive procedures that can treat IHD?

• coronary angioplasty- percutaneous transluminal coronary angioplasty (PTCA): uses balloon catheter & intravascular stents

• coronary artery bypass graft surgery (CABG): can be done off pump

• laser angioplasty: for definitive large clots that are already identified

• mechanical atherectomy: device that scrapes areas with plaque

done after initial preventative measures and medications fail to reduce symptoms

How does an angioplasty with stent work?

inserts catheter with balloon into heart to access coronary arteries. balloon dilates and crushes cholesterol plaque against artery wall. once catheter and balloon are removed, stent remains in place to prevent reobstruction

Angiography and angioplasty are usually done __

at the same time

angiography = imaging procedure that uses dye to visualize inside blood vessels

• during angioplasty, when inserting catheter, they also insert dye to map and visualize blockages in vessels

How does CABG (coronary artery bypass graft surgery) work?

establish new pathway to avoid blocked area = bypass

• heart can’t be beating during this surgery, so use heart-lung machine that takes blood, filters, and repumps back into circulation

• shocks heart to start beating again

If a patient presents with a high risk of IHD (unstable coronary syndromes, unstable angina, or recent MI) in a dental setting, how should you proceed?

• avoid any elective care in the 1st six months after an MI

• emergency care can be done to target management of pain and infection

  • support patient with vasodilators avail, need IV line, EKG, and pulse oxymeter connected

If a patient has an intermediate risk (mild angina, previous MI >6 mo ago) in a dental setting, how should you proceed?

reduce stress, pre-treatment vital signs, sedation maybe, limit epi, no epi cords

__ is not recommended for patients with a history of previous bypass graft surgery, with or without intravascular stents performed > 6 mo ago

antibiotic prophylaxis

• they may be considered immediately after surgery and up to first 6 months

If a patient with IHD is in the dental setting, what medications should you be cautious of?

anticoagulants

When does ischemia occur?

when myocardial oxygen demand is not met adequately

__ plays a large role in IHD.

atherosclerosis

Ischemia can lead to: (3)

• contractile dysfunction

• arrhythmia

• infarction

What are some common diagnostic tests for IHD? (3)

• cardiac perfusion tests

• electrical conduction

• cardiac enzymes

What common modalities are available for treatment of IHD? (3)

• drugs that improve coronary circulation

• angioplasty

• bypass graft surgery