Quiz 3: Cardiac Flashcards Preview

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Flashcards in Quiz 3: Cardiac Deck (28):
1

AMI

Acute Myocardial Infarction Common Symptoms: intense chest pressure, with impending sense of doom and pain to the left arm; other symptoms may include chest heaviness or burning, pain radiation to other areas, indigestion, vomiting, nausea and diaphoresis

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Angina Pectoris

• Stable Angina: Myocardial ischemia, Chest discomfort upon exertion

• Unstable Angina: Can occur without exertion (more severe), Transient ischemia

- Platelet aggregation

- Coronary artery spasms

- Coronary thrombosis

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ECG AMI Diagnosis

• ECG changes depend on the location and severity of myocardial necrosis

• 100% specificity, 50% sensitivity (myocardial infarctions that do not produce characteristic ECG changes)

4

Biochemical Markers of AMI

• AST - Aspartate aminotransferase

• LDH - (LD) Lactic dehydrogenase

• CK - Creatine kinase

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Creatine kinase (CK)

• Takes at least 6 hours for there to be an “enzyme leak”.

• Enzymes should be re-assessed every 8 hours for the first 24 hours

• Enzyme is helpful in gauging the size of the AMI CK Isoenzymes found with Agarose gel electrophoresis with fluorescent detection.

CK3 skeletal muscle

CK2 heart muscle

CK1 brain

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Measuring CK Levels

• Immunoinhibition/precipitation - Antibody to M subunit - Multiply results by 2 - Interference from CK-1 (BB)

• Most modern methods use two-site (“sandwich”) heterogeneous immunoassay - Measures CK-MB mass, rather than activity - Gives rise to a pseudo-percentage, often called the “CK- MB index”

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AST

AST: Found in liver and heart – now more commonly measured as a liver enzyme

• Increased levels in AMI, but not specific

8

LDH Ratios (Normal and Disease State)

• Normal ratios: LD1 < LD2; LD5 < LD4

• LD1 > LD2 – Myocardial infarction, hemolytic anemia, pernicious anemia

• LD5 > LD4 –Liver disease

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5 LDH Isoenzymes

LD1 – heart, rbc’s, kidney

LD2 – heart, rbc’s, kidney (Less than LD1) (LD2 makes up the largest fraction)

LD3 – lungs and other tissues

LD4 – wbc’s, lymph nodes, muscle, liver

LD5 - liver, skeletal muscle

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Less Common Biomarkers for AMI

• C-reactive Protein

• Fibrinogen

• Lipoprotein (a)

• Homocysteine

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C-Reactive Protein

• Evaluation of inflammatory processes, arthritis and autoimmune disease

• Also found in atherosclerotic plaque, may enhance expression of adhesion molecules, alter LDL cholesterol uptake by macrophages

• High sensitivity methods with detection limits of 0.2 mg/L allow differentiation of low level inflammation implication in coronary artery disease (CAD)

12

Fibrinogen

• Large glycoprotein - final step in the coagulation cascade

• Normal levels are 200-400 mg/dL

• Levels also correlate positively with other risk factors, increasing with LDL cholesterol and decreasing with increased HDL cholesterol levels

• Elevated fibrinogen associated with 1.5 fold increased risk of AMI or coronary death

13

Lipoprotein (a)

• LDL particle containing the apolipoprotein B-100 molecule and an apoprotein (a) molecule

• Plasma concentration is from 1-100 mg/dL, but most values are < 20mg/dL

• When chronically elevated, Lp (a) may be proatherogenic

• Recent studies show that asymptomatic individuals with high levels had a risk of CAD events 1.7 times those with lower levels

14

Homocysteine

• Amino acid byproduct of the metabolism of the essential amino acid methionine

• Assoc. with Vit. B6/12 and Folic Acid

• A link was established between moderate levels and atherosclerosis, and studies show homocysteine is associated with cardiovascular events

• Homocysteine lowering therapy has had conflicting results with respect to outcomes

• Measurement remains controversial

15

Myoglobin

• Intracellular heme protein that aids in the transport of oxygen

• Abundant in both cardiac/skeletal muscle

• Elevations detected within 1-4 hours (peak) after AMI symptoms; returns to normal after 12 hours

• Nonspecific (increases in MI and Renal damage) but sensitive marker--primarily used for negative predictive value.

• Usually measured by sandwich, nephelometric, turbidimetric, or fluorescence immunoassay

16

Troponin Complex

• A contraction-regulating protein found on the thin filaments of striated muscle, made of three non-identical subunits (T,I, and C)

• Troponin has become the most sensitive and specific test for myocardial damage

• Troponin C is the calcium-sensitive subunit and contains four Ca++ binding sites

• Troponin I is the inhibitory subunit, binds actin in the relaxed state

• Troponin T binds to tropomyosin and actin

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Troponin T and I

• Proteins found in thin filament of muscle

• Early release due to cytosolic pool

• Sustained release due to myofibrils

• Cardiac troponin not released from skeletal muscles

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Troponin I

• Specific for cardiac muscle

• It rises 3-6 hours post AMI, peaks at 14-20 hours and remains elevated 5-10 days

• Studies also show its utility in risk stratification

• TnI is useful in clinical conditions where other markers are ambiguous such as in chronic renal patients.

• Most commercial assays measure TnI

19

Troponin T

• Troponin T is also specific for cardiac muscle, rises 3-4 hrs post MI and peaks in 10- 24 hours. Remains elevated for 10-14 days.

• Troponin T has been shown to be useful in risk stratification; and in detecting peri-operative MI during procedures

• May also be elevated in renal disease

20

cTnT vs cTnI

• cTnT remains positive after AMI longer than cTnI.

• Abnormal cTnT found more frequently in patients with chronic renal failure than cTnI due to non-ischemic myocardial damage.

21

Congestive Heart Failure

• A condition where the heart can’t pump enough blood to the body’s other organs

• Can result from: - Coronary artery disease - Past MI with scar tissue that interferes with function - High blood pressure - Heart valve disease - Cardiomyopathy - Infection of the valves and/or heart muscle As a result of decreased cardiac function, body fluids may build up in the lungs and limbs.

22

BNP

1 of 4 natriuretic hormones

Antagnonists to renin-angiotensin- aldosterone system Decrease blood pressure by vasodilation and renal excretion of Na and water Helps diagnose presence and severity of congestive heart failure, increased in CHF due to enhanced atrial & ventricular synthesis. Brain natriuretic peptide (BNP) are naturally occurring peptide hormones synthesized in the brain, increased in patients with kidney disease

23

POCT for Cardiac Markers

• Whole blood platforms.

• Quantitative and qualitative assays available

• Can significantly reduce assay TAT.

• Precision and sensitivity less than central laboratory platforms

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POCT for AMI

• STEMI: ECG, no cardiac markers needed

• NSTEMI: troponin increased dramatically, POCT adequate

• UA/NSTEMI: variability in performance of POCT devices.

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Relative Appearances of Markers

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ECG Markers

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Negative Risk Factors

HDLc > 60mg/dL

LDLc < 100mg/dL

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Congestive Heart Failure

  • B-Natriuretic Peptide (BNP) is active, increases Na and water excretion, causing vasodilation and drop in BP; antagonist to renin-angiotensin-aldosterone which increases BP
  • N-terminal pro-BNP is inactive

Released by ventricular walls due to hypertension and volume overload