Quiz 3: Cardiac Flashcards
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
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
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)
Biochemical Markers of AMI
- AST - Aspartate aminotransferase
- LDH - (LD) Lactic dehydrogenase
- CK - Creatine kinase
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
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”
AST
AST: Found in liver and heart – now more commonly measured as a liver enzyme
• Increased levels in AMI, but not specific
LDH Ratios (Normal and Disease State)
- Normal ratios: LD1 < LD2; LD5 < LD4
- LD1 > LD2 – Myocardial infarction, hemolytic anemia, pernicious anemia
- LD5 > LD4 –Liver disease
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
Less Common Biomarkers for AMI
- C-reactive Protein
- Fibrinogen
- Lipoprotein (a)
- Homocysteine
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)
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
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
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
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
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
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
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
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
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.
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.
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
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
POCT for AMI
- STEMI: ECG, no cardiac markers needed
- NSTEMI: troponin increased dramatically, POCT adequate
- UA/NSTEMI: variability in performance of POCT devices.
Relative Appearances of Markers
ECG Markers
Negative Risk Factors
HDLc > 60mg/dL
LDLc < 100mg/dL
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
