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Clinic Laboratory Tests in Cardiac Disease

Clinic Laboratory Tests in Cardiac Disease. Prof. Dr. ARZU SEVEN. Cardiac markers should be: absolutely heart specific highyl sensitive able to differentiate irreversible damage from reversible able to detect reocclusion and reinfarction able to monitor reperfusion therapy.

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Clinic Laboratory Tests in Cardiac Disease

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  1. Clinic Laboratory Tests in Cardiac Disease Prof. Dr. ARZU SEVEN

  2. Cardiac markers should be: • absolutely heart specific • highyl sensitive • able to differentiate irreversible damage from reversible • able to detect reocclusion and reinfarction • able to monitor reperfusion therapy

  3. able to estimate size of infarct and prognosis • stable • able to make measurements rapidly • easy to perform • cost effective

  4. Ruling out AMI requires a test with high diagnostic sensitivity. • Ruling in AMI requires a test with high specificity. • A single test that will quickly and accurately assess AMI (acute myocardial infarction) does not exist.

  5. A combination of markers is used : • An early marker that increases within 6 hr. after onset of symptoms • A definite marker that increases after 6-9 hrs. and remains high for several days

  6. Enzymes as Cardiac Markers • Creatine kinase (CK or CPK) • Aspartate amino transferase (AST) • Lactate dehydrogenase (LDH or LD)

  7. Creatine Kinase • A cytoplasmic and mitochondriac enzyme • Total CK is %40 sensitive and %80 specific • CK-1(BB) : Brain • CK-2(MB) :Myocardium • CK-3(MM) :Skeletal muscle ,heart • CK-3 has 3 isoforms :CK-31, CK-32 and CK-33 (posttranslational products) • CK-2 has 2 isoforms

  8. Half life :CK-31 > CK-32>CK-33, CK-21>CK-22 • CK-MB (CK-2) has the most specificity for cardiac muscle (>%85) • CK-MB (CK-2) accounts for only 3-20 % of total CK activity in heart • Normal skeletal muscle contains 1 % CK-2

  9. CK-2 is increased in severe skeletal muscle injury (trauma/surgery ),chronic muscle disease (muscular dystrophy,polymyositis ) and extreme exercise. Reason:Regeneration process of muscle (reexpression of CK-MB genes ) In AMI,CK-MB increases at least 4-6 hr.after onset of chest pain,makes a peak at 12-24 hr. and returns to baseline level in 2-3 days (t 1/2 is 10-12 hr )

  10. Factors that might affect the classic pattern : 1-Size of infarction 2-CK-2 composition in myocardium 3-Concomitant skelatal muscle injury andreperfusion

  11. Differentation of increased CK-2 due to heart or muscle  monoclonic anti CK-2 antibody based assays %relative index (%RI)= CK-2 activity /total CK X %100 helpful in the detection of AMI

  12. CK-22: the predominant isoform in blood collected 2-6 hr. after AMI .It makes a peak ≈10-18 hr.,decreases rapidly 12-24 hr concomitantly asCK-21 gradually increases.

  13. Following trombolitic therapy in AMI patients,greater than two fold increases of CK-2 occur within 90 min. of reperfusion • The rate of which CK-2 isoform is released from the myocardium to circulation appears to be the more useful index of coronary reperfusion • CK22 ∕ CK-21 ratio→best discriminant within 1 hr. after treatment

  14. Lactate Dehydrogenase (LDH) • A cytoplasmic enzyme found in skeletal, muscle, liver, heart, kidney and red blood cells • 5 izoenzymes, composed of 4 subunit peptides of 2 distinct types:M (muscle ),H (heart)

  15. LDH isoenzyme determination increases specificity for cardiac tissue. • LD1 (HHHH):moves fastest towards anode • LD5 (MMMM):moves closest towards cathode • LD2 (HHHM ) • LD3 (HHMM ) • LD4 (HMMM ) • LD1 in heart,kidney(cortex),red blood cells • LD5 in liver,skeletal muscle

  16. In healthy adults: • 14-26 % LD1 (slow removal ) • 29-39% LD2 • 20-26% LD3 • 8-16 % LD4 • 6-16 % LD5 (rapid disappearance )

  17. Not a tissue specific enzyme • In AMItotal LD -elevation at 12-18 hr • peak at 48-72 hr • return to baseline level after 6-10 days

  18. LD 1 (heart) • elevation at 10-12 hr • clinical specificity 85-90 in patients suspected of AMI • peak at 72-144 hr • return to normal >10 days

  19. Total LD patern ≈LD1 pattern (contrast with total CK and CK-2 pattern) • Because of its prolonged half life,LD-1 is a clinically sensitive (%90) marker for infarction when measured after 24 hr.

  20. LD1∕LD2 >1,0 →FLIPPED PATTERN (clinical sensitivity %75 ,clinical specificity 85-90 in patients suspected of AMI) • if CK-2 values are diagnostic for AMI,cancel LD isoenzyme test request, because LD isoenzyme results don’t increase the clinical specificity of diagnostic CK-2 results for AMI

  21. As with CK-2 in skeletal muscle, the heart specific LD-1 isoenzyme in skeletal muscle can increase twofold during a 9-wk exercise training,with paralel decreases in LD-5 • LD and isoenzymes play no role in unstable and stable angina.

  22. Aspartate aminotransferase (AST ) • Widely distributed in many tissues • Highest concentrations are found in cardiac tissue,liver and skeletal muscle. • Clinical utility in hepatocellular disorders and skeletal involvement. • Unuseful in diagnosis of AMI • Beginsto rise within 6-8 hr. • Makes a peak at 24 hr. • Generally returns to normal within 5 days.

  23. Myoglobin • O2 binding protein of cardiac and skeletal muscle. • Low molecular weight and cytoplasmic location-early appearance in circulation after muscle injury • Cleared rapidly by kidney→unreliable as a long term marker of cardiac damage Cardiac muscle trauma, skeletal muscle trauma, Crush injury and AMI cause an increase in myoglobin levels.

  24. serum myoglobin methods are unable to distinguish the tissue of origin • reference intervals vary according to age,rate and sex 1. age myoglobulin 2. male > female 3. black > white

  25. very sensitive early diagnostic marker for AMI (%90-100) ,poor clinical specificity (%60-95) • rises as early as 1 hr. after AMI, peaks in 4-12 hr  reflects the early course of myocardial necrosis, lasts for 24 hr. • the role of myoglobin in the detection of AMI is within 0-4hr. (CK-2 is within its reference level).

  26. To improve clinical specificity,carbonic anhydrase III (CAIII) should be measured. • After AMI,CK-2 and myoglobin increase,but CA III remains unchanged.In severe skeletal muscle trauma (exercise,shock and i.m injection ),CK-2,myoglobin and CAIII increase.

  27. If myoglobin remains unchanged and within reference levels on multiple,early samplings within 3-6 hr. after onset of chest pain,there is 100 %certainty that muscle (either skeletal or cardiac ) injury has NOT occurred recently—Negative predictor • Myoglobin/total CK >5 reperfusion indicator (clinical sensitivity 75 %,clinical specificity 96 % )

  28. Cardiac Troponins • Contractile proteins found in muscle that play role in actin-myosin interaction • Complex of 3 protein subunits : 1. troponin C: calcium binding component 2. troponin I: inhibitory component 3. troponin T:tropomyozin_binding component

  29. Subunits exist in many isoforms like CK • Distribution of these isoforms varies between cardiac muscle and slow/fast twitch skeletal muscle • Only 2 major isoforms of troponin C are found in human heart and skeletal muscle • Troponin is located in ; 1. myofibril (%94-97) 2. cytoplasm (%3-6)

  30. Cardiac troponin I and T have different amino acid sequences • Human cTn I has an additional 3I AA residue compared to skeletal muscle Tn I (cardiac specificity) • 11 AA residue gives troponin T unique cardiac specificity • Early release kinetics of both cTnI and cTnT are similiar to CK-2 after AMI

  31. Elevation at 4-8 hr. • Remains elevated at 4-10 days (replaces LD isoenzyme assay in the detection of patients presenting late after AMI) • Cardiac specificity of troponin I and T eliminate the false clinical impression of AMI in patients with high CK-2 after skeletal muscle injury

  32. Troponin T (cTnT) • Clinical sensitivity is similiar to that of CK-2 in the 48 hr. after the onset of pain (%50-65) • Rises within a few hrs. after chest pain,peaks by day 2 →Like CK-2, cTnT is insufficient for effective early diagnosis • However cTnT remains high for a longer time (up to 7-10 days) giving high clinical sensitivity (>%90) up to 5-7 days after AMI .

  33. When AMI patients are grouped separately from other cardiovascular pathologies  • Clinical specificity for cTnT  %40-60 • “ “ “ CK-2  %75-80 • When AMI patients are grouped with unstable angina and minor myocardial injury  specificity for cTnT improves to >%80

  34. Troponin I (cTnI) • Comparable to CK-2 for diagnostic sensitivity of AMI in the first 48-72 hr. • After 72-96 hr cTnI sensitivity increases • Has serial rise and fall kinetics similiar to CK-2 after AMI during 48-72 hr, remains elevated 3-7 days

  35. In patients with high CK-2 concentrations due to acute skeletal muscle injury following marathon racing, Duchenne’s muscular dystrophy, chronic renal failure requiring dialysis,cTnI is NOT elevated • cTnI should be measured in patients with falsely increased CK-2 values for the detection of cardiac injury • cTnI has(+) predictive value (%95) and (-) predictive value (%100)

  36. cTnI is successful: • in ruling out AMI patients with cocaine induced chest pain • in accurately detecting cardiac injury in patients with blunt chest trauma • in accurately determining high incidence of cardiac injury in critically ill patients • in risk stratification analysis

  37. neither cTnI nor cTnT offered advantages over myoglobin in the early (< 2 hr) screening for AMI, both troponins could identify AMI > 6 hr after presentation. • elevation of troponin T or I within 6 hr of symptoms • increased risk of complication • need for intervention

  38. increased cTnI in unstable angina predicts a poorer clinical outcome • to determine the effects of reperfusion, cTnT should be measured at the time of trombolytic therapy initiation and 90 min. after therapy

  39. BNP and NT – pro BNP (Brain natriuretic peptide) • To diagnose congestive heart failure • To grade the severity of heart failure • To differentiate between heart failure and lung disease • To monitor the effects of therapy for heart failure NT pro BNP is a marker in the blood for BNP, a hormone that rises during cardiac stress

  40. Homocysteine • An amino acid • Toomuchhomocysteine in theblood is relatedto a higher risk of coronaryheartdiseases, strokeandperipheralvasculardiseases. • Has an effect on atherosclerosis. • Highlevels of homocysteinearetheresult of lack of certain B Vitms. ,inheritanceordietaryexcessandhavebeenimplicated in vascularwallinjury.

  41. Testing for plasma homocysteine levels can improve the assessment of risk, particularly in patients with a personal family history of cardiovascular disease.

  42. CRP • Sensitive marker of acute and chronic inflammation and infection and in such cases is increased several hundred- fold. • Useful in predicting the risk for a thrombotic event ( a blood clot causing MI ) • Heart patients who have persistant CRP levels between 4-10 mg/dl with clinical evidence of low grade inflammation should be considered to be at increased risk for thrombosis.

  43. CRP protein resultsmay be affectedbytheuse of -oral contraceptives -NSAID’s -steroids -salicylates -IUD Homocysteinelevelsmay be affectedby -smoking -DM -coffee

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