LAB WORKUP OF ACUTE MI: LAB WORKUP OF ACUTE MI DR . MOHAMMED SADIQ AZAM DNB cardiology resident kims Why do it?: Why do it? To determine the presence or absence of myocardial infarction for diagnosis and differential diagnosis. To c haracterize the locus, nature (STEMI or NSTEMI), and extent of myocardial infarction (ie, to estimate infarct size) To detect recurrent ischemia or myocardial infarction (extension of myocardial infarction) To detect early and late complications of myocardial infarction To estimate the patient's prognosis Estimating the risks…: Estimating the risks… Laboratory evaluation is particularly helpful in the presence of comorbid conditions that may affect the patient's prognosis and influence his or her care. Such comorbidities include the following: Diabetes Renal or hepatic failure Anemia Bleeding disorders Respiratory failure Routine blood investigations: Routine blood investigations CBC: CBC Anemia : Increased demand state, anemic hypoxia, assess post TLT bleed Leucocytosis : Common , doesn’t necessarily mean infection Platelet count: Prior to giving GpIIb / IIIa , to assess HIT Chem Profile: Chem Profile Electrolytes: Esp Na (in HF), K (ACEI/ARB, use of Aldosterone antag ) Serum Magnesium Creatinine: If starting ACEI/ARB ESR: May remain ekevated for weeks LDH: Rises within 24 hrs of MI and reaches peak within 3-6 days, baseline in 8-12 days. sPO2: Monitor, gives good assessment of oxygenation. No need for ABG, can cause bleeds if TLT is given Slide7: RBS Lipid profile This may be helpful if obtained upon presentation, because levels can change after 12-24 hours of an acute illness. C-reactive protein and other inflammation markers Consider measuring C-reactive protein (CRP) levels and other inflammation markers upon presentation if an ACS is suspected. SPECIFIC INVESTIGATIONS: SPECIFIC INVESTIGATIONS BIOMARKERS What is a Biomarker?: What is a Biomarker? Biological marker (biomarker) : A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Type 0 biomarker : A marker of the natural history of a disease and correlates longitudinally with known clinical indices. Type I biomarker : A marker that captures the effects of a therapeutic intervention in accordance with its mechanism of action. Surrogate end point (type 2 biomarker) : A marker that is intended to substitute for a clinical end point; a surrogate end point is expected to predict clinical benefit (or harm or lack of benefit or harm) on the basis of epidemiological, therapeutic, pathophysiological, or other scientific evidence. The Ideal Cardiac Biomarker: The Ideal Cardiac Biomarker Absolute cardiac specificity Specific for irreversible injury Early release High tissue sensitivity Stable release Predictable clearance Complete release ( infarct sizing) Measurable by conventional methods Role of Cardiac Biomarkers: Role of Cardiac Biomarkers The ACC/AHA guidelines on unstable angina/NSTEMI recommend that in patients with suspected myocardial infarction, cardiac biomarkers should be measured at presentation. Several studies have shown that implementation of point-of-care testing (POCT) for cardiac biomarkers may improve early diagnosis as well as decrease patient length of stay. If initial markers are negative and have been measured within 6 hours of symptom onset, the biomarkers should be remeasured within 8-12 hours after symptom onset. Remeasuring cardiac enzyme levels at regular intervals for the first 24 hours is a reasonable approach to improving the sensitivity of detection of myocardial necrosis, and the degree of positivity can be important for prognostication . BIOMARKERS of MYOCARDIAL NECROSIS: BIOMARKERS of MYOCARDIAL NECROSIS OF THE PAST: Lactate dehydrogenase ( LDH) Myosin Light Chains Aspartate aminotransferase (AST ) OF THE PRESENT: CK CK-MB Isoenzyme cTnT & cTnI Myoglobin NECROSIS BIOMARKERS OF THE PAST: NECROSIS BIOMARKERS OF THE PAST Lactate dehydrogenase ( LDh ) Myosin Light Chains Aspartate aminotransferase (AST ) Lactate dehydrogenase (LD): Lactate dehydrogenase (LD) myocytes , sktl musc , liver, kidney, platlts & RBCs 5 major LD isoenzymes , LD1–LD5 LD1 & LD2 – MI ( LD1 > LD2 ) LD4 & LD5 – hepatic or S kl muscle injury LD2, LD3 & LD4 – platelets/Lymphatic (Total activity)LD → 24–48 h , peak-3–6 d & N in 8–14 d LD1 > LD2 pattern → 10–12 h , peak-2 to 3d & N in 7–10 d ↑LD1 & ↑ratio – sens & spec - 75–90% Myosin Light Chains: Myosin Light Chains cardiac isoform of MLC is also produced by slow-twitch skeletal muscle Aspartate aminotransferase (AST,SGOT): Aspartate aminotransferase ( AST,SGOT) skltl muscle, liver, RBCs & myocardium T½(mitochondrial)- 10 d, (cytoplasmic)- 10 h. Isoenzymes not fractionated for clinical use 6–8 h ,peak 18–24 h, N- 4 to 5 d NECROSIS BIOMARKERS OF THE PRESENT: NECROSIS BIOMARKERS OF THE PRESENT CK CK-MB Isoenzyme cTnT & cTnI Myoglobin Creatinine Kinase (CK): Creatinine Kinase (CK) The 3 CK isoenzymes are as follows: CK with muscle subunits (CK-MM), which is found mainly in skeletal muscle CK with brain subunits (C K-BB ), which is found predominantly in the brain CK-MB, which is found mainly in the heart Creatine Kinases: Creatine Kinases CK is formed by two subunits, B and M, and has isoforms CK-MB, CK-BB and CK-MM. CK exists in various types of tissue. CK-MB predominates in cardiac muscle. up to ~45% of total CK in cardiac muscle < 1% of total CK in skeletal muscle CPK-MB: CPK-MB Appears in blood: within 3-6 hours of onset of attack Peak : 12 - 24 hours Returns to normal: within 2 - 3 days (no long stay in blood ) Advantages : - useful for early diagnosis of MI - useful for diagnosis reinfarction Disadvantages : not used for delayed admission (more than 2 days) not 100% specific (elevated in sk.ms damage) CPK-MB: CPK-MB A ratio of CK-MB mass: CK activity 2.5 suggests MI. CK-MB from skeletal muscle produces a plateau pattern. CK-MB from MI peaks at approximately 12~24 hour . N → CK-MB2/CKMB1≈1.0, totl CK-MB<1.5 IU/L ABN → >2.5 IU/L CK-MB, CK-MB2/CK-MB1 ratio ≥1.5 (6-h ∆MI sens 95.7% & speci 93.9%) Kontos et al: Kontos et al Positive test for AMI, (1) 0- or 3-h CK-MB above diagnostic cutoff (2) an ↑ in CK-MB by 3 ng/mL within 3 h (3) a doubling of CK-MB within 3 h Using this definition, a sensitivity of 93% and a specificity of 98% CK-MB Sensitivity & Specificity: CK-MB Sensitivity & Specificity initial sensitivity of CK-MB for the detection of AMI -23–57% Additional CK-MB improves sensitivity repeat testing at 3 h after initial presentation –sensitivity 88% sensitivity maximized when CK-MB performed over a 9-h evaluation period CK-MB has excellent specificity-97–99% Troponins: Troponins Three subunits including troponin C, I, and T. The complex regulates the contraction of striated muscle. TnC binds to calcium ions. TnI binds to actin and inhibits actin-myosin interaction. TnT binds to tropomyosin, attaching to thin filament . TnC-cTnT-cTnI and cTnI-TnC complexes: TnC-cTnT-cTnI and cTnI-TnC complexes cTnT and cTnI: cTnT and cTnI Not early biomarkers of necrosis ↑ diagnostic sensitivity and specificity at pt presentation, 6–9 h later & at 12–24 h if clinical suspicion is ↑ and earlier results are negative ↑ in conc is prolonged release varies among individuals and is unpredictable ↓ useful in reocclusion or for infarct sizing Tool for risk stratification detection of MI up to 2 wk; high specificity for cardiac tissue cTnT and cTnI: ↑cardiac trop EXCEEDS − ↑CK-MB BY 13-15 FOLD powerful predictor of future AC Events, even when ↑CK-MB or ST deviation is absent Sensitivity( initial measurement)cardiac trop -51 to 66% 0 h & 4 h - sensitivity ↑ from 51% -94% ( tropT ) and 66% -100%(trop I) specificity -89–98% cTnT and cTnI Slide29: 100 % cardiac specific With greater sensitivity for diagnosing minor damage of MI Appears in blood within 6 hours after onset of infarction peak : around 24 hours Disappears from blood after about one week (stays longer) So, useful for diagnosis of delayed admission cases Prognostic marker (relation between level in blood & extent of cardiac damage ) TROPONIN I TnI CUT OFFs: TnI CUT OFFs CORRELATION OF TnI & PROGNOSIS: CORRELATION OF TnI & PROGNOSIS NEJM 1996;335:1342-9 Myoglobin: Myoglobin The major protein responsible for O2 supply of striated muscle . It is released into blood rapidly (as early as 1 hour) after damage to muscle cell . Urine myoglobin levels rise within 1-4 hours from the onset of chest pain. Early detectable, more sensitive but non- cardiospecific . High negative predictive value (~96%). Myoglobin: - not specific for cardiac tissue (also in sk.ms. & renal tissue) - appears in blood EARLIER than other markers (within 1-4 hours) So, with high sensitivity - BUT: Returns to normal in 24 hours So, not for delayed admission cases (after one day of onset of attack) Myoglobin Comparison: Comparison CK and CK-MB may be elevated in renal and muscular disorders . Elevated cTnI level in uremic patients has been a source of great controversy. Elevated cTnT has been found in regenerating skeletal muscle and in patients with ESRD. Myoglobin is more suitable for the detection of reinfarction . Timing Summary: Timing Summary TEST ONSET PEAK DURATION CK/CK-MB 4-8 hours 18-24 hours 36-48 hours Troponins 3-12 hours 18-24 hours Up to 10 days Myoglobin 1-4 hours 6-7 hours 24 hours LDH 6-12 hours 24-48 hours 6-8 days Recommendations for use of biochemical markers for diagnosis of myocardial infarction: Recommendations for use of biochemical markers for diagnosis of myocardial infarction 1- Recommended for all patients complaining of chest pain (with clinical examination & ECG) 2- Sample Type: plasma Timing: i . on admission ii. serial ( at least every one hour in a period 6-9 hours) should be referenced to admission & onset of pain 3- Test should be with low turnaround time less than one hour (accepted) less than half an hour is preferred Recommendations for use of biochemical markers for diagnosis of myocardial infarction: Recommendations for use of biochemical markers for diagnosis of myocardial infarction 4- Types of Markers used : two types Early markers: as Myoglobin: appears in blood early (within less 4 fours) BUT not specific & not persists for long period (less than 2 days) Definitive markers: Troponin: appears in blood later than myoglobin (within 6 hours) BUT 100% specific, prognostic & stays longer (one week) 5- Troponin is currently the marker of choice should be available in all cardiac & emergency centers (if not, CK-MB mass is the second choice) Quantitative vs Qualitative Biomarker Testing: Quantitative vs Qualitative Biomarker Testing Qualitative testing of trop →appropriate quantitative assays may vary by up to 30-fold Q ualitative testing help avoid discord between point-of-care testing & quantitative testing in main lab Quantitative assays necessary for monitoring the release & clearance of markers Qualitative →∆ of MI Quantitative →risk stratification , reperfusion monitoring & prognosis assessment Serial Sampling: Serial Sampling When initial results are negative Serial sampling at presentation, 6–9 h later, and after 12 h is recommended if the earlier results are negative and clinical suspicion remains high THANK YOU: THANK YOU ANY QUESTIONS?