Acute Coronary Syndrome

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ACS talk prepared Y2008 - emphasis on diagnosis of AMI and ACS via use of biomarkers.

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  • Acute Coronary Syndrome

    1. 1. Acute Coronary SyndromeFrank W Meissner, MD, RDMS, FACP, FACC, FCCP, CPHIMS, CCDS
    2. 2. Ruptured Plaque Thrombus Inflammatory Cells Few SMCs Activated Macrophages
    3. 3. Sheer Force - Engine of Plaque Rupture The Mattress Analogy Jump from 10 ft Step Ladder Box Mattress Water Mattress Unstable plaque has semi-liquid cholesterol core
    4. 4. ACS Pathophysiology Plaque rupture, thrombosis and microembolization Plaque rupture Platelet-thrombin micro-emboli Inflammation, spasm endothelial dysfunction ThrombusCutoff TnT Curve CK-MB CK-MB Microvascular CK-MB 1st 2nd 3rd Obstruction embolus embolus embolus
    5. 5. ACS Risk AssessmentEffective Triage Tx to Tertiary Center Early Risk AssessmentEarly Choice ofRevascularization Medical Therapy Inform Patient and Family
    6. 6. Risk Stratification-ACS Clinical Features ECG Troponin I or T Inflammatory Markers Renal Dysfunction Novel Markers
    7. 7. High Risk Features I Chest Pain Prolonged rest pain >10 min Recurrent Pain esp accelerated tempo in preceding 48hrs Rest angina not relieved by nitrates Early post infarction angina
    8. 8. High Risk Features II Hemodynamic Instability (Systolic blood pressure <90mmHg, cool periphery, diaphoresis) Associated Heart Failure, Mitral Regurgitation or Gallop Rhythm Associated Syncope
    9. 9. High Risk Features III Poor LV function Previous Revascularisation (PCI,CABG) Prior Aspirin Treatment Diabetes Renal Dysfunction
    10. 10. Killip Classification of AMI I No signs of heart failure or pump failure II Lung crackles, S3, elevated jugular venous pressure III Frank pulmonary edema IV Cardiogenic shock (BP <90 mmHg) + peripheral vasoconstrictionKillip T, and Kimball JT: Treatment of myocardial infarction in a coronary care unit: a two year experience of 250 patients.American Journal of Cardiology 1967; 20: 457-464.
    11. 11. Low Risk Features Nature of Pain No Recurrence of Chest pain During Observation Exertional Symptoms Only Few Risk Factors
    12. 12. Baseline ECG & Outcome Six-Month Mortality 10% ST ↓ 8% ST ↑Mortality 6% 4% T-wave 2% inversion 0% 0 30 60 90 120 150 180 Days from Randomization
    13. 13. EKG High Risk FeaturesDynamic ST changes esp ST depressionTransient ST ElevationT inversion> 0.2 mvQ wavesBundle branch blockVentricular Tachycardia
    14. 14. Value of EKG in ACS (+) EKG = evidence of infarction, ischemia, or strain; left ventricular hypertrophy; left bundle-branch block; or paced rhythm.
    15. 15. Troponin Structure/Function •Troponin T (39.7 Kd) binds troponin complex to tropomyosin strand •Troponin C (18 Kd) binds calcium and initiates contraction •Troponin I (22.5 Kd) inhibits contraction in the resting state
    16. 16. Diagnostic Performance Post Troponin I CK-MB AMI Incr 4-6 hr 4-6 hr Pk 14-24 hr 10-24 hr Nml 5-7 d 2-3 d
    17. 17. Diagnostic PerformanceSensitivity Troponin I CK-MB Myo 0-2 hr 25% 7% 22% 2-4 hr 70% 12% 27% 4-6 hr - 73% 81% 6-8 hr 96% 90% 95%
    18. 18. Diagnostic PerformanceSpecificity Troponin I CK-MB Myo 0-2 hr 100% 100% 92% 2-4 hr 100% 93% 80% 4-6 hr - 95% 70% 6-8 hr 99% 90% 50%
    19. 19. Prognostic Value of Pos. Troponin T in ACS est RR 3.8 30.0 (2.6-5.5) 22.5% RR 3.9 15.0 (2.9-5.3) 7.5 0 322 3634 1849 737 Death Death/MI Neg Column 1 Pos (Trop I + T) Column 2
    20. 20. Cardiac Marker Release Patterns 50 Myoglobin CK-MB 15 Troponin T or I LD1Multiples of 10 UpperReference 5 Limit Normal Range 0 1 2 3 4 5 6 7 10 Days After Onset of AMI Wu, A. H., Journal of Clinical Immunoassay 1994;17, 45-48
    21. 21. Etiologies for Troponin Elevation TROPONIN False +ve AMI NSTEMI (e.g. heterophilic antibodies) Clinical Chemistry 44: 2212-2214, 1998. False Increase of Cardiac Troponin I with Heterophilic Antibodies. Fitzmaurice, TF et al. Pericarditis Iatrogenic Pulmonary Embolism •Cardiac Surgery Sepsis Shock •PCI Acute LVF •Cardioversion Trauma •Cardiotoxin Drugs Hypertension/Hypotension •EP Ablation Drug T oxicityJeremias A & Gibson M. Narrative Review: Alternative Causes for Elevated Cardiac Troponin Levels when Acute Coronary Syndromes Are Excluded. Ann Int Med. 142(9); 786-791. 2005
    22. 22. Diagnosis MI? Biomarker indicators of MI Troponin is preferred biomarker for Dx of MI cTnT or cTnI > 99th %ile on any determination CK-MB > 99th %ile on two successive measurements or > 2X ULN on any sampleESC/ACC Consensus – J Am Coll Cardiol 2000; 36: 959-69
    23. 23. Pulmonary Embolism Troponin T Time-Release Curve Time-release curve of cTnT (µg/L) in nine patients with confirmed PE who developed a cTnT ≥0.1 µg/L (A) and 6 patients with microinfarction (B) Muller-Bardorff et al. Clin Chem 48 (4): 673
    24. 24. Troponin Level & Survival Three-year Kaplan- Meier curves for group 1 versus group 2 patientsPerna et al. Am Heart J 2002:143: 814-20
    25. 25. Prob of Death ƒ(creaClr & Troponin T level) Aviles et al. N Engl J Med 2002;346:2047-2052
    26. 26. CRP & outcome by quartiles15.00 N=272 *χ2 for trend <0.001 N=287 11.25 * N=263 14.5%7.50 11.5% N=262 3.75 8.0% *2.6% 5.3% 0.3% 0 <0.3mg/dL 0.3-0.5mg/dL 0.5-1.1mg/dL >1.1mg/dL Death Death/MI
    27. 27. “Time is Myocardium”Ischemia Infarction Ischemia Necrosis AMI = Ischemia + Necrosis 100% Acute chest pain Remaining % Muscle Lost Muscle Infarct 50% Shortness of breath ECG changes 0% Before Infarct After Infarct
    28. 28. “Time is Myocardium”Ischemia Infarction Ischemia Necrosis AMI = Ischemia + Necrosis 100% Acute chest pain Remaining % Muscle Lost Muscle Infarct 50% Shortness of breath ECG changes 0% Before Infarct After Infarct
    29. 29. What is IMA? Human Serum Albumin (HSA) is a circulating protein in blood with a metal binding site at the N-terminus.The N-terminus is damaged during an ischemic event, resultingin Ischemia Modified Albumin (IMA™). IMA is unable to bindmetals at the N-terminus. Bar Or et al, European Journal of Biochemistry, 2001
    30. 30. BNP & ACSNatriuretic peptides in unstable coronary artery disease: ReviewJernberg T, et al., European Heart Journal; 17(25): 1486-93, 2004.
    31. 31. Lethal Chest Pain I AMI Unstable Angina Pulmonary Embolism Critical Aortic Stenosis IHSS Pericarditis with Tamponade Aortic Dissection
    32. 32. Lethal Chest Pain II Spontaneous Tension Pneumothorax Pneumomediastinum Decompression Sickness (‘Chokes’) Lymphoma 1° PAH Oncological Disease - Met to T-spine
    33. 33. Lethal Chest Pain III Boerhauve’s Syndrome Acute Cholecystitis Acute Pancreatitis Perforated Gastric Ulcer Ruptured Viscus Bowel Infarction
    34. 34. Non-life Threatening Barlowe’s Syndrome Pericarditis without tamponade Pleurisy - viral or rheumatological Tietze’s Syndrome (costochondritis) “Floating rib syndrome”, “slipping rib syndrome”, Cyriax or Davies- Colley’s Syndrome
    35. 35. Non-life threatening Herpes Zoster Cervical or Thoracic Disk Disease Thoracic outlet syndromes Rib fracture Shoulder pain/injury Peptic ulcer disease “Nutcracker esophagus”
    36. 36. Non-life threatening Non-surgical GB colic Splenic flexure syndrome Irritable bowel syndrome SBO Dental disease or TMJ
    37. 37. Non-life threatening Hyperventilation syndrome Panic Disorder Depression Somatization disorder Conversion reaction Factitious chest pain
    38. 38. If the Troponin is Normal The Hard Work Has Just Begun! R/O MI is not a diagnosis Patient’s do not care what they do not have, they want to know what they have

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