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ACUTE CHEST PAIN NEW APPROACHES TO AN OLD PROBLEM

ACUTE CHEST PAIN NEW APPROACHES TO AN OLD PROBLEM. Peter J. Paganussi MD, FACEP Assistant Clinical Professor Georgetown University School of Medicine Staff Physician / Department of Emergency Medicine INOVA Fairfax Hospital. Total # of Patients - 5400.

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ACUTE CHEST PAIN NEW APPROACHES TO AN OLD PROBLEM

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  1. ACUTE CHEST PAINNEW APPROACHESTO AN OLD PROBLEM Peter J. Paganussi MD, FACEP Assistant Clinical Professor Georgetown University School of Medicine Staff Physician / Department of Emergency Medicine INOVA Fairfax Hospital

  2. Total # of Patients - 5400

  3. Total # Chest Pains - 3790

  4. Total # of Patients - 3790

  5. Discharged Chest Pains 1484 (39%) • 5% missed MI rate = 74.2 Patients • Missed MI malpractice payout = $500,000 to $1,000,000 per patient • Potential liability Fairfax ED = $37 to $74 Million

  6. Average hospital cost per patient = $1400/day Average length of stay = 2 to 3 days Total cost = $6.5 to $9.7 Million Admitted Chest Pains 2306 (61%) 30% to 50% = 692 to 1153 Patients Potential cost savings = $1.9 to $4.8 Million

  7. Myocardial Markers and Perfusion Imaging in the Evaluation of the Emergency Department Chest Pain Patient Michael C. Kontos, MD Associate Director, Acute Cardiac Care Director, Nuclear Cardiology Assistant Professor, Cardiology, Radiology and Emergency Medicine Medical College of Virginia Richmond, Virginia

  8. Emergency Department Visits-US 95,000,000 ED Visits annually 8,000,000 Chest pain (8.4%) 3,000,000 5,000,000 Sent home (40 %) Possible or actual MI (60 %) 40,000 (MI) 2,900,000 1,000,000 800,000 Non-cardiac AMI UA (60 %) (20 %) (20 %)

  9. Physician Insurers Association of AmericaAMI Study 1996 Malpractice Claims By Specialty Group %All ClaimsMean Payment Family Practice 32 % $162,000 Internal Medicine 22 % $252, 000 Emergency Medicine 15 % $181,000 Cardiology 7 % $155,000

  10. Cardiac MarkersDevelopment • AST 1954 • LDH 1955 • CK 1960 • CK-MB isoenzymes 1970 • CK-MB mass 1985 • Myoglobin 1975 • TnT 1988 • TnI 1992

  11. Current Myocardial Markers • Myoglobin • CK-MB • Troponin

  12. Timing of Marker Appearance JACC 2000;36:970

  13. Cardiac MarkersMyoglobin • Advantages • Rapid release • High early sensitivity • Most useful for excluding MI • Disadvantages • Not cardiac specific; false positives with: • skeletal muscle damage • renal failure • specificities of 77-97% • false negative if the patient presents very early

  14. Myoglobin- -Diagnostic Accuracy Study # Patients Time SN SPStone 108 admission 97 95Grenadier 15 3 100 NAIsakov 178 admission 95 NAOhman 82 admission 87 82Mair 126 2-4 82 91Vrenna 60 6-8 95 97Bakker 290 4 36 87Tucker 110 6 87 95De Winter 309 4 84 96Montague 89 admission 56 81Gornall 98 admission 43 98Laurino 100 4-6 70 81 De Winter 309 5 87 97 (90 ug/L) 95 86 (50 ug/L)

  15. Cardiac MarkersCK-MB • Advantages • Newer immunassays are rapid and cost effective • Diagnostic standard for MI • High specificity • Disadvantages • Not completely cardiac specific • Early sensitivity low

  16. Improving Sensitivity: Marker Combinations • No marker has optimal diagnostic accuracy at all time points • Sensitivity can be improved by combining two markers • Early rising marker (eg, myoglobin) • Later rising, more specific marker (eg, troponin) • Caveats for interpreting study results: • Number of samples and sample timing • Number of patients with MI • Overall MI prevalence

  17. Improving SensitivityMarker Combinations Sens Spec Initial MB 46% 99% Initial MB or Myo 64% 89% 0 or 3 hr MB 78% 99% 0 or 3 hr MB or Myo 94% 86% 0 or 3 hr MB or 93%98% doubling of MB Kontos et al AJC 1999;83:155

  18. Cardiac MarkersMarker Combinations Sens Spec # TP# FP Initial MB 46% 99% Initial MB or Myo 64% 89% 0 or 3 hr MB 78% 99% 0 or 3 hr MB or Myo 94% 86% 22 230 0 or 3 hr MB or 93% 98%20 21 doubling of MB Kontos et al AJC 1999;83:155

  19. MCV Critical Pathway Chest Pain Marker Strategy

  20. Is <8 hours Sufficient for Diagnosis of MI? Patient 1 Patient 2 Time CK-MB TnI CK-MB TnI hours ng/mL ng/mL ng/mL ng/mL 0 hr 1.5 <0.5 1.8 <0.5 3 hr 1.9 3.1 6 hr 2.6 8.0 8 hr 14.6 <0.5 14.3 <0.5 13 hr 23.2 4.6 22.3 3.0

  21. Cardiac Markers Troponin • Structural Proteins • TnT-binds to tropomyosin • TnI-inhibits A/M coupling • TnC-binds calcium • Cardiac specific • Highly sensitive • Prolonged elevations post MI

  22. Cardiac Events, TnTFRISC Substudy Lindahl Circ 1996;93:1651

  23. 30 and 90 day Cardiac and All Cause Mortality Based on Peak TnI Value 30 Day Cardiac Mortality 90 Day Cardiac Mortality

  24. Outcomes Based on Peak TnI ValueExcluding Patients with MI Death Death/MI Death/MI Death/MI Death/MI Revasc Sig Dis Sig Dis/+Stress

  25. Why do Troponin Elevations Predict Adverse Outcomes? • More objective marker of an ACS • Down stream thrombus/platelet embolization • Increased prevalence of: • Significant coronary disease • Multi-vessel coronary disease • Visible thrombus • Suboptimal coronary flow • Reduced systolic function

  26. Benefit of GP IIb/IIIa and Troponin (+)30 Day MI/Death

  27. 14 Day Outcomes, TnI (+) and (-)Enoxaparin vs UFH Troponin (+) Troponin (-) Morrow JACC 2000;36:1812

  28. Cardiac MarkersComparison Between TnI and TnT • Troponin T • only one assay available • Troponin I • multiple assays available • different values for similar TnI concentrations • Overall diagnostic sensitivity similar between TnT and TnI

  29. Troponin IAssay Variations 16.8 ng/mL 13.7 ng/mL 9.2 ng/mL 5.3 ng/mL 2.5 ng/mL

  30. TroponinChoice of Diagnostic Value • Upper Reference Level (Manufacturers’ Cut-off value; URL) • higher specificity, decreased sensitivity • Lower Limit of Detectability (LLD) • higher sensitivity • results in more FPs related to assay variability • Optimal diagnostic value • chosen by ROC curve analysis

  31. Troponin ROC Curve LLD 0.5 ng/ml Sn 97 % Sp 86 % Opt 1.0 ng/ml Sn 96 % Sp 93 % URL 2.5 ng/ml Sn 87 % Sp 97 % Optimal LLD MUL Sensitivity (True Positive) • 1- Specificity (False Positive)

  32. Troponin False Positives • Analytical False Positives • hemolysis, clotting • heterophile antibodies, Rheumatoid factor • Non-Perfect Gold Standard • Comparison with CK and CK-MB • Biological False Positives • Myocarditis • Cardiac contusion • Radio Frequency Ablation • Transplant rejection • Pulmonary embolism

  33. TroponinFalse Negatives • Sample Timing • Imperfect gold standard • Choice of diagnostic value • Inability to detect ischemia alone

  34. Frequency of Elevated TnT in U/A11 Studies, 1731 patients Overall 33 % TnT (+) Rottbauer et al Eur Heart J 1996;17 (Supp);17:1

  35. Sensitivity of TnI For Cardiac Events Kontos JACC 2000;36:1818

  36. The Acute Coronary Syndrome Risk Plaque Rupture Intracoronary Thrombus Asymptomatic Unstable Angina Reduced Blood Flow Myocardial Infarction perfusion imaging Myocardial Ischemia ECG Myocardial Necrosis Diagnostic Focus CK-MB, TnI

  37. Acute Perfusion Imaging in the ED • Technetium-99m sestamibi and tetrofosmin are radioisotopes that do not redistribute • Patients can be injected during symptoms and imaged after stabilization • Images will provide a “snapshot” of the blood flow at the time of injection

  38. Acute Perfusion Imaging in the EDInformation Obtained • Myocardial perfusion • Wall motion • Wall thickening • Ejection fraction

  39. Cardiac Events, (+) and (-) Mibi % Kontos JACC 1997;30:976

  40. Sensitivity for Cardiac EventsSestamibi and TnI % Kontos Circ 1999;99:2073

  41. Limitations of Acute Imaging • Can’t tell the difference between • acute ischemia • acute infarction • old infarction • Requires 24 hour imaging capability • Imperfect sensitivity

  42. Myocardial Perfusion ImagingSensitivity • Overall Sensitivity: 92 % (175/191) • Mean risk area: 16 + 10 % of LV • 16 patients had MI but (-) MPI • Median peak CK: 235 U/L • Median peak CK-MB: 12 ng/ml • Mean EF: 58 % • Cath in 12 patients: • 0 V in 5 • 1 V in 3 • 2 V in 4

  43. Role of Perfusion Imaging • Level 3--Probable Unstable Angina • Rule in ACS---early intervention • Rule out ACS--early stress testing and discharge • Level 4--Possible Unstable Angina • Rule in unsuspected ACS--prevent “missed MI”

  44. LEVEL 3Probable Unstable Angina • Moderate probability of MI or ischemia • Diagnostic criteria: • ECG-non-ischemic • Symptoms--prolonged (>30 min) • typical symptoms w/o known CAD • atypical symptoms in pt with known CAD • Disposition • Observe in CCU-Fast track protocol • Diagnostic strategy • Early markers • MPI

  45. Case 2003146 • 50 yo female with 2 hr substernal CP • 11 pm ECG: NSST • Triaged as Level 3 • Rest mibi : normal • 7 am markers: CK 150 U/L MB 1.3 ng/ml TnI <.1 ng/ml • 9 am stress test: normal • 12 pm discharge home

  46. LEVEL 4Possible Unstable Angina • Low probability of MI and low-moderate Probability of unstable angina • Diagnostic criteria: • ECG-non-ischemic • Symptoms • Suggestive symptoms <30 min • Prolonged atypical symptoms • Cocaine-associated chest pain • Disposition • ED evaluation • Diagnostic strategy • MPI

  47. ED Perfusion ImagingCocaine Chest Pain • 216 pts with acute imaging • 5 patients (+) (2 %) • 2 MIs • 211 patients (-) • no MIs • 2 with significant coronary disease No MIs 2 MIs (-) MPI (+) MPI Kontos Ann Emer Med 1999;33:639

  48. Case 5906303 • 54 yo male presented at 00:19 with two day history of intermittent chest discomfort • described as burping sensation • no radiation • Now continuous for 1 1/2 hrs • Risk factors--tob, HTN • ECG:

  49. Case 5906303 • Initial triage level 4 • Mibi shows high grade inferior defect, absent WM • ECG repeated at 4:30 am

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