1 / 53

Cardiac Biomarkers

Cardiac Biomarkers. W. Frank Peacock, M.D., FACEP Professor, Emergency Medicine Cleveland Clinic. Biomarker?. What is a biomarker? An expensive lab test Commonly Protein with levels that correspond to Diagnosis Prognosis Most common method of measurement ELISA. Lab-test-ology.

grayson
Download Presentation

Cardiac Biomarkers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cardiac Biomarkers W. Frank Peacock, M.D., FACEP Professor, Emergency Medicine Cleveland Clinic

  2. Biomarker? • What is a biomarker? • An expensive lab test • Commonly Protein with levels that correspond to • Diagnosis • Prognosis • Most common method of measurement • ELISA

  3. Lab-test-ology Sensitivity TP/(TP+FN) Specificity TN/(TN+FP)

  4. Lab-test-ology • LOB • LOD • CV • 99th %ile

  5. CV vs LODAssay w LOD 5 pg/mL 99th %ile LOD

  6. CV and 99th%ile The box of undetectableness 10% CV Where is the 99th%ile? 99% of the normal range for cTnI 99% Cutoff 7 pg/ml

  7. CV and 99th%ile 30% CV 20% CV 10% CV 99% of the normal range for cTnI 99% Cutoff 7 pg/ml

  8. 80 70 60 TnI 50 40 CKMB 30 20 Myo 10 0 0 2 4 6 8 12 18 24 32 48 72 Hours After Onset of MI Historical timing of cardiac necrosis markers

  9. 7.5 8 6.0 6 3.7 Mortality at 42 Days (% of Patients) 3.4 4 1.7 2 1.0 831 174 148 134 50 67 0 0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 >9.0 Risk Cardiac Troponin I (ng/ml) Ratio 1.0 1.8 3.5 3.9 6.2 7.8 TIMI IIIB: Troponin I Levels Predict Mortality In UA/NSTEMI Antman EA, et al. N Engl J Med. 1996;335:1342-1349

  10. 2000 • Emergency docs • This crap is useless in almost all patients • Only helpful if positive • Rarely positive, <5% of chest pain • The rest of chest pain requires other testing • Cardiologists own troponin • Tactics-TIMI 18 • IF it is detectable, it is an MI, otherwise forget it • If positive, don’t even bother thinking, just call the cath lab

  11. C Statistic Area Under the Receiver Operator Characteristic (ROC) Curve C Stat = 1.0 A PERFECT Test C Stat = 0.69 OK test C Stat = 75 AUC = C Statistic C Stat = 50% REALLY BAD TEST

  12. 718 consecutiveED suspect AMI MI/USA 238 (33.1%) Reichlin T. N Engl J Med 2009;361:858-67.

  13. ACEP Marker Recommendations Can you trust them? • Level A recommendations Don’t use markers to exclude non-AMI ACS (ie, unstable angina) • Level B recommendations Use any of the following to exclude NSTEMI • 8-12 hours after symptom onset • A single (-) CK-MB mass, TnI, or TnT • Serial measures if < 8 hours after symptom onset • Baseline and 90 mins • A (-) myoglobin with a (-) CKMB, or (-) Tn • (-) 2-hour delta • CK-MB and Tn

  14. 80 70 60 TnI 50 40 CKMB 30 20 Myo 10 0 0 2 4 6 8 12 18 24 32 48 72 Hours After Onset of MI Historical timing of cardiac necrosis markers hsTnI

  15. If It Moves, It Is Bad Logistic regression models showing the odds ratios for predicting ACS MACE: MI, revascularization (PCI or CABG), or positive testing (>70% stenosis at catheterization, [+] MPI or non-invasive stress testing) within 30 days of index visit. McMullin N. AJEM 2009.

  16. Event Free vscTnTValues Cumulative proportion free of events Normal <0.01 g/L Marginal <0.01-0.09 g/L Frank elevation >0.01 g/L P=0.004 Days after admission to the hospital AJC 93:278, 2004

  17. You can’t have it both ways…

  18. Tn, its not just for AMI anymore

  19. Tn Elevation w/o Overt Cardiac Ischemia • Trauma • contusion, ablation, pacing, ICD firings, cardioversion, endomyocardial biopsy, cardiac surgery, interventional closure of ASDs • CHF • Aortic valve disease and HOCM with significant LVH • HTN • Hypotension, often with arrhythmias • Postoperative noncardiac surgery patients who seem to do well • Renal failure • Critically ill patients, esp with diabetes, respiratory failure, gi bleeding, sepsis • Drug toxicity, egadriamycin, 5 FU, herceptin, snake venoms, carbon monoxide poisoning • Hypothyroidism • Abnormalities in coronary vasomotion, including coronary vasospasm • Apical ballooning syndrome • Inflammatory diseases • myocarditis, eg. Parvovirus B19, Kawasaki disease, sarcoid, smallpox vaccination, or myocardial extension of BE • Post PCI patients who appear to be uncomplicated • Pulmonary embolism, severe pulmonary hypertension • Sepsis • Burns, esp if TBSA > 30% • Infiltrative diseases including amyloidosis, hemachromatosis, sarcoidosis and scleroderma • Acute neurological disease • CVA, subarchnoid bleeds • Rhabdomyolysis with cardiac injury • Transplant vasculopathy • Vital Exhaustion

  20. What now? • Cardiologists are in a tizzy • All these “false positives” • Emergency docs think this is great • There is no such thing as a false positive when your talking about being DEAD

  21. Do we really gotta be doing serial troponin’s anymore??? Reichlin T. N Engl J Med 2009;361:858-67.

  22. 2012 • The decade of 2000-10 • Will be remembered as when the cardiologists owned troponin • Used to be an MI marker • Those days are gone • Emergency Medicine • Taking troponin back from the cardiologists! • IT IS NOT AN AMI MARKER ANYMORE • Now it’s a 14 day death marker • I don’t care about 30 days or 180 days from now • I REALLY don’t care about a year from now

  23. Myocardial InfarctionIt’s a changing world • An MI used to be • >40 and sweating with chest pain • Positive markers in 8-12 hours • Now • It aint >40 • It aint sweating • It aint even chest pain

  24. It would be really great if they had it written on their forehead!!

  25. If you think this is the way they look… In 2011, you will miss 423,600 Acute Myocardial Infarction’s 1/3 have no chest pain Canto JG et al. JAMA. 2000;283:3223-3229

  26. % With Chest Pain During AMIStratified by Age SOB W&D N/V Syncope Confused

  27. This one is having an AMI When your laying naked around the ER, they all look the same……

  28. Closing Time • You don’t have to go home, but you can’t stay here…. • Semisonic

  29. The ER docs challenge Admit them all: and let the insurance company sort them out… Discharge them alland let God sort them out…

  30. Emergency Medicine Roulette What % are discharged from the ED??

  31. 14 Asia-Pacific region EDs • >18yo with >5 mins CP • Risk stratification (blinded to care team) • TIMI<1, ECG non-dx, • Negative 0 & 2hr POC Tn, CKMB, myo • Endpoint: 30 day MACE Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3

  32. TIMI Risk Score • Risk factors: • Age 65 years • 3 risk factors for CAD • Prior coronary stenosis 50% • ST-segment deviation on ECG • 2 anginal events in last 24 hours • Use of ASA in last 7 days • Elevated serum cardiac markers CK-MB or troponin Rate of Composite Endpoint (Days 1-14), % Number of Risk Factors1 Each risk factor is assigned 1 point, and the total represents a given patient’s TIMI Risk Score1 Event rates (all-cause mortality, MI, or urgent revascularization) increase with each 1-point increase in score (P<0.001 by chi square test for trend)1 • Antman EM et al. JAMA. 2000;284:835-842.

  33. N=3582 • 30 day MACE in 421 (11·8%) • Most often NSTEMI • ADP identified 9·8% (352/3582) as low risk • 3 (0·9%) had 30 day MACE Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3

  34. Potential costs savings in low risk negative ADP patients • Hospital LOS • Median 26·0 h (IQR 9·9–37·0) • Mean 43·2 h (95% CI 36·2–51·2) Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3

  35. He is a 67 year old, hypertensive, obese man. He took an aspirin this morning, he still smokes and has high cholesterol. Many of his family have CAD. He has been a diabetic for 15 years, and 4 years ago he had an MI. George is sitting in his barat his restaurant across the streetfrom the Emergency Department Age > 65, 3 risk factors, H/O MI, took asa: TIMI Risk score = 419.9% chance of death, MI, or UTVR in the next 14 days

  36. George is laying in the ED, diaphoretic, with crushing CP, nauseated, BP = 100/70 He is a 67 year old, hypertensive, obese man. He took an aspirin this morning, he still smokes and has high cholesterol. Many of his family have CAD. He has been a diabetic for 15 years, and 4 years ago he had an MI. TIMI Risk score = 419.9% chance of death, MI, or UTVR in the next 14 days

  37. Can we discharge you?? Derivation by blinded sampling (N= 703) • 130 (18.5%) AMI • None w initially undetectable hs-cTnT • Sn 100.0%, NPV 100.0% • 27.7% would have ‘ruled out’ for AMI • 2 (1.0%) died or had AMI w/in 6 months • (1 peri-procedural AMI, 1 non-cardiac death) Validation by standard practice (N= 915) • 1 patient (0.6%) with initially undetectable hscTnT developed subsequent elevation (to 17ng/L) • Sn 99.8% (99.1-100.0) • NPV 99.4% (96.6-100.0). Body, et al. JACC, 2011

  38. European Society of Cardiology • A Tn @ presentation cannot R/O NSTEMI • Repeated Tn 3 hours after admit or more CP. • LOE 1B • Tn is preferred over CKMB • Myoglobin is not specific or sensitive enough • Is not recommended.

  39. ESC Guidelines • Due to improved analytical sensitivity, low troponin levels can be detected in stable angina and in healthy patients. • The mechanisms of this troponin release are not yet explained, but ANY measurable troponin is associated with an unfavourable prognosis.

  40. 16 14 12 10 Frequency 8 6 4 2 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 More pg/ml cTNI Low Level TroponinsOne Cut-off or Two? AMI Sp=85% Myocardial necrosis AMI Sp=99% Wait and see, do more tests

  41. The Now and Then of High Sensitivity Troponins Last decade Next decade Good bye specificity 2 cutpoints? Second marker copeptin, ST-2, MPO, IMA, etc Hello sensitivity Exclude ischemia? Challenges The role of cardiology consults EDUCATION………… • Detectable Tn • 99th %ile cutpoint • Great specificity • Better sensitivity • No real clinical disposition impact for the ER • Serial testing of less necessary

  42. So next time you want to get a troponin…. • Risk stratify (after decide it might be ACS) • You want to send that patient home? • Put on your thinking cap! • AMI? Something else? • Can always repeat

  43. Results 25 participating hospitals N=1,360 patients Overall Mean DTBT 115.770.1 minutes Median 100; IQR=73,138 Central lab Mean DTBT 119.2  70.5 minutes Median 103; IQR=76,141 Point of Care Mean DTBT 68.2 40.8 minutes Median 62.5, IQR=43,83.5 Saves about 1 hour Peacock WF et al. Acad Emerg Med. 2004;11:569–570.

  44. Delay = Death N= 13,934,542 • Adverse events increase with the mean LOS in similar patients in the same ED shift • OR for Death if LOS ≥6 v <1 hr cohorts • Hi Acuity 1.79 Low Acuity 1.71 BMJ 2011; 342:d2983

  45. Overcrowding = Long waits Long waits = Death • N= 62,495 • Risk ratio for DEATH • Per hour of ED stay = 1.1 (p < 0.001) • Per hour of ED wait = 1.2 (p=0.01) MJA 2006; 184: 208–212

  46. Delay = Bad Care • N=42,780 • Long ED stays less often received guideline-recommended NSTEMI therapies Ann Emerg Med. 2007; 50; 489-96

  47. Delay = Bad Care • N=694 patients Delayed/No antibiotics • OR 1.05 for each additional WR patient • OR 1.14 for each additional WR hour Ann Emerg Med. 2007;50:510-516

  48. Delay = Bad Care • N=13,758 • Nontreatment of pain associated with waiting room number OR = 1.03 for each additional waiting patient Ann Emerg Med. 2008;51:1-5.]

  49. Delay = Bad Care • N=162 “boarded” patients (waiting for room) • Undesirable event • Missed meds, lab results, arrhythmias, or other adverse events • 27.8% had an undesirable event Ann Emerg Med. 2009;54:381-385.]

More Related