Troponin and other diagnostic tests

1. Troponin and other diagnostic tests Rob Siegel, MD Jacobi Cardiology

2. Learning Objectives • When to order troponin • How to interpret troponin values • Clarify troponin confusion • Review DDx of troponin elevation

3. Case #1: In the ED • Chief complaint: Chest pain • 67 M with no prior cardiac history • Risk factors are HTN • Presents with two hours of nonexertional epigastric pain radiating to his chest; episode resolved spontaneously 30 minutes before reaching the ED. Nonpleuritic.

4. Case #1, continued • PMH: HTN, GERD • PSH: Inguinal hernia, age 22 • Medication: , HCTZ 25mg PO daily, Maalox Plus PRN • NKDA • SH: Quit tobacco 20 years ago. No E/D • FH: Father had MI age 77, no other MI in family, no CVA

5. Case #1, continued • 136/72 P84 R24 SpO2=99%RA • Pleasant, conversant, NAD • JVP<8cm H2O, no bruits • CTA, no crackles • RRR, II/VI midsystolic murmur at LSB • Warm extremities without edema

6. Case #1, continued • CXR: wnl • EKG: normal sinus rhythm at 82, T-wave inversions in III and aVF; no prior EKG

7. Case #1, summarized • This is a patient with atypical chest pain, and a somewhat low pre-test probability of acute coronary syndrome • (EKG is not completely normal, and the patient has hypertension)

8. Case #1: What do you do? • 1) Discharge home with outpatient medical clinic follow-up • 2) Admit to telemetry; rule out for MI with troponin; if rules out, obtain stress test • 3) Stat cardiac catheterization

9. This will get more advanced • I promise. This case, and the next slide, will sounds a little like kindergarten to most of you. • But there’s an important point here. Please bear with me.

10. Troponin is a diagnostic test • You know how to interpret a diagnostic test. • You start with a pre-test probability. • (If it’s really low or really high, you don’t get the test.) • If it’s intermediate, you get the test. • Afterward, you have a post-test probability. You act on the result.

11. A diagnostic test has a receiver-operator curve. Diagnostic Performance of Cardiac Troponin Assays at Presentation This one is Jacobi’s Reichlin T et al. N Engl J Med 2009;361:858-867 Reichlin T et al. N Engl J Med 2009;361:858-867

12. Troponin helps you diagnose one condition. • And, with a couple of unimportant exceptions, one condition only. • What is that condition?

13. The Most Important Point • Troponin is a diagnostic test • To help determine whether acute coronary syndrome is present • It’s not really useful in other situations (with a couple rare exceptions)

14. Acute Coronary Syndrome (ACS) • Also known as coronary artery plaque rupture • This is the condition we were worried about in the case: We were concerned that the patient could have ACS with atypical symptoms

15. Acute coronary syndrome

16. Troponin was developed to help rule out acute ACS • It was not developed for any other purpose • Many studies have validated its use in this scenario • When we use it to make other clinical decisions, we’re using it for a sort of off-label indication

17. NPV/PPV Jacobi’s troponin Reichlin T et al. N Engl J Med 2009;361:858-867

18. Your patient has a single negative troponin value. • When should you check troponin again? • (Remember, you’re trying to rule out acute coronary syndrome.)

19. If negative at presentation, check troponin again at least 4 hours after onset of symptoms Reichlin T et al. N Engl J Med 2009;361:858-867

20. Your inpatient has ruled out. When to check troponin again? • Unless the patient has an episode that raises concern for ACS:Do not check troponin again. (If you do, you’re using the assay in a way that nobody ever intended.)

21. Your inpatient has ruled in. When to check troponin again? It takes about a week for troponin level to return to normal after ACS. Short answer: Do not check again during this hospitalization. • (Longer answer: If there is new concern for ACS one week after ruling out, then check again then.)

22. Congratulations! • This talk is complete. You now know everything you need to know about the clinical utility of troponin. • The rest of the talk will address troponin-related information that does not assist in clinical decision-making.

23. Troponin confusion hall of fame • “If the troponin is positive, that means you need to start heparin.” • “Isn’t there a new type of MI called a ‘Type 2 Myocardial Infarction,’ and this is the same as demand ischemia?” • “But where is the troponin coming from if it’s not coming from the heart?”

24. Case #2 • CC: Chest pain • 67 year-old man with HTN, DM, CHOL • Notes one month of progressive angina. Exercise tolerance was unlimited one month ago; then began to develop substernal chest pressure with exertion with climbing five flights of stairs.

25. Case #2, continued • During the past month he gets chest pressure with less and less exertion. Yesterday he felt angina with climbing one-half flight of stairs. • This morning, while eating breakfast, he developed angina at rest. • He continues to have chest pain in the ED despite receiving NTG from EMS.

26. Case #2, continued • PMH: HTN, CHOL, DM • PSH: None • Medication: Metformin, Lisinopril, ASA, Simvastatin • NKDA • SH: No T/E/D • FH: Father had MI age 57; no other CAD; no history of CVA

27. Case #2, continued • 118/70 P92 R24 SpO2=98% on 2L NC • Pleasant, conversant, quiet • JVP<8 • CTA, no crackles • RRR, no murmur, S4 • No edema • Guaiac negative brown stool

28. Case #2, continued • C7 and CBC are normal • CXR is normal • EKG is normal sinus rhythm, downsloping ST segment depressions in leads I, aVL, V5, and V6 • Troponin is pending

29. When to start heparin? Single best answer: • 1) If troponin I is greater than 0.1 g/L • 2) If troponin I is greater than 0.5 g/L • 3) If troponin I is greater than 5 g/L • 4) None of the above

30. ACS Spectrum • STEMI • NSTEMI • Unstable angina

31. Acute coronary syndrome

32. ACS Spectrum • STEMI (troponin doesn’t matter) • NSTEMI (troponin is positive) • Unstable angina (troponin is negative) Treat all of the above with heparin unless there is a contraindication to heparin

33. Unstable Angina v. NSTEMI • The only difference here is in the terminlology (and in the troponin level) • Treatment for the two conditions is essentially the same

34. Case #2, review • Patient with multiple cardiac risk factors, comes in with (very) typical history of acute coronary syndrome, now with chest pain at rest • Troponin measurement has almost no role in establishing the diagnosis, because the diagnosis of ACS is already essentially certain • Give this patient heparin!

35. Case #3 • Has many similarities to case #2, in case #2 the decision-making was simple, while in case #3 the decision making is complex.

36. Case #3 • CC: Chest pain • 67 year-old man with HTN, CHOL, PUD • Notes one month of progressive angina. Exercise tolerance was unlimited one month ago; then began to develop substernal chest pressure with exertion with climbing five flights of stairs.

37. Case #3, continued • PMH: HTN, CHOL, PUD • PSH: None • Medication: HCTZ, Simvastatin, Omeprazole • NKDA • SH: No T/E/D • FH: Father had MI age 77; no other CAD; no history of CVA

38. Case #3, continued • 118/70 P108 R24 SpO2=98% on 2L NC • Pleasant, conversant, pale • JVP<8 • CTA, no crackles • RRR, no murmur, S4 • No edema • Guaiac positive black stool

39. Case #3, continued • C7 is normal • CBC shows hemoglobin=6, hematocrit=19, MCV=71 • CXR is normal • EKG is sinus tachycardia, downsloping ST segment depressions in leads I, aVL, V5, and V6 • Troponin is pending

40. When to start heparin? Single best answer: • 1) If troponin I is greater than 0.1 g/L • 2) If troponin I is greater than 0.5 g/L • 3) If troponin I is greater than 5 g/L • 4) None of the above

41. Case #3: Summary • Patient presents with severe angina in context of severe anemia with active bleeding • Most likely explanation for angina: Demand ischemia, caused by anemia(Patient cannot deliver enough oxygen to myocardium due to anemia)

42. Cases 2 and 3 compared

43. Case #2 and 3: Take-home point • Do give heparin for unstable angina, regardless of troponin • Do not give heparin for troponin elevation alone,unless there’s another reason to give heparin • In case #3, heparin could be lethal

44. NPV/PPV Reichlin T et al. N Engl J Med 2009;361:858-867

45. Troponin confusion hall of fame • “If the troponin is positive, that means you need to start heparin.” • “Isn’t there a new type of MI called a ‘Type 2 Myocardial Infarction,’ and this is the same as demand ischemia?” • “But where is the troponin coming from if it’s not coming from the heart?”

46. “Type 2 Myocardial Infarction” • This is not a clinically helpful concept • It does not help you think through how to manage your patient • Slightly useful in research studies • Very useful to the patient billing office--we get reimbursed well for MI

47. Myocardial Infarction Types • Type 1 (ACS)“Spontaneous myocardial infarction related to ischaemia due to a primary coronary event such as plaque erosion and/or rupture, fissuring, or dissection.” • Type 2“Myocardial infarction secondary to ischaemia due to either increased oxygen demand or decreased supply, e.g. coronary artery spasm, coronary embolism, anaemia, arrhythmias, hypertension, or hypotension.”

48. MI Types, Continued • Type 3 (ACS that kills you before you can measure troponin)“Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischaemia, accompanied by presumably new ST elevation, or new LBBB, or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, but death occurring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood.”

49. Don’t Memorize This • Type 4aMyocardial infarction associated with PCI • Type 4bMyocardial infarction associated with stent thrombosis as documented by angiography or at autopsy • Type 5Myocardial infarction associated with CABG Universal Definition of Myocardial Infarction Kristian Thygesen*, Joseph S. Alpert, Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. J Am Coll Cardiol, 2007; 50: 2173-2195.

50. Troponin confusion hall of fame • “If the troponin is positive, that means you need to start heparin.” • “Isn’t there a new type of MI called a ‘Type 2 Myocardial Infarction,’ and this is the same as demand ischemia?” • “But where is the troponin coming from if it’s not coming from the heart?”