Presentation is loading. Please wait.

Presentation is loading. Please wait.

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

Similar presentations


Presentation on theme: "Troponin and other diagnostic tests Rob Siegel, MD Jacobi Cardiology."— Presentation transcript:

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

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 Reichlin T et al. N Engl J Med 2009;361: Jacobi’s troponin

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:

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 Case 2Case 3 Angina?Yes Ischemia?Yes Etiology?ACSBleeding Heparinize?YesNo! Troponin?+/-

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:

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 4a Myocardial infarction associated with PCI Type 4b Myocardial infarction associated with stent thrombosis as documented by angiography or at autopsy Type 5 Myocardial 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: *

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?”

51 Differential diagnosis So now you have a troponin level that is elevated. Your pre-test probability for ACS was very low; troponin should not have been ordered. Now you’re in a clinical scenario that the troponin-validation studies do not address. What to do?

52 Don’t memorize this Cardiac diseases and interventions Cardiac amyloidosis/Cardiac contusion/Cardiac surgery/Cardioversion and implantable cardioverter defibrillator shocks/Closure of atrial septal defects/Coronary vasospasm/Dilated cardiomyopathy/Heart failure/Hypertrophic cardiomyopathy/Myocarditis/Percutaneous coronary intervention/Post cardiac transplantation/Radiofrequency ablation/Supraventricular tachycardia Non-cardiac diseases Critically ill patients/High dose chemotherapy/Primary pulmonary hypertension/Pulmonary embolism/Renal failure/Subarachnoid haemorrhage/Scorpion envenoming/Sepsis and septic shock/Stroke/Ultra-endurance exercise (marathon) Peter Ammann, Matthias Pfisterer, Thomas Fehr, Hans Rickli. Raised cardiac troponins: Causes extend beyond acute coronary syndromes. BMJ May 1; 328(7447):

53 Siegel 6-category Troponin DDx Thrombosis Trauma Demand “Sick” Brain Annoying

54 Thrombosis Pulmonary embolism Troponin is elevated in 30-50% of cases of clinically proven PE Acute Coronary Syndrome Give heparin!

55 Trauma Electrical Even a single ICD shock can cause troponin elevation Mechanical Surgery. Cardiac ablation procedures. Trauma. (Check troponin after chest trauma.)

56 Supply/Demand Mismatch Increased myocardial oxygen demand Tachycardia, hypertrophy, fever, surgery Decreased myocardial oxygen supply Hypoxia, anemia, hypotension

57 Demand, continued: Tachycardia Tachycardia alone has been implicated as a cause of troponin elevation in case series. In one series of 21 patients with elevated cTnI levels and normal coronary angiograms, tachycardia was determined to be the explanation of the troponin elevation in six patients. A second series described four patients with troponin elevations after episodes of supraventricular tachycardia (SVT), who had no evidence of CHD.

58 Demand, continued: Tachycardia Myocardial troponin can be released as a consequence of tachycardia alone in the absence of myodepressive factors, inflammatory mediators, and CHD. Bakshi TK; Choo MK; Edwards CC; Scott AG; Hart HH; Armstrong GP. Causes of elevated troponin I with a normal coronary angiogram. Intern Med J 2002 Nov;32(11):520-5.

59 Demand, continued: Hypertrophy In a series of 74 consecutive patients without clinical evidence of active myocardial ischemia referred for routine echocardiography, seven of 25 patients in the tertile with the greatest LV mass had an elevated cTnI. In contrast, one patient in the intermediate range, and none of patients in the lowest tertile had elevated troponin. Hamwi, SM, Sharma, AK, Weissman, NJ, et al. Troponin-I elevation in patients with increased left ventricular mass. Am J Cardiol 2003; 92:88

60 Demand, continued: Hypertrophy LVH can lead to occult subendocardial ischemia via increased oxygen demand from increased muscle mass, coupled with decreased flow reserve due to remodeled coronary microcirculation. Similar observations have been made in the setting of aortic valve disease. Cardiac troponin I in aortic valve disease. Nunes JP; Mota Garcia JM; Farinha RM; Carlos Silva J; Magalhaes D; Vidal Pinheiro L; Abreu Lima C. Int J Cardiol 2003 Jun;89(2-3):281-5.

61 “Sick” Sepsis Not only does this cause demand ischemia, it may also cause degradation of intramyocyte troponin molecules, allowing them to permeate the cell membrane (hypothetical) Autoimmune/infiltrative Myocarditis, amyloid

62 Brain Subarachnoid hemorrhage (SAH) Acute CVA Troponin is elevated in about 27% of patients with acute stroke, and in SAH case series. Probably due to catecholinergic surge; autopsy studies demonstrate myocardial band necrosis in some of these patients Trooyen M, Indredavik B, Rossvoll O, Slordahl SA. [Myocardial injury in acute stroke assessed by troponin I] Tidsskr Nor Laegeforen 2001 Feb 10;121(4): Tung, P, Kopelnik, A, Banki, N, et al. Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke 2004; 35:548. Naidech, AM, Kreiter, KT, Janjua, N, et al. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 2005; 112:2851. Homma, S, Grahame-Clarke, C. Editorial comment--myocardial damage in patients with subarachnoid hemorrhage. Stroke 2004; 35:552.

63 Annoying Lab error Proximity to mice Chronic Kidney Disease Can have positive troponin for years. Also have poor prognosis and CAD, too. If they also get atypical chest pain, should we cath these people or not?

64 Siegel 6-category Troponin DDx Thrombosis (ACS, PE) Trauma (Electrical, mechanical) Demand (Demand, supply) “Sick” (Sepsis, immune/infiltrative) Brain (Large CVA, SAH) Annoying (Lab error, CKD)

65 Troponin without ACS It’s like a positive RPR without syphilis: It can be a hint that you’re missing a diagnosis. It can also end up being clinically useless There is no clear evaluation strategy, other than to think through the DDx of elevated troponin and see if it helps improve your patient’s diagnosis

66 Troponin without ACS, cont. When you get this, should you look for or treat CAD? Get a stress test? Get a cath? Change your LDL treatment goal?

67 Troponin without ACS, cont. "There are currently no data from randomized, controlled trials evaluating the efficacy of therapies aimed at reducing risk in patients with troponin elevations in the absence of an ACS." -Up-To-Date That said, you probably should give aspirin and beta blockers--in case you’re missing an ACS, the benefit is huge and the risks of these treatments are minimal. (Quadramed recommends this.)

68 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?”

69 Myocyte Necrosis is not necessary to make troponin In rat cardiomyocytes, only 15 minutes of mild ischemia has been shown to be enough to cause troponin release This interval is too short to induce cell death McDonough JL, Arrell DK, Van Eyk JE. Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. Circ Res 1999;84: 9-20.

70 Increased preload alone can cause troponin release. Troponin degradation has been demonstrated with increased preload, independent of myocardial ischemia, in isolated rat hearts. Preload induces troponin I degradation independently of myocardial ischemia. Feng J; Schaus BJ; Fallavollita JA; Lee TC; Canty JM Jr. Preload induces troponin I degradation independently of myocardial ischemia. Circulation 2001 Apr 24;103(16):

71 Causes of Troponin Elevation where Heparin Can Be Lethal Demand ischemia from anemia/hypovolemia from blood loss--can appear clinically similar to ACS Pericarditis Subarachnoid hemorrhage Large CVA Traumatic cardiac contusion Thoracic aortic dissection All of the above can present with EKG changes; list is not complete

72 Degree of troponin elevation as an aid to diagnosis “This cannot be demand ischemia alone. The troponin level is too high.” If there is any clinical study showing the maximum troponin level achievable in any condition, I am not aware of it. (With the exception of ICD shocks, where we think we know the upper limit.) STEMI can present with surprisingly low troponin values.

73 In almost every study, In a broad array of conditions, The higher the peak troponin value, the worse the mortality. Has been demonstrated in studies of ACS, PE, CVA, ESRD, sepsis Degree of troponin elevation as an aid to prognosis

74 Troponin Predicts Mortality Antman TM, Tenasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996;335:

75 Why is troponin better than CK? Because it is more accurate than CK, and also more sensitive than CK-MB for detecting ACS. (However, troponin stays elevated longer, which is a drawback.) The figure on the following slide comes from: Omland T, de Lemos JA, Sabatine MS, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009;361:

76 ROC troponin/myoglobin/CK- CK-MB

77 Time course of serum markers in acute myocardial infarction Larue C, Calzolari C, Bertinchant JP, Leclercq F, Grolleau R, Pau B. Cardiac-specific immunoenzymometric assay of troponin I in the early phase of acute myocardial infarction. Clin Chem. 1993;39:972–979.

78 Thank you.


Download ppt "Troponin and other diagnostic tests Rob Siegel, MD Jacobi Cardiology."

Similar presentations


Ads by Google