Topic. Updates on Definition of Myocardial Infarction

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1 Topic Updates on Definition of Myocardial Infarction

2 In the past, general consensus for MI?

3 Definition of MI by WHO - Combination of 2 of 3 characteristics - 1. Typical Symptoms 2. Enzyme Rise 3. Typical ECG Findings

4 ECG Findings of MI?

5 ECG Changes; Myocardial Ischemia That May Progress to MI 1. Patients with ST segment elevation: New or presumed new ST segment elevation at J point in 2 contiguous leads with 0.2 mv in leads V1, V2, or V3 and 0.1mV in other leads. Contiguity is defined by the lead sequence avl, I, inverted avr, II, avf, III 2. Patients without ST segment elevation: a. ST segment depression b. T wave abnormalities only Alpert JS, et al. The Joint ESC/ACC Committee.J Am Coll Cardiol 2000;36:

2 mv in leads V1, V2, or V3 and 0.1mV in other leads.

6 ECG Changes; Myocardial Ischemia That May Progress to MI Patients with ST segment elevation: New or presumed new ST segment elevation at J point in 2 contiguous leads with 0.2 mv in leads V1, V2, or V3 and 0.1mV in other leads. Contiguity is defined by the lead sequence avl, I, inverted avr, II, avf, III J point 60~80 msec V 1 PQ point (isoelectric point) ST 60 or ST 80 V 2 V 3

7 ECG Changes in Established MI Any Q wave leads V1 through V3 Q wave 30ms in leads I, II, avl, avf, V4, V5, or V6. (Q wave changes; in any 2 contiguous leads, and be 1mm in depth) Alpert JS, et al. The Joint ESC/ACC Committee.J Am Coll Cardiol 2000;36: A Q wave of any size is normal in leads III and avr because of their rightward orientations. Wagner GS. Marriott s Practical electrocardiography, 13 th ed

8 Adverse outcome by initial ECG Death or MI % ST Elevation & Depression ST Depression only ST Elevation only T Wave Inversion only No ST or T Wave Change Days RISK study group J Intern Med 1993;234:293

9 Appearance of Events during Transient Coronary Occlusion ECG changes Angina Filling pressure Contraction failure Relaxation failure Ischemia Occlusion sec

10 However, the development of more sensitive & specific serological biomarkers allows detection of ever smaller amounts of myocardial necrosis.

11 Redefinition of MI by ESC/ACC - Criteria of Acute MI - Biochemical markers (Tn-T / Tn-I / CK-MB) with at least one of the following: 1. Ischemic symptoms : Typical or Atypical 2. Pathologic Q wave on ECG 3. ECG changes : ST segment elevation or depression Alpert JS, et al. The Joint ESC/ACC Committee.J Am Coll Cardiol 2000;36:

12 Biochemical markers for detecting myocardial necrosis 1. Troponin T or I > normal value on at least one occasion during the first 24h 2. Maximal value of CK-MB > normal value on two successive samples, or maximal value > 2 X normal 3. Values for CK-MB should rise and fall Sampling time: On hospital admission, at 6 to 9h and again at 12 to 24h if prior samples are negative ESC/ACC Joint Committee JACC 2000;36:959

13 Molecular markers of AMI Marker Time to initial elevation Mean time to peak elevation Time to return to normal range Myoglobin 1 ~ 4 hr 6 ~ 7 hr 24 hr ctn-i 3 ~ 12 hr 24 hr 5 ~ 10 d ctn-t 3 ~ 12 hr 12 hr ~ 2 d 5 ~ 14 d CK-MB 3 ~ 12 hr 24 hr 48 ~ 72 hr CK-MB isoform 2 ~ 6 hr 18 hr unknown LDH 10 hr 24 hr 10 ~ 14 d Adams J et al. Circulation 1993;88:750

14 Advances in biomarkers, ECG, imaging, interventions, clinical investigations, global perspectives, and implications. Definition of myocardial infarction will be subject to a variety of changes in the future as a result of scientific advance.

16 Clinical features of ischemia The term myocardial infarction : reflects cell death of cardiac myocytes caused by ischemia, which is the result of a perfusion imbalance between supply and demand. Possible ischemic symptoms : chest, upper extremity, jaw, or epigastric discomfort with exertion or at rest. (lasts at least 20 min) : dyspnoea, diaphoresis, nausea,or syncope : may be atypical! European Heart Journal (2007) 28,

17 Pathology-1 Complete necrosis of all myocardial cells at risk requires at least 2 4 h or longer Myocardial infarctions (classified by size) : microscopic (focal necrosis) : small (<10% of the LV myocardium) : moderate (10 30% of the LV myocardium) : large (>30% of the LV myocardium) Myocardial infarction (pathologically): acute, healing, healed. J Am Coll Cardiol 2000;36:

18 Pathology-2 Cardiac death with or without ECG changes suggestive of ischemia : new ECG changes (ST elevation), and symptoms of ischemia classified as having had a fatal MI even if cardiac biomarker evidence of infarction is lacking : classified as having had a fatal MI : evidence of fresh thrombus by coronary angiography (if performed) and/or at autopsy

Clinical classification of MI ; not include myocardial cell death associated with mechanical injury from CABG; nor does it include myocardial necrosis

19 Clinical classification of MI ; not include myocardial cell death associated with mechanical injury from CABG; nor does it include myocardial necrosis below causes (CRF, HF, DC cardioversion, EP ablation, sepsis, myocarditis, cardiac toxins, or infiltrative diseases) European Heart Journal (2007) 28,

20 Biomarker evaluation-1 Myocardial cell death from the damaged myocytes myoglobin, cardiac troponin T and I, CK, LDH, etc. An elevated value of cardiac troponin in the absence of clinical evidence of ischemia should prompt a search for other etiologies of myocardial necrosis. Jaffe AS et al.it s time for a change to a troponin standard. Circulation 2000;102:

21 Khan IA et al. Am J Emerg Med 1999 Ammann P et al. J Am Coll Cardiol 2003 Elevations of troponin in the absence of overt ischemic heart disease

22 Biomarker evaluation-2 The preferred biomarker : cardiac troponin (I or T) : nearly absolute myocardial tissue specificity & high clinical sensitivity. : An increased value for cardiac troponin is defined as a measurement exceeding the 99 th percentile of a normal reference population (URL=upper reference limit). : Detection of a rise and/or fall of the measurements is essential to the diagnosis of AMI. Blood samples (troponin) should be drawn on first assessment (often some hours after the onset of Sx) and 6 9 h later. CK-MB; the best alternative ( total CK: not recommended) Jaffe AS. Chasing troponin: how low can you go if you can see the rise? J Am Coll Cardiol 2006;48:

23 Reinfarction Traditionally, CK-MB has been used to detect reinfarction. However, recent data suggest that troponin values provide similar information. Apple FS et al. Clin Chem 2005 In patients where recurrent MI is suspected an immediate measurement of the employed cardiac marker (a second sample should be obtained 3 6 h later) 20% increase of the value in the second sample Reinfarction Westgard JO et al. Textbook of Clinical Chemistry and Molecular Diagnostics, 4th edn). St Louis, MO: Elsevier Saunders; p

24 The value of Troponin in ACS

25 Prognostic evaluation by Troponin T levels Recent Risk of Death or MI (%) Chest pain 24 hours 30 days 6 months TnT (+) TnT (-) <1 <2 <5 Hamm CW et al Circulation 2000;102:118

26 The risk of mortality in UA/NSTEMI by Troponin I Mortality at 42 Days (% of patients) to < to < to < to < to <9.0 > Cardiac Troponin I (ng/ml) Antman et al. NEJM 1996;335:1342

27 Cardiac death or MI according to Troponin T levels % Cardiac death or MI P< > < 0.06 Time from inclusion(days) Lindahl et al Circulation 1996;93:1658

28 Mortality rate by CRP and rapid ctnt assay status 10% 9.1% Mortality at 14 days 8% 6% 4% 2% 4.7% 5.6% 0% TnT early positive CRP >=1.55mg/dL CRP>=1.55 and TnT early positive TIMI IIA JACC 1998;31:1460

29 134 pts. peak troponin I level greater than the lower limit of detectability (0.04 ng/ml) but less than the 10% coefficient of variation cutoff value for diagnosis of myocardial infarction (0.26 ng/ml).

31 Electrocardiographic detection ECG manifestations of acute myocardial ischemia ( in the absence of LVH and LBBB) European Heart Journal (2007) 28,

ECG changes associated with prior MI Savage RM et al. Circulation 1977;55: 279 285.

32 ECG changes associated with prior MI Savage RM et al. Circulation 1977;55: Horan LG et al. Significance of the diagnostic Q wave of myocardial infarction. Circulation 1971;43:

33 Common ECG pitfalls in diagnosing MI European Heart Journal (2007) 28,

34 Reinfarction ST elevation 0.1 mv reoccurs in a patient having a lesser degree of ST elevation or new pathognomonic Q waves, in at least two contiguous leads, particularly when associated with ischemic Sx for 20 min or longer. The re-elevation of the ST segment can, however, also be seen in threatening myocardial rupture and should lead to additional diagnostic work-up. ST depression or LBBB on their own should not be considered valid criteria for MI. European Heart Journal (2007) 28,

35 Imaging techniques echocardiography, radionuclide ventriculography, myocardial perfusion scintigraphy (MPS), magnetic resonance imaging (MRI), Positron emission tomography (PET) and X-ray computed tomography (CT)

36 Echocardiography Assessment of many nonischemic causes of acute chest pain such as peri-myocarditis, valvular heart disease, cardiomyopathy, pulmonary embolism, or aortic dissection. detect complications of MI : myocardial free wall rupture, acute VSD, and MR secondary to papillary muscle rupture or ischemia. cannot distinguish RWMA due to myocardial ischaemia from infarction.

37 Radionuclide assessment of perfusion A NL echocardiogram or resting ECG-gated scintigram : 95 98% negative predictive value for excluding AMI imaging techniques are useful for early triage and discharge of patients with suspected MI. positive predictive value of imaging techniques is not high : old infarction, acute ischaemia, stunning, or hibernation. Non-ischaemic conditions ( CMP, inflammatory, infiltrative dis.) Buda AJ. The role of echocardiography in the evaluation of mechanical complications of acute myocardial infarction. Circulation 1991;84(Suppl I): I-109 I-121.

38 Cardiac CT Can differential diagnosis Triple A for Acute chest pain at once 1. Acute coronary syndrome 2. Acute aortic syndrome 3. Acute pulmonary embolism

39 Myocardial infarction associated with revascularization procedures-1 Peri-procedural MI : associated with the instrumentation of the heart that is required during mechanical revascularization procedures by either PCI or CABG. During PCI : side-branch occlusion, disruption of collateral flow, distal embolization, coronary dissection, slow flow or no-reflow phenomenon, and microvascular plugging extensive inflammation of non-infarcted myocardium surrounding small islets of myocardium necrosis. During CABG, numerous additional factors can lead to peri-procedural necrosis.

40 Diagnostic criteria for myocardial infarction with PCI The occurrence of procedure-related cell necrosis can be detected by measurement of cardiac biomarkers before or immediately after the procedure, and again at 6 12 and h. increases > 3 times the 99th percentile URL as PCI-related myocardial infarction (type 4a). A separate subcategory of myocardial infarction (type 4b) is related to stent thrombosis as documented by angiography and/or autopsy Gustavsson CG et a. Troponin must be measured before and after PCI to diagnose procedure-related myocardial injury. Scand Cardiovasc J 2004;38:75 79.

41 Diagnostic criteria for myocardial infarction with CABG Any increase of cardiac biomarkers after CABG related to an impaired outcome.-(ck-mb, troponin) biomarkers alone: not diagnosing MI (type 5) biomarker values > 5 times the 99 th percentile of the NL reference range during the first 72 h following CABG Any one of the following criteria Dx of CABG related MI ( type 5 MI) 1. new pathological Q-waves or new LBBB 2. angiographically documented new graft or native coronary artery occlusion 3. imaging evidence of new loss of viable myocardium European Heart Journal (2007) 28,

42 CONCLUSIONS

43 Under these conditions any one of the following criteria meets the Dx for MI Detection of rise/or fall of cardiac biomarkers ( troponin) with at least one value above the 99 th percentile of the URL together with evidence of myocardial ischemia with at least one of the following 1. Sx of ischemia 2. ECG changes indicative of new ischemia (new ST-T change or LBBB) 3. Development of pathological Q waves in the ECG 4. Imaging evidence of new loss of viable myocardium or new RWMA

44 Sudden, unexpected cardiac death, (cardiac arrest), often with Sx suggestive of MI, and accompanied by presumably new ST elevation, or new LBBB, and/or evidence of fresh thrombus by coronary angiography and/or autopsy. For PCI in pts with NL baseline troponin values, increase if biomarkers greater than 3x99 th percentile URL defining PCI-related MI. A subtype related to a documented stent thrombosis is recognized.

45 For CABG in pt with NL baseline troponin values, increases of biomarkers greater than 5x99 th percentile URL plus either new pathological Q waves or new LBBB, or angiographically documented new graft or native coronary artery occlusion, or imaging evidence of new loss of viable myocardium defining CABG-related MI. Pathological findings of an AMI

46 Criteria for prior MI Any one of the following criteria meets the Dx for prior MI: 1. Development of new pathological Q waves with or without Sx 2. Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause. 3. Pathological findings of a healed MI

The Universal Definition of Myocardial Infarction 3 rd revision, 2012

The Universal Definition of Myocardial Infarction 3 rd revision, 2012 Joseph S. Alpert, MD Professor of Medicine, University of Arizona College of Medicine, Tucson, AZ; Editor-in-Chief, American Journal