A. Overview of MI Diagnosis [1,2,31]
[Figure] "Evaluation of Angina"

1. Clinical Suspicion
   1. Symptoms - typical and atypical chest pain
   2. Medical History - especially history of MI, smoking, hypertension, high cholesterol
   3. Chest pain radiating down BOTH arms has likelihood ratio of ~7 for new MI
   4. About 1/3 of patients with MI present without chest pain [3]
   5. Women, diabetics, and elderly all more likely to present without chest pain [3]
   6. Overall, 26% of MIs in men and 34% in women are unrecognized (based on ECG) [4]
   7. All patients with possible MI should undergo "rule-out" evaluation (see below)
   8. Increasing numbers of patients have atypical presentations
   9. Risk factor assessment should play major role in triage decisions
   10. Relief of chest pain after nitroglycerin does not distinguish coronary from other causes [32]
2. ECG Changes [2,5]
   1. ECG should be performed in anyone with even mild suspicion of cardiac ischemia
   2. This is critically important given high incidence of MI without chest pain (~33%) [3]
   3. Over 80% of patients with MI have ECG changes consistent with ischemia
   4. ECG should be done during medical history, and must not be delayed
   5. Baseline ECG (that is, pre-symptomatic) is very useful in evaluation
   6. Apparent increasing number of asymptomatic MIs should increase ECG screening [4]
   7. New left bundle branch block (LBBB) increases likelihood of acute MI
   8. ECG differential of ST elevation is critical in assessment [30]
3. Serum Cardiac Protein Testing [6]
   1. Myeloperoxidase (MPO)
   2. Cardiac Troponin I
   3. Cardiac Troponin T - not affected by renal dysfunction [7]
   4. Creatine Kinase MB isozyme (CK-MB)
   5. Malondialdehyde-modified LDL (released from ruptured plaques; see below)
4. Echocardiography - assess for wall motion abnormalities
5. Myocardial Perfusion Scanning [8]
   1. Technetium-99m sestamibi (Tc99m) SPECT imaging may help rule-out cardiac ischemia
   2. Real-time emergency room assessment of cardiac perfusion
   3. Can reduce unnecessary hospitalizations for "rule-out MI" patients
6. Diagnostic Criteria for MI [9]
   1. Usually requires both ECG changes and rise and fall of cardiac protein levels [5]
   2. Some criteria allow either ECG OR cardiac protein changes with ischemic chest pain
   3. Unstable angina defined by one or more of these criteria without meeting MI definition
   4. Suggest that purely objective criteria be used in most studies
7. Other Modalities
   1. Coronary Angiography - diagnostic and therapeutic
   2. Magnetic resonance imaging (MRI) can be used to evaluate healed MI [3]
   3. NT-proBNP guided care reduced duration of emergency room visits in dyspnea patients [17]
8. TIMI Risk Score can be used to estimate risk of death in ST-elevation MI [10]
   1. Consists of 8 clinical parameters
   2. Age, physical examination, time to reperfusion therapy
   3. 14 total points (increasing points = increasing risk)
9. Simplified Mortality Risk Index [11]
   1. Similar derivation as TIMI risk score but simplified (ST-elevation MI only)
   2. Age, systolic blood pressure, heart rate account for 86% of optimal prognostic markers
   3. Risk Index=(Heart rate x {Age/10}e2)/systolic blood pressure
   4. Risk group 1 (index <12.5) has 30 day mortality 0.8%
   5. Risk group 5 (index >30) has 30 day mortality 17.4%
10. Risk Factors for Unrecognized MI [4]
    1. Increased age
    2. Diabetes mellitus
    3. Previous MI
    4. Hypertension
11. Electated plasma C-reactive proteins within 12-24 hours of symptom onset is an independent risk (3.0X) for mortality or heart failure in acute MI patients [33]

B. Types of ECG Changes [2,5,12]

1. High Likelihood for MI [2,30]
   1. New ST Segment Elevation: 5.0 to 54 fold increased likelihood of MI
   2. New Q Wave: 5-25X increased likelihood
   3. New LBBB
   4. ST elevation associated with 2.25X increased risk of 30 day death
   5. A normal ECG reduces likelihood of MI from ~5X
   6. Presence of new LBBB in patients with ACS symptoms should increase consideration of thrombolysis or PCI [13]
   7. Presence of LBBB pre-MI increases difficulty in clearly diagnosing MI
   8. Clinical impression and cardiac enzymes are most helpful for evaluating MI in patients with chronic LBBB [14]
   9. Overall, however, elevated creatine kinase is associated with poorer outcomes than ECG changes [12]
   10. Differential diagnosis of new ST segment elevation should be considered [30]
2. Q Wave (~75% transmural)
   1. ST elevation (up-sloping): first change, resolves over time
   2. Pathologic Q waves: new waves of duration > 0.04 seconds and >0.1mV (>1mm)
   3. T wave Inversion: in leads where infarction occurs
   4. Transmural infarctions probably require >1 hour of ischemia
   5. Q wave and non-Q wave MI treated with thrombolytics have similar outcomes [15]
3. Non-Q Wave (usually subendocardial)
   1. Subendocardial infarctions usually leads to ST depression and T wave inversion
   2. ~25% of patients with ST depression and elevated CK-MB eventually develop ST elevation MI
   3. T wave inversion, usually anterior (chest) leads and biphasic T waves
   4. Subendocardial infarctions usually require 20-60 minutes of ischemia
4. Chronology of ECG Changes
   1. ECG changes usually occur in ST elevation MI
   2. Within minutes, J point eelevation with tall, "hyperacute" T waves develop
   3. This is followed by ST segment elevation and reciprocal lead ST depression
   4. ST elevation usually with MI
   5. ST elevation implies ischemic injury (unless variant angina)
   6. Q wave develops (necrosis) within 24 hours and ST elevation normalizes if ischemic passed
   7. T wave inversion, blunting or biphasic
   8. Chronic ST depression occurs with angina
5. Thrombolytic Agents
   1. Effective thrombolysis may lead to development of q waves early in course
   2. However, actual transmural damage occurs primarily in therapeutic failures
   3. Most damage is subendocardial only if there is clinical reperfusion
   4. Thus, thrombolysis can alter typical ECG chronology
6. Note that ST Segment Changes may be caused by non-ischemic and non-cardiac events
   1. Pericarditis and Myocarditis
   2. Aortic Dissection
   3. Abdominal Processes - eg. acute pancreatitis, cholecystitis
7. Overall sensitivity of ECG for all MIs is 50-70%
8. Initial ECG and MI Prognosis [12,16]
   1. Most typical ECG changes are associated with increased 30-day mortality (univariate)
   2. Absolute ST deviation (depression + elevation) associated with 1.5-2.5X increased mortality at 30 days
   3. Increased QRS duration for anterior infarct associated with 1.5X increased mortality
   4. ECG prior evidence of infarction had ~2.5X increased mortality risk
   5. Presence of LBBB at baseline makes ECG analysis during MI very difficult [13]
   6. Overall, 8-12% of patients with MI die within 30 days

C. Location of MI by ECG [5]

1. Coronary Anatomy
   [Figure] "Coronary Vessel Anatomy"
   1. Left Main (LMA) bifurcates in 1-2 cm into left anterior descending (LAD) and circumflex
   2. The LAD supplies the left ventricle (LV) anterior wall, the major muscle mass
   3. The circumflex artery (CFX) supplies the posterior LV wall and sometimes inferior wall
   4. The Right Coronary Artery (RCA) supplies mainly the right ventricle (RV)
   5. RV branches supply the LV inferior wall and usually the sinoatrial (SA) and AV nodes
2. Anterior Wall Infarction (LAD 100%)
   1. Direct Changes: Classically in V1-V3 (V5); may include I, aVL, V5 and V6 (lateral areas)
   2. Reciprocal Changes: II, III, aVF (>1.0mm depression in aVF suggests proximal lesion)
   3. New RBBB with Q wave in V1 is specific but insensitive marker of proximal LAD occlusion
3. Inferior Wall (RCA 80%, CFX 20%)
   1. Direct: II, III, aVF
   2. Reciprocal: I, aVL, V leads
   3. Greater ST elevation in III versus II or >1mm leads I, aVL suggests RCA over CFX
   4. CFX involvement manifests as greater ST elevation in II than III
   5. Conduction abnormalities also common with inferior MI (immediately to within days)
   6. AV nodal dysfunction is most common conduction anomaly, including complete AV block
4. Posterior Wall (CFX)
   1. V1 and V2 with tall R wave development and ST depression
   2. The R waves and ST depressions are "reciprocal" for posterior Q waves and ST elevation
   3. Accompanying lateral changes may occur with large Circumflex involvement
   4. Very difficult to evaluate on ECG; changes may not occur
5. RV Infarction (Proximal RCA 100%) [18]
   1. Direct: V1 ST elevation; V4 "negative" R wave
   2. Most sensitive is V4R ST elevation >1mm with upright T wave in that lead
   3. ST elevation often seen in II, III, aVF with elevation greater in III than II
   4. Reciprocal in aVL, I
   5. Strongly suspect in all patients with hypotension with MI, or with inferior MI
   6. Right Sided ECG leads V3-V5 (V3R-V5R) should be used in all patients with inferior MI
   7. RV infarction often present in cardiogenic shock, associated with high mortality
6. Presence of LBBB makes ECG diagnosis and location of MI very insensitive [13]
7. Reperfusion
   1. Resolution of ST segment elevation (and reciprocal changes) simplest indicator
   2. T wave inversion within 4 hours of MI
   3. T wave inversion after 4 hours consistent with normal ECG evoluation of MI, not reperfusion
   4. Accelerated idioventricular rhythm (AIVR) is highly specific for reperfusion
   5. AIVR is a benign rhythm 60-120 bpm initiated by late, coupled ventricular premature beats
   6. Polymorphic VTach or VFib may occur on reperfusion, but usually indicate ongoing ischemia

D. Blood Test Results [19]
[Figure] "Serum Enzymes in Acute MI"

1. Cardiac Troponins [6,28]
   1. All muscle cells contain troponin protein complexes consisting of T, I and C proteins
   2. Cardiac myocytes have their own troponin T and I isozymes
   3. Troponins T and I are released from dead/dying cardiac myocytes early in ischemia
   4. Cardiac troponins may also be released from intermittantly ischemic cells
   5. Baseline (at presentation) Troponin T levels is an accurate predictor of 30-day mortality
   6. Troponin I elevation at 6 hours shows best correlation (>90%) with cardiac events
   7. Elevated troponin T in unstable angina predicts eventual MI
   8. An elevation of Troponin T at presentation is diagnostic of infarction
   9. Increasing baseline levels of Troponin T correlate well with worsening prognosis
   10. Troponin I is more specific for cardiac cells than Troponin T
   11. Troponin T elevation can occur in MI, dermatomyositis, polymyositis, renal disease
   12. Troponin T may be more sensitive than Troponin I
   13. Both Troponins I and T are more sensitive and specific for cardiac damage than CK-MB
   14. Serum or plasma Troponin T <0.01µg/L predicts <1.0% risk of MI within 30 days in patients with acute coronary syndromes [28]
   15. Ongoing low level troponin (T) release occurs in late stage heart failure [20]
   16. Patients with normal CK-MB and elevation of cardiac troponin have "micro-infarction"
2. Myeloperoxidase (MPO) [29]
   1. MPO is an abundant leukocyte enzyme elevated in fissured atherosclerotic plaques [21]
   2. Plasma levels evaluated as predictor of any cardiovascular event in patients with angina
   3. MPO levels at presentation also predicted risk of major cardiac events at 1 and 6 months
   4. Risk ratios in the 2-4X range, even after correction for baseline troponin levels [21]
3. Creatine Kinase (CK) elevation (normal 25-125U/L)
   1. MB isozyme specifically (MM=striated muscle; BB=brain)
   2. Note that normal skeletal muscle has <5% MB form
   3. However, chronic skeletal muscle disease induces >5% CK-MB levels
   4. Peaks 20-24 hours after beginning of MI, increases within 6-12 hrs
   5. Six hour CK MB is elevated in only 35% of patients with cardiac events
   6. CK-MB is less sensitive and less specific for MI than Troponin T or I [6]
4. Other Muscle Proteins
   1. Lactate Dehydrogenase (LDH) - LDH1/LDH2 > 1 implies MI, peaks 2-3 days post event
   2. AST peaks 24-48hrs post-MI
   3. Myoglobin
5. Malondialdehyde-Modified LDL (mdaLDL) [21]
   1. mdaLDL is an aldehyde modification of Lysine residue in apoB moiety in LDL
   2. mdaLDL is released with ischemic injury of endothelium and/or plaque rupture
   3. Plasma levels of mdaLDL are increased in patients with acute coronary syndromes
   4. mdaLDL levels can distinguish between acute MI/unstable angina versus stable angina
   5. mdaLDL may be an extremely useful marker for triaging patients with chest pain
6. Leukocytosis
   1. Occurs in patients in setting of ischemia
   2. Primarily neutrophilia due to stress response
   3. Both epinephrine and cortisol cause neutrophil demargination from vessels
   4. Immature neutrophil forms should not be seen in MI
7. Troponin I or T are superior to other markers for detecting cardiac cell death [6]
8. MPO may be the most sensitive test for cardiac specific ischemia and MI risk [29]
9. Renal insufficiency is an independent risk for death in elderly patients with MI [22,23]
10. Hyponatremia on admission or shortly thereafter is a ~2X risk for 30-day mortality in ST-elevation MI [34]

E. Echocardiography

1. Wall motion abnormalities (WMA) evaluated
2. For interpretation, baseline echocardiogram should be available
   1. Comparison of new WMA to old echo
   2. Useful for posterior wall (Circumflex disease) abnormalities (often not seen on ECG)
3. Dobutamine echocardiography not used in setting of acute ischemia / infarction
4. However, dobutamine echocardiography may be useful for evaluating stable angina
5. Early evaluation of ventricular function after MI [24]
   1. Echocardiography is the test of choice
   2. However, significant myocardial stunning occurs after MI
   3. Stunned myocardium remains viable, and typically recovers

F. Other Cardiac Imaging

1. Single-photon emission computed tomography (SPECT) is a functional test (dual isotope)
2. Contrast-enhanced magnetic resonance imaging (CMR) is indirect functional test [27]
3. CMR may detect smaller subendocardial MI's than SPECT [25]

G. MI Rule Out Protocols [26]

1. Any patient with possible MI reporting to physician or emergency department
2. Medical history, physical, and careful lab evaluations are key elements here
3. Patients presenting with possible MI should have 12-24 hour rule out evaluation
4. Nearly all patients with moderate or high risk symptoms should be hospitalized
5. Major issue is differentiating MI from unstable angina (12-24 hours observation)
6. MI rule out observation includes frequent ECGs, cardiac enzyme analyses
   1. ECG may be done at 0,6 and 12 hours or at 0 and 24 hours
   2. Continuous cardiac rhythm monitoring is required
   3. CK-MB requires 12-24 hours for definitive evaluation
   4. Troponins I and T require 6 or fewer hours for definitive evaluation [6]
   5. Therefore, Troponins should be used for triage decisions in all at risk patients [6]
7. All patients in rule out MI protocols should receive aspirin and oxygen
8. Nitrates should generally not be given unless cardiac symptoms or ECG changes occur

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