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Acute Myocardial Infarction

Peter B. Berger, M.D. Duke University School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best Evidence

Definition/Key Clinical Features

• Sudden injury to the myocardium resulting from decreased coronary perfusion
• Heaviness, pressure, squeezing, or tightness in the chest for > 30 min
• Discomfort radiates to arms, neck, or jaw
• Diaphoresis, nausea, emesis
• Dyspnea
• Dizziness
• Arrhythmia, cardiac arrest
• Almost always caused by thrombotic occlusion
• Most elderly patients present with shortness of breath, and many present with dizziness or symptoms of arrhythmia
• In one fourth of patients, symptoms are mild or absent

• Esophagitis
• Pulmonary embolism
• Aortic dissection
• Spontaneous pneumothorax
• Pericarditis
• Cholecystitis

Clinical Definition of MI - Myocardial Infarction  (American College of Cardiology)

• Acute, evolving, or recent MI
  • Biochemical markers of myocardial necrosis (i.e., typical rise and gradual fall of troponin or more rapid rise and fall of creatine kinase-myocardial band [CK-MB]) with at least one of the following:
    • Ischemic symptoms
    • Development of pathologic Q waves on the ECG
    • ECG changes indicative of ischemia (i.e., ST segment elevation or depression)
    • Coronary artery intervention (e.g., primary coronary angioplasty)
  • Pathologic findings of an acute MI
• Established MI
  • Development of new pathologic Q waves on serial ECGs; patient may or may not remember previous symptoms; biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed
  • Pathologic findings of a healed or healing MI

Physical Exam

• History and physical exam are useful for excluding other causes of chest pain rather than confirming MI
• Vital signs often normal, but sinus tachycardia may be present
• Patient may be anxious and distressed
• Hypertension or hypotension may be present
• Pulse may be rapid or slow
• Lung exam is typically normal
• Cardiac exam may reveal dyskinetic apical pulsation, third or fourth heart sound, murmur of ischemic mitral regurgitation, abnormal splitting of second heart sound

ECG

• Elevated ST segment indicates > 90% likelihood of MI and high risk of mortality

Laboratory

• CK-MB assays: lack specificity, because CK and CK-MB levels require ≥ 3 hr of profound ischemia to rise
• Myoglobin level: rises more rapidly than CK but also lacks specificity
• Troponin level: cardiac-specific; elevated level predicts subsequent cardiac events

Imaging

• Echocardiography: treatment should not be delayed for echocardiography when symptoms and ECG indicate acute MI; may be useful in patients with left bundle branch block or abnormal ECGs without ST segment elevation whose symptoms are atypical and in whom the diagnosis is uncertain
• Radionuclide imaging: sensitive and specific for MI

Predischarge Exercise Testing

• Generally recommended before discharge from the hospital to assess functional capacity and ability to return to activities of daily living and work
• Contraindications: spontaneous postinfarction angina, congestive heart failure, hypotension, malignant ventricular arrhythmia; perform coronary angiography instead

Coronary Angiography

• Patients who have received thrombolytic therapy: recommended only for those with hemodynamic instability or those with spontaneous or exercise-induced ischemia following uncomplicated MI
• Patients who have not received thrombolytic therapy: may be helpful for those with hemodynamic compromise, postinfarction chest pain, or possible multivessel disease or reduced ventricular function

Best Therapy     

Emergent Therapy   (Remember  MONA = Morphine/analgesis, Oxygen, Nitroglycerin, Aspirin/antiplatelets/antithrombus Rx)

• Evaluate symptomatic patients < 10 min after arrival in ER
• Avoid delay in treatment
• Assess heart rate and BP
• Perform 12-lead ECG
• Administer oxygen for the first several hours after admission
• Administer analgesia immediately (as Morphine IV)
• Administer aspirin as soon as MI is diagnosed, and continue indefinitely
• Administer sublingual nitroglycerin if BP > 90 mm Hg
• Admit to hospital with continuous ECG monitoring
• Admit high-risk patients to CCU

Reperfusion Therapy

• Best therapy achieves coronary patency most rapidly, depending on the capabilities of the institution

Thrombolytic Therapy

• Should be administered < 60 min after presentation, < 30 min if possible
• Indications
  • ST segment elevation in = or > 2 leads and < 12 hr of chest pain
  • Classic symptoms of infarction and a bundle branch block that precludes detection of ST segment elevation
  • 6-12 hr of chest pain on presentation
• Contraindications
  • Significant bleeding
  • Risk of intracerebral bleeding (e.g., advanced age, low body weight, hypertension, warfarin use, previous stroke, GI bleeding, recent surgery)
• Thrombolytic agents
  • Front-loaded, weight-adjusted t-PA & I.V. heparin: moderately superior to other thrombolytic regimens but much more expensive; associated with a greater frequency of intracerebral hemorrhage than streptokinase
  • Streptokinase & I.V. heparin: contraindicated in patients who have recently received a dose of streptokinase
  • Streptokinase and subcutaneous heparin
  • Combination of I.V. t-PA and streptokinase given concurrently with I.V. heparin
  • Reteplase (recombinant t-PA): given as two boluses, together with aspirin and I.V. heparin; as effective as t-PA
  • Combination therapy: a thrombolytic agent plus a glycoprotein IIb/IIIa inhibitor; not currently indicated

Thrombolytic & anticoagulant Rx   (Not part of ACP Medicine  Best Dx/Best Rx 2006 ) IV Streptokinase (Streptase) Rx 1.5 million u IV over 1 hr. PROTOCOL FOR IV STREPTOKINASE INFUSION: -Stat 1/2 tab aspirin (160 mg) to be chewed. -Insert 18 gauge heparin lock for blood sampling & 20 gauge heparin lock for drug administration. -Draw (before heparin flush) PTT, CPK, CPK MB, AST, LDH, CBC, BUN, lytes, glucose, & type & hold 2 units of whole blood for 48 hrs. -Prepare 1.5 million U of streptokinase in 50 cc NS, & infuse over 1 hr (at 50 cc/hr). -BP q10 min while streptokinase running. -Notify M.D. if systolic BP falls by >20 mmHg. -Stat EKG upon completion of streptokinase infusion. -Start heparin 12,500 units subc q12h for at least 24h. -CPK q4h for 24 hr, then daily for 2 more days. -*** Consider hydrocortisone 100 mg IV before & q 8 12 hr during streptokinase Rx may minimize allergic reactions.  OR tPA Rx 15 mg IV bolus, then 50 mg (0.75mg/kg) over 30 min, then 35mg (0.50mg/kg) over 60 min.      (Total dose <100mg). PROTOCOL FOR  t PA (tissue plasminogen activator) IV INFUSION -Insert 18 gauge heparin lock for blood sampling & 20 gauge heparin lock for drug administration. -Draw (before heparin flush) the following blood tests: PTT, Protime, fibrinogen, CBC, type & hold 3 units of whole blood -or 48 hr, & CPK, CPK MB, AST, LDH. -Heparin 5000 u IV push. -t PA IV 15 mg IV bolus, then 50 mg (0.75mg/kg) over 30 min, then 35mg (0.50mg/kg) over 60 min. (Total dose <100mg). -Lidocaine 1 mg/kg IVP over 1 min interval, then Lidocaine 1 gm in 250 cc D5W at 1 4 mg/min. -Heparin 1000 u/hr IV drip. -EKG q30 min x4, then at 3, 6, 12 hr post, then daily. -CPK MB q1h x3, then q6h x4, then daily CBC q8h x2d, then daily PTT 4 hr after initiation of heparin IV, q6h x4, then daily. Have pharmacist to adjust dose to obtain PTT 2 2.5x control. Do not initiate warfarin (Coumadin). -Four hr after completion of t PA infusion, obtain: discard initial 5 cc blood) Protime, PTT, fibrinogen, CBC. IV TNKase (Tenecteplase) single IV bolus over 5 seconds; <60 kg give 30 mg; 60-69 kg give 35 mg; 70-79 kg give 40 mg; 80-89 kg 45 mg; >90 kg give 50 mg. IV Anistreplase (Eminase) Rx 30 units IV over 2- 5 min. or                 IV Retavase (Reteplase) 10 U and 10 U double bolus dosing give 30 min apart. (6/1999) CONTRAINDICATION for t PA infusion Rx: CVA & TIA within 12 months. CNS tumor or AV malformation. Intracranial or intrspinal surgery or trauma within 2 months. General surgery, abrasive wounds or fracture < 2 wks, or hip surgery < 3 wks. Recent traumatic CPR resuscitation. GI bleeding < 3 months, liver failure, uremia. Pregnancy. Over 75 y.o. or serious advance illness, such as cancer. Hypertension systolic > 180 or, diastolic > 110 mmHg. SBE, acute pericarditis, high likelihood of left heart thrombus (eg. mitral stenosis with atrial fibrillation). Diabetic hemorrhagic retinopathy or other hemorrhagic opthalmic conditions. Septic thrombophlebitis or occluded AV cannula at seriously infected site. Patients on warfarin (Coumadin). Hemostatic defects as from severe liver or renal disease. OR

Immediate Angioplasty

• Preferred therapy for acute MI at institutions where it can be performed without delay; associated with lower morbidity and mortality than thrombolytic therapy alone
• Alternative treatment strategy for patients with ST segment elevation MI initially assessed at a hospital without on-site cardiac surgery facilities
• Combined use of stents and platelet glycoprotein inhibitors may normalize antegrade blood flow and reduce need for repeat procedures the following year

Coronary Artery Bypass Surgery

• Achieves reperfusion more slowly than thrombolytic therapy and primary coronary angioplasty
• Should be reserved for patients in whom primary coronary angioplasty is precluded or has failed and those with a ventricular septal defect, severe mitral regurgitation, or myocardial rupture

Adjunctive Medical Therapy

• I.V. heparin: recommended for patients with suspected MI who are not treated with thrombolytics; should be discontinued > 24 hr before discharge
• Low-molecular-weight heparin: may be as effective as unfractionated heparin; optimal dose is unknown; avoid in renal failure
• Direct thrombin inhibitors: bivalirudin may reduce incidence of reinfarction but has been associated with increased bleeding events
• Beta blockers: recommended for all patients with acute MI and without contraindications as early as possible, whether or not they receive reperfusion therapy; patients with the largest infarctions benefit the most; continue indefinitely in the absence of contraindications or side effects
• ACE inhibitors: use in all patients with significant ventricular dysfunction (i.e., ejection fraction < 40%) contraindications; begin within the first 48 hr of infarction and increase cautiously to avoid hypotension
• I.V. nitroglycerin: indicated in patients with persistent/recurrent chest pain after reperfusion therapy and those who do not receive reperfusion therapy
• Prophylactic antiarrhythmic therapy: not recommended for patients without malignant ventricular ectopy
• Calcium channel antagonists: indicated in patients with ischemia that persists despite use of aspirin, beta blockers, nitrate therapy, and I.V. heparin
• Magnesium: indicated in patients with MI who have torsade de pointes–type ventricular tachycardia and those with magnesium deficiency

Preventive Therapy

Lipid-Lowering Therapy

• Measure cholesterol < 24 hr after presentation; prescribe HMG-CoA reductase inhibitors for those patients with LDL level >130 mg/dl
• Exercise
• Weight reduction in overweight patients
• Avoidance of dietary saturated fat and cholesterol
• Smoking cessation

Aspirin

• Dose: 81-162 mg

Holter Monitoring

• When used before discharge, can help identify patients at increased risk for sudden cardiac death
• Routine antiarrhythmic therapy not recommended

Risk-Factor Modification

• Treatment of hypertension and hypercholesterolemia
• Smoking cessation
• Cardiac rehabilitation
• Exercise program

Best Evidence     

Berger PB, et al: Circulation 100:14, 1999 [PMID 10393675]

Braunwald E, et al: J Am Coll Cardiol 40:1366, 2002 [PMID 12383588]

Keeley EC, et al: Lancet 361:13, 2003 [PMID 12517460]

Myocardial infarction redefined: J Am Coll Cardiol 36:959, 2000 [PMID 10987628]

Rana JS, et al: Am Heart J 147:841, 2004 [PMID 15131540]

March 2006

2004 Update: ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction:  
Executive Summary and Recommendations