A. Overview of Complications of Myocardial Infarction (MI)

1. Cardiac Muscle Function Post-MI [1]
   1. Normal myocardium
   2. Post-MI Ischemia
   3. Stunned Myocardium
   4. Hibernating Myocardium
   5. Additional Myocardial Infarction
2. Inadequate Pump Function Post-MI
   1. Systemic Hypoperfusion without hypotension [32]
   2. Cardiogenic Shock [31]
   3. Congestive Heart Failure (hypotension present)
3. Arrhythmias
4. Valve Rupture
5. Wall Aneurysm
6. Wall Rupture
7. Clot Formation
8. Cerebrovascular Accident
9. Mortality (unrelated to sudden death from arrhythmias)
10. Nearly all complications occur during hospitalization or shortly thereafter
11. Women, particularly younger women, appear to have higher risks in peri-MI period and higher acute and longer term mortality than men [2,29,30]

B. Post-MI Ischemia

1. Detection by ECG (ST segment depression) most sensitive, specific non-invasive test
2. ST segment deviation present in the ECG lead showing initial maximal deviation at 90 min after thrombolysis predicts mortality [37]
3. Symptoms also helpful (specific) but not very sensitive
   1. In general, symptoms or signs of ischemia indicates further myocardium at risk
   2. For EF >30% on echocardiogram (localized wall motion abnormality), consider stress test
   3. Coronary angiography should strongly be considered with EF <30-40%
   4. Episodes of ischemia within 48 hours of MI should not be evaluated by exercise tests
   5. In general, patients with recurrent ischemia should undergo cardiac angiography [3,4]
4. Detection of ischemia by ambulatory ECG monitoring
   1. Patients were given 48 hour ambulatory ECG monitoring 5-7 days after MI
   2. Incidence of ischemia by ECG monitoring was 23%
   3. One year mortality in patients with ischemia by ECG was11.6% vs. 3.9% without ischemia
   4. ECG monitoring was better for predicting subsequent events than an exercise stress test
5. Detection of ischemia 1-6 months post-MI does not predict subsequent events
6. Evaluation by nuclear medicine tests in asymptomatic patients post-MI (see below)
7. Treatment with pravastatin post-MI in elderly with normal cholesterol reduced the incidence of recurrent MI, stroke, hospitalization, and death by 30-45% [27]

C. Stunned Myocardium [1]

1. Myocardial muscle dysfunction post-MI frequently leads to CHF
2. The type and extent of myocardial muscle damage determine the severity of CHF
3. Varying degrees of cardiac muscle dysfunction have been observed post-MI [1]
   1. Frank myocardial necrosis - cell death followed by fibrosis
   2. Stunned myocardium
   3. Hibernating myocardium
4. Role of Reperfusion Injury [14]
   1. Re-oxygenation of ischemic tissue leads to production of reactive oxygen species (ROS) and activation of a variety of other deleterious pathways
   2. This is called reperfusion injury and is common after opening occluded coronary arteries
   3. In cardiac cells, reperfusion is mediated through activated mitochondrial PTP membrane protein; protection is mediated through activating kinase family RJSK proteins [6]
   4. Ischemic preconditioning can reduce infarct size in patients undergoing elective PCI
   5. Various pharmacologic approaches to prevent reperfusion injury in development
5. Stunned Myocardium
   1. Reversible muscle dysfunction which persists after restoration of blood flow
   2. Response of cardiac muscle to persistently low ATP production
   3. Hibernation is reduction in myocardial function in response to decreased blood flow
   4. Myocardial stunning and hibernation occur after MI, CABG, and prolonged angioplasties
   5. Revascularization proceedures can restore myocardial function even after months
   6. Nearly 40% of of regions with Q waves after MI may be improved by revascularization
6. Detection of Viable Myocardium Post-MI (see below)
   1. Dobutamine echocardiography - measures contractile reserve
   2. Thallium-201 exercise treadmill test - cell membrane integrity (live versus dead cells)
   3. PET (positron emission tomography) - myocardial perfusion (glucose tracer)
   4. SPECT (single photon emission tomography) - myocardial perfusion
7. Sensitivity and Specificity of Myocardial Function Tests
   1. Given for each test as sensitivity / specificity (in percentages, %) for viable tissue
   2. Dobutamine echo 80% / 80%
   3. Thallium Scan >90% / ~50%
   4. PET and SPECT ~80% / ~60%

D. Congestive Heart Failure (CHF) [16]

1. LV failure occurs more often in LAD based (Anterior) MIs
2. RV failure often occur in inferior MI's [7]
   1. Due to right coronary artery (RCA) lesion in most cases (96%)
   2. Left circumflex lesions may also precipitate RV failure
3. Evaluation of LV Function (Ejection Fraction, EF) Post-MI
   1. All patients should have an evaluation of LV function prior to discharge after MI [3]
   2. An additional LV EF determination should be done 3-6 weeks post-MI
   3. In many patients, stunned myocardium will return to function within 3-4 weeks [1]
4. Prediction of LV EF following first MI
   1. LV EF>40% in following patients:
   2. ECG is interpretable and without previous Q-Wave MI
   3. No history of CHF
   4. Index MI that is not a Q wave anterior infarction
   5. This evaluation should be corroborated with echocardiography or other LV function test
5. Cardiogenic Shock [7,34]
   1. Usually defined as systolic blood pressure (SBP) <90mm/hr for >1 hour
   2. Required that SBP is not responsive to fluids and is due to cardiac dysfunction
   3. Cardiac index <2.2L/min/m2 and pulmonary capillary wedge pressure >18mm Hg
   4. Four causes of shock post-MI: rupture of LV free wall, ventricular septal defect, papillary muscle rupture, cardiogenic shock
   5. Patients with cardiogenic shock often respond to inotropic agents
   6. Free wall rupture is an emergency and presents with tamponade (pericardial effusion)
   7. Papillary muscle rupture usually presents with acute pulmonary edema or right sided congestion, and VSD with acute pulmonary edema
   8. RV infarction often present in cardiogenic shock, associated with high mortality
   9. Cardiogenic shock in the setting of acute MI should be treated with PCI if possible [5]
6. Treatment of LV Dysfunction Post-MI
   1. ACE inhibitor (ACE-I) such as enalapril within 6-48 hours post-MI standard of care
   2. ACE-I are as effective as ß-blockers post-MI in patients with impaired LV function [35]
   3. Angiotensin II receptor blockers (AT2RB) are second line after ACE-I [36]
   4. Eplerenone, a selective aldosterone blocker, 25-50mg po qd, added to standard medical therapy in post-MI patients with LV EF<40% reudces mortality 15% [22]
   5. Carvidilol, a non-specific adrenergic blocker, given 3-21 days after MI in patients with LV EF <40% reduces mortality [8]
   6. Escalating doses of ß1-selective blockers also show benefits on LV function

E. Arrhythmias

1. Most common complication of MI
   1. Serious arrhythmias most commonly occur within 24-36 hours of onset of MI
   2. These are often treatable because patient is hospitalized
   3. Risk for death or stroke from serious arrhythmias very high in first year post-MI
   4. Risk of death overall post-MI is about 10% in first year
   5. Majority of these deaths are believed to be due arrhythmias
2. Risk Factors for post-MI Arrhythmias
   1. Larger size infarction
   2. Pre-existing MI
   3. Reduced LV EF
   4. All patients with serious arrhythmias post-MI should undergo cardiac angiography
   5. Elevated fatty acid levels in myocardium may contribute to VFib in ischemic hearts [13]
3. Reduced LV EF
   1. Most important risk factor for severe ventricular arrhythmias
   2. LV EF <30%, most strongly associated with arrythymias, sudden death [6]
   3. Patients with CAD, LV dysfunction, and inducible VTach have higher risk of arrhythmic and overall death than patients with non-inducible VTach [33]
   4. Patients with LV EF <30% after MI who received an implantible defibrillator (ICD) prophylactically had 30% reduction in death at 20 months [15]
   5. Risk for sudden death post-MI with LV EF <30% is highest within 30 days of MI [6]
   6. Death rate in first month is 1.4% / month and declines to 0.14% / month over 2 years [6]
4. Ventricular Arrhythmias
   1. ß-Blockers should be used prophylactically post-MI to prevent arrhythmias
   2. ß-Blockers prevent post-MI arrhythmias and REDUCE mortality in short and long term
   3. ICD reduce risk of death in many subsets of patients after MI [15,20]
   4. ICD prolong life 20% more than amiodarone after MI but are more costly [9]
   5. Type IA agents clearly decrease the arrhythmias with definite INCREASE in mortality
   6. Amiodarone reduces mortality 10-20% post-MI [9,26]
   7. Amiodarone reduced arrhythmia related [10] and all-cause mortality [26]
   8. Amiodarone use is supported post-MI with low EF and serious arrythmias [10,11]
   9. ICD are generally more effective and better tolerated, more costly than amiodarone
   10. D-sotolol increased mortality in patients with reduced LV EF post-MI [12]
   11. Calcium blocking agents show no benefit post-MI
5. Asymptomatic Ventricular Arrhythmias
   1. Data from patients in GISSI-2 MI trialsuggest arrhythmias are a marker for injury
   2. Two-fold increase in incidence of death within 5 years if arrhythmias present
   3. >10 PVC/hour or complex ventricular arrhythmias 1.5-2X risk for death within 6 months
   4. Significant reduction with ß-blockers
   5. Patients with low EF post-MI do not need routine arrhythmia specialist evaluation
   6. However, patients with significant arrhythmias post-MI should see a specialist
   7. Patients with LV EF <30% post-MI may benefit from prophylactic ICD implantation [15]
6. VTach, Ventricular Fibrillation (VFib) and Sudden Death
   1. Sudden cardiac death is most common cause of death post-MI
   2. More likely in larger infarctions within first 6-24 hours
   3. Other risks include younger age, higher pre-MI PVC frequency, continued ischemia
   4. These arrhythmias are significant and should be suppressed medically
   5. First, correct all electrolyte abnormalities (particularly potassium; maintain >4.5mM)
   6. Intravenous lidocaine or amiodarone are usual anti-arrhythmics
   7. Lidocaine/mexilitine should be avoided long term due to efficacy and safety issues
   8. High dose amiodarone may prolong survival in post-MI setting of arrythmias
   9. Over 1.8 years post-MI, amiodarone reduced death or VFib by over 40% in patients with with >10 VPDs per hour or VTach [11]
   10. In post-MI patients who survive sudden death, ICD device prolongs survival
   11. In post-MI patients with significant arrhythmias, ICD device prolongs survival
   12. ICD has been superior to amiodarone in multiple trials [9]
   13. Prophylactic ICD reduces mortality after MI in patients with LV EF <30% [15]
7. Bradycardia Usually Occurs Inferior MIs
   1. RCA usually feeds inferior heart wall and AV node
   2. RCA occlusion leads to blood supply disruption to AV node
   3. Result can be AV block (1° or 2° type 1); may be asymptomatic
   4. Higher degree block (2° type 2 or 3°) may respond to atropine or require pacing
   5. High degree block shown to be atropine resistant but responds to aminophylline [17]
   6. Suggests that high adenosine concentrations play a role in post-inferior MI bradycardia
8. Bundle Branch Blocks (BBB) [28]
   1. New BBB (Left or Right) or RBBB and Left anterior hemiblock may accompany acute MI
   2. Overall, ~13% of patients develop a new BBB, and prevalence of LBBB ~ RBBB
   3. Blocks which occur with inferior MIs typically resolve
   4. Blocks which occur with with anterior MIs may require permanent pacemaker
   5. Development of a new BBB is associated with increased risk for in-hospital death
   6. New LBBB had 34% increased risk, new RBBB had 64% increased risk for death in-hospital

F. Valve Rupture

1. Usually due to rupture of chordae tendinea
2. Acute Mitral Regurgitation: Pulmonary Edema and Cardiogenic shock
3. Acute Tricuspid Regurgitation: Peripheral Edema and decreased Cardiac Output
4. Patients with acute valve rupture usually require emergency surgery

G. Wall Aneurysm

1. Prolonged ST elevations without angina may signify aneurysm formation
2. Majority of these aneurysms are pseudoaneurysms [25]
   1. Consists of ruptured myocardium contained by pericardial adhesions or epicardium
   2. Due to death of myocardium without complete rupture
   3. Outpouching on echocardiography or other visualizing method
   4. Other causes include CABG, chest trauma and endocarditis
3. Wall aneuryms formation is most common with anterior MIs versus other types of MIs
4. Potential for clot formation on damaged cardiac wall surface
   1. Embolization may follow as clots form on wall and are released
   2. Embolization is most common following large, usually anterior MI [18]
5. Potential for wall rupture exists - particularly 3-5 days post MI
6. Echocardiography
   1. Usually recommended after large MIs to rule out aneurysm and clot
   2. Myocardial muscle stunning post-MI leads to wall-motion abnormalities
   3. This muscle is often still viable, and will return to function over weeks
   4. Therefore, measured ejection fraction (EF) shortly after MI is not prognostic [1]
   5. In general, ~30 days should elapse prior to measuring EF after MI

H. Wall Rupture [23]

1. Ventricular Septal Rupture
   1. Incidence greatly reduced with modern reperfusion strategies
   2. Incidence ~0.2% of MIs
   3. Risk factors include anterior MI, increased age, possibly female sex
   4. Results in right to left shunt and increased pulmonary blood flow
   5. Chest pain, shortness of breath, hypotension
   6. Harsh holosystolic murmur, S3, pulmonary edema
2. Free Wall Rupture
   1. May lead to cardiac tamponade and electromechanical dissociation [24]
   2. Incidence ~3% overall, not reduced with thrombolysis (angioplasty may reduce)
   3. Incidence increased with larger infarct size and usually occurs 3-5 days post-MI
   4. Anigna, pleuritic pain, syncope, hyptotension, arrhythmia, nausea
   5. Cardiogenic shock not uncommon
3. Medical Therapy
   1. Mechanical support with intra-aortic balloon pump usually required
   2. Afterload reduction
   3. Diuretics
   4. Inotropic agents are usually required
   5. Mechanical ventilation often required
4. Early surgical repair is strongly advised, regardless of clinical status
   1. In-hospital mortality rate ~45% for surgically treated patients
   2. 90% in-hospital mortality for medically treated patients
   3. Cardiogenic shock is particularly poor prognosis
5. ß-blockers given peri-MI appear to reduce risk of wall rupture substantially

I. Clot Formation

1. Stroke is the most common and major event following clots [19]
   1. Reduced ejection fraction (EF) is the key risk factor
   2. For every 5% reduction in EF, there is an 18% increase in stroke risk [19]
   3. Older age is a risk for cerebrovascular events also
2. Other peripheral embolic events (eg. renal)
3. Right Heart clots leading to pulmonary emboli
4. Risk Factors for Clot Development
   1. Anterior MI, especially when aneurysmal dilation occurs
   2. Absence of use of aspirin or anti-coagulation
   3. Atrial Fibrillation
   4. Dyskinetic and akinetic wall motion
5. Anti-coagulation is effective in reducing clot formation and preventing complications
6. Anti-platelet agents (such ASA) have shown no benefit in this regard
7. Recommend anti-coagulation (see below) in all anterior MI's, aneurysm, EF < ~20%

J. Stroke [38]

1. Stroke risk within 30 days of incident MI ~44X higher than general population
2. Stroke risk 2-3 years after initial MI 2-3X higher than non-MI population
3. 95% of increased stroke risk after MI was thromboembolic
4. Large anterior wall MI associated with increased risk of thromboembolic stroke
5. Increased risk of hemorrhagic stroke associated with thrombolysis with BP >175 [21]

K. Anti-Clotting Agents Post-MI

1. Warfarin (Coumadin®)
   1. Oral anti-coagulant shown to decrease risk of death post-MI in controlled studies
   2. Strongly consider in Anterior MI, Aneurysm, AFib, ASA allergy, failed ASA, Diabetes
   3. Maintain INR 2-3X
   4. Optimal Dosing is not clear; may be added to low dose aspirin
2. Aspirin (ASA)
   1. Shown to decrease the rate of complications post-MI and to decrease rate of primary and secondary myocardial infarctions
   2. Effectiveness is believed to be due to platelet effects.
   3. Early in course, aspirin is as effective as warfarin, with slightly fewer side effects
   4. No benefit in preventing clot formation post-MI
   5. Optimal dosing not clear
3. Pentoxifylline (Trental®)
   1. May decrease blood viscosity
   2. Originally approved for reduction in intermittent claudication (symptoms)
   3. Reasonable choice in patients with peripheral arterial disease (PAD)
   4. May help in patients with HTN, age >50 years, diabetes, high cholesterol
   5. No absolutely clear benefit post-MI or in PAD
4. Dipyridamole (Persantine®)
   1. Reduces platelet aggregation
   2. Dilates coronary arteries through adenosine effect
   3. May be useful in intermittent claudication, post-CABG, angioplasty
   4. Reduces risk of recurrent stroke when used with ASA
   5. Little benefit has in fact been demonstrated

L. Myocardial Viability and Perfusion

1. An assessment of added myocardium at risk is indicated 3-6 weeks post-MI (see above)
2. Types of Tests
   1. Exercise-thallium tests are preferred to evaluate ischemic versus infarcted tissue
   2. Dobutamine Echocardiography can be used to evaluate myocardial reserve function
   3. PET and SPECT imaging are good for evaluating myocardial perfusion
3. Thallium 201 Stress test
   1. Localizes with similar distribution as potassium
   2. Not taken up by dead myocardium
   3. Can be used to localize infarction very precisely, that is, "cold" area or no uptake
   4. Stress: coronary vasodilation, either by exercise or chemical vasodilation
   5. Exercise induced stress is a functional test with higher sensitivity / specificity than pharmacologically-based stres tests (such as adenosine), which evaluate structure only
4. Technetium (99mTc)-MIBI Scan
   1. More radiation, faster excretion than thallium
   2. Net dose of radiation exposure less with technitium
   3. Strictly a perfusion agent, no uptake into cells
   4. Higher quality scans obtained more rapidly than thallium
   5. Technetium-MIBI is very sensitive to perfusion defects
   6. Technetium-MIBI does not distinguish well between ischemic and infarcted myocardium
5. Radionucleotide-Ventriculogram (RVG)
   1. Most reliable method for calculation of ejection fraction
   2. Also demonstrates wall motion abnormalities well
6. Indications for catheterization post-MI
   1. Exercise Treadmill Test - positive
   2. Pain and/or shortness of breath with low workload
   3. At least 2mm ST depression and/or reperfusion abnormalities on nuclear medicine scan
   4. Cardiogenic shock [5]
   5. Catheterization for high risk patients who are candidates for PTCA or cardiac surgery

M. Bypass Graft Surgery (CABG)

1. Decreases incidence of fatal, but not non-fatal, MI
2. CABG is a palliative procedure with the following indications:
   1. Left Main Disease >50% occlusion
   2. Triple Vessel Disease (even with <50% stenosis); especially in low EF states
   3. Two vessel disease including proximal LAD
   4. Single vessel disease with failed or impossible PTCA with symptoms (relieves angina)
3. Increases survival in patients with L main stenosis, 3 VD, and some patients with 2 VD
4. Increases survival in patients with impaired LV function and in LV aneurysm
5. Not indicated for stable single vessel disease

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