Chapter 24. Myocardial Revascularization after Acute Myocardial Infarction

The ability of surgical interventions to minimize myocardial loss after myocardial infarction has advanced dramatically over the past two decades. Acute myocardial infarction still afflicts approximately 1.5 million individuals each year in the United States,1 and 30% of these patients die before reaching the hospital, whereas 5% die during hospital admission.1 Prompt medical attention, including transport to the hospital, diagnosis, and treatment of the myocardial infarction, is critical to patient survival. Since 1989, the death rate from acute myocardial infarctions has declined 24%, while the actual number of deaths declined only 7%.2 Over the last 40 years, especially during the 1980s, new pharmacologic agents, interventional cardiology procedures, and coronary artery bypass surgical techniques have advanced and have led to a decrease in the overall morbidity and mortality associated with acute myocardial infarction. Despite this overall improvement, mechanical and electrical complications such as cardiogenic shock, rupture of the ventricular septum or free wall, acute mitral regurgitation, pericarditis, tamponade, and arrhythmias challenge the medical community caring for patients presenting with acute myocardial infarction on a daily basis.3 Of these complications, cardiogenic shock complicating acute myocardial infarctions has the most significant impact on in-hospital mortality and long-term survival. The loss of more than 40% of functioning left ventricular mass and its accompanying systemic inflammatory response are major causes of cardiogenic shock and are determined by the degree of preinfarction ventricular dysfunction, the size of the infarcted vessel, and pathologic level of inflammatory mediators.4,5 Restoration of blood flow to the threatened myocardium offers the best chance of survival following acute coronary occlusion, but the means and timing of revascularization continue to be a highly debated and studied topic. Thrombolytics, percutaneous transluminal coronary angioplasty (PTCA), intracoronary stenting, and coronary artery bypass (CABG) surgery have decreased the mortality associated with acute myocardial infarctions. Advances in myocardial preservation and mechanical support lead the surgical armamentarium in the treatment of acute myocardial infarctions.

Myocardial ischemia resulting from coronary occlusion for as little as 60 seconds causes ischemic zone changes from a state of active systolic shortening to one of passive systolic lengthening.6 Occlusions for less than 20 minutes usually cause reversible cellular damage and depressed function with subsequent myocardial stunning. Furthermore, reperfusion of the infarct leads to variable amounts of salvageable myocardium. After 40 minutes of ischemia followed by reperfusion, 60 to 70% of the ultimate infarct is salvageable, but this decreases dramatically to 10% after 3 hours of ischemia.7,8 Animal model evidence has also demonstrated that 6 hours of regional ischemia produces extensive transmural necrosis.9 The exact timing in humans is even more difficult to analyze because of collateral flow, which is a major determinant of myocardial necrosis in the area at risk in humans.8 The collateral blood supply is extremely variable, especially in patients with long-standing coronary disease. However, collateral flow is jeopardized with arrhythmias, hypotension, or the rise of left ventricular end-diastolic pressure above tissue capillary pressure.7 Thus loss of collateral flow to the infarct area may lead to the cellular death of salvageable myocardium. Control of blood pressure and prevention of arrhythmias are vital during this immediate time after infarction.

Table 24-1 outlines the effects of anatomic, physiologic, and therapeutic variables on the evolution of final infarct size.

Definition

Cardiogenic shock is defined clinically as a systolic blood pressure below 80 mm Hg in the absence of hypovolemia, peripheral vasoconstriction with cold extremities, changes in mental status, and urine output of less than 20 mL/h. Hemodynamic parameters for cardiogenic shock include cardiac index less than 1.8 L/min/m2, stroke volume index less than 20 mL/m2, mean pulmonary capillary wedge pressure greater than 18 mm Hg, tachycardia, and a systemic vascular resistance of over 2400 dyn·sec/cm5. These patients are defined as type IV by the Killip classification, a widely used system to classify myocardial infarctions.10

Prevalence

Shock is the most common cause of in-hospital mortality after myocardial infarction.11 The in-hospital mortality associated with cardiogenic shock has remained unchanged at approximately 80% despite the development of new treatment modalities.12 Cardiogenic shock occurs in 2.4 to 12.0% of patients with acute myocardial infarction.13 Since 1975, the incidence of cardiogenic shock complicating acute myocardial infarctions has remained constant at 7.5%, ranging between 5 and 15% (Fig. 24-1).11 The progressive reduction in time delay from symptom onset to treatment may account for these constant figures. Previously, patients with excessive time delays would have died before reaching the hospital or soon thereafter, as it is known that treatment delays increase 1-year mortality exponentially (Fig. 24-2).14

Pathophysiology and Infarct Size

Shock is directly related to the extent of the myocardium involved, and infarctions resulting in loss of at least 40% of the left ventricle have been found on autopsy in patients with cardiogenic shock.4,15 Autopsy findings also revealed marginal extension of the recent infarct and focal areas of necrosis in patients with cardiogenic shock.4 Extensive three-vessel disease is usually found in individuals with cardiogenic shock, and extension of the infarct is an important determinant in those individuals.4,15 Limiting the size of the infarct and its extension is one of the key therapeutic interventions in patients with myocardial infarction.

The management of patients with acute myocardial infarctions demands expeditious treatment and decision making. With the ultimate goal of reperfusing the ischemic myocardium, treatment strategies should be directed toward reducing myocardial oxygen demand, maintaining circulatory support, and protecting the threatened myocardium before irreversible damage and expansion of the infarct occur.

Clinical assessment and risk stratification begins at triage during presentation, where electrocardiographic changes and cardiac biomarkers are used to identify patients suitable for revascularization versus medical management. At our center, clinical algorithms have been instituted to rapidly aid decision making.16 Patients presenting with ongoing chest pain for more than 20 minutes and ST-segment elevation in two contiguous leads or new (or not known to be old) left bundle branch block or anterolateral ST depression are classified as having ST-segment Elevation Myocardial Infarction (STEMI). These patients are referred for primary percutaneous intervention in the cardiac catheterization suite 24 hours a day, 7 days a week, if no contraindications exist. The other group of patients, those with non–ST segment Elevation Myocardial Infarction (NSTEMI), present with chest pain at rest for 10 minutes or more and ST-segment depression greater than 0.5 mm or ST-segment elevation 0.6 to 1 mm or T-Wave inversions greater than 1 mm or positive troponin levels or a history of unstable angina in a patient with coronary artery disease risk factors. These patients are treated medically with a combination of antiplatelet therapy, intravenous heparin, and other traditional medications discussed in the following.

Both clinical and basic science research have demonstrated that reperfusion is the main treatment option for acute myocardial infarction. Unfortunately, the majority of patients with myocardial infarction receive only conservative medical management; only 40% of patients having an acute myocardial infarction receive thrombolytic therapy, the most common means of reperfusion.17

Coronary insufficiency can result in three states of impaired myocardium: infarcted, hibernating, and stunned. Each state requires separate clinical interventions and carries different prognostic implications. Infarcted myocardium is irreversible myocardial cell death owing to prolonged ischemia. Hibernating myocardium is a state of impaired myocardial and left ventricular function at rest resulting from reduced coronary blood flow and impaired coronary vasodilator reserve that can be restored to normal if a normal myocardial oxygen supply–demand relationship is reestablished.18 Hibernating myocardium is defined as contractility-depressed myocardial function secondary to severe chronic ischemia that improves clinically immediately after myocardial revascularization. Stunned myocardium is left ventricular dysfunction without cell death that occurs after restoration of blood flow after an ischemic episode. If a patient survives the insult resulting from a temporary period of ischemia followed by reperfusion, the previously ischemic areas of cardiac muscle eventually demonstrate improved contractility (Table 24-2).

Hibernating Myocardium

Hibernation may be acute or chronic. Carlson and associates31 showed that hibernating myocardium was present in up to 75% of patients with unstable angina and 28% with stable angina. The entity also occurs after myocardial infarction. Angina after myocardial infarction commonly occurs at a distance from the area of infarction.19 In fact, mortality is significantly higher in patients with ischemia at a distance (72%) compared with ischemia adjacent to the infarct zone (33%).19 It is the hibernating myocardium that may be in jeopardy and salvageable, although its presence is usually incidental to the occurrence of the acute infarction. By distinguishing between hibernating myocardium and irreversibly injured myocardium, a more aggressive approach to restoring or improving blood flow to the area at risk is reasonable. Function often improves immediately after revascularization of appropriately selected regions.

Stunned Myocardium

In the 1970s it was observed that after brief episodes of severe ischemia, prolonged dysfunction upon reperfusion with gradual return of contractile activity occurred. In 1982 Braunwald and Kloner20 coined the phrase stunned myocardium. Stunning is a fully reversible process despite the severity and duration of the insult if the cells remain viable. However, myocardial dysfunction, biochemical alterations, and ultrastructural abnormalities continue to persist after return of blood flow. Within 60 seconds of coronary occlusion, the ischemic zone changes from a state of active shortening to one of passive shortening. Coronary occlusion lasting less than 20 minutes is the classic model reproducing the stunning phenomenon.21 The most likely mechanisms of myocardial stunning are listed in Table 24-3.21,22

Stunned myocardium can occur adjacent to necrotic tissue after prolonged coronary occlusion and can be associated with demand-induced ischemia, coronary spasm, and cardioplegia-induced cardiac arrest during cardiopulmonary bypass. Clinically these regions are edematous, and even hemorrhagic, and can lead to both systolic and diastolic dysfunction.23 They also have a propensity for arrhythmias, which can lead to more extensive ventricular stunning and hypotension with subsequent infarction of these regions.

Diagnosis of Viable Myocardium

Mechanisms to identify patients with myocardial stunning and hibernation include ECG findings, radionuclide imaging, positron emission tomography (PET), dobutamine echocardiography, and more recently magnetic resonance imaging (MRI). Thallium identifies perfusion-related defects of the myocardium and can distinguish between viable and scarred myocardium as well. However, early redistribution of thallium does not distinguish between hibernating and scarred myocardium because many segments with irreversible defects by thallium improve after reperfusion. Redistribution imaging and reinjection imaging improve the predictive value of thallium imaging in distinguishing hibernating myocardium.

PET measures the metabolic activity of myocardial cells. It has high positive and negative predictive values. It is now regarded as the best method to determine myocardial viability, particularly in patients with severe left ventricular dysfunction in whom other modalities are less accurate.24

Dobutamine echocardiography identifies hibernating and stunned myocardium by monitoring changes in segmental wall motion while the heart is stressed inotropically and chronotropically by dobutamine infusion. It has high specificity, sensitivity, and, more importantly, positive predictive value.25

MRI has also been established as an effective method to assess hibernating myocardium.26 It has been proved to accurately diagnose the degree of both acute and chronic myocardial infarction and predict functional recovery.27,28 A number of advantages exist with cardiac MRI, such as superior image resolution allowing accurate indentification of transmural infarction (Fig. 24-3). By providing morphologic, functional, and metabolic information, it may ultimately supplant other modalities for the diagnosis of cardiac injury and recovery.

Finally, multislice computed tomography has been used to measure hibernating myocardium, and early data suggest it may be a reliable and sensitive method compared with MRI, although its use in clinical practice is limited.29

Randomized trials have shown beneficial effects of early reperfusion within 12 hours and possibly up to 24 hours after acute myocardial infarction.10,12,30,31 Early reperfusion clearly reduces infarct size in the major areas at risk. Controlled reperfusion may even be superior. The arguments are more difficult to make for patients outside the 24-hour window; however, patients with ongoing ischemia often have ischemic border regions that are prone to arrhythmias and necrosis. In addition, these patients are at risk for prolonged periods of hypotension with resulting end-organ injury and further left ventricular dysfunction. Even if revascularization does not appear critical, ventricular unloading with IABP or LVAD may provide the bridge to recovery needed in patients dying after myocardial infarction. The major limiting factors to aggressive surgical management are major comorbidities, which make continuation of life undesirable or unlikely, and an unclear neurologic status, especially after a period of cardiopulmonary arrest.

Although restoration of blood flow to ischemic regions is essential, the accompanying reperfusion injury initially can worsen rather than improve myocardial dysfunction. The area at risk is affected not only by reperfusion but also by the conditions of reperfusion and the composition of the reperfusate.32 Thus controlling reperfusion itself may aid in reducing myocardial infarct size and ventricular injury.

At the cellular level, myocardial ischemia results in a change in energy production from aerobic to anaerobic metabolism. The consequences of ischemia vary from decreased adenosine triphosphate production and increased intracellular calcium to decreased amino acid precursors such as aspartate and glutamate. These changes can be reversed only by reperfusion.

However, as oxygen is reintroduced into a region, oxygen free radical generation ensues with resulting cellular damage. Cellular swelling and/or contracture leads to a "no-reflow phenomenon" that limits the recovery of some myocytes and possibly adds to irreversible injury of others. The production of oxygen free radicals during ischemia and at the time of reperfusion is the leading mechanism proposed to explain cellular injury. Four basic types of reperfusion injury have been described: lethal cell death, microvascular injury, stunned myocardium, and reperfusion arrhythmias (Table 24-4).

Buckberg and coworkers33–38 conducted studies of controlled reperfusion after ischemia and produced a clinical application for controlled reperfusion. The surgical strategy of controlled reperfusion, especially as espoused by Buckberg and associates, includes several elements. First, extracorporeal circulation is established as expeditiously as possible with venting of the left ventricle as required. Initially, antegrade cardioplegia is delivered using either a warm Buckberg solution to rebuild adenosine triphosphate stores or cold high-potassium cardioplegia to achieve rapid diastolic arrest. We routinely add retrograde cardioplegia to ensure global cooling, even in areas of active ischemia. The temperatures of the anterior and inferior walls of the ventricle are measured to ensure adequate cooling. After each distal anastomosis, cold cardioplegia is infused into each graft and the aorta at 200 mL/min over 1 minute. This is followed by retrograde infusion through the coronary sinus for 1 minute. After completion of the final distal anastomosis, warm substrate-enriched blood cardioplegia is given at 150 mL/min for 2 minutes into each anastomosis and the aorta. After removal of the aortic cross-clamp, regional blood cardioplegia is given at 50 mL/min into the graft supplying the region at risk for 18 minutes. This controlled rate of reperfusion minimizes cellular edema and myocyte damage. The proximal vein grafts are then completed, followed by reestablishment of normal blood flow. To decrease oxygen demand, the heart is allowed to beat in the empty state for 30 minutes. After this time, the patient is weaned off bypass.

Application of the Buckberg solution and technique has been shown to be effective in improving mortality rates and myocardial function after acute coronary occlusion. With ischemic times averaging 6 hours, a prevalence of multivessel disease, and cardiogenic shock, the overall mortality in patients with acute coronary arterial occlusions who underwent surgical revascularization applying this method of reperfusion was 3.9%. Postoperative ejection fractions averaged 50%.39 Surgical revascularization in this series using controlled reperfusion compared favorably with PTCA in several large series. The superior results of this method for the treatment of cardiogenic shock, a 9% mortality, have brought this method to the forefront in the treatment of cardiogenic shock.

Methods of Reperfusion

Role of Thrombolytic Therapy

Because myocardial salvage depends on reperfusion of occluded coronary arteries, rapid dissolution of an occluding thrombus with thrombolytic therapy is an appealing intervention. Intracoronary streptokinase in patients with acute myocardial infarction demonstrates that thrombolytic therapy is a safe and efficient way to achieve the desired early reperfusion.40 Following this study, a number of multi-institutional megatrials showed the effectiveness of thrombolytic therapy in treating acute myocardial infarctions.

The trial of the Italian Group for the Study of Streptokinase in Myocardial Infarction (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardio, [GISSI])41 and the Second International Study of Infarct Survival [ISIS-2])42 found a reduced hospital mortality in patients treated with streptokinase. The effectiveness of tissue-type t-PA also has been evaluated in randomized studies. The Thrombolysis in Myocardial Infarction (TIMI) study43 and the European Cooperative Study Group (ECSG)44 demonstrated the effectiveness of t-PA for the treatment of acute myocardial infarction.

When streptokinase and t-PA were compared, two studies failed to demonstrate any difference in mortality.45,46 A third study, however, the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, supported the use of t-PA by demonstrating a more rapid and complete restoration of coronary flow that resulted in improved ventricular performance and reduced mortality.47,48

Although thrombolysis improves survival and ventricular function, the patency of infarct-related arteries is reported to be between 50 and 85%.41–48 Normal flow should be achieved in 60% of patients by today's standards. Thrombolytic therapy works well but is not without complications, including bleeding and intracranial hemorrhage.49 Bleeding is usually minor and occurs mostly at the sites of vascular puncture. Intracranial hemorrhage and stroke rates are around 1% and are an "acceptable" risk. The relative benefits of thrombolytic therapy appear to decrease as patient age increases, and a higher risk of intracranial hemorrhage in the elderly may partially account for these findings.47,50,51 Careful selection of patients suitable for fibrinolytic therapy is warranted, especially in an increasingly older population.

Cardiogenic Shock

Thrombolytic therapy for patients presenting in cardiogenic shock or heart failure does not appear to improve survival in this population but may decrease the incidence of patients developing heart failure after myocardial infarction.52

Summary

Thrombolytic agents for the treatment of myocardial infarction have demonstrated several important points. Survival is improved by decreasing time to reperfusion. The GUSTO trial showed that patients treated within the first hour had the greatest improvement in survival, with a 1% reduction in mortality for each hour of time saved.47,48 Thrombolytic therapy is easy to administer in the community by trained personnel, although a significant risk of bleeding exists in certain patients. Because the time to reperfusion is a critical element in preserving myocardium, thrombolytic therapy is ideal for most communities without percutaneous interventional capabilities. In this setting, thrombolytics may be used for treatment of patients with acute myocardial infarction.

Role of Percutaneous Transluminal Coronary Angioplasty

Since the first reported use of PTCA by Gruntzig and associates74 in 1979, the efficacy of this procedure in the treatment of coronary artery disease has been well recognized. A number of studies have evaluated the efficacy of primary PTCA in the treatment of acute myocardial infarction. Overall, PTCA hospital mortality rates range from 6 to 9%.53–56

Several different strategies employing PTCA for acute myocardial infarction have been developed and examined through clinical trials. Primary, rescue, immediate, delayed, and elective PTCA are options for the treatment of acute myocardial infarction. Primary PTCA uses angioplasty as the method of reperfusion in patients presenting with acute myocardial infarction. Rescue, immediate, delayed, and elective PTCA all are done in conjunction with or following thrombolytic therapy. Rescue PTCA is done after recurrent angina or hemodynamic instability after thrombolytic therapy. Immediate PTCA is performed in conjunction with thrombolytic therapy, and delayed PTCA occurs during the intervening hospitalization. Finally, elective PTCA is done following thrombolytic therapy and medical management when a positive stress test is obtained during the same hospitalization or soon thereafter.

Primary PTCA functions in several roles for the treatment of acute myocardial infarctions. Because there are some absolute and relative contraindications to thrombolytics, PTCA is the one of best methods of reperfusion in patients with acute myocardial infarction, according to studies that evaluated PTCA as first-line therapy. Several studies evaluated the role of PTCA compared with thrombolytic therapy. The first study, the Primary Angioplasty in Myocardial Infarction Study Group trial in 1993, concluded that immediate PTCA without thrombolytics reduced occurrence of reinfarction and death and was associated with a lower rate of intracranial hemorrhage.53 Since then, more than 20 studies have compared PTCA to thrombolysis. The results from these studies have consistently and conclusively demonstrated the superiority of PTCA to thrombolysis, regardless of the thrombolytic agent used. The findings include a lower short-term mortality rate, lower rates of reinfarction, reduced stroke and intracranial hemorrhage rates, and a decreased composite end point of death, reinfarction, and stroke.57 These findings have been reconfirmed on long-term follow-up. A higher overall rate of bleeding was observed, likely because of vascular access complications. Myocardial salvage is similar for PTCA and thrombolytic therapy. However, primary PTCA may be slightly less costly than thrombolytic therapy.54

There are limits to the use of primary PTCA. Logistic and economic constraints apply to invasive modes of therapy. Catheterization laboratories and personnel must be ready at all times. This is not practical in most communities, and transportation to tertiary care centers raises costs considerably.

Intracoronary Stents

The use of intracoronary stents after myocardial infarction has expanded as PTCA has become more prevalent. Benefits of stenting include lowered rates of restenosis and abrupt closure, and a reduced need for target revascularization after PTCA. Although the STENT-PAMI trial in 1999 using first-generation stents showed lower restenosis rates compared with thrombolysis, a trend toward higher mortality was seen, and its effectiveness as first-line therapy was questioned.58 Composite end points of death, reinfarction, and urgent target vessel revascularization at 30 days have now been shown to be lower in subsequent studies, such as the CADILLAC, ISAR-2, and ADMIRAL trials, which employed newer-generation stents.59–61 In these trials, abciximab, a glycoprotein IIb/IIIa inhibitor, was added to primary stenting. A striking reduction in restenosis rates with stenting plus abciximab versus PTCA alone was evident at 12-month follow-up in the CADILLAC study (41 versus 22%).59 Current data suggest that stenting combined with antiplatelet therapy provides superior benefit to PTCA alone. Drug-eluting stents offer the potential to lower restenosis even further through the use of anti-inflammatory medication delivered via the stent. Most recently, patients in the STRATEGY trial treated with drug-eluting stents after acute ST-elevation myocardial infarction (STEMI) had a significantly lower composite end point of death, reinfarction, stroke, and angiographic evidence of restenosis at 8-month follow-up compared with bare-metal stenting plus abciximab (50 versus 19%).62 Using propensity score matching, retrospective analysis of patients post acute myocardial infarction in Massachusetts has shown a slight 2-year mortality benefit for drug-eluting stents when compared with bare-metal stents (10.7 versus 12.8%), as well as a lower need for repeat revascularization.63 Further prospective studies are under way to determine if long-term data confirm these findings.

Antithrombotic agents continued for 12 to 18 hours after PTCA and stenting are an important adjunctive therapy to prevent further ischemic complications. Traditional agents, such as heparin, have been replaced by glycoprotein IIb/IIIa inhibitors, which may have survival benefit when used after PTCA.64 Newer agents, such as direct thrombin inhibitors, have been introduced with the hope of reducing bleeding and/or heparin-associated complications. The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)65,66 trial investigated bivalirudin, a direct thrombin inhibitor, versus heparin plus a glycoprotein IIb/IIIa inihibitor for use after primary PTCA with or without stenting. Both 30-day and 1-year outcomes revealed decreased hemorrhagic events, and 1-year cardiac mortality was lower in patients treated with bivalirudin, despite a higher 24-hour risk of stent thrombosis in the bivalirudin cohort. Concerns regarding increased thrombogenicity with drug-eluting stents persist; further research is warranted to ensure that late in-stent thrombosis does not preclude use in this setting. Intracoronary stenting with adjunctive antiplatlelet medications has been embraced by the medical community for off-label use after acute myocardial infarction since its recent introduction.

Cardiogenic Shock

Primary PTCA may play a greater role in patients presenting in cardiogenic shock, and percutaneous interventions have become more common over the past 10 years (Fig. 24-4). The GISSI-1 and GISSI-2 trials demonstrated no benefit from intravenous thrombolysis, with mortality rates of 70%.41,45 In patients presenting in or developing cardiogenic shock after acute myocardial infarction, PTCA improved survival to 40 and 60%.67 This improvement was even greater when angioplasty was successful; in-hospital survival rates increased to 70%. In most of these series an IABP was used in conjunction with PTCA. The SHOCK trial showed that revascularization by PTCA or CABG within 12 hours of the onset of cardiogenic shock results in improved 1- and 6-year survival rates versus medical stabilization followed by delayed revascularization (32.8 for PTCA/CABG versus 19.6% for initial medical stablization, 6-year follow-up) in this high-risk group, particularly for those under the age of 75 years (Fig. 24-5).12,30,31 Subgroup analysis in patients undergoing successful PTCA or with TIMI Grade 3 coronary flow after PTCA in the SHOCK trial revealed that 1-year survival was even higher, at 61%.68 Independent predictors of mortality include age, hypotension, lower TIMI flow, and multivessel PTCA.

Summary

Primary PTCA or intracoronary stenting should be performed as first-line therapy in patients with acute myocardial infarction and those with contraindications to thrombolytic therapy. Patients with established or developing cardiogenic shock should be revascularized early by PTCA or stenting rather than initial medical stabilization by thrombolytic therapy. Specialized centers that have 24-hour catheterization facilities can provide primary PTCA or stenting as a first-line therapy. Rescue PTCA after failed thrombolytic therapy for patients with ongoing ischemia or clinical compromise is also recommended. Finally, elective PTCA should be performed on patients who have recurrent or provokable angina before hospital discharge.

Role of Coronary Artery Bypass Grafting

The role of surgical revascularization in the treatment of acute myocardial infarction has changed considerably over the past 30 years. Improvements in intraoperative management and myocardial preservation techniques have strengthened the surgeon's armamentarium. However, the development and use of thrombolytic therapy and PTCA offer effective alternatives to surgery.

During the 1980s, reports appeared recommending surgical revascularization in preference to medical therapy for acute myocardial infarction.69,70 Mortality rates under 5% were reported. Critics argued that these studies lacked randomization or consecutive entry of patients, preoperative stratification was absent, and enzyme levels were not included. Inherent bias that favored surgery in low-risk patients was believed to be the reason for the excellent outcomes.71

At the time these reports surfaced, thrombolytic therapy and interventional cardiology were emerging as alternative options for acute infarction. With the availability of thrombolytics and PTCA, large multicenter trials began looking at the efficacy and usefulness of these two techniques. Randomized trials using CABG were not done, and thus this option was never established as an alternative for acute myocardial infarction.

However, several centers continued to use surgical revascularization to treat acute myocardial infarction. Excellent results were achieved by coordinated community and hospital systems. However, practical, logistic, and economic constraints relegate surgical revascularization to a third option behind thrombolytics and PTCA for the primary treatment of acute myocardial infarction.

There continue to be several scenarios that require emergent or urgent surgical revascularization. Failure of thrombolytics, PTCA, or intracoronary stenting with acute occlusion may require surgical intervention. Additionally, CABG for postinfarction angina has become a critical step in the pathway of treating acute myocardial infarction. Finally, surgical revascularization may be indicated in patients with multivessel disease or left main coronary artery disease developing cardiogenic shock after myocardial infarction.

Timing after Infarction

If surgical revascularization within 6 hours after the onset of symptoms is feasible, the mortality rate is improved over that of medically treated, nonrevascularized patients.69,70 Although these early studies were not controlled and were criticized for selection bias, they did demonstrate that surgical revascularization may be performed with an acceptable mortality in the presence of acute myocardial infarction with improved myocardial protection, anesthesia, and surgical techniques. However, with the advent of thrombolytic therapy, PTCA, and an aging population, the surgical patient we encounter today bears little resemblance to the patient population represented in these early data.

Recent analyses of the New York State Cardiac Surgery Registry, which included every patient undergoing a cardiac operation in the last decade in the state of New York, resulted in valuable information regarding the optimal timing of CABG in acute myocardial infarction. In this large and contemporary patient population, there is a significant correlation between hospital mortality and time interval from acute myocardial infarction to time of operation, particularly if CABG was performed within 1 week of acute myocardial infarction. In addition, patients with transmural and nontransmural acute myocardial infarction have different trends in mortality when the time course is taken into consideration. Mortality for the nontransmural group peaked if the operation was performed within 6 hours of acute myocardial infarction, and then decreased precipitously (Table 24-5).72 On the other hand, mortality for the transmural group remained high during the first 3 days before returning to baseline.73 Multivariate analyses confirmed that CABG within 6 hours for the nontransmural group and 3 days for the transmural group were independently associated with in-hospital mortality.72,73 Optimal timing of CABG in patients with acute myocardial infarction is a controversial subject. Early surgical intervention has the advantage of limiting the infarct expansion and ventricular remodeling that may result in possible ventricular aneurysm and rupture.74 However, there is the theoretical risk of reperfusion injury, which may lead to hemorrhagic infarction resulting in extension of infarct size, poor infarct healing, and scar development.75 The data from these studies caution against early revascularization, particularly among patients with transmural acute myocardial infarction within 3 days of onset. Some have advocated the use of mechanical support to stabilize and allow elective rather than emergent surgery.76,77 Using mechanical support "prophylactically" instead of CABG to improve outcome, however, would require placement of such support in many unnecessary cases. If revascularization cannot be delayed, aggressive mechanical support (such as an LVAD) must be available because mortality is most likely a result of pump failure. Furthermore, mechanical circulatory support has been shown to be efficacious as a bridge to ventricular recovery or transplantation for this patient cohort.77 Although emergent cases such as structural complications and ongoing ischemia clearly cannot be delayed, nonemergent cases, particularly patients with transmural acute myocardial infarction, may benefit from delay of surgery. Early surgery after transmural acute myocardial infarction has a significantly higher risk and surgeons should be prepared to provide aggressive cardiac support including LVADs in this ailing population. Waiting in some cases may be warranted.

Risk Factors

In addition to timing of surgery as discussed in the preceding, risk factors include urgency of the operation, increasing patient age, renal insufficiency, number of previous myocardial infarctions, hypertension,78 reoperation, cardiogenic shock, depressed left ventricular function, and the need for cardiopulmonary resuscitation, left main disease, female gender, left ventricular wall motion score, IABP, and transmural infarction.79 Characteristics associated with better outcome early after myocardial infarction include preservation of left ventricular ejection fraction, male gender, younger patients, and subendocardial versus transmural myocardial infarction.

Cardiogenic Shock

Surgical revascularization in acute myocardial infarction complicated by cardiogenic shock has been shown to improve survival. Cardiogenic shock, as discussed earlier, is accompanied by 80 to 90% mortality rates; various mechanisms of cardiogenic shock are shown in Fig. 24-6. DeWood and colleagues80 were the first to demonstrate improved results with revascularization in patients with cardiogenic shock complicating acute myocardial infarction. Patients who were stabilized with an IABP and underwent emergent surgical revascularization had survival rates of 75%. Early surgical revascularization is associated with survival rates of 40 to 88% in patients in cardiogenic shock resulting from nonmechanical causes. Guyton and coworkers81 reported an 88% in-hospital survival and a 3-year survival of 88%, with no late deaths reported. Furthermore, the SHOCK trial demonstrated survival benefit in early revascularization by CABG or PTCA within 12 hours of the diagnosis of cardiogenic shock for patients of all ages.30,31 Patients comprising the CABG cohort in the SHOCK trial had more severe disease, with higher rates of three-vessel disease, left main coronary artery disease, diabetes, and elevated mean coronary jeopardy scores than the PTCA cohort.82 Despite this, 87.2% of these patients achieved successful and complete revascularization with CABG, compared with successful revascularizaton in 77.2% with PTCA and only 23.1% with complete revascularization with PTCA. Overall, mortality was no different between groups at 1 year (Fig. 24-7). On subgroup analysis, patients older than age 75, with left main coronary disease or three-vessel disease, or with diabetes had trends toward better survival at 30 days and 1 year after CABG compared to PTCA. Thus, for patients in cardiogenic shock, surgical revascularization has become an established and viable option for select patient groups.

Advantages of Coronary Artery Bypass Grafting

Reported survival rates are similar for CABG and PTCA in the treatment of acute myocardial infarction. To date there have been no large randomized clinical trials comparing CABG with PTCA and thrombolytics after myocardial infarction. For patients with stable angina and elective revascularization for ischemic heart disease, a number of trials have been conducted comparing CABG with stenting.83–86 In these studies, trends favoring CABG for multivessel disease were seen after 2 years in composite cardiac event end points, rate of reinfarction, and mortality; revascularization rates were five times higher in the stenting groups.87 Most notably, survival after CABG for two or more diseased vessels was significantly higher than stenting with 2-year follow-up in a retrospective study of the New York State Cardiac Surgery Reporting System and Percutaneous Coronary Intervention Reporting System.88 These results must be interpreted with caution, however, as patients with acute infarctions less than 24 hours pretreatment were excluded. Because of the lack of prospective, randomized trials, recommendations must be based on retrospective and observational studies. CABG offers several potential advantages. First, surgical revascularization is the most definitive form of treatment of the occlusion. CABG offers the longest patency of revascularized stenotic and occluded arteries in elective cases; 90% of internal mammary artery grafts are patent at 10 years. Second, CABG also offers more complete revascularization, because all vessel lesions are treated. This concept becomes especially important in patients with multivesssel disease or those in cardiogenic shock, in whom remote myocardium may continue to be comprised with only "culprit vessel" revascularization and inadequate restoration of collateral flow.89 A complete revascularization returns global myocardial perfusion to normal levels and offers the best chance for myocardial salvage. Third, difficult distal obstructions can be reached. Fourth, there is controlled reperfusion to reverse ischemic injury and reduce reperfusion injury. Fifth, as with other forms of reperfusion, CABG interrupts the progression of ischemia and necrosis and limits infarct size.

Disadvantages of Coronary Artery Bypass Grafting

Disadvantages of immediate surgical revascularization include the high mortality associated with early CABG. Off-pump procedures may reduce perioperative complications in high-risk patients, but are not yet widely practiced and have limitations.90 Rapid availability of catheterization and operating room personnel for emergency procedures imposes logistic and economic constraints. Thus, CABG is not readily applicable to the vast majority of patients in the community, and to provide this would strain health care resources. Second, it is difficult to analyze published results of CABG for acute myocardial infarction because randomized trials have not been done. Comparisons thus far have used medically treated patients as controls. Patients in the surgical group may be at lower risk; this might explain their progression to operation rather than continuing medical treatment. Crossover of patients from medical to surgical treatment also may have skewed the data.

Summary

Surgical revascularization following acute myocardial infarction can be performed with excellent results when the timing and patient cohort are appropriate. Most patients do not need such measures and would not benefit from this aggressive form of therapy. However, patients with mechanical complications, those in cardiogenic shock, and those with postinfarction angina are likely to benefit from early CABG.

The early use of aortic counterpulsation with an intra-aortic balloon pump (IABP) demonstrated the safety but not efficacy of this device for patients in cardiogenic shock following acute myocardial infarction.91 Although survival was not improved, aortic counterpulsation did improve the myocardial oxygen requirements and myocardial energetics were reduced in patients in shock. The use of IABP is also effective for temporary hemodynamic stabilization in complications of acute myocardial infarction, such as ventricular septal rupture acute mitral valve insufficiency,92 postinfarct angina,93 ventricular arrythmias,94 and acute heart failure following infarction.95 As revascularization techniques for the repair of occluded coronary arteries of patients in cardiogenic shock have improved, use of aortic counterpulsation has found a role as an adjuvant to treatment protocols.

IABP counterpulsation in combination with early reperfusion is effective in the treatment of acute myocardial infarction complicated by cardiogenic shock.80,96 Although the major improvement in survival is caused by early reperfusion, patients who had combined reperfusion and IABP additionally have improved long-term survival. IABP improves circulatory physiology and decreases end-organ damage in the early shock period before the myocardium is reperfused and recovers function.

Aortic counterpulsation decreases the reocclusion rate, recurrent ischemia, and need for emergency PTCA in patients who have coronary artery patency established by emergency cardiac catheterization after acute myocardial infarction.97 Prophylactic counterpulsation for 48 hours sustains patency in coronary arteries after patency is reestablished after myocardial infarction. No increase in vascular or hemorrhagic complications is observed as compared with controls.97

Weaning from the IABP should take place only after there is clear evidence of myocardial and end-organ recovery. In general, inotropic requirements should be reduced first to minimize myocardial stress. The one exception is the development of limb ischemia resulting from the IABP catheter.

Circulatory support devices are reserved for patients who are hemodynamically unstable; however, intervention should not be delayed until after irreversible end-organ injury occurs. This group of shock patients has a mortality rate of 80%, and survival data with the use of assist devices reflect the critical condition of patients treated. Mortality rates have changed very little in the last 20 years despite improvements in medical and surgical therapy.

Patients in cardiogenic shock who are candidates for circulatory assist devices may be divided into two groups: individuals who have stunned myocardium and need a bridge to recovery, and those who have irreversible myocardial damage and need a bridge to cardiac transplantation. For example, if a patient with a previously normal ventricle develops a large myocardial infarction, we prefer short-term support, because enough recovery may occur to allow a fruitful existence with the native heart. However, if a patient with preexisting heart failure has another infarction, the need to definitively bridge the patient to transplant with a long-term implantable device is apparent. This approach is supported by results from a multicenter study, in which overall survival at 6 and 12 months was higher in patients who underwent direct LVAD implantation rather than revascularization followed by LVAD, in patients suffering cardiogenic shock (Fig. 24-8).98 Difficulty arises in assessing the results of mechanical assistance for patients after acute myocardial infarction and cardiogenic shock because of these different objectives.

Mechanical assist devices augment systemic perfusion and prevent end-organ damage while resting the stunned ventricle with complete or partial pressure-volume unloading.99 Early studies of implantable LVADs have shown that end-organ function is an early predictor of mortality. Treatment of patients before end-organ deterioration is essential to improving the odds for long-term survival. In addition to affecting end-organ function, assist devices promote "reverse remodeling" by improving myocardial contractility and calcium handling, altering the extracellular matrix, and decreasing myocardial fibrosis.100,101 Recent studies have shown that circulatory support early after myocardial infarction improved survival and offered a feasible bridge to recovery or transplantation.77,102

Decisions regarding specific device use depend on the degree of circulatory support needed and many other factors. Selection criteria for device placement include:

1. Potential reversibility of cardiac dysfunction

2. Cause of the cardiac dysfunction

3. Degree of right and left ventricular dysfunction

4. Amount of circulatory support needed

5. Importance of the device for myocardial functional recovery

6. Patient size

7. Anatomical location of collapse or deterioration

8. Whether the patient is a candidate for cardiac transplantation

9. Whether the patient can be anticoagulated

10. Expected duration of support

11. The patient's age and severity of comorbid conditions

At the New York Presbyterian Hospital (Columbia Center), several circulatory assist devices are available to aid treatment of each group. Short-term devices that can be placed percutaneously include the IABP, extracorporeal membrane oxygenation, and percutaneous assist devices. Devices that require sternotomy and are beneficial for short-term use include both pulsatile and newer axial flow devices. These devices primarily treat stunned myocardium, but they are capable of bridging to transplant. These devices are easy to insert, do not require excision of ventricular muscle, and do not compromise ventricular function after device removal. These devices can be removed without the need to reinstitute cardiopulmonary bypass. These devices are effective in patients who require emergency support secondary to cardiogenic shock.

Percutaneous assist devices are an excellent option for patients in cardiogenic shock after catheter-based or surgical revascularization as a short-term bridge for recovery or transplant. Current devices include the Impella Recovery system (Impella Cardiosystems AG, Aachen, Germany) and the TandemHeart system (Cardiac Assist Inc., Pittsburgh, PA). These devices require vascular access, which can be obtained percutaneously, and angiography to guide placement. The TandemHeart provides up to 4 L/min of support producing a higher mean blood pressure and cardiac output, and lowering pulmonary capillary wedge pressure.103 Clinical results of this device in a randomized trial in 42 patients suffering cardiogenic shock after acute myocardial infarction have shown an improvement in cardiac output, decreased pulmonary capillary wedge pressure, but no difference in 30-day overall mortality.104 Likewise, the Impella device can provide either 2.5 L/min or 5 L/min depending on the model, and in small series, may offer superior hemodynamic support when compared with an IABP.105

Many of the implantable assist devices are suitable for bridging to transplantation. Initial reports of increased mortality in this high-risk patient population have been refuted by studies reporting higher than usual survival in acute myocardial infarction patients who received ventricular assist device support. At our facility, more than 80% of this patient cohort have survived until transplantation, a result threefold better than that seen in databases of extracorporeal systems.

Second-generation assist devices employ axial flow rotors that can generate up to 6 L of flow (partial unloading of the left ventricle). These devices are driven by an electromagnetically actuated impeller drive shaft, contain fewer moving parts, and are smaller than pulsatile devices, thus making them less prone to mechanical failure and driveline infections, at least in theory.106 The major disadvantages to axial flow pumps are the need for systemic anticoagulation, the lack of pulsatile flow, and incomplete pressure-volume unloading of the left ventricle; these concerns have limited its use in the post-myocardial infarction setting and further research is needed to clarify its therapeutic potential for these patients.

A full discussion of short-term and long-term mechanical circulatory support is reported in Chapters 18 and 66.

New York Presbyterian (Columbia Center) Approach

Patients who are potential transplant candidates and those who are dying of cardiogenic shock after myocardial infarction are all candidates for placement of a long-term implantable left ventricular assist device (LVAD) (Fig. 24-9). If at all possible, a coronary angiogram is obtained to allow revascularization with or without LVAD insertion. Surgery is delayed if the culprit vessel can be opened with angioplasty and the patient stabilized in the catheterization laboratory. If hemodynamics continue to deteriorate, the patient is taken directly to the operating suite, even if infarction occurred earlier than 6 hours before the planned procedure. Hemodynamic observations that favor early CABG are pulmonary artery pressures of less than 60/30 mm Hg and cardiac output of more than 3 L/min. If the hemodynamics are worse, early implantation of a long-term implantable LVAD may be needed, especially if the mixed venous oxygen saturation is less than or equal to 50%. The decision to place a long-term LVAD is influenced by the patient score on a screening scale designed for this purpose (Table 24-6). These scores were selected to identify end-organ dysfunction (lung, liver, or kidney) and operative constraints (right-sided heart failure and bleeding). We have nearly a 90% survival if the summed scores are less than 5 points, versus 30% survival with summed scores greater than 5 points.107 For this reason, if the total score is greater than 5 points, an attempt is made to stabilize the patient before beginning long-term LVAD insertion. Patients with lower scores are offered temporary LVAD.

If a patient is not a potential transplant candidate, our approach is more conservative, because we do not have a safety net if coronary revascularization fails and a temporary support device is inserted. An angiogram must be obtained; if hemodynamics are not favorable and no acute ischemia is present, we delay surgery until pulmonary arterial pressures fall. If the patient is ischemic, we proceed with CABG as described in the following. If the patient cannot be separated from bypass without high-dose inotropic support, including alpha agonists, if the cardiac index is less than 2 L/min/m2, and if left-sided filling pressures remain high with mixed venous oxygen saturations of less than 50%, short-term LVAD support is instituted. IABP alone in this patient population often does not prevent death and almost always results in significant renal, hepatic, and pulmonary dysfunction that significantly complicates patient recovery even if adequate cardiac function returns. Most important, stressing the heart with high-dose inotropic agents and high filling pressures when it is weakest during the early reperfusion period after acute infarction may compromise border zone regions. This concern is especially true of patients with older infarctions (more than 6 hours). We err on the side of implanting this short-term device early, because the survival rate is only 7% if the device is inserted after a cardiac arrest in the recovery room.

Operative Techniques for Acute Myocardial Infarction

Anesthesia

Anesthesia is provided by a rapid narcotics-based regimen with perfusion and surgical teams prepared to respond to catastrophic hypotension or cardiac arrest. Transesophageal probes are always placed in these patients if possible. As the patient is prepped, a test dose followed by a loading dose of aprotinin is given.

Bleeding

Bleeding is a significant complication of emergency CABG and often results in further myocardial depression and pulmonary hypertension. Cytokine release induced by infusion of blood products and thromboxane A2 released by cardiopulmonary bypass stimulate pulmonary hypertension, which can be catastrophic in the setting of right ventricular ischemia. Use of aminocaproic acid for reoperative, emergency, or high-risk CABG is common in many institutions.

The use of clopidogrel deserves special mention, and its expanding administration can pose unique problems for the cardiac surgeon. Clopidogrel, an oral irreversible antagonist of the 5′-adenosine diphosphate that inhibits platelet activation and aggregation, is used extensively in patients with acute coronary syndromes and has been shown to lower cardiovascular risk by up to 20%, and reduce reinfarction and stroke rates;108,109 in addition, it is commonly given before percutaneous interventions and after intracoronary stenting to prevent thrombosis. Higher loading doses have been used with increasing efficacy against ischemic complications, which will likely expand its use in the future.110 However, patients frequently require surgical revascularization after medical therapy or cardiac catheterization while taking clopidogrel. The risk of bleeding after clopidogrel and cardiac surgery can be substantial. In multiple reports, the risk of reoperation for hemorrhage in patients receiving clopidogrel within 7 days of cardiac surgery is six times higher, and patients required more blood, platelet, and fresh-frozen plasma transfusions.111,112 Because of these complication rates and the inability to reverse clopidogrel's effect on platelets, surgery is often delayed until platelet function is restored, which may take 7 to 10 days, or the life of the platelets. Emergent surgery while taking clopidogrel necessitates frequent blood product transfusions and confers significant morbidity, and possibly mortality. Further study is underway to determine if current dosing regimens after acute myocardial infarction can be reduced to lessen bleeding complications.

Choice of Conduits

For emergency cases, the choice of conduit should not differ from elective cases in most circumstances. The internal mammary artery is not associated with a higher number of complications compared with saphenous vein grafting in emergent situations and can be used in most circumstances.113,114

Intraoperative Considerations

Decompression of the ventricle during revascularization after acute coronary occlusion decreases muscle damage and improves functional outcome by decreasing wall tension and reducing oxygen consumption (Figs. 24-10 and 24-11).38 Indeed, ventricular decompression reduces metabolic energy consumption by 60%. Diastolic basal arrest, by avoiding the energy of contraction, is the second most important means of minimizing oxygen consumption and further reduces metabolic energy consumption by 30%. Cooling of the patient and heart has an impact only on the final 10% of basal energy requirements.

Reduction of myocardial energy consumption is best achieved by early institution of cardiopulmonary bypass to maintain a high perfusion pressure. If a coronary salvage catheter has been placed across a tight coronary lesion, the catheter is left in place until just before cross-clamping. Antegrade and retrograde catheters are placed before cross-clamping to allow quick instillation of retrograde cardioplegia and protection of the territory supplied by the occluded or compromised vessel. The standard Buckberg protocol is followed, including warm induction to allow regeneration of depleted adenosine triphosphate stores.

If the territory at risk is grafted by saphenous vein, this anastamosis is performed first to allow direct instillation of cardioplegia into the territory at risk. The proximal anastomoses should be performed before removal of the cross-clamp to allow complete perfusion of the entire heart upon removal of the cross-clamp. The role of off-pump CABG in this setting is appealing, but remains unproved.

Although large ventricular aneurysms are treated by resection and patch, debate surrounds smaller aneurysms. Our group does not resect small aneurysms, but some groups are more aggressive. If an aneurysm is resected, the defect is repaired with a patch of bovine pericardium sewn to the fibrotic rim of the endoaneurysm surface. The native left ventricular wall is closed over the patch.

Utilization of the Dor procedure (endoventricular circular patch plasty repair) in the post myocardial infarction setting is a controversial subject. Recent data have shown that surgical remodeling improves systolic function, ejection fraction, and intraventricular dyssynchrony, whereas other data suggest no added benefit when added to CABG.115–118 Further investigation is needed to definitively answer this question.

Postoperative Care

A higher incidence of complications in shock patients compared with nonshock emergencies has been reported. Guyton and associates81 report a 47% complication rate associated with cardiogenic shock compared with 13% for patients with nonshock emergencies. This increase in complications probably reflects the preoperative condition of the patients rather than the treatment itself. Long-term follow-up in patients after emergency surgical revascularization shows that survival rates are closely correlated with postoperative ejection fraction and left ventricular size.119,120

Improving outcomes in patients suffering acute myocardial infarction can occur through pharmacologic advances, optimization of existing practices, and application of new technology. Various medications have been described that reduce ischemic-reperfusion injury and limit infarct size in animal models, such as oxygen-derived free radical scavengers, folic acid, nitric oxide inhibitors, and others;121 clinical study of these promising drugs will determine their efficacy. Sudden death after myocardial infarction may be reduced with administration of omega-3 fatty acids.122 Reducing transport time to the hospital after the onset of symptoms and implementation of clinical guidelines have been initiatives of many hospitals and emergency services. The increased number of local hospitals able to perform primary percutaneous interventions has meant quicker revascularization, and thus improved outcomes.14 This trend should continue in the future. Mechanical circulatory support has advanced greatly over the past 10 years, and pumps have become smaller, safer, less invasive, easier to use, and easier to implant. The indications for LVAD use are expanding in this population, and they may allow myocardial recovery to occur in select patients requiring hemodynamic support after acute infarction. The option of living long term with these devices has also become a reality. Finally, the rapidly emerging field of cellular therapy holds great promise for repair of damaged myocardium. A number of cell types, such as endothelial progenitor cells, mesenchymal stem cells, skeletal myoblasts, resident cardiac stem cells, and embryonic stem cells, are being investigated;123 the optimal cell type, mode of delivery (intracoronary artery infusion, intravenous infusion, transendocardial injection, and transepicardial injection), and timing of administration have yet to be determined. Nevertheless, early clinical trials suggest that cellular therapy may offer benefits. One-year follow-up of 59 patients suffering acute myocardial infarction in the TOPCARE-AMI trial who received either circulating progenitor cells or bone marrow–derived progenitor cells demonstrated increased cardiac function and reduced ventricular dimensions, without adverse events.124 Precultured mesenchymal cells also offer great promise by allowing cells from an unrelated donor to be administered without the complications of individual tissue harvest. The safety of these cells given intravenously after percutaneous revascularization in acute myocardial infarction was recently published, and efficacy studies are ongoing.125 Numerous other clinical trials are underway to address questions regarding mechanisms of benefit, cell viability, and dosing. Future randomized clinical trials will be required to establish outcome benefit.

The treatment of acute myocardial infarction should be divided into two approaches. Uncomplicated acute myocardial infarction can be treated in most community hospitals. In most areas of the country, these patients are treated effectively with thrombolytic therapy and medical management. For communities and facilities that have catheterization laboratories, primary angioplasty may be more cost effective and produces improved results. At this time, emergency coronary artery bypass surgery is not the most cost-effective approach; randomized, controlled studies to demonstrate advantages of emergency CABG have not yet been performed.

The approach to acute myocardial infarctions complicated by cardiogenic shock presents a more difficult problem. Mortality rates are high with medical management. Reperfusion therapy is the only real hope for improved survival in this group of patients. Thrombolytic therapy is associated with poor outcomes. Early PTCA and CABG are the primary options in all patients, including those greater than age 75. Mechanical circulatory assistance has an important role for supporting patients until the myocardium recovers. Use of pharmacologic agents and means to control reperfusion are important areas of current research and development. Assist devices and artificial heart programs offer indispensable options and must be considered in this patient population, especially because all therapies offer suboptimal results.

1. Early reperfusion within 24 hours of acute myocardial infarction using thrombolysis, PTCA, intracoronary stenting, and CABG provides the best chance for myocardial salvage and long-term survival.

2. Primary PTCA and intracoronary stenting are first-line therapies for patients suffering acute myocardial infarction, whereas thrombolysis is an acceptable alternative in select patient populations.

3. CABG after acute myocardial infarction may be appropriate for patients with ongoing angina or failure of percutaneous intervention, certain patients in cardiogenic shock, and those with structural complications of myocardial ischemia.

4. Circulatory assistance in the form of IABP and ventricular assist device insertion can provide temporary support until recovery or bridge to transplantation can occur in high-risk patients in cardiogenic shock.

5. Early institution of bypass, ventricular decompression, controlled reperfusion, and use of the Buckberg solution are important intraoperative techniques during CABG.