ACUTE INTERVENTIONS FOR MYOCARDIAL REPERFUSION

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SELECTED TOPICS IN EMERGENCY CARDIAC CARE

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ACUTE INTERVENTIONS FOR MYOCARDIAL REPERFUSION Michael Brown, DO, Christopher D'Haem, DO, FACC, Duane Berkompas, MD, FACC, Joel M. Cohn, MD, FACC

Acute myocardial infarction (AMI) occurs approximately every 20 minutes in the United States. Annually, 1.5 million persons are affected; in one third of these it is a fatal event.5According to the World Health Organization (WHO) myocardial infarction is diagnosed by satisfying two of the three following criteria:86 1. Clinical history of ischemic chest pain 2. Changes on serially obtained electrocardiogram (ECG) tracings 3. Rise and fall in serum cardiac markers

The primary goal of treatment in AM1 is reperfusion of the infarctrelated artery in as short a time as possible. Prompt reperfusion has been shown to decrease mortality3*50, 51, 58, Io7 and to preserve left ventricular f~nction.'~ Present strategies for acute reperfusion include the use of thrombolytic agents and a variety of catheter-based interventions. This article presents a brief review of these strategies and discusses the subsets of patients who may be better served by a particular type of intervention. THROMBOLYTIC THERAPY

Thrombolytic therapy is the most widely used method to achieve acute reperfusion, and when administered within the first 12 hours from the onset of symptoms reduces mortality by approximately 300/o. 3, 50. 51, 58, 107 Further breakdown of the first 6 hours shows a relative mortality reducFrom the Thoracic and Cardiovascular Institute, Department of Internal Medicine, Michigan State University, East Lansing, Michigan

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tion of 30% between 0 and 1 hour, 25% between 2 and 3 hours, and 18% between 4 and 6 hours, underscoring the importance of avoiding delays in thrombolytic administration. In the emergency department, a streamlined system of triage can contribute significantly toward reducing the time to thrombolytic agent admini~tration.~~ It is currently recommended that a protocol be developed that yields a targeted clinical examination and a 12-lead ECG within 10 minutes and a door-to-needle time of less than 30 minutes.86 Presently approved fibrinolytic agents include streptokinase, alteplase (rt-PA), anisoylated plasminogen activator complex (APSAC), and the newest agent, reteplase (r-PA). Comparison studies between streptokinase and alteplase,sl reteplase and altepla~e,'~, 92 and reteplase and streptokinasez4have been conducted. In the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-I) trial alteplase was compared with streptokinase and demonstrated a small but statistically significant reduction in mortality (6.9% vs. 7.870,re~pectively).~' The Recombinant Plasminogen Activator Angiographic Phase I1 International Dose-Finding Study (Rapid 1) and the Reteplase (r-PA) versus Alteplase Patency Investigation During Myocardial Infarction (Rapid 2) trials examined the time from drug administration to the development of normal (TIMI 3) flow between alteplase and reteplase. It was found that reteplase achieved higher patency rates and more complete perfusion than did altepla~e'~, 92; however, preliminary data from the GUSTO-I11 trial, investigating differences in mortality reduction between reteplase and alteplase, found no statistical difference in mortality or in the incidence of stroke and bleeding between the two agents.24Comparison of streptokinase and reteplase was undertaken in the INJECT trial and demonstrated both agents to be equivalent in terms of mortality benefit and incidence of stroke and bleeding.56 Despite their availability, current thrombolytic agents still have significant limitations. Of the patients treated with presently available agents, only 50% will achieve normal coronary perfusion (TIMI 3 flow). In the ensuing hours to days, 50% of this subset will develop recurrent ischemia. Ultimately, only 25% of patients will maintain optimal coronary p e r f u ~ i o n . ~ ~ Intravenous thrombolytic therapy has become the standard of care over the last decade for AMI. From the large amount of data on outcomes following thrombolytic therapy, several observations have emerged. First, thrombolytic therapy is widely available and easy to administer. Second, thrombolytic agents can be given by physicians, trained nurses, and paramedics. A catheterization laboratory with sophisticated equipment and skilled technical support is not necessary. Third, the benefit is highest in those who are treated soon after development of infarction symptoms, and this can be accomplished in rural community hospitals as well as large metropolitan medical centers.67 Efforts to improve thrombolytic therapy continue. Development of mutant and variant types of rt-PA and more specific and potent anticoagulants and antithrombotic agents are presently in pr0gress.~5

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ADJUNCTIVE PHARMACOTHERAPY IN ACUTE MYOCARDIAL INFARCTION

Supplemental oxygen by nasal prongs is administered routinely in the initial hours of AM1 and is especially indicated if the saturation is less than 90%. Although there are no data on morbidity or mortality reduction, experimental results suggest that ST elevation and ischemic injury are reduced.71,72 The rationale for its use is that even uncomplicated patients are sometimes initially modestly hypoxemic owing to ventilation-perfusion mismatch and excessive lung Intravenous nitroglycerine at a dose of 10-20 pg/min titrated by 5-10 pg/min every 5 to 10 minutes (while monitoring hemodynamic effect and clinical response) is indicated during the first 24 to 48 hours in patients with AMI. The intravenous route is preferred because of ease of titration, onset of action, and ability of rapid termination in the event of side effects. The primary action is coronary and peripheral vascular dilatation. There is both clinical and experimental evidence that nitrate therapy reduces infarct size, improves regional wall motion, and may prevent left ventricular remodeling that occurs after a large infarction.l6.60, lo9 Combined data from randomized controlled trials of nitrate use in AM1 demonstrate a small but statistically significant mortality benefit.59Nitrate therapy is contraindicated when the systolic blood pressure is less than 90 mm Hg or when the heart rate is less than 50 bpm. It should be used with extreme caution in patients with suspected right ventricular infarction. These patients depend especially on ventricular preload to maintain cardiac output and may become severely hypotensive during nitrate admini~tration.~~ Analgesia such as morphine sulfate should be administered promptly at the time of diagnosis of AM1 to alleviate pain and attenuate the sympathetic drive. Sympathetic overactivity increases myocardial oxygen demand and increases occurrence of ventricular tachyarrhythmias.6, Beta-adrenergic-blocking agents administered in the first few hours of AM1 decrease myocardial oxygen demand and reduce the magnitude and rate of myocardial infarction. Several clinical trials have demonstrated a reduction in recurrent ischemia, reinfarction, and mortality 74, 97 Relative contraindications to beta blocker therwith beta apy include heart rate less than 60 bpm, systolic blood pressure less than 100 mm Hg, prolonged first-degree or higher atrioventricular block, severe chronic obstructive pulmonary disease or asthma, severe peripheral vascular disease, or insulin-dependent diabetes mellitus. Calcium channel blockers have not been shown to decrease mortality in AM1 and may even be harmful in certain patient It has been suggested that these agents are used too frequently in AM1 and that beta blockers are a more appropriate choice for most patients.84 Magnesium produces systemic vasodilatation, has antiplatelet activity, suppresses automaticity, and protects the myocardium against cal-

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cium overload.*,lo,28, 57, lo8 Meta-analysis of seven trials demonstrated a significant mortality benefit.8,95 This was not confirmed in the large ISIS4 trial, however.59Until the results of another large trial (Magnesium in Coronary Disease [Magic]) are available, intravenous magnesium administered early in AM1 is probably reasonable. Although an optimal dose is not established, 2 g over 5 to 15 minutes followed by 18 g over 24 hours has been successful.9 In patients treated with a thrombolytic agent, the recommendation for heparin depends on the agent used. Non-fibrin-specific thrombolytic agents such as streptokinase produce a systemic fibrinolysis. The evidence for use of heparin when these thrombolytic agents are used is equiv0ca1.l~~ Data suggest, however, that when alteplase (a fibrin-specific agent) is used, intravenoG heparin leads to higher rates of infarctrelated artery perfusion.13,26* 55 Intravenous heparin bolus and 48-hour infusion is therefore recommended for patients with AM1 given alteplase to achieve an aPTT of 50 to 75 seconds (1.5-2 times control). For patients receiving a nonselective fibrinolytic agent, intravenous heparin is recommended for only those at high risk for systemic emboli (e.g., large MI, atrial fibrillation, previous embolus, or left ventricular thrombus).8s Based on data from angioplasty trials, high-dose heparin to achieve an activated clotting time of 300 to 350 seconds is recommended for 79 patients undergoing primary angioplasty as the route of reperfu~ion.~~, Hirudin and the synthetic version, hirulog, is a newer direct antithrombin with several advantages over heparin: it does not require antithrombin I11 for its activity, is not neutralized by plasma protein, inhibits clot-bound thrombin, and does not require dose monitoring except in renal failure. Early trials in AM1 were promising, but largescale trials had to be modified owing to excess intracerebral hemorrhage.7.45.101 Platelet adhesion, aggregation, and degranulation at the site of coronary plaque rupture play a pivotal role in the pathogenesis of AMI. Aspirin is effective in reducing the incidence of recurrent myocardial infarction and death. A dose of 325 mg given on presentation to the emergency department is currently recommended, although 160 mg has 42 Ticlopidine is an antiplatelet agent with been shown to be effe~tive.3~~ a different mechanism of action than aspirin. This inhibitory effect is delayed for 2 to 3 days, making it a less desirable agent when rapid antiplatelet effect is desired. More recently, abciximab (a human-mouse chimeric FAB fragment of monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor) has reduced adverse outcomes at angioplasty by 35% at 30 days and at 6 m~nths.~~,'OO Two additional trials in the setting of a n g i o ~ l a s t yand ~~ refractory unstable anginag1were stopped early because of a reduction in the composite end point (i.e., death, MI, or need for repeat revascularization by 40% or more). Several trials are presently testing abciximab to determine effectiveness as a thrombolytic agent and to reduce complications associated with primary balloon angioplasty and intracoronary stenting in AMI.

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RESCUE PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY

Thrombolytic agents fail to establish reperfusion in up to 25% to 40% of patients experiencing AMI, resulting in reduced left ventricular ejection fraction and higher mortality rates.12,77, 96, 99 Even when left ventricular function is similar, survivors of myocardial infarction with a patent infarct artery have an improved long-term outcome in comparison with those whose infarct artery is occluded (the so-called open artery hyp~thesis).~~, 62 Although 90-minute vessel patency is considered the standard for comparison of thrombolytic efficacy and is a strong predictor of myocardial salvage, a significant number of vessels undergo late re~analization.~~ It is, however, the timing of reperfusion that is of fundamental importance. Rescue percutaneous transluminal coronary angioplasty (PTCA)has been advocated to establish antegrade coronary flow in patients who fail to reperfuse following administration of a thrombolytic agent. Advantages are establishment of early vessel patency, salvage of viable myocardium, and improvement in long-term survival.66In the TAM15 trial;' 575 patients were randomized to either emergency angiography and PTCA (if the vessel remained closed following thrombolytic administration) or to deferred angioplasty 5 to 7 days later. In the rescue PTCA group, predischarge vessel patency was 94%. There was also improvement in regional wall motion and decreased recurrent ischemia without an increase in bleeding complications. Patients with previous myocardial infarction particularly benefited with regard to improved left ventricular function. Ellis et a1 published a meta-analysis of 560 patients who underwent rescue PTCA following failed thrombolysis with a variety of thrombolytic regirnen~.~' Average procedural success was 80%. The reocclusion rate was 18% and the hospital mortality rate 10.6%. Mortality was higher (39%) when PTCA was unsuccessful. No significant improvement in predischarge left ventricular ejection fraction was shown. The high reocclusion and mortality rates may be due to the selection of a higher risk subset having more complex vessel lesion morphology and larger thrombus burden refractory to thrombolysis. The RESCUE trial randomized 150 patients presenting from 1.5 to 8 hours postacute anterior MI and thrombolysis failure to PTCA or continued medical therapy30 Procedural success was 95%. A statistically significant 60% decrease in the 30-day combined endpoint of mortality and CHF was demonstrated (6.5% vs. 16.4%). Despite the reported success of rescue PTCA, several concerns remain. The clinical recognition of thrombolysis failure is often difficult and may lead to an additional delay in reperfusion.62,64 Clinical markers of reperfusion, such as resolution of chest pain, normalization of STsegment elevation, and reperfusion arrhythmia are of limited predictive value in identifying thrombolysis failure. In the TAM1 trials, for example, chest pain completely resolved in only 29% of patients but was associ-

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ated with a patency rate of 84Y0.l~Immediate catheterization of all patients to determine the number with persistent occlusion is costly, impractical, and generally associated with higher rates of bleeding complication^.^^^ 99 Investigational methods to improve identification of reperfusion, such as continuous electrocardiographic ST-segment monitoring and serum analysis of myoglobin and creatine kinase isoforms that rise early after recanalization, await further testing in larger numbers of patients.29,65 Comparative data suggest that rescue PTCA is more successful with combination or nonspecific plasminogen activators (e.g., streptokinase or urokinase with or without t-PA) than with t-PA alone.”,20* 31, 40, 48, 49, 53, 78,98,99, lo6 In the pooled analysis by Ellis et al, the rates of PTCA success and reocclusion with streptokinase and urokinase, or a combination, were 84% and 14%, respectively, compared with 76% and 24%, respectively (with t-PA alone).31 The safety of rescue PTCA has been questioned based on the high mortality of up to 44% in patients in whom rescue PTCA fails.’, 49, Io6 Additionally, Gacioch and Topol demonstrated significantly more intraprocedural adverse events, including hypotension, ventricular fibrillation, and bradyarrhythmia for rescue PTCA of the right coronary artery compared with the left anterior descending The mechanism for the complication in the right coronary group may be due to an exaggerated Bezold-Jarisch reflex, showering of emboli into the distal microcirculation, or reperfusion injury. In summary, nonrandomized and randomized data suggest that rescue PTCA may be helpful in patients for whom thrombolytic therapy has failed. This strategy should be considered in any patient with a large amount of myocardium at risk, with cardiogenic shock and a persistently occluded artery, or with a previous myocardial infarction. Adjunctive mechanical and pharmacologic therapy with intracoronary stents and glycoprotein IIb/IIIa platelet receptor antagonists may improve angioplasty success and reduce reocclusion. DIRECT ANGIOPLASTY

In light of the deficiencies associated with thrombolytic therapy, increased interest in performing immediate cardiac catheterization and direct angioplasty when appropriate in the patient with AM1 has evolved over the last 5 years. Advantages of this approach include 1)few, if any, contraindications; 2) immediate assessment for presence of multivessel coronary artery disease and possible need for emergent bypass graft surgery; 3) immediate knowledge of the success of reestablishing normal .~ observational coronary flow; and 4) lower risk for ~ t r o k e Numerous studies have shown that direct angioplasty is safe, is extremely successful in reestablishing coronary flow, and results in low 30-day mortality and morbidity. To compare thrombolysis to direct angioplasty, four randomized studies were completed in the early 1 9 9 0 ~ .47,~82, ,

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In each of the four studies, patients who presented within 6 to 12 hours from the onset of symptoms and with electrocardiographic evidence of AM1 were randomized either to direct angioplasty or thrombolytic therapy. Note that front-loaded alteplase (t-PA) was not used in any of these trials. A total of 745 patients was enrolled in the four studies. The success of direct angioplasty averaged 92.5% but ranged from 80% to 99%. The average in-hospital mortality rate for thrombolytics was 4.52% and for direct angioplasty was 3.22%, which was not statistically significant. In the PAMI study47 the in-hospital mortality rate was significantly decreased with direct angioplasty, but the thrombolytic group had twice the expected stroke rate, and the actual incidence of cardiac death was similar for both treatment groups. A subgroup analysis of the PAMI study also assessed mortality according to high-risk versus low-risk ~atients.9~ High-risk patients were classified as those with an anterior infarction, over the age of 70 years, and heart rate greater than 100 bpm. The in-hospital mortality rate for direct angioplasty in this high-risk group was 2.0%, but 10.4% for patients treated with thrombolysis. The mortality rate in the low-risk group for direct angioplasty was 3.1% and for thrombolysis was 2.2%. Despite these results, no study has ever randomized high-risk patients to direct angioplasty versus thrombolysis, and these criteria are not used in clinical practice to determine which therapy to offer patients. A point of concern for some was the time to treatment for direct angioplasty versus thrombolytic therapy. In the four previous studies, thrombolytic therapy was initiated 30 to 60 minutes more rapidly than direct angioplasty could be accomplished.44, 47, 82, I1O Remember, however, that recanalization of the infarct-related artery following thrombolysis occurs an average of 60 minutes following administration, and direct angioplasty results in a higher rate of patency and normal flow. In addition, reocclusion of the successfully recanalized coronary artery can occur in up to 30% of patients following thrombolysis but is rarely seen after direct angioplasty. A criticism of these trials is that they were performed in highvolume catheterization laboratories by experienced cardiac interventionalists. To assess the outcome of patients treated by direct angioplasty in community hospitals, two observational nonrandomized studies have been rep0rted.3~. 83 Every and c011eagues~~ reported the outcomes of over 3000 patients treated for AM1 in the Seattle area from 1988 to 1994. The success rate of direct angioplasty was 89%, the in-hospital and 3-year mortality for direct angioplasty versus thrombolysis was not statistically significant, and the rates of procedures and costs at hospital discharge and 3 years later were lower for the thrombolytic therapy group. In the second study, the National Registry of Myocardial Infarction (NRMI), data were collected from over 30,000 patients treated by either direct angioplasty or thrombolytic therapy in a broad range of hospitals. The overall in-hospital mortality rate for the thrombolytic group was 5.4% and was 5.2% for the direct angioplasty group. The mortality rate if patients were in cardiogenic shock was 52% for patients treated with

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thrombolytics and was 32.4% if they were treated by direct angioplasty. The rate of recurrent ischemia was 9.8% for the direct angioplasty group and was 14.6% for the thrombolytic therapy. Two points must be noted: 1) Neither study was randomized. Direct angioplasty was more commonly performed in unstable patients. Indeed, in a follow-up of the NRMI 2 study, the incidence of cardiogenic shock was three times higher in the direct angioplasty group. 2) Direct angioplasty was performed infrequently at many of the participating hospitals, suggesting an institutional selection bias. In the NRMI 2 study, 46% of hospitals performed only five direct angioplasty procedures over the 17 months of the study, and only 9% had more than 25 cases. To further assess current use of thrombolytic therapy, specifically front-loaded t-PA, the GUSTO IIb study was performed to compare this thrombolytic regimen with direct angioplasty.%Over 1000 patients presenting within 12 hours of onset of symptoms were randomized. In this study, 85% of patients treated by direct angioplasty were done by operators performing more than 75 cases per year. The study endpoint was the composite outcome of death, nonfatal reinfarction, and nonfatal disabling stroke at 30 days. For patients treated with front-loaded t-PA, the composite endpoint was 13.7%; for the direct angioplasty group, 9.6% ( p = 0.033). The benefit of direct angioplasty over t-PA was greater than the benefit of front-loaded t-PA over streptokinase in the widely publicized GUSTO-I trial. This section would not be complete without mentioning the current trend in direct angioplasty that has resulted in even more favorable results for AM1 patients, namely, the use of intracoronary stents. The concept of using stents in the setting of AM1 began 2 years ago when the method used to deploy stents changed. Intracoronary ultrasonography allowed interventional cardiologists to realize that proper stent deployment in the coronary artery required high balloon inflation pressures. When stents were properly deployed with this technique, the risk of subacute closure dramatically declined61,75 and with it the fear of placing stents in a thrombus-containing artery. Previous experience with stents had already proven their benefit in decreasing acute closure, treatment of dissection, and reducing restenosis following balloon angioplasty.38,85, It was a natural extension for interventional cardiologists to believe that stents could be of benefit in "sealing" the ulcerated plaque that led to the infarction. Four studies have now been reported in which stents were placed electively in the setting of AMI.54,73,93, Io3 In these studies, a total of 322 patients received stents, the primary success rate ranged from 96% to loo%, the 1-month mortality rate ranged from 0% to 1.59'0, the incidence of nonfatal repeat infarction ranged from 0% to 3%, and the need for repeat revascularization (either PTCA or CABG) ranged from 1.4% to 2.2%. Although the results of these studies were obtained in a nonrandomized manner, they form the basis for an accumulating amount of evidence that in suitable coronary lesions at the time of AM1 insertion of coronary stents may result in the most optimal therapeutic

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modality yet offered patients. Further studies are required to validate the long-term benefit of this approach to direct angioplasty for AMI. ADJUNCTIVE DEVICES FOR PERCUTANEOUS CORONARY INTERVENTION IN ACUTE MYOCARDIAL INFARCTION

Other devices have had a limited interventional experience in the setting of AMI. The directional coronary atherectomy (DCA) catheter employs a cutter that is housed in a cylindrical tube with a longitudinal opening on one side to excise atheromatous material. The material is stored in a nose cone. Ideal lesions in which to use DCA include eccentric and ostial lesions.22,lo2 Although few reports of its application in AM1 have been published, it is not regarded as a first-choice method for reperfusion therapy for AM1 because it fails to excise thrombus adequately and because of the high restenosis rate.87 The yo tabla tor is a high-speed rotational atherectomy device that uses a brass burr coated with diamond chips passed over a steerable guidewire to ablate atherosclerotic plaque. The particulate . debris is passed to the microcirculation and is trapped by macrophages. Calcified lesions, ostial lesions, lesions situated on a bend, and distal lesions in tortuous vessels are particularly amenable to rotational athere~tomy.'~ Because it is generally recommended to avoid rotary ablation in vessels with thrombus, this device has no significant role in AMI. The transluminal extraction-endarterectomy catheter (TEC) is a flexible tube containing two rotating blades that cut and aspirate thrombus and atheromatous material. Because thrombus plays a key role in the pathophysiology of a myocardial infarction, the TEC may be effective in this setting.68The TEC has also been effective in the treatment of degenerated saphenous vein grafts, which contain complex thrombotic material.81 A new thrombosuction catheter to remove fresh thrombus from degenerated saphenous vein bypass grafts and proximal native coronary arteries was recently described.lo4This device uses a saline jet to create a local Venturi effect, thus aspirating thrombus through a catheter sidehole. The role of this and similar thrombus-fragmenting devices awaits further testing. CARDIOGENIC SHOCK

Patients with cardiogenic shock represent a specific subgroup of AM1 patients. Cardiogenic shock is the leading cause of death in patients hospitalized with AM1 and in selected series has a 7% to 8% incidence. Cardiogenic shock may be present on emergency department presentation, may develop in a delayed fashion, and has a mortality of 80% to 90% in historically controlled series. Early recognition and management

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are paramount; this next section focuses on newer more aggressive treatment modalities. Cardiogenic shock can be defined as 1)clinical signs of hypoperfusion, and 2) systolic blood pressure under 90 m Hg without inotropic or intra-aortic balloon pump (IABP) support and after volume replacement.32Causes of cardiogenic shock include left ventricular dysfunction with pump failure, right ventricular infarction, ventricular septa1 rupture, acute severe mitral regurgitation, and cardiac tamponade. Left ventricular pump failure is the most common cause, and a high systemic vascular resistance can maintain blood pressure even in the face of a profound decrease in stroke volume. A rising heart rate may be the first important clinical clue in the diagnosis of an early "preshock An early emergency echocardiogram may help delineate the specific cause of cardiogenic shock. Early general treatment measures in the emergency department include correction of hypovolemia, hypoxemia, and acidemia. Early aspirin administration and full heparinization are warranted. Circulatory support is of utmost importance with sympathomimetic amines like dopamine or norepinephrine. Inotropes like dobutamine and milrinone are useful in the low-output state not associated with severe hypotension. Inotropic drug therapy, however, has not been shown to improve survival. Thrombolytic therapy has been universally disappointing in the treatment of cardiogenic shock. Many of the large thrombolytic trials have specifically excluded patients with cardiogenic shock, but one placebo-controlled trial (GISSI I) using streptokinase without adjunctive aspirin or heparin showed a 70% mortality. More aggressive, invasive modalities for the treatment of cardiogenic shock (e.g., PTCA, IABP, or bypass surgery) have been studied, but none to date in randomized prospective trials. Angioplasty (PTCA) has raised some excitement, however, and there are 17 published studies (with an aggregate of 453 patients) from which some information is available. The pooled in-hospital mortality rate was 4670, with a PTCA success rate of only 73%. Clearly delineated in these trials was a correlation of lower mortality with successful angioplasty--66% survival with successful PTCA versus an 80% mortality rate with an angioplasty failure.52 Coronary artery bypass graft (CABG) surgery performed in 19 studies of 323 pooled patients with cardiogenic shock has showed the lowest in-hospital mortality rate, 32?'0.~' Selection bias may have occurred in this study because patients with the least shock and fewest comorbidities are often selected for surgery. Furthermore, some of these patients underwent procedures after medical stabilization. IABP counterpulsation has been shown to increase cardiac output, improve both coronary and systemic perfusion, and augment myocardial metabolism. IABP is the most commonly used circulatory support device but has not been shown to decrease mortality from cardiogenic shock without adjunctive PTCA or CABG. IABP counterpulsation has been

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shown to be highly effective in initial clinical stabilization of 87 patients with refractory hypotension and hypoperfu~ion.~~ In most centers it is considered routine practice to use IABP support during angioplasty for cardiogenic shock. Further randomized trials will test whether IABP support in conjunction with thrombolytic therapy improves mortality in patients with cardiogenic shock owing to left ventricular dysfunction. Other means of mechanical support, including percutaneous cardiopulmonary bypass, have been reported on in small numbers of patients. Cardiogenic shock remains a challenging state during AM1 but some conclusions can be drawn. Early recognition and stabilization with inotropic agents in the emergency department is paramount. If the technology is available, rapid IABP support should be employed. Emergent catheterization and angioplasty in nonrandomized trials demonstrates a less than 50% mortality rate and if available represents the best therapy. If on-site catheterization facilities are not available, then stabilization and rapid transfer are appropriate. Thrombolytic therapy has shown no advantage in limited trials, and at present cannot be recommended. Finally, recognizing patients with large infarctions and resting tachycardia in the preshock state should also be considered for emergent direct angioplasty. RECOMMENDATIONS

In a recent consensus statement published by the American Heart Association and the American College of Cardiology on the management of AMI, guidelines were established for when direct angioplasty should be offered to patients.2As a result of the data, which indicate outcomes are best when direct angioplasty is performed rapidly and by experienced operators, the guidelines suggest that 1. PTCA be performed within 60 to 90 minutes of diagnosis 2. Documented clinical success with establishment of nearly normal flow in 90% of patients without need for emergent CABG, stroke, or death 3. The need for emergency CABG be under 5% among all patients treated in this manner 4. The performance of PTCA should be greater than 85% of patients brought for emergent catheterization 5. The mortality rate among all patients be under 12%

Interventional cardiologists offering direct angioplasty to patients must follow these criteria. When these guidelines can be met, direct angioplasty becomes the treatment of choice in AMI for the following situations: 1. Patients in cardiogenic shock or with pulmonary edema 2. Patients ineligible owing to contraindications for thrombolytic therapy 3. Any patient presenting early (within 12 h) after the onset of

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symptoms in a geographic proximity to a proficient interventional catheterization laboratory 4. Patients in whom the infarct-related vessel is suspected of being a saphenous vein bypass graft because these respond with mixed results to thrombolytic therapy Another relative indication is in the setting of a patient with clinical presentation suggestive of AM1 but with a nondiagnostic electrocardiogram. A final caveat is that when direct angioplasty is considered (because only 18% of hospitals in the United States offer this service) withholding thrombolysis to transport the patient to a facility for this procedure is not recommended. All data, regardless of which therapy is offered, consistently document the importance of early reperfusion in decreasing mortality. Thus, the primary goal of any therapy offered in this setting must remain the expeditious and rapid restoration of coronary flow and patency.

References 1. Abbottsmith CW, Topol EJ, George BS, et a1 Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. J Am Coll Cardiol 16:770-778, 1990 2. ACC/AHA Guidelines for management of patients with acute MI. J Am Coll Cardiol 28:1328-1428, 1996 3. AIMS Trial Study Group: Effect of intravenous APSAC on mortality after acute myocardial infarction: Preliminary report of a placebo-controlled clinical trial. Lancet 1:842-847, 1988 4. Altura BM, Altura BT, Carella A, et al: Mg2+ - Ca2+interaction in contractility of vascular smooth muscle: Mg2+versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels. Can J Physiol Pharmacol 65:729-745, 1987 5. Antman EM, Braunwald E: Acute myocardial infarction. In Braunwald E (ed): Heart Disease: A Textbook of Cardiovascular Medicine, ed 5. Philadelphia, WB Saunders, 1997, p 1184 6. Antman EM: General hospital management. In Julian DG, Braunwald E, (eds): Management of Acute Myocardial Infarction. Philadelphia, WB Saunders, 4244, 1994 7. Antman EM: Hirudin in acute myocardial infarction: Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A trial. Circulation 901624-1630, 1994 8. Antman EM, Lau J, Kupelnick B, et al: A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts: Treatments of myocardial infarction. JAMA 268:240-248, 1992 9. Antman EM: Magnesium in acute MI: Timing is critical. Circulation 922367-2372, 1995 10. Arsenian MA: Magnesium and cardiovascular disease. Prog Cardiovasc Dis 35:271310, 1993 11. Bairn Ds, Diver DJ, Knatterud GL, et al: PTCA "salvage" for thrombolytic failures-implications from TIMI 11-A [abstr]. Circulation 78(suppl 11):112, 1988 12. Bassand J-F', Machecourt J, Cassagnes J, et al: Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (AFSAC) in acute myocardial infarction: Effects on infarct size and left ventricular function. J Am Coll Cardiol 13:988, 1989 13. Bleich SD, Nichols TC, Schumacher RR, et al: Effect of heparin on coronary arterial

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