Venu Menon and Christopher M. Huff
INTRODUCTION AND EPIDEMIOLOGY OF ST-ELEVATION MYOCARDIAL INFARCTION
This chapter focuses on the diagnosis and management of ST-elevation myocardial infarction (STEMI). STEMI represents the most urgent presentation among the acute coronary syndromes (ACSs). This condition mobilizes a health care network with the aim of promptly restoring coronary perfusion in order to improve myocardial salvage and patient survival. This is a distinct clinical entity from unstable angina (UA) and non–ST-elevation myocardial infarction (NSTEMI), which were discussed in the previous chapter. In contrast to UA, which is characterized by ST depressions or T-wave inversions without elevated cardiac biomarkers, and NSTEMI, which is characterized by elevated cardiac biomarkers without ST-segment elevations, STEMI usually presents with ST elevations that are localizing in the territory of the infarcted myocardium.
Acute myocardial infarction (AMI) or onset of angina is the usual initial clinical presentation for coronary disease, although about 20% of individuals with a coronary event do not even present to the hospital. For these individuals, sudden cardiac death (SCD) due to ischemia-triggered ventricular fibrillation (VF) is the initial manifestation of symptomatic coronary disease. Unless defibrillation occurs within minutes, death ensues quickly. Fortunately, automated external defibrillators have become more available and are now found in many public places. Rates of neurologically intact survival for out-of-hospital cardiac arrest due to VF, are highly variable across the United States and are dependent on early defibrillation, effective bystander cardiopulmonary resuscitation (CPR), prompt emergency medical services (EMS) intervention, rates of revascularization, implementation of hypothermia protocols, and adequate postarrest care.
More than half a million hospital presentations per year are attributable to STEMI. This condition is responsible for higher in-hospital mortality than UA or NSTEMI. Whereas the early management decision in UA/NSTEMI is deciding whether a patient should be directed to an early invasive approach versus conservative management, in STEMI, the focus is on rapid pharmacologic or mechanical reperfusion.
Issues such as risk stratification, fibrinolysis, primary percutaneous coronary intervention (PCI), adjunctive medical therapy, and discharge planning are discussed in the following text. A controversial issue is whether patients with suspected AMI should be directed to the nearest hospital or to a facility with cardiac catheterization and surgical capabilities. Important patient characteristics and logistical considerations are reviewed that may favor one approach over another. This chapter follows the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.
CLINICAL PRESENTATION
STEMI typically presents with substernal chest discomfort that is described as a pressure or heavy sensation that lasts more than 30 minutes. Symptoms are often described as “vicelike” or “an elephant sitting on my chest.” Patients may display the Levine sign by clutching their fist over their chest. STEMI is often accompanied by dyspnea, nausea, vomiting, and diaphoresis. Atypical symptoms are more common in diabetics, women, and the elderly (similar to UA/NSTEMI patients). There is a subset (~20%) of patients who have myocardial infarction (MI) in the absence of clinically recognized symptoms. Successful reperfusion is dependent on early recognition of symptoms by the patient with prompt activation of the EMS. As a goal, EMS personnel should arrive at the subject’s location within 10 minutes of system activation. Unfortunately almost 40% of patients with STEMI fail to activate EMS. EMS-transported patients have significantly shorter delays in both symptom onset to arrival as well as door to reperfusion time.
DIAGNOSIS
The sine qua non for the diagnosis of STEMI is recognizing ST elevations in a typical coronary distribution or a new left bundle branch block (LBBB) in the setting of typical (or atypical) symptoms. In the NCDR ACTION registry, performance and transmission of an out-of-hospital 12-lead EKG was associated with a greater and more timely use of reperfusion therapy with a trend toward lower mortality likely because it facilitates early activation of the STEMI protocol. Waiting for cardiac biomarkers to return before making a diagnosis of AMI and initiating emergency therapy is inappropriate (class III recommendation). A brief phase before ST elevations appear is often unrecognized. This phase is characterized by hyperacute T waves in the infarct-related territory. The hyperacute electrocardiogram (ECG) findings rapidly progress to typical ST elevations. ST elevations are usually convex or “tombstone” in appearance, although they can be concave. STEMI is diagnosed when at least 1-mm ST elevations are recognized in two or more contiguous leads. Figures 41.1 to 41.4 show various ECG examples of STEMI. Patients with STEMI in the posterior circulation can manifest with ST depression across the anterior precordial leads. In patients with initial nondiagnostic ECG findings, serial repeat EKGs are warranted.
FIGURE 41.1 Anterior ST-elevartion AMI. There is also ST elevation in leads I and aVL, suggesting a left anterior descending artery occlusion proximal to a major diagonal branch.
FIGURE 41.2 Anterior ST-elevation AMI. In addition to ST elevation in leads I and aVL, there is also QRS prolongation, suggesting a left anterior descending artery occlusion proximal to a major diagonal branch and a major septal perforator.
FIGURE 41.3 Anterior ST-elevation AMI in the setting of a preexisting RBBB. ST elevation is noted in leads V3 to V6depression and the concordance or discordance of the ST segment with the QRS.
FIGURE 41.4 Inferior ST-elevation AMI. There is also ST elevation in leads V1 to V3, suggesting RV involvement. RV leads should also be done to confirm RV involvement (i.e., occlusion proximal to acute marginal branch).
The ECG can also help to localize the location of the coronary occlusion. For example, high lateral (i.e., I and aVL) ST elevations that accompany an anterior MI indicate a left anterior descending artery occlusion proximal to a major diagonal branch. An anterior STEMI with ST-segment elevation in lead V1 and QRS complex prolongation indicates a left anterior descending artery occlusion proximal to a major septal perforator. Most STEMIs (70% to 80%) eventually progress into Q waves in the region of the infarcted myocardium.
Although the ECG is diagnostic in the setting of STEMI, other conditions that cause ST elevations must be simultaneously screened for and evaluated. These include acute pericarditis, hyperkalemia, left ventricular hypertrophy, early repolarization, and ventricular aneurysm (Table 41.1).
TABLE
41.1 Differential for ST-Segment Elevation
From Wang K, Asinger RW, Marriott HJ. ST-segment elevation in conditions other than acute myocardial infarction. N Engl J Med. 2003;349:2128–2135, with permission from the Massachusetts Medical Society.
A posterior MI is an important STEMI equivalent. This is often seen in the setting of an inferior or inferolateral MI. The ECG findings are a tall R wave in V1 with ST depressions in V1 to V2. It is critical to recognize an isolated posterior infarction as a STEMI, because patient prognosis hinges on the prompt restoration of coronary flow.
The other STEMI equivalent to consider is a new or presumably new complete LBBB. Not surprisingly, patients who present with a complete LBBB have high in-hospital mortality rates (up to 25%), in part due to the fact that they are nearly 80% less likely to receive reperfusion therapy than patients who present with recognizable ST elevations. However, even with reperfusion therapy, mortality rates are higher in patients with new complete LBBB than with ST elevation, attesting to the high-risk nature of this population. Although ischemic changes are interpretable in the context of a right bundle branch block (RBBB), this task becomes more difficult with a complete LBBB. There are criteria that can help diagnose a LBBB as an AMI with good specificity (Table 41.2), which look at the degree of ST elevation or depression and the concordance or discordance of the ST segment with the QRS.
TABLE
41.2 ECG Criteria for the Presence of AMI in the Setting of LBBB
Adapted from Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle branch block. GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators. N Engl J Med. 1996;334:481–487.
RISK STRATIFICATION
Killip Class, TIMI Risk Score, GRACE Score, ACTION-GWTG Risk Score
Since all patients with STEMI are initially eligible for reperfusion therapy, risk models are used primarily to determine prognosis and not to direct therapy as in UA/NSTEMI risk models. Initial information for risk stratification comes from the physical exam. Assessing for signs of heart failure is a useful tool for risk stratification. Patients who present with cardiogenic shock have a 30-day mortality rate of approximately 60% (Table 41.3). Cardiac biomarkers (troponin I or T and total CK and CK-MB isoenzyme) supplement the physical exam by gauging infarct size and providing additional prognostic information.
TABLE
41.3 Killip Class—30-Day Mortality
From Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators. Circulation. 1995;91:1659–1668, with permission from Wolters Kluwer Health.
Risk models have been created that provide clinicians with a more accurate prediction of risk. These models combine multiple variables that are most predictive for future adverse cardiac outcomes. The thrombolysis in myocardial infarction (TIMI) risk score is an easily used and validated model that has important prognostic implications. It incorporates eight variables that are readily available from the history, physical exam, and ECG (Fig. 41.5). In a fibrinolytic treated population, a TIMI risk score of greater than eight predicts an approximately 35% incidence of death at 30 days. This is in contrast to a score of zero to one, for which the 30-day mortality rate is <2%. The strongest variable that predicts an adverse prognosis is advanced age (where age ≥75 years receives 3 points and age 65 to 74 years receives 2 points). Other variables include hypotension, tachycardia, or Killip class II to IV at presentation, history of diabetes or hypertension, low body weight, anterior ST elevation (also complete LBBB), and a time to treatment of >4 hours.
FIGURE 41.5 TIMI risk model for prediction of short-term mortality in STEMI patients. (From Morrow DA, Antman EM, Charlesworth A, et al. TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: an intravenous nPA for treatment of infarcting myocardium early II trial substudy. Circulation. 2000;102:2031–2037, with permission from Wolters Kluwer Health.)
The GRACE score was designed to improve the risk prediction of in-hospital mortality in patients with ACS. It can be used in patients with ST-elevation and non–ST-elevation myocardial infarction. Risk is determined based on Killip class, systolic blood pressure, heart rate, age, creatinine level, presence or absence of cardiac arrest at admission, ST-segment deviation, and presence or absence of cardiac biomarkers. A score of ≤60 is associated with a ≤0.2% probability of in-hospital mortality whereas a score of ≥250 is associated with a ≥52% probability of in-hospital mortality.
A mortality model and risk score utilizing a contemporary set of patients is that derived from the ACTION Registry. In this validated model, patients with a risk score of <40 had an observed mortality rate of 4% compared with a 12% observed mortality rate in subjects with a score >50.
MANAGEMENT
Initial Approach
The initial assessment of a patient suspected of having an AMI is to establish intravenous access and start supplemental oxygen for individuals who are hypoxic or who show signs or respiratory distress. Simultaneously, a targeted history and physical exam should be obtained. The history and physical exam provide prognostic information, but also can suggest an alternative diagnosis and help identify mechanical complications of STEMI. It is important to rule out other causes of chest pain such as aortic dissection. Pain arising from a gall stone, renal stone, pancreatitis, esophageal dys-motility, pneumothorax, pleuritis as well as impending herpes zoster may frequently mimic this presentation.
If reperfusion with fibrinolysis is considered, the history and physical exam should screen for contraindications to its use. Because the most feared complication with the use of fibrinolytics is intracranial hemorrhage (ICH), patients with an increased risk for this complication must be identified. Risk factors for ICH are advanced age, female gender, uncontrolled hypertension, and low body weight. Patients with coagulopathies (e.g., patients on Coumadin therapy) are also at increased risk for bleeding. Absolute and relative contraindications to fibrinolysis are listed in Table 41.4.
TABLE
41.4 Contraindications to Fibrinolysis
Adapted from Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:671-719.
Reperfusion Therapy
Time is of paramount importance in reinstituting coronary flow. The greatest improvement on mortality comes from reperfusion within the first hour, the so-called golden hour. Reperfusion therapy can be considered up to 12 hours from the onset of chest pain and even longer in select cases. In order to facilitate rapid coronary reperfusion, a pharmacologic or mechanical approach should be decided on quickly. The current goal for door-to-lytic time is 30 minutes, whereas the goal for door-to-balloon time is 90 minutes if the patient presents to a PCI capable facility and 120 minutes if the patient requires transfer for PCI.
In general, if primary PCI can be performed immediately (i.e., the patient presents to a center capable of performing PCI), this is the preferred choice for reperfusion (class I recommendation). This information comes from a metaanalysis of 23 trials that randomized nearly 8,000 STEMI patients to fibrinolytic therapy versus primary PCI. The hospitals included in the analysis were largely experienced providers of coronary intervention and were able to deliver mechanical reperfusion in a timely fashion, although some studies enrolled patients who were transferred for primary PCI versus given immediate fibrinolysis. This study was a contemporary analysis, as stents were used in 12 of the trials and glycoprotein (GP) IIb/IIIa inhibitors were used in eight. General inclusion criteria required that patients have ischemic symptoms within the previous 6 to 12 hours and at least 1-mm ST elevations in contiguous leads or a new/presumable new complete LBBB. Patients also needed to be candidates for fibrinolysis to be eligible for enrollment. A notable exception was the SHOCK trial, as this study enrolled patients with cardiogenic shock and chest pain within the preceding 36 hours. Since the SHOCK trial was the outlier to the overall analysis, the analysis was performed with and without this study. Most patients (76%) received fibrin-specific (i.e., t-PA) lytic agents, whereas the remainder received streptokinase. This analysis revealed a short-term survival advantage as well as a reduction in recurrent MI and hemorrhagic stroke in those who received primary PCI. Short-term mortality was 7% in the primary PCI group, compared to 9% in the fibrinolytic group (p = 0.0002). Long-term mortality was also significantly reduced (p = 0.0019). Thus, among patients who present within 12 hours of the onset of chest pain to a tertiary care center that is capable of performing primary PCI expeditiously, data supports the use of mechanical reperfusion.
When individuals present to a community hospital without primary PCI capabilities, the question becomes whether to transfer the patient to a primary PCI center or to administer immediate fibrinolysis. Fibrinolysis is limited by postlysis TIMI 3 flow of <50% at 90 minutes and risk of reocclusion, which results in inadequate myocardial salvage and heightened rates of recurrent ischemia and reinfarction. There is also a definite risk for ICH (up to 0.9% in many trials and even greater in high-risk patients). There are also numerous contraindications to consider. These limitations have led to trials that specifically addressed if delaying immediate reperfusion to allow transfer for primary PCI may be beneficial.
A subanalysis from the previously mentioned metaanalysis examined the studies that transferred patients for primary PCI versus giving immediate fibrinolytics. The mean time that was required for transfer to a primary PCI center was 39 minutes. Mortality was similar between the two groups (p = 0.057), although a composite outcome that included death, reinfarction, or stroke was reduced by transfer for primary PCI (p < 0.001).
Another meta-analysis specifically addressed this issue using available clinical trial information. This study examined only trials that randomized patients to either immediate fibrinolysis or transfer to a center capable of performing primary PCI. The inclusion criteria were similar to the previous meta-analysis: acute STEMI within 6 to 12 hours from the onset of chest pain and eligibility to receive a fibrinolytic agent. Six trials were available for analysis, involving nearly 4,000 patients. A few of these trials deserve special comment. The AIR-PAMI study randomized patients who were high risk to one of the above reperfusion strategies. High risk was defined as age >70 years, heart rate >100 beats/min (bpm), systolic blood pressure <100 mm Hg, Killip class II/III, complete LBBB, or anterior MI. Although this was the smallest study included in the meta-analysis, there was no noticeable harm in transferring high risk patients for PCI. The CAPTIM trial was unique in that patients were randomized to a reperfusion strategy before arrival to the hospital, which enabled fibrinolytics to be given in an even more timely fashion. This was the only trial that showed a nonsignificant trend in mortality favoring fibrinolysis. The PRAGUE-2 trial examined the optimal reperfusion strategy based on time from the onset of chest pain. The study was stopped prematurely, as mortality was increased 2.5-fold among patients who presented more than 3 hours from the onset of chest pain who received fibrinolysis (15% with fibrinolysis and 6% with primary PCI, p < 0.02). In Patients who presented within 3 hours from the onset of chest pain, mortality was similar between the two reperfusion strategies (7.4% with fibrinolysis and 7.3% with primary PCI).
So, while transferring a STEMI patient for primary PCI versus immediately administering fibrinolysis is controversial, some patient characteristics and logistical considerations favor one approach over another. According to the 2011 ACCF/AHA/SCAI guidelines for PCI, if a patient presents with STEMI and can undergo PCI within 120 minutes of first medical contact, this is the preferred approach. Conversely, if the patient cannot receive PCI within 120 minutes of first medical contact, and there are no contraindications to fibrinolysis, fibrinolytics should be administered within 30 minutes of hospital presentation (class I recommendation). It is important to note that the effectiveness of fibrinolytics are highly time dependent with a marked efficacy when administered in the first hour following STEMI onset. Accordingly, for patients who are at high risk for bleeding or who present more than 3 hours after the onset of chest pain, transfer for primary PCI is favored. Additionally, patients who are in cardiogenic shock benefit from mechanical revascularization, but have not been shown to have a mortality reduction with fibrinolysis. Lastly, in the elderly who have an increased risk of ICH, patients with contraindications to fibrinolytics or when the diagnosis of STEMI is in doubt, PCI should be considered. When interhospital transfer for primary PCI is planned, the DIDO (door in to door out) time at the originating hospital is an important performance measure and should ideally be <30 minutes. This benchmark is associated with optimal door to balloon times and lower in-hospital mortality.
Fibrinolytic Therapy
A large body of research involving tens of thousands of patients documented the benefit of fibrinolytic therapy in reducing infarct size, preserving left ventricular function, and improving survival in AMI patients. For every 1,000 patients treated with fibrinolytics within 1 hour of onset of symptoms, the number of lives saved is 26, while treatment within 3 to 6 hours from the onset of chest pain saves 18 lives. There is still a survival advantage from 6 to 12 hours, although it is smaller in magnitude than giving lytics closer to the onset of chest pain. Accordingly, fibrinolysis is indicated for 1 mm or more of ST elevations in contiguous leads, or a new complete LBBB within 12 hours from the onset of chest pain. Patients with stuttering infarcts may benefit from lytics up to 24 hours after the onset of chest pain. Asymptomatic patients more than 24 hours out from the onset of chest pain should not receive lytic therapy (class III recommendation).
If lytic therapy is selected, it is important to know the different agents used for fibrinolysis and which are available at a given institution. Additionally, contraindications to the use of fibrinolytics should be reviewed in every eligible patient. The choice of one agent over another is made according to hospital availability and physician experience with a given agent.
Streptokinase, a first-generation fibrinolytic agent, is capable of lysing circulating and clot-bound fibrin. Allergic reactions are common, and reexposure to streptokinase should be avoided. This is the least expensive lytic agent, at around $500 per dose. Streptokinase may not require adjunctive heparin therapy unless the patient is at high risk for emboli (i.e., atrial fibrillation or known left ventricular thrombus). Accordingly, lysis with streptokinase is associated with a slightly less ICH risk (0.5% compared to 0.7% for fibrin-specific agents). This property makes streptokinase attractive if an individual is not a candidate for PCI and is at high risk for ICH. An example would be a small, elderly, hypertensive female with a history of a remote ischemic stroke who presents with an extensive anterior MI and refuses PCI.
Fibrin-specific agents activate plasminogen directly and are relatively selective against clot-bound fibrin rather than circulating fibrinogen. Allergic reactions do not occur with these agents, as can occur with streptokinase. Fibrin-specific agents include alteplase (tPA), reteplase (rPA), and tenect-eplase (TNK-tPA). Because these fibrin-specific agents do not produce a systemically lytic state and because they activate platelets, the use of heparin therapy appears to improve and maintain vessel patency.
The GUSTO-I trial was a landmark study published in 1993 that compared streptokinase to various fibrin-specific strategies. Up until this trial there was no known advantage of one agent over another. This trial studied >40,000 patients with AMI and revealed the superiority of accelerated tPA over streptokinase. Accelerated tPA with intravenous heparin resulted in a 14% reduction in mortality and higher rates of TIMI 3 flow at 90 minutes (54% vs. 31%) compared to streptokinase-based regimens. The accelerated tPA dose is a 15-mg bolus, then 0.75 mg/kg (up to 50 mg) over 30 minutes, followed by 0.5 mg/kg over 60 minutes (up to 35 mg).
Reteplase is less fibrin-specific than alteplase. This agent is equivalent to alteplase in terms of efficacy, although it is easier to administer (two 10-mg boluses administered 30 minutes apart). Tenecteplase is the easiest lytic to administer, because it is given as a single bolus (dose ranges from 30 to 50 mg, adjusted for body weight). See Table 41.5 for dosing. This agent is more fibrin specific and has a slower plasma clearance than the other fibrin-specific agents. The ASSENT 2 trials showed the noninferiority of tenecteplase compared to alteplase. In this trial, there was also less major bleeding with tenecteplase, and a trend toward less ICH in elderly women. Equivalent efficacy, enhanced safety, and ease of administration make tenecteplase an attractive fibrinolytic agent.
TABLE
41.5 Weight-based Dosing of Tenecteplase
Reprinted from Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:671–719, with permission from Elsevier.
Percutaneous Coronary Intervention
When PCI is selected for reperfusion, eligibility criteria are the same as those used for fibrinolytics: 1 mm or more of ST elevations in contiguous leads or a new/presumably new complete LBBB within 12 hours of the onset of chest pain. A posterior MI should be treated as a STEMI equivalent. The goal of PCI is to achieve optimal revascularization of the infarct-related artery by establishing TIMI 3 flow. Multivessel revascularization at the time of primary PCI is usually not indicated (class III recommendation), except in patients with cardiogenic shock.
Several approaches to PCI exist in the setting of STEMI. Most data support the use of primary PCI. In primary PCI, fibrinolytics are not given prior to intervention. Patients either present directly to a PCI center, or they are transferred (without fibrinolysis) from a community hospital to a center capable of performing PCI. As mentioned previously, the downside in transferring a patient for primary PCI is the delay in time that is required until mechanical reperfusion can occur.
In a pharmacoinvasive strategy patients who receive fibrinolysis are transferred for early PCI regardless of reperfusion status. The TRANSFER AMI trial evaluated this strategy in high-risk STEMI patients. In TRANSFER AMI, patients who received fibrinolysis followed by PCI within 6 hours of presentation had a 6% absolute and 46% relative reduction in the composite endpoint of death, reinfarction, recurrent ischemia, heart failure, and shock when compared with patients who received fibrinolysis followed by rescue or delayed PCI. Based on these results, patients who are high risk and receive fibrinolysis as the primary reperfusion strategy should be transferred to a PCI-capable facility as soon as possible (class IIa recommendation). Table 41.6 lists the criteria for defining high-risk patients. For low-risk patients this same management strategy is considered a class IIb recommendation.
TABLE
41.6 ACC/AHA Recommendations for Triage and Transfer for PCI: High-risk Definition
Adapted from Kushner FG, Hand M, King SB, et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update). J Am Coll Cardiol. 2009;54:2205–2241.
With facilitated PCI, all STEMI patients without a contraindication routinely receive full or half-dose fibrinolysis prior to transfer for PCI. This strategy is not favored because of negative results in the ASSENT 4 and FINESSE trials. In the ASSENT 4 trial, STEMI patients were randomized to either full-dose tenecteplase plus PCI or primary PCI with unfractionated heparin (UFH). Patients who received fibrinolysis had an increased incidence of the composite endpoint of death, cardiogenic shock, or congestive heart failure (CHF). In the FINESSE trial, STEMI patients were randomized to abciximab followed by PCI, abciximab and reteplase followed by PCI, or primary PCI with abciximab given in the cath lab. The primary endpoint was a composite of death from all causes, VF occurring >48 hours following randomization, or cardiogenic shock and CHF within 90 days. The primary outcome did not differ between the groups, however, there was a significant increase in major and minor bleeding in the patients who received fibrinolysis. Given this, facilitated PCI is no longer recommended as a management strategy for STEMI patients.
The role of late or delayed PCI in asymptomatic individuals 12 to 24 hours after the initial event is unclear as there is a paucity of evidence. In the BRAVE 2 trial, performance of PCI in this time window was associated with a decreased infarct size on SPECT. Performance of PCI in hemodynamically stable patients with an occluded infarct artery >72 hours after the initial event is unwarranted. The OAT trial was a randomized study that enrolled patients with total occlusion of the infarct-related artery 3 to 28 days after MI. Patients were randomized to PCI with stenting and optimal medical management versus medical management alone. The primary endpoint was a composite of death, MI, and New York Heart Association (NYHA) class IV heart failure. PCI with stenting did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up. Consequently, AHA recommends against PCI of an occluded infarct-related artery >24 hours after STEMI if the patient is hemodynamically stable and does not have signs of severe ischemia (class III recommendation).
Historically, STEMI patients who were selected for mechanical reperfusion underwent percutaneous transluminal coronary angioplasty (PTCA). With the advent of intracoronary stents, randomized trials were designed to determine if PCI using intracoronary stents would improve outcomes. A meta-analysis that involved nearly 3,000 patients with STEMI who were randomized to PTCA versus PCI with intracoronary stents revealed an advantage to the use of stents. This analysis documented a reduction in the composite endpoint of death, MI, and target vessel revascularization at 6 months by the use of stents (14% vs. 26%, p < 0.0001), a difference that was driven by a reduction in the need for target vessel revascularization. The largest trial in this analysis was the CADILLAC trial. This study showed no reduction in death or MI from the use of stents, although there was less clinical and angiographic restenosis at follow-up.
Drug-eluting stents (DES) dramatically reduce restenosis compared to bare metal stents. However, because they were not initially evaluated in patients with AMI, the use of a drug-eluting stents in this setting is considered “off-label.” Since 2005, several trials have demonstrated the benefit of drug-eluting stents in the setting of AMI. One such trial, HORIZONS-AMI, randomly assigned STEMI patients to either paclitaxel-eluting stents or bare metal stents. At 12 months, the rate of ischemia-driven target vessel revascularization was significantly lower in patients treated with paclitaxel-eluting stents. In addition, paclitaxel-eluting stents were not inferior to bare metal stents in the rates of the combined safety endpoint of death, stroke, stent thrombosis, or reinfarction. In 2009, a meta-analysis of data from 18 registries and 13 randomized trials further supported the benefit of drug-eluting stents compared to bare metal stents in patients with STEMI. In the registries and randomized trials, drug-eluting stents significantly reduced the rate of target vessel revascularization without increasing the rate of death or MI. Accordingly, the 2011 ACCF/AHA/SCAI PCI guideline states that DES can be used as an alternative to BMS in cases where the risk of restenosis is high, as long as the patient can tolerate and comply with prolonged dual antiplatelet therapy (DAPT) (class I recommendation). Safety of DES stents, especially in the year following implantation, is closely linked to compliance with dual antiplatelet therapy. Consequently, patients who are likely to be noncompliant with dual antiplatelet therapy and those requiring an urgent noncardiac surgical intervention may benefit from placement of bare metal stents or balloon angioplasty alone.
With the success of intracoronary stents and adjunctive antiplatelet as well as antithrombotic therapy, PCI is usually successful in achieving TIMI 3 flow in the infarct-related artery in >90% of subjects. Thrombus aspiration catheters have been shown to improve ST-segment resolution and myocardial blush, and are associated with improved clinical outcomes. In the TAPAS study, patients who received aspiration thrombectomy were significantly more likely to have complete resolution of ST-segment elevation when compared with patients who underwent conventional balloon angioplasty and PCI (56.6% vs. 44.2%, p <0.001). At 1 year, there was also a significant reduction in the rates of cardiac death (3.6% vs. 6.7%, p = 0.02) and cardiac death or nonfatal reinfarction (5.6% vs. 9.9%, p = 0.009). Based on current guidelines, thrombus aspiration is considered reasonable during PCI in patients with STEMI who have a high clot burden and short ischemic times.
Coronary artery bypass grafting (CABG) is still indicated for left main disease, failed PCI, or mechanical complications of infarction (e.g., myocardial rupture). Additionally, patients with three-vessel disease (or two-vessel disease that includes the proximal left anterior descending artery) in the setting of left ventricular dysfunction or diabetes may have a better clinical outcome with surgery.
Antiplatelet Agents
Just as aspirin is the cornerstone of treatment for all UA/NSTEMI patients, it is also a class I recommendation for STEMI patients (see Fig. 41.4). Aspirin is associated with a mortality benefit similar to that achieved by streptokinase. Unless there is a serious contraindication to its use, a loading dose of 162 to 325 mg of nonenteric coated aspirin is currently recommended for all STEMI patients (class I recommendation). If there is any question as to whether the patient received aspirin prior to arrival in the emergency department, another dose should be given. If the patient is vomiting, aspirin can be given by rectal suppository if necessary (at the same dose). All post-PCI STEMI patients should receive aspirin indefinitely. Whereas previous guidelines recommended high dose aspirin for at least one month, the 2011 PCI guideline states that 81 mg of aspirin is reasonable (class IIa recommendation). When significant hypersensitivity to aspirin exists, clopidogrel should be given in its place (class I recommendation).
Thienopyridines should be used routinely in all patients with STEMI regardless of whether or not reperfusion therapy is received and should be continued for at least 1 year (class I recommendation). An important caveat with thienopyridines is the increased risk for major bleeding during surgery. It is currently recommended that clopidogrel and prasugrel be held for 5 and 7 days, respectively, prior to CABG, unless the need for urgent revascularization outweighs the risk of potential excessive bleeding (class I recommendation). In patients in whom PCI is planned, a loading dose of clopidogrel or prasugrel should be given prior to or at the time of PCI. Currently, the recommended loading dose of clopidogrel is 300 to 600 mg (class I recommendation). Although results of the CURRENT-OASIS 7 trial suggest that patients may benefit from a 600 mg clopidogrel loading dose compared to 300 mg, there is currently insufficient data to establish superior safety and efficacy of this higher loading dose. The recommended loading dose of prasugrel is 60 mg (class I recommendation).
Prasugrel is considered to be superior to clopidogrel in onset of action and potency of platelet inhibition. The TRITON-TIMI 38 investigators evaluated the efficacy and safety of prasugrel compared to clopidogrel in 13,608 patients with moderate to high-risk ACS undergoing PCI. Patients who received prasugrel had significantly fewer ischemic events, including stent thrombosis. The risk of major bleeding, including fatal hemorrhage, was higher with the use of prasugrel though overall mortality did not differ between the two groups.
Currently, the AHA/ACC guidelines do not consider one agent superior to another; however, clopidogrel is preferred in certain situations. Prasugrel is not recommended in patients with a history of transient ischemic attack (TIA) or stroke due to the risk of ICH (class III recommendation). Also, in patients who have received fibrinolysis, clopidogrel is the thienopyridine of choice. This recommendation is based on results of the CLARITY-TIMI 28 trial. This trial revealed that in STEMI patients who undergo fibrinolysis, there is a reduction in the composite endpoint of occluded infarct-related artery, death, or recurrent MI before angiography by the addition of clopidogrel to aspirin, heparin, and standard medical therapy. The recommended loading dose of clopidogrel following fibrinolysis is 300 mg if given within 24 hours of fibrinolysis and 600 mg thereafter (class I recommendation).
In patients who receive PCI, thienopyridine therapy should be continued for at least 1 year (class I recommendation). Fifteen months of therapy is preferred in patients undergoing drug-eluting stent placement (class IIb recommendation). If the risk of bleeding outweighs the potential benefit of thienopyridine therapy, earlier discontinuation should be considered. The maintenance dose of clopidogrel and prasugrel is 75 mg and 10 mg daily, respectively.
Ticagrelor is a reversible and direct-acting oral antagonist of the platelet adenosine diphosphate receptor P2Y12. It provides faster and greater platelet inhibition than clopidogrel, without an increase in bleeding complications. Based on results of the PLATO trial, it is now considered an acceptable alternative to clopidogrel or prasugrel (class I recommendation). PLATO was a multicenter, randomized trial that evaluated the benefit of ticagrelor compared to clopidogrel in patients with ACS. At 1 year, the primary end point, a composite of death from vascular causes, MI, or stroke, was significantly less in patients who received ticagrelor without an increase in major bleeding. Patients who receive ticagrelor should not be treated with high-dose aspirin, as high-dose aspirin has been associated with worse outcomes in these patients.
GP IIb/IIIa Inhibitors
The benefits of GP IIb/IIIa inhibition during primary PCI in the pre DAPT era are well documented. An analysis that included ADMIRAL, CADILLAC, ISAR-2, and the RAPPORT trials revealed a reduction in rates of the composite endpoint of death, recurrent MI, or target revascularization by 6 months with the adjunctive use of abciximab during PCI compared to placebo (OR = 80, 95% CI 0.67 to 0.97). The efficacy of these agents in the setting of dual oral antiplatelet therapy is less certain. The dose of abciximab is a 0.25-mg/kg intravenous bolus, followed by an infusion of 0.125 mg/kg for 12 hours. Based on the 2011 ACCF/AHA/SCAI PCI guideline treatment with abciximab, eptifibatide, or tirofiban is reasonable at the time of PCI in selected patients with STEMI (class IIa recommendation). The routine use of these agents prior to arrival in the cardiac catheterization lab is not recommended (class III recommendation).
Antithrombotic Agents
All STEMI patients should receive anticoagulant therapy, which has traditionally been unfractionated heparin (UFH). The dose of UFH varies depending on the reperfusion strategy selected. The dose is 60 U/kg as a bolus (maximum 4,000 U), followed by 12-U/kg/h infusion (maximum 1,000 U/h) to achieve a partial thromboplastin time (PTT) of 45 to 65 seconds in patients undergoing fibrinolysis or patients undergoing PCI with an adjunctive GP IIb/IIIa inhibitor. The goal of intraprocedural activated clotting time (ACT) in this case is 200 to 250 seconds. For patients undergoing PCI without adjunctive GP IIb/IIIa inhibitor, the dose of UFH is 80 U/kg as a bolus, followed by 18-U/kg/h infusion to achieve a PTT of 50 to 75 seconds and an ACT of 300 to 350 seconds during the PCI. In general, heparin should not be continued after PCI, because there is increased risk for major bleeding and no incremental benefit. Exceptions to this rule include patients at high risk for systemic emboli, such as with large anterior infarction/left ventricular thrombus and atrial fibrillation. Deep venous thrombosis should be prevented during periods of immobilization by subcutaneous UFH, 5,000 to 7,000 U, twice to three times per day when therapeutic doses of heparin are not being used.
Bivalirudin is considered an acceptable alternative to UFH for primary PCI (class I recommendation). This recommendation is based on results of the HORIZONS AMI trial. This trial randomized 3,600 patients to either bivarlirudin and provisional GP IIb/IIIa inhibitor or UFH and planned GP IIb/IIIa inhibitor prior to primary PCI. Only 7.5% of patients in the bivalirudin group received a GP IIb/IIIa inhibitor. The primary end points were major bleeding and the 30-day rate of combined adverse clinical events (major bleeding, death, reinfarction, target-vessel revascularization, and stroke). Patients in the bivalirudin group had a significant reduction in the primary end point, most of which was due to a reduction in the rate of major bleeding. The benefit of bivalirudin was maintained at 1 year. The use of bivalirudin in the setting of fibrinolysis was evaluated in the HERO-2 trial. In this trial, 17,073 STEMI patients were randomized to streptokinase and bivalirudin or streptokinase and UFH. The primary endpoint of mortality was not reduced by bivalirudin, although reinfarction was reduced by 30% within 96 hours. There was a small increase in mild to moderate bleeding with bivalirudin. If this agent is selected, the dose is 0.75 mg/kg bolus, followed by an infusion at 1.75 mg/kg/h with a PTT not to exceed 75 seconds. Thus, according to ACC/AHA guidelines, it is reasonable to consider bivalirudin as an alternative to UFH in patients who have been treated with streptokinase and have a known heparin allergy (class IIa indication).
Fondaparinux is a synthetic heparin pentasaccharide that acts through antithrombin to selectively inhibit factor Xa. The dose is 2.5 mg/d given subcutaneously. Its efficacy in STEMI was evaluated in the OASIS-6 trial. In this trial patients were classified as stratum 1, meaning UFH was not indicated, or stratum 2, meaning UFH was indicated. Patients in stratum 1 were randomly assigned to fondaparinux or placebo. Patients in stratum 2 were randomly assigned to fondaparinux or UFH. Primary PCI was performed in 0.2% of stratum 1 patients and 53% of stratum 2 patients. Thromrbolysis was performed in 78% of stratum 1 patients and 16% of stratum 2 patients. The most common thrombolytic used was streptokinase and a quarter of patients did not receive any form of reperfusion therapy. For the entire population (strata 1 and 2), there was a significant reduction in the primary endpoint of death or reinfarction at 30 days (9.7 vs.11.2%, HR 0.86). When the strata were evaluated individually, there was a significant reduction in the primary endpoint in strata 1 (11.2% vs. 14.0%, HR 0.79) but not strata 2 (8.3% vs. 8.7%, HR 0.96). The lack of benefit in strata 2 was due to worse outcomes in patients undergoing primary PCI. The use of fondaparinux in primary PCI was associated with an increase in guiding catheter thrombosis and in coronary dissection, no reflow, and abrupt closure. Based on these results, the use of fondaparinux as the sole anticoagulant during primary PCI is a class III recommendation. Currently, if a patient receives fondaparinux then undergoes PCI, the ACC/AHA recommends additional IV treatment with an anticoagulant that possesses anti-IIa activity such as heparin, enoxaparin, or bivalirudin. Based on results of the FUTURA/OASIS 8 trial, standard-dose heparin is preferable to low-dose heparin as there is no increase in major bleeding and a statistically significant reduction in CV death, MI, TVR, and stent or catheter thrombosis.
Low-molecular-weight heparin (LMWH) may be considered as an alternative to UFH in patients undergoing fibrinolysis (class IIb recommendation). The ASSENT-3 trial tested various antithrombotic regimens with weight-based tenecteplase. LMWH was represented by enoxaparin initiated by 30-mg intravenous bolus, followed by 1.0 mg/kg subcutaneously every 12 hours up to discharge or revascularization, for a maximum of 7 days. Tenecteplase plus enoxaparin reduced a composite endpoint of death, in-hospital reinfarction, or in-hospital refractory ischemia compared to UFH. The ExTRACT-TIMI 25 trial randomized 20,506 STEMI patients undergoing fibrinolysis to either enoxaparin throughout the index hospitalization or UFH for 48 hours. The primary endpoint was death or nonfatal MI at 30 days. The enoxaparin group had a significant reduction in the primary endpoint, primarily due to a significant reduction in reinfarction (3.0% vs. 4.5%). The enoxaparin group also had a significant reduction in urgent revascularization (2.1% vs. 2.8%). Unfortunately, the interpretation of this study is limited by the difference in duration of therapy between the two groups. The mean duration of enoxaparin therapy was 7 days, whereas the mean duration of therapy with UFH was 48 hours. Currently, based on ACC/AHA guidelines, patients who undergo reperfusion with fibrinolytics should receive anticoagulant therapy with UFH, enoxaparin, or fondaparinux for a minimum of 48 hours and preferably the duration of the index hospitalization, up to 8 days (class I recommendation). If more than 48 hours of therapy is required, enoxaparin or fondaparinux are preferable to UFH because of the risk of heparin-induced thrombocytopenia (class I recommendation). For patients undergoing PCI after having received enoxaparin, additional dosing in the cardiac catheterization lab should be based on the time at which the last dose was received. If the last dose was within 8 hours, no additional enoxaparin should be given. If the last dose was given 8 to 12 hours earlier, or if the patient has received less than 2 subcutaneous doses, an IV dose of 0.3 mg/kg should be given. If the last dose was given >12 hours earlier, another 1 mg/kg subcutaneous dose should be administered (class I recommendation). For patients who are >75 years old or who have renal insufficiency (creatinine >2.5 mg/dL for men and >2.0 mg/dL for women) the use of a LMWH is not recommended (class III recommendation).
Anti-Ischemic Agents
Nitroglycerin and beta-blockers are first-line antiischemic agents (class I recommendation). Nitroglycerin is initiated by a 0.4-mg sublingual tablet (repeated several times every 5 minutes if symptoms persist and hypotension does not develop), followed by intravenous infusion of 10 to 20 µg/min (titrated up until resolution of symptoms or until hypotension develops). An intravenous dose of 200 µg/min is considered a ceiling, although the dose is occasionally increased to 400 µg/min if needed. Notably, large-scale randomized trials have failed to observe any reduction in mortality with nitroglycerin, and indications for this agent in the setting of STEMI are thus to relieve ischemia, hypertension, or pulmonary congestion. Nitrates should not be utilized in the setting of a suspected right ventricular (RV) infarction as venous pooling can result in significant hypotension. Sildenafil use within 24 hours of presentation is a class III recommendation against the use of nitroglycerin. Similar caution is applicable to other PDE5 inhibitors.
Beta-blockers are administered along with nitroglycrerin and help to blunt the reflex tachycardia that may occur from their use. A large body of evidence supports the use of beta-blockers (class I recommendation). A pooled analysis from the prefibrinolytic era in >24,000 patients (dominated by the ISIS-1 trial) documented a 14% reduction in 7-day mortality (23% long-term reduction) among patients who received beta-blockade. Interestingly, in the reperfusion era, only the CAPRICORN trial with carvedilol has shown a mortality reduction with a beta-blocker. Other trials in the reperfusion era have only shown reduced reinfarction or recurrent ischemia.
Oral beta-blockers should be administered in the first 24 hours to all STEMI patients without a contraindication (class I recommendation). Medical contraindications to beta-blockers include significant conduction abnormalities (marked first-degree AV block, or second/third-degree block), asthma, or decompensated heart failure. The use of beta blockade with metoprolol in the COMMIT trial was associated with an increased risk of precipitating cardiogenic shock. Blunting the heart rate in patients with compensatory tachycardia likely resulted in this finding. Current guidelines highlight caution in patients at risk for cardiac shock. Risk factors include age > 70, systolic blood pressure <120 mm Hg, heart rate > 110 or < 60 bpm, and delay in reperfusion. Patients with a contraindication to beta-blocker therapy within the first 24 hours of STEMI should be reevaluated for candidacy throughout the hospitalization (class I recommendation). If there are contraindications to beta-blocker use, a nondihydropyridine calcium channel blocker (i.e., diltiazem or verapamil) may be considered to control anginal symptoms. Morphine (1 to 5 mg intravenously) is also considered a class I anti-ischemic medication and is particularly helpful for anxious patients and to control the pain of infarction.
Secondary Prevention
Inhibition of the Renin–Angiotensin–Aldosterone System
Angiotensin-converting enzyme inhibitors (ACE-I) are indicated in all STEMI patients with a left ventricular ejection fraction (LVEF) <40% or in patients with a preserved LVEF and hypertension, diabetes, or chronic kidney disease (class I recommendation). The ACC/AHA also recommends that ACE-I be started and continued indefinitely in any STEMI patient who is not low risk (low risk defined as normal LVEF, well-controlled cardiovascular risk factors, and revascularization has been performed). Low-risk patients recovering from STEMI have a class IIa indication for ACE-I therapy. An angiotensin receptor blocker (ARB) may be used in the place of an ACE-I in patients who are ACE-I intolerant unless there is a history of angioedema (class I recommendation). If an ARB is used, candesartan and valsartan are the preferred agents as they have demonstrated efficacy in STEMI patients.
Aldosterone blockade is also beneficial in a select group of post-MI patients. The EPHESUS trial evaluated the efficacy of long-term aldosterone blockade with eplerenone in acute MI patients with a LVEF < 40%. Patients were enrolled 3 to 14 days after acute MI. Inclusion in the study required either heart failure (rales, a third heart sound, or pulmonary congestion on chest radiography) or diabetes. Patients with a serum creatinine >2.5 or a serum potassium > 5 were excluded. Study participants were randomly assigned to eplerenone or placebo. Patients in the eplerenone group had a significant reduction in mortality (14.4% vs. 16.7%), cardiovascular mortality (12.3% vs. 14.6%), and combined cardiovascular mortality or hospitalization for cardiac events (26.7% vs. 30.0%). Currently, the ACC/AHA recommends the use of aldosterone blockade in post-MI patients who: have an EF < 40%, are already receiving therapeutic doses of ACE-I and beta-blockade, and have either heart failure or diabetes, assuming the patient does not have significant renal dysfunction or hyperkalemia (class I recommendation).
Vasopressors, Inotropes, and Antiarrhythmics
Inotropic or vasopressor agents (i.e., dopamine, dobutamine, norepinephrine) are not used routinely in the setting of STEMI, as these agents can cause increased myocardial ischemia. If possible, patients in cardiogenic shock should first receive mechanical support with an intra-aortic balloon pump (IABP). If the patient does not respond to an IABP, an inotrope or vasopressor can then be added. Dobutamine may also be used for RV infarction that does not respond to intravenous fluids.
Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) should be treated with immediate unsynchronized electric shock. If the arrhythmia is refractory to electric shock, 300 mg of IV amiodarone should be administered followed by repeat electric shock (class IIa recommendation). When present, electrolyte and acid–base disturbances should be corrected. For shock refractory VT or VF, treatment with boluses of IV procainamide may be considered (class IIb recommendation). Prophylactic antiarrhythmic therapy in the setting of STEMI is not recommended (class III recommendation).
A patient with sustained polymorphic VT or symptomatic sustained monomorphic VT should receive unsynchronized electric shock (class I recommendation). Treatment of stable sustained monomorphic VT includes Amiodarone 150 mg IV over 10 minutes or synchronized electrical cardioversion (class I recommendation). For refractory polymorphic VT, attempts should be made to reduce adrenergic stimulation and myocardial ischemia with beta-blockers, IABP use, and reperfusion therapy (class IIa recommendation). Procainamide therapy may be considered if the VT is not associated with angina, pulmonary edema, or hypotension (class IIb recommendation).
Lipid Management
A fasting lipid profile should be checked within 24 hours of presentation in all patients with STEMI. Target LDL-C is <100 mg/dL (class I recommendation) and further reduction in LDL-C to <70 mg/dL is reasonable (class IIa recommendation). Regardless of LDL-C level HMG-CoA reductase inhibitors (statins) should be initiated in all patients with STEMI (class I recommendation). Based on clinical trial data, atorvastatin has been studied most extensively at a dose of 80 mg daily. Gemfibrozil, niacin, and fish oil should be considered for patients with a low HDL (class IIa recommendation).
Secondary Prevention—Goals
Smoking—complete cessation and with no environmental exposure
Blood pressure control—<140/90 and <130/80 for patients with diabetes or chronic kidney disease
Physical activity—30 min/d, 5 d/wk (preferably 7 d/wk)
BMI—8.5 to 24.9 kg/m2
Waist circumference—men < 40 inches and women <35 inches
Diabetes management—HbA1c <7%
Influenza vaccination—patients with cardiovascular disease should receive an annual influenza vaccination
Mechanical Devices
Intra-Aortic Balloon Pump
The use of an IABP is recommended for patients in cardiogenic shock. A pulmonary artery catheter should also be used during the management of cardiogenic shock. Shock can result from early pump failure that may respond to multivessel revascularization. Hemodynamic instability may remain after revascularization for a period of time. The differential for hemodynamic instability after revascularization includes hypovolemia, anemia, RV infarction, and mechanical complications. Mechanical complications to consider in every AMI patient with hemodynamic instability/cardiogenic shock include papillary muscle dysfunction/rupture, ventricular septal defect, and myocardial free wall rupture with tamponade. Electrical complications may occur during the course of the AMI, either before or after reperfusion, and an IABP may be considered for unstable ventricular arrhythmias. Moreover, an IABP is indicated for patients with recurrent myocardial ischemia that is refractory to pharmacologic therapy until revascularization may be performed. Therefore the IABP is used for stabilization until revascularization, as a bridge to CABG or repair of a mechanical complication, or for continued hemodynamic instability after revascularization.
Temporary Right Ventricular Pacing
RV pacing may be indicated in the management of conduction disturbances. Bradyarrhythmias are common in the setting of inferior MIs, especially with RV involvement. If such a patient exists who does not respond to chronotropic agents such as dobutamine or dopamine, temporary RV pacing may be needed until electrical and hemodynamic stability returns. Complete heart block can be seen with anterior MIs that involve a large septal perforator branch.
Implantable Cardioverter–Defibrillator Implantation in Patients after STEMI
Several trials have been performed to evaluate the efficacy of implantable cardioverter–defibrillator (ICD) insertion in patients after MI. The following discussion outlines some of these trials and discusses the current ACC/AHA guidelines.
The DINAMIT trial evaluated the role of prophylactic ICD insertion in patients with a LVEF of ≤ 35% and a history of MI in the preceding 6 to 40 days. Patients with NYHA class IV heart failure, sustained VT > 48 hours after MI, and who had received CABG or three-vessel PCI as management for their MI were excluded. While the patients who received an ICD had less death due to arrhythmia compared to controls, at a mean follow-up of 30 months, there was no significant difference in all-cause mortality (7.5% vs. 6.9%). The IRIS trial also evaluated the benefit of prophylactic ICD insertion in patients with a recent MI (5 to 31 days). Results again showed no difference in all-cause mortality between patients who did and did not receive an ICD.
MADIT II evaluated the benefit of delaying ICD insertion until at least 1 month after MI. The trial enrolled 1,232 patients with a history of MI more than 30 days prior to enrollment (more than 90 days if bypass surgery was performed) and an LVEF ≤ 30%. Patients were randomized to prophylactic ICD implantation or standard medical therapy.
At an average follow-up of 20 months, ICD implantation significantly reduced all-cause mortality (14.2% vs. 19.8% for standard therapy). This survival benefit was entirely due to a reduction in SCD (3.8% vs. 10.0% for standard therapy).
The SCD-HeFT trial randomized 2,521 patients with ischemic or nonischemic cardiomyopathy, a LVEF ≤ 35%, and NYHA class II or III heart failure to ICD implantation, amiodarone, or placebo. At 5 years, all-cause mortality was significantly reduced in patients who received an ICD (29% vs. 36% with placebo). This benefit did not differ based on the etiology of heart failure, but was nullified in patients with NYHA class III symptoms. Amiodarone therapy was not beneficial.
Based on multiple studies, including the above trials, the current ACC/AHA guidelines for ICD insertion are as follows: An ICD should be inserted in any patient with VF or sustained hemodynamically significant VT that occurs 48 hours after acute MI (class I recommendation). This is provided that the arrhythmia is not secondary to recurrent ischemia or MI. Patients whose MI occurred at least 40 days prior, who have a LVEF of ≤ 35% and NYHA class II or III heart failure, should also receive an ICD (class I recommendation). In addition, patients with NYHA class I heart failure are candidates for ICD insertion if their LVEF is ≤ 30% at least 40 days after MI (class I recommendation). If a patient receives CABG, the LVEF and NYHA functional class should be reassessed 90 days after the procedure to determine ICD candidacy. An ICD should not be inserted in patients without ventricular arrhythmia 48 hours after STEMI and who have an LVEF > 35% 40 days after the MI or 3 months after bypass grafting (class III recommendation).
Wearable cardioverter–defibrillators have been used in patients who are considered at risk for SCD but do not meet the above criteria, such as patients waiting for reassessment of LVEF after coronary artery revascularization. The efficacy of wearable cardioverter–defibrillators was initially evaluated by a clinical trial that consisted of two components. The first component (the WEARIT study) enrolled 177 patients with a LVEF < 30% and NYHA class III or IV heart failure. The second component (the BIROAD study) enrolled 112 patients with a recent MI or recent CABG who were considered high risk for SCD but did not meet criteria for an ICD or refused implantation. At the end of the 901 patient month observational period, there were six successful and two unsuccessful defibrillation attempts. Both unsuccessful attempts were because the device was being worn incorrectly. There were six instances of SCD during the study; in five cases the device was not being worn and in one case it was being worn incorrectly. While wearable cardioverter–defibrillators are currently not recognized in the ACC/AHA guidelines, there appears to be benefit to their use in select patients.
Pericarditis
Acute pericarditis develops in 10% to 15% of AMI patients within 2 to 4 days. Pain that occurs within the first 24 hours of a STEMI is unlikely to be secondary to pericarditis. Perircardial effusion is common, although frank tamponade is infrequent. Unlike ischemic pain, pericarditic pain is more often sharp, worse with deep inspiration and recumbency. A pericardial friction rub is helpful in making the diagnosis, although it is not always present. The ECG may show diffuse ST elevation with PR depression. The treatment consists of aspirin (650 mg, three to four times per day). Alternatively, 600 to 800 mg of ibuprofen four times per day may be used. Indomethacin is effective, although it should be avoided given its reduction in coronary blood flow and gastrointestinal toxicity. Colchicine, 0.6 mg twice a day, may be added to aspirin or ibuprofen for refractory cases. Steroids should be avoided if possible, because of the concern for increased risk of myocardial rupture.
Dressler syndrome is the finding of pleuropericarditis 1 to 2 weeks after the infarct. This inflammatory reaction occurs in 1% to 2% of AMI patients. The clinical course is usually benign, although constrictive pericarditis may result. The treatment is generally the same as for acute pericarditis.
PREDISCHARGE RISK STRATIFICATION
Stress testing is a widely used mechanism for risk stratification after AMI. In STEMI patients who do not receive a left heart catheterization, exercise testing to assess for myocardial ischemia should be performed while in the hospital or early after discharge (class I recommendation). If the patient has baseline abnormalities that prevent ECG interpretation, echocardiography or nuclear imaging should be added to standard exercise testing (class I recommendation). It should also be considered prior to the hospital discharge of STEMI patients in order to guide cardiac rehabilitation or determine the significance of a lesion seen on coronary angiography (class IIb recommendation). Exercise testing should not be performed within 2 to 3 days of STEMI or in patients with UA, decompenrsated heart failure, or life-threatening arrhythmias (class III recommendation). It should also not be used to risk stratify patients who have already received a cardiac catheterization (class III recommendation).
Every patient after an AMI should have an assessment of left ventricular function. Patients with moderate to severe left ventricular dysfunction are at higher risk for adverse events. For these individuals, the use of beta-blockers and ACE inhibitors is especially important. Additionally, the implantation of an ICD may be indicated, after a period of convalescence from an AMI.
SUMMARY
STEMI is a distinctly different clinical entity than UA/NSTEMI, with a higher early mortality. Risk models such as the TIMI and GRACE risk scores are used to determine prognosis, not to guide therapy. In STEMI there is a limited window of opportunity (generally <12 hours and preferably <3 to 6 hours) for revascularization to preserve left ventricular function and improve survival. Primary PCI is preferred over fibrinolytic therapy if it can be performed rapidly and potentially even if there is a delay in transport to a PCI center. Certain patient characteristics and logistical considerations favor one approach over another. Fibrinolysis is a viable option if primary PCI is not available in a timely fashion. High-risk patients who receive fibrinolysis should be transferred as soon as possible to a facility that is capable of performing PCI. Failed fibrinolysis is characterized by continued ischemia, hemodyrnamic instability, or incomplete ST-segment resolution.
All STEMI patients should receive aspirin, a thienorpyridine or P2Y12 receptor antagonist, and an anticoagulant agent such as heparin, enoxaparin, fondaparinux, or bivalirrudin. The dose of heparin varies depending on the use of adjunctive medicines. Because of the risk of coronary complications and catheter thrombosis, fondaparinux should not be used as the sole anticoagulant during PCI. Clopidogrel, prasugrel, or ticagrelor should be given to all STEMI patients who receive PCI, with the duration of therapy depending on the type of stent placed. GP IIb/IIIa inhibitors may be beneficial during PCI, although their role during fibrinolyrsis is less clear. Beta-blockers and nitrates are first-line antirischemic agents and should be used judiciously. Calcium channel blockers may be used if the patient has a significant intolerance to beta-blockers. Statins are important across the spectrum of ACSs, including STEMI. ACE inhibitors are indicated when the patient becomes hemodynamically stable (usually not before 6 hours), and are especially useful for anterior MIs, in the presence of left ventricular dysfunction, and in diabetics. ARB may be substituted if the patient is intolerant to ACE-I, unless there is a history of angioedema. Aldosterone antagonists such as eplerenone are indicated in post-MI patients who have an EF < 40%, are already receiving therapeutic doses of ACE-I and beta-blockade, and have either heart failure or diabetes, assuming the patient does not have significant renal dysfunction or hyperkalemia.
AMI patients should be monitored for the development of mechanical and electrical complications. Mechanical complications are life-threatening conditions that necessitate the use of an IABP and urgent surgical repair. Electrical complications may necessitate the use of antiarrhythmics and potentially RV pacing for bradyarrhythmias. Once patients are revascularized, they should be risk stratified in order to identify residual ischemia and determine the need for future ICD implantation.
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QUESTION AND ANSWERS
Questions
1. In the TIMI risk score model, the variable that has the strongest prediction for subsequent 30-day mortality is:
a. Low body weight (i.e., <67 kg)
b. Tachycardia
c. Advanced age (i.e., >75 years)
d. Killip class II to IV at presentation
e. Left bundle branch block (LBBB) at presentation
2. Which of the following is not included in the differential diagnosis for electrocardiographic ST elevations?
a. ST-elevation myocardial infarction (STEMI)
b. Left ventricular aneurysm
c. Hypokalemia
d. Pericarditis
e. Left ventricular hypertrophy
3. Risk factors for intracranial hemorrhage (ICH) during administration of fibrinolytics include all of the following except:
a. Uncontrolled hypertension
b. Advanced age
c. Female gender
d. Preexisting coagulopathy
e. Morbid obesity
4. All of the following are class III recommendations except:
a. Performing revascularization of non-infarctrelated arteries at the time of primary percutaneous coronary intervention (PCI)
b. Waiting for cardiac biomarkers to return before making the diagnosis of a STEMI
c. Administering fibrinolytics to asymptomatic patients more than 24 hours from the onset of chest pain
d. The use of a low-molecular-weight heparin (LMWH) along with fibrinolytics in patients with renal insufficiency
e. The use of an oral ACE inhibitor within 24 hours of an anterior STEMI
5. The fibrinolytic agent associated with the lowest rate of ICH is:
a. Alteplase (tPA)
b. Streptokinase
c. Reteplase (rPA)
d. Tenecteplase (TNK-tPA)
6. Fondaparinux should not be used as the sole anticoagulant during PCI because there is a risk of:
a. Coronary artery dissection
b. Catheter thrombosis
c. No reflow
d. All of the choices
7. If a patient with STEMI and normal renal function is going for primay PCI and last received enoxaparin 9 hours prior, the additional enoxaparin dose that should be given is:
a. 0.5 mg/kg IV
b. 0.3 mg/kg IV
c. 1 mg/kg subcutaneously
d. 0.3 mg/kg subcutaneously
8. Which STEMI patient has a class I indication for risk stratification by exercise stress testing before discharge?
a. A 75-year-old male who received fibrinolysis 48 hours ago and is now chest pain free without ST elevations on his ECG
b. A 65-year-old female who received a PCI to her left anterior descending artery 4 days ago and had no other stenosis >50% on coronary angiogram
c. A 52-year-old male who received fibrinolysis 6 days ago and has pulmonary rales and a third heart sound on physical exam.
d. A 68-year-old female who received thrombolysis for an inferior STEMI 4 days ago and has had intermittent atrial fibrillation
9. Which patient should receive an implantable cardioverter–defibrillator (ICD)?
a. A 65-year-old female with an anterior STEMI 24 hours ago, for which she received a PCI to her left anterior descending (LAD), who is now having multiple runs of asymptomatic sustained ventricular tachycardia (VT)
b. A 52-year-old male with a left ventricular ejection fraction (LVEF) of 35% by echocardiogram performed 60 days after coronary artery bypass grafting (CABG)
c. A 58-year-old male with a LVEF of 25% and a normal electrophysiologic study 45 days after PCI for an anterior STEMI
d. A 62-year-old female with an EF of 40% 6 months after CABG
10. What is the goal waist circumference in women after a STEMI?
a. <20 inches
b. <25 inches
c. <30 inches
d. <35 inches
Answers
1. Answer C: Advanced age (>75 years) predicts the worst outcome for 30-day mortality and receives 3 points in the risk model. The other variables listed receive 1 to 2 points each. Hypotension (i.e., systolic blood pressure <90 mm Hg) at presentation is also a high-risk variable and receives 3 points in the risk model.
2. Answer C: Among the electrolyte abnormalities, hyperkalemia, not hypokalemia can cause ST elevations that mimic STEMIs.
3. Answer E: Low body weight, not morbid obesity, is a risk factor for ICH.
4. Answer E: The use of an oral ACE inhibitor is generally recommended early in the hospital course as long as the patient is hemodynamically stable (usually at least 6 hours after presentation). In contrast, the use of an intravenous ACE inhibitor during the first 24 hours is not recommended. Non–infarct-related coronaries should not be revascularized except in the setting of cardiogenic shock. Fibrinolytics are recommended for STEMI within 12 hours from the onset of chest pain. Administering fibrinolytics 12 to 24 hours from the onset of chest pain is generally not recommended, however individuals with stuttering chest pain during this time period may still be eligible to receive fibrinolytics. In individuals with renal insufficiency who also receive fibrinolytics, the use of UFH is preferred over LMWH.
5. Answer B: Among the various fibrinolytic agents, streptokinase does not necessitate the use of heparin. This may help to explain the smaller incidence of ICH seen with this agent.
6. Answer D: The OASIS-6 trial showed that the use of fondaparinux during PCI was associated with an increased incidence of catheter thrombosis, coronary artery dissection, no reflow, and acute vessel closure.
7. Answer B: According to the ACC/AHA guidelines, if the last dose was within 8 hours, no additional enoxaparin should be given. If the last dose was given 8 to 12 hours earlier, an IV dose of 0.3 mg/kg should be given. If the last dose was given >12 earlier, another 1 mg/kg subcutaneous dose should be administered.
8. Answer D: Because this patient is over 72 hours removed from her event and has not yet received left heart catheterization, an exercise stress test is indicated to assess for inducible ischemia. Patients should not receive exercise stress testing within 48 to 72 hours of STEMI. In addition, risk stratification by exercise testing is a class III indication in patients whose coronary angiogram during PCI showed no significant stenosis other than the target lesion. Patients with unstable angina, decompensated congestive heart failure (CHF), or life-threatening arrhythmias should not receive exercise stress testing.
9. Answer C: ICD implantation is indicated if a patient is >40 days post-myocardial infarction (MI) or 90 days post-CABG and the EF is ≤ 30% (New York Heart Association [NYHA] Class I) or ≤35% (NYHA Class II or III). Ventricular fibrillation (VF) or hemodynamically significant ventricular tachycardia (VT) > 48 hours after MI is also an indication for ICD implantation.
10. Answer D: For secondary prevention following acute MI, the goal waist circumference for men is <40 inches and women is < 35 inches.