cardiac literature 2007″>American Journal of Emergency Medicine (2008) 26, 817-833

Review

The Cardiac Literature 2007

Amal Mattu MD^a,?, Michael C. Bond MD^a, William J. Brady MD^b,?

^aDepartment of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA

^bDepartment of Emergency Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA

Received 2 February 2008; accepted 10 February 2008

1. Acute coronary syndromes: evaluation

Assali AR, Teplitsky I, Ben-Dor I, et al. Prognostic importance of Right ventricular infarction in an acute myocardial infarction cohort referred for contemporary percutaneous reperfusion therapy. Am Heart J 2007;153: 231-237.

The authors evaluated 666 consecutive patients with ST-elevation myocardial infarction who underwent Primary percutaneous coronary intervention within 12 hours. They excluded patients with cardiogenic shock and patients with contraindications to routine therapies. Of the remaining patients, 329 had anterior wall myocardial infarction (MI), 264 had inferior (230 inferior + 34 lateral) wall MI, and 73 had right ventricular (RV) MI. The authors noted that mortality at hospital discharge, at 30 days, and at 6 months was highest in patients with RV MI (5.5%, 9.6%, and 12.3%, respectively). Mortality statistics for patients with anterior MI (2.4%, 4.6%, and 7.3%, respectively) were intermediate, and mortality for patients without any RV involvement were the lowest (0.8%, 1.1%, and 3%, respectively). Morbidity was also noted to be much higher in the RV MI group. Within the RV MI group, complete revascularization of the RCA including the major RV branch was associated with higher rates of RV function and improved 30-day mortality (odds ratio, 0.4), highlighting that these patients do have a much better outcome when treated aggressively.

The primary message in this article is that the emergency physician must continuously consider RV involvement in the STEMI patient and aggressively manage these patients, including emergent resuscitation. The most reliable method of diagnosing RV involvement in the ED with electrocardiogram (ECG) is to obtain right-sided precordial leads and review for ST-segment elevation . There are also some very specific (though not that sensitive) clues to RV MI using Standard ECG lead placement as well. When a patient with an inferior or lateral MI is noted to have STE in lead V₁ with simultaneous ST depression in V₂, there almost always is RV involvement-recall that lead V₁ essentially serves as a right-sided lead. Another valuable electrocardiographic clue, the magnitude of STE in lead III relative to the other inferior leads, that is,

* Corresponding authors.

E-mail addresses: [email protected] (A. Mattu), [email protected] (W.J. Brady).

when the STE in lead III is significantly more prominent than in lead II (eg, more than 2-3 mm more prominent), an RV MI is highly likely.

Hollander JE, Robey JL, Chase MR, et al. Relationship between a clear-cut alternative noncardiac diagnosis and 30-day outcome in emergency department patients with chest pain. Acad Emerg Med 2007;14:210-215.

The authors of this study compared chest pain patients discharged from the ED with specific etiologies (eg, gastric reflux, chest wall pain, pneumonia, pulmonary embolism [PE], and others) vs those individuals with “chest pain, uncertain cause.” The investigators enrolled 1995 patients in an urban ED with potential acute coronary syndrome (ACS). Overall, 77 (4%) had a final diagnosis of acute myocardial infarction. There were 599 patients (30%) that were given a specific noncardiac diagnosis. Compared to the patients who were not given a specific noncardiac diagnosis (ie, a diagnosis of “chest pain, uncertain cause”), the specific noncardiac diagnosis patients did have a lower rate of adverse outcomes by 30 days (risk ratio, 0.45). However, the primary teaching point is that these patients still had a 30-day event (death, myocardial infarction, or need for urgent revascularization) rate of 4%. These individuals included 2 patients who were diagnosed with Musculoskeletal pain, 3 patients with gastrointestinal reflux disease, 4 patients with pneumonia, and 12 patients with other assorted noncardiac diagnoses (11 of whom died). It is uncertain how many of these patients actually died of ACS as other possible causes of death could have included pneumonia, PE, and others.

This study shows that even when patients do not have ACS as a cause of their pain, they still can have a poor 30-day outcome. Therefore, all patients with chest pain of uncertain cause or chest pain with a clear-cut noncardiac diagnosis require close scrutiny and medical follow-up.

Gallagher MJ, Ross MA, Raff GL, et al. The diagnostic accuracy of 64-slice computed tomography coronary angiography compared with stress nuclear imaging in emergency department Low-risk chest pain patients. Ann Emerg Med 2007;49:125-136.

Goldstein JA, Gallagher MJ, O‘Neill WW, et al. A randomized controlled trial of multi-slice coronary computed tomography for evaluation of acute chest pain. J Am Coll Cardiol 2007;49:863-871.

0735-6757/$ - see front matter doi:10.1016/j.ajem.2008.02.009

Hollander JE, Litt HI, Chase M, et al. Computed tomography coronary angiography for rapid disposition of low-risk emergency department patients with chest pain syndromes. Acad Emerg Med 2007;14:112-116.

The authors of the first article compared multidetector computed tomographic angiography vs stress nuclear imaging (rest and stress sestamibi) in patients who were considered low risk by the Reilly/ Goldman criteria and had negative serial ECGs and cardiac biomarkers. The CTA was considered positive if the patients had coronary stenosis greater than 50% or calcium score greater than 400; Stress testing was considered positive if there were reversible Perfusion defects. If patients had positive tests, they went for cardiac catheterization to evaluate for significant stenoses. Patients who did not have a catheterization were followed to determine if they had adverse cardiac events by 30 days. Of

85 patients evaluated, only 7 (8%) actually had the target condition (positive catheterization or adverse event by 30 days). The CTA detected 6 of the 7 patients (86% sensitivity), whereas stress testing identified 5 of the 7 individuals (71% sensitivity). The limitations of this study include lack randomization and gold standard as well as small number of participants. And, of course, the sensitivity of CTA for significant coronary obstruction was rather disappointing.

In the second study, the same authors randomized 197 low-risk chest pain patients to either receive multislice CTA or “standard of care” evaluation, defined here as serial ECGs and biomarkers followed by stress testing. Patients with stenoses greater than 70% noted on CTA underwent catheterization, whereas patients with intermediate lesions or nondiagnostic scans underwent nuclear stress testing. Patients with minimal disease noted on CTA were discharged and followed for 6 months. All of these patients did well. Overall, CTA ruled in (using catheterization as the gold standard) or ruled out (based on 6-month follow-up) significant coronary disease in 75% of patients studied. However, 25% of the patients undergoing CTA ended up in the indeterminate group, thus requiring another dose of radiation via nuclear medicine testing. Twelve percent of these patients then received a third dose of radiation in the catheterization laboratory because of an abnormal stress test. Overall, the CTA was helpful in many patients, and the authors indicate that use of CTA reduced costs by approximately ?$300 per patient evaluated on average, but it did mandate increased radiation

monitor in the ED actually make a difference in these patients? With ED overcrowding, many institutions will see multiple admitted CP patients waiting indefinitely for inpatient beds, occupying cardiac monitored ED beds, whereas sicker patients sit in the waiting room or in the hallways, forcing the ED to go on EMS diversion. Do all those CP patients truly need monitored beds in the ED?

The authors evaluated 992 consecutive ED patients with a primary complaint of CP who underwent cardiac monitoring in the ED. The population was certainly not low risk-14% had MI and 12% unstable angina as their final hospital diagnosis. Only 17 patients (1.7%) of all patients developed a serious dysrhythmia in the ED. On the basis of evaluation of the patients who developed dysrhythmias, the authors derived a decision rule stating that patients can be removed from cardiac monitoring if they are (1) pain-free at the initial physician assessment and (2) have a normal or nonspecific ECG result. The rule had 100% sensitivity for serious dysrhythmias, and application of the rule would have allowed immediate removal (right after the ECG) of 29% of these CP patients from cardiac monitoring. The authors provide a few cautions. This study was only a “derivation” study, and it should not necessarily indicate a change in practice until after the “validation” study is performed. Secondly, because the number of patients developing serious dysrhythmias was low (17 patients), the confidence interval for the rule varies from 80% to 100%. Finally, although the study hospital was a tertiary care hospital, it is unclear how long the patients stayed in the ED. Presumably if patients had a short ED length of stay, the chances of a dysrhythmia in the ED might be a bit lower than if they had a prolonged ED length of stay.

Nevertheless, this is one more piece of evidence that we are unnecessarily conservative in our decisions regarding which “chest pain, possible ACS” patients require cardiac Telemetry monitoring. We certainly should consider removing more of these patients from their monitors in favor of hallway spaces if there are potentially sicker patients waiting for beds. In addition, even if the admitting physicians choose to use cardiac monitoring on these patients upstairs, it should not obligate us to conduct cost, time, and resource-inefficient practices in the ED.

1. Acute coronary syndrome risk factors and special populations

exposure in 25% of patients in whom the study was nondiagnostic.

In the third study, the authors evaluated low-risk chest pain patients- defined as TIMI score of 2 or less with a negative result in ECG, with CTA. If the CTA was negative (stenosis, b50%; calcium score, b400), patients were discharged and followed for 30 days. The authors evaluated 54 patients, of whom they were able to discharge 46 from the ED after the negative CTA. None had adverse events in the 30-day period. Although this study was the least rigorous of the 3 studies (in that it was nonrandomized and there was no control group), it is possible that this type of study, if reproduced on larger scales, will lead to changes in physician practice. Recall that early studies of CT for PE were all less than ideal, but multiple outcomes studies were then published that essentially showed that if the CT of the lungs is normal, the Adverse event rate for a few months is extraordinarily low. We anticipate that if more of these studies stating that outcomes after a negative CTA for chest pain are good, physicians will start accepting CTA as part of their standard chest pain evaluation and disposition protocols.

Gatien M, Perry JJ, Stiell IG, et al. A clinical decision rule to identify which chest pain patients can safely be removed from cardiac monitoring in the emergency department. Ann Emerg Med 2007;50:136-143.

Should every admission for “chest pain, suspected ACS” be admitted to a monitored bed? The bulk of evidence indicates that the yield of inpatient cardiac monitoring is extremely low, but inpatient practice is outside our control-yet impacts the ED with reducED throughput-so dogma often dictates that even low-risk chest pain (CP) patients are placed in telemetry beds at admission. However, we do have control over our own ED, so we should pose this same question to ourselves: how often does that cardiac

Hsu CW, Chen HH, Sheu WH, et al. Initial Serum glucose level as a prognostic factor in the first acute myocardial infarction. Ann Emerg Med 2007;49:618-626.

Prior studies [1-3] have indicated that serum hyperglycemia at the time of admission (regardless of diabetes mellitus [DM] status) is an independent predictor of cardiac outcome including CHF, cardiogenic shock, and death in patients with acute myocardial infarction. This study is likely the first such article on this topic in an emergency medicine journal.

The authors performed a 3-year retrospective study looking at 198 patients (159 men, 39 women) with a first acute myocardial infarction (MI). Patients were separated into 3 groups based on their initial serum glucose level as follows: the first group had normal glucose levels less than 140 mg/dL, the second group had intermediate serum glucose levels of 140-200 mg/dL, and the third group had high levels greater than 200 mg/ dL. After adjusting for sex, age, DM status, reperfusion therapy, and infarct subtype, the investigators then evaluated the 1-month and 1-year mortality of the patients.

The investigators found a direct correlation between admission glucose levels and 1-month mortality as follows: odds ratio for mortality in the intermediate glucose level group was 3.87 and in the high glucose level group was 5.16. High glucose level was also an important risk factor for 1-year mortality (hazard ratio, 3.08).

The presence of hyperglycemia may simply be caused by the release of stress hormones, which in turn may be the result of severe Cardiac damage. If hyperglycemia is simply associated with more significant MIs, does that indicate that we need to treat those patients with antiischemic agents more aggressively? Or is there evidence that aggressive treatment of the

hyperglycemia itself can improve outcomes? Perhaps it is too early to tell. However, the reader should be reminded that early research on stroke and sepsis found an association between hyperglycemia and outcomes in patients with these conditions, and based on subsequent research, it is now generally accepted that aggressive management of serum glucose levels is associated with improved outcomes. It just may be that future studies will produce the similar findings for patients with acute MI also.

Zarich SW, Nesto RW. Implications and treatment of Acute hyperglycemia in the setting of acute myocardial infarction. Circulation 2007;115:e436-e439.

This “Clinician Update” provides a nice review of the association of acute hyperglycemia with ACS. Here are some key points that the authors make.

• Acute hyperglycemia (generally defined as serum glucose greater than 140 mg/dL) is present in up to 50% of all STEMI patients despite only 20% to 25% of STEMI patients have previously diagnosed DM.
• As noted in the previous article, elevated serum glucose at admission is an independent predictor of both inhospital and long-term outcome regardless of whether the patient has previously diagnosed DM. In fact, for every 18 mg/dL increase in glucose level, there is a 4% relative increase in mortality for non-DM patients. When the admission glucose is greater than 200 mg/dL, the mortality is similar between DM and non-DM patients with acute MI.
• Acute hyperglycemia in STEMI patients is associated with reduced TIMI grade 3 flow (a measure of coronary artery patency) before intervention and is the most important predictor of the absence of coronary perfusion; it is also associated with diminished ST-segment resolution after PCI, and these effects appear to be most associated with acute hyperglycemia rather than chronic hyperglycemia.
• Hyperglycemia is associated with adverse effects on Platelet function, thrombolysis, and coagulation.
• In contrast to hyperglycemia (which is generally associated with “relative insulinopenia”), hyperinsulinemia experimentally is asso- ciated with enhanced Myocardial blood flow, and Insulin infusion at the time of reperfusion appears to have a “profound” antiinflamma- tory effect and appears to reduce infarct size.
• The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines [4] state that “tight glucose control in DM during and after STEMI has been shown to lower acute and 1-year mortality rates” although the findings appear to be true for non- DM patients as well.
• The authors indicate that there is an upcoming study sponsored by the NIH that will evaluate the use of insulin infusions in STEMI patients. “In the meantime,” they say, “it appears prudent for the clinician to monitor and restore normoglycemia as soon as possible after presentation to optimize outcomes in STEMI.”

1. Management of STEMI

Wijeysundera HC, Vijayaraghavan R, Nallamothu BK, et al. Rescue angioplasty or repeat fibrinolysis after failed Fibrinolytic therapy for ST-segment myocardial infarction. J Am Coll Cardiol 2007;49:422-430.

Clinicians that will be spending time working in rural environments or internationally will find this article most useful. It is important to remember that outside of certain institutions with interventional capability (both nationwide and worldwide), fibrinolytic therapy is still the most common form of acute reperfusion therapy that is used for STEMI. Unfortunately, fibrinolytic therapy restores normal coronary flow in only half of STEMI patients by 90 minutes, and fibrinolytics are probably even less effective in elderly patients and those with cardiogenic shock. So what do you do in STEMI patients when fibrinolytic agents fail?

The traditional choices for failed fibrinolysis have been repeat dosing vs “rescue” PCI. The authors of this article performed a meta-analysis of randomized trials of failed fibrinolysis in STEMI patients to determine the most appropriate strategy. They included 8 trials enrolling 1177 patients with variable follow-up periods (hospital discharge through 6 months). The authors found that neither rescue PCI nor repeat fibrinolytic use was associated with reductions in mortality, but rescue PCI was associated with significant risk reductions in heart failure and reinfarction compared to conservative treatment and repeat fibrinolytic use. Both therapies were associated with increased risk of minor bleeding. The authors conclude that the best evidence appears to favor rescue PCI over consecutive fibrinolytic agents when patients with STEMI fail primary fibrinolysis.

Srinivas VS, Skeif B, Negassa A, et al. Effectiveness of glycoprotein IIb/IIIa inhibitor use during primary coronary angioplasty: results of propensity analysis using the New York State percutaneous coronary intervention reporting system. Am J Cardiol 2007;99:482-485.

Montalescot G, Antoniucci D, Kastrati A, et al. Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta- analysis on individual patients‘ data with long-term follow-up. Eur Heart J 2007;28:443-449.

The last ACC/AHA guidelines for management of STEMI [4] list abciximab as a class IIa medication in patients getting Primary PCI; in contrast, eptifibatide (Integrilin, Schering-Plough, Kenilworth, NJ) and tirofiban (Aggrastat, Medicure Pharma, Somerset, NJ) have a class IIb rating. Here are 2 more articles that have come out recently supporting the use of glycoprotein inhibitors (GPI) in primary PCI for STEMI.

In the first article, the researchers evaluated a state registry involving all patients at 41 centers in New York state who underwent primary PCI for STEMI between 2000 and 2002, including 7321 patients. Of these patients, 5748 (78.5%) patients received adjunctive GPI. Overall, patients who received the GPIs had lower Inhospital mortality (3% vs 6.2%). The reduction in mortality held true for low-to-moderate risk as well as high-risk STEMI patients.

The second article was a meta-analysis of studies of abciximab use in primary PCI of STEMI, but they focused only on patients who received stents (vs Balloon angioplasty). They evaluated 1101 patients who had been randomized to either abciximab (n = 550) or placebo (n = 551) with up to 3 years of follow-up. They found that patients who had received abciximab had a lower mortality rate (10.9% vs 14.3%) and reinfarction rate (2.3% vs 5.5%). Major bleeding was not significantly different (2.5% with abciximab vs 2% with placebo). When the Composite end point of death or reinfarction was used, the study demonstrated a 37% relative risk reduction with abciximab use in patients undergoing primary stenting for acute STEMI. The authors point out that “this risk reduction translates into 61 major events prevented for every 1000 patients treated” and that when DM patients were specifically assessed, the benefit increased “5-fold in diabetics with 347 deaths or MI prevented for every 1000 diabetics treated.”

Rakowski T, Zalewski J, Legutko J, et al. Early abciximab administration before primary percutaneous coronary intervention improves infarct-related artery patency and left ventricular function in high-risk patients with anterior wall myocardial infarction: a randomized study. Am Heart J 2007;153:360-365.

A veritable avalanche of literature is being published supporting the use of GPIs in conjunction with primary PCI for STEMI. The literature seems to be most supportive for using abciximab. What is still uncertain is whether abciximab should be started as soon as possible or whether it can simply be started in the catheterization laboratory. In this study, the researchers sought to answer this question. They randomized 59 nonshock patients with first- time anterior wall STEMI to receive either early abciximab (initiated before

transfer to catheterization laboratory) or late abciximab (initiated immedi- ately before catheterization). The average time from randomization to angiography for both groups was approximately 60 to 65 minutes.

Patients in the early group had improved infarct-related patency, improved 60-minute ST-segment resolution, a lower extent of myocardial injury, and less adverse 30-day myocardial remodeling. The authors did not evaluate mortality, although the study was probably too small to detect differences in this parameter.

The main limitations to the study are its small size and fairly focused group evaluated-nonshock patients with first-time anterior wall STEMI. In addition, it was not double-blinded or placebo-controlled. One would also expect potentially greater benefits to early abciximab in these high-risk patients who had a fairly long duration to angiography (60-65 minutes). Nevertheless, the study supports the concept that earlier use of abciximab in high-risk STEMI patients with delays to PCI is beneficial.

Raveendran G, Ting HH, Best PJ, et al. Eptifibatide vs abciximab as adjunctive therapy during primary percutaneous coronary intervention for acute myocardial infarction. Mayo Clin Proc 2007;82:196-202.

As noted above, the in 2004 the ACC/AHA guidelines for management of STEMI [4] stated that GPIs were “reasonable” before PCI; however, they did not classify the glycoprotein inhibitors as being equivalent. They gave abciximab a class IIa rating, whereas eptifibatide and tirofiban received class IIb ratings. Since that time, more published studies have been reported supporting these latter 2 drugs. Many of the studies, such as this one, are “noninferiority” studies where the researchers try to prove that the study drug is as good as, and not worse than, the standard drug.

Briefly, 576 patients with either STEMI or new Left bundle branch block received primary PCI with adjunctive GPI. Three hundred twenty- seven patients (57%) received abciximab (Ab) and 249 (43%) received eptifibatide (Ep). The choice of agent was left to the cardiologists. Rates of inhospital death or MI did not differ between the 2 groups (Ab, 5%; Ep, 6%), even after adjustment for various patient characteristics. Estimated rates of death, MI, or target vessel revascularization at 1-year follow-up were similar (Ab, 22.3%; Ep, 20.9%). There was no difference in Bleeding complications either. The conclusion of the study was that there is no difference in outcomes with either abciximab or eptifibatide when used as adjunctive therapy for primary PCI.

Bates ER. Role of intravenous beta-blockers in the treatment of ST-elevation myocardial infarction. Circulation 2007;115:2904-2906. (editorial).

?-Blockers (BBs) have been part of the ED treatment protocol for ACS patients for quite some time. This editorial nicely reviews the literature on early use of BBs in patients with STEMI and explains why serious doubts have recently emerged in the cardiologic community regarding whether we should actually be giving these medications in the early course of ACS. Recall that last year in this series, we discussed a review article in the Canadian Journal of Cardiology [5] that also addressed this topic, but it is worth addressing this issue once more. Bear in mind that the following discussion pertains to early (ie, within the first few hours) management of patients with ACS, and it does not relate to continued inhospital and long- term use of BBs.

The traditional teaching that BBs are beneficial in the early course of ACS is largely based on 3 studies from the 1980s in which BBs were used as monotherapy for STEMI. This hardly seems relevant to modern-day management of patients with ACS who are aggressively managed with antiplatelet medications, antithrombins, and aggressive reperfusion. The more recent GUSTO-1 trial (1998) [6] used fibrinolytic agents for STEMI followed by early intravenous (IV) atenolol. The use of the early IV BBs in this study was associated with increased death, heart failure, shock, recurrent ischemia, and pacemaker use than when patients received early oral administration. This trend occurred despite exclusion of patients with

preexisting hypotension, bradycardia, or signs of heart failure. In spite of the results of the GUSTO-1 trial, recommendations for early use of IV BBs persisted.

In 2005, the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) [7] was published and cast serious doubt on whether this traditional practice has merit. The COMMIT study evaluated nearly 46 000 patients with suspected STEMI. The researchers compared early intravenous BB use followed by continued oral metoprolol therapy (average, 15 days) vs placebo. There was no significant difference between the 2 groups for mortality. The BB group did have a slight reduction in rate of reinfarction (2.0% vs 2.5%) and ventricular fibrillation (2.5% vs 3.0%). However, the BB group had a higher rate of developing cardiogenic shock (5.0% vs 3.9%, occurring mainly within 24 hours). Cardiogenic shock was most likely to occur in elderly patients (N70 years of age), patients with systolic blood pressure less than 120 mm Hg, patients with a heart rate greater than 110 beats per minute-note that this last exclusion represents a current target group for which we would most want to use BBs-and patients with Killip class greater than 1 (evidence of Mild heart failure). In addition, patients receiving the BB had an increased rate of developing heart failure requiring treatment (14.1% vs 12.7%), increased rate of developing persistent hypotension (6.0% vs 2.9%), and increased rate of developing bradycardia (5.4% vs 2.2%). The recommendations of the authors of both the GUSTO-1 trial and the COMMIT trial was to withhold ?-blockers early in the course of treatment and to instead initiate oral ?-blocker therapy later in the course (still within 24 hours) once the patient’s hemodynamic status is deter- mined to be stable. Initiation of the ?-blockers orally within 24 hours still meets the Joint Commission on the Accreditation of Healthcare organizations “core measures” that everyone is concerned about. There seems to be a myth that the core measures require BBs to be given in the ED. This is, in fact, false…the core measures require BBs to be initiated within 24 hours of ED arrival, not necessarily in the ED [8].

The author of this editorial concludes with a few thoughts that seem to be slowly gaining support in the cardiologic community: “It may be time to remove routine intravenous ?-blocker therapy from our acute treatment protocols for STEMI and instead focus on initiating oral ?-blocker (and angiotensin-converting enzyme inhibitor) therapy the next day when hemodynamic stability has been established. This technique would remove the early risk associated with ?-blockers while retaining their hospital benefit on reinfarction and ventricular fibrillation rates.”

Kraft PL, Newman S, Hanson D, et al. Emergency physician discretion to activate the cardiac catheterization team decreases Door-to-balloon time for acute ST-elevation myocardial infarction. Ann Emerg Med 2007;50: 520-526.

Kurz MC, Babcock C, Sinha S, et al. The impact of emergency physician- initiated primary percutaneous coronary intervention on mean door-to- balloon time in patients with ST-segment elevation myocardial infarction. Ann Emerg Med 2007;50:527-534.

Singer AJ, Schembekar A, Visram F, et al. Emergency department activation of an interventional cardiology team reduces door-to-balloon times in ST-segment elevation myocardial infarction. Ann Emerg Med 2007;50:538-544.

Magid D, Bradley E. Emergency physician activation of the cath lab: saving time, saving lives. Ann Emerg Med 2007;50:535-537. (editorial accom- panying above articles).

There has been a great deal of interest in the cardiologic and emergency medicine communities in finding ways of reducing the time to balloon inflation in patients with STEMI going for primary PCI. The ACC/ AHA guidelines have for years recommended a 90-minute maximum for door-to-balloon inflation (D2B) in these patients (ie, the time from hospital

arrival to balloon inflation in the infarct-related artery). The contention is that primary PCI loses its advantage over immediate fibrinolytic agents if the time to balloon inflation is more than 90 minutes; if D2B becomes greater than 90 minutes, it can be argued that immediate use of fibrinolytic therapy would have been a better choice of treatment. Unfortunately, most patients in the United States that are treated with primary PCI for STEMI do not have D2B in the infarct-related artery within 90 minutes.

One idea that is gaining popularity as a method of decreasing the time from D2B is to have the treating emergency physician “make the call” in mobilizing the catheterization laboratory team. Traditionally, this decision is made by the interventional cardiologist. By having the emergency physician solely take this responsibility, it eliminates the time that would be required to contact the cardiologist, discuss the case, and transmit the ECG and then have that cardiologist call the interventional team. Part of the reason that many hospitals have not moved to having the emergency physician make the call is the concern that it will lead to frequent mobilization of the team for patients who are not having an STEMI, that is, overcall of the diagnosis, in comparison to when the cardiologists make the decision. Earlier this year, a prospective study published in the cardiologic literature demonstrated significant reductions in D2B times (113.5 minutes reduced to 75.5 minutes on average) with only rare overcall of STEMI by the emergency physicians [9]. In the November 2007 issue of Annals of Emergency Medicine, 3 more trials were published (with an accompanying editorial) attesting to the use of emergency physician activation of the team for STEMI.

The first study, by Kraft et al, was a retrospective study from Beaumont Hospital (Royal Oak, MI), a 279-bed community hospital in Michigan. Cardiologist activation of the team was associated with an average D2B time of 147 minutes between June 2004 and November 2004 (37 patients). Because of the long D2B time, the hospital changed to an emergency physician-activated protocol, without any other changes. In the subsequent 6 months (51 patients), the average D2B time was 106 minutes, a reduction of 41 minutes. The reduction was especially notable during off- hours (average reduction of D2B by 55 minutes during nights/weekends vs 25 minutes during normal hours when the team and cardiologist were already inhouse). All patients in the emergency physician-activated cohort received Emergency revascularization, indicating no overcalls by the emergency physicians.

The second study, by Kurz et al, was a larger study performed at Advocate Lutheran General Hospital (Park Ridge, IL), a 608-bed tertiary care center in Illinois between January 1, 2004, and August 31, 2006. Consecutive patients with STEMI totaling 172 were enrolled. During the first 19 months, cardiologists were responsible for team activation (95 patients), and during the final 13 months, emergency physicians were responsible for team activation (77 patients). During the emergency physician-activation phase, D2B time improved by an average of 40 minutes (similar to the above study), from 131 to 91 minutes. Percutaneous coronary intervention was “inappropriately initiated” by the emergency physician in only one case, and no patients with STEMI were overlooked, resulting in 100% sensitivity and 99.6% specificity. The rate of D2B within 90 minutes increased in this study from 22% to 56% with emergency physician team activation.

The final study, by Singer et al, was performed at Stony Brook University Medical Center, a 500-bed subUrban academic medical center in Stony Brook, New York, that has both an emergency medicine residency and an interventional cardiologic fellowship. Like the studies above, this was another “before-and-after” trial, in which 43 patients with STEMI were evaluated during the 2 years before implementation of a new emergency physician-activation protocol, and 54 patients with STEMI were evaluated after implementation of the new protocol (study periods were 2001-2004). The researchers found that when the new protocol of emergency physician- activation of the team was used, the average D2B time decreased from 176 minutes (almost 3 hours when the cardiologists were responsible for team activation) to 108 minutes-a 68-minute reduction. The difference persisted regardless of whether the PCI was done during off-hours vs normal work hours. The proportion of patients getting their D2B within 90 minutes increased from 2.8% to 29.0%. The authors do not comment on the rate of

emergency physician overcall in this study. The authors go on to say that they continued to use this protocol and with some further refinements, they have managed to reduce D2B time an additional 20 minutes in 2006, with a resulting 90-minute D2B success rate of 52%.

The accompanying editorial summarizes the data above and concludes with a nice perspective: “Fifteen years ago…debate centered on whether fibrinolytic therapy should be administered by emergency physicians or cardiologists.” This question has long since been resolved. Emergency physicians have shown that they can accurately identify reperfusion- eligible STEMI patients and that Door-to-needle times are shorter when they initiate therapy themselves. It is important that we insure that “emergency physician activation, like emergency physician administration of fibrinolytic therapy, becomes the standard of care across the country.” The only way that this will happen, though, is for emergency physicians to become the experts in electrocardiography. We must commit ourselves to continued improvement in ECG interpretation./a> and be confident to make the call.

Larson DM, Menssen KM, Sharkey SW, et al. “False-positive” cardiac Catheterization laboratory activation among patients with suspected ST-segment elevation myocardial infarction. JAMA 2007;298:2754-2760.

Masoudi FA. Measuring the quality of primary PCI for ST-segment elevation myocardial infarction—time for balance. JAMA 2007;298:2790-2791.

With all the focus on getting patients with STEMI to the catheterization laboratory (CL) as soon as possible, one must certainly wonder if patients are being overdiagnosed in the rush. We have become quite expert at avoiding the missed MIs (“false-negatives”) based on ECG misinterpreta- tion. But how often are we (emergency physicians and cardiologists) making “false-positive” diagnoses of STEMI and sending patients who do not have infarction to the CL? The researchers in this study from the Minneapolis Heart Institute (Minneapolis, MN) looked at that question.

The researchers evaluated 1345 patients with presumed STEMI between March 2003 and November 2006 that were referred for primary PCI to Abbott Northwestern Hospital in Minneapolis (Minn). Patients were referred in from 30 community and Rural hospital EDs as well as the primary PCI hospital ED. When the diagnosis of STEMI was made at the referring hospital, CL activation occurred before transfer, and the patients would bypass the ED at Abbott Northwestern Hospital and proceed directly to the CL where the patient was met by the interventional cardiologist and the team. In cases of diagnostic uncertainty, the ECG could be faxed to the cardiologist for review before CL activation.

In light of the articles discussed above, I should point out that the treating cardiologists consistently agreed with the emergency physicians regarding the decision to perform angiography on these patients. Of the 1345 patients in the study, 5 patients died before catheterization and 3 individuals were excluded because of renal failure. Of the remaining 1337 patients, the interventional cardiologists only declined to take 2 patients for angiography because they read the ECG as nondiagnostic.

Regarding ECG interpretation, in patients who had negative catheter- izations and negative biomarkers, the most common etiologies of false- positive CL activations were early repolarization, nondiagnostic ECGs, pericarditis, previous MIs, LBBB, and left ventricular (LV) hypertrophy. One could surmise that improved skills in ECG interpretation could have prevented a handful of these CL activations.

The researchers report that the prevalence of false-positive CL activations was between 9% and 14% depending on the definition used (based on coronary anatomy and also cardiac biomarker results). This high rate of false-positive activation, especially when one considers the financial consequences of unnecessary CL activation as well as the toll on the team members. In addition, angiography is certainly not a benign procedure. But to be fair, there are some problems with the researchers’ retrospective decisions about which patients needed invasive management and that ones did not. As the editorial points out, in some patients “such as those

ultimately diagnosed with stress cardiomyopathy (also known as Takotsubo cardiomyopathy) or coronary artery spasm, coronary angiography was likely an appropriate diagnostic test even though PCI was ultimately not performed.” In addition, one of the criteria they used to define a “false- negative” CL activation was the inability to find a “Culprit coronary artery.” This occurred in 14% of the patients; however, 2.7% of these patients died within 30 days. This is not the normal prognosis for noncardiac patients in an ED, so it is probably good that the patients were treated aggressively. There are some other limitations as well, but the key teaching points are emergency physicians and cardiologists frequently overcall STEMI, and we need to consider the consequences of these overcalls. It is certainly better to overcall than to undercall STEMI, but is a 10% overcall rate acceptable? Future studies, editorials, and guidelines will address this issue, but at the very least, one way that we can improve these numbers will certainly be with improved skills in ECG interpretation.

1. Management of non-STE ACS

Stone GW, Bertrand ME, Moses JW, et al. Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the acuity timing trial. JAMA 2007;297:591-602.

Mahaffey KW, Harrington RA. Optimal timing for use of glycoprotein IIb/ IIIa inhibitors in acute coronary syndromes: questions, answers, and more questions. JAMA 2007;297:636-639. (editorial accompanying above article).

There is increasing support that GPIs are beneficial before primary PCI in patients with STEMI, as noted above. However, there is debate regarding the optimal timing of the initiation of these medications. Should we start the medications early in the ED? Or is it acceptable to wait and let the cardiologists start the medications in the catheterization laboratory? There is conflicting evidence on this topic.

In this study, 9207 “moderate and high-risk” ACS patients were randomized to receive either early “upstream” administration or deferred selective administration of GPIs. The 30-day outcome of composite Ischemic events (death, MI, or unplanned revascularization for ischemia) was not statistically different between the 2 groups (7.9% in the deferred group vs 7.1% in the upstream group; P = .044), although the deferred group was noted to have a significantly lower rate of major bleeding (4.9% vs 6.1%; P b .001). Although the study did not determine an optimal strategy, it did indicate that there is no clear benefit to early administration of GPIs, and in fact, it suggests that there may be increased bleeding complications.

The authors of the editorial, who report affiliations with several pharmaceutical companies, present a nice counterinterpretation of the study. They point out that although the 7.9% vs 7.1% difference was not statistically different, it did represent a 12% trend to worse outcome with the deferred medication group. They also point out that, on average, patients received PCI approximately 5 hours after randomization, so there is probably not much actual difference between the early and delayed group. This last point, in our opinion, represents the biggest problem with the study. In actual practice, according to the CRUSADE registry [10], the average time to PCI for non-STE ACS patients was 23.4 hours during weekdays and

46.3 hours during weekends. It is possible, though unproven, that longer duration of therapy with GPIs before PCI would be more beneficial. The final problem was that the choice of medications was left to the discretion of the treating physicians-unfractionated heparin vs Low Molecular Weight Heparin, the choice of which GPI, and others. In addition, 10% had already been started on a GPI before randomization.

We do not usually include studies in this series that have so many major confounders, but given its message and the related attention, it is worth knowing about it. In the end, we still do not have an answer. The most sensible thing to do is to simply discuss with your cardiologist whether they want the GPI started in the ED.

Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST- elevation myocardial infarction: executive summary. Circulation 2007;116:803-877.

The 2007 revision of the ACC/AHA set of the guidelines regarding the management of patients with Non-ST-segment elevation acute coronary syndromes (NSTE-ACS) was published August 14, 2007. This includes both patients with non-STEMI (NSTEMI) as well as patients with high-risk unstable angina (not the low-risk “chest pain, rule-out MI” patients who comprise most the admissions). This mammoth 74-page document represents the work of several major US organizations in collaboration, including the ACC, AHA, American College of Emergency Physicians (ACEP), the Society for Cardiovascular Angiography and Interventions, and the Society of thoracic surgeons. As noted above, appropriate process and systems of care are best established in a multidisciplinary fashion. Thus, we would encourage discussion with the local cardiovascular consultants in the development of appropriate systems of care for the ACS patient.

Onset and recognition of symptoms

• The document includes a section that provides an appropriate reminder that ACS need not present with CP. “Anginal equivalents” can include dyspnea, diaphoresis, extreme fatigue, and others. The elderly are known also to present with stroke symptoms, syncope, or change of mental status.
• One third of all acute MIs present with symptoms other than CP, and this is especially common in the elderly, in women, in patients with DM, and in patients with prior heart failure.
• The authors specifically bring up the fact unexplained dyspnea is common among acute MI patients and is often misdiagnosed.
• The 5 most important factors in the initial history, in order of importance, are (1) nature of anginal symptoms, (2) history of coronary artery disease (CAD), (3) male sex, (4) older age, and (5) increasing number of Traditional risk factors. Note here that the initial history is most important and that risk factor profile (or lack of risk factors) has limited use in the acute setting.
• The response of the symptoms to nitroglycerin (NTG) and/or a

“gastrointestinal (GI) cocktail” is neither sensitive nor specific.

• • • Electrocardiograms 1% to 6% of normal ECGs are associated with NSTEMI, and 4% are associated with unstable angina. Approxi- mately 4% of acute MI patients have STE isolated to the posterior leads. Isolated posterior STEMI does qualify for Emergent reperfusion therapy; therefore, obtain posterior leads on patients when the initial standard ECG is nondiagnostic and the clinical suspicion for infarction is high.
  1. Initial evaluation and management-early risk stratification
     • A 12-lead ECG should be obtained and shown to an experienced emergency physician as soon as possible after ED arrival, with a goal of within 10 minutes for all patients with chest pain or anginal equivalent presentations.
     • If the initial ECG is nondiagnostic, but symptoms are highly concerning for ACS, serial ECGs, initially at 15-minute to 30-minute intervals should be considered to evaluate for possible evolving changes. Note that they do not specify the duration of serial ECGs, but the important point is that the second ECG should be done within 30 minutes. Continuous 12-lead ECG monitoring is a reasonable alternative to serial electrocardiography.
     • “It is reasonable” to obtain leads V₇ to V₉ when the initial ECG is nondiagnostic. Look for posterior involvement when symptoms are concerning, but the initial ECG is nondiagnostic. Specifically, these leads often help identify left circumflex occlusions, which sometimes are not apparent on the standard 12-lead ECG.
  2. Initial evaluation and management-immediate management
     • In patients with suspected ACS in whom follow-up ECGs and biomarkers remain normal, a stress test should be performed to provoke ischemia. This can be done in the ED, in a chest pain unit,

     or in the hospital. If the patient is risk-stratified to low-risk, Outpatient stress testing within 72 hours is reasonable.

     • • • • The article also mentions that when patients are discharged from Chest pain units for outPatient evaluation and stress testing, follow-up within 72 hours is usually “appropriate.”
         • Low-risk patients who are referred for outpatient stress testing should be given “appropriate precautionary pharmacotherapy (eg, aspirin [ASA], sublingual NTG, and/or ?-blockers) while awaiting results of the stress test.”
         • In patients risk-stratified to low-risk or intermediate-risk for CAD who have normal ECGs and biomarkers, coronary CT angiography is reasonable as an alternative to stress testing.
       1. Early hospital care-antiischemic and analgesic therapy
          • Initiate sublingual (SL) NTG as usual, and consider IV NTG for persistent ischemia after 3 SL tablets, for patients with CHF and for patients with hypertension.
          • Nitrates should not be given to patients with (1) systolic blood pressure of less than 90-mm Hg or more than a 30-mm Hg decrease from the patient’s baseline; (2) bradycardia less than 50 beats per minute; (3) tachycardia greater than 100 beats per minute unless heart failure is present; (4) RV MI; or (5) who have taken sildenafil within 24 hours or tadalafil within 48 hours (note that the timing of Nitrate use after vardenafil is uncertain at this time).
          • Oral ?-blockers should be initiated within the first 24 hours for patients who do not have 1 or more of the following: (1) signs of acute CHF; (2) evidence of low-output state; (3) increased risk for cardiogenic shock (risk factors for cardiogenic shock in NSTE-ACS include N70 year old; systolic blood pressure, b120 mm Hg; pulse rate, N110 beats per minute or pulse rate b60 beats per minute, and increased time since onset of symptoms of NSTE-ACS); or (4) other relative contraindica- tions to ?-blockade (PR interval N240 milliseconds, second or third degree heart block, or active/decompensated reactive airway disease).
            • It may be reasonable to administer IV ?-blockers at the time of presentation for hypertension if the patient has none of the 4 types of contraindications listed above.
            • Listed as class III, Level of evidence A, are IV ?-blockers: “It may be harmful to administer IV ?-blockers to unstable angina/ non-ST-segment elevation MI (UA/NSTEMI) patients who have contraindications to ? blockade, signs of CHF or low- output state, or other risk factors for cardiogenic shock.” Note that class III indicates “risk greater than or equal to benefit, treatment should not be performed because it is not helpful, may be harmful, no additional studies needed;” level of evidence A means the recommendation is based on the highest level of evidence.
            • The primary change in the ED use of ?-blockers is largely based on the results of the 2005 COMMIT study [7]. In that study, early IV use of ?-blockers was found to increase the chances of patients developing cardiogenic shock, and there was no overall benefit on mortality. Recommendations now are focused on simply initiating the ?-blockers within 24 hours to confer the beneficial effects-reduction in ventricular dysrhythmias, sudden death, and reinfarction-but without the dangers of predisposing to cardiogenic shock.
          • Patients with continuing or frequently recurring ischemia in whom ?-blockers are contraindicated should receive verapamil or diltiazem in the absence of significant LV dysfunction or other contraindications.
          • An angiotensin converting enzyme inhibitor (ACE-I) should be administered orally within 24 hours to patients with CHF or LV ejection fraction less than 40% unless the patient is hypotensive; an angiotensin receptor blocker is an acceptable alternative agent if the patient cannot take an ACE-I. Note that there is no need to administer these in the ED; in fact, there’s evidence that routine

          early administration of ACE-Is in ACS increases the incidence of cardiogenic shock.

          • • • Intravenous morphine “is reasonable” in patients with uncontrolled ischemic chest pain despite NTG provided that other therapies are also being used to manage the ischemia. The recommendation for morphine was downgraded from class I (significant support that the intervention provides benefit) in the last guidelines to class IIa (reasonable support that the intervention provides benefit) this time, largely based on a study [11] from the CRUSADE registry that showed an association between use of morphine and mortality in ACS patients.
              • Other than ASA, nonsteroidal antiinflammatory agents (includ- ing cyclooxygenase 2 selective agents) should be discontinued during the short-term treatment and hospitalization because of increased risks of mortality, reinfarction, hypertension, CHF, and myocardial rupture.
            1. Antiplatelet therapy
               • The ASA therapy should be initiated as soon as possible, ideally in the nonenteric coated form.
               • If the patient cannot tolerate ASA because of a severe allergy, use clopidogrel (300 mg loading dose followed by maintenance dose).
               • If the patient has a history of GI bleeding, add a proton pump inhibitor when giving ASA and/or clopidogrel.
               • For patients in whom early invasive therapy is planned, ASA should be supplemented with either clopidogrel (300 mg loading dose) or an IV GPI before angiography. There is controversy in the emergency medicine literature regarding whether we truly need to be initiating these medications in the ED. Many cardiac surgeons prefer that clopidogrel, especially, be withheld until the need for bypass surgery has been ruled out (based on the catheterization results) because of the perioperative bleeding complications associated with clopidogrel. However, there is increasing support for the early administration of these medica- tions, and we anticipate that this will become standard practice in coming years.
               • If a GPI is chosen, the guidelines recommend that abciximab be used only if there is no significant delay to catheterization. If there is going to be a delay to catheterization or if the decision to perform catheterization is uncertain, then eptifiba- tide or tirofiban is preferable. Again, please note that, if the patient is going to be managed conservatively without mechanical intervention, the data do not support GPI therapy in general.
               • The guidelines allow for combined use of ASA, clopidogrel, and GPI in addition to plus anticoagulants as a reasonable choice as well. Specifically, the guidelines state that this combined treatment plan may be reasonable if a patient has received ASA and clopidogrel (plus anticoagulants) and has persistent or recurrent Ischemic pain. Still, the guidelines appear to make this recom- mendation optional rather than mandatory or “highly recom- mended,” for any specific patient groups.
               • If a conservative (noninvasive) strategy is chosen, clopidogrel should be added to ASA and anticoagulant therapy “as soon as possible after admission.”
            2. Anticoagulant therapy
               • Anticoagulant therapy should be added to antiplatelet medications as soon as possible after presentation in high-risk patients with NSTE-ACS, not the usual, low-risk chest pain patients who comprise most admissions.
               • If invasive therapy is planned, use either enoxaparin or unfractionated heparin . These have the highest class rating (class I) and level of evidence (level A). Alternatively, bivalirudin or fondaparinux can be used (class I, level B).
               • If Conservative therapy is planned, give either enoxaparin or UFH. Fondaparinux is also reasonable. All 3 are listed as class I medications.
               • If conservative therapy is planned and the patient has an increased risk of bleeding (or Heparin-induced thrombocytopenia), fondapar- inux is preferred.
            3. Initial conservative vs initial invasive strategies (note that this section is very relevant to EDs that are not supported by on-site invasive catheterization laboratories).
               • An Early invasive strategy (ie, diagnostic catheterization with intent to perform PCI or coronary artery bypass graft [CABG] if needed) is indicated in NSTE-ACS patients who have refractory pain or hemodynamic or electrical instability.
               • An early invasive strategy is also indicated in NSTE-ACS patients who have an elevated risk for “clinical events” (ie, bad outcomes). These risk factors include the following emergency medicine relevant issues.
                 • Elevated troponin level;
                 • New or presumably new ST segment depression;
                 • Signs or symptoms of CHF;
                 • New or worsening Mitral regurgitation;
                 • Hemodynamic instability;
                 • sustained ventricular tachycardia;
                 • Percutaneous coronary intervention within 6 months;
                 • Prior CABG; and/or
                 • High risk score (eg, TIMI score or Global Registry of Acute coronary events [GRACE] score)
               • Note that if you are managing a patient with NSTE-ACS in the ED and the patient has any of the factors noted above, it would be reasonable to transfer that patient from the ED to a hospital that can perform PCI.
               • An early invasive approach is not recommended (class III) in patients with extensive comorbidities (eg, pronounced liver disease, respiratory failure, or cancer) in whom the risks of revascularization and the comorbid conditions are likely to outweigh the benefits of revascularization.
            4. Special patient groups and populations
               • Women, elderly patients, and patients with chronic kidney disease. There is no special short-term management here except to consider dosing renally excreted medications based on estimated creatinine clearance because these patient groups often end up with bleeding complications because of overdosing of antiplatelet and antic- oagulant medications.
                 • The elderly in particular are at higher risk for inappropriate dosing of these medications. Remember that the elderly often have altered pharmacokinetics because of reduced muscle mass, renal and/or Hepatic dysfunction, and reduced volume of distribution.
               • Patients with diabetes. There is no special short-term manage- ment here.
               • Cocaine and methamphetamine users. Short-term management is similar to standard ACS patients except that calcium channel blockers are preferred to ?-blockers. Fibrinolytics are acceptable for STEMI if rapid PCI is not available.
                 • Listed as a class IIb (possibly helpful, not significant evidence) is the use of combined ?-blocking and ?-blocking agents (eg, labetalol) for patients with hypertension (systolic blood pressure great than 150 mm Hg) or sinus tachycardia (pulse rate, N100 beats per minute) provided that the patient has received a vasodilator such as NTG or a calcium channel blocker within the prior hour. This last recommendation is a concerning statement that, in our opinion, should not have been included. Although the guidelines support this statement as class IIb with level of evidence C (“very limited data”), many clinicians will take this statement as an endorsement of using labetalol. There is limited evidence stating that labetalol is helpful with some data suggesting the potential for harm.
                 • Also of concern is that there are no statements regarding the potential dangers of using ?-blockers in the setting of true cocaine-chest pain (ie, vasoconstriction from cocaine).
               1. Cardiac arrest

               SOS-KANTO Study Group. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study. Lancet 2007;369:920-926.

               Ewy GA. Cardiac arrest—guideline changes urgently needed. Lancet 2007;369:882-884. (editorial accompanying above article)

               The authors of this study performed a Multicenter observational study of 4068 patients who had out-of-hospital cardiac arrest. The study was performed in the Kanto region of Japan and included 58 emergency hospitals and emergency medical services (EMS) units. Patients were evaluated between September 2002 and December 2003, so the 2000 AHA Resuscitation guidelines were probably being used. Patients younger than 18 years and those with terminal illnesses and/or do-not-resuscitate (DNR) orders were excluded. Four hundred thirty-nine patients (11%) received cardiac-only resuscitation from bystanders, 712 (17%) received conventional cardiopulmonary resuscitation with compressions plus ventilations and 2917 (72%) received no bystander CPR. A major point is that most “eligible” cardiac arrest victims did not receive any bystander compressions or ventilations.

               The researchers evaluated many subgroups of the patients, including whether the probable cause of the cardiac arrest was cardiac vs noncardiac (eg, respiratory arrest or drug overdose), findings at EMS arrival (eg, apnea, initial arrest rhythm), time to bystander intervention, time to first automatic external defibrillator analysis, and whether the bystander was a lay person or an off-duty medical worker. Initial resuscitation definitions included chest compressions only (Cardiac resuscitation [CR], chest compressions only) and standard CPR (chest compressions with mouth- to-mouth ventilations). The primary end point they evaluated was Favorable neurologic outcome after 30 days.

               The number of patients with favorable neurologic outcomes at 30 days was better overall if the patients received some kind of intervention-CR or CPR vs no intervention (5.0% vs 2.2%). It was somewhat surprising to note that the addition of mouth-to-mouth ventilations was not associated with any benefit in any subgroup. In fact, in patients who were presumed to have been more likely having a primary cardiac cause of the arrest (patients apneic and/ or with ventricular fibrillation [VF]/pulseless ventricular tachycardia [VT] rhythm at EMS arrival), CR was actually associated with more frequent favorable neurologic outcomes than traditional CPR (6.2% vs 3.1% for apneic patients; 19.4% vs 11.2% for VF/pulseless VT rhythms). Patients who had resuscitation started by bystanders within 4 minutes of arrest also fared better for Good neurologic outcomes if they received only CR instead of CPR (10.1% vs 5.1%).

               The accompanying editorial appropriately discusses the limitations of current resuscitation guidelines-a major flaw of which is that they do not distinguish between primary cardiac arrest (because of a sudden cardiac event) and respiratory arrest (because of a primary pulmonary problem such as drug overdose or drowning). In the latter group, traditional bystander CPR still makes sense. However, when patients have sudden cardiac arrest because of primary cardiac events, there are several reasons why the addition of mouth-to-mouth ventilation is ineffective and possibly harmful as follows:

               The need for mouth-to-mouth ventilations greatly decreases the frequency of bystander-initiated Resuscitative efforts, which is a very important determinant of survival.

            5. Mouth-to-mouth ventilations significantly decrease the rate of chest compressions. It is estimated that bystanders performing 2 ventila- tions have to stop compressions for at least 16 seconds. Past studies have indicated that the traditional 15:2 CPR ratio results in a compression rate of 60/min [12], markedly less than the currently recommended 100/min.
            6. Mouth-to-mouth ventilations result in increased positive intrathoracic pressure that reduces venous return and cardiac output and coronary and cerebral blood flow.
            7. With sudden primary cardiac arrest, the pulmonary veins and left side of the heart are already filled with oxygenated blood and so the ventilations do not improve oxygenation.

               Bohm K, Rosenqvist M, Herlitz J, et al. Survival is similar after standard treatment and chest compression only in out-of-hospital bystander

               cerebral perfusion. Conclusion of Ewy deserves to be repeated here: “It is interesting that [CCOR], a technique that has not been advocated or taught and is most often performed by individuals not trained in CPR, results in a survival rate similar to that of guidelines-advocated approach, on which millions of hours and millions of dollars have been spent in education and advocacy…… …It is now time for changes in the guidelines.”

               cardiopulmonary resuscitation. Circulation 2007;116:2908-2912.

               Iwami T, Kawamura T, Hiraide A, et al. Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007;116:2900-2907.

               Ewy GA. Continuous-chest-compression cardiopulmonary resuscitation for cardiac arrest. Circulation 2007;116:2894-2896. (editorial accompanying above studies).

               Out-of-hospital (OOH) sudden cardiac arrest is typically associated with a survival-to-hospital-discharge rate of less than 5% in adults. Evidence indicates that survival from sudden CA can be improved with adequate chest compressions (at 100 times/min); however, previous guidelines that called for a 15:2 compression-ventilation (mouth-to-mouth) rate were found to be associated with suboptimal compression rates. In fact, mannequin studies indicated that when even trained rescuers provided the 2 ventilations, it resulted in 16 seconds of hands-off time (ie, no compressions)-the end result was that compression rates were very low. The recent change in recommendations to a 30:2 ratio is based on these concerns, but this change was based on consensus opinion, not actually on good data. Perhaps an even higher ratio of compressions to ventilations would be better.

               In the first study, Bohm and colleagues evaluated 11 275 patients who were victims of OOH CA, received bystander CPR, and were reported to the Swedish Cardiac Arrest Register between 1990 and 2005. Standard CPR was performed in 73% (8209 patients) and chest-compressions-only resuscitation (CCOR) was performed in 10% (1145 patients). The remaining 17% of patients received mouth-to-mouth resuscitation only and were excluded. The researchers found no significant difference in 1-month survival between the 2 groups (7.2% for standard CPR, 6.7% for CCOR). There was also no significant difference in outcomes when ambulance- Response times were considered.

               In the second study, Iwami and colleagues evaluated 4902 patients who had witnessed CA between 1998 and 2003. Of this group, 783 received standard CPR, 544 received CCOR, and 3550 (72%) received no bystander CPR at all. Excluding very-long duration CAs (N15 minutes), the CCOR group had higher 1-Year survival with favorable neurologic outcome than the group that received no bystander CPR (4.3% vs 2.5%), and the group that received standard CPR showed similar results (4.1%). For the very- long-duration CAs, neurologically favorable 1-year survival was expectedly poor regardless of the type of CPR, though slightly greater in the standard CPR group (2.2% for standard CPR, 0.3% for CCOR, and 0% if no CPR). The authors conclude that CCOR and standard CPR produce similar outcomes in CA, though they suggest that for prolonged CA, the addition of rescue breathing may be of some help.

               The accompanying editorial by Ewy summarizes these and other studies that have consistently demonstrated in human and Porcine models that CCOR for patients with sudden CA is associated with outcomes that are at least as good as standard CPR. Bear in mind that when patients have sudden CA (ie, from a primary cardiac cause), the arterial blood is already fully saturated with oxygen in most cases. This observation is not the case for patients who arrest from respiratory failure (eg, the decompensating asthmatic, the opiate overdose, and others)-those patients clearly need early ventilation. The recommendations for Rescue breathing may actually be an impediment to survival because so many laypersons would rather not attempt resuscitation at all than to perform mouth-to-mouth ventilations, and when they do perform the ventilations, chest compression rates are suboptimal. Furthermore, other studies [13] have demonstrated that mouth-to-mouth ventilations (ie, positive pressure ventilation) increase intrathoracic pressure that decreases venous return as well as coronary and

               Kliegel A, Janata A, Wandaller C, et al. Cold infusions alone are effective for induction of therapeutic hypothermia but do not keep patients cool after cardiac arrest. Resuscitation 2007;73:46-53.

               The AHA guidelines recommend that prehospital victims of cardiac arrest whose (1) initial rhythm is VF/pulseless VT that (2) survive to ED arrival with a restored pulse rate and (3) are unconscious upon arrival should receive therapeutic hypothermia for 12 to 24 hours. The goal core temperature is 32 to 34?C (approximately 90?F-93?F). The recommenda- tion is based on 2 studies [14,15] that indicated that these patients had a higher survival with favorable Neurologic recovery compared to nonchilled patients. Although these past studies were limited to prehospital patients who met the 3 criteria listed above, many authorities suggest that we should consider extending the indications to Inhospital CArdiac arrest patients and also to patients with other presenting arrest rhythms besides VF/pulseless VT (ie, pulseless electrical activity or asystole). Please note that the recommendations are not currently appropriate for pregnant patients, pediatric patients, and patients in cardiogenic shock. Also it is important to avoid overcooling the patients, which may cause coagulopathies, infections, or dysrhythmias.

               The question that often arises, then, is how to cool the patients.

               The authors of this study nicely demonstrated something that has also been shown in prior studies-cooled IV fluids work very well in accomplishing this task. Twenty adult patients who were victims of witnessed, normothermic cardiac arrest of presumed cardiac etiology were enrolled in the study. All patients were still comatose upon enrollment (Glasgow Coma Score, b8) but had a systolic blood pressure greater than 90 mm Hg after the initial resuscitation. Patients were treated with 30 mL/kg of crystalloids that had been cooled to 4?C. The bolus was given for 30 minutes through 2 peripheral IV lines. If the temperature dropped below 33?C or evidence of pulmonary edema developed, the infusion were stopped. All patients were chemically paralyzed and sedated.

               Of the 20 patients, 13 (65%) patients achieved the target temperature within 60 minutes. The other 7 (35%) patients achieved the target temperature after an additional 10 mL/kg bolus for 10 minutes. The average rate of cooling using this technique was a 2?C/h; note that prior literature on this technique actually reported a 4?C/h drop [16-20]. None of the patients developed pulmonary edema or other complications, and none dropped their temperature below the goal temperature. The only negative finding with regard this treatment was that the cold infusions, even when repeated after 6 hours, were unable to maintain the hypothermic state; consequently, other means of cooling were needed for maintenance. The authors did not evaluate whether more frequent boluses of cold IV fluids or continuous infusions would have been successful for maintenance of hypothermia.

               The teaching point here is that if therapeutic hypothermia is desired, cold IV fluid infusions through peripheral intravenous lines is effective, safe, and inexpensive. Other additional methods may then be needed for maintenance of hypothermia for the recommended 12 to 24 hours.

               Garot P, Lefevre T, Eltchaninoff H, et al. Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction. Circulation 2007;115:1354-1362.

               Gorjup V, Radsel P, Kocjancic ST, et al. Acute ST-elevation myocardial infarction after successful cardiopulmonary resuscitation. Resuscitation 2007;72:379-385.

               What do you do when patients demonstrate evidence of STEMI after resuscitation from cardiac arrest? There really is no clear standard or consensus recommendation regarding their treatment. Should they receive immediate PCI or fibrinolysis, just as would “routine” STEMI patients? Should these interventions occur emergently or in delayed fashion? Or should they simply receive supportive care for 24 hours with catheterization occurring the next day? Surprisingly, there are no definite recommendations on how to proceed with these patients. Here are 2 studies that provide some information indicating that when such patients are managed very aggressively, they can do well.

               In the first article, the authors reviewed 186 patients who underwent immediate PCI after successful resuscitation for cardiac arrest complicating acute STEMI. The patients were diagnosed with STEMI based on having at least one ECG demonstrating ST-segment elevation with angiographic evidence of an infarct-related artery. Of these patients, 156 patients had resuscitation in the prehospital arena, whereas 32 had inhospital cardiac arrest. Percutaneous coronary intervention was successful in 161 (87%). The 6-month survival rate was 100/186 (54%), and 46% remained free of neurologic sequelae at 6 months. Interestingly, the success rates of PCI were similar to those that are routinely obtained in studies of STEMI patients presenting with cardiogenic shock. Independent predictors of 6-month survival-similar to other resuscitation studies-included shorter interval between onset of cardiac arrest and arrival of a first responder, shorter interval between the onset of cardiac arrest and return of spontaneous circulation, and absence of diabetes.

               In the second article, the authors reviewed 135 patients who were diagnosed with STEMI after resuscitation from cardiac arrest. Forty-nine (36%) of the patients regained consciousness, and 86 (64%) remained unconscious during initial evaluation. The delay from collapse to advanced cardiac life support initiation was longer in the comatose patients (5.8 vs 0.5 minutes) and in those with a lower proportion of VF/pulseless VT (76% vs 96%). Primary PCI was performed in all but one conscious patient with success rate (96% vs 94%) and hospital survival without neurologic deficit (100% vs 94.8%) comparable to patients without cardiac arrest. Even in comatose patients, primary PCI was successful in 82%. Hospital survival in these initially comatose patients was 51%, and survival with good neurologic status was 29%.

               These articles provide strong evidence that patients with STEMI who have cardiac arrest, whether conscious or comatose after resuscitation, derive significant benefit from aggressive management with PCI. In addition, these articles provide further evidence of the importance of rapid initiation of resuscitative efforts by bystanders or medical personnel.

               Richling N, Herkner H, Holzer M, et al. Thrombolytic therapy vs Primary percutaneous intervention after ventricular fibrillation cardiac arrest due to Acute ST-segment elevation myocardial infarction and its effect on outcome. Am J Emerg Med. 2007;25(5):545-550.

               The authors of this Austrian study retrospectively examined STEMI patients who developed witnessed ventricular fibrillation cardiac arrest. Nearly all of the patients had out-of-hospital cardiac arrest with subsequent CPR. ST-segment elevation myocardial infarction was diagnosed via ECG and cardiac biomarker abnormalities. After return of spontaneous circula- tion, patients were treated in the hospital with either fibrinolytic agents (101 patients [69%]) or PCI (46 patients [31%]). The decision to use either treatment was dependent on the treating physician and was primarily based on the availability of a catheterization laboratory. When fibrinolytic therapy was used, front-loaded tPA or tenecteplase was administered, and patients in both groups received other standard treatments. Survival and neurologic recovery at 6 months were the primary end points.

               The authors found that 93 (63%) of the 147 patients survived for 6 months, and 79 (53%) of the 147 patients survived with good neurologic recovery (conscious and alert with minimal or moderate disability) regardless of the type of reperfusion therapy used. In fact, there was a trend toward better outcome when fibrinolytic agents were given though the

               difference was not statistically significant. This trend may have been related to time delays to balloon inflation compared to fibrinolytic administration- for patients receiving medical therapy, the door-to-needle time averaged 39 minutes (range, 25-90 minutes), whereas for patients receiving PCI, the door-to-catheter time averaged 119 minutes (range, 104-205 minutes). Any conclusion is just speculative, however, as the study does not constitute an effective comparison between the 2 therapies. Bleeding complications in patients with greater than 10 minutes of CPR time who then received fibrinolytic agents were no different from those patients with prolonged CPR that did not receive fibrinolysis.

               Although this is a relatively small study, there are a few points worthy of discussion as follows: (1) aggressive reperfusion therapy in STEMI patients with cardiac arrest can result in very good long-term outcomes; (2) when PCI is not readily available, the use of fibrinolytic agents may be associated with favorable outcomes; (3) CPR greater than

               10 minutes should not be considered a contraindication to the use of fibrinolytic therapy.

               Knafelj R, Radsel P, Ploj T, et al. Primary percutaneous coronary intervention and Mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation 2007;74:227-234.

               Mild induced therapeutic hypothermia (MIH) has been suggested as a Treatment intervention in patients who have been resuscitated from out-of- hospital VF cardiac arrest [21]. The previous articles have discussed PCI and/or fibrinolysis in this same population. Should we combine these therapies (PCI + MIH) if a patient with STEMI has a VF cardiac arrest and then regains spontaneous circulation? This study sheds some light on this question.

               The authors compared 40 consecutive patients who were comatose survivors of VF arrest with STEMI after return of spontaneous circulation undergoing primary PCI + MIH between 2003 and 2005; these patients were compared to 32 consecutive resuscitated patients with VF and STEMI who underwent only PCI (ie, no MIH was performed) between 2000 and 2003. There was no significant difference between the 2 groups for general characteristics, cardiac arrest circumstances, or angiographic findings; there were also no significant differences between the patients with MIH vs no MIH for blood pressure, need for vasopressors or inotropes, use of aortic balloon counterpulsation, need for repeat cardioversion/defibrillation, use of antiarrhythmics, or oxygen requirements during mechanical ventilation. However, patients receiving MIH had a significantly improved survival with good neurologic outcome, defined by cerebral performance category 1 or 2 (1 = normal mental performance, 2 = mild disability, 3 = severe disability, 4 = vegetative state). Overall, 55% of the MIH group (vs 16% of the no-MIH group) was discharged with good neurologic outcome, an impressive outcome for cardiac arrest patients.

               The method for induction of MIH is worth mentioning-patients were sedated with a midazolam infusion and paralyzed with norcuronium to prevent shivering. Cool IV fluids (30 mL/kg of normal saline at 4?C) were infused for 30 minutes to induce hypothermia, and ice packs were placed on the head, neck, axilla, abdomen, and inguinal regions to maintain a core body temperature between 32?C and 34?C for 24 hours. Patients were then allowed to rewarm passively. Exclusion criteria for MIH were recurrent malignant ventricular arrhythmias, profound cardiogenic shock on admis- sion, pregnancy, and known coagulopathies.

               There are certainly some limitations to the study. The retrospective, nonrandomized format allowed for some possible selection bias. In addition, resuscitative efforts from 2003 to 2005 may have been more aggressive and allowed for a better outcome than the efforts used between 2000 and 2003 (eg, greater emphasis on quick door-to-balloon time, greater use of antiplatelet medications such as GIIb/IIIa receptor antagonists, and others). The authors certainly admit that this study is not proof of the superiority of combining PCI + MIH vs PCI alone, but Combination therapy does certainly seem feasible and in-line with other literature pertaining to cardiac arrest with subsequent STEMI. None in the AHA, ACC, or the European Society

               acute pericarditis“>of Cardiology currently has any formal recommendations regarding the management of patients with cardiac arrest who demonstrate evidence of STEMI after resuscitation.

               1. Acute pericarditis

               Imazio M, Trinchero R. Triage and management of acute pericarditis. Int J Cardiol 2007;118:286-294.

               This article is a good review article to update what we should consider in patient with acute pericarditis (AP).

               Introduction/etiologies

               • As many as 5% of patients presenting to the ED with chest pain have AP in some studies.
               • There are a multitude of Potential causes-infectious, noninfec- tious, and idiopathic-that are responsible for AP. However, viral and idiopathic causes account for 80% to 90% of cases of AP in immunocompetent patients from developed countries. Therefore, an extensive search for an underlying cause is unnecessary in most cases seen in North America. Empiric treatment is perfectly appropriate for most patients even without ever finding a specific cause.
                 • On the other hand, there is a subgroup of patients in whom empiric treatment alone is not appropriate and usually is not effective. Instead, those patients should receive an aggressive workup for the underlying cause and specific treatment once the cause is identified. That subgroup of patients is identified by the presence of “poor prognostic features” noted below.
               • The etiology of AP in Developing countries is very different, with tuberculosis-related AP predominating. The authors provide the example that 70% to 80% of cases from sub-Saharan Africa and more than 90% of human immunodeficiency virus -related cases of AP are tuberculous. In developed countries, tuberculous pericarditis should be strongly considered among immigrants/ visitors from developing countries and among patients with HIV.

            8. History and physical examination
               • “Typical” pericardial pain is sharp, usually radiates to the trapezius ridge because of involvement of the phrenic nerve, and is typically worsened by inspiration, coughing, swallowing, and some changes in posture (supine or Left lateral decubitus position); it is usually improved when the patient is upright or leaning forward.
               • Atypical descriptions include severe or crushing pain, which may lead to misdiagnosis as cardiac ischemia.
               • The pericardial friction rub is considered pathognomonic and according to the authors “guarantees the diagnosis, but its absence does not exclude it” (sensitivity reported to be 33%- 85%). In contrast to pleural rubs, pericardial rubs are not affected by respirations.
            9. Diagnostic testing
               • The ECG evolves through 4 stages in up to 60% of cases; therapy may accelerate or alter the progression through these stages.
                 • Stage I: diffuse STE (typically concave-upwards) with PR segment depression; PR segment depression tends to be most prominent in the inferior leads and in leads V₅ to V₆; PR segment elevation in Lead aVR is common as well.
                 • Stage II: normalization of the ST and PR segments.
                 • Stage III: widespread T-wave inversion (TWI). The TWI most frequently occur after the STsegments have returned to baseline; if the TWIs occur while the ST segments are still elevated, it is almost always cardiac ischemia and not pericarditis.
                 • stage IV: normalization of the T waves.
               • Acute pericarditis may be associated with elevations of creatine kinase myocardial band and/or troponin, especially if there is associated myocarditis (myopericarditis). The elevations of cardiac biomarkers in AP are not associated with an adverse prognosis, unlike ACS.
               • Echocardiography is generally recommended in all cases to evaluate for a pericardial effusion and also to evaluate for concomitant heart disease or other cardiac Pathologic findings.
                 • Up to 60% of cases of AP are associated with a pericardial effusion.
                 • Classification of pericardial effusion size: small effusion, less than 10 mm of echocardiographic-free space (anterior plus posterior); moderate effusion, 10 to 20 mm; and severe effusion, greater than 20 mm. The effusion echocardiographic-free spaces are measured at the onset of the QRS complex in diastole.
            10. Treatment
                • Ibuprofen should be considered the preferred antiinflammatory for AP because of its side effect profile. Administer no more than 800 mg every 6 to 8 hours.
                • Aspirin (at least 650 mg) administered every 6 to 8 hours followed by gradual tapering for 3 to 4 weeks is an alternative. Aspirin is definitely preferred in post-MI patients.
                • Gastroprotection should be added in every case.
                • Corticosteroids should be avoided in first episode and recurrent cases of AP, as they have been found to be an independent risk factor for further recurrences because they promote viral replica- tion. Steroids should be considered only in patients with ibuprofen- unresponsive pericarditis as a “last resort.”
                • If corticosteroids are used, high dosages should be administered (eg, prednisone, 1-1.5 mg/kg per day) with tapering to begin slowly after a full month and transition to ibuprofen until the prednisone taper has ended. More rapid tapering is often associated with recurrence.
                • Colchicine has also been found to be effective in first episode AP as well as recurrences. Colchicine use during first episode AP significantly decreases the duration of symptoms and also the incidence of recurrences. The recommended dose is 2 mg/d for 1 to 2 days, followed by a maintenance dose of 1 mg/d (0.5 mg twice a day).
                  • The major side effect associated with the use of colchicine is diarrhea (8% in one study), and in these cases, a lower dose should be attempted.
                  • Care should also be exercised in the presence of renal insufficiency, in which colchicine levels will rise, and in other patients taking drugs that are metabolized through the Cytochrome P450 system.
                  • Reduced dosages of colchicines should also be used in patients greater than 70 years of age.
            11. Disposition
                • Clinical features associated with a poor prognosis in AP include all of the following and are indications for admission:
                  • Fever more than 38?C;
                  • Subacute onset;
                  • Immunosuppression;
                  • Trauma;
                  • Oral anticoagulant therapy;
                  • Myopericarditis;
                  • Severe pericardial effusion;
                  • Cardiac tamponade; and
                  • Lack of response to aspirin or ibuprofen after at least one week of therapy
                • Patients without poor prognostic features can be considered low risk and assigned to outpatient treatment with ibuprofen and gastroprotection.

                Imazio M, Cecchi E, Demichelis B, et al. Indicators of poor prognosis of acute pericarditis. Circulation 2007;115:2739-2744.

                This article confirms the significance of the poor prognosis features noted in the prior article. The authors reviewed 453 adult patients with AP, excluding post-MI pericarditis. A specific cause, that is, excluding

                idiopathic, was found in 76 (16.8%) patients; autoimmune in 33 patients (7.3%); neoplastic in 23 (5.1%); tuberculosis in 17 (3.8%); and purulent in 3 (0.7%). After a follow-up of 31 months, complications (recurrence, tamponade, or constriction) occurred in 95 patients (21.0%). Groups that were found to be at highest risk of these complications were patients with large effusions, patients who failed to respond to aspirin or ibuprofen, patients with fever more than 38?C, and patients who presented with a subacute course. These patients were also the same groups that had a higher risk of having a specific cause for their AP (rather than an unknown etiology). The authors state that patients with one of these poor prognostic features should be strongly considered for admission at the time of their initial episode. Essentially, the purpose of the admission is not only to provide supportive treatment and monitoring for complications, but importantly, an aggressive workup for the underlying cause (and directed treatment) is indicated in these patients. Patients without these poor prognostic features can just be treated empirically with ibuprofen/aspirin and colchicine, as

                indicated in the previous article.

                1. Cardiogenic pulmonary edema

                Plaisance P, Pirracchio R, Berton C, et al. A randomized study of out-of- hospital continuous positive airway pressure for acute cardiogenic pulmonary oedema: physiological and clinical effects. Eur Heart J 2007;28:2895-2901.

                Last year in this series we reviewed articles [22,23] demonstrating the use of noninvasive ventilation (NIV) in the early management of cardiogenic pulmonary edema (CPE). Various studies have demonstrated that NIV is associated with decreased Intubation rates, intensive care unit use and length of stay, decreased hospital costs, and even decreased mortality. One key, though, is that NIV must be used early in the course of treatment. Logically, one would then assume that application of NIV by Prehospital care providers would be very beneficial. Plaisance and colleagues evaluated this assumption in the Paris EMS system. They conducted a randomized, prospective study in which they compared in various combinations early Continuous positive airway pressure (during the first 15 minutes), late CPAP (between 30 and 45 minutes of treatment), medical treatment alone (the Loop diuretic bumetanide and NTG); and nicardipine infusion was added for afterload reduction if systolic blood pressure remained greater than 160 mm Hg despite NTG, and combinations of medical treatment with early or late CPAP for patients with CPE. The primary end points they evaluated were the effect of early CPAP on a dyspnea Clinical score and on oxygenation (measured via arterial blood gas) at 45 minutes of therapy, and the secondary end points were the effects of early CPAP on tracheal intubation rates, need for inotropic support, and inhospital mortality. The CPAP pressures were 7.5 cm H₂O. One hundred twenty-four patients were enrolled.

                The researchers found that patients receiving early CPAP had greater improvements than patients receiving either medical treatment alone or medical treatment plus late CPAP for dyspnea scores, oyxgenation, and tracheal intubation rates; the patients with early CPAP also had a trend toward lower inhospital mortality (P = .05). In addition, fewer patients in the early CPAP group required inotropic support. Overall, the efficacy of CPAP was so significant that the authors did not observe any clear benefit of adding medical treatment if CPAP was applied early, whereas the addition of late CPAP to medical treatment was associated with significant improvements.

                There are 2 major teaching points here. First, NIV appears to be the best early therapy for CPE. Second, NIV works best when it is applied early. This study demonstrated that even a short 15-minute delay was associated with significant effects on patient outcomes. The authors suggest that the delay in initiation of NIV in patients with CPE might be equated to the delay in aggressive resuscitation of patients with septic shock for outcomes. This article certainly makes a strong argument for the use of prehospital NIV in the CPE management.

                1. Dysrhythmias

                Stiell IG, Clement CM, Symington C, et al. Emergency department use of intravenous procainamide for patients with Acute atrial fibrillation or flutter. Acad Emerg Med 2007;14:1158-1164.

                There is a tremendous amount of disagreement regarding optimal ED management of the patient in recent-onset Atrial fibrillation . Some people advocate Rate control only, then admission. Others recommend chemical cardioversion. And still others recommend electrical cardioversion. The literature indicating that rate control is as good as Rhythm control is not ED based and therefore has limited use for ED practice. There’s also disagreement about which patients require admission and/or anticoagulation.

                For the many physicians who favor rhythm control for recent-onset AF with medications, there is disagreement regarding which drugs are optimal. Various studies have supported dofetilide, flecainide, propafenone, ibutilide, and amiodarone. Unfortunately, none of these drugs have emerged as a clear favorite because of expense, limited availability in the United States, association with Torsades de pointes, or limited efficacy. Last year, we discussed that procainamide is making a comeback in treatment of ventricular tachycardia [24,25]. Is procainamide going to make a comeback for Atrial arrhythmias as well? Here is a study that lends support to the use of procainamide for acute (onset within prior 48 hours) AF. What is most interesting is that this is a retrospective review of patients who were being treated with what is already “routine care” for patients at the University of Ottawa ED (Ottawa, Ontario, Canada). Consequently, the hospital research ethics board approved the protocol without even requiring informed consent. The “routine care” that these patients receive is worth describing here-perhaps as a model for others.

                The researchers evaluated 341 patients (mean, age 64 years) and found that conversion rates were 52.2% for 316 AF cases and 28.0% for 25 atrial flutter cases (AFL); note that AFL was more resistant to procainamide, although electrical cardioversion worked in these resistant patients in all instances. The average dose of procainamide given was 860.7 mg. The medication infusion was discontinued when the patient converted; the majority converted before reaching the full 1-g load. The median time to conversion was 55 minutes. The rate of adverse events was not insignificant; 10% (34 patients) had an adverse event-8.5% developed hypotension, 0.6% developed bradycardia, 0.6% developed atrioventricular block, and 0.3% developed ventricular tachycardia. There were no cases of torsades de pointes, stroke, or death. Most patients (94.4%) were discharged home, and only 2.9% returned with a recurrence of AF within 7 days.

                There are some limitations here (retrospective; no placebo, or comparison group; no follow-up or death registry review; choice of treatment left to the treating ED physician). The authors appropriately suggest that this study should prompt further randomized trials using IV procainamide vs other regimens, and it also demonstrates the efficacy of their current protocol. In addition, the study demonstrates the safety of IV procainamide, a drug that we all should start getting reacquainted with.

                1. Electrocardiography

                Kosuge M, Kimura K, Ishikawa T, et al. Electrocardiographic differentia- tion between acute pulmonary embolism and acute coronary syndromes on the basis of Negative T waves. Am J Cardiol 2007;99:817-821.

                Acute pulmonary embolism very commonly causes T-wave inversions, and in fact, the presence of simultaneous T-wave inversions in the inferior and anteroseptal leads is highly specific for acute PE (APE). The authors of this study make both of these points and studied the sensitivity and specificity of this finding.

                They evaluated the ECGs of 40 patients with APE and 87 patients with ACS that had T-wave inversions in leads V₁ to V₄ on the admission ECG. They also considered various T-wave patterns that would help distinguish between the 2 diagnoses. They found that simultaneous T-wave inversions

                were fairly common in the inferior leads but much less common in the lateral leads in patients with APE. In fact, no patients with APE had T-wave inversions in leads I or aV_l-this pattern only occurred in patients with ACS, a major teaching point. They then narrowed the evaluation to leads V₁ (a septal lead) and III (an inferior lead). They found that T-wave inversions were present simultaneously in leads III and V₁ in only 1% of patients with ACS, compared to 88% of patients with APE (P b .001). The specificity of this simultaneous T-wave finding for APE was 99% (and positive predictive value was 97%).

                Kenigsberg DN, Khanal S, Kowalski M, et al. Prolongation of the QTc interval is seen uniformly during early transmural ischemia. J Am Coll Cardiol 2007;49:1299-1305.

                The authors prospectively analyzed ECGs in 74 patients undergoing elective percutaneous transluminal coronary angioplasty. Electrocardio- grams were obtained in 20-second intervals as the balloons were inflated, essentially causing transmural ischemia, to determine the effect on the ECG. What did they find?

                The first ECG marker of ischemia was prolongation of the QTc interval, which occurred on average after 22 seconds of ischemia. Also of note, prolongation of the QTc occurred in 100% of patients. In contrast, ST-segment and T-wave changes occurred more slowly and less frequently. The magnitude of the QTc prolongation was relatively mild, increasing from an average initial QTc value of 423 milliseconds to an average value of 455 milliseconds (P b .001), with increasing QTc prolongation relative to increasing time of inflation. The primary message is straightforward. Acute coronary syndrome is a cause of QTc prolongation. How might this be useful in the ED? If you are monitoring a patient with intermittent chest pain, a comparison of the QTc during the pain-free state vs the active-pain state could help in determining whether the chest pain is ischemic in origin.

                Jimenez-Candil J, Gonzalez IC, Matas JMG, et al. Short- and long-term prognostic value of the Corrected QT interval in the non-ST-elevation acute coronary syndrome. J Electrocardiol 2007;40:180-187.

                The authors prospectively evaluated 427 consecutive high-risk non- STE ACS patients. The study participants included only patients older than 18 years with anginal symptoms occurring for less than 24 hours before ED arrival; the patients also demonstrated positive cardiac biomarkers and/or electrocardiographic abnormalities in at least 2 anato- mically associated leads (ST-segment depression or T-wave inversion). They correlated the QTc interval on the admission ECG with the patients’ major cardiac events rate; note that major acute cardiac events (MACE) includes death, recurrent ischemia, or need for urgent coronary revascularization. Using what the authors determined as a “best cutoff” of 450 milliseconds, they found the following: patients with QTc greater than 450 milliseconds had a higher rate of inhospital death, 8.8% vs 1.2%, and their rate of MACE was also higher, 72% vs 25%.

                They then performed postdischarge follow-up for a median of

                17 months. They identified 3 independent predictors of Cardiovascular death after discharge as follows: older than 65 years, LV ejection fraction of less than 40%, and QTc greater than 450 milliseconds (14.7 vs 2.1%; P b

                .0001). They also found that coronary revascularization reduced the risk of postdischarge cardiovascular death in patients with QTc greater than 450 milliseconds (5% vs 24%; P b .0001), but it had no significant effect in patients with QTc less than 450 milliseconds. This finding is a particularly interesting finding-recall that the current “standard of care” regarding whether non-STE ACS patients should routinely undergo urgent PCI is still in question. Some cardiologists argue that non-STE ACS patients should all receive early (ie, within 48 hours of admission) PCI, whereas many other cardiologists argue that conservative medical management is sufficient.

                The primary messages from this article are as follows: first, it appears that patients with non-STE ACS are at much higher risk of major cardiac adverse events if they have a QTc greater than 450 milliseconds and thus

                might benefit from more aggressive ED and inhospital management and surveillance; and secondly, it appears that the QTc may be a reasonable tool to use in selecting those patients with non-STE ACS who are best treated with early PCI vs conservative medical treatment alone.

                Yan RT, Yan AT, Allegrone J, et al. Differences between local hospital and core laboratory interpretation of the admission electrocardiogram in patients with acute coronary syndromes and their relation to outcome. Am J Cardiol 2007;100:169-174.

                Last year, in this series, we reviewed an article published in Circula- tion that essentially criticized ECG interpretation skills of emergency physicians when evaluating patients with potential ACS [26]. The authors evaluated patients with ACS that were entered into the GRACE registry. This database is an ongoing registry of adult patients with presumed ACS from 94 different sites in 14 countries across North America, South America, Europe, Australia, and New Zealand. When patients are entered into this registry, the initial treating physician is required to fill out a case report form that includes an ECG interpretation. All ECGs are then reread at a central site (the Canadian Heart Research Center electrocardiographic core laboratory in Toronto, Ontario, Canada) by one of 3 physicians of unknown training background who were blinded to the original site interpretations. The “core laboratory” interpretation, defined as the gold standard in this article, was then compared to the “site” interpretation, and the clinical outcome of the patients was evaluated at 6 months and compared to any discrepancies in ECG interpretations. The discrepancies they looked for were undiagnosed STE, undiagnosed ST depression (STD), and undiagnosed LBBB.

                The researchers identified 786 (17%) of 4687 patients who demon- strated STE, STD, or LBBB that was undiagnosed on the initial ECG by the “site” physicians. Separating this number into the various subcate- gories, 20% of cases of STD were not recognized by the site physicians. In fact, even when the site physicians correctly identified a patient as having an ACS, they still underdiagnosed many. Fourteen percent of patients who were diagnosed by the site physicians as having STD actually had STE or LBBB-meaning that 14% of the patients diagnosed as having non-STE ACS actually may, in fact, have had STEMI and thus been deprived of the benefit of immediate reperfusion therapy. This “underrecognition” rate was similar regardless of the geographic location, hospital characteristics, presence of catheterization laboratory or consultants, teaching vs nonteaching facility, and others.

                These patients were less likely to receive traditional evidence-based therapies, they were less likely to undergo risk stratification, and there was a trend toward fewer inhospital revascularization procedures in these patients. Underrecognition of these high-risk ECG features was also an independent predictor of death or reinfarction at 6 months. This is the second publication to show that misinterpretation of the initial ECG can result in worse patient outcomes.

                This article is quite interesting for a number of reasons; firstly, it focuses on the all-important physician ability to interpret the electrocardiogram in the acute care setting-we must not lose sight of this message and continue to improve our abilities. Furthermore, there are 2 issues of concern that must be considered, including the presence of non-STEMI ST-segment elevation syndromes and the reality of acute care clinical practice. The patient with chest pain and electrocardiographic ST-segment elevation presents a challenge to the treating physician-the rapid identification of STEMI and non-STEMI ST-segment elevation syndromes must be accomplished in rapid fashion, often times with limited data, whereas the press of other clinical duties continues. As has been reported, all patients with electrocardiographic ST-segment elevation and chest pain are not experien- cing STEMI [27,28]. In fact, only a minority of these patients are having STEMI [27,28].

                And, regarding the realities of clinical practice, the ECG must be interpreted within the context of the clinical presentation. Much of the disagreement between interpretations of these ECGs may be because of differences in the Clinical context in which the ECG is used. One

                interpretation takes place at the point of care, whereas the other takes place in isolation without the benefit of having a patient to assess. Point-of-care interpretation likely benefits from the patient’s clinical status and availability of previous tracings. Because there was no final adjudication, to claim that one site vs the other rendered the “correct” interpretation, it seems far-fetched to claim that the core laboratory was correct and, in fact, the correct interpretation.

                Rostoff P, Piwowarska W, Gackowski A, et al. Electrocardiographic prediction of acute left main coronary artery occlusion. Amer J Emerg Med 2007;25:852-855.

                This is another publication on the use of lead aVr. The authors wrote this brief report in response to an article published in November 2006 pertaining to lead aVr [29]. This article discussed that ST-segment elevation in lead aVR in patients with Acute cardiac ischemia has been found to be highly specific for acute occlusion of the left main coronary artery (LMCA). Why should we worry more about ACS with LMCA involvement vs any other ACS case? Very simply, the literature indicates that when a patient has ACS involving the LMCA, they carry a 70% risk of developing cardiogenic shock or dying, and the only treatment that has been demonstrated to improve outcomes in patients with LMCA occlusion is rapid PCI (or often they will need CABG). No medical therapies have been found to reliably improve the prognosis, including thrombolytics. This is not just applicable to patients with STEMI; it also applies if the patient has an ST-depression ACS.

                The authors performed an analysis of published data and report that STE in lead aVr during ACS is 77.6% sensitive, 82.6% specific, and 81.5% accurate for LMCA occlusion. These authors do not specifically comment on what degree of STE is required (0.5 mm vs 1.0 mm), but in our evaluation of the literature, there are 3 patterns that appear to predict LMCA occlusion as follows: (1) STE in lead aVr that is greater in magnitude than the STE in lead V₁; (2) STE in lead aVr with simultaneous STE in lead aVL; or (3) STE in lead aVr greater than 1.5 mm. Also, it is important to bear in mind that these findings only apply when there is evidence of ischemia or infarction in other leads as well, so this is really not applicable to non-ACS patients. For example, some patients with supraventricular tachycardia will develop STE in lead aVR, and this is not clinically predictive of LMCA disease [29].

                For anyone wondering why STE occurs in lead aVr, apparently it is not completely clear. The authors cite one theory that “….it is caused by transmural ischemia of the basal part of the interventricular septum, where the injury’s current is directed toward the right shoulder…” thus producing STE in lead aVr. The bottom line is this-when a patient has evidence of ischemia or infarction on the ECG, scrutinize lead aVr. If there is STE in this lead, consider rapid consultation with an invasive cardiologist for PCI.

                1. Syncope

                Huff JS, Decker WW, Quinn JV, et al. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Ann Emerg Med 2007;49:431-444.

                This clinical policy by ACEP contains some useful information that makes for a nice review article on the topic of syncope. There were 3 major questions that the clinical policies committee explored. We will review the important highlights in each of the query areas. It is important to note the definition of syncope and related terminology. Syncope is defined as a “brief loss of consciousness associated with an inability to maintain postural tone that spontaneously and completely resolves without medical intervention.” The key words here are “spontaneously” (ie, no postictal period with a rapid recovery) and “completely” (no residual neurologic deficit).

                What history and physical examination data help in risk stratification?

                • Risk factors for adverse events include older age, structural heart disease, or history of CAD.

          • Young Patients with syncope that is nonexertional, without a history or signs of cardiovascular disease, a family history of sudden death, and without comorbidities are at low risk of adverse events.
          • The ED evaluation identifies only 20% to 50% of causes of syncope. Inpatient and subspecialty evaluation diagnoses an additional 30%, leaving 15% to 30% of cases without a definite cause.
          • One of the more recent and useful studies, the San Francisco Syncope Study [30], identified 5 characteristics in the ED that were associated with a higher likelihood of an adverse even within 7 days of ED presentation. These characteristics are remembered with the CHESS mnemonic as follows: history of CHF, hematocrit less than 30%, ECG abnormality, shortness of breath, and systolic blood pressure less than 90 mm Hg at arrival. Realize that this rule can only be applied to patients who are not already obvious admissions.
          • There are no clear guidelines regarding younger patients (b35 years) with exertional syncope. However, exertional syncope suggests structural lesions that produce fixed cardiac output, and therefore, we believe that these patients would seem to represent higher risk presentations.
          • Orthostatic hypotension, defined by a systolic reduction in blood pressure greater than 20 mm Hg within 2 minutes of going from a supine to standing position, may be helpful in identifying hypovolemia. However, this finding is also present in up to 40% of asymptomatic patients older than 70 years and in approximately 25% of asymptomatic patients younger than 60 years. The recurrence of symptoms or even syncope upon standing is more significant than the actual systolic blood pressure alterations. The diagnosis of orthostasis as a cause of syncope should be a diagnosis of exclusion, and the physician should remember that there will be high-risk patients with syncope (ie, syncope caused by much more serious causes than hypovolemia) that will have false-positive orthostatic changes.
          • In patients for whom a diagnosis of syncope will be established, an appropriate history and physical examination identify the cause in most patients.
            1. What diagnostic testing modalities assist in risk stratification in the evaluation of the syncope patient?
               • A standard 12-lead ECG is indicated in all patients presenting with syncope. The ECG will identify the cause of syncope in only 5% of patients, but it is noninvasive, inexpensive, and can identify potentially deadly conditions. Look for evidence of ischemia/ infarction, tachydysrhythmias, bradydysrhythmias, atrioventricular blocks, prolonged QT interval, ventricular preexcitation, hyper- trophic cardiomyopathy, and Brugada syndrome.
               • An Abnormal ECG is one of the strongest predictors of serious outcomes.
               • Continuous ECG monitoring in the ED is prudent, but monitoring for more than 24 hours (ie, admission for monitoring) is not likely to increase the diagnostic yield for significant dysrhythmias for most patients.
               • The routine use of laboratory testing (eg, complete blood count, serum chemistries, and others) rarely yields any useful information in the absence of a suggestive history. The San Francisco Syncope Study did suggest that routine hematocrit evaluation was useful and that a level less than 30% was a predictor of adverse outcomes.
               • The routine use of advanced imaging tests (eg, computed tomography, echocardiography) rarely yields any useful informa- tion in the absence of a suggestive history.
            2. Who should be admitted after an episode of syncope of unclear cause?
               • Why do we admit patients? The main reason for admitting a patient “should be that the treating physician suspects that the patient is at risk for significant dysrhythmia or sudden death and that observation might detect that event and enable an intervention.” The problem here, as the authors state, is that the

               value of admission for 24 to 72 hours in preventing a later adverse outcome has never been demonstrated. Even if there is a benefit, there is insufficient evidence or guidance in the literature to describe which patients will benefit from the admission. Most of the published literature uses 6-month and 1-year end points for reporting adverse events rather than 72-hour end points. The San Francisco Syncope Study [30] is the only relatively large study that evaluates Short-term outcomes (ie, a 7-day outcome).

               • The authors summarize their recommendations for admission by stating that patients with syncope should be admitted if they have evidence of active heart failure or structural heart disease; or if they have any “high-risk” factors, which includes older age with associated comorbidities (without a specific age noted), an abnormal ECG, hematocrit less than 30, a history of heart failure, CAD, or structural heart disease.

               Dovgalyuk J, Holstege C, Mattu A, Brady WJ. The electrocardiogram in the patient with syncope. Am J Emerg Med 2007;25:688-701.

               Syncope is a common complaint among ED patients. A great deal of literature has been generated about syncope, including risk prediction, observation unit evaluation protocols, clinical guidelines, and others. However, one topic that surprisingly has not been well described in the literature pertains to electrocardiography-what are the findings that physicians should search for on the ECG of a patient with syncope? This review article describes a list of deadly conditions and their ECG correlates that should be considered in these patients. This list is by no means inclusive of all medical conditions that can cause syncope but rather a list of diseases that typically can be diagnosed or strongly suggested by the ECG.

               1. Acute coronary syndromes (acute MI or acute ischemia).
               2. Wolff-Parkinson-White syndrome (WPW): the most common form of preexcitation, WPW is associated with the classic triad of short PR interval, QRS complex widening greater than 100 milli- seconds, and the ? wave (slurred upstroke of the QRS com- plex). It is important to remember that ? waves, although the most well known of the triad, are often absent in many leads. The short PR interval is actually the most consistent finding in all of the leads.
               3. Brugada syndrome: Brugada syndrome is a purely electrical phenomenon (meaning that patients have structurally normal hearts) that is associated with unpredictable episodes of ventricular tachycardia. Patients may have sudden death, but if the arrhythmia terminates spontaneously, the patient presents instead with syncope. The resting ECG demonstrates a Right bundle branch block morphology with STE in leads V₁ to V₂ [31].
               4. Hypertrophic cardiomyopathy (HCM): hypertrophic cardiomyopa- thy may be associated with episodes of ventricular tachyarrhyth- mias, usually associated with exertion, in relatively young patients. The ECG manifestations of HCM are often nonspecific (high voltage in the precordial leads, left atrial enlargement, tall R waves in Right precordial leads, and Abnormal Q waves in the inferior and/ or lateral leads) [32]. However, the combination of high voltage with deep, narrow Q waves in the inferior and/or lateral leads is highly specific for this entity.
               5. Prolongation of the QT interval: patients with a prolonged QTc interval are at risk for torsades de pointes. Patients are at highest risk when the QTc interval is greater than 500 milliseconds. Major causes of prolonged QTc interval include hypokalemia, hypocalcemia, hypomagnesemia, hypothermia, Elevated intracranial pressure, acute cardiac ischemia, sodium channel blocking drugs, and hereditary long QT syndrome.
               6. Miscellaneous

               Kalay N, Ozdogru I, Cetinkaya Y, et al. Cardiovascular effects of carbon monoxide poisoning. Am J Cardiol 2007;99:322-324.

               Carbon monoxide poisoning is known to cause cardiac dysfunc- tion, but the severity and duration of Cardiac effects are not well known. The authors of this study evaluated 20 patients with CO poisoning. The average Carboxyhemoglobin level in study patients was 29%. Patients with any history of cardiac problems (CAD, valvular disorders, rhythm diseases) were excluded. Patients had echocardiographic and cardiac biomarker evaluation. Patients with positive cardiac biomarkers also went on to have coronary angiography.

               The authors found 6 patients with positive cardiac biomarkers, all of whom went on to have normal angiography. Other patients were noted to have low LV ejection fraction (ie, b45%) with elevated biatrial naturetic peptide levels at admission, although there was a fairly consistent return to baseline by 24 hours. The authors concluded that CO poisoning can cause Myocardial stunning with LV systolic dysfunction and positive cardiac biomarkers, although aggressive supportive care appears to reverse the dysfunction. Persistent cardiac dysfunction beyond 24 hours may be a marker of a poor outcome.

               Wilson W, Taubert KA, Gewitz M, et al. Prevention of Infective endocarditis— guidelines from the American Heart Association. Circulation 2007;116: 1736-1754.

               This AHA guideline on prevention of infective endocarditis (IE) is the first update on the topic since 1997. The authors summarize their primary reasons for revising the IE prophylaxis guidelines based on the following 4 major concepts:

               Infective endocarditis is much more likely to result from frequent exposure to random bacteremias associated with daily activities than from bacteremia caused by a dental, GI tract, or genitourinary tract procedure.

            3. Prophylaxis may prevent an exceedingly small number of cases of IE, if any, in individuals who undergo a dental, gastrointestinal, or genitourinary procedure.
            4. The risk of antibiotic-associated adverse events exceeds the benefit, if any, from Prophylactic antibiotic therapy.
            5. Maintenance of optimal oral health and hygiene may reduce the incidence of bacteremia from daily activities and is more important than prophylactic antibiotics for a dental procedure to reduce the risk of IE.

               The following scenarios are the Cardiac conditions associated with the highest risk of adverse outcome from endocarditis for which prophylaxis with certain procedures is indicated: prosthetic cardiac valve or prosthetic material used for cardiac valve repair; previous IE; congenital heart disease (unrepaired cyanotic congenital heart disease; completely repaired congenital heart defect with prosthetic material or device during the first

               6 months after the procedure; repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device; and cardiac transplantation recipients who develop cardiac valvulopathy). Notable absences from the list groups above include patients with mitral valve prolapse and patients with a history of CABG or coronary stents.

               antibiotic prophylaxis is indicated for groups that fit the criteria above if they undergo any “…Dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of oral mucosa…” Antibiotic prophylaxis is also considered reasonable for groups that fit the above criteria for respiratory tract procedures involving incision or biopsy of respiratory mucosa, for invasive procedures involving infected skin, skin structures, and musculoskeletal tissue. Antibiotic prophylaxis solely to

               prevent IE is no longer recommended for gastrointestinal or genitourinary tract procedures.

               Antibiotics should be given to the groups that meet the above criteria in a single dose 30 to 60 minutes before the procedure. Reasonable antibiotic regimens include those listed in the table.

               Route/ allergy status	Adult	Children
               Oral route Parenteral route Penicillin allergic, oral route Penicillin allergic, parenteral route	Amoxicillin, 2 g Ampicillin, 2 g IM/IV, or cefazolin, 1 g IM/IV, or ceftriaxone, 1 g IM/IV Cephalexin, 2 g, or clindamycin, 600 mg, or azithromycin, 500 mg, or clarithromycin, 500 mg Cefazolin, 1 g IM/IV, or ceftriaxone, 1 g IM/IV, or clindamycin, 600 mg IM/IV	Amoxicillin, 50 mg/kg Ampicillin, 50 mg/kg IM/IV, or cefazolin, 50 mg/kg IM/IV, or ceftriaxone, 50 mg/kg IM/IV Cephalexin, 50 mg/kg, or clindamycin, 20 mg/kg, or azithromycin, 15 mg/kg, or clarithromycin, 15 mg/kg Cefazolin, 50 mg/kg IM/IV, or ceftriaxone, 50 mg/kg IM/IV, or clindamycin, 20 mg/kg IM/IV

               References

               1. Ceriello A. Acute hyperglycaemia: a “new” risk factor during myocardial infarction. Eur Heart J 2005;26:328-31.
               2. Kosiborod M, Rathore SS, Inzucchi SE, et al. Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. Circulation 2005;111:3078-86.
               3. Pinto DS, Skolnick AH, Kirtane AJ, et al. U-shaped relationship of blood glucose with adverse outcomes among patients with ST- segment elevation myocardial infarction. J Am Coll Cardiol 2005;46:178-80.
               4. 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). Circulation 2004;110:588-636.
               5. Fitchett DH, Borgundvaag B, Cantor W, et al. Non ST segment elevation acute coronary syndromes: a simplified risk-orientated algorithm. Can J Cardiol 2006;22:663-77.
               6. Pfisterer M, Cox JL, Granger CB, et al. Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries. J Am Coll Cardiol 1998; 32:634-40.
               7. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1622-32.
               8. Core Options. The Joint Commission measure set definitions. Available at: http://www.coreoptions.com/new_site/jcahocore.html Accessed 1/23/2008, 2008.
               9. Khot UN, Johnson ML, Ramsey C, et al. Emergency department physician activation of the catheterization laboratory and immediate transfer to an immediately available catheterization laboratory reduce door-to-balloon time in ST-elevation myocardial infarction. Circula- tion 2007;116:67-76.
               10. Ryan JW, Peterson ED, Chen AY, et al. Optimal timing of intervention in non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE (Can Rapid risk stratification of

               Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Registry. Circulation 2005;112:3049-57.

               1. Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE quality improvement initiative. Am Heart J 2005;149: 1043-9.
               2. Hostler D, Guimond G, Callaway C. A comparison of CPR delivery with various compression-to-ventilation ratios during two-rescuer CPR. Resuscitation 2005;65:325-8.
               3. Aufderheide TP, Sigurdsson G, Pirrallo RG, et al. Hyperventilation- induced hypotension during cardiopulmonary resuscitation. Circula- tion 2004;109:1960-5.
               4. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-56.
               5. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63.
               6. Kliegel A, Losert H, Sterz F, et al. Cold simple intravenous infusions preceding special endovascular cooling for faster induction of Mild hypothermia after cardiac arrest-a feasibility study. Resuscitation 2005;64:347-51.
               7. Polderman KH, Rijnsburger ER, Peerdeman SM, Girbes AR. Induction of hypothermia in patients with various types of neurologic injury with use of large volumes of ice-cold intravenous fluid. Crit Care Med 2005;33:2744-51.
               8. Kim F, Olsufka M, Carlbom D, et al. Pilot study of rapid infusion of 2 L of 4 degrees C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest. Circulation 2005;112:715-9.
               9. Virkkunen I, Yli-Hankala A, Silfvast T. Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice- cold Ringer’s solution: a pilot study. Resuscitation 2004;62: 299-302.
               10. Bernard S, Buist M, Monteiro O, Smith K. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out- of-hospital cardiac arrest: a preliminary report. Resuscitation 2003;56: 9-13.
               11. Nolan JP, Morley PT, Vanden Hoek TL, et al. Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation 2003;108:118-21.
               12. Collins SP, Lindsell CJ, Peacock WF, Eckert DC, Askew J, Storrow AB. Clinical characteristics of emergency department heart failure patients initially diagnosed as non-heart failure. BMC Emerg Med 2006;6:11.
               13. Peter JV, Moran JL, Phillips-Hughes J, Graham P, Bersten AD. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Lancet 2006;367:1155-63.
               14. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114: e385-484.
               15. Mattu A, Brady WJ. The “cardiac” literature in 2006: an annotated review for the emergency physician. Am J Emerg Med 2007;25:960-76.
               16. Masoudi FA, Magid DJ, Vinson DR, et al. Implications of the failure to identify high-risk electrocardiogram findings for the quality of care of patients with acute myocardial infarction: results of the Emergency Department Quality in Myocardial Infarction (EDQMI) study. Circulation 2006;114:1565-71.
               17. Otto LA, Aufderheide TP. Evaluation of ST-segment elevation criteria for the prehospital electrocardiographic diagnosis of acute myocardial infarction. Ann Emerg Med 1994;23:17-24.
               18. Brady WJ, Perron AD, Martin ML, Beagle C, Aufderheide TP. Electrocardiographic ST-segment elevation in emergency department chest pain center patients: etiology responsible for the ST-segment abnormality. Am J Emerg Med 2001;19:25-8.
               19. Williamson K, Mattu A, Plautz CU, Binder A, Brady WJ. Electrocardiographic applications of lead aVR. Am J Emerg Med 2006;24:864-74.
               20. Quinn JV, Stiell IG, McDermott DA, et al. Derivation of the San Francisco Syncope Rule to predict patients with Short-term serious outcomes. Ann Emerg Med 2004;43: 224-32.
               21. Mattu A, Rogers RL, Kim H, Perron AD, Brady WJ. The Brugada syndrome. Am J Emerg Med 2003;21:146-51.
               22. Kelly BS, Mattu A, Brady WJ. Hypertrophic cardiomyopathy: electrocardiographic manifestations and other important considera- tions for the emergency physician. Am J Emerg Med 2007;25: 72-9.