Appropriate Cardiac Cath Lab Activation: Optimizing Electrocardiogram Interpretation and Clinical Decision- Making for Acute ST-Elevation Myocardial Infarction Ivan C

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Appropriate Cardiac Cath Lab activation: Optimizing electrocardiogram interpretation and clinical decision- making for acute ST-elevation myocardial infarction Ivan C. Rokos, MD, a William J. French, MD, b Amal Mattu, MD, c Graham Nichol, MD, d Michael E. Farkouh, MD, MSc, e James Reiffel, MD, f and Gregg W. Stone, MD f Los Angeles, CA; Baltimore, MD; Seattle, WA; Toronto, ON; and New York, NY

During the last few decades, acute ST-elevation on an electrocardiogram (ECG) in the proper clinical context has been a reliable surrogate marker of acute coronary occlusion requiring primary percutaneous coronary intervention (PPCI). In 2004, the American College of Cardiology/American Heart Association ST-elevation myocardial infarction (STEMI) guidelines specified ECG criteria that warrant immediate angiography in patients who are candidates for primary PPCI, but new findings have emerged that suggest a reappraisal is warranted. Furthermore, as part of integrated and efficient STEMI systems, emergency department and emergency medical services providers are now encouraged to routinely make the time-sensitive diagnosis of STEMI and promptly activate the cardiac catheterization laboratory (Cath Lab) team. Our primary objective is to provide a practical summary of updated ECG criteria for emergency coronary angiography with planned PPCI, thus allowing clinicians to maximize the rate of appropriate Cath Lab activation and minimize the rate of inappropriate Cath Lab activation. We review the evidence for ECG interpretation strategies that either increase diagnostic specificity for “classic” STEMI and left bundle- branch block or improve diagnostic sensitivity in identifying 4 STEMI-equivalents: posterior MI, acute left main occlusion, de Winter ST/T-wave complex, and certain scenarios of resuscitated cardiac arrest. (Am Heart J 2010;160:995-1003.e8.)

The key trigger point for emergency cardiac catheter- diagnosis of STEMI have emerged since 2004, they have ization laboratory (Cath Lab) activation is usually a single not been reviewed by any of the more recent guide- electrocardiogram (ECG) diagnostic of an acute ST-- lines.2-6 Hence, our primary objective is to provide a elevation myocardial infarction (STEMI), which instantly practical summary of updated criteria for emergency reclassifies a patient with chest pain or other acute coronary angiography with planned PPCI, thus allowing cardiac symptoms from “routine evaluation” status to clinicians to maximize the rate of appropriate Cath Lab “high-priority” STEMI procedure (Figure 1). The 2004 activation and minimize the rate of inappropriate Cath American College of Cardiology/American Heart Associ- Lab activation. ation (ACC/AHA) guidelines1 specify ECG criteria that Three background concepts are important. First, ECG warrant immediate angiography in patients who are analysis is a fundamental clinical skill that is used candidates for primary percutaneous coronary interven- routinely by a broad range of clinicians, but high-risk tion (PPCI). Although new findings related to the ECG ECG findings consistent with acute ischemia continue to be overlooked.7 Second, a common “efficiency challenge” involves the need to quickly differentiate and treat the small cohort of acute STEMI patients from the much From the aUCLA-Olive View, Department of Emergency Medicine, Los Angeles, CA, larger group of undifferentiated “chest pain” patients bHarbor-UCLA, Division of Cardiology, Department of Medicine, Los Angeles, CA, (Figure 1). This must be balanced against the potential for c d University of Maryland, Department of Emergency Medicine, Baltimore, MD, University poor resource utilization, especially with the current of Washington-Harborview Center for Pre-Hospital Emergency Care, Seattle, WA, eUniversity Health Network and Li Ka Shing Knowledge Institute, Toronto, ON, and emphasis on early Cath Lab activation by either emer- fColumbia University Medical Center and the Cardiovascular, Research Foundation, gency department (ED) or emergency medical services New York, NY. providers.8,9 Third, a coordinated systems-based ap- Submitted March 29, 2010; accepted August 12, 2010. proach is currently emphasized by the ACC/AHA STEMI Reprint requests: Ivan C. Rokos, MD, FACEP, FAHA, (FACC), UCLA-Olive View Medical 2,3 10 Center, Department of Emergency Medicine, North Annex, 14445 Olive View Drive, guidelines, the ACC Door-2-Balloon (D2B) Alliance, 11 Sylmar, CA 91342-1495. and the AHA Mission: Lifeline initiative. Proposed E-mail: [email protected] efforts within Mission:Lifeline12 to comprehensively 0002-8703/$ - see front matter © 2010, Mosby, Inc. All rights reserved. track all Cath Lab activations and improve overall STEMI doi:10.1016/j.ahj.2010.08.011 system efficiency depend on the existence of clearly American Heart Journal 996 Rokos et al December 2010

Figure 1

STEMI Process #1 empowers frontline providers (ED triage nurses and paramedics) to promptly perform an ECG on all suspected cardiac patients. The STEMI Diagnosis by 12-lead electrocardiography is the key trigger point for a series of events designed to rapidly restore blood flow in an acutely occluded coronary. The STEMI Process #2 includes all the treatments provided in the time interval from STEMI diagnosis to patient arrival in the Cath Lab. The Cath Lab STEMI Procedure begins with emergency coronary angiography, followed by PPCI and other invasive procedures as indicated. STEMI Process #3 represents active participation in a quality improvement registry for the entire system.

defined criteria that distinguish appropriate versus most common (≈80%) ECG finding that is customarily inappropriate Cath Lab activation. reported, respectively, as an infarction of the anterior or To maximize appropriate Cath Lab activations, we inferior region of the heart in registries, clinical trials, and critically review and summarize (Tables I and II) real-time the International Classification of Diseases, Ninth ECG interpretation strategies that accurately identify both Revision, billing codes. STEMI and STEMI-equivalents. Criteria defining the term As specified in a recent expert consensus document,15 STEMI-equivalent have been gradually standardized by actual ECG leads should not be simply referred to as both the National Cardiovascular Data Registry (NCDR) “anterior” or “inferior” because this de-emphasizes the data dictionaries and international consensus,13 and important bioelectric principle that all ECG leads are broadly include any ECG pattern potentially associated bipolar. Thus, an acute coronary occlusion can manifest with an acute coronary occlusion but lacking “classic” on any of the 12 individual leads of a standard ECG with ST-elevation. Efficient STEMI systems of care need to either ST-elevation at the positive pole or ST-depression at maximize diagnostic specificity for both classic STEMI the negative pole. For example, leads V1 through V3 might ECG patterns and new (or presumed new) left bundle- be designated most accurately as “anteroseptal-postero- branch block (ie, a STEMI-equivalent), whereas diagnos- lateral” bipolar leads. This provides the rationale for tic sensitivity should be improved in identifying 4 designating certain types of ST-depression ECG patterns as additional STEMI-equivalents: posterior MI, acute left true STEMI-equivalents (eg, posterior MI, acute left main main occlusion, de Winter ST/T-wave complex, and occlusion, de Winter ST/T-wave complex). certain scenarios of resuscitated cardiac arrest. Moreover, Because current guidelines1 state that timely PPCI is the we propose that clinicians conceptually prioritize 3 ques- preferred reperfusion modality, our review has principal- tions when analyzing any ECG: (1) Are the ST-segments ly focused upon appropriate Cath Lab activation criteria. consistent with acute STEMI or STEMI-equivalent? (2) Has However, in many STEMI-care settings, prompt adminis- chronic ST-segment elevation that does not represent tration of fibrinolytics represents the only realistic acute myocardial infarction been excluded? (3) Is the reperfusion option for an acute coronary occlusion per patient a reasonable candidate for reperfusion therapy the guidelines.1 Fortunately, initial ECG interpretation (PPCI or fibrinolytics)? strategies for detecting acute STEMI or STEMI-equivalent are similar for treatment pathways involving either PPCI or fibrinolysis, but safe fibrinolytic administration also Definitions and background concepts requires review of a standardized Contraindications Checklist.1 Acute myocardial infarction can be defined from various clinical perspectives: electrocardiography, biomarkers, angiography, imaging, and pathology.14 How- ever, the 2004 guidelines1 emphasize the central role of Maximizing diagnostic specificity for the ECG in decision-making during the acute phase and acute coronary occlusion define “classic STEMI” as ≥1 mm ST-elevation in 2 Classic STEMI adjacent leads (class I-A recommendation). Acute and In the proper clinical context, acute ST-elevation persistent ST-elevation, meeting these criteria in either ≥1 mm in 2 contiguous ECG leads represents a reliable leads V1 through V4 or leads II/III/aVF, represents the surrogate marker for an acute coronary occlusion American Heart Journal Rokos et al 997 Volume 160, Number 6

Table I. Comparison of 2004 ACC/AHA guidelines and authors' proposed update for ECG criteria that enhance the rate of appropriate Cath Lab activation for acute MI

Indications for Diagnostic criteria for 2004 ACC/AHA appropriate Cath patients with guideline Proposed update vs. Lab activation symptoms <12 h recommendation ACC/AHA guidelines Comment

Classic STEMI Anterior ST-elevation ≥1mmin2 Class I-A Agree ST-elevation ≥2 mm (men) ≥ contiguous leads V1-V4 and 1.5 mm (women) improves diagnostic specificity.15 Presence of reciprocal changes (ST-depression in opposite leads) improves diagnostic specificity. Inferior ST-elevation ≥1mmin2 Class I-A Agree Presence of reciprocal contiguous leads changes improves diagnostic (II, III, or AVF) specificity. Lateral ST-elevation ≥1mmin2 Class I-A Agree As above. contiguous leads

(I, AVL, V5,orV6)

STEMI-equivalents New or presumed “Presumed new” LBBB Class I-A Proposed demotion in future Unless clinically unstable, new-onset LBBB assumed when prior ACC/AHA guidelines most LBBB should be ECG unavailable” evaluated with biomarkers “New” LBBB when prior and non-emergent ECG available angiography if indicated. An “old” ECG without LBBB does not necessarily confirm that the “new LBBB” is acute. Preexisting LBBB with Concordance noted between None Proposed addition to future Use of these decision criteria Sgarbossa concordance QRS complex and ST/T-wave ACC/AHA guidelines provides N95% specificity complex, with ST elevation and avoids the need to find a ≥1mmin≥1 lead prior ECG for comparison. Discordant ST-elevation ≥ 5 mm is also a Sgarbossa criteria, but some studies found it a weak predictor. Posterior MI (isolated) ST-depression ≥0.5 mm in Fibrinolytics: class IIa-C Proposed clarification in Recent data34 demonstrated Primary PCI leads V1-V3 : class I-A implied future ACC/AHA guidelines that most posterior MIs are Associated T-waves are either currently evaluated with upright or inverted. urgent (rather than Appearance of tall R-waves emergent) angiography, but

in V1-V2 may be delayed. this delay is associated with worse clinical outcomes. Left Main coronary ST-depression ≥ 1mmin None Proposed addition to future Most relevant in any ECG occlusion 6 or more leads ACC/AHA guidelines with diffuse ST-depression Lead aVR with ST-elevation ≥ 1mm ≥1 mm that does not meet ≥ ST-elevation in lead aVR V1 classic STEMI criteria, thus providing a subtle clue that emergency angiography may be warranted de Winter ST/T-wave ST depression ≥1mm None Proposed addition to future Tall T waves and up-sloping complex up-sloping at the J-point in ACC/AHA guidelines ST depression are persistent,

leads V1-V6 not transient. Precordial T waves are tall, Associated with proximal upright, symmetric LAD occlusion Normal QRS duration Hyper-acute T-waves Tall peaked T waves None Potential addition to future Generally prudent to perform immediately following ACC/AHA guidelines serial ECGs, because true symptom onset may HATW generally morph represent acute ischemia, quickly into a classic STEMI but clinical studies pattern13 are lacking. Hyperkalemia is another common cause of tall T waves American Heart Journal 998 Rokos et al December 2010

Table II. Three scenarios for appropriate Cath Lab activation involving out-of-hospital cardiac arrest (OHCA)

First event Second event Action Supplemental action

Acute STEMI diagnosed by Cardiac arrest witnessed by EMS Cath Lab team at STEMI receiving center should Initiate hypothermia protocol prehospital ECG providers, followed by prompt have already been activated based on original in postresuscitation patients defibrillation and ROSC diagnosis of STEMI or STEMI-equivalent who remain unconscious

Bystander witnessed OHCA, Shockable rhythm and ROSC Activate Cath Lab team at cardiac Same as above early activation of 9-1-1, achieved, followed by ECG resuscitation center and early chest diagnostic of acute STEMI or compressions STEMI-equivalent

Same as above Shockable rhythm and ROSC Consider activation of Cath Lab team at cardiac Same as above achieved, but postresuscitation resuscitation center in patients whose clinical ECG is not diagnostic of acute circumstance suggests acute ischemia and who STEMI or STEMI-equivalent are candidates for aggressive intervention

EMS, Emergency medical services. requiring PPCI (Table I and online Appendix items I.a-d). Table III. Classification of appropriate versus inappropriate Cath However, ECG accuracy may be limited by multiple Lab activation conditions: large individual variations in coronary anatomy, preexisting disease, collateral circulation, misplaced Appropriate Cath Lab Activation ⇒ Ideal leads, and technical shortcomings in detecting electrical •Angiography and PPCI performed impulses from certain regions of the heart.15,16 ⇒ Inappropriate Cath Lab activations have a number of Appropriate Cath Lab Activation Reasonable •Angiography without PPCI performed: negative implications, including poor resource utiliza- –Surgical revascularization indicated tion, unnecessary costs, patient safety risk, increased –Coronary anatomy is not amenable to PPCI intervention (ie, Medical therapy) patient anxiety, work-life-sleep issues that may adversely –“Unavoidable angiogram” per index ECG and/or clinical scenario as documented by “ ” the real-time clinicians (eg, Tako-tsubo, myocarditis) affect career longevity of Cath Lab staff (ie, burn-out ), –No PPCI target-lesion identified but cardiac markers become elevated and potential community risk from entire Cath Lab teams •Before angiography, true STEMI per index ECG dies suddenly rushing (ie, driving fast) back to the hospital to treat an •Angiography ± PPCI for ROSC following witnessed OHCA from a shockable rhythm. Some ROSC patients may deteriorate and die before angiography. after-hours STEMI. Initial reports of ED physician Inappropriate Cath Lab Activation ⇒ Goal is <5% rate performance in diagnosing acute STEMI identified a 9% •No Angiography performed (Cath Lab activation cancelled by a physician) rate of false-positive Cath Lab activation (no culprit artery •Angiography without a PPCI target-lesion identified and normal cardiac markers: 17 and negative biomarkers). More recent surveillance of –“Avoidable angiogram” based upon erroneous ECG interpretation “unnecessary” Cath Lab activations (ie, cardiologist did •Advanced co-morbidities: Patient is not a PPCI-candidate not perform emergency coronary angiography) by ED Classification based on retrospective and multidisciplinary peer review of all index physicians demonstrated a 5% rate from a single-center clinical data. Green zone represents the ideal scenario, yellow zone events are 18 experience (n = 249 activations) in Virginia and a 6% reasonable, and red zone occurrences should be minimized (<5%). rate across 14 hospitals (n = 2,213 activations) in a North Carolina STEMI system.19 In contrast, evaluation of resource utilization in STEMI systems, 6 ECG-interpreta- prehospital-ECG interpretation by paramedics (n = 646) tion strategies are reviewed below. from Los Angeles County, California, found a 20% rate of First, the degree of ST-elevation is a continuous inappropriate Cath Lab activation (ie, cardiologist did variable that has been stratified (<1 or ≥1 mm) in the not perform emergency coronary angiography), with an guidelines1 to yield a convenient binary diagnosis additional 5% of suspected STEMI on PH-ECG that never (STEMI absent vs. present, respectively). However, resulted in Cath Lab activation (although PH-ECG evidence exists for increased specificity when diagnostic transmission was rarely used).20 Similar analysis (n = criteria involve ≥2 mm ST-elevation in certain precordial 529) from Orange County, California, found a 23% rate leads.6 In recognition of benign ST-elevation that is of inappropriate Cath Lab activation.21 frequently observed in healthy adults, the NCDR data As proposed previously,22 we believe a <5% rate of dictionaries (Cath-PCI v4.3 and ACTION-GWTG v2.1) inappropriate Cath Lab activation represents a reason- currently set the STEMI threshold in leads V2-V3 at 2 mm able STEMI systems goal. Table III provides our concep- for men and 1.5 mm for women. Similarly, a recent tual framework summarizing appropriate versus AHA/ACC statement15 in conjunction with the Heart inappropriate Cath Lab activation scenarios, recognizing Rhythm Society listed the same criteria (except for that not all Cath Lab activations classified as appropriate men age <40, the threshold is N2.5 mm ST-elevation in actually result in PPCI. To help clinicians optimize leads V2-V3). American Heart Journal Rokos et al 999 Volume 160, Number 6

Table IV. Common STE-mimics worse outcomes (composite of death, heart failure, or shock at 90 days) after multivariate adjustment. Narrow QRS Complex Tall/Wide QRS STE-mimics Complex STE-mimics Fifth, a commonly used ECG computer algorithm demonstrated 90% specificity for identifying acute 26 Benign early repolarization (BER) Left ventricular hypertrophy (LVH) STEMI when evaluated in a clinical trial, thus providing Pericarditis LBBB a reasonable real-time diagnostic aide for clinicians Left ventricular aneurysm Paced rhythm involved in time-pressured ECG interpretation. However, Normal variant “male pattern” Hyperkalemia Preexcitation Brugada syndrome experience with the computer algorithm for prehospital ECGs as part of regional STEMI networks has demon- 23 A comprehensive list of all STE-mimics already exists. strated lower specificity and increased rates of inappropriate Cath Lab activation.9,20,21 Lastly, immediate Wireless transmission and Physician Second, clinician awareness regarding the existence Interpretation (WiPI) of all prehospital-ECGs with sus- of ST-elevation mimics (STE-mimics) is essential and pected STEMI improves the rate of appropriate Cath Lab provides the basis for distinguishing pathologic vs. activation.27 By increasing the number of “critical eyes” nonpathologic ST-elevation.23 At the minimum, clinician that review an ECG in real-time (simultaneously with familiarity should exist broadly for 10 common condi- patient transport), WiPI can provide an important tions (Table IV and online Appendix items III.a-e) with “appropriateness filter” between a prehospital STEMI chronic ST-elevation. Alert and an in-hospital Code STEMI.9 Third, the presence of reciprocal changes on the ECG (ie, ST-depression ≥0.5 mm in leads 180° opposite to those meeting ST-elevation criteria) should exist for all Left bundle-branch block ECGs with acute STEMI based upon bioelectric princi- Left bundle-branch block (LBBB) represents a unique ples, but this reciprocal ST-depression might be of lesser challenge in the acute setting, because it can be cate- magnitude or undetectable due to technical limitations of gorized as either a STE-mimic or a STEMI-equivalent. As the standard 12-lead ECG.15,16 By definition, reciprocal a STE-mimic, chronic LBBB patterns in asymptomatic ST-depression should never occur in ECGs considered patients almost always have persistent ST-elevation normal or those with narrow-complex STE-mimics ≥1 mm in the anteroseptal and/or inferior leads. (except lead aVR with pericarditis). In a fibrinolytic era However, for decades, new (or presumed new) LBBB study,24 the presence of any reciprocal ST-depression in has also been considered a STEMI-equivalent that requires ≥2 leads was associated with N95% diagnostic specificity prompt therapy, with inclusion in guidelines, clinical and positive predictive value for acute MI. More recently, trials, NCDR registries, and Joint Commission acute MI an AHA scientific statement15 recommended that com- core measures. Furthermore, both the ACC/AHA and puterized interpretation algorithms incorporate the European guidelines1,5 strongly recommend (class I-A) location of ST-depression to predict the location of a immediate reperfusion, based predominately on old meta- coronary occlusion. Collectively, these data suggest that analysis data showing reduced mortality in fibrinolytic- clinicians should evaluate every ECG with suspected treated LBBB patients.28 STEMI for reciprocal changes: if present, then appro- Data have gradually accumulated suggesting that priate Cath Lab activation is almost certain; if absent, traditional criteria using new (or presumed new) LBBB the presence of a STE-mimic versus a true STEMI as a STEMI-equivalent results in low diagnostic specificity without reciprocal changes should be carefully but and high rates of inappropriate Cath Lab activation. For expeditiously considered. Observation of reciprocal example, a fibrinolytic era study of 7,725 consecutive changes may be also be helpful in resolving challenging patients with suspected cardiac ischemia presenting to a “semi-STEMI” cases near the 1-mm threshold, where one single ED found only 182 (2.4%) patients with LBBB on clinician may see 1.1 mm of ST-elevation but another ECG, and only 24 (13%) of the 182 with LBBB had an sees only 0.9 mm. acute myocardial infarction using positive biomarkers Fourth, pathologic Q-waves may develop in leads as the gold standard.29 initially demonstrating ST-elevation, and hence their In the modern era, angiographic assessment of “pre- presence supports the diagnosis of true STEMI (but sumed new LBBB” also raised concerns about treating their absence does not exclude acute STEMI).1 Further- these patients emergently as a true STEMI-equivalent. more, a recent APEX-AMI substudy25 analysis of 4,530 A recent single-center PPCI-focused study30 of 7,937 patients with ≤6 hours of symptoms identified 2,514 “chest pain” patients in the ED identified 55 (0.7%) (56%) with a Q wave (defined as ≥40 milliseconds presumed new LBBB, 136 (1.7%) confirmed old LBBB, [1 mm] duration, excluding lead III) already present on and 7,746 (97.6%) without LBBB. In the primary analysis the baseline ECG. Even with contemporary PPCI-based comparing the “new vs old vs no” LBBB cohorts, the rate reperfusion, the cohort with Q waves at baseline had of biomarker-confirmed acute MI was similarly low (7.3%, American Heart Journal 1000 Rokos et al December 2010

5.2%, 6.1%, respectively, P = .75). Thus, N90% of LBBB Although replacement terms like posterolateral MI were patients evaluated in the ED do not have an acute considered, the expert statement ultimately recom- coronary occlusion nor require PPCI. Similarly, a recent mended retaining the term posterior MI for ST-depression analysis from the PPCI-focused Minneapolis interhospital ≥0.5 mm in leads V2 through V3 (or ST-elevation ≥0.5 mm 17 transfer network identified only 36 (2.6%) of 1335 in leads V7-V9) until additional data become available. patients with “presumed new LBBB.” Moreover, 16 (44%) The TRITON-TIMI-38 study33 enrolled patients with of 36 from this cohort did not have a culprit artery both STEMI and non-STEMI, and thus it provided a unique visualized during emergency coronary angiography, and opportunity to evaluate contemporary posterior MI 13 (36%) of 36 had no elevation of serial biomarkers. therapy. According to a recent substudy,34 isolated 5 The latest ESC guidelines acknowledge these more ST-depression in leads V1 through V3 on index ECG was recent findings by stating that biomarker results “may present in 1,198 (8.8%) of the 13,608 enrolled patients sometimes be helpful” in evaluating LBBB patients, thus and retrospectively classified by the core lab as “posterior implying treatment of stable patients with an urgent MI” (26.2%), non-STEMI (53.5%), and unstable angina rather than emergent PCI strategy. Importantly, clinically (20.3%) based upon cardiac markers and angiography. unstable LBBB patients or those with acutely abnormal Despite guideline recommendations,1 the vast majority anterior wall motion by echocardiography should still (1193 [99.6%]) of study patients with isolated ST-depression receive emergency angiography. in leads V1 through V3 were treated with non-emergent PCI Published ECG criteria (Table I and online Appendix (N6 hours after index ECG). However, the cohort of “slowly item II.e) exist that maximize diagnostic specificity for treated” posterior MIs had an acutely occluded coronary detecting a true STEMI-equivalent in the setting of (most commonly the left circumflex) and had a significantly chronic LBBB. A chronic LBBB normally has discor- higher rate of 30-day death or MI as compared with those dance (the direction of the major component of the classified as non-STEMI. QRS complex is opposite that of ST segment/T wave in any lead), whereas QRS/ST concordance (with ST elevation ≥1mmin≥1 lead) appears to be the most Left main coronary occlusion robust predictor of acute ischemia.6,15,31 A recent meta- Acute left main coronary occlusion (LMCO) generally analysis32 found only 20% sensitivity but 98% specificity causes massive ischemia and is rapidly lethal, but a small for the “concordance criteria,” but much of the data is proportion of patients have enough perfusion from right- from the fibrinolytic era when cardiac markers instead sided collaterals to arrive alive at the hospital. A recent of angiography were the gold standard. Cath-PCI Registry analysis35 spanning 2004 to 2008 identified 434 (0.35% of all attempted PCIs in Cath-PCI) with acute STEMI from a left main culprit that was “unprotected” (ie, no prior coronary artery bypass Maximizing diagnostic sensitivity for grafting to distal vessels). Interestingly, about one third acute coronary occlusion of patients did not present in cardiogenic shock, even Posterior myocardial infarction though angiography demonstrated that 85% of these True posterior MI should be treated as a STEMI- patients had N90% stenosis and 55% had complete equivalent, in which case isolated ST-depression LMCO. Importantly, survival to hospital discharge was ≥0.5 mm in leads V1 through V3 represents the dominant 42% in this series. finding (Table I and online Appendix item II.a) on a STEMI-equivalent ECG criteria (Table I and online standard 12-lead ECG.6,15 The use of additional posterior Appendix item II.b) exist for diagnosing the critical chest wall leads (V7-V9 ≥0.5 mm) to detect ST elevation condition of acute LMCO, but these are not mentioned in consistent with posterior MI is often recommended,6,15 any of the guidelines.1-3,5 In 2001, a small series reported but their use remains uncommon in daily practice. that ≥0.5-mm ST-elevation in lead aVR is consistent Clinical trials commonly exclude posterior MI and the with acute LM occlusion, especially when the degree of 1 guidelines reflect this paucity of evidence with a class ST-elevation in aVR is greater than lead V1 and inferior IIa-C recommendation for administering fibrinolytics in ST-depression is present.36 A combined analysis of 3 this subset of patients. Paradoxically, the guidelines1 studies with a total of 75 acute LM occlusions confirmed indirectly imply a class I-A recommendation for PPCI of by angiography demonstrated N75% sensitivity and posterior MI. specificity for these ECG findings.37 A recent AHA scientific statement15 critiqued the term A 2009 AHA scientific statement15 recommended posterior MI (used in the 2004 ACC/AHA guidelines, “when the resting ECG reveals ST-depression N1mm clinical trials, NCDR registries, and International Classi- in 8 or more surface leads coupled with ST-elevation in fication of Diseases, Ninth Revision, codes) because the aVR and/or VI but is otherwise unremarkable, the actual infarct occurs in the lateral wall of the left ventricle automated [computerized] interpretation should suggest when assessed by advanced imaging techniques. ischemia due to multi-vessel or left main coronary artery American Heart Journal Rokos et al 1001 Volume 160, Number 6

obstruction.” A 2010 international consensus document13 the deaths in STEMI patients occur from lethal arrhyth- provided similar STEMI-equivalent criteria for acute mias within 1 to 2 hours of symptom onset. LMCO (or severe angiographic disease): a myocardial Historically, the practice of taking resuscitated OHCA ischemia vector causing ST-depression in 6 or more leads patients for emergency coronary angiography and (maximal in V4-V6) and associated ST-elevation limited planned PPCI was rare and usually restricted to a small to lead aVR and V1. cohort of “ideal” patients: witnessed arrest, early chest compressions, early defibrillation of a shockable rhythm (ventricular tachycardia or fibrillation), early ROSC, hemo- de Winter ST/T-wave complex dynamically and electrically stable on arrival to the In 2008, de Winter et al38 described a novel STEMI- hospital, and clinically perceived on initial assessment to equivalent ECG pattern that signifies acute occlusion of have experienced only minimal neurologic injury from the proximal left anterior descending (LAD). Following ischemia. Although randomized controlled trials of STEMI examination of their Dutch registry, the “de Winter ST/ almost uniformly exclude OHCA, observational registry T-wave” pattern was first recognized in 30 unique data has gradually accumulated and demonstrated good patients (all with normal baseline serum potassium outcomes in resuscitated OHCA patients who traditionally levels) and represented 2% of all angiographically have been considered “less than ideal” candidates for Cath confirmed anterior MIs. Diagnostic criteria on ECG Lab intervention. Thus, both the 2008 International Liai- include 1 to 3 mm of ST-depression that is up-sloping son Committee on Resuscitation41 consensus statement 42 at the J-point in leads V1 through V6 and associated and the 2009 state-of-the-art paper by Ewy and Kern with persistently tall, upright, and symmetric precordial recommended aggressive postresuscitation care involving T-waves (Table I and online Appendix item II.c). both PPCI and invasive hemodynamic support for a The de Winter ST/T-wave complex is distinct from greater proportion of patients resuscitated from OHCA. transient hyper-acute T-waves (HATW) that may occur Despite the International Liaison Committee on Resus- within minutes of an acute coronary occlusion (repre- citation consensus statement, controversy still exists senting another potential STEMI-equivalent ECG pattern) regarding the ability of a postresuscitation ECG to identify but generally morph quickly into a classic STEMI patients with an acute coronary occlusion.43,44 However, pattern.13,38 Transient HATW can be induced with the largest experience to date is the PROCAT45 registry, experimental occlusion of a coronary for a few minutes, which provided compelling new evidence supporting a but they have not been used as inclusion criteria for routine Cath Lab based treatment pathway for OHCA STEMI clinical trials. regardless of ECG pattern after resuscitation. In the In addition, de Winter ST/T-wave complex should not PROCAT registry spanning 2003 to 2008, all 435 resus- be confused with Wellens syndrome,39 in which the citated OHCA patients with no obvious extracardiac ECG demonstrates either biphasic or inverted T waves cause of arrest received emergency coronary angiogra- in leads V2 through V3 (online Appendix item II.d). phy. Of the 134 patients with a post-ROSC ECG Wellens syndrome typically involves a chronic high- demonstrating classic STEMI, 128 (96%) had at least one grade LAD stenosis that can usually be evaluated by non- significant lesion (N50% reduction in luminal diameter) emergent angiography. and 99 (74%) underwent successful PCI. In the remaining 301 patients without classic STEMI on post-ROSC ECG, 176 (58%) had a significant lesion and 78 (26%) received Resuscitated cardiac arrest PCI. Multivariable analysis demonstrated successful PCI For more than a decade, it has been known that to be an independent predictor of survival (OR 2.1, 95% approximately 50% of patients with out-of-hospital CI 1.2-3.7), irrespective of postresuscitation ECG pattern. cardiac arrest (OHCA) and return of spontaneous As compared to a historically low rate of survival circulation(ROSC)haveanacutecoronaryartery (<10%),41 overall survival to hospital discharge was 40% occlusion when evaluated by immediate diagnostic in the PROCAT registry. Moreover, there was a 94% rate angiography.40 Hence, in addition to the acute STEMI of favorable neurologic outcomes in a cohort with a 68% and STEMI-equivalent ECG criteria (Table I) reviewed rate of shockable first rhythm and 85% rate of in-hospital thus far, certain scenarios of OHCA with ROSC appear to therapeutic hypothermia. be gaining acceptance as a trigger for appropriate Cath A recent AHA policy statement proposed the develop- Lab activation (Table II). Many OHCA patients simply ment of cardiac resuscitation centers46 in association represent a dramatic presentation of an acute coronary with an existing network of STEMI receiving centers.11,22 occlusion, with sudden death as both the chief complaint The statement emphasized that optimal postresuscitation and the clinical STEMI-equivalent. Neither the ACC/AHA care is complex, multi-disciplinary, and is probably most guidelines nor the European guidelines1-3,5 comment on efficiently provided in designated hospitals via a coordi- the role of immediate diagnostic coronary angiography nated systems-based approach that is supported by a for OHCA patients, but both acknowledge that most of robust quality improvement infrastructure. Three different American Heart Journal 1002 Rokos et al December 2010

prehospital scenarios warrant consideration with regard elevation on ECG (eg, STEMI-equivalents and certain OCHA to appropriate Cath Lab activation (Table II). Further- scenarios), not all ST-elevation patterns represent “true more, within each general scenario, real-world clinical STEMI” (ie, STE-mimics), and some “true STEMI” patients decision-making likely involves assessment of the “down are not reasonable candidates for an aggressive treatment time” before initiation of certain critical prehospital strategy involving PPCI. Optimal ECG interpretation pro- interventions (ie, time delay from patient collapse to ficiency by all clinicians in identifying both classic STEMI 9-1-1 call, to chest compressions, and to defibrillation) and STEMI-equivalents constitutes a major cornerstone of and each patient's clinical status upon hospital arrival. ongoing efforts to maximize STEMI system efficiency.

Appropriate patient selection Disclosures The final decision point before a Cath Lab activation No external funding sources supported the writing of involves clinical correlation, and hence our deliberate use this manuscript. Dr Stone reports research support from of the term appropriate Cath Lab activation. This broader Boston Scientific, Abbott Vascular, TherOx, and The “ ” term includes both traditional false-positive Cath Lab Medicines Company; consultant to St Jude Medical and activation (ie, technical competency in ECG interpretation Radiant; honoraria from Eli Lilly, Medtronic, and Glaxo- for STEMI and STEMI-equivalents) as well as physician Smith-Kline. The remaining authors do not have financial judgment regarding whether or not an individual patient or industry relationship disclosures relevant to this article. is a “candidate” (class I-A recommendation1) for PPCI. Identification of STEMI and STEMI-equivalent patients for whom Cath Lab activation is “inappropriate” requires frontline physicians to document a brief yet careful References assessment of the overall clinical scenario, age, comorbi- 1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines dities, functional status, do-not-resuscitate status, family for the management of patients with ST-elevation myocardial infarction (committee to revise the 1999 guidelines). J Am Coll perspective, and patient preferences. Cardiol 2004;44:671-719. New findings are also informing appropriate patient 2. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of selection strategies in patients resuscitated from sudden the ACC/AHA 2004 guidelines for the management of patients with cardiac arrest. Interest in early Cath Lab activation and ST-elevation myocardial infarction. J Am Coll Cardiol 2008;51: PPCI-based myocardial reperfusion has traditionally been 210-47. overshadowed by significant concerns regarding mean- 3. Kushner FG, Hand M, Smith SC, et al. Focused update: ACC/AHA ingful neurologic recovery from the initial anoxic insult. guidelines for the management of patients with ST-elevation However, data have gradually accumulated from both myocardial infarction (updating 2004 guidelines and 2007 focused clinical trials and observational registries supporting the update). JACC 2009;54:2205-41. 4. Patel MR, Dehmer GJ, Hirshfeld JW, et al. ACCF/SCAI/STS/AATS/ ability of therapeutic hypothermia to significantly improve AHA/ASNC 2009 appropriateness criteria for coronary revascu- the rate of good cerebral recovery (number needed to larization. J Am Coll Cardiol 2009;53:530-53. 41,46 treat = 6). Thus, baseline neurologic status immedi- 5. Van de Werf F, Bax J, Betriu A, et al. Management of acute ately after ROSC should not preclude early Cath Lab myocardial infarction in patients presenting with persistent ST- 41,46 activation because current AHA expert statements segment elevation: the Task Force on the Management of ST-Segment emphasize deferral of cerebral recovery prognostication Elevation Acute Myocardial Infarction of the European Society of for at least 72 hours after collapse in patients treated with Cardiology. Eur Heart J 2008;29:2909-45. therapeutic hypothermia. Furthermore, although the 6. Fesmire FM, Brady WJ, Hahn S, et al. ACEP clinical policy: “best” hypothermia protocol has yet to be definitively indications for reperfusion therapy in emergency department patients with suspected acute myocardial infarction. Ann Emerg Med 2006; proven, current consensus41,46 suggests initiating cooling 48:358-83. as early as possible (ie, pre-arrival to the Cath Lab) using 7. Masoudi FA, Magid DJ, Vinson DR, et al. Implications of the failure to some approximation of a 4/24/8/@33 protocol (4-hour identify high-risk electrocardiogram findings for the quality of care of induction [1°/h]) to a target temperature of 33°, 24-hour patients with acute myocardial infarction: results of the Emergency maintenance at 33° with minimal temperature variation, Department Quality in Myocardial Infarction (EDQMI) study. and 8 hours of rewarming (0.5°/h) back to normothermia. Circulation 2006;114:1565-71. 8. Bradley EH, Herrin J, Wang Y, et al. Strategies for reducing the door- to-balloon time in acute myocardial infarction. N Engl J Med 2006; Conclusion 355:2308-20. 9. Rokos IC, French WJ, Koenig WJ, et al. Integration of pre-hospital In summary, broad awareness should exist regarding electrocardiograms and ST-elevation myocardial infarction receiving evidence-based triggers for appropriate Cath Lab activa- center (SRC) networks: impact on Door-to-Balloon times across 10 tion. A diverse group of frontline clinicians making these independent regions. JACC Cardiovasc Interv 2009;2:339-46. time-pressured decisions need a comprehensive list of pre- 10. Krumholz HM, Bradley EH, Nallamothu BK, et al. A campaign to cise criteria, because not all “acute MIs” have classic ST- improve the timeliness of primary percutaneous coronary American Heart Journal Rokos et al 1003 Volume 160, Number 6

intervention: Door-to-Balloon: An Alliance for Quality. JACC 28. Indications for fibrinolytic therapy in suspected acute myocardial Cardiovasc Interv 2008;1:97-104. infarction: Fibrinolytic Therapy Trialists' (FTT) Group. Lancet 1994; 11. Jacobs AK, Antman EM, Faxon DP, et al. Development of systems of 343:311-22. care for ST-elevation myocardial infarction patients: executive 29. Kontos MC, McQueen RH, Jesse RL, et al. Can myocardial infarction summary. Circulation 2007;116:217-30. be rapidly identified in emergency department patients who have left 12. Peterson ED, Ohman EM, Brindis RG, et al. Development of systems of bundle-branch block? Ann Emerg Med 2001;37:431-8. care for ST-elevation myocardial infarction patients: evaluation and 30. Chang AM, Shofer FS, Tabas JA, et al. Lack of association between outcomes. Circulation 2007;116:e64-7. LBBB and AMI in symptomatic ED patients. Am J Emerg Med 2009; 13. Nikus K, Pahlm O, Wagner G, et al. Electrocardiographic 27:916-21. classification of acute coronary syndromes: a review by a committee 31. Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic of the International Society for Holter and Non-Invasive Electro- diagnosis of evolving acute MI in the presence of left bundle-branch cardiology. J Electrocardiol 2010;43:91-103. block. GUSTO-1 Investigators. N Engl J Med 1996;334:481-7. 14. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined 32. Tabas JA, Rodriguez RM, Seligman HK, et al. Electrocardiographic —a consensus document of the Joint European Society of Cardiology/ criteria for detecting acute myocardial infarction in patients with left American College of Cardiology Committee for the redefinition of bundle branch block: a meta-analysis. Ann Emerg Med 2008;52: myocardial infarction. J Am Coll Cardiol 2000;36:959-69. 329-36. 15. Wagner GS, Macfarlane P, Wellens H, et al. AHA/ACCF/HRS 33. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus scientific statement. Recommendations for the standardization and clopidogrel in patients with acute coronary syndromes. N Engl J Med interpretation of the electrocardiogram: part VI: acute ischemia/ 2007;357:2001-15. infarction. Circulation 2009;119:e262-70. 34. Pride YB, Tung P, Mohanavelu S, et al. Angiographic and clinical 16. Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute outcomes among patients with acute coronary syndromes presenting myocardial infarction. N Engl J Med 2003;348:933-40. with isolated anterior ST-segment depression: A TRITON-Timi 38 17. Larson DM, Menssen KM. Sharkey SW, et al. “False-positive” cardiac sub-study. JACC Intv 2010;3:806-11. catheterization laboratory activation among patients with suspected 35. Zoghbi GJ, Misra VK, Brott BC, et al. ST-elevation myocardial ST-segment elevation myocardial infarction. JAMA 2007;298: infarction due to left main culprit lesions: PCI outcomes in cath-PCI 2754-60. registry (abstract 2909-09). JACC 2010;55:A183. 18. Kontos MC, Kurz MC, Roberts CS, et al. An evaluation of the 36. Yamaji H, Iwasaki K, Kusachi S, et al. Prediction of acute left main accuracy of emergency physician activation of the cardiac catheter- coronary artery obstruction by 12-lead electrocardiography. ST ization laboratory for patients with suspected ST-segment elevation segment elevation in lead aVR with less ST segment elevation in lead V myocardial infarction. Ann Emerg Med 2010;55:423-30. (1). J Am Coll Cardiol 2001;38:1348-54. 19. Jollis JG, Garvey JL, Monk L, et al. False-positive cath lab activation 37. Rostoff P, Piwowarska W, Gackowski A, et al. Electrocardiographic rates in the RACE regional ST-elevation myocardial infarction prediction of acute left main coronary artery occlusion. Am J Emerg program (abstract 1101-286). JACC 2010;55:A109. Med 2007;25:852-5. 20. Rokos IC, Koenig WJ, Tadeo R, et al. Etiologies of inappropriate 38. de Winter RJ, Verouden NJ, Wellens HJ, et al. A new ECG sign of cardiac catheterization lab activations from pre-hospital electrocar- proximal LAD occlusion. N Engl J Med 2008;359:2071-3. diograms in the Los Angeles County network (abstract 143). 39. de Zwaan C, Bar FW, Wellens HJ. Characteristic electrocardio- Circulation CVQO 2009;2(3 suppl):e33. graphic pattern indicating a critical stenosis high in left anterior 21. Swan PY, Nighswonger B, Boswell GL, et al. Factors associated with descending coronary artery. Am Heart J 1982;103:730-6. false-positive emergency medical services triage for percutaneous 40. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary coronary intervention. West J Emerg Med 2009;10:208-12. angiography in survivors of out-of-hospital cardiac arrest. N Engl J 22. Rokos IC, Larson DM, Henry TD, et al. Rationale for establishing Med 1997;336:1629-33. regional ST-elevation myocardial infarction receiving center (SRC) 41. Neumar RW, Nolan JP, Adrie C, et al. Post-cardiac arrest syndrome: networks. Am Heart J 2006;152:661-7. epidemiology, pathophysiology, treatment, and prognostication. A 23. Wang K, Asinger RW, Marriott HJ. ST-segment elevation in consensus statement from the AHA International Liaison Committee conditions other than acute myocardial infarction. N Engl J Med on Resuscitation. Circulation 2008;118:2452-83. 2003;349:2128-35. 42. Ewy GA, Kern KB. Recent advances in cardiopulmonary resuscitation: 24. Otto LA, Aufderheide TP. Evaluation of ST segment elevation criteria cardiocerebral resuscitation. J Am Coll Cardiol 2009;53:149-57. for the prehospital electrocardiographic diagnosis of acute myocar- 43. Anyfantakis ZA, Baron G, Aubry P, et al. Acute coronary dial infarction. Ann Emerg Med 1994;23:17-24. angiographic findings in survivors of out-of-hospital cardiac arrest. 25. Armstrong PW, Fu Y, Westerhout CM, et al. Baseline Q-wave sur- Am Heart J 2009;157:312-8. passes time from symptom onset as a prognostic marker in ST-segment 44. Muller D, Schnitzer L, Brandt J, et al. The accuracy of an out-of-hospital elevation myocardial infarction patients treated with primary percu- 12-lead ECG for the detection of ST-elevation myocardial infarction taneous coronary intervention. J Am Coll Cardiol 2009;53:1503-9. immediately after resuscitation. Ann Emerg Med 2008;52:658-64. 26. Kudenchuk PJ, Ho MT, Weaver WD, et al. Accuracy of computer- 45. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate interpreted electrocardiography in selecting patients for thrombolytic percutaneous coronary intervention is associated with better survival therapy. MITI Project Investigators. J Am Coll Cardiol 1991;17: after out-of-hospital cardiac arrest: insights from the PROCAT 1486-91. (Parisian Region Out of hospital Cardiac ArresT) registry. Circ 27. Ting HH, Krumholz HM, Bradley EH, et al. Implementation and Cardiovasc Interv 2010;3:200-7. integration of prehospital ECGs into systems of care for acute 46. Nichol G, Aufderheide TP, Eigel B, et al. Regional systems of care for coronary syndrome: a scientific statement from the American Heart out-of-hospital cardiac arrest: a policy statement from the American Association. Circulation 2008;118:1066-79. Heart Association. Circulation 2010;121:709-29. American Heart Journal Rokos et al 1003.e1 Volume 160, Number 6

Appendix. Online Data Supplement

Title: Appropriate cardiac catheterization lab activation: optimizing electrocardiogram interpretation and clinical decision-making for acute ST-elevation myocardial infarction Authors: Rokos, French, Mattu, Nichol, Farkouh, Reiffel, and Stone.

14 Electrocardiogram (ECG) Examples I. Classic STEMI a. Anterior-STEMI with reciprocal changes ⇒ proximal LAD occlusion b. Anterior-STEMI without reciprocal changes ⇒ middle LAD occlusion c. High-lateral STEMI ⇒ diagonal branch occlusion d. Lateral STEMI ⇒ left circumflex occlusion

II. STEMI-equivalents a. Posterior MI (isolated) b. Left main coronary occlusion: lead aVR STE and infero-lateral STD c. de Winter ST/T-wave complex d. Wellens syndrome (distinguish from de Winter ST/T-wave complex e. LBBB with Sgarbossa criteria

III. ST-elevation mimics (STE-mimics) a. Benign early repolarization (BER) b. Acute pericarditis c. Left ventricular aneurysm d. Normal-variant chronic ST-elevation e. Brugada syndrome American Heart Journal 1003.e2 Rokos et al December 2010

I.a Anterior STEMI with reciprocal changes (IRA = proximal LAD)

I.b Anterior STEMI without reciprocal changes (IRA = middle LAD) American Heart Journal Rokos et al 1003.e3 Volume 160, Number 6

I.c “High” Lateral STEMI (IRA = Diagonal branch)

I.d Lateral STEMI (IRA = Left Circumflex) American Heart Journal 1003.e4 Rokos et al December 2010

II. STEMI-equivalents

II.a Posterior MI (Isolated)

II.b Left Main coronary occlusion (LMCO): Lead aVR with ST-elevation and associated infero-lateral ST-depression American Heart Journal Rokos et al 1003.e5 Volume 160, Number 6

II.c de Winter ST/T-wave complex

II.d Wellens syndrome (This is not a STEMI-equivalent. Example provided to compare with leads V2-V3 of de Winter ST/T-wave complex) American Heart Journal 1003.e6 Rokos et al December 2010

II.e LBBB MI with Sgarbossa criteria concordance in V2 through V3

III. ST-elevation mimics (STE-mimics)

III.a Benign early repolarization (BER) American Heart Journal Rokos et al 1003.e7 Volume 160, Number 6

III.b Acute pericarditis

III.c Left Ventricular aneurysm American Heart Journal 1003.e8 Rokos et al December 2010

III.d Normal-variant chronic ST-elevation

III.e Brugada syndrome