《心肺复苏指南》（英文版） Part 8: Stabilization of the Patient With Acute Coronary Syndromes

Circulation Atmegiso tmO Learn and live JOURNAL OF THE AMERICAN HEART ASSOCIATION Part 8: Stabilization of the patient with Acute Coronary syndromes Circulation 2005; 112; 89-110; originally published online Nov 28, 2005; DOI: 10.1161/CIRCULATIONAHA. 105.16656 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, Tx 72514 Copyright o 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online ISSN:15244539 The online version of this article, along with updated information and services, is located on the world wide web at http://circ.ahajournals.org/cgi/content/full/112/24suppl/iv-89 Subscriptions: Information about subscribing to Circulation is online at http://circ.ahajournals.org/subsriptions/ Permissions: Permissions Rights Desk, Lippincott Williams Wilkins, 351 West Cam Street. Baltimore MD 21202-2436 Phone 410-5280-4050. Fax: 410-528-8550 En journalpermissions@lww.com Reprints: Information about reprints can be found online at http://www.Iww.com/static/html/reprints.html Downloaded from circ. ahajournals. org by on February 21, 2006

ISSN: 1524-4539 Copyright © 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/CIRCULATIONAHA.105.166561 Circulation 2005;112;89-110; originally published online Nov 28, 2005; Part 8: Stabilization of the Patient With Acute Coronary Syndromes http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-89 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/static/html/reprints.html Reprints: Information about reprints can be found online at journalpermissions@lww.com Street, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden http://circ.ahajournals.org/subsriptions/ Subscriptions: Information about subscribing to Circulation is online at Downloaded from circ.ahajournals.org by on February 21, 2006

Part 8: Stabilization of the patient with acute Coronary Syndromes A cute myocardial infarction(AMI)and unstable angina rest "and Part 7.3: " Management of Symptomatic Brady (UA)are part of a spectrum of clinical di ardia and Tachycardia") ively identified as acute coronary syndromes(ACS). The pathophysiology common to this spectrum of disease is a An overview of recommended care for the ACS patient is ruptured or eroded atheromatous plaque. -s The electrocar illustrated in Figure l, the Acute Coronary Syndrom diographic (ECG) presentation of these syndromes encom- Igorithm. Part 8 provides details of the care highlighted in asses ST-segment elevation myocardial infarction (STEMD), the numbered algorithm boxes. Box numbers in the text ST-segment depression, and nondiagnostic ST-segment and correspond to the numbered boxes in the algorithm T-wave abnormalities. A non-ST-elevation myocardial in- In this part the abbreviation AMI refers to acute myocar- rction (NSTEMi) is diagnosed cardiac markers are positive with ST-segment depression or with nonspecific or The diagnosis and treatment of AMI, however, will often normal ECGs. Sudden cardiac death may occur with any of differ for patients with STEMI versus NSTEMI. Note care- these conditions. ACS is the most common proximate cause fully which is being discussed of sudden cardiac death 6-10 Effective interventions for patients with ACS, particularly Out-of-Hospital Management STEMI, are extremely time-sensitive. The first healthcare Recognition(Figure 1, Box 1) providers to encounter the ACS patient can have a big impact Treatment offers the greatest potential benefit for myocardial on patient outcome if they provide efficient risk stratification, salvage in the first hours of STEMI. Thus, it is imperative that critical that basic life support(BLS)and advanced cardiovas- ACS as quickly as possible. Delays to therapy occur during 3 cular life support(ACLS)healthcare providers who care for intervals: from onset of symptoms to patient recognition, ACS patients in the out-of-hospital, emergency department during out-of-hospital transport, and during in-hospital eval (ED), and hospital environments be aware of the principles and priorities of assessment and stabilization of these uation. Patient delay to symptom recognition often constitutes the longest period of delay to treatment. atients These guidelines target BLS and ACLs healthcare provid The classic symptom associated with ACs is chest discom ers who treat patients with ACS within the first hours after fort, but symptoms may also include discomfort in other areas onset of symptoms, summarizing key out-of-hospital, ED of the upper body, shortness of breath, sweating, nausea, and and some initial critical-care topics that are relevant to lightheadedness. The symptoms of AMI are characteristically more intense than angina and last >15 minutes. Atypical tions from the acciaha Guidelines, 1.12 which are used symptoms or unusual presentations of ACS are more com- throughout the United States and Canada. 3 As with an medical guidelines, these general recommendations must be Public education campaigns increase public awareness and knowledge of the symptoms of heart attack but have only rea wl tion to individual patients by knowledgeable he transient effects. 20 For patients at risk for ACS(and for their families), physicians should discuss the appropriate use of The primary goals of therapy for patients with ACS are to nitroglycerin and aspirin, activation of the emergency medi- cal services(EMS) system, and location of the nearest Reduce the amount of myocardial necrosis that occurs in hospital that offers 24-hour emergency cardiovascular care. patients with MI, preserving left ventricular (LV) function ecent ACC/AHA guidelines recommend that the patient or and preventing heart failure family members activate the EMS system rather than call Prevent major adverse cardiac events(MACE): death, their physician or drive to the hospital if chest discomfort nonfatal MI, and need for urgent revascularization unimproved or worsening 5 minutes after taking I nitroglyc Treat acute, life-threatening complications of ACS, such as erin tablet or using nitroglycerin spray. 12 ntricular fibrillation (VF)/pulseless ventricular tachycardia(VT), symptomatic bradycardias, and unstable Initial EMS Care(Figure 1, Box 2) chycardias(see Part 7. 2:"Management of Cardiac Ar lalf of the patients who die of AMI do so before reaching the hospital. VF or pulseless VT is the precipitating rhythm in (Circulation. 2005: 112: TV-89-IV-110) o 2005 American Heart Association most of these deaths, 2-23 and it is most likely to develop during the first 4 hours after onset of symptoms. 24-27 Com- This special supplement to Circulation is freely available at munities should develop programs to respond to out-of- hospital cardiac arrest that include prompt recognition of DOI: 10.1161/CIRCULATIONAHA. 105.166561 symptoms of ACS, early activation of the EMS system, an

Part 8: Stabilization of the Patient With Acute Coronary Syndromes Acute myocardial infarction (AMI) and unstable angina (UA) are part of a spectrum of clinical disease collec￾tively identified as acute coronary syndromes (ACS). The pathophysiology common to this spectrum of disease is a ruptured or eroded atheromatous plaque.1–5 The electrocar￾diographic (ECG) presentation of these syndromes encom￾passes ST-segment elevation myocardial infarction (STEMI), ST-segment depression, and nondiagnostic ST-segment and T-wave abnormalities. A non–ST-elevation myocardial in￾farction (NSTEMI) is diagnosed if cardiac markers are positive with ST-segment depression or with nonspecific or normal ECGs. Sudden cardiac death may occur with any of these conditions. ACS is the most common proximate cause of sudden cardiac death.6 –10 Effective interventions for patients with ACS, particularly STEMI, are extremely time-sensitive. The first healthcare providers to encounter the ACS patient can have a big impact on patient outcome if they provide efficient risk stratification, initial stabilization, and referral for cardiology care. It is critical that basic life support (BLS) and advanced cardiovas￾cular life support (ACLS) healthcare providers who care for ACS patients in the out-of-hospital, emergency department (ED), and hospital environments be aware of the principles and priorities of assessment and stabilization of these patients. These guidelines target BLS and ACLS healthcare provid￾ers who treat patients with ACS within the first hours after onset of symptoms, summarizing key out-of-hospital, ED, and some initial critical-care topics that are relevant to stabilization. They also continue to build on recommenda￾tions from the ACC/AHA Guidelines,11,12 which are used throughout the United States and Canada.13 As with any medical guidelines, these general recommendations must be considered within the context of local resources and applica￾tion to individual patients by knowledgeable healthcare providers. The primary goals of therapy for patients with ACS are to ● Reduce the amount of myocardial necrosis that occurs in patients with MI, preserving left ventricular (LV) function and preventing heart failure ● Prevent major adverse cardiac events (MACE): death, nonfatal MI, and need for urgent revascularization ● Treat acute, life-threatening complications of ACS, such as ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT), symptomatic bradycardias, and unstable tachycardias (see Part 7.2: “Management of Cardiac Ar￾rest” and Part 7.3: “Management of Symptomatic Brady￾cardia and Tachycardia”) An overview of recommended care for the ACS patient is illustrated in Figure 1, the Acute Coronary Syndromes Algorithm. Part 8 provides details of the care highlighted in the numbered algorithm boxes. Box numbers in the text correspond to the numbered boxes in the algorithm. In this part the abbreviation AMI refers to acute myocar￾dial infarction, whether associated with STEMI or NSTEMI. The diagnosis and treatment of AMI, however, will often differ for patients with STEMI versus NSTEMI. Note care￾fully which is being discussed. Out-of-Hospital Management Recognition (Figure 1, Box 1) Treatment offers the greatest potential benefit for myocardial salvage in the first hours of STEMI. Thus, it is imperative that healthcare providers evaluate, triage, and treat patients with ACS as quickly as possible. Delays to therapy occur during 3 intervals: from onset of symptoms to patient recognition, during out-of-hospital transport, and during in-hospital eval￾uation. Patient delay to symptom recognition often constitutes the longest period of delay to treatment.14 The classic symptom associated with ACS is chest discom￾fort, but symptoms may also include discomfort in other areas of the upper body, shortness of breath, sweating, nausea, and lightheadedness. The symptoms of AMI are characteristically more intense than angina and last
15 minutes. Atypical symptoms or unusual presentations of ACS are more com￾mon in elderly, female, and diabetic patients.15–19 Public education campaigns increase public awareness and knowledge of the symptoms of heart attack but have only transient effects.20 For patients at risk for ACS (and for their families), physicians should discuss the appropriate use of nitroglycerin and aspirin, activation of the emergency medi￾cal services (EMS) system, and location of the nearest hospital that offers 24-hour emergency cardiovascular care. Recent ACC/AHA guidelines recommend that the patient or family members activate the EMS system rather than call their physician or drive to the hospital if chest discomfort is unimproved or worsening 5 minutes after taking 1 nitroglyc￾erin tablet or using nitroglycerin spray.12 Initial EMS Care (Figure 1, Box 2) Half of the patients who die of AMI do so before reaching the hospital. VF or pulseless VT is the precipitating rhythm in most of these deaths,21–23 and it is most likely to develop during the first 4 hours after onset of symptoms.24 –27 Com￾munities should develop programs to respond to out-of￾hospital cardiac arrest that include prompt recognition of symptoms of ACS, early activation of the EMS system, and (Circulation. 2005;112:IV-89-IV-110.) © 2005 American Heart Association. This special supplement to Circulation is freely available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.105.166561 IV-89

lV-90 Circulation December 13, 2005 of ischemia EMS assessment and care and hospital preparation monitor, support ABCs, Be prepared to provide CPR and defibrillation Notified hospital should mobilize hospital resources to respond to STEMI 3 Check vital signs; evaluate oxygen saturation. Start oxygen at 4 U/min; maintain Aspirin 160 to 325 mg of not given by EMS Obtain/review 12-lead ECG Nitroglycerin sublingual, spray, or IV Obtain initial cardiac marker levels initial electrolyte and coagulation studies Obtain portable chest x-ray (<30 mi 4 (Review initial 12-lead EcO) cious for ischemi stable ane 10 Start adjunctive treatments as Start adjunctive treatments as indicated (see text for contraindications) indicated(see text for contraindications ate risk criteria (Tables 3, 4) Adrenergic receptor blocke nic receptor blockers troponin-positive? Heparin (UFH or LMWH) Heparin (UFH or LMWH Glycoprotein IIb/llla inhibitor 15 it Time from onset of Admit to monitored bed symptoms≤12 hours? Assess risk status ( Tables 3, 4) Repeat ECG/continuou Consider stress test Refractory ischemic chest pair Therapy defined by patient and center Recurrent/persistent ST deviation criteria (Table 2) ate risk criteria ( Tables 3, 4) Early invasive strategy, including goal of 30 min for shock within 48 hours of an AMI troponin-positive? rapes and: Continue ASA, heparin, and other - ACE in as indicat 17 cer (ARB) within HMG CoA reductase inhibitor If no evidence of ischemia HMG CoA reductase inhibitor statin therapy or infarction, can discharg (statin therapy) Not at high risk cardiology to risk-stratity with follow-up F cute Coronary Syndromes Algorithm

Figure 1. Acute Coronary Syndromes Algorithm. IV-90 Circulation December 13, 2005

Part 8: Stabilization of the Patient With Acute Coronary Syndromes Iv-9 if needed, early CPR(see Part 4: Adult Basic Life Support") therapy. We recommend that out-of-hospital paramedics and early access to an automated external defibrillator(AEd acquire and transmit either diagnostic-quality ECGs or their through community AED programs(see Part 5:"Electrical interpretation of them to the receiving hospital with advance Therapies").28 EMS and dispatch system personnel should be notification of the arrival of a patient with ACS( Class IIa). If trained to respond to cardiovascular emergencies. EMS providers identify STEMI on the ECG, it is reasonable Dispatchers and EMs providers must be trained to recog- for them to begin to complete a fibrinolytic checklist(Figure nize symptoms of ACS. Dispatchers should advise patients with no history of aspirin allergy or signs of active or recent strointestinal bleeding to chew an aspirin(160 to 325 mg) Out-of-Hospital Fibrinolysis hile awaiting the arrival of EMS providers(Class Ila). 29 Clinical trials have shown the benefit of initiating fibrinolysis EMS providers should be trained to determine the time of as soon as possible after onset of ischemic-type chest pain in onset of symptoms and to stabilize, triage, and transport the patients with STEMI or new or presumably new left bundle patient to an appropriate facility and to provide prearrival branch block(LBBB). 67. 71 Several prospective studies(LOE notification. EMS providers should monitor vital signs and 1)72-74 have documented reduced time to administration of cardiac rhythm and be prepared to provide CPr and defibril- fibrinolytics and decreased mortality rates when out-of lation if needed hospital fibrinolytics were administered to patients with EMS providers may administer oxygen to all patients STEMI and no contraindications to fibrinoly the patient is hypoxemic, providers should titrate therapy Physicians in the Grampian Region Early Anistreplase based on monitoring of oxyhemoglobin saturation(Class Trial(GREAT)73 administered fibrinolytic therapy to patients ).30-44 If the patient has not taken aspirin and has no history at home 130 minutes earlier than to patients at the hospital of aspirin allergy and no evidence of recent gastrointestinal bleeding, EMs providers should give the patient nonenteric and noted a 50% reduction in hospital mortality rates and greater l-year and 5-year survival rates in those treated aspirin(160 to 325 mg) to chew( Class I). 45-48 earlier 75,76 Delaying fibrinolytic treatment by I hour in- EMS providers should administer up to 3 nitroglycerin creased the hazard ratio of death by 20%o, which is equivalent tablets(or spray) for ongoing symptoms at intervals of 3 to 5 to the loss of 43 lives per 1000 patients over 5 years minutes if permitted by medical control and if the patient A meta-analys of out-of-hospital fibrinolytic trials found remains hemodynamically stable(systolic blood pressure a relative improvement of 17% in outcome associated with [!>90 mm Hg or no more than 30 mm Hg below out-of-hospital fibrinolytic therapy, particularly when therapy baseline], heart rate between 50 and 100 beats per minute was initiated 60 to 90 minutes earlier than in the hospital. 71A [bpm)).4950 EMS providers can administer morphine for chest pain unresponsive to nitroglycerin if authorized by protocol documented decreased all-cause hospital mortality rates hospital stabilization and care is included in the following among patients treated with out-of-hospital fibrinolysis com- pared with in-hospital fibrinolysis(odds ratio [OR]: 0.83 95% confidence interval [CI]: 0.70 to 0.98)with a number Out-of-Hospital ECGs needed to treat of 62 to save I extra life with out-of-hospital Out-of-hospital 12-lead ECGs and advance notification to the ibrinolysis. Results were similar regardless of the trainin receiving facility speed the diagnosis, shorten the time to fibrinolysis, and may be associated with decreased mortality The ECC Guidelines 200077 recommended consideration rates.51-64 The reduction in door-to-reperfusion therapy in- of out-of-hospital fibrinolysis for patients with a transport terval in most studies ranges from 10 to 60 minutes. EMS time >l hour. But in a recent Swiss study (LOE 1), 74 providers can efficiently acquire and transmit diagnostic prehospital administration of fibrinolytics significantly de- quality ECGs to the ED53-58. 65. 6 with a minimal increase(0.2 creased the time to drug administration even in an urban to 5.6 minutes)in the on-scene time interval. 52-56, 65-68 setting with relatively short transport intervals (<15 Qualified and specially trained paramedics and prehospital minutes) nurses can accurately identify typical ST-segment elevation In summary, out-of-hospital administration of fibrinolytics (I mm in 2 or more contiguous leads) in the 12-lead ECG to patients with STEMI with no contraindications is safe with specificity ranging from 91% to 100% and sensitivity feasible, and reasonable( Class lla). This intervention may be ranging from 71% to 97% when compared with emergency performed by trained paramedics, nurses, and physicians fo medicine physicians or cardiologists. 69. 0 Using radio or cell patients with symptom duration of 30 minutes to 6 hours phone, they can also provide advance notification to the System requirements include protocols with fibrinolytic eceiving hospital of the arrival of a patient with ACS.56,61-64 checklists, ECG acquisition and interpretation, experience in We recommend implementation of out-of-hospital 12-lead ACLS, the ability to communicate with the receiving institu- ECG diagnostic programs in urban and suburban EMS tion, and a medical director with training/experience in systems( Class I). Routine use of 12-lead out-of-hospital ECG management of STEMI. A process of continuous quality and advance notification is recommended for patients with improvement is required. Given the operational challenge signs and symptoms of ACS(Class Ila). A 12-lead out-of- required to provide out-of-hospital fibrinolytics, most EMS hospital ECG with advance notification to the ED may be systems should focus on early diagnosis with 12-lead ECG beneficial for STEMI patients by reducing time to reperfusion rapid transport, and advance notification of the ED(verbal

if needed, early CPR (see Part 4: “Adult Basic Life Support”) and early access to an automated external defibrillator (AED) through community AED programs (see Part 5: “Electrical Therapies”).28 EMS and dispatch system personnel should be trained to respond to cardiovascular emergencies. Dispatchers and EMS providers must be trained to recog￾nize symptoms of ACS. Dispatchers should advise patients with no history of aspirin allergy or signs of active or recent gastrointestinal bleeding to chew an aspirin (160 to 325 mg) while awaiting the arrival of EMS providers (Class IIa).29 EMS providers should be trained to determine the time of onset of symptoms and to stabilize, triage, and transport the patient to an appropriate facility and to provide prearrival notification. EMS providers should monitor vital signs and cardiac rhythm and be prepared to provide CPR and defibril￾lation if needed. EMS providers may administer oxygen to all patients. If the patient is hypoxemic, providers should titrate therapy based on monitoring of oxyhemoglobin saturation (Class I).30 – 44 If the patient has not taken aspirin and has no history of aspirin allergy and no evidence of recent gastrointestinal bleeding, EMS providers should give the patient nonenteric aspirin (160 to 325 mg) to chew (Class I).45– 48 EMS providers should administer up to 3 nitroglycerin tablets (or spray) for ongoing symptoms at intervals of 3 to 5 minutes if permitted by medical control and if the patient remains hemodynamically stable (systolic blood pressure [SBP]
90 mm Hg [or no more than 30 mm Hg below baseline], heart rate between 50 and 100 beats per minute [bpm]).49,50 EMS providers can administer morphine for chest pain unresponsive to nitroglycerin if authorized by protocol or medical control. Additional information about out-of￾hospital stabilization and care is included in the following sections. Out-of-Hospital ECGs Out-of-hospital 12-lead ECGs and advance notification to the receiving facility speed the diagnosis, shorten the time to fibrinolysis, and may be associated with decreased mortality rates.51– 64 The reduction in door-to–reperfusion therapy in￾terval in most studies ranges from 10 to 60 minutes. EMS providers can efficiently acquire and transmit diagnostic￾quality ECGs to the ED53,58,65,66 with a minimal increase (0.2 to 5.6 minutes) in the on-scene time interval.52,56,65– 68 Qualified and specially trained paramedics and prehospital nurses can accurately identify typical ST-segment elevation (
1 mm in 2 or more contiguous leads) in the 12-lead ECG with specificity ranging from 91% to 100% and sensitivity ranging from 71% to 97% when compared with emergency medicine physicians or cardiologists.69,70 Using radio or cell phone, they can also provide advance notification to the receiving hospital of the arrival of a patient with ACS.56,61– 64 We recommend implementation of out-of-hospital 12-lead ECG diagnostic programs in urban and suburban EMS systems (Class I). Routine use of 12-lead out-of-hospital ECG and advance notification is recommended for patients with signs and symptoms of ACS (Class IIa). A 12-lead out-of￾hospital ECG with advance notification to the ED may be beneficial for STEMI patients by reducing time to reperfusion therapy. We recommend that out-of-hospital paramedics acquire and transmit either diagnostic-quality ECGs or their interpretation of them to the receiving hospital with advance notification of the arrival of a patient with ACS (Class IIa). If EMS providers identify STEMI on the ECG, it is reasonable for them to begin to complete a fibrinolytic checklist (Figure 2). Out-of-Hospital Fibrinolysis Clinical trials have shown the benefit of initiating fibrinolysis as soon as possible after onset of ischemic-type chest pain in patients with STEMI or new or presumably new left bundle branch block (LBBB).67,71 Several prospective studies (LOE 1)72–74 have documented reduced time to administration of fibrinolytics and decreased mortality rates when out-of￾hospital fibrinolytics were administered to patients with STEMI and no contraindications to fibrinolytics. Physicians in the Grampian Region Early Anistreplase Trial (GREAT)73 administered fibrinolytic therapy to patients at home 130 minutes earlier than to patients at the hospital and noted a 50% reduction in hospital mortality rates and greater 1-year and 5-year survival rates in those treated earlier.75,76 Delaying fibrinolytic treatment by 1 hour in￾creased the hazard ratio of death by 20%, which is equivalent to the loss of 43 lives per 1000 patients over 5 years. A meta-analysis of out-of-hospital fibrinolytic trials found a relative improvement of 17% in outcome associated with out-of-hospital fibrinolytic therapy, particularly when therapy was initiated 60 to 90 minutes earlier than in the hospital.71 A meta-analysis of 6 trials involving 6434 patients (LOE 1)72 documented decreased all-cause hospital mortality rates among patients treated with out-of-hospital fibrinolysis com￾pared with in-hospital fibrinolysis (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.70 to 0.98) with a number needed to treat of 62 to save 1 extra life with out-of-hospital fibrinolysis. Results were similar regardless of the training and experience of the provider. The ECC Guidelines 200077 recommended consideration of out-of-hospital fibrinolysis for patients with a transport time
1 hour. But in a recent Swiss study (LOE 1),74 prehospital administration of fibrinolytics significantly de￾creased the time to drug administration even in an urban setting with relatively short transport intervals (15 minutes).74 In summary, out-of-hospital administration of fibrinolytics to patients with STEMI with no contraindications is safe, feasible, and reasonable (Class IIa). This intervention may be performed by trained paramedics, nurses, and physicians for patients with symptom duration of 30 minutes to 6 hours. System requirements include protocols with fibrinolytic checklists, ECG acquisition and interpretation, experience in ACLS, the ability to communicate with the receiving institu￾tion, and a medical director with training/experience in management of STEMI. A process of continuous quality improvement is required. Given the operational challenges required to provide out-of-hospital fibrinolytics, most EMS systems should focus on early diagnosis with 12-lead ECG, rapid transport, and advance notification of the ED (verbal Part 8: Stabilization of the Patient With Acute Coronary Syndromes IV-91

lV-92 Circulation December 13, 2005 CHEST PAIN CHECKLIST FOR STEMI FIBRINOLYTIC THERAPY Step One: Has patient experienced chest discomfort for greater than 15 minutes and less than 12 hours? Does ECG show STEM or presumably new LBBB? Step Two H ANT of the following is CHECKED YEs, fibrinolysis MAY be contraindicated Systolic BP greater than 180 mm Hg O YES Diastolic BP greater than11mm地 ○YEs Right vs. left arm systolic BP difference greater than 15 mm Hg History of structural central nervous system disease Significant closed headnfacial trauma within the previous 3 months oooo Recent (within 6 wks)major trauma, surgery (including Laser eye surgery), GI/GU bleed Bleeding or dotting problem or on blood thinners ○YEs CPR greater than 10 minutes ○YEs Pregnant female erminal cancer, severe liver or kidney dise Step Three: IfAw ef the following is CHECKED \Is, CONSIDER Transport/ Transfer to PCI Facility Heart rate greater than or equal to 100 bpm AND systolic BP less than 100 mm Hg ○YEs Pulmonary edema(rales Signs of shock (cool, dammy ○Y gure 2. Fibrinolytic Checklist. interpretation or direct transmission of ECG) instead of fibrinolysis when transport can be completed in <60 minutes out-of-hospital delivery of fibrinolysis with a physician in a mobile intensive care unit. There is no direct evidence, however, to suggest that these strategies are safe or effective. Patients judged to be at highest risk for a of-Hospital Triage complicated transfer were excluded from some of these ital and EMS protocols should clearly identify criteria studies for transfer of patients to specialty centers and conditions In summary, at this time there is inadequate evidence to under which fibrinolytics should be initiated before transfer recommend out-of-hospital triage to bypass non-PCI-capable When transfer is indicated, the ACC/AHA guidelines recom- hospitals to bring patients to a PCI center(Class Indetermi- mend a door-to-departure time <30 minutes. 2 It may be nate). Local protocols for EMS providers are appropriate to appropriate for the EMS medical director to institute a policy guide the destination of patients with suspected or confirmed therapy only, particularly for patients who provide medicalSTEMI of out-of-hospital bypass of hospitals that Interven- tional therapy. Patients who require interventional therapy Interfacility Transfer may include those with cardiogenic shock, pulmonary edema, All patients with STEMI and symptom duration of =12 hours large infarctions, and contraindications to fibrinolytic are candidates for reperfusion therapy with either fibrinolysis therapy or PCI(Class D). When patients present directly to a facility At present no randomized studies have directly compared capable of providing only fibrinolysis, 3 treatment options ar triage with an experienced percutaneous coronary interven- available: administering fibrinolytics with admission to that on(PCi) center with medical the local hospital, transferring the patient for primary PCI, or giving hospital.Extrapolation from several randomized trials on fibrinolytics and then transferring the patient to a specialized interfacility transfer78-80 suggests that STEMI patients tri- center. The decision is guided by a risk-benefit assessment aged directly to a primary PCI facility may have better that includes evaluation of duration of symptoms, complica outcomes related to the potential for earlier treatment. A ons, contraindications, and the time delay from patient cost-efficacy substudy of the Comparison of Angioplasty and contact to fibrinolysis versus potential delay to PCI balloon Prehospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) trials suggests that direct transport to a primary In 2 prospective studies (LOE 2)78-80 and a meta-analy PCI facility may be more cost-effective than out-of-hospit is,2 patients with STEMI who presented 3 to 12 hours after

interpretation or direct transmission of ECG) instead of out-of-hospital delivery of fibrinolysis. Triage and Transfer Out-of-Hospital Triage Hospital and EMS protocols should clearly identify criteria for transfer of patients to specialty centers and conditions under which fibrinolytics should be initiated before transfer. When transfer is indicated, the ACC/AHA guidelines recom￾mend a door-to-departure time
30 minutes.12 It may be appropriate for the EMS medical director to institute a policy of out-of-hospital bypass of hospitals that provide medical therapy only, particularly for patients who require interven￾tional therapy. Patients who require interventional therapy may include those with cardiogenic shock, pulmonary edema, large infarctions, and contraindications to fibrinolytic therapy. At present no randomized studies have directly compared triage with an experienced percutaneous coronary interven￾tion (PCI) center with medical management at the local hospital. Extrapolation from several randomized trials on interfacility transfer78 – 80 suggests that STEMI patients tri￾aged directly to a primary PCI facility may have better outcomes related to the potential for earlier treatment. A cost-efficacy substudy of the Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) trial81 suggests that direct transport to a primary PCI facility may be more cost-effective than out-of-hospital fibrinolysis when transport can be completed in
60 minutes with a physician in a mobile intensive care unit. There is no direct evidence, however, to suggest that these strategies are safe or effective. Patients judged to be at highest risk for a complicated transfer were excluded from some of these studies. In summary, at this time there is inadequate evidence to recommend out-of-hospital triage to bypass non–PCI-capable hospitals to bring patients to a PCI center (Class Indetermi￾nate). Local protocols for EMS providers are appropriate to guide the destination of patients with suspected or confirmed STEMI. Interfacility Transfer All patients with STEMI and symptom duration of
12 hours are candidates for reperfusion therapy with either fibrinolysis or PCI (Class I). When patients present directly to a facility capable of providing only fibrinolysis, 3 treatment options are available: administering fibrinolytics with admission to that hospital, transferring the patient for primary PCI, or giving fibrinolytics and then transferring the patient to a specialized center. The decision is guided by a risk-benefit assessment that includes evaluation of duration of symptoms, complica￾tions, contraindications, and the time delay from patient contact to fibrinolysis versus potential delay to PCI balloon inflation. In 2 prospective studies (LOE 2)78 – 80 and a meta-analy￾sis,82 patients with STEMI who presented 3 to 12 hours after Figure 2. Fibrinolytic Checklist. IV-92 Circulation December 13, 2005

Part 8: Stabilization of the Patient With Acute Coronary Syndromes Iv-93 onset of symptoms to a hospital without capability for A direct comparison of the outcome of primary or early PCI primary PCI had better outcome (improved 30-day combined patients with patients who received fibrinolytic therapy only incidence of death, reinfarction, or stroke)when they were was not reported transferred to a skilled PCI center(interventionalist perform- ing >75 procedures per year) rather than receiving fibrino- fer of stable patients for early PCI after successful adminis- lytics at the presenting hospital. In these studies balloon tration of fibrinolytics in community hospitals or the out-of- inflation occurred 75 years of age who develop cardiogenic shock or STEMI presenting >3 hours from onset of symptoms from persistent ischemic symptoms within 36 hours of STEMI of providing primary PCI when the transfer can be accom- ERV if ERV can be pene experienced facilities capable of hospitals that lack primary PCI capability to centers capable should be transferred to med within 18 hours of onset of plished as soon as possible. The ACC/AHa guidelines shock. 12 recommend a treatment delay of no more than 90 minutes. In patients with STEMI presenting l mm(0.1 mv) in included fibrinolytics, and 25% had delayed revascularize 2 or more contiguous precordial leads or 2 or more adjacent limb leads and is classified as ST-elevation MI(STEMI tion%6 Although there was no difference in the 30-day 2. Ischemic ST-segment depression 20.5 mm(0.05 mV)or mortality rate, the mortality rate at 6 months was significantly ynamic T-wave inversion with pain or discomfort(Box d lower in the ERV group(50.3% versus 63. 1%) In a prespeci 9) is classified as high-risk UA/non-ST-elevation MI fied subgroup analysis for patients <75 years of age, early (NSTEMI). Nonpersistent or transient ST-segment eleva- revascularization was associated with a 15. 4% reduction in tion 20.5 mm for <20 minutes is also included in this 30-day mortality and improvement in l-year survival rates. 9 category

onset of symptoms to a hospital without capability for primary PCI had better outcome (improved 30-day combined incidence of death, reinfarction, or stroke) when they were transferred to a skilled PCI center (interventionalist perform￾ing
75 procedures per year) rather than receiving fibrino￾lytics at the presenting hospital. In these studies balloon inflation occurred
93 minutes after decision to treat.80,83– 85 Thus, interfacility transfer is indicated for patients with STEMI presenting
3 hours from onset of symptoms from hospitals that lack primary PCI capability to centers capable of providing primary PCI when the transfer can be accom￾plished as soon as possible. The ACC/AHA guidelines recommend a treatment delay of no more than 90 minutes.12 In patients with STEMI presenting 3 hours from onset of symptoms, the superiority of immediate administration of fibrinolytics in the hospital or transfer for primary PCI is not established (Class Indeterminate). In-Hospital Fibrinolytics and Interfacility Transfer for PCI Data from the 1980s to 1990s did not support a strategy of fibrinolytic therapy combined with transfer for facilitated PCI (LOE 186 – 88 and meta-analyses89 –91). But all of the studies involved in-hospital administration of fibrinolytics, and most were completed before the era of coronary stenting and without use of contemporary pharmacologic therapies or PCI techniques. Three small randomized trials (LOE 1)92–94 sup￾ported the strategy of fibrinolytics plus transfer for PCI; however, the timing of PCI after administration of fibrinolyt￾ics, the inclusion of patients who required transfer for PCI, the use of coronary stents, and the control group interventions differ considerably among these trials. The most recent study79 was fairly small and showed a benefit of early PCI with 1-year follow-up.94 At present there is inadequate evidence to recommend the routine transfer of patients for early PCI (ie, within 24 hours) after successful administration of fibrinolytics in a commu￾nity hospital. The use of out-of-hospital administration of fibrinolytics followed by early PCI has not been specifically studied. Special Transfer Considerations Special transfer considerations are appropriate for patients with signs of shock (pulmonary congestion, heart rate
100 bpm, and SBP 100 mm Hg). The Second National Registry of Myocardial Infarction found that the mortality rate in patients with AMI and shock was lower in those treated with PCI as a primary strategy than in those treated with fibrino￾lysis.95 In the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, 152 pa￾tients with cardiogenic shock were randomly assigned to an early revascularization (ERV) strategy, 150 patients were assigned to a strategy of initial medical stabilization that included fibrinolytics, and 25% had delayed revasculariza￾tion.96 Although there was no difference in the 30-day mortality rate, the mortality rate at 6 months was significantly lower in the ERV group (50.3% versus 63.1%). In a prespeci￾fied subgroup analysis for patients 75 years of age, early revascularization was associated with a 15.4% reduction in 30-day mortality and improvement in 1-year survival rates.97 A direct comparison of the outcome of primary or early PCI patients with patients who received fibrinolytic therapy only was not reported. There is inadequate evidence to recommend routine trans￾fer of stable patients for early PCI after successful adminis￾tration of fibrinolytics in community hospitals or the out-of￾hospital setting. Patients 75 years of age and selected patients
75 years of age who develop cardiogenic shock or persistent ischemic symptoms within 36 hours of STEMI should be transferred to experienced facilities capable of ERV if ERV can be performed within 18 hours of onset of shock.12 ED Evaluation and Risk Stratification (Figure 1, Boxes 3 and 4) Focused Assessment and ECG Risk Stratification ED providers should quickly assess patients with possible ACS. Ideally within 10 minutes of ED arrival, providers should obtain a targeted history while a monitor is attached to the patient and a 12-lead ECG is obtained (if not done in the prehospital setting).98 The evaluation should focus on chest discomfort, associated signs and symptoms, prior cardiac history, risk factors for ACS, and historical features that may preclude the use of fibrinolytics or other therapies. This initial evaluation must be efficient because if the patient has STEMI, the goals of reperfusion are to administer fibrinolyt￾ics within 30 minutes of arrival (30-minute interval “door-to￾drug”) or to provide PCI within 90 minutes of arrival (90-minute interval “door-to– balloon inflation” in the cathe￾terization suite). Potential delay during the in-hospital evaluation period may occur from door to data, from data (ECG) to decision, and from decision to drug (or PCI). These 4 major points of in-hospital therapy are commonly referred to as the “4 D’s.”99 All providers must focus on minimizing delays at each of these points. Out-of-hospital transport time constitutes only 5% of delay to treatment time; in-hospital evaluation consti￾tutes 25% to 33% of this delay.100,101 The physical examination is performed to aid diagnosis, rule out other causes of the patient’s symptoms, and evaluate the patient for complications related to ACS. Although the use of clinical signs and symptoms may increase suspicion of ACS, evidence does not support the use of any single sign or combination of clinical signs and symptoms alone to confirm the diagnosis.102–105 When the patient presents with signs of ACS, the clinician uses ECG findings (Figure 1, Box 4) to classify the patient into 1 of 3 groups: 1. ST-segment elevation or presumed new LBBB (Box 5) is characterized by ST-segment elevation
1 mm (0.1 mV) in 2 or more contiguous precordial leads or 2 or more adjacent limb leads and is classified as ST-elevation MI (STEMI). 2. Ischemic ST-segment depression 0.5 mm (0.05 mV) or dynamic T-wave inversion with pain or discomfort (Box 9) is classified as high-risk UA/non–ST-elevation MI (NSTEMI). Nonpersistent or transient ST-segment eleva￾tion 0.5 mm for 20 minutes is also included in this category. Part 8: Stabilization of the Patient With Acute Coronary Syndromes IV-93

IV-9 Circulation December 13. 2005 3. Normal or nondiagnostic changes in ST segment or T TABLE 1. Fibrinolytic Therapy: Contraindications al waves(Box 13) are inconclusive and require further risk Cautions for Fibrinolytic Use in STEMI From ACC/AHA 2004 stratification. This classification includes patients with Guideline Update normal ecgs and those with St-segment deviation of 180 mm Hg or Cardiac biomarkers should be obtained during the initial DBP >110 mm Hgt evaluation of the patient, but therapeutic decisions and History of prior ischemic stroke >3 months, dementia, or known reperfusion therapy for patients with STEMI should not be intracranial pathology not covered in contraindications delayed pending the results of these tests. Important limita tions to these tests exist because they are insensitive during Traumatic or prolonged(10 minutes) CPR or major surgery the first 4 to 6 hours of presentation unless continuous Recent(within 2 to 4 weeks) internal bleeding persistent pain has been present for 6 to 8 hours. For this reason cardiac biomarkers are not useful in the prehospital Noncompressible vascular punctures setting. 107-112 For streptokinase/anistreplase: prior exposure (5 days ago) or prior Serial marker testing(CK-MB and cardiac troponin)over allergic reaction to these agents time improves sensitivity for detection of myocardial infarc- Pregnancy tion but remains insensitive in the first 4 to 6 hours. 113, 114 Current use of anticoagulants: the higher the INR, the higher the risk of ST-Segment Elevation MI (Figure 1, Boxes 5 Through 8) AVM indicates arteriovenous malformation; SBP, systolic blood pressure, Patients with STEMI usually have complete occlusion of an DBP, diastolic blood pressure, and INR, International Normalized Ratio reperfusion therapy through administration of fibrinolytics or dein ie as advisory for clinical decision making and may not be all-inclusive epicardial coronary vessel. The mainstay of treatment is fOuld be an absolute contraindication in low-risk patients with myocardial (pharmacologic reperfusion) or primary PCI (mechanical reperfusion). Providers should rapidly identify patients STEMI and quickly screen them for indications and contra- indications to fibrinolytic therapy and PCI. dentifies a population at increased risk for MACE. Patients The first physician who encounters a patient with AMI with ischemic-type pain and ECGs consistent with NSTEMI and direct its administration(see Tables I and 2). If the fibrinolytic therapy, and fibrinolysis may be harmful. l tm should be able to determine the need for reperfusion theral or normal or nondiagnostic ecgs do not benefit fro patient meets the criteria for fibrinolytic therapy, a door-to- Although many patients will not have ACs(ie, the ECG needle time(needle time is the beginning of infusion of a change is due to an alternative diagnosis, such as LV fibrinolytic agent)<30 minutes is desired. Results of cardiac biomarkers do not delay the administration of fibrinolytic antiplatelet, antithrombin, and antianginal therapy. These percentage of patients who present early with STEMI. Con- patients usually have a partially or intermittently occluding thrombus. Clinical features can correlate with the dynamic sultation with a cardiologist or the patient's personal physI- nature of clot formation and degradation, eg, waxing and cian delays therapy, is associated with increased hospital mortality rates, and is recommended only in equivocal or waning clinical sympton hospitals with capabilities for angiogra- Serial cardiac markers are often obtained during evalua phy and PCi should have a clear protocol directing ED triage and initial management. Confusion about the method of during evaluation, elevation of cardiac troponin pal int tion, including CK-MB and cardiac troponins. At any point reperfusion, eg fibrinolysis or PCL, delays definitive therapy. patient at increased risk for MACE. Studies have shown tha patients with increased troponin are best managed with UA and NSTEMI (Figure 1, Boxes 9 Through 17) strategy of small-molecule glycoprotein(GP)IIb/Illa inhibi In the absence of ST-segment elevation, patients with ische- tor therapy and an early invasive strategy(cardiac catheter mic-type chest pain can present with ST-segment depression ization with possible revascularization). Troponin serves or nondiagnostic or normal ECGs. ST-segment depression an additional and incremental adjunct to the ECG. Physicians

3. Normal or nondiagnostic changes in ST segment or T waves (Box 13) are inconclusive and require further risk stratification. This classification includes patients with normal ECGs and those with ST-segment deviation of 0.5 mm (0.05 mV) or T-wave inversion of
0.2 mV. Serial cardiac studies (and functional testing) are appropriate. Cardiac Biomarkers New cardiac biomarkers, which are more sensitive than the myocardial muscle creatine kinase isoenzyme (CK-MB), are useful in diagnosis, risk stratification, and determination of prognosis. An elevated level of troponin correlates with an increased risk of death, and greater elevations predict greater risk of adverse outcome.106 Patients with increased troponin levels have increased thrombus burden and microvascular embolization. Cardiac biomarkers should be obtained during the initial evaluation of the patient, but therapeutic decisions and reperfusion therapy for patients with STEMI should not be delayed pending the results of these tests. Important limita￾tions to these tests exist because they are insensitive during the first 4 to 6 hours of presentation unless continuous persistent pain has been present for 6 to 8 hours. For this reason cardiac biomarkers are not useful in the prehospital setting.107–112 Serial marker testing (CK-MB and cardiac troponin) over time improves sensitivity for detection of myocardial infarc￾tion but remains insensitive in the first 4 to 6 hours.113,114 ST-Segment Elevation MI (Figure 1, Boxes 5 Through 8) Patients with STEMI usually have complete occlusion of an epicardial coronary vessel. The mainstay of treatment is reperfusion therapy through administration of fibrinolytics (pharmacologic reperfusion) or primary PCI (mechanical reperfusion). Providers should rapidly identify patients with STEMI and quickly screen them for indications and contra￾indications to fibrinolytic therapy and PCI. The first physician who encounters a patient with AMI should be able to determine the need for reperfusion therapy and direct its administration (see Tables 1 and 2). If the patient meets the criteria for fibrinolytic therapy, a door-to￾needle time (needle time is the beginning of infusion of a fibrinolytic agent)
30 minutes is desired. Results of cardiac biomarkers do not delay the administration of fibrinolytic therapy or referral for PCI. They are normal in a significant percentage of patients who present early with STEMI. Con￾sultation with a cardiologist or the patient’s personal physi￾cian delays therapy, is associated with increased hospital mortality rates, and is recommended only in equivocal or uncertain cases.115 Hospitals with capabilities for angiogra￾phy and PCI should have a clear protocol directing ED triage and initial management. Confusion about the method of reperfusion, eg, fibrinolysis or PCI, delays definitive therapy. UA and NSTEMI (Figure 1, Boxes 9 Through 17) In the absence of ST-segment elevation, patients with ische￾mic-type chest pain can present with ST-segment depression or nondiagnostic or normal ECGs. ST-segment depression identifies a population at increased risk for MACE. Patients with ischemic-type pain and ECGs consistent with NSTEMI or normal or nondiagnostic ECGs do not benefit from fibrinolytic therapy, and fibrinolysis may be harmful.116 Although many patients will not have ACS (ie, the ECG change is due to an alternative diagnosis, such as LV hypertrophy), initial triage and therapy appropriately includes antiplatelet, antithrombin, and antianginal therapy. These patients usually have a partially or intermittently occluding thrombus. Clinical features can correlate with the dynamic nature of clot formation and degradation, eg, waxing and waning clinical symptoms. Serial cardiac markers are often obtained during evalua￾tion, including CK-MB and cardiac troponins. At any point during evaluation, elevation of cardiac troponin places a patient at increased risk for MACE. Studies have shown that patients with increased troponin are best managed with a strategy of small-molecule glycoprotein (GP) IIb/IIIa inhibi￾tor therapy and an early invasive strategy (cardiac catheter￾ization with possible revascularization). Troponin serves as an additional and incremental adjunct to the ECG. Physicians TABLE 1. Fibrinolytic Therapy: Contraindications and Cautions for Fibrinolytic Use in STEMI From ACC/AHA 2004 Guideline Update* Absolute Contraindications • Any prior intracranial hemorrhage • Known structural cerebral vascular lesion (eg, AVM) • Known malignant intracranial neoplasm (primary or metastatic) • Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours • Suspected aortic dissection • Active bleeding or bleeding diathesis (excluding menses) • Significant closed head trauma or facial trauma within 3 months Relative Contraindications • History of chronic, severe, poorly controlled hypertension • Severe uncontrolled hypertension on presentation (SBP
180 mm Hg or DBP
110 mm Hg)† • History of prior ischemic stroke
3 months, dementia, or known intracranial pathology not covered in contraindications • Traumatic or prolonged (
10 minutes) CPR or major surgery (3 weeks) • Recent (within 2 to 4 weeks) internal bleeding • Noncompressible vascular punctures • For streptokinase/anistreplase: prior exposure (
5 days ago) or prior allergic reaction to these agents • Pregnancy • Active peptic ulcer • Current use of anticoagulants: the higher the INR, the higher the risk of bleeding AVM indicates arteriovenous malformation; SBP, systolic blood pressure; DBP, diastolic blood pressure; and INR, International Normalized Ratio. *Viewed as advisory for clinical decision making and may not be all-inclusive or definitive. †Could be an absolute contraindication in low-risk patients with myocardial infarction. IV-94 Circulation December 13, 2005

Part 8: Stabilization of the Patient With Acute Coronary Syndromes 1-95 Step 1: A 2. ST-Segment Elevation or New or Presumably New LBBB: Evaluation for Reperfusion Assess time and risk since onset of symptoms isk of sTemi Risk of fibrinolysis Time required to transport to skilled PCl catheterization suite Step 2: Select reperfusion(fibrinolysis or invasive) strategy Note: If presentation 3 hours ago Invasive strategy is not an option (eg, lack of access to skilled Skilled PCl facility available with surgical backup PCi facility or difficult vascular access) or would be delayed -Medical contact-to-balloon or door-balloon >90 min Medical contact-to-balloon or door-balloon 1 hour .(Door-to-balloon)minus(door-to-needle)is <1hour No contraindications to fibrinolysis e Contraindications to fibrinolysis, including increased risk of bleeding and ICH High risk from STEMI(CHF, Killip class is 23) Diagnosis of STEMI is in doubt Modified from ACC/AHA 2004 Update Recommendations. need to appreciate that other disorders can increase cardiac with MACE. Use of aspirin within the previous 7 days, for troponin, eg, myocarditis, congestive heart failure, and pul- example, would not seem to be an indicator of a bad outcome. out aspirin use was in fact found to be one of the most Risk Stratification powerful predictors. 22 It is possible that aspirin use identified a subgroup of patients at higher risk or on active but failed Braunwald Stratification therapy for CAD. There are many ways to risk-stratify patients with chest pain. The creators of the timi risk score validated it with 3 A well-recognized approach is the one initially proposed and groups of patients, and 4 clinical trials showed a significant later refined by Braunwald and colleagues on the ACC/AHa interaction between the TIMI risk score and outcome. 24-128 Task Force on the Management of Patients With Unstable These findings confirm the value of the tImi risk score as a Angina. 11, 117-120 This approach is based on a combination of guide to therapeutic decisions. A PDA download of this risk historical, clinical, laboratory, and ECG variables assessmentisavailableatwww.TimlOrG Table 3 is a modified version of what has been a work in By classifying patients into I of 3 risk strata, the Braun- progress by Braunwald and colleagues over several publica- wald (Table 3)and TIMI (Table 4)risk scores serve as the tions. 118, 120, 12I Patients are initially risk-stratified according to dominant clinical guides for predicting the risk of MACE in the likelihood that symptoms are due to unstable coronary patients with ACS. Risk stratification is applicable to patients artery disease(CAD). Patients at intermediate or high risk fc at intermediate or high risk of symptoms due to CAD and not CAD are further classified by their risk of MACE. This the larger general population of patients presenting with chest second classification is useful for prospectively identifying pain or symptoms possibly due to anginal equivalents. Risk patients at intermediate or high risk who can benefit from an stratification enables clinicians to direct therapy to those invasive strategy and more aggressive pharmacology with patients at intermediate or high risk of MACE and avoids antiplatelet and antithrombin agents unnecessary therapy and the potential for adverse conse quences in patients who are at lower risk. TIMI Risk score The risk of mace has been further studied and refined The TIMI risk score has become the primary tool for TIMI-IIB and ESSENCE (Efficacy and Safety of Subcuta- gained for patients with higher risk scoresapiey entally Researchers who derived the important Thrombolysis in evaluating therapeutic recommendations. Increm yocardial Ischemia(TIMI) risk score used data from the greater benefit from some of the newer the neous Enoxaparin in Non-Q-Wave Coronary Events) trials One additional product of the TIMI trials is the TIMI for UA/NSTEMi22, 23 and from the In-time trial for grading system of coronary artery blood flow. Investigators from the TIMI study developed and validated a coronary STEMI. 124 The TIMI risk score comprises 7 independent artery perfusion scoring system, characterizing the degree of prognostic variables(Table 4). These 7 variables were sig- reperfusion of a coronary artery on a scale of 0(no flow)to nificantly associated with the occurrence within 14 days of at least one of the primary end points: death, new or recurrent 3(normal, brisk flow). This TIMI grading system is now used MI or need for urgent revascularization The score is derived as an outcome measure in many studies of ACS interventions from complex multivariate logistic regression and includes Indicators for Early Invasive Strategies variables that seem counterintuitive. It is useful to note that Risk stratification(Figure l, Box 12) helps the clinician traditional cardiac risk factors are only weakly associated identify patients with NSTEMI and UA who should be

need to appreciate that other disorders can increase cardiac troponin, eg, myocarditis, congestive heart failure, and pul￾monary embolism. Risk Stratification Braunwald Stratification There are many ways to risk-stratify patients with chest pain. A well-recognized approach is the one initially proposed and later refined by Braunwald and colleagues on the ACC/AHA Task Force on the Management of Patients With Unstable Angina.11,117–120 This approach is based on a combination of historical, clinical, laboratory, and ECG variables. Table 3 is a modified version of what has been a work in progress by Braunwald and colleagues over several publica￾tions.118,120,121 Patients are initially risk-stratified according to the likelihood that symptoms are due to unstable coronary artery disease (CAD). Patients at intermediate or high risk for CAD are further classified by their risk of MACE. This second classification is useful for prospectively identifying patients at intermediate or high risk who can benefit from an invasive strategy and more aggressive pharmacology with antiplatelet and antithrombin agents. TIMI Risk Score The risk of MACE has been further studied and refined. Researchers who derived the important Thrombolysis in Myocardial Ischemia (TIMI) risk score used data from the TIMI-11B and ESSENCE (Efficacy and Safety of Subcuta￾neous Enoxaparin in Non–Q-Wave Coronary Events) trials for UA/NSTEMI122,123 and from the In-TIME trial for STEMI.124 The TIMI risk score comprises 7 independent prognostic variables (Table 4). These 7 variables were sig￾nificantly associated with the occurrence within 14 days of at least one of the primary end points: death, new or recurrent MI, or need for urgent revascularization. The score is derived from complex multivariate logistic regression and includes variables that seem counterintuitive. It is useful to note that traditional cardiac risk factors are only weakly associated with MACE. Use of aspirin within the previous 7 days, for example, would not seem to be an indicator of a bad outcome. But aspirin use was in fact found to be one of the most powerful predictors.122 It is possible that aspirin use identified a subgroup of patients at higher risk or on active but failed therapy for CAD. The creators of the TIMI risk score validated it with 3 groups of patients, and 4 clinical trials showed a significant interaction between the TIMI risk score and outcome.124 –128 These findings confirm the value of the TIMI risk score as a guide to therapeutic decisions. A PDA download of this risk assessment is available at www.TIMI.org. By classifying patients into 1 of 3 risk strata, the Braun￾wald (Table 3) and TIMI (Table 4) risk scores serve as the dominant clinical guides for predicting the risk of MACE in patients with ACS. Risk stratification is applicable to patients at intermediate or high risk of symptoms due to CAD and not the larger general population of patients presenting with chest pain or symptoms possibly due to anginal equivalents. Risk stratification enables clinicians to direct therapy to those patients at intermediate or high risk of MACE and avoids unnecessary therapy and the potential for adverse conse￾quences in patients who are at lower risk. The TIMI risk score has become the primary tool for evaluating therapeutic recommendations. Incrementally greater benefit from some of the newer therapies may be gained for patients with higher risk scores. One additional product of the TIMI trials is the TIMI grading system of coronary artery blood flow. Investigators from the TIMI study developed and validated a coronary artery perfusion scoring system, characterizing the degree of reperfusion of a coronary artery on a scale of 0 (no flow) to 3 (normal, brisk flow). This TIMI grading system is now used as an outcome measure in many studies of ACS interventions. Indicators for Early Invasive Strategies Risk stratification (Figure 1, Box 12) helps the clinician identify patients with NSTEMI and UA who should be TABLE 2. ST-Segment Elevation or New or Presumably New LBBB: Evaluation for Reperfusion Step 1: Assess time and risk Time since onset of symptoms Risk of STEMI Risk of fibrinolysis Time required to transport to skilled PCI catheterization suite Step 2: Select reperfusion (fibrinolysis or invasive) strategy Note: If presentation 3 hours and no delay for PCI, then no preference for either strategy. Fibrinolysis is generally preferred if: An invasive strategy is generally preferred if: ● Early presentation (
3 hours from symptom onset) ● Late presentation (symptom onset
3 hours ago) ● Invasive strategy is not an option (eg, lack of access to skilled PCI facility or difficult vascular access) or would be delayed ● Skilled PCI facility available with surgical backup —Medical contact-to-balloon or door-balloon
90 min ● Medical contact-to-balloon or door-balloon 90 min —(Door-to-balloon) minus (door-to-needle) is
1 hour ● (Door-to-balloon) minus (door-to-needle) is 1 hour ● No contraindications to fibrinolysis ● Contraindications to fibrinolysis, including increased risk of bleeding and ICH ● High risk from STEMI (CHF, Killip class is 3) ● Diagnosis of STEMI is in doubt Modified from ACC/AHA 2004 Update Recommendations.112 Part 8: Stabilization of the Patient With Acute Coronary Syndromes IV-95

lV-96 Circulation December 13, 2005 TABlE 3. Likelih Part l. chest pain p patients Wi Ischemic Etiology and Short-Term Risk thout ST-Segment Elevation: Likelihood of Ischemic Etiology A. High likelihood B. Intermediate likelihood C, Low likelihood likelihood that chest pain is of intermediate likelihood that chest Low likelihood that chest ischemic etiology if patient has any of is of ischemic etiology if patient has ischemic etiology if pater the findings in the column belot No findings in column A and any of dings in column A or B the findings in the column below ay have any of the findings in the Chief symptom is chest or left arm lief symptom is chest or left arm Probable ischemic symptoms pain or discomfit Recent cocaine us Current pain documented · Diabetes mellitus Physical Transient mitral regurgitation Extracardiac vascular disease Chest discomfort reproduced by Pulmonary edema or rales New (or presumed new)transient ST · Fixed o waves · Normal ecg or deviation (20.5 mm)or T-wave Abnormal ST segments or T waves T-wave flattening or version(22 mm)with symptoms that are not new T-wave inversion in leads with dominant R waves Cardiac I or T Any finding in column B above PLUS Normal evaded CK-MB Normal ligh(A)or Intermediate(B) Part ll. Risk of Death or Nonfatal MI Over the Short Term in Patients With Chest Pain With High or Intermediate Likelihood of Ischemia(Columns A nd B in Part D) Intermediate risk w risk Risk is high if patient has any of the Risk is intermediate if patient has any Risk is low if patient has NO high-or of the following findings intermediate-risk features; may have any of the following Accelerating tempo of ischemic · Prior mi or ymptoms over prior 48 hours Peripheral-artery disease Cerebrovascular disease or ·CABG, pnor spinn use Character of Prolonged, continuing (20 min) Prolonged(20 min) rest angina is New-onset functional angina(Class ow resolved (moderate to high ll or M) in past 2 weeks without likelihood of CAD) prolonged rest pain(but with Rest angina(70 years ischemia New or worse mitral regurgitation murmur S3 gallop or new or worsening (0.5 mm) with rest angina Pathologic Q waves or T waves that episode of chest discomfort New or presumably new bundle are not new anch bloc Cardiac Elevated cardiac troponin I or T Any of the above findings PLUs Normal markers levated CK-MB Normal Modified from Braunwald et al. circulation. 2002- 106: 1893-1900

TABLE 3. Likelihood of Ischemic Etiology and Short-Term Risk Part I. Chest Pain Patients Without ST-Segment Elevation: Likelihood of Ischemic Etiology A. High likelihood High likelihood that chest pain is of ischemic etiology if patient has any of the findings in the column below: B. Intermediate likelihood Intermediate likelihood that chest pain is of ischemic etiology if patient has NO findings in column A and any of the findings in the column below: C. Low likelihood Low likelihood that chest pain is of ischemic etiology if patient has NO findings in column A or B. Patients may have any of the findings in the column below: History • Chief symptom is chest or left arm pain or discomfort plus Current pain reproduces pain of prior documented angina and Known CAD, including MI • Chief symptom is chest or left arm pain or discomfort • Age
70 years • Male sex • Diabetes mellitus • Probable ischemic symptoms • Recent cocaine use Physical exam • Transient mitral regurgitation • Hypotension • Diaphoresis • Pulmonary edema or rales • Extracardiac vascular disease • Chest discomfort reproduced by palpation ECG • New (or presumed new) transient ST deviation (0.5 mm) or T-wave inversion (2 mm) with symptoms • Fixed Q waves • Abnormal ST segments or T waves that are not new • Normal ECG or T-wave flattening or T-wave inversion in leads with dominant R waves Cardiac markers • Elevated troponin I or T • Elevated CK-MB Any finding in column B above PLUS • Normal • Normal High (A) or Intermediate (B) Likelihood of Ischemia Part II. Risk of Death or Nonfatal MI Over the Short Term in Patients With Chest Pain With High or Intermediate Likelihood of Ischemia (Columns A and B in Part I) High risk: Risk is high if patient has any of the following findings: Intermediate risk: Risk is intermediate if patient has any of the following findings: Low risk: Risk is low if patient has NO high- or intermediate-risk features; may have any of the following: History Character of pain • Accelerating tempo of ischemic symptoms over prior 48 hours • Prolonged, continuing (
20 min) rest pain • Prior MI or • Peripheral-artery disease or • Cerebrovascular disease or • CABG, prior aspirin use • Prolonged (
20 min) rest angina is now resolved (moderate to high likelihood of CAD) • Rest angina (20 min) or relieved by rest or sublingual nitrates • New-onset functional angina (Class III or IV) in past 2 weeks without prolonged rest pain (but with moderate or high likelihood of CAD) Physical exam • Pulmonary edema secondary to ischemia • New or worse mitral regurgitation murmur • Hypotension, bradycardia, tachycardia • S3 gallop or new or worsening rales • Age
75 years • Age
70 years ECG • Transient ST-segment deviation (0.5 mm) with rest angina • New or presumably new bundle branch block • Sustained VT • T-wave inversion 2 mm • Pathologic Q waves or T waves that are not new • Normal or unchanged ECG during an episode of chest discomfort Cardiac markers • Elevated cardiac troponin I or T • Elevated CK-MB Any of the above findings PLUS • Normal • Normal Modified from Braunwald et al. Circulation. 2002;106:1893–1900. IV-96 Circulation December 13, 2005

Part 8: Stabilization of the Patient With Acute Coronary Syndromes Iv-97 TABLE 4. TIMI Risk Score for Patients With Unstable Angina and Non-ST-Segment Elevation ME: Predictor Variables Point value Predictor Variable of variable Definition Age 265 ≥3 risk factors for CAD Risk factors Family history of CAD Hypercholesterolemia Diabetes Current smoker Aspirin use in last 7 days Recent, severe symptoms of angina 22 anginal events in last 24 hours Elevated cardiac markers CK-MB or cardiac-specific troponin level st deviation≥0.5 ST depression 20.5 mm is significant; transient sT elevation >0.5 mm for <20 minutes is treated as sT-segment depression and is high risk; sT elevation 21 mm for more than 20 minutes places these patients in the STEMI treatment category Prior coronary artery stenosis 250% Risk predictor remains valid even if this information is unknown Risk of≥1 Primary End Calculated TIMI Risk Score Point* in≤14Days Risk Status 0 or 1 13% Primary end points: death, new or recurrent Mi, or need for urgent revascularization. managed with an invasive strategy. Coronary angiography monitoring, establishment of intravenous(Iv) access, and then allows the clinician to determine whether patients are several medications discussed below appropriate candidates for revascularization with PCi or coronary artery bypass grafting(CABG) Oxygen The 2005 AHA Guidelines for CPR and ECC define Administer oxygen to all patients with overt onary high-risk patients with indicators that overlap to a consider- congestion or arterial oxygen saturation <90%(Class I). It is able degree with the more rigorously validated TIMI risk also reasonable to administer to all patients with ACS for the first 6 hours of therapy( Class Ila) New ST-segment depression and positive troponins Supplementary oxygen limited ischemic myocardial injury in Persistent or recurrent symptoms animals, I and oxygen therapy in patients with STEMI Hemodynamic instability or VT reduced the amount of ST-segment elevation. 5 Although Depressed LV function(ejection fraction <40%0) human trial of supplementary oxygen versus room air failed ECG or functional study that suggests multivessel CAD to show a long-term benefit of supplementary oxygen therapy for patients with MI, O short-term oxygen administration is Normal or Nondiagnostic ECG Changes(Boxes 13 beneficial for the patient with unrecognized hypoxemia o to 17) unstable pulmonary function. In patients with severe chronic The majority of patients with normal or nondiagnostic ECGs obstructive pulmonary disease, as with any other pater do not have ACS Patients in this category with ACS are most monitor for hypoventilation often at low or intermediate risk. The physician's goal involves risk stratification(see above)to provide appropriate AsI diagnostic or treatment strategies for an individual patient. Early administration of aspirin(acetylsalicylic acid [ASAD). These strategies then target patients at increased risk for including administration in the out-of-hospital setting, ha benefit while avoiding risk(eg, anticoagulation therapy an been associated with decreased mortality rates in several invasive cardiac catheterization)in patients with low or clinical trials.47129-131 Multiple studies s pport the safety of minimal risk aspirin administration. Therefore, unless the patient has a known aspirin allergy, nonenteric aspirin should be given as I General Therapy for ACs soon as possible to all patients with suspected ACs. Several initial measures are appropriate for all patients with Aspirin produces a rapid clinical antiplatelet effect with suspected ACS in both the out-of-hospital and ED setting. near-total inhibition of thromboxane A2 production. It reduces These include immediate oxygen therapy, continuous cardiac coronary reocclusion and recurrent ischemic events after

managed with an invasive strategy. Coronary angiography then allows the clinician to determine whether patients are appropriate candidates for revascularization with PCI or coronary artery bypass grafting (CABG). The 2005 AHA Guidelines for CPR and ECC define high-risk patients with indicators that overlap to a consider￾able degree with the more rigorously validated TIMI risk score122: ● New ST-segment depression and positive troponins ● Persistent or recurrent symptoms ● Hemodynamic instability or VT ● Depressed LV function (ejection fraction 40%) ● ECG or functional study that suggests multivessel CAD Normal or Nondiagnostic ECG Changes (Boxes 13 to 17) The majority of patients with normal or nondiagnostic ECGs do not have ACS. Patients in this category with ACS are most often at low or intermediate risk. The physician’s goal involves risk stratification (see above) to provide appropriate diagnostic or treatment strategies for an individual patient. These strategies then target patients at increased risk for benefit while avoiding risk (eg, anticoagulation therapy and invasive cardiac catheterization) in patients with low or minimal risk. Initial General Therapy for ACS Several initial measures are appropriate for all patients with suspected ACS in both the out-of-hospital and ED setting. These include immediate oxygen therapy, continuous cardiac monitoring, establishment of intravenous (IV) access, and several medications discussed below. Oxygen Administer oxygen to all patients with overt pulmonary congestion or arterial oxygen saturation 90% (Class I). It is also reasonable to administer supplementary oxygen to all patients with ACS for the first 6 hours of therapy (Class IIa). Supplementary oxygen limited ischemic myocardial injury in animals,31 and oxygen therapy in patients with STEMI reduced the amount of ST-segment elevation.35 Although a human trial of supplementary oxygen versus room air failed to show a long-term benefit of supplementary oxygen therapy for patients with MI,30 short-term oxygen administration is beneficial for the patient with unrecognized hypoxemia or unstable pulmonary function. In patients with severe chronic obstructive pulmonary disease, as with any other patient, monitor for hypoventilation. Aspirin Early administration of aspirin (acetylsalicylic acid [ASA]), including administration in the out-of-hospital setting,47 has been associated with decreased mortality rates in several clinical trials.47,129 –131 Multiple studies support the safety of aspirin administration. Therefore, unless the patient has a known aspirin allergy, nonenteric aspirin should be given as soon as possible to all patients with suspected ACS. Aspirin produces a rapid clinical antiplatelet effect with near-total inhibition of thromboxane A2 production. It reduces coronary reocclusion and recurrent ischemic events after TABLE 4. TIMI Risk Score for Patients With Unstable Angina and Non–ST-Segment Elevation MI: Predictor Variables Predictor Variable Point Value of Variable Definition Age 65 years 1 3 risk factors for CAD 1 Risk factors • Family history of CAD • Hypertension • Hypercholesterolemia • Diabetes • Current smoker Aspirin use in last 7 days 1 Recent, severe symptoms of angina 1 2 anginal events in last 24 hours Elevated cardiac markers 1 CK-MB or cardiac-specific troponin level ST deviation 0.5 mm 1 ST depression 0.5 mm is significant; transient ST elevation
0.5 mm for 20 minutes is treated as ST-segment depression and is high risk; ST elevation 1 mm for more than 20 minutes places these patients in the STEMI treatment category Prior coronary artery stenosis 50% 1 Risk predictor remains valid even if this information is unknown Calculated TIMI Risk Score Risk of >1 Primary End Point* in <14 Days Risk Status 0 or 1 5% Low 2 8% 3 13% Intermediate 4 20% 5 26% High 6 or 7 41% *Primary end points: death, new or recurrent MI, or need for urgent revascularization. Part 8: Stabilization of the Patient With Acute Coronary Syndromes IV-97