13RC1-BOSSAERT The Chain Of Survival of Acute Coronary Syndromes

Transcription

1 13RC1-BOSSAERT The Chain Of Survival of Acute Coronary Syndromes Leo Bossaert University and University Hospital Antwerp, Belgium, European Resuscitation Council Nikolaos Nikolaou Konstantopouleio General Hospital, Athens, Greece, European Resuscitation Council and ESC Acute Cardiac Care Association Introduction The chain of survival concept was introduced in 1967 by Fritz Ahnefeld, die Glieder der Rettungskette, and was later adjusted to describe the sequence of events that are required to successfully resuscitate victims of cardiac arrest (CA). In its current form it consists of four links: 1 early recognition and call for help early cardiopulmonary resuscitation early defibrillation post resuscitation care A similar approach was proposed for patients with an Acute Coronary Syndrome (ACS): 2,3 early recognition and access to emergency medical services early diagnosis early reperfusion early definitive care Prevention of CA is an integral part of the first link of the chain of survival for both CA and ACS. Application of this metaphor in the clinical management of chest pain has the potential to guide implementation of effective interdisciplinary collaboration in regional systems for evidence-based treatment of patients with suspected ACS, eliminating gaps and inconsistencies within and across countries. Guidelines In the past 15 years, the European Society of Cardiology (ESC, published and updated guidelines for STEMI, NSTEMI (ST elevation, and non-st elevation myocardial infarction) and reperfusion and focused also on the implications for management in the emergency department. The ESC and the European Resuscitation Council (ERC, have produced joined statements on common areas of expertise. Based on a review of the same scientific evidence, similar, but not identical because of differences in organisation and practice, guidelines were produced by the American Heart Association (AHA). The ERC produced evidence-based guidelines for the management of cardiac arrest and included recommendations for the early management of ACS. 4 1/10

2 The International Liaison Committee on Resuscitation (ILCOR, was established in 1992 to provide a liaison between all major resuscitation organizations worldwide, including the ERC and the AHA. ILCOR provides a mechanism to collect, review and share international scientific data on resuscitation and to produce statements on specific issues related to resuscitation that reflect international consensus. Every 5 years ILCOR coordinates an evidence-based review of resuscitation science, resulting in a joint publication Consensus on Resuscitation Science. The process for the 2015 review of resuscitation science has started. These science reviews serve as the basis for regional resuscitation organizations, such as the ERC, to update their resuscitation guidelines. 5,6 The ILCOR consensus on science 2015 will focus on 6 domains of emergency medical care: BLS&AED (Basic Life Support and use of Automated External Defibrillators) ALS (Advanced Life Support) PLS (Paediatric Life Support) NLS (Neonatal Life Support) ACS-MI (Acute coronary syndromes and Myocardial Infarction) Education The focus of the ACS domain is the pre-hospital phase of ACS. For the 2015 review the ILCOR task force of ACS has identified 33 topics that are relevant for the healthcare provider in the pre-hospital and early emergency phase. These include: percutaneous coronary intervention (PCI) after return of spontaneous circulation (ROSC), direct transportation to PCI centre, pre-hospital fibrinolysis for STEMI, facilitated PCI, fibrinolysis versus PCI for STEMI, biomarkers and ECG for the early diagnosis of ACS, maximum acceptable time delay to PCI, early drug treatment for ACS, improvement of systems of care for early management of ACS. To improve transparency and uniformity of the review process, the ILCOR has adopted the GRADE methodology to identify, evaluate and summarize resuscitation science. GRADE is based on the review of evidence for each PICO-formulated question (P-patient population, I-intervention, C-comparator, O- outcome). 7 Definitions In the 2000 Guidelines, myocardial infarction (MI) was defined as any myocardial necrosis in the presence of myocardial ischemia. This definition was further refined in 2007 with emphasis on the different conditions which may lead to MI. Further revision was needed in 2012 after the development of more sensitive biomarkers for the diagnosis of MI. 8 The term ACS encompasses three different entities of the acute manifestation of coronary heart disease: STEMI, NSTEMI and unstable angina pectoris (UAP). ST segment elevation on 12-lead ECG differentiates STEMI from NSTEMI ACS. In the absence of ST elevation on surface ECG, elevated cardiac biomarkers indicate NSTEMI. Myocardial necrosis can be the result of myocardial ischaemia due to acute coronary occlusion or due to an imbalance between myocardial oxygen supply and demand. Myocardial injury may not be related to myocardial ischaemia. Diagnosis of MI is based on 12-lead ECG and serial measurement of biomarkers, preferably troponins. Detection of ischaemia can be done using clinical, ECG, wall motion imaging and angiographic criteria. 2/10

3 Specific criteria exist for the diagnosis of AMI in patients undergoing PCI and CABG and also those with stent thrombosis and sudden death related to MI. Epidemiology Each year cardiovascular disease (CVD) causes over 4 million deaths in Europe. This represents 47% of all deaths. CVD mortality is now falling in most European countries, including Central and Eastern European countries, which saw dramatic increases until the beginning of the 21st century. 9 Several European registries indicate an incidence of STEMI of about 66/100,000 per year. 10 NSTEMI is more frequent 132/100,000 per year. The incidence of STEMI is decreasing while the incidence of NSTEMI is increasing. There are differences between countries. 11 Hospital mortality in patients with STEMI is 7% and higher than the 3-5% mortality with NSTEMI. At 6 months, mortalities tend to equalize (12% and 13%, respectively), while in the long term death rates are higher among patients with NSTEMI. 12 This difference in mid- and long-term follow up may be attributed to patients with NSTEMI being older and have more comorbidities. ACS are the commonest cause of sudden cardiac death because of malignant arrhythmias. Although the in-hospital mortality from STEMI has been reduced significantly thanks to modern reperfusion therapy, the overall 30-day mortality is virtually unchanged at about 40%, because most patients with AMI die from lethal arrhythmias before arrival to hospital. 13 The best strategy to improve survival from an ischaemic attack is to implement interdisciplinary regional STEMI systems of care and clinical pathways that will optimise out-of-hospital treatment and facilitate best in-hospital treatment. Diagnosis (Figure 1) Symptoms An ACS may present with prolonged chest pain at rest and recent onset or worsening angina. Atypical presentations are common, particularly in the elderly, in females, and in patients with diabetes, renal failure and dementia. In this case an ACS may present as abdominal pain, nausea and vomiting, shortness of breath, fatigue, palpitations or syncope. 6 Also, CA occurs most often at home in the presence of relatives and after a long period of premonitory symptoms, so there is merit in targeting educational programs at patients and their relatives to teach them how to call for help and initiate resuscitation. 14 3/10

4 Figure 1. Definitions of Acute Coronary Syndromes. (From: Arntz HR, Bossaert LL, Danchin N, Nikolaou NI. European Resuscitation Council Guidelines for Resuscitation Section 5. Initial management of acute coronary syndromes. Resuscitation. 2010;81: With permission: European Resuscitation Council /043) Electrocardiography A 12-lead ECG is the principal investigation to guide management of patients with ACS. In the case of STEMI, immediate reperfusion therapy, either primary PCI (PPCI) or fibrinolysis, is needed. ECG should be obtained and interpreted by trained healthcare providers, ideally within 10 minutes after first medical contact. Pre-hospital recording of a 12-lead ECG enables advance notification of the receiving hospital and saves considerable time in the initiation of treatment after arrival in hospital. Despite the limitations of the ECG to diagnose ACS in the absence of STEMI, trained emergency physicians, paramedics and nurses can identify STEMI reliably. If interpretation of the pre-hospital ECG is not available on-site, field transmission of the ECG is possible. Computer interpretation may be used as an adjunct to interpretation by an experienced clinician. STEMI is diagnosed when ST-segment elevation, measured at the J point, fulfils specific voltage criteria in the absence of left ventricular (LV) hypertrophy or left bundle branch block (LBBB). In patients with clinical suspicion of evolving myocardial ischaemia with new, or presumed new, LBBB, reperfusion therapy should be considered promptly, preferably using primary PCI (PPCI). Ventricle pacing may also mask the presence of an evolving MI and may require urgent angiography to confirm diagnosis and initiate therapy. 15 Right precordial leads should be recorded in all patients with inferior STEMI in order to detect a MI involving the right ventricle. Isolated ST-depression 0.05 mv in leads V 1 to V 3 represents STEMI in the inferobasal portion of the heart. ST segment abnormalities that are typical in non-stemi are ST depression 0.05 mv or T wave inversion 0.1 mv in two adjacent leads with prominent R wave or R:S ratio > 1. 4/10

5 Biomarkers Cardiac specific troponins are the preferred biomarkers for establishing diagnosis and risk stratification in ACS. An MI is diagnosed when cardiac troponin level exceeds the 99 th percentile of a normal reference population. Recently, high-sensitivity assays have been introduced able to measure smaller troponin concentrations making diagnosis possible within 3 hours of presentation. Increased sensitivity of an assay allows detection of low troponin concentrations in patients with stable angina and other cardiac and non-cardiac conditions. It is important to distinguish ACS from other life threatening situations that present with chest pain such as aortic dissection and pulmonary embolism. 16 Imaging Echocardiography can detect ischemic wall motion abnormalities and diagnose aortic dissection, pulmonary embolism, aortic stenosis, hypertrophic cardiomyopathy and pericardial fluid. Echocardiography should therefore be part of evaluation of all patients with suspected ACS. Despite limited availability, nuclear myocardial perfusion imaging, cardiac magnetic resonance and multidetector computed tomography might be helpful in assessing patients with suspected ACS. Treatment All patients with suspected STEMI should be considered for revascularization. Initial management. Pre-hospital recognition and triage of STEMI patients may reduce system related delays to myocardial reperfusion, with patients bypassing non PCI centres and going directly to the catheter laboratory. Fibrinolytic therapy may be given en route to hospital if PPCI is not available. Ambulance crews must be able to recognise and treat CA. 5 These pre-hospital interventions are associated with improved patient outcomes. Prompt relief of pain and anxiety is important to reduce sympathetic tone and myocardial oxygen demands (Figure 2). 5/10

6 Figure 2. Treatment diagram of Acute Coronary Syndromes. (From: Arntz HR, Bossaert LL, Danchin N, Nikolaou NI. European Resuscitation Council Guidelines for Resuscitation Section 5. Initial management of acute coronary syndromes. Resuscitation. 2010; 81: With permission: European Resuscitation Council /043) Legend: ASA: aspirin; UFH: unfractionated heparin. Primary high risk criteria: relevant rise or fall in troponin, dynamic ST- or T- wave changes; secondary high risk criteria: diabetes mellitus, renal insufficiency, LVEF < 40%, early post infarction angina, recent PCI, prior CABG, intermediate to high GRACE risk score. Despite the absence of supporting evidence, morphine is the most frequently used analgesic in patients with nitrate refractory pain, and may also be useful in pulmonary congestion. Oxygen administration should be targeted towards a haemoglobin saturation of 94-98%, or lower, 88-92%, if the patient is at risk from hypercarbia. Nitrates are effective treatment for sustained anginal pain in patients that are stable haemodynamically. They can also be useful in the treatment of acute pulmonary congestion. Nitrates should not be used in patients with systolic blood pressure 90 mmhg, and in patients with suspected right ventricular impairment. Aspirin should be given as soon as possible to all patients with suspected ACS, provided there is no history of true allergy. Aspirin may be given by the first healthcare provider, bystander or with the advice of a dispatcher assistant according to local guidelines. The initial dose of chewable aspirin is mg. Soluble or intravenous aspirin may be equally effective. With STEMI, when not contraindicated, oral beta-blockers should be started only after hospital admission and continued lifelong. Oral beta-blocker treatment is also indicated in both STEMI and 6/10

7 NSTEMI patients with moderate heart failure or LV dysfunction. Intravenous beta-blockers should be reserved only for stable patients with ACS who exhibit tachycardia or hypertension. Angiotensin converting enzyme inhibitors (ACEI) should be considered during the first 24 hours of ACS in patients with heart failure or LV dysfunction. They should be given also to patients with anterior STEMI or diabetes but also in all STEMI patients without contraindications. Angiotensin receptor blockers (ARB) are alternatives to ACE inhibitors for patients with LV dysfunction or heart failure with intolerance to ACEIs. Aldosterone antagonists are indicated in patients with an ejection fraction 40%, heart failure and diabetes, in the absence of renal failure or hyperkalaemia. Cardiac arrest Most deaths occur in the first hours of an ACS, before the patient reaches the hospital, and are caused by ventricular fibrillation. To prevent these preventable deaths, healthcare providers caring for patients with suspected ACS must be trained adequately and equipped properly to treat cardiac arrest. The heart rhythm of these patients should be monitored electrographically, and a defibrillator should be available at the point of first medical contact (FMC). Hospital management Prompt restoration of coronary flow is the single most important therapeutic target in patients with STEMI. This can be achieved using either thrombolytic therapy or primary PCI. STEMI Reperfusion therapy should be initiated as soon as possible for patients with STEMI who present within 12 hours of the onset of symptoms. Reperfusion therapy, preferably PPCI, is also indicated in patients with STEMI and continuing ischaemia who present more than 12 hours from the onset of symptoms. PPCI can also be considered for stable patients hours from symptom onset. Primary PCI (PPCI) with stenting of the coronary artery responsible for the infarct is the preferred method for reperfusion, provided an experienced operator can perform it within 2 hours of first medical contact. However, the best time to PPCI depends also on the amount of myocardium at risk, the time from onset of symptoms onset and the capabilities of the receiving centre. In patients with a large amount of myocardium at risk presenting less than 2 hours after onset of symptoms, first medical contact to PPCI time should be less than 1 hour. PPCI, if performed without delay, is the treatment of choice for STEMI patients with severe acute heart failure or cardiogenic shock, and also after cardiac arrest and ROSC. Fibrinolytic therapy is recommended in patients presenting within 12 hours of onset of symptoms, if PPCI cannot be performed within 2 hours of first medical contact. If the amount of myocardium at risk is large and the risk of bleeding low, fibrinolysis should even be considered if PPCI cannot be performed within 90 minutes. It should be started as soon as possible, ideally within 30 minutes after first medical contact before admission to hospital. Fibrin specific agents such as tenecteplase, alteplace, and 7/10

8 reteplace are preferred to non-fibrin specific agents. The advantage in mortality of PPCI over fibrinolysis declines the longer it takes to obtain PPCI. The difference in mortality is most marked in patients aged less than 65 years, patients presenting with an anterior MI, and those who present early within 2 hours of onset of symptoms. 17 Pre-hospital administration of fibrinolytic therapy has a better outcome than later administration in hospital in patients with STEMI patients presenting within 2 hours of the onset of symptoms. Successful CPR is not a contra-indication for fibrinolytic therapy. Adjunctive anticoagulant and antiplatelet therapy. Aspirin in combination with an ADP receptor inhibitor is recommended as complementary therapy to PPCI. In the recent ESC guidelines for STEMI, prasugrel, ticagrelor, and clopidogrel were considered effective. GP IIb/IIIa inhibitors should be reserved as for rescue therapy if thrombotic complications appear during PPCI. Concomitant anticoagulation is essential for patients undergoing PPCI. Unfractionated heparin (UFH), enoxaparin and bivalirudin are suitable. Aspirin and clopidogrel should be used in combination with fibrinolytic therapy. Anticoagulation should be prescribed to patients treated with fibrinolytics until revascularization or hospital discharge. Enoxaparin intravenously then subcutaneously, and UFH with intravenous dose and infusion adjusted according to weight are the agents of choice for these patients. NSTEMI acute coronary syndrome Urgent coronary angiography is reserved for patients with NSTEMI in refractory ischaemia, hemodynamic instability, severe heart failure, and life threatening arrhythmias. For other patients, an invasive strategy is indicated in the presence of high-risk criteria or recurrent symptoms, within 72 hours of presentation. Other therapeutic measures include anti-ischemic medication, antiplatelet and anticoagulant drugs. Combinations of aspirin with ticagrelor, prasugrel, or clopidogrel if first two drugs are contraindicated, should be continued for 12 months. Fondaparinux has a favourable efficacy-safety profile, but enoxaparin and UFH are alternatives. Anticoagulation should be continued up to an invasive procedure or hospital discharge. The use of GP IIb/IIIa inhibitors should be used only in selected highrisk patients undergoing PCI. PCI after return of spontaneous circulation The majority of adults with out-of-hospital CA have coronary artery disease. Many of them are patients with evolving MI that have sustained a lethal arrhythmia before getting to the hospital. Patients with ST segment elevation on 12-lead ECG after return of spontaneous circulation should undergo early angiography and PCI. Because acute coronary lesions may exist in the absence of ST elevation, PCI should also be considered in all patients suspected of an ACS regardless of findings on surface ECG. 18 Therapeutic hypothermia is indicated for comatose survivors of CA and should be implemented to limit neurological damage in survivors. Evidence suggests the number needed to treat to see a benefit is 6. It can be initiated safely in patients undergoing PPCI. 19 The increased risk of bleeding observed in these patients does not worsen outcome. Adherence to guidelines Adherence to guidelines is associated with better short and long-term outcomes, but their uptake varies between European countries. 20 Despite an increase in the use of evidence-based therapies, these innovations are still underused. Even today, a third of STEMI patients in Europe do not receive reperfusion therapy, range 7-63%. Moreover, there is a trend to underusing invasive treatments in high- 8/10

9 risk subgroups of STEMI patients and overuse in low risk patients. High-risk indicators such as older age, diabetes, renal disease and female gender are reliable predictors that patients will not undergo PCI. This may explain why favourable results in clinical trials cannot be reproduced in routine practice. Therapies for secondary prevention are also underused in ACS patients. Elderly patients take fewer guideline related medications compared to younger patients. Data from prospective trials indicate that education programs to improve the quality of care of ACS patients can improve outcome. Key learning points The concept of chain of survival is valid for ACS. Early recognition, early diagnosis, early reperfusion, and early final treatment improve survival. Interdisciplinary collaboration between pre-hospital, emergency department, and in-hospital providers, and integrated clinical pathways using evidence-based guidelines improve survival. All patients with STEMI should be considered for reperfusion therapy. Primary PCI is the recommended treatment for STEMI when performed promptly and in an experienced centre. PCI improves survival also after cardiac arrest with return of spontaneous circulation. If PPCI cannot be performed within the accepted time limits, fibrinolytic therapy should be given. Pre-hospital initiation of fibrinolysis has greater success than in-hospital treatment. CPR is not a contra-indication for fibrinolysis. 9/10

10 References 1. Cummins R, Ornato J, Thies W, et al. Improving Survival From Sudden Cardiac Arrest: The "Chain of Survival" Concept. Circulation 1991; 83: Ornato J, The ST-Segment Elevation Myocardial Infarction Chain of Survival. Circulation 2007; 116: Bossaert L. The chain of survival of ST elevation myocardial infarction: From evidence to practice. Resuscitation 2009; 80: Arntz HR, Bossaert L, Carli P, Chamberlain D, et al. The pre-hospital management of acute heart attacks. Recommendations of a task force of the European Society for Cardiology and the European Resuscitation Council. European Heart Journal 1998; 19: and Resuscitation 1998; 38: Nolan J, Hazinski M, Billi J, et al International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Part 9: Bossaert L, O'Connor RE, Arntz HR, et al. Acute coronary syndromes. Circulation 2010; 122: and Resuscitation 2010; 81(Suppl 1): Nolan JP, Soar J, Zideman DA, et al. European Resuscitation Council Guidelines for Resuscitation Section 5: Arntz HR, Bossaert L, Nikolaou N. Initial management of acute coronary syndromes. Resuscitation 2010; 81: Guyatt G, Oxman A, Akl E, et al. GRADE guidelines: 1. Introduction. GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011; 64: Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. European Heart Journal 2012; 33: Nichols M, Townsend N, Scarborough P, Luengo-Fernandez R, Leal J, Gray A, Rayner M European Cardiovascular Disease Statistics European Heart Network, Brussels, European Society of Cardiology, Sophia Antipolis. ISBN Widimsky P, Wijns W, Fajadet J, et al. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. European Heart Journal 2010; 31: Müller-Nordhorn J, Binting S, Roll S, Willich SN. An update on regional variation in cardiovascular mortality within Europe. European Heart Journal 2008; 29: Terkelsen CJ, Lassen JF, Norgaard BL, et al. Mortality rates in patients with ST-elevation vs. non-st-elevation acute myocardial infarction: observations from an unselected cohort. European Heart Journal 2005; 26: Dudas K, Lappas G, Stewart S, Rosengren A. Trends in out-of-hospital deaths due to coronary heart disease in Sweden (1991 to 2006). Circulation 2011; 123: Müller D, Agrawal R, Arntz HR. How Sudden Is Sudden Cardiac Death? Circulation 2006; 114: Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with STsegment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. European Heart Journal 2012; 33: Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal 2011; 32: Pinto D, MD; Kirtane A, MD, SM; Nallamothu B, et al. Hospital Delays in Reperfusion for ST-Elevation Myocardial Infarction: Implications When Selecting a Reperfusion Strategy. Circulation 2006; 114: Koster RW, Baubin MA, Bossaert LL, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 2. Adult basic life support and use of automated external defibrillators. Resuscitation 2010; 81: Gräsner JT, Meybohm P, Caliebe A, et al. Postresuscitation care with mild therapeutic hypothermia and coronary intervention after out-of-hospital cardiopulmonary resuscitation: a prospective registry analysis. Critical Care 2011; 15:R Van de Werf F, Ardissino D, Bueno H, et al. Acute coronary syndromes: considerations for improved acceptance and implementation of management guidelines. Expert Reviews in Cardiovascular Therapy 2012; 10: /10