2019 Volume 83 Issue 5 Pages 1085-1196
Acute coronary syndromes (ACS) are a comprehensive disease concept characterized by acute myocardial ischemia caused by disruption of coronary artery plaque and consequent thrombosis-induced severe coronary artery stenosis or occlusion, leading to unstable angina (UA), acute myocardial infarction (AMI) or sudden cardiac death. However, these diagnoses cannot be established without evaluation of the time course of myocardial markers and were thus unsuitable for rapid diagnosis and establishment of the treatment policy in the emergency room. In addition, the prognosis of ACS with coronary artery thrombosis is considerably different from that of stable coronary artery disease (CAD) with organic stenosis of the coronary arteries. In 1992, Fuster et al. proposed that unstable angina pectoris and AMI caused by coronary artery thrombosis are the same disease states and should therefore be included in the category of ACS. The initial diagnosis and decision of management in the clinical setting thus changed considerably after introduction of the concept of ACS based on the underlying mechanism. In recent years, the introduction of cardiac troponin, which can detect even minor myocardial damage unable to be detected by creatine kinase (CK) or CK-MB, has also contributed substantially to the clinical diagnosis and risk stratification of ACS. Five years have passed, since the guidelines for the management of patients with ST-elevation acute myocardial infarction (Chairperson: Kazuo Kimura) was issued by the Japanese Circulation Society (JCS). However, revision of this guideline independently of the guidelines for management of acute coronary syndrome without persistent ST segment elevation (Chairperson: Takeshi Kimura) may not match the present conditions. Although the short-term outcomes of patients with ACS have improved, the long-term outcomes, which can be negatively affected by heart failure, must be further improved. Guidelines for secondary prevention of myocardial infarction (Chairperson: Hisao Ogawa) were issued 7 years ago, and remarkable progress has been made in this field. We therefore comprehensively integrated the 3 guidelines consisting of the guidelines for the management of patients with ST-elevation acute myocardial infarction, the guidelines for management of acute coronary syndrome without persistent ST segment elevation, and the guidelines for secondary prevention of myocardial infarction into “JCS 2018 guideline on diagnosis and treatment of acute coronary syndrome.” At present, ACS guideline including ST-segment elevation acute myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is not available as American College of Cardiology (ACC) /American Heart Association (AHA) guidelines or European Society of Cardiology (ESC) guidelines. We therefore attempted to avoid shortcomings and duplication of the contents from the stage of chapter preparation. However, similar descriptions were found in parts of the manuscript. In the present guidelines, recommendation levels and evidence levels were stated similarly to the conventional Japanese Circulation Society guidelines, ACC/AHA guidelines, and ESC guidelines. In addition, class III recommendations were classified as “no benefit” and “harm” in accordance with the ACC/AHA guidelines. The present guidelines were designed to be used as a reference in Asian countries, not only in Japan, and new efforts were incorporated during the preparation. Guidelines for diagnosis and treatment should be reviewed by all members of group meetings to avoid biased opinions and ways of thinking. However, owing to the extensive contents and many committee members involved in consolidation of the 3 guidelines, it is difficult to hold the meetings of the committee members many times over a long period. Working groups consisting of members who wanted to participate were therefore established to discuss manuscript revisions in a training camp format and hold multiple mail discussions. In particular, we extensively discussed classifications and evidence levels for which opinions were divided, spending as much time on discussion as possible. Guidelines are prepared on the basis of a critical appraisal of evidence obtained from large clinical trials and observation studies of patients with the diseases covered by the guidelines and are designed to standardize and improve the quality of medical treatment. Guideline recommendations are designed for average patients with disease. Guidelines should not be followed uniformly in a medical care setting. Patients for whom the guidelines are indicated as well as differences among individual patients should be considered, and it is important to indicate treatment best suited to the individual patient. The results of diagnosis and treatment performed according to the guidelines as well as problems should be clarified, and improved guidelines should be prepared after several years to contribute to enhancing the levels of diagnosis and treatment provided to patients.
Unapproved techniques, treatments, and drugs not yet approved in Japan or for which adequate evidence supporting effectiveness and usefulness is available from foreign countries or for which expert opinion is largely consistent are appropriately listed in the present guidelines (Tables 1,2). In addition, indications, uses and dosage not approved by health insurance in Japan were also stated if necessary. The health insurance indications are as of December 2018.
The abbreviations used in the guidelines are listed on Pages 1086–1087.
ACS is the clinical spectrum of unstable ischemic heart disease, in which myocardial ischemia/necrosis is caused by rapid narrowing/obstruction of coronary artery as a consequence of atheromatous plaque disruption and thrombogenesis.1,2 In early stage atherosclerosis, intima thickening occurs, due to infiltration and accumulation of macrophages and lipids.3 During atherosclerotic plaque formation, the vessel wall may expand and preserve the vessel lumen (positive remodeling). As the plaque progresses, the lumen becomes narrowed and effort angina may develop. Inflammation plays an important role in the development and progression of atherosclerosis. In some lesions, accumulated lipid components may develop a necrotic core that is rich in inflammatory cells and cholesterol crystal. Fibroatheroma has necrotic core and, if its fibrous cap becomes thin, is prone to rupture (vulnerable plaque). It is generally believed that rupture of vulnerable plaque followed by thrombogenesis is the leading cause of ACS.4 On the other hand, pathological studies have revealed that some patients have intracoronary thrombus without plaque rupture. It is recognized that erosion is one of the mechanisms that leads to thrombus without rupture, and, although not so frequent, calcified nodules are another. ACS may develop from less severe stenotic lesions that don’t cause effort angina.5 It should be emphasized that UA, AMI and sudden cardiac death caused by myocardial ischemia are cardiac events caused by thrombogenesis that are distinct from plaque progression in effort angina, and are addressed together as ACS.
AMI is subdivided into STEMI and non-ST-segment elevation myocardial infarction (NSTEMI), because of the difference in initial stratification of diagnosis and treatment (Figure 1). UA and AMI are clinically differentiated by elevation of cardiac biomarkers. However, it is often difficult to distinguish between UA and NSTEMI at presentation. During initial evaluation, they are managed together as NSTE-ACS.
Diagnostic flow of ACS. ECG, electrocardiogram; NSTE-ACS, non-ST-segment elevation acute coronary syndrome; NSTEMI, non-ST-segemnt elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction.
STEMI is ACS with persistent ST-segment elevation or new left bundle-branch block.
Electrocardiographic ST-segment elevation on electrocardiogram (ECG) generally reflects transmural ischemia caused by acute thrombotic occlusion of a coronary artery. Necrosis occurs first in the subendocardial myocardium and then, with longer durations of coronary occlusion, involves progressively more of the transmural ischemic zone myocardium.6 Reperfusion therapy salvages ischemic myocardium by restoring coronary blood flow. After pioneering studies by Fletcher et al. and Chazov et al.,7,8 Rentrop et al. reported 5 cases of STEMI who underwent reperfusion therapy with intracoronary nitroglycerin and streptokinase infusion in 1979.9 Since then, several studies have demonstrated significant reduction in mortality with intravenous streptokinase in the late 1980 s.10,11 In recent years, percutaneous coronary intervention (PCI) with coronary stent implantation has become widely applied and the prognosis of STEMI has dramatically improved. Because prompt restoration of coronary blood flow is essential to maximize benefits of reperfusion therapy, a strategy to minimize time from onset to reperfusion is of primary importance for patients with STEMI.
Patients with NSTE-ACS have persistent or transient ST-segment depression, T-wave abnormalities or no electrocardiographic changes at presentation. Because patients with NSTE-ACS generally have residual blood flow through a non-obstructive coronary lesion or sufficient collaterals, the management strategy for NSTE-ACS should be clearly distinguished from STEMI. The spectrum of NSTE-ACS is wide and variable, from patients without elevation of cardiac biomarkers to those with hemodynamic collapse due to left main trunk disease. During initial evaluation, prompt diagnosis and risk stratification should be appropriately provided to select the treatment strategy. Because it is often difficult to distinguish between UA and NSTEMI at presentation, they are managed together as NSTE-ACS. By the time of hospital discharge, the final diagnosis is given according to elevation of cardiac biomarkers.12
In the past, elevation of CK/CK-MB was used for clinical diagnosis of MI. In 2000, the ESC and ACC proposed a new definition of MI, a universal definition, in which cardiac troponin was adopted as the preferred cardiac biomarker.13 Because cardiac troponin has higher sensitivity and specificity over CK/CK-MB, numerous patients who were formerly diagnosed as unstable angina by CK/CK-MB criteria are now diagnosed as NSTEMI. The Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) is a prospective registry that enrolled 3,283 Japanese patients with AMI diagnosed by universal definition (type 1 and type 2).14 Nearly half of the patients with NSTEMI did not have elevation of CK/CK-MB, and these NSTEMI patients without CK/CK-MB elevation had favorable short-term outcome as compared to those with CK/CK-MB elevation. Of note, however, long-term outcome after the recovery period for these NSTEMI patients without CK/CK-MB elevation was as poor as NSTEMI patients with CK/CK-MB elevation and worse than those with STEMI. These findings indicate the clinical rationale of a universal definition of myocardial infarction in Japanese patients, and this guideline recommends cardiac troponin as the preferred cardiac biomarker for diagnosis of AMI. Needless to say, symptoms, ECG and imaging findings of myocardial ischemia are also required. Because cardiac troponin may be elevated in some other conditions, including aging, renal dysfunction and congestive heart failure, cardiac troponin should be measured serially to detect its rise and/or fall. The term reinfarction is applied to AMI occurring within 28 days after the index episode of AMI. If the myocardial infarction occurs after 28 days following the index episode, it is referred to as recurrent myocardial infarction. Although the universal definition classified myocardial infarction into 5 types,15 this guideline mainly deals with spontaneous myocardial infarction (type 1) which is caused by thrombogenesis related to atherosclerotic plaque rupture, erosion and so on, and refers to myocardial infarction secondary to an ischemic imbalance (type 2) as in the section of VIII. Conditions Requiring Special Consideration.
ACS refers to a spectrum of clinical presentations, including AMI, UA, and sudden cardiac death, and is often associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery. This section mainly describes AMI, for which abundant epidemiologic evidence is available.
Many epidemiological studies including NIPPON DATA (National Integrated Project for Prospective Observation of Non-communicable Disease And Trends in the Aged) demonstrated that the risk factors for AMI in Japanese are hypertension, diabetes mellitus, smoking, family history, and hypercholesterolemia, similar to those of the Western population.16–18 In the 2000 s, the prevalence of hypertension was about 50% in Japanese AMI patients and was equivalent to that of the Western population, whereas the prevalence of diabetes and smoking was higher in Japanese patients.19,20 Recently, in the general Japanese population, blood pressure control among hypertensive individuals has improved significantly and the smoking rate has decreased, whereas the prevalence of impaired glucose tolerance, dyslipidemia, and metabolic disorder have increased steeply, as demonstrated by research in Hisayama.21 Careful observation of future changes in the prevalence of risk factors for AMI in Japanese and trends is important.
The data from the 30-year MIYAGI-AMI Registry Study, one of the regional epidemiological studies, demonstrated that the overall age-adjusted incidence of AMI (/100,000 persons/year) markedly increased by about 4-fold, from 7.4 in 1979 to 27.0 in 2008.22 However, the current incidence of AMI in Japan is still lower than that in North America and Europe; the incidence of AMI for males (/100,000 persons/year) is 824 in Finland, 823 in United Kingdom, 605 in Canada, 508 in the United States, 314 in France, and 270 in Italy.23 The incidence of AMI showed a male predominance, as demonstrated in the Takashima AMI registry (100.7 in males vs. 35.7 in females in 1999–2001)24 and the Niigata and Nagaoka study (41.9 in males vs. 5.3 in females in 1994–1996).25 Moreover, in the above-mentioned Miyagi AMI Registry, the 3-fold higher incidence of AMI in males remains largely unchanged throughout the last three decades.22 Furthermore, it was reported that the mean age of onset of AMI was older in female patients than in male patients, with an age difference of 10 years, which is similar to results of overseas studies such as the Framingham Heart Study.26 This may be due to the cardiovascular protective effects of female hormones, namely estrogen, which are evident before menopause but rapidly decrease thereafter.
In Western countries, it was previously reported that the age-adjusted incidence of AMI decreased from the late 1980 s to the 2000 s.26,27 This trend was especially evident in STEMI patients.27 The decline in the incidence of AMI may be attributed to the reduction in the prevalence of coronary risk factors and the increase in the prevalence of the pre-critical use of cardioprotective drugs, including angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), b-blockers, and statins.26,27 However, a recent report from the Miyagi AMI Registry Study demonstrated that, during the last 30 years in Japan, the age-adjusted incidence of AMI significantly increased in the first decade (1985–1994), but has remained unchanged in the last 2 decades (1995–2004 and 2005–2014).28 The same trend was noted for male patients, whereas age-adjusted AMI incidence significantly decreased in female patients in the last decade (2005–2014).28 Similarly, it has been recently reported that the incidence of AMI was steadily decreasing in the Kumamoto Prefecture in both sexes between 2004 and 2011.29 In contrast, while the frequency of AMI in the elderly aged 70 years and older has declined from 2005 to 2014 in the Miyagi AMI Registry Study, AMI incidence continues to increase in younger patients aged ≤59 years of both sexes in the past 3 decades.28 Indeed, it was previously reported that the increased prevalence of dyslipidemia in younger AMI patients related to dietary habits and westernized lifestyle was responsible, at least in part, for the increased incidence of AMI in this population.28 Additionally, smoking rates in young people are high, with a rate of ∼50% in males and 30% in females. These results suggest that more strict control of coronary risk factors is needed in young populations to reduce the future occurrence of AMI in Japan. In other Asian countries, Taiwan and Korea, increasing trends in the age-adjusted incidence of AMI have been reported together with westernization of diet and lifestyle and social aging.30,31 However, the latest study in Korea found that the age-adjusted incidence of AMI has declined since 2006, which could be due to, at least in part, the preventive care projects for chronic illnesses and cardio-cerebrovascular diseases since 2000 s in Korea.32 This Korean experience may provide useful information in promoting effective preventative measures in Japan.
The 30-day mortality from AMI in Japan was reported to be 7.1% in the OACIS Study33 and 9.4% in the HIJAMI Study.20 In the J-MINUET Study,34 which is a registry of Japanese patients hospitalized for AMI diagnosed by the new universal definition, there was no significant difference in hospital mortality between STEMI and NSTEMI with CK elevation (7.1% vs. 7.8%), whereas the mortality rate was significantly lower in NSTEMI without CK elevation (1.7%) than in STEMI or NSTEMI with CK elevation.34 Tokyo CCU Network reported that hospital mortality was significantly higher in STEMI patients than NSTEMI patients (7.7 vs. 5.1%) and treatment of dyslipidemia with statins was associated with lower risk in both STEMI and NSTEMI patients based on Killip classification.35
In Western countries, hospital mortality of AMI decreased between the 1980 s and late 2000 s, along with improvement in critical care for AMI (e.g., reperfusion therapy).36 The same trend in reduced hospital mortality of AMI was also noted in Asian countries, Taiwan and Korea, between the late 1990 s and early 2000 s.31 Meanwhile, during the last 30 years in Japan, although in-hospital cardiac mortality of AMI progressively decreased during the 1st and 2nd decades (1985–1994 and 1995–2004), no further improvement was noted in the last decade (2005–2014) irrespective of sex.28 It is important to note that hospital mortality of AMI continues to be higher in female patients than in male patients today.28 It is generally considered that the poorer outcome of female AMI patients could be caused by multiple factors, including higher age, longer time from onset to admission, poorer condition on admission such as coexisting heart failure, and lower rate of performing primary PCI.28,37
A number of western studies have shown that patients with NSTEMI have a worse long-term prognosis compared with those with STEMI. In the GRACE registry, the 6-month post-discharge mortality rate was 3.6% and 6.2% in patients with STEMI and those with NSTEMI, respectively.38 Similarly, the J-MINUET study recently reported that long-term outcome of NSTEMI patients was worse than STEMI patients, a consistent finding with Western countries.14 This could be explained by the fact that NSTEMI patients have more comorbid factors and more extensive CAD than STEMI patients.14 Furthermore, a recent report from the French National Registry survey demonstrated that chronic-phase mortality has consistently declined in STEMI patients between 1995 and 2015, whereas chronic-phase mortality reached a plateau in NSTEMI patients after 2010.39 From now, a national registry for ACS will be launched in Japan and is expected to produce evidence in the Japanese population.
Patients with possible ischemic symptoms need to call medical dispatch number 1-1-9 and be transported to hospital, rather than visiting the hospital themselves.40,41 ACS, especially STEMI, has the risk of sudden cardiac death, and it is important to promote the importance of calling emergency medical services (EMS) in the early phase after onset (regarding symptoms of ACS, please refer to chapter IV 1.2.1 Chest Pain). Patients prescribed with sublingual nitroglycerin tablets can take 1 tablet every 3 to 5 minutes for ongoing symptoms (total of 3 doses), only if they remain hemodynamically stable. However, if nitroglycerin does not relieve ischemic chest pain, patients should immediately call EMS.42
Physicians who first treat patients with suspected ACS on scene assess vital signs and perform a physical examination. They should record and interpret the 12-lead ECG, start initial management (please refer to chapter IV 2. Initial Therapy) and call EMS urgently. Interpretation of computer-assisted ECG in acute phase of STEMI does not always have high diagnostic performance, and should not be used alone to rule out STEMI.43 Patients with suspected STEMI should be transported to a primary PCI capable center,44–47 and in this situation, the physician should report the vital signs and ECG findings to the cardiologist at the primary PCI capable center. See “chapter V 2. Fibrinolysis ” regarding the indication for fibrinolysis for patients with STEMI who arrive at non-primary PCI capable center.
EMS personnel rapidly assess vital signs, monitor the ECG, and take precautions against cardiac arrest. Monitoring of pulse oximeter is also recommended. When patients prescribed with sublingual nitroglycerin tablets remain hemodynamically stable, EMS personnel permit administration of nitroglycerin if requested by patients. In the present state of affairs in Japan, only a physician can administrate nitroglycerin or aspirin if a doctor car or medical helicopter has been dispatched to the scene. Further investigation is needed to confirm the benefit of prehospital administration of nitroglycerin and aspirin by EMS personnel. If available, prehospital 12-lead ECG acquisition in patients with suspected STEMI and notifying the destination hospital are recommended.48 Some studies have shown the benefit of prehospital 12-lead ECG acquisition with destination hospital notification in reducing first-medical contact-to-reperfusion time, door-to-device time, and door-to-needle time compared with no ECG in patients with STEMI.49–57 It has also been reported that the benefit of prehospital 12-lead ECG acquisition with destination hospital notification is a 32% relative reduction in 30-day mortality compared with no ECG in patients with STEMI treated with primary PCI.48 Prehospital 12-lead ECG acquisition with destination hospital notification by EMS personnel can activate the cardiac catheterization laboratory earlier, call the catheterization team earlier, reduce the time from onset to reperfusion, and finally, is expected to improve prognosis in patients with STEMI. However, prehospital 12-lead ECG is not currently widely available in Japan. Thus, raising awareness through participation by cardiologists in regional medical control organizations, for example, is needed in order to promote utilization and familiarity.
In the management of ACS, early diagnosis and rapid treatment are important. The systematic approach for ACS includes primary prevention, recognition of patients, medical therapy, surgical treatment, and rehabilitation, as well as secondary prevention and cooperation with medical institutions. In the treatment strategy for STEMI, it is important to reduce time from onset to reperfusion. The goal of treatment in STEMI are to achieve reperfusion within 120 minutes from onset, which means initiating therapy within 30 minutes from first contact with medical personnel (including EMS personnel) for fibrinolysis, and catheter treatment within 90 minutes from first contact with medical personnel for PCI. Furthermore, when a STEMI patient attends a facility where reperfusion therapy cannot be administered, the goal has been set to keep door-in-door-out time to within 30 minutes.58 In order to achieve earlier reperfusion, it is important to establish an integrated medical system for the treatment of STEMI involving regional medical administration, medical control organizations, emergency medical transport, medical (doctor) associations and specialized health facilities. Regarding prehospital care in patients with ACS, please refer to the JRC (Japan Resuscitation Council) resuscitation guidelines 2015.59
Since it is well established that reperfusion therapy early after the onset of STEMI results in better prognosis, it is important to diagnose and treat STEMI as early as possible. The disease state should be assessed in accordance with the prespecified procedure and initial treatment should be started immediately. It is important to check vital signs, perform continuous ECG monitoring, collect a brief and accurate medical history, record 12-lead ECG, and perform laboratory tests within 10 minutes of hospital arrival.60,61 Regarding reperfusion therapy for STEMI, it is ideal to administer a fibrinolytic agent within 30 minutes of hospital arrival when fibrinolysis is selected, and to inflate the first balloon within 90 minutes of first medical contact (including contact with ambulance attendants) when PCI is selected.51,61,62 For NSTE-ACS, invasive strategy is recommended for moderate- to high-risk patients, but the appropriate timing remains unclear. Timely invasive strategy should be considered after assessing risk based on the thrombolysis in myocardial infarction (TIMI) risk score,63,64 and/or Global Registry of Acute Coronary Events (GRACE) score,65 etc (Figure 2). A meta-analysis of 8 clinical studies involving 5,324 patients showed that, compared with elective invasive strategy, early invasive strategy did not reduce the mortality rate or the incidence of non-fatal myocardial infarction, but may reduce the mortality rate in high-risk patients, including patients with positive cardiac enzymes, diabetes mellitus, a GRACE risk score of >140, and aged 75 years or older.66
Diagnostic flow chart for ACS. ACS, acute coronary syndrome; ECG, electrocardiogram; STEMI, ST-segment elevation myocardial infarction; NSTE-ACS, non-ST-segment elevation acute coronary syndrome.
Medical history is very important information in the diagnosis of ACS and should be collected thoroughly and quickly, since treatment protocol differs depending on diagnosis. Particular attention should be paid to chest pain in terms of site, description, trigger, duration, changes over time, and associated symptoms, etc. In parallel, information on past medical history, coronary risk factors, and family history should be collected to differentiate ACS from other diseases as quickly as possible.67
Chest pain associated with ACS is often described as precordial or retrosternal heaviness, pressure, tightness, choking sensation, or burning sensation, but the complaint is sometimes simply discomfort. It should be noted that chest pain may radiate to the jaw, neck, shoulder, epigastrium, back, and/or arm, and symptoms are sometimes localized in these regions without involving the chest. Stabbing pain, pricking pain, and pain on palpation are mostly non-anginal and unlikely to be affected by respiration, cough, or postural change. Meanwhile, since serious ACS occurs often with atypical or minimal symptoms, ACS cannot be excluded based only on symptoms. Atypical symptoms also often occur in elderly patients, diabetic patients, and women.68–70 In addition, the elderly may complain of shortness of breath as a symptom of myocardial ischemia71 and present only with general malaise, anorexia, syncope, or depressed level of consciousness.
Symptoms of myocardial infarction persist for at least 20 minutes, often for several hours. While approximately half of patients have intense pain requiring morphine hydrochloride, the intensity of symptoms is not always consistent with severity of ACS. Common associated symptoms are cold sweat in men and nausea, vomiting, and dyspnea in women.68,69 Radiation to the jaw, neck, shoulder, back, and arm is more frequently reported in women.68,69,72,73
① The duration of chest pain associated with angina or UA is mostly a few minutes, at most 15 to 20 minutes. Chest pain persisting for 20 seconds or less is unlikely to be anginal pain. Chest pain persisting for 20 minutes or more is likely to be associated with AMI when described as ACS.
② Chest pain occurs not only during physical activity, including walking hastily, walking upstairs, and lifting or carrying a heavy weight, but also at rest. Chest pain is also triggered by mental excitement or meals. Chest pain occurs more frequently in the early morning due to lower threshold. Angina at rest often occurs during nocturnal sleep or in the early morning.
③ Angina at rest, new-onset angina, and angina with changing pattern should be distinguished from one another based on the mode of onset of chest pain and its change over time. While a new single episode of chest pain indicates new-onset angina, frequent recurrence of chest pain indicates angina with changing pattern, and both should be treated aggressively.
④ Chest pain that resolves within 1 to 5 minutes after rest or use of nitroglycerin is often angina.
⑤ When chest pain is accompanied by dyspnea or loss of consciousness, this indicates higher severity, and myocardial infarction should be considered. When chest pain is accompanied by pyrexia, infection, including pneumonia, pleurisy, and pericarditis, should be considered.
⑥ When a patient with a history of ischemic heart disease presents with symptoms that are similar to or more intense than those of ischemic heart disease, ACS is most likely.
The HEART score has been proposed as a score to specify the acute phase risk (all-cause mortality within 6 weeks, myocardial infarction, coronary revascularization) in patients with low-risk chest pain who do not fulfil the criteria for ACS74 (https://www.mdcalc.com/heart-score-major-cardiac-events). The score is an acronym for History, ECG, Age, Risk factors, and initial Troponin, and the score is calculated from these components. The safety of early hospital discharge based on the HEART score has been demonstrated, and the utility of the HEART score in cost reduction including frequency of examinations as well as the superiority of the HEART score for identification of low-risk patients compared to the TIMI and GRACE risk scores have been reported.75–77
It is important to collect past medical history. Questions should be asked as to whether the patient has experienced similar symptoms, has a history of myocardial infarction, has undergone coronary angiography (CAG), coronary angioplasty, or coronary artery bypass, has cerebrovascular or peripheral vascular disease, and has been diagnosed or treated by another physician. For patients with any previous disease, a more appropriate treatment can be selected by considering detailed information on previous diagnosis and treatments given.
A family history of CAD (especially early onset at less than 55 years of age for men and at less than 65 years of age for women) is important.
Every effort should be made to collect information on coronary risk factors. ACS is more probable when at least 3 risk factors (age, smoking, dyslipidemia, diabetes mellitus, hypertension, family history, and renal impairment) are present, in addition to symptoms suggestive of ACS.
Careful examination of physical findings is important not only to diagnose ACS, but also to determine the presence or absence of complications, differentiate ACS from other diseases with chest pain, select treatment, and determine the arterial access site. In particular, the intensity of symptoms of AMI varies individually, and patients with intense symptoms appear anguished and often cannot move because of the pain. In addition, patients should be assessed for previous stroke and dementia based on brief examination of neurological findings. If there is pulmonary edema as a complication, dyspnea, orthopnea, cough, and/or foamy bloody sputum are observed. Patients with shock have a pale face, cold wet skin, blue patchy spots, and cyanosis of the lips and nail bed. Cerebral circulatory disorder due to reduced cardiac output may result in depressed level of consciousness, including confusional state. Inferior AMI with right ventricular (RV) infarction may be accompanied by signs of right heart failure, including jugular venous distention, hepatomegaly, and lower leg edema. Finally, it should be determined whether any finding such as vascular bruit in the carotid artery, abdominal aorta, or femoral artery, anemia, or abdominal aneurysm precludes reperfusion therapy, including urgent cardiac catheterization.
Blood pressure is usually normal in the absence of complications, but intense anxiety or excitement may result in sympathetic activation and a consequent transient increase in blood pressure. In general, inferior AMI is characterized by findings suggestive of parasympathicotonia such as bradycardia due to Bezold-Jarisch reflex, whereas anterior infarction is characterized by findings reflecting sympathicotonia such as tachycardia. Hypotension of ≤90 mmHg for more than 30 minutes or ≥30 mmHg decrease in systolic blood pressure from baseline level is diagnosed as shock. According to a scientific statement from the AHA on the management of cardiogenic shock,78 cardiogenic shock is classified into 4 groups based on intravascular volume (wet or dry) and peripheral circulation (cold or warm). While two thirds of cardiogenic shock related to AMI is the classic “cold and wet” type, the SHOCK trial reported that 28% of patients had “cold and dry” cardiogenic shock.79,80 Palpable pulses in extremities are also important to ensure arterial access for urgent cardiac catheterization.
Third heart sound detected by auscultation, which reflects severe left ventricular (LV) dysfunction with increased LV filling pressure, is used to determine the Killip class (Table 3).81 Systolic murmur in the course of severe ACS indicates LV enlargement, papillary muscle dysfunction, mitral regurgitation due to ruptured chordae tendineae or papillary muscle, or ventricular septal perforation. Mitral regurgitation due to ruptured chordae tendineae or papillary muscle is most pronounced in the cardiac apex, heard as notable holosystolic murmur sometimes with thrill, and accompanied by deteriorating hemodynamics. Systolic murmur due to ventricular septal perforation is similarly described, but is often most pronounced in the fourth intercostal left sternal border. Pericardial rub is rare immediately after onset; instead, it is heard during inspiration 2 to 3 days after the onset of extensive transmural myocardial infarction. Since aortic stenosis may have symptoms in common with angina, patients should be checked for ejection systolic murmur.
(Source: Prepared based on Killip T. 196781)
Moist rales result from leakage of body fluid into the alveoli and/or airways under reduced LV compliance. In auscultation of the lung fields, the presence or absence and extent of moist rales are important and should be assessed together with the aforementioned third heart sound to determine the severity of heart failure based on Killip class (Table 3).81 Attention should be paid to respiratory rate, depth and speed of respiration, comfortable breathing position, and moist rales, especially dorsal moist rales.
Since it has been reported that, of all patients transported to an emergency department due to acute chest pain, STEMI accounts for 5% to 10%, NSTEMI for 15% to 20%, UA for 10%, other cardiac diseases for 15%,82 and non-cardiac diseases for 50%,82–87 ACS should be differentiated from the other diseases based on medical history and physical findings (Table 4). It is important to understand the trigger and the extent of the chest pain, as well as to area(s) to which the chest pain radiates, through a medical interview. The presence of other clinical symptoms such as cold-like symptoms and pyrexia may facilitate differential diagnosis of ACS. ECG, chest x-ray, biochemistry, and echocardiography are useful and essential for differential diagnosis.
(Source: Prepared base on Ibanez B, et al. 2018166)
The most common non-cardiac diseases associated with chest pain are digestive diseases. Reflux esophagitis, which is characterized by heartburn-like burning sensation, is aggravated in the supine position after meals and alleviated by antacids. Esophageal spasm involves pain that arises in the posterior surface of sternum and radiates to the neck and back. Esophageal spasm is neither exertional nor of a certain duration, and is triggered by eating or drinking and often resolves after drinking water. While nitrates and Calcium antagonists may be effective, few specific examinations are available to support a diagnosis. When prandial upper abdominal pain is accompanied by tenderness, peptic ulcer, gallstone, and cholecystitis should be considered.
Chest pain is also attributable to respiratory (pulmonary) diseases, including pulmonary thromboembolism, pleurisy, pneumothorax, and pneumonia, and other common diseases to consider are skin and skeletal diseases, including herpes zoster, intercostal neuralgia, and rib fracture, as well as psychogenic cardiac neurosis.
Prompt differentiation is important for acute pulmonary thromboembolism and acute aortic dissection (AAD). Acute pulmonary thromboembolism often involves precordial and back symptoms as seen in AMI, but is accompanied by dyspnea and tachypnea, and sometimes by shock and loss of consciousness in severe cases. Patients when walking for the first time after postoperative rest in bed or who have an underlying disease such as deep vein thrombosis, abnormal coagulation, or malignant tumor are more vulnerable. AAD often involves more intense and severe pain than myocardial infarction. Tearing sharp pain that suddenly radiates to the back, sometimes accompanied by dyspnea and loss of consciousness, and spreads to the lumbar region and rarely to the lower extremities occurs with progression of dissection. Patients should be carefully checked for any difference (>15 mmHg) in blood pressure between different extremities and for aortic regurgitation murmur. Stanford-A AAD affects the coronary ostium and may be complicated by STEMI (approximately 5% of Stanford-A cases, especially involving the right coronary artery (RCA) ostium). While it is important to judge a disease based on characteristic physical findings, it should be noted that these findings cannot always be used to establish a diagnosis. Definitive diagnosis often requires computed tomography (CT), pulmonary perfusion scintigraphy, and CAG.
Other pathological conditions that induce myocardial ischemia include (1) diseases associated with increased oxygen demand and (2) those associated with decreased oxygen supply. It should be noted that symptoms similar to those of angina occur in these pathological conditions without CAD. In addition, stable angina may be destabilized when complicated by these pathologies.
(1) Diseases associated with increased oxygen demand: high temperature, hyperthyroidism, poorly controlled hypertension, and persistent tachyarrhythmia
(2) Diseases associated with decreased oxygen supply: anemia, pulmonary disease, and increased blood viscosity
Abbreviations: ACS, acute coronary syndrome; ECG, electrocardiogram; STEMI, ST-segment elevation myocardial infarction; AMI, acute myocardial infarction.
ACS is an emergency cardiovascular disease with a risk of cardiac events soon after its onset; therefore, prompt and precise diagnosis and treatment are essential. Although various diagnostic techniques have been developed, the 12-lead ECG is simple, readily available, non-invasive, and inexpensive, making it the most important initial examination for the diagnosis of ACS. The 12-lead ECG plays a central role in diagnostic and triage pathways for ACS and provides important prognostic information.
It is recommended to record a 12-lead ECG within 10 minutes of the patient’s arrival.88,89 ACS is classified according to the presence or absence of ST-segment elevation (STEMI or NSTE-ACS). Reperfusion therapy must be initiated as soon as possible in patients with STEMI, and an optimal treatment strategy based on early risk stratification is needed in those with NSTE-ACS.
It should be appreciated that a normal ECG does not exclude the possibility of ACS.90 ECG must be interpreted considering the presence or absence of symptoms at the time of presentation and time elapsed before recording ECG from symptom onset. Some patients with ACS may have an initially normal ECG because they have no anginal attack at presentation or because the ECG is performed very early after symptom onset. In patients where there is clinical suspicion of ACS in whom initial ECG shows no diagnostic ST-T changes, it is important to repeat the ECG or compare with a previous ECG, which can enhance the accuracy of the diagnosis of ACS.91,92
ST-segment elevation on ECG can represent transmural myocardial ischemia,15 and identify patients who will benefit from reperfusion therapy. In patients with transmural ischemia, ST-segment elevation is present in leads facing the site of ischemia. However, ST-segment elevation can be also observed as a normal finding. In healthy individuals, the magnitude of ST-segment elevation differs according to age, sex, and lead, and ST levels are generally highest in leads V2–3 and higher in males than in females.93 According to the universal definition of myocardial infarction,15 ECG findings suggestive of acute myocardial ischemia are defined as new ST-segment elevation in at least two contiguous leads; ST-segment elevation in leads V2-3 of at least 2.0 mm (0.2 mV) in men aged 40 years and above, at least 2.5 mm (0.25 mV) in men under 40 years of age, or at least 1.5 mm (0.15 mV) in women of any age, and ST-segment elevation in leads other than V2–3 of at least 1.0 mm (0.1 mV). These criteria are applied in the absence of LV hypertrophy or left bundle branch block. The J point is used to determine ST level. ST-segment elevation is also seen in diseases or conditions other than STEMI. It is important to comprehensively make the diagnosis of STEMI considering the medical history, clinical features, and other diagnostic test results.94–96
*In standard 12-lead ECG display, the precordial leads are displayed in their anatomically contiguous order, which makes it easy to understand the positional relationships between the precordial leads and the heart. However, the limb leads are not displayed in their anatomically contiguous order. For the limb leads to be displayed in an anatomically contiguous manner from the left superior-based to right inferior, the display should be aVL, I, −aVR (i.e., the inverse lead of aVR), II, aVF, and III. In this configuration, lead −aVR (+30°) bridges the gap between lead I (0°) and lead II (+60°) and faces the apical and inferolateral regions. This display is known as the ‘Cabrera sequence’. The Cabrera sequence makes it easy to understand the positional relationships between the limb leads and the heart,15,97 and lead grouping such as inferior leads (II, III, and aVF) or lateral leads (I, aVL).
This guideline is applied to patients with new onset left bundle branch brock who have chest pain or those with true posterior AMI who have no significant ST-segment elevation as well as those with ST-segment elevation as mentioned above.
ECG monitoring should be performed as soon as possible in patients with STEMI to detect life-threatening arrhythmias, which often occur in the acute phase of STEMI.98,99 Early reperfusion therapy helps to achieve more myocardial salvage. However, in the very acute phase of STEMI, ECG diagnosis is difficult because the ECG does not yet show ST-segment elevation. In this phase, one should confirm whether hyperacute T waves, which may be seen before ST-segment elevation development, are present or not.15
In patients with anterior STEMI, the more proximal the occlusion, the more extensive is the area at risk. ST-segment depression in inferior leads, ST-segment elevation in lead aVR, and complete right bundle branch block have been shown to be suggestive of the left anterior descending coronary artery (LAD) occlusion proximal to the first septal branch. Especially ST-segment depression in inferior leads is very useful; whereas ST-segment elevation in lead aVR and complete right bundle branch block are shown to have high specificities, but low sensitivities.100,101
In patients with inferior STEMI, those with right ventricular (RV) infarction have a poor prognosis. In addition, administration of nitrates must be avoided in those with RV infarction. RV infarction during inferior STEMI can be accurately diagnosed by ST-segment elevation ≥1.0 mm (0.1 mV) in right precordial lead, especially lead V4R.102–104 In patients with inferior STEMI, ECG should be recorded with an additional right precordial lead (lead V4R) to identify concomitant RV infarction. However, ST-segment elevation in right precordial leads has been reported to be short lived, disappearing within 10 hours after the onset of symptoms in half of patients with inferior AMI and RV infarction.104
ECG diagnosis is often difficult in patients with true posterior AMI caused by occlusion of the left circumflex coronary artery (LCX) because there are no leads facing the LV posterior wall in the standard 12-lead ECG. ST-segment elevation ≥0.5 mm (0.05 mV) in ≥2 contiguous posterior chest leads (lead V7–9) is considered to be diagnostic of posterior AMI.105,106 Even in cases without ST-segment elevation on standard 12-lead ECG, the presence of ST-segment elevation in posterior chest leads is an indication for emergent coronary angiography (CAG) to perform timely reperfusion therapy. It has been reported that ST-segment elevation is present solely in posterior chest leads in about 4% of all patients with AMI.105 If the initial ECG is not diagnostic of STEMI but there is a high clinical suspicion for STEMI, ECG recording with additional posterior leads (leads V7–9) is indicated to exclude true posterior AMI.
ECG can provide useful information about not only the diagnosis of STEMI, but also the culprit artery, the extent of area at risk, and the degree of myocardial damage and prognosis.100,107,108 ECG diagnosis is more difficult in patients with secondary ST-T changes such as ventricular pacing, Wolff-Parkinson-White syndrome, or bundle branch block. In these patients, it is important to comprehensively make the diagnosis of STEMI considering the medical history, clinical features, and other diagnostic test results. In addition, comparison with a previous ECG may be helpful to make the diagnosis of STEMI in this setting. Sgarbossa et al.109 reported the ECG criteria, based on simple ST-T change, for the diagnosis of AMI in patients with left bundle branch block, which are concordant ST-segment elevation ≥1.0 mm (0.1 mV) in leads with a positive QRS complex, concordant ST-segment depression ≥1.0 mm (0.1 mV) in leads V1–3, and discordant ST-segment elevation ≥5.0 mm (0.5 mV) in leads with a negative QRS complex. In particular, concordant ST-segment elevation ≥1.0 mm (0.1 mV) in leads with a positive QRS complex has been reported to be strongly suggestive of STEMI in left bundle branch block. However, these Sgarbossa criteria have been reported to have limited utility in clinical practice because of their low sensitivity.110,111 It is likely that, in patients with left bundle branch block, ECG diagnosis of AMI is possible in limited patients with profound ST-T change. Importantly, AMI patients with left bundle branch block have a worse clinical profile and poorer prognosis.112 Therefore, clinical suspicion of AMI in the presence of left bundle branch block is an indication for emergent CAG to perform timely reperfusion therapy.113
ST-segment changes are considered the most important electrocardiographic feature during acute myocardial ischemia. The changes of T waves, QRS complex, and U waves, and the occurrence of arrhythmias are also useful for the diagnosis of myocardial ischemia. Electrocardiographic findings of myocardial ischemia are described as follows (These findings can be also applied in STEMI).
The presence of acute ischemic changes on admission ECG has been associated with a higher risk of cardiac events; ST-segment depression is an especially strong predictor of poor outcomes in patients with NSTE-ACS.114,115 The presence of even minimal [0.5 mm (0.05 mV)] ST-segment depression has been shown to be independently associated with adverse outcomes.114,115 Furthermore, the degree, extent, and serial changes of ST-segment depression, not only its presence or absence, can facilitate early risk stratification in patients with NSTE-ACS.114 ST-segment elevation is present in leads facing the site of ischemia. Therefore, the culprit artery can be predicted on the basis of the leads showing ST-segment elevation during ischemic attacks. However, in many patients with non-transmural (subendocardial) ischemia, ST-segment depression occurs in leads V4–6 (mainly in lead V5) independently of the culprit artery, for which the underlying mechanism remains unclear. It is thus difficult to predict the culprit artery on the basis of leads with ST-segment depression, but increased cumulative ST-segment depression, an increased number of leads with ST-segment depression on admission, and prolonged ST-segment depression after admission have been shown to be associated with worse clinical outcomes in patients with NSTE-ACS.114,116
In clinical practice, clinicians have used an “11-lead” ECG, neglecting lead aVR. However, lead aVR has a unique position because the positive pole is oriented to the right upper side of the heart. In NSTE-ACS, lead aVR looks into the left ventricular cavity from the right shoulder. Lead aVR is therefore referred to as a “cavity lead,” and ST-segment elevation in this lead might reflect global subendocardial ischemia. ST-segment elevation in lead aVR is highly suggestive of severe ischemia due to left main or multi-vessel disease,114,117–119 which would most likely require urgent coronary artery bypass grafting (CABG).
ST-segment depression can be caused not only by subendocardial ischemia but also by reciprocal changes of ST-segment elevation in the opposite lead. In the interpretation of ST-segment depression on ECG, one should confirm whether ST-segment elevation is present in the opposite lead. In patients with true posterior AMI due to the LCX occlusion, standard 12-lead ECG often shows no ST-segment elevation, but shows precordial ST-segment depression as reciprocal changes of ST-segment elevation in the posterior wall. True posterior AMI should thus be considered in the differential diagnosis of NSTE-ACS. It has been shown that in patients with true posterior AMI, ST-segment depression is more marked in leads V1–3,120 whereas in patients with subendocardial ischemia, ST-segment depression is more apparent in leads V4–6. These different patterns of ST-segment depression in precordial leads may be helpful to differentiate these 2 conditions; however, recording of leads V7–9 is necessary to make the diagnosis of posterior AMI.
In patients with NSTE-ACS, negative T waves are common ECG changes, as well as ST-segment depression, and are associated with a relatively benign prognosis as compared with ST-segment depression.121 However, it is reported that patients with negative T waves in ≥6 leads have a poor prognosis.115 Negative T waves can actually be preceded by a transient ST-segment elevation that resolves by the time ECG is recorded. Therefore, the culprit artery can be predicted on the basis of the distribution of negative T waves. In patients with NSTE-ACS patients, negative T waves in precordial leads suggest severe ischemia of the LV anterior wall due to LAD disease.122 However, this electrocardiographic finding is also frequently observed in patients with severe acute pulmonary thromboembolism or takotsubo syndrome. Acute pulmonary thromboembolism and takotsubo syndrome should be included in the differential diagnosis of ACS in patients who have precordial negative T waves at initial presentation.114,123
The appearance of negative U waves during anginal attack or exercise is known to be a highly specific marker for severe myocardial ischemia in the perfusion territory of the culprit artery. One should confirm whether negative U waves, very small waves following T waves, are present or not during the ischemic attack. Negative U waves distributed primarily around leads V3–5 are highly predictive of significant narrowing of the LAD.124 However, negative U waves appear in patients with other conditions such as elevated blood pressure or aortic regurgitation without myocardial ischemia. Prominent positive U waves distributed primarily around leads V2–3 have also been suggested as reciprocal changes of negative U waves due to posterior wall ischemia.
Myocardial ischemia has been reported to result in slow conduction velocity in ischemic areas. The decreased conduction velocity associated with myocardial ischemia is manifested as QRS prolongation on the surface ECG. QRS prolongation has been shown to be more sensitive than ST-segment changes for the detection of myocardial ischemia. A prolonged QRS duration has also been shown to be a useful predictor of severe CAD such as left main and/or multi-vessel disease.114,125
The presence of abnormal Q waves is helpful to make the diagnosis of prior myocardial infarction.15 However, an isolated Q wave in lead III or a QS complex in lead V1 is seen even in healthy subject.15 Therefore, it is necessary to comprehensively make the diagnosis of myocardial infarction considering clinical features and other diagnostic test results.
ST-T changes are often observed in patients with vasospastic angina, AAD, acute pulmonary thromboembolism, takotsubo syndrome, fulminant myocarditis, or acute pericarditis.15,94–96,114,123,126,127 Also, various circumstances including ventricular hypertrophy, intraventricular conduction disturbance, cardiomyopathy, metabolic disturbance, electrolyte abnormalities, medications such as digitalis, and so on, influence ST-T changes. It is important not to confuse other causes of ST-T changes with ACS by considering clinical features and other diagnostic test results.
Abbreviations: ACS, acute coronary syndrome; CK-MB, creatine kinase MB. *Cardiac troponins: troponin I and troponin T.
To make a clinical diagnosis of AMI, transient increases in biochemical markers reflecting myocardial necrosis are essential, and either prolonged chest pain or ECG findings suggestive of ischemia are also required. However, increases in cardiac biomarkers are often overlooked immediately after onset. For patients with STEMI diagnosed by ECG or symptoms, reperfusion therapy should be started as early as possible without delay to wait for biochemical marker results (Figure 3).128
Cardiac troponin assays for patients with suspected ACS. ACS, acute coronary syndrome.
Regarding biochemical markers, blood release of cardiac enzymes, including CK, CK-MB, myoglobin, GOT, and LDH, as well as myocardial proteins in AMI has been conventionally known and widely used to diagnose and assess the severity of AMI. During the course from ischemia to myocardial necrosis, the myocardial cell membrane is initially injured, releasing cytoplasmic soluble fraction markers (CK, CK-MB, myoglobin, and heart-type fatty acid-binding protein [H-FABP]) into the circulation. Severe prolonged ischemia involves myofibrillar degradation, resulting in release of cardiac myofibrillar proteins including cardiac troponin T, cardiac troponin I, and myosin light chains. In STEMI, cardiac troponin T, which partly (approximately 6%) exists as a soluble fraction in the cytoplasm, has a bimodal release profile with release from the cytoplasm during early ischemia (first peak at 12 to 18 hours of onset) and release due to myofibrillar necrosis (second peak at 90 to 120 hours of onset), contrary to cardiac troponin I, which has a monomodal release profile.129 CK is the most common traditional marker of myocardial necrosis130,131 and has been widely used for diagnosis and prognostic prediction of myocardial infarction.131 CK-MB, which is myocardium-specific, is of high significance in the assessment of myocardial disorder in view of its ratio to total CK. When the skeletal muscle is damaged by shock, direct currents, etc., both total CK and CK-MB increase; however, skeletal muscle damage can be differentiated from myocardial infarction in that the proportion of CK-MB does not exceed 5%. In STEMI, CK-MB begins to increase within 3 to 8 hours, peaks at 10 to 24 hours, and normalizes 3 to 6 days after onset. The maximum blood CK level, which reflects the amount of myocardial necrosis, is observed earlier with higher levels in patients treated with early reperfusion therapy. However, CK, CK-MB, myoglobin, and other biochemical markers are less sensitive than cardiac troponins, requiring more severe tissue damage for the test to be positive. In contrast, cardiac troponins are highly myocardium-specific and never increase in healthy individuals. An increase in cardiac troponin is defined as >99% of the upper limit of normal, and cardiac troponins can be reliably used to detect myocardial micro-injury involving no increase in CK. In the assessment of ACS based on biochemical markers, simplicity of measurement and quick availability of results (preferably within 30 minutes) are important. Commercially available kits can generate results 10 to 12 minutes after blood collection at bedside (point of care system), and are useful for quick qualitative and quantitative assays of cardiac troponin T. Compared with conventional cardiac troponin assays, more sensitive cardiac troponin assays have been shown to be more accurate and useful for diagnosis of ACS within 2 hours of onset.132–134 A higher cardiac troponin level at arrival indicates higher mortality risk.135–138 The measurement of cardiac troponin in patients with suspected ACS is shown in Figure 3. However, it should be noted that cardiac troponins increase in non-ischemic myocardial injury, including heart failure, renal failure, myocarditis, acute pulmonary thromboembolism, and sepsis.139 In addition, ACS due to coronary spasm cannot be excluded even in cardiac troponin-negative patients.
Measurement of cardiac troponin as a myocardial biomarker requires high sensitive assays. For patients suspected of ACS, cardiac troponin should be measured promptly for diagnosis/risk assessment. However, in patients with STEMI, reperfusion therapy should be considered without waiting for the blood results. In patients with NSTE-ACS, even if there is no rise in initial cardiac troponin, it is difficult to judge within 6 hours from the appearance of symptoms, so it should be measured again after 1 to 3 hours from the initial examination. However, at present, there are institutions using qualitative measurements of cardiac troponin (i.e., POC system), in which case retesting will be done after 6 hours from the appearance of symptoms.
In diagnosis of ACS, chest x-ray is important for making a differential diagnosis and assessing the severity. Patients should be checked for enlargement of the cardiac silhouette, pulmonary congestion, pulmonary edema, and pleural effusion. Enlarged cardiac silhouette reflects LV volume overload associated with previous myocardial infarction, acute left heart failure, pericardial effusion, or aortic or MR. Chest x-ray is used alone to differentiate only a few diseases with chest pain, but is useful for morphological diagnosis of rib disease, airway disease, pulmonary/pleural disease, mediastinal disease, cardiac/pericardial disease, and pulmonary/systemic vascular disease. Diseases that require urgent diagnosis and treatment are acute aortic dissection and acute pulmonary thromboembolism. Ascending aortic dissection is sometimes complicated by AMI due to involvement of a coronary artery, which can make the diagnosis difficult. When chest x-ray reveals an enlarged or double shadow of the superior mediastinum or shifted intimal calcification in the aortic wall, acute aortic dissection should be suspected and differentiated by ultrasonography and contrast computed tomography (CT). When chest x-ray reveals disruption or blockage of the pulmonary artery or focal ischemia, acute pulmonary thromboembolism should be suspected, and ultrasonography and contrast CT should be performed. Acute pulmonary thromboembolism should also be suspected when there are no abnormal chest x-ray findings despite dyspnea or hypoxemia. In chest x-ray assessment, imaging posture and conditions should always be confirmed. In emergency or severe patients, x-rays are often taken in the recumbent position using a portable machine without sufficient cessation of inspiration. It should be kept in mind that chest x-ray findings may be underestimated or overestimated in these conditions.
Abbreviations: LV, left ventricular; RV, right ventricular; ACS, acute coronary syndrome; ECG, electrocardiogram.
Echocardiography is beneficial in the care of patients with chest pain in that it can be repeated in an emergency room (ER) to make a diagnosis on site. Echocardiography can be used for diagnosis of ACS to deduce the culprit coronary lesion, identify the extent and severity of myocardial ischemia, assess LV function, and detect mechanical complications. Echocardiography is also useful to differentiate diseases with chest pain other than myocardial ischemia, including acute aortic dissection, acute pulmonary thromboembolism, pericarditis, aortic stenosis, hypertrophic cardiomyopathy, and fulminant myocarditis.
The culprit coronary artery can be deduced from the site and extent of abnormal wall motion.140 In a study by Horowitz et al, in patients with a clinical diagnosis of myocardial infarction, the diagnostic sensitivity of abnormal LV regional wall motion by echocardiography for myocardial infarction was 94% for, compared with 45% for ECG and 52% for a cardiac biomarker (CK-MB) immediately after onset.141 UA can be diagnosed by abnormal LV wall motion that persists after resolution of chest symptoms or ST-T changes. When urgent CAG reveals multi-vessel disease with chronic total occlusion, the target of reperfusion therapy may be determined based on the wall motion and thickness on echocardiogram. Hypotension immediately after onset of myocardial infarction is primarily attributed to vagotonia, as seen in patients with AMI; in these patients, cardiogenic shock can be excluded when echocardiography shows good anterolateral wall motion without extensive RV infarction or mechanical complication. LV free wall rupture is the most serious mechanical complication and is often rapidly fatal. RV early diastolic collapse with pericardial effusion (echo free space) indicates cardiac tamponade even if effusion is not discernible. Ventricular septal perforration (VSP) can be localized by color Doppler echocardiography as shunt flow. Papillary muscle ischemia with dysfunction or rupture results in mitral regurgitation. In particular, papillary muscle rupture rapidly results in serious heart failure due to mitral regurgitation. The ruptured papillary muscle attached to the chordae tendineae is found as a mobile hyperechoic mass on cross-sectional imaging. Echocardiography is also useful to differentiate ACS from other cardiovascular diseases with chest pain, including acute aortic dissection (ascending or abdominal aortic intimal flap, aortic regurgitation, and pericardial effusion), acute pulmonary thromboembolism (right atrial or ventricular enlargement and LV compression), and acute pericarditis (pericardial effusion without abnormal regional wall motion). For patients with a definitive diagnosis of STEMI, however, reperfusion therapy should not be delayed to perform echocardiography. Non-invasive stress echocardiography should be performed for patients in whom ACS cannot be excluded despite lack of recurrent chest pain, ECG changes, or abnormal cardiac troponin. Gibler et al. reported that 82.1% of emergency patients were safely discharged according to an algorithm using exercise echocardiography.142 Bholasingh et al. evaluated the utility of dobutamine stress echocardiography in low-risk emergency patients with chest pain who had no typical ECG changes and were negative for cardiac troponin T, reporting that the subsequent incidence of cardiovascular events was significantly lower in patients negative for dobutamine stress echocardiography.143 Kang et al. reported that the diagnostic sensitivity and specificity of myocardial contrast echocardiography were 93% and 63% for AMI, and 59% and 96% for unstable angina, respectively, in patients complaining of chest pain on exertion or at rest without evidence of ST-segment elevation or abnormal Q waves on ECG. Myocardial contrast echocardiography was more effective in diagnosing ACS than ECG, cardiac troponins, or abnormal LV wall motion alone.144 Tong et al. reported that myocardial contrast echocardiography in an emergency room predicted the short- and long-term prognosis of patients with chest pain quicker than abnormal biomarkers could be detected.145
Abbreviations: ECG, electrocardiogram.
Note: For patients with unknown time of onset, cardiac troponin levels should be assessed with the time of arrival as the onset time.
When patients with chest pain arrive at a hospital, available information (e.g., age, current medical history, past medical history, physical findings, 12-lead ECG, laboratory findings) should be used to determine whether ACS is highly suspected or not. Patients are classified into 4 categories according to the probability of ACS: non-cardiac disease, chronic stable angina, possible ACS, and definite ACS. When definite or probable ACS is diagnosed, it is important for prognostic improvement to stratify the short-term prognosis (cardiac death and non-fatal cardiac event) and promptly treat appropriately. While it is sometimes necessary to determine treatment protocol without waiting for cardiac enzyme results, which are essential for clinical diagnosis of myocardial infarction, it is important to assess the risk quickly based on available information and provide information on predictable prognosis to patients and their families.
Classification of UA accounting for severity, clinical presentation, and treatment status was proposed by Braunwald in 1989 (Table 10).145 There have been many reports that this classification is useful in predicting the short-term prognosis147,148 and contributes to decision of treatment strategy.105,149 In addition, the classification has been shown to correlate with the severity of coronary angiographic lesions150–152 and complications of PCI. Class II (subacute), Class III (acute), Class B (primary UA), and Class C (post-infarction angina) are considered moderate to high risk. Braunwald et al. pointed out that angina at rest persisting for 20 minutes or more, pulmonary edema complicated by ischemia, angina with third heart sounds or rales, and angina with hypotension had poor short-term prognosis.
Abbreviations: UA, unstable angina. (Source: Prepared based on Braunwald E. 1989146)
The TIMI risk score (https://www.mdcalc.com/timi-risk-score-ua-nstemi), which is often used for risk assessment in patients with NSTE-ACS, is calculated from 7 factors: age (≥65 years); at least 3 coronary risk factors (family history, hypertension, hypercholesterolemia, diabetes mellitus, and smoking); known significant (≥50%) coronary stenosis; ST changes ≥0.5 mm on ECG; at least 2 episodes of angina in 24 hours; aspirin use in the past 7 days; and increased cardiac markers; therefore, most of these factors can be assessed immediately after transport of patients (Table 11). As the score increases, the incidence of major cardiovascular complications in the following 2 weeks increases synergistically.64,153 Since treatment strategy for NSTE-ACS differs depending on the risk, early risk assessment is more important.
Abbreviations: CAD, coronary artery disease; ECG, electrocardiogram. (Source: Prepared based on Antman EM, et al. 200064)
Factors influencing the prognosis of STEMI include age, Killip class, time to reperfusion, cardiac arrest, heart rate (tachycardia), systolic blood pressure (hypotension), infarction site (anterior), previous myocardial infarction, diabetes mellitus, smoking status, renal function, sex, and low body weight.37,154–156 Killip classification (Table 3) is convenient in assessment of the severity made primarily based on auscultatory findings and is useful for prediction of the prognosis.81 Cardiogenic shock, classified as Killip Class IV, is the most common cause of in-hospital mortality, with a mortality rate as high as 40% to 70%. However, it has been shown that advances in treatment, primarily early reperfusion therapy, contribute to improvement in survival for patients with shock.63,157,158 Cardiogenic shock associated with myocardial infarction is generally defined as hypotension (<90 mmHg) persisting for at least 30 minutes with signs of peripheral circulatory failure despite adequate LV filling pressure. However, decreased tissue perfusion with blood pressure of 90 mmHg or higher is considered as pre-shock and treatment should be the same as for shock.
The GRACE ACS risk model (https://www.mdcalc.com/grace-acs-risk-mortality-calculator), which is used for overall risk assessment in patients with ACS, including STEMI and NSTE-ACS, is designed to calculate the probability of death and probability of death or myocardial infarction at admission and at 6 months by weighting 8 risk factors: age, heart rate, systolic blood pressure, initial serum creatinine, Killip class, hospitalization due to cardiac arrest, positive cardiac biomarker, and ST-segment deviation (Table 12). This model can be used to stratify the risk (low risk, moderate risk, or high risk) for STEMI and NSTE-ACS separately, and predict the hospital mortality and prognosis at 6 months after being discharged alive for each risk group.65,159 However, no organization in Asia, including Japan, participated in the GRACE study. According to data from the Osaka Acute Coronary Insufficiency Study, the long-term (median, 3.9 years) mortality rate was 2.0%, 6.3%, 11.8%, and 16.8% in patients alive at discharge with GRACE scores of <100, 101 to 120, 121 to 140, and ≥141, respectively.160
The TIMI risk score was the first risk score and has been validated most extensively. The score is easy to use in an ER, since all factors in this risk score can be readily assessed based on medical history and examinations in an ER. However, it was reported that the prediction accuracy of this score was lower than that of the GRACE risk score.161 The GRACE risk score is relatively complex to calculate,159,162 but its clinical utility has been verified extensively. The TIMI and GRACE risk scores, which can be calculated through websites on the Internet, are easy to use in emergency care.
The 12-lead ECG plays a central role in diagnostic and triage pathways for ACS and provides important prognostic information.
The presence of Q waves on the presentation ECG was reported to reflect a more advanced stage of infarct evolution. This ECG marker has been reported to be associated with poor clinical outcomes in patients with STEMI treated with PCI as well as fibrinolysis.163,164 QRS score is a quantitative index of myocardial damage calculated not only by the number of Q waves but also by increased Q wave width and decreased R wave amplitude and width.165 QRS score may be a more accurate indicator of the stages of infarct evolution than the mere presence or absence of Q waves. It has been shown that higher QRS score on the presentation ECG is associated with a larger infarct size, and higher long-term mortality in 2,607 patients with STEMI undergoing primary PCI.108
In patients with anterior STEMI, the more proximal the occlusion, the more extensive the area at risk. ST-segment depression in inferior leads, ST-segment elevation in lead aVR, and complete right bundle branch block have been shown to be suggestive of LAD occlusion proximal to the first septal branch. In particular, ST-segment depression in inferior leads is very useful, whereas ST-segment elevation in lead aVR and complete right bundle branch block are shown to have high specificities, but low sensitivities.100,101
In patients with inferior STEMI, those with RV infarction have a poor prognosis. RV infarction during inferior STEMI can be accurately diagnosed by ST-segment elevation ≥1.0 mm (0.1 mV) in the right precordial lead, especially lead V4R.104 However, ST-segment elevation in right precordial leads has been reported to be short lived, disappearing within 10 hours after onset of symptoms in half of patients with inferior AMI and RV involvement.104
ECG diagnosis is often difficult in patients with bundle branch block. Patients with right or left bundle branch block, especially the latter, have a worse clinical profile and poorer prognosis. and therefore, a clinical suspicion of AMI in the presence of bundle branch block is an indication for emergent CAG to perform timely reperfusion therapy.166
In patients with NSTE-ACS, ST-segment depression ≥0.5 mm (0.05 mV) is a strong predictor of poor outcomes.114 The degree, extent, and serial changes of ST-segment depression, not only its presence or absence, can facilitate early risk stratification in patients with NSTE-ACS.114 ST-segment elevation in lead aVR with extensive ST-segment depression is highly suggestive of severe ischemia due to left main or multi-vessel disease.114
In patients with NSTE-ACS, negative T waves are associated with a relatively benign prognosis as compared with ST-segment depression.121 However, it is reported that patients with negative T waves in ≥6 leads have a poor prognosis.115 In addition, negative T waves in precordial leads suggest severe ischemia of the LV anterior wall due to LAD disease.122
QRS prolongation has been shown to be more sensitive than ST-segment changes for the detection of myocardial ischemia. A prolonged QRS duration is associated with severe ischemia in patients with ACS.114
Abbreviations: BNP, brain natriuretic peptide; NT-proBNP, N-terminal pro B-type natriuretic peptide; AMI, acute myocardial infarction; ACS, acute coronary syndrome.
It has been reported that the short-term mortality rate of patients seen in an emergency department due to chest pain increased linearly from 1.0% to 7.5% according to the increment in cardiac troponin I despite lack of ST elevation on ECG and normal CK-MB,167–169 and the increase in cardiac troponin T is the most useful factor for 30-day prognostic prediction in patients with ST-T change on ECG and increased serum CK-MB in addition to chest pain.170 It has been reported that the measurement of highly sensitive cardiac troponins is useful in early diagnosis of not only STEMI, but also NSTEMI, with a higher level associated with a higher mortality rate.171 Blood C-reactive protein (CRP) is a marker that reflects acute inflammation, and it has been reported that the incidence of early cardiac events was 3 times higher in UA patients with a CRP level ≥0.3 mg/dL than in those with a CRP level <0.3 mg/dL. CRP attracted attention as a marker of unstable atheroma in coronary artery sclerosis,172 and increases in measures of acute inflammatory reaction in UA were considered to indicate persistent instability or possible recurrence even in asymptomatic patients.173 In the CANTOS study, which evaluated the efficacy of an anti-inflammatory IL-1β inhibitor in previous myocardial infarction patients with a highly sensitive CRP level of ≥2 mg/L, the mortality rates from myocardial infarction, stroke, and cardiovascular disease in the 4-year observation period decreased with decreases in CRP, again highlighting CRP as a useful biomarker. The 2014 ACC/AHA Guidelines for Management of NSTE-ACS stated that B-type natriuretic peptide (BNP) is a new biomarker that may provide prognostic information (Class IIb, level B).175
In addition, hyperglycemia is a strong predictor of mortality and heart failure in non-diabetic patients,176 and renal impairment affects the short- and long-term prognosis.177 Since serum creatinine, which is affected by age and sex, is a limited measure of renal function, creatinine clearance and estimated glomerular filtration rate (eGFR) are used.
For ACS, diagnosis, severity assessment, and prognostic prediction can be made based on medical history, brief medical examination, and other examinations, and it is important to collect medical history and obtain physical examination findings quickly and accurately. However, not a few patients with ACS have atypical or no symptoms. In a US study involving more than 430,000 patients with AMI, 33% had no chest pain at presentation, and the chest pain-free group had a higher proportion of elderly patients (74 years vs. 67 years), female patients (49% vs. 38%), diabetic patients (33% vs. 25%), and patients with history of heart failure (26% vs. 12%) than the chest pain group.116 AMI patients with no chest pain tend to have a longer time to hospital presentation and a delayed diagnosis. As a consequence, fewer patients receive appropriate treatment or reperfusion therapy, with a 2.21 times higher hospital mortality, requiring caution.
Coronary care unit (CCU) care is essential for patients considered to be high risk at initial diagnosis, and moderate-risk patients should be managed accordingly. Low-risk patients may be managed on an outpatient basis. Since assessment only at arrival may fail to detect all high-risk patients, treatment protocol should be determined through symptom monitoring, ECG, and assessment of cardiac markers over time, with change in treatment strategy considered if reassessment reveals increased risk.
Guidelines for the management of patients with ST-elevation acute myocardial infarction (JCS 2013) recommend administering oxygen to all STEMI patients for 6 hours after hospital arrival (Class IIa, Evidence level C). That said, the efficacy of routine oxygen administration for AMI patients without hypoxemia was refuted by recent studies.211–214 While oxygen should be given when there are signs of hypoxemia, heart failure, or shock, routine oxygen administration is not recommended. Oxygen saturation should be monitored immediately upon hospital arrival to assess the need for oxygen. Oxygen is not contraindicated when the level of oxygen saturation is unclear. If there is a risk of a hypoxic state occurring after ACS onset, administer oxygen. Further, severe hypoxemia due to a variety of causes can be managed with a ventilator by tracheal intubation. Noninvasive positive-pressure ventilation is reported to be effective for acute cardiogenic pulmonary edema, though a consensus has not been reached regarding its safety and efficacy in AMI patients.
Abbreviations: AMI, acute myocardial infarction; RV, right ventricular.
Nitrates have the pharmacological action of dilating the venous system, arterial system, and coronary arteries. Dilation of peripheral veins reduces LV preload and volume, and dilation of peripheral arteries reduces blood pressure and afterload, which lowers myocardial oxygen consumption. These drugs are also widely used for dilation of coronary and bypassed arteries, to improve blood flow to ischemic myocardium, and to prevent and reverse coronary vasospasm.
Many studies have found nitrates to be effective for pump failure and postinfarction angina in the acute stage of myocardial infarction. They have also become widely used due to their ability to shrink infarcted areas, prevent remodeling of the LV myocardium, and reduce mortality rates. That said, several large clinical trials in Europe and the United States (ESPRIM,215 GISSI-3,216 ISIS-4217) failed to confirm the ability of nitrates to reduce mortality and refuted their effectiveness. Therefore, while nitrates have been shown to improve prognosis by reducing blood pressure, caution must be exercised so that the use of other drugs with antihypertensive action (β-blockers, ACE inhibitors, etc.) is not hindered.
Patients with ischemic chest discomfort can be given nitroglycerin sublingually or via oral spray. If the symptoms do not markedly improve after administration of 1 nitroglycerin tablet, call an ambulance. Intravenous nitroglycerin is indicated for chest discomfort, to control hypertension and treat pulmonary congestion. Nitrates are indicated during the first 24 to 48 hours in patients experiencing repeated ischemic attacks. However, administration should be avoided in patients with systolic blood pressure <90 mmHg, a decrease of ≥30 mmHg from normal blood pressure, severe bradycardia (<50/bpm), tachycardia (>100/bpm), or suspected acute inferior and RV infarction. Caution is warranted in elderly or dehydrated patients, as nitrates can excessively lower blood pressure. Nitrates are contraindicated within 24 hours after taking erectile dysfunction medication (Viagra®, others), as excessively lowering blood pressure can induce myocardial ischemia or shock.218
Persistent chest pain can increase myocardial oxygen consumption, expand the infarct area, and induce arrhythmia. Therefore, prompt analgesia or sedation should be provided. Regardless of whether nitrates were used, morphine hydrochloride can be effective for persistent pain. Further, because morphine hydrochloride is a vasodilator, it is effective for pulmonary congestion, but therefore should not be administered to patients who may have reduced circulating blood volume. If morphine causes blood pressure to decline, elevate the legs to provide fluid loading, but proceed with caution as this can exacerbate pulmonary congestion. Morphine hydrochloride 2–4 mg is given intravenously; if the effect is insufficient, an additional 2–8 mg can be given every 5–15 minutes. However, monitor the respiratory status, fluctuations in blood pressure, and side effects such as vomiting. Use with caution, particularly in inferior AMI, as vagotonia tends to reduce blood pressure in association with vomiting. Intravenous administration of buprenorphine (0.1–0.2 mg) is effective for chest symptoms and diazepam (2.5–5.0 mg) for sedation, but be cautious of respiratory depression.
Abbreviation: ACS, acute coronary syndrome.
Many trials have shown aspirin to be useful for improving the prognosis of AMI. The large ISIS-2 trial10 found that aspirin alone reduced vascular-related mortality by 23±4%, compared to that when combined with thrombolytic therapy. Administration after the acute stage has also been shown to reduce vascular-related mortality. Studies have shown that the sooner aspirin is administered, the greater the improvement in mortality rate.10,219–225 Therefore, except in patients with severe blood disorders, aspirin-induced asthma, or hypersensitivity to aspirin, aspirin should be given as soon as possible. Even outside hospital, patients can chew 162–200 mg of aspirin to obtain a rapid effect. Aspirin should not be used in patients known to be hypersensitive, and caution is needed in patients with blood diseases or severe liver disorders. Further, while bleeding tendency associated with increased hemorrhagic complications of cardiovascular surgery has been reported, an increase in the reoperation rate was not observed.226 Patients with a history of upper gastrointestinal bleeding who take low-dose aspirin have been found to have higher rates of gastrointestinal complications, including peptic ulcer and bleeding.227 Helicobacter pylori eradication or proton-pump inhibitor (PPI) administration is effective for preventing recurrence, though guidelines state that bacterial eradication combined with PPI is more effective than eradication alone.228
Administering clopidogrel to STEMI patients who have undergone PCI has been shown to reduce cardiovascular mortality, nonfatal myocardial infarctions, and total mortality, with only a small increase in major bleeding.229,230 In combination with aspirin, loading STEMI patients with 300 mg of clopidogrel prior to PCI, then starting 75 mg/day the next day, has been shown to reduce the risk of cardiovascular events. See chapter VII section 3.1 for these guidelines on the use of antithrombotic agents during primary PCI.
Clopidogrel has also been shown to be effective in patients who have undergone fibrinolytic therapy and patients who have not undergone reperfusion therapy. Administration of clopidogrel to NSTEMI patients was found to reduce the risk of vascular-related events (cardiovascular death, myocardial infarction, and stroke) compared to that in a control group that received a placebo.231
Abbreviations: PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; DES, drug eluting stent; ECG, electrocardiogram.
Reperfusion therapy for STEMI is now widely accepted as an acute treatment of myocardial infarction and its efficacy has been established in patients within 12 hours of symptom onset. It is of importance to restore coronary blood flow promptly and securely without any complications. In treating STEMI, it is important for improved prognosis to establish TIMI 3 reperfusion as soon as possible with fibrinolysis or PCI. PCI is preferred for treating STEMI in current clinical practice in Japan. The use of PCI as the first line for reperfusion without preceding fibrinolysis is called primary PCI.
In principal, PCI should be performed by accredited, skilled operators, certified by the board of a PCI-related Society in experienced centers.
Prognosis of patients with STEMI depends on the time required to establish reperfusion of the infarct-related culprit artery after symptom onset. Primary PCI is considered appropriate reperfusion therapy when it is performed in patients with STEMI within 12 hours of symptom onset by a skilled team and reperfusion is achieved within 90 minutes from the arrival of the patient at the medical institution. A meta-analysis of 23 randomized controlled trials published in the Lancet in 2003 reported that primary PCI was superior to fibrinolysis in improving the prognosis of patients with STEMI.232 Primary PCI therefore has become a standard of care.
There are however some circumstances, such as in remote areas and outer islands, when primary PCI is not available as first choice and the use of fibrinolysis is adequate due to long distances to PCI-capable medical centers. In these circumstances, it is recommended to transfer the patient to a PCI-capable medical center after fibrinolysis.240–243
It is crucial in treating STEMI to shorten the total ischemic time, the time from symptom onset to reperfusion. Door to balloon time is widely used as an index of early reperfusion in primary PCI for STEMI and PCI-capable medical centers aim for door to balloon time shorter than 90 minutes. The CREDO-Kyoto AMI Registry, a large-scale observational study of AMI in Japan, however, revealed that long-term clinical outcomes were not significantly different between patients who had a door to balloon time shorter than 90 minutes and those who did not.244 On the other hand, treatment outcomes were favorable in patients who obtained reperfusion early, with a total ischemic time shorter than 3 hours, and got worse as total ischemic time got longer. Of note, a door to balloon time shorter than 90 minutes was associated with favorable long-term clinical outcomes only in patients who presented early to medical institutions, that is, within 2 hours of symptom onset. These results indicate the importance of reduction in total ischemic time, which includes door to balloon time. A door to device time shorter than 90 minutes is a minimum acceptable time, but not a target time. The goal should be to make the time from the diagnosis of STEMI to wire crossing of the lesion shorter than 60 minutes, considering the fact that a shorter total ischemic time to recanalization is associated with more favorable prognosis.
Primary PCI with bare metal stents (BMS) is associated with lower incidence of revascularization although it is not associated with a lower mortality rate compared with plain old balloon angioplasty in treating STEMI.246,247 In recent years, drug-eluting stents (DES) have been frequently used in the treatment of STEMI. Many clinical studies have reported that DES and BMS are equivalent with respect to the incidence of death and myocardial infarction, and DES are superior to BMS with respect to the rate of repeat revascularization.248,249 The use of DES is, therefore, more strongly considered when patient characteristics and/or lesion characteristics are potentially associated with a high risk of restenosis. However, bleeding risk due to oral dual antiplatelet therapy (DAPT) and a need for an invasive procedure, e.g. an operation, within several days, should be taken into account before using DES.
With regard to the timing of stent implantation for the infarct-related culprit lesion, a treatment strategy called “deferred” or “delayed” stent implantation was proposed, in which stent implantation was withheld after the initial angioplasty has stabilized the blood flow through the infarct-related culprit lesion. This strategy might reduce the risk of thromboembolism and thereby improve clinical outcomes.
The DANAMI 3-DEFER trial,250 a study that assessed whether delayed stent implantation reduces the risk of impaired myocardial blood flow and improves the clinical course of patients with STEMI compared to conventional PCI, showed no between-group differences in all-cause mortality, heart failure hospitalization, or recurrence of nonfatal myocardial infarction, but confirmed a significantly higher rate of unscheduled target vessel revascularization in the deferred stent group. Routinely delaying stent implantation in patients with STEMI as a treatment strategy is thus considered to have no benefit.
Abbreviation: PCI, percutaneous coronary intervention.
The performance of primary PCI without on-site cardiac surgery is acceptable only when a skilled operating physician performs primary PCI for STEMI requiring emergency treatment. Off-site cardiac surgical backup is mandatory.
Abbreviation: PCI, percutaneous coronary intervention.
Emergency revascularization significantly decreased mortality at 6 months and 1 year after the procedure in patients with STEMI complicated by cardiogenic shock and was especially effective in patients under 75 years of age.158 Even in patients who are 75 years of age or older, emergent revascularization improved survival rate if their functional status was good.252–254 Primary PCI is strongly recommended in patients with cardiogenic shock, because prompt revascularization is critical. According to data collected in Japan, however, primary PCI does not improve prognosis in elderly patients presenting with cardiogenic shock after cardiac arrest.255
Abbreviation: PCI, percutaneous coronary intervention.
In Japan, approximately 100 thousand people suddenly die outside medical institutions every year, and substantial proportion of these deaths is to ACS. Measures and actions against cardiac arrest attributed to ACS are therefore important issues in emergency care.
Primary PCI in patients with ST-segment elevation that is confirmed on 12-lead ECG following cardiac arrest and the return of spontaneous circulation is recommended from the viewpoint of improvement in prognosis and neurologic outcome.260 In patients without ST-segment elevation, emergent CAG should be considered, taking into account the neurologic sequelae, and PCI, if suitable, should be performed when non-cardiogenic causes are excluded and progressive myocardial ischemia is strongly suspected.256–259,261 It is frequently difficult to diagnose myocardial ischemia accurately from electrocardiography in patients following cardiac arrest and the return of spontaneous circulation. The absence of ST-segment elevation, therefore, does not necessarily exclude acute coronary artery occlusion. The use of emergent CAG in preparation for coronary revascularization should be appropriately determined based on the overall clinical findings in patients following cardiac arrest and the return of spontaneous circulation.