<scp>JCS</scp>/<scp>JHRS</scp> 2022 Guideline on Diagnosis and Risk Assessment of Arrhythmia

Abstract

The purpose of diagnosing arrhythmia is to improve symptoms, quality of life (QOL), and prognosis by preventing sudden cardiac death that is caused by fatal ventricular arrhythmias. Organic heart disease, such as myocardial infarction, accounts for the majority of etiologies, whereas inherited diseases, such as Brugada syndrome, are also involved. Risk assessment using various test methods can help to prevent sudden cardiac death to a certain degree. Syncope is a precursor to sudden cardiac death, and the diagnosis of arrhythmic syncope can lead to the prevention of sudden cardiac death. Furthermore, fatal arrhythmia often occurs during activity and exercise, which makes diagnosis equally important in the field of sports. There are also other pathologies that require a detailed diagnosis of arrhythmias, such as detecting atrial fibrillation (AF) in patients with suspected non-fatal arrhythmias or cardiogenic cerebral infarction. Recently, it was decided to summarize the guidelines on the diagnosis and treatment of arrhythmia into 3 major categories, diagnosis, pharmacotherapy, and non-pharmacotherapy. Several guidelines on diagnosis and treatment have already been published for the cardiovascular system; however, there are many descriptions that overlap. Thus, revising the guidelines to make each one for each field more concise and revising multiple guidelines at once would make utilization of the guidelines more effective. Similarly, in the field of arrhythmia, a revised version of the Guideline on the diagnosis and treatment of arrhythmia was published first. The 2020 revised edition of the 2020 JCS/HHRS Guideline on pharmacotherapy of cardiac arrhythmias1 was published in 2020, and for non-pharmacotherapy there is the 2018 JCS/HHRS Guideline on non-pharmacotherapy of cardiac arrhythmias (2018 revision)2 and a Supplementary Edition of the 2021 JCS/HHRS Guideline focused update on non-pharmacotherapy of cardiac arrhythmias.3 Of the aforementioned 3 major categories related to the diagnosis and treatment of arrhythmias, this guideline is intended to address the "diagnosis". It is an attempt to integrate the Guidelines for diagnosis and management of syncope (JCS 2012),4 the Guidelines for clinical cardiac electrophysiologic studies (JCS 2011),5 as well as the Guidelines for exercise eligibility at schools, work-sites, and sports in patients with heart diseases (JCS 2008),6 focusing mainly on revising the Guidelines for risks and prevention of sudden cardiac death (JCS 2010).7 In addition, sections of the Guidelines for diagnosis and management of inherited arrhythmias (JCS 2017)8 related to diagnosis have been partially updated to include information such as the current status and concept of insurance coverage for genetic testing. These revisions aim to provide a comprehensive guide for the proper diagnosis of arrhythmia and to serve as guidelines for the assessment of risks of arrhythmia, including sudden cardiac death. The creation of this guideline was aimed at (1) incorporating the latest findings useful for clinical practice and educating young doctors; (2) striving for consistency with guidelines published in other countries, such as Europe and the USA; (3) including cross-sectional and comprehensive information from several other related guidelines; and (4) proactively incorporating evidence and results of clinical research in Japan. The first half of this guideline provides detailed information on arrhythmia tests and the second half explains which test should be used for which arrhythmic disease, structured to provide a concise overview. Many flowcharts are used to clarify the process from examination to diagnosis, and to ensure that diagnoses of arrhythmia based on evidence and trends both in Japan and abroad can be used in routine medical practice. The guideline is also designed to be widely used by clinicians other than arrhythmia specialists and by doctors involved in general medical care and medical checkups. Care has been taken to maintain consistency with previous guidelines on the diagnosis and treatment of arrhythmia when deciding the level of evidence. Furthermore, examination of evidence-based materials from Europe and the USA was based on the experience and opinions of the team members and support personnel in team meetings, with due consideration of the clinical applicability in Japan (i.e., doctor's ability, regional characteristics, medical resources, insurance system, and others). The Class of Recommendation and Level of Evidence conform with the Japanese Circulation Society Guideline Creation Guide (revision 12 March 2020), while referencing guidelines issued by the American Heart Association (AHA), American College of Cardiology (ACC), and the US Heart Rhythm Society (HRS). The Class of Recommendation related to the indication of each diagnostic method and examination method were classified as I, IIa, IIb, III (No benefit), and III (Harm), with the associated Level of Evidence classified as A, B, or C (Tables 1,2). Class III (No benefit) Class III (Harm) The aforementioned guidelines on the treatment of arrhythmias also include the Class of Recommendation and Level of Evidence as reference findings based on the Minds Clinical Guideline Development Guide 2007,9 with methods for developing treatment guidelines described by the Japan Council for Quality Health Care Evidence-Based Medicine and Guidelines Promoting Project (Minds). However, classification based on research design, which is prioritized in Minds, did not always correlate with the examination and diagnostic methods, so the descriptions were removed. On the other hand, diagnosis using the latest electrocardiogram (ECG) monitors (wearable ECG monitors, heart rate monitors, ECG using smartphones, and others) and artificial intelligence have the potential to grow exponentially and will become widely used in the future. It is difficult to determine the Class of Recommendation for these devices at present, but they have been introduced in detail to convey the trends in Japan and abroad. Persistent severe bradycardia tends to manifest symptoms such as shortness of breath on exertion and chest discomfort, but symptoms do not appear during sleep, at rest, while the condition is gradually developing, or if activity levels are reduced. Prolonged cardiac arrest can also cause dimmed vision or syncope. Despite fewer subjective symptoms, signs of heart failure can be confirmed based on findings such as lower limb edema, cardiac dilatation on chest X-ray, and blood tests. Furthermore, bradycardia is often asymptomatic, showing no subjective symptoms in sports trainees or people who normally have low heart rates. Heart rate increases as a physiological response caused by increased sympathetic nerve activity, such as during exercise, mental excitation, and fever. However, a sudden increase in heart rate causes symptoms with varying severity depending on the level of cardiac function, the duration of the tachycardia, the cause of arrhythmia (supraventricular, ventricular), and the presence or absence of an underlying heart disease. Although supraventricular arrhythmia can cause symptoms such as palpitations, chest pain, and chest discomfort, it has relatively little effect on hemodynamics. Severe and sustained ventricular arrhythmias affect cardiac output and disrupt hemodynamics. They can also result in cerebral hypoperfusion, palpitations with cold sweat, dizziness, dimmed vision, or syncope.10 Tachyarrhythmias with a high incidence of syncope are caused by fatal ventricular arrhythmias such as sustained ventricular arrhythmia and ventricular fibrillation (VF). However, on rare occasions, supraventricular arrhythmias, such as tachycardia atrial fibrillation (AF), 1 : 1 atrioventricular (AV) conduction of atrial flutter, and paroxysmal supraventricular tachycardia (PSVT), may also result in syncope or near-syncopal symptoms. Irregular pulse can indicate extrasystole or AF, but patients also may be asymptomatic or have few symptoms with isolated or infrequent extrasystoles. Patients may present with palpitations or intermittent pulse deficiency when there are repeated or frequent extrasystoles. In paroxysmal AF, the sudden disappearance of AV synchrony causes rapid and/or irregular pulse-to-beat, which may result in severe symptoms. In a survey of 756 patients with symptomatic AF, the most common symptom was palpitations, occurring in 54% of patients, followed by shortness of breath, malaise, syncope or dizziness, and chest pain, while 11% of patients were asymptomatic.11 Reports on paroxysmal AF indicate that 79%, 23%, and 17% of patients have symptoms of palpitations, shortness of breath, as well as syncope and dizziness, respectively, while 5% are asymptomatic. Conversely, in permanent AF, 45%, 47%, and 8% of patients have symptoms of palpitations, shortness of breath, as well as syncope and dizziness, respectively, while 16% are asymptomatic. Therefore, paroxysmal and permanent AF lead to different frequencies and types of symptoms. Symptoms such as shortness of breath, fatigue, and dizziness are observed relatively frequently in patients with bradyarrhythmia. For conditions such as sick sinus syndrome (SSS) and atrioventricular block, the heart rate may not increase sufficiently with physiological heart rate response or exertion (chronotropic incompetence), and patients may complain of symptoms such as shortness of breath, fatigue, and dizziness. These symptoms tend to occur when standing or during exertion and are uncommon while supine or at rest. The same arrhythmia may not always manifest the same symptoms in the same patient. The sudden onset of extreme bradycardia, cardiac arrest, or extreme tachycardia causes a temporary reduction or interruption in blood flow to the brain, resulting in whole cerebral hypoperfusion and causing syncope (Stokes-Adams syndrome). Syncope is defined as rapid onset, transient loss of consciousness, and inability to maintain posture, followed by prompt recovery spontaneously. Symptoms vary depending on the type of arrhythmia, severity of bradycardia, duration of cardiac arrest, and posture. A cardiac arrest with a duration of 2–5 s may cause presyncopal symptoms such as dizziness, lightheadedness, and dimmed vision, whereas if the cardiac arrest lasts >6 s, body posture may not be maintained, and the patient eventually faints.12 However, these symptoms may not appear if the cerebral hypoperfusion is improved when the patient lies down, or if the causative arrhythmia terminates in a short time. Therefore, syncope often involves facial or head injury (see Chapter II.5 for differential diagnosis). Sudden cardiac death is defined as unexpected death within 24 h (or within 1 h) of the onset of acute symptoms assumed to be caused by heart disease. Results of a statistical analysis based on an Utstein-style survey by the Fire and Disaster Management Agency13 showed that 127,718 patients who had a cardiac arrest were transported by ambulance in the fiscal year (FY) 2018, and incidence increased with age stratified by 10-year age groups; patients aged 80–89 years had the highest incidence, accounting for 34% of the total sample. Although there has been no significant change in the number of transported patients or in the sex ratio over the past 10 years, the percentage of old patients has increased. Among the aforementioned 127,718 patients who had a cardiac arrest, 79,400 (62%; male, 57%; female, 43%) experienced cardiogenic cardiac arrest, and 31,819 (25%) were witnessed at the onset, and 25,756 of them were witnessed by members of the public (Figure 1).13 The cardiac arrest occurred at home (66%), in public places (retirement homes, hospitals/clinics, inns/hotels, restaurants, car parks; 24%), on the road (5%), and other sites (5%). The 1-month survival rate of the patient group witnessed by members of the public was 36.2% for patients whose initial ECG waveforms were VF and pulseless ventricular tachycardia (VT), and the 1-month social rehabilitation rate was 25.1%. These rates increased by 5.9 points and 4.6 points, respectively, compared with 10 years earlier. Furthermore, the 1-month survival rate of the patient group witnessed by ambulance officers and others was 55.7%, and the 1-month social rehabilitation rate was 46.1%, which increased by 13.0 points and 11.4 points, respectively. The Japan Society for Holter and Noninvasive Electrocardiology collected Holter ECG records of patients who went into cardiac arrest from 41 medical facilities nationwide and investigated the types of arrhythmias in 132 patients (73% tachyarrhythmia, 27% bradyarrhythmia).14 Tachyarrhythmia was more common than bradyarrhythmia in the younger age group (mean age, 58 years vs. 70 years), with fewer complications such as stroke or heart failure. Tachyarrhythmia halted spontaneously in 38% of cases, which can also be considered near-miss sudden cardiac deaths. These results reiterate the importance of preliminary risk assessment. Factors leading to sudden cardiac death are broadly divided into cardiogenic and non-cardiogenic (see Chapter II.3.4 Table 18). Cardiogenic diseases in Japan include coronary artery disease (50–60%) and cardiomyopathy (30–35%)15 (Figure 2A). Hereditary arrhythmias account for up to 10%, and there are also a small number of valvular diseases (<10%). Hereditary arrhythmias include long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome, early repolarization syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and progressive cardiac conduction disturbance (PCCD). According to the Japan Cardiac Device Treatment Registry database16 of the Japanese Heart Rhythm Society, ≈20% of implantable cardioverter defibrillators (ICDs) were used for primary prevention of ischemic heart disease, and ≈80% for secondary prevention. Given that the appropriate activation rate of ICDs for cases of primary prevention is similar to that of secondary prevention, strict adherence to the indication criteria for implantation can be assumed. On the other hand, there is a risk that sudden cardiac death may not be completely avoided in patients not indicated for ICD. In the Nippon Storm Study,17 1,570 patients fitted with devices, including 68% using ICDs and 32% using implantable cardiac resynchronization therapy devices (CRT-Ds) with biventricular pacing function, were registered by 48 medical facilities over a 2-year period from 2010 (Figure 2B), and a 2-year follow-up was conducted. The mean age of the patients was 62ア14 years, and 78% of them were male. The underlying heart diseases were ischemic heart disease (31%), cardiomyopathy (36%), and hereditary arrhythmias (13%). In patients with ischemic heart disease, the devices were used for secondary prevention 3-fold more often than for primary prevention, whereas in those with cardiomyopathy, Brugada syndrome, and others the frequency was almost similar for primary and secondary prevention. A comparison with several other countries showed that the number of sudden cardiac deaths in the USA ranges from 200,000 to 450,000 people per year,18 while Europe registered 300,000 people per year.19 In Western countries, the major underlying disease is coronary artery disease (80%), but these trends differ significantly when analyzed by age group.15 The cause is often unknown in neonates and infants, while cardiomyopathy and hereditary arrhythmias rank top in the group of children and young adults. In contrast, the incidence of ischemic heart disease increases in adults aged up to 35 years, and the majority of cases are caused by myocardial infarction in adults older than 35 years.20, 21 The prospective cohort Rotterdam Study, which investigated 14,628 people aged ≥45 years, found that between 1990 and 2000 the incidence of sudden cardiac death per 1,000 people per year was 4.7, which decreased to 2.1 from 2001 to 2010.22 This might be due to advances in treatment for coronary artery disease,21 and the effect of implantable defibrillators (ICD, CRT-D). Measures such as risk stratification for primary prevention of cardiomyopathy and hereditary arrhythmias, as well as preventative measures among relatives, are considered important to further reduce sudden cardiac deaths.23-25 The most important risk factors for sudden cardiac death are a history of VT/VF and cardiac arrest, as well as a family history of sudden death.26, 27 Familial risk factors are involved not only in hereditary arrhythmias but also in genetic vulnerability to sudden death at the onset of acute coronary syndrome.28 The genetic mechanisms are multifactorial, and environmental interactions further complicate physiological and pathological mechanisms. Coronary risk factors known to relate to sudden death include hypertension,29 diabetes,26 dyslipidemia,30 and smoking.31 Pathologies associated with sudden death include AF,32 and renal dysfunction.33, 34 These are independent risk factors related to sudden death, and large-scale systematic reviews can rule out a causal relationship with myocardial ischemia.35, 36 A review of 15 studies (39,908 patients, follow-up period of 4.2 years) on hypertensive patients treated with pharmacotherapy found that although antihypertensive drugs reduced the incidence of fatal myocardial infarction, they did not reduce the incidence of sudden death.35 This finding indicates that acute myocardial infarction may not be the main cause of sudden cardiac death. Instead, VT/VF caused by abnormalities in repolarization and modification in the modulation of the autonomic nervous system may result in sudden cardiac death. For example, it has been clarified that prolongation of the interval between the peak and end of the T-waves (Tpeak–Tend) may be a predictive factor for VT/VF and death in hypertensive patients.37 A meta-analysis of 30 prospective studies (304,323 people) on diabetic patients conducted a risk assessment adjusting for several confounding factors (obesity index [body mass index (BMI)], waist-to-hip ratio, smoking, physical activity, alcohol intake, and resting heart rate), and potential intermediate risk factors (coronary artery disease, heart failure, AF, hypercholesteremia, hypertension, etc.), and reported that diabetes itself was a relatively high risk factor for sudden cardiac death.36 The reason is assumed to be that diabetes causes autonomic nervous system disorders that prolong QT and reduce heart rate variability (HRV), which may induce VT/VF. Recently, research has focused on the mechanism of sudden death in obstructive sleep apnea syndrome,38, 39 epileptic seizures,40, 41 and drug abuse,42 in which each pathology plays an independent role in the sudden death. ECG is recognized as the most important test alongside medical history and physical findings, and it is utilized not only to detect arrhythmia but also as part of risk assessment (Table 3). The 12-lead ECG is the most basic examination of the heart. The 12 leads are depicted from a total of 10 electrodes placed on the body surface, including 4 on the limbs and 6 on the chest. The limb leads (I, II, III, aVR, aVL, aVF) depict sagittal sections in vertical and horizontal directions, while the chest leads (V1–6) depict horizontal sections in the anterior–posterior and horizontal directions. Sometimes, a right anterior chest lead such as V3R or V4R and a high chest lead to the may be The 12-lead ECG is useful not only for heart disease but also for detecting findings such as ventricular block, and the of between QT that are associated with sudden prolongation has long been known as a predictive factor for the onset of of the at the end of the is used for risk assessment of right ventricular cardiomyopathy cardiomyopathy and Brugada of T-waves is of or T-waves are often in cardiomyopathy cardiomyopathy, and acute myocardial infarction. of T-waves is useful for the of patients with T-waves not during an (i.e., at are in cases of The interval by from the peak to the end of the indicates in repolarization and is used for risk assessment of various In the is not the interval is and T-waves with are in are often found in coronary artery diseases such as myocardial infarction, cardiomyopathy, and Brugada The incidence of sudden death is as high in with history of heart disease in both and compared with abnormalities in T-waves have also been useful predictive factors for sudden The diagnosis of disease types of Brugada syndrome is based on in the and this information is also used for risk The 12-lead ECG is useful for the diagnosis of The QT interval is on the 12-lead ECG lead or the and It is to using the or other similar sinus arrhythmia the mean of should be QT prolongation in patients with is by the of QT prolongation or QT with factors that cause QT QT prolongation with bradycardia is useful for the diagnosis of conditions such as the presence of AV with a or in T-waves with heart and the of on QT is defined as the between the and QT on a 12-lead which is an index of the of repolarization of the ventricular and are associated with the onset of ventricular arrhythmia and sudden cardiac death. The is often at 70 However, using QT as a clinical index has in years with the of other useful ECG repolarization is often in However, reported that an of the to is and there is little diagnostic in the In addition, an on the lower leads (I, III, I, or leads should be Recently, this finding has in to syndrome). The ECG is a lead ECG with mainly used in care and leads are leads may be used to but it is difficult to determine the vertical of the on a ECG the is increased or Therefore, ischemic be This type of ECG is often used to arrhythmias. The 12-lead ECG whereas the Holter ECG can with a detailed examination including the assessment of arrhythmia onset and activity of the autonomic nervous The is and the is only The electrodes are often leads to the chest. the Holter ECG a of and with to and arrhythmia, respectively. Recently, have been which can be used to during There have also been advances in analysis such that the Holter ECG is to ventricular potential QT and heart rate of which are useful for sudden cardiac death. The of the Holter ECG to detect ventricular tachycardia is useful for sustained A that the cause of sudden cardiac death during Holter ECG found the cause of death was and bradyarrhythmia in and 17% of cases, Although for detecting compared with exercise the Holter ECG for patients who are to an exercise such as and for infants, or for detecting supraventricular or ventricular arrhythmias in patients whose symptoms tend to be by electrocardiogram by an is often indicated when arrhythmia is not with a Holter There are various types of but they can be broadly divided into (1) and (2) (see Chapter for information on implantable The is placed on the chest during an and the ECG is by the this only indicated for patients with symptoms. Although it is used for patients to it is useful for the causal relationship between symptoms and are to the chest to the it is a from several to several to the can be There are also implantable (see Chapter This is also useful for detecting arrhythmia in asymptomatic in which arrhythmia and sudden death can be by exercise include and The 12-lead ECG is a basic test for which with abnormalities due to genetic However, of patients with with genetic have a at rest, and if QT is it often due to On the other hand, the 12-lead ECG is in patients with and there is no QT Therefore, a exercise test is the most useful test for has significant in the of ventricular arrhythmia in There is on the risk of exercise in patients with Brugada However, that and are independent for arrhythmia exercise should be to Chapter for detailed information on exercise in each is by may induce severe conduction disorders in patients with conduction disorders the of may be during exercise in patients with disease and main coronary artery disease, which are severe of ischemic heart disease. A large-scale cohort on asymptomatic with a follow-up clarified that frequent ventricular during exercise were associated with a risk of cardiovascular of cardiovascular disease in the Heart found that age and sex were associated with during exercise and the total rate was significantly increased during the heart rate during exercise is the result of the between of the nervous system and activation of the sympathetic nervous However, a of increase in the nerve exercise the heart rate recovery and as well as the incidence of death and coronary artery A compared the onset and increase in during exercise with those during recovery exercise in of using these to the risk of death. A exercise test was by patients with no history of heart failure, valvular heart disease, or during exercise recovery were more useful for the risk of death than during A or reduced response in patients with years of age during exercise tests is one of the major risk factors for sudden A that conducted exercise tests on young patients with a follow-up found that sudden death occurred in 12 patients and sudden death based on response had a of of predictive of and predictive of It was also found that response during in patients was associated with cardiovascular death, with a predictive of and a predictive of during a follow-up period of Heart rate can be from pulse by the on a It is also to detect AF by pulse (see Chapter for clinical The of h