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

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).

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.

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 cardiac electrophysiological study (EPS) is a general term for studies that analyze local potential information and positional information of electrodes on catheters inserted transvascularly into the heart chamber by cardiac catheterization procedures. An EPS analyzes the characteristics of arrhythmia induction and intracardiac conduction patterns, including programmed stimulation of various regions of the myocardium, as well as intravenous loading of agonists and antiarrhythmic drugs of the autonomic nervous system.² It is also used for diagnosis, including identification of the mechanisms underlying arrhythmia, identification of optimal sites for catheter ablation (hereinafter referred to as ablation), determination of therapeutic effect, and risk determination, including sudden cardiac death.^{2, 132} In contrast to static diagnostic methods using long-term observation such as Holter ECG and implantable loop recorder (ILR), the EPS is dynamic and aims to actively reproduce the pathology, similar to exercise stress and standing load tests.^{2, 4, 132, 133}

The role of the EPS in arrhythmia treatment has changed significantly with advances in non-pharmacotherapy. Its main role has been to identify optimal ablation sites, with the rapid advances in ablation for tachyarrhythmia, but it is now also used to assess the risk of fatal VT/VF from the perspective of preventing sudden death.^{2, 4, 8, 132, 133} Table 4 shows the standard assessment methods for assessing the severity of major arrhythmias,^{2, 132} and Table 5 shows the Class of Recommendation and Level of Evidence.

Many cases of sudden cardiac death are caused by fatal arrhythmias such as AF and VT. The presence of negative factors, such as cardiac dysfunction, genetic abnormalities, depolarization or repolarization abnormalities, and abnormalities in autonomic nervous system activity, form the background to the development of these types of arrhythmias (Figure 4). To prevent sudden cardiac death, it is important to detect these abnormal factors beforehand and to treat affected patients in advance. Test markers that detect abnormal factors are called predictive indices. However, no universal index has yet been defined. Not only the characteristics, but also the examination procedures, measurements, and applicable diseases all differ slightly in each individual, and, depending on the patient or disease, some factors cannot be assessed. Therefore, it is essential to understand and utilize these factors.

Typical tests to detect abnormal factors include LVEF measured by diagnostic imaging such as echocardiography, and inducibility of ventricular arrhythmia by cardiac EPS. However, although the indices of cardiac electrophysiology tests are measured non-invasively and are also used clinically, they are not as effective as LVEF. Indices include ventricular LP,^{246, 247} TWA,²⁴⁸ T-wave variability (TWV),^{247, 249} QT/RR slope, HRV index, HRT,²⁵⁰ and deceleration capacity (DC)²⁵¹ (Table 9). All the predictive indices shown in this guideline can be measured using ECG devices sold in Japan. The Class of Recommendation and Level of Evidence for risk assessment of cardiac events are shown in Table 10.

Please refer to the Japanese Society of Pediatric Cardiology and Cardiac Surgery guidelines regarding the management of school activities for children with arrhythmia but without underlying organic heart disease.³²⁴ The present guideline provides information on strategies for adults. The intensity of exercise or physical activity is expressed in metabolic equivalents of task (METs).^{325, 326} The MET standard is defined as 1 MET, which is equivalent to 1.0 kcal (4.184 kJ)/kg/h, based on the ratio of the working metabolic rate to the resting metabolic rate of a person.^{325, 326} The intensity of physical activity is classified light (<3 METs), moderate (<6 METs), and vigorous (≥6 METs). Undertaking ≥30 min of moderate aerobic exercise for ≥2.5 h/week, ≥20 min of vigorous exercise for ≥75 min/week, or a combination of moderate and vigorous exercise corresponding to 500–1,000 METs/min weekly prevents cardiovascular diseases and provides health benefits, which can be expected to inhibit the onset of arrhythmia.^{327, 328} On the other hand, a person who does not exercise regularly and suddenly starts to exercise, especially vigorous exercise, has a risk of experiencing adverse events, including arrhythmia.^{328, 329}

When considering exercise for arrhythmias, it must first be considered whether there is any underlying heart disease. There are patients with underlying diseases such as myocardial infarction, cardiomyopathy, heart failure, and a history of surgery for congenital heart disease in whom the arrhythmic substrate (structural and/or histological abnormalities in the myocardium) is the cause of the arrhythmia, and other patients in whom changes in cardiovascular dynamics associated with exercise trigger arrhythmia. When there is an underlying heart disease, exercise therapy can be expected to prevent deterioration or progression of the arrhythmic substrate by improving myocardial ischemia and suppressing the sympathetic nervous system. Table 12 shows the Class of Recommendation and Level of Evidence for exercise tolerance in patients with arrhythmia.

The Class of Recommendation and Level of Evidence for risk assessment of imaging tests for sudden cardiac death are shown in Table 40.