Syncope is a common clinical condition, accounting for 1% to 1.5% of patients in the emergency department and 1% to 6% of hospitalized patients. The causes of syncope are numerous, the mechanisms are complex and involve multiple disciplines. The prognosis of syncope varies widely from a benign process in most patients to the consequences of sudden death in a minority of patients; therefore, it is crucial to identify patients with syncope among the many patients with transient loss of consciousness and to clarify the classification of syncope. In recent years, there have been some new concepts in the international assessment of syncope, emphasizing the assessment of patients with syncope in two ways: first, to identify the exact cause for effective treatment targeting the pathological mechanism; second, to identify the patient’s risk, which often depends on the underlying disease rather than on the syncope itself. 1. Identifying syncope among the many patients with transient loss of consciousness Patients with transient loss of consciousness (T-LOC) include all clinical conditions characterized by self-limiting loss of consciousness due to various mechanisms, and syncope is one form of T-LOC (Figure 1). Syncope refers to T-LOC due to transient whole brain tissue ischemia and is characterized by a loss of consciousness that occurs rapidly, is brief, self-limiting, and capable of complete recovery. A T-LOC that satisfies these 4 characteristics is syncope. First, syncope like disorders without loss of consciousness, such as fall episodes, psychogenic pseudosyncope and carotid system ischemia should be excluded. Second, diseases with partial or complete loss of consciousness without cerebrovascular hypoperfusion, such as epilepsy, metabolic diseases including hypoglycemia, hypoxemia, hyperventilation with hypocapnia, and toxicity should be excluded. The diagnosis of transient ischemic attack in the posterior circulatory system as syncope is currently a matter of differing opinion. An important component of the differential diagnosis of syncope is seizures, which can cause T-LOC in which the patient is unresponsive, falls, and then forgets, a condition that occurs only with tonic, clonic, tonic burst, and generalized seizures. In children aphasic seizures and adults with partial complex epilepsy manifest as a change in consciousness rather than loss. Complete relaxation of the body during unconsciousness does not support epilepsy, the only exception being “flaccid seizures”, which are rare. Children with preexisting neurological disease may have no trigger. Both epileptic and syncopal seizures can be accompanied by limb movements. The movements can last for more than a minute in epilepsy and a few seconds in syncope. The convulsions in epileptic seizures are coarse, rhythmic, and generally synchronized, whereas syncopal seizures are generally asynchronous, small in amplitude, and rhythmless. However, synchronous clonus can also occur in patients with syncope. Spasmodic movements in patients with syncope occur only after the onset of loss of consciousness and after a fall, unlike in patients with epilepsy. Syncope usually has a trigger, whereas epilepsy has fewer triggers. Triggers for reflex epilepsy such as flashing lights are different from syncope. Typical seizure aura includes abnormal abdominal sensations and/or rare unpleasant smells. Sensory abnormalities occur rarely in patients with syncope. Seizures often occur with tongue biting, usually on the side of the tongue, whereas syncope is usually on the tip of the tongue. Urinary incontinence may occur in both. Patients may be in a confused state for a longer period of time after a seizure, whereas patients are usually clear-headed immediately after a syncopal seizure (Table 1). Headache, muscle pain, elevated creatine kinase and prolactin are often present after a seizure. 2. Strive to clarify the etiology and pathogenesis of syncope Table 2 lists the classification of syncope based on the main etiology and pathophysiology, emphasizing that syncope presents with the same but different risks. The pathophysiology is characterized by a decrease in blood pressure in the body circulation with a decrease in cerebral blood flow, which is the basis for the pathogenesis of syncope. Interruption of cerebral blood flow for 6-8 seconds is sufficient to cause complete LOC. experience from tilt tests has shown that systolic blood pressure of 60 mmHg is sufficient to cause syncope. Systolic blood pressure is determined by cardiac output (CO) and total peripheral vascular resistance, and a decrease in either can cause syncope, both of which are often present at the same time, but with different magnitudes of effect. Recently, it has been proposed that the determination of the etiologic classification should be followed by the pathogenic classification. For example, bradycardia can be caused by both reflex syncope and lesions of the cardiac conduction system or organic heart disease; on the other hand, syncope caused by one etiology may have different mechanisms, a typical example being vasovagal syncope (VVS), which can cause both bradycardia and It can cause both bradycardia and hypotension. The use of these two classifications allows for a better diagnosis and management of the patient. It is generally accepted that vasovagal syncope is the most important cause of syncope. Cardiogenic syncope is the second leading cause, and the incidence of cardiogenic syncope is higher in hospitalized elderly patients. Syncope due to postural hypotension is less common in patients younger than 40 years of age. Syncope due to postural hypotension is mostly seen in older adults. Reflex syncope is the most common cause of syncope in the younger population; older patients are usually more complex and have a less reliable medical history than the younger population. The Calgary Score is currently used internationally to diagnose VV and consists of 7 questions regarding history, triggers, environment, signs and symptoms of T-LOC (Table 3). All questions were answered as “yes” or “no”. If a question was answered “yes,” points were added or subtracted depending on whether the answer increased the likelihood of VVS. The scores for each question were added together to obtain a total score (range: -14 to +6 points). If the total score was -2 or greater than -2, VVS was diagnosed.c The sensitivity of the Calgary score for diagnosing VVS was 87% (95% CI: 82% to 91%) and the specificity was 32% (95% CI: 24% to 40%). 3. Diagnostic process and risk stratification An initial assessment is required for patients with suspected syncope in T-LOC, and a reassessment is required if necessary. The etiology of syncope can be clarified in about 23% to 50% of patients with syncope by initial assessment, and for patients with unknown cause it is important to risk stratify. The process of syncope diagnosis is shown in Figure 3. 3.1 Preliminary assessment The preliminary assessment includes detailed history taking, physical examination (including measurement of blood pressure in different positions), and ECG. On this basis, other tests can be added as appropriate to ensure accurate diagnosis: ① Carotid sinus massage is recommended first for patients over 40 years of age (but rarely done in China); ② Echocardiography is recommended for patients with a history of heart disease or who suspect that this syncope is related to structural heart disease or other cardiovascular diseases; ③ Real-time ECG monitoring should be given to patients suspected of syncope due to arrhythmias; ④ If syncope is related to postural changes or when reflex syncope is suspected, relevant tests should be performed. such as prone position test and/or upright tilt test; ⑤ Neurological examination or blood tests only if a non-syncopal cause of transient loss of consciousness is suspected. The initial evaluation should clarify the following three key questions: ① Is it a syncopal episode? (ii) Is the cause of the syncope identifiable? (iii) Is there evidence that the patient is at high risk for cardiovascular disease? 3.2 Etiological diagnosis After the initial assessment, the etiology of syncope can be clarified in about 23% to 50% of patients with syncope. Table 4 lists the clinical features that are meaningful for diagnosis after the initial evaluation. Diagnoses that can be obtained by preliminary evaluation: (1) vasovagal syncope: syncope caused by sudden mental stimulation or uprightness, or accompanied by typical syncopal precursors. (2) Situational syncope: syncope occurs during or rapidly after a specific triggering event or situation. (3) Upright syncope: syncope induced by standing and a previous history of postural hypotension. (4) Diagnostic criteria for arrhythmia-related syncope with the following electrocardiographic manifestations: ① persistent sinus bradycardia <40 beats/min in the awake state, or recurrent sinus block or sinus arrest ≥3 seconds. (ii) Mohs II type II or III atrioventricular block. ③ alternating left bundle branch and right bundle branch conduction block. ④Ventricular tachycardia or tachy-type paroxysmal supraventricular tachycardia. ⑤ Non-sustained polymorphic ventricular tachycardia and long QT or short QT interval syndrome. (6) Pacemaker or ICD malfunction with cardiac arrest. (5) Cardiac ischemia-related syncope: syncope with ECG manifestations of acute myocardial ischemia with or without myocardial infarction. (6) Cardiovascular syncope: syncope occurs in patients with atrial mucosal aneurysm, severe aortic stenosis, pulmonary hypertension, pulmonary embolism, or acute aortic coarctation. 3.3 Risk stratification When the cause of syncope is not clear after the initial assessment, immediate assessment of the risk of major cardiovascular events and sudden cardiogenic death is required. Immediate risk (7 to 30 days): Patients at risk of a life-threatening event in the near future after syncope should be hospitalized. Short-term risk factors are identified in the Society Statement on Standard Protocols for the Evaluation of Syncope published by the Canadian Cardiovascular Society in 2011. Primary risk factors refer to independent risk factors reported in multiple studies, and secondary risk factors refer to risk factors reported in one study. Patients with one major risk factor for syncope should have an urgent (within 2 weeks) cardiac evaluation, and patients with one or more minor risk factors should also be considered for urgent cardiac evaluation. The 2009 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of syncope list short-term risk factors that are more detailed than those proposed by the Canadian Cardiovascular Society, but they are essentially the same. Both suggest that patients with risk factors for syncope should be actively managed to prevent cardiovascular events, especially sudden cardiac death. In summary, patients with loss of consciousness or suspected syncope should first be identified as syncope, and the second step is to find the cause of syncope. For unexplained syncope, it is important to risk stratification. Patients with unexplained syncope with high-risk factors and those who have been clearly identified as cardiogenic syncope should be actively diagnosed and treated. Most patients with reflex syncope have a good prognosis and do not require tedious investigations and usually no drug therapy.