Mechanism-based therapy of non-cardiac syncope: a practical guide.

The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.

Repeated Syncope Following COVID-19 Infection.

A 74-year-old woman presented to our hospital with syncope after a coronavirus disease 2019 (COVID-19) infection. Upon admission, she passed out, and an 8 second sinus arrest was detected during telemetry monitoring. During the next syncope episode, telemetry monitoring showed that her heart rate decreased from 80 to 36 bpm, accompanied by a 2.4 second pause. A permanent pacemaker was implanted; however, the patient still experienced syncope. The head-up tilt test revealed a vasodepressor reflex syncope. The need for permanent pacemakers in patients with syncope following COVID-19 therefore remains controversial.

Diagnosis and treatment of recurrent syncope in a middle-aged women.

A 50-year-old female patient, presented with repeated syncope for more than 2 years. Prior assessments were conducted at different hospitals, but no definite abnormalities were found. The patient's fear and anxiety about possible future attacks were escalating. Through a Head-up tilt test, the cause was finally identified as vasovagal syncope. Following a 5-min administration of nitroglycerin, the patient reported palpitations, nausea, and deep, rapid breathing. The electrocardiogram initially showed a first-degree atrioventricular block, progressing swiftly to a second-degree type I atrioventricular block-high atrioventricular block. Immediate intervention was undertaken, but blood pressure was not instantly ascertainable, coinciding with an abrupt loss of consciousness. Subsequent electrocardiographic findings included paroxysmal third-degree atrioventricular block, sinus arrest, and complete cardiac arrest, prompting the initiation of external cardiac compressions. The longest recorded ventricular arrest approximated 15 s, with sinus rhythm resuming post 10 s of cardiac compressions and the patient regaining consciousness. The patient underwent vagal ablation and no longer experienced syncope.

The Rate of Asystolic Reflex Syncope Is Not Influenced by Age.

BACKGROUND: The head-up tilt test (HUT) and other evidence suggest that the vagal effect on the heart decreases with age. OBJECTIVES: The main aim of the study was to assess whether this age effect also affects the rate of asystole in spontaneous reflex syncope (RS). METHOD: We performed an analysis of pooled individual data from 4 studies that recruited patients ≥40 years of age affected by certain or suspected RS who received an implantable loop recorder (ILR) and reported follow-up data on syncope recurrence. We assessed the presence of asystolic syncope of >3 seconds or nonsyncopal asystole of >6 seconds recorded by ILR and compared the findings to tilt test results on the same patients. RESULTS: A total of 1,046 patients received ILR because of unexplained syncope. Of these, 201 (19.2%) had a documentation of an asystolic event of 10-second (Q1-Q3: 6- to 15-second) duration. They were subdivided in 3 age tertiles: ≤60 years (n = 64), 61 to 72 years (n = 72), and ≥73 years (n = 65). The rate of asystolic events was similar in the 3 subgroups (50.1%, 50.1%, and 49.2%, respectively; P = 0.99). Conversely, the rate of asystolic syncope induced during HUT (performed in 169 of 201) was greatly age dependent (31.0%, 12.1%, and 11.1% in increasing age tertiles, respectively; P = 0.009). CONCLUSIONS: The rate of the spontaneous asystolic form of RS documented by ILR is constant at any age >40 years. Conversely, the rate of asystolic syncope induced by HUT is higher in younger patients and decreases with age. The contrasting results between spontaneous and tilt-induced events cast doubt on the concept that asystole in RS is less common in older patients.

The Role of Next-Generation Sequencing in the Management of Patients with Suspected Non-Ischemic Cardiomyopathy after Syncope or Termination of Sudden Arrhythmic Death.

Cardiac arrhythmias and sudden death are frequent in patients with non-ischemic cardiomyopathy and can precede heart failure or additional symptoms where malignant cardiac arrhythmias are mostly the consequence of advanced cardiomyopathy and heart failure. Finding these subgroups and making an early diagnosis could be lifesaving. In our retrospective study, we are presenting arrhythmic types of frequent cardiomyopathies where an arrhythmogenic substrate is less well defined, as in ischemic or structural heart disease. In the period of 2 years, next-generation sequencing (NGS) tests along with standard clinical tests were performed in 208 patients (67 women and 141 men; mean age, 51.2 ± 19.4 years) without ischemic or an overt structural heart disease after syncope or aborted sudden cardiac death. Genetic variants were detected in 34.4% of the study population, with a significant proportion of pathogenic variants (P) (14.4%) and variants of unknown significance (VUS) (20%). Regardless of genotype, all patients were stratified according to clinical guidelines for aggressive treatment of sudden cardiac death with an implantable cardioverter defibrillator (ICD). The P variant identified by NGS serves for an accurate diagnosis and, thus, better prevention and specific treatment of patients and their relatives. Results in our study suggest that targeted sequencing of genes associated with cardiovascular disease is an important addendum for final diagnosis, allowing the identification of a molecular genetic cause in a vast proportion of patients for a definitive diagnosis and a more specific way of treatment. VUS in this target population poses a high risk and should be considered possibly pathogenic in reanalysis.

Relationship between hemodynamic type and syncopal symptoms in pediatric vasovagal syncope.

Vasovagal syncope (VVS) is a clinically common neurally mediated syncope. The relationship between different hemodynamic types of VVS and clinical syncopal symptoms has not been reported. The purpose of this research is to explore relationship between hemodynamic types and syncopal symptoms in pediatric VVS. Two thousand five hundred thirteen patients diagnosed with VVS at the age of 3-18 years, average age was 11.76 ± 2.83 years, including 1124 males and 1389 females, due to unexplained syncope and pre-syncope from single-center of January 2001 to December 2021 were retrospectively analyzed. Subjects were divided into two groups according to the presence or absence of syncopal symptoms: syncope group (1262 cases) and pre-syncope group (1251 cases). (1) Baseline characteristics: age, height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) increased in the syncope group compared with the pre-syncope group; the composition ratio of females was more than that of males in the syncope group; and the composition ratio of VVS-cardioinhibited (VVS-CI) and VVS-mixed (VVS-M) was more in the syncope group than that of the pre-syncope group (all P < 0.05). (2) Univariate analysis: age, height, weight, SBP, DBP, female, VVS-CI, and VVS-M were potential risk factors for the presence of syncopal symptoms (all P < 0.05). (3) Multivariate analysis: VVS-CI and VVS-M were independent risk factors for the presence of syncopal symptoms, with an increased probability of 203% and 175%, respectively, compared to VVS-vasoinhibited (VVS-VI) (all P < 0.01). CONCLUSION: The hemodynamic type of pediatric VVS is closely related to the syncopal symptoms. WHAT IS KNOWN: • There are varying probabilities of syncopal episodes in different hemodynamic types of VVS, and there is a lack of research to assess the comparative risk of syncope in children with different hemodynamic types of VVS. WHAT IS NEW: • The probability in presence of syncopal symptoms varies greatly between different hemodynamic types of VVS. • VVS-CI and VVS-M had a 203% and 175% increased risk in presence of syncopal symptoms compared with VVS-VI, respectively.

Tilt table testing, methodology and practical insights for the clinic.

Tilt table testing (TTT) has been used for decades to study short-term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence-based practice syncope guidelines, proper application and interpretation of TTT in the day-to-day care of syncope patients remain challenging. In this review, we offer practical information on what is needed to perform TTT, how results should be interpreted including the Vasovagal Syncope International Study classification, why syncope induction on TTT is necessary in patients with unexplained syncope and on indications for TTT in syncope patient care. The minimum requirements to perform TTT are a tilt table with an appropriate tilt-down time, a continuous beat-to-beat BP monitor with at least three electrocardiogram leads and trained staff. We emphasize that TTT remains a valuable asset that adds to history building but cannot replace it, and highlight the importance of recognition when TTT is abnormal even without syncope. Acknowledgement by the patient/eyewitness of the reproducibility of the induced attack is mandatory in concluding a diagnosis. TTT may be indicated when the initial syncope evaluation does not yield a certain, highly likely, or possible diagnosis, but raises clinical suspicion of (1) reflex syncope, (2) orthostatic hypotension (OH), (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT in the patient with a certain, highly likely or possible diagnosis of reflex syncope, may be to educate patients on prodromes. In patients with reflex syncope with OH TTT can be therapeutic to recognize hypotensive symptoms causing near-syncope to perform physical countermanoeuvres for syncope prevention (biofeedback). Detection of hypotensive susceptibility requiring therapy is of special value.

Cardioneuroablation for reflex asystolic syncope: Mid-term safety, efficacy, and patient's acceptance.

BACKGROUND: Cardioneuroablation (CNA) is a promising therapy for reflex asystolic syncope; however, convincing data on the mid-term safety and efficacy of this procedure are lacking. OBJECTIVE: The purpose of this study was to assess the mid-term safety, efficacy, and patient acceptance of CNA. METHODS: This prospective observational single-center study included 115 consecutive patients (mean age 39 ± 13 years; 58% female) treated between 2016 and 2022 who completed at least 1-year follow-up. RESULTS: No significant procedure-related acute complications occurred. During median follow-up of 28 months (range 12-75), 95 (83%) remained free from syncope. Of the 20 patients (17%) with syncope recurrence, syncope burden decreased from a mean 17 (median 6.5) to 3.75 (median 2.5) episodes (P = .015). In 9 of 10 patients, pacing system removal was possible. Repeated CNA was needed in 3 patients (3%), whereas pacemaker implantation was performed in 5 (4%). The most frequent mid-term complication of CNA was sinus rhythm acceleration (from 60 ± 14 bpm to 90 ± 16 bpm; P <.0001), which was symptomatic in 31 patients (27%); 8 patients (7%) required chronic beta-blocker and/or ivabradine. Sinus node modification was necessary in 1 patient. Other complaints included dyspnea, chronic chest pain, and decreased exercise capacity, which were mild and reported by 16 patients (14%). Patient acceptance of CNA was very high: 96% stated that it was worth undergoing the procedure. CONCLUSIONS: Mid-term efficacy of CNA exceeds 80%, and acute complications are absent. The most frequent mid-term chronic complication is inappropriate sinus tachycardia, which in 7% required chronic treatment. The procedure is well accepted by patients.

How to recognize pulmonary embolism in syncope patients: A simple rule.

BACKGROUND: Syncope can be the presenting symptom of Pulmonary Embolism (PE). It is not known wether using a standardized algorithm to rule-out PE in all patients with syncope admitted to the Emergency Departments (ED) is of value or can lead to overdiagnosis and overtreatment. METHODS: We tested if simple anamnestic and clinical parameters could be used as a rule to identify patients with syncope and PE in a multicenter observational study. The rule's sensitivity was tested on a cohort of patients that presented to the ED for syncopal episodes caused by PE. The clinical impact of the rule was assessed on a population of consecutive patients admitted for syncope in the ED. RESULTS: Patients were considered rule-positive in the presence of any of the following: hypotension, tachycardia, peripheral oxygen saturation ≤ 93 % (SpO2), chest pain, dyspnea, recent history of prolonged bed rest, clinical signs of deep vein thrombosis, history of previous venous thrombo-embolism and active neoplastic disease. The sensitivity of the rule was 90.3 % (95 % CI: 74.3 % to 98.0 %). The application of the rule to a population of 217 patients with syncope would have led to a 70 % reduction in the number of subjects needing additional diagnostic tests to exclude PE. CONCLUSIONS: Most patients with syncope due to PE present with anamnestic and clinical features indicative of PE diagnosis. A clinical decision rule can be used to identify patients who would benefit from further diagnostic tests to exclude PE, while reducing unnecessary exams that could lead to over-testing and over-diagnosis.

The relationship between demographic factors and syncopal symptom in pediatric vasovagal syncope.

This research proposed to retrospectively analyze 20 years of clinical data and investigate the relationship between demographic factors and syncopal symptom in pediatric vasovagal syncope. A total of 2513 children, 1124 males and 1389 females, age range 3-18 years, who presented to Department of Pediatric Cardiovasology, Children's Medical Center, The Second Xiangya Hospital, Central South University with unexplained syncope or pre-syncope and were diagnosed with vasovagal syncope were retrospectively collected and divided into syncope group (n = 1262) and pre-syncope group (n = 1251). (1) Females had a 36% increased risk of syncope compared to males, a 27% increased risk of syncope for every 1-year increase in age, and a 2% decreased risk of syncope for every 1 cm increase in height. (2) A non-linear relationship between age, height, weight and syncope was observed. When age > 10.67 years, the risk of syncope increases by 45% for each 1-year increase in age; when height < 146 cm, the risk of syncope decreases by 4% for each 1 cm increase in height; when weight < 28.5 kg, the risk of syncope decreases by 10% for each 1 kg increase in weight. Demographic factors are strongly associated with syncopal symptom in pediatric vasovagal syncope and can help to predict the risk.

Dynamic changes in T-wave and QTc interval during tilt table testing: Innocent until proven otherwise.

A16-year-old female underwent tilt table testing, which resulted positive for reflex vasodepressive syncope. 12­lead ECG during syncope showed T-wave inversion in infero-lateral leads, along with QTc interval increase >100 msec compared to baseline. These abnormalities rapidly disappeared in supine position with resumption of consciousness. Complete cardiac evaluation excluded heart disease. T-wave changes and moderate QTc prolongation are relatively common in young (mainly female) patients undergoing tilt table testing and they appear benign in nature. However, in a minority of cases, on the basis of the clinical context and after an accurate ECG analysis, further examinations may be warranted.

Brain MRI and EEG overemployment in patients with vasovagal syncope: results from a tertiary syncope unit.

BACKGROUND: The diagnosis of vasovagal syncope (VVS) is mainly based on history-taking and physical examination. However, brain Magnetic Resonance Imaging (MRI) and Electroencephalogram (EEG) are commonly used in the diagnostic course of VVS, despite not being indicated in the guidelines. This study aims to find the possible associated factors with the administration of brain MRI and EEG in patients with VVS. METHODS: Patients with a diagnosis of VVS from 2017 to 2022 were included. Several demographic and syncope features were recorded. The association of these was assessed with undergoing MRI, EEG, and either MRI or EEG. Univariate and multivariable logistic regression models were also used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 1882 patients with VVS were analyzed, among which 810 underwent MRI (43.04%), 985 underwent EEG (52.34%), and 1166 underwent MRI or EEG (61.96%). Head trauma (OR 1.38, 95% CI 1.06 to 1.80), previous neurologist visit (OR 6.28, 95% CI 4.24 to 9.64), and gaze disturbance during syncope (OR 1.75, 95% CI 1.13 to 2.78) were all positively associated to the performance of brain MRI/EEG. Similar results were found for urinary incontinence (OR 2.415, 95% CI 1.494 to 4.055), amnesia (OR 1.421, 95% CI 1.053 to 1.930), headache after syncope (OR 1.321, 95% CI 1.046 to 1.672), and tonic-clonic movements in head-up tilt table test (OR 1.501, 95% CI 1.087 to 2.093). However, male sex (OR 0.655, 95% CI 0.535 to 0.800) and chest pain before syncope (OR 0.628, 95% CI 0.459 to 0.860) had significant negative associations with performing brain MRI/EEG. CONCLUSION: Based on our findings, performing MRI or EEG was common among VVS patients while it is not indicated in the majority of cases. This should be taken into consideration to prevent inappropriate MRI/EEG when there is a typical history compatible with VVS.

Selected biomarkers of orthostatic intolerance.

Orthostatic intolerance (OI) is defined as a group of diseases which symptoms are typically manifested in a standing position. These symptoms result from cerebral hypoperfusion and disappear in the supine position. We include postural orthostatic intolerance syndrome (POTS), orthostatic hypotension (OH) and vasovagal orthostatic syncope in this group of diseases. Each of them have similar clinical presentation (blurred vision, weakness, dizziness, nausea, headaches, fatigue). However, they vary from each other in biochemical, autonomic and hemodynamic characteristics. The aim of the work is to provide an overview of humoral and non-human markers that are involved in the etiopathogenesis of orthostatic intolerance.

Tilt testing.

Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving sublingual nitroglycerine after 15 min, while monitoring beat-to-beat blood pressure (BP) and recording on video. Tilt testing is time-consuming but it is clinically useful and can guide therapy. Complications are rare. Syncope types include vasovagal syncope where BP falls after >3 min of tilt-up and later the heart rate falls; classic orthostatic hypotension where there is an immediate, progressive BP fall with minimal heart rate change; delayed orthostatic hypotension with a late BP fall after a stable phase but little or no heart rate rise; psychogenic pseudosyncope with apparent loss of consciousness, but no BP fall and a moderate heart rate rise; and postural orthostatic tachycardia syndrome where there is a significant heart rate rise but no BP fall.

Clinical features and response at head-up tilt test of patients with situational syncope.

OBJECTIVE: The study compared clinical characteristics and response at head-up tilt test (HUTT) between situational (SS) and vasovagal syncope (VVS). METHODS: Consecutive patients who underwent nitroglycerin-potentiated HUTT were retrospectively dichotomised into two groups: those with a history of SS and those with a history of VVS. The patients with SS were further subdivided into patients with SS alone and with SS and at least one episode of VVS. RESULTS: 1285 patients were enrolled: 246 (19.1%) had SS (SS alone in 121 and SS+VVS in 125). Patients with SS were older (48.8±20.0 vs 44.4±19.1, p=0.007) and more frequently male (57.3% vs 47.7%, p=0.001). At multivariable analysis, smoking habit (OR 2.28; p<0.0001), history of traumatic syncope (OR 2.29; p=0.0001) and ACE inhibitors/angiotensin II receptor blockers (OR 4.74; p<0.0001) were independently associated with SS. HUTT was positive in 175 (71.1%) patients with SS and in 737 (70.9%) patients with VVS (p=0.9). Patients with SS showed more mixed (42.3% vs 32.0%, p=0.002) and vasodepressor forms (10.6% vs 6.1%, p=0.01) and less cardioinhibitory responses compared with others (18.3% vs 32.8%, p<0.0001). CONCLUSIONS: Compared with VVS, patients with SS have different clinical characteristics and a higher prevalence of hypotensive drugs leading to hypotensive susceptibility. The positivity rate of HUTT is high and similar to that of VVS, although patients with SS show a higher prevalence of hypotensive responses.

Twenty-five years of research on syncope.

Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.

Definitive aetiology of unexplained syncope after cardiovascular autonomic tests in a tertiary syncope unit.

AIMS: Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. METHODS AND RESULTS: Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. CONCLUSION: A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.

[Neurally mediated syncope starting in young or in old age: different prognostic significance?] / La sincope neuromediata ad esordio nel giovane o nell'anziano: diverso significato prognostico?

Neurally mediated syncope (NMS) is the clinical manifestation of the vasovagal reflex activation. Prognosis of this type of syncope is reported as "benign", mainly on the basis of the results of the Framingham study, in which the incidence of mortality, cardiovascular and cerebrovascular events did not differ from that of the control population. However, in this study NMS starting in young age and that starting in advanced age were investigated together, but some elements suggest that we are dealing with two different clinical entities, even if the efferent pathways of the reflex circuit appear to be the same. While it is largely accepted that NMS starting in young age is a manifestation of a non-pathological trait, some lines of evidence suggest that NMS starting in old age is the expression of a pathological process of the autonomic nervous system, up to now not well defined from the nosological point of view: (i) onset in old age per se, (ii) absence of triggers, which means "abnormal activation" (pathological) of the vasovagal reflex, (iii) frequent overlap with situational syncope, carotid sinus hypersensitivity, orthostatic or post-prandial hypotension and other dysautonomic symptoms, and (iiii) it appears to be the human homologue of a recently described syncope starting in dogs in advanced age; in other words, humans and dogs seem to suffer from the same disease. On the basis of these considerations, in future studies the prognostic significance of NMS starting in old age should be investigated separately. At present, the prognosis of NMS, in relation to hard events, remains undefined in the elderly.

A framework to simplify paediatric syncope diagnosis.

This paper aims to improve the diagnosis of syncope and transient loss of consciousness (TLOC) in children. Diagnostic problems stem, first, from some causes spanning various disciplines, e.g. cardiology, neurology and psychiatry, while the most common cause, vasovagal syncope, is not embraced by any specialty. Second, clinical variability is huge with overlapping signs and symptoms. Third, the approach to TLOC/syncope of the European Society of Cardiology (ESC) is underused in childcare. We explain the ESC guidelines using an additional paediatric literature review. Classification of TLOC and syncope is hierarchic and based on history taking. Loss of consciousness (LOC) is defined using three features: abnormal motor control including falling, reduced responsiveness and amnesia. Adding a < 5 min duration and spontaneous recovery defines TLOC. TLOC simplifies diagnosis by excluding long LOC (e.g. some trauma, intoxications and hypoglycaemia) and focussing on syncope, tonic-clonic seizures and functional TLOC. Syncope, i.e. TLOC due to cerebral hypoperfusion, is divided into reflex syncope (mostly vasovagal), orthostatic hypotension (mostly initial orthostatic hypotension in adolescents) and cardiac syncope (arrhythmias and structural cardiac disorders). The initial investigation comprises history taking, physical examination and ECG; the value of orthostatic blood pressure measurement is unproven in children but probably low. When this fails to yield a diagnosis, cardiac risk factors are assessed; important clues are supine syncope, syncope during exercise, early death in relatives and ECG abnormalities.  Conclusions: In adults, the application of the ESC guidelines reduced the number of absent diagnoses and costs; we hope this also holds for children. What is Known: • Syncope and its mimics are very common in childhood, as they are at other ages. • Syncope and its mimics provide considerable diagnostic challenges. What is New: • Application of the hierarchic framework of transient loss of consciousness (TLOC) simplifies diagnosis. • The framework stresses history-taking to diagnose common conditions while keeping an eye on cardiac danger signs.