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.

Bradycardia risk stratification with implantable loop recorder after unexplained syncope.

BACKGROUND: An implantable loop recorder is an effective tool for diagnosing unexplained syncope. However, after a first episode in non-high-risk patients, the usefulness of implantable loop recorder implantation remains unclear. AIMS: To analyse relevant risk factors for significant bradycardia in order to identify patients who do or do not benefit from implantable loop recorder implantation. Also, to study whether implantable loop recorder implantation with remote monitoring is associated with less recurrence of traumatic syncope. METHODS: This was a retrospective monocentric study including patients with implantable loop recorder implantation after unexplained syncope, using remote monitoring and iterative consultations. RESULTS: Two hundred and thirty-seven patients were implanted for unexplained syncope. Significant bradycardia occurred in 53 patients (22.4%): 23 (43.4%) caused by paroxysmal atrioventricular block and 30 (56.6%) caused by sinus node dysfunction, leading to permanent pacemaker implantation in 48 patients. Compared with younger patients, there was a 3.46-fold increase (95% confidence interval 1.92-6.23; P<0.0001) in the risk of significant bradycardia in patients aged≥60 years. Based on multivariable analysis, only "typical syncope" was associated with significant bradycardia occurrence (hazard ratio 3.14, 95% confidence interval 1.75-5.65; P=0.0001). There was no recurrence of significant bradycardia with traumatic complications among patients implanted for traumatic syncope. CONCLUSIONS: This study shows that: (1) implantable loop recorders identify more significant bradycardia in patients aged≥60 presenting with a first non-high-risk typical syncope, suggesting that an implantable loop recorder should be implanted after a first episode of unexplained syncope in such conditions; and (2) after traumatic syncope, implantable loop recorder implantation is safe, and is associated with little or no recurrence of traumatic syncope.

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.

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.

Convulsive Syncope as a Complication of Outpatient Procedures: A Case Series and Review of the Literature.

ABSTRACT: Sports medicine providers often perform various outpatient procedures to manage musculoskeletal and neuropathic conditions. Vasovagal syncope is a rare but a possible complication. Convulsive syncope is one subtype that involves brief extensor stiffening and nonsustained myoclonus and can be easily mistaken for seizures. We present a case series of convulsive syncope as a complication of common sports medicine outpatient procedures. We aim to describe how to identify this condition, and offer risk stratification and management strategies to mitigate the risks of this complication. Sports medicine providers who routinely practice outpatient procedures should be aware of this complication. Simple changes in approaching the procedure may mitigate these risks. High- and intermediate-risk features of the syncopal episode should prompt physicians to seek further evaluation by a specialist to rule out more serious conditions. In all instances, appropriate on-site support and equipment for emergent resuscitation and management should be prepared.

Management of syncope in the Emergency Department: a European prospective cohort study (SEED).

BACKGROUND AND IMPORTANCE: In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe. OBJECTIVES: To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope). DESIGN: Prospective, multicentre, observational cohort study. SETTINGS AND PARTICIPANTS: Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin. MAIN RESULTS: Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3-88.9%), use of an observation/decision unit (0-100%), and percentage high-risk (64.8-88.9%) varies widely between countries. CONCLUSION: This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.

Artificial Intelligence in Enhancing Syncope Management - An Update.

This review looks into the use of Artificial Intelligence (AI) in the management of syncope, a condition characterized by a brief loss of consciousness caused by cerebral hypoperfusion. With rising prevalence, high costs, and difficulty in diagnosis and risk stratification, syncope poses significant healthcare challenges. AI has the potential to improve symptom differentiation, risk assessment, and patient management. Machine learning, specifically Artificial Neural Networks, has shown promise in accurate risk stratification. AI-powered clinical decision support tools can improve patient evaluation and resource utilization. While AI holds great promise for syncope management, challenges such as data quality, class imbalance, and defining risk categories remain. Ethical concerns about patient privacy, as well as the need for human empathy, complicate AI integration. Collaboration among data scientists, clinicians, and ethics experts is critical for the successful implementation of AI, which has the potential to improve patient outcomes and healthcare efficiency in syncope management.

'Size it and fix it': pulsatile abdomen and presyncope post pacemaker implantation.

A 69-year-old obese man who had undergone permanent pacemaker implantation (VVIR, Medtronic) 3 weeks prior presented with a one-day history of experiencing continued, forceful pulsations in his abdomen followed by presyncope.

Serotonin reuptake inhibition for the prevention of vasovagal syncope: a systematic review and meta-analysis.

PURPOSE: Vasovagal syncope is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that serotonin-specific reuptake inhibitors might suppress vasovagal syncope but supporting studies have been small and heterogenous. The purpose of this study was to evaluate the efficacy of serotonin-specific reuptake inhibitors to prevent syncope in patients with recurrent vasovagal syncope by conducting a systematic review and meta-analysis of published studies. METHODS: Relevant randomized controlled trials were identified from the MEDLINE and Embase databases without language restriction from inception to August 2022, and ClinicalTrials.gov. All studies were conducted in clinical syncope populations and compared the benefit of serotonin versus placebo. Weighted relative risks were estimated using random effects meta-analysis techniques. RESULTS: Three studies (n = 204) met inclusion criteria. Patients were 42 ± 13 years of age and 51% female. Serotonin-specific reuptake inhibitors were found to substantially reduce the likelihood of a patient having at least one recurrence of vasovagal syncope [relative risk (RR) 0.34 (0.20-0.60), p < 0.01] with minimal between-study heterogeneity (I2 = 0%, p = 0.67). Serotonin-specific reuptake inhibitors in two reports provided significant protection against clinical presyncope [RR 0.43 (0.24-0.77), p < 0.01], with minimal between-study heterogeneity (I2 = 0%, p = 0.80). CONCLUSIONS: Serotonin-specific reuptake inhibitors may be effective in preventing syncope induced by head-up tilt testing and in syncope in the community in randomized, double-blinded clinical trials.

High spinal cord injury precipitating syncope: a rare indication for pacemaker insertion.

The current evidence for vasovagal syncope management is that cardiac pacing is only indicated in a highly select group of patients where symptoms can be linked to bradycardic episodes. High spinal cord injury can lead to autonomic dysfunction and sympathetic nervous system hypoactivity. A high spinal cord injury can theoretically precipitate profound bradycardia leading to haemodynamic instability and syncope. A patient in his 50s with a history of C2 spinal injury was admitted to our tertiary centre for management of what was initially thought to be septic shock causing hypotension and syncope. With evidence to suggest this patient's presentation may be profound reflex syncope in the context of unopposed parasympathetic signalling, consensus was reached to implant a permanent pacemaker. Remarkably, the patient's haemodynamics stabilised and there were no further episodes of syncope.

Patient factors associated with conveyance decision-making by Emergency Medical Services professionals in patients with a syncope: a cross-sectional factorial survey design.

BACKGROUND: The clinical decision-making of non-conveyance is perceived as complex and difficult by emergency medical services (EMS) professionals. Patients with a transient loss of consciousness (TLOC) based on syncope constitute a significant part of the non-conveyance population. Risk stratification is the basis of the clinical decision-making process by EMS professionals. This risk stratification is based on various patient factors. This study aimed to explore patient factors significantly associated with conveyance decision-making by EMS professionals in patients with a TLOC based on syncope. METHODS: A cross-sectional vignette study with a factorial survey design was conducted. Patient factors were derived from the "National Protocol Ambulance Care", and all possible combinations of these factors and underlying categories were combined, resulting in 256 unique vignettes (2*4*4*4*2 = 256). Patient factors presented either low-risk or high-risk factors for adverse events. Data were collected through an online questionnaire, in which participants received a random sample of 15 vignettes. For each vignette, the respondent indicated whether the patient would need to be conveyed to the emergency department or not. A multilevel logistic regression analysis with stepwise backward elimination was performed to analyse factors significantly associated with conveyance decision-making. In the logistic model, we modelled the probability of non-conveyance. RESULTS: 110 respondents were included, with 1646 vignettes being assessed. Mean age 45.5 (SD 9.3), male gender 63.6%, and years of experience 13.2 (SD 8.9). Multilevel analysis showed two patient factors contributing significantly to conveyance decision-making: 'red flags' and 'prehospital electrocardiogram (ECG)'. Of these patient factors, three underlying categories were significantly associated with non-conveyance: 'sudden cardiac death < 40 years of age in family history' (OR 0.33, 95% CI 0.22-0.50; p < 0.001), 'cardiovascular abnormalities, pulmonary embolism or pulmonary hypertension in the medical history' (OR 0.62, 95% CI 0.43-0.91; p = 0.01), and 'abnormal prehospital ECG' (OR 0.54, 95% CI 0.41-0.72; p < 0.001). CONCLUSION: Sudden cardiac death < 40 years of age in family history, medical history, and abnormal ECG are significantly negatively associated with non-conveyance decision-making by EMS professionals in patients with a TLOC based on syncope. Low-risk factors do not play a significant role in conveyance decision-making.

Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

Risk stratification tools for patients with syncope in emergency medical services and emergency departments: a scoping review.

BACKGROUND: Patients with a syncope constitute a challenge for risk stratification in (prehospital) emergency care. Professionals in EMS and ED need to differentiate the high-risk from the low-risk syncope patient, with limited time and resources. Clinical decision rules (CDRs) are designed to support professionals in risk stratification and clinical decision-making. Current CDRs seem unable to meet the standards to be used in the chain of emergency care. However, the need for a structured approach for syncope patients remains. We aimed to generate a broad overview of the available risk stratification tools and identify key elements, scoring systems and measurement properties of these tools. METHODS: We performed a scoping review with a literature search in MEDLINE, CINAHL, Pubmed, Embase, Cochrane and Web of Science from January 2010 to May 2022. Study selection was done by two researchers independently and was supervised by a third researcher. Data extraction was performed through a data extraction form, and data were summarised through descriptive synthesis. A quality assessment of included studies was performed using a generic quality assessment tool for quantitative research and the AMSTAR-2 for systematic reviews. RESULTS: The literature search identified 5385 unique studies; 38 were included in the review. We discovered 19 risk stratification tools, one of which was established in EMS patient care. One-third of risk stratification tools have been validated. Two main approaches for the application of the tools were identified. Elements of the tools were categorised in history taking, physical examination, electrocardiogram, additional examinations and other variables. Evaluation of measurement properties showed that negative and positive predictive value was used in half of the studies to assess the accuracy of tools. CONCLUSION: A total of 19 risk stratification tools for syncope patients were identified. They were primarily established in ED patient care; most are not validated properly. Key elements in the risk stratification related to a potential cardiac problem as cause for the syncope. These insights provide directions for the key elements of a risk stratification tool and for a more advanced process to validate risk stratification tools.

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.

En mann i 50-årene med brystsmerter og synkope.

BACKGROUND: A man in his fifties with hypertension and no other previous health problems was admitted to the hospital after frequent episodes of retrosternal squeezing chest pain, and an episode of syncope. A recent computer tomography coronary angiography demonstrated normal coronary arteries with no atherosclerosis. CASE PRESENTATION: During admission, the patient developed several episodes of chest pain lasting five to fifteen minutes followed by non-sustained ventricular tachycardia, and initially no ST elevation in the electrocardiogram (ECG). He had normal findings on ECG and magnetic resonance imaging of the heart. During hospitalisation, ST elevations in the ECG were observed in relation to chest pain. Due to ST elevation, invasive coronary angiography was performed, revealing a suspected culprit lesion in the left anterior descending artery, treated with percutaneous coronary intervention (PCI). Despite PCI, he had persistent episodes of chest pain with ST elevation and non-sustained ventricular tachycardia. Vasospastic angina was suspected. INTERPRETATION: The clinical presentation is classical for vasospastic angina. After treatment with calcium channel blocker together with long-acting nitrate, there were no new episodes of chest pain or non-sustained ventricular tachycardia. Because of non-sustained ventricular tachycardia with haemodynamic instability and syncope, an implantable cardioverter-defibrillator was implanted.

An interesting case of infra-hisian block.

INTRODUCTION: The management of patients with conduction disease and supraventricular arrhythmias presents a multitude of clinical challenges.Intra-Hisian block, a condition characterized by delayed or blocked electrical conduction within the His bundle, can result in debilitating symptoms, such as syncope or presyncope. This case report aims to elucidate the diagnostic and therapeutic considerations that were taken in a patient who presented with recurrent syncopal episodes that corresponded to atrial flutter (AFL) and subsequently underwent cavotricuspid isthmus ablation. CASE PRESENTATION: A 65-year-old male with paroxysmal AFL and a pre-existing right bundle branch block and left anterior fascicular block (RBBB+LAFB) experienced recurrent syncopal episodes that were found to be correlated with AFL episodes. Following CTI ablation, an electrophysiology study (EPS) revealed a prolonged HV interval of 101ms, which indicated potential conduction abnormalities. With coronary sinus pacing, an intra-Hisian delay of 211ms was observed. During instances of atrioventricular block, intra-Hisian delay was evident on conducted beats, followed by intra-Hisian block on non-conducted beats. Ultimately, the patient's syncopal episodes prompted the placement of a dual-chamber pacemaker, which resulted in the resolution of symptoms. CONCLUSION: Intra-Hisian block is a condition that is often associated with delayed or blocked electrical conduction within the His bundle. When symptomatic, patients often present with syncope or presyncope. Etiologies of this condition include degenerative changes, myocardial infarction, autoimmune disorders, infections, medications, and more. This case emphasizes the importance of electrophysiology studies (EPS) in the diagnosis and management of patients with intra-Hisian block. Prompt intervention, such as the placement of a dual-chamber pacemaker, can alleviate symptoms and improve patient outcomes. Thus, clinical awareness and utilization of EPS can aid in accurate diagnosis and appropriate treatment selection for patients with conduction abnormalities and supraventricular arrhythmias.cuspid isthmus (CTI) ablation.

Prospective randomized study comparing permanent pacing with rate drop response and closed loop stimulation in patients with vasovagal syncope where permanent pacing is indicated and selected as the appropriate treatment option.

BACKGROUND: Pacing for vasovagal syncope is established. Two pacing algorithms are available. The rate-drop-response (RDR-Medtronic) is triggered by falling heart rate acting with modified rate-hysteresis. The closed loop stimulation or system (CLS-Biotronik) is triggered by impedance changes in the right ventricle reflecting falling volume and rising contractility. These are very different physiologically. Both algorithms carry favorable reports in clinical use. METHODS: A randomized-controlled superiority trial is proposed to compare the two algorithms for the control of vasovagal syncope in patients for whom pacing is indicated by current guidelines in North America and Europe. Available recent evidence may be seen as supporting superiority of CLS. No comparison between the two algorithms has been made. In this trial, patients will be centrally randomized to one or other algorithm on a 1:1 basis. Two-hundred-seventy-six patients in each group will be recruited. Sample size is determined using a confidence interval of 95%, a power of 90%, and a drop-out rate of 10% to detect an 11% difference between CLS and RDR. Recurrent symptom comparison will be made by an independent committee. The Co-primary endpoints will be recurrent syncope burden compared with that in 24-months preimplant, and occurrence of syncope in 24-months follow-up. Each outcome will be compared between the two algorithms. Secondary endpoints will be program and drug therapy changes over 24-months follow-up and quality of life by questionnaire at baseline,1 and 2 years. RESULTS AND CONCLUSIONS: These are anticipated to clarify the device algorithm choice and, therefore, to improve patient care.