Adult vasovagal syncope with abdominal pain diagnosed by head-up tilt combined with transcranial doppler: a preliminary study.

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

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.

Classification of vasovagal syncope from physiological signals on tilt table testing.

BACKGROUND: The diagnostic test for vasovagal syncope (VVS), the most common cause of syncope is head-up tilt test (HUTT) assessment. During the test, subjects experienced clinical symptoms such as nausea, sweating, pallor, the feeling of palpitations, being on the verge of passing out, and fainting. The study's goal is to develop an algorithm to classify VVS patients based on physiological signals blood pressure (BP) and electrocardiography (ECG) obtained from the HUTT. METHODS: After 10 min of supine rest, the subject was tilted at a 70-degree angle on a tilt table for approximately a total of 35 min. 400 µg of glyceryl trinitrate (GTN) was administered sublingually after the first 20 min and monitoring continued for another 15 min. Mean imputation and K-nearest neighbors (KNN) imputation approaches to handle missing values. Next, feature selection techniques were implemented, including genetic algorithm, recursive feature elimination, and feature importance, to determine the crucial features. The Mann-Whitney U test was then performed to determine the statistical difference between two groups. Patients with VVS are categorized via machine learning models including Support Vector Machine (SVM), Gaussian Naïve Bayes (GNB), Multinomial Naïve Bayes (MNB), KNN, Logistic Regression (LR), and Random Forest (RF). The developed model is interpreted using an explainable artificial intelligence (XAI) model known as partial dependence plot. RESULTS: A total of 137 subjects aged between 9 and 93 years were recruited for this study, 54 experienced clinical symptoms were considered positive tests, while the remaining 83 tested negative. Optimal results were obtained by combining the KNN imputation technique and three tilting features with SVM with 90.5% accuracy, 87.0% sensitivity, 92.7% specificity, 88.6% precision, 87.8% F1 score, and 95.4% ROC (receiver operating characteristics) AUC (area under curve). CONCLUSIONS: The proposed algorithm effectively classifies VVS patients with over 90% accuracy. However, the study was confined to a small sample size. More clinical datasets are required to ensure that our approach is generalizable.

Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope.

AIMS: A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex. METHODS AND RESULTS: Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12 b.p.m. and systolic blood pressure (SBP) was 108 ± 19 mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14 b.p.m. within a median of 0.1 min [inter-quartile range (IQR), 0.1-0.7 min] when the SBP was 99 ± 21 mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17 mmHg and the CLS rate was 95 ± 13 b.p.m. The onset of CLS pacing was 1.7 min (IQR, 1.5-3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0 min (IQR, 3.3-8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22 mmHg at baseline to 69 ± 4 mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1 b.p.m.). CONCLUSION: The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect. REGISTRATION: ClinicalTrials.gov identifier: NCT06038708.

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.

Long-term outcomes of cardioneuroablation with and without extra-cardiac vagal stimulation confirmation in severe cardioinhibitory neurocardiogenic syncope.

BACKGROUND: Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA. OBJECTIVE: This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS. METHOD: A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing. RESULTS: Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group. CONCLUSION: This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.

Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Comorbidity of behavioral problems and parental acceptance-rejection in children diagnosed with chest discomfort, palpitations, vasovagal syncope, and underlying heart disease: a multiple case-control study.

BACKGROUND: Children who experience chest discomfort, palpitations, vasovagal syncope, and underlying heart disease often present a complex clinical picture. Not only are they dealing with potential cardiac issues, but they may also exhibit behavioral problems that can complicate the diagnostic and treatment process. Moreover, parental acceptance or rejection can significantly influence the child's well-being and medical outcomes in such cases. This study aims to explore the comorbidity of behavioral problems and parental acceptance-rejection in children diagnosed with these cardiac symptoms and underlying heart disease. METHODS: In a case-control study, the Parental Acceptance - Rejection Questionnaire and Parental version of Strengths and Difficulties Questionnaire (SDQ) was filled by parents of 314 patients from pediatric cardiology clinic. RESULTS: The control group scored substantially lower overall according to SDQ. The vasovagal syncope subgroup was found to have considerably lower scores on the subscale. The group with chest discomfort scored highly in hostility and aggression in the PARQ. In comparison to the other groups, the vasovagal syncope and chest pain group demonstrated higher scores in undifferentiated rejection and total score. CONCLUSION: This study showed a correlation between children's behavioral and emotional problems and cardiac symptoms. This states that children's relationship with their parents has an impact on their symptoms. It will be necessary to conduct further studies to determine a causal association and devise preventative measures.

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.

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.

Potential consequences of cardioneuroablation for vasovagal syncope: A call for appropriately designed, sham-controlled clinical trials.

Cardioneuroablation (CNA) is being increasingly used to treat patients with vasovagal syncope (VVS). Bradycardia, in the cardioinhibitory subtype of VVS, results from transient parasympathetic overactivity leading to sinus bradycardia and/or atrioventricular block. By mitigating parasympathetic overactivity, CNA has been shown to improve VVS symptoms in clinical studies with relatively small sample sizes and short follow-up periods (<5 years) at selected centers. However, CNA may potentially tip the autonomic balance to a state of sympathovagal imbalance with attenuation of cardiac parasympathetic activity. A higher heart rate is associated with adverse cardiovascular events and increased mortality in healthy populations without cardiovascular diseases. Chronic sympathovagal imbalance may also affect the pathophysiology of spectra of cardiovascular disorders including atrial and ventricular arrhythmias. This review addresses potential long-term pathophysiological consequences of CNA for VVS.

Development and validation of a scoring system to predict vasovagal reaction upon whole-blood donation.

BACKGROUND AND OBJECTIVES: Risk factors for vasovagal reaction (VVR) have been extensively studied. With knowledge of the relative importance of these risk factors for VVR, collection staff could take care of blood donors from the same standpoint, leading to improved donor safety. We therefore developed a scoring system to predict VVR, which incorporates registration information. MATERIALS AND METHODS: Pre-syncopal and syncopal symptoms, as well as on- and off-site reactions, are included in this analysis as VVR. We defined the donor status as follows: first-time donors, repeat donors with no history of reaction and repeat donors with a history of reaction. We prepared two datasets: whole-blood donations at a blood donation site in Tokyo between January 2019 and December 2019 were included in training data (n = 361,114), and whole-blood donations between January 2020 and August 2020 were included in testing data (n = 216,211). RESULTS: The most important variable was the donor status, followed by age, estimated blood volume and height. We integrated them into a scoring system. Training and testing datasets were combined (n = 577,325), and VVR rates in groups with scores of 0, 1, 2, 3, 4 and 5 or more were 0.09% (95% CI: 0.081%-0.10%), 0.33% (95% CI: 0.31%-0.36%), 0.87% (95% CI: 0.78%-0.96%), 1.17% (95% CI: 1.05%-1.30%), 2.15% (95% CI: 1.98%-2.32%) and 3.11% (95% CI: 2.90%-3.34%), respectively. CONCLUSION: The scoring system enables staff to significantly predict VVR and may help them to identify donors at increased risk of experiencing syncope, thereby mitigating the negative impact of VVR on donor safety and return by paying close attention to high-risk donors.