Takotsubo Syndrome Associated with Neurally Mediated Reflex Syncope: A Meta-summary of Case Reports and Literature Review.

Background: Neurally mediated reflex syncope (NMRS) has been recently described as a possible trigger of Takotsubo syndrome (TTS). There are few data in the literature about this association. Methods: In the present meta-summary, 6 case reports describing patients who experienced TTS following an NMRS episode were included. Patient characteristics, triggers and type of syncope were collected. Results: A total of 7 patients with a median age of 63.4 years (interquartile range, IQR: 47.5-76) were evaluated; 71.4% were females, mainly in the menopausal state (80%). The TTS triggers were: vasovagal syncope in 6 patients (85.7%) and situational syncope in 1 patient (14.3%). 2 patients underwent a comprehensive clinical evaluation which showed a cardioinhibitory response. Conclusions: NMRS due to sudden orthostatism and emotional stress, mainly with a cardioinhibitory response, has been associated with the onset of TTS, in particular among female patients in a menopausal state.

Cardioneuroablation in patients with vasovagal syncope: An updated systematic review and meta-analysis.

BACKGROUND: Cardioneuroablation (CNA) is a novel procedure that shows promising results in reducing syncope recurrence in patients with refractory vasovagal syncope (VVS). However, its effectiveness and safety remain controversial. OBJECTIVE: We performed an updated meta-analysis evaluating CNA efficacy and safety in patients with refractory VVS. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for CNA studies in patients with refractory VVS. Our primary efficacy end point was syncope recurrence, and our safety end point was periprocedural complications. Prespecified subgroup analyses were performed for (1) the ganglionated plexus (GP) targeting method and (2) the GP location of ablation. RESULTS: We included 27 observational studies and 1 randomized controlled trial encompassing 1153 patients with refractory VVS who underwent CNA. The median age was 39.6 years, and follow-up was 21.4 months. The overall weighted rate of syncope recurrence after CNA was 5.94% (95% confidence interval [CI] 3.37%-9.01%; I2 = 64%), and the rate of periprocedural complications was 0.99% (95% CI 0.14%-2.33%; I2 = 0%). Our prespecified subgroup analysis using the GP targeting method and GP ablation location showed a higher prevalence of syncope recurrence in the electroanatomic mapping subgroup (6.21%; 95% CI 2.93%-10.28%; I2 = 0%) and in the right atrium approach (15.78%; 95% CI 3.61%-33.14%; I2 = 65.2%). CONCLUSION: This study supports the efficacy and safety of CNA in preventing syncope recurrence in patients with VVS. Furthermore, the electroanatomic mapping method of GP targeting and the right atrium approach were associated with a higher syncope recurrence rate than other methods.

Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Cardioneuroablation for Cardioinhibitory Vasovagal Syncope: Rationale, Approaches, and Its Role in Long-Term Management.

Purpose of Review: Cardioneuroablation (CNA) has emerged as a potential alternative to pacemaker therapy in well-selected cases with vasovagal syncope (VVS). In recent years, the number of CNA procedures performed by electrophysiologists has considerably risen. However, some important questions, including proper patient selection and long-term results, remain unanswered. The present article aims to critically review and interpret latest scientific evidence for clinical indications and how to approach long-term management. Recent Findings: CNA is a new approach that has been supported mainly by retrospective or observational data for its use in syncope. Overall, in mixed population studies treated with CNA, 83.3 to 100% have been reported to be free of syncope over follow-up periods of 6 to 52.1 months. For studies including patients who underwent CNA with pure VVS, 73.2 to 100% have been reported to be syncope-free over follow-up periods of 4 to 45.1 months. One large meta-analysis showed 91.9% freedom from syncope after CAN. To date, only one randomized controlled trial with small case number has been performed of CNA compared to non-pharmacological treatment in VVS. In this study of 48 patients with an average of 10 ± 9 spontaneous syncopal episodes prior to study enrollment and 3 ± 2 episodes in the year prior to CNA. After CNA, 92% were free of syncope compared with 46% treated with optimal non-pharmacological treatment to prevent new syncope episodes (P = 0.0004). To date, most studies have included younger patients (< 60 years of age). There are only limited data in patients older than 60, and some studies suggest less of an effect in relatively older patients. Summary: Cardioneuroablation can be performed to decrease syncope recurrence in adult patients aged < 60 years, with severe or recurrent cardioinhibitory syncope without prodromal symptoms, after proven failure of conventional therapies. Due to a paucity of data supporting efficacy in older individuals or for vasodepressor components, CNA in adult patients aged > 60 years or in the presence of a dominant vasodepressor should be considered investigational in severely symptomatic patients after proven failure of pharmacological and non-pharmacological therapies.

Targets for deprescribing in patients with hypertension and reflex syncope.

BACKGROUND: We aimed to identify the target of deprescribing, i.e. the 24-hour SBP increase needed to achieve the greatest reduction of SBP drops. METHOD: Forty hypertensive patients (mean age 73.6 ± 9.3 years, 26 females) with reflex syncope and SBP drops on a screening ABPM were advised to withdraw or to reduce their therapy. The study objective was the reduction of SBP drops <90 mmHg and <100 mmHg on a second ABPM performed within 3 months. RESULTS: Out of a total of 98 drugs taken during ABPM 1, 44 were withdrawn, 16 had a dose reduction and 38 remained unchanged at the time of ABPM 2. 24-hour SBP increased from 119.7 ± 10.1 mmHg to 129.4 ± 13.2 mmHg during ABPM2. Total disappearance of daytime SBP drops <100 mmHg was achieved in 20 (50 %) patients who had 24-hour SBP of 134±13 mmHg and an increase from ABPM 1 of 12 (IQR 5-20) mmHg. Compared with the 20 patients who had persistence of drops, these patients had a greater reduction of the number of hypotensive drugs (67 % versus 19 %, p = 0.002) and a greater rate of withdrawals (62 % versus 29 %, p = 0.003). CONCLUSION: In hypertensive patients with reflex syncope, an increase of 12 mmHg and an absolute value of 24-hour SBP of 134 mmHg appear to represent the optimal goals aimed to prevent SBP drops. Drugs withdrawal, rather than simply dose reduction, is mostly required to achieve the above target.

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.

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.

Recent Advances and Future Directions in Syncope Management: A Comprehensive Narrative Review.

Syncope is a highly prevalent clinical condition characterized by a rapid, complete, and brief loss of consciousness, followed by full recovery caused by cerebral hypoperfusion. This symptom carries significance, as its potential underlying causes may involve the heart, blood pressure, or brain, leading to a spectrum of consequences, from sudden death to compromised quality of life. Various factors contribute to syncope, and adhering to a precise diagnostic pathway can enhance diagnostic accuracy and treatment effectiveness. A standardized initial assessment, risk stratification, and appropriate test identification facilitate determining the underlying cause in the majority of cases. New technologies, including artificial intelligence and smart devices, may have the potential to reshape syncope management into a proactive, personalized, and data-centric model, ultimately enhancing patient outcomes and quality of life. This review addresses key aspects of syncope management, including pathogenesis, current diagnostic testing options, treatments, and considerations in the geriatric population.

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.

Global prevalence of vasovagal syncope: A systematic review and meta-analysis.

Background: Today, vasovagal syncope is a common problem that has become a significant health and social challenge. The present study investigated the global prevalence of vasovagal syncope using a systematic review and meta-analysis.Methods: In this systematic review and meta-analysis study, the global prevalence of vasovagal syncope using the keywords Prevalence, Epidemiology, Vasovagal syncope, and Reflex syncope in PubMed, WoS, Scopus, ScienceDirect databases, and Google scholar search engine without time limit until July 20, 2022, was extracted and transferred to the information management software (EndNote). Then the repeated studies were excluded, and researchers evaluated the remaining studies during three stages (i.e., screening, eligibility, and qualitative assessment). The heterogeneity of studies was investigated using the I2 index, and the analysis of eligible studies was performed using the random effects model. Results: In the review of 12 studies with a sample size of 36,156 people, the global prevalence of vasovagal syncope was reported as 16.4 (95%CI: 6-37.5), and the study of publication bias in the studies through the Egger test shows the absence of publication bias in the studies. Conclusion: The prevalence reported in the studies shows a high prevalence of vasovagal syncope, which requires serious intervention and preventive, diagnostic, and therapeutic measures. It is necessary for health policymakers to take effective measures in this field.

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.

Variability of cardioinhibition in vasovagal syncope: differences between subgroups during cardioinhibition and beyond.

PURPOSE: We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope. METHODS: The study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition. RESULTS: A total of 149 subjects with a median age of 43 (interquartile range 24-60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition. CONCLUSION: Subjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition.

Clinical impact of aging on outcomes of cardioneuroablation for reflex syncope or functional bradycardia: Results from the cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs-The ELEGANCE multicenter study.

BACKGROUND: Cardioneuroablation (CNA) is a novel treatment for reflex syncope. The effect of aging on CNA efficacy is not fully understood. OBJECTIVE: The purpose of this study was to assess the impact of aging on candidacy and efficacy of CNA for treating vasovagal syncope (VVS), carotid sinus syndrome (CSS), and functional bradyarrhythmia. METHODS: The ELEGANCE (cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs) multicenter study assessed CNA in patients with reflex syncope or severe functional bradyarrhythmia. Patients underwent pre-CNA Holter electrocardiography (ECG), head-up tilt testing (HUT), and electrophysiological study. CNA candidacy and efficacy was assessed in 14 young (18-40 years), 26 middle-aged (41-60 years), and 20 older (>60 years) patients. RESULTS: Sixty patients (37 men; mean age 51 ± 16 years) underwent CNA. The majority (80%) had VVS, 8% had CSS, and 12% had functional bradycardia/atrioventricular block. Pre-CNA Holter ECG, HUT, and electrophysiological findings did not differ across age groups. Acute CNA success was 93%, without differences between age groups (P = .42). Post-CNA HUT response was negative in 53%, vasodepressor in 38%, cardioinhibitory in 7%, and mixed in 2%, without differences across age groups (P = .59). At follow-up (8 months, interquartile range 4-15), 53 patients (88%) were free of symptoms. Kaplan-Meier curves did not show differences in event-free survival between age groups (P = .29). The negative predictive value of a negative HUT was 91.7%. CONCLUSION: CNA is a viable treatment for reflex syncope and functional bradyarrhythmia in all ages, and is highly effective in mixed VVS. HUT is a key step in postablation clinical assessment.

Tests for the identification of reflex syncope mechanism.

INTRODUCTION: Treatment efficacy of reflex syncope is mainly related to the mechanism underlying syncope rather than its etiology or clinical presentation. The predominant mechanism underlying reflex syncope can be assigned to hypotensive or to bradycardic phenotypes. AREAS COVERED: Methodology and diagnostic criteria of the most useful tests for the identification of hypotensive and bradycardic phenotypes are discussed. Diagnostic tests for the hypotensive phenotype include office blood pressure measurement with active standing test, home, and wearable blood pressure monitoring, 24-h ambulatory blood pressure monitoring and tilt table test. Diagnostic tests for the bradycardic phenotype include carotid sinus massage, tilt table test and prolonged ECG monitoring. EXPERT OPINION: In reflex syncope, the documentation of bradycardia/asystole during a syncopal episode does not rule out the possibility that a preceding or parallel hypotensive reflex plays an important role. Similarly, even when a hypotensive mechanism is established, the possibility of an associated cardioinhibitory reflex should be investigated. Investigating the mechanism of reflex syncope is mandatory in patients with severe recurrent episodes, with the final aim to develop a personalized treatment strategy. Recent trials have demonstrated the benefits of personalized mechanism-based therapy, thus highlighting the importance of a comprehensive assessment of the mechanisms underlying syncope.

Pediatric syncope: pearls and pitfalls in history taking.

Syncope is a heterogeneous syndrome with complex underlying mechanisms, hence, the spectrum of patients presenting with syncope is broad. The diagnosis of syncope begins with history taking, and an accurate diagnosis can be established through correct history taking and interpretation. Building and interpreting patient history are the main factors that cause a diagnostic yield gap between experts and nonexperts. The most frequent source of error is a clinician's misconception rather than an inaccurate account of patient symptoms. Clinicians can have several diagnostic pitfalls while evaluating patient history, which can be avoided by in-depth understanding of the link between syncope pathophysiology and clinical clues. Furthermore, clinicians need to understand the clinical features of diseases that require differentiation from syncope, such as seizures. The use of confusing terms is one of the barriers that prevents accurate diagnosis and communication between doctors and patients. In this review, we address the terms of syncope and its essential history-taking components in connection with the mechanism of syncope.