Cardioinhibitory Carotid Sinus Research Articles

Head-up tilt test induced asystole and recurrent syncope: a follow-up study

Abstract Introduction Head-up tilt test (HUTT) is a valuable diagnostic tool in unexplained and recurrent syncope, especially when reflex etiology is suspected. If asystole is the dominant feature of reflex syncope, permanent pacemaker therapy may be effective for reducing syncope recurrence. Purpose To investigate syncope recurrence, pacemaker implantation and death of patients with syncope and asystole induced by HUTT and carotid sinus message (CSM). Methods Retrospective analysis of consecutive patients referred for HUTT between January 2017 and December 2021 and selection of those with cardioinhibitory response, defined by syncope or pre-syncope and asystolic pause ≥3 seconds. Patients’ follow-up (FUP) was performed via a phone interview and analysis of clinical records, to assess recurrence of syncope, treatments, and death. Results A total of 44 patients were included: 30 (68,2%) were men, with a median age of 69 years (interquartile range (IQR) of 24). Asystole was experienced after CSMin 41 patients and during tilt test alone in 3 patients. Median FUP was 26 months (IQR 23). There were 19 (44,2%) patients who implanted pacemaker (PM), all with cardioinhibitory carotid sinus syndrome ( I-CSS), 57,9% men, with median age of 74 years (IQR 19) and median duration of asystole during CSMof 6,3 seconds (IQR 3,8). Of these, 5 (26,3%) implanted a unicameral PM and the remaininga bicameral PM, with AAI-DDD mode programming. Two patients had PM-related complications: infection and dislodgment of ventricular lead, both in the first 15 days after implantation. Median atrial and ventricular pacing percentage at last PM consultation was 7% (IQR 28) and 1% (IQR 4), respectively. There was a positive strong correlation between the percentage of atrial pacing at first and at last appointment (p<0,001, r=0,867) and a positive moderated correlation between the percentage of ventricular pacingat first and at last appointment (p=0,022, r=0,586), suggesting a similar degree of pacing along FUP-time. Only three patients (6,8%) had syncope recurrence, all men with CI-CSS, median age of 78; one patient had syncope before implantation PM, other relapsed 2-times with a PMimplanted and the third refused PMimplantation despite 5-time recurrence of symptoms. There was no association between the duration of the asystole during HUTT with implantation of PM nor syncope recurrence (p>0.2). Age at HUTT was significantly associated both with CI-CSS and PM implantation (p=0,001 and p=0,045, respectively). Two patients died, both of oncologic causes. Conclusion In agreement with the literature, our cohort of patients with cardioinhibitory response during HUTT and CSM experienced an overall good prognosis, with no cardiac deaths; there was very low syncope recurrence, not allowing a comparison between the groups with and without pacemaker. Age at HUTT was significantly associated both with CI-CSS and PMimplantation.

Cardioneuroablation for carotid sinus syndrome: a case series

Cardioinhibitory carotid sinus syndrome (CSS) is a neurally-mediated (reflex) syncope, secondary to excessive vagal response to carotid sinus pressure. A growing body of studies have shown that catheter ablation of ganglionated plexi (GPs) or cardioneuroablation (CNA) is effective in treating patients with vaso-vagal syncope (1). To date, no studies systematically evaluated CNA in patients with CSS.

Causes of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: Findings from the SYNCOPACED registry

Few studies have examined the causes of syncope/collapse recurrences in patients with a previously implanted pacemaker for bradyarrhythmic syncope. The purpose of this study was to assess the causes of syncope/collapse recurrences after pacemaker implantation for bradyarrhythmic syncope in a large patient population. The SYNCOpal recurrences in patients treated with permanent PACing for bradyarrhythmic syncope (SYNCOPACED) registry was a prospective multicenter observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for bradyarrhythmic syncope. During follow-up, the time to the first syncope/collapse recurrence was recorded. Patients with syncope/collapse recurrences underwent a predefined diagnostic workup aimed at establishing the mechanism of syncope/collapse. During a median follow-up of 50 months, 213 patients (15.6%) reported at least 1 syncope/collapse recurrence. The risk of syncope/collapse recurrence was highest in patients who underwent implantation for cardioinhibitory vasovagal syncope (26.4%), followed by unexplained syncope and chronic bifascicular block (21.5%), cardioinhibitory carotid sinus syndrome (17.2%), atrial fibrillation needing pacing (15.5%), atrioventricular block (13.6%), and sinus node disease (12.5%) (P = .017). The most frequent cause of syncope/collapse recurrence was reflex syncope (27.7%), followed by orthostatic hypotension (26.3%), pacemaker or lead malfunction (5.6%), structural cardiac disease (5.2%), and atrial and ventricular tachyarrhythmias (4.7% and 3.8%, respectively). In 26.8% of cases, the mechanism of syncope/collapse remained unexplained. In patients receiving a pacemaker for bradyarrhythmic syncope, reflex syncope and orthostatic hypotension are the most frequent mechanisms of syncope/collapse recurrence after implantation. Pacing system malfunction, structural cardiac diseases, and tachyarrhythmias are rare mechanisms. The mechanism remains unexplained in >25% of patients.

Long-Term Mortality in Cardioinhibitory Carotid Sinus Hypersensitivity Patient Cohort.

BackgroundCardioinhibitory carotid sinus hypersensitivity (CICSH) is defined as ventricular asystole ≥ 3 seconds in response to 5-10 seconds of carotid sinus massage (CSM). There is a common concern that a prolonged asystole episode could lead to death directly from bradycardia or as a consequence of serious trauma, brain injury or pause-dependent ventricular arrhythmias.ObjectiveTo describe total mortality, cardiovascular mortality and trauma-related mortality of a cohort of CICSH patients, and to compare those mortalities with those found in a non-CICSH patient cohort.MethodsIn 2006, 502 patients ≥ 50 years of age were submitted to CSM. Fifty-two patients (10,4%) were identified with CICSH. Survival of this cohort was compared with that of another cohort of 408 non-CICSH patients using Kaplan-Meier curves. Cox regression was used to examine the relation between CICSH and mortality. The level of statistical significance was set at 0.05.ResultsAfter a maximum follow-up of 11.6 years, 29 of the 52 CICSH patients (55.8%) were dead. Cardiovascular mortality, trauma-related mortality and the total mortality rate of this population were not statistically different from that found in 408 patients without CICSH. (Total mortality of CICSH patients 55.8% vs. 49,3% of non-CICSH patients; p: 0.38).ConclusionAt the end of follow-up, the 52 CICSH patient cohort had total mortality, cardiovascular mortality and trauma-related mortality similar to that found in 408 patients without CICSH.

Incidence and predictors of syncope recurrence after cardiac pacing in patients with carotid sinus syndrome

BackgroundCardiac pacing is the treatment of choice for cardioinhibitory carotid sinus syndrome (CSS), but syncope recurrence occurs in up to 20% of patients within 3 years. The present study aims at assessing incidence and identifying predictors of syncope recurrence in patients receiving pacing therapy for CSS. MethodsThe Syncope Clinics of two large regional hospitals in Northern Italy, both following European Syncope Guidelines, combined to perform this study. Retrospective analysis of 3127 consecutive patients undergoing carotid sinus massage (CSM) was performed 2004–2014. Ten-second supine and standing CSM was systematically assessed in patients aged >40 years with suspected reflex syncope as part of the initial evaluation. Syncope recurrence was investigated in those paced for CSS having >6 months' available follow-up. Data were collected from clinical records and patient interviews. ResultsCSS was diagnosed in 261 patients (8.3%). Pacemakers were implanted in 158, with follow-up data available in 112: 19 (17%) experienced 73 syncope recurrences during a mean follow-up of 89 ± 42 months, yielding an incidence of 0.5 episodes per patient/year. Prodrome, predisposing situations preceding syncope and chronic nitrate therapy were more frequent in patients reporting recurrence. Prodrome and predisposing situations remained independent predictors of post-implantation recurrence on multivariable analysis. ConclusionsCSS is a frequent cause of syncope, if CSM is performed during the initial evaluation. Most patients treated by pacing remain asymptomatic during long-term follow-up. In those who have recurrence, its incidence is very low. Prodrome and predisposing situations are predictors of post-implantation recurrence, suggesting presence of hypotensive susceptibility.

Relationship Between Phosphate and Sodium Nitrite Ingestion and Vascular Hardness of Longevity Elderly Population in Okinawa Prefecture

Cardiac pacing is the treatment of choice for cardioinhibitory carotid sinus syndrome (CSS), but syncope recurrence occurs in up to 20% of patients within 3 years. The present study aims at assessing incidence and identifying predictors of syncope recurrence in patients receiving pacing therapy for CSS.The Syncope Clinics of two large regional hospitals in Northern Italy, both following European Syncope Guidelines, combined to perform this study. Retrospective analysis of 3127 consecutive patients undergoing carotid sinus massage (CSM) was performed 2004–2014. Ten-second supine and standing CSM was systematically assessed in patients aged >40 years with suspected reflex syncope as part of the initial evaluation. Syncope recurrence was investigated in those paced for CSS having >6 months' available follow-up. Data were collected from clinical records and patient interviews.CSS was diagnosed in 261 patients (8.3%). Pacemakers were implanted in 158, with follow-up data available in 112: 19 (17%) experienced 73 syncope recurrences during a mean follow-up of 89 ± 42 months, yielding an incidence of 0.5 episodes per patient/year. Prodrome, predisposing situations preceding syncope and chronic nitrate therapy were more frequent in patients reporting recurrence. Prodrome and predisposing situations remained independent predictors of post-implantation recurrence on multivariable analysis.CSS is a frequent cause of syncope, if CSM is performed during the initial evaluation. Most patients treated by pacing remain asymptomatic during long-term follow-up. In those who have recurrence, its incidence is very low. Prodrome and predisposing situations are predictors of post-implantation recurrence, suggesting presence of hypotensive susceptibility.

073_16760 Predictors of Syncopal Recurrence after Cardiac Pacing in Patients with Carotid Sinus Syndrome

In cardio-inhibitory Carotid Sinus Syndrome (CI-CSS), syncopal recurrence is expected to occur in up to the 20% of patients after pacing therapy. The present study analyzes post-implantation syncopal recurrence in CI-CSS, to identify predictors of recurrence. We retrieved electronic records

Cardioinhibitory Carotid Sinus Syndrome - a mathematical model.

Carotid sinus massage (CSM) is a simple clinical test for stimulating the carotid sinus reflex. During CSM, firm longitudinal massage is applied at the point of maximal pulsation over the carotid bifurcation resulting in relative bradycardia. CSM is used to diagnose Cardioinhibitory Carotid Sinus Syndrome (CICSS). CICSS is an age-related disorder, characterized by profound symptomatic cardioinhibition (> 3 seconds pause) following CSM. CICSS prevalence increases with age and is responsible for 1 to 20% of all pacemaker implantations per year. Treatment options for CSS are limited and much debate still remains around its underlying etiology. In this paper we present a first computer simulation of carotid sinus massage (CSM) in older adults and demonstrate its ability to simulate normal heart rate responses to CSM. Importantly we demonstrate that our mathematical model requires inclusion of model elements to simulate autonomic control of perinodal T-cell activity in order to replicate the profound cardioinhibitory response observed in CICSS. Our model findings implicate CSS as a candidate biomarker of biological aging and frailty.

The role of cardiac pacing therapy in the management of carotid sinus syndrome

Carotid sinus syndrome is characterized by a hypersensitive carotid sinus and syncope. Although we have clear guidelines for the diagnosis and treatment of carotid sinus syndrome, the efficacy of pacing therapy with this indication has not been the subject of many studies. This study aimed to assess the efficacy and safety of pacing therapy in the treatment of patients with carotid sinus syndrome and to determine the factors contributing to symp- toms recurrence after pacemaker implantation. This study was retrospective and included 32 patients in whom a pacemaker was implanted due to carotid sinus syn- drome at the Pacemaker Center, Clinical Center of Serbia, be- tween April 2005 and April 2012. Carotid sinus massage and head-up tilt test (HUTT) were performed to select patients with cardioinhibitory and mixed type carotid sinus syndrome, who were enrolled to the study. The mean age of patients was 65.6 ± 11.5 years and 20 (62.5%) were men. The mean follow-up period was 4.3 ± 1.9 years. HUTT was performed in 3 (9.4%) patients. Twenty-seven (84.4%) patients presented with cardioinhibitory and 5 (15.6%) with mixed type of carotid sinus syndrome. After pacemaker implantation, 22 (68.7%) patients had no further symptoms, 8 (25.0%) had syncope and 2 (6.3%) presyncope.The mixed type of the disease (HR 3.1; 95% CI 1.4-5.1; p = 0.021) and implanta- tion of pacemaker in WI mode (HR 1.8; 95% CI 1.1-3.2; p = 0.034) were independent predictors of symptoms recurrence. There were 3 (9.4%) perioperative surgical complications. Pacemaker therapy is an effective and safe treat- ment for patients with carotid sinus syndrome. As predictors of symptoms persistence after pacemaker implantation in our population, we identified the implantation of pacemaker in WI mode and the mixed type of carotid sinus syndrome.

Prevention of falls in old people – a review

SummaryPhysical training, if including specific different training modalities, reduces the fall risk in healthy community-dwelling older people, as does a home hazards modification programme. Vitamin D supplementation in older individuals with low levels of vitamin D, adjustment of psychotropic medication, and structured modification of multi-pharmacy are all drug-focused programmes that reduce the number of falls. Anti-slip shoe devices during icy conditions for older people who walk outdoors and multifaceted podiatry in patients with specific foot disability reduce the fall risk. First eye cataract surgery and pacemakers in patients with cardio-inhibitory carotid sinus hypersensitivity are surgical interventions that reduce the fall risk. Multi-factorial preventive programmes that include training, both individually designed and generally prescribed, also reduce the fall frequency. With this in mind, we ought to initiate fall preventive programmes in older people, especially in high- risk groups, to reduce the number of falls and fallers in society.

Prevention of falls in the elderly: A review

Falls often result in soft tissue injuries, dislocations, fractures, longstanding pain and reduced quality of life. Therefore, fall preventive programmes have been developed. In this review, we evaluate programmes that in randomized controlled trials (RCT) have been shown with fall reducing effect. Physical exercise that includes several training modalities, especially balance and strength training, is the only intervention programme that reduces both the number of fallers and the number of falls in community dwellers. Home hazards modification reduces the fall risk in community-living elderly but has the best effects in high risk groups when the programme is led by occupational therapists. Vitamin D supplement in those with low levels of vitamin D, adjustment of psychotropic medication and modification of multi-pharmacy are drug-related programmes that reduce the fall risk. Anti-slip shoe devices in elderly who walk outdoors during icy conditions and multifaceted podiatry to patients with specific foot disability are interventions targeted at the lower extremities with a fall-reducing effect. First eye cataract surgery and pacemakers in patients with cardio-inhibitory carotid sinus hypersensitivity are surgical procedures with fall-reducing effect. Multifactorial standardized preventive programmes that include an exercise component and individually-designed subject-specific programmes also reduce the number of falls. Fall preventive interventions should be provided to elderly by a structured approach, especially to high risk groups, as to reduce the number of falls and fallers.

Prevention of falls in the elderly—a review

The proportion of elderly in the society increases and fall frequency increases with advancing age. Many falls result in fractures and also soft tissue injuries, longstanding pain, functional impairment, reduced quality of life, increased mortality, and excess in healthcare costs. Due to the magnitude of these negative effects, a variety of single- and multicomponent fall-preventive intervention programs has been initiated.This review identifies programs that, in randomized controlled trials (RCTs), have been shown with fall-reductive effects.The most effective strategies in community-dwelling elderly include regular physical training with program that includes several different training modalities. Modification of the overall or patient-specific risk factor profile in home hazard modification program has been proven to decrease fall risk in community-living elderly. The elderly in the community benefit also from wearing antislip shoe devices when walking in icy conditions, from adjustment of psychotropic medication, and from structured modification of multipharmacy. If vitamin D levels in blood are low, supplementation is beneficial as is the first eye cataract surgery and pacemaker implantation in patients with cardioinhibitory carotid sinus hypersensitivity. In addition to modification of specific risk factors, generalized and individualized multifactorial preventive programs, all including some sort of physical training, have been found to decrease the fall risk. In summary, there is now strong evidence in the literature that structured fall-preventive programs in the elderly, especially in high-risk groups, are beneficial in reducing both the number of fallers and the number of falls in community.

Treatment of Reflex Syncope

This review assesses the role of all types of therapy for reflex syncope including physical counter-measures, diet, behavior, drugs and implantable devices. There are no drugs currently demonstrated to have convincingly beneficial effect by randomized controlled trial. However, provided that the patient experiences warning of an impending attack physical counter-measures are demonstrably effective. Implantable cardiac pacemakers have a role in a carefully selected minority of patients with vasovagal syncope. Pacing, dual chamber of cardio-inhibitory Carotid Sinus Syndrome is the treatment of choice. Modification of lifestyle in terms of fluid, caffeine and salt consumption is necessary in many cases but has little scientific background. Educating and reassuring the patient is an important part of management. The patient must understand that attacks are not as dangerous as they might seem in most cases and learning to anticipate those permits evasive measures.

The intravenous adenosine test: a new test for the identification of bradycardia pacing indications? A pilot study in subjects with bradycardia pacing indications, vasovagal syncope and controls

Intravenous adenosine has recently been used in the diagnosis of unexplained syncope, but there is no consensus as to the meaning of a 'positive' test. The objective is to determine the sensitivity and specificity of intravenous adenosine testing in the diagnosis of bradycardia-pacing indications [sinus node dysfunction(SND), atrio-ventricular block (AVB) and cardio-inhibitory carotid sinus syndrome (CSS)]. Pilot cohort study. Patients-(i) Bradycardia-pacing group: Consecutive patients referred for pacing for SND, AVB and CSS; (ii) Consecutive head-up tilt (HUT)-positive VVS patients. Controls-(i) Simple controls (S-Con: normal examination/ECG) and (ii) Electrophysiology controls (EP-Con: consecutive subjects referred for accessory pathway ablation). Pacing referrals and EP-Con had electrophysiology studies to confirm referral diagnosis and exclude others. All subjects had bolus injection of 20 mg intravenous adenosine during continuous ECG and blood pressure monitoring (positive test: >or=6 s asystole, >or=10 s high-degree AVB post-injection). Sensitivity, specificity, safety and tolerability of the test were measured. Of 264 potential participants (4 SND, 8 AVB, 7 CSS, 10 VVS, 10 EP-Con and 11 S-Con) 50 were studied. All (100%) of the bradycardia-pacing group were adenosine test-positive, as were 6 (60%) VVS. None (0%) and 3 (27%) of the EP- and S-Con groups were positive. Adenosine testing was 100% sensitive and 86% specific for bradycardia-pacing indications, and 100% specific using the diagnostically 'clean' EP-Con results. There were no significant adverse or side effects. Adenosine testing reliably identified patients with definitive bradycardia-pacing indications in whom alternative diagnoses were excluded. Further work is needed to evaluate the role of this test in the diagnosis of unexplained syncope.

Evaluation of Sinus and Atrioventricular Nodes Function in Patients with Vasovagal Syncope

Evaluation of sinus and atrioventricular nodes function as a potential factor responsible for prolonged bradycardia, asystole, or both in patients with cardioinhibitory and non-cardioinhibitory vasovagal syncope (VVS). The study included 258 patients (mean age = 47.7 +/- 17.2 years; range 18-62; 147 females) with a history of VVS. They were divided among four groups, according to results of head-up tilt test (HUTT). All patients underwent standard HUTT, carotid sinus massage (CSM), and rapid transesophageal atrial pacing for evaluation of total sinus node recovery time (SNRT), and corrected sinus node recovery time (CNRT), resting and intrinsic heart rate (IHR), and Wenckebach point (WP). Values of SNRT > 1,500 ms, CNRT > 525 ms, WP < 130 bpm, and CSM-induced pause >3 seconds were considered abnormal. SNRT, CNRT, and WP before and after pharmacological blockade, resting heart rate, and IHR did not differ significantly among the study groups. The prevalence of mild sinus node dysfunction (SND), decreased value of WP, and cardioinhibitory carotid sinus hypersensitivity was similar among all study groups. The prevalence of mild SND, abnormal atrioventricular conduction, and carotid sinus hypersensitivity (CSH) was similar among patients with VVS regardless of the type of vasovagal reaction. SND and CSH do not seem to play an important role in the pathogenesis of cardioinhibitory vasovagal reaction.

Less syncope and milder symptoms in patients treated with pacing for induced cardioinhibitory carotid sinus syndrome: a randomized study

The aim of this study was to examine the effect on symptoms in patients with induced cardioinhibitory carotid sinus syndrome (ICSS) when treated or not treated with a pacemaker. Sixty patients with a history of syncope or pre-syncope and ICSS were randomized to receive a permanent pacemaker (P group, n = 30) or no pacing (NP group, n = 30). ICSS was defined as a ventricular pause (i.e. asystole) lasting 3 s or more in response to carotid sinus stimulation. The patients were seen at 3 and 12 months and at symptoms. At 12 months, the rate of syncope in the NP group was 40% (n = 12) compared with 10% (n = 3) in the P group (P = 0.008). The majority (11 of 12) of the syncope recurrences in the NP group occurred during the first 3 months. Pre-syncope occurred in two patients (7%) in the NP group and in eight (27%) in the P group. Ten patients (33%) with recurrent syncope in the NP group later crossed-over to receive pacemaker implant. A history of syncope or pre-syncope, plus ICSS, was a strong predictor of subsequent syncope or pre-syncope. Most of the new symptoms occurred within 3 months. Pacemaker treatment effectively reduced syncope and/or resulted in milder symptoms.

Cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism of spontaneous neurally mediated syncope

We correlated the finding of cardioinhibitory carotid sinus hypersensitivity (CSH) with that observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR). We included 18 consecutive patients with suspected recurrent neurally mediated syncope and positive cardioinhibitory response during carotid sinus massage (max pause 5.5 +/- 1.6 s) who had subsequent documentation of a spontaneous syncope by means of an ILR. They were compared with a 2:1 age- and sex-matched group of 36 patients with a clinical diagnosis of recurrent neurally mediated syncope and negative response to carotid sinus massage, tilt testing and ATP test. Asystole >3 s was observed at the time of the spontaneous syncope in 16 (89%) of CSH patients and in 18 (50%) of the control group (P = 0.007). Sinus arrest was the most frequent finding among CSH patients but not among controls (72 vs. 28%, P = 0.003). After ILR documentation, 14 CSH patients with asystole received dual-chamber pacemaker implantation; during 35 +/- 22 months of follow-up, 2 syncopal episodes recurred in 2 patients (14%), and pre-syncope occurred in another 2 patients (14%). Syncope burden decreased from 1.68 (95% confidence interval 1.66 - 1.70) episodes per patient per year before to 0.04 (0.038-0.042) after pacemaker implant (98% relative risk reduction). In patients with suspected neurally mediated syncope, the finding of cardioinhibitory CSH predicts an asystolic mechanism at the time of spontaneous syncope and, consequently, suggests a possible benefit of cardiac pacing therapy.

Atrial fibrillation precipitated by carotid sinus massage in a patient with unexplained syncope

Carotid sinus massage (CSM) is a useful tool in the investigation of unexplained syncope, but is associated with risks. To describe the first reported case of atrial fibrillation precipitated by CSM during the investigation of a patient with recurrent unexplained syncope. A 58-year-old female underwent CSM as part of a tilt test protocol for the investigation of recurrent unexplained syncope. Left CSM revealed the diagnosis of mixed cardioinhibitory and vasodepressor carotid sinus syndrome but also precipitated atrial fibrillation, an arrhythmia previously unreported as a complication of the procedure. CSM is a useful tool in the investigation of patients with recurrent unexplained syncope, but may cause atrial fibrillation in addition to other previously described complications and should, therefore, be used with caution.

EEG Changes with Carotid Sinus Baroreflex during Carotid Endarterectomy

ABSTRACT.We describe EEG changes in three patients in whom the carotid sinus baroreflex was precipitated during carotid endarterectomy. In all instances, the EEG showed diffuse attenuation and slowing of the baseline anesthetic pattern in association with bradycardia. This can help alert the surgeon to the changes occurring as a result of the cardioinhibitory carotid sinus baroreflex and guide appropriate timely intervention.

Randomized clinical trials of neurally mediated syncope.

Evidence for therapy of neurally mediated syncope is generally weak. Many drugs have been used for the treatment of vasovagal syncope (beta-blockers, disopyramide, scopolamine, clonidine, theophylline, fludrocortisone, ephedrine, dihydroergotamine, etilefrine, midodrine, clonidine, serotonin reuptake inhibitors, enalapril). In general, although the results have been satisfactory in uncontrolled trials or short-term controlled trials, the majority of long-term placebo-controlled prospective trials have not been able to show a benefit of the active drug over placebo. Only two well-designed double-blind placebo-controlled randomized trials have been performed-one for etilefrine and the other for atenolol-and both were unable to show a superiority of the active drug versus placebo. Four randomized clinical trials of pacing therapy-three positive and one negative-have been performed in patients affected by vasovagal syncope. The relationship between carotid sinus hypersensitivity and spontaneous, otherwise unexplained, syncope has been demonstrated. Cardiac pacing appears to be beneficial in carotid sinus syndrome; its efficacy has been demonstrated by two randomized controlled trials and confirmed by several pre-post comparative studies, one controlled trial, and one prospective observational study. There is evidence and general agreement that cardiac pacing is useful in patients with cardioinhibitory or mixed carotid sinus syndrome. Usefulness of the treatment is less well established and divergence of opinion exists with regard to cardiac pacing in patients with cardioinhibitory vasovagal syncope. The evidence fails to support the efficacy of beta-blocking drugs. As yet there are insufficient data to support the use of any other pharmacologic therapy for vasovagal syncope.