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Background Ambulatory blood pressure (BP) monitoring has long been used to monitor BP in hypertension and lately emerged as a useful tool to detect hypotensive susceptibility in reflex syncope. However, hemodynamic characteristics in reflex syncope have not been sufficiently explored. The present study investigated the differences between ambulatory BP monitoring profiles associated with reflex syncope and normal population. Methods and Results This is an observational study comparing ambulatory BP monitoring data from 50 patients with reflex syncope and 100 controls without syncope, age‐ and sex‐matched 1:2. Mean 24‐hour systolic (SBP) and diastolic BP, pulse pressure (24‐hour PP), dipping status, and number of daytime SBP drops P =0.002), higher 24‐hour diastolic BP (85.2±9.6 versus 79.1±10.6 mm Hg, P P P Conclusions Patients with reflex syncope have lower 24‐hour SBP but higher 24‐hour diastolic BP and more frequent daytime SBP drops

SUMMARY This review recapitulates the head-up tilt test, which is commonly used for evaluation of orthostatic syndromes and dysautonomia. Tilt test evaluates autonomic system responses to orthostatic stress. Established tilt testing includes monitoring of heart rate and blood pressure; adding capnography and cerebral blood flow monitoring expands its diagnostic yield and allows assessing cerebral blood flow regulation. Common syndromes detectable by the tilt test are neurally mediated syncope (vasodepressor, cardiovagal, or mixed), orthostatic hypotension, postural orthostatic tachycardia syndrome, hypocapnic cerebral hypoperfusion, and orthostatic cerebral hypoperfusion syndrome. This review describes relevant physiology, tilt test protocols, diagnostic criteria for orthostatic syndromes, grading test results, diagnostic accuracy, limitations of the tilt test, and safety considerations.

OBJECTIVE Most of the research on vasovagal reactions has focused on the contributions of cardiovascular activity to the development of symptoms. However, other research suggests that additional mechanisms like hyperventilation may contribute to the process. The goal of the present investigation was to examine the influences of cardiovascular and respiratory variables on vasovagal symptoms. METHODS This study was part of a randomized controlled trial investigating the effects of behavioral techniques on the prevention of vasovagal reactions in blood donors. Data from the no-treatment control group were analyzed. The final sample was composed of 160 college and university students. Observational and self-report measures of symptoms were obtained. Physiological variables were measured mainly using respiratory capnometry. RESULTS Although respiration rate remained stable throughout donation, change in end-tidal carbon dioxide was associated with requiring treatment for a reaction during donation (odds ratio = 0.57, 95% confidence interval [CI] = 0.41 to 0.79, p = .001) and self-reported symptoms measured in the postdonation period using the Blood Donation Reactions Inventory (β = -0.152, 95% CI = -0.28 to -0.02, t = -2.32, p = .022). Individuals with higher levels of predonation anxiety displayed larger decreases in end-tidal carbon dioxide throughout the procedure (F(2,236) = 3.64, p = .043, ηp = 0.030). Blood Donation Reactions Inventory scores were related to changes in systolic (β = -0.022, 95% CI = -0.04 to -0.004, t = -2.39, p = .019) and diastolic blood pressure (β = -0.038, 95% CI = -0.06 to -0.02, t = -4.03, p < .001). CONCLUSIONS Although the vasovagal reaction has traditionally been viewed as a primarily cardiovascular event, the present results suggest that hyperventilation also plays a role in the development of vasovagal symptoms.

Background Syncope is a symptom associated with a wide range of pathological conditions, ranging from benign to life threatening. The most frequent is the reflex syncope that may be challenging to treat because of the complex and partially unknown pathophysiological mechanism that has to be addressed by the chosen therapy. Areas of uncertainty Head-up tilt testing is so far the only clinical test able to reproduce reflex syncope, but its diagnostic yield has been recently redefined. A new mechanism such as adenosine-sensitive syncope and idiopathic atrioventricular block have been recently described, and the appropriate therapy is not yet established. There is uncertainty on the efficacy of theophylline and on the use of cardiac pacing in these patients. Data sources Clinical trial published data and position paper from the main expert groups on fludrocortisone, midodrine, etilefrine, beta-blockers, and cardiac pacing as useful therapies for patients affected by reflex syncope. Therapeutic advances Theophylline proved in observational trials to be efficient in preventing reflex syncope recurrences in patients with documented spontaneous paroxysmal conduction disorders comparable to cardiac pacing in a subgroup of patients. Reboxetine and sibutramine may elicit a significant pressor and tachycardic effect able to delay the onset of symptoms during head-up tilt testing. Droxidopa has short-term effects on improving the symptoms because of orthostatic hypotension. Cardiac pacing is effective in preventing reflex syncope recurrences with best results when the indication for pacemaker implantation was based on the documentation of bradycardia or asystole during the spontaneous event by a cardiac monitor. External compression using elastic bandage or compressive stockings is able to prevent the decrease in blood pressure in patients with orthostatic hypotension. Conclusions The optimal management of the complex diagnostic and therapeutic options can be achieved following a standardized and evidence-based approach to the patient with syncope.

Background A vasovagal reaction is a commonly encountered event in outpatient procedures. There is a paucity of discussion on vasovagal reactions (VVRs) in the dermatologic surgery literature. However, recent investigations in the physiology, evaluation, and treatment of VVRs have been reported in other specialties. Objective A comprehensive review of the physiology, evaluation, treatment, and prevention of VVRs. Materials and methods A search as performed using the PubMed/MEDLINE databases. Search terms included "vasovagal," "vasovagal reaction," "syncope," "reflex syncope," "neurocardiogenic syncope," and "fainting." Results Studies demonstrate greater understanding in the physiology of a vasovagal reaction. Although permanent sequelae are uncommon, it is important to respond in a prompt manner. A variety of treatment and prevention options are presented. Conclusion Vasovagal reactions should be carefully evaluated. Additional studies may provide greater data in understanding and managing vasovagal reactions.

Background: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. Methods: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class Results: Time- and frequency-domain heart rate variability demonstrated significant decrease in all autonomic parameters, showing an important parasympathetic and sympathetic activity reduction at 2-year post-cardioneuroablation ( P P >0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation ( P Conclusions: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Background: Increased parasympathetic activity is thought to play important roles in syncope events of patients with vasovagal syncope (VVS). However, direct measurements of the vagal control are difficult. The novel deceleration capacity (DC) of heart rate measure has been used to characterize the vagal modulation. This study aimed to assess vagal control in patients with VVS and evaluate the diagnostic value of the DC in VVS. Methods: Altogether, 161 consecutive patients with VVS (43±15 years; 62 males) were enrolled. Tilt table test was positive in 101 and negative in 60 patients. Sixty-five healthy subjects were enrolled as controls. DC and heart rate variability in 24-hour ECG, echocardiogram, and biochemical examinations were compared between the syncope and control groups. Results: DC was significantly higher in the syncope group than in the control group (9.6±3.3 versus 6.5±2.0 ms, P P =0.614). In multivariable logistic regression analyses, DC was independently associated with syncope (odds ratio=1.518 [95% CI, 1.301–1.770]; P =0.0001). For the prediction of syncope, the area under curve analysis showed similar values when comparing single DC and combined DC with other risk factors ( P =0.1147). From the receiver operator characteristic curves for syncope discrimination, the optimal cutoff value for the DC was 7.12 ms. Conclusions: DC>7.5 ms may serve as a good tool to monitor cardiac vagal activity and discriminate VVS, particularly in those with negative tilt table test.

The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features. In part 2, criteria for pacemaker choice and programming in atrioventricular blocks and neurally mediate syncope are proposed. The atrioventricular blocks can be paroxysmal or persistent, isolated or associated with sinus node disease. Neurally mediated syncope can be related to carotid sinus syndrome or cardioinhibitory vasovagal syncope. In sinus rhythm, with persistent atrioventricular block, we considered appropriate the activation of mode-switch algorithms, and algorithms for auto-adaptive management of the ventricular pacing output. If the atrioventricular block is paroxysmal, in addition to algorithms mentioned above, algorithms to maximize intrinsic atrioventricular conduction should be activated. When sinus node disease is associated with atrioventricular block, the activation of rate-responsive function in patients with chronotropic incompetence is appropriate. In permanent atrial fibrillation with atrioventricular block, algorithms for auto-adaptive management of the ventricular pacing output should be activated. If the atrioventricular block is persistent, the activation of rate-responsive function is appropriate. In carotid sinus syndrome, adequate rate hysteresis should be programmed. In vasovagal syncope, specialized sensing and pacing algorithms designed for reflex syncope prevention should be activated.

Background: Vasovagal syncope (VVS) is the most common cause of syncope in children. Neuropeptide Y (NPY) plays an important role in the regulation of blood pressure (BP), as well as myocardial contractility. This study aimed to explore the role of plasma NPY in VVS in children. Methods: Fifty-six children who were diagnosed with VVS (VVS group) using head-up tilt test (HUT) and 31 healthy children who were selected as controls (control group) were enrolled. Plasma NPY concentrations were detected. The independent t-test was used to compare the data of the VVS group with those of the control group. The changes in plasma NPY levels in the VVS group during the HUT, as well as hemodynamic parameters, such as heart rate (HR), BP, total peripheral vascular resistance (TPVR), and cardiac output (CO), were evaluated using the paired t-test. Furthermore, the correlations between plasma NPY levels and hemodynamic parameters were analyzed using bivariate correlation analysis. Results: The BP, HR, and plasma NPY (0.34 ± 0.12 pg/ml vs. 0.46 ± 0.13 pg/ml) levels in the supine position were statistically low in the VVS group compared to levels in the control group (all P < 0.05). Plasma NPY levels were positively correlated with the HR (Pearson, R = 0.395, P < 0.001) and diastolic BP (Pearson, R = 0.311, P = 0.003) when patients were in the supine position. When patients in the VVS group were in the supine position, elevated TPVR (4.6 ± 3.7 mmHg·min−1·L−1 vs. 2.5 ± 1.0 mmHg·min−1·L−1, respectively, P < 0.001; 1 mmHg = 0.133 kPa) and reduced CO (1.0 ± 0.7 L/min vs. 2.4 ± 1.3 L/min, respectively, P < 0.001) were observed in the positive-response period compared with baseline values. The plasma NPY levels were positively correlated with TPVR (Spearman, R = 0.294, P = 0.028) but negatively correlated with CO in the positive-response period during HUT (Spearman, R= −0.318, P = 0.017). Conclusions: Plasma NPY may contribute to the pathogenesis of VVS by increasing the TPVR and decreasing the CO during orthostatic regulation. Key words: Cardiac Output; Children; Neuropeptide Y; Total Peripheral Vascular Resistance; Vasovagal Syncope

Background Vasovagal reflex is the most common form of syncope, but the pathophysiological mechanisms that initiate the reflex are not well understood. We aimed to study supine and early orthostatic levels of the neurohormones involved in control of circulatory homeostasis in relation to the onset of tilt‐induced vasovagal syncope (VVS). Methods and Results A total of 827 patients who were investigated for unexplained syncope with head‐up tilt test (HUT) and optional nitroglycerin provocation (Italian protocol) had blood samples collected while supine and after 3‐minutes of HUT. Of these, 173 (20.9%) patients developed VVS during drug‐free HUT, 161 of whom (males 44.7%; age 45±21 years) had complete data. We analyzed levels of epinephrine, norepinephrine, C‐terminal pro–arginine vasopressin, C‐terminal endothelin‐1, and midregional fragments of pro–atrial natriuretic peptide and pro‐adrenomedullin in relation to time from tilt‐up to onset of VVS. We applied a linear regression model adjusted for age and sex. The mean time to syncope was 11±7 minutes. Older age (β=0.13; SE=0.03, P, See Editorial Williford et al

Background: Several studies suggest that vasovagal syncope has a genetic origin, but this is unclear. We assessed whether plausible gene variants associate with vasovagal syncope. Methods: We studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. The diagnosis was ascertained with the Calgary Syncope Score. Common genetic variants were genotyped for 12 genes for vascular signaling, potassium channels, the HTR1A (serotonin 5-HT1A receptor), SLC6A4 (serotonin reuptake transporter), and COMT (catecholamine O-methyltransferase). Sex-specific associations between genotypes and phenotypes were tested. Results: In 9 out of 12 variants, there was no significant association between genotype and phenotype. However, the HTR1A (−1019) G alleles associated with syncope in males, but not in females ( P =0.005). CC and GG males had 9% versus 77% likelihoods of syncope. The SLC6A4 promoter L alleles associated with decreased syncope in males but increased in females ( P =0.059). The LL and SS males had 25% and 47% syncope likelihoods, whereas females had 75% and 50% syncope likelihoods. The COMT c.472 A alleles associated with decreased syncope in males but increased in females ( P =0.017). The GG and AA males had 50% and 15% syncope likelihoods, whereas females had 52% and 73% syncope likelihoods. Conclusions: There is a sex-dependent effect of alleles of serotonin signaling and vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope.

Purpose Little is known about the autonomic response to active standing in vasovagal syncope, and most works have focused on children or adolescents. The aim of this work was to study the changes in cardiac autonomic modulation in adult patients with vasovagal syncope through heart rate variability analysis with linear and short-term complexity (alpha-1) indexes during supine position and active standing, in patients with positive or negative head-up tilt test (HUTT). Methods Twenty-five patients with vasovagal syncope were included. Heart rate variability linear and short-term complexity (alpha-1) indexes were recorded during an active standing test (15 minutes in each position) and compared among patients grouped by HUTT outcome and between positions. Results During supine position, positive HUTT (+HUTT) patients had longer mean RR (1016 [850-1051] milliseconds), higher pNN50 (17.7 [9.2-26.2]), lower sympathovagal balance (1.3 [0.5-1.7]), and alpha-1 (0.9 [0.8-1.0]) than negative HUTT (-HUTT) patients (871 [776-969] milliseconds, 8.8 [2.1-14.5], 2.9 [1.3-3.9], and 1.2 [1.0-1.1], respectively). During active standing, heart rate and alpha-1 increased in both groups; in +HUTT patients, pNN50 decreased, whereas sympathovagal balance increased. The magnitude of change between positions of sympathovagal balance and alpha-1 was 6.1 and 4.8 times larger in +HUTT than -HUTT patients, respectively. Conclusions The underlying cardiac autonomic mechanism in vasovagal syncope may involve different autonomic patterns in subjects with a history of recurrent syncope and +HUTT or -HUTT.

Background Biatrial, extensive, and complex ablation strategies have been published for the treatment of neurally mediated syncope, sinus node dysfunction, and functional atrioventricular block. We have developed a less extensive and more specific approach compared with previously published cardioneuroablation strategies, called cardio-neuromodulation. It is based on tailored vagolysis of the sinoatrial node through partial ablation of the anterior right-ganglionated plexus, preferentially through a right-sided approach. Methods Patients with syncope were enrolled between December 2016 and December 2017. They were assigned to group A if they had a positive head-up tilt test and to group B if they presented with a pause ≥3 seconds. The area to target during cardio-neuromodulation was designed offline on a computed tomographic scan. Slow heart rates and pauses were compared during 24-hour rhythm registration at baseline, at 1-month follow-up, and 6-month follow-up. Syncope burden was assessed before the procedure and at 3- and 6-month follow-up. Results Twenty patients underwent cardio-neuromodulation through a right-sided approach (12 in group A, 8 in group B). The first application of radiofrequency energy led to a P-P interval shortening >120 ms in all 20 patients. After a mean±SD ablation time of 7±4 minutes and mean ablated surface area of 11±6 mm 2 , the P-P interval shortened by 219±160 ms ( P P P Conclusions These data indicate that cardio-neuromodulation, through a right-sided and computed tomographic–guided procedure, is safe, fast, and highly reproducible in preventing inappropriate functional sinus bradycardia and syncope recurrence.

Objectives: To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. Methods: MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Results: Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15–0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25–2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. Conclusions: There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder.

Background Syncope is a sudden transient loss of consciousness and postural tone caused by cerebral hypoperfusion. The most common form is vasovagal syncope ( VVS ). Presyncopal progressive early hypotension in older VVS patients is caused by reduced cardiac output ( CO ); younger patients have reduced systemic vascular resistance ( SVR ). Using a priori criteria for reduced CO (↓ CO ) and SVR (↓ SVR ), we studied 48 recurrent young fainters comparing subgroups of VVS with VVS ‐↓ CO , VVS ‐↓ SVR , and both VVS ‐↓ CO &↓ SVR . Methods and Results Subjects were studied supine and during 70‐degrere upright tilt with a Finometer to continuously measure blood pressure, CO , and SVR and impedance plethysmography to estimate thoracic, splanchnic, pelvic, and calf blood volumes, blood flows, and vascular resistances and electrocardiogram to measure heart rate and rhythm. Central blood volume was decreased in all VVS compared to control. VVS ‐↓ CO was associated with decreased splanchnic blood flow and increased splanchnic blood pooling compared to control. Seventy‐five percent of VVS patients had reduced SVR , including 23% who also had reduced CO . Many VVS ‐↓ SVR increased CO during tilt, with no difference in splanchnic pooling, caused by significant increases in splanchnic blood flow and reduced splanchnic resistance. VVS ‐↓ CO &↓ SVR patients had splanchnic pooling comparable to VVS ‐↓ CO patients, but SVR comparable to VVS ‐↓ SVR . Splanchnic vasodilation was reduced, compared to VVS ‐↓ SVR , and venomotor properties were similar to control. Combined splanchnic pooling and reduced SVR produced the earliest faints among the VVS groups. Conclusions Both ↓ CO and ↓ SVR occur in young VVS patients. ↓ SVR is predominant in VVS and is caused by impaired splanchnic vasoconstriction.

Introduction Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. Case A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 μg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. Discussion Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. Conclusions Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

To provide a detailed semiology to aid the clinical recognition of psychogenic pseudosyncope (PPS), which concerns episodes of apparent transient loss of consciousness (TLOC) that mimic syncope.We analyzed all consecutive tilt-table tests from 2006 to 2012 showing proven PPS, i.e., apparent TLOC had occurred without EEG changes or a decrease in heart rate (HR) or blood pressure (BP). We analyzed baseline characteristics, video data, EEG, ECG, and continuous BP measurements on a 1-second time scale. Data were compared with those of 69 cases of tilt-induced vasovagal syncope (VVS).Of 800 tilt-table tests, 43 (5.4%) resulted in PPS. The majority (74%) were women. The median duration of apparent TLOC was longer in PPS (44 seconds) than in VVS (20 seconds, p0.05). During the event, the eyes were closed in 97% in PPS but in only 7% in VVS (p0.0001). A sudden head drop or moving down the tilt table was more common in PPS than in VVS (p0.01), but jerking movements occurred more frequently in VVS (p0.0001). In PPS, both HR and BP increased before and during apparent TLOC (p0.0001).PPS is clinically distinct from VVS and can be diagnosed accurately with tilt-table testing and simultaneous EEG monitoring. Compared with VVS, eye closure during the event, long periods of apparent TLOC, and high HR and BP are highly specific for PPS. Improved understanding of the semiology of PPS as a clinical entity is vital to ensure accurate diagnosis.

Background Autonomic modification through catheter ablation of ganglionated plexi ( GPs ) in the left atrium has been reported previously as a treatment for vasovagal syncope. This study aimed to observe the long‐term outcome in a larger cohort. Methods and Results A total of 57 consecutive patients (aged 43.2±13.4 years; 35 women) with refractory vasovagal syncope were enrolled, and high‐frequency stimulation and anatomically guided GP ablation were performed in 10 and 47 cases, respectively. A total of 127 GP sites with positive vagal response were successfully elicited and ablated, including 52 left superior, 19 left lateral, 18 left inferior, 27 right anterior, and 11 right inferior GP s. During follow‐up of 36.4±22.2 months (range 12–102 months), 52 patients (91.2%) remained free from syncope. Prodromes recurred in 16 patients. No statistical differences were found between the high‐frequency stimulation and anatomically guided ablation groups in either freedom from syncope (100% versus 89.4%, P =0.348) or recurrent prodromes (50% versus 76.6%, P =0.167). The deceleration capacity, heart rate, and heart rate variability measurements demonstrated a reduced vagal tone lasting for at least 12 months after the procedure, with improved tolerance of repeated head‐up tilt testing. No complications were observed except for transient sinus tachycardia that occurred in 1 patient. Conclusions Left atrial GP ablation showed excellent long‐term clinical outcomes and might be considered as a therapeutic option for patients with symptomatic vasovagal syncope .

There have been reports on the use of octreotide in patients with orthostatic hypotension, postural tachycardia syndrome, and orthostatic syncope. However, there are little if any data on the use of octreotide in patients who have failed multiple other medications. This study was a retrospective chart analysis and was approved by our Institutional Review Board. A total of 12 patients were identified for inclusion in this study. The diagnosis of orthostatic intolerance was based on patient history, physical examination, and response to Head Up Tilt Table testing. These patients had failed multiple medications and were ultimately treated with octreotide. In a retrospective chart review, we collected data, including demographic information, presenting symptoms, laboratory data, tilt-table response, standing heart rate, standing blood pressure before and after treatment (wherever available), and treatment outcomes. Twelve patients aged 33 6 18 years, eight (66.7%) females, were found to have symptoms of refractory orthostatic intolerance and failed multiple regimens of medication and were ultimately treated with octreotide administration. Five patients (41.7%) had demonstrated a postural tachycardia syndrome pattern, five (41.7%) a neurocardiogenic, and two (16.6%) a dysautonomic response on a Head Up Tilt Table. Symptoms of syncope and orthostatic palpitations improved in six (50%) of the patients. Standing heart rate was significantly reduced after octreotide administration (80 6 8 versus 108 6 13; P , 0.05). The standing systolic blood pressure was increased after octreotide administration (107 6 26 versus 116 6 22). Three patients (25%) reported complete elimination of syncope, whereas another three had reduction in the frequency of their syncope. However, symptoms of fatigue improved only in two (29%) of the seven patients. Octreotide may improve symptoms in some patients with refractory orthostatic intolerance.

Neurocardiogenic syncope is induced by a hyperrecruitment of parasympathetic nerve tone elicited by emotional stress or pain. The presence of a transient loss of consciousness associated with involuntary motor activity or with urinary incontinence and the misinterpretation of anamnestic data or of electroencephalogram (EEG) abnormalities often leads to wrong diagnosis of epilepsy in children with this disorder.Careful and systematic history taking, pressure measurement, electrocardiogram (ECG), and, in selected cases, head-up tilt table testing are generally enough to rule out a cardiogenic or a neurocardiogenic syncope. Simultaneous EEG-ECG Holter represents a useful instrument for differential diagnosis between neurocardiogenic syncope and epilepsy.We report 3 case reports to demonstrate how simultaneous EEG-ECG Holter can contribute to characterize functional heart-brain interactions and the exact sequence of the physiopathologic events leading to the loss of consciousness in cases in which the clinical borders with epileptic disorders are particularly subtle.

Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in acute care settings. Moreover, OH may be more prevalent in the elderly due to the increased use of vasoactive medications and the concomitant decrease in physiologic function, such as baroreceptor sensitivity. OH may result in the genesis of a presyncopal state or result in syncope. OH is defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review of symptoms, and measurement of supine and standing BP with appropriate clinical tests should narrow the differential diagnosis and the cause of OH. The fall in BP seen in OH results from the inability of the autonomic nervous system (ANS) to achieve adequate venous return and appropriate vasoconstriction sufficient to maintain BP. An evaluation of patients with OH should consider hypovolemia, removal of offending medications, primary autonomic disorders, secondary autonomic disorders, and vasovagal syncope, the most common cause of syncope. Although further research is necessary to rectify the disease process responsible for OH, patients suffering from this disorder can effectively be treated with a combination of nonpharmacologic treatment, pharmacologic treatment, and patient education. Agents such as fludrocortisone, midodrine, and selective serotonin reuptake inhibitors have shown promising results. Treatment for recurrent vasovagal syncope includes increased salt and water intake and various drug treatments, most of which are still under investigation.

Vasovagal syncope is very frequent and benign and the vast majority of subjects do not need any specific treatment, but only reassurance and education. An unknown but small percentage of patients require specific treatment when syncope is very frequent or is responsible for major trauma. For these patients, there are some evidence-based therapies available and some first-line treatments appear to be established. The therapeutic choice mainly depends on the presence and duration of prodromal symptoms. In subjects aged < 70 years with well recognizable prodromes, the first-line treatment is counterpressure manoeuvres. In patients with no or minimal prodromes, but with tilt testing and carotid sinus massage (CSM) both positive, cardiac pacing appear to be the first-line therapy. However, an area of uncertainty remains, represented by patients with no or minimal prodromes and negative CSM. For these patients, appropriate treatment (drugs, tilt training, cardiac pacing, relaxation-based treatment) can be chosen by considering the clinical context, the risk of trauma and possible comorbidities, in addition to utilizing the little or controversial knowledge available, as well as common sense.

Background— Chronic orthostatic intolerance (COI) occurs in postural tachycardia syndrome (POTS) and in some individuals with repeated neurocardiogenic syncope/presyncope (NCS), without POTS. This study addressed whether patients with COI and POTS or NCS have neurocirculatory abnormalities during supine rest. Methods and Results— Adult patients referred for COI who had POTS (n=90, mean±SEM age 40±1 years, 86% women) or NCS (n=36, 41±2 years old, 78% women) underwent measurements of plasma levels of catecholamines and forearm hemodynamics. Comparison data were obtained from 32 age- and gender-matched normal volunteers (39±2 years old, 81% women). The POTS group had a relatively fast mean heart rate (79±2 bpm) during supine rest compared with the NCS group (69±1.6 bpm, P =0.03) and normal volunteers (66±3 bpm, P =0.0004). The POTS group also had higher mean arterial norepinephrine (1.61±0.11 nmol/L, n=37) and epinephrine (0.39±0.03 nmol/L, n=37) concentrations than the NCS group (1.03±0.12 nmol/L, n=20, P =0.0012; 0.21±0.03 nmol/L, n=20, P =0.0005) and normal volunteers (1.13±0.11 nmol/L, n=20, P =0.006; 0.17±0.03 nmol/L, n=15, P =0.0001). The NCS group had higher mean forearm vascular resistance (52±6 U) than the POTS group (36±2 U, P =0.003). Conclusions— Overall, POTS features increased heart rate and sympathetic nervous and adrenomedullary hormonal system outflows during supine rest. Increased sympathetic outflow may contribute to the relative tachycardia in POTS. NCS features forearm vasoconstriction during supine rest but not sympathoneural or adrenomedullary activation.

Purpose of review This review focuses on the common and uncommon adverse events that occur during or after whole-blood donation. The incidence of seeking outside medical care for an adverse event is at least 1 in 3400 blood donations. Physicians may encounter blood donors with adverse events and should be familiar with their prognosis and treatment. Recent findings There are 15 million whole-blood donations per year in the United States, and one third of the donors develop one or more adverse events. A recent study defined the common complications based on a postdonation interview as bruise (23%), sore arm (10%), fatigue (80/%), and vasovagal reaction (7%). A 2003 American Red Cross national donor complication database from 7,000,000 whole-blood donations classified reported donor complications and the incidence of outside medical care. Descriptive studies have been published on vasovagal syncopal reactions, antecubital nerve injuries (irritations), and arterial punctures, and the medical outcomes for these entities have been more precisely defined. The effect of blood donor adverse events on donor retention rates is a new area that is just beginning to be studied. Summary The incidence of complications and types of complications is more precisely defined today. Medical outcomes are better defined for vasovagal reactions, nerve injuries (irritations), and arterial puncture. These data should help physicians who encounter these entities.

Background— The main purpose of our study was to define an animal model of vagal hyperreactivity and its genetic transmission. Methods and Results— We first investigated the vagal reactivity with phenylephrine in conscious rabbits. Barosensitivity and the maximal bradycardic response were measured at the upper mean blood pressure plateau. Hyperreactive (H) animals were selected and crossbred with normal (N) ones. Results showed no significant difference between calculated barosensitivity values after the different doses of phenylephrine. In contrast, an increase of the values and a great dispersion appeared 1 to 5 beats after the end of the ramp. Marked pauses (6000 to 20 000 ms) were obtained with some rabbits, which were blocked by atropine. A significant excess of hyperreactive offspring was observed in H×H crossings compared with N×N ones (39.4% male and 42.3% female offspring versus 14.4% and 4.4%, respectively). Few female offspring were hyperreactive compared with males in N×H and N×N crossings (4.1% versus 23.4% and 4.4% versus 14.4%, respectively). Conclusions— This study describes the first model of spontaneous vagal pauses. The inheritance could be polygenic with a partial sex-limited character.

Background— In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear. Methods and Results— Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating 3 H-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[ 18 F]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171±30 pmol/min, N=16) was higher and in NCS (62±9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102±9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106±18 pmol/min, N=11). Both patient groups had normal cardiac extraction of 3 H-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[ 18 F]fluorodopamine-derived radioactivity. Conclusions— POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia.

Background— The purpose of this study was to assess the effect of the serotonin reuptake inhibitor paroxetine hydrochloride (Paxil, SmithKline Beecham) on cardiovascular reflexes. We hypothesized that Paxil prevents neurally mediated syncope (NMS) by attenuating the sympathoinhibition and vagotonia associated with a vasovagal reaction. Methods and Results— In a double-blind randomized study, 25 healthy subjects with a positive response to either carotid sinus massage (CSM) or lower body negative pressure (LBNP) received Paxil (20 mg/d) or placebo for 6 weeks. Arterial baroreflex sensitivity (BRS), muscle sympathetic nerve activity (SNA), baroreflex control of SNA, blood pressure, and heart rate responses to CSM and LBNP were measured at baseline and at 6 weeks. Nineteen subjects completed the study (Paxil, n=9; placebo, n=10). In the Paxil group, BRS decreased significantly compared with baseline (15.8±4.0 ms/mm Hg versus 11.0±2.6 ms/mm Hg, P =0.05); however, all 9 subjects continued to have a positive response to LBNP with presyncope. Paxil did not attenuate the sympathoinhibition or vagotonia associated with a positive LBNP response and had no significant effect on baroreflex control of SNA. In the control group, no significant change in BRS was noted compared with baseline. Seven out of 9 subjects who had a positive LBNP response at baseline had a repeat positive LBNP response, and the subject with a positive CSM at baseline had a negative response at 6 weeks. Conclusions— Paxil decreases arterial BRS but does not prevent the presyncope associated with LBNP. The effect of Paxil on the autonomic reflexes in patients with neurally mediated syncope remains unclear.

Background — Previous reports that used head-up tilt testing and adenosine administration have suggested that adenosine may be an important endogenous mediator that may trigger a vasovagal response in susceptible patients. However, little is known regarding endogenous adenosine plasma levels (APLs) during vasovagal syncope provoked by tilt testing. The aim of this study was to determine whether APLs differ in patients with a positive head-up tilt test compared with those with a negative test and whether APLs are modified during tilt-induced vasovagal syncope. Methods and Results — APLs (mean±SEM) were measured during head-up tilt test in 26 patients who presented with unexplained syncope. In the 15 patients with a negative test, APLs were 0.39±0.03 μmol/L at baseline, 0.22±0.03 μmol/L immediately after tilting, and 0.44±0.03 μmol/L after 45 minutes. APLs were significantly higher in the 11 patients with a positive test (2.66±0.67 μmol/L at baseline and 3.22±0.85 μmol/L immediately after tilting) than in those with a negative test. During tilt testing–induced syncope, APLs increased to reach 4.03±0.66 μmol/L (ie, a 52% increase compared with baseline levels; P Conclusions — This study showed that APLs were higher in patients with a positive tilt test than in patients with a negative test and that they increased during tilt testing–induced syncope. These observations suggest that adenosine release may be involved in the triggering mechanism of syncope induced during tilt testing.

Patients with frequent vasovagal syncope have a poor quality of life and often resist treatment with standard pharmacologic approaches. Although the evidence is weak, clinical vasovagal syncope is probably associated with some degree of bradycardia. Studies of temporary pacing during tilt table tests showed that pacing prevented syncope in a little over half of patients who developed a vasovagal response. Six open-label studies of permanent pacing show that permanent pacemaker therapy is associated with substantial improvement over medical therapy. The roles of specific pacemaker modes have not been determined, although there is some evidence that rate-drop responsiveness helps. The second Vasovagal Pacemaker Study will quantify the true benefits of pacing for vasovagal syncope and assess the role of rate-drop response algorithms.

To describe the combination of tilt-induced vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS) and aid its clinical recognition.We identified people with tilt-induced VVS/PPS from 2 tertiary syncope referral centers. For each case, 3 controls with tilt-induced VVS were selected at random from the same center. Clinical characteristics were compared between both groups adjusting for multiple comparisons.Of 1,164 tilt-table tests, 23 (2%) resulted in VVS/PPS; these 23 cases were compared with 69 VVS controls. VVS and PPS coincided more often than chance would predict: 2% vs 0.6%, p0.001. Typical VVS prodromes and triggers were reported in all people with VVS/PPS and in controls with VVS. Attack frequency was significantly higher in the VVS/PPS (2 per month, range 0.1-60) than in the VVS group (0.25 per month, range 0.02-4; p0.001). Delayed recovery of consciousness was more frequently reported in the VVS/PPS group (likelihood ratio [+LR] 8.14, 95% confidence interval [CI] 3.94-16.84), as well as episodes without prodromes (+LR 5.57, 95% CI 2.53-12.26), atypical triggers (+LR 5.00, 95% CI 2.04-12.24), eye closure (+LR 3.75, 95% CI 1.68-8.35), and apparent loss of consciousness1 minute (+LR 2.86, 95% CI 1.98-4.13).VVS/PPS presents with a complex phenotype. High attack frequency, delayed recovery of consciousness, apparent loss of consciousness1 minute, ictal eye closure, atypical triggers, and the absence of prodromes may serve as indicators that PPS coincides with VVS.

In general, syncope in children and adolescents is a benign event. Syncope during exercise may identify patients with a potentially fatal condition. Catecholaminergic polymorphic ventricular tachycardia is characterized by life-threatening ventricular arrhythmias, usually polymorphic ventricular tachycardia or ventricular fibrillation, occurring under conditions of exercise or emotional stress. Catecholaminergic polymorphic ventricular tachycardia is a familial condition that presents with exercise-induced syncope or sudden death in children or young adults. Detailed evaluation should be considered for patients who have syncope during exercise, injure themselves during the fall (i.e., unprotected faint with no antecedent warning prodrome), or who have a family history of syncope, early sudden cardiac death, myocardial disease, or arrhythmias.

Background — The effect of orthostatic stress on dynamic cerebral autoregulation (CA) in normal subjects and patients with recurrent vasovagal syncope (VVS) is unclear. This study assessed the dynamic CA responses of both groups to head-up tilt. Methods and Results — Seventeen patients with recurrent VVS and 17 pair-matched control subjects underwent 70° head-up tilt for up to 30 minutes. Bilateral middle cerebral artery blood flow velocities (CBFV) were measured with transcranial Doppler ultrasound along with noninvasive beat-to-beat blood pressure (BP), heart rate, and transcutaneous and end-tidal CO 2 concentrations. Indices of dynamic CA were derived for periods before, during, and after tilt. Eight normal subjects who developed VVS in an identical protocol but who had no previous clinical history of syncope were also studied. CBFV and transcutaneous and end-tidal CO 2 levels declined significantly during head-up tilt in all groups ( P P =0.027 and P =0.012, respectively) and after ( P =0.002 and P =0.007, respectively) syncope. Conclusions — Dynamic CA is preserved in patients and control subjects initially after head-up tilt. Autoregulatory function remains intact in nonsyncopal control subjects during prolonged orthostasis but deteriorates in patients and syncopal control subjects immediately before and after VVS.

Syncope in childhood is a common problem. In most children, syncope is benign, secondary to a disturbance in autonomic control of heart rate and blood pressure. It is increasingly evident that neurally mediated syncope is a heterogeneous group of conditions, necessitating a reclassification of autonomic disorders. New entities, such as postural orthostatic tachycardia and cerebral vasoconstrictive syncope, are recognized. The key to the diagnosis of syncope is a careful history. Tilt testing can be useful when the history is unclear. Unfortunately tilt test protocols vary, affecting specificity and sensitivity. The mainstay of therapy is reassurance. If symptoms are troublesome, Fludrocortisone and B-blockers remain the favored drugs. The efficacy of Midodrine and Serotonin Uptake Inhibitors is currently under review. Cardiac pacing is effective for those patients with severe episodes and demonstrated asystole. It is not known whether pacing would be effective for the majority who have neurally mediated syncope without significant bradycardia.

Syncope is defined as a sudden transient loss of consciousness and postural tone due to cerebral hypoperfusion. Although no permanent medical sequelae should result from syncope itself, isolated or recurrent events are often dramatic and disrupt the lifestyle of affected individuals. Syncope is a common clinical problem that affects up to 3.5% of the general population.1 Strikingly, in close to 40% of cases, the exact cause of syncope remains elusive, and ≈30% of affected patients will experience recurrent episodes.1 Neurally mediated syncope (NMS) is a common type of syncope (Figure 1⇓); clinical descriptions of it have been present in the medical literature for >100 years. Despite its prevalence, significant gaps in our understanding of its pathophysiology and treatment remain. The purpose of this review is to critically evaluate proposed theories that attempt to explain the pathophysiological mechanisms of NMS. Figure 1. Causes of syncope. NMS and orthostatic intolerance (OI) are the most frequent causes of unexplained syncope. Other causes may be hypoadrenergic (HypoAdr), cardiac (Card), neurological (Neurol), psychiatric (Psych), and/or idiopathic (Idiop). The development of arterial vasodilation in the setting of relative or absolute bradycardia characterizes NMS. This syndrome has also been known as vasovagal reaction, neurocardiogenic syncope, emotional fainting, or reflex syncope. Related processes include situational fainting (ie, shaving syncope), hyperadrenergic and hypoadrenergic conditions, and hypotensive reactions resulting from drug administration. We have classified NMS into several categories. These include central (for example, occurring in response to strong emotional stimulation), postural (associated with the upright position), and situational (after the specific stimulation of sensory or visceral afferents). Another classification considers the final hemodynamic characteristics of the patient and includes categories such as vasodepressor, bradycardic, or mixed NMS.2 One other classification relates to the clinical characteristics of the syncope and its response to treatment. This categorization includes malignant …

Syncope is a common clinical presentation. Although most commonly benign, it may herald a pathology with a poor prognosis. The work-up of syncope includes a careful history, physical examination, electrocardiogram, risk stratification, and appropriately directed testing. The key factor in the investigation of syncope is the presence (or absence) of structural heart disease or an abnormal electrocardiogram. The most useful investigation in unexplained syncope with a normal heart is the tilt table test for evaluating predisposition to neurocardiogenic (vasovagal) syncope. In the setting of structural heart disease or an abnormal electrocardiogram, electrophysiologic studies play a more important role. The utility of noninvasive cardiac monitoring for symptom-rhythm correlation may be limited by infrequent symptoms. The availability of external and implantable loop recorders allows prolonged periods of monitoring to increase diagnostic yield. The management of patients with syncope may be complex. Early referral to a cardiac electrophysiologist is warranted in patients who are at high risk.

Background —Tilt testing is used to establish the diagnosis of neurally mediated syncope. However, applicability of the tilt test is limited by test sensitivity and length of time required to perform the test. We hypothesized that adenosine could facilitate the induction of neurally mediated syncope through its sympathomimetic effects and therefore could be used as an alternative to routine tilt testing. Methods and Results —In protocol 1, the yield of adenosine tilt testing (12 mg while upright, followed by 60° tilt for 5 minutes) and a 15-minute isoproterenol tilt test were compared in 84 patients with a negative 30-minute drug-free tilt test. In protocol 2, 100 patients underwent an initial adenosine tilt test followed by our routine tilt test (30-minute drug-free tilt followed by a 15-minute isoproterenol tilt). Six additional control patients underwent microneurography of the peroneal nerve to compare the sympathomimetic effects during bolus administration of adenosine and continuous infusion of isoproterenol. In protocol 1, the yields of adenosine (8 of 84, 10%) and isoproterenol (7 of 84, 8%) tilt testing were comparable ( P =NS). In protocol 2, the yields of adenosine (19 of 100, 19%) and routine (22 of 100, 22%) tilt testing were also comparable ( P =NS). Although the yield of adenosine tilt testing was comparable in both protocols, patients with a negative adenosine tilt test but a positive routine tilt test usually required isoproterenol to elicit the positive response. Microneurography confirmed discordant sympathetic activation after adenosine and isoproterenol administration. Conclusions —Adenosine is effective for the induction of neurally mediated syncope, with a diagnostic yield comparable to routine tilt testing. However, the discordant results obtained with adenosine and the isoproterenol phase of routine tilt testing suggest that adenosine and isoproterenol tilt testing may have complementary roles in eliciting a positive response. Therefore, a tilt protocol that uses an initial adenosine tilt followed, if necessary, by an isoproterenol tilt would be expected to increase the overall yield and reduce the duration of tilt testing.

The most common indication for a permanent pacemaker is symptomatic bradycardia. An atrial-based pacemaker (dual-chamber or atrial) usually is preferred, except in patients with chronic atrial fibrillation. Several prospective, randomized trials recently have been completed to evaluate new indications for permanent pacemakers. A dual-chamber pacemaker with an optimal atrioventricular interval can reduce the left ventricular outflow tract gradient by >50% in patients with hypertrophic cardiomyopathy. This has been associated with symptomatic improvement in the majority of patients, but an important placebo effect appears likely. Pacing also has been evaluated in patients with medically refractory dilated cardiomyopathy. Despite encouraging initial studies, routine implantation of a permanent pacemaker in dilated cardiomyopathy is not indicated. In patients with cardioinhibitory or mixed vasovagal syncope and carotid sinus hypersensitivity, implantation of a pacemaker markedly decreases syncopal episodes. Pacemaker therapy is clearly indicated in patients with atrial fibrillation associated with symptomatic bradycardia, and exciting new data on the use of pacing to prevent atrial fibrillation appear promising. The best pacing modality for this indication may be dual-site atrial pacing. Finally, permanent pacemakers play an important role in the treatment of symptomatic long QT syndrome, usually in combination with beta-blockers.

Background —The dynamic autonomic processes leading to vasovagal syncope are poorly understood. Methods and Results —We used complex demodulation to continuously assess changes in respiration, R-R interval, and arterial pressure (blood pressure) variability during 60 degree head-up tilt in 25 healthy subjects with tilt-induced vasovagal syncope and 25 age-matched nonsyncopal control subjects. Coherence and transfer function analyses were used to examine the relation between respiration and R-R interval variability before syncope. Baseline blood pressure, R-R, and ventilation were similar between syncope subjects and control subjects. Syncope subjects experienced an increase in tidal volume and decrease in BP beginning 3 minutes before impending syncope (systolic blood pressure Conclusions —Vasovagal syncope is preceded by a period of hyperpnea and cardiorespiratory decoupling followed by an abrupt increase in cardiovagal tone. Respiratory pumping without inspiratory cardiac slowing may partially counteract preload reduction until sudden bradycardia precipitates syncope.

Background In the present study, we tested the hypothesis that baroreflex sensitivity is reduced in patients with vasovagal syncope compared with normal control subjects. Methods and Results We investigated 30 patients with vasovagal syncope (mean age, 43.6±16.7 years; 14 men and 16 women) and 32 normal control subjects (mean age, 41.8±17.0 years; 24 men and 8 women). Cardiopulmonary baroreceptor sensitivity was assessed by measuring the change in forearm vascular resistance during subhypotensive lower body negative pressure (LBNP). Carotid baroreflex sensitivity was assessed by measuring the change in RR interval during the manipulation of carotid transmural pressure. Phenylephrine baroreceptor sensitivity was assessed on the basis of the linear regression slope of the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. In patients with vasovagal syncope, during the application of −10 mm Hg LBNP, forearm vascular resistance decreased by 0.7±11.6 U versus an increase of 8.3±6.2 U in control subjects ( P =.002). Phenylephrine baroreceptor sensitivity was 11±7 ms/mm Hg in patients versus 14±6 ms/mm Hg in control subjects ( P =NS). Carotid baroreflex sensitivity was 4±6 versus 4±2 ms/mm Hg in patients and control subjects, respectively ( P =NS). Conclusions In patients with vasovagal syncope, during the application of subhypotensive LBNP, there is impaired forearm vasoconstriction or paradoxical forearm vasodilation. This suggests impaired cardiopulmonary baroreceptor inactivation or paradoxical activation of these receptors and is consistent with reduced cardiopulmonary baroreceptor sensitivity.

A variety of experimental and clinical reports have engendered a different approach to cardiac arrhythmias as well as other cardiovascular conditions. The focus of a new paradigm is the autonomic nervous system and its important role in various pathological states. From an overall standpoint, this new paradigm can be encompassed by the term “autonomic modulation,” which would include autonomic nerve stimulation or autonomic denervation to modulate the autonomic activity in physiological or pathophysiological functions of the heart as well as other visceral organ systems. Article see p 279 Vaso-vagal syncope is the most common form of neurally mediated syncope.1 The pathophysiology of vaso-vagal syncope is still controversial, but it is thought to be related to prolonged orthostatic stress, which causes increased peripheral venous pooling with a subsequent fall in venous return to the heart. This in turn causes a hypercontractile state, which leads to activation of ventricular mechanoreceptors and a sudden increase in the afferent neural traffic to the brain. The result is sympathetic withdrawal and parasympathetic enhancement that manifests as hypotension (vasodepressor type), bradycardia (cardioinhibitory type), and syncope.1 In other words, vaso-vagal syncope is a disorder caused by an abnormally amplified autonomic reflex involving both sympathetic and parasympathetic components. Over the past 2 decades, β-blockers, α-agonists, mineralocorticoids, selective serotonin reuptake inhibitors, and dual-chamber pacemaker implantation all produced initial promising but later disappointing results.1–3 Vaso-vagal syncope continues to be a vexing clinical arrhythmia. In this issue of Circulation Arrhythmia and Electrophysiology , Yao et al4 reported 10 patients who had drug-refractory, frequent, and highly symptomatic vaso-vagal syncope. Based on the hypothesis that …

Vasodepressor syncope is characterized hemodynamically by a sudden fall in total peripheral resistance with little associated change in cardiac output. The failure of the cardiac output to compensate for the fall in peripheral resistance is a striking feature of the fainting reaction. Possible explanations for this phenomenon are the presence of neurogenic myocardial inhibition or markedly limited volume of blood available to the heart. The effects of atropine injections, inflation of antigravity suit, negative pressure breathing, and albumin infusions on the syncopal reaction were studied. Results favor the causative role of limited venous inflow in the cardiac output response.