Efficacy of tilt training in the treatment of neurally mediated syncope. A randomized study.

Recurrent neurally mediated syncope represents a common clinical event and a therapeutic challenge. Recently tilt training has been proposed for the treatment of recurrent neurally mediated syncope. To evaluate the efficacy of tilt training in preventing tilt-induced syncope and its feasibility, this controlled, randomized study was undertaken. Sixty-eight consenting patients (25 males and 43 females, mean age 40 +/- 19) with recurrent neurally mediated syncope and 2 consecutive positive nitroglycerin-potentiated head-up tilt tests were randomized to tilt training (35 patients) or no treatment (controls, 33 patients). The tilt training programme consisted of daily 30-min sessions of upright standing against a vertical wall 6 days a week for at least 3 weeks, until a reevaluation tilt test (3 patients of both groups dropped out). On this third head-up tilt test, 19 (59%) of 32 tilt trained patients and 18 (60%) of 30 controls still had a positive test. Treated patients performed a mean number of 15 +/- 7 sessions (median 16) and only 11 patients (34%) did all the programmed sessions. Only 1 patient (3%) discontinued treatment because of intolerance, while all other patients did not perform tilt training adequately, because of poor compliance. Thus, in our study tilt training was not effective in reducing tilt testing positivity rate in patients with neurally mediated syncope. Because of poor compliance, tilt training appears to be a feasible treatment only for highly motivated patients, but not for the majority of patients with recurrent neurally mediated syncope.     

Significance of circulatory epinephrine levels in exercise-induced neurally mediated syncope

BACKGROUND AND HYPOTHESIS: Previous research has failed to document temporal changes in epinephrine levels in patients with neurally mediated syncope associated with exercise. The purpose of this study was to investigate the role of circulatory catecholamines in exercise-induced neurally mediated syncope, specifically focusing on epinephrine levels. METHODS: The present study deals with temporal changes of circulatory catecholamine levels during head-up tilt tests (40 min, 80 degree tilt) in 62 patients with syncope of unknown origin, 7 of whom had syncope associated with exercise (exercise-induced group, 19+/-3 years). Data were compared with 10 control subjects (control group, 45+/-23 years). Of the 55 patients with syncope not associated with exercise, 32 tested positive for the head-up tilt tests (positive group, 31+/-16 years) and 23 patients tested negative (negative group, 46+/-19 years). Blood samples for circulatory catecholamine assay were obtained from the antecubital vein in the baseline supine position 2 min after the tilt started, every 10 min during tilt, and at the time of the onset of symptoms or the end of tilt. Levels of norepinephrine and epinephrine were determined using the high-pressure liquid chromatography (HPLC) method (pg/ml). RESULTS: Plasma norepinephrine levels among the four groups were similar at the supine position and during tilt testing. In contrast, patients in the exercise-induced group had significantly higher maximum epinephrine levels during head-up tilt testing than the other three groups (288+/-191 vs. 148+/-117, 66+/-31, and 54+/-27 pg/ml, respectively, p < 0.05). Patients in the positive group had higher maximum epinephrine levels than those in the negative group (p <0.05). Also, patients in the exercise-induced group and those in the positive group had a significantly shorter tilt-testing time than patients in the negative and control groups. CONCLUSIONS: A marked increase of epinephrine was observed during head-up tilt testing in patients with neurally mediated syncope associated with exercise. The present findings further accelerate the identification of the role of epinephrine in the mechanisms behind neurally mediated syncope associated with exercise.     

Hemodynamic significance of heart rate in neurally mediated syncope

BACKGROUND: Vasovagal and vasodepressor syncope are used interchangeably in the literature to describe the common faint syndrome, now collectively named neurally mediated syncope. The significance of heart rate (HR) in these reflex-induced reactions remains unclear. Hypothesis: The study was undertaken to investigate the hemodynamic significance of HR in tilt-induced neurally mediated syncope. METHODS: In all, 113 patients with syncope of unknown etiology were studied by head-up tilt test with invasive hemodynamic monitoring. Thirty-five patients (15 women, 20 men, age range 21 to 72 years) developed syncope and were enrolled for analysis. The hemodynamic data were compared between patients who developed bradycardia (vasovagal group, n = 15) and those without bradycardia (vasodepressor group, n = 20). RESULTS: The baseline hemodynamic data (mean +/- standard deviation) and the hemodynamic responses after 10-min headup tilt were similar between patients in the vasovagal and vasodepressor groups. During syncope, patients with vasovagal reaction developed hypotension and paradoxical bradycardia (HR = 52.4 +/- 5.9 beats/min), while patients with vasodepressor reaction developed a precipitous drop in arterial blood pressure with inappropriate HR (105 +/- 21 beats/min) compensation. Patients with vasovagal syncope manifested a significantly lower cardiac index and a significantly higher systemic vascular resistance index than patients with vasodepressor syncope (1.47 +/- 0.29 vs. 1.97 +/- 0.41 1/min/m2, p < 0.001 and 2098 +/- 615 vs. 1573 +/- 353 dynes x s x cm(-5) x m2, p < 0.003, respectively). A positive correlation existed between HR and cardiac index (r = 0.44, p = 0.008) during syncope in the patients studied. CONCLUSIONS: These findings suggest that the hemodynamic characteristics of vasovagal and vasodepressor reactions are different, and that HR plays a significant role in neurally mediated syncope.     

Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans

Previous studies suggest that neuronal norepinephrine transporter function may regulate the distribution of sympathetic activity among blood vessels, heart, and kidney; we tested the functional relevance in humans. Sixteen healthy men (26+/-1 years) ingested 8 mg of the selective norepinephrine reuptake transporter inhibitor reboxetine or a matching placebo on 2 separate days in a double-blind, randomized, crossover fashion. We monitored heart rate, thoracic bioimpedance, blood pressure, glomerular filtration rate, and renal blood flow. Ninety minutes after ingestion of the test medication, subjects were tilted to a 45 degrees head-up position, where they remained for an additional 30 minutes. Reboxetine increased supine systolic blood pressure through an increase in cardiac output whereas systemic vascular resistance decreased. Furthermore, reboxetine increased heart rate, particularly with a head-up tilt. Supine plasma renin activity was 0.71+/-0.15 ng angiotensin (Ang)/L per mL/h with placebo and 0.36+/-0.07 ngAng/L per mL/h with reboxetine (P<0.01). Supine plasma Ang II concentrations were also decreased with reboxetine. Both plasma renin activity and Ang II concentrations remained suppressed during head-up tilt. On placebo, renal vascular resistance increased with head-up tilt. The response was abolished with norepinephrine reuptake inhibition. We conclude that norepinephrine reuptake function profoundly influences the distribution of sympathetic activity between the heart, vasculature, and kidney in humans. All of these changes are physiologically relevant because they lead to corresponding changes in organ function.     

Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia

It has been proposed that prolonged cardiac asystole mimicking an episode of sudden cardiac death may occur as a manifestation of neurally mediated hypotension-bradycardia syndrome. To assess this possibility, electrocardiographic and hemodynamic findings during upright tilt testing were evaluated in six survivors of suspected asystolic sudden cardiac arrest with normal conventional electrophysiologic evaluation (Group I). These observations were compared with findings in two control groups: six patients with syncope but without evident asystole and with normal conventional electrophysiologic evaluation but demonstrable neurally mediated hypotension-bradycardia (Group II), and six patients with syncope in whom conventional electrophysiologic evaluation provided a presumptive diagnosis (Group III). Patients in all three groups ranged in age from 16 to 59 years. During head-up tilt testing (either alone or with isoproterenol infusion), patients in both Groups I and II developed syncope in less than or equal to 5 min, whereas patients in Group III remained asymptomatic. Patients in Groups I and II exhibited a similar tilt-induced decrease in mean arterial pressure (-46 +/- 9 and -40 +/- 9 mm Hg, respectively, p = NS) and heart rate (-44 +/- 28 and -49 +/- 12 beats/min, respectively, p = NS). In contrast, patients in Group III manifested only a moderate decrease in mean arterial pressure (-14 +/- 5 mm Hg) and had an increase in heart rate (+14 +/- 8 beats/min). Both mean arterial pressure and heart rate changes in Group I and Group II patients differed significantly (p less than 0.001) from values in Group III patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal influences on cardiovascular norepinephrine transporter responses in healthy women

Gender differences in human cardiovascular norepinephrine transporter function may be mediated through female sex hormones. We studied 16 healthy eumenorrheic women (25+/-1 years) during the early follicular phase (day 5+/-0) and midluteal phase (day 22+/-0) of the menstrual cycle. In a randomized, crossover, double-blind fashion, subjects ingested 8 mg of the selective norepinephrine transporter inhibitor reboxetine or placebo. We monitored heart rate, blood pressure, and thoracic bioimpedance at rest and during standard autonomic function tests, including head-up tilt. Venous estradiol and progesterone concentrations were higher in the luteal than in the follicular phase but did not differ between placebo and norepinephrine transporter inhibition testing days. On placebo, hemodynamics at rest and in response to different stressors were mostly identical between cycle phases. In the supine position, norepinephrine transporter inhibition increased blood pressure and stroke volume to a greater extent during the follicular than during the luteal phase. Conversely, the increase in heart rate and cardiac output with norepinephrine transporter inhibition was augmented in the luteal compared with the follicular phase. During head-up tilt with norepinephrine transporter inhibition, blood pressure and stroke volume decreased to a greater extent in the follicular than in the luteal phase. The tachycardic response to head-up tilt with norepinephrine transporter inhibition was augmented in the follicular phase. Our study suggests that sex hormones alter the hemodynamic response to norepinephrine transporter inhibition in women. The phenomenon may be explained by an effect of female sex hormones on norepinephrine transporter function, on compensatory cardiovascular responses, or both.     

Different mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt in patients with unexplained syncope: important role of epinephrine in nitroglycerin-induced syncope

INTRODUCTION: A reduction in left ventricular volume and an increase in epinephrine levels have been reported in tilt-induced neurally mediated syncope. To compare the mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt and to investigate the role of catecholamines, the temporal changes in plasma levels of norepinephrine and epinephrine and in left ventricular volume were measured. METHODS AND RESULTS: The first study population consisted of 90 patients with syncope of unknown etiology and 12 control subjects. The second study population consisted of 43 patients with unexplained syncope. In the first study, head-up tilt (80 degree angle) was conducted for 40 minutes, and norepinephrine and epinephrine levels were measured. In the second study, all patients were randomly allocated to either isoproterenol test (20 patients) or nitroglycerin test (23 patients) for 20-minute head-up tilt. Isoproterenol infusion was given at a rate of 1 to 3 microg/min. Intravenous infusion of nitroglycerin was started at 250 microg/hour with increasing dosages up to 1,500 microg/hour. Norepinephrine and epinephrine were measured in peripheral venous blood. Left ventricular volumes were measured by echocardiography with patients in the supine position and during head-up tilt every 1 minute. End-diastolic volume and end-systolic volume were calculated. In the first study, 61 patients demonstrated a positive response and 29 patients demonstrated a negative response. Plasma norepinephrine changes during head-up tilt were not significantly different, whereas epinephrine levels were significantly higher in the positive patients than in the negative and control subjects (148 +/- 118 pg/mL vs 66 +/- 31 pg/mL and 55 +/- 27 pg/mL). Thirteen of the 20 patients given isoproterenol and 15 of the 23 patients given nitroglycerin showed a positive head-up tilt (65.0% vs 65.2%; P = NS). During isoproterenol and nitroglycerin infusion head-up tilt, epinephrine in the positive group determined by the nitroglycerin test was significantly higher than that in the other three groups (103 +/- 38 pg/mL vs 60 +/- 33 pg/mL, 31 +/- 21 pg/mL, and 50 +/- 52 pg/mL). In contrast, end-systolic volume was significantly smaller in the positive group than in the other three groups based on findings of the isoproterenol test. CONCLUSION: The findings suggest that nitroglycerin triggers head-up tilt-induced syncope by increasing epinephrine levels, whereas isoproterenol induces syncope by decreasing left ventricular volume.     

Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study

OBJECTIVES: The purpose of the study was to determine whether the well tolerated serotonin reuptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in patients resistant to or intolerant of previous traditional therapies. BACKGROUND: Serotonergic mechanisms play a major role in the processes leading to neurocardiogenic vasovagal syncope, and serotonin reuptake inhibitors have been reported to be effective in preventing refractory syncope. METHODS: Sixty-eight consecutive patients (26 men and 42 women, mean age 44.7+/-16.5 years) with recurrent syncope and positive head-up tilt test and in whom standard therapies with beta-adrenergic blocking agents, vagolytic, negative inotropic or mineral corticoid agents were ineffectual or poorly tolerated were referred for study. Patients randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then reperformed after one month of treatment, and the clinical effect was noted over a mean follow-up of 25.4+/-7.9 months. RESULTS: The response rates (negative tilt test) after one month of treatment were 61.8% versus 38.2% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up spontaneous syncope was reported in six patients (17.6%) in the paroxetine group as compared to 18 patients (52.9%) in the placebo group (p < 0.0001). Only one patient (2.9%) asked to be discontinued from the drug for severe side effects. CONCLUSIONS: Paroxetine was found to significantly improve the symptoms of patients with vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients.     

The effect of atropine in vasovagal syncope induced by head-up tilt testing.

AIMS: This single-blinded, randomized, placebo-controlled study was designed and undertaken to assess the efficacy of intravenous atropine administration on haemodynamic impairment induced by head-up tilt testing in patients with vasovagal syncope. METHODS AND RESULTS: One hundred and thirteen consecutive patients (62 male and 51 female, mean age 46.3 years) with recurrent syncope, no evidence of cardiac, neurological or metabolic disease and a positive head-up tilt test were included in the study. Within 2 weeks of the first head-up tilt test all patients underwent a second tilt test. During this second test, all patients were randomized to receive a bolus of either atropine (0.02 mg. kg(-1)) or placebo (isotonic saline solution). The administration of atropine or placebo was performed at the onset of the haemodynamic modifications (heart rate and/or blood pressure fall) in conjunction with typical vasovagal prodromal symptoms. Treatment was taken as effective when symptoms aborted and the test was completed. In 29 of 113 patients the second tilt test was negative and these patients were excluded from final data analysis. Forty-one patients received placebo, which was effective in nine cases (21.9%). Atropine was administered to 43 patients and was effective in 30 cases (69.7%, P<0.01 vs placebo). The effects of treatment were analysed further to consider the haemodynamic patterns of tilt-induced vasovagal reflex. In the cardio-inhibitory form, placebo was never effective (15 cases), while atropine was effective in 15 of 18 cases (83.3%, P<0.001 vs placebo). In the vasodepressor form, placebo was effective in nine of 26 patients (34.6%), while atropine was effective in 15 of 25 cases (60.0%, no significant difference vs placebo). CONCLUSIONS: Atropine is fully effective in the cardio-inhibitory form of tilt-induced vasovagal reflex, but is limited in the vasodepressor form.     

Clinical spectrum of neurally mediated reflex syncopes.

AIMS: The clinical features of the various types of neurally mediated reflex syncope have not been systematically investigated and compared. We sought to assess and compare the clinical spectrum of neurally mediated reflex syncopes. METHODS AND RESULTS: Four hundred sixty-one patients with syncope were prospectively evaluated and 280 had neurally mediated reflex syncope. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. Typical vasovagal syncope was diagnosed in 39 patients, situational syncope in 34, carotid sinus syncope in 34, tilt-induced syncope in 142 and complex neurally mediated syncope (positive response to both carotid sinus massage and tilt test) in 31. The clinical features of situational, carotid sinus, tilt-induced and complex neurally mediated syncope were very similar. By contrast, typical vasovagal syncope differed from other neurally mediated syncopes not only in terms of its precipitating factors (fear, strong emotion, etc.), which constituted predefined diagnostic criteria, but also in the variety of its clinical features (lower age and prevalence of organic heart disease, higher prevalence of prodromal symptoms, and of autonomic prodromes, longer duration of prodromes, higher prevalence of symptoms during the recovery phase and lower prevalence of trauma). CONCLUSION: The clinical spectrum of neurally mediated reflex syncopes demonstrates much overlap between them. However, when the afferent neural signals are localized in cortical sites, as in typical vasovagal syncope, symptoms are more frequent and of longer duration.     

Endothelial function and peripheral vasomotion in the brachial artery in neurally mediated syncope

BACKGROUND: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation. HYPOTHESIS: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope. METHODS: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group. RESULTS: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05). CONCLUSIONS: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.     

Methodology of head-up tilt testing in patients with unexplained syncope

Prolonged 60 degree head-up tilt has been shown to be valuable in the investigation of unexplained syncope, diagnosing neurally mediated bradycardia/hypotension or malignant vasovagal syndrome. To evaluate the methodology of tilt testing, the following were examined: reproducibility of results, tilt duration, angle of tilt, method of tilt support and effect of age in patients and control subjects. Seventy-one patients with recurrent unexplained syncope underwent 60 min of 60 degree tilt; 53 (75%) had an abnormal test with vasovagal syncope at 24 +/- 10 min (mean +/- SD). Tilting to 60 degrees resulted in an abnormal test in only 2 (7%) of 27 control subjects without cardiovascular symptoms (p less than 0.001); and 5 (15%) of 34 patients with syncope and documented conduction tissue disease (p less than 0.001). Of 15 youthful fainters, 3 (20%) had vasovagal reactions as did 1 (8%) of 12 asymptomatic youthful control subjects. These 12 control subjects also underwent tilting with a saddle support and 7 (67%) had vasovagal reactions. It is concluded that the duration of tilting at 60 degrees should be 45 min (mean time to syncope +2 x SD in the 53 patients with abnormal results). Twenty percent of patients with an abnormal tilt test may not demonstrate syncope with repeat tilting. Saddle tilt testing in unexplained syncope may result in a loss of specificity. Tilting at less than 60 degrees results in a loss of sensitivity. Head-up tilt may be less useful in youthful subjects with vasovagal syncope than in other subjects.     

Endogenous opioids and epinephrine in nitroglycerin provocation tilt test in patients with neurally mediated syncope

Endogenous opioids and catecholamines are involved in autonomic activity. Nitroglycerin provocation tilt is a useful modality for evaluating neurally mediated syncope. Endogenous opioids and epinephrine might play an important role in nitroglycerin provocation tilt. To investigate whether or not opioids and catecholamines are involved in the pathogenesis of nitroglycerin provocation tilt, we measured the temporal changes of the plasma levels of beta endorphin, norepinephrine, and epinephrine in 64 patients with syncope of unknown etiology, and compared the findings with those of 16 patients who underwent isoproterenol provocation tilt (1-3 microg/min) test with a positive response. We performed a 20 minute control tilt (80 degrees) followed by a nitroglycerin provocation tilt of 20 minutes with the intravenous infusion of nitroglycerin. Nitroglycerin infusion was started at 250 microg/h, and was increased by 250 microg/h every 3 minutes up to 1500 microg/h during the tilt test. Beta-endorphin, norepinephrine, and epinephrine were measured in peripheral venous blood in the supine position 2, 10, and 20 minutes after the start of the tilt test, and also at the onset of syncope. Twenty-six patients had a positive response to the control tilt (group 1), and 22 patients had a positive response to nitroglycerin provocation tilt (group 2). The remaining 16 patients had a negative response to both control tilt and nitroglycerin provocation tilt (group 3), compared with isoproterenol provocation tilt patients (group 4). Beta-endorphin and epinephrine only significantly increased in groups 1 and 2 (beta-endorphin; from 7.3 +/- 3.3 pg/mL to 19.9 +/- 17.7 pg/mL, in group 1, P < 0.05; from 7.3 +/- 2.9 to 16.5 +/- 10.7 pg/mL, in group 2, P < 0.05; epinephrine; from 42 +/- 58 pg/mL to 157 +/- 161 pg/mL, in group 1, P < 0.05: from 33 +/- 25 to 202 +/- 252 pg/mL, in group 2, P < 0.05), but not in groups 3 and 4. Beta-endorphin and epinephrine might participate in the pathophysiology in conventional tilt-induced as well as nitroglycerin provocation tilt-induced syncope in patients with neurally mediated syncope.     

A novel tilt table testing protocol for investigating patients suspected to have neurally mediated syncope

We have observed that a series of 3 Valsalva maneuvers performed at 1-minute intervals between the 15th and 18th minute of a drug-free tilt table test resulted in intense presyncope and hypotension in a 32 yr old male with micturition syncope. In contrast, five apparently healthy subjects tolerated a 70 degree head-up tilt table test for 45 min with five Valsalva maneuvers incorporated into the testing protocol. Thus, we hypothesize that the use of a series of Valsalva maneuvers during a drug free head-up tilt table test might improve the diagnostic yield without compromising test specificity in patients suspected to have neurally mediated syncope.     

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF). PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation. RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients. CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.     

Neurocardiogenic mechanisms of unexplained syncope in idiopathic dilated cardiomyopathy

Syncope in patients with advanced heart failure is a sign of poor prognosis. The cause of syncope in patients with dilated cardiomyopathy (DC) is not fully recognized and may remain elusive even after standardized evaluation. The purpose of the present study was to examine the implication of neurally mediated mechanisms in the pathophysiology of syncopal episodes in patients with DC. Twenty-six patients (21 men, 5 women; mean age 59 +/- 2 years, range 38 to 79) with DC and left ventricular ejection fractions 相似文献   

Heart rate variability and the outcome of head-up tilt in syncopal children

OBJECTIVE: This study evaluated autonomic nervous system function in 5 young (6-10 years old) and 5 older (10-15 years) children with recurrent episodes of neurally mediated syncope and a positive tilt-test result, 10 with syncope but a negative test result and 30 age-matched healthy volunteers. METHODS: Time- (SDNN, SDNNi, SDANNi, rMSSD, pNN50) and frequency-domain indices (LF, HF, LF/HF) of heart rate variability (HRV) were measured during a 24-hour Holter recording and for 5 min. segments before and during 90 degrees head-up tilt (tests lasted 30 min. or until syncope occurred). RESULTS: 24-hour HRV-indices were within the normal range for all syncopal patients. Mean RR interval and HRV-indices, except LF/HF, were higher in the older children with a positive test result before they were tilted and during the first 5 min. of head-up tilt. HRV-indices tended to be lower after tilt in the younger children with a positive test result. SDNN and LF in older children with a positive test result and LF/HF in the younger ones increased during the 5 min preceding the syncope. No difference was observed between syncopal children with a negative test result and controls. CONCLUSION: This study confirms that patients with vasovagal syncope have no chronic differences from normal subjects in autonomic nervous system activity. The modulation of the autonomic tone during head-up tilt is abnormal in children who faint during the test, but younger and older patients respond differently to the orthostatic stimulus.     

A controlled trial of acute and long-term medical therapy in tilt-induced neurally mediated syncope.

To study the efficacy of medical treatment for preventing syncopal recurrences in patients affected by tilt-induced neurally mediated syncope, a randomized placebo-treatment prospective study was performed in 30 patients (10 men and 20 women, mean age 42 +/- 21 years) who had syncope reproduced in 2 consecutive head-up tilt-table tests without pharmacologic intervention (n = 20) or during isoproterenol infusion (n = 10). Patients were randomly assigned to 2 groups: 15 to placebo, and 15 to drug therapy (determined on the basis of serial pharmacologic tilting tests). Therapy was either atenolol (n = 7), dihydroergotamine (n = 2), domperidone (n = 2), cafedrine (n = 1), or elastic compression stockings, alone or in association with drugs (n = 3). During a mean of 10 +/- 7 months of follow-up, syncope recurred in 3 patients (20%) in the treatment group and in 4 (27%) in the placebo group; actuarial rates of absence of syncopal recurrences after 20 months were 70 and 67%, respectively. Thus, the outcome of either treated or untreated patients was favorable (with a low recurrence rate of syncope), and the usefulness of tilting-guided medical therapy remains uncertain.     

Novel SCN5A mutation (Q55X) associated with age-dependent expression of Brugada syndrome presenting as neurally mediated syncope.

BACKGROUND: An association between Brugada syndrome and neurally mediated syncope has been described. Although mutations in SCN5A have been identified in Brugada syndrome, the genetic link between Brugada syndrome and neurally mediated syncope has not been determined. OBJECTIVES: The purpose of the study was to clinically and genetically characterize a man with recurrent syncope that originally was diagnosed as neurally mediated syncope at age 8 years but subsequently manifested as Brugada syndrome at age 17 years. METHODS: The proband underwent clinical examination, which included head-up tilt test, sodium channel provocation test, and electrophysiologic study. Genetic screening of SCN5A was performed for the proband and his family members. The biophysical properties of a mutant SCN5A channel in a heterologous expression system were studied using whole-cell, patch clamp technique. RESULTS: The proband showed positive head-up tilt test, coved-type ST elevation recorded from the third intercostal space, and positive pilsicainide provocation test. Ventricular fibrillation was inducible at programmed electrical stimulation, consistent with characteristics of both Brugada syndrome and neurally mediated syncope. A novel nonsense SCN5A mutation (Q55X) was identified in the proband, his mother, and his asymptomatic brother. The heterologously expressed mutant channel was nonfunctional. CONCLUSION: We genetically determined an SCN5A mutation in a patient showing the combined phenotype of neurally mediated syncope and Brugada syndrome. Neurally mediated syncope and Brugada syndrome may share, at least in part, a common pathophysiologic mechanism.     

A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE).

AIMS: Recently, some studies revealed the efficacy of pacemaker implantation in decreasing recurrences in patients with vasovagal syncope. As these studies were not blinded or placebo-controlled, the benefits observed might have been due to a bias in the assessment of outcomes or to a placebo effect of the pacemaker. We performed a randomized, double-blind, placebo-controlled study in order to ascertain if pacing therapy reduces the risk of syncope relapse. METHODS AND RESULTS: Twenty-nine patients (53 +/- 16 years; 19 women) with severe recurrent tilt-induced vasovagal syncope (median 12 syncopes in the lifetime) and 1 syncopal relapse after head-up tilt testing underwent implantation of a pacemaker, and were randomized to pacemaker ON or to pacemaker OFF. During a median of 715 days of follow-up, 8 (50%) patients randomized to pacemaker ON had recurrence of syncope compared to 5 (38%) of patients randomized to pacemaker OFF (p = n.s.); the median time to first syncope was longer in the pacemaker ON than in pacemaker OFF group, although not significantly so (97 [38-144] vs 20 [4-302] days; p = 0.38). There was also no significant difference in the subgroups of patients who had had a mixed response and in those who had had an asystolic response during head-up tilt testing. CONCLUSION: Our data were unable to show a superiority of active pacing versus inactive pacing in preventing syncopal recurrence in patients with severe recurrent tilt-induced vasovagal syncope.