Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study

INTRODUCTION: The efficacy of midodrine for the management of patients with neurocardiogenic syncope was assessed prospectively in a randomized control study. METHODS AND RESULTS: Patients who had at least monthly occurrences of syncope and a positive tilt-table test were included in the study. A total of 61 patients were randomly allocated to treatment either with midodrine or with fluid, salt tablets, and counseling. Midodrine was given at a starting dose of 5 mg three times a day and increased up to a dose of 15 mg three times a day when required. Midodrine was given during the daytime every 6 hours. Thirty-one patients were assigned to treatment with midodrine; the other 30 patients were advised to increase their fluid intake and were instructed to recognize their prodromes and abort the progression to syncope. Patients were followed-up for at least 6 months. A quality-of-life questionnaire was administered at the time of randomization and 6 months after. At the 6-month follow-up, 25 (81%) of 31 midodrine-treated patients and 4 (13%) of the 30 fluid-therapy patients had remained asymptomatic (P < 0.001). One patient had to discontinue taking midodrine due to severe side effects and another six patients experienced minor side effects that did not require drug discontinuation. CONCLUSION: Midodrine appeared to provide a significant benefit in patients with neurocardiogenic syncope. To prevent recurrence of symptoms, dose adjustments were required in about one third of patients.     

Preliminary Observations on the Use of Midodrine Hydrochloride in the Treatment of Refractory Neurocardiogenic Syncope

Recurrent episodes of neurocardiogenic syncope that occur without warning are a common cause of recurrent syncope that can be identified during head upright tilt table testing. While the use of beta blockers, theophyllines, fludrocortisone, disopyramide, and serotonin reuptake inhibitors can be useful in the prevention of episodes, some patients are either unresponsive to or poorly tolerant of these agents. We investigated the use of the peripheral alpha stimulating agent midodrine in preventing both tilt-induced and spontaneous neurocardiogenic syncope. Twenty-five patients (16 women, 9 men, mean age 30 ± 23 years) with severe recurrent syncope and a positive head upright tilt table study (refractory to or intolerant of standard therapies) were placed on midodrine 5–10 mg orally three times per day, (two patients required 15 mg/day). Of these, twelve became asymptomatic and five had a marked reduction in symptoms. We conclude that midodrine may be an effective therapy in patients with recurrent neurocardiogenic syncope refractory to other forms of therapy.     

Midodrine hydrochloride in the management of older adults with neurocardiogenic syncope and orthostatic hypotension: A prospective observational study

BackgroundMidodrine hydrochloride has been shown to be effective in the management of syncope in adults with reflex syncope, orthostatic hypotension and orthostatic intolerance syndromes; however, its use, tolerability and side effects have not been monitored specifically in the older old, particularly not over a prolonged period of time.ObjectivesWe aim to document changes in patients’ symptoms, drug dosages employed and adverse drug reactions to midodrine therapy in older adults with a diagnosis of neurocardiogenic syncope assessed and managed at a specialist falls and syncope outpatient unit.MethodsProspective observational study of 135 consecutive subjects with a mean age of 84 years started on midodrine after comprehensive geriatric assessment, structured falls evaluation, positive tilt table testing (TT) or a mixed/vasodepressor response to carotid sinus massage (CSM).ResultsNinety-seven individuals (71%) commenced on midodrine treatment and followed up for a mean of 2.7 years, reported either significant improvement or abolition of symptoms across all TT/CSM diagnosis. Forty-nine percent of individuals achieved sustained clinical improvement after an initial dosage of 2.5 mg three times per day and only four patients required dosages above 7.5 mg three times daily. One hundred and one individuals (75%) continued midodrine until the end of the monitoring period, and although 19 subjects developed adverse drug reactions, most were minor and only six resulted in drug withdrawal.ConclusionsMidodrine hydrochloride appears to be safe and well tolerated in older adults and should be considered, independent of age, in the management of patients with symptomatic orthostatic hypotension, vasovagal syncope and vasodepressor or mixed carotid sinus syndrome. This observation requires further confirmation by larger multicenter randomised control studies.     

Recurrent Supine Syncope:

Supine Syncope. Introduction : Syncope occasionally may occur in the supine patient due to severe brady- or tachyarrhythmia. However, recurrent syncope upon assumption of the supine position as a result of a neurally mediated reflex mechanism has not been reported previously.
Methods and Results : Two young patients, both of whom had significant systemic illnesses, experienced recurrent episodes of presyncope and/or syncope shortly after assuming the supine position. During ambulatory ECG monitoring, symptoms were provoked only by lying down and were associated with transient bradycardia. Head-up tilt table testing was undertaken as part of the syncope evaluation and was nondiagnostic in both cases. However, both patients exhibited a transient cardioinhibitory response with reproduction of typical symptoms upon return of the table to the supine position ("reverse tilt"). During follow-up (8 and 14 months), both patients improved with pharmacologic treatment (disopyramide in one case and midodrine in the other).
Conclusion : Presyncope or syncope upon lying down can he an unusual manifestation of the neurally mediated faint.     

Efficacy of orthostatic self-training in medically refractory neurocardiogenic syncope

BACKGROUND: Orthostatic self-training is effective in the prevention of neurocardiogenic syncope, though the success of this method in drug refractory patients has not been reported. STUDY OBJECTIVE AND METHODS: This study examined the effectiveness of orthostatic self-training in 15 patients with head-up tilt testing (HUT)-inducible neurocardiogenic syncope, who were intolerant of, or refractory to standard drug therapy. They were enrolled in a home orthostatic self-training program for up to 30 min/session, twice daily. Head-up tilt testing was repeated within 4 weeks after onset of the training program, using the same protocol as at baseline. Orthostatic self-training was continued once daily, for up to 30 min, for a mean follow-up period of 11 months, in the drug-free state. RESULTS: Syncope was not reinducible by follow-up HUT, and spontaneous syncope occurred in no patient during the follow-up period. CONCLUSIONS: Home orthostatic self-training, up to 30 min once daily following an initial twice daily program, was highly effective in the suppression of recurrent neurocardiogenic syncope in patients intolerant of, or refractory to standard drug therapy.     

Cardiac Pacing During Neurocardiogenic (Vasovagal) Syncope

Cardiac Pacing and Neurocardiogenic Syncope. Head-up tilt testing is increasingly being used as a diagnostic modality in patients with unexplained syncope who are thought to have neurocardiogenic (vasovagal) mechanisms of syncope. Although large-scale placebo-controlled trials are still awaited, pharmacologic therapy is usually effective in preventing syncope or presyncope in this patient population. However, the role of permanent pacemaker therapy remains controversial. Because hypotension is usually associated with paradoxical bradycardia and occasionally asystole, it has been argued that permanent pacemaker therapy may be useful in preventing syncope and, thus, injury, in the so-called "malignant vasovagal cardioinhibitory response" in which the onset of syncope is thought to be abrupt. The onset of hypotension, however, usually precedes bradycardia during neurocardiogenic syncope, and pacing may thus not prevent syncope or presyncope in these patients. The role of cardiac pacing in patients with neurocardiogenic syncope is reviewed.     

Effectiveness of paroxetine in the treatment of refractory vasovagal syncope in young patients

OBJECTIVES: The aim of the study was to assess whether the well-tolerated serotonin re-uptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in young patients resistant to or intolerant of previous traditional therapies. BACKGROUND: Serotonergic mechanisms may play a major role in the pathophysiology of neurocardiogenic syncope, and serotonin re-uptake inhibitors have been recently reported to be effective in preventing episodes. METHODS: Forty-one consecutive young patients (13 male and 28 female), aged less than thirty years with recurrent syncope and positive head-up tilt test, and in whom standard therapies with beta-blocking, vagolytic, negative inotropic or mineral corticoid agents were ineffectual, poorly tolerated or contraindicated, randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then re-performed after one month of treatment, and the clinical effect was noted over a mean follow-up of 27.1 +/- 6.6 months. RESULTS: The response rates (negative tilt test) after one month of treatment were 57.1 versus 33.3% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up, spontaneous syncope was observed in 4 patients (19%) in the paroxetine group and in 12 patients (60%) in the placebo group (p < 0.001). Only one patient (4.8%) asked to be discontinued from the drug for severe recurrent headache. CONCLUSIONS: Paroxetine significantly improved symptoms of young patients with recurrent vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients.     

Midodrine: a role in the management of neurocardiogenic syncope

Objective—To determine the benefit of midodrine, an α agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope.
Setting—Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope).
Patients—16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt.
Design and intervention—Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation.
Results—Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4 ). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo ( p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects.
Conclusions—Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms.

Keywords: midodrine;  neurocardiogenic syncope;  head up tilt test     

Efficacy of Orthostatic Self‐Training in Medically Refractory Neurocardiogenic Syncope

Background.?Orthostatic self‐training is effective in the prevention of neurocardiogenic syncope, though the success of this method in drug refractory patients has not been reported. Study objective and methods.?This study examined the effectiveness of orthostatic self‐training in 15 patients with head‐up tilt testing (HUT)‐inducible neurocardiogenic syncope, who were intolerant of, or refractory to standard drug therapy. They were enrolled in a home orthostatic self‐training program for up to 30 min/session, twice daily. Head‐up tilt testing was repeated within 4 weeks after onset of the training program, using the same protocol as at baseline. Orthostatic self‐training was continued once daily, for up to 30 min, for a mean follow‐up period of 11 months, in the drug‐free state. Results.?Syncope was not reinducible by follow‐up HUT, and spontaneous syncope occurred in no patient during the follow‐up period. Conclusions.?Home orthostatic self‐training, up to 30 min once daily following an initial twice daily program, was highly effective in the suppression of recurrent neurocardiogenic syncope in patients intolerant of, or refractory to standard drug therapy.     

Initial experience with an implantable loop recorder in patients with unexplained syncope

Patients with recurrent syncope undiagnosed after extensive noninvasive and invasive testing pose a diagnostic and therapeutic dilemma. Holter monitoring is non-diagnostic in 90% of cases. Recent developments in loop recorder technology permit longterm ECG monitoring in patients with recurrent unexplained syncope. The implantable loop recorder monitors a single lead electrogram continuously using 2 sensing electrodes on the device shell. The device was implanted in 20 patients (11 male, 9 female) with the history of recurrent syncope. During a mean follow-up of 12+/-6 months after device implantation, 11 patients (55%) experienced syncope (8 pts) or presyncope (3 pts). In the remaining 9 patients, no syncope occurred. In all 11 patients with syncope or presyncope during follow-up, loop recording definitively determined whether an arrhythmia was the cause of symptoms or not. Diagnosis included bradycardia in one patient, tachycardia in two patients, in one patient two rhythm disturbances were revealed: frequent ventricular premature beats with bigemini and atrial flutter. Two patients had a neurocardiogenic syncope. Syncope was nonarrhythmic in 5 patients. An implantable loop recorder is useful for establishing the diagnosis if symptoms are recurrent but too infrequent for conventional monitoring techniques.     

Changes in Plasma Epinephrine Concentration and in Heart Rate During Head-Up Tilt Testing in Patients with Neurocardiogenic Syncope:

Sympathetic Activation in Neurocardiogenic Syncope. Introduction : Tilt table testing is widely used in the management of patients with neurocardiogenic syncope. However, the exact pathophysiologic mechanism of this disorder is still under debate. Likewise, therapy of these patients continues to represent a challenge in many cases. Therefore, the present study aimed to gain further insight into the pathophysiology of this syndrome and to examine easily accessible clinical parameters that can improve therapy selection.
Methods and Results : In 16 patients with neurocardiogenic syncope, changes in endogenous catecholamine concentrations were determined during repeated tilt table testing before and during treatment with metoprolol. Tachycardia preceded syncope in 8 of 10 responders compared to only 1 of 6 nonresponders (P < 0.05). In responders, the relative increase in epinephrine levels averaged 197%± 51% during drug-free tilting and 75%± 33% during repeated testing while on β-blocker therapy (P < 0.05). In nonresponders, there was a smaller relative increase in epinephrine averaging 137%± 35% at baseline tilt. During repeated tilt testing, a similar increase was observed in these patients with recurrent syncope (156%± 104%; P = NS compared to baseline).
Conclusion : In patients with neurocardiogenic syncope who show both an increase in epinephrine concentration during tilt test and sinus tachycardia prior to the onset of symptoms, β-blocker treatment is very effective. These findings confirm the major role of sympathetic activation as a trigger of syncope. Particularly, heart rate changes at the onset of syncope may allow early identification of patients responding to antiadrenergic therapy.     

Successful treatment of malignant neurocardiogenic syncope with repeated tilt training program

Recent reports have shown that repeated tilt-table testing or tilt training is a very effective therapy for the treatment of neurocardiogenic syncope induced by head-up tilt testing. The present patient experienced repeated syncopal or presyncopal attacks and had shown prolonged asystole on an electrocardiogram during syncope. The presyncope could be reproducibly induced by head-up tilt testing. Oral propranolol and/or disopyramide therapies failed to prevent his symptoms. Tilt training (2 sessions/day) was repeated every day for 4 weeks at home, and then head-up tilt testing was performed again. The syncope or presyncope was not induced by head-up tilt testing. The patient has continued with this training and has had no symptoms during the follow-up period of 1 year.     

Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study

OBJECTIVES: Intravenous albumin has been used to prevent paracentesis-induced circulatory dysfunction (PICD) in cirrhotics; however, its use is costly and controversial. Splanchnic arterial vasodilatation is primarily responsible for PICD. There are no reports of use of midodrine in the prevention of PICD. In this pilot study, we evaluated midodrine and albumin in the prevention of PICD.
METHODS: Forty patients with cirrhosis underwent therapeutic paracentesis with midodrine or albumin in a randomized controlled trial at a tertiary center. Effective arterial blood volume was assessed by plasma renin activity.
RESULTS: Plasma renin activity at baseline and at 6 days after paracentesis did not differ in the two groups (43.18 ± 10.73 to 45.90 ± 8.59 ng/mL/h, P = 0.273 in the albumin group and 44.44 ± 8.44 to 41.39 ± 10.21 ng/mL/h, P = 0.115 in the midodrine group). Two patients had an increase in plasma renin activity of more than 50% from baseline in the albumin group, and none in the midodrine group. A significant increase in 24-h urine volume and urine sodium excretion was noted in the midodrine group. Midodrine therapy was cheaper than albumin therapy.
CONCLUSIONS: The study suggests that midodrine may be as effective as albumin in preventing PICD in cirrhotics, but at a fraction of the cost, and can be administered orally. Midodrine also resulted in an increase in 24-h urine volume and sodium excretion.     

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.     

Upright postures and isoproterenol infusion for provocation of neurocardiogenic syncope: A comparison of standing and head-up tilting

Head-up tilt testing has proved to be useful in provocation of neurocardiogenic syncope. The purpose of this study was to examine whether simply assuming an upright posture by standing can be an alternative to the head-up tilt testing for diagnosis of neurocardiogenic syncope. Eight-four patients with recurrent unexplained syncope and 22 normal volunteers were recruited into the study. Forty-seven patients with syncope and all normal volunteers received the standing test. Thirty-seven of the patients with syncope received head-up tilt testing (90 degrees). All subjects lay down for 5 minutes and then assumed an upright posture until syncope or presyncope occurred or until a maximum of 10 minutes was reached in each stage of the test. The tests included four stages: baseline and infusion of 1, 2, or 3 μg/min isoproterenol in each of the successive stages. Five subjects could not tolerate the procedure, and further testing was terminated. Overall, the standing test was positive in 83% of the patients with syncope, and its specificity was 74%. The head-up tilt testing was positive in 75% of the patients with syncope. The duration of assuming an upright posture before occurrence of syncope or presyncope was significantly longer in the syncope-tilting group in the third stage (p < 0.01) and the fourth stage (p < 0.05) compared with the syncope-standing group. However, the curves of the time course for cumulative positive rates were not significantly different (p = 0.0739) in the two groups. The standing test can serve as an alternative to head-up tilt testing and can be applied to patients with recurrent unexplained syncope for confirmation of the diagnosis.     

A patient treated with tilt training and midodrine after 68 seconds asystole during head-up tilt table testing

Neurocardiogenic syncope is a relatively common cause of syncope and is diagnosed by head-up tilt testing. A 21-year-old man was examined for frequent syncope episodes which occurred after episodes of blood drawing and standing in queue. Syncope developed in tilt table testing. After about 68 seconds, sinus rhythm returned. Recent reports have shown that tilt training is a very effective therapy for recurrent neurocardiogenic syncope. In our case, the patient was treated with midodrine 2.5 mg once a day and a tilt training programme. Therapy resulted in improvement and during a follow-up of six months, no major events occurred.     

Tilt training for recurrent neurocardiogenic syncope: effectiveness, patient compliance, and scheduling the frequency of training sessions

Unsatisfactory results obtained with medical therapy and dual-chamber pacing for prevention of recurrent neurocardiogenic syncope necessitated the development of new treatment modalities. Tilt-training, a novel treatment for recurrent neurocardiogenic syncope based on exercise sessions with prolonged upright posture (either on a tilt-table or standing on foot against a wall), was shown to be effective in preventing the recurrence of neurocardiogenic syncope. The purpose of this study was to demonstrate the long-term beneficial effects of a transient tilt training program lasting 2 months. Thirty-two patients with recurrent neurocardiogenic syncope (mean number of syncope episodes in the last 6 months was 3.4 +/- 2.3) constituted the study group. All of the patients were tilt test positive. The patients were taught a tilt training program with 2 phases (in-hospital training with repeated tilt procedures until 3 consecutive negative results were obtained and home exercises with standing against a wall) and home exercises lasted a maximum of 2 months. After this training program, the patients received no treatment and were followed for the recurrence of syncope. At the end of the follow-up period (376 +/- 45 days), 81% of the patients were free of recurrent syncope. This study revealed that similar successful results can also be obtained with a transient tilt training program as a first line treatment strategy. Less interference with the daily activities of the patients is the major advantage of this strategy. The ease of performance and high effectiveness rate will most likely result in more frequent utilization of this treatment modality.     

Transcranial Doppler monitoring during head upright tilt table testing in patients with suspected neurocardiogenic syncope.

The aim of the present study was to evaluate the mechanism of cerebrovascular autoregulation in patients with neurocardiogenic syncope using bilateral transcranial Doppler (TCD) monitoring during head upright tilt table testing (HUT). Two hundred and six patients were prospectively studied. One hundred and fifty-nine subjects (77%) had a prior history of syncope and 47 (23%) had presyncope. Ninety-nine patients (48%) had syncope or presyncope during HUT with a 76% fall in diastolic middle cerebral artery blood flow velocity (D-MCA-BFV). Systolic MCA-BFV (S-MCA-BFV) fell by 33%. Deepening of the dicrotic notch in the Doppler waveform always preceded the fall in D-MCA-BFV. Patients without syncope or presyncope (n=96) had smaller changes in cerebral blood flow velocities during HUT and only twenty-two subjects had transient deepening of the dicrotic notch. Eleven subjects had presyncope during HUT due to an exaggerated response to nitrates with progressive arterial hypotension without bradycardia and changes during TCD monitoring that were intermediate between positive and negative HUT. In conclusion, patients with neurocardiogenic syncope have changes in cerebral blood flow during the event. TCD monitoring during HUT helps to assess these alterations.     

Sinus Tachycardia with Atrioventricular Block:

Sinus Tachycardia with AV Block During VVS. Introduction : Neurocardiogenic (vasovagal) syncope is characterized by hypotension and bradycardia. The presence of sinus tachycardia along with AV block during syncope in patients with neurocardiogenic syncope has not been described previously.
Methods and Results : Two female patients (18 and 16 years old) with recurrent syncope and documented sinus tachycardia at the time of syncope are described. Patient 1 had recurrent episodes of syncope. During one of these episodes, which occurred while she was being monitored, sinus tachycardia along with high-grade AV block was seen at the time of syncope and hypotension. Patient 2 had a history of recurrent syncope and seizure. During one of these episodes, she was documented to have ventricular asystole lasting for about 39 seconds. The sinus rate was 480 msec at the beginning, before slowing down to 960 msec prior to restoration of sinus rhythm with 1:1 AV conduction. The same scenario was repeated during head-up tilt testing. Both patients were treated successfully with oral disopyramide and, during a follow-up of 28 months and 9 months, have remained symptom-free.
Conclusion : Sinus acceleration along with high-grade AV block during syncope and hypotension can occur in some patients with neurocardiogenic syncope. The exact mechanism of this phenomenon is unclear.     

Clinical efficacy of propantheline bromide in neurocardiogenic syncope: Pharmacodynamic implications

Summary The pharmacological response with tilt-table testing predicts long-term efficacy in neurocardiogenic syncope. However, beta-blockers for neurocardiogenic syncope are often not tolerated or are ineffective. Since cholinergic tone is important in the efferent part of the neurocardiogenic reflex, we investigated the pharmacodynamics and efficacy of propantheline bromide in preventing neurocardiogenic syncope. We studied 16 patients (11 males) with a mean age of 48.8 (± 15.1) years with presyncope or syncope and who had positive baseline tilt-table studies at a mean of 15.8 (± 10.3) minutes into the upright 60° tilt. They were given propantheline bromide orally, an anticholinergic agent, at a dose of 64.3 (± 21.8) mg/day for 7 days, and tilt-table testing was repeated 1 hour after readministration of propantheline bromide, 30 mg orally. After propantheline bromide treatment, 13 of 16 patients (81%) had no inducible presyncope or syncope on repeat tilt-table testing. In this group of responders, the mean minimum heart rate during upright tilt-table testing increased from 43.2 (± 77.3) beats/min to 77.3 (± 17.2) beats/min after propantheline bromide (p<0.005). More significantly, the minimum mean arterial blood pressure increased from 42.2 (± 25) mmHg to 81.3 (± 16.7) mmHg (p<0.0005) during upright tilt. At a follow-up of 15.2 (± 7.4) months, in the responder group (12 patients with long-term follow-up), the average dose of propantheline bromide was 32.5 (± 23.8) mg/day, which was significantly reduced from the initial dose (p<0.05). A clinical recurrence of symptoms occurred in only 4 out of 12 patients on propantheline bromide (33%), none of which were directly attributable to drug failure. It was concluded from this study that propantheline bromide is highly effective in preventing neurocardiogenic syncope. In addition, propantheline bromide's effectiveness is more than would be expected by prevention of cardioinhibition in neurocardiogenic syncope and would support a role for direct cholinergic control of vascular tone.This work was presented in part at the American Heart Association 67th Scientific Sessions, Dallas, Texas, November 14, 1994.