Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: results of a controlled study of etilefrine versus placebo. Cardiac pacing does not improve orthostatic tolerance in patients with vasovagal syncope. Closed loop stimulation in prevention of vasovagal syncope. Inotropy Controlled Pacing in Vasovagal Syncope (INVASY): a multicentre randomized, single blind, controlled study. A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt. Failure of propranolol to prevent tilt-evoked systemic vasodilatation, adrenaline release and neurocardiogenic syncope. Midodrine: a role in the management of neurocardiogenic syncope. Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal Syncope International Study. Determining the optimal pacing intervention rate for vasovagal syncope. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. DDD pacing with rate drop response function versus DDI with rate hysteresis pacing for cardioinhibitory vasovagal syncope. Effects of intravenous etilefrine in neurocardiogenic syncope induced by head-up tilt testing. Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial. Usefulness of intravenous metoprolol to prevent syncope induced by head-up tilt. A Randomized Trial Oral Propranolol versus Metroprolol in Treatment of Neurally Medicated Cyncope. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. Is DDD superior to VVI pacing in mixed carotid sinus syndrome? An acute and medium-term study. Treatment of vasodepressor carotid sinus syndrome with midodrine: a randomized, controlled pilot study. The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. A study comparing VVI and DDI pacing in elderly patients with carotid sinus syndrome. Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators. [Evaluation of the effects of diverse therapeutic treatments versus no treatment of patients with neurocardiogenic syncope]. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. Inhibitory effect of enalapril on neurally mediated syncope in elderly patients. A controlled trial of acute and long-term medical therapy in tilt-induced neurally mediated syncope. Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome. Is a pacemaker indicated for vasovagal patients with severe cardioinhibitory reflex as identified by the ATP test? A preliminary randomized trial. Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study. Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study. Malignant vasovagal syncope: a randomised trial of metoprolol and clonidine. Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). Efficacy of a patient-activated pharmacologic pump using phenylephrine as active drug and prodromal symptoms as a marker of imminent loss of consciousness to abort tilt-induced syncope. 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). Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study. Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients' well-being. DDDR pacing driven by contractility versus DDI pacing in vasovagal syncope: a multicenter, randomized study. Less syncope and milder symptoms in patients treated with pacing for induced cardioinhibitory carotid sinus syndrome: a randomized study. Usefulness of transdermal scopolamine for vasovagal syncope. Long-term effects of pharmacological therapy for vasovagal syncope on the basis of reproducibility during head-up tilt testing. The effect of atropine in vasovagal syncope induced by head-up tilt testing. Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results. Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study. Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. Comparative study of the efficacy of metoprolol and verapamil in patients with syncope and positive head-up tilt test response.
This study assessed the efficacy of oral etilefrine (10 mg three times a day) in preventing a positive response to head-up tilt testing.
                Previous reports have suggested that oral etilefrine can be effective either in preventing a positive response to head-up tilt testing or in reducing syncopal recurrences in patients with vasovagal syncope. Up to now most studies assessing drug therapy in these patients have been uncontrolled.
                This was a randomized double-blind crossover study of etilefrine versus placebo in 30 consecutive patients with syncope and a baseline positive head-up tilt test. After the first test, patients had no treatment for 3 days and were randomized to receive etilefrine or placebo for 4 additional days. They underwent tilt testing under treatment and again after 3 days of washout; they then received the alternative treatment for 4 days, and a third test was performed.
                Head-up tilt test results were negative in 13 (43%) patients with etilefrine and 15 (50%) with placebo (p = NS). Therefore, the statistical power of the study was only 10%. The rate of positive responses decreased with repeated testing irrespective of the assigned treatment: A positive response was obtained during the second head-up tilt test in 20 patients (10 with placebo, 10 with etilefrine) but in only 12 during the third (7 with etilefrine, 5 with placebo) (p < 0.05).
                Oral etilefrine (10 mg three times a day) was not superior to placebo in preventing a positive response to head-up tilt testing. Despite a low statistical power, the high rate of negative response with placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in patients with vasovagal syncope. This study was undertaken to assess the value of dual chamber pacing in the treatment of vasovagal syncope. In a preliminary study, on two patients the time to presyncope during head-up tilt before and after implanting pacemakers was determined. Both patients fainted with similar decreases in blood pressure at almost exactly the same time after tilting. In the main study, nine patients with pacemakers implanted as treatment for syncope were studied, in random order, with pacemakers on and either off or turned to minimum rate. The pacemakers prevented bradycardia but had no effect on the time to syncope in a progressive test of head-up tilt followed by the addition of graded lower body suction. It is concluded that cardiac pacing does not prevent or even delay the onset of postural syncope and infer that bradycardia is an unimportant component of vasovagal attacks. To determine whether dual-chamber rate-adaptive Closed Loop Stimulation (CLS) could prevent recurrence of Vasovagal Syncope (VVS).
                During VVS, an increase in myocardial contractility associated with a reduction of ventricular filling produces an increase in baroreceptor afferent flow and a consequent decrease in the heart rate. The CLS algorithm is a form of rate-adaptive pacing, which responds to myocardial contraction dynamics, by measuring variations in right ventricular intracardiac impedance: during an incipient VVS it could increase paced heart rate and avoid bradycardia, arterial hypotension and syncope.
                Fifty patients (27 males, mean age 59+/-18 year) with severe and recurrent vasovagal syncope and positive Head Up Tilt Test (HUTT) with cardioinhibition, received a CLS pacemaker (INOS2, Biotronik GmbH Co., Germany). The primary end point was recurrence of two VVSs during a minimum of 1 year of follow-up. Randomization between DDD-CLS and DDI mode (40 bpm) pacing was performed only during the first stage of the study (first year): 9/26 randomized to DDI mode (control group) and 17/26 in DDD-CLS mode. All the 24 patients recruited in the second stage of the study (second year) were programmed in DDD-CLS mode.
                Of the nine patients randomized to the DDI mode, seven had recurrences of syncope during the first year. At the end of the first year the nine patients were reprogrammed to the CLS mode and no syncope occurred after reprogramming. The 41 patients programmed to CLS had a mean follow-up of 19+/-4 months: none reported VVS, only four (10%) reported occasional presyncope and their quality of life greatly improved. Positive HUTT at the end of the first year failed to predict the clinical response to CLS pacing.
                The study demonstrates the effectiveness of CLS pacing in preventing cardioinhibitory VVS. A possible placebo effect of pacemaker implantation occurred in 22% of patients. A double-blind randomized trial was designed to determine the efficacy of intravenous and oral disopyramide phosphate in preventing neurally mediated syncope induced by a head-up tilt test.
                Neurally mediated syncope is a frequent cause of syncope and may be induced by head-up tilt testing. Recent uncontrolled trials have suggested that disopyramide may be an effective therapy in patients with neurally mediated syncope.
                Twenty-two consecutive patients with recurrent neurally mediated syncope and two or more successive positive head-up tilt test responses were randomly allocated to receive either intravenous disopyramide or placebo. Head-up tilt testing at 60 degrees was performed for 15 min. If presyncope or syncope was not provoked, isoproterenol infusion was started at a rate of 1 microgram/min and the rate gradually increased until a 25% increase in heart rate was achieved. Eleven patients were subsequently randomized in crossover fashion to receive oral disopyramide (800 mg/day) or placebo during 1 week. The primary end point was prevention of syncope or presyncope provoked by head-up tilt testing.
                Head-up tilt test results were positive for syncope in 12 (75%) of 16 patients receiving intravenous placebo and in 12 (60%) of 20 patients receiving disopyramide (p = 0.55 Fisher exact test, 95% confidence interval [CI] -14% to 40%). In the intravenous phase, complete crossover was achieved in 15 patients. Head-up tilt test results during this phase were positive in 13 patients (87%) receiving placebo and in 12 patients (80%) receiving disopyramide (p = 0.50 Fisher exact test, 95% CI -19% to 32%) and were positive in all patients receiving their initially randomized drug or placebo. In the oral phase, head-up tilt results were positive in only two patients (18%) assigned to placebo and in three patients (27%) receiving disopyramide (p = 0.54 Fisher exact test, 95% CI -42% to 24%). A mean follow-up time of 29 +/- 8 months was obtained in 21 of the 22 patients. Syncope recurred in 3 (27%) of the 11 patients receiving disopyramide and 3 (30%) of the 10 patients not treated pharmacologically (p > 0.05).
                Intravenous disopyramide was ineffective for the prevention of neurally mediated syncope provoked by head-up tilt testing. No significant effect was observed after oral therapy with disopyramide. There was a striking decrease in the incidence of positive tilt test results over time regardless of intervention, thus discouraging the use of head-up tilt as the single method of assessing therapeutic efficacy. Recurrence of syncope after the investigative protocol was infrequent over long-term follow-up regardless of treatment group. In patients with neurocardiogenic syncope, head-up tilt often evokes acute loss of consciousness accompanied by vasodilatation, increased plasma adrenaline and systemic hypotension. Since hypotension increases adrenaline levels and adrenaline can produce skeletal muscle vasodilatation by activating beta2 receptors, adrenaline might induce a positive feedback loop precipitating circulatory collapse. We hypothesized that propranolol, a non-selective beta-blocker, would prevent adrenaline-induced vasodilatation and thereby prevent syncope. Eight subjects with recurrent neurocardiogenic syncope and previously documented tilt-induced syncope with elevated plasma adrenaline levels participated in the present study. Subjects underwent tilt table testing after receiving oral propranolol or placebo in a double-blind randomized crossover fashion. Haemodynamic and neurochemical variables were measured using intra-arterial monitoring, impedance cardiography, arterial blood sampling and tracer kinetics of simultaneously infused [3H]noradrenaline and [3H]adrenaline. The occurrence of tilt-induced neurally mediated hypotension and syncope, duration of tilt tolerance, extent of the decrease in SVRI (systemic vascular resistance index) and magnitude of plasma adrenaline increases did not differ between the propranolol and placebo treatment phases. SVRI was inversely associated with fractional increase in plasma adrenaline during both phases. One subject did not faint when on propranolol; this subject's response is discussed in the context of central effects of propranolol. In this small, but tightly controlled, study, propranolol did not prevent tilt-induced vasodilatation, syncope or elevated plasma adrenaline. To determine the benefit of midodrine, an alpha agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope.
                Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope).
                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.
                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.
                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.
                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. Etilefrine is an alpha-agonist agent with a potent vasoconstrictor effect, which is potentially useful in preventing vasovagal syncope by reducing venous pooling and/or by counteracting reflex arteriolar vasodilatation. The present multicenter, randomized, placebo-controlled study was designed to evaluate the efficacy of this drug for the long-term management of patients with recurrent vasovagal syncope.
                In the 20 participating centers, 126 patients with recurrent vasovagal syncope (at least 3 episodes in the last 2 years) and a positive baseline head-up tilt response were randomly assigned to placebo (63 patients) or etilefrine at a dosage of 75 mg/d (63 patients) and were followed up for 1 year or until syncope recurred. The primary end-point of the study was the first recurrence of syncope. There were no differences between the 2 study groups in the patients' baseline characteristics. During follow-up, the group treated with etilefrine had a similar incidence of first syncopal recurrence to that of placebo group both in the intention-to-treat analysis (24% versus 24%) and in on- treatment analysis (26% versus 24%). Moreover, the median time to the first syncopal recurrence did not significantly differ between the 2 study groups (106 days in the etilefrine arm and 112 days in the placebo arm).
                Oral etilefrine is not superior to placebo in preventing spontaneous episodes of vasovagal syncope. Randomized controlled studies are essential to assess the real usefulness of any proposed therapy for patients with vasovagal syncope. In this study, patients with rate hysteresis pacemakers implanted for vasovagal syncope were re-studied using serial tilt testing to determine whether, once triggered, pacing was more effective if the intervention rate was higher than the standard rate.
                Twenty patients (mean age 55.4 years, range 23-81, 14 male) were studied, with randomisation to either initial standard rate (80-90 beats/min) intervention, or to initial high rate (120 beats/min) intervention. Although 18 of the 20 reported complete abolition of syncope since pacing, only 8 patients could be objectively assessed. The respective mean time to tilt down after symptom onset with standard and high rate intervention was 193+/-234s and 185+/-143s, (P>0.05).
                Repeat tilt testing was only of limited value in assessing the benefit of pacing. There was no advantage with high rate intervention in delaying the loss of consciousness (or intolerable symptoms) after the initial onset of symptoms. The aim of this study was to assess the efficacy of lipophilic beta-blockers in preventing recurrent neurocardiogenic syncope and the value of head-up tilt test (HUT) in predicting response to therapy. The efficacy of beta-blockers in recurrent syncope is controversial. The value of HUT in predicting efficacy of therapy has not been investigated. Fifty-six patients (44+/-18 years, 36 women) with recurrent syncope (> 1 event in the last 6 months) of suspected neurocardiogenic origin were included in the study. Independent of the response to HUT, patients were randomized to receive metoprolol or propanolol at the maximal tolerated dose (28 patients, group A, 86+/-23 vs 98+/-29 mg/d) or no pharmacological therapy (28 patients, group B). The primary endpoint was the first recurrence of syncope. During the 1-year of follow-up, 20 patients of group A and 8 of group B had no recurrence. In group A, of 20 patients without recurrences 12 had a positive and 8 a negative HUT result while of 8 patients with recurrences 5 had a positive and 3 a negative response to HUT. In the group B, of 20 patients with recurrences 10 had a positive and 10 a negative HUT result while of 8 patients without recurrences 4 had a positive and 4 a negative response to HUT. In a multivariate Cox-regression analysis, medical therapy was the only independent factor for predicting recurrence of syncope (P = 0.004); HUT had no influence in this regard (P = 0.773). In conclusion, lipophilic beta-blockers appear efficacious in preventing recurrent syncope of suspected neurocardiogenic origin. The efficacy of therapy seems to be not predicted by HUT. The effectiveness of cardiac pacing in preventing vasovagal syncope remains controversial. However, DDI pacing with rate hysteresis has been reported to prevent the recurrence of cardioinhibitory vasovagal syncope in up to 35% of affected subjects and to reduce the overall incidence of syncopal episodes in the others. Recently, DDD pacing with a new promising rate drop response function (Medtronic Thera-I model 7960) has become available in clinical practice.
                The aim of the present open trial was to test the effectiveness of this new pacing modality in patients with cardioinhibitory vasovagal syncope.
                The study population included 20 patients (12 males and 8 females; mean age 61.1 +/- 14 yrs) with recurrent syncope (mean number of prior episode = 6.8, range 5-11) and cardioinhibitory responses during two head-up tilt tests: the first diagnostic and the second during drug therapy with either beta-blockade or etilephrine. The study patients were randomized to receive either DDI pacing with rate hysteresis (8 patients) or DDD pacing with rate drop response function (11 patients). The head-up tilt test performed 1 month after pacemaker implantation was positive in 3 of 12 patients (25%) with DDD pacing with rate drop response function and in 5 of 8 patients (62.5%) with DDI pacing with rate hysteresis. The mean duration of follow-up was 17.7 +/- 7.4 months. During follow-up no patients with a DDD pacemaker with rate drop response function had syncope, while 3 of 8 patients with a DDI pacemaker with rate hysteresis had recurrence of syncope (P < 0.05).
                These data suggest that DDD pacing with rate drop response function is effective in cardioinhibitory vasovagal syncope and may be preferable to DDI pacing with rate hysteresis. nan This clinical investigation was performed to compare the effects of permanent dual-chamber cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope.
                Patients from 14 centers were randomized to receive either a DDD pacemaker provided with rate-drop response function or the beta-blocker atenolol at the dosage of 100 mg once a day. Inclusion criteria were age >35 years, >/=3 syncopal spells in the preceding 2 years, and positive response to tilt table testing with syncope occurring in association with relative bradycardia. The primary outcome was the first recurrence of syncope after randomization. Enrollment was started in December 1997, and the first formal interim analysis was performed on July 30, 2000. By that time, 93 patients (38 men and 55 women; mean age, 58.1+/-14.3 years) had been enrolled and randomized, although follow-up data were available for all patients (46 patients in the pacemaker arm, 47 patients in the pharmacological arm). The interim analysis showed a significant effect in favor of permanent cardiac pacing (recurrence of syncope in 2 patients [4.3%] after a median of 390 days) compared with medical treatment (recurrence of syncope in 12 patients [25.5%] after a median of 135 days; OR, 0.133; 95% CI, 0.028 to 0.632; P=0.004). Consequently, enrollment and follow-up were terminated.
                DDD pacing with rate-drop response function is more effective than beta-blockade for the prevention of syncopal recurrences in highly symptomatic vasovagal fainters with relative bradycardia during tilt-induced syncope. Intravenous metoprolol was found to be significantly more effective than placebo in preventing head-up tilt-table induced neurally mediated syncope. The reproducibility of acute tilt-table testing is only 63% and suggests caution in the interpretation of acute drug testing during tilt-table studies. Beta-blockers has been claimed to be useful in chronic prophylaxis of neurally mediated syncope with frequent recurrences. However, efficacy of cardioselective and non-cardioselective beta-blockers has never been compared in a randomized study.
                From October 2003 to December 2004, 62 patients (32 men, mean age 44.8 +/- 19.3 years) who had at least one episode of syncope per month during previous 6-months and had positive tilt test were enrolled in this study. The patients were randomly assigned to receive either propranolol (Group I, n = 31) or metoprolol (Group II, n = 31). After one month, efficacy of treatment was also tested by a repeat head-up tilt test (HUTT).
                There were no statistically significant differences between the two groups with respect to the HUTT pattern (P=0.25) and requirement for sublingual NTG during test (P=0.20). After one month of treatment, oral beta-blockers prevented the occurrence of syncope during second HUTT in 11 patients (35.5%) in the Group I and 9 (29%) patients in the Group II (P=0.58) and delayed the occurrence of symptoms in 9 Group I patients (29%) and 8 Group II patients (16%) (P=0.77). During the 16-months follow-up, 53 patients (85.5%) remained free of syncope. No statistically significant difference was observed between the two groups with respect to recurrence of syncope (P=0.47). In both groups, the patients in whom treatment efficacy was proved by a negative tilt test had similar recurrence of syncope as those patients who had a positive tilt test (Both P>0.05).
                Both cardioselective and noncardioselective oral beta-blockers were similarly effective in preventing recurrence of syncope in patients with neurally-mediated syncope. In both groups, HUTT performed one month after the treatment had no role in prediction of responders. Three previous small randomized trials have reported that pacemaker therapy is beneficial for patients with severe recurrent vasovagal syncope. However, because these trials were not double blind, they may have been biased in their assessment of outcomes and had a placebo effect of surgery.
                To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope.
                A randomized double-blind trial of pacemaker therapy in outpatients referred to syncope specialists at 15 centers from September 1998 to April 2002. In the year prior to randomization, patients had had a median of 4 episodes of syncope. Patients were followed up for up to 6 months.
                After implantation of a dual chamber pacemaker, 100 patients were randomly assigned to receive dual-chamber pacing (DDD) with rate drop response or to have only sensing without pacing (ODO).
                Time to first recurrence of syncope.
                No patients were lost to follow-up. Of the 52 patients randomized to ODO, 22 (42%) had recurrent syncope within 6 months compared with 16 (33%) of 48 patients in the DDD group. The cumulative risk of syncope at 6 months was 40% (95% confidence interval [CI], 25%-52%) for the ODO group and 31% (95% CI, 17%-43%) for the DDD group. The relative risk reduction in time to syncope with DDD pacing was 30% (95% CI, -33% to 63%; 1-sided P =.14). Lead dislodgement or repositioning occurred in 7 patients. One patient had vein thrombosis, another had pericardial tamponade leading to removal of the pacemaker system, and a third had infection involving the pacemaker generator.
                In this double-blind randomized trial, pacing therapy did not reduce the risk of recurrent syncope in patients with vasovagal syncope. Because of the weak evidence of efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first-line therapy for patients with recurrent vasovagal syncope. The aim of this study was to evaluate the importance of atrial synchronism for pacing therapy of patients with mixed carotid sinus syndrome. In 23 patients (21 m, two f; mean age 69 +/- 8 years) affected by symptomatic mixed carotid sinus syndrome we performed: (1) Research of ventriculo-atrial conduction, orthostatic hypotension and pacemaker effect; and (2) Carotid sinus massage in the standing position during VVI and DVI temporary pacing. Next, all patients received a permanent DDD pacemaker and entered a 2 month two period single-blind, randomized, cross-over study on DVI/DDD versus VVI mode. During the DVI/DDD period, no syncope occurred in any patients, minor symptoms persisted in 11 (48%) of them; during VVI period syncopes recurred in three patients, symptoms requiring the withdrawal of VVI pacing and premature DVI/DDD reprogramming in eight patients, minor symptoms in 17 (74%). A comparison between 14 patients, who preferred DVI/DDD period (Group A), and the remaining nine patients who noted no preference between DVI/DDD and VVI period (Group B) was performed on the basis of the preimplant evaluation. Group A patients had a greater pacemaker effect (-34 +/- 16 mmHg vs -16 +/- 14 mmHg) and a higher prevalence of symptomatic pacemaker effect (50% vs 0%), of ventriculo-atrial conduction (78% vs 44%) and of orthostatic hypotension (50% vs 11%), while the entity of the systolic pressure fall caused by carotid sinus massage was similar in the two groups either during VVI mode (Group A -51 +/- 16 mmHg vs Group B -56 +/- 27 mmHg) or DVI mode (Group A -38 +/- 17 mmHg vs Group B -45 +/- 17 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS) To evaluate the efficacy of treatment of the vasodepressor form of carotid sinus hypersensitivity (carotid sinus syndrome (CSS)) with midodrine.
                A prospective, double-blind, randomized, controlled trial of crossover design.
                A dedicated outpatient facility with access to tilt-table, digital arterial photoplethysmography, and 24-hour ambulatory blood pressure (BP) monitoring equipment.
                Ten older adults (4 male, 6 female, mean age 75, range 66-86 years) with a history of unexplained syncope who displayed an asymptomatic decrease in systolic BP (SBP) of more than 50 mmHg or a symptomatic decrease of more than 30 mmHg within 30 seconds of carotid sinus massage (CSM).
                Symptom reproduction and BP and heart rate changes were evaluated after CSM in supine and semierect positions on the right and then left sides. These measurements were performed on the final day of placebo and active-treatment phases. Ambulatory 24-hour BP monitoring took place on the penultimate and final days of each treatment phase.
                Eight patients were symptomatic after their initial CSM. The mean+/-standard deviation SBP decrease after initial CSM was 54+/-22 mmHg. Initial mean 24-hour ambulatory BP was 127/70+/-7/5 mmHg. Eight patients reported symptoms after CSM at the end of the placebo phase. The mean SBP decrease at the end of the placebo phase was 49+/-12 mmHg. The mean 24-hour ambulatory BP was 127/69+/-9/7 mmHg. One patient reported symptoms after CSM at the end of the active-treatment phase. The mean SBP decrease at the end of the active-treatment phase was 36+/-9 mmHg. The mean 24-hour ambulatory BP at the end of the treatment phase was 133/75+/-7/6 mmHg. The differences in symptom reporting and mean SBP decrease after CSM were both significant (P<.01 and P=.03, respectively).
                The results of this pilot study suggest that treatment of vasodepressor CSS with midodrine significantly reduced the rate of symptom reporting and attenuated SBP decreases after CSM but increased mean 24-hour ambulatory BP. This study was done to evaluate pacemaker therapy for severe recurrent vasovagal syncope.
                Nonrandomized studies have suggested that permanent pacing might help control the symptoms of recurrent vasovagal syncope. The study goal was to evaluate the effect of permanent pacemaker implantation on syncope in patients with frequently recurrent vasovagal syncope.
                Patients with > or = 6 lifetime episodes of syncope and with a tilt-table test that induced syncope or presyncope, as well as a relative bradycardia, were randomized to receive a dual-chamber pacemaker or not. The pacemaker prevented bradycardia and provided high-rate pacing if a predetermined drop in heart rate occurred (rate-drop response). The primary outcome was the first recurrence of syncope. Patients also completed a detailed diary recording presyncopal episodes.
                A total of 284 patients was originally planned and a pilot study of 60 patients was initiated. At the planned first formal interim analysis of efficacy of the pilot study, an unanticipated large treatment effect was observed which fulfilled the prespecified criteria for early termination of the study. At that time, there were 54 patients enrolled, randomized evenly to no pacemaker or to pacemaker. In the no-pacemaker and pacemaker groups the mean ages were 40 and 46 years; 74% and 70% patients, respectively, were female. The baseline tilt-table test showed a slowest heart <60/min or longest heart period >1000 ms in 60% of no-pacemaker patients and 72% of pacemaker patients. There was a marked reduction in the postrandomization risk of syncope in pacemaker patients (relative risk reduction 85.4%, 95% confidence interval 59.7% to 94.7%; 2p=0.000022).
                Dual-chamber pacing with rate-drop response reduces the likelihood of syncope in patients with recurrent vasovagal syncope. To determine whether single chamber ventricular demand (VVI) pacing is adequate for elderly patients with carotid sinus syndrome.
                Prospective double blind randomised cross over study.
                Tertiary referral centre.
                30 consecutive patients aged over 60 years with carotid sinus syndrome referred for cardiac pacing.
                Patients underwent dual chamber pacemaker implantation and were then randomised to two three-month periods of VVI and DDI pacing.
                Responses to cardiovascular tests (vasodepression during carotid sinus massage, pacemaker effect, postural blood pressure measurements, and response to head up tilt), and symptoms.
                11 patients developed profound hypotension during upright carotid sinus massage while pacing VVI compared with only two while pacing DDI. The upright pacemaker effect was greater in VVI (VVI, -31 (SD 19) mm Hg v DDI, -4 (12) mm Hg; P < 0.001). Postural blood pressure measurements and responses to head up tilt did not vary. Eleven patients were unable to tolerate VVI pacing and had to be withdrawn early from this limb of the study (group A). Fourteen of the remainder completed diary cards and did not express a preference (group B). No patient preferred VVI. Group A patients were older (group A, 78 (6) years v group B, 70 (9) years; P < 0.05), were more likely to be female (group A, 73% v group B, 14%; P < 0.01), and were more likely to have orthostatic hypotension while pacing DDI (group A, 46% v group B, 0%; P < 0.01). Group A and B patients could not be differentiated by other prepacing clinical or haemodynamic variables.
                Elderly patients with carotid sinus syndrome are likely to develop symptomatic hypotension following VVI pacing. The optimum pacing mode for individual patients cannot be predicted by simple cardiovascular tests before pacing. BACKGROUND-This study was performed to compare implantation of a DDI pacemaker with rate hysteresis with no implant in respect to syncopal recurrences in patients with severe cardioinhibitory tilt-positive neurally mediated syncope. METHODS AND RESULTS-Forty-two patients from 18 European centers were randomized to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19 patients) or no pacemaker (23 patients). Inclusion criteria were >/=3 syncopes over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope International Study types 2A and 2B) response to tilt testing. The median number of previous syncopal episodes was 6; asystolic response to tilt testing was present in 36 patients (86%) (mean asystole, 13.9+/-10.2 seconds). All patients were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean, 3.7+/-2.2). One patient (5%) in the pacemaker arm experienced recurrence of syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In the no-pacemaker arm, the median time to first syncopal recurrence was 5 months, with a rate of 0.44 per year. On repeated tilt testing performed within 15 days after enrollment, positive responses were observed in 59% of patients with pacemakers and in 61% of patients without pacemakers (P=NS). CONCLUSIONS-In a limited, select group of patients with tilt-positive cardioinhibitory syncope, DDI pacing with hysteresis reduced the likelihood of syncope. The benefit of the therapy was maintained over the long term. Even in untreated patients, the syncopal recurrence burden was low. A negative result of tilt testing was not a useful means to evaluate therapy efficacy. Head-up tilt test was introduced in clinical practice to assess vasovagal syncope and its use has further been extended to evaluate the efficacy of drug administration in these patients. Nevertheless, the effects of tilt test on vasovagal syncope have never been compared with those obtained by ethylephrine or propranolol administration. One hundred and sixty-nine consecutive patients with vasovagal syncope and positive baseline or nitrate-potentiated tilt test (60 degrees upright position for 45 min, or until syncope occurred; 5 mg sublingual isosorbide dinitrate administration if no symptoms occurred) were randomly distributed among three groups: Group A (57 control patients discharged without medical therapy); Group B (56 patients discharged with 75 mg/die ethylephrine); Group C (56 patients discharged with 80 mg/die propranolol). Tilt test was repeated after 1 month, while clinical outcome was evaluated monthly for a mean follow-up of 37.1 +/- 15.6 months. No significant differences in acute tilt-induced syncope recurrence rates were obtained among groups at test repetition since 70.2% of Group A, 69.6% of Group B and 62.5% of Group C experienced syncope. At 3-year follow-up 82.4% of Group A, 83.9% of Group B and 87.5% of Group C (NS among groups) remained symptom free, the most important clinical result being obtained in untreated patients. These data suggest that tilt test execution may prevent syncope recurrence as ethylephrine or propranolol administration. Irrespective of the therapeutical choice, the "controlled reproduction" of symptoms and some psychophysical training of patients to avoid precipitating circumstances, to recognize early symptoms promptly to be reverted by Trendelemburg position, may produce the same clinical improvement as (empiric) ethylephrine or propranolol therapy. 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.
                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.
                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.
                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.
                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. A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings. 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. The natural history of patients with severe carotid sinus syndrome, and the efficacy of permanent pacemaker treatment are not clearly known. A randomized treatment/nontreatment prospective study was performed in 60 patients affected by carotid sinus syndrome whose symptoms were judged to involve risk of major trauma or interfered with their daily activity. They were randomly assigned to 2 groups: 28 patients to no therapy (nonpacing group), and 32 to VVI (n = 18) or DDD (n = 14) pacemaker implant (pacing group). Syncope recurred in 16 patients (57%) of the nopacing group (mean follow-up 36 +/- 10 months) and in only 3 (9%) of the pacing group (mean follow-up 34 +/- 10 months) (p = 0.0002); moreover, 19 (68%) in the nonpacing group needed a secondary pacemaker implant because of the severity of symptoms. The actuarial rate of absence of syncopal recurrence after 1, 2, 3 and 4 years was 64, 54, 38 and 38%, respectively, for the nonpacing group, and 100, 97, 93 and 84%, respectively, for the pacing group (p = 0.0001). The actuarial rate of absence of minor symptoms after 1, 2, 3 and 4 years was 21, 14, 7 and 7%, respectively, for the nonpacing group and 66, 43, 27 and 27%, respectively, for the pacing group (p = 0.002). Reproducibility of carotid sinus reflex was tested after 15 +/- 8 months in 54 patients; an abnormal response to carotid sinus massage persisted in all 54. In conclusion, symptoms recur in most patients with untreated carotid sinus syndrome, and pacing is a useful therapy for preventing recurrences. A previous observational study suggested that, in syncopal elderly patients with vasovagal syndrome, a test using adenosine-5'-triphosphate (intravenous ATP 20 mg. 2 ml-1) could identify a subgroup of patients at high risk of severe cardioinhibitory response and guide the therapeutic strategy. To test one aspect of these results prospectively, we designed a small study focusing only on vasovagal patients with abnormal response to ATP testing.
                Twenty patients hospitalized for syncope, which was considered to be vasovagal, and exhibiting an abnormal ATP test--defined by a longer than 10 s cardiac pause--were randomized to two groups: half to implantation with a dual-chamber pacemaker and half to usual medical care. All patients who were not hospitalized for recurrences were assessed every 6 months in the clinic or by telephone.
                At baseline, the randomized patient groups were similar in their demographic and health characteristics and in the results of their ATP tests, for example the mean cardiac pause (21.4 +/- 9.3 vs 15.9 +/- 3.7 s) and the mean interval between escape beats during the pause (7.29 +/- 4.2 vs 7.48 +/- 3.3 s). During a mean follow-up of 52 months, recurrences appeared in six of the 10 usual-care patients (range 0.2-29 months) but in none of the implanted patients (P < 0.02).
                This limited trial (1) supports the conclusion that patients with an abnormal ATP test who receive a dual-chamber pacemaker suffer fewer recurrences than those who are monitored only; and (2) consequently further supports the hypothesis that, among vasovagal patients, a cardiac pause of longer than 10 s in patients administered ATP identifies those at high risk of symptomatic vagal cardiac inhibition. To compare the therapeutic efficacy of placebo, propranolol, and fluoxetine in patients with vasovagal syncope (VVS).
                Ninety-six consecutive patients with VVS were randomized to treatment with placebo, propranolol, or fluoxetine and followed-up for 6 months. Before and during treatment, they reported their syncopal and presyncopal episodes and graded their well-being, expressed as the general evaluation of life, general activities, and everyday activities (each scaled from 1 = very good to 5 = very bad). Two patients refused follow-up. Among the remaining 94, no difference between groups was observed regarding the distribution of time of vasovagal events (syncopes or presyncopes) during follow-up (log-rank test). No difference was also observed when syncopes and presyncopes were assessed separately. Eighteen patients discontinued therapy. Among the remaining 76 ('on-treatment' analysis), the mean time to a vasovagal episode (syncope or presyncope) was significantly longer in the fluoxetine group when compared with the two other groups (log-rank test, P < 0.05). A significant difference in favour of fluoxetine was also observed regarding presyncopes. The difference between groups regarding the syncope-free period was not significant. During therapy, patients' well-being was improved (decreased) only in the fluoxetine-group (13.4 +/- 0.7 vs. 15.4 +/- 0.9 before treatment, P < 0.01).
                Fluoxetine seems to be equivalent to propranolol and placebo in the treatment of VVS. However, it improves patients' well-being and might be more effective in reducing presyncopes and total vasovagal events in some patients with recurrent VVS. The efficacy of midodrine for the management of patients with neurocardiogenic syncope was assessed prospectively in a randomized control study.
                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.
                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. To evaluate the efficacy of head up tilt guided treatment with metoprolol and clonidine in preventing the recurrence of syncope in patients with malignant vasovagal syncope.
                20 patients (9 men and 11 women, mean age 33 (SD 17), range 14 to 62 years) with severe symptoms.
                Randomised double blind crossover trial; efficacy was assessed by head up tilt testing.
                Metoprolol was more effective than clonidine in abolishing syncope (19/20 v 1/20, P < 0.001) but clonidine showed some beneficial effects on time to syncope and severity of hypotension in 12 patients. During an average follow up of 15 (3) months there was a significant reduction in the recurrence of symptoms compared with the previous year in patients who had tilt up guided treatment (18 metoprolol, 1 clonidine).
                Treatment guided by head up tilting is a reliable method of treating patients with malignant vasovagal syndrome. Metoprolol was an effective long term treatment for preventing syncope. High doses were more effective and a careful dose titration period helped to minimise withdrawal symptoms and side effects. The aim of the study was to determine whether cardiac pacing reduces falls in older adults with cardioinhibitory carotid sinus hypersensitivity (CSH).
                Cardioinhibitory carotid sinus syndrome causes syncope, and symptoms respond to cardiac pacing. There is circumstantial evidence for an association between falls and the syndrome.
                A randomized controlled trial was done of consecutive older patients (>50 years) attending an accident and emergency facility because of a non-accidental fall. Patients were randomized to dual-chamber pacemaker implant (paced patients) or standard treatment (controls). The primary outcome was the number of falls during one year of follow-up.
                One hundred seventy-five eligible patients (mean age 73 +/- 10 years; 60% women) were randomized to the trial: pacemaker 87; controls 88. Falls (without loss of consciousness) were reduced by two-thirds: controls reported 669 falls (mean 9.3; range 0 to 89), and paced patients 216 falls (mean 4.1; range 0 to 29). Thus, paced patients were significantly less likely to fall (odds ratio 0.42; 95% confidence interval: 0.23, 0.75) than were controls. Syncopal events were also reduced during the follow-up period, but there were much fewer syncopal events than falls-28 episodes in paced patients and 47 in controls. Injurious events were reduced by 70% (202 in controls compared to 61 in paced patients).
                There is a strong association between non-accidental falls and cardioinhibitory CSH. These patients would not usually be referred for cardiovascular assessment. Carotid sinus hypersensitivity should be considered in all older adults who have non-accidental falls. nan 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.
                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.
                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. Neurally mediated syncope is the most frequent cause of syncope in patients without structural heart disease. Its most common trigger is a reduction in venous return to the heart due to excessive venous pooling in the legs. We conducted a double-blind, randomized, crossover trial to investigate the efficacy of midodrine, a selective alpha-1 adrenergic agonist that decreases venous capacitance, in preventing neurally mediated syncope triggered by passive head-up tilt. Twelve patients with history of recurrent neurally mediated syncope, which was reproduced during head-up tilt, were randomized to receive a nonpressor dose of midodrine (5mg) or placebo on day 1 and the opposite on day 3. One hour after drug or placebo administration, patients underwent 60-degree head-up tilt lasting 40 minutes (unless hypotension or bradycardia developed first). In the supine position, midodrine produced no significant change in blood pressure or heart rate. The responses to head-up tilt were significantly different on the midodrine and the placebo day: on the placebo day, 67% (8/12) of the subjects suffered neurally mediated syncope, whereas only 17% (2/12) of the subjects developed neurally mediated syncope on the midodrine day (p < 0.02). These results indicate that midodrine significantly improves orthostatic tolerance during head-up tilt in patients with recurrent neurally mediated syncope. We sought to assess the relative therapeutic efficacy of propranolol, nadolol and placebo in recurrent vasovagal syncope (VVS).
                Central and peripheral mechanisms have been implicated in the pathogenesis of VVS. Propranolol, nadolol and placebo have different sites of action on central and/or peripheral mechanisms. It has not yet been clarified whether one of the aforementioned treatments is more efficient than the others in reducing clinical episodes and exerting a beneficial effect on patients' well-being.
                We studied 30 consecutive patients with recurrent VVS and a positive head-up tilt test. All were serially and randomly assigned to propranolol, nadolol or placebo. Therapy with each drug lasted three months. On the day of drug crossover, patients reported the total number of syncopal and presyncopal attacks during the previous period. They also gave a general assessment of their quality of life, taking into account: 1) symptom recurrence; 2) drug side effects; and 3) their personal well-being during therapy (scale 0 to 4: 0 = very bad/discontinuation; 1 = bad; 2 = good; 3 = very good; 4 = excellent). At the end of the nine-month follow-up period, they reported whether they preferred a specific treatment over the others.
                Spontaneous syncopal and presyncopal episode recurrence during each three-month follow-up period was reduced by all drugs tested (analysis of variance [ANOVA]: chi-square = 67.4, p < 0.0001 for syncopal attacks; chi-square = 60.1, p < 0.0001 for presyncopal attacks) No differences were observed in the recurrence of syncope and presyncope among the three drugs. All drugs improved the patients' well-being (ANOVA: chi-square = 61.9, p < 0.0001).
                Propranolol, nadolol and placebo are equally effective treatments in VVS, as demonstrated by a reduction in the recurrence of syncope and presyncope, as well as an improvement in the patients' well-being. Recent clinical trials have shown that selected patients with recurrent vasovagal syncope (VVS) may benefit from permanent cardiac pacing. In a previous study using head-up tilt testing (HUT) the authors demonstrated that the increase in sympathetic activity preceding syncope could be sensed by a microaccelerometer located in the tip of a ventricular pacing lead and used to drive a rate adaptive pacer. They compared in a single blind randomized crossover study, DDDR pacing driven by this system, with conventional DDI pacing in patients with recurrent VVS. Twenty-three patients (age 61.8 +/- 15.2 years, 19 men) with recurrent VVS were enrolled at seven European centers and underwent implantation of a "MiniLivingD/Best" pacing system. Inclusion criteria were (1) > 6 cumulative syncopal episodes or > or = 1 syncope within 6 months of a positive HUT, and (2) a positive HUT with bradycardia. Using a crossover study design, the pacemakers were randomly programmed for two successive periods of 6 months to DDDR or DDI mode. The numbers of episodes of syncope and presyncope, and quality-of-life (QOL), were assessed at the end of each period. During the 6 months before implant, the mean number of syncopal episodes per patient was 3.2 +/- 9. During pacing in the DDDR mode, 0.09 +/- 0.29 syncope/presyncope per patient was observed, while during the DDI period 0.48 +/- 0.73 episodes per patient were reported (P < 0.05). QOL scores were 77.40 +/- 11.32 in the DDDR mode versus 74.45 +/- 14.59 in the DDI mode (NS). In patients with recurrent VVS, symptomatic recurrences were less frequent during contractility-driven DDDR pacing, than during DDI pacing. QOL was similar in the two pacing modes. The aim of this study was to examine the effect on symptoms in patients with induced cardioinhibitory carotid sinus syndrome (ICSS) when treated or not treated with a pacemaker.
                Sixty patients with a history of syncope or pre-syncope and ICSS were randomized to receive a permanent pacemaker (P group, n = 30) or no pacing (NP group, n = 30). ICSS was defined as a ventricular pause (i.e. asystole) lasting 3 s or more in response to carotid sinus stimulation. The patients were seen at 3 and 12 months and at symptoms. At 12 months, the rate of syncope in the NP group was 40% (n = 12) compared with 10% (n = 3) in the P group (P = 0.008). The majority (11 of 12) of the syncope recurrences in the NP group occurred during the first 3 months. Pre-syncope occurred in two patients (7%) in the NP group and in eight (27%) in the P group. Ten patients (33%) with recurrent syncope in the NP group later crossed-over to receive pacemaker implant.
                A history of syncope or pre-syncope, plus ICSS, was a strong predictor of subsequent syncope or pre-syncope. Most of the new symptoms occurred within 3 months. Pacemaker treatment effectively reduced syncope and/or resulted in milder symptoms. We studied short-term effectiveness of transdermal scopolamine in a group of patients with unexplained syncope provoked during head-up tilt testing. This double-blind randomized trial of transdermal scopolamine demonstrated no significant effect of preventing vasovagal syncope. The purpose of this study was to determine the efficacy of long-term pharmacological therapy selected on the basis of a head-up tilt test (HUT) in patients in whom reproducibility of the HUT response was demonstrable in the initial study. The HUT (80 degrees upright) was performed for 15 min with or without an infusion of isoproterenol (0.01-0.03 microgram/kg per min) in 54 patients with recurrent unexplained syncope. When vasovagal syncope was induced (positive response), the HUT was repeated to examine the test reproducibility. Vasovagal syncope was induced in 24 patients during HUT alone, and in 30 patients during the HUT with isoproterenol. Acute reproducibility was observed in 49/54 (91%) patients. In the tilt-positive patients, HUT was repeated after an intravenous administration of propranolol (0.1 mg/kg) or disopyramide (1 mg/kg) (acute test). Propranolol proved effective in 21 (80%) of 26 patients, and disopyramide in 13 (56%) of 23 patients. Thereafter, evaluation was done on the long-term clinical follow-up of the pharmacological intervention selected on the basis of the acute test in the 34 patients in whom the HUT could not induce vasovagal syncope after the oral administration of the pharmacological agent (propranolol 60 mg/day, disopyramide 300 mg/day). Thirty-two of 34 patients (94%) did not develop syncopal attacks during a 44 +/- 12-month period. Thus, in patients with unexplained syncope, HUT appears to have a high degree of acute reproducibility, and the acute drug response guided by HUT may be used to develop an effective long-term pharmacological therapy. 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.
                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).
                Atropine is fully effective in the cardio-inhibitory form of tilt-induced vasovagal reflex, but is limited in the vasodepressor form.
                Copyright 1999 The European Society of Cardiology. The objective of this investigation was the assessment of the response rate of oral atenolol in patients with vasovagal syncope after 1 month of treatment. We randomized into two groups all patients referred to our unit who had had at least one episode of syncope or two episodes of presyncope 1 month before presentation and had a positive isuprel Tilt Table Test (TTT). Group 1 (Gr 1) received oral atenolol, and group 2 (Gr 2) received placebo medication. After a 1-month period patients were reassessed for degree of their symptoms and underwent repeated TTT. Forty-two patients were enrolled in the study. Gr 1 and Gr 2 were comparable in age (38 +/- 13 years vs 43 +/- 14 years, p = 0.216 and sex (male/female = 6:15 vs 10:11, p = 0.204). The severity of attack was similar in both groups. Eight patients in Gr 1 and six patients in Gr 2 had mitral valve prolapse (p = 0.5). No significant differences were seen in systolic blood pressure (122 +/- 17 vs 117 +/- 16 mmHg, p = 0.334), diastolic blood pressure (70 +/- 11 vs 72 +/- 11 mm Hg, p = 0.677), and heart rate (79 +/- 12 vs 79 +/- 13, p = 0.98) between the two groups. The response rates (negative TTT) after 1 month of treatment were 62% versus 5% (p = 0.0004) in the atenolol and control group, respectively. Moreover, patients who received atenolol reported feeling better compared with those who received placebo (71% vs 29%, p = 0.02). In conclusion, atenolol significantly improved symptoms of patients with vasovagal syncope.(ABSTRACT TRUNCATED AT 250 WORDS) This study was designed to evaluate the efficacy of atenolol for the long-term management of patients with vasovagal syncope. The primary hypothesis was that atenolol is not superior to placebo for the treatment of vasovagal syncope.
                There is no definitive well-controlled analysis of the efficacy of beta-adrenergic blocking agents in patients with recurrent vasovagal syncope.
                This is a prospective, randomized, double-blind, placebo-controlled study. Fifty patients with recurrent vasovagal syncope were included (at least two episodes in the last year). A baseline tilt test was performed. Twenty patients (40%) had a positive tilt test. Intravenous atenolol prevented a second positive tilt in five patients. The patients were randomized to receive either atenolol or a placebo (26 patients atenolol 50 mg/day, 24 patients placebo). The follow-up procedure lasted one year. The primary end point of the study was the time to first recurrence of syncope.
                In the intention-to-treat analysis, the group treated with atenolol had a similar number of patients with recurrent syncopal episodes as the placebo group. The Kaplan-Meier actuarial estimates of time to first syncopal recurrence showed that the probability of remaining free of syncope drops similarly in both groups and that there was no statistical difference between both curves (patients treated with atenolol vs. the placebo) with a log-rank test p value of 0.4517.
                The recurrence of neurocardiogenic syncope in highly symptomatic patients treated with atenolol is similar to that of patients treated with placebo. Previous studies that assessed the effects of beta-blockers in preventing vasovagal syncope provided mixed results. Our goal was to determine whether treatment with metoprolol reduces the risk of syncope in patients with vasovagal syncope.
                The multicenter Prevention of Syncope Trial (POST) was a randomized, placebo-controlled, double-blind, trial designed to assess the effects of metoprolol in vasovagal syncope over a 1-year treatment period. Two prespecified analyses included the relationships of age and initial tilt-test results to any benefit from metoprolol. All patients had >2 syncopal spells and a positive tilt test. Randomization was stratified according to ages <42 and > or =42 years. Patients received either metoprolol or matching placebo at highest-tolerated doses from 25 to 200 mg daily. The main outcome measure was the first recurrence of syncope. A total of 208 patients (mean age 42+/-18 years) with a median of 9 syncopal spells over a median of 11 years were randomized, 108 to receive metoprolol and 100 to the placebo group. There were 75 patients with > or =1 recurrence of syncope. The likelihood of recurrent syncope was not significantly different between groups. Neither the age of the patient nor the need for isoproterenol to produce a positive tilt test predicted subsequent significant benefit from metoprolol.
                Metoprolol was not effective in preventing vasovagal syncope in the study population. Head-up tilt testing is a reliable diagnostic tool for patients with recurrent unexplained syncope. It has also been used to assess the drug efficacy for the treatment of patients with syncope. The objective of this study was to assess the efficacy of verapamil compared with metoprolol in a randomized crossover design for patients with syncope and a positive tilt test response. Twenty-eight patients with a positive head-up tilt test were randomized to receive either metoprolol or verapamil; the test was repeated after 7 days of therapy. Of the 15 patients initially given metoprolol, 2 (13.3%) did not respond; both were crossed over to verapamil, to which they remained unresponsive. Of the 13 patients who initially received verapamil, 8 (61%) did not respond; after crossing over to metoprolol therapy, 1 remained unresponsive. Overall, 20 of 23 patients receiving metoprolol had negative results on repeat tilt testing, whereas only 5 of 15 patients receiving verapamil had negative results (p < 0.001). In conclusion, the results of this study suggest that verapamil is considerably less efficacious than metoprolol in managing neurocardiogenic syncope.