Reproducibility of isoproterenol tilt-table tests in patients with syncope.

To assess the reproducibility of head-up tilt-table testing 46 patients each underwent 2 isoproterenol tilt-table tests 1 to 6 weeks apart. Of 20 patients with an initially asymptomatic negative test result, 17 (85%) had a second negative test result. Of 20 patients whose initial test ended in syncope, 18 had a second test ending in syncope (n = 12) or presyncope (n = 6). Five of 6 patients whose first test ended in presyncope had a second test that ended in presyncope, and 1 had a second test that was asymptomatic. Finally, a total of 14 patients had at least 1 test (either the first or second) ending in presyncope, and 11 of these (79%) had another test ending in presyncope or syncope. The dose-dependence of isoproterenol was irreproducible. The reproducibility of the duration of head-up tilt necessary to elicit symptoms of presyncope or syncope was determined in the 23 patients who had these symptoms on both tests. Symptoms developed monoexponentially with duration of head-up tilt with half-times of 1.4 to 2.6 minutes, but these times did not correlate significantly between tests. In a selected subgroup of 12 patients who developed syncope in the first test and either presyncope or syncope in the second test during administration of isoproterenol (5 micrograms/min), the time of onset of presyncope correlated well (r = 0.73, p = 0.007) as did that of syncope (r = 0.86, p = 0.012). Finally, hemodynamic changes during symptoms were compared between the 2 tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of diagnostic accuracy of sublingual nitroglycerin test and low-dose isoproterenol test in patients with unexplained syncope

Despite the widespread use of head-up tilt testing as a means for diagnosing vasovagal syncope, standardization of test methodology remains a controversial issue. The aim of this study was to compare the diagnostic value of head-up tilt testing potentiated with sublingual nitroglycerin with that of head-up tilt testing potentiated with low-dose isoproterenol. For this purpose, 71 patients with unexplained syncope (mean age 43 years) and 30 asymptomatic controls were studied. All underwent the sublingual nitroglycerin and low-dose isoproterenol tests on separate days in a randomized fashion. The protocol of the 2 tests was similar and consisted of 2 phases. Initially, subjects were tilted at 60 degrees for 20 minutes without medication; then, if syncope did not occur, patients and controls received sublingual nitroglycerin (300 microg) or low-dose intravenous isoproterenol (mean infusion rate 1.3 +/- 0.5 microg/min) and continued to be tilted at 60 degrees for a further 20 minutes. During the sublingual nitroglycerin test, a positive response (syncope associated with sudden hypotension and bradycardia) occurred in 35 patients (49%), a negative response in 36 (51%), and drug intolerance in none (0%). During the low-dose isoproterenol test, these percentages were 41%, 59%, and 6%, respectively. A concordant response was observed in 53 cases (75%). Among controls, 3 subjects (10%) had a positive response to the sublingual nitroglycerin test and 4 (13%) to the low-dose isoproterenol test. It is concluded that sublingual nitroglycerin and low-dose isoproterenol are equivalent tests for evaluating patients with unexplained syncope. The sublingual nitroglycerin test, however, is simpler, better tolerated, and safer than the low-dose isoproterenol test and, thus, more suitable for routine clinical use.     

Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing

OBJECTIVE: To determine the clinical characteristics of subgroups of patients with unexplained syncope having electrophysiologic studies and head-up tilt testing and to assess the efficacy of various therapies. DESIGN: Retrospective study. SETTING: Inpatient services of a tertiary referral center. PATIENTS: Eighty-six consecutively referred patients with unexplained syncope. MEASUREMENTS: All patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing. MAIN RESULTS: Twenty-nine (34%) patients (group 1) had abnormal electrophysiologic results, with sustained monomorphic ventricular tachycardia induced in 72%. Thirty-four (40%) patients (group 2) had syncope provoked by head-up tilt testing. The cause of syncope remained unexplained in 23 (26%) patients (group 3). Structural heart disease was present in 76%, 6%, and 30% of groups 1, 2, and 3, respectively. In group 1, pharmacologic or nonpharmacologic therapy was recommended based on electrophysiologic evaluation. All group 2 patients had negative results on head-up tilt testing while receiving oral beta blockers (27 patients) or disopyramide (7 patients). Group 3 patients did not receive any specific therapy. During a median follow-up period of 18.5 months, syncope recurred in 9 (10%) patients. CONCLUSIONS: The combination of electrophysiologic evaluation and head-up tilt testing can identify the underlying cause of syncope in as many as 74% of patients presenting with unexplained syncope. Therapeutic strategies formulated according to the results of these diagnostic tests appear to prevent syncope effectively in most 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.     

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

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

Methodology of 80 degrees head-up tilt testing with and without low dose isoproterenol provocation in Japanese patients with neurally mediated syncope

The usefulness of 80 degrees head-up tilt testing with and without low dose isoproterenol provocation was evaluated for the diagnosis of neurally mediated syncope (NMS) in Japanese. Head-up tilt testing was performed in 114 consecutive patients with clinical diagnoses of NMS (68 men, 46 women, mean age 46 +/- 21 years), and 57 times in 36 healthy volunteers (26 men, 10 women, mean age 31 +/- 8 years) who had no history of syncope or presyncope. Head-up tilt testing used an 80 degrees angle for 30 minutes (passive tilt), and if the passive tilt resulted in negative response, isoproterenol was infused at 0.01-0.02 microgram/kg/min and the tilt repeated for 10 minutes (isoproterenol tilt). A positive response was defined as the development of syncope or a presyncopal state associated with hypotension, bradycardia or cardiac arrest. The sensitivities of passive tilt testing for a positive response after 5-, 10-, 15-, 20-, 25- and 30-minute tilting were 1%, 9%, 14%, 19%, 24%, and 28%, respectively, and specificities after 5-, 10-, 15-, 20-, 25- and 30-minute tilting were 100%, 95%, 91%, 88%, 86%, and 84%, respectively. The sensitivities of isoproterenol tilt testing with 0.01 and 0.02 microgram/kg/min were increased to 37% and 48%, respectively. This improvement was statistically significant between the passive tilt and isoproterenol tilt testing with a dose of 0.02 microgram/kg/min (p < 0.01). However, specificities were comparable with those of the passive tilt testing (84% and 82%, respectively). In conclusion, 80 degrees passive tilt testing for 30 minutes showed a low sensitivity (28%) but acceptable specificity (84%). Low-dose isoproterenol provocation was useful for improving sensitivity (48%) while maintaining a comparable specificity (82%).     

Methodology of isoproterenol-tilt table testing in patients with syncope.

To assess the impact of isoproterenol, duration of tilt, symptom development and hemodynamic changes on the outcome of tilt table tests, 100 patients with syncope underwent successive 80 degrees head-up tilt for 10 min during infusions of 0, 2 and 5 micrograms/min of isoproterenol. All 15 patients with another cause of syncope had a normal test result and 66 (78%) of the 85 patients with syncope of unknown origin had a test that resulted in syncope or presyncope. Isoproterenol was required to produce syncope or presyncope in greater than 90% of positive tests and 66% to 80% of positive tests required a dose of 5 micrograms/min of isoproterenol. Without isoproterenol, symptoms did not develop until after greater than or equal to 4 min of head-up tilt. With either 2 or 5 micrograms/min of isoproterenol, the half-time of symptom onset was 0.7 to 1.9 min and the rate of symptom development did not depend on the dose of isoproterenol. During syncope, the mean heart rate, systolic blood pressure and rate-pressure product each decreased significantly from 132 +/- 21 to 67 +/- 25 beats/min, 117 +/- 19 to 60 +/- 16 mm Hg and 15.3 +/- 2.9 to 4.2 +/- 2.2 x 10(3) mm Hg/min, respectively. During presyncope, mean trough rate-pressure product (5.5 +/- 2 x 10(3) mm Hg/min) was significantly higher (p = 0.027) than during syncope.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized study of tilt test angle in patients with undiagnosed syncope.

BACKGROUND: A widely used tilt test protocol involves passive head-up tilt followed by tilt with isoproterenol infusion if necessary. Little is known about the effects of passive tilt angle and duration, duration of isoproterenol infusion or hemodynamic diagnostic criteria. OBJECTIVES: To assess whether tilt angle and duration of isoproterenol infusion affected test outcomes in patients with undiagnosed syncope. PATIENTS AND METHODS: Two hundred one syncope patients (87 men, age 45+/-20 years, median five faints) were randomly assigned to undergo 60 degrees versus 80 degrees tilt for 45 min, then, if necessary, to receive isoproterenol 30 ng/kg/min for 20 min or less. Positive tests ended in presyncope or syncope. RESULTS: Overall, 49% and 71% of patients fainted at 60 degrees and 80 degrees, respectively (P=0.002). In the drug-free stage, 27% and 50% of patients fainted at 60 degrees and 80 degrees, respectively (P=0.0005). In the 119 patients who received isoproterenol, there was no significant difference in the probability of a positive isoproterenol test at 60 degrees and 80 degrees, respectively (31% compared with 43% of exposed patients, P=0.25). Symptoms developed in adults during drug-free tilt linearly with time at both 60 degrees and 80 degrees at 0.6% and 1.1%/min, respectively, while symptoms during isoproterenol tilt reached an asymptote after about 10 min. Rate-systolic pressure products of 7000 mmHg/min and 9000 mmHg/min best distinguished positive from negative passive and isoproterenol stages, respectively. CONCLUSIONS: The positive yield of passive tilt tests is higher at 80 degrees and increases linearly with the duration of tilt. A subsequent 10 min isoproterenol infusion maximizes positive yield. Evidence-based outcome criteria accurately distinguish negative from positive tilt tests.     

Poor reproducibility of false-positive tilt testing results in healthy volunteers.

Positive responses to head-up tilt testing occur in healthy subjects. However, the reproducibility of "false-positive" tilt testing results has not been clarified. To study the reproducibility of "false-positive" responses, we prospectively performed 2 tilt tests separated by 1 to 10 (mean 3.2) weeks in 20 healthy males aged 23 to 40 years (mean 30 years). The baseline tilt test (80 degrees for 30 minutes) ended positive in 4 (20%) subjects on the initial test and 2 (10%) on the second test with only 1 (5%) who had consecutive positive responses. No additional positive responses were noted during the isoproterenol (0.01 microgram/kg/min)-tilt test for 10 minutes. We demonstrated that a false-positive response occurred in 5 (25%) of 20 young males who underwent 2 tilt tests, however, only 1 (5%) subject had consecutive positive responses. Poor reproducibility may be characteristic of false-positive responses in head-up tilt testing.     

Reproducibility of sequential head-up tilt testing in patients with recent syncope, normal ECG and no structural heart disease.

AIMS: To assess the reproducibility of the response to sequential head-up tilt tests. METHODS AND RESULTS: A head-up tilt test was performed early after syncope in 127 patients with a normal ECG and no structural heart disease. Patients with a positive response (82 patients) were randomized to two (1 week and 2 weeks later) or one (2 weeks later) additional head-up tilt tests, and patients with a negative response (45 patients) were randomized to a second head-up tilt test 1 or 2 weeks after the first. The reproducibility of a positive response in the second head-up tilt test was 80% after 1 week and 53% after 2 weeks (P<0.01). Only 53% of the patients with a positive response to a first and second head-up tilt test had a positive response to a third (P=0.01). Intra-individual variation in the time to a positive response was wide. The reproducibility of the cardioinhibitory responses was very poor. Reproducibility of a negative response was 80%. CONCLUSIONS: In patients with recent syncope, the rate of positive responses decreases with sequential head-up tilt tests. Furthermore, the time to a positive response in different head-up tilt tests shows important intra-individual variations, and the reproducibility of the cardioinhibitory responses is very poor. In contrast, the reproducibility of the negative responses is high.     

Usefulness of head-up tilt test in evaluating patients with syncope of unknown origin and negative electrophysiologic study

The vasovagal nature of syncope, which remained unexplained despite full clinical and electrophysiologic investigation, was evaluated by means of 60 degrees head-up tilt test for 60 minutes. Thirty patients (17 men and 13 women, mean age 65 years, 19 with and 11 without organic heart disease) with 1 to 28 (mean 5) episodes of syncope of unknown origin were studied. Head-up tilt test was considered positive if syncope developed in association with hypotension, bradycardia, or both. During baseline head-up tilt 15 patients (50%) had a positive response. Ten patients had a vasodepressor response (marked hypotension without marked bradycardia) and 5 had a mixed response (marked hypotension with marked bradycardia). None of 8 control subjects became symptomatic during the test. Baseline head-up tilt test was positively reproducible in 10 of 14 patients (71%). Nine of these 10 patients underwent serial head-up tilt tests after drug administration to determine the pathogenesis of vasovagal syncope. Atropine prevented tilt-induced syncope in 3 of 8 patients (37.5%), propranolol in 2 of 8 (25%) and etilephrine in 7 of 7 (100%). Seven patients received long-term drug treatment with drugs selected on the basis of acute drug testing. One responder to atropine received transdermal scopolamine and 6 received etilephrine. None of these 7 patients had syncopal recurrences or death during a mean follow-up of 12 months. Head-up tilt is a very sensitive and highly specific test to unmask susceptibility to vasovagal reaction in patients with syncope of unknown origin. Withdrawal of alpha-sympathetic stimulation is a principal mechanism responsible for vasodilation and syncope during head-up tilt.(ABSTRACT TRUNCATED AT 250 WORDS)     

Utility of upright tilt-table testing in the evaluation and management of syncope of unknown origin.

PURPOSE: Vasovagally mediated hypotension and bradycardia are believed to be common, but difficult to diagnose, causes of syncope. Upright tilt-table testing has been proposed as a possible way to test for vasovagal episodes. This study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin. PATIENTS AND METHODS: Twenty-five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/minute given intravenously), in an attempt to provoke bradycardia, hypotension, or both. Of the 25 patients, there were 14 males and 11 females, with a mean age of 50 +/- 16 years. Six control patients with no history of syncope were also studied. All tilt-positive patients received therapy with either beta-blockers, disopyramide, transdermal scopolamine, or hydroflurocortisone, the efficacy of which was evaluated by another tilt-table test. RESULTS: Syncope occurred in six patients (24%) during the baseline tilt and in nine patients (36%) during isoproterenol infusion (total positives, 60%). None of the controls had syncope during the test. All patients who had positive test results eventually became tilt-table-negative by therapy, and over a mean follow-up period of 16 +/- 2 months no further episodes have occurred. CONCLUSION: From this study we conclude that upright tilt-table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy.     

Head-up tilt table testing with low dose sublingual isosorbide dinitrate in the evaluation of unexplained syncope: a comparison with isoproterenol infusion

OBJECTIVES: To investigate the value of head-up tilt table testing (HUTT) with low-dose isosorbide dinitrate (ISDN) in the evaluation of patients with unexplained syncope and to compare the results of HUTT with ISDN and HUTT with isoproterenol. PATIENTS AND METHODS: Forty-three patients with unexplained syncope (21 women, with a mean age of 45.4 18 years) and 18 control subjects without syncope (eight women, with a mean age of 45.8 12 years) were tilted (80 ) for 30 min (passive period). When this period was negative, 2.5 mg sublingual ISDN was administered and patients were observed for an additional 15 min (ISDN period). The first 25 patients studied (10 women, with a mean age of 46.2 18 years) were tested again after a mean period of three weeks using the isoproterenol protocol. After the passive period, intravenous isoproterenol was administered (1 to 3 g/min) to patients lying in the supine position, and they were tilted again (80 ) for 10 min (isoproterenol period). RESULTS: During the passive period, 10 of 43 patients (23%) had a positive response compared with none in the control group. Syncope was observed in another 14 patients and in two control subjects during the ISDN period. The positivity rate (sensitivity) and specificity of HUTT with low dose ISDN were 56% and 89%, respectively. Among the patients (n=25) tested with the isoproterenol protocol, 14 (56%) patients had syncope. The agreement rate between the protocols was 78.9%. CONCLUSIONS: The total positivity rate of HUTT significantly increased with the use of the low dose ISDN, while specificity remained high. Due to its simplicity and tolerability, the ISDN protocol can be chosen when the results of the passive period tilt testing are negative.     

Tilt table evaluation for control pediatric patients: Comparison with symptomatic patients

This study was designed to evaluate pediatric control patients during head-up tilt in comparison with symptomatic neurocardiogenic syncope patient head-up tilt responses. Twenty-three pediatric control (c) patients (13 females, 10 males; 11.9 ± 3.1 years) were tested with head-up tilt (HUT) and compared with 66 symptomatic (s) patients. Baseline drug-free HUT (cHUT-1), a second drug-free HUT (cHUT-2), and a final HUT with isoproterenol infusion (cHUT-3) were each performed at 80° tilt angle for 30 min or until positive. For comparison, 66 symptomatic patients (41 females, 25 males; 13.6 ± 2.5 years) underwent drug-free HUT (sHUT-1); negative responders during sHUT-1 underwent follow-up HUT with isoproterenol (sHUT-2). HUT data were compared for both groups at both 30 and 20 min tilt duration. Twelve control patients (52%) had a symptomatic response during cHUT-1 at 18±8 min. During cHUT-2, 5 of 23 patients were positive at 13±5 min; each had previously tested positive during cHUT-1. Two patients, each positive in cHUT-1 and cHUT-2, refused cHUT-3. The only patient testing positive during cHUT-3 was test positive in cHUT-1 but negative for cHUT-2. In comparison, 43 of 66 (65%) symptomatic patients tested positive during drug-free sHUT-1 at 11±6 min. Subsequently, 20 of the 23 negative patients underwent HUT with isoproterenol (sHUT-2), with 8 of 20 testing positive. Thus, 51 of 66 symptomatic patients (77%) were called “true positives.” Chi-square analysis for comparison of 30 min cHUT-1 (12/23 positive patients) versus sHUT-1 (43/66 positive patients) yielded no statistical difference. However, analysis of data limited to 20 min tilt duration showed 7 of 23 positive cHUT-1 versus 38 of 66 positive sHUT-1 patient responses (p = 0.025). It is concluded that (1) pediatric HUT is relatively nonspecific in a control population (52% false positive), (2) concordance for consecutive positive control tilts is low, (3) isoproterenol does not increase overall predisposition to positive pediatric control patient response, and (4) an 80° tilt protocol limited to 20 min duration may help differentiate between false and true positive responses.     

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

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.     

Syncope of undetermined nature after electrophysiologic study. Usefulness of the head-up tilt test in the diagnosis of vaso-vagal origin and in the choice of treatment

The vaso-vagal nature of syncopes which remained unexplained despite full clinical and electrophysiological investigation was evaluated by means of 60 degrees head-up tilt test for 60 minutes. Thirty patients (16 men and 14 women, mean age 63.6 years, 19 with and 11 without organic heart disease) with 1 to 28 (mean 5.1) episodes of syncope of unknown origin were studied together with 11 asymptomatic control subjects. Head-up tilt test was considered positive if syncope developed in association with hypotension and/or bradycardia. During baseline head-up tilt 15 patients (50%) showed a positive test, with vasodepressor response (marked hypotension without marked bradycardia) in 10 cases and with mixed response (marked hypotension with marked bradycardia) in 5 cases. None of the control subjects became symptomatic during the test. Mean time to syncope was 24.9 minutes. Baseline head-up tilt test was reproducibly positive in 10 out of 14 patients (71%). Eight of these 10 patients underwent serial head-up tilt tests after atropine (0.04 mg/Kg i.v. in 1 minute), propranolol (0.2 mg/Kg i.v. in 3 minutes) and etilefrin (15-30 mg/day orally for 2-3 days) to determine the pathogenesis of vaso-vagal syncope. Atropine prevented tilt-induced syncope in 3 out of 7 patients (43%), propranolol in 2 out of 7 (29%) and etilephrine in 6 out of 6 (100%). Seven patients were chronically treated with drugs selected on the basis of acute drug testing. One patient-responder to atropine received transdermal scopolamine and the other 6 received etilephrine. None of these 7 patients had syncopal recurrences or death during a mean follow-up of 7.7 months, except 1 who experienced another episode of syncope after having discontinued etilephrine 4 months before. These results suggest that: 1) head-up tilt is a very sensitive and highly specific test to unmask susceptibility to vaso-vagal reaction in patients with syncope of unknown origin; 2) withdrawal of alpha-sympathetic stimulation is the principal mechanism responsible for vasodilation and syncope during head-up tilt; 3) alpha-sympathomimetic agents, such as etilephrine, are effective in preventing spontaneous episodes of vaso-vagal syncope during a short-term follow-up.     

Tilt testing in neurocardiogenic syncope: isosorbide versus isoproterenol

OBJECTIVE: To compare the diagnostic value of pharmacological stimulation with sublingual isosorbide dinitrate and intravenous isoproterenol during tilt testing in patients with neurocardiogenic syncope and with a negative tilt test without pharmacological provocation. METHODS AND RESULTS: One hundred and twenty patients with a history of neurocardiogenic syncope (aged 15 to 77 years) and 50 healthy volunteers (aged 25 to 70 years) were prospectively submitted to head-up tilt (HUT). Those who did not develop syncope or presyncope during passive HUT for 30 minutes underwent repeated HUT with isoproterenol infusion at 4 microg/min (ISOP HUT), for 10 minutes, and, subsequently, were tilted after sublingual administration of 5 mg of isosorbide dinitrate (ISDN HUT) for another 12 minutes. ISDN HUT was always performed after ISOP HUT. Sensitivity and specificity of passive HUT were 41% (95% C.I. 32.9% to 51.0%) and 100%, respectively. Sensitivity of ISOP HUT was 51.4% (95% C.I. 39.2% to 63.6%) and specificity 70% (95% C.I. 55.4% to 82.1%) and for ISDN HUT were 70% (95% C.I. 57.9% to 80.4%) and 88% (95% C.I. 75.7% to 95.5%), respectively. The accuracy of ISDN HUT was significantly higher than the accuracy of ISOP HUT 77.5% (95% C.I. 68.9% to 84.6%). There were fewer side effects during ISDN HUT. CONCLUSION: Sublingual isosorbide dinitrate is at least as sensitive as isoproterenol to assess patients with suspected neurocardiogenic syncope and with a negative tilt test without provocation. The low rate of side effects and the higher accuracy of ISDN HUT, along with the simplicity of this challenge compared to ISOP HUT, suggest that sublingual isosorbide dinitrate should be preferred as a provocative agent to evaluate neurocardiogenic syncope after a negative passive tilt test.     

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

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

晕厥患者倾斜试验评价

提出对晕厥患者进行倾斜试验以明确病因的方法。着重研究了有关影响因素如不同原发疾病、不同异丙肾上腺素给药浓度、不同倾斜持续时间以及不同抑制晕厥发作药物对该试验的影响及意义。结果显示，倾斜试验是诊断血管迷走性晕厥的重要方法。     

Clinical spectrum and prevalence of neurologic events provoked by tilt table testing

BACKGROUND: Motor activity occurring during neurocardiogenic syncope can mimic true neurologic events. OBJECTIVE: To assess the prevalence and type of apparent neurologic events associated with tilt table testing. METHODS: The records of consecutive patients undergoing tilt table testing for the evaluation of syncope were reviewed. Patients underwent a 70 degrees upright tilt for 40 minutes, followed by a 20-minute tilt while receiving isoproterenol hydrochloride. The results of tilt table tests were considered positive when clinical symptoms were reproduced in association with a decline in blood pressure. Clinical variables and neurologic events were analyzed. RESULTS: Tilt table tests were performed on 694 patients during the study period, and the results were positive in 222 of them. Eighteen patients (8%) had apparent neurologic events during tilt table testing. Eleven patients (5%) had apparent tonic-clonic seizure-like activity, and 7 patients (3%) had non-tonic-clonic neurologic events, including focal seizures (n = 3), dysarthria or aphasia (n = 2), unilateral extremity dysesthesia (n = 1), and reproduction of temporal lobe epilepsy symptoms (n = 1). The patients with tonic-clonic seizure-like activity had a significantly lower systolic blood pressure reading at the termination of tilt table testing than all other patients whose tilt table test results were positive (P =.04). The heart rate at the time of test termination was significantly lower in the patients with tonic-clonic seizure-like activity and non-tonic-clonic neurologic events (P<.01) than in those with positive test results and no provoked neurologic events, and asystole was provoked more frequently in these 2 patient populations (P =.03). CONCLUSIONS: Neurologic events are common during episodes of neurocardiogenic syncope, and this diagnosis should be considered in the evaluation of unexplained seizure-like activity.