The patient populations were drawn from HUT data base at Samsung Medical Center, Seoul, Korea between January 1995 and February 2006.

We defined the episode of syncope as a sudden and brief loss of consciousness with a loss of postural tone and spontaneous recovery from the loss of consciousness. We counted episodes of syncope from HUT data base at Samsung Medical Center.

Patients were included if they had had two or more episodes of syncope before HUT and showed a positive response of HUT. Patients were excluded from the study if they had other causes of syncope (including orthostatic syncope, neurologic cause, cardiac cause, unknown cause, and medication-related syncope). One thousand and fifty-one consecutive patients with neurally mediated syncope, diagnosed following HUT, were eligible for this study, and their records were retrospectively reviewed. The study was approved by the Regional Committee for Ethnics in Medical Research. We also defined patient's syncopal episode as specific situational syncope (micturition or defecation syncope) if he/she experienced syncopal episodes under more specific situation.

All patients underwent HUT in fasting state after obtaining informed consent. HUT consisted of two phases. The first phase of HUT was performed while patients were tilted to an angle of 70° for 30 minutes, or until symptoms appeared. If the first phase produced a negative response, the second phase with isoproterenol provocation was performed while maintaining the same degrees of tilting as the first phase for 15 minutes. Isoproterenol was intravenously administered at an initial rate of 1 µg/min. The infusion rate was increased by 1 µg/min every 3 minutes to a maximum of 5 µg/min. Electrocardiogram (ECG) was continuously monitored. Each patient's blood pressure was non-invasively measured beat-to-beat using a Finapres (OhMeda Monitoring System, Englewood, CO, USA) during the HUT.12 A positive response of HUT was defined when syncope or presyncope was reproduced in association with hypotension (the systolic blood pressure < 80 mmHg), bradycardia (a sinus arrest > 3 seconds or heart rate < 45 beats/min in the first phase, heart rate < 60 beats/min in the second phase), or both. A positive response of HUT was defined when syncope or presyncope was reproduced in association with hypotension. Positive responses were classified into three types (vasodepressive, cardioinhibitory, mixed) according to the criteria provided in the previous study: A vasodepressive response was defined as significant systolic blood pressure decrease < 80 mmHg. A cardioinhibitory response was defined as abrupt sinus arrest or heart rate decrease (sinus arrest > 3 seconds or heart rate < 45 beats/min in the first phase, heart rate < 60 beats/min in the second phase). A mixed response was defined as significant decrease of systolic blood pressure and heart rate.13

Means were calculated for continuous variables, and frequencies were measured for categorical variables. Distributions, which were not normally distributed, were described as medians and interquartile ranges. Comparisons were made by Wilcoxon rank-sum test for continuous variables, and the Chi-square test was used for categorical variables. A p value < 0.05 was considered statistically significant. Data were analyzed with statistical analysis system (SAS) software, version 9.13 (SAS Inc., Cary, NC, USA).

Of 1,051 patients, 497 (47.3%) patients were male and 554 (52.7%) patients were female. One hundred and thirty-six (13.0%) patients suffered defecation syncope and 128 patients (12.2%) had micturition syncope. The mean age of the study subjects was 36.0 ± 16.4 years at HUT. The first syncopal episode developed at ages 2-75 years in a skewed distribution, with a mode of 15 years, a median age of 22 years [interquartile ranges (IOR): 15, 38], and mean age of 27.8 ± 16.2 years. The mean time interval between first and last syncopal episodes was 7.5 ± 9.4 years. They had a mean 6.2 ± 15.5 syncopal episodes prior to HUT (Table 1). The first onset of neurally mediated syncope occurred most frequently at the age interval of 15-19 years old (Fig. 1). Although the recurrence of syncope decreased over time, 33 patients (3.18%) still experienced recurrent episodes 30 years after the first syncope (Fig. 2).

The patterns of a positive HUT were as follows. The vasodepressive type was noted in 726 (69.1%) patients, the cardioinhibitory type in 68 (6.5%) patients, and the mixed type in 257 (24.4%) patients (Table 1).

Ages at HUT and the first syncope were not significantly different between male and female patients. However, female patients had longer time interval between first and last syncopal episodes (8.2 ± 9.5 years vs. 6.8 ± 9.2 years, p = 0.002) and more episodes of syncope prior to HUT (7.2 ± 9.4 vs. 5.0 ± 6.4, p = 0.001) than male patients. Micturition syncope (20.0% vs. 5.2%) was observed more frequently in male patients than in female patients. To the contrary, however, defecation syncope (16.3% vs. 9.3%) was observed more frequently in female patients than in male patients (Table 2). The pattern of positive HUT was not significantly different between two groups (Table 3).

This study was retrospective in design and performed at a single tertiary referral center. Referral bias might affect the results of our study. Surveys of young adult with syncope showed that about 50% of patients did not consult a physicians.11 Therefore, this may compromise the accuracy of the data presented in Fig. 2. We evaluated only the natural history and clinical characteristics of patients with recurrent neurally mediated syncope at the time of HUT. Therefore, we did not address the pattern of the episodes with regard to symptom-free intervals in patients with recurrent neurally mediated syncope in general population.