neurocardiogenic syncope has a peak incidence in subjects in their late teens and early twenties .
the positive rate of ttt with or without a history of syncope ranges from 23.8 to 74% [ 3 - 6 ] .
many researchers have studied treatments of neurocardiogenic syncope including salt intake , physical maneuvers , beta - blockers , midodrine , fludrocortisones , paroxetine , and cardiac pacing ; however , the results are conflicting .
in general , the prognosis of patients with neurocardiogenic syncope is benign , although some patients experience not only recurrent syncopal episodes but also serious head injuries despite treatment .
therefore , the identification of high - risk patients is important for treatment and follow - up .
the frequency of previous syncopal episodes has been reported to be the most powerful predictor of recurrent neurocardiogenic syncope [ 16 - 21 ] .
no other prognostic factors have been confirmed for males in their late teens and early twenties .
therefore , this study sought to identify prognostic factors for neurocardiogenic syncope in males in their late teens and early twenties .
subjects with underlying disease or abnormal electrocardiograms ( ecgs ) and those taking any medications were excluded .
abnormal ecgs included rhythms other than sinus rhythm , right- or left - axis deviation , left- or right - ventricular hypertrophy , mobitz type 2 second - degree atrioventricular block , complete atrioventricular block , left bundle - branch block , and pathological q - wave and abnormal st - segment or t - wave changes .
the subjects were monitored throughout testing with 3-lead electrocardiography and automated blood pressure cuff measurements every 2 minutes .
the ttt consisted of passive and drug - provocation phases . after a 5-minute rest in the supine position ,
the subjects were tilted head - up to a 70 angle on the table for 30 minutes during the passive phase .
if the passive phase was negative , the subjects were given sublingual nitroglycerin ( 0.4 mg ) and tilted to the same angle for another 20 minutes during the drug - provocation phase .
positive results were classified into the following three types : type 1 ( mixed ) was defined as hypotension and heart rate 40 - 60/minutes ; type 2 ( cardioinhibitory ) was defined as heart rate < 40/minutes or asystole for  3 seconds ; and type 3 ( vasodepressor ) was defined as pure hypotension without bradycardia .
hypotension was defined as decreased blood pressure causing syncope or signs of poor tissue perfusion .
the subjects with positive results were educated on the prevention of syncope , including the avoidance of predisposing factors , lying down at the onset of prodromal symptoms , fluid or salt intake , and physical maneuvers .
the subjects were followed in the outpatient clinic or by telephone on a regular basis for 12 months . all subjects provided informed consent .
we analyzed the frequency of previous syncope , the ttt phase that gave a positive result , the ttt duration until a positive result , the types of neurocardiogenic syncope , and the recurrence rate of syncope during the follow - up period .
the results are expressed as the mean  sd or median ( interquartile range , iqr ) for data that were not distributed normally .
the mann - whitney u test and kruskal - wallis test were used for statistical analysis of data that were not distributed normally .
univariate and multivariate logistic regression analyses were used to identify variables associated with the recurrence of syncope during the follow - up period .
we analyzed the frequency of previous syncope , the ttt phase that gave a positive result , the ttt duration until a positive result , the types of neurocardiogenic syncope , and the recurrence rate of syncope during the follow - up period .
the results are expressed as the mean  sd or median ( interquartile range , iqr ) for data that were not distributed normally .
the mann - whitney u test and kruskal - wallis test were used for statistical analysis of data that were not distributed normally .
univariate and multivariate logistic regression analyses were used to identify variables associated with the recurrence of syncope during the follow - up period .
of the 665 male subjects ( mean age , 22.0 years ; range , 17 to 27 ) who underwent testing , 305 ( 45.8% ) had positive results on ttt . of the subjects with positive results ,
82 were excluded because of abnormal ecgs or loss to follow - up ( fig .
we followed 223 subjects ( mean age , 21.1 years ; range , 18 to 26 ) for 12 months .
there were 45 ( 20.2% ) subjects with positive results during the passive phase and 178 ( 79.8% ) during the drug - provocation phase ( fig .
1 ) . there were 146 ( 65.5% ) , 39 ( 17.5% ) , and 38 ( 17.0% ) type 1 to 3 subjects , respectively .
the frequency of recurrence of syncopal episodes during the follow - up period was 1.3  2.4 .
no recurrences occurred in 95 of 116 subjects ( 81.9% ) with one previous syncopal episode , 36 of 54 subjects ( 66.7% ) with two or three syncopal episodes , and 25 of 53 subjects ( 47.2% ) with four or more syncopal episodes .
the subjects with four or more previous syncopal episodes in their lifetime had significantly more recurrences of syncopal episodes than did those with fewer than four ( 1 , 2 - 3 , and  4 ; 0 [ iqr , 0 to 0.5 ] , 0 [ iqr , 0 to 2 ] , and 3 [ iqr , 0 to 9.5 ] , respectively ; p = 0.001 ) ( fig .
the subjects with positive results during the passive phase had significantly more recurrences of syncope than did those with positive results only during the drug - provocation phase ( 1 [ iqr , 0 to 4 ] and 0 [ iqr , 0 to 1 ] , respectively ; p = 0.022 ) ( fig .
( n = 7 of 45 ) with positive results during the early passive phase (  12 minutes ) had significantly more recurrences of syncopal episodes than did subjects ( n = 38 of 45 ) with positive results during the late passive phase ( > 12 minutes ) ( 4 [ iqr , 3 to 7 ] and 0 [ iqr , 0 to 4 ] , respectively ; p = 0.011 ) ( fig .
however , there were no significant differences between the subjects with positive results during the early (  10 minutes , n = 146 of 178 ) and late ( > 10 minutes , n = 32 of 178 ) drug - provocation phases ( 0 [ iqr , 0 to 2 ] and 0 [ iqr , 0 to 0.5 ] , respectively ; p = 0.614 ) or among the types of neurocardiogenic syncope ( types 1 to 3 ; 0 [ iqr , 0 to 1 ] , 0 [ iqr , 0 to 3 ] , and 0 [ iqr , 0 to 3 ] , respectively ; p = 0.435 ) and the recurrence of syncope . frequent previous syncopal episodes (  4 ; p = 0.001 ) and positive results during the passive phase of ttt ( p = 0.001 ) were significantly associated with the recurrence of syncope ( table 2 ) .
of the 665 male subjects ( mean age , 22.0 years ; range , 17 to 27 ) who underwent testing , 305 ( 45.8% ) had positive results on ttt . of the subjects with positive results ,
82 were excluded because of abnormal ecgs or loss to follow - up ( fig .
we followed 223 subjects ( mean age , 21.1 years ; range , 18 to 26 ) for 12 months .
there were 45 ( 20.2% ) subjects with positive results during the passive phase and 178 ( 79.8% ) during the drug - provocation phase ( fig .
1 ) . there were 146 ( 65.5% ) , 39 ( 17.5% ) , and 38 ( 17.0% ) type 1 to 3 subjects , respectively .
the frequency of recurrence of syncopal episodes during the follow - up period was 1.3  2.4 .
no recurrences occurred in 95 of 116 subjects ( 81.9% ) with one previous syncopal episode , 36 of 54 subjects ( 66.7% ) with two or three syncopal episodes , and 25 of 53 subjects ( 47.2% ) with four or more syncopal episodes .
the subjects with four or more previous syncopal episodes in their lifetime had significantly more recurrences of syncopal episodes than did those with fewer than four ( 1 , 2 - 3 , and  4 ; 0 [ iqr , 0 to 0.5 ] , 0 [ iqr , 0 to 2 ] , and 3 [ iqr , 0 to 9.5 ] , respectively ; p = 0.001 ) ( fig .
the subjects with positive results during the passive phase had significantly more recurrences of syncope than did those with positive results only during the drug - provocation phase ( 1 [ iqr , 0 to 4 ] and 0 [ iqr , 0 to 1 ] , respectively ; p = 0.022 ) ( fig .
3 ) . the subjects ( n = 7 of 45 ) with positive results during the early passive phase (  12 minutes )
had significantly more recurrences of syncopal episodes than did subjects ( n = 38 of 45 ) with positive results during the late passive phase ( > 12 minutes ) ( 4 [ iqr , 3 to 7 ] and 0 [ iqr , 0 to 4 ] , respectively ; p = 0.011 ) ( fig .
however , there were no significant differences between the subjects with positive results during the early (  10 minutes , n = 146 of 178 ) and late ( > 10 minutes , n = 32 of 178 ) drug - provocation phases ( 0 [ iqr , 0 to 2 ] and 0 [ iqr , 0 to 0.5 ] , respectively ; p = 0.614 ) or among the types of neurocardiogenic syncope ( types 1 to 3 ; 0 [ iqr , 0 to 1 ] , 0 [ iqr , 0 to 3 ] , and 0 [ iqr , 0 to 3 ] , respectively ; p = 0.435 ) and the recurrence of syncope .
frequent previous syncopal episodes (  4 ; p = 0.001 ) and positive results during the passive phase of ttt ( p = 0.001 ) were significantly associated with the recurrence of syncope ( table 2 ) .
this prospective , observational study elucidated prognostic factors for neurocardiogenic syncope in males in their late teens and early twenties in whom the incidence of neurocardiogenic syncope is high .
we found that most subjects ( 81.9% ) with one previous syncopal episode had no recurrence and that frequent previous syncopal episodes in their lifetime (  4 ) , a positive result during the passive phase of ttt , and positive results during the early passive phase (  12 minutes ) were significantly related to the recurrence rate of syncope .
therefore , a positive result during the early passive phase of ttt and frequent previous syncopal episodes might be prognostic factors for neurocardiogenic syncope in males in their late teens and early twenties .
in previous studies , the frequency of syncope before ttt was the most powerful predictor for recurrent syncope [ 16 - 20 ] .
female gender , a history of bronchial asthma , and the number of previous syncopal episodes may predict recurrences of neurocardiogenic syncope . however , the ttt phase or period associated with positive results as prognostic factors have not been studied in males in their late teens and early twenties .
neurocardiogenic syncope occurs frequently during prolonged motionless standing , and the passive phase is similar to this situation .
the drug - provocation phase is performed on subjects who can tolerate the passive phase .
therefore , subjects with a positive result during the passive phase would tend toward a high recurrence rate of syncope .
furthermore , subjects with a positive result during the early passive phase could be more susceptible to a shorter duration of motionless standing .
. the mechanisms of each type and the relationship between the type and prognosis are debatable . for patients suspected of neurocardiogenic syncope , it is important to obtain a medical history and to perform ttt .
patients with positive results during the early passive phase of ttt and with more frequent episodes of previous syncope need to be followed closely and treated optimally .
the follow - up period of our subjects was relatively short ; therefore , future prospective studies are needed to ascertain the recurrence of syncope in more subjects for longer periods of time at various centers .
there are different ttt protocols ( e.g. , the westminster protocol using isoproterenol for the drug - provocation phase ) .
a positive result during the early passive phase of ttt and frequent previous syncopal episodes are significant prognostic factors for neurocardiogenic syncope in males in their late teens and early twenties .
the follow - up period of our subjects was relatively short ; therefore , future prospective studies are needed to ascertain the recurrence of syncope in more subjects for longer periods of time at various centers .
there are different ttt protocols ( e.g. , the westminster protocol using isoproterenol for the drug - provocation phase ) .
a positive result during the early passive phase of ttt and frequent previous syncopal episodes are significant prognostic factors for neurocardiogenic syncope in males in their late teens and early twenties .
 background / aimsthis study elucidated the prognostic factors for neurocardiogenic syncope in males in their late teens and early twenties.methodstilt-table testing ( ttt ) was performed on 665 males ( age range , 17 to 27 years ) following the italian protocol . 
 the subjects were tilted head - up at a 70 angle on a table for 30 minutes during the passive phase . 
 if the passive phase was negative , the subjects were given sublingual nitroglycerin and tilted to the same angle for 20 minutes during the drug - provocation phase . 
 the subjects with positive results were followed without medication . 
 we analyzed factors related to the recurrence rate of syncope.resultsof 305 subjects ( 45.8% ) with positive results , 223 ( age range , 18 to 26 years ) were followed for 12 months . 
 the frequency of previous syncopal episodes  4 ( p = 0.001 ) and a positive result during the passive phase ( p = 0.022 ) were significantly related to a high recurrence rate . 
 a positive result during the early passive phase (  12 minutes ) was significantly related to a higher recurrence rate than was that during the late passive phase ( > 12 minutes ; p = 0.011).conclusionsa positive result during the early passive phase of ttt and frequent previous syncopal episodes were prognostic factors for neurocardiogenic syncope in men in their late teens and early twenties . 
INTRODUCTION
METHODS
Statistical analysis
RESULTS
Baseline characteristics
Tilt-table test and follow-up results
Factors related to the recurrence of syncope
DISCUSSION
Limitations
Conclusions