© 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
Psychiatric profile, quality of life and risk of syncopal recurrence in patients with tilt-induced vasovagal syncope
aDepartment of Cardiology, Umberto I Hospital Via Circonvallazione 50, 30174 Mestre-Venice, Italy; bDepartment of Neurology, Umberto I Hospital Mestre-Venice, Italy; cDepartment of Cardiology, Valduce Hospital Como, Italy
Manuscript submitted 22 February 2005. Revision received 25 July 2005. Accepted after revision 7 May 2005.
*Corresponding author. Tel.: +39 041 260 7201; fax: +39 041 260 7235. E-mail address: francogiada{at}hotmail.com (F. Giada)
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Abstract |
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AIM: The aim of this study was to investigate the prevalence of psychiatric disorders and quality of life (QoL) in patients with tilt-induced vasovagal syncope and no other comorbidities, and their relationship with the syncopal burden and the risk of recurrence.
METHODS: We studied 61 patients with recurrent syncope and positive tilt testing. Controls consisted of 61 sex- and age-matched healthy subjects. Psychiatric diagnoses were formulated on the basis of a structured interview and the Minnesota Multiphase Personality Inventory-2 questionnaire. QoL was assessed by means of the Short-Form Health Survey questionnaire. Patients were followed up for at least 1 year.
RESULTS: The presence of psychiatric disorders was higher among patients than controls (71% vs. 23%, P<0.001), with a prevalence of anxiety (28% vs. 5%), mood (18% vs. 3%), and somatization disorders (29% vs. 3%). The scores of all the QoL scales were statistically lower in patients than controls. An inverse correlation was found between QoL scale scores and syncopal burden. The presence of psychiatric disorders was predictive of syncopal recurrence during follow-up.
CONCLUSION: Psychiatric disorders are common in patients with tilt-induced vasovagal syncope, and seem to predict the risk of recurrence. QoL is impaired in these patients, and is inversely correlated with the syncopal burden.
Key Words: vasovagal syncope, psychiatric disorders, quality of life, tilt testing
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Introduction |
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The relationship between syncope and disorders within the mental sphere, though not thoroughly explored, has long been known [1
–3]. Indeed, syncope is such a frequent symptom in some psychiatric illnesses that, according to the American Psychiatric Association (APA) (DSM-IV), it constitutes one of the criteria on which the diagnosis of anxiety, depression, and somatization disorders is based [4].
Data on the prevalence of psychiatric disorders and quality of life (QoL) in patients with vasovagal syncope are somewhat scant and incomplete [5–9]. Nevertheless, various factors seem to suggest the presence of an association between vasovagal syncope and psychological factors. Indeed, in patients with vasovagal syncope, mental stress and particular emotional states can facilitate and/or trigger the neurally mediated reaction that underlies the syncopal episode [10,11]. Furthermore, it is well known that, when patients are reassured of the substantially benign nature of their problem, they have significantly fewer syncopal recurrences [12]. Finally, it should be pointed out that one of the only drugs shown to be efficacious in preventing vasovagal syncope in a placebo-controlled study [13] was paroxetine, an inhibitor of serotonin re-uptake commonly used as an anti-depressant.
The aim of the present study was to evaluate the prevalence of psychiatric disorders and QoL in patients with tilt-induced vasovagal syncope and without other comorbidities, and to investigate their relationship with the syncopal burden and the risk of recurrence.
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Subjects
To participate in the study, patients had to fulfil all the following inclusion criteria: age over 18 years (since the method used for psychological evaluation is valid only for adult subjects); recurrent syncope with at least one syncopal episode in the last 6 months; positive head-up tilt testing with vasovagal response and reproduction of the patient's spontaneous symptoms (to confirm the neurally mediated origin of syncopal spells); negative diagnostic work-up for other causes of syncope. The diagnosis of syncope, as well as the differentiation of true syncope from other non-syncopal conditions, was based on the European Guidelines on Syncope [14]
. The following constituted exclusion criteria: presence of structural heart disease and/or other concomitant pathological conditions; declared psychiatric disorders; treatment with psychiatric drugs. Consecutive patients with recurrent syncope referred to the syncope unit of our cardiology department for head-up tilt testing (HUT) evaluation, were considered. The control group consisted of healthy, sex- and age-matched nurses of the cardiovascular department with no history of syncope or pre-syncope, who knew in advance that their responses would be blindly judged.
Head-up tilt testing
For HUT we used the ‘Italian Protocol’ [15–17]. This involves a first phase of tilt at 60° for 20 min without drug challenge; if this proves negative, it is followed immediately by a second phase of tilt at the same angle for 15 min, after sublingual administration of 400 µg of nitroglycerin spray. HUT was considered positive for vasovagal response if it elicited syncope with full reproduction of the patient's spontaneous symptoms, associated with a sudden and significant fall in blood pressure and heart rate. To avoid influence on quality of life scores, reassurance and counselling were given to the patients only after psychiatric and quality of life evaluations.
Psychiatric evaluation
All subjects taking part in the study underwent a structured interview with a psychologist, and were asked to complete the Minnesota Multiphase Personality Inventory-2 (MMPI-2) questionnaire for psychological assessment. Patients underwent the interview and completed the MMPI-2 at least 3 days after HUT, in order to minimize the psychological impact of the procedure.
The MMPI-2 is a widely recognized tool for assessing the psychological profile of adult subjects [18,19]. Made up of over 500 items, the questionnaire uses specific scales to explore various psychological problems. The clinical scales of MMPI-2 include the following individual's trait of personality: hypochondriasis, depression, hysteria, psychopathic deviance, paranoia, psychasthenia, schizophrenia, mania, and social introversion. The higher the score assigned on each scale, the greater the personality disorder. The score is considered pathological when higher than 65 points. All enrolled subjects were asked to complete the MMPI-2 questionnaire alone at home and to return it to the syncope unit. The questionnaires were evaluated by means of special software (MMPI-2 Psy-System, OS, Florence, Italy).
Clinical diagnoses were formulated by two expert psychologists of the Department of Neurology, working ‘blind’ (i.e. they did not know if the subjects were patients or controls), on the basis of the interview and the questionnaire results and classified, in accordance with the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) [4], in the following groups: anxiety disorders, mood disorders, somatization disorders, and personality disorders. In subjects with multiple psychiatric disorders, the assigned diagnosis represented the most severe aspect of their condition. Patients and controls were also evaluated for the presence of stressful life events (main stressors), such as family problems, job conflicts and social problems.
Quality of life
QoL was assessed by means of the Short-Form Health Survey (SF-36) questionnaire. The SF-36 is an international standardized tool for assessing the general state of health, on eight specific scales. The SF-36 measures two major dimensions of health: the physical and the psycho-social domains [20,21]. The lower the score assigned on each scale, the higher the degree of impairment of that particular aspect of QoL. Like the MMPI-2, the SF-36 was distributed to the patients at least three days after HUT. The questionnaire was analysed ‘blind’ by two expert psychologists.
Follow-up
After reassurance and counselling, patients were followed up without any medications for at least one year. Patients were asked to keep a clinical diary, specifying the number, severity and time of syncopal events, the circumstances in which they occurred and any associated traumas.
Statistical analysis
Statistical analysis was carried out by means of the SPSS 9.0 statistical package (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean±standard deviation; comparison between groups was made by using Student's t-test for unpaired data in the case of variables with normal distribution, and by the Mann–Whitney non-parametric test in the case of variables with non-linear distribution. Discrete variables were expressed as percentages; comparison between groups was made by using the chi-square test. Differences between patients with and patients without psychiatric disorders were assessed by ANOVA and chi-square test, as appropriate. Correlation among different variables was assessed by means of the Pearson correlation matrix, and the logistic regression model. Statistical significance was considered to be P<0.05.
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Patient characteristics
During the recruitment period (January 2002 to December 2002), 230 patients with recurrent syncope were referred for HUT evaluation, and 81 of these (35%) met all inclusion and exclusion criteria. Only 61 of the eligible patients gave informed consent and took part in the study. Only two of the eligible control subjects refused to participate in the study.
The demographic and clinical characteristics of patients and controls are reported in Table 1. There were no differences between the two groups in terms of gender, age, marital status, number of children, socio-economic status and level of education, in the presence of main stressors.
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Psychiatric evaluation
Patients had significantly higher mean scores than control subjects on the scales assessing hypochondriasis, depression, hysteria, psychasthenia and mania (Fig. 1). The mean number of scales on which pathological scores (>65) were recorded was higher in patients than in controls (1.5±1.9 vs. 0.4±0.1, P<0.001, respectively).
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The number of subjects with at least one psychiatric disorder according to the APA (DSM-IV) criteria was statistically higher among patients than controls (71% vs. 23%, P<0.001), with a prevalence of anxiety disorders (28% vs. 5%, P<0.001), mood disorders (18% vs. 3%, P<0.01), and somatization disorders (29% vs. 3%, P<0.001) (Fig. 2). By contrast, there were no statistical differences between the two groups with regard to personality disorders. In neither group were any cases of drug or alcohol abuse recorded. In the syncope group ten patients had two simultaneous psychiatric disorders and two patients had three, while in the control group two co-existing psychiatric disorders were detected only in two subjects. There was no significant difference between patients with psychiatric disorders and those without, in terms of age, gender, number of syncopal episodes, duration of symptoms, syncopal rate, and occurrence of syncope-related injury (Table 1). Among these variables none was significantly predictive of the presence of psychiatric disorders, using a logistic regression model. No significant differences were observed in the scores on the clinical scales of MMPI-2 between patients with more than six syncopal episodes and those with fewer than six, between patients with and without syncope-related injury, or between patients over and those under 40 years of age. Finally, no significant correlation was observed between the MMPI-2 clinical scales and the patient's syncopal burden, that is to say, the number of syncopal episodes during the lifetime and the duration of symptoms.
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QoL evaluation
The scores of all the SF-36 scales proved to be statistically lower in patients than in controls, in both the physical and psycho-social domains, and were also significantly lower in patients with psychiatric disorders than in those without (Table 2). No significant differences were observed in the scores on the SF-36 scales between patients with and without syncope-related injury, or between patients over and those under 40 years of age. Patients with more than six syncopal episodes showed a significant reduction on the scales of physical functioning (P<0.001) and general health (P<0.01) in comparison with those with fewer than six episodes. The number of syncopal episodes during the patient's lifetime was significantly correlated with physical functioning (r=–0.379, P<0.01) and physical role (r=–0.293, P<0.05). The number of syncopes in the last 6 months was correlated with physical functioning (r=–0.257, P<0.05), physical role (r=–0.297, P<0.05), bodily pain (r=–0.316, P<0.05), and general health (r=–0.255, P<0.05). The syncopal rate was correlated with physical role (r=–0.348, P<0.01).
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Follow-up
During follow-up (mean duration 15±2 months), at least one syncopal recurrence occurred in 25 of 43 patients with psychiatric disorders, and in 3 of 18 patients without psychiatric diagnoses (58% vs. 17%, P<0.05). No patients experienced syncope-related trauma. Using a logistic regression model, the presence of any psychiatric disorders was significantly predictive of syncopal recurrence (hazard ratio = 6.94, 95% confidence interval = 1.7–27.6, P=0.006).
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Discussion |
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Main findings
In the present study, we observed a higher frequency of pathological scores on the various MMPI-2 scales among patients than among controls, with the highest scores being recorded on the scales for hypochondriasis, depression, hysteria, psychasthenia and mania. The number of individuals with psychiatric disorders was also higher among patients than controls, especially with regard to anxiety, mood, and somatization disorders. All the observed psychiatric disorders were mild or moderate. Moreover, we observed a marked reduction in all the QoL scales in patients in comparison with controls, and in patients with psychiatric disorders versus those without. Finally, no correlation was found between psychiatric diagnosis and the patient's syncopal burden; however, the presence of psychiatric disorders constituted a risk factor for syncopal recurrence. Indeed, 58% of our patients with psychiatric disorders had at least another syncopal episode during the subsequent follow-up versus only 17% of patients without psychiatric disorders. This finding seems to suggest that in predisposed patients, frequent syncope triggers psychiatric morbidity, which in turn increases the likelihood of recurrence. This observation, in agreement with those reported by Kapoor et al. [1]
, Linzer et al. [2] and Kouakam et al. [23] on syncope of unexplained origin, suggests that psychiatric evaluation may be valuable in identifying which patients with tilt-induced vasovagal syncope have an high risk of recurrence and really need long-term treatment.
Comparison with previous studies
A few clinical studies have reported a high prevalence of psychiatric disorders, such as anxiety, depression and somatization disorders, in patients with unexplained syncope [1–3,22,23]. Moreover, some studies [5,6,9] have found that patients with recurrent syncope of various origins also suffer from a significant reduction in their quality of life. The above-mentioned studies, however, present some confounding factors that deserve to be highlighted. The first is the poor homogeneity of the study population. Indeed, enrolled patients had syncope of various origins, or were suffering from unexplained syncope [1–3,9,21]. Moreover, the patients studied were very often affected by other comorbidities, in addition to syncope [5,6,9]. Therefore, we cannot rule out the possibility that these concomitant illnesses may have affected the psychological profile and quality of life of the patients examined [20]. Finally, these studies lack a suitable control group that is representative of the general population [9,23]. This last point is of fundamental importance, in that epidemiological studies have revealed that the prevalence of psychiatric disorders in the general population is somewhat high, and is steadily rising [24]. Indeed, at least 20% of the general population in Italy suffers from psychiatric disturbances [25]. Thus, the lack of comparison with a control group made up of healthy subjects may lead to misinterpretation of the results recorded on syncope patients. Our results, obtained in patients with tilt-induced vasovagal syncope and without other comorbidities, are in line with the results observed in patients with unexplained syncope [1–3,22,23] or in patients with syncope of various origins [5,6,9].
Minor findings
In patients with unexplained syncope, psychiatric disorders were most frequently encountered in young and in female patients [1–3]. Our results do not support a similar pattern in patients with vasovagal syncope. The explanation for these discrepancies between the results of the present study and those of the studies quoted above is unclear. It may, however, lie in the small sample size, and in the different patient population studied. Indeed, our population was made up only of patients with tilt-induced vasovagal syncope, while in the previous studies were included subjects with various causes of syncope.
In this study we observed a significant, although quite weak, inverse correlation between syncopal burden and the scales of SF-36 in the physical domain, i.e. in the dimension of health most sensitive to the clinical manifestations of medical conditions. Our data, in agreement with those published by Rose et al. [9], seem to suggest an association between the syncopal burden and the QoL of patients with recurrent syncope. Furthermore, these results are supported by data from Sheldon et al. [26] on the effects of pacemakers in patients with recurrent vasovagal syncope. Indeed, these authors found a significant improvement in QoL in subjects who experienced a reduction in syncopal recurrences following pacemaker implantation.
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Limitations |
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The present study evaluated highly selected and symptomatic, middle-aged patients who had been referred to a treatment facility for syncope. These patients may not, therefore, be fully representative of all subjects with vasovagal syncope. Moreover, patients with both syncope and psychological problems may represent a group of patients who continue to seek ‘answers’ to their condition, and are probably referred more often than those without any such problems. This could represent a referral bias. Finally, the control group was comprised solely of healthy subjects. Since the way of selection conditions the results, it is possible that with a control group made up of subjects with other paroxysmal disorders, the results might be different. However, in the study of Kouakam et al [23]
, in which a group of patients with unexplained syncope was compared with patients referred for arrhythmia management, a high prevalence of psychiatric disorders was observed in patients with syncope in comparison with those with arrhythmias.
As this was a case-controlled observational study, no conclusion can be drawn as to whether the psychiatric disorders were the cause or the result of the recurrent syncopal episodes [27]. Only through prospective randomized studies in which the effects of psychiatric therapy on syncopal recurrences are evaluated can any causal relationship be established among psychiatric profile and syncopal burden. Studies of case series including small numbers of patients [28,29] seem to suggest such a relationship.
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Conclusions |
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Psychiatric disorders and vasovagal syncope are closely related. Indeed, patients with recurrent vasovagal syncope which is tilt inducible, frequently display minor psychiatric conditions and suffer a significant impairment of QoL, even in the absence of co-morbidities. Moreover, the presence of a psychiatric disorder seems to predict an increased risk of syncopal recurrence. Future studies have to establish whether the psychiatric disorders are the cause or the effect of recurrent syncope.
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References |
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