Effectiveness of midodrine treatment in patients with recurrent vasovagal syncope not responding to non-pharmacological treatment (STAND-trial)

Initial treatment of vasovagal syncope (VVS) consists of advising adequate fluid and salt intake, regular exercise, and physical counterpressure manoeuvres. Despite this treatment, up to 30% of patients continue to experience regular episodes of VVS. We investigated whether additional Midodrine treatment is effective in these patients. In our study, patients with at least three syncopal and/or severe pre-syncopal recurrences during non-pharmacological treatment were eligible to receive double-blind cross-over treatment starting either with Midodrine or placebo. Treatment periods lasted for 3 months with a wash-out period of 1 week in-between. At baseline and after each treatment period, we collected data about the recurrence of syncope and pre-syncope, side effects, and quality of life (QoL). Twenty-three patients (17% male, mean age 32) included in the cross-over trial received both Midodrine and placebo treatment. The proportion of patients who experienced syncopal and pre-syncopal recurrences did not differ significantly between Midodrine and placebo treatment (syncope: 48 vs. 65%, P= 0.22; pre-syncope: 74 vs. 78%, P> 0.99). The median number of syncopes and pre-syncopes per 3 months were also not significantly different during Midodrine and placebo treatment (0 vs. 1; P= 0.57; and 6 vs. 8; P= 0.90). The occurrence of side effects was similar during Midodrine and placebo treatment (48 vs. 57%; P= 0.75). Also, QoL did not differ significantly. Our findings indicate that additional Midodrine treatment is less effective in patients with VVS not responding to non-pharmacological treatment than reported as first-line treatmen

Diagnosing vasovagal syncope based on quantitative history-taking: validation of the Calgary Syncope Symptom Score

Aims It can be difficult to distinguish vasovagal syncope, the most common cause of transient loss of consciousness (T-LOC), from other causes of syncope by history taking. The Calgary Syncope Symptom Score (Calgary Score) is a toot developed for this purpose. We studied its performance in a series of patients presenting with T-LOC. Methods and results We calculated the Calgary Score for 380 patients presenting with T-LOC to a number of departments of our university hospital. Diagnoses of vasovagal syncope based on the Calgary Score were then compared with the final diagnosis, obtained after additional testing and 2 years of follow-up. The sensitivity of the Calgary Score was 87% (95% CI: 82-91%), at a specificity of 32% (95% Cl: 24-40%). Most items of the Calgary Score were less discriminative in our study group than in the original population. Incorrectly labelling patients with syncope as vasovagal was most common in patients with psychogenic pseudosyncope (specificity 21%) but also occurred in patients with cardiac syncope (specificity 32%). Conclusion The sensitivity of the Calgary Score was comparable with the one in the original study, but its specificity was much lower, limiting its value in patients presenting with T-LOC in a general hospital settin

Association between psychological complaints and recurrence of vasovagal syncope

Vasovagal syncope (VVS), the most common cause of transient loss of consciousness (T-LOC), is often accompanied by higher levels of psychological distress. We investigated to what extent psychological complaints interact with the effects of non-pharmacological treatment in patients with frequently recurring VVS. Patients with ≥3 episodes of VVS in the 2 years prior to the start of the study openly received non-pharmacological treatment. Before treatment initiation, we determined the level of general psychological complaints by the Symptom Checklist 90-R (SCL-90-R) questionnaire. We regularly evaluated syncopal recurrence during follow-up. We compared the SCL-90-R scores of VVS patients in our study with the corresponding scores of healthy Dutch subjects (reference population). We examined whether patients with more recurrences during follow-up had higher SCL-90-R scores at baseline and whether this association changed when adjusting for other factors associated with recurrence using logistic regression. Total SCL-90-R scores were higher in our cohort of patients with frequent episodes of VVS than in the reference population (142 vs. 118; p < 0.001). During the first 6 months of treatment, 42% of patients experienced syncopal recurrence(s). The SCL-90-R scores of these patients were significantly higher compared with patients without syncopal recurrence in this period (160 vs. 130; p = 0.01). After adjusting for other predictors of recurrence, especially the number of episodes before inclusion, the association between SCL-90-R scores and recurrence remained intact. Levels of general psychological complaints are higher in patients with syncopal recurrence during non-pharmacological treatment of VVS, even after adjusting for previous syncopal episode

Drugs and pacemakers for vasovagal, carotid sinus and situational syncope

Background Neurally mediated reflex syncope is the most common cause of transient loss of consciousness. In patients not responding to nonpharmacological treatment, pharmacological or pacemaker treatment might be considered. Objectives To examine the effects of pharmacological therapy and pacemaker implantation in patients with vasovagal syncope, carotid sinus syncope and situational syncope. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2008), PubMed (1950 until February 2008), EMBASE on OVID (1980 until February 2008) and CINAHL on EBSCOhost (1937 until February 2008). No language restrictions were applied. Selection criteria We included parallel randomized controlled trials and randomized cross-over trials of pharmacological treatment (beta-blockers, fludrocortisone, alpha-adrenergic agonists, selective serotonine reuptake inhibitors, ACE inhibitors, disopyramide, anticholinergic agents or salt tablets) or dual chamber pacemaker treatment. Studies were included if pharmacological or pacemaker treatment was compared with any form of standardised control treatment (standard treatment), placebo treatment, or (other) pharmacological or pacemaker treatment. We did not include non-randomized studies. Data collection and analysis Two reviewers independently assessed the risk of bias. Using a standardised data extraction form, they extracted characteristics and results of the various studies. In a consensus meeting they discussed any disagreements that had occurred during data extraction. If no agreement could be reached, a third reviewer was asked to make a decision. Summary estimates with 95% confidence intervals of treatment effect were calculated using relative risks, rate ratios or weighted means differences depending on the type of outcome reported. Main results We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median sample size of 42. A wide range of control treatments were used with 22 studies using a placebo arm. Blinding of patients and treating physicians was applied in eight studies. Results varied considerably between studies and between types of outcomes. For vasovagal syncope, the occurrence of syncope upon provocational head-up tilt testing was lower upon treatment with beta-blockers, ACE-inhibitors and anticholinergic agents compared to standard treatment. For carotid sinus syncope, the occurrence of syncope upon carotid sinus massage was lower on midodrine treatment compared to placebo treatment in one study. Authors' conclusions There is insufficient evidence to support the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope. Larger studies using patient relevant outcomes are neede

Influence of age and gender on the occurrence and presentation of reflex syncope

BACKGROUND: The clinical history is the cornerstone of diagnosing patients with transient loss of consciousness (TLOC). Reflex syncope is the most common cause of TLOC in patients across all ages. Knowledge of the variation in incidence and clinical features of reflex syncope by age and gender provides important background information to acquire an accurate diagnosis. METHODS: In a cohort of 503 patients presenting with TLOC we established a final diagnosis after systematic evaluation and two years of follow-up. The occurrence of prodromal signs, symptoms, and triggers in patients with reflex syncope was analyzed by both age ( or = 60 years) and gender. RESULTS: Reflex syncope was the most frequently obtained diagnosis (60.2%) in patients of all ages presenting with TLOC. Its occurrence was higher in patients under 40 years (73.4%), than above 60 years of age (45.3%). Pallor (79.9%), dizziness (73.4%), and diaphoresis (63.0%) were the most frequently reported prodromal signs and symptoms. Most triggers and prodromal signs and symptoms were more common in patients under 40 years of age and in women. CONCLUSIONS: Reflex syncope is nearly twice as common in patients under 40 years of age than in patients aged 60 years or above. Typical signs and symptoms of reflex syncope are more common in younger patients and in women. Therefore, age and gender provide important diagnostic information and can help to decide whether additional testing is necessar