Background— Previous studies that assessed the effects of β-blockers in preventing vasovagal syncope provided mixed results. Our goal was to determine whether treatment with metoprolol reduces the risk of syncope in patients with vasovagal syncope. Methods and Results— The multicenter Prevention of Syncope Trial (POST) was a randomized, placebo-controlled, double-blind, trial designed to assess the effects of metoprolol in vasovagal syncope over a 1-year treatment period. Two prespecified analyses included the relationships of age and initial tilt-test results to any benefit from metoprolol. All patients had >2 syncopal spells and a positive tilt test. Randomization was stratified according to ages <42 and ≥42 years. Patients received either metoprolol or matching placebo at highest-tolerated doses from 25 to 200 mg daily. The main outcome measure was the first recurrence of syncope. A total of 208 patients (mean age 42±18 years) with a median of 9 syncopal spells over a median of 11 years were randomized, 108 to receive metoprolol and 100 to the placebo group. There were 75 patients with ≥1 recurrence of syncope. The likelihood of recurrent syncope was not significantly different between groups. Neither the age of the patient nor the need for isoproterenol to produce a positive tilt test predicted subsequent significant benefit from metoprolol. Conclusions— Metoprolol was not effective in preventing vasovagal syncope in the study population.

Aims Our goal was to develop historical criteria for the diagnosis of vasovagal syncope. Methods and results We administered a 118-item historical questionnaire to 418 patients with syncope and no apparent structural heart disease. The prevalence of each item was compared between patients with positive tilt tests and those with syncope of other, known causes. The contributions of symptoms to diagnoses were estimated with logistic regression, point scores were developed, and the scores were tested using receiver operator characteristic analysis. The accuracy of the decision rule was assessed with bootstrapping. Data sets were complete for all subjects. The causes of syncope were known in 323 patients and included tilt-positive vasovagal syncope (235 patients) and other diagnoses such as complete heart block and supraventricular tachycardias (88 patients). The point score correctly classified 90% of patients, diagnosing vasovagal syncope with 89% sensitivity and 91% specificity. The decision rule suggested that 68% of an additional 95 patients with syncope of unknown cause and a negative tilt test have vasovagal syncope. Conclusion A simple point score of historical features distinguishes vasovagal syncope from syncope of other causes with very high sensitivity and specificity.

Aims To determine the effect of family history on the likelihood of vasovagal syncope. Methods and results Sixty-two medical students and 228 first-degree relatives were studied. Vasovagal syncope was ascertained with the Calgary syncope symptom score. The effects of the sex of the subject and parental syncope history on the likelihood of offspring fainting were described using Kaplan–Meier estimates and analysed using proportional hazards regression. The prevalence of vasovagal syncope was 32% and the median age of first faint in those who fainted was 14 years. More females than males fainted [42 vs. 31%; P=0.02; hazard ratio (HR) 1.34 (95% CI 1.07–1.68)]. An individual with two fainting parents was more likely to faint than one with no fainting parents [P<0.0001; HR 3.4 (95% CI 1.7–7.03)]. In the proportional hazards model, offspring of either sex whose mother faints are more likely to faint than those whose mother does not faint [HR 2.86 (95% CI 1.54–5.31)]. Having a father who faints significantly increases the risk of syncope in sons [HR 4.12 (95%CI 1.39–12.31)], but not in daughters [HR 1.18 (95% CI 0.56–3.34)]. Conclusion Family history and sex of subject are important predictors of vasovagal syncope in offspring.

Background —Patients with resuscitated ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) benefit from implantable cardioverter-defibrillators (ICDs) compared with medical therapy. We hypothesized that the patients who benefit most from an ICD are those at greatest risk of death. Methods and Results —In the Canadian Implantable Defibrillator Study (CIDS), 659 patients with resuscitated ventricular tachyarrhythmias were randomly assigned to receive an ICD or amiodarone and were then followed for a mean of 3 years. There were 98 and 83 deaths in the amiodarone and ICD groups, respectively. We used multivariate Cox analysis to assess the impact of baseline parameters on the mortality in the amiodarone group. Reduced left ventricular ejection fraction, advanced age, and poor NYHA status identified high-risk patients ( P =0.0001 to 0.0009). Quartiles of risk were constructed, and the mortality reduction associated with ICD treatment in each quartile was assessed. There was a significant interaction between risk quartile and the ICD treatment effect ( P =0.011). In the highest risk quartile, there was a 50% relative risk reduction (95% CI 21% to 68%) of death in the ICD group, whereas in the 3 lower quartiles, there was no benefit. Patients who are most likely to benefit from an ICD can be identified with a simple risk score (≥2 of the following factors: age ≥70 years, left ventricular ejection fraction ≤35%, and NYHA class III or IV). Thirteen of 15 deaths that were prevented by the ICD occurred in patients with ≥2 risk factors. Conclusions —In CIDS, patients at highest risk of death benefited most from ICD therapy. These can be identified easily on the basis of age, poor ventricular function, and poor functional status.