Mary Lou Koshman

Risk Factors for Syncope Recurrence After a Positive Tilt-Table⇓ Test in Patients With Syncope

BACKGROUND Recent work with head-up tilt-table testing has suggested that many patients with syncope may have recurrent neurally mediated episodes of bradycardia, hypotension, or both. The purpose of this study was to determine how to identify patients at high risk of a recurrence of neuromediated syncope after a positive isoproterenol/tilt-table test. METHODS AND RESULTS A cohort of 101 drug-free patients in a university hospital outpatient clinic with syncope and a positive isoproterenol/tilt-table test underwent baseline assessment of demographic variables, symptomatic burden, and hemodynamic and clinical responses to tilt testing. The primary outcome measure was the time to the first recurrent syncopal spell. The actuarial probabilities of remaining syncope free after 1 and 2 years were 72% and 60%, respectively. Multivariate proportional hazards analysis demonstrated that the most powerful predictor of a recurrence of syncope was the logarithm of the number of preceding syncopal spells (P<.001). Other predictive variables included the duration of syncopal symptoms, tilt test symptomatic outcome, and trough heart rate. The probability of a recurrence of syncope also varied with the logarithm of the frequency of preceding spells (P=.008). The median frequency of pretest spells was 0.3/month; after the tilt test, the median frequency dropped approximately 90% to 0.03 per month. CONCLUSIONS The risk of a recurrence of syncope after a positive tilt-table test can be predicted with simple pretest and intratest variables.

The relationship between health-related quality of life and frequency of spells in patients with syncope

Chronic syncope has a wide range of symptom burden, and anecdotal data suggest substantial but variable physical and psychosocial morbidity. We hypothesized that health-related quality of life (HRQL) is impaired in syncope patients and the degree of impairment is proportional to syncope frequency. The EuroQol EQ-5D was completed by 136 patients (79 female and 57 male) with mean age 40 (SD = 17) prior to assessment. HRQL was substantially impaired in syncope patients compared to population norms in all five dimensions of health measured by the EQ-5D. In patients with six or more lifetime syncopal spells there was a significant (P < 0.001) negative relationship between the frequency of spells and overall perception of health, which was not evident in those who had a history of less than six lifetime spells. These relationships were maintained after controlling for comorbid conditions.

Effect of beta blockers on the time to first syncope recurrence in patients after a positive isoproterenol tilt table test.

Isoproterenol-headup tilt table testing provides a diagnosis of neuromediated syncope in many patients who faint. The involvement of beta-adrenoceptor stimulation in the provocation of syncope suggests that beta blockers might chronically prevent syncope. To assess this, a cohort of 153 syncope patients (age 39 +/- 20 years) underwent baseline assessment of demographic variables, symptomatic burden, and hemodynamic and clinical responses to tilt testing. Fifty-two patients then received beta blockers, and 101 did not receive drug therapy. The primary outcome was the time to the first recurrent syncopal spell. Actuarial survival analysis was used. Syncope recurred in 17 of 52 patients who received beta blockers and in 28 of 101 patients who were untreated. The actuarial probability of remaining free of syncope was similar in both groups. For example, the probability of remaining free of syncope 12 months following the tilt test was 0.72 in both populations. Thus, treatment with beta blockers may not have a significant effect in preventing syncope recurrence following a positive tilt test.

Effect of Dual-Chamber Pacing With Automatic Rate-Drop Sensing on Recurrent Neurally Mediated Syncope

We tested the hypotheses that a dual-chamber pacemaker that paces when intrinsic rate drops abruptly would reduce the number of syncopal spells and improve the quality of life in patients with highly recurrent neurally mediated syncope. Twelve patients with highly frequent neurally mediated syncope and at least 1 syncopal spell after tilt testing received dual-chamber pacemakers with automatic rate-drop sensing. The pacemakers were implanted 17+/-26 months after tilt testing, and the patients then were followed for 12+/-2 months. We compared the time to the first recurrence of syncope, syncope frequency, and quality of life for the 2 periods between tilt testing and pacemaker implantation, and between implantation and last follow-up. Only 6 of 12 patients fainted after pacemaker insertion. The median time to syncope recurrence before and after pacing was 7 days and 5.3 months, respectively. The geometric mean frequency of faints before and after pacing was 5.0 spells/month (95% confidence interval 2.7 to 9.2) and 0.30 spells/month (95% confidence interval 0.2 to 0.4), p <0.001. After 6 months the mean perception of health on the 100-point EuroQol scale rose from 55 to 82 (p = 0.003), and the general health perception on the SF-36 scale rose from 51 to 72 (p = 0.005). Permanent dual-chamber pacing with automatic rate-drop sensing in patients with highly frequent syncope is associated with a marked reduction in the likelihood of syncope and a marked improvement in quality of life.

Comparison of Patients With Syncope of Unknown Cause Having Negative or Positive Tilt-Table Tests

Many patients without an identified cause of syncope have negative tilt tests. We hypothesized that many of these might be falsely negative tilt tests. If so, then patients with negative and positive tilt tests should have similar pretest clinical characteristics, post-test probabilities of remaining free of syncope, and similar risk factors for syncope recurrence after the tilt-table test. Demographic characteristics and historic features were compared between 153 syncope patients with a positive tilt test, and 74 syncope patients with a negative tilt test and no obvious cause of syncope. Patients with negative and positive tests had similar numbers of syncopal spells, durations of symptoms, frequency of spells, and peak heart rate during tilt test, but patients with negative tests were older (48 +/- 19 vs 39 +/- 20 years). The actuarial probabilities of remaining free of syncope were very similar, with 2-year risks of syncope of 41% and 37% in patients with negative and positive tests, respectively. The regression coefficients of risk factors predicting syncope recurrence were similar for both populations, and the confidence intervals of all regression coefficients decreased when the populations were combined. The outcome of tilt testing did not predict the clinical outcome of patients. Patients with syncope and either negative or positive tilt tests share many pretest and post-test clinical characteristics, suggesting that they may be part of the same population.

Timing of First Recurrence of Syncope Predicts Syncopal Frequency After a Positive Tilt Table Test Result

OBJECTIVES This study sought to determine whether the time to first recurrence of syncope after a positive isoproteremol-tilt table test result accurately predicts the eventual frequency of syncope. BACKGROUND Both patient care and future clinical trials involving patients with neuromediated syncope will require a simple measure that reflects the frequency of syncope. The time from tilt table testing to the first recurrence of syncope might be such a measure. METHODS A cohort of 46 patients with syncope, in a university outpatient clinic, who had at least one syncopal spell after a positive isoproterenol-tilt table test result were followed up for up to 6.5 years (mean [+/-SD] 48 +/- 14 months). The time from tilt table testing to the first recurrence of syncope was correlated. RESULTS A total of 40 of 46 patients had more than one recurrent spell, with a median of eight recurrent spells. The time to the first syncopal spell predicted the frequency of spells with r = -0.79 (p < 0.001), whereas the time to the second spell predicted the frequency with r = -0.92 (p < 0.001). Patients who fainted within 1 month of tilt testing had a geometric mean frequency of 1.35 spells/month (95% confidence limits 0.49, 3.74) compared with patients who fainted 1 to 24 months after testing (0.12 spells/months; 95% confidence limits 0.07 to 0.18, p < 0.001). Finally, the frequency of syncopal spells bore no relation to the duration of follow-up. CONCLUSIONS The time to the first recurrent spell predicts the frequency of syncopal spells after a positive tilt table test result, and the instantaneous risk of syncope is constant.

Isoproterenol Tilt-Table Testing in Patients With Syncope and Structural Heart Disease *

We studied 55 patients with syncope and structural heart disease using both tilt-table testing and electrophysiologic studies. Although sustained ventricular tachycardia was found in 21 of 55 patients (38%), and neuromediated syncope in 18 of 51 patients (35%), only 16% of patients with ventricular tachycardia had a positive tilt-table test.

Can patients with neuromediated syncope safely drive motor vehicles

This study is a retrospective analysis of patients in a community-based university clinic, and only patients with a positive isoproterenol tilt-table test result were included. There are numerous tilt-test protocols in use in various centers, and their comparative sensitivities, specificities, and cross-validities are unknown. Indeed, our protocol may be less specific than prolonged drug-free head-up tilt in younger patients. Thus, the estimates in this study may not be generalizable. Finally, the estimates were based on patients recollections of accidents, and it is possible that the number of accidents is underreported. Nonetheless, the risk of syncope causing harm appears to be so low that most patients may be allowed to drive.

Antiarrhythmic activity of quinine in humans

BACKGROUND Quinine is the diastereomer of quinidine. In dogs, it has similar effects on conduction time but does not prolong epicardial repolarization time or ventricular refractoriness. It has antiarrhythmic effects in both cats and dogs. We assessed the antiarrhythmic potential of quinine in suppressing ventricular arrhythmias in humans. METHODS AND RESULTS Patients underwent open-label, dose-ranging trials of quinine with daily doses of 600, 1200, and 1800 mg in a twice-daily dosing regimen. In 17 patients with frequent spontaneous ventricular ectopy, oral quinine suppressed arrhythmia in 11 of 12 patients who finished the study and was not tolerated by 4 patients, and 1 patient withdrew from the study. The mean effective daily dosage was 927 mg, the mean effective trough serum level was 11 mumol/L (range, 4 to 17 mumol/L), and the half-life was 20 +/- 7 hours. In a second open-label, dose-ranging trial in 10 patients with inducible ventricular tachycardia and reduced left ventricular systolic function (left ventricular ejection fraction, 35 +/- 16%), quinine suppressed inducibility of ventricular tachycardia in 3 of 10 patients. At a basic pacing cycle length of 500 milliseconds, ventricular effective refractory period was prolonged (279 +/- 21 versus 247 +/- 10 milliseconds, quinine versus drug free, P = .003). In the remaining patients, ventricular tachycardia cycle length was prolonged (373 +/- 48 versus 253 +/- 30 milliseconds, quinine versus drug free, P < .001). The corrected QT interval was not prolonged. CONCLUSIONS Quinine is an effective and convenient antiarrhythmic drug for the suppression of ventricular arrhythmias in humans.

Usefulness of clinical factors in predicting outcomes of passive tilt tests in patients with syncope

Pretest patient selection affects the outcome of many diagnostic tests; this may be true for tilt-table tests. We assessed the impact of patient age, sex, and symptom burden on the outcome of passive tilt tests. Two hundred one patients with idiopathic syncope (87 men, aged 45 +/- 20 years, median 5 fainting spells each) underwent passive, drug-free tilt tests for 45 minutes. Positive tests were defined as those ending in clinically reminiscent presyncope or syncope. Seventy-eight patients (39%) had a positive tilt test. Patients had a wide range of symptom burden, having a median 5 syncopal spells (interquartile range [IQR] 2.5 to 17.5) over a median 52.5 months (IQR 12 to 180) with a median frequency of 0.17 spells/month (IQR 0.042 to 0.67). None of these measures of symptom burden predicted tilt-test outcome (p = 0.33 to 0.46). In contrast, the age of the patient strongly predicted tilt-test outcome. The likelihood of a positive test was 75% in 36 patients < 25 years old and 31% in 165 patients > or = 25 years of age (p < 0.0001, chi-square for 2 x 5 table). Younger patients also fainted more quickly: patients < 25 years old fainted within 22 minutes of tilt and reached a clearly asymptotic value, whereas the likelihood of a positive tilt in patients > or = 25 years old increased linearly with time, and did not reach an asymptote. Measures of symptom burden do not predict test outcome, and younger patients are more likely to faint during passive tilt testing.