Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole.

AIM: The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial. METHODS AND RESULTS: We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%). CONCLUSION: In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing. STUDY REGISTRATION: ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546.

The yield of long-term electrocardiographic recordings in refractory focal epilepsy.

OBJECTIVE: To determine the incidence of clinically relevant arrhythmias in refractory focal epilepsy and to assess the potential of postictal arrhythmias as risk markers for sudden unexpected death in epilepsy (SUDEP). METHODS: We recruited people with refractory focal epilepsy without signs of ictal asystole and who had at least one focal seizure per month and implanted a loop recorder with 2-year follow-up. The devices automatically record arrhythmias. Subjects and caregivers were instructed to make additional peri-ictal recordings. Clinically relevant arrhythmias were defined as asystole ≥ 6 seconds; atrial fibrillation < 55 beats per minute (bpm), or > 200 bpm and duration > 30 seconds; persistent sinus bradycardia < 40 bpm while awake; and second- or third-degree atrioventricular block and ventricular tachycardia/fibrillation. We performed 12-lead electrocardiography (ECG) and tilt table testing to identify non-seizure-related causes of asystole. RESULTS: We included 49 people and accumulated 1060 months of monitoring. A total of 16 474 seizures were reported, of which 4679 were captured on ECG. No clinically relevant arrhythmias were identified. Three people had a total of 18 short-lasting (<6 seconds) periods of asystole, resulting in an incidence of 2.91 events per 1000 patient-months. None of these coincided with a reported seizure; one was explained by micturition syncope. Other non-clinically relevant arrhythmias included paroxysmal atrial fibrillation (n = 2), supraventricular tachycardia (n = 1), and sinus tachycardia with a right bundle branch block configuration (n = 1). SIGNIFICANCE: We found no clinically relevant arrhythmias in people with refractory focal epilepsy during long-term follow-up. The absence of postictal arrhythmias does not support the use of loop recorders in people at high SUDEP risk.

Benefit of dual-chamber pacing with Closed Loop Stimulation in tilt-induced cardio-inhibitory reflex syncope (BIOSync trial): study protocol for a randomized controlled trial.

BACKGROUND: The efficacy of dual-chamber cardiac pacing in neuro-mediated reflex syncope with a cardio-inhibitory response to the Tilt-Table test (TT) has not been definitively assessed so far. The lack of reproducibility of results from previous studies may be partially explained by discrepancies in subject selection and some weaknesses in design and methods. The European Society of Cardiology (ESC) has set a class IIb indication to pacemaker implantation in this population recommending further research. METHODS/DESIGN: The BIOSync study is a multicenter, patient- and outcome-assessor-blind, randomized, parallel-arm, placebo-controlled trial with the objective of assessing the clinical benefit of cardiac pacing in patients with frequently recurrent reflex syncope, suspected (but not proven) to be triggered by asystolic pauses as showing a VASIS 2B response to the TT (>3-s pause regardless of blood pressure drop). The primary and secondary endpoints are time to first post-implantation recurrence of syncope or the combination of pre-syncope or syncope, respectively. One hundred and twenty-eight consenting patients will be 1:1 randomized to dual-chamber cardiac pacing 'on' or 'off' after pacemaker implantation, and followed up until the first adjudicated primary endpoint event for a maximum of 2 years. The so-called Closed Loop Stimulation function on top of dual-chamber pacing is the pacing mode selected in the study active arm. Participating patients are asked to self-report syncopal symptoms at least every 3 months with self-administered questionnaires addressed to an independent Adjudication Committee. Patients and members of the Adjudicating Committee are blinded to randomization. The study is designed to detect a 40% relative reduction in the 2-year incidence of syncopal recurrences with 80% statistical power. DISCUSSION: The BIOSync study is designed to definitively assess the benefit of pacing against placebo in reflex syncope patients with a cardio-inhibitory response to the TT. The study will also provide important information on the efficiency of the TT in appropriately selecting reflex syncope patients for cardiac pacing. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02324920 (27 October 2016, date last accessed).

Daily, weekly, monthly, and seasonal patterns in the occurrence of vasovagal syncope in an older population.

AIMS: The aim of this study was to assess the frequency of vasovagal episodes over the day, week, month, and seasons. METHODS AND RESULTS: This study was part of the multi-centre International Study on Syncope of Uncertain Etiology-2 (ISSUE-2), which included patients, aged 30 years or older, with severe neurally mediated syncope between June 2002 and July 2004. The Implantable Loop Recorder (ILR) was used to document the syncope-related ECG periods. For this study patients with recorded syncopal episodes after ILR-implantation was selected. At least one episode was documented in 106 patients. A higher number of episodes were documented during the morning than during other periods of the day (P < 0.01). There was no difference between various days of the week, episodes per month, or between seasons. There was no difference between age and gender groups, although elderly patients seemed to be responsible for the peak in the morning. CONCLUSION: A circadian pattern in the frequency of vasovagal episodes exists, with a peak in the morning. This is in accordance with reports of diurnal variations in blood pressure and heart rate. No difference was observed in syncope distribution between days of the week, months, or seasons.

Reproducibility of nitrate-stimulated tilt testing in patients with suspected vasovagal syncope and a healthy control group.

OBJECTIVE: Nitrate-stimulated tilt testing may be used to diagnose vasovagal syncope or to guide therapy. To date, the reproducibility of the test in patients with clinically suspected vasovagal syncope and healthy controls is undetermined. A high reproducibility is a prerequisite for correct interpretation of the test result. This study investigates the reproducibility of a nitrate-stimulated tilt test in patients with clinically suspected vasovagal syncope and a healthy control group. METHODS AND RESULTS: We studied 43 patients (24 women, 19 men) with a typical history of vasovagal syncope and 18 healthy controls (3 women, 15 men). We used a combined tilt protocol with a 30-minute passive and 15-minute nitrate-stimulated phase. The second tilt test was performed 16 +/- 12 days after the first. In both patients and controls, overall positive tilt responses were reproduced in the second test in 100%. In contrast to this, the reproducibility of an overall negative test was 50% in patients but 93% in controls. Overall hemodynamic responses to tilt were reproducible in 80%. CONCLUSION: Nitrate-stimulated tilt testing in both patients with suspected vasovagal syncope and controls has an excellent reproducibility of positive results but a moderate reproducibility of negative results. Importantly, these results are still valid at a repeat interval of 2 weeks and longer. These data suggest that in patients with suspected vasovagal syncope, a nitrate-stimulated tilt test may provide a suitable tool to evaluate the efficacy of a therapeutic approach.

Nitrate-stimulated tilt testing enhances the predictive value of the tilt test on the risk of recurrence in patients with suspected vasovagal syncope.

OBJECTIVE: Nitrate-stimulated tilt testing may be used to diagnose vasovagal syncope and to guide therapy. However, to date the predictive value of the test is undetermined. This study analyses the risk of recurrence of syncope in vasovagal patients on the basis of a nitrate-stimulated tilt result and other clinical factors. METHODS AND RESULTS: We used a combined passive and nitrate-stimulated tilt protocol. One year after the test a questionnaire, asking about recurrence of syncope and other demographic factors, was sent to 131 patients. Passive tilting was found not to be a useful predictor; recurrence rates after a positive and negative test were 26% and 30%, respectively, and non-significant. With the addition of sublingual nitrates the test became a significant predictor; recurrence rates were 34 (34%) with a positive and 4 (13%) with a negative tilt test (p = 0.031). Univariate analysis of the clinical factors revealed that gender and pre-test symptomatology were significant predictors of recurrence. Multivariate analysis revealed no additional relationships. CONCLUSION: In patients with suspected vasovagal syncope, a positive tilt test with sublingual nitrates together with the clinical factors gender and symptomatology, are predictors for recurrence of syncope during one year of follow-up. Without specific therapy the prognosis of vasovagal syncope is good.

Diagnostic value of nitrate stimulated tilt testing without preceding passive tilt in patients with suspected vasovagal syncope and a healthy control group.

BACKGROUND: The contribution of the passive tilt phase, in a combined nitrate stimulated tilt protocol may be low yielding. In order to develop a shortened, and thus easier to perform test, we investigated the optimal duration of a nitrate tilt protocol without a preceding passive phase. METHODS: Thirty-eight consecutive patients (18F/20M; mean age 46 +/- 16) with clinically suspected vasovagal syncope and 31 control subjects (15F/16M; mean age 40 +/- 18) were tested. The subjects were tilted to 70 degrees for a maximum period of 30 minutes, and sublingual nitroglycerin 0.4 mg spray was administrated directly after attaining erect posture. Receiver operator characteristics (ROC) analysis was done to determine the optimal test duration. RESULTS: In the patient group 31 (82%) and in controls 5 (16%) had a positive test. Sensitivity, specificity, and accuracy at test end were 82, 84, and 83%, respectively. ROC analysis revealed that a maximum accuracy of 83% was attained at 14 minutes, with a sensitivity and specificity of 79 and 87%, respectively. CONCLUSION: Nitrate stimulated tilt testing, without a preceding passive tilt phase, and limited to a test duration of 15 minutes, provides an accurate, sensitive, and specific method to provoke vasovagal reactions in subjects with clinically suspected vasovagal syncope.