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

Ritme cardíac; Síncope reflex neurològic; Prova de la taula d’inclinacióRitmo cardíaco; Síncope reflejo neuromediado; Prueba de la mesa inclinadaCardiac pacing; Neuro-mediated reflex syncope; Tilt-Table testBackground: 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.All study-related costs are being directly supported by the sponsor of the study (BIOTRONIK SE & Co. KG, Berlin, Germany). No further funding is provided

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study

Duration; Holding area; Insertable cardiac monitorDuració; Sala d'espera; Monitor cardíac inseribleDuración; Sala de espera; Monitor cardíaco insertableBACKGROUND: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. METHODS: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. RESULTS: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. CONCLUSIONS: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.This study was sponsored by Medtronic, Inc

Differences in the yield of the implantable loop recorder between secondary and tertiary centers

Background: The implantable loop recorder (ILR) is a useful tool for diagnosis of syncope or palpitations. Its easy use and safety have extended its use to secondary hospitals (those without an Electrophysiology Lab). The aim of the study was to compare results between secondary and tertiary hospitals. Methods: National prospective and multicenter registry of patients with an ILR inserted for clinical reasons. Data were collected in an online database. The follow-up ended when the first diagnostic clinical event occurred, or 1 year after implantation. Data were analyzed according to the center of reference; hospitals with Electrophysiology Lab were considered Tertiary Hospi­tals, while those hospitals without a lab were considered Secondary Hospitals. Results: Seven hundred and forty-three patients (413 [55.6%] men; 65 ± 16 year-old): 655 (88.2%) from Tertiary Centers (TC) and 88 (11.8%) from Secondary Centers (SC). No differences in clinical characteristics between both groups were found. The electrophysi­ologic study and the tilt table test were conducted more frequently in Tertiary Centers. Fol­low-up was conducted for 680 (91.5%) patients: 91% in TC and 94% in SC. There was a higher rate of final diagnosis among SC patients (55.4% vs. 30.8%; p < 0.001). Tertiary Hospital patients showed a trend towards a higher rate of neurally mediated events (20% vs. 4%), while bradyarrhythmias were more frequent in SC (74% vs. 60%; p = 0.055). The rate of deaths and adverse events was similar in both populations. Conclusions: Patients with an ILR in SC and TC have differences in terms of the use of complementary tests, but not in clinical characteristics. There was a higher rate of diagnosis in Secondary Hospital patients.

Impact of dual-chamber pacing with closed loop stimulation on quality of life in patients with recurrent reflex vasovagal syncope: results of the SPAIN study

[Aims]: Reflex vasovagal syncope (VVS) is the most common cause of syncope and patients with recurrent episodes may severely impair quality of life (QoL). This pre-specified analysis evaluated whether the clinically significant reduction in syncope burden demonstrated by dual-chamber pacing with closed loop stimulation (DDD-CLS) reported in the SPAIN trial translates into improved QoL.[Methods and results]: Patients aged ≥40 years with ≥5 VVS episodes and cardioinhibitory response induced by head-up tilt testing were included. Patients were randomized 1:1 to active DDD-CLS pacing algorithm for 12 months followed by sham DDI mode for the remaining 12 months (Group A) or vice versa (Group B). QoL was assessed using the Short Form-36 (SF-36) health survey, Physical Component Score (PCS), and Mental Component Score (MCS) before randomization (baseline) and at 12- and 24-month follow-up. Fifty-four patients were enrolled from 11 participating centres. No significant carryover effect was detected for any variable, and the only period effect was observed in the vitality subdomain (P = 0.033). Mean SF-36 scores were higher in the DDD-CLS group vs. the DDI group for the eight subdomains and significantly different in physical role, bodily pain, and vitality (P < 0.05). The analysis of component summary scores indicated that DDD-CLS benefited both mental and physical components with significant differences in PCS when compared with the DDI group.[Conclusion]: Dual-chamber pacing with closed loop stimulation determined a significant and clinically relevant improvement in QoL across both mental and physical components in patients with recurrent VVS.This work was supported by the Research Agency of the Spanish Society of Cardiology. The trial was designed, sponsored, and conducted by the syncope working group and the Research Agency of the Spanish Society of Cardiology. The Research Agency of the Spanish Society of Cardiology received an unrestricted research grant from BIOTRONIK Spain. Medical Writing services were supported by BIOTRONIK SE & Co. KG (Berlin, Germany)

Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope: The SPAIN Study.

Pacing in vasovagal syncope remains controversial. The authors evaluated dual-chamber pacing with closed loop stimulation (DDD-CLS) in patients with cardioinhibitory vasovagal syncope. This randomized, double-blind, controlled study included Canadian and Spanish patients age ≥40 years, with high burden syncope (≥5 episodes, ≥2 episodes in the past year), and a cardioinhibitory head-up tilt test (bradycardia 3 s). Patients were randomized to either DDD-CLS pacing for 12 months followed by sham DDI mode pacing at 30 pulses/min for 12 months (group A), or sham DDI mode for 12 months followed by DDD-CLS pacing for 12 months (group B). Patients in both arms crossed-over after 12 months of follow-up or when a maximum of 3 syncopal episodes occurred within 1 month. A total of 46 patients completed the protocol; 22 were men (47.8%), and mean age was 56.30 ± 10.63 years. The mean number of previous syncopal episodes was 12 (range 9 to 20). The proportion of patients with ≥50% reduction in the number of syncopal episodes was 72% (95% confidence interval [CI]: 47% to 90%) with DDD-CLS compared with 28% (95% CI: 9.7% to 53.5%) with sham DDI mode (p = 0.017). A total of 4 patients (8.7%) had events during DDD-CLS and 21 (45.7%) during sham DDI (hazard ratio: 6.7; 95% CI: 2.3 to 19.8). Kaplan-Meier curve was significantly different between groups in time to first syncope: 29.2 months (95% CI: 15.3 to 29.2 months) versus 9.3 months (95% CI: 6.21 months, NA; p  DDD-CLS pacing significantly reduced syncope burden and time to first recurrence by 7-fold, prolonging time to first syncope recurrence in patients age ≥40 years with head-up tilt test-induced vasovagal syncope compared with sham pacing. (Closed Loop Stimulation for Neuromediated Syncope [SPAIN Study]; NCT01621464)

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study

Abstract Background Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. Methods The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. Results A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55–61). Patient preparation and patient education accounted for 10 min (IQR: 5–20) and 10 min (IQR: 8–15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0–2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. Conclusions The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. Trial registration ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015