Jean Claude Deharo

Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole Third International Study on Syncope of Uncertain Etiology (ISSUE-3): A Randomized Trial

Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope.nnMethods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P =0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient.nnConclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope.nnClinical Trial Registration— URL: . Unique identifier: [NCT00359203][1].nn# Clinical Perspective {#article-title-19}nn [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00359203&atom=%2Fcirculationaha%2F125%2F21%2F2566.atom

Benefit of Pacemaker Therapy in Patients With Presumed Neurally Mediated Syncope and Documented Asystole Is Greater When Tilt Test Is Negative An Analysis From the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)

Background—In the Third International Study on Syncope of Uncertain Etiology (ISSUE-3), cardiac pacing was effective in reducing recurrence of syncope in patients with presumed neurally mediated syncope (NMS) and documented asystole but syncope still recurred in 25% of them at 2 years. We have investigated the role of tilt testing (TT) in predicting recurrences. Methods and Results—In 136 patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An asystolic response predicted a similar asystolic form during implantable loop recorder monitoring, with a positive predictive value of 86%. The corresponding values were 48% in patients with non–asystolic TT and 58% in patients with negative TT (P=0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT–) with asystolic neurally mediated syncope received a pacemaker. Syncope recurred in 8 TT+ and in 1 TT– patients. At 21 months, the estimated product-limit syncope recurrence rates were 55% and 5%, respectively (P=0.004). The TT+ recurrence rate was similar to that seen in 45 untreated patients (control group), which was 64% (P=0.75). The recurrence rate was similar between 14 patients with asystolic and 12 with non–asystolic responses during TT (P=0.53). Conclusions—Cardiac pacing was effective in neurally mediated syncope patients with documented asystolic episodes in whom TT was negative; conversely, there was insufficient evidence of efficacy from this data set in patients with a positive TT even when spontaneous asystole was documented. Present observations are unexpected and need to be confirmed by other studies. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463358.

2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction

Fred M. Kusumoto, MD, FHRS, FACC, Chair, Mark H. Schoenfeld, MD, FHRS, FACC, FAHA, CCDS, Vice-Chair, Bruce L. Wilkoff, MD, FHRS, CCDS, Vice-Chair, Charles I. Berul, MD, FHRS, Ulrika M. Birgersdotter-Green, MD, FHRS, Roger Carrillo, MD, MBA, FHRS, Yong-Mei Cha, MD, Jude Clancy, MD, Jean-Claude Deharo, MD, FESC, Kenneth A. Ellenbogen, MD, FHRS, Derek Exner, MD, MPH, FHRS, Ayman A. Hussein, MD, FACC, Charles Kennergren, MD, PhD, FETCS, FHRS, Andrew Krahn, MD, FRCPC, FHRS, Richard Lee, MD, MBA, Charles J. Love, MD, CCDS, FHRS, FACC, FAHA, Ruth A. Madden, MPH, RN, Hector Alfredo Mazzetti, MD, JoEllyn Carol Moore, MD, FACC, Jeffrey Parsonnet, MD, Kristen K. Patton, MD, Marc A. Rozner, PhD, MD, CCDS, Kimberly A. Selzman, MD, MPH, FHRS, FACC, Morio Shoda, MD, PhD, Komandoor Srivathsan, MD, Neil F. Strathmore, MBBS, FHRS, Charles D. Swerdlow, MD, FHRS, Christine Tompkins, MD, Oussama Wazni, MD, MBA

Impact of extending device longevity on the long-term costs of implantable cardioverter-defibrillator therapy: a modelling study with a 15-year time horizon

AIMSnTo determine the long-term costs of extending device longevity in four patient populations requiring a single-chamber implantable cardioverter-defibrillator (ICD) or requiring cardiac resynchronization therapy with defibrillation (CRT-D) device over a 15-year time window.nnnMETHODS AND RESULTSnWe considered patient populations with an accepted indication for a single-chamber ICD for prevention of sudden cardiac death in the context of preserved (Population A) or impaired (Population B) left ventricular function; or with indication for a CRT-D device in the context of heart failure in New York Heart Association class II (Population C) or III (Population D). Expected patient survival and a cost analysis, including the cost of complications, was undertaken from a hospital perspective. Extended device longevity of 5 vs. 9 years for ICDs (Populations A and B); 4 vs. 7 years for CRT-Ds (Populations C and D) were considered. Over a 15-year time horizon, total, yearly, and per diem savings, per patient, from extending ICD longevity to 9 years were €10 926.91, €728.46, and €1.99 for Population A, and €7661.32, €510.75, and €1.40 for Population B. Total, yearly, and per diem savings from extending CRT-D longevity to 7 years were €13 630.38, €908.69, and €2.49 for Population C, and €10 968.29, €731.22, and €2.00 for Population D. Avoidance of a generator replacement amounted up to 46.6-62.5% of the saving.nnnCONCLUSIONnExtending device longevity has an important effect on the long-term cost of device therapy, both for ICD and CRT-D. This has important implications for device choice.

The European Lead Extraction ConTRolled (ELECTRa) study: a European Heart Rhythm Association (EHRA) Registry of Transvenous Lead Extraction Outcomes

AimsnThe European Lead Extraction ConTRolled Registry (ELECTRa), is a prospective registry of consecutive transvenous lead extraction (TLE) procedures conducted by the European Heart Rhythm Association (EHRA) in order to identify the safety and efficacy of the current practice of TLE.nnnMethods and resultsnEuropean centres performing TLE, invited by the organizing committee on behalf of EHRA, prospectively recruited all consecutive patients undergoing TLE at their institution. The primary endpoint was TLE safety defined by pre-discharge major procedure-related complications including death. Secondary endpoints included clinical and radiological success and overall complication rates. Outcomes were compared between Low Volume (LoV) vs. High Volume (HiV) centers (LoVu2009<u200930 and HiVu2009≥u200930 procedures/year). A total of 3555 consecutive patients (pts) of whom 3510 underwent TLE at 73 centres in 19 European countries were enrolled between November 2012 and May 2014. The primary endpoint of in-hospital procedure-related major complication rate was 1.7% [95% CI 1.3-2.1%] (58/3510 pts) including a mortality of 0.5% [95% CI 0.3-0.8%] (17/3510 pts). Approximately two-thirds (37/58) of these complications occurred during the procedure and one-third (21/58) in the post-operative period. The most common procedure related complications were those requiring pericardiocentesis or chest tube and/or surgical repair (1.4% [95% CI 1.0-1.8%]). Complete clinical and radiological success rates were 96.7% [95% CI 96.1-97.3%] and 95.7% [95% CI 95.2-96.2%], respectively. The all cause in-hospital major complications and deaths were significantly lower in HiV centres vs. LoV centres (2.4% [95% CI 1.9-3.0%] vs. 4.1% [95% CI 2.7-6.0%], Pu2009=u20090.0146; and 1.2% [95% CI 0.8-1.6%] vs. 2.5% [95% CI 1.5-4.1%] Pu2009=u20090.0088), although those related to the procedure did not reach statistical significance. Radiological and clinical successes were more frequent in HiV vs. LoV centres.nnnConclusionnThe ELECTRa study is the largest prospective registry on TLE and confirmed the safety and efficacy of the current practice of TLE. Lead extraction was associated with a higher success rate with lower all cause complication and mortality rates in high volume compared with low volume centres.

ELECTRa (European Lead Extraction ConTRolled) Registry—Shedding light on transvenous lead extraction real-world practice in Europe

With the growing recognition of the clinical need and wider indications for cardiovascular implantable electronic devices (CIED), the number of implant procedures has increased considerably. Consequently, the rate of complications related to these devices has also increased. Transvenous lead extraction (TLE) is the gold standard in the treatment of CIED-related infective complications and is often required in the management of lead malfunction. An increasing number of centers currently perform TLE procedures. The ELECTRa (European Lead Extraction ConTRolled) Registry is the first large prospective multicenter registry of consecutive patients undergoing TLE in Europe, conducted by the European Heart Rhythm Association (EHRA) and managed by the European Society of Cardiology (ESC) EURObservational Research Department. The primary objective of the registry is to evaluate the acute and long-term safety of TLE; the secondary objective is to describe the characteristics of the patients, the leads, the indications for TLE, and the tools and techniques currently used for TLE. About 100 centers will be enrolled on a voluntary basis from European countries; they are anonymous and stratified on the basis of their volume of activity into high-volume centers (>u200930xa0patients/year) and low-volume centers: (≤u200930xa0patients/year). Each participating center will have to enroll and follow up for 1xa0year consecutively assessed patients undergoing TLE from November 2012 to January 2014. The target is to achieve a sample size of at least 3,500 patients for statistical analysis. Data will be collected using a Web-based system and will be audited at randomly selected centers. The official start was on 6 November. Eighty-nine centers have joined so far, 65 centers are currently active, those who have already obtained the approval of their own ethics committee, and 1,099 patients were enrolled at the end of June 2013. The independence of the registry, the consecutiveness of the patient enrolment, and the monitoring of the study are characteristics of this registry that will contribute to the scientific validity of the objectives to be achieved.ZusammenfassungDank der zunehmenden Wahrnehmung eines klinischen Bedürfnisses und breiterer Indikationen, ist die Anzahl an CIED-Implantationen stark angestiegen – und somit auch die Anzahl an Komplikationen, die von diesen Geräten ausgehen. Die Transvenöse Elektrodenextraktion (Transvenous Lead Extraction (TLE)) ist die bewährte Methode für die Behandlung von CIED-bezogenen infektiösen Komplikationen und wird oft im Management von Elektrodenfehlfunktionen gebraucht. Immer mehr Herzzentren bieten nun TLE an.Das ELECTRa (European Lead Extraction ConTRolled)-Register ist das erste großflächige, multizentrische Register für TLE-Patienten in Europa. Es wird von der European Heart Rhythm Association (EHRA) realisiert und von der ESC EURObservational Research Department verwaltet.Primärziel des Registers ist es, die kurz- und langfristige Sicherheit von TLE zu erfassen; sekundär dazu sollen die Patienteneigenschaften, die Elektroden, die Indikationen für TLE, und die Instrumente und Techniken, die aktuell für das Verfahren verwendet werden, beschrieben und festgehalten werden.Rund 100 Herzzentren in europäischen Ländern werden freiwillig teilnehmen; diese werden anonym eingetragen und stratifiziert nach Aktivitätsvolumen in Hochvolumen- (>u200930 Patienten/Jahr) und Niedrigvolumenzentren (≤u200930 Patienten/Jahr).Jedes teilnehmende Zentrum muss alle konsekutiv bewertete TLE-Patienten, die zwischen November 2012 und Januar 2014 einer TLE unterzogen wurden bzw. werden, eintragen und 1 Jahr lang nach der OP beobachten. Ziel dabei ist es, einen ausreichend großen Probenumfang für die statistische Analyse zu erreichen (mindestens 3.500 Patienten). Sämtliche Daten werden mit einem webbasierten System gesammelt und in zufällig ausgewählten Zentren überprüft.Offizieller Startschuss war am 6. November 2012. Seitdem haben sich 89 Zentren gemeldet, davon sind 65 – diejenigen, die bereits die Zustimmung des eigenen Ethikkomitees haben – jetzt aktiv. Das Ergebnis: bis Ende Juni 2013 waren bereits 1.099 Patienten eingetragen.Die Unabhängigkeit des Registers, die konsekutive Patienteneintragung und die Überwachung der Studie werden gemeinsam zur wissenschaftlichen Validität der erreichten Zielen beitragen.

Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole

Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope.nnMethods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P =0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient.nnConclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope.nnClinical Trial Registration— URL: . Unique identifier: [NCT00359203][1].nn# Clinical Perspective {#article-title-19}nn [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00359203&atom=%2Fcirculationaha%2F125%2F21%2F2566.atom

Oral anticoagulant therapy for stroke prevention in patients with atrial fibrillation undergoing ablation: results from the First European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA)

The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey of patients undergoing atrial fibrillation (AF) ablation, conducted to collect patient-based data on current clinical practices in AF ablation in context of the latest AF Guidelines and contemporary oral anticoagulant therapies. The EP Research Network Centres were asked to prospectively enrol consecutive patients during a 6-week period (September/October 2014). Data were collected via the web-based case report form. We present the results pertinent to the use of antithrombotic therapies. Thirteen countries prospectively enrolled 455 eligible consecutive patients [mean age 59 ± 10.8 years, 131 (28.8%) females]. The mean CHA2DS2-VASc score was 1.12 ± 1.06 [137 patients (30.1%) had a score of ≥2]. Before ablation, 443 patients (97.4%) were on anticoagulant therapy [143 (31.4%) on non-vitamin K antagonist oral anticoagulants (NOACs) and 264 (58.0%) on vitamin K antagonists (VKAs)]. Of the latter, 79.7% underwent ablation without VKA interruption, whilst a variety of strategies were used in patients taking NOAC. After ablation, most patients (89.3%) continued the same anticoagulant as before, and 2 (0.4%) were not prescribed any anticoagulation. At discharge, 280 patients (62.2%) were advised oral anticoagulation for a limited period of mean 3.8 ± 2.2 months. On multivariate analysis, CHA2DS2-VASc, AF duration, prior VKA use, and estimated AF ablation success were significantly associated with the decision on short-term anticoagulation. Our results show the increasing use of NOAC in patients undergoing AF ablation and emphasize the need for more information to guide the periprocedural use of both NOACs and VKAs in real-world setting.

Safety, feasibility, and outcome results of cardiac resynchronization with triple-site ventricular stimulation compared to conventional cardiac resynchronization

BACKGROUNDnThe nonresponder rate to cardiac resynchronization therapy (CRT) may be due to incomplete resynchronization, with dyssynchrony persisting in approximately 30% of patients. We hypothesized that CRT with triple-site ventricular stimulation (TRIV) may improve resynchronization and its outcomes.nnnOBJECTIVEnThe purpose of this study was to assess the feasibility and safety of TRIV and collected data on clinical outcomes to dimension future studies.nnnMETHODSnOur pilot randomized trial was designed to assess the safety and feasibility of TRIV with 2 right ventricular leads and 1 left ventricular leads compared to conventional CRT. The primary end-point was the rate of severe adverse events at 6 months. Secondary end-points included functional improvement parameters, quality-of-life (QOL) score, and changes of echocardiographic indices at 6 and 12 months in a subset of patients.nnnRESULTSnSeventy-six patients were enrolled at 11 centers and randomized to control or TRIV arm. All implant procedures but one were successful. At 6 months, there was no statistical difference between proportions of patients with at least 1 severe adverse event in both groups (34.1% vs 25.7%, P = .425). There also was no difference between functional improvement parameters, 6-minute walking distances (P = .40), QOL scores (P = .27), and echographic indices. At 12 months, the proportions of patients with a left ventricular ejection fraction gain of more than 5%, 10%, or 15% were significantly superior with TRIV.nnnCONCLUSIONnTRIV pacing is an effective and safe technique and may provide a greater benefit in ventricular remodeling than conventional CRT. Further studies are needed to assess its long-term benefit.

Mechanism of syncope without prodromes with normal heart and normal electrocardiogram

BACKGROUNDnUnexplained syncope, no prodromes, and normal heart has been described as a distinct clinical and biological entity.nnnOBJECTIVEnThe purpose of this study was to assess the mechanism of syncope.nnnMETHODSnIn this prospective multicenter study, 58 patients presenting with unexplained syncope, no prodromes, and a normal heart received an implantable loop recorder (ILR) and were followed up until a diagnosis was established. Their outcomes were compared with those of 389 patients affected by reflex syncope with prodromes who received an ILR.nnnRESULTSnDuring a mean observation period of 16 ± 13 months, a diagnostic event was documented by the ILR in 29 patients (50%); an asystolic pause of 11 ± 5 seconds (range 3.5-22 seconds) was present at the time of the diagnostic event in 19 patients (66%). Compared with patients affected by reflex syncope with prodromes, patients with unexplained syncope, no prodromes, and a normal heart more frequently had an asystolic syncope (66% vs 47%; P = .001), and this was more frequently due to idiopathic paroxysmal atrioventricular block (47% vs 21%; P = .04). Ten patients with asystolic pauses underwent cardiac pacing, and 8 patients underwent oral theophylline treatment. During the subsequent 17 ± 12 months of follow-up, syncope recurred in 1 patient on theophylline and presyncope occurred in 1 patient with pacemaker.nnnCONCLUSIONnA long asystolic pause, frequently due to idiopathic paroxysmal atrioventricular block, played a role in the mechanism of syncope in two-thirds of patients who had electrocardiographic documentation of a diagnostic event. When a specific therapy was administered in patients with asystolic syncope, the short outcome was favorable.