Right versus left atrial pacing in patients with sick sinus syndrome and paroxysmal atrial fibrillation (Riverleft study): study protocol for randomized controlled trial.

BACKGROUND: The incidence of sick sinus syndrome will increase due to population ageing. Consequently, this will result in an increase in the number of pacemaker implantations. The atrial lead is usually implanted in the right atrial appendage, but this position may be ineffective for prevention of atrial fibrillation. It has been suggested that pacing distally in the coronary sinus might be more successful in preventing atrial fibrillation episodes. The aim of this trial is to study the efficacy of distal coronary sinus versus right atrial appendage pacing in preventing atrial fibrillation episodes in patients with sick sinus syndrome. METHODS/DESIGN: This study is designed as a multicenter, randomized controlled trial. Patients with sick sinus syndrome and at least one atrial fibrillation episode of 30 seconds or more in the six months before recruitment will be eligible for participation in this study.All participants will be randomized between pacing distally in the coronary sinus and right atrial appendage. Randomization is stratified for all participating centers. Conventional dual-chamber pacemakers with advanced home monitoring functionality will be implanted. The ventricular lead will be implanted in the right ventricular apex. The first three months of the 36-month follow-up period are considered as run-in time. During the pre-randomization visit and follow-up, an interview, electrocardiogram and pacemaker assessment will be performed, prescribed antiarrhythmic medication will be reviewed and patients will be asked to complete an SF-36 questionnaire. An echocardiographic examination will be conducted in the pre-randomization phase and at the end of each follow-up year. Home monitoring will be used to send daily reports in case of atrial fibrillation episodes. DISCUSSION: This randomized controlled trial is the first in which home monitoring will be used to compare atrial fibrillation recurrences between pacing in the distal coronary sinus or right atrial appendage. Home monitoring gives the opportunity to accurately detect atrial fibrillation episodes and to study characteristics of atrial fibrillation episodes. Should distal coronary sinus pacing significantly diminish atrial fibrillation recurrences, this study will redefine the preferential location of an atrial lead for preventive pacing. TRIAL REGISTRATION: Current Controlled Trials ISRCTN65911661, registered on 8 July 2013.

Unique cardiac Purkinje fiber transient outward current ß-subunit composition: a potential molecular link to idiopathic ventricular fibrillation.

RATIONALE: A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (I(to)) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF I(to) and that its overexpression might specifically alter PF I(to) properties and repolarization. OBJECTIVE: To assess the potential role of DPP6 in PF I(to). METHODS AND RESULTS: Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle I(to) had similar density, but PF I(to) differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, I(to) density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K(+)-channel interacting ß-subunit K(+)-channel interacting protein type-2, essential for normal expression of I(to) in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small I(to); I(to) amplitude was greatly enhanced by coexpression with K(+)-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K(+)-channel interacting protein type-2 failed to alter I(to) compared with Kv4.3/K(+)-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF I(to) composition) greatly enhanced I(to) compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that I(to) enhancement can greatly accelerate PF repolarization. CONCLUSIONS: These results point to a previously unknown central role of DPP6 in PF I(to), with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation.

Clinical characteristics and acute results of catheter ablation for outflow tract ventricular tachycardia or premature beats.

PURPOSE: Contemporary outcome data of catheter ablation for outflow tract tachycardia (OTT) and ventricular premature beats (VPBs) are rare. The aim of this study was to describe the clinical characteristics, the acute procedure success rate, and the long-term survival of patients who underwent an ablation procedure for OTT or VPBs. METHODS: The study was a single-center retrospective cohort study. All 82 consecutive OTT and VPB first ablation procedures between 1999 and 2009 were included. Patients with structural heart disease were excluded. RESULTS: Mean age was 46 ± 13 years. Forty-three percent of the patients were male. All patients were alive after a median follow-up duration of 31 months (interquartile range, 14-65 months). Eighty-nine percent suffered from palpitations and 12 % had a history of syncope. Ventricular tachycardia was documented in 73 % and monomorphic VPBs in 99 %. Seventy-three percent of the patients were ablated in the right ventricular outflow tract, 15 % in the left ventricular outflow tract, and 12 % in the coronary cusps. Radiofrequency energy was used in 95 % of the patients, cryo energy in 9 %. Acute success was achieved in 78 %. Six patients (7 %) experienced a complication (five pericardial effusions, one pseudo-aneurysm of the femoral artery). Three patients needed pericardiocentesis (4 %). CONCLUSION: Ablation for OTT and VPB is successful in the vast majority of cases, with a low but still existing complication rate. Long-term survival was excellent, underscoring the benign nature of this arrhythmia.

A complex double deletion in LMNA underlies progressive cardiac conduction disease, atrial arrhythmias, and sudden death.

BACKGROUND: Cardiac conduction disease is a clinically and genetically heterogeneous disorder characterized by defects in electrical impulse generation and conduction and is associated with sudden cardiac death. METHODS AND RESULTS: We studied a 4-generation family with autosomal dominant progressive cardiac conduction disease, including atrioventricular conduction block and sinus bradycardia, atrial arrhythmias, and sudden death. Genome-wide linkage analysis mapped the disease locus to chromosome 1p22-q21. Multiplex ligation-dependent probe amplification analysis of the LMNA gene, which encodes the nuclear-envelope protein lamin A/C, revealed a novel gene rearrangement involving a 24-bp inversion flanked by a 3.8-kb deletion upstream and a 7.8-kb deletion downstream. The presence of short inverted sequence homologies at the breakpoint junctions suggested a mutational event involving serial replication slippage in trans during DNA replication. CONCLUSIONS: We identified for the first time a complex LMNA gene rearrangement involving a double deletion in a 4-generation Dutch family with progressive conduction system disease. Our findings underscore the fact that if conventional polymerase chain reaction-based direct sequencing approaches for LMNA analysis are negative in suggestive pedigrees, mutation detection techniques capable of detecting gross genomic lesions involving deletions and insertions should be considered.

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

INTRODUCTION: Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. METHODS: Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. RESULTS: In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P < 0.001). CONCLUSION: SC ICD generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this study. MDT ICDs had the longest service time.

Usefulness of a pacing guidewire to facilitate left ventricular lead implantation in cardiac resynchronization therapy.

BACKGROUND: Intraoperative measurements of left ventricular (LV) pacing and sensing values were assessed using a novel 0.014-inch guidewire (Visionwire, Biotronik GmbH, Berlin, Germany) enabling pacing and sensing at the distal tip before final LV lead implantation. METHODS: Twenty-two consecutive patients selected for cardiac resynchronization therapy were studied. RESULTS: Significant correlation was found between the LV pacing threshold as assessed by the Visionwire and values after final LV lead implantation (r = 0.92, P < 0.001). Correlation for LV sensing was also significant (r = 0.72, P < 0.001). No significant correlation was present with respect to phrenic nerve stimulation. However, no phrenic nerve stimulation at 10 V/0.5 ms using the Visionwire identified 88% of patients without phrenic nerve stimulation at 10 V/0.5 ms with subsequent LV lead measurements. CONCLUSION: This technique may facilitate transvenous LV lead implantation by preventing implantation in a unsuitable target vessel with respect to pacing and sensing values or phrenic nerve stimulation, thereby reducing procedure and fluoroscopy time.

Analysis of 57,148 transmissions by remote monitoring of implantable cardioverter defibrillators.

INTRODUCTION: Remote monitoring of implantable cardioverter defibrillators (ICD) is designed to decrease the number of ambulatory visits and facilitate the early detection of adverse events. We examined the impact of remote monitoring on clinical workload by a comprehensive analysis of transmitted events. METHODS: The study population consisted of 146 recipients of ICD capable of remote monitoring. Data were transmitted daily or in case of pre-specified events (e.g., arrhythmia, out-of-range lead and/or shock impedance). Transmitted events were classified as clinical (disease-related) or system-related. Event rates/patient/month were calculated and compared according to events classification and clinical groups. RESULTS: During a mean follow-up of 22 +/- 16 months, a total of 57,148 remote transmissions were recorded. Of these transmissions, 1009 (1.8%) were triggered by a pre-specified event, including induced ventricular fibrillation (VF) episodes during defibrillation threshold testing. The median number of events/patient/month was 0.14. Event rates were similar in patients with primary and secondary prevention indications for ICD (0.15 vs. 0.11). After exclusion of the induced VF episodes, 5.6% of transmitted events were classified as system-related and 94.4% as clinical. The median number of clinical events/patient/month was 0.023. The clinical event-free rates were 62% and 45%, at 1 and 4 years, respectively. CONCLUSION: Remote monitoring of ICD patients is feasible. Despite the large number of data transmissions, remote monitoring imposed a minimal additional burden on the clinical workload. The rate of triggered data transmissions by critical events was, relatively, very low.

Recurrent ventricular fibrillation caused by coronary artery spasm leading to implantable cardioverter defibrillator implantation.

Coronary artery spasm has been known to induce ischaemia and ventricular arrhythmias. We present a case of recurrent ventricular fibrillation caused by spasm-associated transmural myocardial ischaemia. During an intra-coronary acetylcholine provocation test, severe coronary spasm could be induced. The patient was treated with a hybrid approach of medication and an implantable defibrillator.

LV lead fixation in a coronary vein may be the cause and result of thrombosis.

A recently implanted left ventricular lead was fixated in the coronary sinus due to thrombosis while attempting to reposition the lead because of phrenic nerve stimulation.

The BRIGHT study: bifocal right ventricular resynchronization therapy: a randomized study.

AIMS: The BRIGHT study evaluated bifocal right ventricular (RV) (apex and outflow tract) pacing in a single, blind, randomized crossover study in patients eligible for cardiac resynchronization therapy (CRT). Forty-two patients were enrolled with the following characteristics: chronic drug refractory heart failure New York Heart Association (NYHA) class III-IV; ejection fraction (EF)<35%; QRS width >or= 120 ms; and a left bundle branch block. The aim of the study was to assess an improvement in left ventricular (LV) EF, 6 min walk test, Minnesota quality-of-life score, and NYHA classification. Methods and result Patients were randomized to receive either bifocal pacing or the control mode, each for a period of 3 months. Parameters were measured prior to randomization and after 3 months of control or bifocal pacing. Eight patients failed to make the 7 month follow-up, three patients died (one prior to randomization at the first month), five patients dropped out, and three patients refused further participation. One patient had a persistent lead problem, which was subsequently replaced with an LV lead, and one patient suffered with persistent atrial fibrillation. Compared with baseline, bifocal pacing improved EF from 26 +/- 12% to 36 +/- 11% (P < 0.0008), NYHA classification decreased from 2.8 +/- 0.4 to 2.3 +/- 0.7 (P < 0.007). Furthermore, the 6 min walk test improved from 372 +/- 129 m to 453 +/- 122 m (P < 0.05), and the Minnesota Living with Heart Failure scores decreased from 33 +/- 20 to 24 +/- 21 (P < 0.006). In the control group, no significant changes in any parameters were observed. Eight patients did not tolerate reprogramming from DDD BRIGHT to control pacing, with symptoms disappearing in all patients after reprogramming to bifocal pacing. CONCLUSION: Bifocal RV pacing in patients with a classic indication for CRT shows improvement in all parameters.

Reversible left bundle branch block induced congestive heart failure. A case report.

Intraventricular conduction delay in the form of left bundle branch block plays an important role in the genesis and the progression of congestive hart failure. We report on the clinical course of a patient and the improvement in functional status after the disappearance of left bundle branch block, despite withholding cardiac resynchronization therapy.

Acute subclavian or axillary vein occlusion during biventricular pacemaker implantation.

During biventricular pacemaker implantation, multiple punctures of the subclavian vein were performed and venous occlusion was apparent during the procedure, which in one case was stopped before lead insertion and in the other patient new access has to be forced through the occlusion by removing one of the already implanted leads. For implanting physicians, it is important to know that acute venous occlusion may occur during lead implantation.

Use of advanced mapping and remote magnetic navigation to ablate left ventricular fascicular tachycardia.

Ablation of idiopathic left ventricular, or fascicular tachycardia can be aided by electroanatomical mapping. The addition of a floppy, magnetically enabled ablation catheter may improve maneuvering as well as decrease mechanically induced arrhythmias and mechanical block. We describe a case of fascicular tachycardia in which both these modalities were used in a sequential fashion. Integration of these modalities should prove even more helpful.

Left ventricular lead placement within a coronary sinus side branch using remote magnetic navigation of a guidewire: a feasibility study.

BACKGROUND: A novel magnetic navigation system (MNS) allowing remote guidance of catheters and guidewires might assist in implantation of left ventricular (LV) pacing leads. OBJECTIVE: To assess the feasibility of deploying a LV pacing lead into a coronary sinus (CS) side branch using a magnetically guided wire and of performing the procedure without a CS guiding sheath. METHODS: Twenty-one patients were included in this study. Nine underwent CRT device implantation using a MNS to steer the guidewire (MNS group) while 12 patients were conventionally implanted (control group). In 6 patients in the MNS group, the procedure was performed using a CS guiding sheath. In 3 others, the decision was to perform the procedure without a CS sheath. In these patients the wire was advanced manually, while the external magnets oriented it toward the CS os. In the CS, "vector based" navigation was used to guide the wire to the desired side branch. RESULTS: In all 9 patients in the MNS group, the target vessel could be successfully engaged by the magnetically guided wire. In 7, the LV lead was lodged in the target vessel. In 2 patients, the LV lead was repositioned in an anterolateral side branch due to instability or inability to engage the vessel with it. Mean total procedure time was 164 +/- 58 minutes (without sheath 229 +/- 52 vs with sheath 132 +/- 26 minutes; P = 0.007). Mean fluoroscopy time was 28 +/- 9 minutes. For control patients, the procedure and fluoroscopy time were similar (144 +/- 41 minutes and 26 +/- 12 minutes, respectively). No major complications occurred. CONCLUSION: LV lead implantation can be performed using a remote magnetically steered guidewire. Though the lead could be implanted without a CS guiding sheath, longer procedure times were required.

Characteristics of bifocal pacing: right ventricular apex versus outflow tract. An interim analysis.

Bifocal RIGHT ventricular stimulation (BRIGHT) is an ongoing, randomized, single-blind, crossover study of atrial synchronized bi-right ventricular (RV) pacing in patients in New York Heart Association heart failure functional class III, a left ventricular ejection fraction <35%, left bundle branch block and QRS complexes >/=120 ms. This analysis compared the electrical and handling characteristics, and the complications of pacing at the RV apex (Ap) with passive, versus RV outflow tract (OT) with active fixation leads. A mean of 1.6 +/- 0.9 and 2.2 +/- 2.0 attempts were needed to position the Ap and OT leads, respectively (ns). R-wave amplitudes at Ap versus OT were 23 +/- 13 mV versus 14 +/- 8 mV (n = 36, P < 0.001). R-wave amplitudes at the Ap remained stable between implant and M7. R-wave amplitudes at the OT could not be measured after implantation. In two patients, atrioventricular block occurred during active fixation at the OT. Conduction recovered spontaneously within 4 months. Ventricular fibrillation was induced in one patient during manipulation of an Ap lead in the RV. Marked differences were found between leads positioned in the OT versus Ap, partly related to the difference in lead design. Mean R-wave amplitude was higher at the Ap that at the OT. Ease and success rate of lead implant was similar in both positions.

Twiddler's syndrome detected by home monitoring device.

Lead fracture due to twiddler's syndrome, was detected in a 68-year-old patient 1 month after implantation of an ICD by means of the incorporated home monitoring system. The patient was admitted and the lead replaced. This case illustrates the clinical benefit of the home monitoring system.

Ice mapping during cryothermal ablation of accessory pathways in WPW: the role of the temperature time constant.

AIM: Cryothermal energy has the ability reversibly to demonstrate loss of function with cooling, ice mapping, at less deep temperatures. The purpose of this study was to investigate the time course of the temperature during ice mapping of accessory pathways. METHODS AND RESULTS: Thirteen patients with the Wolff-Parkinson-White (WPW) syndrome underwent cryoablation. After identification of a prospective ablation site, ice mapping was performed by cooling the tip to a minimum of -30 degrees C. Successful ice mapping was defined by loss of accessory pathway (AP) conduction. A total of 104 ice maps were analyzed. Successful ice mapping was demonstrated in 17 attempts. There was no significant difference in mapping temperature between successful and unsuccessful ice mapping (-29.4+/-3.2 degrees Celsius vs -30.4+/-1.7 degrees Celsius). The temperature time constant tau during successful ice mapping was significantly shorter compared with unsuccessful ice mapping (7.0+/-1.1 s vs 10.1+/-1.3 s; P<0.0001). The response time (RT) to mapping temperature of -30 degrees C was significantly prolonged in unsuccessful ice mapping attempts (35.8+/-4.5 s vs 53.5+/-11.0 s; P<0.0001). Significant correlations were found between successful ice mapping and the temperature time constant, and between RT and the temperature time constant (P<0.001). CONCLUSION: The ability to identify prospective ablation sites by ice mapping was demonstrated. Successful ice mapping attempts were characterized by a short temperature time constant and a short response time to mapping temperature with a sudden disappearance of pathway conduction.

Transthoracic defibrillation of short-lasting ventricular fibrillation: a randomised trial for comparison of the efficacy of low-energy biphasic rectilinear and monophasic damped sine shocks.

BACKGROUND: Biphasic rectilinear shocks are more effective than monophasic shocks for transthoracic atrial defibrillation and for ventricular arrhythmias during electrophysiological testing. We undertook the present study to compare the efficacy of 100 J rectilinear biphasic waveform shocks with 150 J monophasic damped sine waveform shocks for transthoracic defibrillation of true ventricular fibrillation during defibrillation threshold testing (DFT). The second aim of the study was to analyse the influence of patch positions on the efficacy of defibrillation. METHODS: 50 episodes of 14 patients (age ranging from 37 to 82 years) who underwent DFT testing were randomised for back-up shocks with either a sequence of 100 and 200 J biphasic waveform, or a sequence of 150 and 360 J conventional monophasic shocks. A binary search protocol was used at implantation and before hospital discharge. Patients were also randomised to an anteroposterior position versus a right-anterior-apical position. A crossover was performed between implantation and pre-hospital discharge for biphasic versus monophasic sequence as well as for the 2 different positions. RESULTS: After failed internal shocks, 27 episodes were treated with biphasic, and 23 with monophasic shocks. The first attempt by the external device did not terminate II episodes (2 biphasic, 9 monophasic). The first shock efficacy was significantly greater with biphasic than with monophasic shocks (p < 0.02). The overall success rate was 93% with biphasic shocks and 64% with monophasic shocks. In multivariate regression analysis including patch position, arrhythmia duration, type of waveform, testing order and session, only waveform was associated with successful defibrillation (p < 0.02). CONCLUSION: For transthoracic defibrillation of ventricular fibrillation, low-energy rectilinear biphasic shocks are more effective than monophasic shocks. The position of the defibrillation shock pads has no influence on the biphasic shock efficacy, but anteroposterior pad position is more effective using monophasic shocks.