The effect of atrial fibrillation intervention on nocturnal respiratory events in elderly patients with persistent AF.

BACKGROUND: Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are associated. This study investigated the impact of AF intervention on 6-month home sleep testing data. METHODS: Sixty-seven patients (aged 66 to 86, 53% male) with persistent AF were randomized (1:1:1) to direct current cardioversion (DCCV) (22 patients), permanent pacemaker (PPM) + atrioventricular node ablation (AVNA) + DCCV (22 patients) or AF ablation (23 patients). Baseline and 6-month multichannel home sleep tests with the Watch-PAT200 (Itamar Medical Lts., Caesarea, Israel) were recorded. Implantable cardiac monitors (ICMs) (Medtronic Reveal XT, Minneapolis, Minnesota) in the DCCV and AF ablation groups, and PPM Holters in the 'pace and ablate' group were utilized to assess cardiac rhythm beat-to-beat throughout the study period. RESULTS: The prevalence of moderate-to-severe SDB [apnoea-hypopnoea index (AHI) ≥ 15/h] was 60%. At 6 months there was no change in AHI, Epworth sleepiness scale, sleep time, % REM sleep, respiratory desaturation index or central apnoeic events. Twenty-five patients (15 AF ablation, 9 DCCV and 1 following DCCV post-AVNA) maintained SR at 6 months confirmed on ICMs in these patients. AHI fell from 29.8 ± 26.6/h to 22.2 ± 20.4/h; P = 0.049. CONCLUSIONS: SDB is highly prevalent in patients with persistent AF. Restoration of sinus rhythm, and the associated long-term recovery of haemodynamics, is associated with a significant reduction in AHI. This implicates reversal of fluid shift from the lower limbs to the neck region, a key mechanism in the pathogenesis of SDB.

Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension and paroxysmal AF.

A central iliac arteriovenous anastomosis, the 'coupler' (ROX Medical, California, USA) results in a significant reduction in blood pressure in hypertensive patients. This study assessed the change in AF burden following coupler implantation in patients with paroxysmal AF (PAF) and hypertension. Good blood pressure control using the coupler results in a significant reduction in AF burden.

A double-blind, randomised, placebo-controlled, cross-over study assessing the use of XEN-D0103 in patients with paroxysmal atrial fibrillation and implanted pacemakers allowing continuous beat-to-beat monitoring of drug efficacy.

PURPOSE: The ultrarapid delayed rectifier current (IKur) carried by Kv1.5 channels, which are solely expressed in the atrium, is a potential target for safer treatment of paroxysmal atrial fibrillation (PAF). XEN-D0103 is a nanomolar ion channel blocker that selectively inhibits potassium ion flux through the Kv1.5 ion channel. The efficacy of XEN-D0103 in reducing AF burden was assessed in patients with DDDRp permanent pacemakers (PPMs) and PAF. METHODS: A double-blind, placebo-controlled, cross-over study was performed in patients with PAF and DDDRp PPMs with advanced atrial and ventricular Holters allowing beat-to-beat arrhythmia follow-up. All anti-arrhythmic drugs were withdrawn before randomised treatment. After baseline assessment, patients were randomly assigned to two treatment periods of placebo then XEN-D0103 50 mg bd, or XEN-D0103 50 mg bd then placebo. RESULTS: Fifty-four patients were screened and 21 patients were eligible and included in the randomised trial. All 21 patients completed both treatment periods. The primary endpoint was change in AF burden assessed by PPM. There was no significant difference in AF burden on treatment with XEN-D0103 versus placebo. There was a reduction in the mean frequency of AF episodes (relative reduction 0.72, 95% CI 0.66 to 0.77; p < 0.0001). XEN-D0103 was safe and well tolerated, and there were no serious adverse events. XEN-D0103 did not have any apparent effect on heart rate compared to placebo. CONCLUSIONS: XEN-D0103 did not reduce AF burden in patients with PAF and dual chamber pacemakers providing beat-to-beat monitoring. XEN-D0103 was well tolerated and did not have any apparent effect on heart rate. Although single-ion channel blockade with XEN-D0103 did not affect AF in this study, there might be a potential for this agent to be used in combination with other atrially specific drugs in the treatment of AF. EUDRACT TRIAL REGISTRATION NUMBER: 2013-004456-38.

Results of the first investigator-initiated randomized clinical trial of nMARQTM, PVACTM, and thoracoscopic ablation for paroxysmal atrial fibrillation.

Aims: To investigate the effect of minimally invasive thoracoscopic surgical ablation and nMARQ irrigated multi-electrode phased radiofrequency (RF) ablation to treat paroxysmal atrial fibrillation (AF) compared with PVAC multi-electrode phased RF ablation, with beat-to-beat device-derived Holter monitoring throughout the study duration. Methods and results: An investigator-initiated prospective trial of patients with paroxysmal AF randomized (1:1:1) to initial surgical, nMARQ or PVAC ablation. All patients had continuous beat-to-beat monitoring with an ILR or pacemaker to evaluate and document AF recurrence. There was a strong trend (P = 0.050) toward difference in AF outcome, with surgical AF ablation more efficacious than catheter ablation. At one year, the proportion of patients with less than 1% AF burden after one procedure and off all antiarrhythmic drugs was 63, 56, and 90% for PVAC, nMARQ and surgical ablations respectively. There were significantly more repeat ablations in the catheter ablation groups (P = 0.008): 25% PVAC, 27% nMARQ, 0% surgery. However, 7 of 20 (35%) of patients undergoing surgical ablation suffered a procedural complication, including two sternotomies for bleeding and one death. This was higher than for catheter ablation (P < 0.001). Surgical ablation took longer to perform (P < 0.001) and had a longer hospital admission (P < 0.001) than catheter ablation. Conclusion: Surgical AF ablation required significantly fewer repeat procedures than catheter ablation, and there was a clear trend towards improved arrhythmia outcome. However, it was associated with a significantly higher rate of procedural complications. Surgical ablation for paroxysmal AF is promising, however more prospective outcome data is required. Clinical Trial Registration: NCT01504451, http://clinicaltrials.gov/show/NCT01504451.

Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial.

AIMS: This prospective, multicentre study (PRECISION GOLD) evaluated the incidence of asymptomatic cerebral embolism (ACE) after pulmonary vein isolation (PVI) using a new gold multi-electrode radiofrequency (RF) ablation catheter, pulmonary vein ablation catheter (PVAC) GOLD. Also, procedural efficiency of PVAC GOLD was compared with ERACE. The ERACE study demonstrated that a low incidence of ACE can be achieved with a platinum multi-electrode RF catheter (PVAC) combined with procedural manoeuvres to reduce emboli. METHODS AND RESULTS: A total of 51 patients with paroxysmal atrial fibrillation (AF) (age 57 ± 9 years, CHA2DS2-VASc score 1.4 ± 1.4) underwent AF ablation with PVAC GOLD. Continuous oral anticoagulation using vitamin K antagonists, submerged catheter introduction, and heparinization (ACT ≥ 350 s prior to ablation) were applied. Cerebral magnetic resonance imaging (MRI) scans were performed within 48 h before and 16-72 h post-ablation. Cognitive function assessed by the Mini-Mental State Exam at baseline and 30 days post-ablation. New post-procedural ACE occurred in only 1 of 48 patients (2.1%) and was not detectable on MRI after 30 days. The average number of RF applications per patient to achieve PVI was lower in PRECISION GOLD (20.3 ± 10.0) than in ERACE (28.8 ± 16.1; P = 0.001). Further, PVAC GOLD ablations resulted in significantly fewer low-power (<3 W) ablations (15 vs. 23%, 5 vs. 10% and 2 vs. 7% in 4:1, 2:1, and 1:1 bipolar:unipolar energy modes, respectively). Mini-Mental State Exam was unchanged in all patients. CONCLUSION: Atrial fibrillation ablation with PVAC GOLD in combination with established embolic lowering manoeuvres results in a low incidence of ACE. Pulmonary vein ablation catheter GOLD demonstrates improved biophysical efficiency compared with platinum PVAC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01767558.

The development of AF over time in patients with permanent pacemakers: objective assessment with pacemaker diagnostics demonstrates distinct patterns of AF.

AIMS: To describe the long-term patterns of atrial fibrillation (AF) in patients with permanent pacemakers. METHODS AND RESULTS: A total of 2092 pacemaker Holter downloads were analysed in 323 patients with dual chamber permanent pacemakers, describing a cumulative 1031 patient-years of beat-to-beat monitoring. Four subtypes of AF were applied: (i) non-progressive low-burden PAF (NPLB-PAF, n = 120): such patients never have >1% AF burden throughout follow-up; (ii) chronic progressive PAF (CP-PAF, n = 55): AF burden increases but is never 100%; (iii) relapsing-remitting PAF (RR-PAF, n = 78): AF burden has reduced at least once by more than 2% and is never 100%; (iv) persistent AF (PersAF, n = 70): 100% AF burden for at least 28 days. Overall, mean AF burden rose 0.34% per year (P < 0.0001). After accounting for age, heart failure (HF) had a significant interaction with AF burden (P = 0.0022), but HATCH score and CVA/TIA did not. There were no differences in the frequency or duration of monitoring between the four AF subtypes. Atrial fibrillation episode frequency discriminated between subtypes (P = 0.0004). Eighteen of 70 (26%) patients with PersAF had pacemaker documented episodes of sinus rhythm (i.e. reversion to 'paroxysmal AF') after the onset of PersAF. CONCLUSION: In this cohort, the development of AF over time appears more complex than current definitions suggest. Atrial fibrillation can remain low burden without progression, remit-relapse, or progress as is described in currently accepted definitions. More frequent episodes of AF indicated a favourable subtype. Persistent AF is not inevitable, and can revert to paroxysmal AF. CLINICAL TRIAL REGISTRATION: NCT02016950, http://clinicaltrials.gov/show/NCT02016950.

The effect of C-reactive protein reduction with a highly specific antisense oligonucleotide on atrial fibrillation assessed using beat-to-beat pacemaker Holter follow-up.

PURPOSE: C-reactive protein (CRP) is known to be strongly associated with atrial fibrillation (AF). However, it is not clear if CRP is a causal factor for AF. ISIS-CRPRx is a novel antisense oligonucleotide that reduces CRP production by specifically inhibiting mRNA translation. The effect of ISIS-CRPRx on AF was evaluated. METHODS: A double-blind phase II trial of ISIS-CRPRx in patients with paroxysmal AF and DDDRP permanent pacemakers (PPMs) with advanced atrial and ventricular Holters allowing beat-to-beat arrhythmia follow-up. RESULTS: Twenty six patients were screened and seven patients dosed with ISIS-CRPRx. After 4 weeks of baseline assessment, patients were randomly assigned to two treatment periods of either placebo then ISIS-CRPRx or ISIS-CRPRx then placebo. All patients were followed up for 8 weeks after the active treatment period. There was a 63.7 % (95 % CI 38.4 to 78.6 %, p = 0.003) relative reduction in CRP on treatment with ISIS-CRPRx versus baseline. Sensitivity analyses demonstrated a consistent treatment effect. The primary end-point was change in AF burden assessed by PPM. There was no significant difference in AF burden on treatment with ISIS-CRPRx versus baseline (OR 1.6, 95 % CI -2.42 to 5.62, p = 0.37). ISIS CRPRx was safe and well tolerated and there were no serious adverse events. CONCLUSIONS: Treatment with ISIS-CRPRx did not reduce AF burden in patients with paroxysmal AF and PPMs, despite a large relative reduction in CRP. In this population, highly specific CRP reduction had no clinically discernable effect upon paroxysmal AF. However, average levels of CRP at baseline were relatively low, so it remains possible that AF patients with higher levels of CRP may benefit from CRP-directed therapy.

Transient loss of consciousness in a patient with a Brugada like ECG.

Syncope in a patient with a Brugada syndrome channelopathy carries significant prognostic implications and warrants consideration of implantable cardioverter defibrillator (ICD) implantation. We report a case of a 62-year-old gentleman who presented with a transient loss of consciousness and an electrocardiogram (ECG) suggestive of type 1 Brugada syndrome. Further investigation revealed evidence of a silent myocardial infarction and negative ventricular tachycardia stimulation and Ajmaline testing. Careful review of the ECG's subsequently showed the type 1 pattern was present in only V1.

Catheter ablation of recurrent scar-related ventricular tachycardia using electroanatomical mapping and irrigated ablation technology: results of the prospective multicenter Euro-VT-study.

INTRODUCTION: Ventricular tachycardia (VT) late after myocardial infarction is an important contributor to morbidity and mortality. This prospective multicenter study assessed the efficacy and safety of electroanatomical mapping in combination with open-saline irrigated ablation technology for ablation of chronic recurrent mappable and unmappable VT in remote myocardial infarction. METHODS AND RESULTS: In 8 European institutions, 63 patients (89% males) were enrolled in the study. All patients had remote myocardial infarction and presented with a median number of 17 (range 1-380) VTs in the preceding 6 months. Incessant VT was present in 14 patients (22%). Left ventricular ejection fraction measured 30 +/- 13%. A mean of 3 VTs were targeted per patient and 22% of all patients had only unmappable VT. The mean follow-up period was 12 +/- 3 months. A total of 164 VTs were targeted during catheter ablation. Ablation was acutely successful in 51 patients (81%). One patient (1.5%) experienced a major complication with degeneration of VT into ventricular fibrillation necessitating cardiopulmonary resuscitation maneuvers. However, no death occurred acutely or within the first 30 days after catheter ablation. During the follow-up, 19 of the initially successful ablated patients (37%) and 31 of all ablated patients (49%) developed some type of VT recurrence. CONCLUSIONS: The results of this multicenter study demonstrate the high acute success rate and a low complication rate of irrigated tip catheter ablation of all clinical relevant VTs in remote myocardial infarction. However, during the follow-up a relevant number of recurrences occurred.

Standardized stimulation protocol to predict the long-term success of radiofrequency ablation of postinfarction ventricular tachycardia.

BACKGROUND: The ability to predict the success of radiofrequency ablation (RFA) is an essential step in the management of ventricular tachycardia (VT) in patients with ischemic heart disease. METHODS: This study tested a standardized programmed stimulation protocol and pre-specified definitions of procedural outcome. Consecutive patients referred for RFA of delayed post infarction VT were enrolled. Programmed stimulation was performed at the beginning and the end of an RFA procedure, and consisted of an 8 beat drive followed by up to 5 extrastimuli. Immediate success was defined as no inducible monomorphic VT, and a modified result was defined as the inducibility of VT with > 2 extrastimuli beyond those required at baseline. Procedural failure was defined when these criteria were not met. Recurrences of sustained VT and arrhythmic deaths were monitored during long-term follow-up. RESULTS: The study enrolled 112 patients. Immediate procedural success was achieved in 38%, a modified result in 34%, and procedural failure in 28% of patients. During a mean follow-up of 78 +/- 16 months, recurrent sustained VT was observed in 25 patients. VT recurrence was 3% (3/79) in patients with a successful or modified result, compared with 67% (22/33) in those who had undergone unsuccessful procedures (P < 0.001). CONCLUSIONS: This standardized stimulation protocol and definitions of procedural success, enabled us to predict with high accuracy a VT recurrence-free long-term follow-up. This may have implications in recommending devices or other treatments after RFA for postinfarction VT.

Dynamic alterations in right atrial activation during atrial fibrillation.

Atrial fibrillation (AF) is usually considered to be a disorganized rhythm. However, several reports have described areas of organized right atrial (RA) activation during AF. We describe a patient with focal paroxysmal AF with a consistent pattern of organized RA activity despite typically disorganized left atrial activity. The sequence of RA activation varied, depending on which pulmonary vein foci initiated the AF.

Interatrial transseptal electrical conduction: comparison of patients with atrial fibrillation and normal controls.

INTRODUCTION: This study analyzed the electrophysiologic properties of interatrial transseptal electrical conduction at Bachmann's bundle and the ostium of the coronary sinus (CS os) in response to pulmonary vein (PV) stimuli, which mimicked spontaneous ectopy. METHODS AND RESULTS: Forty patients with atrial fibrillation (AF) referred for ablation (15 persistent AF and 25 paroxysmal AF) and 15 control patients were enrolled in the study. During decremental extra-stimulus pacing from the PVs, right atrial activation was analyzed using noncontact mapping and multipolar catheters. The refractory periods and conduction times were calculated for Bachmann's bundle, CS os, and left atrium. The dispersion of refractoriness was calculated as the difference between the refractory periods of Bachmann's bundle and the CS os. The refractory period at Bachmann's bundle was 244 msec in the persistent AF group, 213 msec in the paroxysmal AF group, and 199 msec for controls. The refractory period at the CS os was 220 msec in the persistent AF group, 201 msec in the paroxysmal AF group, and 193 msec for controls. The dispersion of refractoriness was 54 msec in the persistent AF group; this was significantly greater than in paroxysmal AF at 32 msec (P < 0.05) and controls at 13 msec (P < 0.01). During decremental pacing, lengthening of conduction times at both Bachmann's bundle and the CS os were significantly greater in the persistent AF group compared with paroxysmal AF or control groups. A higher dispersion of refractoriness was associated with a higher incidence of inducible AF and a lower rate of ablation success. CONCLUSION: There are differences between the left to right interatrial electrical connections between patients with persistent AF, paroxysmal AF and controls.

Paroxysmal cycle length shortening in the pulmonary veins during atrial fibrillation correlates with arrhythmogenic triggering foci in sinus rhythm.

INTRODUCTION: The focal origin of atrial fibrillation (AF) is identified by recording atrial ectopic beats or the ectopic activity that precedes AF. We hypothesized that arrhythmogenic pulmonary veins (PVs) also could be identified during persistent AF. METHODS AND RESULTS: Patients with persistent AF referred for focal ablation were enrolled prospectively. During AF, bipolar electrograms were recorded from each PV for a minimum of 120 seconds, as well as from the right atrium and coronary sinus. The cycle length of activity in each PV was measured during AF and plotted on a frequency histogram. Following cardioversion to sinus rhythm, arrhythmogenic PVs were identified from reinitiation of AF or from ectopic beats. Ten patients were enrolled and 37 PVs analyzed. During AF, 17 PVs demonstrated bimodal cycle length frequency histograms, with periods of paroxysmal short cycle length recording. Following cardioversion, 14 PVs were identified as arrhythmogenic as defined earlier. Each of these arrhythmogenic PVs showed paroxysmal short cycle length recording during AF. Sensitivity was 87%, specificity 91%, positive predictive value 87%, and negative predictive value 100%. CONCLUSION: The arrhythmogenic PVs responsible for the focal activity that triggers AF also demonstrate paroxysmal short cycle length recording during sustained AF. These results demonstrate that arrhythmogenic PVs still can be identified reliably, even during sustained AF.