Steve Furniss

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

Abstract 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 natural history of atrial fibrillation in patients with permanent pacemakers: is atrial fibrillation a progressive disease?

ObjectivesAtrial fibrillation (AF) is thought to be a progressive arrhythmia, starting with short paroxysmal episodes, until eventually, it becomes permanent. Evidence for this is limited to studies with short follow-up or with minimal cardiac rhythm monitoring. We utilised the continuous rhythm monitoring capabilities of implanted pacemakers to define better the natural history of AF.MethodsThe study included 356 patients with pacemaker devices capable of continuous atrial rhythm monitoring (186 male, mean age (±SD) 79.5u2009±u20098.9xa0years). All clinical records, including history/physical examination reports, laboratory results, ECGs and Holter monitoring data were reviewed. Patients were included if AF episodes >30xa0s were documented. Permanent pacemaker diagnostic data were reviewed at least every 12xa0months. ACC/AHA/ESC guidelines were used to define AF episodes as paroxysmal, persistent or long-standing persistent/permanent.ResultsStudy follow-up period (±SD) was 7.2u2009±u20093.1xa0years. Over the study period, 179 of 356 patients (50.3xa0%) had at least one episode of persistent AF. Of the 356 patients, 314 (88.2xa0%) had paroxysmal AF and 42 (11.8xa0%) had persistent AF at the time of diagnosis. The predominant AF subtype, at latest follow-up, was paroxysmal for 192 patients (53.9xa0%), persistent for 77 (21.6xa0%) and long-standing persistent/permanent for 87 (24.4xa0%). Univariable predictors of progression to persistent AF were (1) male gender, (2) increasing left atrial diameter (LAD), (3) reduced atrial pacing (AP) and (4) increasing ventricular pacing.ConclusionsAlthough many patients with AF will have persistent episodes, long-term continuous pacemaker follow-up demonstrates that the majority will have a paroxysmal, as opposed to persistent, form of the arrhythmia.

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

AIMSnTo describe the long-term patterns of atrial fibrillation (AF) in patients with permanent pacemakers.nnnMETHODS AND RESULTSnA 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.nnnCONCLUSIONnIn 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.nnnCLINICAL TRIAL REGISTRATIONnNCT02016950, http://clinicaltrials.gov/show/NCT02016950.

Phased multipolar radiofrequency pulmonary vein isolation is as effective and safe as conventional irrigated point-to-point ablation. A prospective randomised 1-year implantable cardiac monitoring device follow-up trial.

PurposePulmonary vein isolation (PVI) is conventionally performed using 3D electroanatomical mapping to guide point-to-point ablation. The Pulmonary Vein Ablation Catheter (PVAC)® is a phased multipolar ablation (PMRA) catheter designed for rapid PVI using radiological anatomical information. Comparison of these methods of PVI using continuous beat-to-beat monitoring was undertaken.MethodsFifty patients with drug-refractory, symptomatic paroxysmal atrial fibrillation (PAF) were recruited. Patients all had REVEAL® XT ILR or a DDDRP permanent pacemaker (PPM) inserted prior to PVI. PPM was programmed to monitoring mode (ODO). Patients were randomised 1:1 to undergo PVI with either point-to-point irrigated radiofrequency ablation (Conv) or PMRA technology. Follow-up was performed at 0, 3, 6, 9, and 12xa0months using Holter downloads to assess arrhythmia burden. Outcomes were examined following a 3-month blanking period.ResultsThe AF burden pre-ablation, at 3-month and at 12-month post-ablations, was not significantly different (pre-ablation AF burdens (meanu2009±u2009SE) Conv 16.6u2009±u20095.0xa0%, PVAC 17.0u2009±u20095.6xa0%, 3xa0months Conv 4.0u2009±u20091.6xa0%, PVAC 4.7u2009±u20091.5xa0%, 12xa0months Conv 4.3u2009±u20092.3xa0%, PVAC 3.8u2009±u20091.5xa0%). In both groups, there was a significant reduction in AF burden from pre-ablation (at 3xa0months pu2009=u20090.01, pu2009=u20090.04, at 12xa0months pu2009=u20090.04, pu2009=u20090.03 for Conv and PMRA groups, respectively). Overall success rate for zero AF recurrence at 12xa0months was 54xa0%.ConclusionPMRA PVI is comparable to conventional technology for AF extinction at 1xa0year. The PMRA is as safe as conventional technology but enables the operator to perform the procedure faster. Device monitored success rates were lower than other studies not utilising such intensive monitoring confirming that sporadic ECG monitoring is not sufficient to detect all AF recurrence.Trial registration:NCT01095770. URL: https://clinicaltrials.gov/ct2/show/NCT01095770

It’s good to talk! Changes in coronary revascularisation practice in PCI centres without onsite surgical cover and the impact of an angiography video conferencing system

Introduction:u2002 Percutaneous coronary intervention (PCI) activity has increased more than 6 fold in the last 15u2003years. Increased demand has been met by PCI centres without on‐site surgical facilities. To improve communication between cardiologists and surgeons at a remote centre, we have developed a video conferencing system using standard internet links. The effect of this video data link (VDL) on referral pattern and patient selection for revascularisation was assessed prospectively after introduction of a joint cardiology conference (JCC) using the system.

The evaluation of pulmonary vein isolation and wide-area left atrial ablation to treat atrial fibrillation in patients with implanted permanent pacemakers: the Previously Paced Pulmonary Vein Isolation Study

Background The practise of catheter ablation for atrial fibrillation (AF) is increasing rapidly and is recommended as the treatment of choice in many patient subgroups. At present, the efficacy of this procedure has been assessed by means of electrocardiographic recording, intermittent Holter monitoring and evaluation of patient symptoms. We sought to evaluate the true efficacy of this procedure in patients with sophisticated permanent pacemakers capable of continuous long-term cardiac rhythm monitoring. Methods Twenty-five patients (aged 63.7 (9.4), 20 men), seven with persistent AF and 18 with prolonged paroxysmal AF, underwent a mean of 1.7 AF ablation procedures. All the patients had previously been implanted with a pacemaker or atrial defibrillator device. Data were downloaded from the device Holter before catheter ablation and at 2, 4, 6 and 8u2005months postprocedure(s). The primary outcome measure was AF burden. The secondary outcomes were patient symptom and quality-of-life measures. Results Initial AF burden was 43.8 (35.5)%. After catheter ablation(s), this was significantly reduced at 2u2005months to 23.8 (35.4)% (p=0.023), at 4u2005months to 21.4 (34.1)% (p=0.008), at 6u2005months to 14.5 (28.1)% (p=0.002) and at 8u2005months to 15.0 (29.4%) (p=0.003). Only nine (36%) of 25 patients demonstrated no recurrence of arrhythmia during follow-up completion, consistent with a long-term cure. Quality-of-life indices showed significant improvement after ablation. Conclusions Catheter ablation for AF significantly improves patient symptoms and reduces AF burden after long-term beat-to-beat monitoring by implanted cardiac pacemaker and defibrillator devices. However, AF recurrence is common after these procedures.

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

PurposeThe 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.MethodsA 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 50xa0mg bd, or XEN-D0103 50xa0mg bd then placebo.ResultsFifty-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; pu2009<u20090.0001). 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.ConclusionsXEN-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 number2013-004456-38

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

AimsnTo 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.nnnMethods and resultsnAn 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 (Pu2009=u20090.050) 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 (Pu2009=u20090.008): 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 (Pu2009<u20090.001). Surgical ablation took longer to perform (Pu2009<u20090.001) and had a longer hospital admission (Pu2009<u20090.001) than catheter ablation.nnnConclusionnSurgical 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.nnnClinical Trial RegistrationnNCT01504451, http://clinicaltrials.gov/show/NCT01504451.

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

PurposeC-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.MethodsA 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.ResultsTwenty six patients were screened and seven patients dosed with ISIS-CRPRx. After 4xa0weeks 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 8xa0weeks after the active treatment period. There was a 63.7xa0% (95xa0% CI 38.4 to 78.6xa0%, pu2009=u20090.003) 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, 95xa0% CI −2.42 to 5.62, pu2009=u20090.37). ISIS CRPRx was safe and well tolerated and there were no serious adverse events.ConclusionsTreatment 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.

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

&NA; 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.