Imperial College London

Dr P Boon Lim

Faculty of MedicineNational Heart & Lung Institute

Honorary Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 2115p.b.lim Website

 
 
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Location

 

Cardiology DepartmentBlock B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

108 results found

Handa BS, Li X, Qureshi N, Mann I, Kanagaratnam P, Peters NS, Ng FSet al., 2019, Granger Causality-based analysis to accurately identify specific electrophenotypes of myocardial fibrillation, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 4188-4188, ISSN: 0195-668X

Conference paper

Qureshi N, Kim S, Cantwell C, Afonso V, Bai WJ, Ali R, Shun-Shin M, Louisa M-L, Luther V, Leong K, Lim E, Wright I, Nagy S, Hayat S, Ng FS, Koa-Wing M, Linton N, Lefroy D, Whinnett Z, Davies DW, Kanagaratnam P, Peters N, Lim PBet al., 2019, Voltage during atrial fibrillation is superior to voltage during sinus rhythm in localizing areas of delayed enhancement on magnetic resonance imaging: An assessment of the posterior left atrium in patients with persistent atrial fibrillation, Heart Rhythm, Vol: 16, Pages: 1357-1367, ISSN: 1547-5271

BackgroundBipolar electrogram voltage during sinus rhythm (VSR) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent AF, but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance.ObjectivesWe hypothesized that given adequate temporal sampling, the spatial distribution of mean AF voltage (VmAF) should better correlate with delayed-enhancement MRI (MRI-DE) detected atrial fibrosis than VSR.MethodsAF was mapped (8s) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660±28 points/map). Following cardioversion, VSR was mapped (557±326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients.Results(i) The time course of VmAF was assessed from 1-40 AF-cycles (∼8s) at 1113 locations. VmAF stabilized with sampling >4s (mean voltage error=0.05mV). (ii) Paired point analysis of VmAF from segments acquired 30s apart (3,667-sites, 15-patients), showed strong correlation (r=0.95, p<0.001). (iii) Delayed-enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33±13%. VmAF distributions (median[IQR]) were 0.21[0.14-0.35]mV in DE vs. 0.52[0.34-0.77]mV in Non-DE regions. VSR distributions were 1.34[0.65-2.48]mV in DE vs. 2.37[1.27-3.97]mV in Non-DE. A VmAF threshold of 0.35mV yielded sensitivity/specificity 75%/79% in detecting MRI-DE, compared with 63%/67% for VSR (1.8mV threshold).ConclusionThe correlation between low-voltage and posterior LA MRI-DE is significantly improved when acquired during AF vs. sinus rhythm. With adequate sampling, mean AF voltage is a reproducible marker reflecting the functional response to the underlying persistent AF substrate.

Journal article

Shun-Shin MJ, Leong KMW, Ng FS, Linton NWF, Whinnett ZI, Koa-Wing M, Qureshi N, Lefroy DC, Harding SE, Lim PB, Peters NS, Francis DP, Varnava AM, Kanagaratnam Pet al., 2019, Ventricular conduction stability test: a method to identify and quantify changes in whole heart activation patterns during physiological stress, EP-Europace, Vol: 21, Pages: 1422-1431, ISSN: 1099-5129

AIMS: Abnormal rate adaptation of the action potential is proarrhythmic but is difficult to measure with current electro-anatomical mapping techniques. We developed a method to rapidly quantify spatial discordance in whole heart activation in response to rate cycle length changes. We test the hypothesis that patients with underlying channelopathies or history of aborted sudden cardiac death (SCD) have a reduced capacity to maintain uniform activation following exercise. METHODS AND RESULTS: Electrocardiographical imaging (ECGI) reconstructs >1200 electrograms (EGMs) over the ventricles from a single beat, providing epicardial whole heart activation maps. Thirty-one individuals [11 SCD survivors; 10 Brugada syndrome (BrS) without SCD; and 10 controls] with structurally normal hearts underwent ECGI vest recordings following exercise treadmill. For each patient, we calculated the relative change in EGM local activation times (LATs) between a baseline and post-exertion phase using custom written software. A ventricular conduction stability (V-CoS) score calculated to indicate the percentage of ventricle that showed no significant change in relative LAT (<10 ms). A lower score reflected greater conduction heterogeneity. Mean variability (standard deviation) of V-CoS score over 10 consecutive beats was small (0.9 ± 0.5%), with good inter-operator reproducibility of V-CoS scores. Sudden cardiac death survivors, compared to BrS and controls, had the lowest V-CoS scores post-exertion (P = 0.011) but were no different at baseline (P = 0.50). CONCLUSION: We present a method to rapidly quantify changes in global activation which provides a measure of conduction heterogeneity and proof of concept by demonstrating SCD survivors have a reduced capacity to maintain uniform activation following exercise.

Journal article

Luther V, Agarwal S, Chow A, Koa-Wing M, Cortez-Dias N, Carpinteiro L, de Sousa J, Balasubramaniam R, Farwell D, Jamil-Copley S, Srinivasan N, Abbas H, Mason J, Jones N, Katritsis G, Lim PB, Peters NS, Qureshi N, Whinnett Z, Linton NWF, Kanagaratnam Pet al., 2019, Ripple-AT study: A multicenter and randomized study comparing 3d mapping techniques during atrial tachycardia ablations, Circulation: Arrhythmia and Electrophysiology, Vol: 12, Pages: 1-13, ISSN: 1941-3084

BACKGROUND: Ripple mapping (RM) is an alternative approach to activation mapping of atrial tachycardia (AT) that avoids electrogram annotation. We tested whether RM is superior to conventional annotation based local activation time (LAT) mapping for AT diagnosis in a randomized and multicenter study. METHODS: Patients with AT were randomized to either RM or LAT mapping using the CARTO3v4 CONFIDENSE system. Operators determined the diagnosis using the assigned 3D mapping arm alone, before being permitted a single confirmatory entrainment manuever if needed. A planned ablation lesion set was defined. The primary end point was AT termination with delivery of the planned ablation lesion set. The inability to terminate AT with this first lesion set, the use of more than one entrainment manuever, or the need to crossover to the other mapping arm was defined as failure to achieve the primary end point. RESULTS: One hundred five patients from 7 centers were recruited with 22 patients excluded due to premature AT termination, noninducibility or left atrial appendage thrombus. Eighty-three patients (pts; RM=42, LAT=41) completed mapping and ablation within the 2 groups of similar characteristics (RM versus LAT: prior ablation or cardiac surgery n=35 [83%] versus n=35 [85%], P=0.80). The primary end point occurred in 38/42 pts (90%) in the RM group and 29/41pts (71%) in the LAT group (P=0.045). This was achieved without any entrainment in 31/42 pts (74%) with RM and 18/41 pts (44%) with LAT (P=0.01). Of those patients who failed to achieve the primary end point, AT termination was achieved in 9/12 pts (75%) in the LAT group following crossover to RM with entrainment, but 0/4 pts (0%) in the RM group crossing over to LAT mapping with entrainment (P=0.04). CONCLUSIONS: RM is superior to LAT mapping on the CARTO3v4 CONFIDENSE system in guiding ablation to terminate AT with the first lesion set and with reduced entrainment to assist diagnosis. CLINICAL TRIALS REGISTRATION: https:/

Journal article

Sau A, Howard J, Al-Aidarous S, Ferreira-Martins J, Al-Khayatt B, Lim PB, Kanagaratnam P, Whinnett Z, Peters N, Sikkel M, Francis D, Sohaib SMAet al., 2019, Meta-analysis of randomized controlled trials of atrial fibrillation ablation with pulmonary vein isolation versus without, JACC: Clinical Electrophysiology, Vol: 5, Pages: 968-976, ISSN: 2405-5018

ObjectivesThis meta-analysis examined the ability of pulmonary vein isolation (PVI) to prevent atrial fibrillation in randomized controlled trials (RCTs) in which the patients not receiving PVI nevertheless underwent a procedure.BackgroundPVI is a commonly used procedure for the treatment of atrial fibrillation (AF), and its efficacy has usually been judged against therapy with anti-arrhythmic drugs in open-label trials. There have been several RCTs of AF ablation in which both arms received an ablation, but the difference between the treatment arms was inclusion or omission of PVI. These trials of an ablation strategy with PVI versus an ablation strategy without PVI may provide a more rigorous method for evaluating the efficacy of PVI.MethodsMedline and Cochrane databases were searched for RCTs comparing ablation including PVI with ablation excluding PVI. The primary efficacy endpoint was freedom from atrial fibrillation (AF) and atrial tachycardia at 12 months. A random-effects meta-analysis was performed using the restricted maximum likelihood estimator.ResultsOverall, 6 studies (610 patients) met inclusion criteria. AF recurrence was significantly lower with an ablation including PVI than an ablation without PVI (RR: 0.54; 95% confidence interval [CI]: 0.33 to 0.89; p 1⁄4 0.0147; I2 1⁄4 79.7%). Neither the type of AF (p 1⁄4 0.48) nor the type of non-PVI ablation (p 1⁄4 0.21) was a significant moderator of the effect size. In 3 trials the non-PVI ablation procedure was performed in both arms, whereas PVI was performed in only 1 arm. In these studies, AF recurrence was significantly lower when PVI was included (RR: 0.32; 95% CI: 0.14 to 0.73; p 1⁄4 0.007, I2 78%ConclusionIn RCTs where both arms received an ablation, and therefore an expectation amongst patients and doctors of benefit, being randomized to PVI had a striking effect, reducing AF recurrence by a half.

Journal article

Mann I, Sasikaran T, Sandler B, Babalis D, Johnson N, Falaschetti E, Copley A, Tayebjee M, Todd D, Shepherd E, McCready J, Poulter N, Kanagaratnam Pet al., 2019, Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation (AVATAR-AF): design and rationale, American Heart Journal, Vol: 214, Pages: 36-45, ISSN: 0002-8703

Atrial Fibrillation (AF) ablation using the cryoballoon is effective at reducing symptomatic AF episodes. The prevalence of AF is increasing with the aging population and access to such treatment would be enhanced by reducing the resource requirements. Relinquishing electrical mapping of the pulmonary veins (PV) removes the need for PV catheters, electrical recording equipment and staff trained in using this equipment. Moreover, the majority of complications are peri-procedural so overnight hospitalization maybe unnecessary. We tested this streamlined approach to AF ablation against medical therapy using the endpoint of time to all hospital episodes. METHODS: The AVATAR-AF study is a prospective, multicenter, randomized controlled trial testing the primary hypothesis that AF ablation done without PV mapping or overnight hospitalization is more effective than anti-arrhythmic drugs at reducing all hospital episodes related to recurrent atrial arrhythmias. We included a third arm to test a secondary hypothesis that confirming PV entrance block as per consensus guidelines can improve outcomes. Three hundred twenty-one patients with documented paroxysmal AF will be randomized in a 1:1:1 manner to one of three investigation arms: (1) AVATAR protocol cryoballoon ablation without assessment of acute PV isolation or overnight hospitalization; (2) medical therapy with anti-arrhythmic drugs; or (3) conventional cryoballoon ablation with assessment of acute PV isolation. The primary endpoint is defined as the time to all hospital episodes (including outpatient consultation) related to treatment for atrial arrhythmia. CONCLUSION: The AVATAR-AF study will determine whether the resource utilization for AF ablation can be reduced whilst maintaining superiority over medical therapy.

Journal article

Mann I, Coyle C, Qureshi N, Nagy SZ, Koa-Wing M, Lim PB, Francis DP, Whinnett Z, Peters NS, Kanagaratnam P, Linton NWFet al., 2019, Evaluation of a new algorithm for tracking activation during atrial fibrillation using multipolar catheters in humans, JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Vol: 30, Pages: 1464-1474, ISSN: 1045-3873

Journal article

Keene D, Shun-Shin M, Arnold A, Howard J, Lefroy D, Davies W, Lim PB, Ng FS, Koa-Wing M, Qureshi N, Linton N, Shah J, Peters N, Kanagaratnam P, Francis D, Whinnett Zet al., 2019, Quantification of Electromechanical Coupling to Prevent Inappropriate Implantable Cardioverter-Defibrillator Shocks, JACC: Clinical Electrophysiology, Vol: 5, Pages: 705-715, ISSN: 2405-500X

Objective To test specialised processing of laser Doppler signals for discriminating ventricular fibrillation(VF) from common causes of inappropriate therapies.BackgroundInappropriate ICD therapies remain a clinically important problem associated with morbidity and mortality.Tissue perfusion biomarkers, to assist automated diagnosis of VF, suffer the vulnerability of sometimes mistaking artefact and random noise for perfusion, which could lead to shocks being inappropriately withheld. MethodsWe developed a novel processing algorithm that combines electrogram data and laser Doppler perfusion monitoring, as a method for assessing circulatory status. We recruited 50 patients undergoing VF induction during ICD implantation. We recorded non-invasive laser Doppler and continuous electrograms, during both sinus-rhythm and VF. For each patient we simulated two additional scenarios that may lead to inappropriate shocks: ventricular-lead fracture and T-wave oversensing. We analysed the laser Doppler using three methods for reducing noise: (i)Running Mean, (ii)Oscillatory Height, (iii)a novel quantification of Electro-Mechanical coupling which gates laser Doppler against electrograms. We additionally tested the algorithm during exercise induced sinus tachycardia.ResultsOnly the Electro-mechanical coupling algorithm found a clear perfusion cut-off between sinus rhythm and VF (sensitivity and specificity 100%). Sensitivity and specificity remained 100% during simulated lead fracture and electrogram oversensing. (AUC: Running Mean 0.91, Oscillatory Height 0.86, Electro-Mechanical Coupling 1.00). Sinus tachycardia did not cause false positives.ConclusionsQuantifying the coupling between electrical and perfusion signals increases reliability of discrimination between VF and artefacts that ICDs may interpret as VF. Incorporating such methods into future ICDs may safely permit reductions of inappropriate shocks.

Journal article

Sau A, Howard J, Al-Aidarous S, Martins J, Al-Khayatt B, Lim PB, Kanagaratnam P, Whinnett Z, Peters N, Sikkel M, Francis D, Sohaib SMAet al., 2019, Efficacy of pulmonary vein isolation in preventing atrial fibrillation: meta-analysis of randomized controlled trials with an invasive control procedure, Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ Publishing Group, Pages: A31-A31, ISSN: 1355-6037

Introduction Pulmonary vein isolation (PVI) is a commonly used element in treatment of atrial fibrillation (AF) but has never been tested in an intentionally placebo (sham) controlled trial. Nevertheless there have been several randomized controlled trials (RCTs) in which both arms receive an ablation procedure but the only difference between treatment arms is inclusion or omission of PVI. As long as both doctor and patient have reason to believe that the procedures in both arms are effective, such RCTs could be an effective proxy for placebo controlled trials.Methods Medline and Cochrane databases were searched for RCTs comparing catheter ablation including PVI with left atrial ablation excluding PVI. The primary efficacy endpoint was freedom from AF/atrial tachycardia at 6 months. A random-effects meta-analysis was performed using the restricted maximum likelihood (REML) estimator.Results Overall, seven studies (909 patients) met inclusion criteria. Across the 7 trials, mean age was 57.3, 70.2% of participants were male. In four trials (352 patients) the non-PVI ablation procedure was performed in both arms, while PVI was performed in only one arm. The non-PVI ablation procedures were complex fractionated atrial electrogram ablation (2 studies), ganglionated plexi ablation (1 study) and focal impulse and rotor modulation (1 study). In these, AF recurrence was significantly lower when PVI was included (RR 0.48, 95% CI 0.26-0.90, I2 64.4%)In an analysis of all 7 studies, AF recurrence was significantly lower in ablation with an ablation strategy including PVI compared to one without PVI (Figure 1, RR 0.67, 95% CI 0.53-0.85, p = 0.001, I2 0%). Neither type of AF (persistent vs. paroxysmal, p=0.43) nor type of non-PVI ablation (p=0.35) were significant moderators of the effect size. A sensitivity analysis omitting each study in turn showed similar results to the primary analysis. In particular exclusion of the retracted OASIS trial showed results similar to the primar

Conference paper

Leong KMW, Ng FS, Jones S, Chow J-J, Qureshi N, Koa-Wing M, Linton NWF, Whinnett ZI, Lefroy DC, Davies DW, Lim PB, Peters NS, Kanagaratnam P, Varnava AMet al., 2019, Prevalence of spontaneous type I ECG pattern, syncope, and other risk markers in sudden cardiac arrest survivors with Brugada syndrome, PACE - Pacing and Clinical Electrophysiology, Vol: 42, Pages: 257-264, ISSN: 0147-8389

IntroductionA spontaneous type I electrocardiogram (ECG) pattern and/or unheralded syncope are conventionally used as risk markers for primary prevention of sudden cardiac arrest/death (SCA/SCD) in Brugada syndrome (BrS). In this study, we determine the prevalence of conventional and newer markers of risk in those with and without previous aborted SCA events.MethodsAll patients with BrS were identified at our institute. History of symptoms was obtained from medical tests or from interviews. Other markers of risk were also obtained, such as presence of (1) spontaneous type I pattern, (2) fractionated QRS (fQRS), (3) early repolarization (ER) pattern, (4) late potentials on signal‐averaged ECG (SAECG), and (5) response to programmed electrical stimulation.ResultsIn 133 patients with Bars, 10 (7%) patients (mean age = 39 ± 11 years; nine males) were identified with a previous ventricular fibrillation/ventricular tachycardia episode (n = 8) or requiring cardio‐pulmonary resuscitation (n = 2). None of these patients had a prior history of syncope before their SCA event. Only two (20%) patients reported a history of palpitations or dizziness. None had apneic breathing and three (30%) patients had a family history of SCA. From their ECGs, a spontaneous pattern was only found in one (10%) of these patients. Further, 10% of patients had fQRS, 17% had late potentials on SAECG, 20% had deep S waves in lead I, and 10% had an ER pattern in the peripheral leads. No significant differences were observed in the non‐SCA group.ConclusionThe majority of BrS patients with previous aborted SCA events did not have a spontaneous type I and/or prior history of syncope. Conventional and newer markers of risk appear to only have limited ability to predict SCA.

Journal article

Sutton R, Lim PB, 2019, Cardioneuroablation: Present status as a tenable therapy for vasovagal syncope, TURK KARDIYOLOJI DERNEGI ARSIVI-ARCHIVES OF THE TURKISH SOCIETY OF CARDIOLOGY, Vol: 47, Pages: 1-3, ISSN: 1016-5169

Journal article

Kim M-Y, Sikkel MB, Hunter RJ, Haywood GA, Tomlinson DR, Tayebjee MH, Ali R, Cantwell CD, Gonna H, Sandler B, Limb E, Furniss G, Mrcp DP, Begg G, Dhillon G, Hill NJ, O'Neill J, Francis DP, Lim PB, Peters NS, Linton NWF, Kanagaratnam Pet al., 2018, A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1624-1634, ISSN: 1045-3873

INTRODUCTION: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence AV dissociation. METHODS AND RESULTS: High frequency stimulation was delivered through a Smart-Touch™ catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. 3D locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia or no effect. CARTO™ maps were exported, registered and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated atrioventricular dissociation effects (AVD-GP). There were 10 AVD-GPs (IQR 11.5) per patient. 80% (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups were very similar. Highest probability of AVD-GPs (>20%) were identified in: infero-septal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). CONCLUSION: It is feasible to map the entire left atrium for AVD-GPs prior to AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterise the autonomic network. This article is protected by copyright. All rights reserved.

Journal article

Arnold A, Shun-Shin M, Keene D, Howard J, Sohaib S, wright I, Cole G, Qureshi N, lefroy D, Koa-Wing M, Linton N, Lim P, Peters N, Davies D, muthumala A, Tanner M, ellenbogen K, Kanagaratnam P, Francis D, Whinnett Zet al., 2018, His resynchronization versus biventricular pacing in patients with heart failure and left bundle branch block, Journal of the American College of Cardiology, Vol: 72, Pages: 3112-3122, ISSN: 0735-1097

Background His bundle pacing is a new method for delivering cardiac resynchronization therapy (CRT).Objectives The authors performed a head-to-head, high-precision, acute crossover comparison between His bundle pacing and conventional biventricular CRT, measuring effects on ventricular activation and acute hemodynamic function.Methods Patients with heart failure and left bundle branch block referred for conventional biventricular CRT were recruited. Using noninvasive epicardial electrocardiographic imaging, the authors identified patients in whom His bundle pacing shortened left ventricular activation time. In these patients, the authors compared the hemodynamic effects of His bundle pacing against biventricular pacing using a high-multiple repeated alternation protocol to minimize the effect of noise, as well as comparing effects on ventricular activation.Results In 18 of 23 patients, left ventricular activation time was significantly shortened by His bundle pacing. Seventeen patients had a complete electromechanical dataset. In them, His bundle pacing was more effective at delivering ventricular resynchronization than biventricular pacing: greater reduction in QRS duration (−18.6 ms; 95% confidence interval [CI]: −31.6 to −5.7 ms; p = 0.007), left ventricular activation time (−26 ms; 95% CI: −41 to −21 ms; p = 0.002), and left ventricular dyssynchrony index (−11.2 ms; 95% CI: −16.8 to −5.6 ms; p < 0.001). His bundle pacing also produced a greater acute hemodynamic response (4.6 mm Hg; 95% CI: 0.2 to 9.1 mm Hg; p = 0.04). The incremental activation time reduction with His bundle pacing over biventricular pacing correlated with the incremental hemodynamic improvement with His bundle pacing over biventricular pacing (R = 0.70; p = 0.04).Conclusions His resynchronization delivers better ventricular resynchronization, and greater improvement in hemodynamic parameters, than biventricular pacing.

Journal article

Ferreira-Martins J, Howard J, Al-Khayatt BM, Shalhoub J, Sohaib A, Shun-Shin M, Novak P, Leather R, Sterns L, Lane C, Lim P, Kanagaratnam P, Peters N, Francis D, Sikkel Met al., 2018, Outcomes of paroxysmal AF ablation studies are affected more by study design and patient mix than ablation technique, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1471-1479, ISSN: 1045-3873

Objective: We tested whether ablation methodology and study design can explain the varying outcomes in terms of AF-free survival at 1 year.Background:There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta-regression.Methods: Data was collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta-regression using the individual study arm as the unit.Results: Success rates did not change regardless of the technique used to produce pulmonary vein isolation. Neither were adjunctive lesion sets associated with any improvement in outcome.Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. ECG method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%, p<0.001) or in patients who had implantable loop recorders (by 21%, p=0.006), rather than less thorough periodic Holter monitoring.Conclusions: Outcomes of AF ablation studies involving pulmonary vein isolation are not affected by the technologies used to produce PVI. Neither do adjunctive lesion sets change the outcome. Achieving high success rates in these studies appears to be dependent more on patient mix and on the thoroughness of AF detection protocols. This should be carefully considered when quoting success rates of AF ablation procedures which are derived from such studies.

Journal article

Handa BS, Roney CH, Houston C, Qureshi N, Li X, Pitcher DS, Chowdhury RA, Lim PB, Dupont E, Niederer S, Cantwell C, Peters NS, Ng FSet al., 2018, Analytical approaches for myocardial fibrillation signals, Computers in Biology and Medicine, Vol: 102, Pages: 315-326, ISSN: 0010-4825

Atrial and ventricular fibrillation are complex arrhythmias, and their underlying mechanisms remain widely debated and incompletely understood. This is partly because the electrical signals recorded during myocardial fibrillation are themselves complex and difficult to interpret with simple analytical tools. There are currently a number of analytical approaches to handle fibrillation data. Some of these techniques focus on mapping putative drivers of myocardial fibrillation, such as dominant frequency, organizational index, Shannon entropy and phase mapping. Other techniques focus on mapping the underlying myocardial substrate sustaining fibrillation, such as voltage mapping and complex fractionated electrogram mapping. In this review, we discuss these techniques, their application and their limitations, with reference to our experimental and clinical data. We also describe novel tools including a new algorithm to map microreentrant circuits sustaining fibrillation.

Journal article

Virag N, Erickson M, Taraborrelli P, Vetter R, Lim PB, Sutton Ret al., 2018, Predicting vasovagal syncope from heart rate and blood pressure: A prospective study in 140 subjects, Heart Rhythm, Vol: 15, Pages: 1404-1410, ISSN: 1547-5271

BACKGROUND: We developed a vasovagal syncope (VVS) prediction algorithm for use during head-up tilt with simultaneous analysis of heart rate (HR) and systolic blood pressure (SBP). We previously tested this algorithm retrospectively in 1155 subjects, showing sensitivity 95%, specificity 93% and median prediction time of 59s. OBJECTIVE: This study was prospective, single center, on 140 subjects to evaluate this VVS prediction algorithm and assess if retrospective results were reproduced and clinically relevant. Primary endpoint was VVS prediction: sensitivity and specificity >80%. METHODS: In subjects, referred for 60° head-up tilt (Italian protocol), non-invasive HR and SBP were supplied to the VVS prediction algorithm: simultaneous analysis of RR intervals, SBP trends and their variability represented by low-frequency power generated cumulative risk which was compared with a predetermined VVS risk threshold. When cumulative risk exceeded threshold, an alert was generated. Prediction time was duration between first alert and syncope. RESULTS: Of 140 subjects enrolled, data was usable for 134. Of 83 tilt+ve (61.9%), 81 VVS events were correctly predicted and of 51 tilt-ve subjects (38.1%), 45 were correctly identified as negative by the algorithm. Resulting algorithm performance was sensitivity 97.6%, specificity 88.2%, meeting primary endpoint. Mean VVS prediction time was 2min 26s±3min16s with median 1min 25s. Using only HR and HR variability (without SBP) the mean prediction time reduced to 1min34s±1min45s with median 1min13s. CONCLUSION: The VVS prediction algorithm, is clinically-relevant tool and could offer applications including providing a patient alarm, shortening tilt-test time, or triggering pacing intervention in implantable devices.

Journal article

Kyriacou A, Rajkumar CA, Pabari P, Sohaib SMA, Willson K, Peters N, Lim P, Kanagaratnam P, Hughes A, Mayet J, Whinnett Z, Francis Det al., 2018, Distinct impacts of heart rate and right atrial-pacing on left atrial mechanical activation and optimal AV delay in CRT, Pacing and Clinical Electrophysiology, Vol: 41, Pages: 959-966, ISSN: 0147-8389

AbstractBackgroundControversy exists regarding how atrial activation mode and heart rate affect optimal AV delay in cardiac resynchronisation therapy. We studied these questions using high‐reproducibility haemodynamic and echocardiographic measurements.Methods20 patients were hemodynamically optimized using non‐invasive beat‐to‐beat blood pressure at rest (62±11 bpm), during exercise (80±6 bpm) and at 3 atrially‐paced rates: 5, 25 and 45 bpm above rest, denoted Apaced,r+5, Apaced,r+25 and Apaced,r+45 respectively. Left atrial myocardial motion and transmitral flow were timed echocardiographically.ResultsDuring atrial‐sensing, raising heart rate shortened optimal AV delay by 25±6 ms (p < 0.001). During atrial pacing, raising heart rate from Apaced,r+5 to Apaced,r+25 shortened it by 16±6 ms; Apaced,r+45 shortened it 17±6 ms further (p < 0.001).In comparison to atrial‐sensed activation, atrial pacing lengthened optimal AV delay by 76±6 ms (p < 0.0001) at rest, and at ∼20 bpm faster, by 85±7 ms (p < 0.0001), 9±4 ms more (p = 0.017). Mechanically, atrial pacing delayed left atrial contraction by 63±5 ms at rest and by 73±5 ms (i.e. by 10±5 ms more, p < 0.05) at ∼20 bpm faster.Raising atrial rate by exercise advanced left atrial contraction by 7±2 ms (p = 0.001). Raising it by atrial pacing did not (p = 0.2).ConclusionsHemodynamic optimal AV delay shortens with elevation of heart rate. It lengthens on switching from atrial‐sensed to atrial‐paced at the same rate, and echocardiography shows this sensed‐paced difference in optima results from a sensed‐paced difference in atrial electromechanical delay.The reason for the widening of the sensed‐paced difference in AV optimum may be physiological stimuli (e.g. adrenergic drive) advancing left atrial contraction during exercise but not with fast atrial pacing.

Journal article

Shun-Shin M, Arnold A, Keene D, Howard J, Sohaib A, Lim PB, Tanner M, Lefroy D, Peters N, Kanagaratnam P, Davies DW, Francis D, Whinnett Zet al., 2018, The magnitude of LV activation time reduction with His bundle pacing over biventricular pacing in LBBB predicts the incremental improvement in acute cardiac function, European-Society-of-Cardiology Congress, Publisher: OXFORD UNIV PRESS, Pages: 385-385, ISSN: 0195-668X

Conference paper

Arnold AD, Shun-Shin MJ, Sohaib A, Chiew K, Howard JP, Keene D, Leong K, Ahmad Y, Cole G, Lefroy D, Kanagaratnam P, Varnava A, Francis DP, Whinnett ZIet al., 2018, Automated, high-precision echocardiographic and haemodynamic assessment of the effect of atrioventricular interval during right ventricular pacing in obstructed hypertrophic cardiomyopathy, European-Society-of-Cardiology Congress, Publisher: OXFORD UNIV PRESS, Pages: 729-729, ISSN: 0195-668X

Conference paper

Arnold AD, Shun-Shin MJ, Keene D, Howard J, Lefroy DC, Davies DW, Lim PH, Kanagaratnam P, Koa-Wing M, Wright IJ, Qureshi NA, Tanner MA, Muthumala AG, Linton N, Peters NS, Francis DP, Whinnett ZIet al., 2018, His bundle pacing can overcome left bundle branch block to produce greater improvements in acute haemodynamic function and ventricular activation than biventricular pacing, Heart Rhythm Society Scientific Sessions, Publisher: Elsevier, Pages: S40-S41, ISSN: 1547-5271

Conference paper

Luther V, Qureshi N, Lim PB, Koa-Wing M, Jamil-Copley S, Ng FS, Whinnett Z, Davies DW, Peters NS, Kanagaratnam P, Linton Net al., 2018, Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 404-411, ISSN: 1045-3873

BACKGROUND: Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. METHODS: We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. RESULTS: Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). CONCLUSIONS: The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach.

Journal article

Sau A, Taraborrelli P, Moore P, Lim PBet al., 2018, Cardioinhibitory and vasodepressor responses to different stressors on head-up tilt, EUROPACE, Vol: 20, Pages: 115-115, ISSN: 1099-5129

Journal article

Leong KMW, chow J-J, Ng FS, Falaschetti E, Qureshi N, Koa-Wing M, Linton N, Whinnett Z, Lefroy D, Davies DW, Lim PB, Peters N, Kanagaratnam P, Varnava Aet al., 2017, Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy, American Journal of Cardiology, Vol: 121, Pages: 349-355, ISSN: 0002-9149

Implantable cardio-defibrillators (ICDs) have proven benefit in preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC), making risk stratification essential. Data on the predictive accuracy on the European Society of Cardiology (ESC) risk scoring system has been conflicting. We independently evaluated the ESC risk scoring system in our cohort of HC patients from a large tertiary centre and compared this to previous guidance by the American College of Cardiology Foundation and Heart Association (ACCF/AHA). Risk factor profiles, 5-year SCD risk estimates and ICD recommendations as defined by the ACCF/AHA and ESC guidelines, were retrospectively ascertained for 288 HC patients with and without SCD or equivalent events at our centre. In the SCD group (n=14), a significantly higher proportion of patients would not have met the criteria for an ICD implant using the ESC scoring algorithm than ACCF/AHA guidance (43%vs7%, p=0.029). In those without SCD events (n=274), a larger proportion of individuals not requiring an ICD was identified using the ESC risk score model compared to the ACCF/AHA model (82%vs57%; p<0.0001). Based on risk stratification criteria alone, 5 more individuals with a previously aborted SCD event would not have received an ICD with the ESC risk model than the ACCF/AHA risk model. In conclusion, we found that the current ESC scoring system potentially leaves more high-risk patients unprotected from sudden death in our cohort of patients.

Journal article

Leong KMW, Ng FS, Roney C, Cantwell C, Shun-Shin M, Linton N, Whinnett Z, Lefroy D, Davies DW, Harding S, Lim PB, Francis D, Peters N, Varnava A, Kanagaratnam Pet al., 2017, Repolarization abnormalities unmasked with exercise in sudden cardiac death survivors with structurally normal hearts, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 115-126, ISSN: 1045-3873

BACKGROUND: Models of cardiac arrhythmogenesis predict that non-uniformity in repolarization and/or depolarization promotes ventricular fibrillation and is modulated by autonomic tone, but this is difficult to evaluate in patients. We hypothesize that such spatial heterogeneities would be detected by non-invasive ECG imaging (ECGi) in sudden cardiac death (SCD) survivors with structurally normal hearts under physiological stress. METHODS: ECGi was applied to 11 SCD survivors, 10 low-risk Brugada Syndrome patients (BrS) and 10 controls undergoing exercise treadmill testing. ECGi provides whole heart activation maps and > 1200 unipolar electrograms over the ventricular surface from which global dispersion of activation recovery interval (ARI) and regional delay in conduction were determined. These were used as surrogates for spatial heterogeneities in repolarization and depolarization. Surface ECG markers of dispersion (QT and Tpeak-end intervals) were also calculated for all patients for comparison. RESULTS: Following exertion, the SCD group demonstrated the largest increase in ARI dispersion compared to BrS and control groups (13±8 ms vs 4±7 ms vs 4±5 ms; p = 0.009), with baseline dispersion being similar in all groups. In comparison, surface ECG markers of dispersion of repolarisation were unable to discriminate between the groups at baseline or following exertion. Spatial heterogeneities in conduction were also present following exercise but were not significantly different between SCD survivors and the other groups. CONCLUSION: Increased dispersion of repolarization is apparent during physiological stress in SCD survivors and is detectable with ECGi but not with standard ECG parameters. The electrophysiological substrate revealed by ECGi could be the basis of alternative risk-stratification techniques. This article is protected by copyright. All rights reserved.

Journal article

Su J, Manisty C, Parker KH, Simonsen U, Nielsen-Kudsk JE, Mellemkjaer S, Connolly S, Lim PB, Whinnett ZI, Malik IS, Watson G, Davies JE, Gibbs S, Hughes AD, Howard Let al., 2017, Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension., Journal of the American Heart Association, Vol: 6, ISSN: 2047-9980

BACKGROUND: In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. CONCLUSIONS: Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases.

Journal article

Leong KMW, Ng FS, yao C, Roney C, Linton N, Whinnett Z, lefroy D, Davies DW, Lim PB, Harding S, Peters N, Kanagaratnam P, Varnava Aet al., 2017, ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction Delay in Type I Brugada ECG, Circulation: Arrhythmia and Electrophysiology, Vol: 10, ISSN: 1941-3084

Background: The substrate location and underlying electrophysiological mechanisms that contribute to the characteristic ECG pattern of Brugada syndrome (BrS) are still debated. Using noninvasive electrocardiographical imaging, we studied whole heart conduction and repolarization patterns during ajmaline challenge in BrS individuals.Methods and Results: A total of 13 participants (mean age, 44±12 years; 8 men), 11 concealed patients with type I BrS and 2 healthy controls, underwent an ajmaline infusion with electrocardiographical imaging and ECG recordings. Electrocardiographical imaging activation recovery intervals and activation timings across the right ventricle (RV) body, outflow tract (RVOT), and left ventricle were calculated and analyzed at baseline and when type I BrS pattern manifested after ajmaline infusion. Peak J-ST point elevation was calculated from the surface ECG and compared with the electrocardiographical imaging–derived parameters at the same time point. After ajmaline infusion, the RVOT had the greatest increase in conduction delay (5.4±2.8 versus 2.0±2.8 versus 1.1±1.6 ms; P=0.007) and activation recovery intervals prolongation (69±32 versus 39±29 versus 21±12 ms; P=0.0005) compared with RV or left ventricle. In controls, there was minimal change in J-ST point elevation, conduction delay, or activation recovery intervals at all sites with ajmaline. In patients with BrS, conduction delay in RVOT, but not RV or left ventricle, correlated to the degree of J-ST point elevation (Pearson R, 0.81; P<0.001). No correlation was found between J-ST point elevation and activation recovery intervals prolongation in the RVOT, RV, or left ventricle.Conclusions: Magnitude of ST (J point) elevation in the type I BrS pattern is attributed to degree of conduction delay in the RVOT and not prolongation in repolarization time.

Journal article

Leong KMW, Ng FS, Patil S, Lim PBet al., 2017, An electrocardiogram opinion from an National Health Service walk-in centre, Emergency Medicine Journal, Vol: 34, Pages: 631-632, ISSN: 1472-0205

Journal article

Sau A, Sikkel MB, Luther V, Wright I, Guerrero F, Koa-Wing M, Lefroy D, Linton N, Qureshi N, Whinnett Z, Lim PB, Kanagaratnam P, Peters NS, Davies DWet al., 2017, The sawtooth EKG pattern of typical atrial flutter is not related to slow conduction velocity at the cavotricuspid isthmus., Journal of Cardiovascular Electrophysiology, Vol: 28, Pages: 1445-1453, ISSN: 1045-3873

INTRODUCTION: We hypothesized that very high density mapping of typical atrial flutter (AFL) would facilitate a more complete understanding of its circuit. Such very high density mapping was performed with the Rhythmia mapping system using its 64 electrode basket catheter. METHODS AND RESULTS: Data were acquired from 13 patients in AFL. Functional anatomy of the right atrium (RA) was readily identified during mapping including the Crista Terminalis and Eustachian ridge. The leading edge of the activation wavefront was identified without interruption and its conduction velocity (CV) calculated. CV was not different at the cavotricuspid isthmus (CTI) compared to the remainder of the RA (1.02 vs. 1.03 m/s, p = 0.93). The sawtooth pattern of the surface EKG flutter waves were compared to the position of the dominant wavefront. The downslope of the surface EKG flutter waves represented on average, 73% ± 9% of the total flutter cycle length. During the downslope the activation wavefront travelled significantly further than during the upslope (182 ± 21 ms vs. 68 ± 29 ms, p < 0.0001) with no change in conduction velocity between the two phases (0.88 vs. 0.91 m/s, p = 0.79). CONCLUSION: CV at the CTI is not slower than other RA regions during typical AFL. The gradual downslope of the sawtooth EKG is not due to slow conduction at the CTI suggesting that success of ablation at this site relates to anatomical properties rather than presence of a "slow isthmus". This article is protected by copyright. All rights reserved.

Journal article

Leong KMW, Guerrero F, Lim PB, 2017, Cavotricuspid-Isthmus Dependent Flutter or Left-Sided Atrial Tachycardia?, Journal of Invasive Cardiology, Vol: 29, Pages: E92-E93, ISSN: 1042-3931

A 52-year-old man with previous mitral valve replacement, cavotricuspid isthmus, and left-sided roof-line ablation for previous typical atrial flutter and tachycardia presented with recurrence of symptoms with an atrial tachycardia measuring 260 ms cycle length on electrocardiogram. Rhythmia electroanatomical mapping (Boston Scientific) was performed to understand the mechanism of arrhythmia and to guide ablative treatment.

Journal article

Masoud S, Lim PB, Kitas GD, Panoulas Vet al., 2017, Sudden cardiac death in patients with rheumatoid arthritis, WORLD JOURNAL OF CARDIOLOGY, Vol: 9, Pages: 562-573, ISSN: 1949-8462

Journal article

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