Publications by authors named "Phang Boon Lim"

76 Publications

Tilt testing remains a valuable asset.

Eur Heart J 2021 Feb 24. Epub 2021 Feb 24.

Cardiac Arrhythmia Center, Cardiovascular Division, University of Minnesota, Minneapolis, MN, USA.

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.
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http://dx.doi.org/10.1093/eurheartj/ehab084DOI Listing
February 2021

Electroanatomic Characterization and Ablation of Scar-Related Isthmus Sites Supporting Perimitral Flutter.

JACC Clin Electrophysiol 2021 Jan 20. Epub 2021 Jan 20.

Imperial College Healthcare, London, United Kingdom. Electronic address:

Objectives: The authors reviewed 3-dimensional electroanatomic maps of perimitral flutter to identify scar-related isthmuses and determine their effectiveness as ablation sites.

Background: Perimitral flutter is usually treated by linear ablation between the left lower pulmonary vein and mitral annulus. Conduction block can be difficult to achieve, and recurrences are common.

Methods: Patients undergoing atrial tachycardia ablation using CARTO3 (Biosense Webster Inc., Irvine, California) were screened from 4 centers. Patients with confirmed perimitral flutter were reviewed for the presence of scar-related isthmuses by using CARTO3 with the ConfiDense and Ripple Mapping modules.

Results: Confirmed perimitral flutter was identified in 28 patients (age 65.2 ± 8.1 years), of whom 26 patients had prior atrial fibrillation ablation. Scar-related isthmus ablation was performed in 12 of 28 patients. Perimitral flutter was terminated in all following correct identification of a scar-related isthmus using ripple mapping. The mean scar voltage threshold was 0.11 ± 0.05 mV. The mean width of scar-related isthmuses was 8.9 ± 3.5 mm with a conduction speed of 31.8 ± 5.5 cm/s compared to that of normal left atrium of 71.2 ± 21.5 cm/s (p < 0.0001). Empirical, anatomic ablation was performed in 16 of 28, with termination in 10 of 16 (63%; p = 0.027). Significantly less ablation was required for critical isthmus ablation compared to empirical linear lesions (11.4 ± 5.3 vs. 26.2 ± 17.1 min; p = 0.0004). All 16 cases of anatomic ablation were reviewed with ripple mapping, and 63% had scar-related isthmus.

Conclusions: Perimitral flutter is usually easy to diagnose but can be difficult to ablate. Ripple mapping is highly effective at locating the critical isthmus maintaining the tachycardia and avoiding anatomic ablation lines. This approach has a higher termination rate with less radiofrequency ablation required.
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http://dx.doi.org/10.1016/j.jacep.2020.10.017DOI Listing
January 2021

A New Era in Epicardial Access for the Ablation of Ventricular Arrhythmias: The Epi-Co Registry.

JACC Clin Electrophysiol 2021 01 30;7(1):85-96. Epub 2020 Sep 30.

Sussex Cardiac Centre, Brighton, United Kingdom.

Objectives: This multicenter registry aimed to assess the reproducibility and safety of intentional coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial access in the setting of ventricular tachycardia ablation.

Background: Epicardial ablation for ventricular tachycardia is not a widespread technique due to the significant potential complications associated with subxiphoid puncture. The first experience in 12 patients showed that intentional coronary vein exit and carbon dioxide insufflation was technically feasible.

Methods: A branch of the coronary sinus was cannulated by means of a diagnostic JR4 coronary catheter. Intentional perforation at the distal portion of that branch was performed with a high tip load 0.014-inch angioplasty wire. A microcatheter was advanced over the wire into the pericardial space. Carbon dioxide was then insufflated into the pericardial space, allowing direct visualization of the anterior pericardial space to facilitate subxiphoid puncture.

Results: Intentional coronary vein exit was attempted in 102 consecutive patients in 16 different centers and successfully completed in 101 patients. Significant pericardial adhesions were confirmed in 3 patients, preventing carbon dioxide insufflation and epicardial ablation. None of the punctures were complicated with inadvertent right ventricular puncture or damage to a coronary artery. Significant bleeding (>80 ml) due to coronary vein exit occurred in 5 patients, without hemodynamic compromise. None of the patients required surgery.

Conclusions: Coronary vein exit and carbon dioxide insufflation can be safely and reproducibly achieved to facilitate subxiphoid pericardial access in the setting of ventricular tachycardia ablation.
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http://dx.doi.org/10.1016/j.jacep.2020.07.027DOI Listing
January 2021

Electrocardiographic predictors of successful resynchronization of left bundle branch block by His bundle pacing.

J Cardiovasc Electrophysiol 2021 Feb 4;32(2):428-438. Epub 2021 Jan 4.

National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.

Background: His bundle pacing (HBP) is an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy (CRT) in patients with heart failure and left bundle branch block (LBBB). It is not known whether ventricular activation times and patterns achieved by HBP are equivalent to intact conduction systems and not all patients with LBBB are resynchronized by HBP.

Objective: To compare activation times and patterns of His-CRT with BVP-CRT, LBBB and intact conduction systems.

Methods: In patients with LBBB, noninvasive epicardial mapping (ECG imaging) was performed during BVP and temporary HBP. Intrinsic activation was mapped in all subjects. Left ventricular activation times (LVAT) were measured and epicardial propagation mapping (EPM) was performed, to visualize epicardial wavefronts. Normal activation pattern and a normal LVAT range were determined from normal subjects.

Results: Forty-five patients were included, 24 with LBBB and LV impairment, and 21 with normal 12-lead ECG and LV function. In 87.5% of patients with LBBB, His-CRT successfully shortened LVAT by ≥10 ms. In 33.3%, His-CRT resulted in complete ventricular resynchronization, with activation times and patterns indistinguishable from normal subjects. EPM identified propagation discontinuity artifacts in 83% of patients with LBBB. This was the best predictor of whether successful resynchronization was achieved by HBP (logarithmic odds ratio, 2.19; 95% confidence interval, 0.07-4.31; p = .04).

Conclusion: Noninvasive electrocardiographic mapping appears to identify patients whose LBBB can be resynchronized by HBP. In contrast to BVP, His-CRT may deliver the maximum potential ventricular resynchronization, returning activation times, and patterns to those seen in normal hearts.
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http://dx.doi.org/10.1111/jce.14845DOI Listing
February 2021

Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies.

Clin Med (Lond) 2021 Jan 26;21(1):e63-e67. Epub 2020 Nov 26.

Hammersmith Hospital, London, UK.

The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.
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http://dx.doi.org/10.7861/clinmed.2020-0896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850225PMC
January 2021

Non-invasive detection of exercise-induced cardiac conduction abnormalities in sudden cardiac death survivors in the inherited cardiac conditions.

Europace 2021 Feb;23(2):305-312

Institute of Cardiovascular Science, University College London & Bart's Heart Centre, Bart's Health NHS Trust, London, UK.

Aims : Rate adaptation of the action potential ensures spatial heterogeneities in conduction across the myocardium are minimized at different heart rates providing a protective mechanism against ventricular fibrillation (VF) and sudden cardiac death (SCD), which can be quantified by the ventricular conduction stability (V-CoS) test previously described. We tested the hypothesis that patients with a history of aborted SCD due to an underlying channelopathy or cardiomyopathy have a reduced capacity to maintain uniform activation following exercise.

Methods And Results : Sixty individuals, with (n = 28) and without (n = 32) previous aborted-SCD event underwent electro-cardiographic imaging recordings following exercise treadmill test. These included 25 Brugada syndrome, 13 hypertrophic cardiomyopathy, 12 idiopathic VF, and 10 healthy controls. Data were inputted into the V-CoS programme to calculate a V-CoS score that indicate the percentage of ventricle that showed no significant change in ventricular activation, with a lower score indicating the development of greater conduction heterogeneity. The SCD group, compared to those without, had a lower median (interquartile range) V-CoS score at peak exertion [92.8% (89.8-96.3%) vs. 97.3% (94.9-99.1%); P < 0.01] and 2 min into recovery [95.2% (91.1-97.2%) vs. 98.9% (96.9-99.5%); P < 0.01]. No significant difference was observable later into recovery at 5 or 10 min. Using the lowest median V-CoS scores obtained during the entire recovery period post-exertion, SCD survivors had a significantly lower score than those without for each of the different underlying aetiologies.

Conclusion : Data from this pilot study demonstrate the potential use of this technique in risk stratification for the inherited cardiac conditions.
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http://dx.doi.org/10.1093/europace/euaa248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868885PMC
February 2021

The ectopy-triggering ganglionated plexuses in atrial fibrillation.

Auton Neurosci 2020 11 21;228:102699. Epub 2020 Jul 21.

Myocardial Function Section, NHLI, Imperial College London, UK; Department of Cardiology, Imperial College Healthcare NHS Trust, London, UK; Imperial Centre for Cardiac Engineering, Imperial College London, London, UK. Electronic address:

Background: Epicardial ganglionated plexuses (GP) have an important role in the pathogenesis of atrial fibrillation (AF). The relationship between anatomical, histological and functional effects of GP is not well known. We previously described atrioventricular (AV) dissociating GP (AVD-GP) locations. In this study, we hypothesised that ectopy triggering GP (ET-GP) are upstream triggers of atrial ectopy/AF and have different anatomical distribution to AVD-GP.

Objectives: We mapped and characterised ET-GP to understand their neural mechanism in AF and anatomical distribution in the left atrium (LA).

Methods: 26 patients with paroxysmal AF were recruited. All were paced in the LA with an ablation catheter. High frequency stimulation (HFS) was synchronised to each paced stimulus for delivery within the local atrial refractory period. HFS responses were tagged onto CARTO™ 3D LA geometry. All geometries were transformed onto one reference LA shell. A probability distribution atlas of ET-GP was created. This identified high/low ET-GP probability regions.

Results: 2302 sites were tested with HFS, identifying 579 (25%) ET-GP. 464 ET-GP were characterised, where 74 (16%) triggered ≥30s AF/AT. Median 97 (IQR 55) sites were tested, identifying 19 (20%) ET-GP per patient. >30% of ET-GP were in the roof, mid-anterior wall, around all PV ostia except in the right inferior PV (RIPV) in the posterior wall.

Conclusion: ET-GP can be identified by endocardial stimulation and their anatomical distribution, in contrast to AVD-GP, would be more likely to be affected by wide antral circumferential ablation. This may contribute to AF ablation outcomes.
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http://dx.doi.org/10.1016/j.autneu.2020.102699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511599PMC
November 2020

Anatomical Distribution of Ectopy-Triggering Plexuses in Patients With Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2020 09 27;13(9):e008715. Epub 2020 Jul 27.

Myocardial Function Section, Imperial Centre for Translational and Experimental Medicine (M.-Y.K., B.C.S., M.B.S., C.D.C., F.S.N., N.S.P., P.B.L., N.W.F.L., P.K.), Imperial College London, United Kingdom.

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http://dx.doi.org/10.1161/CIRCEP.120.008715DOI Listing
September 2020

Granger Causality-Based Analysis for Classification of Fibrillation Mechanisms and Localization of Rotational Drivers.

Circ Arrhythm Electrophysiol 2020 03 16;13(3):e008237. Epub 2020 Feb 16.

National Heart & Lung Institute, Imperial College London, United Kingdom (B.S.H., X.L., N.A.Q., I.M., R.A.C., Z.I.W., N.W.F.L., P.B.L., P.K., N.S.P., F.S.N.).

Background: The mechanisms sustaining myocardial fibrillation remain disputed, partly due to a lack of mapping tools that can accurately identify the mechanism with low spatial resolution clinical recordings. Granger causality (GC) analysis, an econometric tool for quantifying causal relationships between complex time-series, was developed as a novel fibrillation mapping tool and adapted to low spatial resolution sequentially acquired data.

Methods: Ventricular fibrillation (VF) optical mapping was performed in Langendorff-perfused Sprague-Dawley rat hearts (n=18), where novel algorithms were developed using GC-based analysis to (1) quantify causal dependence of neighboring signals and plot GC vectors, (2) quantify global organization with the causality pairing index, a measure of neighboring causal signal pairs, and (3) localize rotational drivers (RDs) by quantifying the circular interdependence of neighboring signals with the circular interdependence value. GC-based mapping tools were optimized for low spatial resolution from downsampled optical mapping data, validated against high-resolution phase analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart left ventricular wedge preparations (n=12), and adapted for sequentially acquired intracardiac electrograms during human persistent atrial fibrillation mapping (n=16).

Results: Global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions (50% resolution: =0.006, =0.38, 12.5% resolution, =0.004, =0.41) with a phase analysis derived measure of disorganization, locations occupied by phase singularities. In organized VF with high causality pairing index values, GC vector mapping characterized dominant propagating patterns and localized stable RDs, with the circular interdependence value showing a significant difference in driver versus nondriver regions (0.91±0.05 versus 0.35±0.06, =0.0002). These findings were further confirmed in human VF. In persistent atrial fibrillation, a positive correlation was found between the causality pairing index and presence of stable RDs (=0.0005,=0.56). Fifty percent of patients had RDs, with a low incidence of 0.9±0.3 RDs per patient.

Conclusions: GC-based fibrillation analysis can measure global fibrillation organization, characterize dominant propagating patterns, and map RDs using low spatial resolution sequentially acquired data.
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http://dx.doi.org/10.1161/CIRCEP.119.008237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069398PMC
March 2020

Ripple-AT Study: A Multicenter and Randomized Study Comparing 3D Mapping Techniques During Atrial Tachycardia Ablations.

Circ Arrhythm Electrophysiol 2019 08 9;12(8):e007394. Epub 2019 Aug 9.

Imperial College Healthcare, London (V.L., M.K.-W., G.K., P.B.L., N.S.P., N.Q., Z.W., N.W.F.L., P.K.).

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://www.clinicaltrials.gov. Unique identifier: NCT02451995.
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http://dx.doi.org/10.1161/CIRCEP.118.007394DOI Listing
August 2019

Quantification of Electromechanical Coupling to Prevent Inappropriate Implantable Cardioverter-Defibrillator Shocks.

JACC Clin Electrophysiol 2019 06 27;5(6):705-715. Epub 2019 Mar 27.

Department of Cardiology, Imperial College Hospitals National Health Service Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Objectives: This study sought to test specialized processing of laser Doppler signals for discriminating ventricular fibrillation (VF) from common causes of inappropriate therapies.

Background: Inappropriate implantable cardioverter-defibrillator (ICD) therapies remain a clinically important problem associated with morbidity and mortality. Tissue perfusion biomarkers, implemented to assist automated diagnosis of VF, sometimes mistake artifacts and random noise for perfusion, which could lead to shocks being inappropriately withheld.

Methods: The study tested a novel processing algorithm that combines electrogram data and laser Doppler perfusion monitoring as a method for assessing circulatory status. Fifty patients undergoing VF induction during ICD implantation were recruited. Noninvasive laser Doppler and continuous electrograms were recorded during both sinus rhythm and VF. Two additional scenarios that might have led to inappropriate shocks were simulated for each patient: ventricular lead fracture and T-wave oversensing. The laser Doppler was analyzed using 3 methods for reducing noise: 1) running mean; 2) oscillatory height; and 3) a novel quantification of electromechanical coupling which gates laser Doppler relative to electrograms. In addition, the algorithm was tested during exercise-induced sinus tachycardia.

Results: Only the electromechanical coupling algorithm found a clear perfusion cut off between sinus rhythm and VF (sensitivity and specificity of 100%). Sensitivity and specificity remained at 100% during simulated lead fracture and electrogram oversensing. (Area under the curve running mean: 0.91; oscillatory height: 0.86; electromechanical coupling: 1.00). Sinus tachycardia did not cause false positive results.

Conclusions: Quantifying the coupling between electrical and perfusion signals increases reliability of discrimination between VF and artifacts that ICDs may interpret as VF. Incorporating such methods into future ICDs may safely permit reductions of inappropriate shocks.
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http://dx.doi.org/10.1016/j.jacep.2019.01.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597902PMC
June 2019

Evaluation of a new algorithm for tracking activation during atrial fibrillation using multipolar catheters in humans.

J Cardiovasc Electrophysiol 2019 09 2;30(9):1464-1474. Epub 2019 Jul 2.

Department of Bioengineering, Imperial College London, London, UK.

Background: Conventional mapping techniques during atrial fibrillation (AF) are difficult to apply because of cycle length irregularity. Mapping studies are usually restricted to short durations of AF in limited regions because of the laborious manual annotation of local activation time (LAT). The purpose of this study was to test an automated algorithm to map activation during AF, with comparable accuracy to manual annotation.

Methods: Left atrial (LA) mapping was performed using a 20-pole double loop catheter (AFocusII) in 30-second data segments from 16 patients. The new algorithm (RETRO-Mapping) was designed to detect wavefront propagation between electrodes, and display activating wavefronts on a two-dimensional representation of the catheter. Activation patterns were validated against their bipolar electrograms and with isochronal maps. The mapping protocol was approved by the research ethics committee (13/LO1169 and 14/LO1367).

Results: During AF, uniform wavefront activation direction (mean ± SD, degrees) from manually constructed isochronal maps was comparable to RETRO-Propagation Map (RETRO-PM) and RETRO-Automated Direction (RETRO-AD): 1 ± 6.9 for RETRO-PM; and 2 ± 6.6 for RETRO-AD. There was no significant difference in activation direction assigned to 1373 uniform wavefronts during AF when comparing RETRO-PM with RETRO-AD (Bland-Altman mean difference: -0.1 degrees; limits of agreement: -8.0 to 8.3; 95% CI -0.4 to 0.2; (r = 0.01) R2 = < 0.005; P = .77).

Conclusion: We have developed and validated a new technique to map activation during AF. This technique shows comparable accuracy to that of conventional isochronal mapping with careful manual adjustment of LAT.
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http://dx.doi.org/10.1111/jce.14033DOI Listing
September 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 2019 09 3;16(9):1357-1367. Epub 2019 Jun 3.

Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom. Electronic address:

Background: Bipolar electrogram voltage during sinus rhythm (V) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent atrial fibrillation (AF), but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance.

Objective: The purpose of this study was determine whether, given adequate temporal sampling, the spatial distribution of mean AF voltage (V) better correlates with delayed-enhancement magnetic resonance imaging (MRI-DE)-detected atrial fibrosis than V.

Methods: AF was mapped (8 seconds) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660 ± 28 points/map). After cardioversion, V was mapped (557 ± 326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients.

Results: The time course of V was assessed from 1-40 AF cycles (∼8 seconds) at 1113 locations. V stabilized with sampling >4 seconds (mean voltage error 0.05 mV). Paired point analysis of V from segments acquired 30 seconds apart (3667 sites; 15 patients) showed strong correlation (r = 0.95; P <.001). Delayed enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33% ± 13%. V distributions were (median [IQR]) 0.21 [0.14-0.35] mV in DE vs 0.52 [0.34-0.77] mV in non-DE regions. V distributions were 1.34 [0.65-2.48] mV in DE vs 2.37 [1.27-3.97] mV in non-DE. V threshold of 0.35 mV yielded sensitivity of 75% and specificity of 79% in detecting MRI-DE compared with 63% and 67%, respectively, for V (1.8-mV threshold) CONCLUSION: The 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.
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http://dx.doi.org/10.1016/j.hrthm.2019.05.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722483PMC
September 2019

Ventricular conduction stability test: a method to identify and quantify changes in whole heart activation patterns during physiological stress.

Europace 2019 Sep;21(9):1422-1431

National Heart & Lung Institute, Imperial College London, London, UK.

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.
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http://dx.doi.org/10.1093/europace/euz015DOI Listing
September 2019

Cardioneuroablation: Present status as a tenable therapy for vasovagal syncope.

Turk Kardiyol Dern Ars 2019 01;47(1):1-3

Department of Cardiology, National Heart and Lung Institute, Imperial College, Hammersmith Hospital, London, UK.

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http://dx.doi.org/10.5543/tkda.2018.96898DOI Listing
January 2019

Prevalence of spontaneous type I ECG pattern, syncope, and other risk markers in sudden cardiac arrest survivors with Brugada syndrome.

Pacing Clin Electrophysiol 2019 02 6;42(2):257-264. Epub 2019 Jan 6.

Imperial College Healthcare NHS Trust, London, UK.

Introduction: A 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.

Methods: All 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.

Results: In 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.

Conclusion: The 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.
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http://dx.doi.org/10.1111/pace.13587DOI Listing
February 2019

His Resynchronization Versus Biventricular Pacing in Patients With Heart Failure and Left Bundle Branch Block.

J Am Coll Cardiol 2018 12;72(24):3112-3122

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

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.
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http://dx.doi.org/10.1016/j.jacc.2018.09.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290113PMC
December 2018

Outcomes of paroxysmal atrial fibrillation ablation studies are affected more by study design and patient mix than ablation technique.

J Cardiovasc Electrophysiol 2018 11 30;29(11):1471-1479. Epub 2018 Oct 30.

Department of Medicine, Royal Jubilee Hospital, Victoria, Canada.

Objective: We tested whether ablation methodology and study design can explain the varying outcomes in terms of atrial fibrillation (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 were 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 (PVI). Neither was 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. The electrocardiography 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 those with the less thorough periodic Holter monitoring.

Conclusions: Outcomes of AF ablation studies involving PVI 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. These should be carefully considered when quoting the success rates of AF ablation procedures that are derived from such studies.
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http://dx.doi.org/10.1111/jce.13745DOI Listing
November 2018

A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas.

J Cardiovasc Electrophysiol 2018 12 5;29(12):1624-1634. Epub 2018 Oct 5.

Myocardial Function Section, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, UK.

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 atrioventricular (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. Three dimensional 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 (AVD-GP) effects. There were 10 AVD-GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD-GPs (>20%) was identified in: inferoseptal 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 before 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 characterize the autonomic network.
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http://dx.doi.org/10.1111/jce.13723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369684PMC
December 2018

Analytical approaches for myocardial fibrillation signals.

Comput Biol Med 2018 11 17;102:315-326. Epub 2018 Jul 17.

ElectroCardioMaths, Imperial Centre for Cardiac Engineering, National Heart & Lung Institute, Imperial College London, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.compbiomed.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215772PMC
November 2018

High-Density Electroanatomical Mapping to Identify Point of Epicardial to Endocardial Breakthrough in Perimitral Flutter.

JACC Clin Electrophysiol 2017 06 1;3(6):637-639. Epub 2017 Feb 1.

Myocardial Function Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Electrophysiology, Imperial College Healthcare National Health Service Trust, Hammersmith Hospital, London, United Kingdom.

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http://dx.doi.org/10.1016/j.jacep.2016.11.007DOI Listing
June 2017

Predicting vasovagal syncope from heart rate and blood pressure: A prospective study in 140 subjects.

Heart Rhythm 2018 09 30;15(9):1404-1410. Epub 2018 Apr 30.

Imperial Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom; National Heart & Lung Institute, Imperial College, London, United Kingdom.

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 59 seconds.

Objective: The purpose of this prospective, single-center study of 140 subjects was to evaluate this VVS prediction algorithm and to assess whether retrospective results were reproduced and clinically relevant. The primary endpoint was VVS prediction: sensitivity and specificity >80%.

Methods: In subjects referred for 60° head-up tilt (Italian protocol), noninvasive 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 the 140 subjects enrolled, data were usable for 134. Of 83 tilt-positive subjects (61.9%), 81 VVS events were correctly predicted by the algorithm, and of 51 tilt-negative subjects (38.1%), 45 were correctly identified as negative by the algorithm. Resulting algorithm performance was sensitivity 97.6% and specificity 88.2%, meeting the primary endpoint. Mean VVS prediction time was 2 minutes 26 seconds ± 3 minutes 16 seconds (median 1 minute 25 seconds). Using only HR and HR variability (without SBP), mean prediction time reduced to 1 minute 34 seconds ± 1 minute 45 seconds (median 1 minute 13 seconds).

Conclusion: The VVS prediction algorithm is a clinically relevant tool and could offer applications, including providing a patient alarm, shortening tilt-test time, and triggering pacing intervention in implantable devices.
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http://dx.doi.org/10.1016/j.hrthm.2018.04.032DOI Listing
September 2018

Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?

J Cardiovasc Electrophysiol 2018 03 1;29(3):404-411. Epub 2018 Feb 1.

Imperial College Healthcare, London, UK.

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.
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http://dx.doi.org/10.1111/jce.13425DOI Listing
March 2018

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.

Am J Cardiol 2018 02 7;121(3):349-355. Epub 2017 Nov 7.

Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:

Implantable cardiodefibrillators (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 have been conflicting. We independently evaluated the ESC risk scoring system in our cohort of patients with HC from a large tertiary center and compared this with 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 center. 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 compared with ACCF/AHA guidance (43% vs 7%, 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 with the ACCF/AHA model (82% vs 57%; 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 compared with 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.
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http://dx.doi.org/10.1016/j.amjcard.2017.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812921PMC
February 2018

Repolarization abnormalities unmasked with exercise in sudden cardiac death survivors with structurally normal hearts.

J Cardiovasc Electrophysiol 2018 01 7;29(1):115-126. Epub 2017 Dec 7.

National Heart & Lung Institute, Imperial College London, London, UK.

Background: Models of cardiac arrhythmogenesis predict that nonuniformity 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 noninvasive 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 >1,200 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 repolarization 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.
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http://dx.doi.org/10.1111/jce.13375DOI Listing
January 2018

ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction Delay in Type I Brugada ECG.

Circ Arrhythm Electrophysiol 2017 Oct;10(10)

From the National Heart and Lung Institute, Imperial College London, United Kingdom (K.M.W.L., F.S.N., C.R., N.W.F.L., Z.I.W., P.B.L., S.E.H., N.S.P., P.K.); Imperial College Healthcare NHS Trust, London, United Kingdom (K.M.W.L., F.S.N., P.T., N.W.F.L., Z.I.W., D.C.L., D.W.D., P.B.L., N.S.P., P.K., A.M.V.); and Medtronic Ltd, Watford, United Kingdom (C.Y.).

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; =0.007) and activation recovery intervals prolongation (69±32 versus 39±29 versus 21±12 ms; =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 , 0.81; <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.
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http://dx.doi.org/10.1161/CIRCEP.117.005107DOI Listing
October 2017

The sawtooth EKG pattern of typical atrial flutter is not related to slow conduction velocity at the cavotricuspid isthmus.

J Cardiovasc Electrophysiol 2017 Dec 14;28(12):1445-1453. Epub 2017 Sep 14.

Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, UK.

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 (Boston Scientific) 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) was 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 electrocardiogram (EKG) flutter waves was 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 traveled significantly further than during the upslope (182 ± 21 milliseconds vs. 68 ± 29 milliseconds, P < 0.0001) with no change in CV 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 the presence of a "slow isthmus."
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http://dx.doi.org/10.1111/jce.13323DOI Listing
December 2017

An electrocardiogram opinion from an National Health Service walk-in centre.

Emerg Med J 2017 Sep;34(9):620

Imperial College Healthcare NHS Trust, London, UK.

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http://dx.doi.org/10.1136/emermed-2016-206406DOI Listing
September 2017

Sudden cardiac death in patients with rheumatoid arthritis.

World J Cardiol 2017 Jul;9(7):562-573

Sherry Masoud, Phang Boon Lim, Cardiology Department, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W1 20HS, United Kingdom.

An increased cardiovascular morbidity and mortality, including the risk of sudden cardiac death (SCD), has been shown in patients with rheumatoid arthritis (RA). Abnormalities in autonomic markers such as heart rate variability and ventricular repolarization parameters, such as QTc interval and QT dispersion, have been associated with sudden death in patients with RA. The interplay between these parameters and inflammation that is known to exist with RA is of growing interest. In this article, we review the prevalence and predictors of SCD in patients with RA and describe the potential underlying mechanisms, which may contribute to this. We also review the impact of biologic agents on arrhythmic risk as well as cardiovascular morbidity and mortality.
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http://dx.doi.org/10.4330/wjc.v9.i7.562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545140PMC
July 2017