Publications by authors named "Prapa Kanagaratnam"

119 Publications

Size matters in atrial fibrillation: the underestimated importance of reduction of contiguous electrical mass underlying the effectiveness of catheter ablation.

Europace 2021 May 5. Epub 2021 May 5.

Division of Cardiology, University of British Columbia, 740 Hillside Ave, Vancouver, BC V8T 1Z4, Canada.

Evidence has accumulated over the last century of the importance of a critical electrical mass in sustaining atrial fibrillation (AF). AF ablation certainly reduces electrically contiguous atrial mass, but this is not widely accepted to be an important part of its mechanism of action. In this article, we review data showing that atrial size is correlated in many settings with AF propensity. Larger mammals are more likely to exhibit AF. This is seen both in the natural world and in animal models, where it is much easier to create a goat model than a mouse model of AF, for example. This also extends to humans-athletes, taller people, and obese individuals all have large atria and are more likely to exhibit AF. Within an individual, risk factors such as hypertension, valvular disease and ischaemia can enlarge the atrium and increase the risk of AF. With respect to AF ablation, we explore how variations in ablation strategy and the relative effectiveness of these strategies may suggest that a reduction in electrical atrial mass is an important mechanism of action. We counter this with examples in which there is no doubt that mass reduction is less important than competing theories such as ganglionated plexus ablation. We conclude that, when considering future strategies for the ablative therapy of AF, it is important not to discount the possibility that contiguous electrical mass reduction is the most important mechanism despite the disappointing consequence being that enhancing success rates in AF ablation may involve greater tissue destruction.
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http://dx.doi.org/10.1093/europace/euab078DOI Listing
May 2021

COVID-19 and its impact on the cardiovascular system.

Open Heart 2021 03;8(1)

Cardiology, Imperial College Healthcare NHS Trust, London, UK.

Objectives: The clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK.

Methods: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention.

Results: Mean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.

Conclusion: Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.
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http://dx.doi.org/10.1136/openhrt-2020-001472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969760PMC
March 2021

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

Eur Heart J 2021 Feb 18. Epub 2021 Feb 18.

Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK.

Background: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.

Methods And Results: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).

Conclusions: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.
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http://dx.doi.org/10.1093/eurheartj/ehab075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928984PMC
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

Targeting the ectopy-triggering ganglionated plexuses without pulmonary vein isolation prevents atrial fibrillation.

J Cardiovasc Electrophysiol 2021 Feb 19;32(2):235-244. Epub 2021 Jan 19.

Myocardial Function Section, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Ganglionated plexuses (GPs) are implicated in atrial fibrillation (AF). Endocardial high-frequency stimulation (HFS) delivered within the local atrial refractory period can trigger ectopy and AF from specific GP sites (ET-GP). The aim of this study was to understand the role of ET-GP ablation in the treatment of AF.

Methods: Patients with paroxysmal AF indicated for ablation were recruited. HFS mapping was performed globally around the left atrium to identify ET-GP. ET-GP was defined as atrial ectopy or atrial arrhythmia triggered by HFS. All ET-GP were ablated, and PVs were left electrically connected. Outcomes were compared with a control group receiving pulmonary vein isolation (PVI). Patients were followed-up for 12 months with multiple 48-h Holter ECGs. Primary endpoint was ≥30 s AF/atrial tachycardia in ECGs.

Results: In total, 67 patients were recruited and randomized to ET-GP ablation (n = 39) or PVI (n = 28). In the ET-GP ablation group, 103 ± 28 HFS sites were tested per patient, identifying 21 ± 10 (20%) GPs. ET-GP ablation used 23.3 ± 4.1 kWs total radiofrequency (RF) energy per patient, compared with 55.7 ± 22.7 kWs in PVI (p = <.0001). Duration of procedure was 3.7 ± 1.0 and 3.3 ± 0.7 h in ET-GP ablation group and PVI, respectively (p = .07). Follow-up at 12 months showed that 61% and 49% were free from ≥30 s of AF/AT with PVI and ET-GP ablation respectively (log-rank p = .27).

Conclusions: It is feasible to perform detailed global functional mapping with HFS and ablate ET-GP to prevent AF. This provides direct evidence that ET-GPs are part of the AF mechanism. The lower RF requirement implies that ET-GP targets the AF pathway more specifically.
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http://dx.doi.org/10.1111/jce.14870DOI Listing
February 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

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

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.

BMJ Open 2020 10 5;10(10):e044566. Epub 2020 Oct 5.

Department of Medicine, University of Cambridge, Cambridge, UK

Objectives: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics.

Design: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials.

Setting: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit.

Participants: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included.

Main Outcome Measures: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers.

Results: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials.

Conclusions: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.
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http://dx.doi.org/10.1136/bmjopen-2020-044566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536634PMC
October 2020

Within-patient comparison of His-bundle pacing, right ventricular pacing, and right ventricular pacing avoidance algorithms in patients with PR prolongation: Acute hemodynamic study.

J Cardiovasc Electrophysiol 2020 11 5;31(11):2964-2974. Epub 2020 Oct 5.

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

Aims: A prolonged PR interval may adversely affect ventricular filling and, therefore, cardiac function. AV delay can be corrected using right ventricular pacing (RVP), but this induces ventricular dyssynchrony, itself harmful. Therefore, in intermittent heart block, pacing avoidance algorithms are often implemented. We tested His-bundle pacing (HBP) as an alternative.

Methods: Outpatients with a long PR interval (>200 ms) and intermittent need for ventricular pacing were recruited. We measured within-patient differences in high-precision hemodynamics between AV-optimized RVP and HBP, as well as a pacing avoidance algorithm (Managed Ventricular Pacing [MVP]).

Results: We recruited 18 patients. Mean left ventricular ejection fraction was 44.3 ± 9%. Mean intrinsic PR interval was 266 ± 42 ms and QRS duration was 123 ± 29 ms. RVP lengthened QRS duration (+54 ms, 95% CI 42-67 ms, p < .0001) while HBP delivered a shorter QRS duration than RVP (-56 ms, 95% CI -67 to -46 ms, p < .0001). HBP did not increase QRS duration (-2 ms, 95% CI -8 to 13 ms, p = .6). HBP improved acute systolic blood pressure by mean of 5.0 mmHg (95% CI 2.8-7.1 mmHg, p < .0001) compared to RVP and by 3.5 mmHg (95% CI 1.9-5.0 mmHg, p = .0002) compared to the pacing avoidance algorithm. There was no significant difference in hemodynamics between RVP and ventricular pacing avoidance (p = .055).

Conclusions: HBP provides better acute cardiac function than pacing avoidance algorithms and RVP, in patients with prolonged PR intervals. HBP allows normalization of prolonged AV delays (unlike pacing avoidance) and does not cause ventricular dyssynchrony (unlike RVP). Clinical trials may be justified to assess whether these acute improvements translate into longer term clinical benefits in patients with bradycardia indications for pacing.
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http://dx.doi.org/10.1111/jce.14763DOI Listing
November 2020

Discriminating electrocardiographic responses to His-bundle pacing using machine learning.

Cardiovasc Digit Health J 2020 Jul-Aug;1(1):11-20

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

Background: His-bundle pacing (HBP) has emerged as an alternative to conventional ventricular pacing because of its ability to deliver physiological ventricular activation. Pacing at the His bundle produces different electrocardiographic (ECG) responses: selective His-bundle pacing (S-HBP), non-selective His bundle pacing (NS-HBP), and myocardium-only capture (MOC). These 3 capture types must be distinguished from each other, which can be challenging and time-consuming even for experts.

Objective: The purpose of this study was to use artificial intelligence (AI) in the form of supervised machine learning using a convolutional neural network (CNN) to automate HBP ECG interpretation.

Methods: We identified patients who had undergone HBP and extracted raw 12-lead ECG data during S-HBP, NS-HBP, and MOC. A CNN was trained, using 3-fold cross-validation, on 75% of the segmented QRS complexes labeled with their capture type. The remaining 25% was kept aside as a testing dataset.

Results: The CNN was trained with 1297 QRS complexes from 59 patients. Cohen kappa for the neural network's performance on the 17-patient testing set was 0.59 (95% confidence interval 0.30 to 0.88; <.0001), with an overall accuracy of 75%. The CNN's accuracy in the 17-patient testing set was 67% for S-HBP, 71% for NS-HBP, and 84% for MOC.

Conclusion: We demonstrated proof of concept that a neural network can be trained to automate discrimination between HBP ECG responses. When a larger dataset is trained to higher accuracy, automated AI ECG analysis could facilitate HBP implantation and follow-up and prevent complications resulting from incorrect HBP ECG analysis.
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http://dx.doi.org/10.1016/j.cvdhj.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484933PMC
September 2020

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

Meta-Analysis of Randomized Controlled Trials of Atrial Fibrillation Ablation With Pulmonary Vein Isolation Versus Without.

JACC Clin Electrophysiol 2019 08 31;5(8):968-976. Epub 2019 Jul 31.

National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Cardiac Electrophysiology, Bart's Heart Centre, St Bartholomew's Hospital, London, United Kingdom; Department of Cardiology, King George Hospital, Ilford, United Kingdom. Electronic address:

Objectives: This 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.

Background: PVI 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.

Methods: Medline 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.

Results: Overall, 6 studies (n = 610) 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 = 0.0147; I = 79.7%). Neither the type of AF (p = 0.48) nor the type of non-PVI ablation (p = 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 = 0.007, I 78%).

Conclusions: In 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.
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http://dx.doi.org/10.1016/j.jacep.2019.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709782PMC
August 2019

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

Ablation versus Anti-Arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent Atrial Fibrillation (AVATAR-AF): Design and rationale.

Am Heart J 2019 08 3;214:36-45. Epub 2019 May 3.

Imperial College London, London, UK; Imperial College Healthcare NHS Trust, London, UK. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ahj.2019.04.015DOI Listing
August 2019

Optimum lesion set and predictors of outcome in persistent atrial fibrillation ablation: a meta-regression analysis.

Europace 2019 Aug;21(8):1176-1184

International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, UK.

Aims: Ablation of persistent atrial fibrillation (PsAF) has been performed by many techniques with varying success rates. This may be due to ablation techniques, patient demographics, comorbidities, and trial design. We conducted a meta-regression of studies of PsAF ablation to elucidate the factors affecting atrial fibrillation (AF) recurrence.

Methods And Results : Databases were searched for prospective studies of PsAF ablation. A meta-regression was performed. Fifty-eight studies (6767 patients) were included. Complex fractionated atrial electrogram (CFAE) ablation reduced freedom from AF by 8.9% [95% confidence interval (CI) -15 to -2.3, P = 0.009). Left atrial appendage [LAA isolation (three study arms)] increased freedom from AF by 39.5% (95% CI 9.1-78.4, P = 0.008). Posterior wall isolation (PWI) (eight study arms) increased freedom from AF by 19.4% (95% CI 3.3-38.1, P = 0.017). Linear ablation or ganglionated plexi ablation resulted in no significant effect on freedom from AF. More extensive ablation increased intraprocedural AF termination; however, intraprocedural AF termination was not associated with improved outcomes. Increased left atrial diameter was associated with a reduction in freedom from AF by 4% (95% CI -6.8% to -1.1%, P = 0.007) for every 1 mm increase in diameter.

Conclusion : Linear ablation, PWI, and CFAE ablation improves intraprocedural AF termination, but such termination does not predict better long-term outcomes. Study arms including PWI or LAA isolation in the lesion set were associated with improved outcomes in terms of freedom from AF; however, further randomized trials are required before these can be routinely recommended. Left atrial size is the most important marker of AF chronicity influencing outcomes.
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http://dx.doi.org/10.1093/europace/euz108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680367PMC
August 2019

Left atrial appendage occlusion for stroke despite oral anticoagulation (resistant stroke). Results from the Amplatzer Cardiac Plug registry.

Rev Esp Cardiol (Engl Ed) 2020 Jan 27;73(1):28-34. Epub 2019 Apr 27.

Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece.

Introduction And Objectives: Despite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment.

Methods: We analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications.

Results: A total of 115 patients (11%) with RS were identified. The CHADS-VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5±1.5 vs 4.3±1.6; P <.001; 3.9±1.3 vs 3.1±1.2; P <.001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P=.1). With a mean clinical follow-up of 16.2±12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction).

Conclusions: Patients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients.
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http://dx.doi.org/10.1016/j.rec.2019.02.013DOI Listing
January 2020

Multicentre randomised trial comparing contact force with electrical coupling index in atrial flutter ablation (VERISMART trial).

PLoS One 2019 3;14(4):e0212903. Epub 2019 Apr 3.

Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Leeds, United Kingdom.

Introduction: Electrical coupling index (ECI) and contact force (CF) have been developed to aid lesion formation during catheter ablation. ECI measures tissue impedance and capacitance whilst CF measures direct contact. The aim was to determine whether the presence of catheter / tissue interaction information, such as ECI and CF, reduce time to achieve bidirectional cavotricuspid isthmus block during atrial flutter (AFL) ablation.

Methods: Patients with paroxysmal or persistent AFL were randomised to CF visible (range 5-40g), CF not visible, ECI visible (change of 12%) or ECI not visible. Follow-up occurred at 3 and 6 months and included a 7 day ECG recording. The primary endpoint was time to bidirectional cavotricuspid isthmus block.

Results: 114 patients were randomised, 16 were excluded. Time to bidirectional block was significantly shorter when ECI was visible (median 30.0 mins (IQR 31) to median 10.5mins (IQR 12) p 0.023) versus ECI not visible. There was a trend towards a shorter time to bidirectional block when CF was visible. Higher force was applied when CF was visible (median 9.03g (IQR 7.4) vs. 11.3g (5.5) p 0.017). There was no difference in the acute recurrence of conduction between groups. The complication rate was 2%, AFL recurrence was 1.1% and at 6 month follow-up, 12% had atrial fibrillation.

Conclusion: The use of tissue contact information during AFL ablation was associated with reduced time taken to achieve bidirectional block when ECI was visible. Contact force data improved contact when visible with a trend towards a reduction in the procedural endpoint. ClinicalTrials.gov trial identifier: NCT02490033.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212903PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447159PMC
December 2019

Improving haemodynamic optimization of cardiac resynchronization therapy for heart failure.

Physiol Meas 2019 05 1;40(4):04NT01. Epub 2019 May 1.

Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Hills Rd, Cambridge CB2 0QQ, United Kingdom.

Objective: Optimization of cardiac resynchronization therapy using non-invasive haemodynamic parameters produces reliable optima when performed at high atrial paced heart rates. Here we investigate whether this is a result of increased heart rate or atrial pacing itself.

Approach: Forty-three patients with cardiac resynchronization therapy underwent haemodynamic optimization of atrioventricular (AV) delay using non-invasive beat-to-beat systolic blood pressure in three states: rest (atrial-sensing, 66  ±  11 bpm), slow atrial pacing (73  ±  12 bpm), and fast atrial pacing (94  ±  10 bpm). A 20-patient subset underwent a fourth optimization, during exercise (80  ±  11 bpm).

Main Results: Intraclass correlation coefficient (ICC, quantifying information content mean  ±SE) was 0.20  ±  0.02 for resting sensed optimization, 0.45  ±  0.03 for slow atrial pacing (p   <  0.0001 versus rest-sensed), and 0.52  ±  0.03 for fast atrial pacing (p   =  0.12 versus slow-paced). 78% of the increase in ICC, from sinus rhythm to fast atrial pacing, is achieved by simply atrially pacing just above sinus rate. Atrial pacing increased signal (blood pressure difference between best and worst AV delay) from 6.5  ±  0.6 mmHg at rest to 13.3  ±  1.1 mmHg during slow atrial pacing (p   <  0.0001) and 17.2  ±  1.3 mmHg during fast atrial pacing (p   =  0.003 versus slow atrial pacing). Atrial pacing reduced noise (average SD of systolic blood pressure measurements) from 4.9  ±  0.4 mmHg at rest to 4.1  ±  0.3 mmHg during slow atrial pacing (p   =  0.28). At faster atrial pacing the noise was 4.6  ±  0.3 mmHg (p   =  0.69 versus slow-paced, p   =  0.90 versus rest-sensed). In the exercise subgroup ICC was 0.14  ±  0.02 (p   =  0.97 versus rest-sensed).

Significance: Atrial pacing, rather than the increase in heart rate, contributes to ~80% of the observed information content improvement from sinus rhythm to fast atrial pacing. This is predominantly through increase in measured signal.
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http://dx.doi.org/10.1088/1361-6579/ab152cDOI Listing
May 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

Right ventricular pacing for hypertrophic obstructive cardiomyopathy: meta-analysis and meta-regression of clinical trials.

Eur Heart J Qual Care Clin Outcomes 2019 10;5(4):321-333

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

Aims: Right ventricular pacing for left ventricular outflow tract gradient reduction in hypertrophic obstructive cardiomyopathy remains controversial. We undertook a meta-analysis for echocardiographic and functional outcomes.

Methods And Results: Thirty-four studies comprising 1135 patients met eligibility criteria. In the four blinded randomized controlled trials (RCTs), pacing reduced gradient by 35% [95% confidence interval (CI) 23.2-46.9, P < 0.0001], but there was only a trend towards improved New York Heart Association (NYHA) class [odds ratio (OR) 1.82, CI 0.96-3.44; P = 0.066]. The unblinded observational studies reported a 54.3% (CI 44.1-64.6, P < 0.0001) reduction in gradient, which was a 18.6% greater reduction than the RCTs (P = 0.0351 for difference between study designs). Observational studies reported an effect on unblinded NYHA class at an OR of 8.39 (CI 4.39-16.04, P < 0.0001), 450% larger than the OR in RCTs (P = 0.0042 for difference between study designs). Across all studies, the gradient progressively decreased at longer follow durations, by 5.2% per month (CI 2.5-7.9, P = 0.0001).

Conclusion: Right ventricular pacing reduces gradient in blinded RCTs. There is a non-significant trend to reduction in NYHA class. The bias in assessment of NYHA class in observational studies appears to be more than twice as large as any genuine treatment effect.
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http://dx.doi.org/10.1093/ehjqcco/qcz006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775860PMC
October 2019

Arrhythmia Mechanisms Revealed by Ripple Mapping.

Arrhythm Electrophysiol Rev 2018 Dec;7(4):261-264

Department of Bioengineering, Imperial College London UK.

Ripple mapping is a novel method of 3D intracardiac electrogram visualisation that allows activation of the myocardium to be tracked visually without prior assignment of local activation times and without interpolation into unmapped regions. It assists in the identification of tachycardia mechanism and optimal ablation site, without the need for an experienced computer-operating assistant. This expert opinion presents evidence demonstrating the benefit of Ripple Mapping, compared with traditional electroanatomic mapping techniques, for the diagnosis and management of atrial and ventricular tachyarrhythmias during electrophysiological procedures.
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http://dx.doi.org/10.15420/aer.2018.44.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304800PMC
December 2018

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