Imperial College London

ProfessorNicholasPeters

Faculty of MedicineNational Heart & Lung Institute

Professor of Cardiac Electrophysiology
 
 
 
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Contact

 

+44 (0)20 7594 1880n.peters Website

 
 
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Assistant

 

Ms Anastasija Schmidt +44 (0)20 7594 1880

 
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Location

 

330ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

362 results found

Brook J, Kim M-Y, Koutsoftidis S, Pitcher D, Agha-Jaffar D, Sufi A, Jenkins C, Tzortzis K, Ma S, Jabbour R, Houston C, Handa B, Li X, Chow J-J, Jothidasan A, Bristow P, Perkins J, Harding S, Bharath A, Ng FS, Peters N, Cantwell C, Chowdhury Ret al., 2020, Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling, Pflügers Archiv European Journal of Physiology, ISSN: 0031-6768

We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap-junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting Porcine (n=9) and human (n=4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. 1mM of carbenoxolone was administered at 5ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed.We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9±4.1ms to 67.2±2.7ms) indicating conduction slowing. The features with the largest percentage change between baseline to Carbenoxolone were Fractionation +185.3%, Endpoint amplitude -106.9%, S-Endpoint Gradient +54.9%, S Point, -39.4%, RS Ratio +38.6% and (-dV/dt)max -20.9%.The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically-induced proarrhythmic substrates.

Journal article

Davies HJ, Williams I, Peters NS, Mandic DPet al., 2020, In-Ear SpO2: A Tool for Wearable, Unobtrusive Monitoring of Core Blood Oxygen Saturation., Sensors (Basel), Vol: 20

The non-invasive estimation of blood oxygen saturation (SpO2) by pulse oximetry is of vital importance clinically, from the detection of sleep apnea to the recent ambulatory monitoring of hypoxemia in the delayed post-infective phase of COVID-19. In this proof of concept study, we set out to establish the feasibility of SpO2 measurement from the ear canal as a convenient site for long term monitoring, and perform a comprehensive comparison with the right index finger-the conventional clinical measurement site. During resting blood oxygen saturation estimation, we found a root mean square difference of 1.47% between the two measurement sites, with a mean difference of 0.23% higher SpO2 in the right ear canal. Using breath holds, we observe the known phenomena of time delay between central circulation and peripheral circulation with a mean delay between the ear and finger of 12.4 s across all subjects. Furthermore, we document the lower photoplethysmogram amplitude from the ear canal and suggest ways to mitigate this issue. In conjunction with the well-known robustness to temperature induced vasoconstriction, this makes conclusive evidence for in-ear SpO2 monitoring being both convenient and superior to conventional finger measurement for continuous non-intrusive monitoring in both clinical and everyday-life settings.

Journal article

Bachtiger P, Peters NS, Walsh SLF, 2020, Machine learning for COVID-19-asking the right questions, LANCET DIGITAL HEALTH, Vol: 2, Pages: E391-E392

Journal article

Handa BS, Li X, Aras KK, Qureshi NA, Mann I, Chowdhury RA, Whinnett ZI, Linton NWF, Lim PB, Kanagaratnam P, Efimov IR, Peters NS, Ng FSet al., 2020, Response by Handa et al to Letter Regarding Article, "Granger Causality-Based Analysis for Classification of Fibrillation Mechanisms and Localization of Rotational Drivers"., Circ Arrhythm Electrophysiol, Vol: 13

Journal article

Feeny AK, Chung MK, Madabhushi A, Attia ZI, Cikes M, Firouznia M, Friedman PA, Kalscheur MM, Kapa S, Narayan SM, Noseworthy PA, Passman RS, Perez MV, Peters NS, Piccini JP, Tarakji KG, Thomas SA, Trayanova NA, Turakhia MP, Wang PJet al., 2020, Artificial Intelligence and Machine Learning in Arrhythmias and Cardiac Electrophysiology., Circ Arrhythm Electrophysiol, Vol: 13

Artificial intelligence (AI) and machine learning (ML) in medicine are currently areas of intense exploration, showing potential to automate human tasks and even perform tasks beyond human capabilities. Literacy and understanding of AI/ML methods are becoming increasingly important to researchers and clinicians. The first objective of this review is to provide the novice reader with literacy of AI/ML methods and provide a foundation for how one might conduct an ML study. We provide a technical overview of some of the most commonly used terms, techniques, and challenges in AI/ML studies, with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology, with emphasis on disease detection and diagnosis, prediction of patient outcomes, and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate validation, adoption, and deployment of AI technologies into clinical practice.

Journal article

Kim M-Y, Sandler B, Sikkel MB, Cantwell CD, Leong KM, Luther V, Malcolme-Lawes L, Koa-Wing M, Ng FS, Qureshi N, Sohaib A, Whinnett ZI, Fudge M, Lim E, Todd M, Wright I, Peters NS, Lim PB, Linton NWF, Kanagaratnam Pet al., 2020, The Anatomical Distribution of the Ectopy-Triggering Ganglionated Plexus in Patients with Atrial Fibrillation., Circ Arrhythm Electrophysiol

Journal article

Kim M-Y, Sandler B, Sikkel MB, Cantwell CD, Leong KM, Luther V, Malcolme-Lawes L, Koa-Wing M, Ng FS, Qureshi N, Sohaib A, Whinnett ZI, Fudge M, Lim E, Todd M, Wright I, Peters NS, Lim PB, Linton NWF, Kanagaratnam Pet al., 2020, The ectopy-triggering ganglionated plexuses in atrial fibrillation, Autonomic Neuroscience, ISSN: 1566-0702

BackgroundEpicardial ganglionated plexus (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 “ET-GP” are upstream triggers of atrial ectopy/AF and have different anatomical distribution to AVD-GP.ObjectivesWe mapped and characterised ET-GP to understand their neural mechanism in AF and anatomical distribution in the left atrium (LA).Methods26 patients with paroxysmal AF were recruited. All were paced in the LA with an ablation catheter. HFS (80 ms) was synchronised to each paced stimulus (after 20 ms delay) 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.Results2302 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.ConclusionET-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.

Journal article

Ng FS, Handa B, Li X, Peters Net al., Towards mechanism-directed electrophenotype-based treatments for atrial fibrillation, Frontiers in Physiology, ISSN: 1664-042X

Current treatment approaches for persistent atrial fibrillation (AF) have a ceiling of success of around 50%. This is despite 15 years of developing adjunctive ablation strategies in addition to pulmonary vein isolation to target the underlying arrhythmogenic substrate in AF. A major shortcoming of our current approach to AF treatment is its predominantly empirical nature. This has in part been due to a lack of consensus on the mechanisms that sustain human AF.6 In this article, we review evidence suggesting that the previous debates on AF being eitheran organised arrhythmia with a focal driver ora disorganised rhythm sustained by multiple wavelets, may prove to be a false dichotomy. Instead,a range of fibrillation electrophenotypes exists along a continuous spectrum, and the predominant mechanism in an individual case is determined by the nature and extent of remodelling of the underlying substrate. We propose moving beyond the current empirical approach to AF treatment, and highlight the need to prescribe AF treatments based on the underlying AFelectrophenotype, and review several possible novel mapping algorithms that may be useful in discerning the AF electrophenotype to guide tailored treatments, including Granger Causality mapping.

Journal article

Ciaccio EJ, Coromilas J, Wan EY, Yarmohammadi H, Saluja DS, Biviano AB, Wit AL, Peters NS, Garan Het al., 2020, Slow uniform electrical activation during sinus rhythm is an indicator of reentrant VT isthmus location and orientation in an experimental model of myocardial infarction., Comput Methods Programs Biomed, Vol: 196

BACKGROUND: To validate the predictability of reentrant circuit isthmus locations without ventricular tachycardia (VT) induction during high-definition mapping, we used computer methods to analyse sinus rhythm activation in experiments where isthmus location was subsequently verified by mapping reentrant VT circuits. METHOD: In 21 experiments using a canine postinfarction model, bipolar electrograms were obtained from 196-312 recordings with 4mm spacing in the epicardial border zone during sinus rhythm and during VT. From computerized electrical activation maps of the reentrant circuit, areas of conduction block were determined and the isthmus was localized. A linear regression was computed at three different locations about the reentry isthmus using sinus rhythm electrogram activation data. From the regression analysis, the uniformity, a measure of the constancy at which the wavefront propagates, and the activation gradient, a measure that may approximate wavefront speed, were computed. The purpose was to test the hypothesis that the isthmus locates in a region of slow uniform activation bounded by areas of electrical discontinuity. RESULTS: Based on the regression parameters, sinus rhythm activation along the isthmus near its exit proceeded uniformly (mean r2= 0.95±0.05) and with a low magnitude gradient (mean 0.37±0.10mm/ms). Perpendicular to the isthmus long-axis across its boundaries, the activation wavefront propagated much less uniformly (mean r2= 0.76±0.24) although of similar gradient (mean 0.38±0.23mm/ms). In the opposite direction from the exit, at the isthmus entrance, there was also less uniformity (mean r2= 0.80±0.22) but a larger magnitude gradient (mean 0.50±0.25mm/ms). A theoretical ablation line drawn perpendicular to the last sinus rhythm activation site along the isthmus long-axis was predicted to prevent VT reinduction. Anatomical conduction block occurred in 7/21 experiments, but comprised only small po

Journal article

Lyon A, Babalis D, Morley-Smith AC, Hedger M, Suarez Barrientos A, Foldes G, Couch LS, Chowdhury RA, Tzortzis KN, Peters NS, Rog-Zielinska EA, Yang YH, Welch S, Bowles CT, Rahman Haley S, Bell AR, Rice A, Sasikaran T, Johnson NA, Falaschetti E, Parameshwar J, Lewis C, Tsui S, Simon A, Pepper J, Rudy JJ, Zsebo KM, MacLeod KT, Terracciano CM, Hajjar RJ, Banner N, Harding SEet al., 2020, Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL, Gene Therapy, ISSN: 0969-7128

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. Enrolled subjects were randomised to receive a single intracoronary infusion of 1x1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort, which may help guide future trial design.

Journal article

Ciacci A, Falkenberg M, Manani KA, Evans TS, Peters NS, Christensen Ket al., 2020, Understanding the transition from paroxysmal to persistent atrial fibrillation, Physical Review Research, Vol: 2, Pages: 023311-023311

Atrial fibrillation (AF) is the most common cardiac arrhytmia, characterisedby the chaotic motion of electrical wavefronts in the atria. In clinicalpractice, AF is classified under two primary categories: paroxysmal AF, shortintermittent episodes separated by periods of normal electrical activity, andpersistent AF, longer uninterrupted episodes of chaotic electrical activity.However, the precise reasons why AF in a given patient is paroxysmal orpersistent is poorly understood. Recently, we have introduced the percolationbased Christensen-Manani-Peters (CMP) model of AF which naturally exhibits bothparoxysmal and persistent AF, but precisely how these differences emerge in themodel is unclear. In this paper, we dissect the CMP model to identify the causeof these different AF classifications. Starting from a mean-field model wherewe describe AF as a simple birth-death process, we add layers of complexity tothe model and show that persistent AF arises from the formation of temporallystable structural re-entrant circuits that form from the interaction ofwavefront collisions during paroxysmal AF. These results are compatible withrecent findings suggesting that the formation of re-entrant drivers in fibroticborder zones perpetuates persistent AF.

Journal article

Normahani P, Sounderajah V, Harrop-Griffiths W, Chukwuemeka A, Peters N, Standfield N, Collins M, Jaffer Uet al., 2020, Achieving good-quality consent: review of literature, case law and guidance, British Journal of Surgery, ISSN: 0007-1323

BackgroundInformed consent is an integral part of clinical practice. There is widespread agreement amongst health professionals that obtaining procedural consent needs to move away from a unidirectional transfer of information to a process of supporting patients in making informed, self‐determined decisions. This review aimed to identify processes and measures that warrant consideration when engaging in consent‐based discussions with competent patients undergoing elective procedures.MethodsFormal written guidance from the General Medical Council and Royal College of Surgeons of England, in addition to peer‐reviewed literature and case law, was considered in the formulation of this review.ResultsA framework for obtaining consent is presented that is informed by the key tenets of shared decision‐making (SDM), a model that advocates the contribution of both the clinician and patient to the decision‐making process through emphasis on patient participation, analysis of empirical evidence, and effective information exchange. Moreover, areas of contention are highlighted in which further guidance and research are necessary for improved enhancement of the consent process.ConclusionThis SDM‐centric framework provides structure, detail and suggestions for achieving meaningful consent.

Journal article

Handa B, Li X, Baxan N, Roney C, Shchendrygina A, Mansfield C, Jabbour R, Pitcher D, Chowdhury RA, Peters N, Ng FSet al., 2020, Ventricular fibrillation mechanism and global fibrillatory organisation are determined by gap junction coupling and fibrosis pattern, Cardiovascular Research, ISSN: 0008-6363

AimsConflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganised multiple-wavelet activation to organised rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.Methods and ResultsOptical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact (CF), diffuse (DiF) and patchy (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum.Enhanced GJ coupling with rotigaptide (n = 10) progressively organised fibrillation in a concentration-dependent manner; increasing FDI (0nM: 0.53±0.04, 80nM: 0.78±0.03, p < 0.001), increasing RA sustained VF time (0nM:44±6%, 80nM: 94±2%, p < 0.001) and stabilised RAs (maximum rotations for a RA; 0nM:5.4±0.5, 80nM: 48.2±12.3, p < 0.001). GJ uncoupling with carbenoxolone progressively disorganised VF; the FDI decreased (0µM: 0.60±0.05, 50µM: 0.17±0.03, p < 0.001) and RA-sustained VF time decreased (0µM: 61±9%, 50µM: 3±2%, p < 0.001).In CF, VF activity was disorganised and the RA-sustained VF time was the lowest (CF: 27±7% versus PF: 75±5%, p < 0.001). Global fibrillatory organisation measured by FDI was highest in PF (PF: 0.67±0.05 versus CF: 0.33±0.03, p < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411&plusm

Journal article

Roney CH, Wit AL, Peters NS, 2020, Challenges associated with interpreting mechanisms of AF, Arrhythmia & electrophysiology review, Vol: 8, Pages: 273-284, ISSN: 2050-3369

Determining optimal treatment strategies for complex arrhythmogenesis in AF is confounded by the lack of consensus regarding the mechanisms causing AF. Studies report different mechanisms for AF, ranging from hierarchical drivers to anarchical multiple activation wavelets. Differences in the assessment of AF mechanisms are likely due to AF being recorded across diverse models using different investigational tools, spatial scales and clinical populations. The authors review different AF mechanisms, including anatomical and functional re-entry, hierarchical drivers and anarchical multiple wavelets. They then describe different cardiac mapping techniques and analysis tools, including activation mapping, phase mapping and fibrosis identification. They explain and review different data challenges, including differences between recording devices in spatial and temporal resolutions, spatial coverage and recording surface, and report clinical outcomes using different data modalities. They suggest future research directions for investigating the mechanisms underlying human AF.

Journal article

Bachtiger P, Plymen CM, Pabari PA, Howard JP, Whinnett ZI, Opoku F, Janering S, Faisal AA, Francis DP, Peters NSet al., 2020, Artificial intelligence, data sensors and interconnectivity: future Opportunities for heart failure, Cardiac Failure Review, Vol: 6, Pages: e11-e11, ISSN: 2057-7540

A higher proportion of patients with heart failure have benefitted from a wide and expanding variety of sensor-enabled implantable devices than any other patient group. These patients can now also take advantage of the ever-increasing availability and affordability of consumer electronics. Wearable, on- and near-body sensor technologies, much like implantable devices, generate massive amounts of data. The connectivity of all these devices has created opportunities for pooling data from multiple sensors - so-called interconnectivity - and for artificial intelligence to provide new diagnostic, triage, risk-stratification and disease management insights for the delivery of better, more personalised and cost-effective healthcare. Artificial intelligence is also bringing important and previously inaccessible insights from our conventional cardiac investigations. The aim of this article is to review the convergence of artificial intelligence, sensor technologies and interconnectivity and the way in which this combination is set to change the care of patients with heart failure.

Journal article

Handa B, Li X, Aras KK, Qureshi NA, Mann I, Chowdhury R, Whinnett ZI, Linton NWF, Lim PB, Kanagaratnam P, Efimov IR, Peters N, Ng FSet al., 2020, Granger causality-based analysis for classification of fibrillation mechanisms and localisation of rotational drivers, Circulation: Arrhythmia and Electrophysiology, Vol: 12, Pages: 258-273, ISSN: 1941-3084

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: P=0.006, R2=0.38, 12.5% resolution, P=0.004, R2=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, P=0.0002).

Journal article

Tarkin JM, Cole GD, Gopalan D, Flora R, McAdoo SP, Mason JC, Peters NS, Pusey CD, Varnava Aet al., 2020, Multimodal imaging of granulomatosis with polyangiitis aortitis complicated by severe aortic regurgitation and complete heart block, Circulation: Cardiovascular Imaging, Vol: 13, Pages: 1-3, ISSN: 1941-9651

Journal article

Li X, Handa BS, Peters NS, Ng FSet al., 2020, Classification of fibrillation subtypes with single-channel surface electrocardiogram, UK Workshop on Computational Intelligence (UKCI), Publisher: Springer International Publishing, Pages: 472-479, ISSN: 2194-5357

Atrial fibrillation (AF) and ventricular fibrillation (VF) are complex heart rhythm disorders with increasing prevalence. Mechanisms sustaining these arrhythmias are different, and subsequently, the required treatments options differ. Although many algorithms have been developed for differentiating fibrillation from normal sinus rhythm, very few methods exist to differentiate between different forms of AF and VF from surface electrocardiogram (ECG). To address the issue, we propose a novel ECG classification method to differentiate fibrillation that is completely chaotic from forms where it is organized with key driving sites. Differentiating fibrillation organisation from ECGs may aid patient selection, and identify those who may benefit from targeted ablation treatment. Evaluation using real-world data sets based on rat VF model shows that the proposed method could recognise the correct Fibrillation subtype from the single-channel electrocardiogram with an accuracy of 88.89 % .

Conference paper

Falkenberg McGillivray M, Ford A, Li A, Lawrence R, Ciacci A, Peters N, Christensen Ket al., 2019, Unified mechanism of local drivers in a percolation model of atrial fibrillation, Physical Review E, Vol: 100, ISSN: 2470-0045

The mechanisms of atrial fibrillation (AF) are poorly understood, resulting in disappointing success rates of ablative treatment. Different mechanisms defined largely by different atrial activation patterns have been proposed and, arguably, this dispute has slowed the progress of AF research. Recent clinical evidence suggests a unifying mechanism of local drivers based on sustained re-entrant circuits in the complex atrial architecture. Here, we present a percolation inspired computational model showing spontaneous emergence of AF that strongly supports, and gives a theoretical explanation for, the clinically observed diversity of activation. We show that the difference in surface activation patterns is a direct consequence of the thickness of the discrete network of heart muscle cells through which electrical signals percolate to reach the imaged surface. The model naturally follows the clinical spectrum of AF spanning sinus rhythm, paroxysmal and persistent AF as the decoupling of myocardial cells results in the lattice approaching the percolation threshold. This allows the model to make the novel prediction that for paroxysmal AF, re-entrant circuits emerge near the endocardium, but in persistent AF they emerge deeper in the bulk of the atrial wall. If experimentally verified, this may go towards explaining the lowering ablation success rate as AF becomes more persistent.

Journal article

Li X, Roney C, Handa B, Chowdhury R, Niederer S, Peters N, Ng FSet al., 2019, Standardised framework for quantitative analysisof fibrillation dynamics, Scientific Reports, Vol: 9, ISSN: 2045-2322

The analysis of complex mechanisms underlying ventricular fibrillation (VF) and atrial fibrillation (AF) requires sophisticatedtools for studying spatio-temporal action potential (AP) propagation dynamics. However, fibrillation analysis tools are oftencustom-made or proprietary, and vary between research groups. With no optimal standardised framework for analysis, resultsfrom different studies have led to disparate findings. Given the technical gap, here we present a comprehensive framework andset of principles for quantifying properties of wavefront dynamics in phase-processed data recorded during myocardial fibrillationwith potentiometric dyes. Phase transformation of the fibrillatory data is particularly useful for identifying self-perpetuating spiralwaves or rotational drivers (RDs) rotating around a phase singularity (PS). RDs have been implicated in sustaining fibrillation,and thus accurate localisation and quantification of RDs is crucial for understanding specific fibrillatory mechanisms. In thiswork, we assess how variation of analysis parameters and thresholds in the tracking of PSs and quantification of RDs couldresult in different interpretations of the underlying fibrillation mechanism. These techniques have been described and appliedto experimental AF and VF data, and AF simulations, and examples are provided from each of these data sets to demonstratethe range of fibrillatory behaviours and adaptability of these tools. The presented methodologies are available as an opensource software and offer an off-the-shelf research toolkit for quantifying and analysing fibrillatory mechanisms.

Journal article

Falkenberg M, Hickey D, Terrill L, Ciacci A, Peters NS, Christensen Ket al., 2019, Identifying Potential Re-Entrant Circuit Locations From Atrial Fibre Maps., Comput Cardiol (2010), Vol: 2019, Pages: 1-4, ISSN: 2325-8861

Re-entrant circuits have been identified as potential drivers of atrial fibrillation (AF). In this paper, we develop a novel computational framework for finding the locations of re-entrant circuits from high resolution fibre orientation data. The technique follows a statistical approach whereby we generate continuous fibre tracts across the tissue and couple adjacent fibres stochastically if they are within a given distance of each other. By varying the connection distance, we identify which regions are most susceptible to forming re-entrant circuits if muscle fibres are uncoupled, through the action of fibrosis or otherwise. Our results highlight the sleeves of the pulmonary veins, the posterior left atrium and the left atrial appendage as the regions most susceptible to re-entrant circuit formation. This is consistent with known risk locations in clinical AF. If the model can be personalised for individual patients undergoing ablation, future versions may be able to suggest suitable ablation targets.

Journal article

Ciaccio EJ, Wan EY, Saluja DS, Acharya UR, Peters NS, Garan Het al., 2019, Addressing challenges of quantitative methodologies and event interpretation in the study of atrial fibrillation, Computer Methods and Programs in Biomedicine, Vol: 178, Pages: 113-122, ISSN: 0169-2607

Atrial fibrillation (AF) is the commonest arrhythmia, yet the mechanisms of its onset and persistence are incompletely known. Although techniques for quantitative assessment have been investigated, there have been few attempts to integrate this information to advance disease treatment protocols. In this review, key quantitative methods for AF analysis are described, and suggestions are provided for the coordination of the available information, and to develop foci and directions for future research efforts. Quantitative biologists may have an interest in this topic in order to develop machine learning and tools for arrhythmia characterization, but they may perhaps have a minimal background in the clinical methodology and in the types of observed events and mechanistic hypotheses that have thus far been developed. We attempt to address these issues via exploration of the published literature. Although no new data is presented in this review, examples are shown of current lines of investigation, and in particular, how electrogram analysis and whole-chamber quantitative modeling of the left atrium may be useful to characterize fibrillatory patterns of activity, so as to propose avenues for more efficacious acquisition and interpretation of AF data.

Journal article

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

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

Journal article

Slotwiner DJ, Tarakji KG, Al-Khatib SM, Passman RS, Saxon LA, Peters NS, McCall D, Advisorset al., 2019, Transparent sharing of digital health data: A call to action, Heart Rhythm, Vol: 16, Pages: e95-e106, ISSN: 1547-5271

Journal article

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

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

Journal article

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

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

Journal article

Sau A, Al-Aidarous S, Howard J, Shalhoub J, Sohaib A, Shun-Shin M, Novak PG, Leather R, Sterns LD, Lane C, Kanagaratnam P, Peters NS, Francis DP, Sikkel MBet al., 2019, Optimum lesion set and predictors of outcome in persistent atrial fibrillation ablation: a meta-regression analysis, Europace, Vol: 21, Pages: 1176-1184, ISSN: 1099-5129

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.

Journal article

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

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

Journal article

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

Journal article

Lagarto J, Dyer B, Dunsby C, Peters N, French P, Dunsby C, Lyon Aet al., 2019, In vivo label-free optical monitoring of structural and metabolic remodeling of myocardium following infarction, Biomedical Optics Express, Vol: 10, Pages: 3506-3521, ISSN: 2156-7085

Cardiac remodeling following myocardial infarction (MI) involves structural and functional alterations in the infarcted and remote viable myocardium that can ultimately lead to heart failure. The underlying mechanisms are not fully understood and, following our previous study of the autofluorescence lifetime and diffuse reflectance signatures of the myocardium in vivo at 16 weeks post MI in rats [Biomed. Opt. Express 6(2), 324 (2015)], we here present data obtained at 1, 2 and 4 weeks post myocardial infarction that help follow the temporal progression of these changes. Our results demonstrate that both structural and metabolic changes in the heart can be monitored from the earliest time points following MI using label-free optical readouts, not only in the region of infarction but also in the remote non-infarcted myocardium. Changes in the autofluorescence intensity and lifetime parameters associated with collagen type I autofluorescence were indicative of progressive collagen deposition in tissue that was most pronounced at earlier time points and in the region of infarction. In addition to significant collagen deposition in infarcted and non-infarcted myocardium, we also report changes in the autofluorescence parameters associated with reduced nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD), which we associate with metabolic alterations throughout the heart. Parallel measurements of the diffuse reflectance spectra indicated an increased contribution of reduced cytochrome c. Our findings suggest that combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy could provide a useful means to monitor cardiac function in vivo at the time of surgery.

Journal article

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