Publications by authors named "Nicholas S Peters"

205 Publications

Reusable snorkel masks adapted as particulate respirators.

PLoS One 2021 5;16(4):e0249201. Epub 2021 Apr 5.

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

Introduction: During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject's face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/.

Conclusion: Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249201PLOS
April 2021

Novel Low-Voltage MultiPulse Therapy to Terminate Atrial Fibrillation.

JACC Clin Electrophysiol 2021 Mar 25. Epub 2021 Mar 25.

George Washington University, Washington, DC, USA. Electronic address:

Objectives: This first-in-human feasibility study was undertaken to translate the novel low-voltage MultiPulse Therapy (MPT) (Cardialen, Inc., Minneapolis, Minnesota), which was previously been shown to be effective in preclinical studies in terminating atrial fibrillation (AF), into clinical use.

Background: Current treatment options for AF, the most common arrhythmia in clinical practice, have limited success. Previous attempts at treating AF by using implantable devices have been limited by the painful nature of high-voltage shocks.

Methods: Forty-two patients undergoing AF ablation were recruited at 6 investigational centers worldwide. Before ablation, electrode catheters were placed in the coronary sinus, right and/or left atrium, for recording and stimulation. After the induction of AF, MPT, which consists of up to a 3-stage sequence of far- and near-field stimulation pulses of varied amplitude, duration, and interpulse timing, was delivered via temporary intracardiac leads. MPT parameters and delivery methods were iteratively optimized.

Results: In the 14 patients from the efficacy phase, MPT terminated 37 of 52 (71%) of AF episodes, with the lowest median energy of 0.36 J (interquartile range: 0.14 to 1.21 J) and voltage of 42.5 V (interquartile range: 25 to 75 V). Overall, 38% of AF terminations occurred within 2 seconds of MPT delivery (p < 0.0001). Shorter time between AF induction and MPT predicted success of MPT in terminating AF (p < 0.001).

Conclusions: MPT effectively terminated AF at voltages and energies known to be well tolerated or painless in some patients. Our results support further studies of the concept of implanted devices for early AF conversion to reduce AF burden, symptoms, and progression.
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http://dx.doi.org/10.1016/j.jacep.2020.12.014DOI Listing
March 2021

Interpretable XGBoost Based Classification of 12-lead ECGs Applying Information Theory Measures From Neuroscience.

Comput Cardiol (2010) 2020 14;47. Epub 2020 Aug 14.

Centre for Complexity Science, Imperial College London, London, United Kingdom.

Automated ECG classification is a standard feature in many commercial 12-Lead ECG machines. As part of the Physionet/CinC Challenge 2020, our team, "Mad-hardmax", developed an XGBoost based classification method for the analysis of 12-Lead ECGs acquired from four different countries. Our aim is to develop an interpretable classifier that outputs diagnoses which can be traced to specific ECG features, while also testing the potential of information theoretic features for ECG diagnosis. These measures capture high-level interdependencies across ECG leads which are effective for discriminating conditions with multiple complex morphologies. On unseen test data, our algorithm achieved a challenge score of 0.155 relative to a winning score of 0.533, putting our submission in 24th position from 41 successful entries.
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http://dx.doi.org/10.22489/CinC.2020.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610399PMC
August 2020

The Impact of the Covid-19 Pandemic on Uptake of Influenza Vaccine: A UK-Wide Observational Study.

JMIR Public Health Surveill 2021 Feb 18. Epub 2021 Feb 18.

National Heart & Lung Institute, Imperial College London, Hammersmith Hospital CampusDu Cane Road, London, GB.

Background: In the face of the Covid-19 pandemic, the UK National Health Service (NHS) flu vaccination eligibility is extended this season to ~32.4 million (48.8%) of the population. Knowing intended uptake will inform supply and public health messaging to maximise vaccination.

Objective: The objective of this study was to measure the impact of the Covid-19 pandemic on acceptance of flu vaccination in the 2020-21 season, specifically focusing on those previously eligible who routinely decline vaccination and the newly eligible.

Methods: Intention to receive influenza vaccine in 2020-21 was asked of all registrants of the NHS's largest electronic personal health record by online questionnaire on 31st July 2020. Of those who were either newly or previously eligible but had not previously received influenza vaccination, multivariable logistic regression and network diagrams were used to examine reasons to have or decline vaccination.

Results: Among 6,641 respondents, 945 (14.2%) were previously eligible but not vaccinated, of whom 536 (56.7%) intended to receive flu vaccination in 2020/21, as did 466 (68.6%) of the newly eligible. Intention to receive the flu vaccine was associated with increased age, index of multiple deprivation (IMD) quintile, and considering oneself at high risk from Covid-19. Among those eligible but intending not to be vaccinated in 2020/21, 164 (30.2%) gave misinformed reasons. 47 (49.9%) of previously unvaccinated healthcare workers would decline vaccination in 2020/21.

Conclusions: In this sample, Covid-19 has increased acceptance of flu vaccination in those previously eligible but unvaccinated and motivates substantial uptake in the newly eligible. This study is essential for informing resource planning and the need for effective messaging campaigns to address negative misconceptions, also necessary for Covid-19 vaccination programmes.

Clinicaltrial: Not applicable.
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http://dx.doi.org/10.2196/26734DOI Listing
February 2021

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

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

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

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

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

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

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

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

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

Left Atrial Enhancement Correlates With Myocardial Conduction Velocity in Patients With Persistent Atrial Fibrillation.

Front Physiol 2020 12;11:570203. Epub 2020 Nov 12.

ElectroCardioMaths Programme of The Imperial Centre for Cardiac Engineering, Imperial College London, London, United Kingdom.

Background: Conduction velocity (CV) heterogeneity and myocardial fibrosis both promote re-entry, but the relationship between fibrosis as determined by left atrial (LA) late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMRI) and CV remains uncertain.

Objective: Although average CV has been shown to correlate with regional LGE-CMRI in patients with persistent AF, we test the hypothesis that a localized relationship exists to underpin LGE-CMRI as a minimally invasive tool to map myocardial conduction properties for risk stratification and treatment guidance.

Method: 3D LA electroanatomic maps during LA pacing were acquired from eight patients with persistent AF following electrical cardioversion. Local CVs were computed using triads of concurrently acquired electrograms and were co-registered to allow correlation with LA wall intensities obtained from LGE-CMRI, quantified using normalized intensity (NI) and image intensity ratio (IIR). Association was evaluated using multilevel linear regression.

Results: An association between CV and LGE-CMRI intensity was observed at scales comparable to the size of a mapping electrode: -0.11 m/s per unit increase in NI ( < 0.001) and -0.96 m/s per unit increase in IIR ( < 0.001). The magnitude of this change decreased with larger measurement area. Reproducibility of the association was observed with NI, but not with IIR.

Conclusion: At clinically relevant spatial scales, comparable to area of a mapping catheter electrode, LGE-CMRI correlates with CV. Measurement scale is important in accurately quantifying the association of CV and LGE-CMRI intensity. Importantly, NI, but not IIR, accounts for changes in the dynamic range of CMRI and enables quantitative reproducibility of the association.
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http://dx.doi.org/10.3389/fphys.2020.570203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693630PMC
November 2020

Belief of having had unconfirmed Covid-19 infection reduces willingness to participate in app-based contact tracing.

NPJ Digit Med 2020 Nov 6;3(1):146. Epub 2020 Nov 6.

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

Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). The UK National Health Service (NHS) Track and Trace Service has plans for a nationwide app that notifies the need for self-isolation to those in contact with a person testing positive for COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. The objective of this study was to measure the determinants of willingness to participate in an NHS app-based contact-tracing programme using a questionnaire within the Care Information Exchange (CIE)-the largest patient-facing electronic health record in the NHS. Among 47,708 registered NHS users of the CIE, 27% completed a questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation-related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded 'no', 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact-tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48-0.67]; OR for 3-4/10 = 0.744 [CI 0.64-0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585-0.908]). In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing over an appropriate age range is 60%-close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact tracing to be an effective intervention to help suppress an epidemic. Difficulty comprehending government advice and uncertainty of diagnosis, based on a public health policy of not testing to confirm self-reported COVID-19 infection during lockdown, therefore reduce willingness to adopt a government contact-tracing app to a level below the threshold for effectiveness as a tool to suppress an epidemic.
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http://dx.doi.org/10.1038/s41746-020-00357-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648058PMC
November 2020

Toward Mechanism-Directed Electrophenotype-Based Treatments for Atrial Fibrillation.

Front Physiol 2020 28;11:987. Epub 2020 Aug 28.

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

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. In this article, we review evidence suggesting that the previous debates on AF being an organized arrhythmia with a focal driver a disorganized 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 remodeling of the underlying substrate. We propose moving beyond the current empirical approach to AF treatment, highlight the need to prescribe AF treatments based on the underlying AF electrophenotype, and review several possible novel mapping algorithms that may be useful in discerning the AF electrophenotype to guide tailored treatments, including Granger Causality mapping.
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http://dx.doi.org/10.3389/fphys.2020.00987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493660PMC
August 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

Survey of current perspectives on consumer-available digital health devices for detecting atrial fibrillation.

Cardiovasc Digit Health J 2020 Jul-Aug;1(1):21-29. Epub 2020 Aug 28.

Division of Cardiology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.

Background: Many digital health technologies capable of atrial fibrillation (AF) detection are directly available to patients. However, adaptation into clinical practice by heart rhythm healthcare practitioners (HCPs) is unclear.

Objective: To examine HCP perspectives on use of commercial technologies for AF detection and management.

Methods: We created an electronic survey for HCPs assessing practice demographics and perspectives on digital devices for AF detection and management. The survey was distributed electronically to all members of 3 heart rhythm professional societies.

Results: We received 1601 responses out of 73,563 e-mails sent, with 43.6% from cardiac electrophysiologists, 12.8% from fellows, and 11.6% from advanced practice practitioners. Most respondents (62.3%) reported having recommended patient use of a digital device for AF detection. Those who did not had concerns about their accuracy (29.6%), clinical utility of results (22.8%), and integration into electronic health records (19.8%). Results from a 30-second single-lead electrocardiogram were sufficient for 42.7% of HCPs to recommend oral anticoagulation for patients at high risk for stroke. Respondents wanted more data comparing the accuracy of digital devices to conventional devices for AF monitoring (64.9%). A quarter (27.3%) of HCPs had no reservations recommending digital devices for AF detection, and most (53.4%) wanted guidelines from their professional societies providing guidance on their optimal use.

Conclusion: Many HCPs have already integrated digital devices into their clinical practice. However, HCPs reported facing challenges when using digital technologies for AF detection, and professional society recommendations on their use are needed.
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http://dx.doi.org/10.1016/j.cvdhj.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452829PMC
August 2020

In-Ear SpO: A Tool for Wearable, Unobtrusive Monitoring of Core Blood Oxygen Saturation.

Sensors (Basel) 2020 Aug 28;20(17). Epub 2020 Aug 28.

Department of Electrical and Electronic Engineering, Imperial College London, London SW7 2AZ, UK.

The non-invasive estimation of blood oxygen saturation (SpO) 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 SpO 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 SpO 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 SpO monitoring being both convenient and superior to conventional finger measurement for continuous non-intrusive monitoring in both clinical and everyday-life settings.
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http://dx.doi.org/10.3390/s20174879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506719PMC
August 2020

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling.

Pflugers Arch 2020 10 1;472(10):1435-1446. Epub 2020 Sep 1.

Faculty of Medicine, National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.

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. A total of 1 mM of carbenoxolone was administered at 5 ml/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) increased between baseline and carbenoxolone (47.9 ± 4.1-67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and 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) - 20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates.
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http://dx.doi.org/10.1007/s00424-020-02446-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476990PMC
October 2020

Machine learning for COVID-19-asking the right questions.

Lancet Digit Health 2020 08 10;2(8):e391-e392. Epub 2020 Jul 10.

National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. Electronic address:

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http://dx.doi.org/10.1016/S2589-7500(20)30162-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351424PMC
August 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

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 2020 Nov 15;196:105666. Epub 2020 Jul 15.

Department of Medicine - Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

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 r= 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 r= 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 r= 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 portions of the isthmus lateral boundaries; thus detection of sinus rhythm conduction block alone was insufficient to entirely define the VT isthmus.

Conclusions: Uniform activation with a low magnitude gradient during sinus rhythm is present at the VT isthmus exit location but there is less uniformity across the isthmus lateral boundaries and at isthmus entrance locations. These factors may be useful to verify any proposed VT isthmus location, reducing the need for VT induction to ablate the isthmus. Measured computerized values similar to those determined herein could therefore be assistive to sharpen specificity when applying sinus rhythm mapping to localize EP catheter ablation sites.
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http://dx.doi.org/10.1016/j.cmpb.2020.105666DOI Listing
November 2020

Challenges Associated with Interpreting Mechanisms of AF.

Arrhythm Electrophysiol Rev 2020 Feb;8(4):273-284

Imperial Centre for Cardiac Engineering, Imperial College London, London, UK.

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.
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http://dx.doi.org/10.15420/aer.2019.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358959PMC
February 2020

Artificial Intelligence and Machine Learning in Arrhythmias and Cardiac Electrophysiology.

Circ Arrhythm Electrophysiol 2020 08 6;13(8):e007952. Epub 2020 Jul 6.

Division of Cardiovascular Medicine, Stanford University, CA (S.M.N., M.V.P., M.P.T., P.J.W.).

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.
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http://dx.doi.org/10.1161/CIRCEP.119.007952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808396PMC
August 2020

Understanding the transition from paroxysmal to persistent atrial fibrillation.

Phys Rev Res 2020 Jun-Aug;2(2):023311. Epub 2020 Jun 9.

Blackett Laboratory, Imperial College London, London SW7 2BW, United Kingdom.

Atrial fibrillation (AF) is the most common cardiac arrhytmia, characterized by the chaotic motion of electrical wavefronts in the atria. In clinical practice, AF is classified under two primary categories: paroxysmal AF, short intermittent episodes separated by periods of normal electrical activity; and persistent AF, longer uninterrupted episodes of chaotic electrical activity. However, the precise reasons why AF in a given patient is paroxysmal or persistent is poorly understood. Recently, we have introduced the percolation-based Christensen-Manani-Peters (CMP) model of AF which naturally exhibits both paroxysmal and persistent AF, but precisely how these differences emerge in the model is unclear. In this paper, we dissect the CMP model to identify the cause of these different AF classifications. Starting from a mean-field model where we describe AF as a simple birth-death process, we add layers of complexity to the model and show that persistent AF arises from reentrant circuits which exhibit an asymmetry in their probability of activation relative to deactivation. As a result, different simulations generated at identical model parameters can exhibit fibrillatory episodes spanning several orders of magnitude from a few seconds to months. These findings demonstrate that diverse, complex fibrillatory dynamics can emerge from very simple dynamics in models of AF.
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http://dx.doi.org/10.1103/PhysRevResearch.2.023311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326608PMC
June 2020

Identifying Potential Re-Entrant Circuit Locations From Atrial Fibre Maps.

Comput Cardiol (2010) 2019 Nov;2019:1-4

Blackett Laboratory, Imperial College London, London, United Kingdom.

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.
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http://dx.doi.org/10.22489/CinC.2019.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279949PMC
November 2019

Artificial Intelligence, Data Sensors and Interconnectivity: Future Opportunities for Heart Failure.

Card Fail Rev 2020 Mar 12;6:e11. Epub 2020 May 12.

Imperial Centre for Cardiac Engineering, National Heart and Lung Institute, Imperial College London, UK.

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.
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http://dx.doi.org/10.15420/cfr.2019.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265101PMC
March 2020

Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern.

Cardiovasc Res 2021 Mar;117(4):1078-1090

National Heart & Lung Institute, Imperial College London, 4th Floor, ICTEM Building, 72 Du Cane Road, London W12 0NN, UK.

Aims: Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized 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 Results: Optical 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 fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (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 organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P < 0.001), increasing RA-sustained VF time (0 nM: 44 ± 6%, 80 nM: 94 ± 2%, P < 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM: 5.4 ± 0.5, 80 nM: 48.2 ± 12.3, P < 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM: 0.60 ± 0.05, 50 µM: 0.17 ± 0.03, P < 0.001) and RA-sustained VF time decreased (0 µM: 61 ± 9%, 50 µM: 3 ± 2%, P < 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF: 27 ± 7% vs. PF: 75 ± 5%, P < 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF: 0.67 ± 0.05 vs. CF: 0.33 ± 0.03, P < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411 ± 266 ms vs. compact: 354 ± 38 ms, P < 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.

Conclusion: The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.
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http://dx.doi.org/10.1093/cvr/cvaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983010PMC
March 2021

Multimodal Imaging of Granulomatosis With Polyangiitis Aortitis Complicated by Severe Aortic Regurgitation and Complete Heart Block.

Circ Cardiovasc Imaging 2020 02 10;13(2):e009879. Epub 2020 Feb 10.

Department of Cardiology, Imperial College Healthcare NHS Trust, United Kingdom (J.M.T., G.D.C., N.S.P., A.V.).

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http://dx.doi.org/10.1161/CIRCIMAGING.119.009879DOI Listing
February 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

Unified mechanism of local drivers in a percolation model of atrial fibrillation.

Phys Rev E 2019 Dec;100(6-1):062406

Blackett Laboratory, Imperial College London, London SW7 2AZ, United Kingdom.

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 reentrant 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 AF, and persistent AF as the decoupling of myocardial cells results in the lattice approaching the percolation threshold. This allows the model to make the prediction that, for paroxysmal AF, reentrant 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.
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http://dx.doi.org/10.1103/PhysRevE.100.062406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314598PMC
December 2019

Standardised Framework for Quantitative Analysis of Fibrillation Dynamics.

Sci Rep 2019 11 13;9(1):16671. Epub 2019 Nov 13.

National Heart and Lung Institute, Hammersmith Campus, Imperial College London, 72 Du Cane Rd, London, W120UQ, UK.

The analysis of complex mechanisms underlying ventricular fibrillation (VF) and atrial fibrillation (AF) requires sophisticated tools for studying spatio-temporal action potential (AP) propagation dynamics. However, fibrillation analysis tools are often custom-made or proprietary, and vary between research groups. With no optimal standardised framework for analysis, results from different studies have led to disparate findings. Given the technical gap, here we present a comprehensive framework and set of principles for quantifying properties of wavefront dynamics in phase-processed data recorded during myocardial fibrillation with potentiometric dyes. Phase transformation of the fibrillatory data is particularly useful for identifying self-perpetuating spiral waves 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 this work, we assess how variation of analysis parameters and thresholds in the tracking of PSs and quantification of RDs could result in different interpretations of the underlying fibrillation mechanism. These techniques have been described and applied to experimental AF and VF data, and AF simulations, and examples are provided from each of these data sets to demonstrate the range of fibrillatory behaviours and adaptability of these tools. The presented methodologies are available as an open source software and offer an off-the-shelf research toolkit for quantifying and analysing fibrillatory mechanisms.
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http://dx.doi.org/10.1038/s41598-019-52976-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853901PMC
November 2019

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