Imperial College London

Dr Daniel Keene MBChB, MSc (Distinction), MRCP, PhD

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Cardiology (Clinical)
 
 
 
//

Contact

 

d.keene

 
 
//

Location

 

Block B Hammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

48 results found

Pharithi RB, Ayeni M, Makharia M, Keene D, Khiani Ret al., 2024, Optimizing conduction system pacing lead placement utilizing the image overlay technique., Pacing Clin Electrophysiol, Vol: 47, Pages: 260-264

The His-bundle has several locations from which conduction system pacing can be achieved. Some locations offer better sensing, thresholds and paced QRS durations. Existing techniques to aid repositioning of an already deployed, but sub-optimally placed lead, include either simple memory of the initial lead position combined with its observation on an x-ray review screen or utilizing an additional vascular access and pacing lead with the first lead serving as a real-time marker (Two-lead technique). We describe a novel, readily available, cost-efficient, imaging-based approach to assist in the re-positioning of a pacing lead for His-bundle pacing (the Image Overlay Technique).

Journal article

Sau A, Ahmed A, Chen JY, Pastika L, Wright I, Li X, Handa B, Qureshi N, Koa-Wing M, Keene D, Malcolme-Lawes L, Varnava A, Linton NWF, Lim PB, Lefroy D, Kanagaratnam P, Peters NS, Whinnett Z, Ng FSet al., 2024, Machine learning-derived cycle length variability metrics predict spontaneously terminating ventricular tachycardia in implantable cardioverter defibrillator recipients, European Heart Journal: Digital Health, Vol: 5, Pages: 50-59, ISSN: 2634-3916

AimsImplantable cardioverter defibrillator (ICD) therapies have been associated with increased mortality and should be minimized when safe to do so. We hypothesized that machine learning-derived ventricular tachycardia (VT) cycle length (CL) variability metrics could be used to discriminate between sustained and spontaneously terminating VT.Methods and resultsIn this single-centre retrospective study, we analysed data from 69 VT episodes stored on ICDs from 27 patients (36 spontaneously terminating VT, 33 sustained VT). Several VT CL parameters including heart rate variability metrics were calculated. Additionally, a first order auto-regression model was fitted using the first 10 CLs. Using features derived from the first 10 CLs, a random forest classifier was used to predict VT termination. Sustained VT episodes had more stable CLs. Using data from the first 10 CLs only, there was greater CL variability in the spontaneously terminating episodes (mean of standard deviation of first 10 CLs: 20.1 ± 8.9 vs. 11.5 ± 7.8 ms, P < 0.0001). The auto-regression coefficient was significantly greater in spontaneously terminating episodes (mean auto-regression coefficient 0.39 ± 0.32 vs. 0.14 ± 0.39, P < 0.005). A random forest classifier with six features yielded an accuracy of 0.77 (95% confidence interval 0.67 to 0.87) for prediction of VT termination.ConclusionVentricular tachycardia CL variability and instability are associated with spontaneously terminating VT and can be used to predict spontaneous VT termination. Given the harmful effects of unnecessary ICD shocks, this machine learning model could be incorporated into ICD algorithms to defer therapies for episodes of VT that are likely to self-terminate.

Journal article

Kaza N, Keene D, Vijayaraman P, Whinnett Zet al., 2023, Frontiers in conduction system pacing: treatment of long PR in patients with heart failure, European Heart Journal Supplements, Vol: 25, Pages: G27-G32, ISSN: 1554-2815

Patients with heart failure who have a prolonged PR interval are at a greater risk of adverse clinical outcomes than those with a normal PR interval. Potential mechanisms of harm relating to prolonged PR intervals include reduced ventricular filling and also the potential progression to a higher degree heart block. There has, however, been relatively little work specifically focusing on isolated PR prolongation as a therapeutic target. Secondary analyses of trials of biventricular pacing in heart failure have suggested that PR prolongation is both a prognostic marker and a promising treatment target. However, while biventricular pacing offers an improved activation pattern, it is nonetheless less physiological than native conduction in patients with a narrow QRS duration, and thus, may not be the ideal option for achieving therapeutic shortening of atrioventricular delay. Conduction system pacing aims to preserve physiological ventricular activation and may therefore be the ideal method for ventricular pacing in patients with isolated PR prolongation. Acute haemodynamic experiments and the recently reported His-optimized pacing evaluated for heart failure (HOPE HF) Randomised Controlled Trial demonstrates the potential benefits of physiological ventricular pacing on patient symptoms and left ventricular function in patients with heart failure.

Journal article

Vernooy K, Keene D, Huang W, Vijayaraman Pet al., 2023, Implant, assessment, and management of conduction system pacing., Eur Heart J Suppl, Vol: 25, Pages: G15-G26, ISSN: 1520-765X

His bundle pacing and left bundle branch pacing, together referred to as conduction system pacing, have (re)gained considerable interest over the past years as it has the potential to preserve and/or restore a more physiological ventricular activation when compared with right ventricular pacing and may serve as an alternative for cardiac resynchronization therapy. This review manuscript dives deeper into the implantation techniques and the relevant anatomy of the conduction system for both pacing strategies. Furthermore, the manuscript elaborates on better understanding of conduction system capture with its various capture patterns, its potential complications as well as appropriate follow-up care. Finally, the limitations and its impact on clinical care for both His bundle pacing and left bundle branch pacing are being discussed.

Journal article

Ali N, Saqi K, Arnold AD, Miyazawa AA, Keene D, Chow J-J, Little I, Peters NS, Kanagaratnam P, Qureshi N, Ng FS, Linton NWF, Lefroy DC, Francis DP, Boon Lim P, Tanner MA, Muthumala A, Agarwal G, Shun-Shin MJ, Cole GD, Whinnett ZIet al., 2023, Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics., Europace, Vol: 25

AIMS: Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit. METHODS AND RESULTS: We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1. Ventricular activation pattern, timing, and high-precision acute haemodynamic response were studied during LBBP with and without anodal capture. We recruited 21 patients with a mean age of 67 years, of whom 14 were males. We measured electrocardiogram timings and haemodynamics in all patients, and in 16, we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that RV septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration and total ventricular activation times were shorter (116 ± 12 vs. 129 ± 14 ms, P < 0.01 and 83 ± 18 vs. 90 ± 15 ms, P = 0.01). This required higher outputs (3.6 ± 1.9 vs. 0.6 ± 0.2 V, P < 0.01) but without additional haemodynamic benefit (mean difference -0.2 ± 3.8 mmHg compared with pacing without anodal capture, P = 0.2). CONCLUSION: Left bundle branch pacing with anodal capture advances RV activation by stimulating the RV septal myocardium. However, this requires higher outputs and does not improve acute haemodynamics. Aiming for anodal capture may therefore not be necessary.

Journal article

Shi X, Sau A, Li X, Patel K, Bajaj N, Varela M, Wu H, Handa B, Arnold A, Shun-Shin M, Keene D, Howard J, Whinnett Z, Peters N, Christensen K, Jensen HJ, Ng FSet al., 2023, Information theory-based direct causality measure to assess cardiac fibrillation dynamics, Journal of the Royal Society Interface, Vol: 20, ISSN: 1742-5662

Understanding the mechanism sustaining cardiac fibrillation can facilitate the personalization of treatment. Granger causality analysis can be used to determine the existence of a hierarchical fibrillation mechanism that is more amenable to ablation treatment in cardiac time-series data. Conventional Granger causality based on linear predictability may fail if the assumption is not met or given sparsely sampled, high-dimensional data. More recently developed information theory-based causality measures could potentially provide a more accurate estimate of the nonlinear coupling. However, despite their successful application to linear and nonlinear physical systems, their use is not known in the clinical field. Partial mutual information from mixed embedding (PMIME) was implemented to identify the direct coupling of cardiac electrophysiology signals. We show that PMIME requires less data and is more robust to extrinsic confounding factors. The algorithms were then extended for efficient characterization of fibrillation organization and hierarchy using clinical high-dimensional data. We show that PMIME network measures correlate well with the spatio-temporal organization of fibrillation and demonstrated that hierarchical type of fibrillation and drivers could be identified in a subset of ventricular fibrillation patients, such that regions of high hierarchy are associated with high dominant frequency.

Journal article

Ali N, Arnold AD, Miyazawa AA, Keene D, Peters NS, Kanagaratnam P, Qureshi N, Ng FS, Linton NWF, Lefroy DC, Francis DP, Lim PB, Kellman P, Tanner MA, Muthumala A, Shun-Shin M, Whinnett ZI, Cole GDet al., 2023, Septal scar as a barrier to left bundle branch area pacing, PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY, Vol: 46, Pages: 1077-1084, ISSN: 0147-8389

Journal article

Sau A, 2023, Artificial intelligence-enabled electrocardiogram to distinguish atrioventricular re-entrant tachycardia from atrioventricular nodal re-entrant tachycardia, Cardiovascular Digital Health Journal, Vol: 4, Pages: 60-67, ISSN: 2666-6936

BackgroundAccurately determining arrhythmia mechanism from a 12-lead electrocardiogram (ECG) of supraventricular tachycardia can be challenging. We hypothesized a convolutional neural network (CNN) can be trained to classify atrioventricular re-entrant tachycardia (AVRT) vs atrioventricular nodal re-entrant tachycardia (AVNRT) from the 12-lead ECG, when using findings from the invasive electrophysiology (EP) study as the gold standard.MethodsWe trained a CNN on data from 124 patients undergoing EP studies with a final diagnosis of AVRT or AVNRT. A total of 4962 5-second 12-lead ECG segments were used for training. Each case was labeled AVRT or AVNRT based on the findings of the EP study. The model performance was evaluated against a hold-out test set of 31 patients and compared to an existing manual algorithm.ResultsThe model had an accuracy of 77.4% in distinguishing between AVRT and AVNRT. The area under the receiver operating characteristic curve was 0.80. In comparison, the existing manual algorithm achieved an accuracy of 67.7% on the same test set. Saliency mapping demonstrated the network used the expected sections of the ECGs for diagnoses; these were the QRS complexes that may contain retrograde P waves.ConclusionWe describe the first neural network trained to differentiate AVRT from AVNRT. Accurate diagnosis of arrhythmia mechanism from a 12-lead ECG could aid preprocedural counseling, consent, and procedure planning. The current accuracy from our neural network is modest but may be improved with a larger training dataset.

Journal article

Kaza N, Htun V, Miyazawa A, Simader F, Porter B, Howard JP, Arnold AD, Naraen A, Luria D, Glikson M, Israel C, Francis DP, Whinnett Z, Shun-Shin MJ, Keene Det al., 2023, Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a systematic review and meta-analysis, EUROPACE, Vol: 25, Pages: 1077-1086, ISSN: 1099-5129

Journal article

Keene D, Anselme F, Burri H, Perez OC, Curila K, Derndorfer M, Foley P, Geller L, Glikson M, Huybrechts W, Jastrzebski M, Kaczmarek K, Katsouras G, Lyne J, Verdu PP, Restle C, Richter S, Timmer S, Vernooy K, Whinnett Zet al., 2023, Conduction system pacing, a European survey: insights from clinical practice, EUROPACE, ISSN: 1099-5129

Journal article

Coyle C, Koutsoftidis S, Kim M-Y, Porter B, Keene D, Luther V, Handa B, Kay J, Lim E, Malcolme-Lawes L, Koa-Wing M, Lim PB, Whinnett ZI, Ng FS, Qureshi N, Peters NS, Linton NWF, Drakakis E, Kanagaratnam Pet al., 2023, Feasibility of mapping and ablating ectopy-triggering ganglionated plexus reproducibly in persistent atrial fibrillation, Journal of Interventional Cardiac Electrophysiology: an international journal of arrhythmias and pacing, ISSN: 1383-875X

BackgroundAblation of autonomic ectopy-triggering ganglionated plexuses (ET-GP) has been used to treat paroxysmal atrial fibrillation (AF). It is not known if ET-GP localisation is reproducible between different stimulators or whether ET-GP can be mapped and ablated in persistent AF. We tested the reproducibility of the left atrial ET-GP location using different high-frequency high-output stimulators in AF. In addition, we tested the feasibility of identifying ET-GP locations in persistent atrial fibrillation.MethodsNine patients undergoing clinically-indicated paroxysmal AF ablation received pacing-synchronised high-frequency stimulation (HFS), delivered in SR during the left atrial refractory period, to compare ET-GP localisation between a custom-built current-controlled stimulator (Tau20) and a voltage-controlled stimulator (Grass S88, SIU5). Two patients with persistent AF underwent cardioversion, left atrial ET-GP mapping with the Tau20 and ablation (Precision™, Tacticath™ [n = 1] or Carto™, SmartTouch™ [n = 1]). Pulmonary vein isolation (PVI) was not performed. Efficacy of ablation at ET-GP sites alone without PVI was assessed at 1 year.ResultsThe mean output to identify ET-GP was 34 mA (n = 5). Reproducibility of response to synchronised HFS was 100% (Tau20 vs Grass S88; [n = 16] [kappa = 1, SE = 0.00, 95% CI 1 to 1)][Tau20 v Tau20; [n = 13] [kappa = 1, SE = 0, 95% CI 1 to 1]). Two patients with persistent AF had 10 and 7 ET-GP sites identified requiring 6 and 3 min of radiofrequency ablation respectively to abolish ET-GP response. Both patients were free from AF for > 365 days without anti-arrhythmics.ConclusionsET-GP sites are identified at the same location by different stimulators. ET-GP ablation alone was able to prevent AF recurrence in persistent AF, and further studies would be warranted

Journal article

Ali N, Arnold AD, Miyazawa AA, Keene D, Chow J-J, Little I, Peters NS, Kanagaratnam P, Qureshi N, Ng FS, Linton NWF, Lefroy DC, Francis DP, Lim PB, Tanner MA, Muthumala A, Shun-Shin MJ, Cole GD, Whinnett Zet al., 2023, Comparison of methods for delivering cardiac resynchronization therapy: an acute electrical and haemodynamic within-patient comparison of left bundle branch area, His bundle, and biventricular pacing, EP Europace, Vol: 25, Pages: 1060-1067, ISSN: 1099-5129

AimsLeft bundle branch area pacing (LBBAP) is a promising method for delivering cardiac resynchronization therapy (CRT), but its relative physiological effectiveness compared with His bundle pacing (HBP) is unknown. We conducted a within-patient comparison of HBP, LBBAP, and biventricular pacing (BVP).Methods and resultsPatients referred for CRT were recruited. We assessed electrical response using non-invasive mapping, and acute haemodynamic response using a high-precision haemodynamic protocol. Nineteen patients were recruited: 14 male, mean LVEF of 30%. Twelve had time for BVP measurements. All three modalities reduced total ventricular activation time (TVAT), (ΔTVATHBP -43 ± 14 ms and ΔTVATLBBAP −35 ± 20 ms vs. ΔTVATBVP −19 ± 30 ms, P = 0.03 and P = 0.1, respectively). HBP produced a significantly greater reduction in TVAT compared with LBBAP in all 19 patients (−46 ± 15 ms, −36 ± 17 ms, P = 0.03). His bundle pacing and LBBAP reduced left ventricular activation time (LVAT) more than BVP (ΔLVATHBP −43 ± 16 ms, P < 0.01 vs. BVP, ΔLVATLBBAP −45 ± 17 ms, P < 0.01 vs. BVP, ΔLVATBVP −13 ± 36 ms), with no difference between HBP and LBBAP (P = 0.65). Acute systolic blood pressure was increased by all three modalities. In the 12 with BVP, greater improvement was seen with HBP and LBBAP (6.4 ± 3.8 mmHg BVP, 8.1 ± 3.8 mmHg HBP, P = 0.02 vs. BVP and 8.4 ± 8.2 mmHg for LBBAP, P = 0.3 vs. BVP), with no difference between HBP and LBBAP (P = 0.8).ConclusionHBP delivered better ventricular resynchronization than LBBAP because right ventricular activation was slower during LBBAP. But LBBAP was not inferior to HBP with respect to LV electrical resynchronization and acute haemodynamic response.

Journal article

Simader FA, Howard JP, Ahmad Y, Saleh K, Naraen A, Samways JW, Mohal J, Reddy RK, Kaza N, Keene D, Shun-Shin MJ, Francis DP, Whinnett Z, Arnold ADet al., 2023, Catheter ablation improves cardiovascular outcomes in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials, EUROPACE, Vol: 25, Pages: 341-350, ISSN: 1099-5129

Journal article

Whinnett ZI, Shun-Shin MJ, Tanner M, Foley P, Chandrasekaran B, Moore P, Adhya S, Qureshi N, Muthumala A, Lane R, Rinaldi A, Agarwal S, Leyva F, Behar J, Bassi S, Ng A, Scott P, Prasad R, Swinburn J, Tomson J, Sethi A, Shah J, Lim PB, Kyriacou A, Thomas D, Chuen J, Kamdar R, Kanagaratnam P, Mariveles M, Burden L, March K, Howard JP, Arnold A, Vijayaraman P, Stegemann B, Johnson N, Falaschetti E, Francis DP, Cleland JGF, Keene Det al., 2023, Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 25, Pages: 274-283, ISSN: 1388-9842

Journal article

Zuhair M, Keene D, Kanagaratnam P, Lim PBet al., 2023, Percutaneous Neuromodulation for Atrial Fibrillation, Cardiac Electrophysiology Clinics, ISSN: 1877-9182

Journal article

Arnold AD, Shun-Shin MJ, Ali N, Keene D, Howard JP, Francis DP, Whinnett ZIet al., 2023, Contributions of Atrioventricular Delay Shortening and Ventricular Resynchronization to Hemodynamic Benefits of Biventricular Pacing, JACC-CLINICAL ELECTROPHYSIOLOGY, Vol: 9, Pages: 117-119, ISSN: 2405-500X

Journal article

Reddy RK, Howard JP, Ahmad Y, Shun-Shin MJ, Simader FA, Miyazawa AA, Saleh K, Naraen A, Samways JW, Katritsis G, Mohal JS, Kaza N, Porter B, Keene D, Linton NW, Francis DP, Whinnett ZI, Luther V, Kanagaratnam P, Arnold ADet al., 2023, Catheter Ablation for Ventricular Tachycardia After MI: A Reconstructed Individual Patient Data Meta-analysis of Randomised Controlled Trials., Arrhythm Electrophysiol Rev, Vol: 12, ISSN: 2050-3369

BACKGROUND: The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised controlled trials comparing ablation to medical therapy in patients developing VT after MI. METHODS: We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included. RESULTS: Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI [0.41-0.96]; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI [0.67-1.23]; p=0.53; I2=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses. CONCLUSION: In patients with postinfarct VT, catheter ablation reduces mortality.

Journal article

Sau A, Ibrahim S, Ahmed A, Handa B, Kramer DB, Waks JW, Arnold AD, Howard JP, Qureshi N, Koa-Wing M, Keene D, Malcolme-Lawes L, Lefroy DC, Linton NWF, Lim PB, Varnava A, Whinnett ZI, Kanagaratnam P, Mandic D, Peters NS, Ng FSet al., 2022, Artificial intelligence-enabled electrocardiogram to distinguish cavotricuspid isthmus dependence from other atrial tachycardia mechanisms, European Heart Journal – Digital Health, Vol: 3, Pages: 405-414, ISSN: 2634-3916

Aims:Accurately determining atrial arrhythmia mechanisms from a 12-lead electrocardiogram (ECG) can be challenging. Given the high success rate of cavotricuspid isthmus (CTI) ablation, identification of CTI-dependent typical atrial flutter (AFL) is important for treatment decisions and procedure planning. We sought to train a convolutional neural network (CNN) to classify CTI-dependent AFL vs. non-CTI dependent atrial tachycardia (AT), using data from the invasive electrophysiology (EP) study as the gold standard.Methods and results:We trained a CNN on data from 231 patients undergoing EP studies for atrial tachyarrhythmia. A total of 13 500 five-second 12-lead ECG segments were used for training. Each case was labelled CTI-dependent AFL or non-CTI-dependent AT based on the findings of the EP study. The model performance was evaluated against a test set of 57 patients. A survey of electrophysiologists in Europe was undertaken on the same 57 ECGs. The model had an accuracy of 86% (95% CI 0.77–0.95) compared to median expert electrophysiologist accuracy of 79% (range 70–84%). In the two thirds of test set cases (38/57) where both the model and electrophysiologist consensus were in agreement, the prediction accuracy was 100%. Saliency mapping demonstrated atrial activation was the most important segment of the ECG for determining model output.Conclusion:We describe the first CNN trained to differentiate CTI-dependent AFL from other AT using the ECG. Our model matched and complemented expert electrophysiologist performance. Automated artificial intelligence-enhanced ECG analysis could help guide treatment decisions and plan ablation procedures for patients with organized atrial arrhythmias.

Journal article

Kaza N, Keene D, Whinnett ZI, 2022, Generating Evidence to Support the Physiologic Promise of Conduction System Pacing: Status and Update on Conduction System Pacing Trials., Card Electrophysiol Clin, Vol: 14, Pages: 345-355

Conduction system pacing avoids the potential deleterious effects of right ventricular pacing in patients with bradycardia and provides an alternative approach to cardiac resynchronization therapy. We focus on the available observational and randomized evidence and review studies supporting the safety, feasibility, and physiologic promise of conduction system approaches. We evaluate the randomized data generated from the available clinical trials of conduction system pacing, which have led to the recent inclusion of CSP in international guidelines. The scope for future randomized trials will building on the physiologic promise of conduction system approaches and offering information on clinical end points is explored.

Journal article

Keene D, Whinnett Z, 2022, Advances in cardiac resynchronisation therapy: review of indications and delivery options, HEART, Vol: 108, Pages: 889-897, ISSN: 1355-6037

Journal article

Keene D, Miyazawa AA, Johal M, Arnold AD, Ali N, Saqi KA, March K, Burden L, Francis DP, Whinnett Z, Shun-Shin MJet al., 2022, Optimizing atrio-ventricular delay in pacemakers using potentially implantable physiological biomarkers, Pacing and Clinical Electrophysiology, Vol: 45, Pages: 461-470, ISSN: 0147-8389

BackgroundHemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices.We assess whether laser Doppler can be used instead of BP to optimize AV delay.MethodsFifty eight patients underwent 94 AV delay optimizations with biventricular or His-bundle pacing using laser Doppler and simultaneous noninvasive beat-by-beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40–320 ms), with automatic quality control checking precision of the optimum.Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality.Results55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms).An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms.ConclusionsLaser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.

Journal article

Ahmad Y, Kane C, Arnold AD, Cook C, Keene D, Shun-Shin M, Cole G, Al-Lamee R, Francis D, Howard Jet al., 2022, Randomized blinded placebo-controlled trials of renal sympathetic denervation for hypertension: a meta-analysis, Cardiovascular Revascularization Medicine, Vol: 34, Pages: 112-118, ISSN: 1553-8389

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension.MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed.Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation.ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

Journal article

Bachtiger P, Petri CF, Scott FE, Ri Park S, Kelshiker MA, Sahemey HK, Dumea B, Alquero R, Padam PS, Hatrick IR, Ali A, Ribeiro M, Cheung W-S, Bual N, Rana B, Shun-Shin M, Kramer DB, Fragoyannis A, Keene D, Plymen CM, Peters NSet al., 2022, Point-of-care screening for heart failure with reduced ejection fraction using artificial intelligence during ECG-enabled stethoscope examination in London, UK: a prospective, observational, multicentre study, The Lancet Digital Health, Vol: 4, ISSN: 2589-7500

BACKGROUND: Most patients who have heart failure with a reduced ejection fraction, when left ventricular ejection fraction (LVEF) is 40% or lower, are diagnosed in hospital. This is despite previous presentations to primary care with symptoms. We aimed to test an artificial intelligence (AI) algorithm applied to a single-lead ECG, recorded during ECG-enabled stethoscope examination, to validate a potential point-of-care screening tool for LVEF of 40% or lower. METHODS: We conducted an observational, prospective, multicentre study of a convolutional neural network (known as AI-ECG) that was previously validated for the detection of reduced LVEF using 12-lead ECG as input. We used AI-ECG retrained to interpret single-lead ECG input alone. Patients (aged ≥18 years) attending for transthoracic echocardiogram in London (UK) were recruited. All participants had 15 s of supine, single-lead ECG recorded at the four standard anatomical positions for cardiac auscultation, plus one handheld position, using an ECG-enabled stethoscope. Transthoracic echocardiogram-derived percentage LVEF was used as ground truth. The primary outcome was performance of AI-ECG at classifying reduced LVEF (LVEF ≤40%), measured using metrics including the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity, with two-sided 95% CIs. The primary outcome was reported for each position individually and with an optimal combination of AI-ECG outputs (interval range 0-1) from two positions using a rule-based approach and several classification models. This study is registered with ClinicalTrials.gov, NCT04601415. FINDINGS: Between Feb 6 and May 27, 2021, we recruited 1050 patients (mean age 62 years [SD 17·4], 535 [51%] male, 432 [41%] non-White). 945 (90%) had an ejection fraction of at least 40%, and 105 (10%) had an ejection fraction of 40% or lower. Across all positions, ECGs were most frequently of adequate quality for AI-ECG interpretation at the p

Journal article

Whinnett Z, Tanner M, Chandrasekaran B, Foley P, Moore P, Adhya S, Qureshi N, Muthumala A, Behar J, Lane RE, Rinaldi CA, Agarwal S, Farwell D, Leyva F, Bassi S, Ng GA, Scott P, Prasad R, Swinburn J, Tomson J, Kyriacou A, Thomas DE, Chuen J, Kamdar R, Lim PB, Sethi A, Shah J, Vijayaraman P, Johnson N, Falaschetti E, Mariveles M, Kanagaratnam P, Cleland J, Francis D, Keene Det al., 2021, His-Optimized Pacing in Patients With a Long PR Interval, Narrow QRS and Heart Failure: Results of the Hope-hf Clinical Trial, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E587-E587, ISSN: 0009-7322

Conference paper

Arnold AD, Shun-Shin MJ, Ali N, Keene D, Howard JP, Chow J-J, Qureshi NA, Koa-Wing M, Tanner M, Lefroy DC, Linton NWF, Ng FS, Lim PB, Peters NS, Kanagaratnam P, Francis DP, Whinnett ZIet al., 2021, Left ventricular activation time and pattern are preserved with both selective and non-selective his bundle pacing, Heart Rhythm O2, Vol: 2, Pages: 439-445, ISSN: 2666-5018

BackgroundHis bundle pacing (HBP) can be achieved in two ways: selective HBP (S-HBP), where the His bundle is captured alone, and non-selective HBP (NS-HBP), where local myocardium is also captured resulting a pre-excited ECG appearance.ObjectiveWe assessed the impact of this ventricular pre-excitation on left and right ventricular dys-synchrony.MethodsWe recruited patients who displayed both S-HBP and NS-HBP. We performed non-invasive epicardial electrical mapping for left and right ventricular activation time (LVAT and RVAT) and pattern.Results20 patients were recruited. In the primary analysis, the mean within-patient change in LVAT from S-HBP to NS-HBP was -5.5ms (95% confidence interval: -0.6 to -10.4, non-inferiority p<0.0001). NS-HBP did not prolong RVAT (4.3ms, -4.0 to 12.8, p=0.296) but did prolong QRS duration (QRSd, 22.1ms, 11.8 to 32.4, p = 0.0003). In patients with narrow intrinsic QRS (n=6), NS-HBP preserved LVAT (-2.9ms, -9.7 to 4.0, p=0.331) but prolonged QRS duration (31.4ms, 22.0 to 40.7, p=0.0003) and mean RVAT (16.8ms, -5.3 to 38.9, p=0.108) compared to S-HBP. Activation pattern of the left ventricular surface was unchanged between S-HBP and NS-HBP but NS-HBP produced early basal right ventricular activation that was not seen in S-HBP.ConclusionCompared to S-HBP, local myocardial capture during NS-HBP produces pre-excitation of the basal right ventricle resulting in QRS duration prolongation. However, NS-HBP preserves the left ventricular activation time and pattern of S-HBP. Left ventricular dys-synchrony is not an important factor when choosing between S-HBP and NS-HBP in most patients.

Journal article

Arnold AD, Shun-Shin MJ, Keene D, Howard JP, Chow J-J, Lim E, Lampridou S, Miyazawa AA, Muthumala A, Tanner M, Qureshi NA, Lefroy DC, Koa-Wing M, Linton NWF, Boon Lim P, Peters NS, Kanagaratnam P, Auricchio A, Francis DP, Whinnett ZIet al., 2021, Electrocardiographic predictors of successful resynchronization of left bundle branch block by his bundle pacing, Journal of Cardiovascular Electrophysiology, Vol: 32, Pages: 428-438, ISSN: 1045-3873

BackgroundHis 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.ObjectiveTo compare activation times and patterns of His-CRT with BVP-CRT, LBBB and intact conduction systems.MethodsIn 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.ResultsForty-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).ConclusionNoninvasive 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.

Journal article

Keene D, Shun-Shin MJ, Arnold AD, March K, Qureshi N, Ng FS, Tanner M, Linton N, Lim PB, Lefroy D, Kanagaratnam P, Peters NS, Francis DP, Whinnett ZIet al., 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, Journal of Cardiovascular Electrophysiology, Vol: 31, Pages: 2964-2974, ISSN: 1045-3873

AimsA 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.MethodsOutpatients 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]).ResultsWe 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).ConclusionsHBP 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

Journal article

Arnold AD, Howard JP, Gopi AA, Chan CP, Ali N, Keene D, Shun-Shin MJ, Ahmad Y, Wright IJ, Ng FS, Linton NWF, Kanagaratnam P, Peters NS, Rueckert D, Francis DP, Whinnett ZIet al., 2020, Discriminating electrocardiographic responses to His-bundle pacing using machine learning., Cardiovascular Digital Health Journal, Vol: 1, Pages: 11-20

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; P <.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.

Journal article

Bohm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Konstantinidis D, Choi JW, East C, Lee DP, Ma A, Ewen S, Cohen DL, Wilensky R, Devireddy CM, Lea J, Schmid A, Weil J, Agdirlioglu T, Reedus D, Jefferson BK, Reyes D, D'Souza R, Sharp ASP, Sharif F, Fahy M, DeBruin V, Cohen SA, Brar S, Townsend RRet al., 2020, Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial, LANCET, Vol: 395, Pages: 1444-1451, ISSN: 0140-6736

Journal article

Pucci N, Kwan CH, Yates DC, Arnold AD, Keene D, Whinnett ZI, Mitcheson PDet al., 2020, Effect of fields generated through wireless power transfer on implantable biomedical devices, 2019 IEEE PELS Workshop on Emerging Technologies: Wireless Power Transfer (WoW), Publisher: IEEE, Pages: 1-5

This paper assesses the safety of pacemakers when exposed to the electromagnetic (EM) field generated by high frequency inductive power transfer (HF-IPT) systems. It includes both simulation and experimental results, showing temperature variations to ensure conformity with the EN standards, changes in detected lead impedance and determining whether EM field strength can affect the operating mode of the device. This is the first time the interaction between 6.78MHz, 100W HF-IPT systems and pacemaker devices was tested up to distances of 5 cm to 10 cm, Temporary decrease of detected lead's impedance and interruption of communications are the most relevant effects recorded through in-vitro tests. No permanent alteration of the device's operation was recorded, indicating good early stage evidence of safety for pacemaker users in proximity of this new emerging technology.

Conference paper

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00801259&limit=30&person=true