Publications by authors named "Ahran D Arnold"

19 Publications

  • Page 1 of 1

Randomized blinded placebo-controlled trials of renal sympathetic denervation for hypertension: A meta-analysis.

Cardiovasc Revasc Med 2021 Jan 30. Epub 2021 Jan 30.

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

Background: The 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.

Methods: We 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.

Results: 6 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.

Conclusions: The 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.
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http://dx.doi.org/10.1016/j.carrev.2021.01.031DOI 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

His-Purkinje Conduction System Pacing: State of the Art in 2020.

Arrhythm Electrophysiol Rev 2020 Nov;9(3):136-145

Geisinger Heart Institute, Geisinger Commonwealth School of Medicine, Wilkes-Barre, Pennsylvania, US.

Conduction system pacing involves directly stimulating the specialised His-Purkinje cardiac conduction system with the aim of activating the ventricles physiologically, in contrast to the dyssynchronous activation produced by conventional myocardial pacing. Since the first report of permanent His bundle pacing (HBP) in 2000, the stylet-driven technique of its earliest incarnation has been superseded by a more successful stylet-less approach. Widespread uptake has led to a much greater evidence base. Single-centre observational studies have now been supported by large multicentre, international registries, mechanistic studies and the first randomised controlled trials. New evidence has elucidated mechanisms of HBP and illustrated the nature and magnitude of its potential benefits for preventing pacing-induced cardiomyopathy and correcting bundle branch block. Left bundle branch pacing (LBBP) is a newer technique in which the lead is fixed deep into the left side of the intraventricular septum to allow capture of the left bundle, distal to the His bundle. LBBP holds promise as a method for physiological pacing that overcomes some of the fixation, threshold and sensing challenges of HBP. In this state-of-the-art review of His-Purkinje conduction system pacing, the authors assess recent evidence and current practice and explore emerging and future directions in this rapidly evolving field.
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http://dx.doi.org/10.15420/aer.2020.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675135PMC
November 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

Drug-Eluting Stents Versus Bypass Surgery for Left Main Disease: An Updated Meta-Analysis of Randomized Controlled Trials With Long-Term Follow-Up.

Am J Cardiol 2020 10 30;132:168-172. Epub 2020 Jun 30.

The Cardiovascular Research Foundation, New York, New York; Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.

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http://dx.doi.org/10.1016/j.amjcard.2020.06.059DOI Listing
October 2020

Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients.

Pharmacol Res Perspect 2020 08;8(4):e00631

Department of Gastroenterology, Ealing Hospital, London North West University Healthcare NHS Trust, Southall, UK.

We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID-19. Pentoxifylline is an immunomodulator with anti-inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor-mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS-CoV-2 infection. This agent has been used clinically for many years and has a favorable profile of safety and tolerability. Pre-clinical data support pentoxifylline as effective in cytokine-driven lung damage. Clinical studies of pentoxifylline in radiation and cytokine-induced lung damage in humans are positive and consistent with anti-inflammatory efficacy. Pentoxifylline is a readily available, off-patent and inexpensive drug, suitable for large-scale use including in resource-limited countries. Current trials of therapeutics are largely focused on the inhibition of viral processes. We advocate urgent randomized trials of pentoxifylline for COVID-19 as a complementary approach to target the host responses.
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http://dx.doi.org/10.1002/prp2.631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383088PMC
August 2020

Bias, heterogeneity, and uncertainty in meta-analysis.

Eur Heart J 2020 07;41(28):2712

National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0HS, UK.

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http://dx.doi.org/10.1093/eurheartj/ehaa394DOI Listing
July 2020

Improving ultrasound video classification: an evaluation of novel deep learning methods in echocardiography.

J Med Artif Intell 2020 Mar;3

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

Echocardiography is the commonest medical ultrasound examination, but automated interpretation is challenging and hinges on correct recognition of the 'view' (imaging plane and orientation). Current state-of-the-art methods for identifying the view computationally involve 2-dimensional convolutional neural networks (CNNs), but these merely classify individual frames of a video in isolation, and ignore information describing the movement of structures throughout the cardiac cycle. Here we explore the efficacy of novel CNN architectures, including time-distributed networks and two-stream networks, which are inspired by advances in human action recognition. We demonstrate that these new architectures more than halve the error rate of traditional CNNs from 8.1% to 3.9%. These advances in accuracy may be due to these networks' ability to track the movement of specific structures such as heart valves throughout the cardiac cycle. Finally, we show the accuracies of these new state-of-the-art networks are approaching expert agreement (3.6% discordance), with a similar pattern of discordance between views.
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http://dx.doi.org/10.21037/jmai.2019.10.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100611PMC
March 2020

Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).

J Am Heart Assoc 2020 04 26;9(7):e013684. Epub 2020 Mar 26.

NIHR Imperial Biomedical Research Centre Imperial College London and Imperial College Healthcare NHS Trust London United Kingdom.

Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow-up of 1462 (interquartile range, 929-1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01-1.43; <0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9-3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42-0.89; =0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.
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http://dx.doi.org/10.1161/JAHA.119.013684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428631PMC
April 2020

Mortality after drug-eluting stents vs. coronary artery bypass grafting for left main coronary artery disease: a meta-analysis of randomized controlled trials.

Eur Heart J 2020 09;41(34):3228-3235

Center for Interventional Vascular Therapy, Columbia University Medical Center, NewYork-Presbyterian Hospital, 161 Fort Washington Avenue, New York, NY 10032, USA.

Aims: The optimal method of revascularization for patients with left main coronary artery disease (LMCAD) is controversial. Coronary artery bypass graft surgery (CABG) has traditionally been considered the gold standard therapy, and recent randomized trials comparing CABG with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have reported conflicting outcomes. We, therefore, performed a systematic review and updated meta-analysis comparing CABG to PCI with DES for the treatment of LMCAD.

Methods And Results: We systematically identified all randomized trials comparing PCI with DES vs. CABG in patients with LMCAD. The primary efficacy endpoint was all-cause mortality. Secondary endpoints included cardiac death, myocardial infarction (MI), stroke, and unplanned revascularization. All analyses were by intention-to-treat. There were five eligible trials in which 4612 patients were randomized. The weighted mean follow-up duration was 67.1 months. There were no significant differences between PCI and CABG for the risk of all-cause mortality [relative risk (RR) 1.03, 95% confidence interval (CI) 0.81-1.32; P = 0.779] or cardiac death (RR 1.03, 95% CI 0.79-1.34; P = 0.817). There were also no significant differences in the risk of stroke (RR 0.74, 95% CI 0.35-1.50; P = 0.400) or MI (RR 1.22, 95% CI 0.96-1.56; P = 0.110). Percutaneous coronary intervention was associated with an increased risk of unplanned revascularization (RR 1.73, 95% CI 1.49-2.02; P < 0.001).

Conclusion: The totality of randomized clinical trial evidence demonstrated similar long-term mortality after PCI with DES compared with CABG in patients with LMCAD. Nor were there significant differences in cardiac death, stroke, or MI between PCI and CABG. Unplanned revascularization procedures were less common after CABG compared with PCI. These findings may inform clinical decision-making between cardiologists, surgeons, and patients with LMCAD.
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http://dx.doi.org/10.1093/eurheartj/ehaa135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557472PMC
September 2020

His bundle pacing, learning curve, procedure characteristics, safety, and feasibility: Insights from a large international observational study.

J Cardiovasc Electrophysiol 2019 10 2;30(10):1984-1993. Epub 2019 Aug 2.

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

Background: His-bundle pacing (HBP) provides physiological ventricular activation. Observational studies have demonstrated the techniques' feasibility; however, data have come from a limited number of centers.

Objectives: We set out to explore the contemporary global practice in HBP focusing on the learning curve, procedural characteristics, and outcomes.

Methods: This is a retrospective, multicenter observational study of patients undergoing attempted HBP at seven centers. Pacing indication, fluoroscopy time, HBP thresholds, and lead reintervention and deactivation rates were recorded. Where centers had systematically recorded implant success rates from the outset, these were collated.

Results: A total of 529 patients underwent attempted HBP during the study period (2014-19) with a mean follow-up of 217 ± 303 days. Most implants were for bradycardia indications. In the three centers with the systematic collation of all attempts, the overall implant success rate was 81%, which improved to 87% after completion of 40 cases. All seven centers reported data on successful implants. The mean fluoroscopy time was 11.7 ± 12.0 minutes, the His-bundle capture threshold at implant was 1.4 ± 0.9 V at 0.8 ± 0.3 ms, and it was 1.3 ± 1.2 V at 0.9 ± 0.2 ms at last device check. HBP lead reintervention or deactivation (for lead displacement or rise in threshold) occurred in 7.5% of successful implants. There was evidence of a learning curve: fluoroscopy time and HBP capture threshold reduced with greater experience, plateauing after approximately 30-50 cases.

Conclusion: We found that it is feasible to establish a successful HBP program, using the currently available implantation tools. For physicians who are experienced at pacemaker implantation, the steepest part of the learning curve appears to be over the first 30-50 cases.
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http://dx.doi.org/10.1111/jce.14064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038224PMC
October 2019

Editorial commentary: His bundle pacing: The road ahead.

Trends Cardiovasc Med 2019 08 13;29(6):333-334. Epub 2018 Oct 13.

Geisinger Heart Institute, Geisinger Commonwealth School of Medicine, Geisinger Wyoming Valley Medical Center, MC 36-10, 1000 E Mountain Blvd, Wilkes-Barre, PA 18711, USA. Electronic address:

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http://dx.doi.org/10.1016/j.tcm.2018.10.004DOI Listing
August 2019

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

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

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

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

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

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

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

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

Cardiac Rhythm Device Identification Using Neural Networks.

JACC Clin Electrophysiol 2019 05 27;5(5):576-586. Epub 2019 Mar 27.

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

Objectives: This paper reports the development, validation, and public availability of a new neural network-based system which attempts to identify the manufacturer and even the model group of a pacemaker or defibrillator from a chest radiograph.

Background: Medical staff often need to determine the model of a pacemaker or defibrillator (cardiac rhythm device) quickly and accurately. Current approaches involve comparing a device's radiographic appearance with a manual flow chart.

Methods: In this study, radiographic images of 1,676 devices, comprising 45 models from 5 manufacturers were extracted. A convolutional neural network was developed to classify the images, using a training set of 1,451 images. The testing set contained an additional 225 images consisting of 5 examples of each model. The network's ability to identify the manufacturer of a device was compared with that of cardiologists, using a published flowchart.

Results: The neural network was 99.6% (95% confidence interval [CI]: 97.5% to 100.0%) accurate in identifying the manufacturer of a device from a radiograph and 96.4% (95% CI: 93.1% to 98.5%) accurate in identifying the model group. Among 5 cardiologists who used the flowchart, median identification of manufacturer accuracy was 72.0% (range 62.2% to 88.9%), and model group identification was not possible. The network's ability to identify the manufacturer of the devices was significantly superior to that of all the cardiologists (p < 0.0001 compared with the median human identification; p < 0.0001 compared with the best human identification).

Conclusions: A neural network can accurately identify the manufacturer and even model group of a cardiac rhythm device from a radiograph and exceeds human performance. This system may speed up the diagnosis and treatment of patients with cardiac rhythm devices, and it is publicly accessible online.
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http://dx.doi.org/10.1016/j.jacep.2019.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537849PMC
May 2019

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

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

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

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

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

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

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

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

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

Background: His bundle pacing is a new method for delivering cardiac resynchronization therapy (CRT).

Objectives: The authors performed a head-to-head, high-precision, acute crossover comparison between His bundle pacing and conventional biventricular CRT, measuring effects on ventricular activation and acute hemodynamic function.

Methods: Patients with heart failure and left bundle branch block referred for conventional biventricular CRT were recruited. Using noninvasive epicardial electrocardiographic imaging, the authors identified patients in whom His bundle pacing shortened left ventricular activation time. In these patients, the authors compared the hemodynamic effects of His bundle pacing against biventricular pacing using a high-multiple repeated alternation protocol to minimize the effect of noise, as well as comparing effects on ventricular activation.

Results: In 18 of 23 patients, left ventricular activation time was significantly shortened by His bundle pacing. Seventeen patients had a complete electromechanical dataset. In them, His bundle pacing was more effective at delivering ventricular resynchronization than biventricular pacing: greater reduction in QRS duration (-18.6 ms; 95% confidence interval [CI]: -31.6 to -5.7 ms; p = 0.007), left ventricular activation time (-26 ms; 95% CI: -41 to -21 ms; p = 0.002), and left ventricular dyssynchrony index (-11.2 ms; 95% CI: -16.8 to -5.6 ms; p < 0.001). His bundle pacing also produced a greater acute hemodynamic response (4.6 mm Hg; 95% CI: 0.2 to 9.1 mm Hg; p = 0.04). The incremental activation time reduction with His bundle pacing over biventricular pacing correlated with the incremental hemodynamic improvement with His bundle pacing over biventricular pacing (R = 0.70; p = 0.04).

Conclusions: His resynchronization delivers better ventricular resynchronization, and greater improvement in hemodynamic parameters, than biventricular pacing.
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http://dx.doi.org/10.1016/j.jacc.2018.09.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290113PMC
December 2018

Permanent His Bundle Pacing for Cardiac Resynchronization Therapy in Patients With Heart Failure and Right Bundle Branch Block.

Circ Arrhythm Electrophysiol 2018 09;11(9):e006613

Geisinger Heart Institute, Wilkes-Barre, PA (A.N., T.D.B., P.V.).

Background Cardiac resynchronization therapy utilizing biventricular pacing is an effective therapy for patients with left ventricular (LV) systolic dysfunction, left bundle branch block, and heart failure. Benefits of biventricular pacing may be limited in patients with right bundle branch block (RBBB). Permanent His bundle pacing (HBP) has recently been reported as an option for cardiac resynchronization therapy. The aim of the study was to assess the feasibility and outcomes of HBP in patients with RBBB and heart failure. Methods HBP was attempted as a primary or rescue (failed LV lead implant) strategy in patients with reduced LV ejection fraction, RBBB, QRS duration ≥120 ms, and New York Heart Association class II to IV heart failure. Implant characteristics, New York Heart Association functional class, and echocardiographic data were assessed in follow-up. Results Mean age was 72±10 years, female 15%, with an average LV ejection fraction of 31±10%. HBP was successful in 37 of 39 patients (95%) with narrowing of RBBB in 78% cases. His capture and bundle branch block correction thresholds were 1.1±0.6 V and 1.4±0.7 V at 1 ms, respectively. During a mean follow-up of 15±23 months, there was a significant narrowing of QRS from 158±24 to 127±17 ms ( P=0.0001), increase in LV ejection fraction from 31±10% to 39±13% ( P=0.004), and improvement in New York Heart Association functional class from 2.8±0.6 to 2±0.7 ( P=0.0001) with HBP. Increase in capture threshold occurred in 3 patients. Conclusions Permanent HBP was associated with significant narrowing of QRS duration and improvement in LV function in patients with RBBB and reduced LV ejection fraction. Permanent HBP is a promising option for cardiac resynchronization therapy in patients with RBBB and reduced LV ejection fraction.
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http://dx.doi.org/10.1161/CIRCEP.118.006613DOI Listing
September 2018