Imperial College London

DrAhranArnold

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Cardiology
 
 
 
//

Contact

 

ahran.arnold

 
 
//

Location

 

Fellows' RoomBlock B Hammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

68 results found

Leong AM, Arnold AD, Whinnett ZI, 2024, Implantable Cardioverter Defibrillator Tachycardia Therapies: Past, Present and Future Directions., J Cardiovasc Dev Dis, Vol: 11

Implantable cardioverter defibrillators (ICDs) have a long history and have progressed significantly since the 1980s. They have become an essential part of the prevention of sudden cardiac death, with a proven survival benefit in selected patient groups. However, with more recent trials and with the introduction of contemporary heart failure therapy, there is a renewed interest and new questions regarding the role of a primary prevention ICD, especially in patients with heart failure of non-ischaemic aetiology. This review looks at the history and evolution of ICDs, appraises the traditional evidence for ICDs and looks at issues relating to patient selection, risk stratification, competing risk, future directions and a proposed contemporary ICD decision framework.

Journal article

Kandzari DE, Townsend RR, Kario K, Mahfoud F, Weber MA, Schmieder RE, Pocock S, Tsioufis K, Konstantinidis D, Choi J, East C, Lauder L, Cohen DL, Kobayashi T, Schmid A, Lee DP, Ma A, Weil J, Agdirlioglu T, Schlaich MP, Shetty S, Devireddy CM, Lea J, Aoki J, Sharp ASP, Anderson R, Fahy M, DeBruin V, Brar S, Böhm M, SPYRAL HTN-ON MED Investigatorset al., 2023, Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications., J Am Coll Cardiol, Vol: 82, Pages: 1809-1823

BACKGROUND: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. OBJECTIVES: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications. METHODS: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis. RESULTS: The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients. CONCLUSIONS: There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral

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

Nesti M, Luca F, Duncker D, De Sensi F, Malaczynska-Rajpold K, Behar JM, Waldmann V, Ammar A, Mirizzi G, Garcia R, Arnold A, Mikhaylov EN, Kosiuk J, Sciarra Let al., 2023, Antiplatelet and Anti-Coagulation Therapy for Left-Sided Catheter Ablations: What Is beyond Atrial Fibrillation?, JOURNAL OF CLINICAL MEDICINE, Vol: 12

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

Sau A, Kapadia S, Al-Aidarous S, Howard J, Sohaib A, Sikkel MB, Arnold A, Waks JW, Kramer DB, Peters NS, Ng FSet al., 2023, Temporal trends and lesion sets for persistent atrial fibrillation ablation: a meta-analysis with trial sequential analysis and meta-regression, Circulation: Arrhythmia and Electrophysiology, Vol: 16, Pages: 536-545, ISSN: 1941-3084

BACKGROUND: Ablation for persistent atrial fibrillation (PsAF) has been performed for over 20 years, although success rates have remained modest. Several adjunctive lesion sets have been studied but none have become standard of practice. We sought to describe how the efficacy of ablation for PsAF has evolved in this time period with a focus on the effect of adjunctive ablation strategies. METHODS: Databases were searched for prospective studies of PsAF ablation. We performed meta-regression and trial sequential analysis. RESULTS: A total of 99 studies (15 424 patients) were included. Ablation for PsAF achieved the primary outcome (freedom of atrial fibrillation/atrial tachycardia rate at 12 months follow-up) in 48.2% (5% CI, 44.0-52.3). Meta-regression showed freedom from atrial arrhythmia at 12 months has improved over time, while procedure time and fluoroscopy time have significantly reduced. Through the use of cumulative meta-analyses and trial sequential analysis, we show that some ablation strategies may initially seem promising, but after several randomized controlled trials may be found to be ineffective. Trial sequential analysis showed that complex fractionated atrial electrogram ablation is ineffective and further study of this treatment would be futile, while posterior wall isolation currently does not have sufficient evidence for routine use in PsAF ablation. CONCLUSIONS: Overall success rates from PsAF ablation and procedure/fluoroscopy times have improved over time. However, no adjunctive lesion set, in addition to pulmonary vein isolation, has been conclusively demonstrated to be beneficial. Through the use of trial sequential analysis, we highlight the importance of adequately powered randomized controlled trials, to avoid reaching premature conclusions, before widespread adoption of novel therapies.

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

Reddy R, Ahmad Y, Arnold A, Howard Jet al., 2023, Cerebral embolic protection devices during transcatheter aortic valve implantation: a meta-analysis of randomized controlled trials, Journal of the Society for Cardiovascular Angiography & Interventions, Vol: 2, ISSN: 2772-9303

Background:Stroke is a feared complication of transcatheter aortic valve replacement (TAVR), which embolic protection devices (EPDs) may mitigate. This systematic review and meta-analysis synthesized randomized controlled trials (RCTs) to evaluate the effect of EPDs in TAVR.Methods:All RCTs comparing EPDs with control during TAVR were systematically identified. Prespecified primary end points were all stroke, disabling stroke, nondisabling stroke, and all-cause mortality. Safety and neuroimaging parameters were assessed. Sensitivity analyses were stratified by EPD type. Study registration was a priori (CRD42022377939).Results:Eight trials randomizing 4043 patients were included. There was no significant difference between EPDs and control for all stroke (relative risk [RR], 0.88; 95% CI, 0.65-1.18; P = .39; I2 = 0%), disabling stroke (RR, 0.67; 95% CI, 0.31-1.46; P = .32; I2 = 8.6%), nondisabling stroke (RR, 0.99; 95% CI, 0.71-1.40; P = .97; I2 = 0%), or all-cause mortality (RR, 0.87; 95% CI, 0.43-1.78; P = .71; I2 = 2.3%). There were no differences in safety end points of bleeding, vascular complications, or acute kidney injury. EPDs did not result in differences in total lesion volume or the number of new lesions. The Sentinel EPD significantly reduced the risk of disabling stroke (RR, 0.42; 95% CI, 0.20-0.88; P = .022; I2 = 0%) but did not affect all stroke, nondisabling stroke, or all-cause mortality.Conclusion:The totality of randomized data for EPDs during TAVR demonstrated no safety concerns or significant differences in clinical or neuroimaging end points. Analyses restricted to the Sentinel EPD demonstrated large, clinically meaningful reductions in disabling stroke. Ongoing RCTs may help validate these results.

Journal article

Kanagaratnam P, Francis DP, Chamie D, Coyle C, Marynina A, Katritsis G, Paiva P, Szigeti M, Cole G, de Andrade Nunes D, Howard J, Esper R, Khan M, More R, Barreto G, Meneguz-Moreno R, Arnold A, Nowbar A, Kaura A, Mariveles M, March K, Shah J, Nijjer S, Lip GY, Mills N, Camm AJ, Cooke GS, Corbett SJ, Llewelyn MJ, Ghanima W, Toshner M, Peters N, Petraco R, Al-Lamee R, Boshoff ASM, Durkina M, Malik I, Ruparelia N, Cornelius V, Shun-Shin Met al., 2023, A randomised controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalised with COVID-19: the C19-ACS trial, Journal of Thrombosis and Haemostasis, Vol: 21, Pages: 2213-2222, ISSN: 1538-7836

BACKGROUND: Patients hospitalised with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with COVID-19 and coronary disease risk factors. PATIENTS/METHODS: A randomised controlled open-label trial across acute hospitals (UK and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. The trial terminated early due to low recruitment. At 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted OR 0.73, 95%CI 0.38 to 1.41, p=0.355). Significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR 1.46, 95% CrI 0.88 to 2.37, Pr(Beta>0)=93%; adjusted OR 1.50, 95% CrI 0.91 to 2.45, Pr(Beta>0)=95%) and median time to discharge home was two days shorter (95% CrI -4 to 0, 2% probability that it was worse). CONCLUSIONS: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

Journal article

Simader F, Arnold A, Whinnett Z, 2023, Comparison of methods for delivering cardiac resynchronization therapy: electrical treatment targets and mechanisms of action, EXPERT REVIEW OF MEDICAL DEVICES, Vol: 20, Pages: 337-348, ISSN: 1743-4440

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

Ahmad Y, Howard JP, Arnold AD, Madhavan MV, Cook CM, Alu M, Mack MJ, Reardon MJ, Thourani VH, Kapadia S, Thyregod HGH, Sondergaard L, Jorgensen TH, Toff WD, Van Mieghem NM, Makkar RR, Forrest JK, Leon MBet al., 2023, Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a meta-analysis of randomized trials, EUROPEAN HEART JOURNAL, Vol: 44, Pages: 836-852, ISSN: 0195-668X

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

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

Bressi E, Luermans JG, Arnold AD, Grieco Det al., 2023, Editorial: Electrical management of heart failure: shaping the future of cardiac pacing and electrophysiology., Front Cardiovasc Med, Vol: 10, ISSN: 2297-055X

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

Ahmad Y, Howard JP, Seligman H, Arnold AD, Madhavan MV, Forrest JK, Geirsson A, Mack MJ, Lansky AJ, Leon MBet al., 2022, Early Surgery for Patients With Asymptomatic Severe Aortic Stenosis: A Meta-Analysis of Randomized Controlled Trials, Journal of the Society for Cardiovascular Angiography and Interventions, Vol: 1

Background: Guidelines provide class I recommendations for aortic valve intervention for patients with symptomatic severe aortic stenosis (AS) or reduced ejection fraction, but the cornerstone of management for asymptomatic patients has been watchful waiting. This is based on historical nonrandomized data, but randomized controlled trials (RCTs) have now been performed of early surgical aortic valve replacement (SAVR) for asymptomatic severe AS. We performed a meta-analysis of RCTs comparing early SAVR to watchful waiting for asymptomatic severe AS, focusing on individual end points of death and heart failure (HF) hospitalization. Methods: We systematically identified all RCTs comparing early SAVR to watchful waiting in patients with asymptomatic severe AS and synthesized the data in a random-effects meta-analysis. The prespecified primary end point was all-cause mortality. Results: Two trials randomizing 302 patients were included. Early SAVR lead to a 55% reduction in all-cause mortality (hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P =.014). There was no heterogeneity (I2 = 0.0%). Early SAVR also lead to a 79% reduction in HF hospitalization (hazard ratio, 0.21; 95% confidence interval, 0.05-0.96; P =.044). Conclusions: In patients with severe asymptomatic AS and normal ejection fraction, early SAVR reduces death and HF hospitalization compared to initial conservative management. This challenges current treatment standards and has implications for the clinical care of these patients and for guidelines.

Journal article

Ribeiro HDM, Arnold A, Howard JP, Shun-Shin MJ, Zhang Y, Francis DP, Lim PB, Whinnett Z, Zolgharni Met al., 2022, ECG-based real-time arrhythmia monitoring using quantized deep neural networks: A feasibility study, COMPUTERS IN BIOLOGY AND MEDICINE, Vol: 143, ISSN: 0010-4825

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

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

Howard J, Wood F, Finegold J, Nowbar A, Thompson DM, Arnold A, Rajkumar C, Connolly S, Cegla J, Stride C, Sever P, Northon C, Thom S, Shun-Shin M, Francis Det al., 2021, Side effect patterns in a crossover trial of statin, placebo and no treatment, Journal of the American College of Cardiology, Vol: 78, Pages: 1210-1222, ISSN: 0735-1097

BackgroundMost people who begin statins abandon them, most commonly because of side-effects. ObjectivesAssess daily symptom scores on statin, placebo and no treatment in participants who had abandoned statins.MethodsParticipants received 12 one-month medication bottles, 4 containing atorvastatin 20mg, 4 placebo and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the nocebo ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. Results60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% confidence interval 4.7 to 11.3) in no-tablet months. It was higher in statin months (16.3, 13.0 to 19.6, p<0.001), but also in placebo months (15.4, 12.1 to 18.7, p<0.001), with no difference between the two (p=0.388). The corresponding nocebo ratio was 0.90.In the individual-patient daily data, neither symptom intensity on starting (odds ratio 1.02, 95% CI 0.98 to 1.06, p=0.28) nor extent of symptom relief on stopping (1.01, 95% CI 0.98 to 1.05, p=0.48) distinguished between statin and placebo.Stopping was no more frequent for statin than placebo (p=0.173), and subsequent symptom relief was similar between statin and placebo.6 months after the trial, 30/60 (50%) of participants were back taking statins. ConclusionsThe majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo.

Journal article

Arnold AD, 2021, Discriminating electrocardiographic responses to Hisbundle pacing using machine learning (vol 1, pg 11, 2020), CARDIOVASCULAR DIGITAL HEALTH JOURNAL, Vol: 2, Pages: 150-150, ISSN: 2666-6936

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

Howard JP, Wood F, Finegold J, Nowbar A, Thompson D, Arnold AD, Rajkumar C, Christopher SB, Connolly S, Cegla J, Sever PS, Norton C, Thom S, Shun-Shin M, Francis Det al., 2020, A Three-arm N-of-1 Trial With Statin, Placebo and Tablet Free Periods, to Verify Side Effects and Identify Their Cause: The SAMSON Trial, Scientific Sessions of American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E480-E481, ISSN: 0009-7322

Conference paper

Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DPet al., 2020, N-of-1 trial of a statin, placebo, or No treatment to assess side effects., New England Journal of Medicine, Vol: 383, Pages: 2182-2184, ISSN: 0028-4793

Journal article

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=00409602&limit=30&person=true