Imperial College London

DrJamesHoward

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Cardiology (Cardiac MR and AI)
 
 
 
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james.howard1 Website CV

 
 
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Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

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179 results found

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, 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

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, 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

Foley M, Rajkumar CA, Ahmed-Jushuf F, Nour D, Fung CH, Seligman H, Pathimagaraj RH, Petraco R, Sen S, Nijjer S, Howard JP, Ahmad Y, Allahwala U, Bhindi R, Chamie D, Doi S, Kuwata S, Kaihara T, Koga M, Ishibashi Y, Higuma T, Tanabe Y, Nakayama M, Kawase Y, Watanabe A, Funayama N, Horinaka R, Hijikata N, Takahashi T, Matsuo H, Hansen PS, Manica A, Weaver J, Alzuhairi K, Yong T-H, Warisawa T, Francis DP, Shun-Shin MJ, Al-Lamee RKet al., 2023, The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually., Cardiovasc Revasc Med

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

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

Seligman H, Patel SB, Alloula A, Howard JP, Cook CM, Ahmad Y, de Waard GA, Pinto ME, van de Hoef TP, Rahman H, Kelshiker MA, Rajkumar CA, Foley M, Nowbar AN, Mehta S, Toulemonde M, Tang M-X, Al-Lamee R, Sen S, Cole G, Nijjer S, Escaned J, Van Royen N, Francis DP, Shun-Shin MJ, Petraco Ret al., 2023, Development of artificial intelligence tools for invasive Doppler-based coronary microvascular assessment., Eur Heart J Digit Health, Vol: 4, Pages: 291-301

AIMS: Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity. METHODS AND RESULTS: A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman's rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias -1.68 cm/s, 95% confidence interval (CI) -2.13 to -1.23 cm/s, P < 0.001 with limits of agreement (LOA) -4.03 to 0.68 cm/s; console flow vs. expert flow bias -2.63 cm/s, 95% CI -3.74 to -1.52, P < 0.001, 95% LOA -8.45 to -3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console). CONCLUSION: An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment.

Journal article

Prasad M, Ahmad Y, Howard JP, Ben-Ami J, Madhavan MV, Kirtane AJ, McEntegart M, Flattery E, Stone GW, Leon MB, Moses JWet al., 2023, Long-term Incidence of Myocardial Infarction and Death After CABG and PCI for Isolated Left Anterior Descending Artery Disease: A Meta-analysis of Randomized Controlled Trials, Journal of the Society for Cardiovascular Angiography and Interventions, Vol: 2

Background: To compare the long-term incidence of myocardial infarction (MI) and death in patients randomized to coronary artery bypass grafting (CABG) vs percutaneous coronary intervention (PCI) for treatment of isolated left anterior descending (LAD) coronary artery disease. Methods: We systematically identified all randomized controlled trials comparing PCI with stenting to CABG with a left internal mammary artery (LIMA) graft in patients with isolated LAD disease who had at least 4 years of follow-up. The primary outcome of interest was MI. Secondary outcomes were all-cause mortality and target vessel revascularization (TVR). Results: Four trials were included in the current analysis, with a total of 573 patients randomized to CABG with a LIMA (n = 285) vs PCI (n = 288) and followed for 4 to 10 years. At latest follow-up (weighted mean 8.3 years), there was no statistically significant difference in the risk of MI between CABG and PCI (relative risk [RR], 1.33; 95% CI, 0.62-2.83; P =.46), nor was there a statistically significant difference in mortality between the groups (RR, 1.04; 95% CI, 0.70-1.65; P =.84). There was a significantly lower risk of TVR after CABG compared with PCI (RR, 0.27; 95% CI, 0.15-0.46; P <.001). Conclusions: The current meta-analysis suggests that there is insufficient evidence that CABG with a LIMA confers protection against MI or death compared to PCI with a stent for isolated LAD disease. CABG was, however, associated with reduced rates of TVR.

Journal article

Warisawa T, Cook CM, Kawase Y, Howard JP, Ahmad Y, Seligman H, Rajkumar C, Toya T, Doi S, Nakajima A, Tanigaki T, Omori H, Nakayama M, Vera-Urquiza R, Yuasa S, Sato T, Kikuta Y, Nishina H, Al-Lamee R, Sen S, Lerman A, Akashi YJ, Escaned J, Matsuo H, Davies JEet al., 2023, Physiology-guided PCI versus CABG for left main coronary artery disease: insights from the DEFINE-LM registry., Cardiovasc Interv Ther, Vol: 38, Pages: 287-298

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74-0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04-13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG. State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line d

Journal article

Zaman S, Padayachee Y, Shah M, Samways J, Auton A, Quaife NM, Sweeney M, Howard JP, Tenorio I, Bachtiger P, Kamalati T, Pabari PA, Linton NWF, Mayet J, Peters NS, Barton C, Cole GD, Plymen CMet al., 2023, Smartphone-based remote monitoring in heart failure with reduced ejection fraction: retrospective cohort study of secondary care use and costs, JMIR Cardio, Vol: 7, ISSN: 2561-1011

BACKGROUND: Despite effective therapies, the economic burden of heart failure with reduced ejection fraction (HFrEF) is driven by frequent hospitalizations. Treatment optimization and admission avoidance rely on frequent symptom reviews and monitoring of vital signs. Remote monitoring (RM) aims to prevent admissions by facilitating early intervention, but the impact of noninvasive, smartphone-based RM of vital signs on secondary health care use and costs in the months after a new diagnosis of HFrEF is unknown. OBJECTIVE: The purpose of this study is to conduct a secondary care health use and health-economic evaluation for patients with HFrEF using smartphone-based noninvasive RM and compare it with matched controls receiving usual care without RM. METHODS: We conducted a retrospective study of 2 cohorts of newly diagnosed HFrEF patients, matched 1:1 for demographics, socioeconomic status, comorbidities, and HFrEF severity. They are (1) the RM group, with patients using the RM platform for >3 months and (2) the control group, with patients referred before RM was available who received usual heart failure care without RM. Emergency department (ED) attendance, hospital admissions, outpatient use, and the associated costs of this secondary care activity were extracted from the Discover data set for a 3-month period after diagnosis. Platform costs were added for the RM group. Secondary health care use and costs were analyzed using Kaplan-Meier event analysis and Cox proportional hazards modeling. RESULTS: A total of 146 patients (mean age 63 years; 42/146, 29% female) were included (73 in each group). The groups were well-matched for all baseline characteristics except hypertension (P=.03). RM was associated with a lower hazard of ED attendance (hazard ratio [HR] 0.43; P=.02) and unplanned admissions (HR 0.26; P=.02). There were no differences in elective admissions (HR 1.03, P=.96) or outpatient use (HR 1.40; P=.18) between the 2 groups. These differences were sustai

Journal article

Warisawa T, Cook CM, Ahmad Y, Howard JP, Seligman H, Rajkumar C, Toya T, Doi S, Nakajima A, Nakayama M, Vera-Urquiza R, Yuasa S, Sato T, Kikuta Y, Kawase Y, Nishina H, Al-Lamee R, Sen S, Lerman A, Matsuo H, Akashi YJ, Escaned J, Davies JEet al., 2023, Deferred Versus Performed Revascularization for Left Main Coronary Disease With Hemodynamic Significance., Circ Cardiovasc Interv, Vol: 16

BACKGROUND: The majority of randomized controlled trials of revascularization decision-making excludes left main coronary artery disease (LMD). Therefore, contemporary clinical outcomes of patients with stable coronary artery disease and LMD with proven ischemia remain poorly understood. The aim of this study was to assess the long-term clinical outcomes of physiologically significant LMD according to the treatment strategies of revascularization versus revascularization deferral. METHODS: In this international multicenter registry of stable LMD interrogated with the instantaneous wave-free ratio, patients with physiologically significant ischemia (instantaneous wave-free ratio ≤0.89) were analyzed according to the coronary revascularization (n=151) versus revascularization deferral (n=74). Propensity score matching was performed to adjust for baseline clinical characteristics. The primary end point was a composite of death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization of left main stem. The secondary end points were as follows: cardiac death or spontaneous LMD-related myocardial infarction; and ischemia-driven target lesion revascularization of left main stem. RESULTS: At a median follow-up period of 2.8 years, the primary end point occurred in 11 patients (14.9%) in the revascularized group and 21 patients (28.4%) in the deferred group (hazard ratio, 0.42 [95% CI, 0.20-0.89]; P=0.023). For the secondary end points, cardiac death or LMD-related myocardial infarction occurred significantly less frequently in the revascularized group (0.0% versus 8.1%; P=0.004). The rate of ischemia-driven target lesion revascularization of left main stem was also significantly lower in the revascularized group (5.4% versus 17.6%; hazard ratio, 0.20 [95% CI, 0.056-0.70]; P=0.012). CONCLUSIONS: In patients who underwent revascularization for stable coronary artery disease and physiologically significant LMD determined by instantaneous wave-fre

Journal article

Kirtane AJ, Sharp ASP, Mahfoud F, Fisher NDL, Schmieder RE, Daemen J, Lobo MD, Lurz P, Basile J, Bloch MJ, Weber MA, Saxena M, Wang Y, Sanghvi K, Jenkins JS, Devireddy C, Rader F, Gosse P, Sapoval M, Barman NC, Claude L, Augustin D, Thackeray L, Mullin CM, Azizi M, RADIANCE Investigators and Collaboratorset al., 2023, Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials., JAMA Cardiol, Vol: 8, Pages: 464-473

IMPORTANCE: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. OBJECTIVE: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. DATA SOURCES: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. STUDY SELECTION: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. DATA EXTRACTION AND SYNTHESIS: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. MAIN OUTCOMES AND MEASURES: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. RESULTS: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mea

Journal article

Zaman S, Vimalesvaran K, Howard JP, Chappell D, Varela M, Peters NS, Francis DP, Bharath AA, Linton NWF, Cole GDet al., 2023, Efficient labelling for efficient deep learning: the benefit of a multiple-image-ranking method to generate high volume training data applied to ventricular slice level classification in cardiac MRI., J Med Artif Intell, Vol: 6

BACKGROUND: Getting the most value from expert clinicians' limited labelling time is a major challenge for artificial intelligence (AI) development in clinical imaging. We present a novel method for ground-truth labelling of cardiac magnetic resonance imaging (CMR) image data by leveraging multiple clinician experts ranking multiple images on a single ordinal axis, rather than manual labelling of one image at a time. We apply this strategy to train a deep learning (DL) model to classify the anatomical position of CMR images. This allows the automated removal of slices that do not contain the left ventricular (LV) myocardium. METHODS: Anonymised LV short-axis slices from 300 random scans (3,552 individual images) were extracted. Each image's anatomical position relative to the LV was labelled using two different strategies performed for 5 hours each: (I) 'one-image-at-a-time': each image labelled according to its position: 'too basal', 'LV', or 'too apical' individually by one of three experts; and (II) 'multiple-image-ranking': three independent experts ordered slices according to their relative position from 'most-basal' to 'most apical' in batches of eight until each image had been viewed at least 3 times. Two convolutional neural networks were trained for a three-way classification task (each model using data from one labelling strategy). The models' performance was evaluated by accuracy, F1-score, and area under the receiver operating characteristics curve (ROC AUC). RESULTS: After excluding images with artefact, 3,323 images were labelled by both strategies. The model trained using labels from the 'multiple-image-ranking strategy' performed better than the model using the 'one-image-at-a-time' labelling strategy (accuracy 86% vs. 72%, P=0.02; F1-score 0.86 vs. 0.75; ROC AUC 0.95 vs. 0.86). For expert clinicians performing this task manually the intra-observer variability was low (Cohen's κ=0.90), but the inter-observer variability was higher (Cohen's &kap

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

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, ISSN: 0195-668X

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 Clin Electrophysiol, Vol: 9, Pages: 117-119

Journal article

Madhavan MV, Howard JP, Brener MI, Der Nigoghossian C, Chen S, Makkar R, Osmancik P, Reddy VY, Holmes DR, Stone GW, Leon MB, Ahmad Yet al., 2023, Long-Term Outcomes of Randomized Controlled Trials Comparing Percutaneous Left Atrial Appendage Closure to Oral Anticoagulation for Nonvalvular Atrial Fibrillation: A Meta-Analysis., Struct Heart, Vol: 7

BACKGROUND: Oral anticoagulation (OAC) has been considered the standard of care for stroke prophylaxis for patients with nonvalvular atrial fibrillation; however, many individuals are unable or unwilling to take long-term OAC. The safety and efficacy of percutaneous left atrial appendage closure (LAAC) have been controversial, and new trial data have recently emerged. We therefore sought to perform an updated meta-analysis of randomized clinical trials (RCTs) comparing OAC to percutaneous LAAC, focusing on individual clinical endpoints. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 2000 through December 2021 for all RCTs comparing percutaneous LAAC to OAC in patients with nonvalvular atrial fibrillation. Fixed and random effects meta-analyses of hazard ratios (HRs) were performed using the longest follow-up duration available by intention-to-treat. The prespecified primary endpoint was all-cause mortality. RESULTS: Three RCTs enrolling 1516 patients were identified. The weighted mean follow-up was 54.7 months. LAAC was associated with a reduced risk of all-cause mortality (HR 0.76; 95% confidence interval [CI], 0.59-0.96; p = 0.023), hemorrhagic stroke (HR 0.24; 95% CI, 0.09-0.61; p = 0.003), and major nonprocedural bleeding (HR 0.52; 95% CI, 0.37-0.74; p < 0.001). There was no significant difference between LAAC and OAC for any other endpoints. CONCLUSIONS: The available evidence from RCTs suggests LAAC therapy is associated with reduced long-term risk of death compared with OAC. This may be driven by reductions in hemorrhagic stroke and major nonprocedural bleeding. There were no significant differences in the risk of all stroke. Further large-scale clinical trials are needed to validate these findings.

Journal article

Kelshiker MA, Seligman H, Howard JP, Rahman H, Foley M, Nowbar AN, Rajkumar CA, Shun-Shin MJ, Ahmad Y, Sen S, Al-Lame R, Petraco Ret al., 2022, Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis (vol 43, pg 1582, 2022), EUROPEAN HEART JOURNAL, ISSN: 0195-668X

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., 2022, Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a systematic review and meta-analysis, EUROPACE, ISSN: 1099-5129

Journal article

Howard J, Chow K, Chacko L, Fontana M, Cole G, Kellman P, Xue Het al., 2022, Automated inline myocardial segmentation of joint T1 and T2 mapping using deep learning, Radiology: Artificial Intelligence, Vol: 1, Pages: 1-1, ISSN: 2638-6100

Purpose:To develop an artificial intelligence (AI) solution for automated segmentation and analysis of joint cardiac MRI T1 and T2 short-axis mapping.Materials and Methods:In this retrospective study, a joint T1 and T2 mapping sequence was used to acquire 4240 maps from 807 patients across 2 hospitals (March-November 2020). 509 maps from 94 consecutive patients were assigned to a holdout testing set. A convolutional neural network was trained to segment the endocardial and epicardial contours using an edge probability estimation approach. Training labels were segmented by an expert cardiologist. Predicted contours were processed to yield mapping values for each of the 16 AHA segments. Network segmentation performance and segment-wise measurements on the testing set were compared with two experts on the holdout testing set. The AI model was fully integrated using Gadgetron inline AI to run on MRI scanners.Results:A total of 3899 maps (92%) were deemed artifact-free and suitable for human segmentation. AI segmentation closely matched that of each expert (mean Dice coefficient 0.82 ± [SD] 0.07, 0.86 ± 0.06), comparing favorably with interexpert agreement (0.84 ± 0.06). AI-derived segment-wise values for native T1, postcontrast T1 and T2 mapping correlated with experts (R2 0.96, 0.98, 0.87, respectively versus expert 1; 0.97, 0.99, 0.97 versus expert 2) and fell within the range of interexpert reproducibility (R2 = 0.97, 0.99, 0.90). The AI has since been deployed at two hospitals, enabling automated inline analysis.Conclusion:Automated inline analysis of joint T1 and T2 mapping allows accurate segment-wise tissue characterization, with performance equivalent to human experts.

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., 2022, Catheter ablation improves cardiovascular outcomes in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials, EUROPACE, ISSN: 1099-5129

Journal article

Saleh K, Varnava A, Shun-Shin MJ, Ali N, Mohal J, Chiew K, Hanif MA, Merzah AJ, Howard JP, Jurak P, Leinveber P, Kanagaratnam P, Francis DP, Whinnett ZI, Arnold Aet al., 2022, Ultra-high-frequency ECG assessment of QRS fragmentation predicts sudden cardiac death risk in inherited arrhythmia syndromes, Publisher: OXFORD UNIV PRESS, Pages: 678-678, ISSN: 0195-668X

Conference paper

Kaza N, Htun V, Miyazawa A, Simader F, Porter B, Howard JP, Arnold A, Francis DP, Whinnett ZI, Shun-Shin MJ, Keene Det al., 2022, A systematic review and meta-analysis of upgrade to biventricular or conduction system pacing approaches, Publisher: OXFORD UNIV PRESS, Pages: 736-736, ISSN: 0195-668X

Conference paper

Padayachee Y, Shah M, Auton A, Samways J, Quaife N, Kamalati T, Tenorio I, Bachtiger P, Howard JP, Cole GD, Barton C, Peters NS, Plymen CM, Zaman Set al., 2022, Smartphone-based remote monitoring (RM) in chronic heart failure reduces emergency hospital attendances, unplanned admissions and secondary care costs: a retrospective cohort study, ESC Congress, Publisher: Oxford University Press, Pages: 2816-2816, ISSN: 0195-668X

Conference paper

Ashkir Z, Teoh Z, Ganesananthan S, Ahmed-Jushuf F, Beattie CJ, Asher A, Kelshiker M, Howard J, Al-Lamee Ret al., 2022, Medication adherence assessment and reporting in cardiovascular randomised controlled trials, Publisher: OXFORD UNIV PRESS, Pages: 2865-2865, ISSN: 0195-668X

Conference paper

Vimalesvaran K, Uslu F, Zaman S, Howard J, Bharath A, Cole Get al., 2022, Machine learning can accurately detect abnormal aortic valves in CMR, Publisher: OXFORD UNIV PRESS, Pages: 236-236, ISSN: 0195-668X

Conference paper

Pathimagaraj R, Foley M, Nowbar A, Rajkumar C, Shun-Shin M, Howard J, Al-Lamee Ret al., 2022, A Symptom-Stratified Analysis of the Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina Trial, Publisher: ELSEVIER SCIENCE INC, Pages: B80-B80, ISSN: 0735-1097

Conference paper

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

Ganesananthan S, Rajkumar C, Foley M, Thompson D, Nowbar A, Seligman H, Petraco R, Sen S, Nijjer S, Thom S, Wensel R, Davies J, Francis D, Shun-Shin M, Howard J, Al-Lamee Ret al., 2022, Cardiopulmonary exercise testing and efficacy of percutaneous coronary intervention: A substudy of the ORBITA trial, European Heart Journal, Vol: 43, Pages: 3132-3145, ISSN: 0195-668X

AimsOxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. We examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome. We also determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI).Methods and resultsPatients with severe single vessel coronary artery disease were randomised 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomisation treadmill CPET, dobutamine stress-echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period. 195 patients with CPET data were randomised (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score (+0.82 segments; 95%CI, 0.40 to 1.25, P=0.0068) and lower FFR (-0.07; -0.12 to -0.02, P=0.011) compared to those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score (oxygen-pulse plateau presence [Pinteraction=0.026] and oxygen-pulse gradient [Pinteraction=0.023]) and Seattle angina physical-limitation score (oxygen-pulse plateau presence [Pinteraction=0.037]). Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse and oxygen-uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI.ConclusionAlthough selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel coronary artery disease.

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

Foley M, Hall K, Howard J, Ahmad Y, Gandhi M, Mahboobani S, Okafor J, Rahman H, Hadjiloizou N, Ruparelia N, Mikhail G, Malik I, Kanaganayagam G, Sutaria N, Rana B, Ariff B, Barden E, Anderson J, Afoke J, Petraco R, Al-Lamee R, Sen Set al., 2022, Aortic valve calcium score is associated with acute stroke in transcatheter aortic valve replacement patients, Journal of the Society for Cardiovascular Angiography & Interventions, Vol: 1, Pages: 1-6, ISSN: 2772-9303

BackgroundTranscatheter aortic valve replacement (TAVR) is the treatment of choice for patients with severe aortic stenosis who are at a moderate or higher surgical risk. Stroke is a recognised and serious complication of TAVR, and it is important to identify patients at higher stroke risk. This study aims to discover if aortic valve calcium score calculated from pre-TAVR computed tomography is associated with acute stroke in TAVR patients.MethodsWe conducted a retrospective, observational cohort study of 433 consecutive patients undergoing TAVR between January 2017 and December 2019 at the Hammersmith Hospital.ResultsThis cohort had a median age of 83 years (interquartile range, 78-87), and 52.7% were male. Fifty-two patients (12.0%) had a history of previous stroke or transient ischemic attack. Median aortic valve calcium score was 2145 (interquartile range, 1427-3247) Agatston units. Twenty-two patients had a stroke up to the time of discharge (5.1%). In a logistic regression model, aortic valve calcium score was significantly associated with acute stroke (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.01-1.53; P = .02). Acute stroke was also significantly associated with peripheral arterial disease (OR, 4.32; 95% CI, 1.65-10.65; P = .0018) and a longer procedure time (OR, 1.01; 95% CI, 1.00-1.02; P = .0006).ConclusionsAortic valve calcium score from pre-TAVR computed tomography is an independent risk factor for acute stroke in the TAVR population. This is an additional clinical value of the pre-TAVR aortic valve calcium score and should be considered when discussing periprocedural stroke risk.

Journal article

Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, Gregson J, Newsome S, Gulati A, Pua CJ, Halliday BP, Lota AS, Buchan RJ, Whiffin N, Kanapeckaite L, Baruah R, Jarman JWE, O'Regan DP, Barton PJR, Ware JS, Pennell DJ, Adriaans BP, Bekkers SCAM, Donovan J, Frenneaux M, Cooper LT, Januzzi JL, Cleland JGF, Cook SA, Deo RC, Heymans SRB, Prasad SKet al., 2022, Precision phenotyping of dilated cardiomyopathy using multidimensional data., Journal of the American College of Cardiology, Vol: 79, Pages: 2219-2232, ISSN: 0735-1097

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to trad

Journal article

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