Imperial College London

DrJamesHoward

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Cardiology (Cardiac MR and AI)
 
 
 
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Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

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201 results found

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., 2024, The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually., Cardiovasc Revasc Med, Vol: 59, Pages: 60-66

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

Sreenivasan J, Reddy RK, Jamil Y, Malik A, Chamie D, Howard JP, Nanna MG, Mintz GS, Maehara A, Ali ZA, Moses JW, Chen S-L, Chieffo A, Colombo A, Leon MB, Lansky AJ, Ahmad Yet al., 2024, Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Trials., J Am Heart Assoc, Vol: 13

BACKGROUND: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI. METHODS AND RESULTS: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P<0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; P<0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; P=0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; P=0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; P<0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; P=0.07). CONCLUSIONS: In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.

Journal article

Foley MJ, Rajkumar CA, Ahmed-Jushuf F, Simader F, Pathimagaraj RH, Nijjer S, Sen S, Petraco R, Clesham G, Johnson T, Harrell FE, Kellman P, Francis D, Shun-Shin M, Howard J, Cole GD, Al-Lamee Ret al., 2024, A double-blind, randomised, placebo-controlled trial of the coronary sinus Reducer in refractory angina: design and rationale of the ORBITA-COSMIC trial., EuroIntervention, Vol: 20, Pages: e216-e223

The coronary sinus Reducer (CSR) is an hourglass-shaped device which creates an artificial stenosis in the coronary sinus. Whilst placebo-controlled data show an improvement in angina, these results are unreplicated and are the subject of further confirmatory research. The mechanism of action of this unintuitive therapy is unknown. The Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia, and Microvascular Resistance (ORBITA-COSMIC) trial is a randomised, placebo-controlled, double-blind trial investigating the efficacy of the CSR. Patients with (i) established epicardial coronary artery disease, (ii) angina on maximally tolerated antianginal medication, (iii) evidence of myocardial ischaemia and (iv) no further options for percutaneous coronary intervention or coronary artery bypass grafting will be enrolled. Upon enrolment, angina and quality-of-life questionnaires, treadmill exercise testing and quantitative stress perfusion cardiac magnetic resonance (CMR) imaging will be performed. Participants will record their symptoms daily on a smartphone application throughout the trial. After a 2-week symptom assessment phase, participants will be randomised in the cardiac catheterisation laboratory to CSR or a placebo procedure. After 6 months of blinded follow-up, all prerandomisation tests will be repeated. A prespecified subgroup will undergo invasive coronary physiology assessment at prerandomisation and follow-up. The primary outcome is stress myocardial blood flow on CMR. Secondary outcomes include angina frequency, quality of life and treadmill exercise time. (ClinicalTrials.gov: NCT04892537).

Journal article

Vimalesvaran K, Zaman S, Howard J, Aziminia N, Giannoudi M, Procter H, Varela M, Uslu F, Ariff B, Linton N, Levelt E, Bharath A, Cole Get al., 2024, Aortic stenosis assessment from the 3-chamber cine: ratio of balanced steady-state-free-precession (bSSFP) blood signal between the aorta and left ventricle predicts severity, Journal of Cardiovascular Magnetic Resonance, ISSN: 1097-6647

Background:Cardiovascular magnetic resonance (CMR) imaging is an important tool for evaluating the severity of aortic stenosis (AS), co-existing aortic disease, and concurrent myocardial abnormalities. Acquiring this additional information requires protocol adaptations and additional scanner time, but is not necessary for the majority of patients who do not have AS. We observed that the relative signal intensity of blood in the ascending aorta on a balanced steady state free precession (bSSFP) 3-chamber cine was often reduced in those with significant aortic stenosis. We investigated whether this effect could be quantified and used to predict AS severity in comparison to existing gold-standard measurements.Methods:Multi-centre, multi-vendor retrospective analysis of patients with AS undergoing CMR and transthoracic echocardiography (TTE). Blood signal intensity was measured in a ~1cm2 region of interest (ROI) in the aorta and left ventricle (LV) in the 3-chamber bSSFP cine. Because signal intensity varied across patients and scanner vendors, a ratio of the mean signal intensity in the aorta ROI to the LV ROI (Ao:LV) was used. This ratio was compared using Pearson correlations against TTE parameters of AS severity: aortic valve peak velocity, mean pressure gradient and the dimensionless index. The study also assessed whether field strength (1.5 T vs. 3 T) and patient characteristics (presence of bicuspid aortic valves (BAV), dilated aortic root and low flow states) altered this signal relationship.Results:314 patients (median age 69 [IQR 57–77], 64% male) who had undergone both CMR and TTE were studied; 84 had severe AS, 78 had moderate AS, 66 had mild AS and 86 without AS were studied as a comparator group. The median time between CMR and TTE was 12 weeks (IQR 4–26). The Ao:LV ratio at 1.5 T strongly correlated with peak velocity (r = -0.796, p=0.001), peak gradient (r = -0.772, p=0.001) and dimensionless index (r = 0.743, p = 0.001). An Ao:LV ratio of &

Journal article

Rajkumar CA, Foley MJ, Ahmed-Jushuf F, Nowbar AN, Simader FA, Davies JR, O'Kane PD, Haworth P, Routledge H, Kotecha T, Gamma R, Clesham G, Williams R, Din J, Nijjer SS, Curzen N, Ruparelia N, Sinha M, Dungu JN, Ganesananthan S, Khamis R, Mughal L, Kinnaird T, Petraco R, Spratt JC, Sen S, Sehmi J, Collier DJ, Sohaib A, Keeble TR, Cole GD, Howard JP, Francis DP, Shun-Shin MJ, Al-Lamee RK, ORBITA-2 Investigatorset al., 2023, A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina., N Engl J Med, Vol: 389, Pages: 2319-2330

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. RESULTS: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. CONCLUSIONS: Among patients with stable angina who were receivi

Journal article

Kailey BS, Koa-Wing M, Sutaria N, Mott T, Sohaib A, Qureshi N, Shi C, Padam P, Howard J, Kanagaratnam Pet al., 2023, Left atrial appendage occlusion for atrial fibrillation and bleeding diathesis., J Cardiovasc Electrophysiol, Vol: 34, Pages: 2552-2562

BACKGROUND: Patients with atrial fibrillation (AF) and likelihood of bleeding can undergo left atrial appendage occlusion (LAAO) as an alternative method of stroke prophylaxis. Short-term anti-thrombotic drugs are used postprocedure to offset the risk of device-related thrombus, evidence for this practice is limited. OBJECTIVES: To investigate optimal postimplant antithrombotic strategy in high bleeding-risk patients. METHODS: Patients with AF and high-risk for both stroke and bleeding undergoing LAAO were advised their perioperative drug therapy by a multidisciplinary physician panel. Those deemed to be at higher risk of bleeding from anti-thrombotic drugs were assigned to minimal treatment with no antithrombotics or Aspirin-alone. The remaining patients received standard care (STG) with a 12 week course of dual-antiplatelets or anticoagulation postimplant. We compared mortality, device-related thrombus, ischemic stroke, and bleeding events during the 90 days postimplant and long-term. Event-free survival was assessed using Kaplan-Meier survival analysis, with logrank testing for statistical significance. RESULTS: Seventy-five patients underwent LAAO of whom 63 patients (84%) had a prior serious bleeding event. The 42 patients on minimal treatment were older (74.3 ± 7.7 vs. 71.2 ± 7.2) with higher HASBLED score (3.6 ± 0.9 vs. 3.3 ± 1.2) than the 33 patients having standard care. There were no device-related thrombi or strokes in either group at 90 days postprocedure; STG had more bleeding events (5/33 vs. 0/42, p = 0.01) with associated deaths (3/33 vs. 0/42, p = 0.05). During long-term follow-up (median 2.2 years), all patients transitioned onto no antithrombotic drugs (43 patients [61%]) or a single-antiplatelet (29 patients [39%]). There was no evidence of early minimal treatment adversely affecting long-t

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

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

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

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

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

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

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, CARDIOVASCULAR INTERVENTION AND THERAPEUTICS, Vol: 38, Pages: 287-298, ISSN: 1868-4300

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

Vimalesvaran K, Bharath A, Cole G, Linton N, Zaman S, Howard Jet al., 2023, Novel cmr radiomic correlates with aortic stenosis severity in a single 3-chamber view, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A206-A207, ISSN: 1355-6037

Conference paper

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, CIRCULATION-CARDIOVASCULAR INTERVENTIONS, Vol: 16, ISSN: 1941-7640

Journal article

Vimalesvaran K, Bharath A, Howard J, Cole G, Zaman S, Ariff Bet al., 2023, Late gadolinium enhancement following covid-19 infection does not predict outcome: a single-centre study, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A214-A215, ISSN: 1355-6037

Conference paper

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, Journal of Medical Artificial Intelligence, Vol: 6, ISSN: 2617-2496

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

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

Ahmad Y, Madhavan MV, Stone GW, Francis DP, Makkar R, Bhatt DL, Howard JPet al., 2023, Sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a systematic review and meta-analysis of randomized trials (vol 8, pg 383, 2022), EUROPEAN HEART JOURNAL-QUALITY OF CARE AND CLINICAL OUTCOMES, Vol: 9, Pages: 203-203, ISSN: 2058-5225

Journal article

Foley MJ, Hall K, Howard JP, 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 RK, Sen Set al., 2023, Aortic Valve Calcium Score Is Associated With Acute Stroke in Transcatheter Aortic Valve Replacement Patients, Publisher: ELSEVIER SCIENCE INC, Pages: S91-S91, ISSN: 1936-8798

Conference paper

Foley MJ, Rajkumar CA, Ahmed-Jushuf F, Nour D, Fung CH, Seligman H, Pathimagaraj RH, Petraco R, Sen S, Nijjer S, Howard JP, Ahmad Y, Chamie D, Warisawa T, Shun-Shin MJ, Francis DP, Al-Lamee RKet al., 2023, The Ability of Contemporary Interventional Cardiologists to Judge the Ischaemic Impact of a Coronary Lesion From Visual Inspection, Publisher: ELSEVIER SCIENCE INC, Pages: S30-S30, ISSN: 1936-8798

Conference paper

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

On Y, Vimalesvaran K, Galazis C, Zaman S, Howard J, Linton N, Peters N, Cole G, Bharath AA, Varela Met al., 2023, Automatic Aortic Valve Pathology Detection from 3-Chamber Cine MRI with Spatio-Temporal Attention Maps, Pages: 648-657, ISSN: 0302-9743

The assessment of aortic valve pathology using magnetic resonance imaging (MRI) typically relies on blood velocity estimates acquired using phase contrast (PC) MRI. However, abnormalities in blood flow through the aortic valve often manifest by the dephasing of blood signal in gated balanced steady-state free precession (bSSFP) scans (Cine MRI). We propose a 3D classification neural network (NN) to automatically identify aortic valve pathology (aortic regurgitation, aortic stenosis, mixed valve disease) from Cine MR images. We train and test our approach on a retrospective clinical dataset from three UK hospitals, using single-slice 3-chamber cine MRI from N = 576 patients. Our classification model accurately predicts the presence of aortic valve pathology (AVD) with an accuracy of 0.85 ± 0.03 and can also correctly discriminate the type of AVD pathology (accuracy: 0.75 ± 0.03 ). Gradient-weighted class activation mapping (Grad-CAM) confirms that the blood pool voxels close to the aortic root contribute the most to the classification. Our approach can be used to improve the diagnosis of AVD and optimise clinical CMR protocols for accurate and efficient AVD detection.

Conference paper

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., 2023, Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis (vol 43, pg 1582, 2022), EUROPEAN HEART JOURNAL, Vol: 44, Pages: 27-27, ISSN: 0195-668X

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, STRUCTURAL HEART-THE JOURNAL OF THE HEART TEAM, Vol: 7, ISSN: 2474-8706

Journal article

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