Imperial College London

DrJamesHoward

Faculty of MedicineNational Heart & Lung Institute

Clinical Lecturer
 
 
 
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Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

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126 results found

Cook CM, Howard JP, Ahmad Y, Shun-Shin MJ, Sethi A, Clesham GJ, Tang KH, Nijjer SS, Kelly PA, Davies JR, Malik IS, Kaprielian R, Mikhail G, Petraco R, Warisawa T, Al-Janabi F, Karamasis GV, Mohdnazri S, Gamma R, Stathogiannis KE, de Waard GA, Al-Lamee R, Keeble TR, Mayet J, Sen S, Francis DP, Davies JEet al., 2021, Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes., Int J Cardiol, Vol: 342, Pages: 7-14

OBJECTIVES: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. METHODS: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. RESULTS: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa

Journal article

Rajkumar CA, Ganesananthan S, Ahmad Y, Seligman H, Thornton GD, Foley M, Nowbar AN, Howard JP, Francis DP, Keeble TR, Grunwald IQ, Al-Lamee RK, Malik IS, Shun-Shin MJet al., 2021, Mechanical thrombectomy with retrievable stents and aspiration catheters for acute ischaemic stroke: a meta-analysis of randomised controlled trials., EuroIntervention

BACKGROUND: Retrievable stents and aspiration catheters have been developed to provide more effective arterial recanalisation in acute ischaemic stroke. AIMS: The aim of this analysis was to test the effect of mechanical thrombectomy on mortality and long-term neurological outcome in patients presenting with acute large-vessel anterior circulation ischaemic stroke. METHODS: A structured search identified randomised controlled trials of thrombectomy (using a retrievable stent or aspiration catheter) versus control on a background of medical therapy which included intravenous thrombolysis if appropriate. The primary endpoint was disability at 90-day follow-up as assessed by the modified Rankin scale (mRS). Secondary endpoints included all-cause mortality and symptomatic intracranial haemorrhage. A Bayesian mixed-effects model was used for analysis. RESULTS: Twelve (12) trials met the inclusion criteria, comprising a total of 1,276 patients randomised to thrombectomy and 1,282 patients to control. Randomisation to thrombectomy significantly reduced disability at 90 days (OR 0.52, 95% credible interval 0.46 to 0.61, probability(control better)&lt;0.0001). Furthermore, thrombectomy reduced the odds of functional dependence at 90 days, indicated by an mRS score &gt;2 (OR 0.44, CrI 0.37 to 0.52, pr&lt;0.0001). Thrombectomy reduced all-cause mortality at 90 days (16.1% vs 19.2%, OR 0.81, 95% CrI 0.66 to 0.99, pr=0.024). The frequency of symptomatic intracranial haemorrhage was similar between thrombectomy (4.2%) and control (4.0%) (OR 1.12, 95% CrI 0.76 to 1.68, pr=0.72). CONCLUSIONS: In patients with an acute anterior circulation stroke, modern device thrombectomy significantly reduces death and subsequent disability. The magnitude of these effects suggests that universal access to this treatment strategy should be the standard of care.

Journal article

Seligman H, Nijjer S, van de Hoef TP, de Waard GA, Mejía-Rentería H, Echavarría-Pinto M, Shun-Shin MJ, Howard JP, Cook CM, Warisawa T, Ahmad Y, Androshchuk V, Rajkumar CA, Nowbar A, Kelshiker MA, van Lavieren MA, Meuwissen M, Danad I, Knaapen P, Sen S, Al-Lamee R, Mayet J, Escaned J, Piek JJ, van Royen N, Davies J, Francis D, Petraco Ret al., 2021, Phasic Flow Patterns of Right versus Left Coronary Arteries in Patients Undergoing Clinical Physiological Assessment., EuroIntervention

BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest this is less pronounced or even reversed in the right coronary artery. AIMS: This study aims to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) Study. 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia both in the RCA and LCA (mean diastolic-to-systolic velocity ratio was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest , LCAhyp , RCArest and RCAhyp , p&lt;0.001 for between vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom = 1.55 ± 0.35, RCAco-dom =1.40 ± 0.27, RCAnon-dom = 1.35, (SD not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases (97.9%) overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had negligible impact on DSVR in both RCA and LCA (DSVR x hyperaemic stenosis resistance R 2 = 0.018, p=0.03 and DSVR x coronary flow reserve R 2 &lt;0.001, p=0.98). CONCLUSIONS: In patients with CAD undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.

Journal article

Rajkumar C, Shun-Shin M, Seligman H, Ahmad Y, Warisawa T, Cook C, Howard J, Ganesananthan S, Amarin L, Khan C, Ahmed A, Nowbar A, Foley M, Assomull R, Keenan N, Sehmi J, Keeble T, davies J, Tang K, Gerber R, Cole G, O'Kane P, Sharp A, Khamis R, Kanaganayagam G, Petraco R, Ruparelia N, Malik I, Nijjer S, Sen S, Francis D, Al-Lamee Ret al., 2021, Placebo-controlled efficacy of percutaneous coronary intervention for focal and diffuse patterns of stable coronary artery disease, Circulation: Cardiovascular Interventions, Vol: 14, Pages: 809-818, ISSN: 1941-7640

Background Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from ORBITA to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom endpoints.Methods164 patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment prior to randomization. Focal disease was defined as 0.03 iFR unit drop within 15mm, rather than over a longer distance. Analyses were performed using regression modelling. ResultsIn the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (focal mean FFR and iFR 0.600.15 and 0.650.24, diffuse 0.780.10 and 0.880.08 respectively, p<0.0001). With adjustment for this difference, PCI for focal stenoses resulted in significantly greater reduction in stress echo ischemia than PCI for diffuse disease (p<0.05). The effect of PCI on between-arm pre-randomization-adjusted exercise time was 9.32 seconds (95% CI, -17.1 to 35.7s; p=0.487). When stratified for pattern of disease, there was no detectable difference between focal and diffuse CAD (Pinteraction=0.700). PCI improved Seattle Angina Questionnaire angina frequency score and freedom from angina more than placebo (p=0.034; p=0.0035). However, there was no evidence of interaction between the physiological pattern of CAD and these effects (Pinteraction=0.436; Pinteraction=0.908).ConclusionPCI achieved significantly greater reduction of stress echocardiography ischemia in focal compared to diffuse CAD. However, for symptom endpoints, no such difference was observed.

Journal article

Howard J, Francis D, 2021, Machine learning with convolutional neural networks for clinical cardiologists, Heart, ISSN: 1355-6037

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, 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

Patel R, Thong EHE, Batta V, Bharath AA, Francis D, Howard Jet al., 2021, Automated Identification of Orthopedic Implants on Radiographs Using Deep Learning., Radiol Artif Intell, Vol: 3

Accurate identification of metallic orthopedic implant design is important for preoperative planning of revision arthroplasty. Surgical records of implant models are frequently unavailable. The aim of this study was to develop and evaluate a convolutional neural network for identifying orthopedic implant models using radiographs. In this retrospective study, 427 knee and 922 hip unilateral anteroposterior radiographs, including 12 implant models from 650 patients, were collated from an orthopedic center between March 2015 and November 2019 to develop classification networks. A total of 198 images paired with autogenerated image masks were used to develop a U-Net segmentation network to automatically zero-mask around the implants on the radiographs. Classification networks processing original radiographs, and two-channel conjoined original and zero-masked radiographs, were ensembled to provide a consensus prediction. Accuracies of five senior orthopedic specialists assisted by a reference radiographic gallery were compared with network accuracy using McNemar exact test. When evaluated on a balanced unseen dataset of 180 radiographs, the final network achieved a 98.9% accuracy (178 of 180) and 100% top-three accuracy (180 of 180). The network performed superiorly to all five specialists (76.1% [137 of 180] median accuracy and 85.6% [154 of 180] best accuracy; both P < .001), with robustness to scan quality variation and difficult to distinguish implants. A neural network model was developed that outperformed senior orthopedic specialists at identifying implant models on radiographs; real-world application can now be readily realized through training on a broader range of implants and joints, supported by all code and radiographs being made freely available. Supplemental material is available for this article. Keywords: Neural Networks, Skeletal-Appendicular, Knee, Hip, Computer Applications-General (Informatics), Prostheses, Technology Assess-ment, Observer Perform

Journal article

El Hajj SC, Toya T, Warisawa T, Nan J, Lewis BR, Cook CM, Rajkumar C, Howard JP, Seligman H, Ahmad Y, Doi S, Nakajima A, Nakayama M, Goto S, Vera-Urquiza R, Sato T, Kikuta Y, Kawase Y, Nishina H, Nakamura S, Matsuo H, Escaned J, Akashi YJ, Davies JE, Lerman Aet al., 2021, Correlation of Intravascular Ultrasound and Instantaneous Wave-Free Ratio in Patients With Intermediate Left Main Coronary Artery Disease, CIRCULATION-CARDIOVASCULAR INTERVENTIONS, Vol: 14, Pages: 601-608, ISSN: 1941-7640

Journal article

Mann I, Linton NWF, Coyle C, Howard JP, Fudge M, Lim E, Qureshi N, Koa-Wing M, Whinnett Z, Lim PB, Ng FS, Peters NS, Francis DP, Kanagaratnam Pet al., 2021, RETRO-MAPPING A New Approach to Activation Mapping in Persistent Atrial Fibrillation Reveals Evidence of Spatiotemporal Stability, CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, Vol: 14, ISSN: 1941-3149

Journal article

Lane ES, Azarmehr N, Jevsikov J, Howard JP, Shun-shin MJ, Cole GD, Francis DP, Zolgharni Met al., 2021, Multibeat echocardiographic phase detection using deep neural networks, COMPUTERS IN BIOLOGY AND MEDICINE, Vol: 133, ISSN: 0010-4825

Journal article

Ahmad Y, Howard J, 2021, Long-term follow-up after ultrathin versus conventional second-generation drug-eluting stents: a systematic review and meta-analysis of randomized controlled trials, European Heart Journal, Vol: 42, Pages: 2643-2654, ISSN: 0195-668X

AimsContemporary 2nd-generation thin-strut drug-eluting stents (DES) are considered standard of care for revascularization of patients undergoing percutaneous coronary intervention. A previous meta-analysis of 10 randomized controlled trials (RCTs) with 11 658 patients demonstrated a 16% reduction in the 1-year risk of target lesion failure (TLF) with ultrathin-strut DES compared with conventional 2nd-generation thin-strut DES. Whether this benefit is sustained longer term is not known, and newer trial data may inform these relative outcomes. We therefore sought to perform an updated systematic review and meta-analysis of RCTs comparing clinical outcomes with ultrathin-strut DES (≤70 µm strut thickness) with conventional 2nd-generation thin-strut DES.Methods and resultsWe performed a random-effects meta-analysis of all RCTs comparing ultrathin-strut DES to conventional 2nd-generation thin-strut DES. The pre-specified primary endpoint was long-term TLF, a composite of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included the components of TLF, stent thrombosis (ST), and all-cause death. There were 16 eligible trials in which 20 701 patients were randomized. The weighted mean follow-up duration was 2.5 years. Ultrathin-strut DES were associated with a 15% reduction in long-term TLF compared with conventional 2nd-generation thin-strut DES [relative risk (RR) 0.85, 95% confidence interval (CI) 0.76–0.96, P = 0.008] driven by a 25% reduction in CD-TLR (RR 0.75, 95% CI 0.62–0.92, P = 0.005). There were no significant differences between stent types in the risks of MI, ST, cardiac death, or all-cause mortality.ConclusionsAt a mean follow-up of 2.5 years, ultrathin-strut DES reduced the risk of TLF, driven by less CD-TLR compared with conventional 2nd-generation thin-strut DES, with similar risks of MI, ST, cardiac death, and

Journal article

Howard J, Stowell C, Cole G, Ananthan K, Camelia D, Pearce K, Rajani R, Sehmi J, Vimalesvaran K, Kanaganayagam G, McPhail E, Ghosh A, Chambers J, Singh A, Zolgharni M, Rana B, Francis D, Shun-Shin Met al., 2021, Automated left ventricular dimension assessment using artificial intelligence developed and validated by a UK-wide collaborative, Circulation: Cardiovascular Imaging, Vol: 14, Pages: 405-415, ISSN: 1941-9651

Background: Echocardiography artificial intelligence (AI) requires training and validation to standards expected of humans. We developed an online platform and established the Unity Collaborative to build a dataset of expertise from 17 hospitals for training, validation, and standardisation of such techniques. Methods: The training dataset were 2056individual frames drawn at random from 1265parasternal long-axis video-loops of patients undergoing clinical echocardiography in 2015-2016. Nine experts labelled these images using our online platform. From this, we trained a convolutional neural network to identify key points. Subsequently, 13 experts labelled a validation dataset of the end-systolic and end-diastolic frame from100new video-loops, twice each. The 26-opinionconsensus was used as the reference standard. The primary outcome was “precision SD”, the standard deviation of difference between AI measurement and expert consensus. Results: In the validation dataset, the AI’s precision SD for left ventricular internal dimension was 3.5mm. For context, precision SD of individual expert measurements against the expert consensus was 4.4mm. Intraclass correlation coefficient (ICC) between AI and expert consensus was 0.926 (95% CI 0.904–0.944), compared with 0.817 (0.778–0.954) between individual experts and expert consensus. For interventricular septum thickness, precision SD was 1.8mm for AI (ICC 0.809; 0.729–0.967), versus 2.0 for individuals (ICC 0.641; 0.568–0.716). For posterior wall thickness, precision SD was 1.4mm for AI (ICC 0.535; 95% CI 0.379–0.661), versus 2.2mm for individuals(0.366; 0.288 to 0.462).We present all images and annotations. This highlights challenging cases, including poor image quality, tapered ventricles, and indistinct boundaries. Conclusions: Experts at multiple institutions successfully cooperated to build a collaborative AI. This performed as well as individual experts. Future echocardiogr

Journal article

Howard J, Reiber JHC, 2021, Automated analysis of coronary angiograms using artificial intelligence: a window into the cath lab of the future, EUROINTERVENTION, Vol: 17, Pages: 16-17, ISSN: 1774-024X

Journal article

Azarmehr N, Ye X, Howard JP, Lane ES, Labs R, Shun-Shin MJ, Cole GD, Bidaut L, Francis DP, Zolgharni Met al., 2021, Neural architecture search of echocardiography view classifiers, JOURNAL OF MEDICAL IMAGING, Vol: 8, ISSN: 2329-4302

Journal article

Ahmad Y, Howard J, 2021, Meta-analysis of usefulness of cerebral embolic protection during transcatheter aortic valve implantation, American Journal of Cardiology, Vol: 146, Pages: 69-73, ISSN: 0002-9149

One of the most feared complications of transcatheter aortic valve implantation (TAVI) is stroke, with increased mortality and disability observed in patients suffering a stroke after TAVI. There has been no significant decline in stroke rates seen over the last 5 years; attention has therefore been given to strategies for cerebral embolic protection. With the emergence of new randomized trial data, we sought to perform an updated systematic review and meta-analysis to examine the effect of cerebral embolic protection during TAVI both on clinical outcomes and on neuroimaging parameters. We performed a random-effects meta-analysis of randomized clinical trials of cerebral embolic protection during TAVI. The primary end point was the risk of stroke. The risk of stroke was not significantly different with the use of cerebral embolic protection: relative risk (RR) 0.88, 95% confidence interval (CI) 0.57 to 1.36, p = 0.566. Nor was there a significant reduction in the risk of disabling stroke, non-disabling stroke or death. There was no significant difference in total lesion volume on MRI with cerebral embolic protection: mean difference -74.94, 95% CI -174.31 to 24.4, p = 0.139. There was also not a significant difference in the number of new ischemic lesions on MRI: mean difference -2.15, 95% -5.25 to 0.96, p = 0.176, although there was significant heterogeneity for the neuroimaging outcomes. In conclusion, cerebral embolic protection during TAVI is safe but there is no evidence of a statistically significant benefit on clinical outcomes or neuroimaging parameters.

Journal article

Thompson D, Al-Lamee R, Foley M, Dehbi HM, Thom S, Davies JE, Francis DP, Patel P, Gupta P, ORBITA Investigatorset al., 2021, Achieving optimal adherence to medical therapy by telehealth: Findings from the ORBITA medication adherence sub-study, Pharmacology Research and Perspectives, Vol: 9, Pages: e00710-e00710, ISSN: 2052-1707

INTRODUCTION: The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. METHODS: Prescribing data were collected throughout the trial. Self-reported adherence was assessed, and urine samples collected at pre-randomization and at follow-up for direct assessment of adherence using high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). RESULTS: Self-reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre-randomization and at follow-up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. CONCLUSIONS: Adherence levels were high throughout the study when quantified by self-reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online.

Journal article

Foley M, Rajkumar CA, Shun-Shin M, Ganesananthan S, Seligman H, Howard J, Nowbar AN, Keeble TR, Davies JR, Tang KH, Gerber R, O'Kane P, Sharp ASP, Petraco R, Malik IS, Nijjer S, Sen S, Francis DP, Al-Lamee Ret al., 2021, Achieving optimal medical therapy: insights from the ORBITA trial., Journal of the American Heart Association, Vol: 10, Pages: 1-20, ISSN: 2047-9980

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this i

Journal article

Howard JP, Francis DP, 2021, Response to "Drucebo effect - the challenge we should all definitely face!", ARCHIVES OF MEDICAL SCIENCE, Vol: 17, Pages: 544-545, ISSN: 1734-1922

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., 2021, Randomized blinded placebo-controlled trials of renal sympathetic denervation for hypertension: a meta-analysis, Cardiovascular Revascularization Medicine, 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

Al-Hity S, Bhamra N, Kumar R, Gupta KK, Howard J, Jolly K, Darr Aet al., 2021, Personal protective equipment guidance during a global pandemic: A statistical analysis of National perceived confidence, knowledge and educational deficits amongst UK-based doctors, INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Vol: 75, ISSN: 1368-5031

Journal article

Ahmad Y, Howard J, Madhavan MV, Leon MB, Makkar RRet al., 2021, Single versus dual antiplatelet therapy after transcatheter aortic valve replacement: a meta-analysis of randomized clinical trials, Cardiovascular Revascularization Medicine, ISSN: 1553-8389

BackgroundGuidelines recommend dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) but guidelines predate the publication of the largest randomized trial. There have been few trials in the field to date, and with a small number of total patients; pooling their results may therefore be helpful.MethodsWe systematically identified all randomized trials comparing SAPT to DAPT after TAVR. The primary endpoint was the risk of major bleeding. Secondary endpoints included all bleeding, life-threatening bleeding, stroke, myocardial infarction, death and cardiac death.ResultsFour trials, randomizing 1086 participants, were eligible (541 randomized to SAPT and 545 randomized to DAPT). The weighted mean follow-up was 9.1 months. The risk of major bleeding was significantly increased after DAPT (relative risk (RR) 2.36, 95% confidence interval (CI) 1.27 to 4.40, P = 0.007). There was a similar increased risk for all bleeding (RR 1.65, 95% CI 1.24 to 2.19, P < 0.001), although not for life-threatening bleeding (RR 1.44, 95% CI 0.74 to 2.77, P = 0.282). There were no significant differences in the risk of stroke, myocardial infarction (MI), death or cardiac death. There was no heterogeneity observed for any endpoint (I2 = 0.0%).ConclusionsDAPT after TAVR is associated with an increased risk of major bleeding and all bleeding. There is no evidence of a significant difference between DAPT or SAPT for the risks of stroke, MI, death or cardiac death. However, the total number of patients randomized is small and the duration of follow-up is short. Larger scale randomized trials with longer follow-up are required to assess for any potential differences in ischemic endpoints or mortality.

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

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

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 from the Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E480-E481, ISSN: 0009-7322

Conference paper

Gitto M, Gentile F, Nowbar AN, Chieffo A, Al-Lamee Ret al., 2020, Gender-Related Differences in Clinical Presentation and Angiographic Findings in Patients with Ischemia and No Obstructive Coronary Artery Disease (INOCA): A Single-Center Observational Registry, INTERNATIONAL JOURNAL OF ANGIOLOGY, Vol: 29, Pages: 250-255, ISSN: 1061-1711

Journal article

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

Warisawa T, Cook CM, Howard JP, Nour D, Doi S, Nakayama M, Uelani T, Yamanaka F, Kikuta Y, Shiono Y, Nishina H, Matsuo H, Escaned J, Akashi YJ, Davies JEet al., 2020, Clinical outcomes of patients with diffuse coronary artery disease following physiology-guided treatment strategy: insights from AJIP registry, Publisher: OXFORD UNIV PRESS, Pages: 1400-1400, ISSN: 0195-668X

Conference paper

Howard JP, Zaman S, Ragavan A, Hall K, Leonard G, Sutanto S, Ramadoss V, Razvi Y, Linton NF, Bharath A, Shun-Shin M, Rueckert D, Francis D, Cole Get al., 2020, Automated analysis and detection of abnormalities in transaxial anatomical cardiovascular magnetic resonance images: a proof of concept study with potential to optimize image acquisition, International Journal of Cardiovascular Imaging, Vol: 37, Pages: 1033-1042, ISSN: 1569-5794

The large number of available MRI sequences means patients cannot realistically undergo them all, so the range of sequences to be acquired during a scan are protocolled based on clinical details. Adapting this to unexpected findings identified early on in the scan requires experience and vigilance. We investigated whether deep learning of the images acquired in the first few minutes of a scan could provide an automated early alert of abnormal features. Anatomy sequences from 375 CMR scans were used as a training set. From these, we annotated 1500 individual slices and used these to train a convolutional neural network to perform automatic segmentation of the cardiac chambers, great vessels and any pleural effusions. 200 scans were used as a testing set. The system then assembled a 3D model of the thorax from which it made clinical measurements to identify important abnormalities. The system was successful in segmenting the anatomy slices (Dice 0.910) and identified multiple features which may guide further image acquisition. Diagnostic accuracy was 90.5% and 85.5% for left and right ventricular dilatation, 85% for left ventricular hypertrophy and 94.4% for ascending aorta dilatation. The area under ROC curve for diagnosing pleural effusions was 0.91. We present proof-of-concept that a neural network can segment and derive accurate clinical measurements from a 3D model of the thorax made from transaxial anatomy images acquired in the first few minutes of a scan. This early information could lead to dynamic adaptive scanning protocols, and by focusing scanner time appropriately and prioritizing cases for supervision and early reporting, improve patient experience and efficiency.

Journal article

Rajkumar C, Shun-Shin M, Seligman H, Ahmad Y, Warisawa T, Cook C, Howard J, Amarin L, Nowbar A, Foley M, Assomull R, Keenan N, Sehmi J, Keeble T, Davies J, Tang K, Gerber R, Cole G, O'Kane P, Sharp A, Khamis R, Kanaganayagam G, Petraco R, Ruparelia N, Malik I, Nijjer S, Sen S, Francis D, Al-Lamee Ret al., 2020, Placebo-Controlled Efficacy of Percutaneous Coronary Intervention for Focal and Diffuse Patterns of Stable Coronary Artery Disease: A Secondary Analysis From ORBITA, 32nd Annual Transcatheter Cardiovascular Therapeutics Symposium (TCT CONNECT), Publisher: ELSEVIER SCIENCE INC, Pages: B165-B165, ISSN: 0735-1097

Conference paper

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