Imperial College London

ProfessorDarrelFrancis

Faculty of MedicineNational Heart & Lung Institute

Professor of Cardiology
 
 
 
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Contact

 

+44 (0)20 7594 3381d.francis Website

 
 
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Assistant

 

Miss Juliet Holmes +44 (0)20 7594 5735

 
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Location

 

Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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650 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

Haldar S, Khan HR, Boyalla V, Kralj-Hans I, Jones S, Lord J, Onyimadu O, Sathishkumar A, Bahrami T, Clague J, De Souza A, Francis D, Hussain W, Jarman J, Jones DG, Chen Z, Mediratta N, Hyde J, Lewis M, Mohiaddin R, Salukhe T, Murphy C, Kelly J, Khattar R, Toff WD, Markides V, McCready J, Gupta D, Wong Tet al., 2021, Thoracoscopic surgical ablation versus catheter ablation as first-line treatment for long-standing persistent atrial fibrillation: the CASA-AF RCT, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-122, ISSN: 2050-4365

<jats:sec id="abs1-1"> <jats:title>Background</jats:title> <jats:p>Standalone thoracoscopic surgical ablation may be more effective than catheter ablation in patients with long-standing persistent atrial fibrillation.</jats:p> </jats:sec> <jats:sec id="abs1-2"> <jats:title>Objectives</jats:title> <jats:p>To determine whether or not surgical ablation is clinically superior to catheter ablation as the first-line treatment strategy in long-standing persistent atrial fibrillation.</jats:p> </jats:sec> <jats:sec id="abs1-3"> <jats:title>Design</jats:title> <jats:p>This was a prospective, multicentre, randomised control trial.</jats:p> </jats:sec> <jats:sec id="abs1-4"> <jats:title>Setting</jats:title> <jats:p>Four NHS tertiary centres in England.</jats:p> </jats:sec> <jats:sec id="abs1-5"> <jats:title>Participants</jats:title> <jats:p>Adults with long-standing persistent atrial fibrillation, who had European Heart Rhythm Association symptom scores &gt; 2 and who were naive to previous catheter ablation or thoracic/cardiac surgery.</jats:p> </jats:sec> <jats:sec id="abs1-6"> <jats:title>Interventions</jats:title> <jats:p>Minimally invasive thoracoscopic surgical ablation and conventional catheter ablation (control intervention).</jats:p> </jats:sec> <jats:sec id="abs1-7"> <jats:title>Mai

Journal article

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

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

Journal article

Nowbar AN, Francis DP, Al-Lamee RK, 2021, Quality of Life Assessment in Trials of Revascularization for Chronic Stable Angina: Insights from ORBITA and the Implications of Blinding, CARDIOVASCULAR DRUGS AND THERAPY, ISSN: 0920-3206

Journal article

Banerjee M, Chiew D, Patel K, Johns I, Chappell D, Linton N, Cole G, Francis D, Szram J, Ross J, Zaman Set al., 2021, The impact of artificial intelligence on clinical education: Perceptions of postgraduate trainee doctors in London (UK) and recommendations for trainers., BMC Medical Education, Vol: 21, Pages: 1-10, ISSN: 1472-6920

BackgroundArtificial intelligence (AI) technologies are increasingly used in clinical practice. Although there is robust evidence that AI innovations can improve patient care, reduce clinicians’ workload and increase efficiency, their impact on medical training and education remains unclear.MethodsA survey of trainee doctors’ perceived impact of AI technologies on clinical training and education was conducted at UK NHS postgraduate centers in London between October and December 2020. Impact assessment mirrored domains in training curricula such as ‘clinical judgement’, ‘practical skills’ and ‘research and quality improvement skills’. Significance between Likert-type data was analysed using Fisher’s exact test. Response variations between clinical specialities were analysed using k-modes clustering. Free-text responses were analysed by thematic analysis.Results210 doctors responded to the survey (response rate 72%). The majority (58%) perceived an overall positive impact of AI technologies on their training and education. Respondents agreed that AI would reduce clinical workload (62%) and improve research and audit training (68%). Trainees were skeptical that it would improve clinical judgement (46% agree, p=0.12) and practical skills training (32% agree, p<0.01). The majority reported insufficient AI training in their current curricula (92%), and supported having more formal AI training (81%).ConclusionsTrainee doctors have an overall positive perception of AI technologies’ impact on clinical training. There is optimism that it will improve ‘research and quality improvement’ skills and facilitate ‘curriculum mapping’. There is skepticism that it may reduce educational opportunities to develop ‘clinical judgement’ and ‘practical skills’. Medical educators should be mindful that these domains are protected as AI develops. We recommend that ‘Applied AI&r

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

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

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

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

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

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

Zaman S, Seligman H, Lloyd FH, Patel KT, Chappell D, O'Hare D, Cole GD, Francis DP, Petraco R, Linton NWFet al., 2021, Aerosolised fluorescein can quantify FFP mask faceseal leakage: a cost-effective adaptation to the existing point of care fit test, CLINICAL MEDICINE, Vol: 21, Pages: E263-E268, ISSN: 1470-2118

Journal article

Seligman H, Zaman S, Pitcher DS, Shun-Shin MJ, Hepworth Lloyd F, Androschuk V, Sen S, Al-Lamee R, Miller DM, Barnett HW, Haji GS, Howard LS, Nijjer S, Mayet J, Francis DP, Ces O, Linton NWF, Peters NS, Petraco Ret al., 2021, Reusable snorkel masks adapted as particulate respirators, PLoS One, Vol: 16, Pages: 1-11, ISSN: 1932-6203

ntroductionDuring viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject’s face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/.ConclusionFull-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks.

Journal article

Mikhail G, Khawaja SA, Mohan P, Jabbour R, Bampouri T, Bowsher G, Hassan AMM, Huq F, Baghdasaryan L, Wang B, Sethi A, Sen S, Petraco R, Ruparelia N, Nijjer S, Malik IS, Foale R, Bellamy M, Kooner J, Rana BS, Cole G, Sutaria N, Kanaganayagam G, Nihoyannopoulos P, Fox K, Plymen CM, Pabari P, Howard L, Davies R, Hajoi G, Lo Giudice F, Kanagaratnam P, Anderson J, Chukwuemeka A, Khamis R, Varnava A, Baker CSR, Francis D, Asaria P, Al-Lamee Ret al., 2021, COVID-19 and its impact on the cardiovascular system, Open Heart, Vol: 8, Pages: 1-9, ISSN: 2053-3624

Objectives: The clinical impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare NHS Trust, United Kingdom.Methods: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7th March to 7th April 2020. Patient data was collected for baseline demographics, co-morbidities and in-hospital outcomes, especially relating to cardiovascular intervention.Results:Mean age was 67.4±16.1 years and 62.2%(n=310) were male. 64.1%(n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4%(n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%,p<0.001). Only 4 COVID-19 patients had invasive coronary angiography,2 underwent percutaneous coronary intervention and 1 required a permanent pacemaker implantation. 7.0%(n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39,1.31-4.40,p=0.005) and history of hypertension (OR 1.88 ,1.01-3.55,p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.Conclusion:Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

Journal article

Nowbar AN, Rajkumar C, Al-Lamee RK, Francis DPet al., 2021, Controversies in revascularisation for stable coronary artery disease, CLINICAL MEDICINE, Vol: 21, Pages: 114-118, ISSN: 1470-2118

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

McCreanor V, Nowbar A, Rajkumar C, Barnett AG, Francis D, Graves N, Boden WE, Weintraub WS, Al-Lamee R, Parsonage WAet al., 2021, Cost-effectiveness analysis of percutaneous coronary intervention for single-vessel coronary artery disease: an economic evaluation of the ORBITA trial, BMJ Open, Vol: 11, Pages: 1-8, ISSN: 2044-6055

Objective To evaluate the cost-effectiveness of percutaneous coronary intervention (PCI) compared with placebo in patients with single-vessel coronary artery disease and angina despite anti-anginal therapy.Design A cost-effectiveness analysis comparing PCI with placebo. A Markov model was used to measure incremental cost-effectiveness, in cost per quality-adjusted life-years (QALYs) gained, over 12 months. Health utility weights were estimated using responses to the EuroQol 5-level questionnaire, from the Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial and UK preference weights. Costs of procedures and follow-up consultations were derived from Healthcare Resource Group reference costs and drug costs from the National Health Service (NHS) drug tariff. Probabilistic sensitivity analysis was undertaken to test the robustness of results to parameter uncertainty. Scenario analyses were performed to test the effect on results of reduced pharmaceutical costs in patients undergoing PCI, and the effect of patients crossing over from placebo to PCI due to refractory angina within 12 months.Setting Five UK NHS hospitals.Participants 200 adult patients with stable angina and angiographically severe single-vessel coronary artery disease on anti-anginal therapy.Interventions At recruitment, patients received 6 weeks of optimisation of medical therapy for angina after which they were randomised to PCI or a placebo procedure.Outcome measures Incremental cost-effectiveness ratio (ICER) expressed as cost (in £) per QALY gained for PCI compared with placebo.Results The estimated ICER is £90 218/QALY gained when using PCI compared with placebo in patients receiving medical treatment for angina due to single-vessel coronary artery disease. Results were robust under sensitivity analyses.Conclusions The ICER for PCI compared with placebo, in patients with single-vessel coronary artery disease and angina on anti-angi

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

Leong KMW, Ng FS, Shun-Shin MJ, Koa-Wing M, Qureshi N, Whinnett Z, Linton NF, Lefroy D, Francis DP, Harding SE, Davies DW, Peter NS, Lim PB, Behr E, Lambiase PD, Varnava A, Kanagaratnam Pet al., 2021, Non-invasive detection of exercise-induced cardiac conduction abnormalities in sudden cardiac death survivors in the inherited cardiac conditions, EUROPACE, Vol: 23, Pages: 305-312, ISSN: 1099-5129

Journal article

Piepoli MF, Ponikowski PP, Volterrani M, Francis DP, Coats AJSet al., 2021, Do Cheyne and Stokes have an important message for modern-day patients with heart failure? Yes, they do, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 23, Pages: 321-323, ISSN: 1388-9842

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

Naderi H, Robinson S, Swaans MJ, Bual N, Cheung W-S, Reid L, Shun-Shin M, Asaria P, Pabari P, Cole G, Kanaganayagam GS, Sutaria N, Bellamy M, Fox K, Nihoyannopoulos P, Petraco R, Al-Lamee R, Nijjer SS, Sen S, Ruparelia N, Baker C, Mikhail G, Malik I, Khamis R, Varnava A, Francis D, Mayet J, Rana Bet al., 2021, Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide, PERFUSION-UK, Vol: 36, Pages: 547-558, ISSN: 0267-6591

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

Haldar S, Khan HR, Boyalla V, Kralj-Hans I, Jones S, Lord J, Onyimadu O, Satishkumar A, Bahrami T, De Souza A, Clague JR, Francis DP, Hussain W, Jarman JW, Jones DG, Chen Z, Mediratta N, Hyde J, Lewis M, Mohiaddin R, Salukhe TV, Murphy C, Kelly J, Khattar RS, Toff WD, Markides V, McCready J, Gupta D, Wong T, CASA-AF Investigatorset al., 2020, Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial., European Heart Journal, Vol: 41, Pages: 4471-4480, ISSN: 0195-668X

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688.

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

Seligman H, Sen S, Nijjer S, Al-Lamee R, Clifford P, Sethi A, Hadjiloizou N, Kaprielian R, Ramrakha P, Bellamy M, Khan MA, Kooner J, Foale RA, Mikhail G, Baker CS, Mayet J, Malik I, Khamis R, Francis D, Petraco Ret al., 2020, Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers, Interventional Cardiology Review, Vol: 15, Pages: e16-e16, ISSN: 1756-1477

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff.

Journal article

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