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
to

712 results found

Al-Lamee RK, Foley M, Rajkumar CA, Francis DPet al., 2022, Revascularization in stable coronary artery disease, BMJ-BRITISH MEDICAL JOURNAL, Vol: 377, ISSN: 0959-535X

Journal article

Ahmad Y, Madhavan M, Stone GW, Francis DP, Makkar R, Bhatt DL, Howard JPet al., 2022, Sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a systematic review and meta-analysis of randomized trials, EUROPEAN HEART JOURNAL-QUALITY OF CARE AND CLINICAL OUTCOMES, Vol: 8, Pages: 383-390, ISSN: 2058-5225

Journal article

Miyazawa AA, Francis DP, Whinnett ZI, 2022, Basic Principles of Hemodynamics in Pacing., Card Electrophysiol Clin, Vol: 14, Pages: 133-140

Pacing therapy aims to improve overall cardiac function by normalizing cardiac electrical activation. Although hemodynamic measurements allow the impact of cardiac pacing on cardiac function to be quantified, the protocol is crucial to minimize the effect of noise and achieve greater precision. Multiple steps can be undertaken to optimize accuracy of hemodynamic measurements. These include comparing with a reference state, using an average of a set number of beats, making repeated measurements, ensuring all beats are included, and pacing at faster heart rates. These measurements can aid comparison between different pacing modalities and guide optimal programming.

Journal article

Nowbar AN, Howard JP, Shun-Shin MJ, Rajkumar C, Foley M, Basu A, Goel A, Patel S, Adnan A, Beattie CJ, Keeble TR, Sohaib A, Collier D, McVeigh P, Harrell FE, Francis DP, Al-Lamee RKet al., 2022, Daily angina documentation versus subsequent recall: development of a symptom smartphone app., Eur Heart J Digit Health, Vol: 3, Pages: 276-283

AIMS: The traditional approach to documenting angina outcomes in clinical trials is to ask the patient to recall their symptoms at the end of a month. With the ubiquitous availability of smartphones and tablets, daily contemporaneous documentation might be possible. METHODS AND RESULTS: The ORBITA-2 symptom smartphone app was developed with a user-centred iterative design and testing cycle involving a focus group of previous ORBITA participants. The feasibility and acceptability were assessed in an internal pilot of participants in the ongoing ORBITA-2 trial. Seven days of app entries by ORBITA-2 participants were compared with subsequent participant recall at the end of the 7-day period. The design focus group tested a prototype app. They reported that the final version captured their symptoms and was easy to use. In the completion assessment group, 141 of 142 (99%) completed the app in full and 47 of 141 (33%) without reminders. In the recall assessment group, 29 of 29 (100%) participants said they could recall the previous day's symptoms, and 82% of them recalled correctly. For 2 days previously, 88% said they could recall and of those, 87% recalled correctly. The proportion saying they could recall their symptoms fell progressively thereafter: 89, 67, 61, 50%, and at 7 days, 55% (P < 0.001 for trend). The proportion of recalling correctly also fell progressively to 55% at 7 days (P = 0.04 for trend). CONCLUSION: Episode counts of angina are difficult to recall after a few days. For trials such as ORBITA-2 focusing on angina, daily symptom collection via a smartphone app will increase the validity of the results.

Journal article

Howard J, Francis D, 2022, Machine learning with convolutional neural networks for clinical cardiologists, Heart, Vol: 108, Pages: 973-981, ISSN: 1355-6037

Journal article

Kelshiker M, Seligman H, Howard JAMES, Rahman H, Foley M, Nowbar A, Rajkumar C, Shun-Shin M, Ahmad Y, Sen S, Al-Lamee R, Cole G, Hoole S, Morris P, Rigo F, Mayet J, Francis D, Petraco Ret al., 2022, Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis, European Heart Journal, Vol: 43, Pages: 1582-1593, ISSN: 0195-668X

Aims: This meta-analysis aims to quantify the association of reduced coronary flow with all3 cause mortality and major adverse cardiovascular events (MACE) across a broad range of patient groups and pathologies. Methods and Results: We systematically identified all studies between 1st January 2000 and1st August 2020, where coronary flow was measured and clinical outcomes were reported. The endpoints were all-cause mortality and MACE. Estimates of effect were calculated from published hazard ratios using a random-effects model. 79 studies, including 59,740 subjects were included. Abnormal coronary flow reserve (CFR) was associated with a higher incidence of all-cause mortality (HR 3.78, 95% CI 2.39-5.97) and a higher incidence of MACE (HR 3.42, 95% CI 2.92-3.99). Each 0.1-unit reduction in CFR was associated with a proportional increase in mortality (per 0.1 CFR unit HR 1.16, 95% CI 1.04-1.29) and MACE (per 0.1 CFR unit HR 1.08, 95% CI 1.04-1.11)). In patients with isolated coronary microvascular dysfunction, an abnormal CFR was associated with a higher incidence of mortality (HR 5.44, 95% CI 3.78-7.83) and MACE (HR 3.56, 95% CI 2.14-5.90). Abnormal CFR was also associated with a higher incidence of MACE in patients with acute coronary syndromes (HR 3.76, 95% CI 2.35-6.00), heart failure (HR 6.38, 95% CI 1.95-20.90), heart transplant (HR 3.32, 95% CI 2.34-4.71) and diabetes mellitus (HR 7.47, 95% CI 3.37-16.55). Conclusions: Reduced coronary flow is strongly associated with increased risk of all-cause mortality and MACE across a wide range of pathological processes. This finding supports recent recommendations that coronary flow should be measured more routinely in clinical practice to target aggressive vascular risk modification for individuals at higher risk

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 I, Shun-Shin MJet al., 2022, Mechanical thrombectomy with retrievable stents and aspiration catheters for acute ischaemic stroke: a meta-analysis of randomised controlled trials, EUROINTERVENTION, Vol: 17, Pages: E1425-+, ISSN: 1774-024X

Journal article

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

Journal article

Nowbar AN, Rajkumar C, Foley M, Ahmed-Jushuf F, Howard JP, Seligman H, Petraco R, Sen S, Nijjer SS, Shun-Shin MJ, Keeble TR, Sohaib A, Collier D, McVeigh P, Harrell FE, Francis DP, Al-Lamee RKet al., 2022, A double-blind randomised placebo-controlled trial of percutaneous coronary intervention for the relief of stable angina without antianginal medications: design and rationale of the ORBITA-2 trial, EUROINTERVENTION, Vol: 17, Pages: 1490-+, ISSN: 1774-024X

Journal article

Kaura A, Hartley A, Panoulas V, Glampson B, Shah ASV, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Thursz MR, Elliott P, Hemmingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Trickey A, Sterne JA, Haskard DO, Melikian N, Francis DP, Koenig W, Shah AM, Kharbanda R, Perera D, Patel RS, Channon KM, Mayet J, Khamis Ret al., 2022, Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study, PLoS Medicine, Vol: 19, ISSN: 1549-1277

BACKGROUND: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. METHODS AND FINDINGS: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not

Journal article

Seligman H, Nijjer SS, van de Hoef TP, de Waard GA, Mejia-Renteria H, Echavarria-Pinto M, Shun-Shin MJ, Howard JP, Cook CM, Warisawa T, Ahmad Y, Androshchuk V, Rajkumar C, 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 JE, Francis DP, Petraco Ret al., 2022, Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment, EUROINTERVENTION, Vol: 17, Pages: 1260-+, ISSN: 1774-024X

Journal article

Keene D, Miyazawa AA, Johal M, Arnold AD, Ali N, Saqi KA, March K, Burden L, Francis DP, Whinnett Z, Shun-Shin MJet al., 2022, Optimizing atrio-ventricular delay in pacemakers using potentially implantable physiological biomarkers, Pacing and Clinical Electrophysiology, Vol: 45, Pages: 461-470, ISSN: 0147-8389

BackgroundHemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices.We assess whether laser Doppler can be used instead of BP to optimize AV delay.MethodsFifty eight patients underwent 94 AV delay optimizations with biventricular or His-bundle pacing using laser Doppler and simultaneous noninvasive beat-by-beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40–320 ms), with automatic quality control checking precision of the optimum.Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality.Results55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms).An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms.ConclusionsLaser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.

Journal article

Ahmad Y, Kane C, Arnold AD, Cook C, Keene D, Shun-Shin M, Cole G, Al-Lamee R, Francis D, Howard Jet al., 2022, Randomized blinded placebo-controlled trials of renal sympathetic denervation for hypertension: a meta-analysis, Cardiovascular Revascularization Medicine, Vol: 34, Pages: 112-118, ISSN: 1553-8389

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension.MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed.Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation.ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

Journal article

Zaman S, Petri C, Vimalesvaran K, Howard J, Bharath A, Francis D, Peters N, Cole GD, Linton Net al., 2022, Automatic diagnosis labeling of cardiovascular MRI by using semisupervised natural language processing of text reports, Radiology: Artificial Intelligence, Vol: 4, ISSN: 2638-6100

A semisupervised natural language processing (NLP) algorithm, based on bidirectional transformers, accurately categorized diagnoses from cardiac MRI text of radiology reports for the labeling of MR images; the model had a higher accuracy than traditional NLP models and performed faster labeling than clinicians.

Journal article

Gallone G, Baldetti L, Angelini F, Saglietto A, Bellettini M, Beneduce A, Ranotti V, Chiarito M, Leone PP, Pagnesi M, De Filippo O, Landra F, Bruno F, Marengo G, Collino M, Ferrante G, Stefanini GG, Colombo A, Al-Lamee R, Francis DP, Jolicoeur ME, Henry TD, Giannini F, D'Ascenzo F, De Ferrari GMet al., 2022, The Placebo Effect on Symptoms, Quality of Life, and Functional Outcomes in Patients With Angina Pectoris: A Meta-analysis of Randomized Placebo-Controlled Trials, CANADIAN JOURNAL OF CARDIOLOGY, Vol: 38, Pages: 113-122, ISSN: 0828-282X

Journal article

Whinnett Z, Tanner M, Chandrasekaran B, Foley P, Moore P, Adhya S, Qureshi N, Muthumala A, Behar J, Lane RE, Rinaldi CA, Agarwal S, Farwell D, Leyva F, Bassi S, Ng GA, Scott P, Prasad R, Swinburn J, Tomson J, Kyriacou A, Thomas DE, Chuen J, Kamdar R, Lim PB, Sethi A, Shah J, Vijayaraman P, Johnson N, Falaschetti E, Mariveles M, Kanagaratnam P, Cleland J, Francis D, Keene Det al., 2021, His-Optimized Pacing in Patients With a Long PR Interval, Narrow QRS and Heart Failure: Results of the Hope-hf Clinical Trial, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E587-E587, ISSN: 0009-7322

Conference paper

Whinnett Z, Tanner M, Chandrasekaran B, Foley P, Moore P, Adhya S, Qureshi N, Muthumala A, Behar J, Lane RE, Rinaldi CA, Agarwal S, Farwell D, Leyva F, Bassi S, Ng GA, Scott P, Prasad R, Swinburn J, Tomson J, Kyriacou A, Dewi ET, Chuen J, Kamdar R, Lim PB, Sethi A, Shah J, Vijayaraman P, Johnson N, Falaschetti E, Mariveles M, Kanagaratnam P, Cleland J, Francis D, Keene Det al., 2021, His-Optimized Pacing in Patients With a Long PR Interval, Narrow QRS and Heart Failure: Results of the Hope-hf Clinical Trial, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E587-E587, ISSN: 0009-7322

Conference paper

Ahmad Y, Francis DP, Bhatt DL, Howard JPet al., 2021, Renal Denervation for Hypertension A Systematic Review and Meta-Analysis of Randomized, Blinded, Placebo-Controlled Trials, JACC-CARDIOVASCULAR INTERVENTIONS, Vol: 14, Pages: 2614-2624, ISSN: 1936-8798

Journal article

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 G, 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, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 342, Pages: 7-14, ISSN: 0167-5273

Journal article

Hartley A, Khamis R, Al-Lamee R, Shun-Shin M, Haskard D, Francis Det al., 2021, The placebo-controlled effect of percutaneous coronary intervention on exercise induced changes in anti- malondialdehyde-LDL antibody levels in stable coronary artery disease: a substudy of the ORBITA Trial, Frontiers in Cardiovascular Medicine, Vol: 8, ISSN: 2297-055X

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significantcomponent of oxidized LDL. The effects of exercise on levels of MDA-LDL and antiMDA-LDL antibodies are not well understood. Furthermore, it is not known whetherthese can be modified in patients with coronary artery disease by percutaneouscoronary intervention (PCI).Methods: The Objective Randomised Blinded Investigation with optimal medicalTherapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multicentre randomised trial of PCI versus placebo procedure for angina relief. Serumsamples were available at four time-points: pre-randomisation pre- (P1) and post- (P2)exercise and post-randomisation (six-weeks following the PCI or placebo procedure),pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developedassays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.Results: 196 of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severesingle vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial hadblood available for analysis. With exercise at pre-randomisation (P2 - P1) there wasno significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p=0.287);however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to-0.014, p<0.0001; -0.016, 95% CI -0.024 to -0.008, p=0.0002, respectively). PCI didnot have a significant impact on either the pre-exercise values (P3 controlling for P1)of MDA-LDL (p=0.102), IgG (p=0.444) or IgM anti-MDA-LDL(p=0.909). Nor did PCIimpact the exercise induced changes in these markers (P4 controlling for P1, P2, andP3) for MDA-LDL (p=0.605), IgG (p=0.725) or IgM anti-MDA-LDL (p=0.171). Prerandomisation ischaemia on stress echo did not impact these interactions.Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies inpatients with severe single vessel coronary disease, possibly indicating an inductionin homoeostatic

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

Ratneswaren A, Hadjiloizou N, Ahmad Y, Sen S, Maliq I, Parker K, Francis D, Hughes AD, Davies JE, Mayet Jet al., 2021, Coronary haemodynamics associated with left ventricular hypertrophy in aortic stenosis and hypertension, Publisher: OXFORD UNIV PRESS, Pages: 1728-1728, ISSN: 0195-668X

Conference paper

Stowell C, Howard J, Demetrescu C, Bhattacharyya S, Mangion K, Vimalesvaran K, Cole G, Rajani R, Sehmi J, Alzetani M, Zolgharni M, Rana B, Francis D, Shun-Shin Met al., 2021, Fully automated global longitudinal strain assessment using artificial intelligence developed and validated by a UK-wide echocardiography expert collaborative, Publisher: OXFORD UNIV PRESS, Pages: 2-2, ISSN: 0195-668X

Conference paper

Wustmann K, Constantine A, Davies JE, Li W, Pennell D, Wort S, Kempny A, Price L, McCabe C, Mohiaddin R, Francis D, Gatzoulis M, Dimopoulos Ket al., 2021, Prognostic implications of pulmonary wave reflection and reservoir pressure in patients with pulmonary hypertension, International Journal of Cardiology: Congenital Heart Disease, Vol: 5, Pages: 1-8, ISSN: 2666-6685

BackgroundRight ventricular (RV) coupling to the pulmonary circulation influences the response of the RV to the increased afterload caused by pulmonary hypertension (PH), which ultimately determines prognosis. A methodology that accounts for pulsatile flow is required when assessing ventriculo-arterial coupling. We applied wave intensity analysis (WIA) methods to assess the compliance of the main pulmonary artery (PA) in patients with or without PH and compared this to PA distensibility, RV function and clinical outcomes.MethodsHigh-fidelity blood pressure and Doppler flow velocity tracings were obtained simultaneously during cardiac catheterisation for suspected PH. RV volumes, main PA distensibility and ventriculo-arterial coupling (Emax/Ea) were analysed using cardiovascular magnetic resonance.ResultsThe study included 17 ​PH patients and 6 controls. Wave speed, reservoir and excess pressure were higher in PH patients compared to controls (p ​< ​0.01 for all). Waveforms relating to RV ejection, microvascular wave reflection and late systolic proximal deceleration were higher in PH patients compared to controls (p ​< ​0.01 for all) and related to echocardiographic findings, including PA Doppler notching and shortened acceleration time. Wave speed, reservoir pressure and excess pressure were strongly correlated to main PA distensibility, RV function and Emax/Ea. A higher total pressure integral was associated with an increased risk of death (all-cause mortality).ConclusionThe reservoir-excess pressure model, in combination with conventional clinical imaging, provides valuable information on the pathophysiology of PH that standard haemodynamic parameters do not. Future studies should further investigate the prognostic implications of WIA in PH, and its potential role in clinical practice.

Journal article

Arnold AD, Shun-Shin MJ, Ali N, Keene D, Howard JP, Chow J-J, Qureshi NA, Koa-Wing M, Tanner M, Lefroy DC, Linton NWF, Ng FS, Lim PB, Peters NS, Kanagaratnam P, Francis DP, Whinnett ZIet al., 2021, Left ventricular activation time and pattern are preserved with both selective and non-selective his bundle pacing, Heart Rhythm O2, Vol: 2, Pages: 439-445, ISSN: 2666-5018

BackgroundHis bundle pacing (HBP) can be achieved in two ways: selective HBP (S-HBP), where the His bundle is captured alone, and non-selective HBP (NS-HBP), where local myocardium is also captured resulting a pre-excited ECG appearance.ObjectiveWe assessed the impact of this ventricular pre-excitation on left and right ventricular dys-synchrony.MethodsWe recruited patients who displayed both S-HBP and NS-HBP. We performed non-invasive epicardial electrical mapping for left and right ventricular activation time (LVAT and RVAT) and pattern.Results20 patients were recruited. In the primary analysis, the mean within-patient change in LVAT from S-HBP to NS-HBP was -5.5ms (95% confidence interval: -0.6 to -10.4, non-inferiority p<0.0001). NS-HBP did not prolong RVAT (4.3ms, -4.0 to 12.8, p=0.296) but did prolong QRS duration (QRSd, 22.1ms, 11.8 to 32.4, p = 0.0003). In patients with narrow intrinsic QRS (n=6), NS-HBP preserved LVAT (-2.9ms, -9.7 to 4.0, p=0.331) but prolonged QRS duration (31.4ms, 22.0 to 40.7, p=0.0003) and mean RVAT (16.8ms, -5.3 to 38.9, p=0.108) compared to S-HBP. Activation pattern of the left ventricular surface was unchanged between S-HBP and NS-HBP but NS-HBP produced early basal right ventricular activation that was not seen in S-HBP.ConclusionCompared to S-HBP, local myocardial capture during NS-HBP produces pre-excitation of the basal right ventricle resulting in QRS duration prolongation. However, NS-HBP preserves the left ventricular activation time and pattern of S-HBP. Left ventricular dys-synchrony is not an important factor when choosing between S-HBP and NS-HBP in most patients.

Journal article

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

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

Journal article

Seligman H, Zaman S, Pitcher DS, Shun-Shin MJ, Lloyd FH, Androshchuk 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, Correction: Reusable snorkel masks adapted as particulate respirators, PLoS One, Vol: 16, Pages: 1-1, ISSN: 1932-6203

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

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.

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