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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695 results found

Chow J-J, Leong KMW, Shun-Shin MJ, Ormerod JOM, Koa-Wing M, Lefroy DC, Lim PB, Linton NWF, Ng FS, Qureshi NA, Whinnett ZI, Peters NS, Francis DP, Varnava AM, Kanagaratnam Pet al., 2023, Ventricular Conduction Stability Noninvasively Identifies an Arrhythmic Substrate in Survivors of Idiopathic Ventricular Fibrillation., J Am Heart Assoc, Vol: 12

Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion following normal cardiac investigations. We sought to determine if exercise-induced changes in electrical substrate could distinguish patient groups with various ventricular arrhythmic pathophysiological conditions and identify patients susceptible to VF. Methods and Results Computed tomography and exercise testing in patients wearing a 252-electrode vest were combined to determine ventricular conduction stability between rest and peak exercise, as previously described. Using ventricular conduction stability, conduction heterogeneity in idiopathic VF survivors (n=14) was compared with those surviving VF during acute ischemia with preserved ventricular function following full revascularization (n=10), patients with benign ventricular ectopy (n=11), and patients with normal hearts, no arrhythmic history, and negative Ajmaline challenge during Brugada family screening (Brugada syndrome relatives; n=11). Activation patterns in normal subjects (Brugada syndrome relatives) are preserved following exercise, with mean ventricular conduction stability of 99.2±0.9%. Increased heterogeneity of activation occurred in the idiopathic VF survivors (ventricular conduction stability: 96.9±2.3%) compared with the other groups combined (versus 98.8±1.6%; P=0.001). All groups demonstrated periodic variation in activation heterogeneity (frequency, 0.3-1 Hz), but magnitude was greater in idiopathic VF survivors than Brugada syndrome relatives or patients with ventricular ectopy (7.6±4.1%, 2.9±2.9%, and 2.8±1.2%, respectively). The cause of this periodicity is unknown and was not replicable by introducing exercise-induced noise at comparable frequencies. Conclusions In normal subjects, ventricular activation patterns change little with exercise. In contrast, patients with susceptibility to VF experience activation heterogeneity following exercise that requires f

Journal article

Ali N, Arnold AD, Miyazawa AA, Keene D, Chow J-J, Little I, Peters NS, Kanagaratnam P, Qureshi N, Ng FS, Linton NWF, Lefroy DC, Francis DP, Lim PB, Tanner MA, Muthumala A, Shun-Shin MJ, Cole GD, Whinnett Zet al., 2023, Comparison of methods for delivering cardiac resynchronization therapy: an acute electrical and haemodynamic within-patient comparison of left bundle branch area, His bundle, and biventricular pacing, EP Europace, Vol: 25, Pages: 1060-1067, ISSN: 1099-5129

AimsLeft bundle branch area pacing (LBBAP) is a promising method for delivering cardiac resynchronization therapy (CRT), but its relative physiological effectiveness compared with His bundle pacing (HBP) is unknown. We conducted a within-patient comparison of HBP, LBBAP, and biventricular pacing (BVP).Methods and resultsPatients referred for CRT were recruited. We assessed electrical response using non-invasive mapping, and acute haemodynamic response using a high-precision haemodynamic protocol. Nineteen patients were recruited: 14 male, mean LVEF of 30%. Twelve had time for BVP measurements. All three modalities reduced total ventricular activation time (TVAT), (ΔTVATHBP -43 ± 14 ms and ΔTVATLBBAP −35 ± 20 ms vs. ΔTVATBVP −19 ± 30 ms, P = 0.03 and P = 0.1, respectively). HBP produced a significantly greater reduction in TVAT compared with LBBAP in all 19 patients (−46 ± 15 ms, −36 ± 17 ms, P = 0.03). His bundle pacing and LBBAP reduced left ventricular activation time (LVAT) more than BVP (ΔLVATHBP −43 ± 16 ms, P < 0.01 vs. BVP, ΔLVATLBBAP −45 ± 17 ms, P < 0.01 vs. BVP, ΔLVATBVP −13 ± 36 ms), with no difference between HBP and LBBAP (P = 0.65). Acute systolic blood pressure was increased by all three modalities. In the 12 with BVP, greater improvement was seen with HBP and LBBAP (6.4 ± 3.8 mmHg BVP, 8.1 ± 3.8 mmHg HBP, P = 0.02 vs. BVP and 8.4 ± 8.2 mmHg for LBBAP, P = 0.3 vs. BVP), with no difference between HBP and LBBAP (P = 0.8).ConclusionHBP delivered better ventricular resynchronization than LBBAP because right ventricular activation was slower during LBBAP. But LBBAP was not inferior to HBP with respect to LV electrical resynchronization and acute haemodynamic response.

Journal article

Whinnett ZI, Shun-Shin MJ, Tanner M, Foley P, Chandrasekaran B, Moore P, Adhya S, Qureshi N, Muthumala A, Lane R, Rinaldi A, Agarwal S, Leyva F, Behar J, Bassi S, Ng A, Scott P, Prasad R, Swinburn J, Tomson J, Sethi A, Shah J, Lim PB, Kyriacou A, Thomas D, Chuen J, Kamdar R, Kanagaratnam P, Mariveles M, Burden L, March K, Howard JP, Arnold A, Vijayaraman P, Stegemann B, Johnson N, Falaschetti E, Francis DP, Cleland JGF, Keene Det al., 2023, Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 25, Pages: 274-283, ISSN: 1388-9842

Journal article

Lane ES, Jevsikov J, Shun-shin MJ, Dhutia N, Matoorian N, Cole GD, Francis DP, Zolgharni Met al., 2023, Automated multi-beat tissue Doppler echocardiography analysis using deep neural networks, MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING, ISSN: 0140-0118

Journal article

Arnold AD, Shun-Shin MJ, Ali N, Keene D, Howard JP, Francis DP, Whinnett ZIet al., 2023, Contributions of Atrioventricular Delay Shortening and Ventricular Resynchronization to Hemodynamic Benefits of Biventricular Pacing., JACC Clin Electrophysiol, Vol: 9, Pages: 117-119

Journal article

Al Saikhan L, Park C, Tillin T, Jones S, Francis D, Mayet J, Chaturvedi N, Hughes ADet al., 2023, Sex-differences in associations of LV structure and function measured by echocardiography with long-term risk of mortality and cardiovascular morbidity., Front Cardiovasc Med, Vol: 10, ISSN: 2297-055X

BACKGROUND: Three-dimensional echocardiography (3DE) measures of the left ventricle (LV) predict outcomes in high risk individuals, but their prognostic value in the general population is unknown. We aimed to establish whether 3DE was associated with mortality and morbidity in a multi-ethnic community-based sample, if associations differed by sex, and explored potential mechanisms explaining sex differences. METHODS: 922 individuals (69.7 ± 6.2 years; 717 men) from the SABRE study underwent a health examination including echocardiography. Associations between 3DE LV measures (ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), LV remodeling index (LVRI) and LV sphericity index (LVSI), and all-cause mortality and a composite cardiovascular endpoint [comprising new onset (non)fatal coronary heart disease, heart failure hospitalization, new-onset arrhythmias and cardiovascular mortality] were determined using multivariable Cox regression over a median follow-up of 8 years (all-cause mortality) and 7 years (composite cardiovascular endpoint). RESULTS: There were 123 deaths and 151 composite cardiovascular endpoints. Lower EF, higher LV volumes and LVSI were associated with increased all-cause mortality, and higher LV volumes were associated with the composite cardiovascular endpoint independent of potential confounders. Associations between LV volumes, LVRI, LVSI, and mortality differed by sex (p interaction <0.1). In men increased LV volumes and LVSI and decreased LVRI and EF were associated with higher mortality, but associations were null or reversed in women (hazard ratios (95% CI) men vs. women: EDV 1.25 (1.05, 1.48) vs. 0.54 (0.26, 1.10); ESV, 1.36 (1.12, 1.63) vs. 0.59 (0.33, 1.04); LVRI, 0.79 (0.64, 0.96) vs. 1.70 (1.03, 2.80); LVSI, 1.27 (1.05, 1.54) vs. 0.61 (0.32, 1.15); and EF, 0.78 (0.66, 0.93) vs. 1.27 (0.69, 2.33). Similar sex differences were observed for associations with the composite cardiovascular ou

Journal article

Ganesananthan S, Rajkumar CA, Foley M, Francis D, Al-Lamee Ret al., 2022, Remote digital smart device follow-up in prospective clinical trials: early insights from ORBITA-2, ORBITA-COSMIC, and ORBITA-STAR, EUROPEAN HEART JOURNAL SUPPLEMENTS, Vol: 24, Pages: H32-H42, ISSN: 1520-765X

Journal article

Kaza N, Htun V, Miyazawa A, Simader F, Porter B, Howard JP, Arnold AD, Naraen A, Luria D, Glikson M, Israel C, Francis DP, Whinnett Z, Shun-Shin MJ, Keene Det al., 2022, Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a systematic review and meta-analysis, EUROPACE, ISSN: 1099-5129

Journal article

Simader FA, Howard JP, Ahmad Y, Saleh K, Naraen A, Samways JW, Mohal J, Reddy RK, Kaza N, Keene D, Shun-Shin MJ, Francis DP, Whinnett Z, Arnold ADet al., 2022, Catheter ablation improves cardiovascular outcomes in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials, EUROPACE, ISSN: 1099-5129

Journal article

Asaria P, Bennett J, Elliott P, Rashid T, Daby H, Douglass M, Francis D, Fecht D, Ezzati Met al., 2022, Contributions of event rates, pre-hospital deaths and hospital case fatality to variations in myocardial infarction mortality in 326 districts in England: spatial analysis of linked hospitalisation and mortality data, The Lancet Public Health, Vol: 7, Pages: e813-e824, ISSN: 2468-2667

Background: Myocardial infarction (MI) mortality varies substantially within high-income countries. There is limited guidance on what interventions – primary and secondary prevention and/or improving care pathways and quality – can reduce and equalise MI mortality. Our aimwas to understand the contribution of incidence (event rate), pre-hospital deaths and hospital case-fatality, to how MI mortality varies within England.Methods: We used linked data on hospitalisation and deaths from 2015-2018 with geographical identifiers to estimate MI death and event rates, pre-hospital deaths and hospital case fatality for men and women aged 45 years and older in 326 districts in England. Data were analysed in a Bayesian spatial model that accounted for similarities and differences inspatial patterns of fatal and non-fatal MI. Results: The 99th to 1st percentile ratio of age-standardised MI death rate was 2.63 (95% credible interval 2.45-2.83) in women and 2.56 (2.37-2.76) in men across districts, with death rate highest in north of England. The main contributor to this variation was MI event rate, with a 99th to 1st percentile ratio of 2.55 (2.39-2.72) (women) and 2.17 (2.08-2.27) (men) across districts. Pre-hospital mortality was greater than hospital case fatality in every district. Prehospital mortality had a 99th to 1st percentile ratio 1.60 (1.50-1.70) in women and 1.75 (1.66-1.86) in men across districts and made a greater contribution to case-fatality variation thanhospital case fatality which had a 99th to 1st percentile ratio of 1.39 (1.29-1.49) (women) and1.49 (1.39-1.60) (men). The contribution of case fatality to variation in deaths across districtswas largest in middle ages. Pre-hospital mortality was slightly higher in men than women inmost districts and age groups, whereas hospital case fatality was higher in women in virtuallyall districts at ages up to and including 65-74 years; after this age, it became similar betweenthe sexes.3Interpretation: Mos

Journal article

Sedlacek K, Polasek R, Jansova H, Grieco D, Kucera P, Kautzner J, Francis DP, Wichterle Det al., 2022, Inadvertent QRS prolongation by an optimization device-based algorithm in patients with cardiac resynchronization therapy, PLOS ONE, Vol: 17, ISSN: 1932-6203

Journal article

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

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

Journal article

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

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

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

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

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

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

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

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

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

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