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

611 results found

Warisawa T, Howard JP, Kawase Y, Tanigaki T, Omori H, Cook CM, Ahmad Y, Francis DP, Akashi YJ, Matsuo H, Davies JEet al., 2020, Difference in functional assessment of individual stenosis severity in serial coronary lesions between resting and hyperemic pressure-wire pullback: Insights from the GIFT registry., Int J Cardiol, Vol: 312, Pages: 10-15

BACKGROUND: Identifying the individual hemodynamic significance of tandem coronary artery lesions can be complicated by the crosstalk phenomenon which occurs between serial stenoses under hyperemic conditions. Physiological assessments performed under resting conditions are considered to be, theoretically, less affected by the hemodynamic interaction between serial coronary stenoses. The purpose of this study was to assess whether pressure-wire (PW) pullback measurements at rest and during hyperemia provided different information as to which stenosis appeared to be most functionally significant. METHODS: In consecutive patients with angiographically discrete serial lesions, physiological lesion predominance (i.e. proximal or distal) was defined according to the pressure gradient along the vessels on PW-pullback trace. We used instantaneous wave-free ratio (iFR) based assessment as the reference standard and compared fractional flow reserve (FFR) based and hyperemic-iFR based lesion predominance. RESULTS: Eighty-eight vessels (70 patients, mean age 70.3 ± 9.4 years, 80% male) were included in this study. Median iFR, FFR and hyperemic-iFR were 0.85 (interquartile range [IQR]: 0.74 to 0.91), 0.73 (IQR: 0.65 to 0.80) and 0.60 (IQR: 0.49 to 0.71), respectively. When judged against iFR-pullback based physiological assessment, lesion predominance changed in 22.7% (20/88) in FFR and in 20.5% (18/88) in hyperemic-iFR, respectively. There was no statistical difference between FFR and hyperemic-iFR for the impact on these changes (p = 0.77). CONCLUSIONS: In serial coronary lesions, hyperemic PW-pullback disagreed with resting PW-pullback on the lesion-specific identification of ischemia in approximately 20% of cases, either in whole cardiac cycle or in wave-free period.

Journal article

Marquis-Gravel G, Moliterno DJ, Francis DP, Jüni P, Rosenberg YD, Claessen BE, Mentz RJ, Mehran R, Cutlip DE, Chauhan C, Quella S, Zannad F, Goodman SGet al., 2020, Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review., J Am Coll Cardiol, Vol: 76, Pages: 435-450

The role of percutaneous coronary interventions in addition to medical therapy for patients with stable coronary artery disease continues to be debated in routine clinical practice, despite more than 2 decades of randomized controlled trials. The residual uncertainty arises from particular challenges facing revascularization trials. Which endpoint do doctors care about, and which do patients care about? Which participants should be enrolled? What background medical therapy should we use? When is placebo control relevant? In this paper, we discuss how these questions can be approached and examine the merits and disadvantages of possible options. Engaging multiple stakeholders, including patients, researchers, regulators, and funders, to ensure the design elements are methodologically valid and clinically meaningful should be an aspirational goal in the development of future trials.

Journal article

Warisawa T, Cook CM, Rajkumar C, Howard JP, Seligman H, Ahmad Y, El Hajj S, Doi S, Nakajima A, Nakayama M, Goto S, Vera-Urquiza R, Sato T, Kikuta Y, Kawase Y, Nishina H, Petraco R, Al-Lamee R, Nijjer S, Sen S, Nakamura S, Lerman A, Matsuo H, Francis DP, Akashi YJ, Escaned J, Davies JEet al., 2020, Safety of Revascularization Deferral of Left Main Stenosis Based on Instantaneous Wave-Free Ratio Evaluation., JACC Cardiovasc Interv, Vol: 13, Pages: 1655-1664

OBJECTIVES: The aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR). BACKGROUND: The overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR. METHODS: This multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death. RESULTS: At a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all). CONCLUSIONS: Deferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.

Journal article

Piepoli MF, Ponikowski PP, Volterrani M, Francis DP, Coats AJSet al., 2020, DoCheyne andStokes have an important message for modern-day patients with heart failure?Yes, they do, EUROPEAN JOURNAL OF HEART FAILURE, ISSN: 1388-9842

Journal article

Ahmad Y, Howard JP, Arnold AD, Ali ZD, Francis D, Moses JW, Leon MB, Kirtane AJ, Karmpaliotis D, Stone GWet al., Drug-eluting stents versus bypass surgery for left main disease: an updated meta-analysis of randomized controlled trials with long-term follow-up, American Journal of Cardiology, ISSN: 0002-9149

Journal article

Ahmad Y, 2020, Complete revascularisation by percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: an updated meta-analysis and meta-regression of randomized trials, Journal of the American Heart Association, Vol: 9, Pages: 1-83, ISSN: 2047-9980

BackgroundFor patients with ST‐segment–elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non‐infarct‐related artery has been controversial. This up‐to‐date meta‐analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease.Methods and ResultsWe systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit‐only revascularization for multivessel disease in STEMI and performed a random‐effects meta‐analysis. The primary efficacy end point was cardiovascular death analyzed on an intention‐to‐treat basis. Secondary end points included all‐cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit‐only revascularization. Across all patients, complete revascularization was superior to culprit‐only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47–0.98; P=0.037; I2=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54–0.79; P<0.0001; I2=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28–0.51; P<0.0001; I2=64.7%). The difference in all‐cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69–1.04; P=0.108; I2=0.0%).ConclusionsFor patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice gu

Journal article

Ziff OJ, Samra M, Howard JP, Bromage DI, Ruschitzka F, Francis DP, Kotecha Det al., 2020, Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment, BMC MEDICINE, Vol: 18, ISSN: 1741-7015

Journal article

Kaura A, Sterne J, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah A, Channon K, Weber J, Thursz M, Elliott P, Hemingway H, Williams B, Asselbergs F, OSullivan M, Lord G, Melikian N, Johnson T, Francis D, Shah A, Perera D, Kharbanda R, Patel R, Mayet Jet al., Invasive versus non-invasive management of elderly patients with non-ST elevation myocardial infarction: cohort study based on routine clinical data, The Lancet, ISSN: 0140-6736

BackgroundPrevious trials suggest lower long-term mortality after invasive rather than non-invasive management among patients with non-ST elevation myocardial infarction (NSTEMI), but these excluded very elderly patients.MethodsWe estimated the effect of invasive versus non-invasive management within 3 days of peak troponin on survival in NSTEMI patients aged ≥80 years, using routine clinical data collected during 2010–2017 (NIHR Health Informatics Collaborative). Propensity scores based on pre-treatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and also compared rates of hospital admission for heart failure.FindingsOf 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin, whilst 375 were excluded because of extreme propensity scores. The remaining 1500 patients (56% non-invasive management) had a median age 86 (IQR 82-89) years. During median follow-up of 3.0 (IQR 1.2-4.8) years, there were 613 (41%) deaths. Using inverse probability weighting, adjusted cumulative 5-year mortality was 36% and 55% in the invasive and non-invasive management groups, respectively. The mortality hazard ratio comparing invasive with non-invasive management was 0.64 (95% CI 0.52-0.79) after multivariable adjustment for clinical characteristics and propensity score and inclusion of patients who died within three days. Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0.67, 95% CI 0.48–0.93).

Journal article

Kaura A, Arnold AD, Vasileios P, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, OSullivan M, Lord GM, Melikian N, Lefroy DC, Francis DP, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet Jet al., 2020, Prognostic significance of troponin level in 3,121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study), Journal of the American Heart Association, Vol: 9, ISSN: 2047-9980

Background-—Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of theresult is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronaryangiography, and all-cause mortality in real-world patients presenting with AF.Methods and Results-—We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results 7 were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median followup of 1462 (interquartile range, 929–1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associatedwith a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01–1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9–3.4) at 250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography.The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42–0.89; P=0.01).Conclusions-—Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.

Journal article

Azarmehr N, Ye X, Howes JD, Docking B, Howard JP, Francis DP, Zolgharni Met al., 2020, An optimisation-based iterative approach for speckle tracking echocardiography, MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING, Vol: 58, Pages: 1309-1323, ISSN: 0140-0118

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 GV, Mohdnazri S, Gamma R, de Waard GA, Al-Lamee R, Keeble TR, Mayet J, Sen S, Francis DP, Davies JEet al., 2020, How Do Fractional Flow Reserve, Whole-Cycle PdPa, and Instantaneous Wave-Free Ratio Correlate With Exercise Coronary Flow Velocity During Exercise-Induced Angina?, CIRCULATION-CARDIOVASCULAR INTERVENTIONS, Vol: 13, ISSN: 1941-7640

Journal article

Howard JP, Tan J, Shun-Shin MJ, Mahdi D, Nowbar AN, Arnold AD, Ahmad Y, McCartney P, Zolgharni M, Linton NWF, Sutaria N, Rana B, Mayet J, Rueckert D, Cole GD, Francis DPet al., 2020, Improving ultrasound video classification: an evaluation of novel deep learning methods in echocardiography., J Med Artif Intell, Vol: 3

Echocardiography is the commonest medical ultrasound examination, but automated interpretation is challenging and hinges on correct recognition of the 'view' (imaging plane and orientation). Current state-of-the-art methods for identifying the view computationally involve 2-dimensional convolutional neural networks (CNNs), but these merely classify individual frames of a video in isolation, and ignore information describing the movement of structures throughout the cardiac cycle. Here we explore the efficacy of novel CNN architectures, including time-distributed networks and two-stream networks, which are inspired by advances in human action recognition. We demonstrate that these new architectures more than halve the error rate of traditional CNNs from 8.1% to 3.9%. These advances in accuracy may be due to these networks' ability to track the movement of specific structures such as heart valves throughout the cardiac cycle. Finally, we show the accuracies of these new state-of-the-art networks are approaching expert agreement (3.6% discordance), with a similar pattern of discordance between views.

Journal article

Ahmad Y, 2020, Mortality after drug-eluting stents versus coronary artery bypass grafting for left main coronary artery disease: A meta-analysis of randomized controlled trials, European Heart Journal, ISSN: 0195-668X

Aims The optimal method of revascularization for patients with left main coronary artery disease (LMCAD) is controversial. Coronary artery bypass graft surgery (CABG) has traditionally been considered the gold standard therapy, and recent randomized trials comparing CABG with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have reported conflicting outcomes. We, therefore, performed a systematic review and updated meta-analysis comparing CABG to PCI with DES for the treatment of LMCAD.Methods and results We systematically identified all randomized trials comparing PCI with DES vs. CABG in patients with LMCAD. The primary efficacy endpoint was all-cause mortality. Secondary endpoints included cardiac death, myocardial infarction (MI), stroke, and unplanned revascularization. All analyses were by intention-to-treat. There were five eligible trials in which 4612 patients were randomized. The weighted mean follow-up duration was 67.1 months. There were no significant differences between PCI and CABG for the risk of all-cause mortality [relative risk (RR) 1.03, 95% confidence interval (CI) 0.81–1.32; P = 0.779] or cardiac death (RR 1.03, 95% CI 0.79–1.34; P = 0.817). There were also no significant differences in the risk of stroke (RR 0.74, 95% CI 0.35–1.50; P = 0.400) or MI (RR 1.22, 95% CI 0.96–1.56; P = 0.110). Percutaneous coronary intervention was associated with an increased risk of unplanned revascularization (RR 1.73, 95% CI 1.49–2.02; P < 0.001).Conclusion The totality of randomized clinical trial evidence demonstrated similar long-term mortality after PCI with DES compared with CABG in patients with LMCAD. Nor were there significant differences in cardiac death, stroke, or MI between PCI and CABG. Unplanned revascularization procedures were less common after CABG compared with PCI. These findings may inform clinica

Journal article

Bachtiger P, Plymen CM, Pabari PA, Howard JP, Whinnett ZI, Opoku F, Janering S, Faisal AA, Francis DP, Peters NSet al., 2020, Artificial intelligence, data sensors and interconnectivity: future Opportunities for heart failure, Cardiac Failure Review, Vol: 6, Pages: e11-e11, ISSN: 2057-7540

A higher proportion of patients with heart failure have benefitted from a wide and expanding variety of sensor-enabled implantable devices than any other patient group. These patients can now also take advantage of the ever-increasing availability and affordability of consumer electronics. Wearable, on- and near-body sensor technologies, much like implantable devices, generate massive amounts of data. The connectivity of all these devices has created opportunities for pooling data from multiple sensors - so-called interconnectivity - and for artificial intelligence to provide new diagnostic, triage, risk-stratification and disease management insights for the delivery of better, more personalised and cost-effective healthcare. Artificial intelligence is also bringing important and previously inaccessible insights from our conventional cardiac investigations. The aim of this article is to review the convergence of artificial intelligence, sensor technologies and interconnectivity and the way in which this combination is set to change the care of patients with heart failure.

Journal article

Chacko L, P Howard J, Rajkumar C, Nowbar AN, Kane C, Mahdi D, Foley M, Shun-Shin M, Cole G, Sen S, Al-Lamee R, Francis DP, Ahmad Yet al., 2020, Effects of percutaneous coronary intervention on death and myocardial infarction stratified by stable and unstable coronary artery disease: a meta-analysis of randomized controlled trials, Circulation: Cardiovascular Quality and Outcomes, Vol: 13, ISSN: 1941-7705

Background:In patients presenting with ST-segment–elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post–myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment–elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non–ST-segment–elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials.Methods and Results:We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45–1.03); P=0.07; multivessel disease following ST-segment–elevation myocardial infarction (RR, 0.84 [95% CI, 0.69–1.04]; P=0.11); non–ST-segment–elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72–0.97]; P=0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75–0.93]; P=0.02). In unstable CAD, PCI also reduced cardiac

Journal article

Azarmehr N, Ye X, Sacchi S, Howard JP, Francis DP, Zolgharni Met al., 2020, Segmentation of Left Ventricle in 2D Echocardiography Using Deep Learning, Pages: 497-504, ISBN: 9783030393427

© 2020, Springer Nature Switzerland AG. The segmentation of Left Ventricle (LV) is currently carried out manually by the experts, and the automation of this process has proved challenging due to the presence of speckle noise and the inherently poor quality of the ultrasound images. This study aims to evaluate the performance of different state-of-the-art Convolutional Neural Network (CNN) segmentation models to segment the LV endocardium in echocardiography images automatically. Those adopted methods include U-Net, SegNet, and fully convolutional DenseNets (FC-DenseNet). The prediction outputs of the models are used to assess the performance of the CNN models by comparing the automated results against the expert annotations (as the gold standard). Results reveal that the U-Net model outperforms other models by achieving an average Dice coefficient of 0.93 ± 0.04, and Hausdorff distance of 4.52 ± 0.90.

Book chapter

Al-lamee RK, Shun-Shin M, Howard J, Nowbar A, Rajkumar C, Thompson D, Sen S, Nijjer S, Petraco R, Davies J, Keeble T, Tang K, Malik I, Bual N, Cook C, Ahmad Y, Seligman H, Sharp A, Talwar S, Assomull R, Cole G, Keenan NG, Kanaganayagam GS, Sehmi JS, Wensel R, Harrell F, Mayet J, Thom S, Davies JE, Francis Det al., 2019, Dobutamine Stress Echocardiography Ischaemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echo-Stratified Analysis of ORBITA, Resuscitation Science Symposium (ReSS), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E985-E985, ISSN: 0009-7322

Conference paper

Seligman H, Teixeira-Pinto A, Nowbar A, Francis Det al., 2019, Fragility of the Bond Between Cardiovascular Investigators and Their Readers, CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES, Vol: 12, ISSN: 1941-7705

Journal article

Giannoni A, Gentile F, Navari A, Borrelli C, Mirizzi G, Catapano G, Vergaro G, Grotti F, Betta M, Piepoli MF, Francis DP, Passino C, Emdin Met al., 2019, Contribution of the lung to the genesis of cheyne-stokes respiration in heart failure: plant gain beyond chemoreflex gain and circulation time, 80th SIC National Congress, Publisher: OXFORD UNIV PRESS, Pages: J130-J130, ISSN: 1520-765X

Conference paper

Gitto M, Gentile F, Nowbar AN, Shun-Shin M, Seligman H, Rajkumar C, Howard J, Francis D, Chieffo A, Camici PG, Al-lamee Ret al., 2019, Gender-related differences in clinical presentation and angiographic findings in patients with ischaemia and no obstructive coronary artery disease (INOCA): a single-center observational registry, 80th SIC National Congress, Publisher: OXFORD UNIV PRESS, Pages: J157-J157, ISSN: 1520-765X

Conference paper

Ahmad Y, Vendrik J, Eftekhari A, Howard J, Cook C, Rajkumar C, Malik I, Mikhail G, Ruparelia N, Hadjiloizou N, Nijjer S, Al-Lamee R, Petraco R, Warisawa T, Wijntjens GWM, Koch KT, van de Hoef T, de Waard G, Echavarria-Pinto M, Frame A, Sutaria N, Kanaganayagam G, Ariff B, Anderson J, Chukwuemeka A, Fertleman M, Koul S, Iglesias JF, Francis D, Mayet J, Serruys P, Davies J, Escaned J, van Royen N, Götberg M, Terkelsen CJ, Christiansen CH, Piek JJ, Baan Jr J, Sen Set al., 2019, Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses: A Multicenter Study Using Intracoronary Pressure and Flow, Circulation: Cardiovascular Interventions, Vol: 12, ISSN: 1941-7640

Background:Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation.Methods:Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2).Results:Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s−1 versus post-TAVI 3.04±1.6 mm Hg·cm·s−1 [P=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [P=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74.Conclusions:TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider us

Journal article

Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah A, Channon K, Weber J, Thursz M, Elliott P, Hemingway H, Williams B, Asselbergs F, OSullivan M, Kharbanda R, Lord G, Melikian N, Patel R, Perera D, Shah A, Francis D, Mayet Jet al., 2019, Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres, BMJ-British Medical Journal, Vol: 367, ISSN: 1756-1833

ObjectiveTo determine the relation between age and troponinlevel and its prognostic implication.DesignRetrospective cohort study.SettingFive cardiovascular centres in the UK National Institutefor Health Research Health Informatics Collaborative(UK-NIHR HIC).Participants257948 consecutive patients undergoing troponintesting for any clinical reason between 2010 and2017.Main outcome measureAll cause mortality.Results257948 patients had troponin measured during thestudy period. Analyses on troponin were performedusing the peak troponin level, which was the highesttroponin level measured during the patient’s hospitalstay. Troponin levels were standardised as a multipleof each laboratory’s 99th centile of the upper limitof normal (ULN). During a median follow-up of 1198days (interquartile range 514-1866 days), 55850(21.7%) deaths occurred. A positive troponin result(that is, higher than the upper limit of normal)signified an overall 3.2-fold higher mortality hazard(95% confidence interval 3.1-fold to 3.2-fold) overthree years. The mortality hazard varied markedly withage, from 10.6-fold (8.5-fold to 13.3-fold) in 18-29year olds to 1.5 (1.4 to 1.6) in those older than 90.A positive troponin result was associated with anapproximately 15 percentage points higher absolutethree year mortality across all age groups. The excessmortality with a positive troponin result was heavilyconcentrated in the first few weeks. Results wereanalysed using multivariable adjusted restrictedcubic spline Cox regression. A direct relation wasseen between troponin level and mortality in patientswithout acute coronary syndrome (ACS, n=120049),whereas an inverted U shaped relation was foundin patients with ACS (n=14468), with a paradoxicaldecline in mortality at peak troponin levels >70xULN.In the group with ACS, the inverted U shaped relationpersisted after multivariable adjustment in those whowere managed invasively; however, a direct positiverelation was found between troponin level

Journal article

Al-Lamee R, Shun-Shin M, Howard J, Nowbar A, Rajkumar C, Thompson D, Sen S, Nijjer S, Petraco R, Davies J, Keeble T, Tang K, Malik I, Bual N, Cook C, Ahmad Y, Seligman H, Sharp A, Gerber R, Talwar S, Assomull R, Cole G, Keenan N, Kanaganayagam G, Sehmi J, Wensel R, Harrell Jr F, Mayet J, Thom S, Davies J, Francis Det al., 2019, Dobutamine stress echocardiography ischemia as a predictor of the placebo-controlled efficacy of percutaneous coronary intervention in stable coronary artery disease: the stress echo-stratified analysis of ORBITA, Circulation, Vol: 140, Pages: 1971-1980, ISSN: 0009-7322

BackgroundDobutamine stress echocardiography (DSE) is widely used to test for ischemia in patients with stable coronary artery disease (CAD). In this analysis we studied the ability of pre-randomization stress echo score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial. MethodsOne hundred and eighty-three patients underwent DSE before randomization. The stress echo score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of pre-randomization stress echo to predict the placebo-controlled effect of PCI on response variables was tested using regression modelling.ResultsAt pre-randomization, the stress echo score was 1.561.77 in the PCI arm (n=98) and 1.611.73 in the placebo arm (n=85). There was a detectable interaction between pre-randomization stress echo score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echo score (pinteraction=0.031). With our sample size we were unable to detect an interaction between stress echo score and any other patient-reported response variables: freedom from angina (pinteraction=0.116), physical limitation (pinteraction=0.461), quality of life (pinteraction=0.689), EQ-5D-5L quality of life score (pinteraction=0.789) or between stress echo score and physician-assessed Canadian Cardiovascular Society angina class (pinteraction=0.693), and treadmill exercise time (pinteraction=0.426). ConclusionsThe degree of ischemia assessed by DSE predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echo abnormality caused by a stenosis, the greater the reduction in symptoms from PCI.

Journal article

Howard JP, Cook CM, van de Hoef TP, Meuwissen M, de Waard GA, van Lavieren MA, Echavarria-Pinto M, Danad I, Piek JJ, Gotberg M, Al-Lamee RK, Sen S, Nijjer SS, Seligman H, van Royen N, Knaapen P, Escaned J, Francis DP, Petraco R, Davies JEet al., 2019, Artificial Intelligence for Aortic Pressure Waveform Analysis During Coronary Angiography Machine Learning for Patient Safety, JACC-CARDIOVASCULAR INTERVENTIONS, Vol: 12, Pages: 2093-2101, ISSN: 1936-8798

Journal article

Kaura A, Hartley A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Francis DP, Koenig W, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet J, Khamis Ret al., 2019, HsCRP predicts mortality beyond troponin in 102,337 patients with suspected acute coronary syndrome (CRP-RISK study), Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 1302-1302, ISSN: 0195-668X

Conference paper

Arnold A, Howard J, Chiew K, Kerrigan W, de Vere F, Johns H, Churilov L, Ahmad Y, Keene D, Shun-Shin M, Cole G, Kanagaratnam P, Sohaib S, Varnava A, Francis D, Whinnett Zet al., 2019, Right ventricular pacing for hypertrophic obstructive cardiomyopathy: meta-analysis and meta-regression of clinical trials, European Heart Journal - Quality of Care and Clinical Outcomes, Vol: 5, Pages: 321-333, ISSN: 2058-5225

AimsRight ventricular pacing for left ventricular outflow tract gradient reduction in hypertrophic obstructive cardiomyopathy remains controversial. We undertook a meta-analysis for echocardiographic and functional outcomes.Methods and resultsThirty-four studies comprising 1135 patients met eligibility criteria. In the four blinded randomized controlled trials (RCTs), pacing reduced gradient by 35% [95% confidence interval (CI) 23.2–46.9, P < 0.0001], but there was only a trend towards improved New York Heart Association (NYHA) class [odds ratio (OR) 1.82, CI 0.96–3.44; P = 0.066]. The unblinded observational studies reported a 54.3% (CI 44.1–64.6, P < 0.0001) reduction in gradient, which was a 18.6% greater reduction than the RCTs (P = 0.0351 for difference between study designs). Observational studies reported an effect on unblinded NYHA class at an OR of 8.39 (CI 4.39–16.04, P < 0.0001), 450% larger than the OR in RCTs (P = 0.0042 for difference between study designs). Across all studies, the gradient progressively decreased at longer follow durations, by 5.2% per month (CI 2.5–7.9, P = 0.0001).ConclusionRight ventricular pacing reduces gradient in blinded RCTs. There is a non-significant trend to reduction in NYHA class. The bias in assessment of NYHA class in observational studies appears to be more than twice as large as any genuine treatment effect.

Journal article

Keene D, Arnold A, Jastrzębski M, Burri H, Zweibel S, Crespo E, Chandrasekaran B, Bassi S, Joghetaei N, Swift M, Moskal P, Francis D, Foley P, Shun-Shin M, Whinnett Zet al., 2019, His bundle pacing, learning curve, procedure characteristics, safety, and feasibility: Insights from a large international observational study, Journal of Cardiovascular Electrophysiology, Vol: 30, Pages: 1984-1993, ISSN: 1045-3873

BackgroundHis‐bundle pacing (HBP) provides physiological ventricular activation. Observational studies have demonstrated the techniques feasibility however, data has come from a limited number of centres.ObjectivesWe set out to explore contemporary global practise in HBP focusing on learning curve, procedural characteristics and outcomes.MethodsThis is a retrospective, multi‐centre observational study of patients undergoing attempted HBP at seven centres. Pacing indication, fluoroscopy time, HBP thresholds and lead re‐intervention and deactivation rates were recorded. Where centres had systematically recorded implant success rates from the outset, these were collated.Results529 patients underwent attempted HBP during the study period (2014‐19) with mean follow‐up of 217±303 days. Most implants were for bradycardia indications.In the three centres with systematic collation of all attempts, overall implant success rate was 81% which improved to 87% after completion of 40 cases.All seven centres reported data on successful implants. Mean fluoroscopy time was 11.7±12.0 minutes, His‐bundle capture threshold at implant was 1.4±0.9V at 0.8±0.3 ms and was 1.3±1.2V at 0.9±0.2ms at last device check.HBP lead re‐intervention or deactivation (for lead displacement or rise in threshold) occurred in 7.5% of successful implants.There was evidence of a learning curve: fluoroscopy time and HBP capture threshold reduced with greater experience, plateauing after ~30‐50 cases.ConclusionWe found that it is feasible to establish a successful HBP program, using the currently available implantation tools. For physicians who are experienced at pacemaker implantation the steepest part of the learning curve appears to be over the first 30‐50 cases.

Journal article

ShunShin MJ, Miyazawa AA, Keene D, Sterliński M, Sokal A, Heuverswyn F, Rinaldi CA, Cornelussen R, Stegemann B, Francis DP, Whinnett Zet al., 2019, How to deliver personalized Cardiac Resynchronization Therapy through the precise measurement of the acute hemodynamic response: insights from the iSpot trial, Journal of Cardiovascular Electrophysiology, Vol: 30, Pages: 1610-1619, ISSN: 1045-3873

IntroductionNew pacing technologies offer greater choice of left ventricular pacing sites and greater personalization of cardiac resynchronization therapy (CRT). The effects on cardiac function of novel pacing configurations are often compared using multi‐beat averages of acute hemodynamic measurements. In this analysis of the iSpot trial we explore whether this is sufficient.MethodsThe iSpot trial was an international, prospective, acute hemodynamic trial that assessed seven CRT configurations: Standard CRT, Multispot (posterolateral vein), and Multivein (anterior and posterior vein) pacing. Invasive and non‐invasive blood pressure, and LV dP/dtmax were recorded. Eight beats were recorded before and after an alternation from AAI to the tested pacing configuration and vice‐versa. Eight alternations were performed for each configuration at each of the 5 AV delays.Results25 patients underwent the full protocol of 8 alternations. Only 4 (16%) patients had a statistically significant >3mmHg improvement over conventional CRT configuration (posterolateral vein, distal electrode). However, if only one alternation was analyzed (standard multi‐beat averaging protocol), 15 (60%) patients falsely appeared to have a superior non‐conventional configuration. Responses to pacing were significantly correlated between the different hemodynamic measures: invasive SBP versus non‐invasive SBP r=0.82 (p<0.001); invasive SBP versus LV dP/dt r=0.57, r2=0.32 (p<0.001).ConclusionsCurrent standard multi‐beat acquisition protocols are unfortunately unable to prevent false impressions of optimality arising in individual patients. Personalization processes need to include distinct repeated transitions to the tested pacing configuration in addition to averaging multiple beats. The need is not only during research stages, but also during clinical implementation.

Journal article

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