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

589 results found

Al-Lamee RK, Nowbar AN, Francis DP, 2019, Percutaneous coronary intervention for stable coronary artery disease, Heart, Vol: 105, Pages: 11-19, ISSN: 1355-6037

The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.

Journal article

Hartley A, Shah M, Nowbar AN, Rajkumar C, Howard JP, Francis DPet al., 2018, Key opinion leaders' guide to spinning a disappointing clinical trial result, BMJ, Vol: 363, ISSN: 0959-8138

Journal article

Kim M-Y, Sikkel MB, Hunter RJ, Haywood GA, Tomlinson DR, Tayebjee MH, Ali R, Cantwell CD, Gonna H, Sandler B, Limb E, Furniss G, Mrcp DP, Begg G, Dhillon G, Hill NJ, O'Neill J, Francis DP, Lim PB, Peters NS, Linton NWF, Kanagaratnam Pet al., 2018, A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1624-1634, ISSN: 1045-3873

INTRODUCTION: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence AV dissociation. METHODS AND RESULTS: High frequency stimulation was delivered through a Smart-Touch™ catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. 3D locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia or no effect. CARTO™ maps were exported, registered and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated atrioventricular dissociation effects (AVD-GP). There were 10 AVD-GPs (IQR 11.5) per patient. 80% (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups were very similar. Highest probability of AVD-GPs (>20%) were identified in: infero-septal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). CONCLUSION: It is feasible to map the entire left atrium for AVD-GPs prior to AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterise the autonomic network. This article is protected by copyright. All rights reserved.

Journal article

Sacchi S, Dhutia N, Shun-Shin MJ, Zolgharni M, Sutaria N, Francis DP, Cole GDet al., 2018, Doppler assessment of aortic stenosis: a 25-operator study demonstrating why reading the peak velocity is superior to velocity time integral, EHJ Cardiovascular Imaging / European Heart Journal - Cardiovascular Imaging, Vol: 19, Pages: 1380-1389, ISSN: 2047-2412

Aims Measurements with superior reproducibility are useful clinically and research purposes. Previous reproducibilitystudies of Doppler assessment of aortic stenosis (AS) have compared only a pair of observers and have notexplored the mechanism by which disagreement between operators occurs. Using custom-designed software whichstored operators’ traces, we investigated the reproducibility of peak and velocity time integral (VTI) measurementsacross a much larger group of operators and explored the mechanisms by which disagreement arose. ...................................................................................................................................................................................................Methodsand resultsTwenty-five observers reviewed continuous wave (CW) aortic valve (AV) and pulsed wave (PW) left ventricularoutflow tract (LVOT) Doppler traces from 20 sequential cases of AS in random order. Each operator unknowinglymeasured each peak velocity and VTI twice. VTI tracings were stored for comparison. Measuring the peak is muchmore reproducible than VTI for both PW (coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coeffi-cient of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early and late parts of the envelope aredifficult to trace reproducibly. Dimensionless index improves reproducibility because operators tended to consistentlyover-read or under-read on LVOT and AV traces from the same patient (coefficient of variation 9.3 vs.17.1%; P < 0.001). ...................................................................................................................................................................................................Conclusion It is far more reproducible to measure the peak of a Doppler trace than the VTI, a strategy that reduces measurementvariance by approximately six-fold. Peak measurements are superior to VTI because tracing the steep slopesin th

Journal article

Arnold A, Shun-Shin M, Keene D, Howard J, Sohaib S, wright I, Cole G, Qureshi N, lefroy D, Koa-Wing M, Linton N, Lim P, Peters N, Davies D, muthumala A, Tanner M, ellenbogen K, Kanagaratnam P, Francis D, Whinnett Zet al., 2018, His resynchronization versus biventricular pacing in patients with heart failure and left bundle branch block, Journal of the American College of Cardiology, Vol: 72, Pages: 3112-3122, ISSN: 0735-1097

Background His bundle pacing is a new method for delivering cardiac resynchronization therapy (CRT).Objectives The authors performed a head-to-head, high-precision, acute crossover comparison between His bundle pacing and conventional biventricular CRT, measuring effects on ventricular activation and acute hemodynamic function.Methods Patients with heart failure and left bundle branch block referred for conventional biventricular CRT were recruited. Using noninvasive epicardial electrocardiographic imaging, the authors identified patients in whom His bundle pacing shortened left ventricular activation time. In these patients, the authors compared the hemodynamic effects of His bundle pacing against biventricular pacing using a high-multiple repeated alternation protocol to minimize the effect of noise, as well as comparing effects on ventricular activation.Results In 18 of 23 patients, left ventricular activation time was significantly shortened by His bundle pacing. Seventeen patients had a complete electromechanical dataset. In them, His bundle pacing was more effective at delivering ventricular resynchronization than biventricular pacing: greater reduction in QRS duration (−18.6 ms; 95% confidence interval [CI]: −31.6 to −5.7 ms; p = 0.007), left ventricular activation time (−26 ms; 95% CI: −41 to −21 ms; p = 0.002), and left ventricular dyssynchrony index (−11.2 ms; 95% CI: −16.8 to −5.6 ms; p < 0.001). His bundle pacing also produced a greater acute hemodynamic response (4.6 mm Hg; 95% CI: 0.2 to 9.1 mm Hg; p = 0.04). The incremental activation time reduction with His bundle pacing over biventricular pacing correlated with the incremental hemodynamic improvement with His bundle pacing over biventricular pacing (R = 0.70; p = 0.04).Conclusions His resynchronization delivers better ventricular resynchronization, and greater improvement in hemodynamic parameters, than biventricular pacing.

Journal article

Ferreira-Martins J, Howard J, Al-Khayatt BM, Shalhoub J, Sohaib A, Shun-Shin M, Novak P, Leather R, Sterns L, Lane C, Lim P, Kanagaratnam P, Peters N, Francis D, Sikkel Met al., 2018, Outcomes of paroxysmal AF ablation studies are affected more by study design and patient mix than ablation technique, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1471-1479, ISSN: 1045-3873

Objective: We tested whether ablation methodology and study design can explain the varying outcomes in terms of AF-free survival at 1 year.Background:There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta-regression.Methods: Data was collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta-regression using the individual study arm as the unit.Results: Success rates did not change regardless of the technique used to produce pulmonary vein isolation. Neither were adjunctive lesion sets associated with any improvement in outcome.Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. ECG method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%, p<0.001) or in patients who had implantable loop recorders (by 21%, p=0.006), rather than less thorough periodic Holter monitoring.Conclusions: Outcomes of AF ablation studies involving pulmonary vein isolation are not affected by the technologies used to produce PVI. Neither do adjunctive lesion sets change the outcome. Achieving high success rates in these studies appears to be dependent more on patient mix and on the thoroughness of AF detection protocols. This should be carefully considered when quoting success rates of AF ablation procedures which are derived from such studies.

Journal article

Ahmad Y, Götberg M, Cook C, Howard J, Malik I, Mikhail G, Frame A, Petraco R, Rajkumar C, Demir O, Iglesias JF, Bhindi R, Koul S, Hadjiloizou N, Gerber R, Ramrakha P, Ruparelia N, Sutaria N, Kanaganayagam G, Ariff B, Fertleman M, Anderson J, Chukwuemeka A, Francis D, Mayet J, Serruys P, Davies J, Sen Set al., 2018, Coronary hemodynamics in patients with severe aortic stenosis and coronary Artery disease undergoing transcatheter aortic valve replacement: implications for clinical indices of coronary stenosis severity, JACC: Cardiovascular Interventions, Vol: 11, Pages: 2019-2031, ISSN: 1936-8798

OBJECTIVES: In this study, a systematic analysis was conducted of phasic intracoronary pressure and flow velocity in patients with severe aortic stenosis (AS) and coronary artery disease, undergoing transcatheter aortic valve replacement (TAVR), to determine how AS affects 1) phasic coronary flow; 2) hyperemic coronary flow; and 3) the most common clinically used indices of coronary stenosis severity, instantaneous wave-free ratio and fractional flow reserve. BACKGROUND: A significant proportion of patients with severe aortic stenosis (AS) have concomitant coronary artery disease. The effect of the valve on coronary pressure, flow, and the established invasive clinical indices of stenosis severity have not been studied. METHODS: Twenty-eight patients (30 lesions, 50.0% men, mean age 82.1 ± 6.5 years) with severe AS and coronary artery disease were included. Intracoronary pressure and flow assessments were performed at rest and during hyperemia immediately before and after TAVR. RESULTS: Flow during the wave-free period of diastole did not change post-TAVR (29.78 ± 14.9 cm/s vs. 30.81 ± 19.6 cm/s, p = 0.64). Whole-cycle hyperemic flow increased significantly post-TAVR (33.44 ± 13.4 cm/s pre-TAVR vs. 40.33 ± 17.4 cm/s post-TAVR, p = 0.006); this was secondary to significant increases in systolic hyperemic flow post-TAVR (27.67 ± 12.1 cm/s pre-TAVR vs. 34.15 ± 17.5 cm/s post-TAVR, p = 0.02). Instantaneous wave-free ratio values did not change post-TAVR (0.88 ± 0.09 pre-TAVR vs. 0.88 ± 0.09 post-TAVR, p = 0.73), whereas fractional flow reserve decreased significantly post-TAVR (0.87 ± 0.08 pre-TAVR vs. 0.85 ± 0.09 post-TAVR, p = 0.001). CONCLUSIONS: Systolic and hyperemic coronary flow increased significantly post-TAVR; consequently, hyperemic indices that include systole underestimated coronary stenosis severity in patients with severe AS. Flow during the wave-free per

Journal article

Ahmad Y, Gotberg M, Cook C, Howard J, Malik I, Mikhail G, Frame A, Petraco R, Rajkumar C, Demir O, Iglesias JF, Bhindi R, Koul S, Hadjiloizou N, Gerber R, Ramrakha P, Ruparelia N, Sutaria N, Kanaganayagam G, Ariff B, Fertleman M, Anderson J, Chukwuemeka A, Francis D, Mayet J, Serruys P, Davies J, Sen Set al., 2018, Coronary haemodynamics in patients with severe aortic stenosis and coronary artery disease undergoing Transcatheter Aortic Valve Replacement: implications for clinical indices of coronary stenosis severity, JACC: Cardiovascular Interventions, Vol: 11, Pages: 2019-2031, ISSN: 1936-8798

Objectives In this study, a systematic analysis was conducted of phasic intracoronary pressure and flow velocity in patients with severe aortic stenosis (AS) and coronary artery disease, undergoing transcatheter aortic valve replacement (TAVR), to determine how AS affects 1) phasic coronary flow; 2) hyperemic coronary flow; and 3) the most common clinically used indices of coronary stenosis severity, instantaneous wave-free ratio and fractional flow reserve.Background A significant proportion of patients with severe aortic stenosis (AS) have concomitant coronary artery disease. The effect of the valve on coronary pressure, flow, and the established invasive clinical indices of stenosis severity have not been studied.Methods Twenty-eight patients (30 lesions, 50.0% men, mean age 82.1 ± 6.5 years) with severe AS and coronary artery disease were included. Intracoronary pressure and flow assessments were performed at rest and during hyperemia immediately before and after TAVR.Results Flow during the wave-free period of diastole did not change post-TAVR (29.78 ± 14.9 cm/s vs. 30.81 ± 19.6 cm/s, p = 0.64). Whole-cycle hyperemic flow increased significantly post-TAVR (33.44 ± 13.4 cm/s pre-TAVR vs. 40.33 ± 17.4 cm/s post-TAVR, p = 0.006); this was secondary to significant increases in systolic hyperemic flow post-TAVR (27.67 ± 12.1 cm/s pre-TAVR vs. 34.15 ± 17.5 cm/s post-TAVR, p = 0.02). Instantaneous wave-free ratio values did not change post-TAVR (0.88 ± 0.09 pre-TAVR vs. 0.88 ± 0.09 post-TAVR, p = 0.73), whereas fractional flow reserve decreased significantly post-TAVR (0.87 ± 0.08 pre-TAVR vs. 0.85 ± 0.09 post-TAVR, p = 0.001).Conclusions Systolic and hyperemic coronary flow increased significantly post-TAVR; consequently, hyperemic indices that include systole underestimated coronary stenosis severity in patients with severe AS. Flow during the wave-free period of diastole did not change pos

Journal article

Ahmad Y, Howard J, Arnold A, Shun-Shin MJ, Cook C, Francis D, Sen Set al., 2018, Reply: Assessing the quality of evidence supporting patent foramen ovale closure over medical therapy after cryptogenic stroke, European Heart Journal, Vol: 39, Pages: 3620-3620, ISSN: 1522-9645

This commentary refers to ‘Assessing the quality of evidence supporting patent foramen ovale closure over medical therapy after cryptogenic stroke’, by W.F. McIntyre et al., doi:10.1093/eurheartj/ehy496.

Journal article

Keene D, Arnold A, Shun-Shin MJ, Howard JP, Sohaib SA, Moore P, Tanner M, Quereshi N, Muthumala A, Chandresekeran B, Foley P, Leyva F, Adhya S, Falaschetti E, Tsang H, Vijayaraman P, Cleland JGF, Stegemann B, Francis DP, Whinnett ZIet al., 2018, Rationale and design of the randomized multicentre His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) trial, ESC Heart Failure, Vol: 5, Pages: 965-976, ISSN: 2055-5822

AIMS: In patients with heart failure and a pathologically prolonged PR interval, left ventricular (LV) filling can be improved by shortening atrioventricular delay using His-bundle pacing. His-bundle pacing delivers physiological ventricular activation and has been shown to improve acute haemodynamic function in this group of patients. In the HOPE-HF (His Optimized Pacing Evaluated for Heart Failure) trial, we are investigating whether these acute haemodynamic improvements translate into improvements in exercise capacity and heart failure symptoms. METHODS AND RESULTS: This multicentre, double-blind, randomized, crossover study aims to randomize 160 patients with PR prolongation (≥200 ms), LV impairment (EF ≤ 40%), and either narrow QRS (≤140 ms) or right bundle branch block. All patients receive a cardiac device with leads positioned in the right atrium and the His bundle. Eligible patients also receive a defibrillator lead. Those not eligible for implantable cardioverter defibrillator have a backup pacing lead positioned in an LV branch of the coronary sinus. Patients are allocated in random order to 6 months of (i) haemodynamically optimized dual chamber His-bundle pacing and (ii) backup pacing only, using the non-His ventricular lead. The primary endpoint is change in exercise capacity assessed by peak oxygen uptake. Secondary endpoints include change in ejection fraction, quality of life scores, B-type natriuretic peptide, daily patient activity levels, and safety and feasibility assessments of His-bundle pacing. CONCLUSIONS: Hope-HF aims to determine whether correcting PR prolongation in patients with heart failure and narrow QRS or right bundle branch block using haemodynamically optimized dual chamber His-bundle pacing improves exercise capacity and symptoms. We aim to complete recruitment by the end of 2018 and report in 2020.

Journal article

Cook C, Ahmad Y, Howard J, Shun-Shin M, Sethi A, Clesham G, Tang K, Nijjer S, Kelly P, Davies J, Malik I, Kaprielian R, Mikhail G, Petraco R, Warisawa T, Al-Janabi F, Karamasis G, Gamma R, Al-Lamee R, Keeble T, Mayet J, Sen S, Francis D, Davies Jet al., 2018, Predicting angina-limited exercise capacity using coronary physiology, 30th Annual Symposium on Transcatheter Cardiovascular Therapeutics (TCT), Publisher: ELSEVIER SCIENCE INC, Pages: B42-B42, ISSN: 0735-1097

Conference paper

Ahmad Y, Gotberg M, Cook C, Howard J, Malik I, Mikhail G, Francis D, Mayet J, Davies J, Sen Set al., 2018, Coronary pressure and flow in patients with severe aortic stenosis and coronary artery disease undergoing TAVI: implications for clinical indices of coronary stenosis severity, 30th Annual Symposium on Transcatheter Cardiovascular Therapeutics (TCT), Publisher: ELSEVIER SCIENCE INC, Pages: B4-B4, ISSN: 0735-1097

Conference paper

Cook CM, Ahmad Y, Howard JP, Shun-Shin MJ, Sethi A, Clesham GJ, Tang KH, Nijjer SS, Kelly PA, Davies JR, Malik IS, Kaprielian R, Mikhail G, Petraco R, Al-Janabi F, Karamasis GV, Mohdnazri S, Gamma R, Al-Lamee R, Keeble TR, Mayet J, Sen S, Francis DP, Davies JEet al., 2018, Impact of percutaneous revascularization on exercise hemodynamics in patients with stable coronary disease, Journal of the American College of Cardiology, Vol: 72, Pages: 970-983, ISSN: 0735-1097

BACKGROUND: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD). OBJECTIVES: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD. METHODS: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles. RESULTS: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001). CONCLUSIONS: In patients with SCD and severe single-vessel stenosis, objective physiological

Journal article

Kyriacou A, Rajkumar CA, Pabari P, Sohaib SMA, Willson K, Peters N, Lim P, Kanagaratnam P, Hughes A, Mayet J, Whinnett Z, Francis Det al., 2018, Distinct impacts of heart rate and right atrial-pacing on left atrial mechanical activation and optimal AV delay in CRT, Pacing and Clinical Electrophysiology, Vol: 41, Pages: 959-966, ISSN: 0147-8389

AbstractBackgroundControversy exists regarding how atrial activation mode and heart rate affect optimal AV delay in cardiac resynchronisation therapy. We studied these questions using high‐reproducibility haemodynamic and echocardiographic measurements.Methods20 patients were hemodynamically optimized using non‐invasive beat‐to‐beat blood pressure at rest (62±11 bpm), during exercise (80±6 bpm) and at 3 atrially‐paced rates: 5, 25 and 45 bpm above rest, denoted Apaced,r+5, Apaced,r+25 and Apaced,r+45 respectively. Left atrial myocardial motion and transmitral flow were timed echocardiographically.ResultsDuring atrial‐sensing, raising heart rate shortened optimal AV delay by 25±6 ms (p < 0.001). During atrial pacing, raising heart rate from Apaced,r+5 to Apaced,r+25 shortened it by 16±6 ms; Apaced,r+45 shortened it 17±6 ms further (p < 0.001).In comparison to atrial‐sensed activation, atrial pacing lengthened optimal AV delay by 76±6 ms (p < 0.0001) at rest, and at ∼20 bpm faster, by 85±7 ms (p < 0.0001), 9±4 ms more (p = 0.017). Mechanically, atrial pacing delayed left atrial contraction by 63±5 ms at rest and by 73±5 ms (i.e. by 10±5 ms more, p < 0.05) at ∼20 bpm faster.Raising atrial rate by exercise advanced left atrial contraction by 7±2 ms (p = 0.001). Raising it by atrial pacing did not (p = 0.2).ConclusionsHemodynamic optimal AV delay shortens with elevation of heart rate. It lengthens on switching from atrial‐sensed to atrial‐paced at the same rate, and echocardiography shows this sensed‐paced difference in optima results from a sensed‐paced difference in atrial electromechanical delay.The reason for the widening of the sensed‐paced difference in AV optimum may be physiological stimuli (e.g. adrenergic drive) advancing left atrial contraction during exercise but not with fast atrial pacing.

Journal article

Shun-Shin M, Arnold A, Keene D, Howard J, Sohaib A, Lim PB, Tanner M, Lefroy D, Peters N, Kanagaratnam P, Davies DW, Francis D, Whinnett Zet al., 2018, The magnitude of LV activation time reduction with His bundle pacing over biventricular pacing in LBBB predicts the incremental improvement in acute cardiac function, European-Society-of-Cardiology Congress, Publisher: OXFORD UNIV PRESS, Pages: 385-385, ISSN: 0195-668X

Conference paper

Ahmad Y, Gotberg M, Malik IS, Mikhail GW, Howard JP, Demir OM, Petraco R, Iglesias JF, Francis DP, Mayet J, Davies JER, Sen Set al., 2018, Coronary haemodynamics in patients with severe aortic stenosis and coronary artery disease undergoing TAVI: implications for clinical indices of coronary stenosis severity, European-Society-of-Cardiology Congress, Publisher: OXFORD UNIV PRESS, Pages: 22-23, ISSN: 0195-668X

Conference paper

Accad M, Francis D, 2018, Does evidence based medicine adversely affect clinical judgment?, BMJ, Vol: 362, Pages: k2799-k2799

Journal article

Al-Lamee R, Howard JP, Shun-Shin MJ, Thompson D, Dehbi H-M, Sen S, Nijjer S, Petraco R, Davies J, Keeble T, Tang K, Malik IS, Cook C, Ahmad Y, Sharp ASP, Gerber R, Baker C, Kaprielian R, Talwar S, Assomull R, Cole G, Keenan NG, Kanaganayagam G, Sehmi J, Wensel R, Harrell FE, Mayet J, Thom SA, Davies JE, Francis DPet al., 2018, Fractional flow reserve and instantaneous wave-free ratio as predictors of the placebo-controlled response to percutaneous coronary intervention in stable single-vessel coronary artery disease: physiology-stratified analysis of ORBITA, Circulation, Vol: 138, ISSN: 0009-7322

BACKGROUND : There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS : We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS : Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and

Journal article

Francis DP, Al-Lamee R, 2018, Percutaneous coronary intervention for stable angina in ORBITA Reply, LANCET, Vol: 392, Pages: 28-30, ISSN: 0140-6736

Journal article

Broyd CJ, Rigo F, Nijjer S, Sen S, Petraco R, Al-Lamee R, Foin N, Chukwuemeka A, Anderson J, Parker J, Malik IS, Mikhail GW, Francis DP, Parker K, Hughes AD, Mayet J, Davies JEet al., 2018, Regression of left ventricular hypertrophy provides an additive physiological benefit following treatment of aortic stenosis: Insights from serial coronary wave intensity analysis., Acta Physiologica, Vol: 2018, Pages: e13109-e13109, ISSN: 1748-1708

AIM: Severe aortic stenosis frequently involves the development of left ventricular hypertrophy (LVH) creating a dichotomous haemodynamic state within the coronary circulation. Whilst the increased force of ventricular contraction enhances its resultant relaxation and thus increases the distal diastolic coronary "suction" force, the presence of LVH has a potentially opposing effect on ventricular-coronary interplay. The aim of this study was to use non-invasive coronary wave intensity analysis (WIA) to separate and measure the sequential effects of outflow tract obstruction relief and then LVH regression following intervention for aortic stenosis. METHODS: Fifteen patients with unobstructed coronary arteries undergoing aortic valve intervention (11 surgical aortic valve replacement [SAVR], 4 TAVI) were successfully assessed before and after intervention, and at 6 and 12 months post-procedure. Coronary WIA was constructed from simultaneously acquired coronary flow from transthoracic echo and pressure from an oscillometric brachial cuff system. RESULTS: Immediately following intervention, a decline in the backward decompression wave (BDW) was noted (9.7 ± 5.7 vs 5.1 ± 3.6 × 103  W/m2 /s, P < 0.01). Over 12 months, LV mass index fell from 114 ± 19 to 82 ± 17 kg/m2 . Accompanying this, the BDW fraction increased to 32.8 ± 7.2% at 6 months (P = 0.01 vs post-procedure) and 34.7 ± 6.7% at 12 months (P < 0.001 vs post-procedure). CONCLUSION: In aortic stenosis, both the outflow tract gradient and the presence of LVH impact significantly on coronary haemodynamics that cannot be appreciated by examining resting coronary flow rates alone. An immediate change in coronary wave intensity occurs following intervention with further effects appreciable with hypertrophy regression. The improvement

Journal article

Jackson T, Lenarczyk R, Sterlinski M, Sokal A, Francis D, Whinnett Z, Van Heuverswyn F, Vanderheyden M, Heynens J, Stegemann B, Cornelussen R, Rinaldi CAet al., 2018, Left ventricular scar and the acute hemodynamic effects of multivein and multipolar pacing in cardiac resynchronization, IJC Heart and Vasculature, Vol: 19, Pages: 14-19, ISSN: 2352-9067

BackgroundWe sought to determine whether presence, amount and distribution of scar impacts the degree of acute hemodynamic response (AHR) with multisite pacing.Multi-vein pacing (MVP) or multipolar pacing (MPP) with a multi-electrode left ventricular (LV) lead may offer benefits over conventional biventricular pacing in patients with myocardial scar.MethodsIn this multi-center study left bundle branch block patients underwent an hemodynamic pacing study measuring LV dP/dtmax. Patients had cardiac magnetic resonance scar imaging to assess the effect of scar presence, amount and distribution on AHR.Results24 patients (QRS 171 ± 20 ms) completed the study (83% male). An ischemic etiology was present in 58% and the mean scar volume was 6.0 ± 7.0%. Overall discounting scar, MPP and MVP showed no significant AHR increase compared to an optimized “best BiV” (BestBiV) site. In a minority of patients (6/24) receiver-operator characteristic analysis of scar volume (cut off 8.48%) predicted a small AHR improvement with MPP (sensitivity 83%, specificity 94%) but not MVP. Patients with scar volume > 8.48% had a MPP-BestBiV of 3 ± 6.3% vs. −6.4 ± 7.7% for those below the cutoff. There was a significant correlation between the difference in AHR and scar volume for MPP-BestBiV (R = 0.49, p = 0.02) but not MVP-BestBiV(R = 0.111, p = 0.62). The multielectrode lead positioned in scar predicted MPP AHR improvement (p = 0.04).ConclusionsMultisite pacing with MPP and MVP shows no AHR benefit in all-comers compared to optimized BestBiV pacing. There was a minority of patients with significant scar volume in relation to the LV site that exhibited a small AHR improvement with MPP.

Journal article

Arnold AD, Shun-Shin MJ, Keene D, Howard J, Lefroy DC, Davies DW, Lim PH, Kanagaratnam P, Koa-Wing M, Wright IJ, Qureshi NA, Tanner MA, Muthumala AG, Linton N, Peters NS, Francis DP, Whinnett ZIet al., 2018, His bundle pacing can overcome left bundle branch block to produce greater improvements in acute haemodynamic function and ventricular activation than biventricular pacing, Heart Rhythm Society Scientific Sessions, Publisher: Elsevier, Pages: S40-S41, ISSN: 1547-5271

Conference paper

Kikuta Y, Cook CM, Sharp ASP, Salinas P, Kawase Y, Shiono Y, Giavarini A, Nakayama M, De Rosa S, Sen S, Nijjer SS, Al-Lamee R, Petraco R, Malik IS, Mikhail GW, Kaprielian RR, Wijntjens GWM, Mori S, Hagikura A, Mates M, Mizuno A, Hellig F, Lee K, Janssens L, Horie K, Mohdnazri S, Herrera R, Krackhardt F, Yamawaki M, Davies J, Takebayashi H, Keeble T, Haruta S, Ribichini F, Indolfi C, Mayet J, Francis DP, Piek JJ, Di Mario C, Escaned J, Matsuo H, Davies JEet al., 2018, Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease Primary Results of the International Multicenter iFR GRADIENT Registry, JACC-CARDIOVASCULAR INTERVENTIONS, Vol: 11, Pages: 757-767, ISSN: 1936-8798

ObjectivesThe authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings.BackgroundIn tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested.MethodsAngiographically intermediate tandem and/or diffuse lesions were entered into the international, multicenter iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared.ResultsMean age was 67 ± 12 years (81% male). Paired pre- and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93 ± 0.05; observed actual iFR was 0.92 ± 0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4 ± 0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (−0.18 ± 0.05 lesion/vessel; p = 0.0001) and length (−4.4 ± 1.0 mm/vessel; p < 0.0001).ConclusionsIn tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback

Journal article

Zheng SL, Roddick AJ, Aghar-Jaffar R, Shun-Shin MJ, Francis D, Oliver N, Meeran Ket al., 2018, Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis, JAMA: Journal of the American Medical Association, Vol: 319, Pages: 1580-1591, ISSN: 0098-7484

Importance The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown.Objective To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis.Data Sources MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017.Study Selection Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment.Data Extraction and Synthesis Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed.Main Outcomes and Measures The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia.Results This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], −1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, −0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, −0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, −0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11

Journal article

Rajkumar CA, Nijjer SS, Cole GD, Al-Lamee R, Francis DPet al., 2018, Moving the goalposts into unblinded territory: lessons of DEFER and FAME 2 and their implications for shifting end points in ISCHEMIA, Circulation: Cardiovascular Quality and Outcomes, Vol: 11, ISSN: 1941-7705

At its conception, a randomized controlled trial is carefully designed to detect a significant effect of an intervention on a prespecified primary end point. Each aspect of a trial is deliberately constructed to allow it to answer this principal question. From the moment the first patient is recruited, the primary end point is fixed, and all other outcomes are considered secondary.

Journal article

Khan HR, Kralj-Hans I, Haldar S, Bahrami T, Clague J, De Souza A, Francis D, Hussain W, Jarman J, Jones DG, Mediratta N, Mohiaddin R, Salukhe T, Jones S, Lord J, Murphy C, Kelly J, Markides V, Gupta D, Wong Tet al., 2018, Catheter ablation versus thoracoscopic surgical ablation in long standing persistent atrial fibrillation (CASA-AF): study protocol for a randomised controlled trial, Trials, Vol: 19, ISSN: 1745-6215

BACKGROUND: Atrial fibrillation is the commonest arrhythmia which raises the risk of heart failure, thromboembolic stroke, morbidity and death. Pharmacological treatments of this condition are focused on heart rate control, rhythm control and reduction in risk of stroke. Selective ablation of cardiac tissues resulting in isolation of areas causing atrial fibrillation is another treatment strategy which can be delivered by two minimally invasive interventions: percutaneous catheter ablation and thoracoscopic surgical ablation. The main purpose of this trial is to compare the effectiveness and safety of these two interventions. METHODS/DESIGN: Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre, randomised controlled trial within three NHS tertiary cardiovascular centres specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with symptomatic, long-standing, persistent atrial fibrillation will be randomly allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio. Pre-determined lesion sets will be delivered in each treatment arm with confirmation of appropriate conduction block. All patients will have an implantable loop recorder (ILR) inserted subcutaneously immediately following ablation to enable continuous heart rhythm monitoring for at least 12 months. The devices will be programmed to detect episodes of atrial fibrillation and atrial tachycardia ≥ 30 s in duration. The patients will be followed for 12 months, completing appropriate clinical assessments and questionnaires every 3 months. The ILR data will be wirelessly transmitted daily and evaluated every month for the duration of the follow-up. The primary endpoint in the study is freedom from atrial fibrillation and atrial tachycardia at the end of the follow-up period. DISCUSSION: The CASA-AF Trial is a National Institute for Health

Journal article

Ahmad Y, Demir O, Rajkumar CA, Howard J, Shun-Shin M, Cook C, Petraco R, Jabbour R, Arnold A, Frame A, Sutaria N, Ariff B, Kanaganayagam G, Francis D, Mayet J, Mikhail G, Malik I, Sen Set al., 2018, Optimal antiplatelet strategy after transcatheter aortic valve implantation: a meta-analysis, Open Heart, Vol: 5, ISSN: 2053-3624

Objective International guidelines recommend the use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI). The recommended duration of DAPT varies between guidelines. In this two-part study, we (1) performed a structured survey of 45 TAVI centres from around the world to determine if there is consensus among clinicians regarding antiplatelet therapy after TAVI; and then (2) performed a systematic review of all suitable studies (randomised controlled trials (RCTs) and registries) to determine if aspirin monotherapy can be used instead of DAPT.Methods A structured electronic survey regarding antiplatelet use after TAVI was completed by 45 TAVI centres across Europe, Australasia and the USA. A systematic review of TAVI RCTs and registries was then performed comparing DAPT duration and incidence of stroke, bleeding and death. A variance weighted least squared metaregression was then performed to determine the relationship of antiplatelet therapy and adverse events.Results 82.2% of centres routinely used DAPT after TAVI. Median duration was 3 months. 13.3% based their practice on guidelines. 11 781 patients (26 studies) were eligible for the metaregression. There was no benefit of DAPT over aspirin monotherapy for stroke (P=0.49), death (P=0.72) or bleeding (P=0.91).Discussion Aspirin monotherapy appears to be as safe and effective as DAPT after TAVI.

Journal article

Petraco Da Cunha R, Dehbi H-M, Howard J, Shun-Shin MJ, Sen S, Nijjer S, Mayet J, Davies JE, Francis DFet al., 2018, Effects of disease severity distribution on the performance of quantitative diagnostic methods and proposal of a novel ‘V-plot’ methodology to display accuracy values, Open Heart, Vol: 5, ISSN: 2053-3624

Background Diagnostic accuracy is widely accepted by researchers and clinicians as an optimal expression of a test’s performance. The aim of this study was to evaluate the effects of disease severity distribution on values of diagnostic accuracy as well as propose a sample-independent methodology to calculate and display accuracy of diagnostic tests.Methods and findings We evaluated the diagnostic relationship between two hypothetical methods to measure serum cholesterol (Cholrapid and Cholgold) by generating samples with statistical software and (1) keeping the numerical relationship between methods unchanged and (2) changing the distribution of cholesterol values. Metrics of categorical agreement were calculated (accuracy, sensitivity and specificity). Finally, a novel methodology to display and calculate accuracy values was presented (the V-plot of accuracies).Conclusion No single value of diagnostic accuracy can be used to describe the relationship between tests, as accuracy is a metric heavily affected by the underlying sample distribution. Our novel proposed methodology, the V-plot of accuracies, can be used as a sample-independent measure of a test performance against a reference gold standard.

Journal article

Panoulas VF, Francis DP, Ruparelia N, Malik IS, Chukwuemeka A, Sen S, Anderson J, Nihoyannopoulos P, Sutaria N, Hannan EL, Samadashvili Z, D'Errigo P, Schymik G, Mehran R, Chieffo A, Latib A, Presbitero P, Mehilli J, Petronio AS, Morice M-C, Tamburino C, Thyregod HGH, Leon M, Colombo A, Mikhail GWet al., 2018, Female-specific survival advantage from transcatheter aortic valve implantation over surgical aortic valve replacement: Meta-analysis of the gender subgroups of randomised controlled trials including 3758 patients, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 250, Pages: 66-72, ISSN: 0167-5273

Journal article

Cook CM, Jeremias A, Petraco R, Sen S, Nijjer S, Shun-Shin MJ, Ahmad Y, de Waard G, van de Hoef T, Echavarria-Pinto M, van Lavieren M, Al Lamee R, Kikuta Y, Shiono Y, Buch A, Meuwissen M, Danad I, Knaapen P, Maehara A, Koo B-K, Mintz GS, Escaned J, Stone GW, Francis DP, Mayet J, Piek JJ, van Royen N, Davies JEet al., 2017, Fractional Flow Reserve/Instantaneous Wave-Free Ratio Discordance in Angiographically Intermediate Coronary Stenoses: An Analysis Using Doppler-Derived Coronary Flow Measurements, JACC: Cardiovascular Interventions, Vol: 10, Pages: 2514-2524, ISSN: 1936-8798

ObjectivesThe study sought to determine the coronary flow characteristics of angiographically intermediate stenoses classified as discordant by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR).BackgroundDiscordance between FFR and iFR occurs in up to 20% of cases. No comparisons have been reported between the coronary flow characteristics of FFR/iFR discordant and angiographically unobstructed vessels.MethodsBaseline and hyperemic coronary flow velocity and coronary flow reserve (CFR) were compared across 5 vessel groups: FFR+/iFR+ (108 vessels, n = 91), FFR–/iFR+ (28 vessels, n = 24), FFR+/iFR– (22 vessels, n = 22), FFR–/iFR– (208 vessels, n = 154), and an unobstructed vessel group (201 vessels, n = 153), in a post hoc analysis of the largest combined pressure and Doppler flow velocity registry (IDEAL [Iberian-Dutch-English] collaborators study).ResultsFFR disagreed with iFR in 14% (50 of 366). Baseline flow velocity was similar across all 5 vessel groups, including the unobstructed vessel group (p = 0.34 for variance). In FFR+/iFR– discordants, hyperemic flow velocity and CFR were similar to both FFR–/iFR– and unobstructed groups; 37.6 (interquartile range [IQR]: 26.1 to 50.4) cm/s vs. 40.0 [IQR: 29.7 to 52.3] cm/s and 42.2 [IQR: 33.8 to 53.2] cm/s and CFR 2.36 [IQR: 1.93 to 2.81] vs. 2.41 [IQR: 1.84 to 2.94] and 2.50 [IQR: 2.11 to 3.17], respectively (p > 0.05 for all). In FFR–/iFR+ discordants, hyperemic flow velocity, and CFR were similar to the FFR+/iFR+ group; 28.2 (IQR: 20.5 to 39.7) cm/s versus 23.5 (IQR: 16.4 to 34.9) cm/s and CFR 1.44 (IQR: 1.29 to 1.85) versus 1.39 (IQR: 1.06 to 1.88), respectively (p > 0.05 for all).ConclusionsFFR/iFR disagreement was explained by differences in hyperemic coronary flow velocity. Furthermore, coronary stenoses classified as FFR+/iFR– demonstrated similar coronary flow characteristics to angiographically unobstructed vessels.

Journal article

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