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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577 results found

Keene D, Whinnett Z, Francis D, Shun-Shin M, Arnold Aet al., 2019, His bundle pacing, learning curve, procedure characteristics, safety and feasibility: insights from a large international observational study., Journal of Cardiovascular Electrophysiology, 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

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., J Am Heart Assoc, Vol: 8

Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ([Formula: see text]) and hypercapnia ([Formula: see text]) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91-0.99); the best-fitting curve to express the PG was a hyperbola ( R2≥0.98). Patients with CSR showed increased PG , [Formula: see text] (but not [Formula: see text]), and lung-to-finger circulation time, compared with patients without CSR (all P<0.05). PG was the only predictor of the daytime AHI ( R=0.56, P=0.01) and together with the [Formula: see text] also predicted the nighttime AHI ( R=0.81, P=0.0003) and the 24-hour AHI ( R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length ( R=0.82, P=0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.

Journal article

Nowbar AN, gitto M, Howard J, Francis D, Al-Lamee Ret al., 2019, Mortality from Ischaemic Heart Disease: analysis of data from the World Health Organization and coronary artery disease risk factors from NCD-RisC, Circulation: Cardiovascular Quality and Outcomes, Vol: 12, ISSN: 1941-7705

BackgroundIschemic heart disease (IHD) has been considered the top cause of mortality globally. However, countries differ in their rates and there have been changes over time.Methods and ResultsWe analyzed mortality data submitted to the World Health Organization from 2005 to 2015 by individual countries. We explored patterns in relationships with age, sex, and income and calculated age-standardized mortality rates for each country in addition to crude death rates. In 5 illustrative countries which provided detailed data, we analyzed trends of mortality from IHD and 3 noncommunicable diseases (lung cancer, stroke, and chronic lower respiratory tract diseases) and examined the simultaneous trends in important cardiovascular risk factors. Russia, United States, and Ukraine had the largest absolute numbers of deaths among the countries that provided data. Among 5 illustrative countries (United Kingdom, United States, Brazil, Kazakhstan, and Ukraine), IHD was the top cause of death, but mortality from IHD has progressively decreased from 2005 to 2015. Age-standardized IHD mortality rates per 100 000 people per year were much higher in Ukraine (324) and Kazakhstan (97) than in United States (60), Brazil (54), and the United Kingdom (46), with much less difference in other causes of death. All 5 countries showed a progressive decline in IHD mortality, with a decline in smoking and hypertension and in all cases a rise in obesity and type II diabetes mellitus.ConclusionsIHD remains the single largest cause of death in countries of all income groups. Rates are different between countries and are falling in most countries, indicating great potential for further gains. On the horizon, future improvements may become curtailed by increasing hypertension in some developing countries and more importantly global growth in obesity.

Journal article

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, Warisawa T, Al-Janabi F, Karamasis GV, Mohdnazri S, Gamma R, deWaard GA, Al-Lamee R, Keeble TR, Mayet J, Sen S, Francis DP, Davies JEet al., 2019, Association Between Physiological Stenosis Severity and Angina-Limited Exercise Time in Patients With Stable Coronary Artery Disease, JAMA CARDIOLOGY, Vol: 4, Pages: 569-574, ISSN: 2380-6583

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, 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

Sau A, Howard J, Al-Aidarous S, Ferreira-Martins J, Al-Khayatt B, Lim PB, Kanagaratnam P, Whinnett Z, Peters N, Sikkel M, Francis D, Sohaib SMAet al., Meta-analysis of randomized controlled trials of atrial fibrillation ablation with pulmonary vein isolation versus without, JACC: Clinical Electrophysiology, ISSN: 2405-5018

ObjectivesThis meta-analysis examined the ability of pulmonary vein isolation (PVI) to prevent atrial fibrillation in randomized controlled trials (RCTs) in which the patients not receiving PVI nevertheless underwent a procedure.BackgroundPVI is a commonly used procedure for the treatment of atrial fibrillation (AF), and its efficacy has usually been judged against therapy with anti-arrhythmic drugs in open-label trials. There have been several RCTs of AF ablation in which both arms received an ablation, but the difference between the treatment arms was inclusion or omission of PVI. These trials of an ablation strategy with PVI versus an ablation strategy without PVI may provide a more rigorous method for evaluating the efficacy of PVI.MethodsMedline and Cochrane databases were searched for RCTs comparing ablation including PVI with ablation excluding PVI. The primary efficacy endpoint was freedom from atrial fibrillation (AF) and atrial tachycardia at 12 months. A random-effects meta-analysis was performed using the restricted maximum likelihood estimator.ResultsOverall, 6 studies (610 patients) met inclusion criteria. AF recurrence was significantly lower with an ablation including PVI than an ablation without PVI (RR: 0.54; 95% confidence interval [CI]: 0.33 to 0.89; p 1⁄4 0.0147; I2 1⁄4 79.7%). Neither the type of AF (p 1⁄4 0.48) nor the type of non-PVI ablation (p 1⁄4 0.21) was a significant moderator of the effect size. In 3 trials the non-PVI ablation procedure was performed in both arms, whereas PVI was performed in only 1 arm. In these studies, AF recurrence was significantly lower when PVI was included (RR: 0.32; 95% CI: 0.14 to 0.73; p 1⁄4 0.007, I2 78%ConclusionIn RCTs where both arms received an ablation, and therefore an expectation amongst patients and doctors of benefit, being randomized to PVI had a striking effect, reducing AF recurrence by a half.

Journal article

Howard J, Fisher L, Shun-Shin M, Keene D, Arnold A, Ahmad Y, Cook C, Moon J, Manisty C, Whinnett Z, Cole G, Rueckert D, Francis Det al., 2019, Cardiac rhythm device identification using neural networks, JACC: Clinical Electrophysiology, Vol: 5, Pages: 576-586, ISSN: 2405-5018

BackgroundMedical staff often need to determine the model of a pacemaker or defibrillator (cardiac rhythm devices) quickly and accurately. Current approaches involve comparing a device’s X-ray appearance with a manual flow chart. We aimed to see whether a neural network could be trained to perform this task more accurately.Methods and ResultsWe extracted X-ray images of 1676 devices, comprising 45 models from 5 manufacturers. We developed a convolutional neural network to classify the images, using a training set of 1451 images. The testing set was a further 225 images, consisting of 5 examples of each model. We compared the network’s ability to identify the manufacturer of a device with those of cardiologists using a published flow-chart.The neural network was 99.6% (95% CI 97.5 to 100) accurate in identifying the manufacturer of a device from an X-ray, and 96.4% (95% CI 93.1 to 98.5) accurate in identifying the model group. Amongst 5 cardiologists using the flow-chart, median manufacturer accuracy was 72.0% (range 62.2% to 88.9%), and model group identification was not possible. The network was significantly superior to all of the cardiologists in identifying the manufacturer (p < 0.0001 against the median human; p < 0.0001 against the best human).ConclusionsA neural network can accurately identify the manufacturer and even model group of a cardiac rhythm device from an X-ray, and exceeds human performance. This system may speed up the diagnosis and treatment of patients with cardiac rhythm devices and it is publicly accessible online.

Journal article

Warisawa T, Cook CM, Howard JP, Ahmad Y, Doi S, Nakayama M, Goto S, Yakuta Y, Karube K, Shun-Shin MJ, Petraco R, Sen S, Nijjer S, Al Lamee R, Ishibashi Y, Matsuda H, Escaned J, di Mario C, Francis DP, Akashi YJ, Davies JEet al., 2019, Physiological pattern of disease assessed by pressure-wire pullback has an influence on fractional flow reserve/instantaneous wave-free ratio discordance, Circulation: Cardiovascular Interventions, Vol: 12, ISSN: 1941-7640

BACKGROUND: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in ≈20% of cases. It is unknown whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease influences discordance between FFR and iFR measurement. METHODS AND RESULTS: Three-hundred and sixty intermediate coronary lesions (345 patients; mean age, 64.4±10.3 years; 76% men) with combined FFR, iFR, and iFR pressure-wire pullback were included for analysis from an international multicenter registry. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Lesions were classified into FFR+/iFR+ (n=154; 42.7%), FFR-/iFR+ (n=38; 10.6%), FFR+/iFR- (n=41; 11.4%), and FFR-/iFR- (n=127; 35.3%) groups. The physiological pattern of disease was classified according to the iFR pullback recordings as predominantly physiologically focal (n=171; 47.5%) or predominantly physiologically diffuse (n=189; 52.5%). Median FFR and iFR were 0.80 (interquartile range, 0.75-0.85) and 0.89 (interquartile range, 0.86-0.92), respectively. FFR disagreed with iFR in 22% (79 of 360). The physiological pattern of disease was the only influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR- (58.5% [24 of 41]), and predominantly physiologically diffuse was significantly associated with FFR-/iFR+ (81.6% [31 of 38]; P<0.001 for pattern of disease between FFR+/iFR- and FFR-/iFR+ groups). CONCLUSIONS: The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

Journal article

Sharp A, Sohaib A, Shun-Shin M, Pabari P, Wilson K, Rajkumar C, Hughes A, Kanagaratnam P, Mayet J, Whinnett Z, Kyriacou A, Francis Det al., 2019, Improving haemodynamic optimization of cardiac resynchronization therapy for heart failure., Physiol Meas

Objective&#13; Optimization of cardiac resynchronization therapy using non-invasive haemodynamic parameters, produces reliable optima when performed at high atrial paced heart rates. Here we investigate whether this is a result of increased heart rate or atrial pacing itself.&#13; &#13; Approach&#13; 43 patients with cardiac resynchronization therapy underwent haemodynamic optimization of AV delay using non-invasive beat-to-beat systolic blood pressure in three states: rest (atrial-sensing, 66±11bpm), slow atrial pacing (73±12bpm), and fast atrial pacing (94±10bpm). A 20-patient subset underwent a fourth optimization, during exercise (80±11bpm). &#13; &#13; Main results&#13; Intraclass correlation coefficient (ICC, quantifying information content mean ±SE) was 0.20±0.02 for resting sensed optimization, 0.45± 0.03 for slow atrial pacing (p&lt;0.0001 versus rest-sensed), and 0.52±0.03 for fast atrial pacing (p=0.12 versus slow-paced). 78% of the increase in ICC, from sinus rhythm to fast atrial pacing, is achieved by simply atrially pacing just above sinus rate.&#13; &#13; Atrial pacing increased signal (blood pressure difference between best and worst AV delay) from 6.5±0.6 mmHg at rest to 13.3±1.1 mmHg during slow atrial pacing (p&lt;0.0001) and 17.2±1.3 mmHg during fast atrial pacing (p=0.003 versus slow atrial pacing). &#13; &#13; Atrial pacing reduced noise (average SD of systolic blood pressure measurements) from 4.9±0.4mmHg at rest to 4.1±0.3mmHg during slow atrial pacing (p=0.28). At faster atrial pacing the noise was 4.6±0.3mmHg (p=0.69 versus slow-paced, p=0.90 versus rest-sensed). &#13; &#13; In the exercise subgroup ICC was 0.14±0.02 (p=0.97 versus rest-sensed).&#13; &#13; Significance&#13; Atrial pacing, rather than the increase in heart rate, contributes to ~80% of the observed in

Journal article

Seligman H, Shun-Shin M, Vasireddy A, Cook C, Ahmad Y, Howard J, Sen S, Al-Lamee R, Nijjer S, Chamie D, Davies J, Mayet J, Francis D, Petraco Ret al., 2019, Fractional flow reserve derived from microcatheters versus standard pressure wires: a stenosis-level meta-analysis, Open Heart, Vol: 6, ISSN: 2053-3624

Aims: To determine the agreement between sensor-tipped microcatheter (MC) and pressure wire (PW) derived Fractional Flow Reserve (FFR). Methods and results: Studies comparing FFR obtained from MC (FFRMC, Navvus Microcatheter System, ACIST Medical Systems, Minnesota, USA) versus standard PW (FFRPW) were identified and a meta-analysis of numerical and categorical agreement was performed. The relative levels of drift and device failure of MC and PW systems from each study were assessed. Six studies with 440 lesions (413 patients) were included. The mean overall bias between FFRMC and FFRPW was -0.029 (FFRMC lower). Bias and variance were greater for lesions with lower FFRPW (p <0.001). Using a cut-off of 0.80, 18% of lesions were re-classified by FFRMC versus FFRPW (with 15% being false-positives). The difference in reported drift between FFRPW and FFRMC was small. Device failure was more common with MC than PW (7.1% versus 2%). Conclusion: FFRMC systematically overestimates lesion severity, with increased bias in more severe lesions. Using FFRMC changes revascularisation guidance in approximately 1 out of every 5 cases. Pressure wire drift was similar between systems. Device failure was higher with MC.

Journal article

Rajkumar CA, Suh WM, Francis DP, 2019, Upcoding of clinical information to meet appropriate use criteria for percutaneous coronary intervention, Circulation: Cardiovascular Quality and Outcomes, Vol: 12, Pages: e005025-e005025, ISSN: 1941-7705

Journal article

Kaura A, Panoulas V, Glampson B, Davies J, Woods K, Mulla A, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Kharbanda R, Lord GM, Melikian N, Patel R, Perera D, Shah A, Francis D, Mayet Jet al., 2019, UNEXPECTED INVERTED U-SHAPED RELATIONSHIP BETWEEN TROPONIN LEVEL AND MORTALITY EXPLAINED BY REVASCULARIZATION IN BOTH PATIENTS WITH AND WITHOUT ACUTE CORONARY SYNDROME (TROP-RISK STUDY), 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 1086-1086, ISSN: 0735-1097

Conference paper

Kaura A, Hartley A, Panoulas V, Benjamin G, Davies J, Woods K, Mulla A, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, Kharbanda R, Lord GM, Melikian N, Patel R, Perera D, Shah A, Francis D, Koenig W, Mayet J, Khamis Ret al., 2019, HSCRP PREDICTS MORTALITY BEYOND TROPONIN IN 102,337 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME IN THE UK NATIONAL INSTITUTE FOR HEALTH RESEARCH CRP-RISK STUDY, 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 10-10, ISSN: 0735-1097

Conference paper

Shun-Shin MJ, Leong KMW, Ng FS, Linton NWF, Whinnett ZI, Koa-Wing M, Qureshi N, Lefroy DC, Harding SE, Lim PB, Peters NS, Francis DP, Varnava AM, Kanagaratnam Pet al., 2019, Ventricular conduction stability test: a method to identify and quantify changes in whole heart activation patterns during physiological stress, EP-Europace, ISSN: 1099-5129

AIMS: Abnormal rate adaptation of the action potential is proarrhythmic but is difficult to measure with current electro-anatomical mapping techniques. We developed a method to rapidly quantify spatial discordance in whole heart activation in response to rate cycle length changes. We test the hypothesis that patients with underlying channelopathies or history of aborted sudden cardiac death (SCD) have a reduced capacity to maintain uniform activation following exercise. METHODS AND RESULTS: Electrocardiographical imaging (ECGI) reconstructs >1200 electrograms (EGMs) over the ventricles from a single beat, providing epicardial whole heart activation maps. Thirty-one individuals [11 SCD survivors; 10 Brugada syndrome (BrS) without SCD; and 10 controls] with structurally normal hearts underwent ECGI vest recordings following exercise treadmill. For each patient, we calculated the relative change in EGM local activation times (LATs) between a baseline and post-exertion phase using custom written software. A ventricular conduction stability (V-CoS) score calculated to indicate the percentage of ventricle that showed no significant change in relative LAT (<10 ms). A lower score reflected greater conduction heterogeneity. Mean variability (standard deviation) of V-CoS score over 10 consecutive beats was small (0.9 ± 0.5%), with good inter-operator reproducibility of V-CoS scores. Sudden cardiac death survivors, compared to BrS and controls, had the lowest V-CoS scores post-exertion (P = 0.011) but were no different at baseline (P = 0.50). CONCLUSION: We present a method to rapidly quantify changes in global activation which provides a measure of conduction heterogeneity and proof of concept by demonstrating SCD survivors have a reduced capacity to maintain uniform activation following exercise.

Journal article

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, 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

Arnold A, Keene D, Howard J, Shun-Shin M, Whinnett Z, Francis Det al., Quantification of electro-mechanical coupling to prevent inappropriate implantable cardioverter defibrillator shocks, JACC: Clinical Electrophysiology, ISSN: 2405-500X

Objective To test specialised processing of laser Doppler signals for discriminating ventricular fibrillation(VF) from common causes of inappropriate therapies.BackgroundInappropriate ICD therapies remain a clinically important problem associated with morbidity and mortality.Tissue perfusion biomarkers, to assist automated diagnosis of VF, suffer the vulnerability of sometimes mistaking artefact and random noise for perfusion, which could lead to shocks being inappropriately withheld. MethodsWe developed a novel processing algorithm that combines electrogram data and laser Doppler perfusion monitoring, as a method for assessing circulatory status. We recruited 50 patients undergoing VF induction during ICD implantation. We recorded non-invasive laser Doppler and continuous electrograms, during both sinus-rhythm and VF. For each patient we simulated two additional scenarios that may lead to inappropriate shocks: ventricular-lead fracture and T-wave oversensing. We analysed the laser Doppler using three methods for reducing noise: (i)Running Mean, (ii)Oscillatory Height, (iii)a novel quantification of Electro-Mechanical coupling which gates laser Doppler against electrograms. We additionally tested the algorithm during exercise induced sinus tachycardia.ResultsOnly the Electro-mechanical coupling algorithm found a clear perfusion cut-off between sinus rhythm and VF (sensitivity and specificity 100%). Sensitivity and specificity remained 100% during simulated lead fracture and electrogram oversensing. (AUC: Running Mean 0.91, Oscillatory Height 0.86, Electro-Mechanical Coupling 1.00). Sinus tachycardia did not cause false positives.ConclusionsQuantifying the coupling between electrical and perfusion signals increases reliability of discrimination between VF and artefacts that ICDs may interpret as VF. Incorporating such methods into future ICDs may safely permit reductions of inappropriate shocks.

Journal article

Francis DP, Nallamothu BK, 2019, PCI guided by fractional flow reserve at 5 years, New England Journal of Medicine, Vol: 380, Pages: 103-103, ISSN: 0028-4793

Journal article

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

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

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

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 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

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, 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

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

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, 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

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