Imperial College London

Dr Fu Siong Ng

Faculty of MedicineNational Heart & Lung Institute

Reader in Cardiac Electrophysiology
 
 
 
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Contact

 

+44 (0)20 7594 2735f.ng Website

 
 
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Location

 

430ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
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188 results found

Ardissino M, Morley A, Slob E, Schuermans A, Rayes B, Raisi-Estabragh Z, de Marvao A, Burgess S, Rogne T, Honigberg M, Ng FSet al., 2024, Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association, European Heart Journal, Vol: 45, Pages: 443-454, ISSN: 0195-668X

Background and AimsLow birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function.MethodsUncorrelated (r2 < .001), genome-wide significant (P < 5 × 10−8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini–Hochberg correction.ResultsLower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06–1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility.ConclusionsThe results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation.

Journal article

Ng FS, Reddy R, Ardissino M, Morley A, Schuermans A, Hill P, Williamson C, Honigberg M, de Marvao Aet al., 2024, Genetically-proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations, European Journal of Preventive Cardiology, ISSN: 2047-4873

Aims: Current guidelines advise against the use of lipid lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is inceasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL lowering, overall and through PCSK9 drug targets, on congenital malformations.Methods: Instrumental variants influencing LDL levels overall and through PCSK9-inhibitor drug targets were extracted from genome-wide association study (GWAS) summary data for LDL on 1,320,016 individuals. Instrumental variants influencing circulating PCSK9 levels (pQTLs) and liver PCSK9 gene expression levels (eQTLs) were extracted respectively from a GWAS on 10,186 individuals and from the Genotype-Tissue Expression (GTEx) project. Gene-outcome association data was extracted from the 7th release of GWAS summary data on the FinnGen cohort (n=342,499) for eight categories of congenital malformations affecting multiple systems.Results: Genetically-proxied LDL-lowering through PCSK9 was associated with higher odds of malformations affecting multiple systems (OR 2.70, 95% CI 1.30-5.63, p=0.018), the skin (OR 2.23, 95% CI 1.33–3.75, p=0.007), and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal and limb association (VACTERL) (OR 1.51, 95% CI 1.16–1.96, p=0.007). An association was also found with obstructive defects of the renal pelvis and ureter, but this association was suggestive for horizontal pleiotropy. Lower PCSK9 pQTLs were associated with the same congenital malformations. Conclusion: These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.

Journal article

Katritsis G, Kailey B, Luther V, Jamil Copley S, Koa-Wing M, Balasundram A, Malcolme-Lawes L, Qureshi N, Boon Lim P, Ng FS, Cortez Diaz N, Carpinteiro L, de Sousa J, Martin R, Das M, Murray S, Chow A, Peters NS, Whinnett Z, Linton NW, Kanagaratnam Pet al., 2024, Characterisation of Conduction System Activation in the Post-Infarct Ventricle using Ripple Mapping., Heart Rhythm

BACKGROUND: Three dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVES: We used Ripple Mapping to distinguish conduction system activation to that of adjacent myocardium, to characterise the conduction system in the post-infarct LV. METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing VT ablation. Ripple Maps were viewed from the end of the P wave to QRS onset in 1ms increments. Clusters of >3 Ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24pts (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the location of the left posterior fascicle (LPF) in 22pts (92%) and at the location of the left anterior fascicle (LAF) in 15pts (63%). The LAF was shorter (41.4 vs 68.8mm, p= 0.0005) activating for a shorter duration (40.6 vs 64.9ms, p=0.002). 14/24pts had LBBB with 11/14 (78%) having Purkinje potential associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4 (1.6 ± 0.6, p=0.039)) and an inverse correlation between breakout sites and QRS duration (p=0.0035). CONCLUSION: We applied Ripple Mapping to present a detailed electroanatomic characterisation of the conduction system in the post-infarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.

Journal article

Sau A, Ahmed A, Chen JY, Pastika L, Wright I, Li X, Handa B, Qureshi N, Koa-Wing M, Keene D, Malcolme-Lawes L, Varnava A, Linton NWF, Lim PB, Lefroy D, Kanagaratnam P, Peters NS, Whinnett Z, Ng FSet al., 2024, Machine learning-derived cycle length variability metrics predict spontaneously terminating ventricular tachycardia in implantable cardioverter defibrillator recipients, European Heart Journal: Digital Health, Vol: 5, Pages: 50-59, ISSN: 2634-3916

AimsImplantable cardioverter defibrillator (ICD) therapies have been associated with increased mortality and should be minimized when safe to do so. We hypothesized that machine learning-derived ventricular tachycardia (VT) cycle length (CL) variability metrics could be used to discriminate between sustained and spontaneously terminating VT.Methods and resultsIn this single-centre retrospective study, we analysed data from 69 VT episodes stored on ICDs from 27 patients (36 spontaneously terminating VT, 33 sustained VT). Several VT CL parameters including heart rate variability metrics were calculated. Additionally, a first order auto-regression model was fitted using the first 10 CLs. Using features derived from the first 10 CLs, a random forest classifier was used to predict VT termination. Sustained VT episodes had more stable CLs. Using data from the first 10 CLs only, there was greater CL variability in the spontaneously terminating episodes (mean of standard deviation of first 10 CLs: 20.1 ± 8.9 vs. 11.5 ± 7.8 ms, P < 0.0001). The auto-regression coefficient was significantly greater in spontaneously terminating episodes (mean auto-regression coefficient 0.39 ± 0.32 vs. 0.14 ± 0.39, P < 0.005). A random forest classifier with six features yielded an accuracy of 0.77 (95% confidence interval 0.67 to 0.87) for prediction of VT termination.ConclusionVentricular tachycardia CL variability and instability are associated with spontaneously terminating VT and can be used to predict spontaneous VT termination. Given the harmful effects of unnecessary ICD shocks, this machine learning model could be incorporated into ICD algorithms to defer therapies for episodes of VT that are likely to self-terminate.

Journal article

Koch C, Reilly-ODonnell B, Gutierrez R, Lucarelli C, Ng FS, Gorelik J, Ivanov AP, Edel JBet al., 2023, Nanopore sequencing of DNA-barcoded probes for highly multiplexed detection of microRNA, proteins and small biomarkers, Nature Nanotechnology, Vol: 18, Pages: 1483-1491, ISSN: 1748-3387

There is an unmet need to develop low-cost, rapid and highly multiplexed diagnostic technology platforms for quantitatively detecting blood biomarkers to advance clinical diagnostics beyond the single biomarker model. Here we perform nanopore sequencing of DNA-barcoded molecular probes engineered to recognize a panel of analytes. This allows for highly multiplexed and simultaneous quantitative detection of at least 40 targets, such as microRNAs, proteins and neurotransmitters, on the basis of the translocation dynamics of each probe as it passes through a nanopore. Our workflow is built around a commercially available MinION sequencing device, offering a one-hour turnaround time from sample preparation to results. We also demonstrate that the strategy can directly detect cardiovascular disease-associated microRNA from human serum without extraction or amplification. Due to the modularity of barcoded probes, the number and type of targets detected can be significantly expanded.

Journal article

Ali N, Saqi K, Arnold AD, Miyazawa AA, Keene D, Chow J-J, Little I, Peters NS, Kanagaratnam P, Qureshi N, Ng FS, Linton NWF, Lefroy DC, Francis DP, Boon Lim P, Tanner MA, Muthumala A, Agarwal G, Shun-Shin MJ, Cole GD, Whinnett ZIet al., 2023, Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics., Europace, Vol: 25

AIMS: Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit. METHODS AND RESULTS: We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1. Ventricular activation pattern, timing, and high-precision acute haemodynamic response were studied during LBBP with and without anodal capture. We recruited 21 patients with a mean age of 67 years, of whom 14 were males. We measured electrocardiogram timings and haemodynamics in all patients, and in 16, we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that RV septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration and total ventricular activation times were shorter (116 ± 12 vs. 129 ± 14 ms, P < 0.01 and 83 ± 18 vs. 90 ± 15 ms, P = 0.01). This required higher outputs (3.6 ± 1.9 vs. 0.6 ± 0.2 V, P < 0.01) but without additional haemodynamic benefit (mean difference -0.2 ± 3.8 mmHg compared with pacing without anodal capture, P = 0.2). CONCLUSION: Left bundle branch pacing with anodal capture advances RV activation by stimulating the RV septal myocardium. However, this requires higher outputs and does not improve acute haemodynamics. Aiming for anodal capture may therefore not be necessary.

Journal article

Shi X, Sau A, Li X, Patel K, Bajaj N, Varela M, Wu H, Handa B, Arnold A, Shun-Shin M, Keene D, Howard J, Whinnett Z, Peters N, Christensen K, Jensen HJ, Ng FSet al., 2023, Information theory-based direct causality measure to assess cardiac fibrillation dynamics, Journal of the Royal Society Interface, Vol: 20, ISSN: 1742-5662

Understanding the mechanism sustaining cardiac fibrillation can facilitate the personalization of treatment. Granger causality analysis can be used to determine the existence of a hierarchical fibrillation mechanism that is more amenable to ablation treatment in cardiac time-series data. Conventional Granger causality based on linear predictability may fail if the assumption is not met or given sparsely sampled, high-dimensional data. More recently developed information theory-based causality measures could potentially provide a more accurate estimate of the nonlinear coupling. However, despite their successful application to linear and nonlinear physical systems, their use is not known in the clinical field. Partial mutual information from mixed embedding (PMIME) was implemented to identify the direct coupling of cardiac electrophysiology signals. We show that PMIME requires less data and is more robust to extrinsic confounding factors. The algorithms were then extended for efficient characterization of fibrillation organization and hierarchy using clinical high-dimensional data. We show that PMIME network measures correlate well with the spatio-temporal organization of fibrillation and demonstrated that hierarchical type of fibrillation and drivers could be identified in a subset of ventricular fibrillation patients, such that regions of high hierarchy are associated with high dominant frequency.

Journal article

Chen JY, Ardissino M, Reddy RK, Mason AM, Raisi-Estabragh Z, Di Angelantonio E, Burgess S, Ng FSet al., 2023, Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study, ESC HEART FAILURE, ISSN: 2055-5822

Journal article

Stabenau HF, Sau A, Kramer DB, Peters NS, Ng FS, Waks JWet al., 2023, Limits of the spatial ventricular gradient and QRST angles in patients with normal electrocardiograms and no known cardiovascular disease stratified by age, sex, and race, JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, ISSN: 1045-3873

Journal article

Ali N, Arnold AD, Miyazawa AA, Keene D, Peters NS, Kanagaratnam P, Qureshi N, Ng FS, Linton NWF, Lefroy DC, Francis DP, Lim PB, Kellman P, Tanner MA, Muthumala A, Shun-Shin M, Whinnett ZI, Cole GDet al., 2023, Septal scar as a barrier to left bundle branch area pacing, PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY, Vol: 46, Pages: 1077-1084, ISSN: 0147-8389

Journal article

Maddalena A, Reddy R, Slob E, Griffiths J, Girling J, Ng FSet al., 2023, Maternal hypertensive traits and adverse outcome in pregnancy: a Mendelian randomization study, Journal of Hypertension, Vol: 41, Pages: 1438-1445, ISSN: 0263-6352

IntroductionHypertensive disorders of pregnancy are associated with adverse feto-maternal outcomes. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of component hypertensive indices on multiple adverse pregnancy outcomes using Mendelian randomization (MR).MethodsUncorrelated (r2<0.001) genome-wide significant (p<5x10-8) single-nucleotide polymorphisms associated with SBP, diastolic blood pressure (DBP) and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of pre-eclampsia or eclampsia, preterm birth, placental abruption and hemorrhage in early pregnancy were extracted from summary statistics of genome-wide association studies in the FinnGen cohort. Two-sample, inverse-variance weighted MR formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically-predicted hypertensive index. ResultsHigher genetically-predicted SBP associated with higher odds of pre-eclampsia or eclampsia (OR 1.81, 95% confidence interval (CI) 1.68–1.96, p=5.45x10-49), preterm birth (OR 1.09 95%CI 1.03–1.16, p=0.005) and placental abruption (OR 1.33, 95%CI 1.05–1.68, p=0.016). Higher genetically-predicted DBP was associated with pre-eclampsia or eclampsia (OR 2.54, 95%CI 2.21–2.92, p=5.35x10-40). Higher genetically-predicted PP was associated with pre-eclampsia or eclampsia (OR 1.68, 95%CI 1.47–1.92, p=1.9×10-14) and preterm birth (OR 1.18, 95%CI 1.06–1.30, p= 0.002).ConclusionThis study provides genetic evidence to support causal associations of SBP, DBP and PP on multiple adverse outcomes of pregnancy. SBP and PP were associated with the broadest range of adverse outcomes, suggesting that optimized management of blood pressure, particularly SBP, is a key priority to improve feto-maternal health.

Journal article

Sau A, Kapadia S, Al-Aidarous S, Howard J, Sohaib A, Sikkel MB, Arnold A, Waks JW, Kramer DB, Peters NS, Ng FSet al., 2023, Temporal trends and lesion sets for persistent atrial fibrillation ablation: a meta-analysis with trial sequential analysis and meta-regression, Circulation: Arrhythmia and Electrophysiology, Vol: 16, Pages: 536-545, ISSN: 1941-3084

BACKGROUND: Ablation for persistent atrial fibrillation (PsAF) has been performed for over 20 years, although success rates have remained modest. Several adjunctive lesion sets have been studied but none have become standard of practice. We sought to describe how the efficacy of ablation for PsAF has evolved in this time period with a focus on the effect of adjunctive ablation strategies. METHODS: Databases were searched for prospective studies of PsAF ablation. We performed meta-regression and trial sequential analysis. RESULTS: A total of 99 studies (15 424 patients) were included. Ablation for PsAF achieved the primary outcome (freedom of atrial fibrillation/atrial tachycardia rate at 12 months follow-up) in 48.2% (5% CI, 44.0-52.3). Meta-regression showed freedom from atrial arrhythmia at 12 months has improved over time, while procedure time and fluoroscopy time have significantly reduced. Through the use of cumulative meta-analyses and trial sequential analysis, we show that some ablation strategies may initially seem promising, but after several randomized controlled trials may be found to be ineffective. Trial sequential analysis showed that complex fractionated atrial electrogram ablation is ineffective and further study of this treatment would be futile, while posterior wall isolation currently does not have sufficient evidence for routine use in PsAF ablation. CONCLUSIONS: Overall success rates from PsAF ablation and procedure/fluoroscopy times have improved over time. However, no adjunctive lesion set, in addition to pulmonary vein isolation, has been conclusively demonstrated to be beneficial. Through the use of trial sequential analysis, we highlight the importance of adequately powered randomized controlled trials, to avoid reaching premature conclusions, before widespread adoption of novel therapies.

Journal article

Reddy R, Ardissino M, Ng FS, 2023, Type 2 diabetes and atrial fibrillation: evaluating causal and pleiotropic pathways using Mendelian randomization, Journal of the American Heart Association, Vol: 12, ISSN: 2047-9980

BackgroundObservational associations between type 2 diabetes (T2D) and atrial fibrillation (AF) have been established, but causality remains undetermined. We performed Mendelian randomization (MR) to study causal effects of genetically predicted T2D on AF risk, independent of cardiometabolic risk factors.Methods and ResultsInstrumental variables included 182 uncorrelated single nucleotide polymorphisms associated with T2D at genome‐wide significance (P <5×10−8). Genetic association estimates for cardiometabolic exposures were obtained from genome‐wide association studies including 188 577 individuals for low‐density lipoprotein‐C, 694 649 individuals for body mass index, and 757 601 for systolic blood pressure. Two‐sample, inverse‐variance weighted MR formed the primary analyses. The MR‐TRYX approach was used to dissect potential pleiotropic pathways, with multivariable MR performed to investigate cardiometabolic mediation. Genetically predicted T2D associated with increased AF liability in univariable MR (odds ratio [OR], 1.08 [95% CI, 1.02–1.13], P=0.003). Sensitivity analyses indicated potential pleiotropy, with radial MR identifying 4 outlier single nucleotide polymorphisms that were likely contributors. Phenomic scanning on MR‐base and subsequent least absolute shrinkage and selection operator regression allowed prioritization of 7 candidate traits. The outlier‐adjusted effect estimate remained consistent with the original inverse‐variance weighted estimate (OR, 1.07 [95% CI, 1.02–1.12], P=0.008). On multivariable MR, T2D remained associated with increased AF liability after adjustment for low‐density lipoprotein‐C and body mass index. Following adjustment for systolic blood pressure, the relationship between T2D and AF became nonsignificant (OR, 1.04 [95% CI, 0.95–1.13], P=0.40).ConclusionsThese data provide novel genetic evidence that while T2D likely causally associates with AF, mediation via systolic blo

Journal article

Ardissino M, Patel KHK, Rayes B, Reddy RK, Mellor GJ, Ng FSet al., 2023, Multiple anthropometric measures and proarrhythmic 12-lead ECG indices: A mendelian randomization study, PLOS MEDICINE, Vol: 20, ISSN: 1549-1277

Journal article

Sau A, Ng FS, Sau A, 2023, The emerging role of artificial intelligence-enabled electrocardiograms in healthcare, BMJ Medicine, Vol: 2, ISSN: 2754-0413

Journal article

Sau A, Pastika L, Ng FS, 2023, Atrial fibrillation phenotypes: the route to personalised care?, HEART, ISSN: 1355-6037

Journal article

Koch C, Reilley-O'Donnell B, Gutierrez R, Lucarelli C, Ng FS, Gorelik J, Ivanov AP, Edel JBet al., 2023, Novel screening platform for highly multiplexed biomarker detection, Publisher: SPRINGER, Pages: S190-S190, ISSN: 0175-7571

Conference paper

Ardissino M, Reddy R, Slob E, Griffiths J, Girling J, Ng FSet al., 2023, Maternal hemodynamic traits and adverse outcomes in pregnancy: a Mendelian randomization study, Publisher: WILEY, Pages: 125-126, ISSN: 1470-0328

Conference paper

Ardissino M, Slob EAW, Reddy RK, Morley AP, Hill P, Williamson C, de Marvao A, Ng FSet al., 2023, GENETICALLY-PROXIED LOW DENSITY LIPOPROTEIN CHOLESTEROL LOWERING VIA PCSK9-INHIBITOR DRUG TARGETS AND RISK OF CONGENITAL MALFORMATIONS, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A309-A310, ISSN: 1355-6037

Conference paper

Chow J-J, Leong KMW, Shun-Shin MJ, Ormerod JOM, Koa-Wing M, Lefroy DC, Lim PB, Linton NWF, Ng FS, Qureshi NA, Whinnett ZI, Peters NS, Francis DP, Varnava AM, Kanagaratnam Pet al., 2023, Ventricular conduction stability noninvasively identifies an arrhythmic substrate in survivors of idiopathic ventricular fibrillation, Journal of the American Heart Association, Vol: 12, Pages: 1-24, ISSN: 2047-9980

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

Journal article

Shen CP, Freed BC, Walter DP, Perry JC, Barakat AF, Elashery ARA, Shah KS, Kutty S, McGillion M, Ng FS, Khedraki R, Nayak KR, Rogers JD, Bhavnani SPet al., 2023, Convolution Neural Network Algorithm for Shockable Arrhythmia Classification Within a Digitally Connected Automated External Defibrillator, JOURNAL OF THE AMERICAN HEART ASSOCIATION, Vol: 12

Journal article

Kappadan V, Sohi A, Parlitz U, Luther S, Uzelac I, Fenton F, Peters NS, Christoph J, Ng FSet al., 2023, Optical mapping of contracting hearts, The Journal of Physiology, Vol: 601, Pages: 1353-1370, ISSN: 0022-3751

Optical mapping is a widely used tool to record and visualize the electrophysiological properties in a variety of myocardial preparations such as Langendorff-perfused isolated hearts, coronary-perfused wedge preparations, and cell culture monolayers. Motion artifact originating from the mechanical contraction of the myocardium creates a significant challenge to performing optical mapping of contracting hearts. Hence, to minimize the motion artifact, cardiac optical mapping studies are mostly performed on non-contracting hearts, where the mechanical contraction is removed using pharmacological excitation–contraction uncouplers. However, such experimental preparations eliminate the possibility of electromechanical interaction, and effects such as mechano-electric feedback cannot be studied. Recent developments in computer vision algorithms and ratiometric techniques have opened the possibility of performing optical mapping studies on isolated contracting hearts. In this review, we discuss the existing techniques and challenges of optical mapping of contracting hearts.

Journal article

Sau A, 2023, Artificial intelligence-enabled electrocardiogram to distinguish atrioventricular re-entrant tachycardia from atrioventricular nodal re-entrant tachycardia, Cardiovascular Digital Health Journal, Vol: 4, Pages: 60-67, ISSN: 2666-6936

BackgroundAccurately determining arrhythmia mechanism from a 12-lead electrocardiogram (ECG) of supraventricular tachycardia can be challenging. We hypothesized a convolutional neural network (CNN) can be trained to classify atrioventricular re-entrant tachycardia (AVRT) vs atrioventricular nodal re-entrant tachycardia (AVNRT) from the 12-lead ECG, when using findings from the invasive electrophysiology (EP) study as the gold standard.MethodsWe trained a CNN on data from 124 patients undergoing EP studies with a final diagnosis of AVRT or AVNRT. A total of 4962 5-second 12-lead ECG segments were used for training. Each case was labeled AVRT or AVNRT based on the findings of the EP study. The model performance was evaluated against a hold-out test set of 31 patients and compared to an existing manual algorithm.ResultsThe model had an accuracy of 77.4% in distinguishing between AVRT and AVNRT. The area under the receiver operating characteristic curve was 0.80. In comparison, the existing manual algorithm achieved an accuracy of 67.7% on the same test set. Saliency mapping demonstrated the network used the expected sections of the ECGs for diagnoses; these were the QRS complexes that may contain retrograde P waves.ConclusionWe describe the first neural network trained to differentiate AVRT from AVNRT. Accurate diagnosis of arrhythmia mechanism from a 12-lead ECG could aid preprocedural counseling, consent, and procedure planning. The current accuracy from our neural network is modest but may be improved with a larger training dataset.

Journal article

Ardissino M, Reddy RK, Ths JG, Girling J, Ng FSet al., 2023, EFFECT OF MATERNAL HEMODYNAMIC TRAITS ON RISK OF ADVERSE PREGNANCY OUTCOMES: A MENDELIAN RANDOMIZATION STUDY, 72nd Annual Scientific Session (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 2216-2216, ISSN: 0735-1097

Conference paper

Chen JY, Ardissino M, Reddy RK, Mason A, Burgess S, Ng FSet al., 2023, EFFECT OF SEX HORMONE BINDING GLOBULIN AND TESTOSTERONE LEVELS ON HEART FAILURE AND CMR-DERIVED LEFT VENTRICULAR PARAMETERS - A MENDELIAN RANDOMIZATION STUDY, 72nd Annual Scientific Session (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 2321-2321, ISSN: 0735-1097

Conference paper

Ardissino M, Patel K, Rayes B, Reddy RK, Ng FSet al., 2023, CAUSAL RELEVANCE OF ADIPOSITY AND HEIGHT ON ECG PHENOTYPES: A MENDELIAN RANDOMIZATION STUDY, 72nd Annual Scientific Session (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 1-1, ISSN: 0735-1097

Conference paper

Coyle C, Koutsoftidis S, Kim M-Y, Porter B, Keene D, Luther V, Handa B, Kay J, Lim E, Malcolme-Lawes L, Koa-Wing M, Lim PB, Whinnett ZI, Ng FS, Qureshi N, Peters NS, Linton NWF, Drakakis E, Kanagaratnam Pet al., 2023, Feasibility of mapping and ablating ectopy-triggering ganglionated plexus reproducibly in persistent atrial fibrillation, Journal of Interventional Cardiac Electrophysiology: an international journal of arrhythmias and pacing, ISSN: 1383-875X

BackgroundAblation of autonomic ectopy-triggering ganglionated plexuses (ET-GP) has been used to treat paroxysmal atrial fibrillation (AF). It is not known if ET-GP localisation is reproducible between different stimulators or whether ET-GP can be mapped and ablated in persistent AF. We tested the reproducibility of the left atrial ET-GP location using different high-frequency high-output stimulators in AF. In addition, we tested the feasibility of identifying ET-GP locations in persistent atrial fibrillation.MethodsNine patients undergoing clinically-indicated paroxysmal AF ablation received pacing-synchronised high-frequency stimulation (HFS), delivered in SR during the left atrial refractory period, to compare ET-GP localisation between a custom-built current-controlled stimulator (Tau20) and a voltage-controlled stimulator (Grass S88, SIU5). Two patients with persistent AF underwent cardioversion, left atrial ET-GP mapping with the Tau20 and ablation (Precision™, Tacticath™ [n = 1] or Carto™, SmartTouch™ [n = 1]). Pulmonary vein isolation (PVI) was not performed. Efficacy of ablation at ET-GP sites alone without PVI was assessed at 1 year.ResultsThe mean output to identify ET-GP was 34 mA (n = 5). Reproducibility of response to synchronised HFS was 100% (Tau20 vs Grass S88; [n = 16] [kappa = 1, SE = 0.00, 95% CI 1 to 1)][Tau20 v Tau20; [n = 13] [kappa = 1, SE = 0, 95% CI 1 to 1]). Two patients with persistent AF had 10 and 7 ET-GP sites identified requiring 6 and 3 min of radiofrequency ablation respectively to abolish ET-GP response. Both patients were free from AF for > 365 days without anti-arrhythmics.ConclusionsET-GP sites are identified at the same location by different stimulators. ET-GP ablation alone was able to prevent AF recurrence in persistent AF, and further studies would be warranted

Journal article

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

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

Journal article

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