Fu Siong Ng

Imperial College London | Imperial · National Heart and Lung Institute

The electrocardiogram (ECG) can capture obesity-related cardiac changes. Artificial intelligence-enhanced ECG (AI-ECG) can identify subclinical disease. We trained an AI-ECG model to predict body mass index (BMI) from the ECG alone. Developed from 512,950 12-lead ECGs from the Beth Israel Deaconess Medical Center (BIDMC), a secondary care cohort, a...

Background Hypertension underpins significant global morbidity and mortality. Hypertension-mediated organ damage is an early indicator of serious cardiovascular sequelae, with multinational guidelines advocating aggressive treatment where detected. Artificial intelligence-enabled electrocardiogram (AI-ECG) offers novel strategies to facilitate pers...

Background With the rising incidence of Type 2 Diabetes Mellitus (T2DM) and the number of undiagnosed cases, there is an urgent need for innovative strategies for early identification of individuals at higher risk. To address this, we explore the utility of deep learning applied to 12-lead electrocardiograms (ECGs) for predicting the risk of incide...

Background Artificial intelligence-enhanced electrocardiograms (AI-ECG) can be used to predict risk of events but existing models suffer from lack of actionability, explainability and biological plausibility, and therefore are not used clinically. Purpose We sought to address these limitations of previous AI-ECG approaches by developing the AI-ECG...

Background and aims Although electrical activity of the normal human heart is well-characterized by the 12-lead electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery w...

Background Ventricular tachycardia (VT) reduces cardiac output through high heart rates, loss of atrioventricular synchrony, and loss of ventricular synchrony. We studied the contribution of each mechanism and explored the potential therapeutic utility of His bundle pacing to improve cardiac output during VT. Methods Study 1 aimed to improve the u...

Cardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart. Their development depends on multiscale morphogenetic processes and, while highly conserved across vertebrate evolution, their role in the pathophysiology of the mature heart is not fully understood. We report variant associations across the allele freq...

Background: While sex differences in right heart phenotypes have been observed, the molecular drivers remain unknown. We used common genetic variation to provide biological insights into sex differences in the structure and function of the right ventricle (RV). Methods: RV phenotypes were obtained from cardiac magnetic resonance imaging in 18,156 w...

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 increasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization t...

Background and Aims Artificial intelligence-enhanced electrocardiograms (AI-ECG) can be used to predict risk of future disease and mortality but has not yet been adopted into clinical practice. Existing model predictions lack actionability at an individual patient level, explainability and biological plausibility. We sought to address these limitat...

Background Atrial fibrillation (AF) is characterised by an irregularly irregular ventricular rhythm. However, the mechanisms by which the regularity of ventricular response is influenced by AF dynamics is yet to be understood. In AF, there is a spectrum of organisation of atrial electrical activity; from organised AF sustained by focal drivers thro...

Background Subtle, prognostically-meaningful ECG features may not be apparent to physicians. In the course of supervised machine learning (ML) training, many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. Purpose To investigate novel neural network (NN)-derived ECG features, that may...

Background Low-density lipoprotein cholesterol (LDL) lowering in pregnancy has been a controversial topic as observational studies have described an increased risk of congenital malformations. With the advent of new, long-lasting LDL lowering therapies such as silencing RNA therapies that exert clinical effects for up to six months after administra...

Aims The cardinal risk factors for cardiovascular disease in adulthood are well-recognised. In addition to these, observational studies have suggested that intrauterine and early developmental factors might play a role. However, observational associations are liable to influence by residual confounding and bias. Additionally, observational and gene...

Introduction: Previous observational studies have suggested an association between endometriosis and higher risk of cardiovascular disease. However, in the observational setting residual confounding could drive the association. Hypothesis: In this study, we hypothesize that endometriosis might be causally related to cardiac disease, structure and f...

Background Subtle prognostically-important ECG features may not be apparent to physicians. In the course of supervised machine learning (ML), many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. Hypothesis: Novel neural network (NN)-derived ECG features can predict future cardiovascular...

Aims Implantable 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. Meth...

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...

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 produce...

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 hi...

Aims Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex‐specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR). Methods and re...

Background and Aims Low 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 (...

Introduction: Measurement of the spatial ventricular gradient (SVG), spatial QRST angles, and other vectorcardiographic measures of myocardial electrical heterogeneity have emerged as novel risk stratification methods for sudden cardiac death and other adverse cardiovascular events. Prior studies of normal limits of these measurements included pri...

Background Observational 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 Results Instrumental variable...

Background: The use of left bundle branch area pacing (LBBAP) for bradycardia pacing and cardiac resynchronization is increasing, but implants are not always successful. We prospectively studied consecutive patients to determine whether septal scar contributes to implant failure. Methods: Patients scheduled for bradycardia pacing or cardiac resy...

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...

Background: Observational studies suggest that electrocardiogram (ECG) indices might be influenced by obesity and other anthropometric measures, though it is difficult to infer causal relationships based on observational data due to risk of residual confounding. We utilized mendelian randomization (MR) to explore causal relevance of multiple anthr...

Introduction: Hypertensive 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 randomiza...

Background Subtle prognostically-important ECG features may not be apparent to physicians. In the course of supervised machine learning (ML), many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. Hypothesis Novel neural network (NN)-derived ECG features can predict future cardiovascular...

Background Low-density lipoprotein cholesterol (LDL) lowering via inhibition of PCSK9 is an important cornerstone in treatment of hypercholesterolemia. There is currently no data regarding safety of PCSK9 inhibitor therapies in pregnancy. Where clinical data is not available, the Mendelian randomization (MR) paradigm can be used to predict effects...

Background Subtle, prognostically-meaningful ECG features may not be apparent to physicians. In the course of supervised machine learning training, many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. These novel neural network (NN)-derived ECG features may have clinical, phenotypic, an...

Background Subtle, prognostically-meaningful ECG features may not be apparent to physicians. In the course of supervised machine learning ML training, many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. These novel neural network (NN)-derived ECG features may have clinical, phenotypic,...

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 R...

Background: Accurately 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 E...

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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...

Background Ablation 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...

Background Observational studies suggest that reproductive factors are associated with cardiovascular disease, but these are liable to influence by residual confounding. This study explores the causal relevance of reproductive factors on cardiovascular disease in women using Mendelian randomization. Methods and Results Uncorrelated ( r ² <0.001),...

Introduction Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. A proposed solution is to advance RV activation through anodal capture, but there is uncertainty regarding the mechanism by which early RV activation is achieved (capture of rig...

Aims: Left 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 results: Patients referred fo...

Importance: Hypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias. Objective: To investigate the association of HDPs with multiple cardiovascu...

Currently, most blood tests in a clinical setting only investigate a handful of markers. A low-cost, rapid, and highly multiplexed platform for the quantitative detection of blood biomarkers has the potential to advance clinical diagnostics beyond the single biomarker paradigm. In this study, we perform nanopore sequencing of barcoded molecular pro...

There is increasing focus on applying deep learning methods to electrocardiograms (ECGs), with recent studies showing that neural networks (NNs) can predict future heart failure or atrial fibrillation from the ECG alone. However, large numbers of ECGs are needed to train NNs, and many ECGs are currently only in paper format, which are not suitable...

Introduction: The association between type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF) has been established in observational studies. This has not been replicated in genetic studies, suggesting that it might be driven by confounding. Hypothesis: Mendelian randomization (MR) uses genetic variants as instrumental variables to study casual...

Aims The response to high frequency stimulation (HFS) is used to locate putative sites of ganglionated plexuses (GPs), which are implicated in triggering atrial fibrillation (AF). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. Methods and results Sixty-three atrial sites were te...

Obesity is global health problem with an estimated three billion people worldwide being classified as overweight or obese. In addition to being associated with a range of adverse health outcomes, obesity is linked to higher risks of atrial and ventricular arrhythmias, as well as sudden cardiac death. Obesity is a multifactorial disease that often c...

Background Hypertensive disorders in pregnancy are major causes of maternal and foetal morbidity and have also been associated with long-term maternal risk of cardiovascular diseases. Whilst many retrospective and prospective cohort studies have explored this relationship, it is difficult to make causal inferences from observational studies due to...

Background Obesity is a growing global health problem that confers higher risks of atrial arrhythmias and sudden cardiac death. Despite this, the proarrhythmic substrate in obesity and its reversibility with weight loss has not been studied in-depth. Purpose To characterise the proarrhythmic substrate in obese patients, and its reversibility with...

Background Cardiovascular disease is a major cause of morbidity and mortality in women. Multiple observational studies have explored the role of female reproductive history on the risk of cardiovascular disease and suggested that factors such as high parity and early menarche are associated with higher rates of cardiovascular disease later in life....

Background: Beta-blocker (BB) and calcium channel blocker (CCB) antihypertensive drugs are commonly used in pregnancy. However, data on their relative impact on maternal and foetal outcomes are limited. We leveraged genetic variants mimicking BB and CCB antihypertensive drugs to investigate their effects on risk of pre-eclampsia, gestational diabe...

Background Accurately determining atrial arrhythmia mechanisms from a 12-lead ECG can be challenging. Given the high success rate of cavotricuspid isthmus (CTI) ablation, identification of CTI-dependent typical atrial flutter (AFL) is important for treatment decisions and procedure planning. We sought to train a convolutional neural network (CNN) t...

Background Small-scale studies have linked obesity (Ob) and metabolic ill-health with proarrhythmic repolarisation abnormalities. Whether these are observed at a population scale, modulated by individuals’ genetics, and confer higher risks of ventricular arrhythmias (VA) are not known. Methods and Results Firstly, using the UK Biobank, the associa...

Micro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumu...

Background Obesity confers higher risks of atrial arrhythmias and sudden cardiac death. Despite this, the proarrhythmic substrate in obesity and its reversibility with weight loss has not been studied in-depth. To address this, the proarrhythmic substrate in obese patients, and its reversibility with bariatric surgery, was characterised using elect...

Atrial fibrillation (AF) is the most common arrhythmia and causes significant morbidity and mortality. Early identification of AF may lead to early treatment of AF and may thus prevent AF-related strokes and complications. However, there is no current formal, cost-effective strategy for population screening for AF. In this review, we give a brief o...

Background A minority of acute coronary syndrome (ACS) cases are associated with ventricular arrhythmias (VA) and/or cardiac arrest (CA). We investigated the effect of VA/CA at the time of ACS on long‐term outcomes. Methods and Results We analyzed routine clinical data from 5 National Health Service trusts in the United Kingdom, collected between...

Background Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birt...

It remains unclear whether the association between obstructive sleep apnoea (OSA), a form of sleep-disordered breathing (SDB), and atrial fibrillation (AF) is causal or mediated by shared co-morbidities such as obesity. Existing observational studies are conflicting and limited by confounding and reverse causality. We performed Mendelian randomisat...

Background The ganglionated plexuses (GP) of the intrinsic cardiac autonomic system may play a role in atrial fibrillation (AF). Objectives We hypothesized that ablating the ectopy-triggering GPs (ET-GP) prevents AF. Methods GANGLIA-AF (NCT02487654) was a prospective, randomized, controlled, 3-centre trial. ET-GP were mapped using high frequency...

Introduction: Cardiovascular risk factors have been associated with adverse maternal and fetal outcomes, including risk of hypertensive disorders of pregnancy such as pre-eclampsia (PE) and low fetal birth weight. However, it is difficult to establish causal relationships from retrospective evidence due to risk of confounding. We applied Mendelian...

Background: Atrial fibrillation (AF) and ventricular fibrillation (VF) are complex heart rhythm disorders and may be sustained by distinct electrophysiological mechanisms. Disorganised self-perpetuating multiple-wavelets and organised rotational drivers (RDs) localising to specific areas are both possible mechanisms by which fibrillation is sustain...

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the...

Background Obesity is associated with electrophysiological remodeling, which manifests as detectable changes on the surface electrocardiogram (ECG). Objective To develop neural networks (NN) to predict body mass index (BMI) from ECGs and test the hypothesis that discrepancies between NN-predicted BMI and measured BMI are indicative of underlying a...

Micro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumu...

Purpose Left atrial (LA) rapid AF activity has been shown to co-localise with areas of successful atrial fibrillation termination by catheter ablation. We describe a technique that identifies rapid and regular activity. Methods Eight-second AF electrograms were recorded from LA regions during ablation for psAF. Local activation was annotated manua...

Engineered heart tissue (EHT) strategies, by combining cells within a hydrogel matrix, may be a novel therapy for heart failure. EHTs restore cardiac function in rodent injury models, but more data are needed in clinically relevant settings. Accordingly, an upscaled EHT patch (2.5 cm × 1.5 cm × 1.5 mm) consisting of up to 20 million human induced p...