What is next for screening for undiagnosed atrial fibrillation? Artificial intelligence may hold the key.

Atrial fibrillation (AF) is increasingly common, though often undiagnosed, leaving many people untreated and at elevated risk of ischaemic stroke. Current European guidelines do not recommend systematic screening for AF, even though a number of studies have shown that periods of serial or continuous rhythm monitoring in older people in the general population increase detection of AF and the prescription of oral anticoagulation. This article discusses the conflicting results of two contemporary landmark trials, STROKESTOP and the LOOP, which provided the first evidence on whether screening for AF confers a benefit for people in terms of clinical outcomes. The benefit and efficiency of systematic screening for AF in the general population could be optimized by targeting screening to only those at higher risk of developing AF. For this purpose, evidence is emerging that prediction models developed using artificial intelligence in routinely collected electronic health records can provide strong discriminative performance for AF and increase detection rates when combined with rhythm monitoring in a clinical study. We consider future directions for investigation in this field and how this could be best aligned to the current evidence base to target screening in people at elevated risk of stroke.

Predicting patient-level new-onset atrial fibrillation from population-based nationwide electronic health records: protocol of FIND-AF for developing a precision medicine prediction model using artificial intelligence.

INTRODUCTION: Atrial fibrillation (AF) is a major cardiovascular health problem: it is common, chronic and incurs substantial healthcare expenditure because of stroke. Oral anticoagulation reduces the risk of thromboembolic stroke in those at higher risk; but for a number of patients, stroke is the first manifestation of undetected AF. There is a rationale for the early diagnosis of AF, before the first complication occurs, but population-based screening is not recommended. Previous prediction models have been limited by their data sources and methodologies. An accurate model that uses existing routinely collected data is needed to inform clinicians of patient-level risk of AF, inform national screening policy and highlight predictors that may be amenable to primary prevention. METHODS AND ANALYSIS: We will investigate the application of a range of deep learning techniques, including an adapted convolutional neural network, recurrent neural network and Transformer, on routinely collected primary care data to create a personalised model predicting the risk of new-onset AF over a range of time periods. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the CPRD-AURUM dataset will be used for external geographical validation. Both comprise a sizeable representative population and are linked at patient-level to secondary care databases. The performance of the deep learning models will be compared against classic machine learning and traditional statistical predictive modelling methods. We will only use risk factors accessible in primary care and endow the model with the ability to update risk prediction as it is presented with new data, to make the model more useful in clinical practice. ETHICS AND DISSEMINATION: Permissions for CPRD-GOLD and CPRD-AURUM datasets were obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences. TRIAL REGISTRATION DETAILS: A systematic review to incorporate within the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT04657900).

Prescription of oral anticoagulants and antiplatelets for stroke prophylaxis in atrial fibrillation: nationwide time series ecological analysis.

AIMS: To investigate trends in the prescription of oral anticoagulants (OACs) and antiplatelet agents for atrial fibrillation (AF). METHODS AND RESULTS: Prescription data for 450 518 patients with AF from 3352 General Practices in England, was obtained from the GRASP-AF registry, 2009-2018. Annualized temporal trends for OAC and antiplatelet prescription were reported according to eligibility based on stroke risk (CHADS2 or CHA2DS2-VASc scores ≥1 or >2, respectively). From 2009 to 2018, the prevalence of AF increased from 1.6% [95% confidence interval (CI) 1.5-1.7%] to 2.4% (2.3-2.5%), and for those with AF the proportion prescribed OAC increased from 47.6% to 75.0% (P-trend < 0.001; relative risk 1.57, 95% CI 1.55-1.60) and for antiplatelet decreased from 37.4% to 9.2% (P-trend < 0.001). In early-years (2009-2013), eligible patients aged ≥80 years were less likely to be prescribed OAC than patients aged <80 years [odds ratio (OR) 0.55, 95% CI 0.51-0.59 for CHADS2≥1 in 2009] (all P-trends < 0.001). This 'OAC prescription gap' reduced over the study period (OR 0.93, 0.90-0.96 in 2018). Whilst the prescription of direct oral anticoagulant (DOAC) as a proportion of all OAC increased from 0.1% (95% CI 0.0-0.2%) in 2011 to 58.8% (58.4-59.2%) in 2018, it was inversely associated with patient age (P-trend < 0.001) and their risk of stroke. CONCLUSION: Between 2009 and 2018, in England, the use of OAC for stroke prophylaxis in AF increased, with DOAC accounting for over half of OAC uptake in 2018. Despite a reduction in the OAC-prescription gap, a new paradox exists relating to DOAC prescription for the elderly and those at higher risk of stroke.

Genetics of congenital and drug-induced long QT syndromes: current evidence and future research perspectives.

The long QT syndrome (LQTS) is a condition characterized by abnormal prolongation of the QT interval with an associated risk of ventricular arrhythmias and sudden cardiac death. Congenital forms of LQTS arise due to rare and highly penetrant mutations that segregate in a Mendelian fashion. Over the years, multiple mutations in genes encoding ion channels and ion channel binding proteins have been reported to underlie congenital LQTS. Drugs are by far the most common cause of acquired forms of LQTS. Emerging evidence suggests that drug-induced LQTS also has a significant heritable component. However, the genetic substrate underlying drug-induced LQTS is presently largely unknown. In recent years, advances in next-generation sequencing technology and molecular biology techniques have significantly enhanced our ability to identify genetic variants underlying both monogenic diseases and more complex traits. In this review, we discuss the genetic basis of congenital and drug-induced LQTS and focus on future avenues of research in the field. Ultimately, a detailed characterization of the genetic substrate underlying congenital and drug-induced LQTS will enhance risk stratification and potentially result in the development of tailored genotype-based therapies.

The use of anticoagulants in the management of atrial fibrillation among general practices in England.

OBJECTIVES: To investigate the use of oral anticoagulants (AC) and antiplatelet agents (AP) in the management of atrial fibrillation (AF) among patients in primary care in England. DESIGN: Epidemiological study. SETTING: 1857 general practices in England representing a practice population of 13.1 million registered patients. PATIENTS: 231,833 patients with a history of AF. MAIN OUTCOME MEASURES: The primary outcome was AC and AP use by CHADS2 score and age groups <30 years, 30-49 years, 50-64 years, 65-79 years and >79 years. RESULTS: 231,833 patients with a history of AF were identified, giving a prevalence among uploading practices of 1.76%. Prevalence of AF varied markedly between practices, related to differing practice age profiles. The total number of patients with AF in a practice was strongly predicted by the number of patients aged 65 years and over in the practice. 57.0% of the AF population had a CHADS2 score ≥2 and 83.7%≥1. 114,212 (49.3%) patients received AC therapy. AC uptake increased with increasing CHADS2 score up to a score of 3, but thereafter reached a plateau. Among 132 099 patients with a CHADS2 score ≥2, 72,211 (54.7%) received an AC, 14 987(11.3%) were recorded as having a contraindication or having declined AC therapy, leaving 44,901 (34.0%) not on AC therapy and without a recorded contraindication or recorded refusal. Among patients not prescribed an AC, 79.9% were prescribed an AP. The use of AC declined in the elderly (for CHADS2 ≥ 2, 47.4% of patients ≥80 years, compared with 64.5% for patients aged <80 years, p<0.001). By contrast, AP uptake was more prevalent among elderly patients. CONCLUSIONS: Over one-third of patients with AF and known risk factors who are eligible for AC do not receive them. There is a high use of AP among patients not receiving AC. Uptake of AC is particularly poor among patients aged 80 years and over.

Application of the UK NHS Improvement Anticoagulation Commissioning Support Document for 'safety indicators' in atrial fibrillation. Results of the European Action on Anticoagulation study.

INTRODUCTION: 'Safety indicators' in the anticoagulant management of atrial fibrillation (AF) are listed in the UK NHS Improvement Document, 'Anticoagulation for AF', aiming to promote quality services. Acceptable clinical event rates are not quantified in the document. OBJECTIVE: To provide clinical evaluation of the relevant safety indicators using data from a recent large European Action on Anticoagulation (EAA) study. RESULTS: 469 clinical events were recorded in 5839 outpatients in the EAA study. The safety indicators listed in the NHS Improvement Document were related to these patients with AF. The relevance of the 'safety indicators' is confirmed by the EAA study for patients starting oral anticoagulation and for those already receiving oral anticoagulation, and quantified. CONCLUSION: The EAA clinical study provides a quantitative basis for the safety indicators' in AF listed in the NHS Commissioning Support Document and emphasises the importance of the document.

Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes.

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death.

X-ray dose reduction in fluoroscopically guided electrophysiology procedures.

This study assessed the efficacy of a new dose reduction regime in fluoroscopically guided electrophysiology (EP) procedures, which included diagnostic electrophysiological investigations, radiofrequency ablation, and biventricular pacing. A modified dose regime for fluoroscopy was implemented in one of our cardiac electrophysiology laboratories. The x-ray system was programmed with a hierarchy of three fluoroscopy doses, and therefore image quality and settings. The default (lowest) dose mode was not expected to be suitable for all patient sizes or for the entirety of all procedures. Staff raised the dose level in a stepped manner as and when required to optimize the imaging requirements of the procedure. Phantom studies indicated that the low dose mode provided adequate image quality for visualizing EP catheters, while significantly lowering patient skin dose. In 52 clinical cases, questionnaires were used to assess the subjective clinical image quality. The mean image quality score for the low dose setting was rated between "adequate" and "good." The fluoroscopy dose level was raised from the lowest level for 6% of the total fluoroscopy time. Procedural Dose Area Product (DAP) meter readings were analyzed for patients prior to (n = 85) and after (n = 150) the implementation of the low dose regime and showed an overall reduction in DAP rate of 74%. The hierarchical dose regime proved to be acceptable in routine clinical practice for EP procedures, leading to significant reductions in patient doses.