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Background Atrial fibrillation (AF) is associated with atrial septal defects (ASDs), but the mechanism of arrhythmia in these patients is poorly understood. We hypothesised that right-sided atrial ectopy may predominate in this cohort. Here, we aimed to localise the origin of spontaneous and provoked atrial ectopy in ASD patients. Methods Following invasive calibration of P-wave axes, 24-h Holter monitoring was used to determine the chamber of origin of spontaneous atrial ectopy. Simultaneous electrogram recording from multiple intra-cardiac catheters was used to determine the chamber of origin of isoprenaline-provoked ectopy. Comparison was made to a group of non-congenital heart disease AF patients. Results Amongst ASD patients, a right-sided origin for spontaneous atrial ectopy was significantly more prevalent than a left-sided origin (24/30 patients with right-sided ectopy vs. 14/30 with left-sided ectopy, P = 0.015). Amongst AF patients, there was no difference in the prevalence of spontaneous right vs. left-sided ectopy. For isoprenaline-provoked ectopy, there was no significant difference in the proportions of patients with right-sided or left-sided ectopy in either group. Conclusions When spontaneous atrial ectopy occurs in ASD patients, it is significantly more prevalent from a right-sided than left-sided origin. Isoprenaline infusion did not reveal the predilection for right-sided ectopy during electrophysiology study.

Initiation of anticoagulation therapy in ischemic stroke patients is contingent on a clinical diagnosis of atrial fibrillation (AF). Results from previous studies suggest thromboembolic risk may predate clinical manifestations of AF. Early identification of this cohort of patients may allow early initiation of anticoagulation and reduce the risk of secondary stroke.This study aims to produce a substrate-based predictive model using cardiac magnetic resonance imaging (CMR) and baseline noninvasive electrocardiographic investigations to improve the identification of patients at risk of future thromboembolism.CARM-AF is a prospective, multicenter, observational cohort study. Ninety-two patients will be recruited following an embolic stroke of unknown source (ESUS) and undergo atrial CMR followed by insertion of an implantable loop recorder (ILR) as per routine clinical care within 3 months of index stroke. Remote ILR follow-up will be used to allocate patients to a study or control group determined by the presence or absence of AF as defined by ILR monitoring.Baseline data collection, noninvasive electrocardiographic data analysis, and imaging postprocessing will be performed at the time of enrollment. Primary analysis will be performed following 12 months of continuous ILR monitoring, with interim and delayed analyses performed at 6 months and 2 and 3 years, respectively.The CARM-AF Study will use atrial structural and electrocardiographic metrics to identify patients with AF, or at high risk of developing AF, who may benefit from early initiation of anticoagulation.

Many biosensors produce single-ended current outputs. Lab-on-chip applications demand parallel readout channels requiring low area current-to-digital converters. High HD2 has limited the current controlled ring oscillator’s (CCROs) adoption as a low area, single-ended converter. This work improves CCRO open loop linearity by 10 dB. A wide-bandwidth current buffer is also designed. A low area (0.0025 mm 2 ), low power ( 357 μW ), single-ended, and 1 MHz bandwidth converter suitable for array readout is presented with the measured performance.

Atrial arrhythmias are common in patients with atrial septal defects (ASD) but the effects of percutaneous closure on atrial arrhythmia prevalence is unclear. We investigated the effects of ASD device closure and the impact of age at time of closure on prevalent atrial arrythmia.Meta-analysis of studies reporting atrial arrhythmia prevalence in adult patients before and after percutaneous closure was performed. Primary outcomes were prevalence of 'all atrial arrhythmia' and atrial fibrillation alone post closure. Sub-group analysis examined the effects of closure according to age in patients;40 years, ≥40 and ≥ 60 years. 25 studies were included.Meta-analysis of all studies demonstrated no reduction in all atrial arrhythmia or atrial fibrillation prevalence post-closure (OR 0.855, 95% CI 0.672 to 1.087, P = .201 and OR 0.818, 95% CI 0.645 to 1.038, P = .099, respectively). A weak reduction in all atrial arrhythmia and atrial fibrillation was seen in patients ≥40 years (OR 0.77, 95% CI 0.616 to 0.979, P = .032 and OR 0.760, 95% CI 0.6 to 0.964, P = .024, respectively) but not ≥60 years (OR 0.822, 95% CI 0.593 to 1.141, P = .242 and OR 0.83, 95% CI 0.598 to 1.152, P = .266, respectively). No data were available in patients40 years. This, and other limitations, prevents conclusive assessment of the effect of age on arrhythmia prevalence.Overall, percutaneous ASD closure is not associated with a reduction in atrial arrhythmia prevalence in this meta-analysis. A weak benefit is seen in patients ≥40 years of age, not present in patients ≥60 years.

Aims In the PARADIGM‐heart failure trial, sacubitril‐valsartan demonstrated a reduction in heart failure admissions and reduced all‐cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear. This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population. Methods and results This is a retrospective single‐centre review of patients switched from angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers to sacubitril‐valsartan between May 2016 and August 2018. Baseline and follow‐up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril‐valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril‐valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril‐valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD. Conclusions Sacubitril‐valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril‐valsartan.

This letter presents a low-power dynamic comparator for ultralow power applications. The prototype is designed in a 65-nm CMOS process with a supply voltage of 1 V and is compared against the widely used double tail latch comparator in terms of power consumption and input referred rms noise. The addition of cross-coupled devices to the input differential pair prevents the comparator internal nodes from fully discharging to ground in contrast to the conventional architecture. This reduces the power consumption while achieving similar noise levels. Measurements demonstrate that the proposed comparator achieves an input referred rms noise voltage of 220 $\mu \text{V}$ against 210 $\mu \text{V}$ for the conventional comparator with a 30% reduction in power. The proposed circuit consumes 0.19-pJ energy per comparison.

Approximately one‐third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one‐third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.

This paper proposes a method to compensate for sampling errors in ADCs when a noisy digital phase locked-loop (DPLL) is used as the clock source. MATLAB Simulink models are used to create a time domain DPLL model with accurate Phase Noise. Time-to-digital converter (TDC) of the locked DPLL provides an estimate of jitter which is used with an analog differentiator to provide an estimate of the ADC sampling error. An improved compensation allows the ADC effective number of bits at high frequency to be improved from 2 bits to 6 bits.

Aims: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. Methods: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. Results: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p

This paper presents behavioural modelling and analysis of Error Feedback (EF) SAR ADCs. The capacitor array model proposed here is based in charge equations, which allows accurate modelling of the feedback in EF-SARs. It also introduces models for the feedback amplifier, including offset, non-linear gain, thermal and flicker noise, as well as sampled kT/C noise for switches and reference noise. The proposed models are implemented and validated in Matlab¯ Simulink¯, showing results with accuracy comparable to transistor-level simulations and simulation times several orders of magnitude faster.

Aims Atrial septal defects (ASD) are associated with atrial arrhythmias, but the arrhythmia substrate in these patients is poorly defined. We hypothesized that bi-atrial fibrosis is present and that right atrial fibrosis is associated with atrial arrhythmias in ASD patients. We aimed to evaluate the extent of bi-atrial fibrosis in ASD patients and to investigate the relationships between bi-atrial fibrosis, atrial arrhythmias, shunt fraction, and age. Methods and results Patients with uncorrected secundum ASDs (n = 36; 50.4 ± 13.6 years) underwent cardiac magnetic resonance imaging with atrial late gadolinium enhancement. Comparison was made to non-congenital heart disease patients (n = 36; 60.3 ± 10.5 years) with paroxysmal atrial fibrillation (AF). Cardiac magnetic resonance parameters associated with atrial arrhythmias were identified and the relationship between bi-atrial structure, age, and shunt fraction studied. Bi-atrial fibrosis burden was greater in ASD patients than paroxysmal AF patients (20.7 ± 14% vs. 10.1 ± 8.6% and 14.8 ± 8.5% vs. 8.6 ± 6.1% for right and left atria respectively, P = 0.001 for both). In ASD patients, right atrial fibrosis burden was greater in those with than without atrial arrhythmias (33.4 ± 18.7% vs. 16.8 ± 10.3%, P = 0.034). On receiver operating characteristic analysis, a right atrial fibrosis burden of 32% had a 92% specificity and 71% sensitivity for predicting the presence of atrial arrhythmias. Neither age nor shunt fraction was associated with bi-atrial fibrosis burden. Conclusion Bi-atrial fibrosis burden is greater in ASD patients than non-congenital heart disease patients with paroxysmal AF. Right atrial fibrosis is associated with the presence of atrial arrhythmias in ASD patients. These findings highlight the importance of right atrial fibrosis to atrial arrhythmogenesis in ASD patients.

In patients with atrial fibrillation, local activation time (LAT) maps are routinely used for characterizing patient pathophysiology. The gradient of LAT maps can be used to calculate conduction velocity (CV), which directly relates to material conductivity and may provide an important measure of atrial substrate properties. Including uncertainty in CV calculations would help with interpreting the reliability of these measurements. Here, we build upon a recent insight into reduced-rank Gaussian processes (GPs) to perform probabilistic interpolation of uncertain LAT directly on human atrial manifolds. Our Gaussian process manifold interpolation (GPMI) method accounts for the topology of the atrium, and allows for calculation of statistics for predicted CV. We demonstrate our method on two clinical cases, and perform validation against a simulated ground truth. CV uncertainty depends on data density, wave propagation direction and CV magnitude. GPMI is suitable for probabilistic interpolation of other uncertain quantities on non-Euclidean manifolds. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

Stakeholders are recognised as drivers of effective conservation of cultural built heritage. Yet, as stakeholders have eclectic views in terms of their interest in, knowledge of and perceptions about the management of historic fabric, their practices are often diverse. The objective of this paper is to gain an understanding of the stakeholders' views drawn from relevant professional field on the issues that act as barriers to conservation and identify the factors that motivate built heritage management in Australia. Using a qualitative research design, two focus groups were conducted in Queensland and New South Wales with purposely selected key informants (N=14) working in the Australian heritage sector. The study presents stakeholders' interest in managing built heritage and the perceptions concerning the application of conservation policy and practices in the Australian built heritage sector, as influenced by the interdisciplinary backgrounds of participants. The paper contributes to an in-depth understanding of the conservation barriers and motivators and their implications for policy and practices in the management of Australian built heritage. The study is based on the perceptions of key informants with diverse interests and knowledge about the conservation of cultural built heritage; this makes the research analysis and implications inclusive and influential from both theoretical and practical points of view.

peer-reviewed This paper presents the design of a low-latency, highly linear current-steering DAC for use in continuous-time ADCs. A detailed analysis of equivalent unary-weighted current-steering DAC topologies in terms of mismatch, noise, and output-impedance related distortion is carried out. From this analysis, we propose a tri-level DAC design that achieves 12-bit static linearity and is suitable for implementation in a continuous-time ADC architecture. To reduce output-impedance related distortion, the design combines DAC slice impedance matching with a proposed compensation technique. By incorporating the tri-level DAC in a continuous-time ADC architecture, the technique demonstrates ~ 8dB improvement in DAC dynamic performance at high frequencies over the Nyquist-band at 100MS/s. The DAC has been verified by simulation results in TSMC 1.2V 65nm CMOS technology. PUBLISHED

Background Uncorrected atrial septal defects (ASD) are associated with atrial arrhythmias (AAs) however little is known about the bi-atrial arrhythmia substrate in these patients and optimal rhythm management strategies remain unclear. Hypothesis We hypothesised that the right atrium (RA) is important to atrial arrhythmogenesis in the ASD cohort and that 1) changes of structural and electrical remodelling and 2) arrhythmia triggers/ectopic foci would be present in the RA of ASD patients. Additionally, we hypothesised that atrial remodelling may be reversible with ASD closure and that percutaneous closure may reduce the prevalence of AAs in this cohort. Methods Comprehensive assessment of atrial arrhythmia substrate was undertaken in unclosed ASD patients and non-congenital heart disease AF control patients. Atrial late gadolinium enhancement cardiac MRI (CMR) was performed prior to ASD closure and bi-atrial fibrosis burden quantified. EP studies were carried out at ASD closure, including bi-atrial voltage mapping, ERP measurement and an isoprenaline infusion with assessment of atrial ectopy. Control patients underwent the same protocol prior to and during AF ablation. Origin of atrial ectopy was also assessed on 24 hour holter monitoring. One year post closure, ASD patients undergo repeat CMR and limited right atrial EP studies Meta-analysis to evaluate the effect of percutaneous ASD closure on the prevalence of AAs is ongoing. Results CMR Assessment of Arrhythmia Substrate; 36 ASD and 36 control patients underwent bi-atrial CMR imaging prior to procedure. Using an ‘image intensity ratio’ threshold of 1.2, both RA and LA fibrosis burden were significantly greater in ASD vs control patients (P Invasive Electrical Assessment of Arrhythmia Substrate; 18 ASD and 18 control patients underwent EP studies. RA mean voltage was significantly lower and proportion of low voltage ( Assessment of Arrhythmia Triggers; During isoprenaline infusion right sided ectopy was seen in 71% of ASD patients compared to 69% of controls (P=N/S) and bi-atrial ectopic foci were present in 43% of ASD patients and 31% of controls (P=N/S). On 24-hour holter monitoring right sided ectopy was more prevalent in ASD vs control patients (P=0.038) and ectopic burden was associated with presence of documented AAs in ASD patients (P=0.04). Effects of Closure: Two patients have had repeat CMR post closure (analysis pending). One patient had repeat EP studies 1 year post closure with a visual reduction in low voltage areas in the RA. Results of meta-analysis are pending. Conclusion This work highlights the bi-atrial nature of the atrial arrhythmia substrate in ASD patients. Further investigation is needed to evaluate the effects of closure on this substrate.