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The purpose of this study was to assess the performance and limitations of low-voltage zones (LVZ) localization by optimized late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) scar imaging in patients with cardiac implantable electronic devices (CIEDs).Scar evaluation by LGE-CMR can assist ventricular tachycardia (VT) ablation, but challenges with electroanatomical maps coregistration and presence of imaging artefacts from CIED limit accuracy.A total of 10 patients underwent VT ablation and preprocedural LGE-CMR using wideband imaging. Scar was segmented from CMR pixel signal intensity maps using commercial software (ADAS-VT, Galgo Medical) with bespoke tools and compared with detailed electroanatomical maps (CARTO). Coregistration of EP and imaging-derived scar was performed using the aorta as a fiducial marker, and the impact of coregistration was determined by assessing intraobserver/interobserver variability and using computer simulations. Spatial smoothing was applied to assess correlation at different spatial resolutions and to reduce noise.Pixel signal intensity maps localized low-voltage zones (V 1.5 mV) with area under the receiver-operating characteristic curve: 0.82 (interquartile range [IQR]: 0.76-0.83), sensitivity 74% (IQR: 71%-77%), and specificity 78% (IQR: 73%-83%) and correlated with bipolar voltage (r = -0.57 [IQR: -0.68 to -0.42]) across patients. In simulations, small random shifts and rotations worsened LVZ localization in at least some cases. The use of the full aortic geometry ensured high reproducibility of LVZ localization (r0.86 for area under the receiver-operating characteristic curve). Spatial smoothing improved localization of LVZ. Results for LVZ with V 0.5 mV were similar.In patients with CIEDs, novel wideband CMR sequences and personalized coregistration strategies can localize LVZ with good accuracy and may assist VT ablation procedures.

Background Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear. Objective The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. Methods In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models. Results Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01–0.38] ms/%; P = .04) and increased local ARI dispersion (effect size –0.13 [–0.23 to –0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01). Conclusion Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias.

The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We identified 40 loci, 13 of which were novel, including 2 potential sex-specific loci, explaining ~11% of the trait variance. Candidate genes at novel loci were involved in myocardial structure and arrhythmogenic cardiomyopathy. Investigation of pleiotropic effects of QT interval variants using phenome-wide association analyses in 302 000 unrelated individuals from the UK Biobank and pairwise genome-wide comparisons with other ECG and cardiac imaging traits revealed genetic overlap with atrial electrical pathology. These findings provide novel insights into how abnormal myocardial repolarization and increased cardiovascular mortality may be linked.

Hemodynamically unstable ventricular tachycardia (VT) is a critical cardiac arrhythmia associated with hemodynamic compromise that requires immediate cardioversion to prevent sudden cardiac death. Since unnecessary cardioverter defibrillators shocks damage the heart and increase the risk of mortality, the discrimination between unstable (i.e. requiring cardioversion) and stable (i.e. not requiring cardioversion) VT is of paramount importance. The aim of this study was to propose and assess non-invasive identification of hemodynamically unstable VT using photoplethysmography (PPG). Seventy-five (n = 75) episodes of VT were recorded in 14 patients undergoing invasive electrophysiological studies for VT catheter ablation. Invasive continuous arterial blood pressure (ABP), PPG and electrocardiogram (ECG) were simultaneously recorded. VTs were classified as unstable if during the first 10 seconds from onset, the mean ABP (P̅VT VT) was P̅VT VT dropped more than 30% with respect to a 10 seconds baseline (i.e. ratio RABP VT VT VT ABP ABP

Background and Significance: Mechanical alternans (MA) is a biomarker associated with mortality and life-threatening arrhythmias in heart failure patients. Despite showing prognostic value, its use is limited by the requirement of measuring the continuous blood pressure (BP), which is costly and impractical. Objective: To develop and test, for the first time, non-invasive MA surrogates based on photoplethysmography (PPG). Methods: Continuous BP and PPG were recorded during clinical procedures and tests in 35 patients. MA was induced either by ventricular pacing (Group A, N = 19) or exercise (Group B, N = 16). MA was categorized as sustained or intermittent if MA episodes were observed in at least 20 or between 12 and 20 consecutive beats, respectively. Eight features characterizing the pulse morphology were derived from the PPG, and MA surrogates were evaluated. Results: Sustained alternans was observed in 9 patients (47%) from Group A, whereas intermittent alternans was observed in 13 patients (68%) from Group A and in 10 patients (63%) from Group B. The PPG-based MA surrogate showing the highest accuracy, $V^{\prime}_{M}$ , was based on the maximum of the first derivative of the PPG pulse. It detected both sustained and intermittent MA with 100% sensitivity and 100% specificity in Group A and intermittent MA with 100% sensitivity and 83% specificity in Group B. Furthermore, the magnitudes of MA and its PPG-based surrogate were linearly correlated ( R 2 = 0.83, p . Conclusion: MA can be accurately identified non-invasively through PPG analysis. This may have important clinical implications for risk stratification and remote monitoring.

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast, connective tissue components and processes for cell growth and extracellular matrix interactions were significantly enriched for QRS. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlighted potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information.

Introduction Electrocardiographic (ECG) markers of ventricular depolarisation and repolarisation are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian Randomisation (MR). Methods We performed a new genome-wide association study (GWAS) for serum calcium in >300,000 European-ancestry participants from UK-Biobank. Independent lead variants were extracted to be used as instrumental variables (figure 1). Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT and QRS intervals using an inverse-weighted method in 76,226 UK-Biobank participants with ECG data, not contributing to the serum calcium GWAS. A secondary analysis wase performed using lead variants from a calcium GWAS corrected for serum albumin. Sensitivity analyses were performed using contemporary methods to test for the presence of horizontal pleiotropy. Results 205 independent lead calcium-associated variants were used as instrumental variables for Mendelian Randomisation. A decrease of 0.1 mmol/L genetically-determined serum calcium, was associated with longer QT (3.01ms (95% CI 2.03, 3.99)) and JT (2.89ms (1.91, 3.87)) intervals. A weak association was observed for QRS duration in secondary analyses only (0.39ms (0.08, 0.69)). Results were concordant in all sensitivity analyses. Conclusion These analyses support a causal effect of serum calcium levels on ventricular repolarisation, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may therefore directly influence cardiovascular disease risk. Further research into the effects of serum calcium concentration on arrhythmogenesis is warranted and calcium variants could be considered for inclusion in genetic risk score models for predictive testing. Conflict of Interest None

Introduction Premature ventricular complexes (PVCs) are frequently detected on routine electrocardiogram monitoring during exercise. The prognostic implications of frequent or repetitive PVCs during exercise are well recognised in individuals with known heart disease, but conflicting results have been reported in individuals without known structural or ischaemic substrates. The aim of this study was to evaluate the relationship between PVC frequency during exercise and the risk of major adverse cardiovascular events (MACE) in a large cohort of ~56,000 individuals without known cardiovascular disease with long-term follow-up. Methods Approximately 77,000 individuals from the UK Biobank study participated in an exercise test using a stationary bicycle in conjunction with a 4-lead electrocardiograph device. We excluded individuals with a known cardiovascular disease or a corrupt/incomplete ECG registration. The number of PVCs in the ECG registration were counted for the remaining individuals (N=56,176) using an in-house developed deep learning algorithm. All registrations with a PVC frequency of ≧5% were reviewed manually and corrected if needed. The study endpoint was MACE, defined as either hospitalization or death due to myocardial infarction, heart failure, or ventricular arrhythmia. The association with MACE was evaluated for a range of PVC counts (up to 30 PVCs during exercise) using uni- and multivariate Cox regression analysis. In the multivariate model we adjusted for established cardiovascular risk factors, including age, sex, body mass index, smoking, diabetes, and heart rate recovery. Results The mean age of all individuals was 56,7 (± 8.2) years and men and women were relatively even numbered (47% men). The median follow-up was 10 years during which N=1,871 (3.3%) individuals reached the study endpoint. The prevalence of PVCs observed during the stress test ranged from N=16,330 (29%) individuals having ≧1 PVC, to N=1758 (x%) and N=856 (1.5%) for >10% and ≧25% PVCs, respectively. Interestingly, having at least 1 PVC was already significantly associated with adverse outcome: hazard ratio (HR) [95% CI]: 1.6 [1.4 – 1.7], p Conclusion Historically, occasional occurrence of PVCs during exercise has been considered benign. However, the results of this study may suggest that also low PVC frequencies may carry relevant prognostic information for cardiovascular disease independent of other cardiovascular risk factors. The mechanisms remain to be investigated, but may include subclinical changes in myocardial functioning. Conflict of Interest None

A murine line haploinsufficient in the cardiac sodium channel has been used to model human Brugada syndrome: a disease causing sudden cardiac death due to lethal ventricular arrhythmias. We explored the effects of cholinergic tone on electrophysiological parameters in wild-type and genetically modified, heterozygous, Scn5a+/− knockout mice. Scn5a+/− ventricular slices showed longer refractory periods than wild-type both at baseline and during isoprenaline challenge. Scn5a+/− hearts also showed lower conduction velocities and increased mean increase in delay than did littermate controls at baseline and blunted responses to isoprenaline challenge. Carbachol exerted limited effects but reversed the effects of isoprenaline with coapplication. Scn5a+/− mice showed a reduction in conduction reserve in that isoprenaline no longer increased conduction velocity, and this was not antagonized by muscarinic agonists.

Mechanical alternans (MA) is a powerful predictor of adverse prognosis in patients with heart failure and cardiomyopathy, but its use remains limited due to the need of invasive continuous arterial pressure recordings. This study aims to assess novel cardiovascular correlates of MA in the intact human heart to facilitate affordable and non-invasive detection of MA and advance our understanding of the underlying pathophysiology. Arterial pressure, respiration, and ECG were recorded in 12 subjects with healthy ventricles during voluntarily controlled breathing at different respiratory rate, before and after administration of beta-blockers. MA was induced by ventricular pacing. A total of 67 recordings lasting approximately 90 s each were analyzed. Mechanical alternans (MA) was measured in the systolic blood pressure. We studied cardiovascular correlates of MA, including maximum pressure rise during systole (dPdtmax), pulse arrival time (PAT), pulse wave interval (PI), RR interval (RRI), ECG QRS complexes and T-waves. MA was detected in 30% of the analyzed recordings. Beta-blockade significantly reduced MA prevalence (from 50 to 11%, p

International audience

BackgroundReduced heart rate (HR) increase (HRI), recovery (HRR), and higher resting HR are associated with cardiovascular (CV) disease, but causal inferences have not been deduced. We investigated causal effects of HRI, HRR, and resting HR on CV risk, all-cause mortality (ACM), atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke (IS) using Mendelian Randomization.Methods11 variants for HRI, 11 for HRR, and two sets of 46 and 414 variants for resting HR were obtained from four genome-wide association studies (GWASs) on UK Biobank. We performed a lookup on GWASs for CV risk and ACM in UK Biobank (N = 375,367, 5.4% cases and N = 393,165, 4.4% cases, respectively). For CAD, AF, and IS, we used publicly available summary statistics. We used a random-effects inverse-variance weighted (IVW) method and sensitivity analyses to estimate causality.ResultsIVW showed a nominally significant effect of HRI on CV events (odds ratio [OR] = 1.0012, P = 4.11 × 10–2) and on CAD and AF. Regarding HRR, IVW was not significant for any outcome. The IVW method indicated statistically significant associations of resting HR with AF (OR = 0.9825, P = 9.8 × 10–6), supported by all sensitivity analyses, and a nominally significant association with IS (OR = 0.9926, P = 9.82 × 10–3).ConclusionOur findings suggest no strong evidence of an association between HRI and HRR and any outcome and confirm prior work reporting a highly significant effect of resting HR on AF. Future research is required to explore HRI and HRR associations further using more powerful predictors, when available.

Supplemental Digital Content is available in the text., Background: ECG markers of ventricular depolarization and repolarization are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian randomization (MR). Methods: Independent lead variants from a newly performed genome-wide association study for serum calcium in >300 000 European-ancestry participants from UK Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT, and QRS intervals using an inverse-weighted method in 76 226 participants not contributing to the serum calcium genome-wide association study. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR pleiotropy residual sum and outlier were performed to test for the presence of horizontal pleiotropy. Results: Two hundred five independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01 ms [95% CI, 2.03 to 3.99]) and JT (2.89 ms [1.91 to 3.87]) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses. Conclusions: These analyses support a causal effect of serum calcium levels on ventricular repolarization, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may, therefore, directly influence cardiovascular disease risk.

The ideal moment to withdraw respiratory supply of patients under Mechanical Ventilation at Intensive Care Units (ICU), is not easy to be determined for clinicians. Although the Spontaneous Breathing Trial (SBT) provides a measure of the patients' readiness, there is still around 15-20% of predictive failure rate. This work is a proof of concept focused on adding new value to the prediction of the weaning outcome. Heart Rate Variability (HRV) and Cardiopulmonary Coupling (CPC) methods are evaluated as new complementary estimates to assess weaning readiness. The CPC is related to how the mechanisms regulating respiration and cardiac pumping are working simultaneously, and it is defined from HRV in combination with respiratory information. Three different techniques are used to estimate the CPC, including Time-Frequency Coherence, Dynamic Mutual Information and Orthogonal Subspace Projections. The cohort study includes 22 patients in pressure support ventilation, ready to undergo the SBT, analysed in the 24 h previous to the SBT. Of these, 13 had a successful weaning and 9 failed the SBT or needed reintubation -being both considered as failed weaning. Results illustrate that traditional variables such as heart rate, respiratory frequency, and the parameters derived from HRV do not differ in patients with successful or failed weaning. Results revealed that HRV parameters can vary considerably depending on the time at which they are measured. This fact could be attributed to circadian rhythms, having a strong influence on HRV values. On the contrary, significant statistical differences are found in the proposed CPC parameters when comparing the values of the two groups, and throughout the whole recordings. In addition, differences are greater at night, probably because patients with failed weaning might be experiencing more respiratory episodes, e.g. apneas during the night, which is directly related to a reduced respiratory sinus arrhythmia. Therefore, results suggest that the traditional measures could be used in combination with the proposed CPC biomarkers to improve weaning readiness. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

The spatial QRS-T angle (QRS-Ta), a non-invasive risk marker for arrhythmia and sudden cardiac death, captures information on the spatiotemporal dynamics of ventricular depolarization and repolarization. QRS-Ta peak is the angle between QRS and T-wave loop maximal amplitudes. We compared QRS-Ta peak with intra-cardiac unipolar electrocardiogram parameters simultaneously recorded in the right ventricle, left ventricle (LV) endocardium and LV epicardium (coronary sinus) in 10 patients with structurally normal hearts. S1S2 restitution protocols were performed by pacing from the LV at intervals decrementing from 1000 ms to the effective refractory period (ERP). Repolarization time (RT), activation time (AT) and activation-recovery interval (ARI), a standard surrogate for local action potential duration, were calculated using standard definitions. Decreasing cycle length (CL) correlated with an increase in QRS-Ta. Two phases were identified 1) A stable QRS-Ta between CLs 1000 to 400ms and 2) a subsequent rapid increase in QRS-Ta with further decrements and a small decrease in QRS-Ta just prior achieving ERP. When plotted against the pacing interval, the QRS-Ta distribution mirrored the repolarisation restitution curve. The QRS-Tangle inversely correlated with mean RT (-0.59, -0.81 / -0.34, P=0.023) and mean ARI (-0.72, -0.73 / -0.42, P

Coronary artery disease (CAD) is the main contributor to cardiovascular mortality in developed countries, making accurate diagnosis of utmost importance. We developed risk scores to assess CAD risk in a population without known cardiovascular disease by combining ECG and a genetic risk score (GRS) for CAD. We analysed data in 52,260 individuals in the UK Biobank study. ECG indices included heart rate, PR, QRS, QT and T-peak-to-T-end intervals, while we built the GRS from publicly available genome-wide association results for CAD that were derived in an independent population. In a training set (N = 39,195), the indices with the strongest CAD prognostic impact were the PR and QT intervals, and the GRS. When combined together into a Multivariate model, both the ECG markers and the GRS were independently associated with CAD. In an independent test set (N = 13,065), we then built three risk scores based on (1) ECG markers, (2) genetic data, and (3) a combination of ECG and genetic data, respectively. The hazard ratio (95% confidence interval) for CAD comparing high versus low-risk individuals was 6.5 (5.1 – 8.3),8.4 (6.4 – 10.8) and 8.4 (6.5 – 10.8) for the three risk scores, respectively. In conclusion, the inclusion of genetic markers into risk scores with ECG markers independently contributes to CAD risk prediction in a large population of individuals without known cardiovascular disease.

A bstract Background Identification of targets for ablation of post-infarction ventricular tachycardias (VTs) remains challenging, often requiring arrhythmia induction to delineate the reentrant circuit. This carries a risk for the patient and may not be feasible. Substrate mapping has emerged as a safer strategy to uncover arrhythmogenic regions. However, VT recurrence remains common. Goal To use computer simulations to assess the ability of different substrate mapping approaches to identify VT exit sites. Methods A 3D computational model of the porcine post-infarction heart was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on endocardial electrogram features and the reentry vulnerability index (RVI - a metric combining activation (AT) and repolarization timings to identify tissue susceptibility to reentry). Since scar transmurality in our model was not homogeneous, parameters derived from all signals (including dense scar regions) were used in the analysis. Potential ablation targets obtained from each electroanatomical map during pacing were compared to the exit site detected during VT mapping. Results Simulation data showed that voltage cut-offs applied to bipolar electrograms could delineate the scar, but not the VT circuit. Electrogram fractionation had the highest correlation with scar transmurality. The RVI identified regions closest to VT exit site but was outperformed by AT gradients combined with voltage cut-offs. The performance of all metrics was affected by pacing location. Conclusions Substrate mapping could provide information about the infarct, but the directional dependency on activation should be considered. Activation-repolarization metrics have utility in safely identifying VT targets, even with non-transmural scars.

Background Radiofrequency catheter ablation (CA) can reduce ventricular tachycardia (VT) burden and registry data suggests an improvement in mortality. However, there is significant heterogeneity in patient morbidity and VT phenotype. A risk prediction model derived from observational data has suggested pre-procedural left ventricular (LV) function, age and underlying ischaemic cardiomyopathy are associated with greater post-procedural mortality. Validation of proposed factors in clinical practice is required to facilitate comprehensive pre-procedural risk stratification and inform decision making. Purpose To determine whether proposed pre-procedural predictors of mortality after VTCA are valid in a UK population and explore any association with other predictors. Method Patients undergoing VTCA at a tertiary electrophysiology centre between 06/07/16 and 31/07/19 were included. Pre-specified characteristics and mortality follow-up data were analysed from electronic health records. Cox regression analysis was undertaken to determine association with mortality. Results 161 patients with mean age of 63 ±15.9 years underwent VTCA of whom 133 (83%) were male. During the follow-up period (16 months, 13-24; median, 1st-3rd quartile) 16 patients died. No deaths occured in the 27 (16%) patients with structurally normal hearts. Chronic kidney disease (CKD) stage III-IV (HR 14.73 [4.9-44.4]), LV ejection fraction Conclusion Proposed risk stratifying factors are validated in our UK centre’s experience. Additionally, CKD and baseline LVID appear to be associated with mortality in our population and warrant further study. Risk factor Hazard ratio Lower confidence interval Upper confidence interval P-value Atrial fibrillation (yes/no) 0.14 0.02 1.11 0.06 Age (years) 1.08 1.02 1.14 Abstract Figure 1: Kaplan-Meier survival curves

Funding Acknowledgements National Institute for Health Research; British Heart Foundation; and The Wellcome Trust and Engineering and Physical Sciences Research Council. Background Accurate identification of targets for catheter ablation therapy of ventricular tachycardias (VTs) in the postinfarction heart remains a significant challenge. Identification of such targets often requires VT-induction to delineate the entry/exit points of the reentrant circuit sustaining the VT. However, inducibility may not be possible due to hemodynamic instability. In this scenario, substrate ablation strategies can still be performed to uncover the arrhythmogenic substrate during sinus or paced rhythm. However, substrate mapping may fail to accurately delineate the reentrant circuit resulting in VT recurrence after the procedure. Purpose To use computer simulations to compare the ability of different electroanatomical maps constructed following typical substrate ablation strategies to identify the VT exit site. Methods An image-based computational model of the porcine post-infarction left ventricle was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on the following features extracted from electrograms computed on the endocardial surface: activation time (AT), bipolar electrogram amplitude, signal fractionation and the reentry vulnerability index (RVI - a metric combining activation and repolarization timings to identify tissue susceptibility to reentry). Potential ablation targets during substrate mapping were compared for: highest 5% AT gradient; lowest 5% bipolar signal amplitudes; areas with fragmented signals (more than one peak); and lowest 5% RVI. The minimum distance, d, between the manually identified VT exit site and the targets was measured. Results The RVI performed better than the other metrics at detecting the VT exit site (see Figure). The minimum distance between sites of lowest RVI and the exit site was 3.2mm compared to 13.1mm and 15.9mm in traditional AT and voltage maps, respectively. As the scar was not transmural, parameters derived from all electrograms (including those located on dense scar regions) were used to construct the electroanatomical maps. This improved the performance of the RVI significantly, making it more specific than the other metrics as can be seen in the Figure. Conclusions Among all metrics investigated here, the RVI identified the vulnerable region closest to VT exit site. This finding suggests that activation-repolarization metrics may improve the detection of pro-arrhythmic regions without having to induce VT. Moreover, the RVI may be particularly well suited for detecting vulnerable regions within non-transmural scars. Abstract Figure. VT and Substrate Mapping

Cardiorespiratory monitoring is crucial for the diagnosis and management of multiple conditions such as stress and sleep disorders. Therefore, the development of ambulatory systems providing continuous, comfortable, and inexpensive means for monitoring represents an important research topic. Several techniques have been proposed in the literature to derive respiratory information from the ECG signal. Ten methods to compute single-lead ECG-derived respiration (EDR) were compared under multiple conditions, including different recording systems, baseline wander, normal and abnormal breathing patterns, changes in breathing rate, noise, and artifacts. Respiratory rates, wave morphology, and cardiorespiratory information were derived from the ECG and compared to those extracted from a reference respiratory signal. Three datasets were considered for analysis, involving a total 59 482 one-min, single-lead ECG segments recorded from 156 subjects. The results indicate that the methods based on QRS slopes outperform the other methods. This result is particularly interesting since simplicity is crucial for the development of ECG-based ambulatory systems. ispartof: Scientific Reports vol:10 issue:5704 ispartof: location:England status: published

Background: Emotions can affect cardiac activity, but their impact on ventricular repolarization variability, an important parameter providing information about cardiac risk and autonomic nervous system activity, is unknown. The beat-to-beat variability of the QT interval (QTV) from the body-surface ECG is a non-invasive marker of repolarization variability, which can be decomposed into QTV related to RR variability (QTVrRRV) and QTV unrelated to RRV (QTVuRRV), with the latter thought to be a marker of intrinsic repolarization variability. Aim: To determine the effect of emotional valence (pleasant and unpleasant) on repolarization variability in healthy volunteers by means of QTV analysis. Methods: 75 individuals (24.5 ± 3.2 years, 36 females) without a history of cardiovascular disease listened to music-excerpts that were either felt as pleasant (n=6) or unpleasant (n=6). Excerpts lasted about 90 s and were presented in a random order along with silent intervals (n=6). QTV and RRV were derived from lead V4 of the ECG and the time-frequency spectrum of RRV, QTV, QTVuRRV and QTVrRRV as well as time-frequency coherence between QTV and RRV were estimated. Analysis was performed in low-frequency (LF), high frequency (HF) and total spectral bands. Results: The heart rate-corrected QT interval showed a small but significant increase from silence (median 347/ interquartile range 31 ms) to listening to music felt as unpleasant (351/30 ms) and pleasant (355/32 ms). The dynamic response of QTV to emotional valence showed a transient phase lasting about 20 s after the onset of each musical excerpt. QTV and RRV were highly correlated in both HF and LF (mean coherence ranging 0.76-0.85). QTV and QTVrRRV decreased during listening to music felt as pleasant and unpleasant with respect to silence and further decreased during listening to music felt as pleasant. QTVuRRV was small and not affected by emotional valence. Conclusions: Emotional valence, as evoked by music, has a small but significant effect on QTV and QTV related to RRV, but not on QTV unrelated to RRV. This suggests that the interaction between emotional valence and ventricular repolarization variability is mediated by cycle length dynamics and not due to intrinsic repolarization variability.

Background: ECG imaging (ECGI) has been used to guide treatment of ventricular ectopy and arrhythmias. However, the accuracy of ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia (VT) in structurally abnormal hearts remains to be fully validated. Methods: During catheter ablation of VT, simultaneous mapping was performed using electroanatomical mapping (CARTO, Biosense-Webster) and ECGI (CardioInsight, Medtronic) in 18 patients. Sites of entrainment, pace-mapping, and termination during ablation were used to define the VT site of origin (SoO). Distance between SoO and the site of earliest activation on ECGI were measured using co-registered geometries from both systems. The accuracy of ECGI versus a 12-lead surface ECG algorithm was compared. Results: A total of 29 VTs were available for comparison. Distance between SoO and sites of earliest activation in ECGI was 22.6, 13.9 to 36.2 mm (median, first to third quartile). ECGI mapped VT sites of origin onto the correct AHA segment with higher accuracy than a validated 12-lead ECG algorithm (83.3% versus 38.9%; P =0.015). Conclusions: This simultaneous assessment demonstrates that CardioInsight localizes VT circuits with sufficient accuracy to provide a region of interest for targeting mapping for ablation. Resolution is not sufficient to guide discrete radiofrequency lesion delivery via catheter ablation without concomitant use of an electroanatomical mapping system but may be sufficient for segmental ablation with radiotherapy.

Publisher's version (útgefin grein), The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease., We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.

International audience; Singing and chanting are ubiquitous across World cultures. It has been theorized that such practices are an adaptive advantage for humans because they facilitate bonding and cohesion between group members. Investigations into the effects of singing together have so far focused on the physiological effects, such as the synchronization of heart rate variability (HRV), of experienced choir singers. Here, we study whether HRV synchronizes for pairs of non-experts in different vocalizing conditions. Using time-frequency coherence (TFC) analysis, we find that HRV becomes more coupled when people make long (> 10 s) sounds synchronously compared to short sounds (< 1 s) and baseline measurements (p < 0.01). Furthermore, we find that, although most of the effect can be attributed to respiratory sinus arrhythmia, some HRV synchronization persists when the effect of respiration is removed: long notes show higher partial TFC than baseline and breathing (p < 0.05). In addition, we observe that, for most dyads, the frequency of the vocalization onsets matches that of the peaks in the TFC spectra, even though these frequencies are above the typical range of 0.04–0.4 Hz. A clear correspondence between high HRV coupling and the subjective experience of “togetherness" was not found. These results suggest that since autonomic physiological entrainment is observed for non-expert singing, it may be exploited as part of interventions in music therapy or social prescription programs for the general population.

BackgroundIdentifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The re-entry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for re-entrant arrhythmia initiation without inducing VT.ObjectiveTo provide the first assessment of RVI’s capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate.Methods18 VT ablation patients (16M, 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analysed off-line. Activation time (AT), activation-recovery interval (ARI), repolarization time (RT) were measured. Vulnerability to re-entry was mapped based on RVI and spatial distribution of AT, ARI and RT. The distance from sites identified as vulnerable to re-entry to the VT site of origin was measured, with distances 20 mm indicating accurate and inaccurate localization, respectively.ResultsThe origin of 18 VTs was identified (n=6 entrainment, n=12 pace-mapping). RVI maps included 1012, 408—2098 (median, 1st—3rd quartiles) points/patient. RVI accurately localized 72.2% VT sites of origin, with median distance equal to 5.1, 3.2—10.1 mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%, OR=0.12, P=0.035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI, and non-significantly larger for sites showing highest AT and ARI gradients.ConclusionRVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies.

Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic risk, and Tpe changes with heart rate are even stronger predictors. However, our understanding of the electrophysiological mechanisms supporting these risk factors is limited. We conducted genome-wide association studies (GWASs) for resting Tpe and Tpe response to exercise and recovery in ∼30,000 individuals, followed by replication in independent samples (∼42,000 for resting Tpe and ∼22,000 for Tpe response to exercise and recovery), all from UK Biobank. Fifteen and one single-nucleotide variants for resting Tpe and Tpe response to exercise, respectively, were formally replicated. In a full dataset GWAS, 13 further loci for resting Tpe, 1 for Tpe response to exercise and 1 for Tpe response to exercise were genome-wide significant (p ≤ 5 × 10−8). Sex-specific analyses indicated seven additional loci. In total, we identify 32 loci for resting Tpe, 3 for Tpe response to exercise and 3 for Tpe response to recovery modulating ventricular repolarization, as well as cardiac conduction and contraction. Our findings shed light on the genetic basis of resting Tpe and Tpe response to exercise and recovery, unveiling plausible candidate genes and biological mechanisms underlying ventricular excitability.

Background: Early prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution. Methods: We analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMR ex ) and recovery from exercise (TMR during recovery, TMR rec ). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMR ex and TMR rec were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631). Results: A total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMR rec was significantly associated with cardiovascular events (hazard ratio, 1.11; P =5×10 -7 ), independent of clinical variables and other ECG markers. TMR rec was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMR ex and TMR rec , of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMR rec genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P =6×10 -3 ). Conclusions: TMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.

Introduction The unipolar electrogram (UEG) provides local measures of cardiac activation and repolarization and is an important translational link between patient and laboratory. A simple theoretical model of the UEG was previously proposed and tested in silico. Method and results The aim of this study was to use epicardial sock‐mapping data to validate the simple model's predictions of unipolar electrogram morphology in the in vivo human heart. The simple model conceptualizes the UEG as the difference between a local cardiac action potential and a position‐independent component representing remote activity, which is defined as the average of all action potentials. UEGs were recorded in 18 patients using a multielectrode sock containing 240 electrodes and activation (AT) and repolarization time (RT) were measured using standard definitions. For each cardiac site, a simulated local action potential was generated by adjusting a stylized action potential to fit AT and RT measured in vivo. The correlation coefficient (cc) measuring the morphological similarity between 13,637 recorded and simulated UEGs was cc = 0.89 (0.72–0.95), median (Q1–Q3), for the entire UEG, cc = 0.90 (0.76–0.95) for QRS complexes, and cc = 0.83 (0.58–0.92) for T‐waves. QRS and T‐wave areas from recorded and simulated UEGs showed cc> 0.89 and cc> 0.84, respectively, indicating good agreement between voltage isochrones maps. Simulated UEGs accurately reproduced the interaction between AT and QRS morphology and between RT and T‐wave morphology observed in vivo. Conclusions Human in vivo whole heart data support the validity of the simple model, which provides a framework for improving the understanding of the UEG and its clinical utility.

BackgroundChronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.ObjectiveThe primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.MethodsTwenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.ResultsThe Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.ConclusionsThe RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.Trial RegistrationISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601International Registered Report Identifier (IRRID)PRR1-10.2196/28873

Background The relationship between structural pathology and electrophysiological substrate in cardiac amyloidosis is unclear. Differences between light‐chain ( AL ) and transthyretin ( ATTR ) cardiac amyloidosis may have prognostic implications. Methods and Results ECG imaging and cardiac magnetic resonance studies were conducted in 21 cardiac amyloidosis patients (11 AL and 10 ATTR ). Healthy volunteers were included as controls. With respect to ATTR , AL patients had lower amyloid volume (51.0/37.7 versus 73.7/16.4 mL, P =0.04), lower myocardial cell volume (42.6/19.1 versus 58.5/17.2 mL, P =0.021), and higher T1 (1172/64 versus 1109/80 ms, P =0.022) and T2 (53.4/2.9 versus 50.0/3.1 ms, P =0.003). ECG imaging revealed differences between cardiac amyloidosis and control patients in virtually all conduction‐repolarization parameters. With respect to ATTR , AL patients had lower epicardial signal amplitude (1.07/0.46 versus 1.83/1.26 mV, P =0.026), greater epicardial signal fractionation ( P =0.019), and slightly higher dispersion of repolarization (187.6/65 versus 158.3/40 ms, P =0.062). No significant difference between AL and ATTR patients was found using the standard 12‐lead ECG . T1 correlated with epicardial signal amplitude (cc=−0.78), and extracellular volume with epicardial signal fractionation (cc=0.48) and repolarization time (cc=0.43). Univariate models based on single features from both cardiac magnetic resonance and ECG imaging classified AL and ATTR patients with an accuracy of 70% to 80%. Conclusions In this exploratory study cardiac amyloidosis was associated with ventricular conduction and repolarization abnormalities, which were more pronounced in AL than in ATTR . Combined ECG imaging–cardiac magnetic resonance analysis supports the hypothesis that additional mechanisms beyond infiltration may contribute to myocardial damage in AL amyloidosis. Further studies are needed to assess the clinical impact of this approach.

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality1,2. We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

The High Frequency (HF) band of the power spectrum of the Heart Rate Variability (HRV) is widely accepted to contain information related to the respiration. However, it is known that this often results in misleading estimations of the strength of the Respiratory Sinus Arrhythmia (RSA). In this paper, different approaches to characterize the change of the RSA with age, combining HRV and respiratory signals, are studied. These approaches are the bandwidths in the power spectral density estimations, bivariate phase rectified signal averaging, information dynamics, a time-frequency representation, and a heart rate decomposition based on subspace projections. They were applied to a dataset of sleep apnea patients, specifically to periods without apneas and during NREM sleep. Each estimate reflected a different relationship between RSA and age, suggesting that they all capture the cardiorespiratory information in a different way. The comparison of the estimates indicates that the approaches based on the extraction of respiratory information from HRV provide a better characterization of the age-dependent degradation of the RSA. ispartof: pages:1588-1591 ispartof: Proceedings of EMBC vol:2019 pages:1588-1591 ispartof: 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) location:Berlin, Germany date:23 Jul - 27 Jul 2019 status: published

AIMS: Action potential duration (APD) alternans is an established precursor or arrhythmia and sudden cardiac death. Important differences in fundamental electrophysiological properties relevant to arrhythmia exist between experimental models and the diseased in vivo human heart. To investigate mechanisms of APD alternans using a novel approach combining intact heart and cellular cardiac electrophysiology in human in vivo. METHODS AND RESULTS: We developed a novel approach combining intact heart electrophysiological mapping during cardiac surgery with rapid on-site data analysis to guide myocardial biopsies for laboratory analysis, thereby linking repolarization dynamics observed at the organ level with underlying ion channel expression. Alternans-susceptible and alternans-resistant regions were identified by an incremental pacing protocol. Biopsies from these sites (n = 13) demonstrated greater RNA expression in Calsequestrin (CSQN) and Ryanodine (RyR) and ion channels underlying IK1 and Ito at alternans-susceptible sites. Electrical restitution properties (n = 7) showed no difference between alternans-susceptible and resistant sites, whereas spatial gradients of repolarization were greater in alternans-susceptible than in alternans-resistant sites (P = 0.001). The degree of histological fibrosis between alternans-susceptible and resistant sites was equivalent. Mathematical modelling of these changes indicated that both CSQN and RyR up-regulation are key determinants of APD alternans. CONCLUSION: Combined intact heart and cellular electrophysiology show that regions of myocardium in the in vivo human heart exhibiting APD alternans are associated with greater expression of CSQN and RyR and show no difference in restitution properties compared to non-alternans regions. In silico modelling identifies up-regulation and interaction of CSQN with RyR as a major mechanism underlying APD alternans.

Background Early prediction of cardiovascular (CV) events in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with CV mortality in heart failure patients. Our objective was to evaluate the CV prognostic value of TMR in the general population and identify any genetic contribution. Methods ECG recordings from 56,780 healthy individuals undergoing exercise stress testing in the UK Biobank study (EST-UKB) were analyzed. TMR was computed for exercise (TMRex) and recovery from exercise (TMRrec). The primary endpoint was CV death or hospitalizations for CV reasons. The secondary and tertiary endpoints were (1) all-cause mortality or hospitalizations for CV reasons and (2) arrhythmic mortality or hospitalizations for arrhythmic reasons. The median follow-up time was 70.7 months. Genome-wide association studies for TMRex and TMRrec were also performed and genetic risk scores (GRSs) were derived and tested for association with endpoints in the full cohort (FULL-UKB; N=402,746, median follow-up time of 85.3 months). Results 1,727 (3.0%) individuals met the primary endpoint in EST-UKB, and 2,326 (4.1%) and 120 (0.2%) met the secondary and tertiary endpoints, respectively. TMRrec was significantly associated with the primary endpoint (hazard ratio (HR) 1.15, P=2 × 10–10, table 1), and both secondary and tertiary endpoints (HR 1.13, P=2 × 10–11 and HR 1.28, P=1 × 10–4, respectively) independent of resting QTc, and resting and recovery heart rate. Despite relatively low heritability (∼5%), we identified 12 genetic loci associated with TMRex and TMRrec, of which nine had been previously associated with other ECG markers. Individuals meeting the primary and secondary endpoints in FULL-UKB (21,328, 5.3% and 28,536, 7.1%, respectively) had higher GRS for TMRrec than unaffected individuals (P=0.026 for both endpoints). No association was found between TMRex or TMRrec and the tertiary endpoint. Individuals in the top 20% of the GRS had significantly higher risk of meeting the primary and secondary endpoints than those in the bottom 20% (HR 1.04, P=0.048, HR 1.04, P=0.024, respectively). Conclusion TMR and TMR GRSs are significantly associated with CV events and all-cause mortality, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization identifies a high-risk substrate for CV events. This work provides support for inclusion of clinical variables, non-invasive markers and GRSs to improve personalised treatment decisions. Conflict of Interest None

Background Reduced heart rate (HR) changes during exercise and recovery post-exercise are strong predictors of cardiovascular (CV) death, suggesting that abnormalities in autonomic balance may precede manifestations of malignant CV events. Cardiac repolarisation is a critical component in modulating the risk of CV death. We therefore hypothesised that assessment of autonomic effects on cardiac repolarisation during exercise may help to improve CV risk prediction in the general population as it is more specific for cardiac ventricular pathophysiology compared to the autonomic effects on the sinus node. Methods A total of 54,203 healthy individuals aged 40–69 years old without prior CV disease who had an exercise stress test from the UK Biobank study were included. HR corrected repolarisation time intervals RTc (an approximation of the QT interval) were measured from the ECG recording at rest (pre-exercise; RTc_rest), peak-exercise (RTc_ex), and 50s post-exercise recovery (RTc_rec) using a custom build algorithm. We also computed the difference between RTc_ex and RTc_rec (dRTc) as a marker of exercise associated repolarization. We finally performed a follow-up analysis to evaluate the prognostic value of these biomarkers. The endpoints studied were CV death or CV hospitalisation. Associations were tested with the Mann-Whitney and multivariate cox analysis. We then evaluated using multivariate Cox analysis whether individuals in the top 20% for were significantly more likely to suffer a CV event than those in the bottom 20%. Results During a median follow-up time of 56 months, 1,460 (2.7%) individuals reached the endpoint. RTc_ex, RTc_rec, and dRTc were all significantly associated with the endpoint (p=4.1E-9, p Conclusion Assessment of repolarisation time during recovery improves prediction of cardiovascular death and hospitalisation in the general population independently from heart-rate changes. This work supports inclusion of clinical variables to improve personalised diagnostics and demonstrates the importance of evaluating repolarisation during exercise stress testing. Conflict of Interest None

Background: The accuracy of ECG imaging (ECGI) in structural heart disease remains uncertain. This study aimed to provide a detailed comparison of ECGI and contact-mapping system (CARTO) electrograms. Methods: Simultaneous epicardial mapping using CARTO (Biosense-Webster, CA) and ECGI (CardioInsight) in 8 patients was performed to compare electrogram morphology, activation time (AT), and repolarization time (RT). Agreement between AT and RT from CARTO and ECGI was assessed using Pearson correlation coefficient, ρ AT and ρ RT , root mean square error, E AT and E RT , and Bland-Altman plots. Results: After geometric coregistration, 711 (439–905; median, first-third quartiles) ECGI and CARTO points were paired per patient. AT maps showed ρ AT =0.66 (0.53–0.73) and E AT =24 (21–32) ms, RT maps showed ρ RT =0.55 (0.41–0.71) and E RT =51 (38–70) ms. The median correlation coefficient measuring the morphological similarity between the unipolar electrograms was equal to 0.71 (0.65–0.74) for the entire signal, 0.67 (0.59–0.76) for QRS complexes, and 0.57 (0.35–0.76) for T waves. Local activation map correlation, ρ AT , was lower when default filters were used (0.60 (0.30–0.71), P =0.053). Small misalignment of the ECGI and CARTO geometries (below ±4 mm and ±4°) could introduce variations in the median ρ AT up to ±25%. Minimum distance between epicardial pacing sites and the region of earliest activation in ECGI was 13.2 (0.0–28.3) mm from 25 pacing sites with stimulation to QRS interval Conclusions: This simultaneous assessment demonstrates that ECGI maps activation and repolarization parameters with moderate accuracy. ECGI and contact electrogram correlation is sensitive to electrode apposition and geometric alignment. Further technological developments may improve spatial resolution.

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works Developing a tool which identifies emotions based on their effect on cardiac activity may have a potential impact on clinical practice, since it may help in the diagnosing of psycho-neural illnesses. In this study, a method based on the analysis of heart rate variability (HRV) guided by respiration is proposed. The method was based on redefining the high frequency (HF) band, not only to be centered at the respiratory frequency, but also to have a bandwidth dependent on the respiratory spectrum. The method was first tested using simulated HRV signals, yielding the minimum estimation errors as compared to classical and respiratory frequency centered at HF band based definitions, independently of the values of the sympathovagal ratio. Then, the proposed method was applied to discriminate emotions in a database of video-induced elicitation. Five emotional states, relax, joy, fear, sadness and anger, were considered. The maximum correlation between HRV and respiration spectra discriminated joy vs. relax, joy vs. each negative valence emotion, and fear vs. sadness with p-value = 0.05 and AUC = 0.70. Based on these results, human emotion characterization may be improved by adding respiratory information to HRV analysis.

Novel methods for assessing baroreflex sensitivity (BRS) using only pulse photoplethysmography (PPG) signals are presented. Proposed methods were evaluated with a data set containing electrocardiogram (ECG), blood pressure (BP), and PPG signals from 17 healthy subjects during a tilt table test. The methods are based on a surrogate of α index, which is defined as the power ratio of RR interval variability (RRV) and that of systolic arterial pressure series variability (SAPV). The proposed α index surrogates use pulse-to-pulse interval series variability (PPV) as a surrogate of RRV, and different morphological features of the PPG pulse which have been hypothesized to be related to BP, as series surrogates of SAPV. A time-frequency technique was used to assess BRS, taking into account the non-stationarity of the protocol. This technique identifies two time-varying frequency bands where RRV and SAPV (or their surrogates) are expected to be coupled: the low frequency (LF, inside 0.04–0.15 Hz range), and the high frequency (HF, inside 0.15–0.4 Hz range) bands. Furthermore, time-frequency coherence is used to identify the time intervals when the RRV and SAPV (or their surrogates) are coupled. Conventional α index based on RRV and SAPV was used as Gold Standard. Spearman correlation coefficients between conventional α index and its PPG-based surrogates were computed and the paired Wilcoxon statistical test was applied in order to assess whether the indices can find significant differences (p < 0.05) between different stages of the protocol. The highest correlations with the conventional α index were obtained by the α-index-surrogate based on PPV and pulse up-slope (PUS), with 0.74 for LF band, and 0.81 for HF band. Furthermore, this index found significant differences between rest stages and tilt stage in both LF and HF bands according to the paired Wilcoxon test, as the conventional α index also did. These results suggest that BRS changes induced by the tilt test can be assessed with high correlation by only a PPG signal using PPV as RRV surrogate, and PPG morphological features as SAPV surrogates, being PUS the most convenient SAPV surrogate among the studied ones.