Heart Rate Variability Synchronizes When Non-experts Vocalize Together

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

The periodic repolarization dynamics index identifies changes in ventricular repolarization oscillations associated with music-induced emotions

The effect of music on cardiovascular dynamics may be useful in a variety of clinical settings. The aim of this study was to assess whether listening to music characterized by different emotional valence affected ventricular periodic repolarization dynamics (PRD), a recently-proposed non-invasive index of sympathetic ventricular modulation. The 12 lead ECG was recorded in 71 healthy volunteers exposed to six 90 s excerpts of pleasant music and unpleasant acoustic stimuli as well as six 90 s intervals of silence. A 20 s interval was allowed between excerpts during which the participants were asked to evaluate the previous excerpt. A simulation study was carried out to assess the capability of the algorithm of tracking fast small changes in PRD. The simulation study shows that the algorithm implemented in this study has a time-frequency resolution sufficient to capture the fast dynamics observed in this study. PRD were higher during listening to both pleasant and unpleasant music than during silence. There was a (weak) trend for the PRD to be higher during listening to pleasant than unpleasant music that may indicate the existence of a (weak) interaction between the valence of music-induced emotions and sympathetic ventricular response. The PRD significantly increased during the 20 s interval in between conditions, possibly reflecting a sympathetic response to the evaluation task and/or to the expectation of the following excerpt

Theoretical assessment of a repolarization time marker based on the intracardiac bipolar electrogram

The spatio-temporal organization of cardiac repolarization modulates the vulnerability to dangerous ventricular arrhythmias. Methodologies that provide accurate assessment of cardiac repolarization are of primary importance for a better understanding of cardiac electrophysiology and represent a potentially useful tool for clinical applications. The most commonly used repolarization time (RT) marker from extracellular recordings is derived from the unipolar electrogram (UEG). However, far field potentials and remote activity may in certain conditions bias this marker. In this paper, a RT marker based on the bipolar electrogram (BEG) is proposed. An analytical expression of the BEG based on a simple model of the cardiac extracellular potential is derived. According to the proposed analytical framework the BEG exhibits a repolarization wave whose extremum (maximum or minimum) corresponds to the average of the local RTs at the two electrodes of the bipole. The amplitude of this extremum is a function of the steepness of phase 3 of the action potentials, inter-electrode distance, conduction velocity and direction of wave-back propagation. A simulation study based on this analytical framework showed that for noisy to good signal quality (SNR of the UEG ≥ 10 dB), and for a typical inter-electrode distance of 2 mm, conduction velocity between 0.2 and 0.6 m/s, and an angle between conduction direction and the inter-electrode axis ≤ π/4, the median absolute error was lower than 6.8 ms while the median linear correlation between estimated and theoretical RT was higher than 0.91. Examples of RT derived from BEG recorded in a structurally normal heart in both the right and left ventricles demonstrate that the proposed procedure is feasible in human in-vivo studies

Sex Differences in the Morphology of RR-Matched T-waves

Evidence of sex-related differences in cardiac risk is emerging, but whether these reflect sex-related differences in ventricular electrophysiology remains unclear. Our aim was to quantify T-wave morphological differences between men and women across different leads and RR interval values. We analysed 12-lead ECG recordings from 23,962 participants in the UK Biobank without known cardiovascular disease, and subsequently clustered them into bins of RR interval. In each cluster, we derived a lead and sex-specific mean warped T-wave (MWT). Then, we quantified differences between MWT in men and women in time and amplitude using linear, d_{w} and d_{a}, and non-linear markers, d_{w}^{NL} and d_{a}^{NL}. Leads V3 and aVR showed the lowest differences between men and women (median d_{w}, d_{w}^{NL}, d_{a} and d_{a}^{NL} of 1.12 ms, 0.69 ms, 3.29 and 1.20, respectively), while V1 showed the largest (5.69 ms, 4.50 ms, 208.94 and 199.45, respectively). Sex-related differences in MWT increased with the RR interval (d_{w}, d_{w}^{NL}, d_{a} and d_{a}^{NL} ranging 1.44 - 5.89 ms, 1.23 - 3.97 ms, 8.58 - 28.38 and 1.53 - 4.41, respectively). These values compare to those found for morphological T-wave variations due to large changes in heart rate (5.66 ms, 2.35 ms, 57.61 and 9.51, respectively). These results indicate sex and lead should be considered when using T-wave morphologies for cardiovascular risk prediction

Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans

Ventricular action potential duration (APD) is an important component of many physiological functions including arrhythmogenesis. APD oscillations have recently been reported in humans at the respiratory frequency. This study investigates the contribution of the autonomic nervous system to these oscillations. In 10 patients undergoing treatment for supraventricular arrhythmias, activation recovery intervals (ARI; a conventional surrogate for APD) were measured from multiple left and right ventricular (RV) endocardial sites, together with femoral artery pressure. Respiration was voluntarily regulated and heart rate clamped by RV pacing. Sympathetic and parasympathetic blockade was achieved using intravenous metoprolol and atropine, respectively. Metroprolol reduced the rate of pressure development (maximal change in pressure over time): 1,271 (± 646) vs. 930 (± 433) mmHg/s; P < 0.01. Systolic blood pressure (SBP) showed a trend to decrease after metoprolol, 133 (± 21) vs. 128 (± 25) mmHg; P = 0.06, and atropine infusion, 122 (± 26) mmHg; P < 0.05. ARI and SBP exhibited significant cyclical variations (P < 0.05) with respiration in all subjects with peak-to-peak amplitudes ranging between 0.7 and 17.0 mmHg and 1 and 16 ms, respectively. Infusion of metoprolol reduced the mean peak-to-peak amplitude [ARI, 6.2 (± 1.4) vs. 4.4 (± 1.0) ms, P = 0.008; SBP, 8.4 (± 1.6) vs. 6.2 (± 2.0) mmHg, P = 0.002]. The addition of atropine had no significant effect. ARI, SBP, and respiration showed significant coupling (P < 0.05) at the breathing frequency in all subjects. Directed coherence from respiration to ARI was high and reduced after metoprolol infusion [0.70 (± 0.17) vs. 0.50 (± 0.23); P < 0.05]. These results suggest a role of respiration in modulating the electrophysiology of ventricular myocardium in humans, which is partly, but not totally, mediated by β-adrenergic mechanisms

Evaluating the Impact of Physiological Variability in Genome-Wide Association Studies of Resting Heart Rate

Genome-wide association studies (GWAS) have discovered hundreds of genetic loci for resting heart rate (RHR). However, the impact of intra-individual variation in RHR on GWAS results is unclear. We evaluated this impact by analyzing two RHR recordings from N 61,000 subjects from UK Biobank. In addition, we modelled variations in RHR as independent white zero-mean Gaussian noise with a standard deviation of 0.5x, 1x, and 2x the standard deviation of the difference between the original RHR values (4,8, and 16 bpm, respectively). The two original RHR recordings were highly correlated (? =0.77), but results from the genetic analyses were s lightly different: the number of genome-wide significant (p < 5x10-8) variants at the locus with the strongest reported association (MYH6): n=39 vs. n=34; the p-value of the corresponding lead-variant, 3.6x10-24 vs. 2.1x10-19; and the estimated heritability 20.0% vs. 16.7%. Simulated data showed an inverse relationship between RHR variation and genetic association strength and heritability. Results formally demonstrate the impact of intra-individual RHR variability on the discovery of genetic variants in single-measurement studies

Interaction between ECG and Genetic Markers of Coronary Artery Disease

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 Method to Minimise the Impact of ECG Marker Inaccuracies on the Spatial QRS-T angle: Evaluation on 1,512 Manually Annotated ECGs

© 2020 The Author(s) The spatial QRS-T angle (QRS-Ta) derived from the vectorcardiogram (VCG) is a strong risk predictor for ventricular arrhythmia and sudden cardiac death with potential use for mass screening. Accurate QRS-Ta estimation in the presence of ECG delineation errors is crucial for its deployment as a prognostic test. Our study assessed the effect of inaccurate QRS and T-wave marker placement on QRS-Ta estimation and proposes a robust method for its calculation. Reference QRS-Ta measurements were derived from 1,512 VCGs manually annotated by three expert reviewers. We systematically changed onset and offset timings of QRS and T-wave markers to simulate inaccurate placement. The QRS-Ta was recalculated using a standard approach and our proposed algorithm, which limits the impact of VCG marker inaccuracies by defining the vector origin as an interval preceding QRS-onset and redefines the beginning and end of QRS and T-wave loops. Using the standard approach, mean absolute errors (MAE) in peak QRS-Ta were >40% and sensitivity and precision in the detection of abnormality (>105°) were 15 ms. Using our proposed algorithm, MAE for peak QRS-Ta were reduced to 94% for inaccuracies up to ±15 ms. Similar results were obtained for mean QRS-Ta. In conclusion, inaccuracies of QRS and T-wave markers can significantly influence the QRS-Ta. Our proposed algorithm provides robust QRS-Ta measurements in the presence of inaccurate VCG annotation, enabling its use in large datasets

Premature atrial and ventricular contractions detected on wearable-format electrocardiograms and prediction of cardiovascular events.

AIMS: Wearable devices are transforming the electrocardiogram (ECG) into a ubiquitous medical test. This study assesses the association between premature ventricular and atrial contractions (PVCs and PACs) detected on wearable-format ECGs (15 s single lead) and cardiovascular outcomes in individuals without cardiovascular disease (CVD). METHODS AND RESULTS: Premature atrial contractions and PVCs were identified in 15 s single-lead ECGs from N = 54 016 UK Biobank participants (median age, interquartile range, age 58, 50-63 years, 54% female). Cox regression models adjusted for traditional risk factors were used to determine associations with atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), stroke, life-threatening ventricular arrhythmias (LTVAs), and mortality over a period of 11.5 (11.4-11.7) years. The strongest associations were found between PVCs (prevalence 2.2%) and HF (hazard ratio, HR, 95% confidence interval = 2.09, 1.58-2.78) and between PACs (prevalence 1.9%) and AF (HR = 2.52, 2.11-3.01), with shorter prematurity further increasing risk. Premature ventricular contractions and PACs were also associated with LTVA (P < 0.05). Associations with MI, stroke, and mortality were significant only in unadjusted models. In a separate UK Biobank sub-study sample [UKB-2, N = 29,324, age 64, 58-60 years, 54% female, follow-up 3.5 (2.6-4.8) years] used for independent validation, after adjusting for risk factors, PACs were associated with AF (HR = 1.80, 1.12-2.89) and PVCs with HF (HR = 2.32, 1.28-4.22). CONCLUSION: In middle-aged individuals without CVD, premature contractions identified in 15 s single-lead ECGs are strongly associated with an increased risk of AF and HF. These data warrant further investigation to assess the role of wearable ECGs for early cardiovascular risk stratification

Analysing electrocardiographic traits and predicting cardiac risk in UK biobank.

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