Insights into sinus arrhythmia of the dog: Acetylcholine perfusion of canine right atrium results in beat-to-beat patterns that mimic sinus arrhythmia supporting exit block in the sinoatrial conduction pathways.

Sinus arrhythmia of the dog is unique because of the pronounced alternating beat-to-beat intervals. The clustering of these short (faster rates) and long (slower rates) intervals is not just influenced by autonomic input from breathing; sinus arrhythmia can persist in the panting or apneic dog. The multiplicity of central and peripheral influences on the sinus node complicates the unraveling of the mechanisms of sinus arrhythmia. Studies of the sinus node suggest that acetylcholine can slow cellular depolarization and block sinoatrial conduction. Electrocardiographic monitoring of the dog supports this notion in that abrupt bifurcation into short and long intervals develop at lower heart rates. We sought to determine whether this phenomenon could be recapitulated in canine atrial preparations perfused with acetylcholine and whether selective pharmacologic blockade of the voltage and calcium clocks could provide insight into its mechanism. Spontaneous beat to beat (A-A) intervals were obtained from monophasic action potential recordings of perfused canine right atrial preparations before and during perfusion with acetylcholine (2-5 µM). The calcium clock was blocked with ryanodine (2-3 µM). The membrane clock was blocked with diltiazem hydrochloride (ICa,L blocker; 0.25 µM) and ZD7288 (If blocker; 3 µM). Hyperpolarization was hindered by blockade of IK,Ado/IK,Ach with tertiapin Q (100 nM) before and during acetylcholine perfusion. Acetylcholine resulted in beat clusters similar to those seen in sinus arrhythmia of the dog. Beat clusters were consistent with intermittent 2:1 and 3:1 sinoatrial conduction block. Tertiapin Q abolished this patterning suggesting a role of IK,Ado/IK,ACh in the mechanism of these acetylcholine-induced beat-to-beat patterns.

Instantaneous and averaged heart rate profiles: Developing strategies for programming pacing rates in dogs.

Pacemakers use heart rate histograms (% beats) and sensor indicated rate histograms (% time) to illustrate rate distributions. When programmed to the rate adaptive modes, these data are used to determine the appropriateness of rate response to activity. These histograms are generated from instantaneous heart rate calculations. In humans, such data are compared to known histographic rate profiles. Such rate profiles during 24 h in the dog are not available. Moreover, data representation differ between Holter monitoring and pacemakers making comparisons challenging. The rate distribution in dogs >7-years of age was determined over 24 h using instantaneous and rolling average heart rate. Such data could serve as a guide to programming pacing rates for dogs. Sinus arrhythmia resulted in dissimilar heart rate profiles depending on the method of determining rate. The long intervals of sinus arrhythmia resulted in median values for the percent of time with an instantaneous heart rate of <50 beats/min (bpm) of 15%, whereas a rolling average heart rate of <50 bpm was 0.2%. Based on the cumulative time of the rolling average rate, dogs spent 26.3% of the day between 70-90 bpm with rates <65 bpm and >90 bpm approximating 30% for each. Rates >160 bpm were uncommon (<1%). However, high variability existed between dogs. This study demonstrated the shortcomings of both instantaneous and averaging methods to evaluate heart rate profiles in the dog and that both methods should be incorporated when making pacing rate decisions during programming.

Lack of association between heart period variability asymmetry and respiratory sinus arrhythmia in healthy and chronic heart failure individuals.

Temporal asymmetry is a peculiar aspect of heart period (HP) variability (HPV). HPV asymmetry (HPVA) is reduced with aging and pathology, but its origin is not fully elucidated. Given the impact of respiration on HPV resulting in the respiratory sinus arrhythmia (RSA) and the asymmetric shape of the respiratory pattern, a possible link between HPVA and RSA might be expected. In this study we tested the hypothesis that HPVA is significantly associated with RSA and asymmetry of the respiratory rhythm. We studied 42 middle-aged healthy (H) subjects, and 56 chronic heart failure (CHF) patients of whom 26 assigned to the New York Heart Association (NYHA) class II (CHF-II) and 30 to NYHA class III (CHF-III). Electrocardiogram and lung volume were monitored for 8 minutes during spontaneous breathing (SB) and controlled breathing (CB) at 15 breaths/minute. The ratio of inspiratory (INSP) to expiratory (EXP) phases, namely the I/E ratio, and RSA were calculated. HPVA was estimated as the percentage of negative HP variations, traditionally measured via the Porta's index (PI). Departures of PI from 50% indicated HPVA and its significance was tested via surrogate data. We found that RSA increased during CB and I/E ratio was smaller than 1 in all groups and experimental conditions. In H subjects the PI was about 50% during SB and it increased significantly during CB. In both CHF-II and CHF-III groups the PI was about 50% during SB and remained unmodified during CB. The PI was uncorrelated with RSA and I/E ratio regardless of the experimental condition and group. Pooling together data of different experimental conditions did not affect conclusions. Therefore, we conclude that the HPVA cannot be explained by RSA and/or I/E ratio, thus representing a peculiar feature of the cardiac control that can be aroused in middle-aged H individuals via CB.

Distribution, Stability, and Continuity of Autonomic Nervous System Responsivity at 18- and 36-Months of Age.

OBJECTIVE: Cardiac autonomic nervous system (ANS) measures, respiratory sinus arrhythmia (RSA) and preejection period (PEP), are valid and reliable indicators of children's sensitivity to their environment; however, there are few studies of ANS measures in children less than three years of age. This study's aim was to summarize the distributions, stability, and continuity of RSA and PEP measures during resting, challenge, and reactivity for children at 18- and 36-months. METHODS: This was a cohort study of racially- and ethnically-diverse, low-income children who completed a developmentally challenging protocol while we simultaneously assessed their RSA and PEP at 18-months (N = 134) and 36-months (N = 102). RESULTS: The ANS resting, challenge, and reactivity measures at 18- and 36-months of age were normally distributed. The RSA resting (r = 0.29), RSA challenge (r = 0.44), PEP resting (r = 0.55) and PEP challenge (r = 0.58) measures were moderately stable but RSA (r = 0.01) and PEP reactivity (r = 0.02) were not stable from 18- to 36-months of age. There was no continuity in the ANS measures from 18- to 36-months of age with statistically significant changes in sample means for all of the ANS measures. DISCUSSION: These developmental changes in ANS are shown at the sample level but there are individual differences in ANS responses from 18- to 36-months that may be affected by adversity or protective factors experienced early in life.

ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function.

RATIONALE: Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the cis-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified. OBJECTIVE: To define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function. METHODS AND RESULTS: We used ATAC-seq on sorted neonatal mouse SAN to compare regions of accessible chromatin in PCs and right atrial cardiomyocytes. PC-enriched assay for transposase-accessible chromatin peaks, representing candidate SAN regulatory elements, were located near established SAN genes and were enriched for distinct sets of TF (transcription factor) binding sites. Among several novel SAN enhancers that were experimentally validated using transgenic mice, we identified a 2.9-kb regulatory element at the Isl1 locus that was active specifically in the cardiac inflow at embryonic day 8.5 and throughout later SAN development and maturation. Deletion of this enhancer from the genome of mice resulted in SAN hypoplasia and sinus arrhythmias. The mouse SAN enhancer also directed reporter activity to the inflow tract in developing zebrafish hearts, demonstrating deep conservation of its upstream regulatory network. Finally, single nucleotide polymorphisms in the human genome that occur near the region syntenic to the mouse enhancer exhibit significant associations with resting heart rate in human populations. CONCLUSIONS: (1) PCs have distinct regions of accessible chromatin that correlate with their gene expression profile and contain novel SAN enhancers, (2) cis-regulation of Isl1 specifically in the SAN depends upon a conserved SAN enhancer that regulates PC development and SAN function, and (3) a corresponding human ISL1 enhancer may regulate human SAN function.

Probing age-related changes in cardio-respiratory dynamics by multimodal coupling assessment.

Quantifying respiratory sinus arrhythmia (RSA) can provide an index of parasympathetic function. Fourier spectral analysis, the most widely used approach, estimates the power of the heart rate variability in the frequency band of breathing. However, it neglects the time-varying characteristics of the transitions as well as the nonlinear properties of the cardio-respiratory coupling. Here, we propose a novel approach based on Hilbert-Huang transform, called the multimodal coupling analysis (MMCA) method, to assess cardio-respiratory dynamics by examining the instantaneous nonlinear phase interactions between two interconnected signals (i.e., heart rate and respiration) and compare with the counterparts derived from the wavelet-based method. We used an online database. The corresponding RSA components of the 90-min ECG and respiratory signals of 20 young and 20 elderly healthy subjects were extracted and quantified. A cycle-based analysis and a synchro-squeezed wavelet transform were also introduced to assess the amplitude or phase changes of each respiratory cycle. Our results demonstrated that the diminished mean and standard deviation of the derived dynamical RSA activities can better discriminate between elderly and young subjects. Moreover, the degree of nonlinearity of the cycle-by-cycle RSA waveform derived from the differences between the instantaneous frequency and the mean frequency of each respiratory cycle was significantly decreased in the elderly subjects by the MMCA method. The MMCA method in combination with the cycle-based analysis can potentially be a useful tool to depict the aging changes of the parasympathetic function as well as the waveform nonlinearity of RSA compared to the Fourier-based high-frequency power and the wavelet-based method.

Increased cardiorespiratory synchronization evoked by a breath controller based on heartbeat detection.

BACKGROUND: The cardiovascular and respiratory systems are functionally related to each other, but the underlying physiologic mechanism of cardiorespiratory coupling (CRC) is unclear. Cardiopulmonary phase synchronization is a form of cardiorespiratory coupling. However, it is difficult to study in experimental data which are very often inherently nonstationary and thus contain only quasiperiodic oscillations. So how to enhance cardiopulmonary synchronization and quantify cardiopulmonary synchronization, the changes in cardiac function under the conditions of cardiopulmonary synchronization, and the physiological mechanisms behind them are the main issues to be discussed in this paper. RESULTS: The results showed that the cardiorespiratory synchronization significantly increased when breathing was controlled by heartbeat detection (p < 0.001). And the respiratory sinus arrhythmia (RSA) obviously decreased (p < 0.01) in the 2/2 mode and increased (p < 0.001) in the 4/4 mode. During the 2/2 breathing pattern compared with spontaneous breathing, systolic blood pressure (SBP) decreased (p < 0.05), and diastolic blood pressure (DBP), mean arterial blood pressure (MBP), and SV decreased significantly (p < 0.01). During the 4/4 breathing pattern compared to 2/2 breathing patterns, DBP, MBP, and cardiac output (CO) increased (p < 0.05), and stroke volume (SV) increased significantly (p < 0.01). When analyzing the relationships among these parameters, the RSA was found to be associated with the respiration rate in all respiratory patterns. CONCLUSIONS: We demonstrated that voluntary cardiorespiratory synchronization (VCRS) can effectively enhance cardiopulmonary phase synchronization, but cardiopulmonary phase synchronization and RSA represent different aspects of the cardiorespiratory interaction. It is found that cardiac function parameters such as the blood pressure and output per stroke could be affected by the number of heartbeats contained in the exhalation and inspiratory phase regulated through VCRS. So we can study cardiopulmonary phase synchronization by VCRS. It can be used to study in experimental data for the physiological mechanism of cardiopulmonary coupling.

Does touch matter? The impact of stroking versus non-stroking maternal touch on cardio-respiratory processes in mothers and infants.

The beneficial effects of touch in development were already observed in different types of skin-to-skin care. In the current study, we aimed at studying potential underlying mechanisms of these effects in terms of parasympatho-inhibitory regulation. We examined the specific impact of affective maternal stroking versus non-stroking touch on the cardio-respiration of both mothers and infants in terms of respiratory sinus arrhythmia (RSA). We compared a 3-min TOUCH PERIOD (stroking or non-stroking touch) with a baseline before (PRE-TOUCH) and after (POST-TOUCH) in 45 dyads (24 stroking/21 non-stroking touch) with infants aged 4-16 weeks. We registered mother-infant ECG, respiration and made video-recordings. We calculated RR-interval (RRI), respiration rate (fR) and (respiratory corrected) RSA and analyzed stroking mean velocity rate (MVR) of the mothers. ANOVA-tests showed a significant different impact on infants' respiratory corrected RSA of stroking touch (increase) versus non-stroking touch (decrease). Further, during and after stroking touch, RRI significantly increased whereas fR significantly decreased. Non-stroking touch had no significant impact on infants' RRI and fR. In the mothers, RRI significantly decreased and fR significantly increased during the TOUCH PERIOD. The mothers' MVR occurred within the range of 1-10 cm/s matching with the optimal afferent stimulation range of a particular class of cutaneous unmyelinated, low-threshold mechano-sensitive nerves, named c-tactile (CT) afferents. We suggest CT afferents to be the a potential missing link between the processing of affective touch and the development of physiological and emotional self-regulation. The results are discussed with regard to the potential role of CT afferents within the building of early self-regulation as part of a multisensory intuitive parenting system and the importance to respect this ecological context of an infant in research and clinical applications.

Unconstrained Estimation of HRV Indices After Removing Respiratory Influences From Heart Rate.

OBJECTIVE: This paper proposes an approach to better estimate the sympathovagal balance (SB) and the respiratory sinus arrhythmia (RSA) after separating respiratory influences from the heart rate (HR). METHODS: The separation is performed using orthogonal subspace projections and the approach is first tested using simulated HR and respiratory signals with different spectral properties. Then, RSA and SB are estimated during autonomic blockade and stress using the proposed approach and the classical heart rate variability (HRV) analysis. Both real- and ECG-derived respiration (EDR) are used and the reliability of the EDR is evaluated. RESULTS: Mean absolute percentage errors lower than [Formula: see text] were obtained after removing previously known respiratory signals from simulated HR. The proposed indices were able to improve the quantification of SB during autonomic withdrawal. In the stress data, differences ( ) among relaxed and stressful phases were found with the proposed approach, using both the real respiration and the EDR, but they disappeared when using the classical HRV. CONCLUSION: A better assessment of the autonomic nervous system' response to pharmacological blockade and stress can be achieved after removing respiratory influences from HR, and this can be done using either the real respiration or the EDR. SIGNIFICANCE: This work can be used to better identify vagal withdrawal and increased sympathetic activation when the classical HRV analysis fails due to the respiratory influences on HR. Furthermore, it can be computed using only the ECG, which is an advantage when developing wearable systems with limited number of sensors.

Non-Contact, Simple Neonatal Monitoring by Photoplethysmography.

This paper presents non-contact vital sign monitoring in neonates, based on image processing, where a standard color camera captures the plethysmographic signal and the heart and breathing rates are processed and estimated online. It is important that the measurements are taken in a non-invasive manner, which is imperceptible to the patient. Currently, many methods have been proposed for non-contact measurement. However, to the best of the authors' knowledge, it has not been possible to identify methods with low computational costs and a high tolerance to artifacts. With the aim of improving contactless measurement results, the proposed method based on the computer vision technique is enhanced to overcome the mentioned drawbacks. The camera is attached to an incubator in the Neonatal Intensive Care Unit and a single area in the neonate's diaphragm is monitored. Several factors are considered in the stages of image acquisition, as well as in the plethysmographic signal formation, pre-filtering and filtering. The pre-filter step uses numerical analysis techniques to reduce the signal offset. The proposed method decouples the breath rate from the frequency of sinus arrhythmia. This separation makes it possible to analyze independently any cardiac and respiratory dysrhythmias. Nine newborns were monitored with our proposed method. A Bland-Altman analysis of the data shows a close correlation of the heart rates measured with the two approaches (correlation coefficient of 0.94 for heart rate (HR) and 0.86 for breath rate (BR)) with an uncertainty of 4.2 bpm for HR and 4.9 for BR (k = 1). The comparison of our method and another non-contact method considered as a standard independent component analysis (ICA) showed lower central processing unit (CPU) usage for our method (75% less CPU usage).

Sinus node dysfunction after surgical atrial fibrillation ablation with concomitant mitral valve surgery: Determinants and clinical outcomes.

OBJECTIVE: We sought to investigate determinants and prognosis of sinus node dysfunction (SND) after surgical ablation of atrial fibrillation (AF) with concomitant mitral valve (MV) surgery. A total of 202 patients who underwent surgical AF ablation with concomitant MV surgery were studied. STUDY DESIGN AND SETTING: SND was defined as electrocardiographic manifestations, such as junctional bradycardia, symptomatic sick sinus syndrome, or symptomatic sinus bradycardia, 7 days after surgery. Baseline clinical and echocardiographic characteristics, rhythm outcomes [AF recurrence or permanent pacemaker (PM) implantation] at 6 and 12 months, and clinical outcomes were compared between patients without SND (n = 165) and those with SND (n = 37) after surgery. RESULTS: Patients with SND showed a significantly larger left atrial volume index (LAVI) and a higher right ventricular systolic pressure than those without SND. In addition, there was a higher likelihood for AF recurrence and PM implantation in patients with SND than in those without SND. Although clinical outcomes did not differ between the two groups, patients with SND had a significantly longer length of hospital stay (p<0.001). In a multivariate analysis, preoperative LAVI was a structural risk factor for SND [hazard ratio (HR): 1.126 per 10 mL/m2; 95% confidence interval (CI): 1.0206-1.236; p = 0.001]. An LAVI cut-off value of 105 mL/m2 showed significant predictive power for SND [sensitivity: 62%; specificity: 64%; area under the curve (AUC): 0.678; p = 0.002]. CONCLUSIONS: In conclusion, preoperative LA size was a structural risk factor for SND after surgical AF ablation during MV surgery. SND was associated with an increased risk for AF recurrence and implantation of permanent PM in patients undergoing concomitant surgical ablation of AF with MV surgery.

ELectrophysiological mechanisms underlying the Inhibitory CArdiac syncope without asystolic significant pause: Therapeutic and prognostic implications. The ELICA randomized trial.

BACKGROUND: The aim of this study was to investigate syncope recurrence in patients with a 2A cardioinhibitory response to the head up tilt testing (HUT). METHODS: In this study, we enrolled 72 consecutive patients affected by syncope with cardioinhibitory response without asystolic significant pause to HUT (2A type). In these patients, we randomly performed electrophysiological study (ES). In case of sino-atrial node, atrio-ventricular node dysfunction, and sustained arrhythmias induction, the ES resulted positive. ES was positive in 9 patients (group A), then treated by catheter ablation, and/or by devices implants. Otherwise, ES resulted negative (group B), and these patients did not receive an interventional treatment. However, after ES, we evaluated syncope recurrence during 360 days follow-up. RESULTS: There was a lower statistical significant syncope recurrence at follow-up, comparing group A to group B of patients [n of events 9 (40.9%) vs 8 (57.1%), P < .05]. At multivariate analysis, ES result was the only factor predicting syncope recurrence at follow-up (hazard ratio = 27.63, 95% confidence interval = 1.02-54.24, P < .005). CONCLUSION: The positivity to ES study, and successful interventional therapies may reduce the burden of syncope recurrence at 360 days follow-up in 2A HUT subjects.Clinical trial number: NCT02861274.

Cardiac vagal dysfunction moderates patterns of craving across the day in moderate to heavy consumers of alcohol.

BACKGROUND: Alcohol craving, a known correlate of vulnerability to Alcohol Use Disorder (AUD), has been found to be inversely related to cardiac vagal tone (CVT). Here we examine how resting CVT, CVT reactivity to a postural challenge, and their interaction influence craving during imposed alcohol abstinence and their usual drinking among moderate to heavy drinkers. METHODS: Participants were recruited from the local community (final n = 29) and assessed for CVT functioning via respiratory sinus arrhythmia (RSA) at rest (RSA-rest) and during a postural challenge (RSA-react). Craving intensity was assessed throughout the day during 3-day periods of imposed alcohol abstinence (abstained days) and drinking as usual (normal days) via Ecological Momentary Assessment (EMA). Multilevel statistical modeling assessed relationships between patterns of CVT and diurnal craving. The primary hypothesis of interest was that the interaction of RSA-rest with RSA-react would be significantly associated with increased craving across the day. RESULTS: Overall, craving increased throughout the day and significantly decreased after drinking (p < 0.001). There was a significant interaction between RSA-rest and RSA-react with plots revealing that this effect was driven by an aberrant craving pattern among participants with higher RSA-rest and a sluggish vagal brake in response to a postural shift-atypical RSA-react. CONCLUSION: Although additional research is needed to corroborate these findings, our results suggest that moderate-heavy drinkers characterized by higher RSA-rest and atypical RSA-react exhibit aberrant patterns of craving across the day that may represent a risk factor for AUD.

Aberrant parasympathetic reactivity to acute psychosocial stress in male patients with schizophrenia spectrum disorders.

Autonomic dysfunction represents a core domain of the pathophysiology of schizophrenia spectrum disorders (SCZ), with aberrant physiologic arousal underlying maladaptive social and cognitive behaviors. Antagonistic parasympathetic and sympathetic systems support autonomic flexibility to appropriately regulate arousal and respond to environmental challenges, which can be modeled using physiologic measures. SCZ patients consistently show heightened basal stress, however, their parasympathetic reactivity to an acute psychosocial stressor is poorly understood. Heart period (HP-arousal), respiratory sinus arrhythmia (RSA-parasympathetic vagal activity), and their relationship were measured in SCZ patients (n = 19) and healthy controls (n = 20) at baseline and during psychosocial stress exposure. Parasympathetic vagal control of arousal, reflected in RSA-HP coupling, was assessed for the first time in SCZ. Patients demonstrated blunted physiologic reactivity (less change in heart period and respiratory sinus arrhythmia), a unique increase in respiratory sinus arrhythmia relative to baseline during recovery, and elevated arousal was associated with poor cognitive performance and greater positive symptoms. Arousal regulation was tightly controlled by parasympathetic activity in controls only, indicated by a strong association between changes in heart period and respiratory sinus arrhythmia. Results are the first to demonstrate maladaptive, inefficient parasympathetic arousal regulation (RSA-HP decoupling) in reaction to psychosocial stress in SCZ, representing an autonomic profile incompatible with appropriate social and emotional functioning.

Adapting detection sensitivity based on evidence of irregular sinus arrhythmia to improve atrial fibrillation detection in insertable cardiac monitors.

Aims: Intermittent change in p-wave discernibility during periods of ectopy and sinus arrhythmia is a cause of inappropriate atrial fibrillation (AF) detection in insertable cardiac monitors (ICM). To address this, we developed and validated an enhanced AF detection algorithm. Methods and results: Atrial fibrillation detection in Reveal LINQ ICM uses patterns of incoherence in RR intervals and absence of P-wave evidence over a 2-min period. The enhanced algorithm includes P-wave evidence during RR irregularity as evidence of sinus arrhythmia or ectopy to adaptively optimize sensitivity for AF detection. The algorithm was developed and validated using Holter data from the XPECT and LINQ Usability studies which collected surface electrocardiogram (ECG) and continuous ICM ECG over a 24-48 h period. The algorithm detections were compared with Holter annotations, performed by multiple reviewers, to compute episode and duration detection performance. The validation dataset comprised of 3187 h of valid Holter and LINQ recordings from 138 patients, with true AF in 37 patients yielding 108 true AF episodes ≥2-min and 449 h of AF. The enhanced algorithm reduced inappropriately detected episodes by 49% and duration by 66% with <1% loss in true episodes or duration. The algorithm correctly identified 98.9% of total AF duration and 99.8% of total sinus or non-AF rhythm duration. The algorithm detected 97.2% (99.7% per-patient average) of all AF episodes ≥2-min, and 84.9% (95.3% per-patient average) of detected episodes involved AF. Conclusion: An enhancement that adapts sensitivity for AF detection reduced inappropriately detected episodes and duration with minimal reduction in sensitivity.

Heart rate and outcomes in patients with heart failure with preserved ejection fraction: A dose-response meta-analysis.

Although elevated resting heart rate is related to poor outcomes in heart failure (HF) with reduced ejection fraction, the association in HF with preserved ejection fraction (HFpEF) remains inconclusive. Therefore, we conducted a dose-response meta-analysis to examine the prognostic role of heart rate in patients with HFpEF.We searched PubMed and Embase databases until April 2017 and manually reviewed the reference lists of relevant literatures. Random effect models were used to pool the study-specific hazard ratio (HR) of outcomes, including all-cause death, cardiovascular death, and HF hospitalization.Six studies with 7 reports were finally included, totaling 14,054 patients with HFpEF. The summary HR (95% confidence interval [CI]) for every 10 beats/minute increment in heart rate was 1.04 (1.02-1.06) for all-cause death, 1.06 (1.02-1.10) for cardiovascular death, and 1.05 (1.01-1.08) for HF hospitalization. Subgroup analyses indicated that these positive relationships were significant in patients with sinus rhythm but not in those with atrial fibrillation. There was also evidence for nonlinear relationship of heart rate with each of the outcomes (All P for nonlinearity < .05).Higher heart rate in sinus rhythm is a risk factor for adverse outcomes in patients with HFpEF. Future trials are required to determine whether heart rate reduction may improve the prognosis of HFpEF.

Reduced dose apixaban resolving dual cardiac chamber thrombi in a patient with ischaemic cardiomyopathy in sinus rhythm.

Left atrial (LA) thrombus is a known sequela of atrial fibrillation (AF) but it is less frequently encountered in patients in sinus rhythm. Left ventricular (LV) dysfunction may predispose patients without evidence of atrial tachyarrhythmias to atrial thrombosis. Warfarin is the standard treatment for cardiac chamber thrombosis and prevention of the associated thromboembolic complications. Despite that apixaban was found to be superior to warfarin in prevention of stroke and systemic embolism in patients with AF, evidence for its use in treatment of cardiac chamber thrombi is scarce and is limited to case reports. We report a case of simultaneously occurring LV and LA thrombi successfully treated with reduced dose apixaban in a patient with ischaemic cardiomyopathy and in sinus rhythm. Although apixaban maybe a potential effective treatment for intracardiac thrombi, further studies are needed to demonstrate efficacy and safety of this agent in larger patient populations.

Prospective relations between intrusive parenting and child behavior problems: Differential moderation by parasympathetic nervous system regulation and child sex.

This study examined children's parasympathetic nervous system (PNS) regulation, which was indexed by respiratory sinus arrhythmia (RSA) during rest, reactivity, and recovery episodes, and sex as moderators of predicted relations between observed intrusive parenting and later observer-rated child behavior problems. Child-caregiver dyads (N=250; 50% girls; 46% Latino/a) completed a series of laboratory assessments yielding independent measures of intrusive parenting at age 4, PNS regulation at age 6, and child behavior problems at age 8. Results indicated that intrusive parenting was related to more internalizing problems among boys who showed low RSA reactivity (i.e., PNS withdrawal from pre-startle to startle challenge), but RSA reactivity did not moderate this relation among girls. Interestingly, RSA recovery (i.e., PNS activation from startle challenge to post-startle) moderated these relations differently for boys and girls. For girls with relatively low RSA post-startle (i.e., less recovery), intrusive parenting was positively related to both internalizing and externalizing problems. However, the reverse was true for boys, such that there was a significant positive relation between intrusive parenting and later externalizing problems among boys who evidenced relatively high RSA post-startle (i.e., more recovery). Findings provide evidence for the moderation of intrusive caregiving effects by children's PNS regulation while highlighting the differential patterning of these relations across distinct phases of the regulatory response and as a function of child sex.

Sinus Bradycardia in Habitual Cocaine Users.

Common physiological manifestations of cocaine are related to its adrenergic effects, due to inhibition of dopamine and norepinephrine uptake at the postsynaptic terminal. Few studies have documented bradycardia secondary to cocaine use, representing the antithesis of its adrenergic effects. We assessed the prevalence of sinus bradycardia (SB) in habitual cocaine users and postulated a mechanism for this effect. One hundred sixty-two patients with a history of cocaine use were analyzed and compared with age- and gender-matched controls. SB was defined as a rate of <60 beats/min and habitual cocaine use as 2 or more documented uses >30 days apart. Propensity score-matching analysis was applied to balance covariates between cocaine users and nonusers and reduce selection bias. Patients with a history of bradycardia, hypothyroidism, or concomitant beta-blocker use were excluded. Mean age of study patients was 44 ± 8 years. SB was observed in 43 of 162 (27%) cocaine users and in 9 of 149 (6%) nonusers (p = 0.0001). Propensity score-matching analysis matched 218 patients from both groups. Among matched patients SB was observed in 25 of 109 (23%) cocaine users and in 5 of 109 (5%) nonusers (p = 0.0001). Habitual cocaine use was an independent predictor of SB and associated with a sevenfold increase in the risk of SB (95% CI 2.52 to 19.74, p = 0.0002). In conclusion, habitual cocaine use is a strong predictor of SB and was unrelated to recency of use. A potential mechanism for SB may be related to cocaine-induced desensitization of the beta-adrenergic receptor secondary to continuous exposure. Symptomatic SB was not observed; thus, pacemaker therapy was not indicated.

The prevalence of electrocardiogram abnormalities in professional divers.

BACKGROUND: The underwater environment presents physiological challenges for the cardiovascular, renal and pulmonary systems. Increases in external hydrostatic pressure reduce the capacity of the venous compartment and cause blood to move toward the lung. The aim of this study was to evaluate retrospectively electrocardiographic (ECG) changes in a cohort of professional divers. METHODS: Between January 2009 and January 2012, 225 randomly selected professional divers, 204 male (91%) and 21 female (9%) attended our clinic for their biannual diving medical assessment. Their ECG records were evaluated retrospectively. RESULTS: The most common ECG abnormality observed was incomplete right bundle branch block (IRBBB) in 30 divers (13.3%). Eleven divers (4.9%) showed right QRS axis deviation (seven with IRBBB). Six divers had a sinus tachycardia; in four divers there was early repolarization; three divers had ventricular extrasystoles; one diver had ST elevation in lead V3; there was one with sinus arrhythmia and another with T-wave inversion in leads V2, V3 and aVF. These ECG changes were evaluated retrospectively by a cardiologist who made various recommendations for further review including bubble contrast echocardiography for IRBBB. CONCLUSIONS: No serious ECG abnormalities were identified, but IRBBB should be further investigated because of its association with persistent (patent) foramen ovale. Rapid cardiological review of ECGs could be achieved using modern communications technology, such as telecardiography, and further clinical investigations directed by specialist recommendation arranged promptly if indicated.