Editorial on the Research Topic Cardiorespiratory Coupling-Novel Insights for Integrative Biomedicine In recent years, integrative physiology is gaining increased attention; novel findings in the ...area of molecular and systemic cardiopulmonary interaction overgrow the classical opinion that the adoption and transport of oxygen and elimination of carbon dioxide are their only functions. The analysis of fluctuations in blood pressure and heart period represents another parameter of clinical importance as risk marker for cardiovascular morbidity and mortality (La Rovere et al., 2011), especially in some cardiac (Malberg et al., 2002) and non-cardiac diseases (Bär et al., 2007) or after specific therapeutic procedures (Acampa et al., 2011), that are able to determine changes at different levels, including arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels (Tu et al., 2019). According to their analysis, xBRS method seems to have a potentially large bias in characterizing the capacity of the arterial baroreflex under resting conditions and seems to be exclusively dominated by the heart rate to systolic blood pressure ratio. Ruiz-Blais et al. specifically evaluated HRV (using time-frequency coherence analysis) in pairs of non-experts in different vocalizing conditions; their results show that HRV becomes more coupled when people make long (>10 s) sounds synchronously and this synchronization persists when the effect of respiration is removed: 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.
In the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study, the causes of ischemic stroke were identified in 43% of cryptogenic stroke patients monitored with implantable cardiac monitor (ICM), but ...one-third of these patients had non-cardioembolic causes. These results suggest the need for an early and comprehensive diagnostic work-up before inserting an ICM.
Background Systemic inflammation is a strong predictor of atrial fibrillation. A key role for electrical remodeling is increasingly recognized, and experimental data suggest that inflammatory ...cytokines can directly affect connexins resulting in gap-junction dysfunction. We hypothesized that systemic inflammation, regardless of its origin, promotes atrial electric remodeling in vivo, as a result of cytokine-mediated changes in connexin expression. Methods and Results Fifty-four patients with different inflammatory diseases and elevated C-reactive protein were prospectively enrolled, and electrocardiographic P-wave dispersion indices, cytokine levels (interleukin-6, tumor necrosis factor-α, interleukin-1, interleukin-10), and connexin expression (connexin 40, connexin 43) were measured during active disease and after reducing C-reactive protein by >75%. Moreover, peripheral blood mononuclear cells and atrial tissue specimens from an additional sample of 12 patients undergoing cardiac surgery were evaluated for atrial and circulating mRNA levels of connexins. Finally, in vitro effects of interleukin-6 on connexin expression were studied in HL-1 mouse atrial myocytes. In patients with active inflammatory diseases, P-wave dispersion indices were increased but rapidly decreased within days when C-reactive protein normalizes and interleukin-6 levels decline. In inflammatory disease patients, both P-wave dispersion indices and interleukin-6 changes were inversely associated with circulating connexin levels, and a positive correlation between connexin expression in peripheral blood mononuclear cells and atrial tissue was demonstrated. Moreover, interleukin-6 significantly reduced connexin expression in HL-1 cells. Conclusions Our data suggest that regardless of specific etiology and organ localization, systemic inflammation, via interleukin-6 elevation, rapidly induces atrial electrical remodeling by down-regulating cardiac connexins. Although transient, these changes may significantly increase the risk for atrial fibrillation and related complications during active inflammatory processes.
Recently, atrial cardiopathy has emerged as possible pathogenic mechanism in cryptogenic stroke and many electrocardiographic (ECG) markers have been proposed in order to detect an altered atrial ...substrate at an early stage. The autonomic nervous system (ANS) plays a well-known role in determining significant and heterogeneous electrophysiological changes of atrial cardiomyocytes, that promote atrial fibrillation episodes in cardioembolic stroke. Conversely, the role of ANS in atrial cardiopathy and cryptogenic stroke is less known, as well as ANS effects on ECG markers of atrial dysfunction. In this paper, we review the evidence linking ANS dysfunction and atrial cardiopathy as a possible pathogenic factor in cryptogenic stroke.
Background Anti-Sjögren's syndrome-related antigen A-antibodies (anti-Ro/SSA-antibodies) are responsible for a novel form of acquired long-QT syndrome, owing to autoimmune-mediated inhibition of ...cardiac human ether-a-go-go-related gene-potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample-size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti-Ro/SSA-antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti-Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate-corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti-Ro/SSA-positive (8.3%). Subjects who were anti-Ro/SSA-positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios OR, 1.67 1.26-2.21 for QTc >470/480 ms; 2.32 1.54-3.49 for QTc >490 ms; 2.77 1.66-4.60 for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT-prolonging drugs were added to the model. Nevertheless, stepwise-fully adjusted OR for the higher cutoffs remained significantly increased in anti-Ro/SSA-positive subjects, particularly for QTc >500 ms (2.27 1.34-3.87). Conclusions Anti-Ro/SSA-antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti-Ro/SSA-positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.
Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current ...evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects.
An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 95% CI, 1.12-4.50 for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction.
Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.
PDF
