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Background: Severely ill patients with coronavirus disease 2019 (COVID‐19) show an increased risk of new‐onset atrioventricular blocks (AVBs), associated with high rates of short‐term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)‐6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL‐6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID‐19. Methods: We investigated (1) the behavior of PR‐interval and PR‐segment in patients with severe COVID‐19 during active phase and recovery, and (2) their association with circulating IL‐6 levels over time. Results: During active disease, COVID‐19 patients showed a significant increase of PR‐interval and PR‐segment. Such atrioventricular delay was transient as these parameters rapidly normalized during recovery. PR‐indices significantly correlated with circulating IL‐6 levels over time. All these changes and correlations persisted also in the absence of laboratory signs of cardiac strain/injury or concomitant treatment with PR‐prolonging drugs, repurposed or not. Conclusions: Our study provides evidence that in patients with severe COVID‐19 and high‐grade systemic inflammation, IL‐6 elevation is associated with a significant delay of atrioventricular conduction, independent of concomitant confounding factors. While transient, such alterations may enhance the risk of severe AVB and associated short‐term mortality. Our data provide further support to current anti‐inflammatory strategies for severe COVID‐19, including IL‐6 antagonists. [ABSTRACT FROM AUTHOR]

Abstract Background Severely ill patients with coronavirus disease 2019 (COVID‐19) show an increased risk of new‐onset atrioventricular blocks (AVBs), associated with high rates of short‐term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)‐6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL‐6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID‐19. Methods We investigated (1) the behavior of PR‐interval and PR‐segment in patients with severe COVID‐19 during active phase and recovery, and (2) their association with circulating IL‐6 levels over time. Results During active disease, COVID‐19 patients showed a significant increase of PR‐interval and PR‐segment. Such atrioventricular delay was transient as these parameters rapidly normalized during recovery. PR‐indices significantly correlated with circulating IL‐6 levels over time. All these changes and correlations persisted also in the absence of laboratory signs of cardiac strain/injury or concomitant treatment with PR‐prolonging drugs, repurposed or not. Conclusions Our study provides evidence that in patients with severe COVID‐19 and high‐grade systemic inflammation, IL‐6 elevation is associated with a significant delay of atrioventricular conduction, independent of concomitant confounding factors. While transient, such alterations may enhance the risk of severe AVB and associated short‐term mortality. Our data provide further support to current anti‐inflammatory strategies for severe COVID‐19, including IL‐6 antagonists.

Aim: To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis. Methods: This prospective cohort study included 49 pregnant participants with ICP at diagnosis and 49 nonaffected controls from a single public hospital. ICP was diagnosed based on clinical symptoms after excluding other causes of pruritus and presence of autoimmune diseases. Total bile acids were not obtained in this cohort. ICP pregnancies were assessed with a functional echocardiography at diagnosis including PR‐interval, isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) for electrical, systolic, and diastolic function, respectively. Controls were assessed at recruitment. Perinatal outcomes were obtained from delivery books. The main outcome was the presence of PR‐interval prolongation or first‐degree fetal heart block, and echographic signs of diastolic and systolic dysfunction. Results: Compared to controls, ICP were above upper limit in conjugated bilirubin (2.0% vs. 20.4%; p = 0.008), aspartate aminotransferase (2.0% vs. 24.5%; p = 0.002), and alanine aminotransferase (4.1% vs. 28.6%; p = 0.002). ICP was associated with a higher PR‐interval (130 ± 12 ms vs. 121 ± 6 ms; p < 0.0001) with five first‐degree fetal heart blocks. IRT was significantly higher in ICP (42 ± 6 ms vs. 37 ± 5 ms; p = 0.0001), with no differences in ICT and ET. PR‐interval trend was only positively correlated with IRT in ICP pregnancies (p = 0.04 and p = 0.34, in ICP and controls, respectively). Conclusions: Our study demonstrates that fetuses affected by maternal ICP are associated with electrical and diastolic myocardial dysfunction. More studies focused on antenatal and postnatal functional echocardiography are necessary to validate our results and consider these markers in the clinical management of ICP pregnancies. [ABSTRACT FROM AUTHOR]

Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap‐junctions containing connexin43 coupling cardiomyocytes and inflammation‐related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms. Methods and Results We analyzed: (1) the PR‐interval in patients with inflammatory diseases of different origins during active phase and recovery, and its association with inflammatory markers; (2) the existing correlation between connexin43 expression in the cardiac tissue and peripheral blood mononuclear cells (PBMC), and the changes occurring in patients with inflammatory diseases over time; (3) the acute effects of interleukin(IL)‐6 on atrioventricular conduction in an in vivo animal model, and on connexin43 expression in vitro. In patients with elevated C‐reactive protein levels, atrioventricular conduction indices are increased, but promptly normalized in association with inflammatory markers reduction, particularly IL‐6. In these subjects, connexin43 expression in PBMC, which is correlative of that measured in the cardiac tissue, inversely associated with IL‐6 changes. Moreover, direct IL‐6 administration increased atrioventricular conduction indices in vivo in a guinea pig model, and IL‐6 incubation in both cardiomyocytes and macrophages in culture, significantly reduced connexin43 proteins expression. Conclusions The data evidence that systemic inflammation can acutely worsen atrioventricular conduction, and that IL‐6‐induced down‐regulation of cardiac connexin43 is a mechanistic pathway putatively involved in the process. Though reversible, these alterations could significantly increase the risk of severe atrioventricular blocks during active inflammatory processes.

Background: The combination of electrical and structural remodeling may have a strong effect on the prognosis of non‐ischemic heart failure (HF). We aimed to clarify whether prolonged PR‐interval and the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) influence the outcomes of patients with non‐ischemic HF. Methods: We studied 262 consecutive hospitalized patients with non‐ischemic HF. In a clinically stable condition, a 12‐lead electrocardiogram and CMR were performed, and the clinical characteristics and outcomes were investigated. Results: During the follow‐up of 967.7 ± 851.8 days, there were 68 (25.9%) cardiac events (HF or sudden death, re‐hospitalization due to HF, or ventricular tachyarrhythmias). In a multivariable analysis, a median rate‐adjusted PR (PRa)‐interval of ≥173.5 ms and the presence of LGE were associated with cardiac events with a hazard ratio of 1.690 and 2.045 (p =.044 and p =.006, respectively). Study subjects were then divided into four groups based on long (≥173.5 ms) or short (<173.5 ms) PRa‐interval and LGE status: short PRa/non‐LGE (n = 80), long PRa/non‐LGE (n = 72), short PRa/LGE (n = 51), and long PRa/LGE (n = 59). Cardiac events were 16.2% in short PRa/non‐LGE, 25.0% in long PRa/non‐LGE, 27.4% in short PRa/LGE, and 38.9% in long PRa/LGE (p =.026), respectively. The multivariable Cox proportional hazard analysis showed that long PRa/LGE was an independent predictor for cardiac events compared to short PRa/non‐LGE (hazard ratio, 3.378, p =.001). Conclusions: The combination of a long PRa‐interval and the presence of LGE provide a better predictive value of cardiac events in non‐ischemic HF. [ABSTRACT FROM AUTHOR]

Background: Electrocardiograph-generated measurements of PR, QRS, and QT intervals are generally thought to be more precise than manual measurements on paper records. However, the performance of different programs has not been well compared.Methods: Routinely obtained digital electrocardiograms (ECGs), including over 500 pediatric ECGs, were used to create over 2000 10 s analog ECGs that were replayed through seven commercially available electrocardiographs. The measurements for PR interval, QRS duration, and QT interval made by each program were extracted and compared against each other (using the median of the programs after correction for program bias) and the population mean values.Results: Small but significant systematic biases were seen between programs. The smallest and largest variation from the population mean differed by 4.7 ms for PR intervals, 5.8 ms for QRS duration, and 12.4 ms for QT intervals. In pairwise comparison programs showed similar accuracy for most ECGs, with the average absolute errors at the 75th percentile for PR intervals being 4-6 ms from the median, QRS duration 4-8 ms, and QT interval 6-10 ms. However, substantial differences were present in the numbers and extent of large, clinically significant errors (e.g at the 98th percentile), for which programs differed by a factor of two for absolute errors, as well as differences in the mix of overestimations and underestimations.Conclusions: When reading digital ECGs, users should be aware that small systematic differences exist between programs and that there may be large clinically important errors in difficult cases. [ABSTRACT FROM AUTHOR]

Objective: In MADIT-CRT, patients with non-LBBB (right bundle branch block or nonspecific ventricular conduction delay) and a prolonged PR-interval derived significant clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) compared to an implantable cardioverter defibrillator (ICD)-only. We aimed to study the long-term outcome of non-LBBB patients by baseline PR-interval with CRT-D versus ICD-only. Methods: Non-LBBB patients ( n = 534) were dichotomized based on baseline PR-interval: normal PR (PR < 230 ms), and markedly prolonged PR (PR ≥ 230 ms). The primary end point was heart failure (HF) or death. Secondary end points were HF only and all-cause death. Results: In patients with a prolonged PR-interval, CRT-D treatment related to a 67 % significant reduction in the risk of HF/death (HR = 0.33, 95 % CI 0.16-0.69, p = 0.003), 69 % decrease in HF (HR = 0.31, 95 % CI 0.14-0.68, p = 0.003), and 76 % reduction in the risk of death (HR = 0.24, 95 % CI 0.07-0.80, p = 0.020) compared to ICD-only (median follow-up 5.8 years). In normal PR-interval patients, CRT-D therapy was associated with a trend towards increased risk of HF/death (HR = 1.49, 95 % CI 0.98-2.25, p = 0.061), and significantly increased mortality (HR = 2.27, 95 % CI 1.16-4.44, p = 0.014). Significant statistical interaction with the PR-interval was demonstrated for all end points. Results were consistent for QRS 130-150 ms and QRS > 150 ms. Conclusion: In MADIT-CRT, non-LBBB patients with a prolonged PR-interval derive sustained long-term clinical benefit with reductions in heart failure or death from CRT-D implantation, compared to an ICD-only. Our findings support implantation of CRT-D in non-LBBB patients with prolonged PR-interval irrespective of baseline QRS duration. [ABSTRACT FROM AUTHOR]

Background: There is a strong interest in PR interval as a predictor for adverse outcomes. However, inconsistent reports have emerged. Objective: The purpose of this study was to test the hypothesis that the significance of PR interval as a predictor depends on the level of contribution of P duration to its length, a contribution that varies across populations. Methods: We tested our hypothesis in 7501 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Participants were divided into two subgroups based on the median P-duration contribution to PR interval (P duration/PR interval * 100). The risk of mortality associated with prolonged (>200 ms) and short (<120 ms) PR interval compared with normal PR interval was examined in all participants and each subgroup. Results: P-duration contribution to the length of PR interval ranged from 30% to 90% (median 70%). During median follow-up of 13.8 years, 2541 deaths occurred. In a multivariable adjusted model, short but not prolonged PR interval was associated with mortality (hazard ratio [HR], (95% confidence interval [CI]): 1.54 (1.18, 2.00) and 1.02 (0.90, 1.16), respectively). However, in a stratified analysis by P-duration contribution to PR interval, both short and prolonged PR interval were associated with mortality in participants with high P-duration contribution (HR (95% CI):1.46 (1.10, 1.94) and 2.00 (1.34, 2.99), respectively) but not in participants with low P-duration contribution (HR (95% CI):1.53 (0.68, 3.41) and 0.99 (0.87, 1.13), respectively); interaction P = .008. Conclusion: PR-interval associations with outcomes are dictated by the level of contribution of P duration to its length, a contribution that has a wide range and is expected to vary across populations. These findings could explain the inconsistent reports of PR-interval associations in different studies and call for caution when using PR interval in risk prediction models. [Copyright &y& Elsevier]

The present study was conducted in chronic open angle glaucoma patients to evaluate their efficacy in reducing IOP and their cardiovascular safety. 48 newly diagnosed patients of glaucoma completed the trial. Patients were divided into three groups and received medications in form of topical instillations. Group I (Timolol 0.5% twice a day), Group II (Brimonidine Tatrate 0.2% twice a day) & Group III (Latanoprost 0.005% once a day) for 12 weeks. All the three medications, significantly decreased IOP (P<0.05), however, Latanoprost caused maximum decrease in IOP, followed by Brimonidine and Timolol. Visual Acquity was not affected by any of the medication. Pulse Rate and PR Interval were decreased in Timolol group significantly (P < 0.001) while Brimonidine and Latanoprost did not alter Pulse Rate. Blood Pressure was not affected by either of medication except Brimonidine which caused reduction in systolic Blood Pressure at 12 weeks. The results of present study demonstrates superiority of Latanoprost over Timolol and Brimonidine as it lacked effect on Pulse Rate, Blood Pressure and HR, besides being more efficacious [ABSTRACT FROM AUTHOR]

Abstract: We investigated (i) the effectiveness of glucosamine (GlcN) in treating adjuvant arthritis (AA) and its cardiac abnormalities (down regulation of cardiac calcium channel and beta-adrenergic proteins) (ii) the effect of AA on pharmacokinetics of GlcN and the cardiac ryanodine-2 target protein. Six groups (n =6/group) of male Sprague–Dawley rats were treated with Mycobacterium butyricum (Inflamed) or saline (Control). One group received GlcN hydrochloride (300mg/kg/day, p.o. commenced on day one); others received GlcN upon developing the early sign of AA; after amelioration of the disease, the GlcN administration continued for one group while discontinued for another. Subsequently, a 25mg/kg verapamil administered, electrocardiographs were recorded and pharmacokinetic delineated. Serum nitrite concentration, body weight, paw thickness and arthritis index were assessed. Cardiac contents of L-type calcium channel, β1-adrenoreceptors and ryanodine-2 receptor were measured. All rats that received M. butyricum, but not GlcN, developed arthritis. GlcN prevented arthritis and improved the signs and symptoms after their emergence. It also restores the down-regulating effect of AA on the cardiac target proteins, pharmacokinetics and response to verapamil. Inflammation did not influence pharmacokinetics of GlcN and the density of ryanodine-2 protein. GlcN has controlling effect on AA and restores the down-regulating effect of AA on cardiac proteins and response to verapamil, perhaps, through its anti-inflammatory properties. [Copyright &y& Elsevier]

In this experimental study we measured the magnetocardiograms (MCGs) of 17 normals at 42 measuring sites in a plane near the chest. The recordings were made in an unshielded environment with a single channel second-order SOUID gradiometer. From these recordings spatial maps were constructed of the atrial depolarisation and repolarisation. The two series of maps were found to be dipolar, but opposite in sign for 14 of the 17 subjects. The relatively small change in the amplitude and pattern of the atrial repolarisation maps built up out confidence in the method of subtracting a computed mean repolarisation map from the maps obtained during the last 40 ms before the QRS-onset. This method of separating His-Purkinje activity from atrial repolarisation led to distinct dipolar patterns in 9 out of the 17 cases. The direction and location of the associated electric current dipole was in good agreement with what can be expected electrophysiologically for His-Purkinje activation. [ABSTRACT FROM AUTHOR]

Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap-junctions containing connexin43 coupling cardiomyocytes and inflammation-related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms. Methods and Results We analyzed: (1) the PR-interval in patients with inflammatory diseases of different origins during active phase and recovery, and its association with inflammatory markers; (2) the existing correlation between connexin43 expression in the cardiac tissue and peripheral blood mononuclear cells (PBMC), and the changes occurring in patients with inflammatory diseases over time; (3) the acute effects of interleukin(IL)-6 on atrioventricular conduction in an in vivo animal model, and on connexin43 expression in vitro. In patients with elevated C-reactive protein levels, atrioventricular conduction indices are increased, but promptly normalized in association with inflammatory markers reduction, particularly IL-6. In these subjects, connexin43 expression in PBMC, which is correlative of that measured in the cardiac tissue, inversely associated with IL-6 changes. Moreover, direct IL-6 administration increased atrioventricular conduction indices in vivo in a guinea pig model, and IL-6 incubation in both cardiomyocytes and macrophages in culture, significantly reduced connexin43 proteins expression. Conclusions The data evidence that systemic inflammation can acutely worsen atrioventricular conduction, and that IL-6-induced down-regulation of cardiac connexin43 is a mechanistic pathway putatively involved in the process. Though reversible, these alterations could significantly increase the risk of severe atrioventricular blocks during active inflammatory processes.