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Background: Undersensing of premature ventricular beats and low-amplitude R waves are primary causes for inappropriate bradycardia and pause detections in insertable cardiac monitors (ICMs)., Objective: The purpose of this study was to develop and validate an enhanced algorithm to reduce inappropriately detected bradycardia and pause episodes., Methods: Independent data sets to develop and validate the enhanced algorithm were derived from a database of ICM-detected bradycardia and pause episodes in de-identified patients monitored for unexplained syncope. The original algorithm uses an auto-adjusting sensitivity threshold for R-wave sensing to detect tachycardia and avoid T-wave oversensing. In the enhanced algorithm, a second sensing threshold is used with a long blanking and fixed lower sensitivity threshold, looking for evidence of undersensed signals. Data reported includes percent change in appropriate and inappropriate bradycardia and pause detections as well as changes in episode detection sensitivity and positive predictive value with the enhanced algorithm., Results: The validation data set, from 663 consecutive patients, consisted of 4904 (161 patients) bradycardia and 2582 (133 patients) pause episodes, of which 2976 (61%) and 996 (39%) were appropriately detected bradycardia and pause episodes. The enhanced algorithm reduced inappropriate bradycardia and pause episodes by 95% and 47%, respectively, with 1.7% and 0.6% reduction in appropriate episodes, respectively. The average episode positive predictive value improved by 62% (P < .001) for bradycardia detection and by 26% (P < .001) for pause detection, with an average relative sensitivity of 95% (P < .001) and 99% (P = .5), respectively., Conclusion: The enhanced dual sense algorithm for bradycardia and pause detection in ICMs substantially reduced inappropriate episode detection with a minimal reduction in true episode detection., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

This study was to investigate the changes of autonomic nerve function and hemodynamics in patients with vasovagal syncope (VVS) during head-up tilt-table testing (HUT). HUT was performed in 68 patients with unexplained syncope and 18 healthy subjects served as control group. According to whether bradycardia, hypotension or both took place during the onset of syncope, the patients were divided during the test into three subgroups: vasodepressor syncope (VD), cardioinhibitory syncope (CI) and mixed syncope (MX) subgroups. Heart rate, blood pressure, heart rate variability (HRV), and deceleration capacity (DC) were continuously analyzed during HUT. For all the subjects with positive responses, the normalized low frequency (LFn) and the LF/HF ratio markedly decreased whereas normalized high frequency (HFn) increased when syncope occurred. Syncopal period also caused more significant increase in the power of the DC in positive groups. These changes were more exaggerated compared to controls. All the patients were indicative of a sympathetic surge in the presence of withdrawal vagal activity before syncope and a sympathetic inhibition with a vagal predominance at the syncopal stage by the frequency-domain analysis of HRV. With the measurements of DC, a decreased vagal tone before syncope stage and a vagal activation at the syncopal stage were observed. The vagal tone was higher in subjects showing cardioinhibitory responses at the syncopal stage. DC may provide an alternative method to understand the autonomic profile of VVS patients.

Bradyarrhythmias in adults with congenital heart disease (CHD) comprise a complex group of arrhythmia disorders with congenital and acquired origins, highly variable long-term sequelae, and complicated treatment options. They can develop across the spectrum of CHD defects and can be encountered at all ages. Although permanent pacing is effective in treating bradyarrhythmias, it is associated with many complications and morbidity, where it is often used early in life. This section discusses the incidence and prevalence of bradyarrhythmias in the CHD population, their timing of occurrence with respect to specific disease entities and interventions, and their short- and long-term clinical sequelae., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals., (Copyright © 2017 the American Physiological Society.)

Background: Syncope is a common problem in the elderly, and a permanent pacemaker is a therapeutic option when a bradycardic etiology is revealed. However, the benefit of pacing when no association of symptoms to bradycardia has been shown is not clear, especially in the elderly., Objective: The aim of this study was to evaluate the effect of pacing on syncope-free mortality in patients aged 80 years or older with unexplained syncope and "positive" invasive electrophysiologic testing (EPT)., Methods: This was an observational study. A positive EPT for the purposes of this study was defined by at least 1 of the following: a corrected sinus node recovery time of >525 ms, a basic HV interval of >55 ms, detection of infra-Hisian block, or appearance of second-degree atrioventricular block on atrial decremental pacing at a paced cycle length of >400 ms., Results: Among the 2435 screened patients, 228 eligible patients were identified, 145 of whom were implanted with a pacemaker. Kaplan-Meier analysis determined that time to event (syncope or death) was 50.1 months (95% confidence interval 45.4-54.8 months) with a pacemaker vs 37.8 months (95% confidence interval 31.3-44.4 months) without a pacemaker (log-rank test, P = .001). The 4-year time-dependent estimate of the rate of syncope was 12% vs 44% (P < .001) and that of any-cause death was 41% vs 56% (P = .023), respectively. The multivariable odds ratio was 0.25 (95% confidence interval 0.15-0.40) after adjustment for potential confounders., Conclusion: In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive EPT, pacemaker implantation was independently associated with longer syncope-free survival. Significant differences were also shown in the individual components of the primary outcome measure (syncope and death from any cause)., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: It is thought that abnormal cardiac impulses of the autonomic nervous system during sleep are responsible for sleep-related bradyarrhythmias. Despite a proposed common etiopathogenesis and having common name of "sleep-related bradyarrhythmias," precise importance of sinoatrial or atrioventricular (AV) node involvement remains elusive. This study aimed to determine whether there is a difference in sleeprelated bradyarrhythmias from the point of view of heart rate variability (HRV)., Methods: Patients were evaluated using 24-hour Holter electrocardiogram monitor. After careful medical evaluation, apparently healthy individuals with sleep-related sinus pauses ≥2 seconds on at least 1 occasion or those in whom Mobitz type I AV block occurred were included. Frequency and time domain analyses were conducted for daytime, nighttime, and 24-hour period., Results: Total of 37 patients with sinus pause(s), 40 patients with Mobitz type I AV block(s), and 40 healthy controls were included. On HRV analyses, all time and frequency domain parameters were better in sinus pause group for daytime, nighttime, and 24-hour average (p<0.05 for all). Results of heart rate-corrected HRV analyses still showed significantly better total power (TP) and very low frequency (VLF) in the sinus pause group compared with AV block group (TP: 7.1x10-3 vs. 5.4x10-3, p=0.011; VLF: 4.9x10-3 vs. 3.7x10-3, p=0.007)., Conclusion: Despite proposed common autonomic mechanisms, sleep-related sinus pause cases demonstrated better HRV profile in comparison with Mobitz type I AV block.

Background: This study was conducted to assess the prevalence and characterization of CAD in high risk patients requiring pacemaker implantation for symptomatic bradyarrhythmias., Methods: This study included 100 patients with symptomatic sinus node dysfunction or atrioventricular block, who were at high risk of CAD or had previously documented atherosclerotic vascular disease (ASCVD). Coronary angiography was performed before pacemaker implantation. CAD was defined as the presence of any degree of narrowing in at least one major coronary artery or its first order branch. Obstructive CAD was defined as ≥50% diameter stenosis. CAD was categorized as single vessel disease (SVD), double vessel disease (DVD), or triple vessel disease (TVD); and obstructive CAD in the arteries supplying the conduction system was sub-classified according to Mosseri's classification., Results: Out of 100 patients (mean age 64.6±10.7 years), 45 (45%) had CAD. 29% patients had obstructive CAD while 16% had non-obstructive CAD. 53.3% patients had SVD, 15.6% had DVD and 31.1% had TVD. Among patients with obstructive CAD; Type I, II, III and IV coronary anatomies were present in 6.9%, 34.5%, 10.3% and 48.3% patients respectively. Presence of CAD significantly correlated with dyslipidemia (p=0.047), history of smoking (p=0.025), and family history of CAD (p=0.002)., Conclusion: Angiographic CAD is observed in a substantial proportion of patients with symptomatic bradyarrhythmias and risk factors for CAD. It could be argued that such patients should undergo a coronary work-up before pacemaker implantation. Treatment of concomitant CAD is likely to improve the long term prognosis of these patients., (Copyright © 2016. Published by Elsevier B.V.)

Aims: It is generally recommended that individuals aspiring to competitive sports should undergo pre-participation cardiovascular assessment, particularly including arrhythmia risk evaluation. In regard to bradyarrhythmias, the 36th Bethesda Conference suggested that asymptomatic cardiac pauses ≤3 s are 'probably of no significance', whereas longer 'symptomatic' pauses may be abnormal. This study focused on assessing the evidence for the '3 s' threshold., Methods: A systematic literature search was undertaken including Embase (1980-) and Ovid Medline (1950-). The following MeSH terms were used in the database searches: Cardiac.mp & pause.mp. Additionally, pertinent publications found by review of citation lists of identified publications were examined. Individuals with reversible causes of bradyarrhythmia (e.g. drugs) were excluded., Results: The study population comprised 194 individuals with cardiac pauses of 1.35-30 s. In 120 athletes, specific records for pause durations were provided, but it was not always clear whether pauses occurred at rest. Among these 120 athletes, 106 had pauses ≤3 s, of whom 92 were asymptomatic and 14 were symptomatic. Fourteen athletes had pauses >3 s, of whom nine were asymptomatic and five were symptomatic. There were no deaths during follow-up (7.46 ± 5.1 years). With respect to symptoms, the ≤3 s threshold had a low-positive predictive value (35.7%) and low sensitivity (26.3%), but good negative predictive value (86.7%) and specificity (91%)., Conclusion: While the evidence is not incontrovertible, the 3 s pause threshold does not adequately discriminate between potentially asymptomatic and symptomatic competitive athletes, and alone should not be used to exclude potential competitors., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Seizures can lead to cardiac arrhythmias by a number of mechanisms including activation/inhibition of cortical autonomic centers, increase in vagal tone through activation of brainstem reflex centers, and respiratory failure. Ictal asystole (IA) is a potential mechanism underlying sudden unexpected death in epilepsy (SUDEP). We analyzed the clinical features of 5 patients who developed IA requiring pacemaker implantation., Methods: Patients with ictal arrhythmias were identified from the video-telemetry and ambulatory EEG database at Greater Manchester Neurosciences Centre, as well as an independent epilepsy residential care facility. Only those who had IA requiring pacemaker implantation were included in the analysis. A total of 5 patients were identified., Results: Of the 5 patients with IA, 4 were female. All 5 patients had focal epilepsy, and four had temporal lobe epilepsy. Ictal asystole occurred with focal seizures with impairment of awareness. Seizure onset was left-sided in 2 patients, right-sided in one, left-sided onset with switch of lateralization in one, and nonlateralized in one patient. Three patients had hippocampal sclerosis, one of whom had undergone epilepsy surgery, one had traumatic encephalomalacia of the temporal lobe, and one patient had no lesions detected on MRI. Interictal epileptiform activity was more pronounced during sleep in all patients. Asystole occurred in association with sleep-related seizures in 4 of 5 patients., Conclusions: Ictal asystole (IA) occurred in association with sleep-related seizures in 4 out of 5 cases, predominantly in patients with temporal lobe epilepsy. These findings may be of relevance to SUDEP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose of Review: This review article focuses on the most significant cardiovascular complications in dialysis patients [sudden cardiac death (SCD), acute coronary syndromes, heart failure, and atrial fibrillation]., Recent Findings: Current and ongoing research aims to quantify the rate and pattern of significant arrhythmia in dialysis patients and to determine the predominant mechanism of SCD. Preliminary findings from these studies suggest a high rate of atrial fibrillation and that bradycardia and asystole may be more frequent than ventricular arrhythmia as a cause of sudden death. A recently published matched cohort study in dialysis patients who received a defibrillator for primary prevention showed that there was no significant difference in mortality rates between defibrillator-treated patients and propensity-matched controls. Two randomized controlled trials are currently recruiting participants and will hopefully answer the question of whether implantable or wearable cardioverter defibrillators can prevent SCD. An observational study using United States Renal Data System data demonstrated how difficult it is to keep hemodialysis patients on warfarin, as more than two-thirds discontinued the drug during the first year. The ISCHEMIA-CKD trial may provide answers about the optimal strategy for the treatment of atherosclerotic coronary disease in patients with advanced chronic kidney disease., Summary: The article reviews the diagnosis of acute coronary syndromes in dialysis patients, current literature on myocardial revascularization, and data on fatal and nonfatal cardiac arrhythmia. The new classification of heart failure in end-stage renal disease is reviewed. Finally, available cohort studies on warfarin for stroke prevention in dialysis patients with atrial fibrillation are reviewed., Competing Interests: Dr. Charytan has received research funding from Medtronic and Janssen pharmaceuticals for work on the MiD and CREDENCE trials, consulting fees from Zoll Medical for work on the steering committee of the WEDHEAD trial and consulting fees from Medtronic.

Background: Cardio-Renal Syndromes were first classified in 2008 and divided into five subtypes. The type 1 Cardio-Renal Syndrome (CRS) is characterized by acute decompensation of heart failure leading to acute kidney injury (AKI). Bradyarrhythmia was not mentioned in the classification as a cause for low cardiac output (CO) in type 1 CRS. Besides, CRS was not previously associated with central nervous system (CNS) injury despite the fact that cardiac, renal and neurological diseases can coexist., Case Presentation: We report the case of a 93-year old diabetic man who presented for obnubilation. He had a slow atrial fibrillation, was not hypotensive and was not taking any beta-blocker. He developed, simultaneously, during his hospitalization, severe bradycardia (<35 beats per minute), oligoanuria and further neurological deterioration without profound hypotension. An ECG revealed a complete atrioventricular (AV) block and all his symptoms were completely reversed after pacemaker insertion. His creatinine decreased progressively afterwards and at discharge, he was conscious, alert and well oriented., Conclusion: Our case highlights the importance of an early recognition of low cardiac output secondary to severe bradyarrhythmia and its concurrent repercussion on the kidney and the brain. This association of the CRS with CNS injury-that we called "Cardio-Renal-Cerebral Syndrome"-was successfully treated with permanent pacemaker implantation.

The aim of this study was to evaluate whether endurance athletes who exhibit deep bradycardia are more prone to arrhythmias and reflex syncope than their non-bradycardic peers. 46 healthy men (ages 19-35) were divided into 3 groups based on whether they were sedentary (SED,<2 h/week) or endurance trained (ET,>6 h/week), and non-bradycardic (NB, resting heart rate (HR)≥60 bpm) or bradycardic (B, resting HR<50 bpm). Resting HR was lower in ETB vs. ETNB and SED (43.8±3.1, 61.3±3.3, 66.1±5.9 bpm, respectively; p<0.001). Thus, 16 SED, 13 ETNB and 17 ETB underwent resting echocardiography, maximal exercise test, tilt test (TT) and 24 h-Holter ECG. Subjects were followed-up during 4.7±1.1 years for training, syncope and cardiac events. Our results showed that incidence of arrhythmias and hypotensive susceptibility did not differ between groups. During follow-up, no episode of syncope or near-syncope was reported. However, cardio-inhibitory syncope occurrence tended to be higher in ETB. Left ventricular end-diastolic diameter index was increased in ETB vs. ETNB and was correlated with resting HR (r=- 0.64; p<0.001). As a result, athletes with deep bradycardia do not present more arrhythmias and more hypotensive susceptibility than their non-bradycardic peers. Cardiac enlargement and autonomic alteration both seem to be involved in an athlete's bradycardia., (© Georg Thieme Verlag KG Stuttgart · New York.)

We have developed a rechargeable fetal micropacemaker in order to treat severe fetal bradycardia with comorbid hydrops fetalis, a life-threatening condition in pre-term non-viable fetuses for which there are no effective treatment options. The small size and minimally invasive form factor of our design limit the volume available for circuitry and a power source. The device employs a fixed-rate and fixed-amplitude relaxation oscillator and a tiny, rechargeable lithium ion power cell. For both research and clinical applications, it is valuable to monitor the electrode-myocardium interface in order to determine that adequate pacemaker output is being provided. This is typically accomplished by observing the minimal stimulus strength that achieves threshold for pacing capture. The output of our simple micropacemaker cannot be programmatically altered to determine this minimal capture threshold, but a safety factor can be inferred by determining the refractory period for ventricular capture at a given stimulus strength. This is done by measuring the minimal timing between naturally occurring QRS complexes and pacing stimuli that successfully generate a premature ventricular contraction. The method was tested in a pilot study in four fetal sheep and the data demonstrate that a relative measure of threshold is obtainable. This method provides valuable real-time information about the electrode-tissue interface.

An 89-year-old woman with severe aortic valve stenosis and bradycardia presented with circulatory shock due to cardiac tamponade. We performed pericardiocentesis, and then diagnosed right ventricular perforation by echocardiography with microcavitation contrast medium just before inserting a drainage tube. We then inserted the drainage tube in the appropriate position and withdrew blood-filled fluid. The patient was haemodynamically stabilised, but haemorrhage from the perforation site continued for a few days. We injected fibrin glue into the pericardial space through the drainage tube and achieved haemostasis. Thus, we avoided surgery to close the perforation in this high-risk patient. There was no recurrence of haemorrhage. She subsequently had elective aortic valve replacement at another hospital. No adhesions in the pericardial space were seen during surgery., (2016 BMJ Publishing Group Ltd.)

Bradyarrhythmias cause symptoms such as syncope, dizziness, or exercise intolerance and lead to the implantation of > 100 000 pacemakers in Germany annually. They are caused either by sinus node dysfunction (sinus bradycardia, sinoatrial block, sinusarrest, preautomatic pauses in paroxysmal atrial fibrillation, chronotropic incompetence) or by atrioventricular (AV) conduction abnormalities (AV block, complex bundle branch block). Optimal therapy of bradycardia crucially depends on ECG documentation which frequently requires Holter monitoring in the case of intermittent bradycardia. The differential diagnosis of the ECG can sometimes be demanding, for instance in distinguishing sinus bradycardia or AV block from blocked supraventricular premature beats, in understanding chronotropic sinus node incompetence, 2:1 AV block, complete AV block in atrial fibrillation, bifascicular and imminent trifascicular bundle branch block or vagally induced bradycardia. This review presents the ECG in bradycardia and provides tips for a confident interpretation., (© Georg Thieme Verlag KG Stuttgart · New York.)

As anorexia patients always go to the psychiatric clinic, little is concerned about the occurrence of sinus bradycardia in these patients for cardiologists and psychiatrists. The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia, and the feature analysis, differential diagnosis and therapeutic principles of this type of sinus bradycardia. We report a case of sinus bradycardia in an anorexia patient with the clinical manifestations, laboratory exams, auxiliary exams, therapeutic methods, and her prognosis, who was admitted to Peking University Third Hospital recently. The patient was a 19-year-old female, who had the manifestation of anorexia. She lost obvious weight in a short time (about 15 kg in 6 months), and her body mass index was 14.8 kg/m(2). The patient felt apparent palpitation, chest depression and short breath, without dizziness, amaurosis or unconsciousness. Vitals on presentation were notable for hypotension, and bradycardia. The initial exam was significant for emaciation, but without lethargy or lower extremity edema. The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute. The laboratory work -up revealed her normal blood routine, electrolytes and liver function. But in her thyroid function test, the free thyroid (FT) hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L (8.9-18.0 ng/L), which were all lower; yet the thyroid stimulating hormone (TSH) was normal 1.48 IU/mL (0.55-4.78 IU/mL). Ultrasound revealed her normal thyroid. Anorexia is an eating disorder characterized by extremely low body weight, fear of gaining weight or distorted perception of body image, and amenorrhea. Anorexia patients who lose weight apparently in short time enhance the excitability of the parasympathetic nerve, and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia, and functional abnormalities of multiple systems such as hypothyroidism. But this kind of sinus bradycardia and hypothyroidism have good prognosis. And asymptomatic sinus bradycardia with reversible causes, because of the great prognosis, they do not need special treatment. Multiple medical and psychiatric disciplines were consulted, and then, family care, nutritional support and psychiatric therapy were given, and she did not need thyroid hormone replacement therapy. The patient's overall clinical status improved gradually during her hospital stay and her heart rate was recovered to 55 beats per minute.

Background: Cardio neuroablation (CNA) is a lesser-known technique for management of patients with excessive vagal activation on the basis of radiofrequency catheter ablation (RFCA) of the areas related to the three main autonomic ganglia around the heart. We investigated the effectiveness of selective and/or stepwise RFCA of these areas via right atrium (RA) and/or left atrium (LA) in the patients with recurrent syncope due to excessive vagal activity., Methods: Twenty-two patients presenting symptomatic functional bradyarrhythmias, neurally mediated reflex syncope (NMS), symptomatic atrioventricular (AV) block, and symptomatic sinus node dysfunction (SND; number = 8, 7, 7, respectively) were enrolled. The three main paracardiac ganglia were targeted via RA and LA in the patients with NMS and SND. The procedure was performed via RA in the patients with AV block, followed by RFCA of all ganglia via LA, if AV conduction disorder persists. The sites showing fragmented potentials were identified by electrical mapping and verified by high-frequency stimulation and ablated until atrial electrical potential was completely eliminated (<0.1 mV)., Results: The patients with NMS and SND were free from new syncopal episode at a mean 12.3 ± 3.4 months and 9.5 ± 3.1 months follow-up, respectively. Ablation from RA was successful in six of seven patients with AV block. Despite the increased heart rate, the resolution of AV block after the RFCA could not be achieved in one patient who had partial resolution with atropine infusion on admission., Conclusion: CNA may be an alternative and safe strategy to reduce NMS episodes, and to treat functional AV block and symptomatic SND, especially in young patients., (© 2015 Wiley Periodicals, Inc.)

Although diagnostically indispensable, magnetic resonance imaging (MRI) has been, until recently, contraindicated in patients with an implantable cardiac device. MR conditional cardiac devices are now widely used, but the mode programming needed for safe MRI has yet to be established. We reviewed the details of 41 MRI examinations of patients with a MR conditional device. There were no associated adverse events. However, in 3 cases, paced beats competed with the patient's own beats during the MRI examination. We describe 2 of the 3 specific cases because they illustrate these potentially risky situations: a case in which the intrinsic heart rate increased and another in which atrial fibrillation occurred. Safe MRI in patients with an MR conditional device necessitates detailed MRI mode programming. The MRI pacing mode should be carefully and individually selected.

Background: In cardiac ischaemia, the accumulation of adenosine may lead to or exacerbate bradyasystole and diminish the effectiveness of catecholamines administered during resuscitation. Aminophylline is a competitive adenosine antagonist. Case studies suggest that aminophylline may be effective for atropine-resistant bradyasystolic arrest., Objectives: To determine the effects of aminophylline in the treatment of patients in bradyasystolic cardiac arrest, primarily survival to hospital discharge. We also considered survival to admission, return of spontaneous circulation, neurological outcomes and adverse events., Search Methods: For this updated review, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform in November 2014. We checked the reference lists of retrieved articles, reviewed conference proceedings, contacted experts and searched further using Google., Selection Criteria: All randomised controlled trials comparing intravenous aminophylline with administered placebo in adults with non-traumatic, normothermic bradyasystolic cardiac arrest who were treated with standard advanced cardiac life support (ACLS)., Data Collection and Analysis: Two review authors independently reviewed the studies and extracted the included data. We contacted study authors when needed. Pooled risk ratio (RR) was estimated for each study outcome. Subgroup analysis was predefined according to the timing of aminophylline administration., Main Results: We included five trials in this analysis, all of which were performed in the prehospital setting. The risk of bias was low in four of these studies (n = 1186). The trials accumulated 1254 participants. Aminophylline was found to have no effect on survival to hospital discharge (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.12 to 2.74) or on secondary survival outcome (survival to hospital admission: RR 0.92, 95% CI 0.61 to 1.39; return of spontaneous circulation: RR 1.15, 95% CI 0.89 to 1.49). Survival was rare (6/1254), making data about neurological outcomes and adverse events quite limited. The planned subgroup analysis for early administration of aminophylline included 37 participants. No one in the subgroup survived to hospital discharge., Authors' Conclusions: The prehospital administration of aminophylline in bradyasystolic arrest is not associated with improved return of circulation, survival to admission or survival to hospital discharge. The benefits of aminophylline administered early in resuscitative efforts are not known.

Aim: Intrapartum fetal bradycardia necessitates immediate operative delivery. Our aim was to investigate the hypothesis that some non-reassuring fetal heart rate (FHR) patterns were present before the onset of terminal bradycardia in infants who developed subsequent brain damage., Material and Methods: From a population-based study of 65,197 deliveries, 190 stillbirths, 115 neonatal deaths, and 136 neurologically high-risk infants were registered by the Miyazaki Perinatal Conference. There were 15 cases of neurologically high-risk infants born at >34 weeks of gestation exhibiting intrapartum terminal bradycardia. Focusing on the brain-damaged infants, we retrospectively analyzed FHR patterns for at least 1 h prior to the bradycardia., Results: Brain damage (cerebral palsy [n = 11] and mental retardation [n = 2]) was diagnosed at 2 years old in 13 out of 15 neurologically high-risk infants. Two infants had bradycardia on admission. In the remaining 11 infants, FHR patterns were reassuring in six (55%) and non-reassuring in five (45%), including late decelerations (n = 4) and variable decelerations (n = 2). Clinically relevant factors in the non-reassuring group included intrauterine infection (n = 3), malpresentation with umbilical cord coiling (n = 1), and unknown causes (n = 1). Clinically relevant features in the reassuring group included cord prolapse (n = 1), vaginal breech delivery (n = 1), shoulder dystocia (n = 1), rupture of membranes (n = 1), and unknown causes (n = 2)., Conclusion: More than half of the brain-damaged infants born at >34 weeks of gestation who exhibited intrapartum terminal bradycardia had unremarkable FHR patterns before abrupt-onset bradycardia. For those with non-reassuring patterns preceding bradycardia, intrauterine infection was the major sentinel event., (© 2015 Japan Society of Obstetrics and Gynecology.)

Swallow syncope is a rare form of situational syncope. We report a case of swallow syncope with invasive confirmation of esophageal hypertension (spasm) and invasive confirmation of a bradycardia mechanism. Awareness of this uncommon disorder is important as a treatable cause of syncope.

Background: Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption., Objectives: The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia., Methods: We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography)., Results: In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function., Conclusions: We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is a frequent comorbidity in patients with pacemaker and is a recognized cause of mortality, morbidity, and quality-of-life impairment. The international MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial established that atrial preventive pacing and atrial antitachycardia pacing (DDDRP) in combination with managed ventricular pacing (MVP) reduce permanent AF occurrence in comparison with standard dual-chamber pacing (DDDR)., Objective: We aimed to determine the role of new-generation atrial antitachycardia pacing (Reactive ATP) in preventing AF disease progression., Methods: Patients with dual-chamber pacemaker and with previous atrial tachyarrhythmias were randomly assigned to DDDR (n = 385 (33%)), MVP (n = 398 (34%)), or DDDRP+MVP (n = 383 (33%)) group. The incidence of permanent AF, as defined by the study investigator, or persistent AF, defined as ≥7 consecutive days with AF, was estimated using the Kaplan-Meier method, while its association with patients' characteristics was evaluated via multivariable Cox regression., Results: At 2 years, the incidence of permanent or persistent AF was 26% (95% confidence interval [CI] 22%-31%) in the DDDR group, 25% (95% CI 21%-30%) in the MVP group, and 15% (95% CI 12%-20%) in the DDDRP+MVP group (P < .001 vs. DDDR; P = .002 vs. MVP). Generalized estimating equation-adjusted Reactive ATP efficacy was 44.4% (95% CI 41.3%-47.6%). Multivariate modeling identified high Reactive ATP efficacy (>44.4%) as a significant predictor of reduced permanent or persistent AF risk (hazard ratio 0.32; 95% CI 0.13-0.781; P = .012) and episodes' characteristics, such as long atrial arrhythmia cycle length, regularity, and the number of rhythm transitions, as predictors of high ATP efficacy., Conclusion: In patients with bradycardia, DDDRP+MVP delays AF disease progression, with Reactive ATP efficacy being an independent predictor of permanent or persistent AF reduction., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Sinus node disease (SND), a common indication to implant a pacemaker, is frequently associated with atrial fibrillation (AF), either at implantation (paroxysmal AF) or during follow-up, which often evolves to persistent or permanent AF. Pacemakers with an atrial lead allow continuous monitoring of the atrial rhythm and enable detection of the burden of AF. Asymptomatic atrial tachyarrhythmias, being associated with increased risk of stroke, have important prognostic implications, and their detection could guide decision-making about antithrombotic prophylaxis. Pacing mode and pacing algorithms can influence the occurrence of AF and atrial tachyarrhythmias. In DDD/DDDR pacing mode, reduction of unnecessary right ventricular pacing positively affects the occurrence and evolution of AF, but patients with a history of atrial tachyarrhythmias maintain an increased risk of arrhythmic events. In the MINERVA study, the use of algorithms that act in the atrium for preventive pacing and atrial antitachycardia pacing while minimizing right ventricular pacing was beneficial in patients with SND and previous atrial tachyarrhythmias, and was associated with a significant reduction in evolution to permanent AF. New information available on therapies delivered at the atrial level by implanted devices suggests clinical advantages that could improve current guidelines for the management of AF and atrial tachyarrhythmias.

A 17-year-old patient with type III Gaucher disease was hospitalized for recurrent syncope. Echocardiography showed calcified aortic and mitral stenosis. Three-dimensional computed tomography showed severely calcified plaques on the ascending aorta, arcus, and abdominal aorta. On follow-up, palpitations and syncope were triggered by emotional stress, followed by severe bradycardia that was resulted in cardiogenic shock; the patient died after 8 h despite all efforts. Gaucher disease should be kept in mind in the differential diagnosis of a young patient with extensive vascular and valvular calcification. Patients with symptomatic severe valvular disease must be referred for early surgery., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

The aim of the study was to evaluate the possible contribution of non-endothelial eNOS to the regulation of blood pressure (BP). To accomplish this, a double transgenic strain expressing eNOS exclusively in the vascular endothelium (eNOS-Tg/KO) has been generated by endothelial-specific targeting of bovine eNOS in eNOS-deficient mice (eNOS-KO). Expression of eNOS was evaluated in aorta, myocardium, kidney, brain stem and skeletal muscle. Organ bath studies revealed a complete normalization of aortic reactivity to acetylcholine, phenylephrine and the NO-donors in eNOS-Tg/KO. Function of eNOS in resistance arteries was demonstrated by acute i.v. infusion of acetylcholine and the NOS-inhibitor L-NAME. Acetylcholine decreased mean arterial pressure in all strains but eNOS-KO responded significantly less sensitive as compared eNOS-Tg/KO and C57BL/6. Likewise, acute i.v. L-NAME application elevated mean arterial pressure in C57BL/6 and eNOS-Tg/KO, but not in eNOS-KO. In striking contrast to these findings, mean, systolic and diastolic BP in eNOS-Tg/KO remained significantly elevated and was similar to values of eNOS-KO. Chronic oral treatment with L-NAME increased BP to the level of eNOS-KO only in C57BL/6, but had no effect on hypertension in eNOS-KO and eNOS-Tg/KO. Taken together, functional reconstitution of eNOS in the vasculature of eNOS-KO not even partially lowered BP. These data suggest that the activity of eNOS expressed in non-vascular tissue might play a role in physiologic BP regulation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The spread of Dengue virus infection is reaching pandemic proportions. Dengue is usually dreaded for causing shock due to capillary leakage. However the clinical spectrum of dengue is vast and the newly incorporated expanded dengue syndrome introduces a wide range of presentations that are rarely observed and appreciated but nevertheless have the potential to cause significant morbidity and even mortality. Cardiac involvement in dengue is one such example., Case Presentation: A 26 year old South-Asian female presented in a state of haemodynamic shock with a history of fever and use of non-steroidal anti inflammatory drugs. Dengue was suspected clinically and later confirmed. Following stabilization and while still in the febrile phase the patient developed bradycardia with dynamic electrocardiogram changes which evolved into complete heart block. However there was no circulatory compromise. Clinical picture was further complicated by the development of dengue haemorhaghic fever and cautious fluid resuscitation was carried out in correlation to clinical and haematological parameters. Impaired coagulation profile necessitated administration of activated factor seven on the backdrop of low platelets and bleeding. Cardiac pacing could be avoided due to maintenance of vitals within acceptable parameters., Conclusion: Expanded dengue syndrome should be given greater appreciation as not all may be benign. Cardiovascular system involvement in dengue has the potential to cause significant morbidity and mortality. Careful interpretation of clinical parameters will help in the institution of the appropriate management and help avoid unnecessary invasive interventions. Screening of dengue patients with timely electrocardiographs would be useful to detect cardiac involvement. Guidance on managing atypical manifestations of dengue expanded syndrome should available to help clinicians dictate treatment.

Background: Heart failure (HF) can be caused by left ventricular (LV) pump failure as well as by bradyarrhythmias. Hemodynamic differences between HF by LV pump failure and that by bradyarrhythmia have not been fully investigated. We hypothesized that HF by LV pump failure could be associated with both reduced cardiac output (CO) and increased LV filling pressure due to associated LV diastolic dysfunction, whereas HF by bradyarrhythmia could be associated with reduced CO but only modestly increased LV filling pressure due to the absence of LV diastolic dysfunction., Methods: In 39 patients with HF by LV pump failure (LV ejection fraction <35%), 24 with HF by bradyarrhythmia, and 22 normal controls, LV volume, ejection fraction, stroke volume, left atrial volume, and early diastolic mitral valve flow to tissue annular velocity ratio (E/E') were measured by echocardiography., Results: Compared to patients with HF by LV pump failure, those with HF by bradyarrhythmia had significantly lower heart rates, less LV dilatation, preserved LV ejection fraction, preserved stroke volume, similarly reduced cardiac index (1.8 ± 0.4 vs. 1.6 ± 0.4 L/min/m(2), n.s.), preserved LV diastolic function (E') (4.4 ± 2.1 vs. 7.1 ± 2.9 cm/s, p < 0.001), less dilated end-systolic LA volume, and preserved E/E' (24 ± 10 vs. 13 ± 7, p < 0.001)., Conclusions: HF by LV pump failure is characterized by both significantly reduced CO and increased LV filling pressure, whereas HF by bradyarrhythmia is characterized by a similar reduction in CO but only modestly increased LV filling pressure.

Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne viral zoonotic disease which is endemic in Turkey. Bradycardia has been reported among pediatric and adult patients with CCHF. But, it remains unclear, whether bradycardia is associated with ribavirin treatment or the severity of CCHF. In this study 26 hospitalized CCHF patients were reviewed in terms of age, gender, history of tick bite, duration of hospitalization, presence of bradycardia, laboratory features, ribavirin treatment, and blood products requirement. The demographic, clinical, laboratory and treatment characteristics of CCHF patients with or without bradycardia were compared. The mean age of the patients was 126.42±48.21 months. There were 8 female and 18 male patients. Sinus bradycardia was noted in 15 patients (mean age was 120.20±50.59 months, 5 female). Ribavirin had been administered 18 (69.2%) patients and 11 of them had bradycardia. There was not statistically significant relationships between bradycardia and ribavirin treatment (p=0.683). Furthermore the occurrence of bradycardia was not associated with disease severity according to Swanepoel severity criteria (p=0.683). We concluded that independent of the disease severity and the ribavirin treatment, transient sinus bradycardia might occur during the clinical course of CCHF in pediatric patients. For this reason clinicians should be aware of this finding and all CCHF patients should be monitored closely., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Seckel syndrome is an uncommon form of microcephalic dwarfism. The authors report a young boy with Seckel syndrome who presented with severe sinus bradycardia with symptoms of syncope and presyncope. Implantation of a permanent pacemaker was necessary in view of the severe symptoms. Although uncommon, cardiac abnormalities have been rarely reported in Seckel syndrome. This is the one of the few reports of rhythm abnormalities in this condition.

Background: Sedation during gastrointestinal endoscopy is often achieved using propofol or midazolam in general population. However, impaired protein synthesis, altered drug metabolism, and compromised hepatic blood flow in patients with liver cirrhosis might affect the pharmacokinetics of sedatives, placing cirrhotic patients undergoing endoscopy at a greater risk of adverse events. The objective of this study was to assess comparative efficacies and safety of propofol and midazolam in cirrhotic patients undergoing endoscopy., Methods: Randomized, controlled trials comparing propofol with midazolam in cirrhotic patients undergoing gastrointestinal endoscopy were selected. We performed the meta-analysis, using a random-effect model, the Review Manager, Version 5.2, statistical software package (Cochrane Collaboration, Oxford, UK) according to the PRISMA guidelines., Results: Five studies between 2003 and 2012, including 433 patients, were included. Propofol provided a shorter time to sedation (weight mean difference: -2.76 min, 95% confidence interval: -3.00 to -2.51) and a shorter recovery time (weight mean difference -6.17 min, 95% confidence interval: -6.81 to -5.54) than midazolam did. No intergroup difference in the incidence of hypotension, bradycardia, or hypoxemia was observed. Midazolam was associated with the deterioration of psychometric scores for a longer period than propofol., Conclusion: This meta-analysis suggests that Propofol sedation for endoscopy provides more rapid sedation and recovery than midazolam does. The risk of sedation-related side effects for propofol does not differ significantly from that of midazolam. The efficacy of propofol in cirrhotic patients undergoing endoscopy is superior to those of midazolam.

Background: Heart rate (HR) is a basic cardiovascular parameter. The relationship between HR and cardiovascular mortality and morbidity has been indicated in clinical trials and epidemiological studies., Aim: The evaluation of the relationship between HR upon hospital admission and the in-hospital prognosis in a group of patients with ST-elevation myocardial infarction (STEMI)., Methods: The medical records of 927 patients were subject to retrospective analysis. The patients were classified on the basis of HR upon hospital admission: < 60 bpm (n = 75), 60-69 bpm (n = 169), 70-79 bpm (n = 245), 80-89 bpm (n = 172), 90-99 bpm (n = 134), and ≥ 100 bpm (n = 132). A group of patients with HR of 60-69 bpm on hospital admission (n = 169) constituted a reference group. Patients with atrioventricular blocks and arrhythmias were excluded from the analysis. Early mortality and co-existing diseases were evaluated in the study population., Results: Patients with HR ≥ 90 bpm demonstrated heart failure symptoms considerably more often than patients with HR of 60-69 bpm (p = 0.0010). In-hospital mortality was significantly higher in patients with a HR of more than 90 bpm and bradycardia. The relationship between HR and cardiovascular mortality is shown with a J-shaped curve., Conclusions: HR is strictly correlated with early cardiovascular mortality in a population of patients with STEMI. The relationship between HR and early mortality is demonstrated by a J-shaped curve.

Background: Because there is limited information on fetal bradyarrhythmia associated with congenital heart defects (CHD), we investigated its prognosis and risk factors., Methods and Results: In our previous nationwide survey of fetal bradyarrhythmia from 2002 to 2008, 38 fetuses had associated CHD. Detailed clinical data were collected from secondary questionnaires on 29 fetuses from 18 institutions, and were analyzed. The 29 fetuses included 22 with isomerism, 4 with corrected transposition of the great arteries (TGA) and 3 with critical pulmonary stenosis; 14 had complete atrioventricular block (AVB), 8 had second-degree AVB, and 16 had sick sinus syndrome; 5 died before birth, and 10 died after birth (5 in the neonatal period). Neonatal and overall survival rates for fetal bradyarrhythmia with CHD were 66% and 48%, respectively. Pacemaker implantation was needed in 17 cases (89%). Beta-sympathomimetics were administered in utero in 13 cases and were effective in 6, but were not associated with prognosis. All cases of corrected TGA or ventricular rate ≥70 beats/min survived. A ventricular rate <55 beats/min had significant effects on fetal myocardial dysfunction (P=0.02) and fetal hydrops (P=0.04), resulting in high mortality., Conclusions: The prognosis of fetal bradyarrhythmia with CHD is still poor. The type of CHD, fetal myocardial dysfunction, and fetal hydrops were associated with a poor prognosis, depending on the ventricular rate.