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Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. In comparing metoprolol succinate with carvedilol, the later has sparked interest in its usage as an important medication for POAF prevention., Methods: We considered randomized controlled studies (RCTs) and retrospective studies that evaluated the efficacy of carvedilol versus metoprolol for the prevention of POAF. After literature search, data extraction, and quality evaluation, pooled data were analyzed using either the fixed-effect or random-effect model using Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes., Results: In meta-analysis 5 RCTs and 2 retrospective studies with a total of 1000 patients were included. The overall effect did not favor the carvedilol over metoprolol groups in terms of mortality rate [risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] or incidence of bradycardia [risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001]., Conclusion: In patients undergoing cardiac surgery, carvedilol may minimize the occurrence of POAF more effectively than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, a large-scale, well-designed randomized controlled trials are required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

The BRASH (bradycardia, renal failure, atrioventricular block, shock, and hyperkalaemia) syndrome is a recently recognized condition which may lead to life-threatening complications if not correctly identified and treated early. We report here the case of a 74-year-old woman with type 2 diabetes, hypertension and atrial flutter who presented to the emergency department with 2-day history of dizziness, presyncope, and bradycardia, and a junctional rhythm at 61 beat per minute on initial ECG. She was on apixaban, digoxin, prazosin, and telmisartan. Serum biochemistry revealed severe hyperkalaemia with a potassium 8.4 mmol/L, creatinine 161 mmol/L, glucose 15.3 mmol/L and an upper normal digoxin level of 1.2 mmol/L (ref. 0.6-1.2). Arterial blood pH was 7.2. Given the constellation of biochemical and clinical findings a diagnosis of BRASH syndrome was made, though her blood pressure values at presentation were rather high (180/65-179/59 mmHg). The patient was rapidly stabilised with the administration of intravenous insulin and dextrose, fluid resuscitation, and zirconium cyclosilicate (SZC), followed by haemodialysis. Following the correction of the serum potassium to 4.7 mmol/L, a further ECG performed 6 hours later, showed a restoration of sinus rhythm with a rate of 65 bpm, normalization of the QRS duration. The digoxin and telmisartan were discontinued, and the patient was commenced on a calcium channel antagonist for hypertension. Clinicians should be alerted to patients who present with either a BRASH (shock) or BRAHH (hypertensive manifestation) where timely intervention is essential to avoid life-threatening brady-and tachyarrhythmias in these patients., Competing Interests: Declaration of Competing Interest None of the authors have any disclosures related to this work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sinus node dysfunction (SND) is a multifaceted disorder most prevalent in older individuals, but may also occur at an earlier age. In most cases, the SND diagnosis is ultimately established by documenting its ECG manifestations. EPS has limited utility. The treatment strategy is largely dictated by symptoms and ECG manifestations. Not infrequently, both bradycardia and tachycardia coexist in the same patients, along with other diseases common in the elderly (e.g., hypertension, coronary artery disease), thereby complicating treatment strategy. Prevention of the adverse consequences of both bradyarrhythmia and tachyarrhythmia is important to reduce susceptibility to syncope, falls, and thromboembolic complications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal disease caused by a defect in the gene encoding lysosomal enzyme α-galactosidase A (GLA). Atrio-ventricular (AV) nodal conduction defects and sinus node dysfunction are common complications of the disease. It is not fully elucidated how frequently AFD is responsible for acquired AV block or sinus node dysfunction and if some AFD patients could manifest primarily with spontaneous bradycardia in general population. The purpose of study was to evaluate the prevalence of AFD in male patients with implanted permanent pacemaker (PM)., Methods: The prospective multicentric screening in consecutive male patients between 35 and 65 years with implanted PM for acquired third- or second- degree type 2 AV block or symptomatic second- degree type 1 AV block or sinus node dysfunction was performed., Results: A total of 484 patients (mean age 54 ± 12 years at time of PM implantation) were enrolled to the screening in 12 local sites in Czech Republic. Out of all patients, negative result was found in 481 (99%) subjects. In 3 cases, a GLA variant was found, classified as benign: p.Asp313Tyr, p.D313Y). Pathogenic GLA variants (classical or non-classical form) or variants of unclear significance were not detected., Conclusion: The prevalence of pathogenic variants causing AFD in a general population sample with implanted permanent PM for AV conduction defects or sinus node dysfunction seems to be low. Our findings do not advocate a routine screening for AFD in all adult males with clinically significant bradycardia., Competing Interests: Declaration of Competing Interest ZF and SH received the travel grants and speaker's honoraria from Takeda. GD received honoraria and travel funding from Sanofi Genzyme, Takeda, Protalix, and Greenovation Biotech GmbH. DG is a consultant for Amicus Therapeutics, Sanofi Genzyme, and Shire; has received research support from Sanofi Genzyme and Shire; and has received speaker honoraria and travel support from Amicus Therapeutics, Sanofi Genzyme, and Shire. AL received consultancy honoraria from Amicus Therapeutics, Sanofi Genzyme, Takeda, and speaker's honoraria from Sanofi Genzyme and Takeda., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AF-RVR) in the emergency department., Objectives: To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR., Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration., Results: Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n = 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I 2  = 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n = 1477, OR: 0.96; 95% CI:0.61 to 1.52; I 2  = 35%] or bradycardia [9 studies, n = 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I 2  = 48%]., Conclusions: Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Shivering is a common complication of spinal anesthesia. Phenylephrine, due to its peripheral vasoconstrictive effect, may limit the core to periphery redistribution of body temperature following spinal anesthesia, and reduce hypothermia and shivering. We hypothesized that prophylactic phenylephrine infusion would reduce shivering and hypothermia in women undergoing cesarean section under spinal anesthesia., Methods: A two-arm randomized, double-blind, placebo-controlled trial in term pregnant patients undergoing cesarean section. In the phenylephrine group (n=75) prophylactic phenylephrine infusion was administered at 25 µg/min immediately after initiation of spinal anesthesia and continued until the end of the operative period. In the placebo group (n=75) a normal saline infusion was administered during the same period. The primary outcome was the incidence of shivering; secondary outcomes were severity of shivering, changes in nasopharyngeal (core) temperature, and incidence of hypotension and bradycardia., Results: The incidence of shivering in the phenylephrine and control groups was 24.0% (95% CI 14.3% to 33.7%) and 53.3% (95% CI 42.0% to 64.6%), respectively. The severity of shivering was greater in the control group (P=0.002) and the mean (±SD) end of surgery core temperature was significantly higher in the phenylephrine group (35.84°C ± 0.60) compared with controls (35.61°C ± 0.48) (P=0.009). The incidence of hypotension was higher in controls (53.4% vs. 2.7%; P <0.001) but bradycardia more frequent in group P (P=0.023)., Conclusion: The incidence of shivering and degree of hypothermia were significantly reduced by a prophylactic phenylephrine infusion during cesarean section under spinal anesthesia., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Malnutrition is associated with a poor prognosis in heart failure, angina pectoris, and peripheral artery disease. However, the clinical importance of the preprocedural nutrition status of patients requiring pacemaker implantation (PMI) for bradycardia is unclear., Methods: We retrospectively enrolled 521 patients (median 79 years) who underwent their first PMI between January 1, 2012 and June 30, 2017. The nutrition status before implantation was assessed by the geriatric nutritional risk index (GNRI). The association between the preprocedural GNRI-based nutritional status and all-cause mortality was investigated., Results: GNRI-based high (GNRI <82) and moderate (GNRI 82 to <92) malnutrition status were found in 9.2% and 34.0%, respectively. During a median follow-up of 1178 days, 71 patients died. The mortality rate, which was analyzed using survival curves, was significantly stratified by the GNRI-based malnutrition status [high: 52.0% (25/48), moderate: 16.9% (30/177), low: 5.4% (16/296), p<0.001). On a multivariate Cox-proportional hazard analysis, GNRI-based high malnutrition status independently predicted all-cause death (hazard ratio: 4.49, 95% confidence interval: 2.59-7.80, p<0.001). A sensitivity analysis based on the controlling nutritional status score showed consistent results. On a receiver operating characteristic curve analysis, GNRI had a high predictive value for all-cause mortality (area under the curve, 0.78, 95% confidence interval: 0.72-0.84, p<0.001)., Conclusions: Preprocedural malnutrition was significantly associated with poor outcomes of patients who underwent PMI. Assessing the nutritional status in advance is important for risk stratification, and improving the nutritional status may be an option for managing these patients., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

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.)

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.)

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.)

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.)

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.)

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.)

Background: Sleep apnea (SA) is associated with cardiovascular diseases and is highly prevalent in patients with pacemakers (PMs)., Objective: To validate a transthoracic impedance sensor with an advanced algorithm (sleep apnea monitoring) for identifying severe SA., Methods: Patients with indications for PM (VVI/DDD) were enrolled regardless of symptoms suggesting SA. Severe SA diagnosis was acknowledged when the full polysomnography gave an apnea-hypopnea index (PSG-AHI) of ≥30 events/h. The PSG-AHI was compared with the respiratory disturbance index evaluated by the SAM algorithm (SAM-RDI) compiled from the device during the same diagnosis night, and the performance of the device and the SAM algorithm was calculated to identify patients with severe SA. The agreement between methods was assessed by using Bland and Altman statistics., Results: Forty patients (mean age 73.8 ± 19.1 years; 67.5% men; body mass index 27.7 ± 4.4 kg/m(2)) were included. Severe SA was diagnosed by PSG in 56% of the patients. We did not retrieve SAM-RDI data in 14% of the patients. An optimal cutoff value for the SAM-RDI at 20 events/h was obtained by a receiver operator characteristic curve analysis, which yielded a sensitivity of 88.9% (95% confidence interval [CI] 65.3%-98.6%), a positive predictive value of 88.9% (95% CI 65.3%-98.6%), and a specificity of 84.6% (95% CI 54.6%-98.1%) (n = 31). The Bland-Altman limits of agreement for PSG-AHI (in events per hour) were [-14.1 to 32.4]., Conclusion: The results suggest that an advanced algorithm using PM transthoracic impedance could be used to identify SA in patients with PMs outside the clinic or at home., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Polymorphic ventricular tachycardia (PMVT) is an unusual ventricular tachyarrhythmia. Perhaps its most unique characteristic is a continuously evolving QRS morphology. Although the most common substrate for PMVT is structural heart disease, the prevalence of sudden cardiac death in the population without structural heart disease is even greater, and the absence of a myocardial substrate would suggest that PMVT is the anticipated cause of sudden cardiac death in this population as well. Mechanistically, PMVT is distinct from ventricular fibrillation. It appears to be a condition of abnormal repolarization and resultant cellular heterogeneities, and the principles of triggering and reentry have been demonstrated to govern its initiation and maintenance. The "channelopathies"-a growing category of inherited or acquired conditions that predispose to PMVT and sudden cardiac death-present a fascinating challenge with potentially dire consequences as there are few indicators of their existence except for subtle, if any, electrocardiographic changes. The ever-expanding number of pharmaceuticals that affect ion channel function further magnifies this risk., (© 2013 Elsevier B.V. All rights reserved.)

Background: Impedance threshold device technology harnesses the patient's normal physiological mechanisms to increase circulation during hypotensive crises. We report the first clinical use of one version of this device on a spontaneously breathing hypotensive pregnant woman., Objective: The objective of our study was to report this case to help Emergency Medical Service rescue personnel to noninvasively treat hypotensive but conscious spontaneously breathing patients., Case Report: A 28-year-old woman who was 21 weeks pregnant developed frank syncope at home but recovered spontaneously. When Emergency Medical Service paramedics arrived, her initial blood pressure and heart rate were 115/80 mm Hg and 125 beats/min, respectively. She suddenly complained of feeling anxious and developed profound bradycardia and hypotension, followed by 20 s of asystole. An impedance threshold device (ResQGARD™) with -7 cmH2O resistance to inspiration was rapidly applied using a facemask. After four spontaneous breaths, blood pressure increased from 62/40 mm Hg to 106/66 mm Hg. She was hemodynamically stable thereafter., Conclusions: In this case report, the multiple physiological effects of inspiration through -7 cmH2O resistance helped this pregnant hypotensive patient to rapidly and noninvasively restore adequate perfusion and reduced the duration of her hypotensive episode. To our knowledge, this is the first report of this technology in a pregnant hypotensive but spontaneously breathing patient., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objective: Despite recent advances in diagnostic procedures, syncope remains unexplained in 15 to 35% of patients. If implantable loop recorder is a validated diagnostic tool for unexplained syncope, results of this strategy are largely issued from randomized studies. We lack the results of surveys. The aim of this study was to report a single center experience with implantable loop recorders, in patients with unexplained syncope., Methods and Results: A device (Medtronic Reveal DX or XT) was implanted in 31 patients between January 2009 and January 2012. During a mean follow-up of 10.5±8.5 months, loop recording definitively determined that an arrhythmia was the cause of symptoms in 10 patients (32%). Fourteen patients (45%) experienced syncope or pre-syncope. In eight of the 14 patients with syncope, during follow-up, no arrhythmic diagnosis could be made (one patient has been diagnosed as presenting epilepsy and seven as having hypotensive vasovagal syncope). In six patients, the ILR showed an arrhythmic aetiology. Four other patients presented an abnormal ILR result without symptoms. Diagnosis included sinusal arrest in four patients, bradycardia in one patient, advanced atrioventricular block in two patients, ventricular arrythmias in two patients, and supraventricular tachycardia of 180/min in one patient. Therapy was instituted in all patients, in whom an arrhythmic cause was found except one who refused the therapy (six pacemaker, two implantable cardioverter-defibrillator implantations, and one cryoablation of atrioventricular nodal reentrant tachycardia confirmed by an invasive exploration)., Conclusion: In this survey, implantable loop recorder implantation led to the diagnosis of an arrhythmic cause in 32% of patients and excluded an arrhythmic cause in 26% of patient with a mean follow-up of 10.5 months., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The hearts of seven elderly dogs in which bradycardia-tachycardia syndrome (BTS) had been diagnosed electrocardiographically were examined post mortem. The clinical basis of the underlying heart disease was invariably mitral or mitral and tricuspid regurgitation. Microscopical examination of the sinoatrial (SA) node and the SA junctional region consistently revealed depletion of SA nodal cells, with a corresponding increase in fibrous or fibro-fatty tissue that interrupted contiguity between the SA node and the surrounding atrial myocardium. The left and right atrial walls showed an increased amount of fibrous tissue in the myocardium and disruption of the muscle bundle architecture (interstitial myocardial fibrosis) to varying degrees. Qualitatively, these changes in the SA node and the SA node region resembled those associated with ageing in elderly people with or without BTS. Thus, it is possible that the pathological process affecting the SA node in these dogs was fundamentally related to ageing and may have caused BTS, in combination with atrial myocardial lesions caused by mitral and tricuspid regurgitation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: The prevalence of patients thought to have epilepsy who are ultimately diagnosed with asystole or bradyarrhythmias not associated with seizures is currently unknown. We studied a tertiary referral population to determine the rate of clinically significant asystole or bradyarrhythmias in patients being evaluated for possible epilepsy in 2 inpatient epilepsy monitoring units (EMU)., Methods: A retrospective cohort of 1606 consecutive patients admitted for video-EEG monitoring at University of New Mexico Hospital from January 2000 to July 2005 and Mayo Clinic Florida from September 2005 to August 2009 was reviewed for clinical presentation and outcome of video-EEG and EKG monitoring. All patients included in the final analysis (n=1433) were admitted with a diagnosis of "possible seizures"., Results: The majority of subjects were under the age of 20 and 10% of subjects were over age 50. The rate of significant cardiac bradyarrhythmias was 0.3% (4/1433). Three of the four subjects with cardiac arrhythmias had symptom onset in childhood. One subject died during the evaluation., Conclusions: The rate of patients admitted for video-EEG monitoring who are ultimately diagnosed with asystole and bradyarrhythmias not associated with epilepsy is low. Symptom may begin in childhood., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Aim: Analyse heart rate variability (HRV) of preterm neonates undergoing a polysomnography in relation to the occurrence of abnormal cardiorespiratory events on one hand and the type of sleep states on the other hand., Methods: To quantify nonlinear HRV, the numerical noise titration technique is used, adapted to neonatal heart rate data. HRV is calculated for 30 preterm neonates with mean post-conceptional age of 36.4weeks, divided into three groups according to the occurrence of abnormal events during the polysomnographies and the eventual home monitoring., Results: Periods of non-REM sleep have lower noise limit values and can be distinguished significantly from periods of REM sleep and from the total recording period. The presence of abnormal events does not influence this finding. Significant differences between groups are only found during non-REM segments by means of the noise limit value computed via numerical noise titration while the linear HRV parameters were not able to discriminate., Conclusion: ECG measurement of a relatively short non-REM sleep period without specific abnormal events is sufficient to define a mature cardiorespiratory pattern in preterm infants.

Background: Syncope may be the result of primary bradycardia or tachycardia, vasovagal syncope, or noncardiac syncope. Risk factors and outcome scores to predict prognosis in patients with syncope have been developed. Although these correlate with morbidity and mortality in patients with syncope, their relationship with the mechanism of syncope has not been investigated., Objective: The purpose of this study was to identify clinical predictors of primary bradycardia in a cohort of patients undergoing prolonged monitoring for unexplained syncope., Methods: One hundred nineteen patients underwent prolonged monitoring with an implantable or external loop recorder after assessment at a single-center, tertiary care arrhythmia service. Fifty-two patients with recurrent syncope during monitoring were classified according to the mechanism of syncope (International Study on Syncope of Uncertain Etiology [ISSUE] classification). Clinical predictors of primary arrhythmic syncope were identified., Results: Twenty patients were classified with primary arrhythmia and 32 patients were classified with nonarrhythmic syncope. Five clinical variables were associated with primary arrhythmia: left bundle branch block, structural heart disease, and syncope without prodrome increased the likelihood of primary arrhythmia; a normal baseline ECG and history of syncope in childhood decreased the likelihood of primary arrhythmia. After multiple logistic regression, risk factors for the diagnosis of primary arrhythmia included syncope without warning symptoms and structural heart disease. The presence of left bundle branch block correlated perfectly with primary arrhythmia, whereas a normal ECG reduced the likelihood of primary arrhythmia., Conclusion: Clinical predictors of primary arrhythmia in patients with recurrent syncope include normal ECG and structural heart disease. Left bundle branch block is an important finding in patients with unexplained syncope.

Background: Transient bradycardic hypotensive events occur in resting rabbits. If the hypotension is due to vasodepression, these events may be a model for vasovagal syncope., Objectives: To determine whether these events are responses to brief stimuli and whether the hypotensive episodes are solely due to rapid-onset bradycardia., Methods: Rabbits were instrumented with subcutaneous electrocardiogram leads, and cannulae were acutely inserted into an ear artery to obtain continuous arterial pressure measurements. Exposure to brief, low-level auditory stimuli at 5 kHz transiently increased the RR interval by approximately 70 ms and decreased mean arterial pressure by approximately 5 mmHg., Results: These evoked bradycardic hypotensive events were almost identical to previously reported spontaneous bradycardic hypotensive events. Intra-aortic telemetric blood pressure monitoring was used to demonstrate that the evoked hypotension reflected prolonged diastole, rather than local ear arterial vasoconstriction. Furthermore, administration of the muscarinic blocker glycopyrrolate abolished not only bradycardia (RR interval 64+/-14 ms to 1+/-1 ms; P<0.0001), but also hypotension (--4.1+/-0.8 mmHg to --0.4+/-0.3 mmHg; P=0.0055). Finally, cardiac pacing abolished the inducible bradycardia (RR interval 51+/-10 ms to 2+/-1 ms; P=0.0006) and its associated hypotension (--4.1+/-0.7 mmHg to --1.2+/-0.3 mmHg; P=0.003)., Conclusions: Brief auditory stimuli evoked a transient bradycardia mediated by cardiac muscarinic receptors and consequent hypotension. This is not a model for vasovagal syncope.

We present a case of unpaced pre-existing congenital heart block in pregnancy, diagnosed for the first time in labour. Our patient was asymptomatic and was managed conservatively with temporary pacing equipment on standby. She had a post-partum cardiology follow-up and was paced in the puerperium. We discuss the aetiopathogenesis and the variable presentation patterns of bradyarrhythmia in pregnancy and the multidisciplinary approach to their management. Our recommendations combine the Advanced Life Support algorithm for treatment of bradycardia and the successful management strategies of several documented case reports in the literature.

Perioperative management of patients with cardiac pacemakers may be challenging because of the increasing sophistication of these devices. We report a case of a patient with paroxysmal atrial fibrillation (PAF) and with a permanent AAIR (bipolar atrial-inhibited adaptive rate) pacemaker who suffered life-threatening episodes of arrhythmias during operation. The first episode was vagally induced PAF during bowel manipulation; the second, induced by the increased pacing threshold from the external electric cardioversion and hyperkalemia. Transcutaneous pacing provided cardiac pacing and stabilized the patient during the second episode. Thorough preoperative evaluation and prophylactic placement of temporary pacing or at least transcutaneous pacing are important for the avoidance and minimization of intraoperative complications in patients with sick sinus syndrome and with an AAI (atrial inhibited) pacemaker.

Background: Endogenous adenosine might cause or perpetuate bradyasystole. Our aim was to determine whether aminophylline, an adenosine antagonist, increases the rate of return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest., Methods: In a double-blind trial, we randomly assigned 971 patients older than 16 years with asystole or pulseless electrical activity at fewer than 60 beats per minute, and who were unresponsive to initial treatment with epinephrine and atropine, to receive intravenous aminophylline (250 mg, and an additional 250 mg if necessary) (n=486) or placebo (n=485). The patients were enrolled between January, 2001 and September, 2003, from 1886 people who had had cardiac arrests. Standard resuscitation measures were used for at least 10 mins after the study drug was administered. Analysis was by intention-to-treat. This trial is registered with the ClinicalTrials.gov registry with the number NCT00312273., Findings: Baseline characteristics and survival predictors were similar in both groups. The median time from the arrival of the advanced life-support paramedic team to study drug administration was 13 min. The proportion of patients who had an ROSC was 24.5% in the aminophylline group and 23.7% in the placebo group (difference 0.8%; 95% CI -4.6% to 6.2%; p=0.778). The proportion of patients with non-sinus tachyarrhythmias after study drug administration was 34.6% in the aminophylline group and 26.2% in the placebo group (p=0.004). Survival to hospital admission and survival to hospital discharge were not significantly different between the groups. A multivariate logistic regression analysis showed no evidence of a significant subgroup or interactive effect from aminophylline., Interpretation: Although aminophylline increases non-sinus tachyarrhythmias, we noted no evidence that it significantly increases the proportion of patients who achieve ROSC after bradyasystolic cardiac arrest.

Background: Patients with epilepsy are at risk of sudden unexpected death. Neurogenic cardiac arrhythmias have been postulated as a cause. Electrocardiograms (ECG) can be monitored by use of an implantable loop recorder for up to 18 months. We aimed to determine the frequency of cardiac arrhythmias in patients with refractory focal seizures over an extended period., Methods: 20 patients received an implantable loop recorder at one hospital in the UK. Devices were programmed to record automatically if bradycardia (<40 beats per min) or tachycardia (>140 beats per min) were detected. Additionally, in the event of a seizure, patients and relatives could initiate ECG recording with an external activator device. Data were analysed at regular intervals and correlated with seizure diaries., Findings: More than 220000 patient-hours were monitored over 24 months, during which ECGs were captured on implantable loop recorders in 377 seizures. One patient withdrew from the study. In 16 patients, median heart rate during habitual seizures exceeded 100 beats per min. Ictal bradycardia (<40 beats per min) was rare, occurring in eight (2.1%) recorded events, in seven patients. Four patients (21%) had bradycardia or periods of asystole with subsequent permanent pacemaker insertion. Three of these four (16% of total) had potentially fatal asystole., Interpretation: Clinical characteristics of patients with peri-ictal cardiac abnormalities are closely similar to those at greatest risk of sudden unexpected death in epilepsy. Asystole might underlie many of these deaths, which would have important implications for the investigation of similar patients and affect present cardiac-pacing policies.

Objective: The study was undertaken to determine whether respiratory distress syndrome (RDS) is associated with an increased risk of nonpulmonary morbidity in neonates born between 34 to 36 weeks' gestation., Study Design: We performed a matched case-control study of 75 infants with (cases) and 75 without (controls) RDS, delivered between 34 and 36 weeks' gestation. Infants with RDS and no other causes for respiratory failure (anomalies, hydrops, asphyxia) were included. Controls were matched for gestational age at birth, year of care, gender, plurality, and race. Inpatient records were reviewed for the incidence of nonpulmonary morbidities before discharge. McNemar test and conditional logistic regression were used to evaluate differences between cases and controls., Results: Our study cohort was 69% male, 48% white, 33% African American, and 19% Hispanic. Cases had longer hospital (11 vs 7days) and neonatal intensive care unit stays (10 vs 7 days), and more frequent apnea-bradycardia (30% vs 5%), pneumonia (12% vs 1%), and suspected sepsis diagnoses (27% vs 3%), P

Unlabelled: We conducted a case control study during six and a half years with the objective to analyse the risk factors for NEC., Population and Methods: All cases of confirmed NEC matched to controls for identical gestational age and period of hospitalization; apnoeas-bradycardias prospectively counted., Results: Forty-five cases were compared to 89 controls. The isolated risk factors were: an intra-uterine growth retardation (OR = 3,65, 95% confidence interval [CI] 95%: 1,54-8,63); a birth weight < 1000 g (OR = 8,16, CI 95%: 1,17-56,62), compared to a weight >/= 1500 g; a triple antibiotherapy (OR = 6,15, CI 95%: 1,16-32,45); an umbilical venous catheterization (OR = 2,64, CI 95%: 1,09-6,44); a number of simple apnoeas-bradycardias >/= 3rd tercile (n = 27) (OR = 4,54, CI 95%: 1,29-15,93), or severe (stimulated or with hypoxia) apnoeas-bradycardias >/= 3rd tercile (n = 8) (OR = 6,15, CI 95%: 1,59-23,75); an haemoglobin level lower than the 1(st) tercile (95 g/L) (OR = 5,90, CI 95%: 1,20-20,13); and milk thickening by Gumilk (OR = 2,78, CI 95%: 1,11-6,90)., Conclusion: In the present practices, anoxo-ischemic factors during the first week of life do not represent an important risk of NEC; a great vigilance must be exercised for indications of the triple antibiotherapy and the treatment of apnoeas-bradycardias.