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Background: Catheter ablation (CA) is a well-established treatment for atrial fibrillation (AF). However, its effects on autonomic function and underlying mechanisms remain poorly understood. This study investigated autonomic and haemodynamic changes following CA and explored their potential implications for patient outcomes. Methods : Seventy-eight patients with AF underwent CA and were followed up at one, three, and six months. Autonomic function was assessed using a combination of head-up tilt (HUT), handgrip (HG), and deep breathing (DB) manoeuvres along with baroreflex sensitivity (BRS) and baroreflex effectiveness index (BEI) evaluation. Heart rate (HR), blood pressure (BP), and their variability were measured at each time point. Results : Significant autonomic alterations were observed after ablation, particularly at one month, with reductions in parasympathetic tone and baroreflex function. These changes gradually normalised by six months. Both pulmonary vein isolation (PVI) and cryoablation (CryO) had similar effects on autonomic regulation. Improvements in quality of life, measured by the AFEQT scores, were consistent with these physiological changes. Conclusions: CA for AF induces significant time-dependent autonomic and haemodynamic changes with recovery over six months. These findings underscore the need for ongoing monitoring and personalised post-ablation management. Further research is required to explore the mechanisms driving these alterations and their long-term impacts on patient outcomes.

Sleep is a complex biobehavioural process essential for overall health, with various dimensions including duration, continuity, timing, and satisfaction. This study investigated the intricate relationships between common sleep disorders such as insomnia and obstructive sleep apnoea (OSA) and their impact on atrial fibrillation (AF), a prevalent arrhythmia with significant health implications. Using a comprehensive review of the current literature, this study examined the pathophysiological mechanisms linking sleep disorders to cardiovascular risks, focusing on autonomic nervous system disturbances, inflammation, and oxidative stress associated with OSA. These findings indicate that sleep disorders significantly elevate the risk of AF through mechanisms such as increased sympathetic activity and structural cardiac remodelling. Additionally, this study highlights the potential benefits of treating sleep disorders, particularly with continuous positive airway pressure (CPAP) therapy, in reducing AF recurrence and improving cardiovascular outcomes. This conclusion emphasises the importance of integrated therapeutic approaches that address both sleep disorders and AF to enhance patient outcomes and quality of life. Future research should explore these connections to develop more effective and holistic treatment strategies.

Background and Objectives: The Fontan procedure, a palliative surgery for univentricular heart physiology, often reduces exercise capacity and quality of life. This study aimed to evaluate the impact of cardiac rehabilitation (CR) on improving outcomes in Fontan patients to inform evidence-based care. Materials and Methods: Fontan patients aged 8-30 participated in a structured CR program for at least three months. The program included weekly aerobic and resistance training sessions with educational and nutritional guidance. Baseline and post-CR assessments included cardiac function, fitness, daily activity, and health-related quality of life (HRQOL). Results : The cohort included ten Fontan patients, of whom six had a right systemic ventricle. CR significantly improved cardiorespiratory fitness, as seen in VO2 max (from 27.92 ± 5.15 to 34.69 ± 1.14 mL/kg/min, p = 0.0089) and percent predicted VO2 (from 0.67 ± 0.18 to 0.90 ± 0.02, p = 0.005). VCO2 increased by +8.68 ± 8.59 mL/kg/min but did not reach statistical significance ( p = 0.05). Most haemodynamic and ventilatory parameters showed no significant improvement. All the SF-36 questionnaire domains showed significant HRQOL gains ( p < 0.001). High adherence (85-93%), no adverse events, and reduced NT-proBNP levels supported the program's safety. Conclusions : This study's findings have important implications for the care of Fontan patients. CR significantly improved exercise capacity and HRQOL in Fontan patients across various anatomies, particularly in the right systemic ventricle. Integrating physical conditioning into standard care could reduce long-term morbidity and mortality; however, further research is needed to refine the protocols and confirm sustained benefits.

Background and Objectives: Atrial fibrillation (AF) is increasingly recognised in paediatric patients, presenting unique challenges in management due to its association with various underlying heart conditions. This study aimed to evaluate the prevalence, management strategies, and outcomes of AF in this population. Materials and Methods : A retrospective analysis was conducted at a tertiary paediatric cardiology centre, including patients aged ≤18 years diagnosed with AF between January 2015 and December 2023. The study focused on demographic details, clinical presentations, treatments, and outcomes. Descriptive statistics were employed to assess treatment efficacy, recurrence rates, and complications. Results : The study included 36 paediatric patients (median age: 15 years, IQR: 13-17; 58% male). Of these, 52.8% had acquired heart disease, 16.7% had congenital heart anomalies, and 16.7% presented with lone AF. The initial management strategies involved electrical cardioversion in 53.3% of patients and pharmacological conversion with amiodarone in 46.7%. Rhythm control therapy was administered to over 80% of the cohort, and 63.9% were placed on oral anticoagulation, predominantly for rheumatic and congenital heart diseases. The overall success rate of rhythm control was 96.2%, with an AF recurrence rate of 3.8%. Ischemic stroke was the most common complication, occurring in three patients, all with underlying rheumatic heart disease. Conclusions : AF in paediatric patients is predominantly associated with rheumatic and congenital heart diseases, though a significant proportion of patients present with lone AF. Despite effective rhythm control in most cases, neurological complications, particularly ischemic strokes in patients with underlying heart disease, remain a critical concern. These findings underscore the need for more comprehensive studies to better understand the aetiology, risk factors, and optimal management strategies for paediatric AF.

Atrial wall thickness (AWT) is a significant factor in understanding the pathological physiological substrate of atrial fibrillation, with a potentially substantial impact on the outcomes of catheter ablation procedures. Precise measurements of the AWT may provide valuable insights for categorising patients with AF and planning targeted interventions. Objectives: The purpose of this study was to evaluate the characteristics of the left atrium (LA) using non-invasive multidetector computed tomography (MDCT) scans and subsequent three-dimensional (3D) image post-processing using novel software designed to calculate atrial thickness dimensions and mass. Methods: We retrospectively analysed 128 consecutive patients (33.6% females; mean age 55.6 ± 11.2 years) referred for AF ablation (37 with persistent AF and 91 with paroxysmal AF) who underwent preprocedural MDCT. The images were post-processed and analysed using the ADAS software (Galgo Medical), automatically calculating the LA volume and regional wall thickness. In addition, the software employed a regional semi-automatic LA parcellation feature that divided the atrial wall into 12 segments, generating atrial wall thickness (AWT) maps per segment for each patient. Results: This study demonstrated considerable variability in the average thickness of LA walls, with the anterior segments being the thickest across the cohort. Distinct sex-specific differences were observed, with males exhibiting greater anterior and septal wall thickness than females. No significant associations were identified between the average AWT and body mass index, LA volume, or sphericity. Survival analysis conducted over 24 months revealed a meaningful relationship between mean anterior wall thickness and recurrence-free survival, with increased thickness associated with a lower likelihood of AF-free survival. No such relationship was observed for the indexed LA volume. Conclusions: The variability in AWT and its association with recurrence-free survival following AF ablation suggest that AWT should be considered when stratifying patients for AF management and ablation strategies. These findings underscore the need for personalised treatment approaches and further research on the interplay of the structural properties of the left atrium as factors that can serve as important prognostic markers in AF treatment.

Introduction: In patients with atrial fibrillation (AF), up to one third have recurrence after a first catheter ablation (CA). Epicardial adipose tissue (EAT) has been considered to be closely related to AF, with a potential role in its recurrence. We aimed to evaluate the association between the volume of EAT measured by cardiac computed tomography (CT) and AF recurrence after CA., Methods: Consecutive AF patients underwent a standardized cardiac CT protocol for quantification of EAT, thoracic adipose volume (TAV) and left atrium (LA) volume before CA. An appropriate cut-off of EAT was determined and risk recurrence was estimated., Results: 305 patients (63.6 % male, mean age 57.5 years, 28.2 % persistent AF) were followed for 24 months; 23 % had AF recurrence at 2-year mark, which was associated with higher EAT (p = 0.037) and LAV (p < 0.001). Persistent AF was associated with higher EAT volumes (p = 0.010), TAV (p = 0.003) and LA volumes (p < 0.001). EAT was predictive of AF recurrence (p = 0.044). After determining a cut-off of 92 cm 3 , survival analysis revealed that EAT volumes > 92 cm 3 showed higher recurrence rates at earlier time points after the index ablation procedure (p = 0.006), with a HR of 1.95 (p = 0.008) of AF recurrence at 2-year. After multivariate adjustment, EAT > 92 cm 3 remained predictive of AF recurrence (p = 0.028)., Conclusion: The volume of EAT measured by cardiac CT can predict recurrence of AF after ablation, with a volume above 92 cm 3 yielding almost twice the risk of arrhythmia recurrence in the first two years following CA. Higher EAT and TAV are also associated with persistent AF., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined heart rate variability (HRV) and baroreflex sensitivity (BRS) disease- and age-related response at 10-and 60-min after an acute high-intensity interval (HIIE) and moderate continuous exercise (MICE) in older adults with and without type 2 diabetes mellitus (T2DM) and healthy young adults., Methods: Twelve older male adults with (57-84 years) and without T2DM (57-76 years) and 12 healthy young male adults (20-40 years) completed an isocaloric acute bout of HIIE, MICE, and a non-exercise condition in a randomized order. Time and Wavelets-derived frequency domain indices of HRV and BRS were obtained in a supine position and offline over 2-min time-bins using Matlab., Results: HIIE but not MICE reduced natural logarithm root mean square of successive differences (Ln-RMSSD) (d = - 0.85; 95% CI - 1.15 to - 0.55 ms, p < 0.001), Ln-high-frequency power (d = - 1.60; 95% CI - 2.24 to - 0.97 ms 2 ; p < 0.001), and BRS (d = - 6.32; 95% CI - 9.35 to - 3.29 ms/mmHg, p < 0.001) in adults without T2DM (averaged over young and older adults without T2DM), returning to baseline 60 min into recovery. These indices remained unchanged in older adults with T2DM after HIIE and MICE. Older adults with T2DM had lower resting Ln-RMSSD and BRS than aged-matched controls (Ln-RMSSD, d = - 0.71, 95% CI - 1.16 to - 0.262 ms, p = 0.001; BRS d = - 3.83 ms/mmHg), 95% CI - 6.90 to - 0.76, p = 0.01)., Conclusions: Cardiovagal modulation following acute aerobic exercise is intensity-dependent only in adults without T2DM, and appears age-independent. These findings provide evidence of cardiac autonomic impairments in older adults with T2DM at rest and following aerobic exercise., (© 2023. The Author(s).)

Background: Impaired left atrial (LA) strain predicts atrial fibrillation (AF) recurrence after catheter ablation (CA), but currently there is no cut-off to guide patient selection for CA. Integrated backscatter (IBS) is a promising tool for noninvasive quantification of myocardial fibrosis. The aim of this study was to compare LA strain and IBS between paroxysmal, persistent, and long-standing persistent AF and evaluate their association with AF recurrence after CA., Methods: Analysis of consecutive patients with symptomatic paroxysmal and persistent AF who underwent CA. LA phasic strain, strain rate and IBS were assessed by two-dimensional speckle-tracking at baseline., Results: We analyzed 78 patients, 31% with persistent AF (46% long-standing AF), 65% male, mean age 59 ± 14 years, who underwent CA and were followed-up for 12 months. AF recurrence occurred in 22 (28%) patients. LA phasic strain parameters were significantly impaired in patients with AF recurrence and were independent predictors of AF recurrence in a multivariable analysis. LA reservoir strain (LASr) < 18% predicted AF recurrence with 86% sensitivity and 71% specificity, with a higher predictive power compared to LA volume index (LAVI). LASr < 22% in paroxysmal AF and LASr < 12% in persistent AF correlated with AF recurrence. Increased IBS was a predictor of AF recurrence in patients with paroxysmal AF., Conclusion: LA phasic strain parameters were predictors of AF recurrence after CA, independently of LAVI and AF subtype. LASr < 18% showed a higher predictive power compared to LAVI. Further studies are needed to investigate the role of IBS as a predictor of AF recurrence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: An ablation catheter and a circular mapping catheter requiring a double transeptal puncture (TSP) for left atrial access have been conventionally used for atrial fibrillation (AF) ablation. Recently, different operators have combined a single transseptal puncture technique with 3D high-density mapping catheters for pulmonary vein isolation (PVI)., Objective: This study aims to compare two strategies, single vs. double TSP, regarding the duration of the procedure, radiation time, complication rates, and outcomes., Methods: Retrospective analysis of a large cohort of consecutive patients that underwent first PVI with radiofrequency energy (RF), using a point-by-point strategy, with a 3D mapping system, either with single or double TSP, according to the operator's choice., Results: 285 patients with a mean age of 59.5 ± 11.6 years (36.5% female, 67.7% paroxysmal AF) underwent a point-by-point catheter ablation with RF between July 2015 and March 2020. The mean CHA2DS2-VASc score was 1.7 ± 1.3. Single TSP was performed in 115 (40.3%) patients and double TSP in 170 (59.6%). The operator's experience (≥5 years of AF ablation procedures) was equally distributed among the two groups. The average procedure time (133 ± 31.7 min vs. 123 ± 35.5 min, for single and double TSP, respectively) did reach a statistical difference between both groups ( p  = 0.008), but there was a substantial advantage regarding fluoroscopy time (13 ± 6.3 min vs. 19 ± 9.1 min, for single and double TSP, respectively; p  < 0.001). Acute major complications present similar rates in both groups (2.6% vs. 2.3%, p  = 0.799). At the 2-year follow-up, both groups had a similar sinus rhythm maintenance rate (76.5% vs. 78.8%, p  = 0.646)., Conclusion: A simplified single-TSP technique using high-density multi-electrode 3D mapping is a safe and highly successful option for AF ablation. This approach yields a substantial reduction in fluoroscopy time, with the potential to avoid acute complications, compared to a conventional double-TSP strategy., Competing Interests: MO has served as a speaker for Medtronic and is a member of the European Advisory Board of Medtronic. MP and AR are employees of Biosense Webster, Portugal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Silva Cunha, Teixeira, Laranjo, Portugal, Valente, Delgado, Pereira, Rocha, Brás, Cruz, Paulo, Lousinha, Guerra, Ferreira and Oliveira.)

The heart failure risk status (HFRS) is a validated dynamic tool for risk score prediction, based on the TriageHF™ algorithm (Medtronic, Minneapolis, MN, USA), for the occurrence of a heart failure (HF) event in the 30 days following a remote monitoring (RM) transmission. The aim of this study was to evaluate the accuracy of the HFRS in predicting an unplanned hospital admission due to HF decompensation in a real-world cohort of patients submitted to cardiac resynchronization therapy (CRT). We conducted a single-center review of a cohort of 40 consecutive HF patients, under RM, with CRT devices using the HFRS of the TriageHF™ algorithm. The correlation of the HFRS with hospital admissions was analyzed. During a mean follow-up of 36 months, a stepwise increase in the HFRS was significantly associated with a higher risk of HF admission (odds ratio, 12.7; 95% confidence interval, 3.2-51.5; P < .001), and the HFRS was demonstrated to have good discrimination for HF hospitalization, with an area under the receiver-operating characteristic curve of 0.812. The TriageHF™ algorithm effectively predicted HF-related hospitalization in a cohort of CRT patients during long-term RM follow-up, providing a novel clinical pathway to optimize the clinical management of this complex population., Competing Interests: The authors report no conflicts of interest for the published content. No funding information was provided., (Copyright: © 2023 Innovations in Cardiac Rhythm Management.)

The abnormal neural control of atria has been considered one of the mechanisms of paroxysmal atrial fibrillation (PAF) pathogenesis. The baroreceptor reflex has an important role in cardiovascular regulation and may serve as an index of autonomic function. This study aimed to analyze the baroreceptor reflex's role in heart rate regulation during upright tilt (HUT) in patients with lone PAF. The study included 68 patients with lone PAF and 34 healthy individuals who underwent baroreflex assessment. Parameters such as baroreflex sensitivity (BRS), number of systolic blood pressure (BP) ramps, and the baroreflex effectiveness index (BEI) were evaluated. The study found that PAF patients had comparable resting BPs and heart rates (HRs) to healthy individuals. However, unlike healthy individuals, PAF patients showed a sustained increase in BP with an upright posture followed by the delayed activation of the baroreceptor function with a blunted HR response and lower BEI values. This indicates a pronounced baroreflex impairment in PAF patients, even at rest. Our data suggest that together with BRS, BEI could be used as a marker of autonomic dysfunction in PAF patients, making it important to further investigate its relationship with AF recurrence after ablation and its involvement in cardiovascular autonomic remodeling.

Introduction: Hypertension, a leading cause of death, was investigated in this study to understand the role of specific brain regions in regulating blood pressure. The lateral parabrachial nucleus (LPBN), Kolliker-fuse nucleus (KF), and periductal grey matter (PAG) were examined for their involvement in hypertension., Methods: Lentiviral vectors were used to alter the activity of these brain regions in hypertensive rats. Over a 75-day period, blood pressure, heart rate, reflex responses, and heart rate variability were measured., Results: Decreasing the activity in the LPBN resulted in a reduced sympathetic outflow, lowering the blood pressure and heart rate. In the KF, the sympathetic activity decreased and chemoreflex variation was attenuated, without affecting the blood pressure. Silencing the PAG had no significant impact on blood pressure or sympathetic tone, but decreased cardiac baroreflex gain., Discussion: These findings highlight the significant role of the LPBN in hypertension-related sympathetic activation. Additionally, LPBN and KF neurons appear to activate mechanisms that control respiration and sympathetic outflow during chemoreceptor activation., Conclusions: The study provided insights into the contribution of the midbrain and pontine regions to neurogenic hypertension and offers potential avenues for future genetic interventions and developing novel treatment approaches.

Background: Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) has been growing as an alternative technique, not only in patients with paroxysmal atrial fibrillation (PAF) but also in persistent atrial fibrillation (AF). Cryoballoon ablation has demonstrated encouraging acute and mid-term results. However, data on long-term follow-up of CB-based PVI are scarce., Objective: We sought to examine efficacy, safety, and long-term outcomes of CBA in PAF and persistent AF in four Portuguese centers., Methods: All patients that were treated with the cryoballoon catheter according to routine practices with a second-generation 28-mm CB in four centers were included. This was a retrospective, non-randomized analysis. Patients were followed-up for >12 months and freedom from atrial arrhythmias (AA) was evaluated at the end of follow-up., Results: Four hundred and six patients (57.7±12.4 years, 66% men) participated. AF was paroxysmal in 326 patients (80.2%) and persistent in 80 (19.7%). The mean procedure time duration was 107.7±50.9 min, and the fluoroscopy time was 19.5±9.7 min. Procedural/periprocedural complications occurred in 30 cases (7.3%), being transient phrenic nerve palsy the most frequent incident (2 out of 3 complications). Anatomic variations of the PV were present in 16.1% of cases. At a mean follow-up of 22.0±15.0 months, 310 patients (76.3%) remained in stable sinus rhythm, with at least one AF episode recurrence documented in 98 cases (24.1%). The recurrence rate was 20.5% in the PAF group and 37.8% in the persistent AF group., Conclusion: In this multicenter experience, a single CBA procedure resulted in 75.9% freedom from AF at a 22-month follow-up. This technique was demonstrated to be a safe and effective option in experienced centers for the treatment of PAF and PersAF., (Copyright © 2023 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: This study aimed to assess whether atrial fibrillation (AF) occurrence or its corresponding daily mean burden (in minutes/day) during the mid to late blanking period after pulmonary vein isolation (PVI), predicts AF recurrence., Methods: Analysis of consecutive first PVI ablation patients undergoing prolonged electrocardiogram (ECG) monitoring during the second and third months after PVI. The clinical variables, total AF burden, and their relationship with time to recurrence were studied., Results: 477 patients with a mean age of 56.9 (SD = 12.3) years (63.7 % male; 71.7 % paroxysmal AF), from which 317 (66.5 %) had an external event recorder between 30 and 90 days after ablation. Median follow-up of 16.0 (P 25:12.0: P 75:33.0) months, 177 (37 %) patients had an AF recurrence, with 106 (22.2 %) having the first episode after 12 months of follow-up. In the group of patients with an event recorder, 80 (25.2 %) had AF documented during the blanking period. Multivariable analysis showed that AF during the blanking period was associated with a 4-fold higher risk of recurrence (HR: 3.98; 95 %CI: 2.95-5.37), and, compared to patients in sinus rhythm, those with an AF burden ≥ 23 min/day had an approximately 7-fold higher risk of recurrence (HR estimate: 6.79; 95 %CI: 4.56-10.10)., Conclusions: The probability of experiencing AF recurrence can be predicted by atrial tachyarrhythmia episodes during the second and third months after PVI. Atrial arrhythmias burden > 23 min/day has a high predictive ability for recurrence., Competing Interests: 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., (© 2022 The Authors.)

We compared response patterns of cardiovagal modulation through heart-rate variability (HRV) and baroreflex sensitivity (BRS) indices at 10 and 60 min after an acute bout of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in active young and older adults. Twelve young (aged 20-40 years) and older (aged 57-76 years) healthy and active male adults performed an isocaloric acute bout of HIIE, MICE, or a non-exercise condition in a randomized order. HRV and BRS indices were analyzed offline with R-R intervals obtained from a supine position. HIIE decreased natural logarithm (Ln) standard deviation of NN intervals (d=-0.53; 95% CI: -0.77 to -0.30 ms, p <0.001), Ln-root mean square of successive differences (d=-0.85; 95% CI: -1.09 to -0.61 ms, p <0.001), Ln-high-frequency power (d=-1.60; 95% CI: -2.11 to -1.10 ms 2 ; p <0.001), and BRS (d=-6.28; 95% CI: -8.91 to -3.64 ms/mmHg, p <0.001) after exercise in young and older adults, whereas MICE did not. Indices returned to baseline after 60 min. We found no evidence of age-associated response patterns in HRV or BRS to a single bout HIIE or MICE in active participants. HIIE reduced cardiovagal modulation in active young and older adults, returning to baseline values 60 min into recovery., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Atrial fibrillation (AF) is the most common sustained arrhythmia in the population and is associated with a significant clinical and economic burden. Rigorous assessment of the presence and degree of an atrial arrhythmic substrate is essential for determining treatment options, predicting long-term success after catheter ablation, and as a substrate critical in the pathophysiology of atrial thrombogenesis. Catheter ablation of AF has developed into an essential rhythm-control strategy. Nowadays is one of the most common cardiac ablation procedures performed worldwide, with its success inversely related to the extent of atrial structural disease. Although atrial substrate evaluation remains complex, several diagnostic resources allow for a more comprehensive assessment and quantification of the extent of left atrial structural remodeling and the presence of atrial fibrosis. In this review, we summarize the current knowledge on the pathophysiology, etiology, and electrophysiological aspects of atrial substrates promoting the development of AF. We also describe the risk factors for its development and how to diagnose its presence using imaging, electrocardiograms, and electroanatomic voltage mapping. Finally, we discuss recent data regarding fibrosis biomarkers that could help diagnose atrial fibrotic substrates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cunha, Laranjo, Heijman and Oliveira.)

Introduction/objectives: By May 2020, SARS-CoV-2 had caused more than 400 000 deaths worldwide. Initially, hydroxychloroquine was a treatment option for COVID-19. More recent studies have questioned its safety and efficacy and, until stronger evidence is available, it was suspended from therapy protocols. We describe our experience treating COVID-19 Portuguese pediatric patients with hydroxychloroquine, having applied a protocol for monitoring cardiac toxicity., Methods: An observational retrospective study of COVID-19 pediatric patients, admitted from March to April 2020 and treated with hydroxychloroquine. Cardiotoxicity was assessed using ECG recordings and corrected QT-time (QTc). Patients were classified into risk-groups depending on QTc value: normal, slightly elevated or severely elevated (>500 ms)., Results: Total of 14 patients, with a median age of 10 years [four months; 17 years], treated with hydroxychloroquine for a median of five days. Hydroxychloroquine was used in monotherapy in six patients (mainly mild disease with comorbidities), and in association with lopinavir/ritonavir (3) and azithromycin (5) in moderate to severe disease. Other QT-prolonging therapies were used in five patients: oseltamivir (3), omeprazole (1), morphine (1) and ketamine (1). At 48 hours of treatment, two patients temporarily suspended hydroxychloroquine due to QTc prolongation (>500 ms). All patients completed the whole treatment. No other side effects or deaths occurred., Conclusion: Clinical trials are evolving to define hydroxychloroquine effectivity and safety. Our considerable pediatric population supports the need for cardiotoxicity monitoring during therapy but suggest its use seems to be safe in COVID-19 pediatric patients, even in association with other QT-prolonging therapies., (© 2021 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U.)

Aims: The present study analysed the patterns of physical activity pre-, during and post-lockdown measures for COVID-19 pandemic in patients with chronic heart failure (CHF) and cardiac implantable electronic devices (CIED) under remote monitoring (RM), and assessed the physical activity patterns during these periods., Methods: The raw data from 95 patients with CHF (age 67,7 ± 15,1 years, 71,5% male) corresponding to 2238 RM transmissions of the Medtronic Carelink™ network platform was obtained. The physical exercise profiles and the impact of the lockdown measures on the physical behaviour during and after the measures were analysed. According to the level of activity duration in the pre-lockdown, lockdown and post-lockdown periods, the patterns of behaviour were identified (non-recoverees, incomplete recoverees, recoverees and full-recoverees)., Conclusion: RM of CHF patients with CIED using the Carelink™ network is useful for close follow-up and identification of heart failure risk status variations. After relieving the confinement measures there were two groups of patients that did not recover the previous physical activity levels. Physical inactivity in patients with CHF can have a significant impact on outcomes., Competing Interests: 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., (© 2021 The Authors.)

Introduction: The omnipolar electrogram method was recently proposed to try to generate orientation-independent electrograms. It estimates the electric field from the bipolar electrograms of a clique, under the assumption of locally plane and homogeneous propagation. The local electric field evolution over time describes a loop trajectory from which omnipolar signals in the propagation direction, substrate and propagation features, are derived. In this work, we propose substrate and conduction velocity mapping modalities based on a modified version of the omnipolar electrogram method, which aims to reduce orientation-dependent residual components in the standard approach. Methods: A simulated electrical propagation in 2D, with a tissue including a circular patch of diffuse fibrosis, was used for validation. Unipolar electrograms were calculated in a multi-electrode array, also deriving bipolar electrograms along the two main directions of the grid. Simulated bipolar electrograms were also contaminated with real noise, to assess the robustness of the mapping strategies against noise. The performance of the maps in identifying fibrosis and in reproducing unipolar reference voltage maps was evaluated. Bipolar voltage maps were also considered for performance comparison. Results: Results show that the modified omnipolar mapping strategies are more accurate and robust against noise than bipolar and standard omnipolar maps in fibrosis detection (accuracies higher than 85 vs. 80% and 70%, respectively). They present better correlation with unipolar reference voltage maps than bipolar and original omnipolar maps (Pearson's correlations higher than 0.75 vs. 0.60 and 0.70, respectively). Conclusion: The modified omnipolar method improves fibrosis detection, characterization of substrate and propagation, also reducing the residual sensitivity to directionality over the standard approach and improving robustness against noise. Nevertheless, studies with real electrograms will elucidate its impact in catheter ablation interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Riccio, Alcaine, Rocher, Martinez-Mateu, Laranjo, Saiz, Laguna and Martínez.)

Thyroid dysfunction is one of the most common adverse effects of amiodarone therapy, ranging from subclinical changes to overt clinical thyrotoxicosis (AIT) and/or hypothyroidism. Due to its heterogeneity, AIT lasts as a defiant entity, leading to a thorny treatment course, particularly in pediatrics. AIT can be classified as either type 1, type 2 or mixed form based on its pathophysiology. Differentiating between the main AIT subtypes is quite relevant, since there is specific treatment for both, however, this distinction may be difficult in clinical practice. We describe a rare case of AIT in a pediatric patient, with an uncommon congenital cardiac malformation, that started amiodarone therapy due to paroxysmal supraventricular tachycardia. AIT was reported 26 months after drug onset, with a sudden and explosive emerging. This case highlights the current AIT management challenges on the highdemanding pediatric field pursuing, ultimately, an enhanced patient´s care., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (©Copyright: the Author(s), 2019.)

Objective: Sudden cardiac death is common in the adult congenital heart disease (ACHD) population. Knowledge and experience about the use of implantable cardioverter defibrillators (ICD) in ACHD patients is very limited. We aimed to characterize a cohort of patients with ACHD and ICDs., Design: Thirty consecutive ACHD patients submitted to an ICD implantation in a single tertiary center were evaluated. Data on baseline clinical features, heart defect, indication for ICD, type of device, appropriate therapies, ICD-related complication, and mortality during follow-up were collected., Results: Of the 30 patients, 56.7% received appropriate therapies due to ventricular tachycardia (VT) or ventricular fibrillation (VF). The rate of inappropriate therapies and device-related complications was 33.3%. Secondary prevention and primary prevention patients with class I indications for ICD had more appropriate therapies than complication, but this relationship was reversed for patients with class II indications. Remote monitoring played an important role in diagnosing new atrial arrhythmias before scheduled visits in 46.2% of patients, leading to a change in medication. VT/VF episodes were associated with a composite of death, cardiac transplantation, and hospital admission (OR 13.0; 95% CI: 2.1-81.5)., Conclusion: ICDs are not only useful in preventing SCD, but also have a major role in diagnosing atrial tachyarrhythmias ahead of scheduled visits. Although improvements in ICD technology might reduce complications and inappropriate therapies, adequate selection of candidates for primary prevention still remains difficult because of the lack of clear indications., (© 2019 Wiley Periodicals, Inc.)

Objective: To estimate the treatment gap between a new epilepsy diagnosis and antiepileptic drug (AED) initiation in the United States., Methods: Retrospective claims-based cohort study using Truven Health MarketScan databases (commercial and supplemental Medicare, calendar years 2010-2015; Medicaid, 2010-2014) and a validation study using PharMetrics Plus Database linked to LRx claims database (2009-2014). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (1 year for persons aged 1 to <2 years; none for persons <1 year), and continuous medical and pharmacy enrollment without epilepsy/seizure diagnosis or AED prescription during baseline. Outcomes included percentage of untreated persons (no AED prescription) up to 3 years' follow-up and comparative outcomes (incidence rate ratio: untreated persons/treated persons), including medical events and health care resource utilization., Results: In the primary study, 59,970 persons met selection (or inclusion) criteria; 36.7% of persons with newly diagnosed epilepsy remained untreated up to 3 years after diagnosis. In the validation study (N = 30,890), 31.8% of persons remained untreated up to 3 years after diagnosis. Lack of AED treatment was associated with an adjusted incidence rate ratio (95% confidence interval) of 1.2 (1.2-1.3) for medical events, 2.3 (2.2-2.3) for hospitalizations, and 2.8 (2.7-2.9) for emergency department visits., Conclusions: One-third of newly diagnosed persons remain untreated up to 3 years after epilepsy diagnosis. The increased risk of medical events and health care utilization highlights the consequences of delayed treatment after epilepsy diagnosis, which might be preventable., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Uhl's disease, also known as Uhl anomaly, is a rare disease secondary to selective but uncontrolled apoptosis of right ventricular myocytes during the perinatal period, after complete cardiac development, leading to the absence of right ventricular myocardium and the direct apposition of endocardium to epicardium without a myocardial layer in between, resulting in right ventricular failure. The present paper describes a case of Uhl's disease with an uncommon presentation. A 28-year-old man was admitted with dyspnea and cyanosis. Transthoracic echocardiography showed severe dilation of the right chambers, impaired right ventricular systolic function and a large ostium secundum atrial septal defect (ASD). Cardiac catheterization revealed pulmonary hypertension, with increased pulmonary capillary wedge pressure (mean 19mmHg) and Qp:QS 0.88:1. At this point, the authors considered that a main diagnosis of ASD could not explain the clinical features and hemodynamic data. A primary disease of the right ventricle was the most likely hypothesis and cardiac magnetic resonance imaging was performed, which demonstrated an extremely thin-walled right ventricle, with almost complete absence of right ventricular free wall myocardium, compatible with Uhl's disease., (Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: In tetralogy of Fallot (TOF), the dominant ventricular tachycardia substrates are slow-conducting anatomical isthmuses. Surgical correction has evolved, which might have influenced isthmus presence and dimensions., Methods: One hundred and forty-two postmortem TOF specimens (84/58 corrected/uncorrected) were studied for isthmus presence. Isthmus 1 is located between the tricuspid annulus and right ventricular (RV) outflow tract (RVOT) patch/RV incision, isthmus 2 between RVOT patch/RV incision and pulmonary valve, isthmus 3 between pulmonary valve and ventricular septal defect (patch), isthmus 4 between ventricular septal defect (patch) and tricuspid annulus. Isthmus width and thickness were measured., Results: Of 84 corrected postmortem TOF specimens (death: 6.6 years (4.0-11.5)), 83 demonstrated isthmus 1 (99%, width=25±10 mm, thickness=5±2 mm), 35 isthmus 2 (42%, width=10±9 mm, thickness=3±2 mm), 83 isthmus 3 (99%, width=10±6 mm, thickness=5±2 mm), and 5 isthmus 4 (6%, width=4±2 mm, thickness=2±1 mm). Transatrial-transpulmonary correction (n=49) as compared with transventricular correction (n=35) prevented isthmus 2 (0% vs 100%, P<0.001). Transatrial-transpulmonary correction at age <1 year (n=7) as compared with ≥1 year (n=42) required a smaller transannular RVOT patch (28±15 vs 45±14 mm, P<0.001). Mode and timing of correction did not influence presence and dimensions of isthmus 3. In corrected and uncorrected TOF specimens (death 1.8 years (0.5-6.6)), the range of isthmus 3 dimensions was broad (width: min=2 mm, max=32 mm; thickness: min=1, max 13 mm) across all ages. Isthmus 3 width and thickness were strongly correlated (r=0.65, P<0.001)., Conclusions: In TOF, the current routine use of transatrial-transpulmonary correction prevents isthmus 2. Correction <1 year reduces transannular patch size, which may influence isthmus 1 width later in life. Mode and timing of correction did not change prevalence and dimensions of isthmus 3, in which dimensions varied widely in uncorrected and corrected TOF., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Hypertension is a prevalent and major health problem, involving a complex integration of different organ systems, including the central nervous system (CNS). The CNS and the hypothalamus in particular are intricately involved in the pathogenesis of hypertension. In fact, evidence supports altered hypothalamic neuronal activity as a major factor contributing to increased sympathetic drive and increased blood pressure. Several mechanisms have been proposed to contribute to hypothalamic-driven sympathetic activity, including altered ion channel function. Ion channels are critical regulators of neuronal excitability and synaptic function in the brain and, thus, important for blood pressure homeostasis regulation. These include sodium channels, voltage-gated calcium channels, and potassium channels being some of them already identified in hypothalamic neurons. This brief review summarizes the hypothalamic ion channels that may be involved in hypertension, highlighting recent findings that suggest that hypothalamic ion channel modulation can affect the central control of blood pressure and, therefore, suggesting future development of interventional strategies designed to treat hypertension.

Knowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction., (Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in developed countries. Reported incidences vary worldwide but incidence of KD has not been established in Portugal., Aim: The aims of the study were to describe the epidemiologic characteristics and estimate incidence rates of KD among hospitalized children in Portugal., Methods: This study was a descriptive, population-based study, which used hospital discharge records of patients <20 years of age diagnosed with KD from the Hospital Register database for 2000-2011. Incidence rates were calculated using the number of KD patients and corresponding National census data., Results: There were 533 hospitalizations of 470 patients with KD as the primary diagnosis in Portugal, 63 hospitalizations were transfers of patients between hospitals and there were no relapses. The mean age at admission was 2.8 years, with male predominance (male-to-female ratio: 1.6:1). Children <5 years and infants <1 year represented 83% and 23% of all the patients admitted, respectively. Mean annual incidence was 6.5 per 100,000 children <5 years, 4.5 per 100,000 infants <1 year and 7.8 per 100,000 infants 1-4 years. We found considerable differences between national territorial regions, with majority of cases in most dense regions. The mean length of hospital stay was 9 days, and the incidence peaked in spring (35%) and spring/winter (63%). Coronary aneurysms were reported in 8.5% of patients with a higher male-to-female ratio (3.4:1) and a lower mean age (1.93 years). Reported mortality was 0.4%., Conclusions: This is the first large-scale epidemiologic study of KD in Portugal. The highest incidences occurred among male children 1-4 years of age and in spring/winter.

Background: Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. Thus far, endothelial dysfunction in patients with no coronary lesions is poorly understood. Our aim was to access the vascular function in adolescents and young adults long term after Kawasaki disease, but without coronary aneurysms or any other cardiac risk factors., Methods: We carried out a single-centre prospective study in a Portuguese population. We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed >5 years ago, with no coronary lesions or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically assessed. Endo-PAT and carotid intima-media thickness assessment were performed to determine vascular function., Results: In total, 43 Kawasaki disease patients were assessed and compared with 43 controls. Kawasaki disease patients presented a decreased reactive hyperaemia index compared with controls (1.59±0.45 versus 1.98±0.41; p<0.001). Augmentation index was similar in both groups (-4.5±7 versus -5±9%; p 0.6). The mean carotid intima-media thickness was not significantly increased in the Kawasaki disease group. There were no statistically significant changes with regard to laboratory data., Conclusions: Children with Kawasaki disease may have long-term sequelae, even when there is no discernible coronary artery involvement in the acute stage of the disease. Further research is needed to assess whether known strategies to improve endothelial function would bring potential benefits to Kawasaki disease patients.

Unlabelled: Introduction Thoracic endovascular aneurysm repair has been employed to treat late complications after aortic coarctation correction. However, its use in children has seldomly been reported. Case report We present the case of a 15-year-old child who presented with a ruptured aneurysm of the descending aorta complicated later by an aortic-oesophageal fistula following aortic coarctation stenting that was managed with multiple bridging endovascular interventions until a definitive repair was performed., Conclusion: Thoracic endovascular aneurysm repair may be used successfully as a bridging intervention to a definitive repair in children with life-threatening aortic complications following aortic coarctation repair.

Introduction: Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT., Methods: The study population consisted of 25 patients with indication for CRT, aged 65±10 years, NYHA functional class ≥III in 52%, QRS width 159±15 ms, left ventricular ejection fraction (LVEF) 29±5%, left ventricular end-systolic volume (LVESV) 150±48 ml, B-type natriuretic peptide (BNP) 357±270 pg/ml, and peak oxygen consumption (peak VO2) 18.4±5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals., Results: HF patients showed a significantly depressed BEI during tilt (31±12% vs. 49±18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB ≤25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min., Conclusions: Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT., (Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Mortality and morbidity by toxic metals is an important issue of occupational health. Lead is an ubiquitous heavy metal in our environment despite having no physiological role in biological systems. Being an homeostatic controller is expected that the autonomic nervous system would show a degree of impairment in lead toxicity. In fact, sympathoexcitation associated to high blood pressure and tachypnea has been described together with baroreflex dysfunction. However, the mechanisms underlying the autonomic dysfunction and the interplay between baro- and chemoreflex are not yet fully clarified. The angiotensinogenic PVN-NTS axis (paraventricular nucleus of the hypothalamus - nucleus tractus solitarius axis) is a particularly important neuronal pathway that could be responsible for the autonomic dysfunction and the cardiorespiratory impairment in lead toxicity. Within the current work, we addressed in vivo, baro- and chemoreceptor reflex behaviour, before and after central angiotensin inhibition, in order to better understand the cardiorespiratory autonomic mechanisms underlying the toxic effects of long-term lead exposure. For that, arterial pressure, heart rate, respiratory rate, sympathetic and parasympathetic activity and baro- and chemoreceptor reflex profiles of anaesthetized young adult rats exposed to lead, from foetal period to adulthood, were evaluated. Results showed increased chemosensitivity together with baroreceptor reflex impairment, sympathetic over-excitation, hypertension and tachypnea. Chemosensitivity and sympathetic overexcitation were reversed towards normality values by NTS treatment with A-779, an angiotensin (1-7) antagonist. No parasympathetic changes were observed before and after A-799 treatment. In conclusion, angiotensin (1-7) at NTS level is involved in the autonomic dysfunction observed in lead toxicity. The increased sensitivity of chemoreceptor reflex expresses the clear impairment of autonomic outflow to the cardiovascular and respiratory systems induced by putative persistent, long duration, alert reaction evoked by the long term exposure to lead toxic effects. The present study brings new insights on the central mechanisms implicated in the autonomic dysfunction induced by lead exposure which are relevant for the development of additional therapeutic options to tackle lead toxicity symptoms., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population., Methods: This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation., Results: Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%., Conclusions: AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients., (Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp.

Introduction: Hypoplastic left heart syndrome (HLHS) is a major cause of cardiac death during the first week of life. The hybrid approach is a reliable, reproducible treatment option for patients with HLHS. Herein we report our results using this approach, focusing on its efficacy, safety and late outcome., Methods: We reviewed prospectively collected data on patients treated for HLHS using a hybrid approach between July 2007 and September 2014., Results: Nine patients had a stage 1 hybrid procedure, with seven undergoing a comprehensive stage 2 procedure. One patient completed the Fontan procedure. Five patients underwent balloon atrial septostomy after the hybrid procedure; in three patients, a stent was placed across the atrial septum. There were three deaths: two early after the hybrid procedure and one early after stage two palliation. Overall survival was 66%., Conclusions: In our single-center series, the hybrid approach for HLHS yields intermediate results comparable to those of the Norwood strategy. The existence of dedicated teams for the diagnosis and management of these patients, preferably in high-volume centers, is of major importance in this condition., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background: The Collaborative Brazilian Pediatric Renal Transplant Registry started in 2004 as a multicenter initiative aiming to analyze, report, and share the results of pediatric kidney transplantation in Brazil. Data from all pediatric kidney transplants performed between January 2004 and December 2013 were recorded electronically and periodically updated. All patients under 18 years old from the participating centers were enrolled. Demographic data, etiology of chronic kidney disease, and patient and graft survival were analyzed. From a total of 2443 pediatric kidney transplants performed in Brazil during the study period, we report data from 1751 pediatric renal transplants performed in 13 centers enrolled in the collaborative study. Median age at transplantation was 12.4 years, and most of recipients were male (56%). The most common underlying renal etiologies were obstructive uropathy (31%) and glomerulopathy (26%)., Methods: According to donor source, 1155 (66%) of transplants were performed with deceased donors (DD). Initial immunosuppression consisted mainly of tacrolimus, mycophenolate, steroids, and induction therapy with anti-IL-2R antibodies., Results: One-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease., Conclusions: The results of this collaborative pediatric transplant study are comparable to international registries. Our effort has been able to maintain an exchange of information, both among the participating centers and with other international registries., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Around 15% of children and adolescents experience at least one episode of syncope until adulthood. Excluding cardiac disease, the majority of syncopes are of reflex origin and benign in nature. In this situation, a tilt test is conducted to reproduce symptoms and to evaluate cardiovascular adaptations to orthostatism, but its mechanisms are not yet well defined. Here, we investigated haemodynamics and autonomic activity during tilt in young patients. Patients (n=113) with unexplained syncope were enrolled. Tilt followed a standard protocol without provocative agents. A positive response (fainters) was defined as a sudden development of syncope or presyncope associated with hypotension, bradycardia, or both. Haemodynamic parameters, autonomic activity, and baroreflex sensibility were evaluated. Data were analysed on baseline; immediately after tilting; on tilt adaptation; before fainting or before tilt-down for non-fainters; and on tilt-down. A total of 45 patients experienced syncope after a mean time of 18 minutes. During tilting up, fainters showed lower blood pressure and peripheral resistance values, which decreased progressively with time together with baroreflex sensibility. Sympathetic tone increased massively along time till syncope. No changes in cardiac output and heart rate were observed. Results show a strong effort of the autonomic nervous system to adapt to orthostatic stress through different magnitudes of sympathetic output, which was maximal before syncope without apparent modifications of parasympathetic tone. These changes suggest an imbalance between both branches of the autonomic nervous system, not enabling a time-progressive adaptation and leading the subject to faint.

We report a case of a patient with recurrent syncope and paroxysmal atrial fibrillation whose clinical status greatly improved after a period of orthostatic training. The potential efficacy of this non-pharmacological measure in modulating the autonomic tone is discussed below., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Infantile hemangioma (IH) is one of the most common childhood tumors. There are various medical or surgical therapeutic options, all with suboptimal results. Recently, the successful use of propranolol for involution of IH was described. We report the results of a single-center experience with this therapeutic option., Objective: To prospectively assess the efficacy and safety of propranolol in children with infantile hemangioma., Methods: We performed a prospective analysis of clinical data of all patients with IH referred to a pediatric cardiology center for baseline cardiovascular assessment prior to propranolol therapy. Propranolol was given at a starting dose of 1 mg/kg/day and titrated to a target dose of 2-3 mg/kg/day according to clinical response. Efficacy was assessed through a photograph-based severity scoring scale. Safety was assessed by collecting data regarding significant side effects., Results: Starting in 2010, 30 patients (15 female) were referred for propranolol treatment of IH, at a median age of six months (1-63 months). The mean target propranolol dose was 2.8 mg/kg/day, with a mean duration of therapy of 12 months. All patients experienced significant reduction of IH size and volume. There were no side effects., Conclusions: In our experience propranolol appears to be a useful and safe treatment option for severe or complicated IH, achieving a rapid and significant reduction in their size. No adverse effects were observed, although until larger clinical trials are completed, potential adverse events should be borne in mind and consultation with local specialists is recommended prior to initiating treatment., (Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Dilated cardiomyopathy is the commonest form of cardiomyopathy in pediatric patients. Various causal factors have been identified, including ionic imbalance. Calcium ions play an essential role in regulating myocardial contractile function, and the harmful role of hypocalcemia as a coadjuvant or even precipitating factor of worsening heart failure has been described in rare case reports. Multiple causative factors may occasionally be present. We describe the first case, to our knowledge, of dilated cardiomyopathy in an infant with severe hypocalcemia and viral myocarditis., (Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background: Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. So far, the presence of endothelial dysfunction in patients with no coronary lesions has not been demonstrated. Peripheral arterial tonometry (Endo-PAT) measures the microvascular function in response to local ischaemia and has been validated in adult population, but its use in children is scarce. Aim To evaluate endothelial dysfunction in children as a long-term complication after Kawasaki disease using Endo-PAT., Methods: We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed for >5 years, with no coronary lesions, or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically accessed. Endo-PAT was performed to determine reactive hyperaemia index and augmentation index., Results: A total of 35 individuals (21 males, age 21 ± 6 years) were evaluated (group 1: 19; controls: 16). Kawasaki disease patients presented significant lower reactive hyperaemia index (1.68 ± 0.49 versus 2.31 ± 0.53; p = 0.001). Augmentation index was similar in both groups (-10 ± 7 versus -11 ± 5; p > 0.005). Most patients with Kawasaki disease disclosed endothelial dysfunction (68%) compared with only 12% in controls., Conclusions: Endo-PAT is feasible and reproducible in the child population. Endothelial dysfunction is a frequent long-term complication in patients after Kawasaki disease with normal appearing coronary arteries. However, these results need validation in a larger population.

Purpose: Postictal generalized EEG suppression (PGES) seems to be a pathophysiologic hallmark in ictal recordings of sudden unexpected death in epilepsy (SUDEP). It has recently been suggested that presence and duration of PGES might be a predictor of SUDEP risk. Little is known about the etiology of PGES., Methods: We conducted a retrospective case-control study in 50 people with convulsive seizures (CS) recorded on digital video-electroencephalography (EEG). One CS per individual was reviewed for presence and duration of PGES by two independent observers: Preictal and postictal heart rate (HR) (1 min before seizure onset and 1, 3, 5, 15, and 30 min after seizure end) and frequency domain measures of heart rate variability (HRV), including the ratio of low frequency (LF) versus high frequency (HF) power, were analyzed. The relationship between PGES and periictal autonomic changes was evaluated, as well as its association with several clinical variables., Key Findings: Thirty-seven individuals (74%) exhibited PGES and 13 (26%) did not. CS resulted in a significant increase of periictal HR and the LF/HF ratio. PGES was associated with neither periictal HR (mean HR difference between PGES+ and PGES- seizures: -2 beats per minute [bpm], 95% confidence interval [CI] -10 to +6 bpm) nor HRV change. There was no association between the duration of PGES and periictal HR change. People with PGES were more likely to be asleep before seizure onset (odds ratio [OR] 4.7, 95% CI 1.2-18.3) and had a higher age of onset of epilepsy (median age 15 vs. 4 years)., Significance: PGES was not associated with substantial changes in measures of cardiac autonomic instability but was more prevalent in CS arising from sleep., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Unlabelled: Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear., Objective: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures., Methods: We studied 28 patients (50% male, mean age 41±14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60° - 6 sessions, 70° - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10° head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24±12 months)., Results: Over the course of the TT program there was a significant increase in total peripheral resistance (1485±225 vs. 1591±187 dyn·s·cm(-5), p<0.05), with a decrease in standard deviation (206±60 vs. 150±42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0±3.2/patient in the 12 months before TT vs. 1.4±0.8/patient post-TT, p<0.05)., Conclusion: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance., (Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Unlabelled: Atrial fibrillation (AF) is a complex disease with multiple mechanisms, involving the interaction between the autonomic nervous system (ANS), electrophysiological properties of the atria and pulmonary veins (PVs), and vulnerability for AF., Aim: We assessed the effects of acute vagal (vagus&#95;stim) and sympathetic stimulation (symp&#95;stim) on atrial conduction, atrial and PV refractoriness and inducibility of AF in an in vivo rabbit model with preserved autonomic innervation., Methods: An open-epicardial approach was used in 17 anesthetized and artificially ventilated New Zealand white rabbits. The ECG was recorded with bipolar subcutaneous electrodes placed in the four limbs. Electrograms were obtained with four monopolar electrodes placed epicardially along the atria, and a circular electrode adapted to the proximal PVs. The cervical vagus nerve and thoracic sympathetic trunk were stimulated with bipolar electrodes. Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs) and conduction times from the high-lateral right atrium (RA) to the high-lateral left atrium (LA) and PVs were quantified at baseline and during vagus&#95;stim, symp&#95;stim, or combined vagal and sympathetic stimulation (dual&#95;stim). Burst pacing (50 Hz, 10 s), alone or combined with vagus&#95;stim, symp&#95;stim or dual&#95;stim, was performed in the right (RAA) and left atrial appendage (LAA) and PVs to test for AF inducibility., Results: At baseline, ERPs were higher in the LAA and there was a delay in the conduction time from RA to PV, compared to the mean activation time from RA to LA. During vagus&#95;stim or dual&#95;stim, ERP decreased significantly at all sites, and baseline interatrial activation times changed from 20 +/- 4 ms to 30 +/- 10 ms and 31 +/- 11 ms, respectively (p < 0.05). Symp&#95;stim resulted in a significant decrease in ERPs only in the LAA, and a reduction of the interatrial interval to 16 +/- 11 ms (p < 0.05 vs baseline). AF inducibility ranged from 35% to 53% with baseline 50 Hz pacing, 65% to 76% during vagus&#95;stim or symp&#95;stim, and 75% to 100% with dual&#95;stim (p < 0.05). AF duration increased significantly during ANS stimulation. In two-thirds of the animals with longer inducible AF, the arrhythmia ceased immediately after cessation of vagus&#95;stim., Conclusions: In the fully innervated rabbit heart in vivo, acute ANS stimulation shortens atrial and PV refractoriness, and significantly changes atrial conduction times, promoting AF induction and prolonging the arrhythmia. This underscores the importance of acute variations in ANS tone and its interactions in the pathophysiology of AF.

Vagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). We evaluated the effects of acute vagal stimulation on atrial conduction, refractoriness of atrial and pulmonary veins (PVs) and inducibility of AF. An open-chest epicardial approach was performed in New Zealand White rabbits with preserved autonomic innervation. Atrial electrograms were obtained with four unipolar electrodes placed epicardially along the atria (n = 22) and an electrode adapted to the proximal left PV (n = 10). The cervical vagus nerve was stimulated with bipolar platinum electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs), dispersion of refractoriness and conduction times from high-lateral right atrium (RA) to high-lateral left atrium (LA) and PVs assessed at baseline and during vagal stimulation. Burst pacing (50 Hz, 10 s), alone or combined with vagal stimulation, was applied to the right (RAA) and left atrial appendage (LAA) and PVs to induce AF. At baseline, ERPs were lower in PVs than in LA and LAA, but did not differ significantly from RA and RAA, and there was a significant delay in the conduction time from RA to PVs compared with the activation time from RA to LA (P < 0.01). During vagal stimulation, ERP decreased significantly at all sites, without significant differences in the dispersion of refractoriness, and the atrial conduction times changed from 39 ± 19 to 49 ± 9 ms (RA to PVs; n.s.) and from 14 ± 7 to 28 ± 12 ms (RA to LA; P = 0.01). Induction of AF was reproducible in 50% of cases with 50 Hz and in 82% with 50 Hz combined with vagal stimulation (P < 0.05). During vagal stimulation, AF cycle length decreased at all sites, and AF duration changed from 1.0 ± 0.9 to 14.0 ± 10.0 s (P < 0.01), with documentation of PV tachycardia in three cases. In 70% of the animals, AF ceased immediately after interruption of vagal stimulation. We conclude that in the intact rabbit heart, vagal activity prolongs interatrial conduction and shortens atrial and PV ERP, contributing to the vulnerability to the induction and maintenance of AF. This model may be useful in the assessment of the autonomic influence in the mechanisms underlying AF.

Introduction: Vagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). In this study, we assessed the effects of acute vagal stimulation (vagus&#95;stim) on atrial conduction times, atrial and pulmonary vein (PV) refractoriness, and vulnerability to induction of AF in the rabbit heart with intact autonomic innervation., Methods: An open-chest epicardial approach was performed in 11 rabbits (New Zealand; 3.9-5.0 kg), anesthetized and artificially ventilated after neuromuscular blockade. A 3-lead ECG was obtained. Atrial electrograms were recorded along the atria, from right to left (four monopolar electrodes), together with a circular electrode adapted for proximal left PV assessment. Acute vagus nerve stimulation was obtained with bipolar electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and the conduction time from right (RA) to left atrium (LA), and from RA to PVs, was measured in basal conditions and during vagus&#95;stim. The atrial effective refractory period (ERP) and dispersion of refractoriness (Disp&#95;A) were analyzed. Vulnerability to AF induction was assessed at the right (RAA) and left (LAA) atrial appendages and the PVs. Atrial stimulation (50 Hz) was performed alone or combined with vagus&#95;stim. Heart rate and blood pressure were monitored., Results: In basal conditions, there was a significant delay in conduction from RA to PVs, not influenced by vagus&#95;stim, and the PV ERPs were shorter than those measured in LA and LAA, but without significant differences compared to RA and RAA. During vagus&#95;stim, conduction times between RA and LA increased from 16+8 ms to 27+6 ms (p < 0.05) and ERPs shortened significantly in RA, LAA and LA (p < 0.05), but not in RAA. There were no significant differences in Disp&#95;A. AF induction was reproducible in 45% of cases at 50 Hz and in 100% at 50 Hz+vagus&#95;stim (p < 0.05). The duration of inducible AF increased from 1.0 +/- 0.2 s to 12.0 +/- 4.5 s with 50 Hz+vagus&#95;stim (p < 0.01). AF lasted >10 s in 45.4% of rabbits during vagus&#95;stim, and ceased after vagus&#95;stim in 4 out of these 5 cases. In 3 animals, PV tachycardia, with fibrillatory conduction, induced with 50 Hz PV pacing during vagus&#95;stim., Conclusions: Vagus&#95;stim reduces interatrial conduction velocity and significantly shortens atrial ERP, contributing to the induction and duration of AF episodes in the in vivo rabbit heart. This model may be useful for the assessment of autonomic influence on the pathophysiology of AF,