Diagnostic and Prognostic Value of Right Ventricular Fat Quantification from Computed Tomography in Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case-control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <-10. Within the scar, a border zone (between -10 HU and -50 HU) and dense scar (<-50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls (p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD (p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value.

Impact of Body Mass Index in the Cardioverter Efficacy of Amiodarone in Persistent Atrial Fibrillation.

BACKGROUND: Amiodarone is an anti-arrhythmic drug that has extensive tissue distribution and substantial storage in the fat tissue. Different studies have described some implications of body fat composition in its pharmacokinetics and pharmacodynamics. However, no clinical studies have described its implications for clinical efficacy. METHODS: We studied 878 patients with persistent atrial fibrillation (AF) treated with a regimen of amiodarone and referred to electrical cardioversion (ECV), included prospectively in two Spanish registries. We analyzed the influence of body mass index (BMI), as well as overweight and obesity, in the efficacy of amiodarone for achieving pharmacologic cardioversion to sinus rhythm (SR) before ECV. RESULTS: A total of 185 patients (21.1%) reverted to SR before ECV. Patients who reverted to SR had a lower BMI than those who did not revert (27.45 ± 4.36 kg/m2 vs. 29.11 ± 4.09 kg/m2; p < 0.001). We observed a progressively lower probability of reverting to SR in overweight and obese patients (normal weight 28.3%, overweight 21.3%, obesity 13.1%; p < 0.001). In the logistic regression, BMI (kg/m2) adjusted for other related variables remained as the main factor inversely related to reversion to SR (OR = 0.904 × kg/m2); CI 75% 0.864-0.946). CONCLUSIONS: We observed a negative relationship between an increased BMI and the efficacy of amiodarone for reversion to SR, suggesting a negative clinical impact of excess body fat in its efficacy.

Current management of atrial fibrillation in routine practice according to the last ESC guidelines: an EHRA physician survey-how are we dealing with controversial approaches?

AIMS: Although guidelines for the management of atrial fibrillation (AF) are regularly published, many controversial issues remain, limiting their implementation. We aim to describe current clinical practice among European Heart Rhythm Association (EHRA) community according to last guidelines. METHODS AND RESULTS: A 30 multiple-choice questionnaire covering the most controversial topics related to AF management was distributed through the EHRA Research Network, National Societies, and social media between January and February 2023. One hundred and eighty-one physicians responded the survey, 61% from university hospitals. Atrial fibrillation screening in high-risk patients is regularly performed by 57%. Only 42% has access to at least one programme aiming at diagnosing/managing comorbidities and lifestyle modifications, with marked heterogeneity between countries. Direct oral anticoagulants are the preferred antithrombotic (97%). Rhythm control is the preferred strategy in most AF phenotypes: symptomatic vs. asymptomatic paroxysmal AF (97% vs. 77%), low vs. high risk for recurrence persistent AF (90% vs. 72%), and permanent AF (20%). I-C drugs and amiodarone are preferred while dronedarone and sotalol barely used. Ablation is the first-line therapy for symptomatic paroxysmal AF (69%) and persistent AF with markers of atrial disease (57%) and is performed independently of symptoms by 15%. In persistent AF, 68% performs only pulmonary vein isolation and 32% also additional lesions. CONCLUSION: There is marked heterogeneity in AF management and limited accordance to last guidelines in the EHRA community. Most of the discrepancies are related to the main controversial issues, such as those related to AF screening, management of comorbidities, pharmacological treatment, and ablation strategy.

Patrones de presión arterial de 24 horas en pacientes con insuficiencia cardiaca estable. Prevalencia y factores asociados / Twenty-four hour ambulatory blood pressure monitoring in patients with stable heart failure. Prevalence and associated factors

Introducción y objetivos: La hipertensión arterial (HTA) está muy presente en la insuficiencia cardiaca (IC). Sin embargo, su prevalencia, su variación circadiana y la relación con los fenotipos de IC es poco conocida. Nuestro objetivo es describir esta prevalencia y sus patrones en la IC.Métodos: Estudio observacional y transversal sobre la IC crónica estable optimizada. Se obtuvo la presión arterial (PA) en consulta y monitorización ambulatoria durante 24 h. Se estimó la prevalencia de HTA, sus patrones diurnos (controlada, no controlada, de bata blanca y enmascarada) y nocturnos (dipper, nondipper y reverse dipper). Se analizaron factores asociados con patrones y fenotipos de IC.Resultados: Entre 2017 y 2021, se incluyó a 266 pacientes con una media de edad de 72±12 años; el 67% eran varones y el 46% tenían IC con FEVI reducida. El 83% tenía HTA: el 68% controlada, el 10% no controlada, el 10% de bata blanca y el 11% enmascarada. El 51% de los pacientes con PA elevada en consulta resultaron en HTA de bata blanca. El 14% de los pacientes con PA normal en consulta tenían HTA enmascarada. Las prevalencias de dipper, nondipper y reverse dipper fueron del 31, el 43 y el 26% respectivamente. La PA sistólica fue menor en la IC con FEVI reducida que en la IC con FEVI conservada (p <0,001).Conclusiones: La monitorización ambulatoria de la PA en IC identificó HTA de bata blanca en más de la mitad de los pacientes con PA elevada en consulta y un porcentaje relevante de HTA enmascarada. La distribución de patrones diurnos fue similar a la de la población sin IC descrita. Sin embargo, la mayoría tuvo un patrón nocturno patológico.(AU)

Introduction and objectives: Hypertension is highly common in heart failure (HF). However, there is limited information on its prevalence, circadian variation, and relationship with the various HF phenotypes. The objective of this study was to describe the prevalence of hypertension and its patterns in HF.Methods: This was a cross-sectional observational study of patients with optimized stable chronic HF. The patients underwent blood pressure (BP) measurement in the office and 24-hour ambulatory monitoring. We estimated the prevalence of hypertension, and its diurnal (controlled, uncontrolled, white coat, and masked) and nocturnal (dipper, nondipper, and reverse dipper) patterns. We also analyzed the factors associated with the different patterns and HF phenotypes.Results: From 2017 to 2021, 266 patients were included in the study (mean age, 72±12 years, 67% male, 46% with reduced ejection fraction). Hypertension was present in 83%: controlled in 68%, uncontrolled in 10%, white coat in 10%, and masked in 11%. Among patients with high office BP, 51% had white coat hypertension. Among those with normal office BP, 14% had masked hypertension. The prevalence of dipper, nondipper, and reverse dipper patterns was 31%, 43%, and 26%, respectively. Systolic BP was lower in HF with reduced ejection fraction than in HF with preserved ejection fraction (P <.001).Conclusions: Ambulatory BP monitoring in HF identified white coat hypertension in more than half of patients with high office BP and masked hypertension in a relevant percentage of patients. The distribution of daytime patterns was similar to that of the population without HF in the literature, but most of the study patients had a pathological nocturnal pattern.(AU)

Influence of body mass index on recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Several studies have shown an independent relationship between body mass index (BMI) and the incidence of atrial fibrillation (AF). However, little is known about the influence of BMI on AF recurrence after electrical cardioversion (ECV). METHODS: We selected 1121 patients who reverted to sinus rhythm after scheduled ECV and were included in three prospective Spanish registries of ECV in persistent AF. The patients were classified according to baseline BMI into three categories (normal weight, overweight, obesity). We assessed the influence of BMI on the rate of AF recurrence at 3 months. RESULTS: We identified 538 patients (48%) who had AF recurrence in the first 3 months after successful ECV. The patients who suffered AF recurrence had a higher BMI than those who remained in sinus rhythm (29.66±4.57 vs. 28.87±4.64 Kg/m2, respectively; p = 0.004). We observed a higher incidence of AF recurrence in the overweight and obese patients (BMI ≥25 kg/m2) than in those classified as normal weight (50.5% vs. 35.6%, respectively; p<0,001). BMI≥25 Kg/m2 was shown to be independently related to of AF recurrence in the multivariate analysis (OR = 1.75, 95% confidence interval = 1.20-2.58; p = 0.004). CONCLUSIONS: Increased BMI is independently related to AF recurrence after ECV. BMI should also be taken into account when making decisions about the indication for ECV in persistent AF.

Dynamics of High-Density Unipolar Epicardial Electrograms During PFA.

BACKGROUND: Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation (IRE). While areas of IRE lead to durable lesions, the surrounding regions, where reversible electroporation occurs, recover. The behavior of local electrograms in areas of different electroporation levels remains unknown. The goal of this study is to characterize electrogram dynamics after PFA in IRE and reversible electroporation areas. METHODS: A total of 6 domestic swine were used. PFA was applied in the epicardium of the right and left ventricles using a focal monopolar catheter. Additional radiofrequency ablations were performed. Epicardial unipolar electrograms were acquired at baseline and for 60 minutes post PFA/radiofrequency ablation using a high-density electrode matrix attached to the epicardium. Electrogram dynamics were analyzed in areas corresponding to different levels of electroporation. Acute lesion formation was assessed after 3 to 5 hours by triphenyl tetrazolium chloride staining. RESULTS: Electrogram analysis demonstrated a clear association between electrogram changes and the level of electroporation. Immediately after PFA, electrograms displayed the following: a significant decrease in R/S-wave amplitude; a large elevation of the ST-segment; and a large decrease in their |(dV/dt)|max. Marked changes in electrograms were observed beyond the lesion area. Thereafter, a gradual recovery was observed. The evolution of all the electrogram parameters throughout the 60 minutes after PFA was significantly different (P<0.05) between the IRE and reversible electroporation areas. Acute lesion staining showed significantly larger depth for PFA lesions compared with radiofrequency ablation. CONCLUSIONS: This study shows that unipolar electrograms can differentiate between reversible electroporation and IRE areas during the first 30 minutes post ablation. Differences after the first 30 minutes are less evident. Our findings could result useful for immediate lesion assessment after PFA and warrant further investigation.

Occupational radiation exposure of electrophysiology staff with reproductive potential and during pregnancy: an EHRA survey.

AIMS: Electrophysiology (EP) is a growing field in cardiology, with an increasing involvement of young people. Nevertheless, concerns about radiation exposure and its impact on reproduction and pregnancy may discourage the choice of an EP career. The study is aimed at investigating the level of awareness and main sources of concern about the effects of radiation on reproductive potential and pregnancy, exploring the safety measures adopted in different EP labs, and verifying the adherence to the current guidelines. METHODS AND RESULTS: An online survey was conducted using the European Heart Rhythm Association (EHRA) infrastructure from April to June 2022. A total of 252 EP personnel (42% women) participated, from 50 countries and different professional roles. Most participants expressed concerns regarding the effects of radiation on reproductive capacity (67.1%) and offspring diseases (68.2%). Only 37.9% of participants were aware of the EHRA 2017 consensus document about occupational radiation exposure. Most participants (80.9%) considered that occupational radiation during pregnancy is not safe. EP female staff were not allowed to work in the EP lab during pregnancy in 48.1% of cases. Zero-fluoroscopy was the preferred choice to continue working in the EP lab during pregnancy. CONCLUSION: EP staff, including both men and women, have concerns about the effects of radiation on reproductive capacity. Despite the recommendations issued by international bodies, implementation of the policies regarding pregnancy and occupational radiation exposure is heterogeneous. Zero-fluoroscopy is the preferred approach to ensure safety during pregnancy in the EP lab.

Reassessment of the electrical connection between the pulmonary veins and the left atrium: A study to determine the different contributions of myocardial fibers along the standard ablation circumference.

Background: Circumferential ablation around the ipsilateral pulmonary veins (PVs) is the standard strategy for atrial fibrillation ablation. The present study seeks to assess which regions of the standard ablation circumference are the main contributors to the venoatrial electrical connection. Methods: A total of 41 patients were included under a specific atrial fibrillation ablation protocol in which the anterior and posterior segments of the standard circumference, between the equatorial line of the superior and the inferior ipsilateral PVs, were ablated first. If PV isolation was not achieved, ablation was extended superiorly or inferiorly, on the basis of the earliest atrial activation recorded during pacing from inside the PV. Complete PV isolation and the length of the areas not requiring ablation (ANRA) at the time of electrical isolation were evaluated. Results: Ablation of the anterior and posterior segments of the standard circumference led to the isolation of 77% left-PV pairs and 51% right-PV pairs (p = 0,015). A superior extension was required in 23% left-PV pairs and in 46% right-PV pairs, while an inferior extension was required only in 10% left-PV pairs and in 11% right-PV pairs. PV isolation was achieved before completing the standard ablation circumference in 97% left-PV pairs and in 94% right-PV pairs, with a median ANRA of 36.9 (IQR: 30.9-42.1) mm in the left PVs [16.0 (IQR: 12.0-19.0) mm superior and 18.8 (IQR: 16.1-24.9) mm inferior, p < 0.01] and 36.9 (IQR: 30.2-41.0) mm in the right PVs [15.1 (IQR: 10.7-19.1) mm superior and 20.6 (IQR: 16.9-23.3) mm inferior, p < 0.01]. Conclusions: The myocardial fibers along the anterior and posterior regions of the standard ablation circumference are the main contributors to the electrical connection between the pulmonary veins and the left atrium. Ablation of these regions results in PV isolation in the majority of patients.

Calibration of a three-state cell death model for cardiomyocytes and its application in radiofrequency ablation.

Objective.Thermal cellular injury follows complex dynamics and subcellular processes can heal the inflicted damage if insufficient heat is administered during the procedure. This work aims to the identification of irreversible cardiac tissue damage for predicting the success of thermal treatments.Approach.Several approaches exist in the literature, but they are unable to capture the healing process and the variable energy absorption rate that several cells display. Moreover, none of the existing models is calibrated for cardiomyocytes. We consider a three-state cell death model capable of capturing the reversible damage of a cell, we modify it to include a variable energy absorption rate and we calibrate it for cardiac myocytes.Main results.We show how the thermal damage predicted by the model response is in accordance with available data in the literature on myocytes for different temperature distributions. When coupled with a computational model of radiofrequency catheter ablation, the model predicts lesions in agreement with experimental measurements. We also present additional experiments (repeated ablations and catheter movement) to further illustrate the potential of the model.Significance.We calibrated a three-state cell death model to provide physiological results for cardiac myocytes. The model can be coupled with ablation models and reliably predict lesion sizes comparable to experimental measurements. Such approach is robust for repeated ablations and dynamic catheter-cardiac wall interaction, and allows for tissue remodelling in the predicted damaged area, leading to more accurate in-silico predictions of ablation outcomes.

Twenty-four hour ambulatory blood pressure monitoring in patients with stable heart failure. Prevalence and associated factors.

INTRODUCTION AND OBJECTIVES: Hypertension is highly common in heart failure (HF). However, there is limited information on its prevalence, circadian variation, and relationship with the various HF phenotypes. The objective of this study was to describe the prevalence of hypertension and its patterns in HF. METHODS: This was a cross-sectional observational study of patients with optimized stable chronic HF. The patients underwent blood pressure (BP) measurement in the office and 24-hour ambulatory monitoring. We estimated the prevalence of hypertension, and its diurnal (controlled, uncontrolled, white coat, and masked) and nocturnal (dipper, nondipper, and reverse dipper) patterns. We also analyzed the factors associated with the different patterns and HF phenotypes. RESULTS: From 2017 to 2021, 266 patients were included in the study (mean age, 72±12 years, 67% male, 46% with reduced ejection fraction). Hypertension was present in 83%: controlled in 68%, uncontrolled in 10%, white coat in 10%, and masked in 11%. Among patients with high office BP, 51% had white coat hypertension. Among those with normal office BP, 14% had masked hypertension. The prevalence of dipper, nondipper, and reverse dipper patterns was 31%, 43%, and 26%, respectively. Systolic BP was lower in HF with reduced ejection fraction than in HF with preserved ejection fraction (P <.001). CONCLUSIONS: Ambulatory BP monitoring in HF identified white coat hypertension in more than half of patients with high office BP and masked hypertension in a relevant percentage of patients. The distribution of daytime patterns was similar to that of the population without HF in the literature, but most of the study patients had a pathological nocturnal pattern.

Regional disparity on patient characteristics and perceptions after implantable cardioverter-defibrillator implantation: results from an EHRA patient survey.

AIMS: The aim of this study was to identify potential regional disparities in characteristics of implantable cardioverter-defibrillator (ICD) recipients, patient perceptions and perspectives after implantation and level of information provided to patients. METHODS AND RESULTS: The prospective, multicentre, and multinational European Heart Rhythm Association patient Survey 'Living with an ICD' included patients already implanted with an ICD (median ICD dwell time - 5 years, interquartile range 2-10). An online questionnaire was filled-in by patients invited from 10 European countries. A total of 1809 patients (the majority in their 40s to 70s, 65.5% men) were enrolled, with 877 (48.5%) from Western Europe (group 1), followed by 563 from Central/Eastern Europe (group 2, 31.1%), and 369 from Southern Europe (group 3, 20.4%). A total of 52.9% of Central/Eastern Europe patients reported increased satisfaction after ICD placement compared with 46.6% from Western and 33.1% from Southern Europe (1 vs. 2 P = 0.047, 1 vs. 3 P < 0.001, 2 vs. 3 P < 0.001). About 79.2% of Central/Eastern and 76.0% of Southern Europe patients felt optimally informed at the time of device implantation compared with just 64.6% from Western Europe (1 vs. 2 P < 0.001, 1 vs. 3 P < 0.001, 2 vs. 3 P = ns). CONCLUSIONS: While physicians in Southern Europe should address the patients' concerns about the impact of the ICD on quality of life, physicians from Western Europe should focus on improving the quality of information provided to their prospective ICD patients. Novel strategies to address regional differences in patients' quality of life and provision of information are warranted.

Detection of microbial biofilms inside the lumen of ureteral stents: two case reports.

BACKGROUND: We report large biofilm structures that covered almost the entirety of the lumen and surface of double-J stents in two postrenal transplant patients, with no development of urinary tract infection. Biofilm bacteria of one patient were integrated by coccus in a net structure, whereas overlapping cells of bacilli were present in the other patient. To the best of our knowledge, this is the first time that high-quality images of the architecture of noncrystalline biofilms have been found inside double-J stents from long-term stenting in renal transplant recipients. CASE PRESENTATION: Two renal transplant recipients, a 34-year-old male and a 39-year-old female of Mexican-Mestizo origin, who underwent a first renal transplant and lost it due to allograft failure, had a second transplant. Two months after the surgical procedure, double-J stents were removed and analyzed using scanning electron microscopy (SEM). None of the patients had an antecedent of UTI, and none developed UTI after urinary device removal. There were no reports of injuries, encrustation, or discomfort caused by these devices. CONCLUSION: The bacterial biofilm inside the J stent from long-term stenting in renal transplant recipients was mainly concentrated on unique bacteria. Biofilm structures from the outside and inside of stents do not have crystalline phases. Internal biofilms may represent a high number of bacteria in the double-J stent, in the absence of crystals.

Serpin-A3 is Associated with Persistent Albuminuria in Adolescents with Secondary Podocytopathy, in a Region with High Prevalence of Chronic Kidney Disease of Unknown Origin

Abstract Background: The state of Aguascalientes, Mexico, has been recognized as a chronic kidney disease hotspot. Screening studies have revealed a high prevalence of persistent albuminuria (pA), histologically characterized by glomerulomegaly, and incomplete podocyte fusion, probably associated with oligonephrony. To date, urinary biomarkers have not been explored in this population. Objective: The aim of the study was to identify the presence of potential biomarkers of early renal injury in patients with pA (pACR) and that correspond with the characteristic nephropathy profile that prevails in this entity. Methods: This is a cross-sectional, analytical, and comparative study. Four groups were recruited: adolescents aged 10-17 years with pACR, isolated albuminuria (iACR), no albuminuria (negative control), and adults with biopsy-confirmed glomerulopathy (positive control). Urinary excretion of SerpinA3, heat-shock protein-72 (HSP-72), podocalyxin (PCX), and nephrin was evaluated in urine samples. SerpinA3 and HSP-72 were analyzed by Western blot, and PCX and nephrin were quantified by enzyme-linked immunosorbent assay. Results: The mean GFR in the pACR group was 113.4 mL/min/1.73m2 and differed significantly only from that of the positive control group (65.1 mL/min/1.73m2). The mean albuminuria value in the pACR group was 48.9 mg/g. SerpinA3 concentration differed between groups (0.08 vs. 0.25 ng/mL, p < 0.001): it was significantly higher in the pACR group compared to the negative controls (p = 0.037). Conclusion: SerpinA3 was significantly associated with pA and could become a biomarker of early kidney injury. Further investigations are required to determine whether SerpinA3 precedes the development of albuminuria and its pathogenic role.

Implantable Cardioverter-Defibrillators in Poland Compared with other European Countries from the Patient's Perspective: Insights from the EHRA Patient Survey.

BACKGROUND: The aim of this study was to compare differences between Polish ICD recipients and ICD recipients from other European countries in terms of quality of life, information provision before ICD implantation, and end-of-life issues. METHODS: This is a sub-analysis of the "Living with an ICD" patient survey (25-item questionnaire) organized by the European Heart Rhythm Association between 12 April 2021 and 5 July 2021 in ten European countries. RESULTS: There were 410 (22.7%) patients from Poland and 1399 (77.3%) from other European countries. A total of 51.0% of Polish patients reported improvement in their quality of life compared with 44.3% in other countries (p = 0.041). Remote monitoring was three times more often utilized in other countries than in Poland (66.8% vs. 21.0%, p < 0.001). While 78.1% of Poles felt well informed before ICD implantation compared with 69.6% of subjects from other countries (p = 0.001), they were less familiar with the ICD deactivation process than others (38.9% vs. 52.5%, p < 0.001). CONCLUSIONS: Despite the less frequent use of remote monitoring and gaps in end-of-life issues, Polish ICD recipients reported more favorable quality of life and a higher level of information received before device placement than patients in other European countries.

Beta-blocker treatment of patients with atrial fibrillation attenuates spontaneous calcium release-induced electrical activity.

AIMS: Atrial fibrillation (AF) has been associated with excessive spontaneous calcium release, linked to cyclic AMP (cAMP)-dependent phosphorylation of calcium regulatory proteins. Because ß-blockers are expected to attenuate cAMP-dependent signaling, we aimed to examine whether the treatment of patients with ß-blockers affected the incidence of spontaneous calcium release events or transient inward currents (ITI). METHODS: The impact of treatment with commonly used ß-blockers was analyzed in human atrial myocytes from 371 patients using patch-clamp technique, confocal calcium imaging or immunofluorescent labeling. Data were analyzed using multivariate regression analysis taking into account potentially confounding effects of relevant clinical factors RESULTS: The L-type calcium current (ICa) density was diminished significantly in patients with chronic but not paroxysmal AF and the treatment of patients with ß-blockers did not affect ICa density in any group. By contrast, the ITI frequency was elevated in patients with either paroxysmal or chronic AF that did not receive treatment, and ß-blocker treatment reduced the frequency to levels observed in patients without AF. Confocal calcium imaging showed that ß-blocker treatment also reduced the calcium spark frequency in patients with AF to levels observed in those without AF. Furthermore, phosphorylation of the ryanodine receptor (RyR2) at Ser-2808 and phospholamban at Ser-16 was significantly lower in patients with AF that received ß-blockers. CONCLUSION: Together, our findings demonstrate that ß-blocker treatment may be of therapeutic utility to prevent spontaneous calcium release-induced atrial electrical activity; especially in patients with a history of paroxysmal AF displaying preserved ICa density.

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.

OBJECTIVES: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk. METHODS: EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to the following: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo, and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% CIs. RESULTS: Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00-1.98) for TDF + HCQ, 0.34 (0.00-2.06) for TDF, and 0.49 (0.00-2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21-1.00) for TDF + HCQ, 0.81 (0.44-1.49) for TDF, and 0.73 (0.41-1.38) for HCQ. Adverse events were generally mild. DISCUSSION: The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo.

Contemporary management of ventricular electrical storm in Europe: results of a European Heart Rhythm Association Survey.

Electrical storm (ES) is a predictor of mortality, and its treatment is challenging. Moreover, not all potential therapeutic strategies are available in all hospitals, and a standardized approach among European centres is lacking. The aim of this European Heart Rhythm Association (EHRA) survey was to assess the current management of patients with ES both in the acute and post-acute phases in 102 different European centres. A 20-item online questionnaire was sent out to the EHRA Research Network Centres. The median number of patients with ES treated annually per centre is 10 (IQR 5-15). The possibility of using autonomic modulation (e.g. percutaneous stellate ganglion block or thoracic epidural anaesthesia) for the acute ES treatment is available in only 29.3% of the centres. Moreover, although over 80% of centres perform ventricular tachycardia ablation, this procedure is available 24/7 in only 16.5% of the hospitals. There is a significant heterogeneity among centres regarding the availability of AADs and their use before deciding to proceed with a non-AAD strategy; specifically, 4.4% of centres use only one drug, 33.3% use two drugs, and 12.2% >two drugs, while about 50% of the centres decide based on individual patient's characteristics. Regarding the type of AADs used for the acute and post-acute management of ES patients, important variability is reported depending upon the underlying heart disease. Most patients considered for percutaneous ablation have structural heart disease. Only 46% of centres refer patients to psychological counselling after ES.

Parametric Study of Pulsed Field Ablation With Biphasic Waveforms in an In Vivo Heart Model: The Role of Frequency.

BACKGROUND: Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation. Unfortunately, the characteristics of the electric field waveforms used in clinical and experimental PFA are not typically reported. This study examines the effect of the frequency of biphasic waveforms and compares biphasic to monophasic waveforms. METHODS: A total of 29 Sprague-Dawley rats were treated with PFA using an epicardial monopolar electrode. Biphasic waveforms with three different frequencies, 90, 260, and 450 kHz (10 bursts of 100 µs duration at 500 V or 800 V) and monophasic waveforms (10 pulses of 100 µs duration at 500 V) were studied. Collateral neuromuscular stimulation and temperature increase in the point of application were directly measured. Lesion formation was assessed 3 weeks after treatment by histopathologic analysis. Computer simulations were used to estimate the electric field lethal threshold for each condition. A previous in vitro study was performed to draw a complete characterization of the studied dependencies. RESULTS: Morphometric analysis demonstrated a significant association between chronic lesion size and waveform characteristics. For the same voltage level, monophasic waveforms yielded the largest lesions compared with any of the biphasic protocols (P<0.05). Increasing PFA frequency was associated with reduced neuromuscular stimulation but also with reduced ablation efficacy. Maximum absolute temperature increase recorded along a complete treatment was 3 °C. Vascular structures inside the lesions were preserved for all conditions. Computer simulation-based analysis showed that waveform frequency had a graded effect on the lethal electric field threshold, with threshold of 600 V/cm for monophasic waveforms versus 2000 V/cm for biphasic waveforms with a frequency of 450 kHz. CONCLUSIONS: Frequency is a major determinant of efficacy in biphasic PFA. Our results highlight the critical need of disclosing waveform characteristics when reporting the results of different PFA systems.

The blanking period after atrial fibrillation ablation: an European Heart Rhythm Association survey on contemporary definition and management.

The use of a blanking period (BP) after an atrial fibrillation (AF) ablation procedure is a common practice, but recent data questions the benign nature of early recurrences of atrial tachyarrhythmias (ERATs). A physician-based survey was carried out by the European Heart Rhythm Association (EHRA) to investigate the current definition and applicability of BP and ERAT management. An online questionnaire was sent to clinical and interventional electrophysiologists. A total of 436 respondents (88% interventional electrophysiologists) reported observing ERATs in 25% (interquartile range 15-35) of patients, less commonly in paroxysmal AF (PAF) compared with persistent AF (persAF). The median reported duration of BP used by respondents was 90 days, with 22% preferring a shorter BP duration for PAF patients compared with persAF. Half of the patients with ERATs are expected to also experience late recurrences (LR). Isolated episodes of ERATs are treated conservatively by 99% of the respondents, but repeat ablation during the BP is preferred by 20% of electrophysiologists for multiple ERATs and by 16% in patients with organized atrial tachyarrhythmias. In conclusion, ERATs are commonly observed after AF ablation, particularly in persAF patients, and are perceived as predictors of LR by half of the respondents. A general adherence to a 90-day BP duration was observed. During this time period, ERAT is mainly treated conservatively, but repeat ablation during the BP is occasionally offered to patients with multiple ERATs and those with organized atrial tachyarrhythmias.