Prognostic Electrocardiographic Signs in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a rare cardiac disease, characterized by the progressive replacement of myocardial tissue with fibrous and fatty deposits. It can involve both the right and left ventricles. It is associated with the development of life-threatening arrhythmias and culminates in sudden cardiac death. Electrocardiography (ECG) has emerged as a pivotal tool, offering diagnostic insights and prognostic information. The specific ECG abnormalities observed in ACM not only contribute to early detection but also hold the key to the prediction of the likelihood of severe complications. The recognition of these nuanced ECG manifestations has become imperative for clinicians as it guides them in the formulation of tailored therapeutic strategies that address both the present symptoms and the potential future risks.

Heart Failure-Related Death in Subjects With Atrial Fibrillation in the United States, 1999 to 2020.

BACKGROUND: Population-based data on heart failure (HF)-related death in patients with atrial fibrillation (AF) are lacking. We assessed HF-related death in people with AF in the United States over the past 21 years and examined differences by age, sex, race, ethnicity, urbanization, and census region. METHODS AND RESULTS: Data were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to determine trends in age-adjusted mortality rates per 100 000 people, due to HF-related death among subjects with AF aged ≥15 years. To calculate nationwide annual trends, we assessed the average annual percent change (AAPC) and annual percent change with relative 95% CIs using joinpoint regression. Between 1999 and 2020, 916 685 HF-related deaths (396 205 men and 520 480 women) occurred among US adults having a concomitant AF. The overall age-adjusted mortality rates increased (AAPC: +4.1% [95% CI, 3.8-4.4]; P<0.001), especially after 2011 (annual percent change, +6.8% [95% CI, 6.2-7.4]; P<0.001) in men (AAPC, +4.8% [95% CI, 4.4-5.1]; P<0.001), in White subjects (AAPC: +4.2% [95% CI, 3.9 to 4.6]; P<0.001) and in subjects aged <65 years (AAPC: +7.5% [95% CI, 6.7-8.4]; P<0.001). The higher percentage of deaths were registered in the South (32.8%). During the first year of the COVID-19 pandemic, a significant excess in HF-related deaths among patients with AF aged >65 years was observed. CONCLUSIONS: A worrying increase in the HF-related mortality rate among patients with AF has been observed in the United States over the past 2 decades.

Risk of incident atrial fibrillation after COVID-19 infection: A systematic review and meta-analysis.

BACKGROUND: Data regarding the risk of atrial fibrillation (AF) during the post-acute phase of COVID-19 are lacking. OBJECTIVE: We assessed the risk of incident AF in COVID-19 recovered patients by performing a systematic review and meta-analysis of the available data. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched Medline and Scopus to locate all articles published up to December 1, 2023, reporting the risk of AF in patients recovered from COVID-19 infection compared with noninfected patients in whom the arrhythmia developed during the same follow-up period. AF risk was evaluated by the Mantel-Haenszel random effects model with hazard ratio as the effect measure with 95% confidence interval (CI); heterogeneity was assessed by Higgins I2 statistic. RESULTS: Overall, 19,478,173 patients (mean age, 56.5 years; 63.0% male) enrolled in 5 observational studies were included in the analysis. Of these, 5,692,510 recovered from severe acute respiratory syndrome coronavirus 2 infection. During a mean follow-up of 14.5 ± 3.2 months, a random effects model revealed a pooled incidence of new-onset AF in 2.6% of cases (95% CI, 1.8%-6.18%). Recovered COVID-19 patients presented with a higher risk of incident AF (hazard ratio, 1.57; 95% CI, 1.24-1.99; P < .0001; I2 = 77.9%) compared with noninfected patients during the same follow-up period. Sensitivity analyses confirmed the yielded results. A multivariable metaregression including age, male sex, history of hypertension, coronary artery disease, and length of follow-up was able to explain a significant part of the heterogeneity (R2 = 54.3%; P = .01). CONCLUSION: Recovered COVID-19 patients have a higher risk of AF events compared with individuals from the general population.

A COVID-19 specific multiparametric and ECG-based score for the prediction of in-hospital mortality: ELCOVID score.

We aimed to develop and validate a COVID-19 specific scoring system, also including some ECG features, to predict all-cause in-hospital mortality at admission. Patients were retrieved from the ELCOVID study (ClinicalTrials.gov identifier: NCT04367129), a prospective, multicenter Italian study enrolling COVID-19 patients between May to September 2020. For the model validation, we randomly selected two-thirds of participants to create a derivation dataset and we used the remaining one-third of participants as the validation set. Over the study period, 1014 hospitalized COVID-19 patients (mean age 74 years, 61% males) met the inclusion criteria and were included in this analysis. During a median follow-up of 12 (IQR 7-22) days, 359 (35%) patients died. Age (HR 2.25 [95%CI 1.72-2.94], p < 0.001), delirium (HR 2.03 [2.14-3.61], p = 0.012), platelets (HR 0.91 [0.83-0.98], p = 0.018), D-dimer level (HR 1.18 [1.01-1.31], p = 0.002), signs of right ventricular strain (RVS) (HR 1.47 [1.02-2.13], p = 0.039) and ECG signs of previous myocardial necrosis (HR 2.28 [1.23-4.21], p = 0.009) were independently associated to in-hospital all-cause mortality. The derived risk-scoring system, namely EL COVID score, showed a moderate discriminatory capacity and good calibration. A cut-off score of ≥ 4 had a sensitivity of 78.4% and 65.2% specificity in predicting all-cause in-hospital mortality. ELCOVID score represents a valid, reliable, sensitive, and inexpensive scoring system that can be used for the prognostication of COVID-19 patients at admission and may allow the earlier identification of patients having a higher mortality risk who may be benefit from more aggressive treatments and closer monitoring.

Conduction system disease management in patients candidate and/or treated for the aortic valve disease: an Italian Survey promoted by Italian Association of Arrhythmology and Cardiac Pacing (AIAC).

BACKGROUND: Conduction system disorders represent a frequent complication in patients undergoing surgical (surgical aortic valve replacement, SAVR) or percutaneous (transcatheter aortic valve implantation, TAVI) aortic valve replacement. The purpose of this survey was to evaluate experienced operators approach in this clinical condition. METHODS: This survey was independently conducted by the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) and it consisted of 24 questions regarding the respondents' profile, the characteristics of participating centres, and conduction disease management in different scenarios. RESULTS: Fifty-five physicians from 55 Italian arrhythmia centres took part in the survey. Prophylactic pacemaker implantation is rare. In case of persistent complete atrioventricular block (AVB), 49% and 73% respondents wait less than one week before implanting a definitive pacemaker after SAVR and TAVI, respectively. In case of second degree AVB, the respondents wait some days more for definitive implantation. Respondents consider bundle branch blocks, in particular pre-existing left bundle branch block (LBBB), the worst prognostic factors for pacemaker implantation after TAVI. The implanted valve type is considered a relevant element to evaluate. In patients with new-onset LBBB and severe/moderate left ventricular systolic dysfunction, respondents would implant a biventricular pacemaker in 100/55% of cases, respectively. CONCLUSIONS: Waiting time before a definitive pacemaker implantation after aortic valve replacement has reduced compared to the past, and it is anticipated in TAVI vs. SAVR. Bundle branch blocks are considered the worse prognostic factor for pacemaker implantation after TAVI. The type of pacemaker implanted in new-onset LBBB patients without severe left ventricular systolic dysfunction is heterogeneous.

A modified approach to percutaneous ultrasound-guided left stellate ganglion block for drug-refractory electrical storm: a case report.

Background: The use of percutaneous stellate ganglion block (SGB) in the management of drug-refractory electrical storm (ES) has been increasingly reported in the last years. Few data are available on the safety, duration, and dosage of local anaesthetic used. Case summary: A 66-year-old male patient with a history of ischaemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD) presented to the emergency room complaining several ventricular arrhythmias and ICD shocks received in the last 24 h. He was treated with many lines of anti-arrhythmic drugs but his condition deteriorated with cardiovascular instability and respiratory distress, so he was intubated. The ES still worsened (82 episodes of ventricular arrhythmias), so we performed an ultrasound-guided left SGB, using a modified technique, with success in suppressing the ventricular arrhythmias. The patient was then treated with electrophysiological study and catheter ablation. Discussion: The ultrasound approach to SGB is feasible in emergency setting, and it is safe and effective also using a modified and easier technique in patient with difficult sonographic visualization of the neck structures. Moreover, it is possible and safe to use a combination of short-acting rapid-onset local anaesthetic with a long-lasting one with a good outcome.

Cardiac conduction disorders in young adults: Clinical characteristics and genetic background of an underestimated population.

BACKGROUND: Cardiac conduction disorder (CCD) in patients <50 years old is a rare and mostly unknown condition. OBJECTIVE: We aimed to assess clinical characteristics and genetic background of patients <50 years old with CCD of unknown origin. METHODS: We retrospectively reviewed a consecutive series of patients with a diagnosis of CCD before the age of 50 years referred to our center between January 2019 and December 2021. Patients underwent complete clinical examination and genetic evaluation. RESULTS: We enrolled 39 patients with a median age of 40 years (28-47 years) at the onset of symptoms. A cardiac implantable electronic device was implanted in 69% of the patients. In 15 of 39 CCD index patients (38%), we found a total of 13 different gene variations (3 pathogenic, 6 likely pathogenic, and 4 variants of uncertain significance), mostly in 3 genes (SCN5A, TRPM4, and LMNA). In our cohort, genetic testing led to the decision to implant an implantable cardioverter-defibrillator in 2 patients for the increased risk of sudden cardiac death. CONCLUSION: Patients with the occurrence of CCD before the age of 50 years present with a high rate of pathologic gene variations, mostly in 3 genes (SCN5A, TRPM4, and LMNA). The presence of pathogenic variations may add information about the prognosis and lead to an individualized therapeutic approach.

Interventricular Septal Hematoma Complicating Left Bundle Branch Area Pacing: A Case Report-The Devil Is Not So Black as He Is Painted.

BACKGROUND: This case report outlines the presentation of an emerging complication arising from left bundle branch area pacing (LBBAP). CASE SUMMARY: A 43-year-old male with no history of cardiac problems experienced recurrent episodes of syncope with no prodromal symptoms. During monitoring in the emergency department, the patient underwent an episode of asystole, leading to LBBAP implantation. The procedure encountered technical challenges, resulting in an interventricular septal hematoma and subsequent ventricular arrhythmias. Despite initial concerns, conservative management led to resolution, demonstrated through echocardiographic follow-ups. DISCUSSION: This report underscores the significance of ventricular arrhythmias as indicators of interventricular septal hematoma, providing insights into its diagnosis, management, and implications for LBBAP procedures.

Comparative Study of Lesions Obtained through Radiofrequency between the Irrigated Ablation Catheter with a Flexible Tip and the Non-Irrigated Catheter in Ex Vivo Porcine Hearts.

BACKGROUND: At the same conditions of delivered power and contact force, open-irrigated radiofrequency ablation catheters are believed to create deeper lesions, while non-irrigated ones produce shallower lesions. This ex vivo study aims to directly compare the lesion dimensions and characteristics of an irrigated ablation catheter with a flexible tip and a non-irrigated solid-tip catheter. METHODS: Radiofrequency lesions were induced on porcine myocardial slabs using both open-tip irrigated and non-irrigated standard 4 mm catheters at three power settings (20 W, 30 W, and 40 W), maintaining a fixed contact force of 10 gr. A lesion assessment was conducted including the lesion depth, depth at the maximum diameter, and lesion surface diameters, with the subsequent calculation of the lesion volume and area being undertaken. RESULTS: Irrigated catheters produced lesions with significantly higher superficial widths at all power levels (3.8 vs. 4.4 mm at 20 W; 3.9 mm vs. 4.4 mm at 30 W; 3.8 mm vs. 4.5 mm at 40 W; p = 0.001, p = 0.019, p = 0.003, respectively). Non-irrigated catheters resulted in significantly higher superficial areas at all power levels (23 mm2 vs. 18 mm2 at 20 W; 25 mm2 vs. 19 mm2 at 30 W; 26 mm2 vs. 19 mm2 at 40 W; p = 0.001, p = 0.005, p = 0.001, respectively). Irrigated catheters showed significantly higher values of lesion maximum depth at 40 W (4.6 mm vs. 5.5 mm; p = 0.007), while non-irrigated catheters had a significantly higher calculated volume at 20 W (202 µL vs. 134 µL; p = 0.002). CONCLUSIONS: Radiofrequency ablation using an irrigated catheter with a flexible tip has the potential to generate smaller superficial lesion areas compared with those obtained using a non-irrigated catheter.

Trends in atrial fibrillation-related mortality in Europe, 2008-2019.

AIMS: Update data regarding the atrial fibrillation (AF)-related mortality trend in Europe remains scant. We assess the age- and sex- specific trends in AF-related mortality in the European states between the years 2008 and 2019. METHODS AND RESULTS: Data on cause-specific deaths and population numbers by sex for European countries were retrieved through the publicly available World Health Organization (WHO) mortality dataset for the years 2008 to 2019. AF-related deaths were ascertained when the ICD-10 code I48 was listed as the underlying cause of death in the medical death certificate. To calculate annual trends, we assessed the average (AAPC) annual % change with relative 95% confidence intervals (CIs) using Joinpoint regression. During the study period, 773 750 AF-related deaths (202 552 males and 571 198 females) occurred in Europe. The age-adjusted mortality rate (AAMR) linearly increased from 12.3 (95% CI: 11.2 to 12.9) per 100 000 population in 2008 to 15.3 (95% CI: 14.7 to 15.7) per 100 000 population in 2019 [AAPC: +2.0% (95% CI: 1.6 to 3.5), p < 0.001] with a more pronounced increased among men [AAPC: +2.7% (95% CI: 1.9 to 3.5), p < 0.001] compared to women [AAPC: +1.7% (95% CI: 1.1 to 2.3), p < 0.001] (p for parallelism 0.01). The higher AAMR increased was observed in some eastern European countries such as Latvia, Lithuania and Poland while the lower were mainly clustered in the central Europe. CONCLUSIONS: Over the last decade, the age-adjusted AF-related mortality has increased in Europe especially among males. Disparities still exist between western and eastern European countries.

Ultrasound-Guided Venous Axillary Access Versus Standard Fluoroscopic Technique for Cardiac Lead Implantation: ZEROFLUOROAXI Randomized Trial.

BACKGROUND: Axillary vein puncture (AVP) and cephalic vein surgical cutdown are recommended in international guidelines because of their low risk of pneumothorax and chronic lead complications. Directly visualizing and puncturing the axillary vein under ultrasound guidance reduces radiation exposure, provides direct needle visualization, and lowers periprocedural complications. Our hypothesis is that ultrasound-guided axillary access is safer and more feasible than the standard fluoroscopic technique. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ultrasound-guided axillary venous access during cardiac lead implantation for pacemakers (PMs) and implantable cardioverter-defibrillator (ICD) implantations. METHODS: Patients were randomized in a 1:1 fashion to either axillary venous access under fluoroscopic guidance or ultrasound-guided axillary venous access. The composite outcome, including pneumothorax, hemothorax, inadvertent arterial puncture, pocket hematoma, pocket infection, lead dislodgement, and death, was evaluated 30 days after implantation. RESULTS: We randomized 270 patients into 2 groups: the standard group for fluoroguided AVP (n = 134) and the experimental group for ultrasound-guided AVP (n = 136). No disparities in baseline characteristics were observed between the groups. The median age of the patients was 81 years, with women comprising 41% of the population. The majority of patients received single- and dual-chamber PMs (87% vs 88%; P = 1.00), and slightly over 10% in both groups received ICDs (13% vs 12%; P = 0.85). In total, we placed 357 leads in PMs and 48 leads in ICDs. Among these, 295 leads were inserted via axillary vein access and 110 via cephalic vein access. Notably, the subclavian vein was never used as a vascular access. The composite outcome was lower in the ultrasound group according to intention-to-treat analysis (OR: 0.55; 95% CI: 0.31-0.99; P = 0.034). The main difference within the composite outcome was the lower incidence of inadvertent axillary arterial puncture in the experimental group (17% vs 6%; P = 0.004). The ultrasound group also exhibited lower total procedural x-ray exposure (10,344 µGy × cm2 vs 7,119 µGy × cm2; P = 0.002) while achieving the same rate of success at the first attempt (61% vs 69%; P = 0.375). CONCLUSIONS: Ultrasound-guided AVP is safer than the fluoroscopy-guided approach because it achieves the same rate of acute success while maintaining low total procedural radiation exposure. Ultrasound AVP should be considered the optimal venous access method for cardiac lead implantation. (Ultrasound Guided Axillary Access vs Standard Fluoroscopic Technique for Cardiac Lead Implantation [ZEROFLUOROAXI]; NCT05101720).

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Zero fluoroscopy catheter ablation of premature ventricular contractions: a multicenter experience.

BACKGROUND: Catheter ablation has become an established treatment option for premature ventricular complexes (PVCs). The use of fluoroscopy exposes patients and medical staff to potentially harmful stochastic and deterministic effects of ionizing radiations. We sought to analyze procedural outcomes in terms of safety and efficacy using a "zero fluoroscopy" approach for catheter ablation of PVCs. METHODS: The present retrospective, multicenter, observational study included 131 patients having undergone catheter ablation of PVCs using "zero fluoroscopy" between 2019 and 2020 in four centers compared with another group who underwent the procedure with fluoroscopy. RESULTS: Median age was 51.0 ± 15.9 years old; males were 77 (58.8%). Among the study population, 26 (19.8%) had a cardiomyopathy. The most frequent PVC origin was right ventricular outflow tract (55%) followed by the left ventricle (16%), LVOT and cusps (13.7%), and aortomitral continuity (5.3%). Acute suppression of PVC was achieved in 127 patients (96.9%). At 12 months, a complete success was documented in 109 patients (83.2%), a reduction in PVC burden in 18 patients (13.7%), and a failure was recorded in four patients (3.1%). Only two minor complications occurred (femoral hematoma and arteriovenous fistula conservatively treated). CONCLUSIONS: The PVC ablation with a "zero" fluoroscopy approach appears to be a safe procedure with no major complications and good rates of success and recurrence in our multicenter experience.

SCN5A mutation is associated with a higher Shanghai Score in patients with type 1 Brugada ECG pattern.

AIMS: Brugada syndrome (BrS) is an inherited arrhythmic disease characterized by a coved ST-segment elevation in the right precordial electrocardiogram leads (type 1 ECG pattern) and is associated with a risk of malignant ventricular arrhythmias and sudden cardiac death. In order to assess the predictive value of the Shanghai Score System for the presence of a SCN5A mutation in clinical practice, we studied a cohort of 125 patients with spontaneous or fever/drug-induced BrS type 1 ECG pattern, variably associated with symptoms and a positive family history. METHODS: The Shanghai Score System items were collected for each patient and PR and QRS complex intervals were measured. Patients were genotyped through a next-generation sequencing (NGS) custom panel for the presence of SCN5A mutations and the common SCN5A polymorphism (H558R). RESULTS: The total Shanghai Score was higher in SCN5A+ patients than in SCN5A- patients. The 81% of SCN5A+ patients and the 100% of patients with a SCN5A truncating variant exhibit a spontaneous type 1 ECG pattern. A significant increase in PR (P = 0.006) and QRS (P = 0.02) was detected in the SCN5A+ group. The presence of the common H558R polymorphism did not significantly correlate with any of the items of the Shanghai Score, nor with the total score of the system. CONCLUSION: Data from our study suggest the usefulness of Shanghai Score collection in clinical practice in order to maximize genetic test appropriateness. Our data further highlight SCN5A mutations as a cause of conduction impairment in BrS patients.

A Comparative Assessment of Myocardial Work Performance during Spontaneous Rhythm, His Bundle Pacing, and Left Bundle Branch Area Pacing: Insights from the EMPATHY Study.

BACKGROUND: Physiological pacing has gained significant interest due to its potential to achieve optimal hemodynamic response. This study aimed to assess left ventricular performance in terms of electrical parameters, specifically QRS duration and mechanical performance, evaluated as myocardial work. We compared His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP) to evaluate their effects. METHODS: Twenty-four patients with class I or IIa indications for pacing were enrolled in this study, with twelve patients undergoing HBP implantation and another twelve undergoing LBBAP implantation. A comprehensive analysis of myocardial work was conducted. RESULTS: Our findings indicate that there were no major differences in terms of spontaneous and HBP activation in myocardial work, except for global wasted work (217 mmHg% vs. 283 mmHg%; p 0.016) and global work efficiency (87 mmHg% vs. 82 mmHg%; p 0.049). No significant differences were observed in myocardial work between spontaneous activation and LBBAP. Similarly, no significant differences in myocardial work were found between HBP and LBBAP. CONCLUSIONS: Both pacing modalities provide physiological ventricular activation without significant differences when compared to each other. Moreover, there were no significant differences in QRS duration between HBP and LBBAP. However, LBBAP demonstrated advantages in terms of feasibility, as it achieved better lead electrical parameters compared to HBP (threshold@0.4 ms 0.6 V vs. 1 V; p = 0.045-sensing 9.4 mV vs. 2.4 mV; p < 0.001). Additionally, LBBAP required less fluoroscopy time (6 min vs. 13 min; p = 0.010) and procedural time (81 min vs. 125 min; p = 0.004) compared to HBP.

Performance of a multi-sensor implantable defibrillator algorithm for heart failure monitoring in the presence of atrial fibrillation.

AIMS: The HeartLogic Index combines data from multiple implantable cardioverter defibrillators (ICDs) sensors and has been shown to accurately stratify patients at risk of heart failure (HF) events. We evaluated and compared the performance of this algorithm during sinus rhythm and during long-lasting atrial fibrillation (AF). METHODS AND RESULTS: HeartLogic was activated in 568 ICD patients from 26 centres. We found periods of ≥30 consecutive days with an atrial high-rate episode (AHRE) burden <1 h/day and periods with an AHRE burden ≥20 h/day. We then identified patients who met both criteria during the follow-up (AHRE group, n = 53), to allow pairwise comparison of periods. For control purposes, we identified patients with an AHRE burden <1 h throughout their follow-up and implemented 2:1 propensity score matching vs. the AHRE group (matched non-AHRE group, n = 106). In the AHRE group, the rate of alerts was 1.2 [95% confidence interval (CI): 1.0-1.5]/patient-year during periods with an AHRE burden <1 h/day and 2.0 (95% CI: 1.5-2.6)/patient-year during periods with an AHRE-burden ≥20 h/day (P = 0.004). The rate of HF hospitalizations was 0.34 (95% CI: 0.15-0.69)/patient-year during IN-alert periods and 0.06 (95% CI: 0.02-0.14)/patient-year during OUT-of-alert periods (P < 0.001). The IN/OUT-of-alert state incidence rate ratio of HF hospitalizations was 8.59 (95% CI: 1.67-55.31) during periods with an AHRE burden <1 h/day and 2.70 (95% CI: 1.01-28.33) during periods with an AHRE burden ≥20 h/day. In the matched non-AHRE group, the rate of HF hospitalizations was 0.29 (95% CI: 0.12-0.60)/patient-year during IN-alert periods and 0.04 (95% CI: 0.02-0.08)/patient-year during OUT-of-alert periods (P < 0.001). The incidence rate ratio was 7.11 (95% CI: 2.19-22.44). CONCLUSION: Patients received more alerts during periods of AF. The ability of the algorithm to identify increased risk of HF events was confirmed during AF, despite a lower IN/OUT-of-alert incidence rate ratio in comparison with non-AF periods and non-AF patients. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/Identifier: NCT02275637.

Brugada Syndrome: More than a Monogenic Channelopathy.

Brugada syndrome (BrS) is an inherited cardiac channelopathy first diagnosed in 1992 but still considered a challenging disease in terms of diagnosis, arrhythmia risk prediction, pathophysiology and management. Despite about 20% of individuals carrying pathogenic variants in the SCN5A gene, the identification of a polygenic origin for BrS and the potential role of common genetic variants provide the basis for applying polygenic risk scores for individual risk prediction. The pathophysiological mechanisms are still unclear, and the initial thinking of this syndrome as a primary electrical disease is evolving towards a partly structural disease. This review focuses on the main scientific advancements in the identification of biomarkers for diagnosis, risk stratification, pathophysiology and therapy of BrS. A comprehensive model that integrates clinical and genetic factors, comorbidities, age and gender, and perhaps environmental influences may provide the opportunity to enhance patients' quality of life and improve the therapeutic approach.

Trends in age- and sex-specific atrial fibrillation/flutter mortality in Italy between 2003 and 2017.

AIMS: We sought to assess the atrial fibrillation/flutter (AF/AFL) mortality rates and relative trends among the Italian population between 2003 and 2017. METHODS: Data regarding the cause-specific mortality and population size by sex in 5-year age groups were extracted from the World Health Organization (WHO) global mortality database. Decedents reporting the codes I48 were extracted accordingly to the International Classification of Disease-10 (ICD-10) coding system. The age-adjusted mortality rates (AAMRs), with relative 95% confidence intervals (CIs), also stratified by sex, were determined using the direct method. Joinpoint regression analyses were used to identify periods with statistically distinct log linear trends in AF/AFL-related death rates. To calculate nationwide annual trends in AF/AFL-related mortality, we assessed the average annual percentage change (AAPC) and relative 95% CIs. RESULTS: Over the study period, 90 623 (57 109 females) AF-related deaths were recorded. The AF/AFL AAMR increased from 8.1 (95% CI: 7.8-8.2) deaths per 100 000 to 18.7 (16.9-20.0) deaths per 100 000 population. Joinpoint regression analysis revealed a linear increase in age-standardized AF/AFL-related mortality [AAPC: +3.6 (95% CI: 3.0-4.3, P  < 0.0001)] in the entire Italian population. Moreover, the mortality rate increased with age, showing a seemingly exponential distribution with a similar trend between males and females. Although the increase was more pronounced among women [AAPC: +3.7 (95% CI: 3.1-4.3, P  < 0.0001)] compared with men [AAPC: +3.4 (95% CI: 2.8-4.0, P  < 0.0001)], the difference did not reach statistical significance ( P  = 0.16). CONCLUSIONS: In Italy, the AF/AFL-related mortality rates linearly increased from 2003 to 2017.