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Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02-0.078) and 0.031 ng/mL (IQR 0.02-0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median ( p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization ( p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02-4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006-3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH ( p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events ( p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death ( p = 0.01) and CV death/HFH ( p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death ( p < 0.001) and CV death/HFH ( p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

Background: The precision of digital anthropometry through 3-dimensional (3D) scanning has been established for relatively large, expensive, non-portable systems. The comparative performance of modern mobile applications is unclear., Subjects/methods: Forty-six adults (age: 23.3 ± 5.3 y; BMI: 24.4 ± 4.1 kg/m 2 ) were assessed in duplicate using: (1) a mobile phone application capturing two individual 2D images, (2) a mobile phone application capturing serial images collected during a subject's complete rotation, (3) a traditional scanner with a time of flight infrared sensor collecting visual data from a subject being rotated on a mechanical turntable, and (4) a commercial measuring booth with structured light technology using 20 infrared depth sensors positioned in the booth. The absolute and relative technical error of measurement (TEM) and intraclass correlation coefficient (ICC) for each method were established., Results: Averaged across circumferences, the absolute TEM, relative TEM, and ICC were (1) 0.9 cm, 1.5%, and 0.975; (2) 0.5 cm, 0.9%, and 0.986; (3) 0.8 cm, 1.5%, and 0.974; and (4) 0.6 cm, 1.1%, and 0.985. For total body volume, these values were (1) 2.2 L, 3.0%, and 0.978; (2) 0.8 L, 1.1%, and 0.997; (3) 0.7 L, 0.9%, and 0.998; and (4) 0.8 L, 1.1%, and 0.996, with segmental volumes demonstrating higher relative errors., Conclusion: A 3D scanning mobile phone application involving full rotation of subjects in front of a smartphone camera exhibited similar reliability to larger, less portable, more expensive 3D scanners. In contrast, larger errors were observed for a mobile scanning application utilizing two 2D images, although the technical errors were acceptable for some applications., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Catheter ablation (CA) of atrial fibrillation is routinely used to obtain rhythm control. Evidence suggest that catheter ablation should be done during uninterrupted oral anticoagulation., Methods: Italian Registry in the setting of atrial fibrillation ablation with rivaroxaban (IRIS) is an Italian multicenter, non-interventional, prospective study which enrolled 250 consecutive atrial fibrillation patients eligible for catheter ablation on rivaroxaban. The decision for rivaroxaban management was left to the physician: uninterrupted or shortly interrupted prior to Catheter ablation. Patients received a follow-up visit at 1 month and 12 months after the procedure., Results: The primary outcome, represented by all-cause death and systemic embolism at 1 month and 12 months was characterized by one transient ischemic attack and one myocardial infarction in the first 30 days. Both events happened in patients with shortly interrupted strategy (P=0.147), and both in patients who underwent radiofrequency ablation (P=0.737). In the primary safety outcome represented by major bleeding we did not register any event in the 12-month follow-up. The secondary outcome constituted by minor bleeding registered 1 event, after the first 30 days since CA., Conclusions: IRIS is the biggest real-life data registry regarding CA ablation on rivaroxaban in Italian setting, proving the safety and efficacy of rivaroxaban.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

Patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Although guideline-directed medical therapy is well established, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF with consequent higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as cornerstones to reduce residual risk of both cardiovascular mortality and readmission for heart failure. The following review will debate about emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the new therapeutic strategies in cardiorenal patients., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Aims: Catheter ablation (CA) of ventricular tachycardia (VT) has become an important tool to improve clinical outcomes in patients with appropriate transvenous implantable cardioverter defibrillator (ICD) shocks. The aim of our analysis was to test whether VT ablation (VTA) impacts long-term clinical outcomes even in subcutaneous ICD (S-ICD) carriers., Methods and Results: International Subcutaneous Implantable Cardioverter Defibrillator (iSUSI) registry patients who experienced either an ICD shock or a hospitalization for monomorphic VT were included in this analysis. Based on an eventual VTA after the index event, patients were divided into VTA+ vs. VTA- cohorts. Primary outcome of the study was the occurrence of a combination of device-related appropriate shocks, monomorphic VTs, and cardiovascular mortality. Secondary outcomes were addressed individually. Among n = 1661 iSUSI patients, n = 211 were included: n = 177 experiencing ICD shocks and n = 34 hospitalized for VT. No significant differences in baseline characteristics were observed. Both the crude and the yearly event rate of the primary outcome (5/59 and 3.8% yearly event rate VTA+ vs. 41/152 and 16.4% yearly event rate in the VTA-; log-rank: P value = 0.0013) and the cardiovascular mortality (1/59 and 0.7% yearly event rate VTA+ vs. 13/152 and 4.7% yearly event rate VTA-; log-rank P = 0.043) were significantly lower in the VTA + cohort. At multivariate analysis, VTA was the only variable remaining associated with a lower incidence of the primary outcome [adjusted hazard ratio 0.262 (0.100-0.681), P = 0.006]., Conclusion: In a real-world registry of S-ICD carriers, the combined study endpoint of arrhythmic events and cardiovascular mortality was lower in the patient cohort undergoing VTA at long-term follow-up., Clinicaltrials.gov Identifier: NCT0473876., Competing Interests: Conflict of interest: A.D.R. is a consultant for Abbott. M.C. has received speaker honoraria from Abbott and Biosense Webster. L.K. worked as a proctor for Boston Scientific. R.T. is a consultant for Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and he received speaker’s honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and LifeTech and research grants from Abbott, Biosense Webster, and LifeTech. A.B. has received consultant and/or speaker fees from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Bristol Myers Squibb, Cook Medical, Daiichi Sankyo, Medtronic, Pfizer, and Spectranetics/Philips., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Ventricular tachycardias (VTs) and electrical storms (ES) are life-threatening conditions mostly seen in the setting of structural heart disease (SHD). Traditional management strategies, predominantly centered around pharmacological interventions with antiarrhythmic drugs, have demonstrated limited efficacy in these cases, whereas catheter ablation is related with more favorable outcomes. However, patients with hemodynamically unstable, recurrent VT or ES may present cardiogenic shock (CS) that precludes the procedure, and catheter ablation in patients with SHD portends a multifactorial intrinsic risk of acute hemodynamic decompensation (AHD), that is associated with increased mortality. In this setting, the use of mechanical circulatory support (MCS) systems allow the maintenance of end-organ perfusion and cardiac output, improving coronary flow and myocardial mechanics, and minimizing the effect of cardiac stunning after multiple VT inductions or cardioversion. Although ablation success and VT recurrence are not influenced by hemodynamic support devices, MCS promotes diuresis and reduces the incidence of post-procedural kidney injury. In addition, MCS has a role in post-procedural mortality reduction at long-term follow-up. The current review aims to provide a deep overview of the rationale and modality of MCS in patients with refractory arrhythmias and/or undergoing VT catheter ablation, underlining the importance of patient selection and timing for MCS and summarizing reported clinical experiences in this field.

Background: Achieving a high biventricular pacing percentage (BiV%) is crucial for optimizing outcomes in cardiac resynchronization therapy (CRT). The HeartLogic index, a multiparametric heart failure (HF) risk score, incorporates implantable cardioverter-defibrillator (ICD)-measured variables and has demonstrated its predictive ability for impending HF decompensation., Objective: This study aimed to investigate the relationship between daily BiV% in CRT ICD patients and their HF status, assessed using the HeartLogic algorithm., Methods: The HeartLogic algorithm was activated in 306 patients across 26 centers, with a median follow-up of 26 months (25th-75th percentile: 15-37)., Results: During the follow-up period, 619 HeartLogic alerts were recorded in 186 patients. Overall, daily values associated with the best clinical status (highest first heart sound, intrathoracic impedance, patient activity; lowest combined index, third heart sound, respiration rate, night heart rate) were associated with a BiV% exceeding 99%. We identified 455 instances of BiV% dropping below 98% after consistent pacing periods. Longer episodes of reduced BiV% (hazard ratio: 2.68; 95% CI: 1.02-9.72; P = .045) and lower BiV% (hazard ratio: 3.97; 95% CI: 1.74-9.06; P =.001) were linked to a higher risk of HeartLogic alerts. BiV% drops exceeding 7 days predicted alerts with 90% sensitivity (95% CI [74%-98%]) and 55% specificity (95% CI [51%-60%]), while BiV% ≤96% predicted alerts with 74% sensitivity (95% CI [55%-88%]) and 81% specificity (95% CI [77%-85%])., Conclusion: A clear correlation was observed between reduced daily BiV% and worsening clinical conditions, as indicated by the HeartLogic index. Importantly, even minor reductions in pacing percentage and duration were associated with an increased risk of HF alerts., (© 2024 Heart Rhythm Society.)

Background: The probability of spontaneous conversion (SCV) to sinus rhythm (SR) in patients presenting to the emergency department (ED) with hemodynamically stable, symptomatic atrial fibrillation (AF) is not well known. Objective: To develop and validate a score to determine the probability of SCV to SR in patients presenting to the ED with hemodynamically stable, symptomatic AF. Methods: This retrospective, observational study enrolled consecutive patients admitted with AF to the ED. Variables associated to SCV during a 6 h "wait-and-see" approach were used to develop and validate a score to determine the probability of SCV to SR in AF patients. The study was divided in two phases: (1) score development and (2) validation of the predictive score. Results: Out of 748 eligible patients, 446 patients were included in the derivation cohort, whereas 302 patients were included in the validation cohort. In the derivation cohort, based on multivariable logistic analysis, a probability score weight was developed including: previous SCV (3 points), AF-related symptom duration < 24 h (5 points), age ≥ 65 years (3 points) and female sex (2 points). The score allowed us to divide patients in three groups based on the probability of SCV to SR during the 6 h observation period. The probability prediction model showed an area under the curve (AUC) of 0.707 and 0.701 in the derivation and validation cohorts, respectively. Conclusions: The proposed score allowed us to predict SCV probability with good accuracy and may help physicians in tailoring AF management in an effective and timely manner.

Background: The mechanism of typical slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) and its anatomical and electrophysiological circuit inside the right atrium (RA) and Koch's Triangle (KT) are not well known., Objective: To identify the potentials of the compact AV node and inferior extensions and to perform accurate mapping of the RA and KT in sinus rhythm (SR) and during AVNRT, to define the tachycardia circuit., Methods: Consecutive patients with typical AVNRT were enrolled in 12 Italian centers and underwent mapping and ablation by means of a basket catheter with small electrode spacing for ultrahigh-density mapping and a modified signal-filtering toolset to record the potentials of the AV nodal structures., Results: Forty-five consecutive cases of successful ablation of typical slow-fast AVNRT were included. The mean SR cycle length (CL) was 784.1 ± 6 ms and the mean tachycardia CL was 361.2 ± 54 ms. The AV node potential had a significantly shorter duration and higher amplitude in sinus rhythm than during tachycardia (60 ± 40 ms vs. 160 ± 40 ms, p < .001 and 0.3 ± 0.2 mV vs. 0.09 ± 0.12 mV, p < .001, respectively). The nodal potential duration extension was 169.4 ± 31 ms, resulting in a time-window coverage of 47.6 ± 9%. The recording of AV nodal structure potentials enabled us to obtain 100% coverage of the tachycardia CL during slow-fast AVNRT., Conclusion: Detailed recording of the potentials of nodal structures is possible by means of multipolar catheters for ultrahigh-density mapping, allowing 100% of the AVNRT CL to be covered. These results also have clinical implications for the ablation of right-septal and para-septal arrhythmias., (© 2024 Wiley Periodicals LLC.)

Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction without obstructive coronary artery disease (MINOCA). It is determined by a coronary artery wall layers separation, which occurs regardless of traumatic or iatrogenic injuries. Even if it is often a missed diagnosis, its incidence is growing along with the improvement of intracoronary imaging techniques that allow for better detection. The main angiographical classification distinguishes three different forms, with slightly different prognoses at long-term follow up. SCAD is a recurrent condition, severely hampering the life quality of affected patients. The predominantly young age of patients with SCAD and the high prevalence of females among them have made the topic increasingly important, especially regarding therapeutic strategies. According to the data, the most recommended treatment is conservative, based on the use of antiplatelet agents and supportive anti-ischemic therapy. However, there are conflicting opinions concerning the need for dual antiplatelet therapy and its duration. In the case of invasive treatment, the choice between percutaneous coronary intervention and coronary artery bypass graft depends on the patient's clinical stability and the interested vessel. The purpose of the current review is to revise the pathophysiological mechanisms underlying SCAD and the current knowledge of its treatment.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.

Pediatric cardiomyopathies (CMs) and electrical diseases constitute a heterogeneous spectrum of disorders distinguished by structural and electrical abnormalities in the heart muscle, attributed to a genetic variant. They rank among the main causes of morbidity and mortality in the pediatric population, with an annual incidence of 1.1-1.5 per 100,000 in children under the age of 18. The most common conditions are dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Despite great enthusiasm for research in this field, studies in this population are still limited, and the management and treatment often follow adult recommendations, which have significantly more data on treatment benefits. Although adult and pediatric cardiac diseases share similar morphological and clinical manifestations, their outcomes significantly differ. This review summarizes the latest evidence on genetics, clinical characteristics, management, and updated outcomes of primary pediatric CMs and electrical diseases, including DCM, HCM, arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), and short QT syndrome (SQTS).

Introduction: The efficacy and safety of emerging therapies for heart failure with reduced ejection fraction (HFrEF) have never been compared in specific subgroups of patients., Methods: PubMed, Cochrane Registry, Web of Science, Scopus, and EMBASE libraries were used to extract data. We used the following keywords: (heart failure with reduced ejection fraction OR HFrEF) AND (treatment OR therapy) OR (cardiovascular death) OR (hospitalization for heart failure). We compared randomized clinical trials for HFrEF emerging therapies focusing on the elderly (patients &gt;65 years old and &gt;75 years old), chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) &lt; 60 mL/min), patients with diabetes mellitus (DM), coronary heart disease (CAD), New York Heart Association (NYHA) class III/IV, women, patients on sacubitril/valsartan (S/V). The primary outcome was the efficacy composite endpoint of cardiovascular death (CVD) and HF hospitalization (HFH)., Results: S/V significantly reduced the primary outcome in patients &gt;65 years old (RR: 0.80; 95% CI: 0.68-0.94) and with CKD (RR: 0.79; 95% CI: 0.69-0.90); dapagliflozin in patients &gt;65 (RR: 0.72; 95% CI: 0.60-0.86) and &gt;75 years old (RR: 0.68; 95% CI: 0.53-0.87), in those with CKD (RR: 0.72; 95% CI: 0.59-0.88), DM (RR: 0.75; 95% CI: 0.63-0.89), and CAD (RR: 0.77; 95% CI: 0.65-0.92); empagliflozin in patients &gt;65 years old (RR: 0.78; 95% CI: 0.66-0.93), those with DM (RR: 0.72; 95% CI: 0.60-0.86), CAD (RR: 0.82; 95% CI: 0.68-0.99), women (RR: 0.59; 95% CI: 0.44-0.79), and in patients on S/V (RR: 0.64; 95% CI: 0.45-0.91); vericiguat in patients with CKD (RR: 0.84; 95% CI: 0.73-0.97) and NYHA class III/IV (RR: 0.87; 95% CI: 0.77-0.98); omecamtiv mecarbil in patients with CAD (RR: 0.90; 95% CI: 0.82-0.99) and NYHA III/IV (RR: 0.88; 95% CI: 0.80-0.97)., Conclusion: Emerging HFrEF therapies show a clinical benefit with the reduction of the primary composite endpoint of CVD and HFH, with each drug being more effective in specific patient population., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aims: Left atrial appendage (LAA) imaging is critical during percutaneous occlusion procedures. 3D-intracardiac echocardiography (ICE) features direct visualization of LAA from multiple cross-sectional planes at a time. We aimed at reporting procedural success of 3D-ICE-guided LAA occlusion and the correlation between pre-procedural transoesophageal echocardiography (TEE) and intraprocedural 3D-ICE for LAA sizing., Methods and Results: Among 274 patients undergoing left atrial appendage occlusion (LAAO) with a Watchman FLX, periprocedural ICE guidance was achieved via a commercially available 2D-ICE catheter (220 patients) or a novel (NUVISION™) 3D-ICE one (54 patients). Primary endpoint was a composite of procedural success and LAA sealing at follow-up TEE. Secondary endpoint was a composite of periprocedural device recapture/resizing plus presence of leaks ≥ 3 mm at follow-up TEE. 3D-ICE measurements of maximum landing zone correlated highly with pre-procedural TEE reference values [Pearson's: 0.94; P < 0.001; bias: -0.06 (-2.39, 2.27)]. The agreement between 3D-ICE-based device selection and final device size was 96.3% vs. 79.1% with 2D-ICE (P = 0.005). The incidence of the primary endpoint was 98.1% with 3D-ICE and 97.3% with 2D-ICE (P = 0.99). 2D-ICE patients had a trend towards a higher incidence of periprocedural device recapture/redeployment (31.5% vs. 44.5%; P = 0.09). The secondary endpoint occurred in 31.5% of 3D-ICE patients vs. 45.9% of 2D-ICE ones (P = 0.065)., Conclusion: Intracardiac echocardiography-guided LAAO showed a very high success, with no major adverse events. A very high level of agreement for LAA sizing was found between pre-procedural TEE and periprocedural 3D-ICE. 3D-ICE performed significantly better than 2D-ICE for FLX size selection and may provide better guidance during device deployment., Competing Interests: Conflict of interest: G.-B.C. received compensation from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. received research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus. D.J.B. is a consultant for Biosense Webster and Stereotaxis. L.D.B. is a consultant for Biosense Webster, Boston Scientific, Stereotaxis, and St. Jude Medical. A.N. received speaker honoraria from Boston Scientfic, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background/objectives: Skeletal muscle mass (SMM) estimation is important but challenging in clinical settings. Criterion methods, such as magnetic resonance imaging (MRI), are often inaccessible. However, surrogate methods, such as dual-energy X-ray absorptiometry (DXA) and multi-frequency bioelectrical impedance analysis (MFBIA), can use MRI-based equations to estimate SMM, although the agreement between these methods is unclear., Subjects/methods: Total and segmental SMM were estimated with DXA and MFBIA using MRI-based equations in 313 healthy adults (120 M, 193 F; age 30.2 ± 13.0 y; BMI 24.6 ± 4.0 kg/m 2 ). DXA total SMM was estimated using the Kim and McCarthy equations, and segmental SMM was estimated using the McCarthy equations. Relationships between DXA and MFBIA SMM were examined using Deming regression, Lin's concordance correlation coefficient (CCC), equivalence testing, Bland-Altman analysis, and related tests., Results: Strong linear relationships were observed for total (R 2 0.95, CCC 0.96-0.97), leg (R 2 0.90, CCC 0.85) and arm (R 2 0.93, CCC 0.93) SMM in the entire sample. Kim equation SMM demonstrated statistical equivalence with MFBIA for total SMM, but the Deming regression slope differed from 1 and proportional bias was present. McCarthy equation total SMM exhibited a regression slope that did not differ from 1, and no proportional bias was present in the entire sample. However, equivalence with MFBIA was not observed. Systematically higher leg and arm SMM values were observed with DXA as compared to MFBIA., Conclusions: While DXA and MFBIA total SMM generally exhibited strong agreement, higher appendicular SMM by DXA highlights technical differences between methods., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: To provide a comprehensive analysis of the current literature comparing the outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS), with particular attention to BAV morphology in patients undergoing TAVR., Methods: Following PRISMA guidelines, all relevant articles with no design restrictions from PubMed, CCTR (Cochrane Controlled Trials Register), and Google Scholar were screened for inclusion. Studies were included if they reported clinical endpoints for SAVR and TAVR or, in BAS treated with TAVR, for type 1 and non-type 1 morphology. Odds ratio and Cohen's D were considered as effect size measurements for qualitative and quantitative variables, respectively., Results: A total of eight studies comparing short-term outcomes between SAVR and TAVR and nine studies with outcomes data between type 1 and non-type 1 BAS treated with TAVR were considered for the final analysis. No statistically significant difference was found for what concerns the rates of death, stroke, and acute kidney injury between SAVR and TAVR. In comparison to patients undergoing SAVR, the incidence of PPI (permanent pacemaker implantation) was greater in the TAVR group (OR 0.35, 95% CI 0.15-0.79, p = 0.01), and the frequency of bleeding events was found to be higher among patients undergoing SAVR (OR 4.3, 95% CI 2.9-6.4, p < 0.001). The probabilities of 30-day mortality, stroke, and any bleeding were not significantly affected by bicuspid valve morphology in TAVR patients. PPI or development of new conduction anomalies was found to be more frequent in type 1 anatomies (OR 0.46, 95% CI 0.30-0.70, p <0.001). Mildly lower post-procedural transprothesic gradients were found in patients with type 1 morphology., Conclusions: In BAS patients, TAVR has comparable short-term outcomes rates with SAVR, but higher PPI rates and lower incidence of bleeding events. In patients undergoing TAVR, type 1 BAS is associated with lower postoperative transvalvular gradients but higher PPI rates and conduction abnormalities.

Multi-ingredient thermogenic supplements can acutely increase resting energy expenditure (REE) and subjective energy. However, less is understood about the effects of chronic consumption on body composition, metabolism, and subjective variables such as mood, sleep quality, and eating behaviors. Fifty-two healthy, exercise-trained participants (50% female; mean ± SD age: 23.5 ± 3.0 years; body fat percentage: 27.3 ± 8.0%) were randomized 2:2:1 to take a whey protein supplement alone (PRO; n = 20), in combination with a thermogenic supplement (PRO + FB; n = 19), or no supplement at all (CON; n = 13) for four weeks. Body composition, anthropometric, metabolic, hemodynamic, and subjective outcomes were collected before and after the intervention. Greater changes in REE occurred in PRO + FB as compared to CON (111.2 kcal/d, 95% CI 2.4 to 219.9 kcal/d, p = 0.04), without significant differences between PRO and CON (42.7 kcal/d, 95% CI -65.0 to 150.3 kcal/d, p = 0.61) or between PRO + FB and PRO (68.5 kcal/d, 95% CI -28.3, 165.3, p = 0.21). No changes in hemodynamic outcomes (blood pressure and heart rate) were observed. In exercising adults, four weeks of supplementation with protein and a multi-ingredient thermogenic product maintained fasted REE as compared to no supplementation, for which a decrease in REE was observed, without differential effects on body composition, anthropometrics, or subjective variables.

Patients with an established diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Despite guideline-directed medical therapy, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF, and patients experiencing WHF carry a substantially higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as arrows in the quiver for clinicians to address the residual risk of HF hospitalization and cardiovascular deaths in patients with WHF. This question-and-answer-based review will discuss the emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC), the new therapeutic approaches to treat WHF and then move on to their timing and safety concerns (i.e., renal profile).

Aims: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thrombo-embolism (TE). CKD concomitantly predisposes towards a pro-haemorrhagic state. Our aim was to evaluate the prognostic value of CKD in patients undergoing percutaneous left atrial appendage occlusion (LAAO)., Methods and Results: A total of 2124 consecutive AF patients undergoing LAAO were categorized into CKD stage 1+2 (n = 1089), CKD stage 3 (n = 796), CKD stage 4 (n = 170), and CKD stage 5 (n = 69) based on the estimated glomerular filtration rate at baseline. The primary endpoint included cardiovascular (CV) mortality, TE, and major bleeding. The expected annual TE and major bleeding risks were estimated based on the CHA2DS2-VASc and HAS-BLED scores. A non-significant higher incidence of major peri-procedural adverse events (1.7 vs. 2.3 vs. 4.1 vs. 4.3) was observed with worsening CKD (P = 0.14). The mean follow-up period was 13 ± 7 months (2226 patient-years). In comparison to CKD stage 1+2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log-rank P-value = 0.04), CKD stage 4 (log-rank P-value = 0.01), and CKD stage 5 (log-rank P-value = 0.001). Left atrial appendage occlusion led to a TE risk reduction (RR) of 72, 66, 62, and 41% in each group. The relative RR of major bleeding was 58, 44, 51, and 52%, respectively., Conclusion: Patients with moderate-to-severe CKD had a higher incidence of the primary composite endpoint. The relative RR in the incidence of TE and major bleeding was consistent across CKD groups., Competing Interests: Conflict of interest: G.B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.dA. received research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo. J.C.G. is a consultant and has received speaker fees from Boston Scientific, Abbott, Medtronic, Biotronik, Pfizer, Bayer, Novartis, Daiichi Sankyo, and Boehringer Ingelheim. M.M. serves as a consultant for Boston Scientific and Abbott. L.D.B. is a consultant for Stereotaxis, Biosense Webster, Boston Scientific, Rhythm Management, and Abbott Medical. J.S. is a consultant for Boston Scientific, Abbott, Baylis, Gore, and FEops, and a proctor for Boston Scientific and Abbott. D.G. is a consultant for Boston Scientific, Abbot, Acutus, and Biosense Webster. A.N. is as a consultant for Abbott, Biosense Webster, Inc., Biotronik, Boston Scientific, Baylis, and Medtronic. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Left ventricular non compaction (LVNC) comprises a heterogeneous group of diseases that can cause heart failure, arrhythmias, and thromboembolic events. In particular, the prevalence of thromboembolism in patients with LVNC is relevant compared to the general population. Atrial fibrillation and left ventricular thrombosis are strong predictors and require anticoagulant treatment in primary or secondary prevention, with a significant reduction in the risk of events. Long-term oral anticoagulation can be considered in patients with LVNC associated with left ventricular systolic dysfunction and sinus rhythm. On the contrary, it is not entirely clear whether the presence of deep intertrabecular recesses that cause blood flow stagnation can itself represent a thrombogenic substrate even in the absence of ventricular dysfunction and in sinus rhythm, thus indicating the use of anticoagulation.This article addresses the open question of the indication for anticoagulant therapy in LVNC, through a review of the current evidence on thromboembolic risk stratification and the initiation of anticoagulant therapy and by proposing a flow-chart as a guide to decision-making according to the clinical picture of the patient.

Purpose: The purpose of this review is to explore the benefits and controversies that telemedicine (TM), applied to patients with heart failure (HF), can provide in terms of diagnosis, therapeutic management, and prognosis improvement. During the coronavirus disease 19 (COVID-19) outbreak, TM emerged as the most effective and feasible method available to ensure continuous care for chronic diseases. Among these, HF, characterized by high mortality, morbidity, and the need for frequent visits, may benefit of the TM role. HF patients are affected by frequent exacerbations undergoing a progressive prognosis impoverishment, strongly depending on the disease's management. A precise clinical handling is always required, with a constant optimization of the therapy, a continuous control of risk factors, and a sensitive attention to any change in symptoms, clinical signs, and laboratory tests. In this context, TM has shown to improve therapy adherence and HF: patients' self-care, impacting the prognosis even if specific results are controversial. Major evidence shows that TM may allow an adequate primary prevention, reducing the impact of the main cardiovascular risk factors. TM can also be useful for the secondary prevention, early detecting a likely HF exacerbation before it becomes clinically manifest, thereby lowering the need for hospitalization. Moreover, an optimal up-titration of the therapy and an increase in treatment adherence are feasible by using TM. However, some studies did not show unambiguous results, and uncertainties still remain., (© 2023. The Author(s).)

Aims: Patients with cardiomyopathies and channelopathies are usually younger and have a predominantly arrhythmia-related prognosis; they have nearly normal life expectancy thanks to the protection against sudden cardiac death provided by the implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) is an effective alternative to the transvenous ICD and has evolved over the years. This study aimed to evaluate the rate of inappropriate shocks (IS), appropriate therapies, and device-related complications in patients with cardiomyopathies and channelopathies who underwent modern S-ICD implantation., Methods and Results: We enrolled consecutive patients with cardiomyopathies and channelopathies who had undergone implantation of a modern S-ICD from January 2016 to December 2020 and who were followed up until December 2022. A total of 1338 S-ICD implantations were performed within the observation period. Of these patients, 628 had cardiomyopathies or channelopathies. The rate of IS at 12 months was 4.6% [95% confidence interval (CI): 2.8-6.9] in patients with cardiomyopathies and 1.1% (95% CI: 0.1-3.8) in patients with channelopathies (P = 0.032). No significant differences were noted over a median follow-up of 43 months [hazard ratio (HR): 0.76; 95% CI: 0.45-1.31; P = 0.351]. The rate of appropriate shocks at 12 months was 2.3% (95% CI: 1.1-4.1) in patients with cardiomyopathies and 2.1% (95% CI: 0.6-5.3) in patients with channelopathies (P = 1.0). The rate of device-related complications was 0.9% (95% CI: 0.3-2.3) and 3.2% (95% CI: 1.2-6.8), respectively (P = 0.074). No significant differences were noted over the entire follow-up. The need for pacing was low, occurring in 0.8% of patients., Conclusion: Modern S-ICDs may be a valuable alternative to transvenous ICDs in patients with cardiomyopathies and channelopathies. Our findings suggest that modern S-ICD therapy carries a low rate of IS., Clinical Trial Registration: URL: http://clinicaltrials.gov/Identifier: NCT02275637., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: Conflict of interest: G.B. reported small speaker fees from Bayer, Boehringer Ingelheim, Boston, Daiichi Sankyo, Janssen, and Sanofi outside of the submitted work. L.S. is a consultant for Boston Scientific, Abbott, and Medtronic and reported small speaker fees from Zoll. M.Z. reported small speaker fees from Abbott, Boston Scientific, and Biotronik. M.C. and S.V. are employees of Boston Scientific, Inc. The other authors did not report other conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose of Review: The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH)., Recent Findings: Evidence has shown that PAH patients' quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients' survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH., (© 2023. The Author(s).)

Despite ongoing developments, prevention and treatment of atherothrombotic cardiovascular disease remains a common challenge. Antithrombotic options for cardiocerebrovascular disease prevention involves a choice between dual antiplatelet therapy (DAPT) and dual pathway inhibition (DPI), which includes an antiplatelet agent and a reduced dose anticoagulant agent. In selected patients at high risk of event and low risk of bleeding, especially those undergoing recent and complex coronary revascularization using drug-eluting stents (DES) ("revascularization-driven effect"), DAPT is superior to single antiplatelet therapy with aspirin. DPI involves a wider potential range of treatment and is superior to single antiplatelet therapy with aspirin, particularly in patients with atherothrombotic involvement in different vascular beds both previously revascularized and not ("no revascularization-driven effect"). After nearly thirty years of randomized trials and observational registries, we have sufficient data to customize antithrombotic therapy in patients at high cardiovascular risk. Therefore, "atherothrombosis stakeholders" must identify the right patient for the right therapy to ensure high levels of efficacy and safety with the best of current therapeutic opportunities.

Aims: The HeartLogic algorithm combines multiple implantable defibrillator (ICD) sensor data and has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation in cardiac resynchronization therapy (CRT-D) patients. We evaluated the performance of this algorithm in non-CRT ICD patients and in the presence of co-morbidities., Methods and Results: The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) from 26 centres. The median follow-up was 26 months [25th-75th percentile: 16-37]. During follow-up, 97 hospitalizations were reported (53 cardiovascular) and 55 patients died. We recorded 1200 HeartLogic alerts in 370 patients. Overall, the time IN the alert state was 13% of the total observation period. The rate of cardiovascular hospitalizations or death was 0.48/patient-year (95% CI: 0.37-0.60) with the HeartLogic IN the alert state and 0.04/patient-year (95% CI: 0.03-0.05) OUT of the alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83-20.51, P < 0.001). Among patient characteristics, atrial fibrillation (AF) on implantation (HR: 1.62, 95% CI: 1.27-2.07, P < 0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21-1.93, P < 0.001) independently predicted alerts. HeartLogic alerts were not associated with CRT-D versus ICD implantation (HR: 1.03, 95% CI: 0.82-1.30, P = 0.775). Comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all P < 0.001) in all groups of patients stratified by: CRT-D/ICD, AF/non-AF, and CKD/non-CKD. After multivariate correction, the occurrence of alerts was associated with cardiovascular hospitalization or death (HR: 1.92, 95% CI: 1.05-3.51, P = 0.036)., Conclusions: The burden of HeartLogic alerts was similar between CRT-D and ICD patients, while patients with AF and CKD seemed more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify periods of significantly increased risk of clinical events was confirmed, regardless of the type of device and the presence of AF or CKD., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Although blast-induced traumatic brain injury (bTBI) has been designated as the signature injury of recent combat operations, its precise pathological mechanism(s) has not been identified thus far. Prior preclinical studies on bTBI demonstrated acute neuroinflammatory cascades which are known to be contributing to neurodegeneration. Danger-associated chemical patterns are released from the injured cells, which activate non-specific pattern recognition receptors, such as toll-like receptors (TLRs) leading to increased expression of inflammatory genes and release of cytokines. Upregulation of specific TLRs in the brain has been described as a mechanism of injury in diverse brain injury models unrelated to blast exposure. However, the expression profile of various TLRs in bTBI has not been investigated thus far. Hence, we have evaluated the expression of transcripts for TLR1-TLR10 in the brain of a gyrencephalic animal model of bTBI. We exposed ferrets to tightly coupled repeated blasts and determined the differential expression of TLRs (TLR1-10) by quantitative RT-PCR in multiple brain regions at 4 hr, 24 hr, 7 days and 28 days post-blast injury. The results obtained indicate that multiple TLRs are upregulated in the brain at 4 hr, 24 hr, 7 days and 28 days post-blast. Specifically, upregulation of TLR2, TLR4 and TLR9 was noted in different brain regions, suggesting that multiple TLRs might play a role in the pathophysiology of bTBI and that drugs that can inhibit multiple TLRs might have enhanced efficacy to attenuate brain damage and thereby improve bTBI outcome. Taken together, these results suggest that several TLRs are upregulated in the brain after bTBI and participate in the inflammatory response and thereby provide new insights into the disease pathogenesis. Therefore, inhibition of multiple TLRs, including TLR2, 4 and 9, simultaneously might be a potential therapeutic strategy for the treatment of bTBI., 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., (Published by Elsevier B.V.)

Background: The HeartLogic algorithm (Boston Scientific) has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation., Objective: The purpose of this study was to determine whether remotely monitored data from this algorithm could be used to identify patients at high risk for mortality., Methods: The algorithm combines implantable cardioverter-defibrillator (ICD)-measured accelerometer-based heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume, night heart rate, and patient activity into a single index. An alert is issued when the index crosses a programmable threshold. The feature was activated in 568 ICD patients from 26 centers., Results: During median follow-up of 26 months [25th-75th percentile 16-37], 1200 alerts were recorded in 370 patients (65%). Overall, the time IN-alert state was 13% of the total observation period (151/1159 years) and 20% of the follow-up period of the 370 patients with alerts. During follow-up, 55 patients died (46 in the group with alerts). The rate of death was 0.25 per patient-year (95% confidence interval [CI] 0.17-0.34) IN-alert state and 0.02 per patient-year (95% CI 0.01-0.03) OUT of the alert state, with an incidence rate ratio of 13.72 (95% CI 7.62-25.60; P <.001). After multivariate correction for baseline confounders (age, ischemic cardiomyopathy, kidney disease, atrial fibrillation), the IN-alert state remained significantly associated with the occurrence of death (hazard ratio 9.18; 95% CI 5.27-15.99; P <.001)., Conclusion: The HeartLogic algorithm provides an index that can be used to identify patients at higher risk for all-cause mortality. The index state identifies periods of significantly increased risk of death., (Copyright © 2023. Published by Elsevier Inc.)

Purpose of Review: Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review, we provide an overview of miRNA biogenesis and their role in the etiology and pathogenesis of myocarditis, evaluating future directions for myocarditis management., Recent Findings: Advances in genetic manipulation techniques allowed to demonstrate the important role of RNA fragments, especially microRNAs (miRNAs), in cardiovascular pathogenesis. miRNAs are small non-coding RNA molecules that regulate the post-transcriptional gene expression. Advances in molecular techniques allowed to identify miRNA's role in pathogenesis of myocarditis. miRNAs are related to viral infection, inflammation, fibrosis, and apoptosis of cardiomyocytes, making them not only promising diagnostic markers but also prognostics and therapeutic targets in myocarditis. Of course, further real-world studies will be needed to assess the diagnostic accuracy and applicability of miRNA in the myocarditis diagnosis., (© 2023. The Author(s).)

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high, and diabetes remains the leading cause of end-stage kidney disease in affected patients. To date, current medications for CKD and type 2 diabetes mellitus have not reset residual risk in patients due to a high grade of inflammation and fibrosis contributing to kidney and heart disease. This question-and-answer-based review will discuss the pharmacological and clinical differences between finerenone and other mineralocorticoid receptor antagonists and then move on to the main evidence in the cardiovascular and renal fields, closing, finally, on the potential role of therapeutic combination with sodium-glucose cotransporter 2 inhibitors (SGLT2is).

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects., (© 2021. The Author(s).)

Introduction: The prediction of ventricular tachyarrhythmias among patients with implantable cardioverter defibrillators is difficult with available clinical tools. We sought to assess whether in patients with heart failure (HF) and reduced ejection fraction with defibrillators, physiological sensor-based HF status, as summarized by the HeartLogic index, could predict appropriate device therapies., Methods: Five hundred and sixty-eight consecutive HF patients with defibrillators (n = 158, 28%) or cardiac resynchronization therapy-defibrillators (n = 410, 72%) were included in this prospective observational multicenter analysis. The association of both HeartLogic index and its physiological components with defibrillator shocks and overall appropriate therapies was assessed in regression and time-dependent Cox models., Results: Over a follow-up of 25 (15-35) months, 122 (21%) patients received an appropriate device therapy (shock, n = 74, 13%), while the HeartLogic index crossed the threshold value (alert, HeartLogic ≥ 16) 1200 times (0.71 alerts/patient-year) in 370 (65%) subjects. The occurrence of ≥1 HeartLogic alert was significantly associated with both appropriate shocks (Hazard ratios [HR]: 2.44, 95% confidence interval [CI]: 1.49-3.97, p = .003), and any appropriate defibrillator therapies. In multivariable time-dependent Cox models, weekly IN-alert state was the strongest predictor of appropriate defibrillator shocks (HR: 2.94, 95% CI: 1.73-5.01, p < .001) and overall therapies. Compared with stable patients, patients with appropriate shocks had significantly higher values of HeartLogic index, third heart sound amplitude, and resting heart rate 30-60 days before device therapy., Conclusion: The HeartLogic index is an independent dynamic predictor of appropriate defibrillator therapies. The combined index and its individual physiological components change before the arrhythmic event occurs., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (K ATP ) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215&#95;G/G of KCNJ11 and rs1799983&#95;T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215&#95;G/G of KCNJ11 and rs1799983&#95;T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the K ATP channel that provides a potential protective effect against IHD.

For several years, the autonomic nervous system has played a central role in the pathophysiological mechanism of atrial fibrillation (AF), so much so that it has been considered one of the cornerstones of Coumel's triangle. The clinical and therapeutic management of AF secondary to sympatho-vagal imbalance represents one of the most important examples of how precision medicine should be applied. Increasing knowledge of this kind of arrhythmias has made it possible to select specific antiarrhythmic drugs and to diversify their use according to vagal or adrenergic AF forms. Ablative strategies, such as cardioneuroablation and non-direct cardiac neuromodulation methods (such as renal denervation and peripheral vagal stimulation), have gradually emerged. In the possibly near future, there will be a development of new acquisitions regarding new pharmacological therapeutic strategies and gene therapy. Finally, finding an AF in patients experiencing syncopal episodes opens a whole chapter regarding interesting, but also complex, diagnostic and therapeutic strategies, ranging from neurally mediated forms to convulsive seizure that could also increase the risk of sudden death., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Heart failure (HF) is a major and still growing medical problem and is characterized by episodes of acute decompensation that are associated with a negative prognosis and a significant burden on the patients, doctors, and healthcare resources. Early detection of incipient HF may allow outpatient treatment before patients severely decompensate, thus reducing HF hospitalizations and related costs. The HeartLogic™ algorithm is an automatic, remotely managed system combining data directly related to HF pathophysiology into a single score, the HeartLogic™ index. This index proved to be effective in predicting the risk of incipient HF decompensation, allowing to redistribute resources from low-risk to high-risk patients in a timely and cost-saving manner. The alert-based remote management system seems more efficient than the one based on scheduled remote transmission in terms of caregivers' workload and alert detection timing. The widespread application of the HeartLogic™ algorithm requires the resolution of logistical and financial issues and the adoption of a pre-defined, functional workflow. In this paper, we reviewed general aspects of remote monitoring in HF patients, the functioning and pathophysiological basis of the HeartLogic index, its efficiency in the management of HF patients, and the economic effects and the organizational revolution associated with its use., Competing Interests: Conflict of interest: L.S. has received consultancy fee from Boston Scientific, Abbott Medical and Medtronic., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: His- Purkinje system pacing (HPSP) techniques have been proposed as alternative to biventricular pacing (BVP) and right ventricular pacing (RVP)., Objective: To compare data regarding clinical, procedural and lead outcomes associated with different pacing techniques., Methods: An accurate search of online scientific libraries (from inception to May, 12,022) was performed. Thirty-three studies were included in the meta-analysis involving 4386 patients, of whom 1324 receiving RVP, 1032 patients receiving BVP, 1069 patients receiving his-bundle pacing (HBP) and 968 patients receiving left bundle branch pacing (LBBP)., Results: LBBP provided a statistically significant increase in LVEF relative to HBP (0.4473 [0.0584; 0.8361] p = 0.0242) and BVP (0.6733 [0.4734; 0.8732] p < 0.0001) in patients with cardiac resynchronization therapy indication. LBBP and HBP significantly decreased QRS duration as compared to BVP, with largest QRS narrowing obtained by LBBP (-0.4951 [-0.9077; -0.0824] p = 0.0187). As compared to LBBP, HBP was associated with a significant increase of pacing threshold (p = 0.0369) and significant reduction of R-wave amplitude over time (p = 0.027). LBBP was associated with significant reduction in RR of hospitalization for HF (HFH) as compared to both BVP (p = 0.0343) and HBP (p = 0.0476), whereas, as compared to RVP, the risk of lead issues was significantly higher with BVP (p = 0.0424) and HBP (p = 0.0298), but not for LBBP (p = 0.425)., Conclusions: As compared to other pacing techniques, LBBP significantly improved LVEF, narrowed QRS duration and reduced HFHs, with steadily lower capture thresholds and higher R-wave amplitude, and without increasing lead issues., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. This research did not receive any specific grant from founding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most frequent regular tachycardia in humans. In this review, we describe the most recent discoveries regarding the anatomical, physiological, and molecular biological features of the atrioventricular junction that could underlie the typical slow-fast AVNRT mechanisms, as these insights could lead to the proposal of a new theory concerning the circuit of this arrhythmia. Despite several models have been proposed over the years, the precise anatomical site of the reentrant circuit and the pathway involved in the slow-fast AVNRT have not been conclusively defined. One possible way to evaluate all the hypotheses regarding the nodal tachycardia circuit in humans is to map this circuit. Thus, we tried to identify the slow potential of nodal and inferior extension structures by using automated mapping of atrial activation during both sinus rhythm and typical slow-fast AVNRT. This constitutes a first step toward the definition of nodal area activation in sinus rhythm and during slow-fast AVNRT. Further studies and technical improvements in recording the potentials of the atrioventricular node structures are necessary to confirm our initial results., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: This report describes the findings of the 2020 Italian Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)., Methods: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers., Results: A total of 10 378 ablation procedures were performed by 66 institutions. Most centers (70%) have an electrophysiology laboratory, and 23% a hybrid cardiac surgery laboratory. All centers have a 3D mapping system. The median number of electrophysiologists and nurses involved in the electrophysiology laboratory was 3.5 and 3, respectively. An electrophysiology technician was involved in 35% of all centers. In 88.2% of cases, catheter ablation was performed for supraventricular arrhythmias; the most frequently treated arrhythmia was atrial fibrillation (39.4%), followed by atrioventricular nodal reentrant tachycardia (18.6%), and common atrial flutter (10.6%). In 72.9% of patients, catheter ablation was performed using a 3D mapping system, with a "near-zero" fluoroscopic approach in 37.7% of all patients., Conclusions: The 2020 Italian Catheter Ablation Registry confirmed that the electrophysiology activity was markedly affected by the COVID-19 pandemic; atrial fibrillation is the most frequently treated arrhythmia with an increasing number of procedures performed with a 3D mapping system and a "near-zero" approach.

Background: Catheter ablation (CA) of atrial fibrillation (AF) is used routinely to establish rhythm control. There is mounting evidence that CA procedures should be performed during continuous oral anticoagulation and direct oral anticoagulants (DOACs) are considered the first anticoagulation strategy. Few real-life data are now available and even less in the Italian panorama., Methods: IRIS is an Italian multicenter, non-interventional, prospective study which will be enrolled consecutive AF patients eligible for CA and treated with Rivaroxaban; patients in treatment with Rivaroxaban proceeded directly to CA while Rivaroxaban-naive patients were scheduled for CA after 4 weeks of uninterrupted anticoagulation unless the exclusion of atrial thrombi. Rivaroxaban was uninterrupted or shortly uninterrupted (<24 hours) prior CA, in line with routinely practice of each operator. Patients will be followed on continuous anticoagulation for 1 month after the ablation. The primary efficacy outcome is the cumulative incidence of all-cause death and systemic embolism while the primary safety outcome is the incidence of major bleeding events. The secondary outcomes are represented by non-major bleeding events. All events must be occurred within the first 30 days after the procedure., Results: Two hundred fifty patients are expected to be enrolled and the study is estimated to be completed by the end of 2022. Up to now 56 patients have been enrolled., Conclusions: This study is the first large Italian prospective study on the management of Rivaroxaban in patients undergoing CA of AF. It aims to depict a comprehensive view of anticoagulation strategy prior CA in several Italian electrophysiology labs.

Proper therapeutic management of patients with heart failure (HF) is a major challenge for cardiologists. Current guidelines indicate to start therapy with angiotensin converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors (ACEi/ARNI), beta blockers (BB), mineralocorticoid receptor antagonists (MRAs) and sodium glucose cotransporter 2 inhibitors (SGLT2i) to reduce the risk of death and hospitalization due to HF. However, certain aspects still need to be defined. Current guidelines propose therapeutic algorithms based on left ventricular ejection fraction values and clinical presentations. However, these last do not always reflect the precise hemodynamic status of patients and pathophysiological mechanisms involved, particularly in the acute setting. Even in the field of chronic management there are still some critical points to discuss. The guidelines do not specify which of the four pillar drugs to start first, nor at what dosage. Some authors suggest starting with SGLT2i and BB, others with ACEi or ARNI, while one of the most recent approach proposes to start with all four drugs together at low doses. The aim of this review is to revise current gaps and perspectives regarding pharmacological therapy management in HF patients, in both the acute and chronic phase.

The feasibility and effectiveness of virtual visits (VVs) for cardiac electrophysiology patients are still unknown. We aimed to assess the feasibility and effectiveness of VVs as compared to in-person visits, and to describe patient experience with virtual care in clinical electrophysiology. We prospectively enrolled patients scheduled to receive a clinical electrophysiology evaluation, dividing them in two groups: a VV group and an in-person visit group. Outcomes of interest were: (1) improvement in symptoms after the index visit, (2) disappearance of remote monitoring (RM) alerts at follow-up, (3) necessity of urgent hospitalization and (4) patient satisfaction measured by the Patient Satisfaction Questionnaire-18 (PSQ-18). This study included 162 patients in the VV group and 185 in the in-office visit group. As compared to in-person visits, VVs resulted in a similar reduction in RM alerts (51.5% vs. 43.2%, p-value 0.527) and in symptomatic patient rates (73.6% vs. 56.9%, p-value 0.073) at follow-up, without differences in urgent hospitalization rates (p-value 0.849). Patient satisfaction with VVs was higher than with in-person evaluation (p-value < 0.012). VVs proved to be as feasible and as effective as in-person visits, with high patient satisfaction. A hybrid model of care including VVs and in-person visits may become the new standard of care after the COVID-19 pandemic is over.

Spatial models jointly simulating population and land-use change provide support for policy-making, by allowing to explore territorial developments under alternative scenarios and resulting impacts in the environment, economy and society. However, their ability to reproduce observed spatial patterns is rarely evaluated through model validation. This lack of insight prevents researchers and policy-makers of fully grasping the ability of existing models to provide sensible projections of future land use and population density. In this article, we address this gap by performing a model validation of the LUISA Territorial Modelling Platform, a spatial model jointly simulating population and land use at a fine resolution (100 m) in the European Union and United Kingdom. In particular, we compare observed and simulated patterns of population and urban residential land-use change for the period of 1990-2015, and evaluate the model performance according to different degrees of urbanisation. The results show that model performance can vary depending on the context, even when the same data and methods are uniformly applied. The model performed consistently well in urban areas characterized by compact urban growth, but poorly where residential development occurred predominantly in scattered patterns across rural areas. Overall, the model tends to favour the formation of densely populated, highly accessible urban conglomerations, which often do not entirely correspond to the observed patterns. Based on the validation results, we propose directions for further model improvement and development. Model validation should be regarded as a critical step, and an integral part, in the process of developing models for policy support., Supplementary Information: The online version contains supplementary material available at 10.1007/s12061-023-09518-x., Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2023.)

Background: The subsequent waves of the COVID-19 pandemic in Italy had a major impact on cardiac care., Methods: A survey to evaluate the dynamic changes in arrhythmia care during the first five waves of COVID-19 in Italy (first: March-May 2020; second: October 2020-January 2021; third: February-May 2021; fourth: June-October 2021; fifth: November 2021-February 2022) was launched., Results: A total of 127 physicians from arrhythmia centers (34% of Italian centers) took part in the survey. As compared to 2019, a reduction in 40% of elective pacemaker (PM), defibrillators (ICD), and cardiac resynchronization devices (CRT) implantations, with a 70% reduction for ablations, was reported during the first wave, with a progressive and gradual return to pre-pandemic volumes, generally during the third-fourth waves, slower for ablations. For emergency procedures (PM, ICD, CRT, and ablations), recovery from the initial 10% decline occurred in most cases during the second wave, with some variability. However, acute care for atrial fibrillation, electrical cardioversions, and evaluations for syncope showed a prolonged reduction of activity. The number of patients with devices which started remote monitoring increased by 40% during the first wave, but then the adoption of remote monitoring declined., Conclusions: The dramatic and profound derangement in arrhythmia management that characterized the first wave of the COVID-19 pandemic was followed by a progressive return to the volume of activities of the pre-pandemic periods, even if with different temporal dynamics and some heterogeneity. Remote monitoring was largely implemented during the first wave, but full implementation is needed., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Arrhythmic death is very common among patients with structural heart disease, and it is estimated that in European countries, 1 per 1000 inhabitants yearly dies for sudden cardiac death (SCD), mainly as a result of ventricular arrhythmias (VA). The scar is the result of cardiac remodelling process that occurs in several cardiomyopathies, both ischemic and non-ischemic, and is considered the perfect substrate for re-entrant and non-re-entrant arrhythmias., Methods: Our aim was to review published evidence on the histological and electrophysiological properties of myocardial scar and to review the central role of cardiac magnetic resonance (CMR) in assessing ventricular arrhythmias substrate and its potential implication in risk stratification of SCD., Results: Scarring process affects both structural and electrical myocardial properties and paves the background for enhanced arrhythmogenicity. Non-uniform anisotropic conduction, gap junctions remodelling, source to sink mismatch and refractoriness dispersion are some of the underlining mechanisms contributing to arrhythmic potential of the scar. All these mechanisms lead to the initiation and maintenance of VA. CMR has a crucial role in the evaluation of patients suffering from VA, as it is considered the gold standard imaging test for scar characterization. Mounting evidences support the use of CMR not only for the definition of gross scar features, as size, localization and transmurality, but also for the identification of possible conducting channels suitable of discrete ablation. Moreover, several studies call out the CMR-based scar characterization as a stratification tool useful in selecting patients at risk of SCD and amenable to implantable cardioverter-defibrillator (ICD) implantation., Conclusions: Scar represents the substrate of ventricular arrhythmias. CMR, defining scar presence and its features, may be a useful tool for guiding ablation procedures and for identifying patients at risk of SCD amenable to ICD therapy., (© 2022. The Author(s).)

Background: The absence of pacing capabilities may reduce the appeal of subcutaneous implantable cardioverter-defibrillator (S-ICD) devices for patients at risk for conduction disorders or with antitachycardia pacing (ATP)/cardiac resynchronization (CRT) requirements. Reports of rates of S-ICD to transvenous implantable cardioverter-defibrillator (TV-ICD) system switch in real-world scenarios are limited., Objective: The purpose of this study was to investigate the need for a subsequent transvenous (TV) device in patients implanted with an S-ICD and its predictors., Methods: All patients implanted with an S-ICD were enrolled from the multicenter, real-world iSUSI (International SUbcutaneouS Implantable cardioverter defibrillator) Registry. The need for a TV device and its clinical reason, and appropriate and inappropriate device therapies were assessed. Logistic regression with Firth penalization was used to assess the association between baseline and procedural characteristics and the overall need for a subsequent TV device., Results: A total of 1509 patients were enrolled (age 50.8 ± 15.8 years; 76.9% male; 32.0% ischemic; left ventricular ejection fraction 38% [30%-60%]). Over 26.5 [13.4-42.9] months, 155 (10.3%) and 144 (9.3%) patients experienced appropriate and inappropriate device therapies, respectively. Forty-one patients (2.7%) required a TV device (13 bradycardia; 10 need for CRT; 10 inappropriate shocks). Body mass index (BMI) >30 kg/m 2 and chronic kidney disease (CKD) were associated with need for a TV device (odds ratio [OR] 2.57 [1.37-4.81], P = .003; and OR 2.67 [1.29-5.54], P = .008, respectively)., Conclusion: A low rate (2.7%) of conversion from S-ICD to a TV device was observed at follow-up, with need for antibradycardia pacing, ATP, or CRT being the main reasons. BMI >30 kg/m 2 and CKD predicted all-cause need for a TV device., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)