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Background: Resynchronization therapy has become a cornerstone in patients with heart failure (HF). Recent advancements in this field have led to the development of the so-called “left bundle branch area pacing” (LBBAP), a form of pacing where a single ventricular catheter directly addresses the left bundle for a more physiological stimulation. The current literature provides encouraging evidence regarding this topic, but there is still limited data for the older population, particularly those aged ≥75 years. This review aims to clarify how LBBAP has been explored in this cohort and if its application could be safe and effective even in the most advanced stages of life. Methods: A search of articles from PubMed was conducted. Patients were considered older if above 75 years of age. Data regarding Italian statistics were obtained from national registries. Results: The current literature supports the safety and effectiveness of LBBAP in older patients across different indications, with outcomes comparable to those reported in younger patients and a suggested cost-effectiveness. Conversely, data regarding patients affected by cardiac amyloidosis are still inconclusive. Conclusions: LBBAP represents a valuable resource for patients of all ages, but frailty is a major issue in the older population that needs to be addressed. The potential integration of this technology with defibrillator capabilities will enable an even more extensive application in the near future.

Mitochondria are central regulators of cardiac homeostasis, integrating energy production, redox balance, calcium handling, and innate immune signaling. In cardiovascular disease (CVD), mitochondrial dysfunction acts as a unifying mechanism connecting oxidative stress, metabolic inflexibility, inflammation, and structural remodeling. Disturbances in mitochondrial quality control—encompassing fusion–fission dynamics, PINK1/Parkin- and receptor-mediated mitophagy, biogenesis, and proteostasis—compromise mitochondrial integrity and amplify cardiomyocyte injury. Excess reactive oxygen species, mitochondrial DNA release, and calcium overload further activate cGAS–STING, NLRP3 inflammasomes, and mPTP-driven cell death pathways, perpetuating maladaptive remodeling. Therapeutic strategies targeting mitochondrial dysfunction have rapidly expanded, ranging from mitochondria-targeted antioxidants (such as MitoQ and SS-31), nutraceuticals, metabolic modulators (SGLT2 inhibitors, metformin), and mitophagy or biogenesis activators to innovative approaches including mtDNA editing, nanocarrier-based delivery, and mitochondrial transplantation. These interventions aim to restore organelle structure, improve bioenergetics, and reestablish balanced quality control networks. This review integrates recent mechanistic insights with emerging translational evidence, outlining how mitochondria function as bioenergetic and inflammatory hubs in CVD. By synthesizing established and next-generation therapeutic strategies, it highlights the potential of precision mitochondrial medicine to reshape the future management of cardiovascular disease.

Background Several novel technologies allowing catheter ablation (CA) with a favorable safety/efficacy profile have been recently developed, but not yet extensively clinically tested in the setting of ventricular tachycardia CA. Methods In this technical report, we overview technical aspects and preclinical/clinical information concerning the application of three novel CA technologies in the ventricular milieu: a pulsed field ablation (PFA) generator (CENTAURI™, Galaxy Medical) to be used with linear, contact force-sensing radiofrequency ablation catheters; a contact force-sensing radiofrequency ablation catheter equipped with six thermocouples and three microelectrodes (QDOT Micro™, Biosense-Webster), allowing high-resolution mapping and temperature-controlled CA; and a flexible and mesh-shaped irrigation tip, contact force-sensing radiofrequency ablation catheter (Tactiflex, Abbott). We also report three challenging VT cases in which CA was performed using these technologies. Results The CENTAURI system was used with the Tacticath™ (Abbott) ablation catheter to perform ventricular PFA in a patient with advanced heart failure, electrical storm, and a deep intramural septal substrate. Microelectrode mapping using QDOT Micro™ helped to refine substrate assessment in a VT patient with congenitally corrected transposition of the great arteries, and allowed the identification of the critical components of the VT circuit, which were successfully ablated. Tactiflex™ was used in two challenging CA cases (one endocardial and one epicardial), allowing acute and mid-term control of VT episodes without adverse events. Conclusion The ideation and development of novel technologies initially intended to treat atrial arrhythmias and successfully implemented in the ventricular milieu is contributing to the progressive improvement in the clinical benefits derived from VT CA, making this procedure key for successful management of increasingly complex patients. Graphical abstract

Background Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca 2+ ) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca 2+ oscillations and the Ca 2+ toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes. Methods and results ACM C-MSC show enhanced spontaneous Ca 2+ oscillations and concomitant increased Ca 2+ /Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca 2+ Entry (SOCE), which leads to enhanced Ca 2+ release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca 2+ handling machinery or CaMKII activity, we demonstrated a causative link between Ca 2+ oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca 2+ signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca 2+ oscillations and fibro-adipogenic differentiation by selectively targeting SOCE. Conclusions Altogether, our results extend the knowledge of Ca 2+ dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.

Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro‐adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low‐density lipoprotein (oxLDL)‐dependent activation of PPARγ, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient‐derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARγ upregulation. By boosting oxLDL in a Pkp2 heterozygous knock‐out mice through high‐fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies. Synopsis ACM mutations are necessary but not sufficient for disease penetrance. The contribution of oxidised lipids as novel pharmacologically targetable cofactors was demonstrated by a multi‐layer approach (patients – in vitro – in vivo ), leading to an advancement in the knowledge of ACM pathogenesis. ACM patients show high oxLDL plasma levels, which stratify ACM phenotype severity. oxLDL worsen adipogenic differentiation of ACM cells by altering the CD36/13HODE/PPARγ axis. By increasing oxLDL in an ACM mouse model with low penetrance, ACM‐specific tissue remodelling, functional and electrical impairments are unveiled. NAC and Atorvastatin can prevent ACM phenotypes in vitro / in vivo . Graphical Abstract ACM mutations are necessary but not sufficient for disease penetrance. The contribution of oxidised lipids as novel pharmacologically targetable cofactors was demonstrated by a multi‐layer approach (patients – in vitro – in vivo ), leading to an advancement in the knowledge of ACM pathogenesis.

Background and Aims: Breast cancer (BC) is the leading cause of cancer in women. Female interventional cardiologists are potentially at a higher risk of developing BC due to occupational radiation exposure. This survey aimed at understanding radiation safety and awareness in current clinical practice, and the occurrence of BC, among female interventional cardiologists. Methods: A survey was conducted worldwide among 64 cardiac laboratories from September 2022 to December 2022. Results: 195 physicians (mean age 41.0 ± 7.4 years) completed the survey: 33 (16.9%) reported being exposed to X‐ray for less than five years, 78 (40%) between five and ten years and 84 (43.1%) for more than ten years; 13 (6.7%) reported performing less than 50 interventional procedures/year, 52 (26.7%) between 50 and 100 and 130 (66.6%) more than 100 procedures/year. 126 physicians reported wearing three or more radiation dosimeters; 72 reported not using tableside X‐ray shielding to protect themselves from direct and scattered radiation. BC occurred in four (2.1%) physicians, all of whom worked in the electrophysiology laboratory for a relatively long time (one with 5–10 years of exposure and three with more than ten years; mean age at cancer presentation was 46.5 ± 3.7 years). All tumours were left‐sided BC. Conclusions: This survey provides a snapshot of occupational radiation exposure of female interventional cardiologists. BC is a possible professional threat in addition to its real‐life epidemiology, with a negative impact on women’s lives in interventional laboratories. All possible efforts should be made to eliminate radiation exposure among interventional laboratory workers.

PurposeTo provide a brief overview of some relevant technological advances in the field of three-dimensional electroanatomical mapping (3D-EAM) that have recently entered the clinical arena and their role in guiding catheter ablation (CA) of complex atrial and ventricular arrhythmias.MethodsIn this technical report, we describe the general features of three novel algorithms featured in the updated CARTO PRIME™ mapping module for CARTO®3 version 7 3D-EAM system (Biosense Webster Inc., Diamond Bar, CA, USA): local activation time (LAT) hybrid, coherent mapping and map replay modules. We also report three challenging arrhythmia cases in which CA was successfully guided by these softwares.ResultsThe LAT hybrid module was used in a case of premature ventricular complex originating from the right coronary cusp. This algorithm facilitated safe positioning of the ablation catheter away from the right coronary ostium, avoiding potential harm to this vital structure. The coherent mapping module helped to identify the critical as well as a bystander isthmus of an atrial macro-re-entrant tachycardia in a grown-up patient with congenital heart disease. The map replay module allowed rapid retrospective activation mapping of two unstable ventricular tachycardias in a case of nonischemic cocaine-associated cardiomyopathy.Conclusion3D-EAM systems offer significant advantages in the management of challenging arrhythmias, and the introduction of novel algorithms underpins improvements in patients’ outcomes. Given the increasing sophistication of these systems, however, a close collaboration among cardiac electrophysiologists, engineers and technicians is highly needed in order to get the best from the available technology.

Atrial high-rate episodes (AHREs) and subclinical atrial fibrillation (AF) are frequently registered in asymptomatic patients with cardiac implantable electronic devices (CIEDs) and insertable cardiac monitors (ICMs). While an increased risk of thromboembolic events (e.g., stroke) and benefits from anticoagulation have been widely assessed in the setting of clinical AF, concerns persist about optimal clinical management of subclinical AF/AHREs. As a matter of fact, an optimal threshold of subclinical episodes’ duration to predict stroke risk is still lacking and recently published randomized clinical trials assessing the impact of anticoagulation on thromboembolic events in this specific setting have shown contrasting results. The aim of this review is to summarize current evidence regarding classification and clinical impact of subclinical AF/AHREs and to discuss the latest evidence regarding the potential benefit of anticoagulation in this setting, highlighting which clinical questions are still unanswered.

Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53 ± 0.04 fold expression difference in ACM vs. HC (p < 0.01). A similar trend was observed when comparing ACM (n = 13) and HC (n = 17) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78 ± 0.05 fold expression change vs. IVT (p = 0.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation.

Myocardial inflammation is an important cause of cardiovascular morbidity and sudden cardiac death in athletes. The relationship between sports practice and myocardial inflammation is complex, and recent data from studies concerning cardiac magnetic resonance imaging and endomyocardial biopsy have substantially added to our understanding of the challenges encountered in the comprehensive care of athletes with myocarditis or inflammatory cardiomyopathy (ICM). In this review, we provide an overview of the current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of myocarditis, ICM, and myopericarditis/perimyocarditis in athletes, with a special emphasis on arrhythmias, patient-tailored therapies, and sports eligibility issues.