INTRODUCTION:The optimal duration of implantable loop recorder (ILR) monitoring remains uncertain and may differ according to the indication for implantation. We evaluated whether the time-dependent diagnostic yield and clinical relevance of ILR-detected arrhythmias differ among patients implanted for syncope, palpitations, cryptogenic stroke, or Brugada syndrome. OBJECTIVE:This study sought to define the time-dependent diagnostic yield of ILRs across clinical indications and to assess whether early and late diagnoses differed in their impact on clinical management. METHODS AND RESULTS:We retrospectively analyzed 1734 consecutive patients undergoing ILR implantation at 5 Italian centers for unexplained syncope, palpitations, cryptogenic stroke, or Brugada syndrome. Diagnosis of interest was defined according to the implant indication: pauses for syncope, supraventricular tachycardia or atrial fibrillation for palpitations, atrial fibrillation for cryptogenic stroke, and ventricular tachycardia or pauses for Brugada syndrome. Median follow-up was 34 months. Maximally selected rank statistics identified 26 months as the global threshold separating early from late diagnoses, while indication-specific optimal diagnostic windows were 14 months for syncope, 13 months for palpitations, 16 months for cryptogenic stroke, and 55 months for Brugada syndrome. In syncope and palpitations, most actionable diagnoses occurred early, and diagnostic efficiency declined markedly after 26 months, with late findings often less clearly related to the index presentation. In cryptogenic stroke, atrial fibrillation detection was most frequent early but could still lead to changes in antithrombotic management later, supporting an individualized "gray-zone" approach to prolonged monitoring. By contrast, Brugada syndrome showed sustained diagnostic yield over extended follow-up, with late ventricular arrhythmias or pauses retaining major prognostic and therapeutic implications, including implantable cardioverter-defibrillator implantation and device-type selection. CONCLUSIONS:The value of ILR monitoring is strongly time- and indication-dependent. Prolonged routine monitoring or reimplantation appears to have limited incremental value in syncope and palpitations when early follow-up is unrevealing, whereas extended surveillance may remain justified in Brugada syndrome and should be individualized after cryptogenic stroke. These observations support indication-driven ILR follow-up strategies rather than a uniform approach based on device longevity alone.

AIMS:Loss-of-function (LOF) mutations of the cardiac Na+ channel (SCN5A) are causatively associated with the Brugada Syndrome (BrS). However, the onset of Ventricular Fibrillation (VF) is a rare event, and critical factors favouring the pathological phenotype remain often elusive. This study explores how concomitant triggering conditions may impact on VF onset in a symptomatic proband carrying the S805L/SCN5A BrS mutation. METHODS AND RESULTS:Clinical, in-vitro, numerical, and structural analyses were performed. A 67-year-old male was resuscitated after cardiac arrest, and clinical analysis upon hospitalisation revealed severe hypokalaemia (2.5 mEq/L). The ECG showed a coved type-I BrS pattern and the SCN5A mutation (S805L) was identified. Patch-clamp studies carried out in a heterologous expression system (HEK293 cells) revealed that WT/S805L channels exhibit two different phenotypes (normal and LOF); the main parameter controlling this distribution is the cell membrane potential. A protected/normal behaviour was observed at -80 mV; conversely, LOF occurred at more negative potentials (-100/-120 mV). Further analyses in isolated outflow tract ventricular cardiomyocytes showed that hypokalaemia (and bradycardia) induced diastolic potential hyperpolarisation, thus favouring the Na+ current LOF. Computational and molecular modelling confirmed our findings and revealed the structural determinant of this alteration. CONCLUSION:WT/S805L Na+ channels exhibit either a LOF or a wild-type-like behaviour depending on the membrane potential. Since hypokalaemia and slow pacing rate induce cell hyperpolarisation and the associated LOF, they represent concurrent elements creating the scenario responsible for the VF and cardiac arrest. These results may represent an interpretative paradigm applicable to other BrS mutations.

Infective endocarditis (IE) is a severe infectious disease affecting cardiac valves (either native or prosthetic) or implantable cardiac devices, and it is associated with high rates of morbidity and mortality. Recent data from the Global Burden of Disease study have shown a significant increase in both the incidence and mortality of IE. One-year mortality following diagnosis can reach up to 30%. IE can present with a wide range of clinical manifestations, and its course may be complicated by systemic embolic events or intracardiac complications such as abscess formation or prosthetic valve dehiscence. Echocardiography remains the first-line imaging modality; however, an integrated multimodality imaging approach is increasingly adopted in contemporary practice, incorporating both cardiac computed tomography and positron emission tomography. A multidisciplinary approach involving cardiologists, cardiac surgeons, internists, infectious disease specialists, and nuclear medicine physicians is often required to ensure accurate diagnosis and effective treatment of IE. The prognosis of infective endocarditis depends on early diagnosis, appropriate antimicrobial therapy, and timely surgical intervention when indicated. This review aims to summarize the current knowledge on IE, from pathophysiological insights to surgical strategies. It also focuses on practical recommendations to address the most pressing unmet clinical needs through a multidisciplinary approach.

INTRODUCTION:Slow-pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT) is highly effective but carries a small risk of atrioventricular block. A fully standardized, safety-driven 3D-guided workflow tailored to AVNRT ablation has not been clearly defined. METHODS AND RESULTS:We retrospectively analyzed 150 consecutive day-hospital patients with invasive electrophysiological confirmation of AVNRT who underwent ablation using the standardized PICENO AVNRT approach between 2017 and 2025. The protocol integrates Koch's triangle pace mapping and voltage-bridge mapping to guide slow-pathway ablation. Acute success was achieved in 100% of patients. No transient or permanent AV block occurred. Fluoroscopy was not required in any case. Mean procedure time was 62 ± 14 min. At 30.5 ± 18.8 months of follow-up, one recurrence (0.7%) was observed. CONCLUSION:A standardized 3D-guided safety-driven workflow for AVNRT ablation is feasible and reproducible in a day-hospital setting, achieving excellent outcomes while eliminating fluoroscopy because of procedural reliability.

Pulmonary vein isolation (PVI) ablation has limited efficacy in persistent atrial fibrillation (PeAF). Anatomical strategies combining PVI, vein of Marshall ethanol infusion (VOM-EI), and an anatomical ablation strategy (AS) targeting key atrial isthmuses have shown promising short-term outcomes in this setting. In this retrospective multicenter observational cohort study, consecutive patients with PeAF who underwent either VOM-EI + AS or PVI-only were included. The primary endpoint was freedom from atrial arrhythmias (AAs) lasting > 30 s off antiarrhythmic drugs (AADs). Procedural characteristics and safety outcomes were also evaluated. After 2:1 propensity score matching, 151 patients treated with VOM-EI + AS were compared with 75 treated with PVI-only. After a median follow-up of 22-month (interquartile range (IQR): 9–35 months), 81

The QDOT Micro catheter allows to perform a very high-power short-duration ablation that produces wider and shallower lesions. This study aims to corroborate the evidences on the safety, acute and long-term efficacy of this catheter by providing a large real-world dataset. The AIR HPSD Registry is a multicentric prospective registry across 26 European centers that enrolled consecutive atrial fibrillation (AF) patients undergoing their first pulmonary vein (PV) isolation. In all patients a wide antrum circumferential ablation aimed at PV isolation was performed using the QDOT Micro catheter in QMode+ (90 w for 4 s) for the whole ablation or in a hybrid mode (QMode + for the posterior wall and QMode guided by ablation index for the anterior wall), according to the operators’ preference. Overall, 982 patients have been enrolled, 38

BACKGROUND:False-positive (FP) alerts from implantable loop recorders increase clinical workload and may delay appropriate intervention. AccuRhythm AI, a cloud-based filtering algorithm, is designed to reduce these alerts in Reveal LINQ and LINQ II devices. This study assessed the algorithm's effect on FP and clinician burden reduction, with a focus on the influence of R-wave sensing amplitude. METHODS:This multicentre, retrospective study included 800 patients with either Reveal LINQ or LINQ II. We analysed automated artificial intelligence (AI) reports and compared FP rates and transmission burden before and after software-based AI activation in the subset of Reveal LINQ patients to assess patient-level changes. The relationship between R-wave amplitude and FP incidence was also evaluated. RESULTS:AI-based filtering, by AccuRhythm AI automatic analysis, reduced false pause alerts by 62% and false atrial fibrillation alerts by 33%, saving 210 clinician hours over 6 months. Patient level analysis, among 465 Reveal LINQ patients, showed FP+ patients (patients with ≥1 false-positive transmission) reduction from 55.5% to 15.1% post-AI (p<0.001), translating to 1128 hours saved. All residual false alerts occurred in patients with R-wave amplitudes <0.4 mV. CONCLUSION:Use of AccuRhythm AI was associated with a significant reduction in FPs and clinician workload while preserving diagnostic accuracy. R-wave amplitude remained a key factor influencing alert specificity, emphasising the continued importance of optimal device implantation and signal quality.

The vein of Marshall (VoM) is a promising therapeutic target for persistent atrial fibrillation (PeAF) treatment. Ethanol infusion into the VoM (VoM-EI) has demonstrated high effectiveness in facilitating mitral isthmus (MI) block, a fundamental part of the anatomical ablation setup for the treatment of PeAF. However, reliable indexes for optimal ethanol delivery are still lacking, and the role of voltage analysis after VoM-EI in predicting MI block has been poorly explored. To evaluate the role of voltage analysis after VoM-EI in predicting acute bidirectional MI block and the need of coronary sinus (CS) radiofrequency (RF) applications. Fifty-three PeAF patients who underwent catheter ablation were retrospectively enrolled. Left atrial (LA) high-density bipolar voltage mapping was performed before and after VoM-EI. Low voltage areas (LVA) were assessed for all LA maps using the area measurement tool, and the difference in area width between pre- and post-VoM-EI was defined as ∆LVA. An anatomical lesion set including VoM-EI, pulmonary vein isolation (PVI) and linear lesion for dome, lateral MI, and cavo-tricuspid isthmus (CTI) was performed. In case of residual conduction across MI, additional endocardial and/or epicardial ablations approaching the CS musculature were performed. The time required to achieve bidirectional MI block (AblTime-MI) was collected and the VoM length was measured. Forty-eight out of 53 patients enrolled (90.5

Brugada Syndrome (BrS) is a genetic disease associated with ventricular arrhythmias and is one of the causes of sudden cardiac death. In particular, dysfunctional cardiac Na + channels (SCN5A) represent the only mechanism supporting the autosomal dominant inheritance. A proband without previous medical history was referred to the intensive care unit after resuscitation showing ECG Type 1 BrS pattern and a significant hypokalemia (2.5 mEq/L). Genetic analysis identified a SCN5A de-novo mutation (S805L) in heterozygosis. This study investigates the causative association between the S805L mutation and the BrS event. First, we expressed wild type (WT) and/or mutated (Hetero and Homo) channels in HEK293T. The application of I/V protocols (hp -120 mV) revealed reduced I Na density in Homo and Hetero (-65% and -26% vs WT at -20 mV), indicating S805L as a loss-of-function (LOF) mutation. However, Hetero I Na density was comparable to WT at more depolarized hp (-80 mV), suggesting alterations in the voltage dependent availability of the channel. Accordingly, steady-state inactivation curves of both Hetero and Homo I Na were right shifted, indicating a gain-of-function (GOF) behaviour (Hetero availability: +13% vs WT at -80 mV). To investigate the possible role of hypokalemia in uncovering the LOF behaviour of the mutation, we reproduced in vitro the hypokalemic condition of the patient testing the effects of external K + (K + out ) on diastolic membrane potential (E diast ) of paced guinea-pig cardiomyocytes. Cells were isolated from the Right Ventricular Outflow Tract, known as site of BrS onset. In comparison to a normokalemic condition, E diast significantly hyperpolarized at 2.5 mM K + out and the effect was greater at low pacing rates (1 Hz) (-16.5 mV vs E diast at 5 mM K + and 4 Hz). Thus, the combination of bradycardia and hypokalemia might represent a mechanism able to unmask the LOF effect of S805L mutation in Hetero conditions. Computational approach on the human ventricular action potential confirmed these findings. In conclusion, S805L-SCN5A is, at the same time, a LOF and GOF mutation causing reduced channel expression with increased channel availability. While the balance between GOF-LOF effects guaranties a “protected” phenotype, the hypokalemic-induced cell hyperpolarization might reduce the GOF, leading to the appearance of the BrS event.

BACKGROUND:Retrograde ethanolization of the vein of Marshall (VOM) has been identified as an adjunct technique in the treatment of persistent atrial fibrillation (AF) and left atrial tachycardia, as stated in the last consensus statement on ablation of AF. However, there is a lack of high-volume data on the technique. METHODS:Through the collection of data from worldwide centers, we performed this international survey that aims to analyze the safety and procedural characteristics of VOM ethanolization in patients referred for treatment of AF or left atrial tachycardia. RESULTS:We included 5579 patients (66 years; range, 20-93) from 26 centers, who underwent VOM ethanolization between 2008 and 2024 for persistent AF (81%), paroxysmal AF (9%), or left atrial tachycardia (10%) under deep sedation (53%) or general anesthesia (47%). A concomitant mitral isthmus line was attempted in 79% of the cases, achieving mitral isthmus block in 98% of patients. There were 0.92% of periprocedural serious adverse events, including 0.09% of peri-procedural death (5 patients). Three patients developed hemodynamic collapse immediately after VOM ethanolization, causing the death of 1 due to anaphylactic shock. One patient died following surgical drainage of pericardial effusion 3 weeks after the procedure. The 3 other deaths were not directly related to VOM ethanolization. Pericardial effusion was observed in 123 patients (2.2%) at the time of or immediately after the procedure, requiring drainage in 20 patients (0.36%) and later in 32 additional patients (0.57%), including 5 (0.09%) requiring drainage. Pacemaker implantation was required in 2 patients (0.04%), 1 for high-grade atrioventricular block and 1 for sinus node dysfunction. CONCLUSIONS:This international survey shows that VOM ethanolization is predominantly performed in patients with persistent AF. It is associated with rare but potentially life-threatening adverse events. Mitral isthmus line ablation results in a very high rate of block when performed concomitantly.

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy that frequently progresses to symptomatic heart failure (HF), often with mildly reduced or reduced ejection fraction (EF). Standard therapies are limited in NYHA III–IV, and Tafamidis is approved only for the early stages. Cardiac contractility modulation (CCM) therapy has shown promise in HF with reduced EF, but its role in ATTR-CM remains unexplored. Methods: This multicentric, prospective pilot study evaluated the safety and efficacy of CCM therapy in ten patients (n = 10) with ATTR-CM, EF between 25 and 45%, and NYHA class III–IV symptoms refractory to optimal medical therapy. All patients underwent implantation of the Optimizer CCM system and were followed for at least 12 months. The primary endpoint was the incidence of worsening heart failure (WHF); secondary endpoints included changes in EF, NYHA class, 6-minute walk test (6MWT), and quality of life metrics. Results: In this cohort (n = 10), CCM therapy significantly reduced WHF episodes (from 0.18 ± 0.09 to 0.025 ± 0.08 hospitalizations/patient-year, p < 0.001) and improved NYHA class and 6MWT (p < 0.001). EF increased by an average of 4.8 ± 6.1%, and 6MWT improved by 31.3 ± 53.3%. Importantly, all patients became eligible for Tafamidis after CCM therapy due to improved functional status. Conclusion: This pilot study suggests that CCM therapy is a feasible and potentially effective option for ATTR-CM patients with advanced HF who are not candidates for existing disease-modifying treatments. These findings support the rationale for larger studies, including the ongoing AMY-CCM registry (NCT05167799), to validate CCM’s therapeutic role in this population.

The Shanghai score system was developed to enhance the risk stratification in Brugada Syndrome (BrS); however, its prognostic value in drug-induced type 1 BrS remains unclear. This study involved 698 patients with drug-induced type 1 BrS, confirmed via pharmacologic challenge (flecainide or ajmaline), from 21 centers in Italy and Switzerland. Patients were classified according to the Shanghai score system: probable/definite BrS (score ≥ 3.5) and possible BrS (score < 3.5). The primary outcome was appropriate ICD therapy or sudden cardiac death (SCD)/sustained ventricular arrhythmias; the secondary outcome includes the identification of clinical predictors of primary outcome events. Kaplan–Meier and Cox regression analyses were used. Our study population included 239 patients (34.2

BACKGROUND Infections related to cardiac implantable electrical devices are among the most challenging and costly complications. Although the absorbable antibiotic-eluting envelope has shown efficacy in reducing infection risk, data on its use in pacemaker (PM) and cardiac resynchronization therapy PM (CRT-P) devices are limited. OBJECTIVES This study aimed to assess the effectiveness of the TYRX envelope in preventing systemic and pocket infections in patients undergoing PM or CRT-P implantation or revision. METHODS This retrospective, multicenter analysis included 896 patients undergoing PM or CRT-P implantation or revision between August 2020 and April 2024. Patients were categorized into 2 groups: the envelope group (n = 350), receiving the TYRX envelope, and the control group (n = 546). RESULTS Over a mean follow-up of 2.2 6 2.1 years, systemic or pocket infections occurred in 1.2% of patients, with significantly fewer infections in the envelope group (0.3%) than the control group (1.8%) (P = .05). The envelope was associated with an 89% reduction in infection risk (incidence rate ratio 0.11, 95% confidence interval 0.05-0.23, P < .001). Kaplan-Meier analysis showed that, at 4 years, the cumulative incidence of infection was 0.4% in the envelope group vs 2.5% in the control group (hazard ratio 7.36, P = .03). CONCLUSIONS In patients with PMs and CRT-Ps, the use of the TYRX envelope is associated with significantly lower occurrence of device-related infections. This benefit was sustained over longterm follow-up, supporting its effectiveness in routine clinical practice.

INTRODUCTION:Vein of Marshall ethanol infusion (VOM-EI) in patients with Atrial Fibrillation (AFib) triggers local injury, which may increase the subsequent radiofrequency catheter ablation (RFCA) success rate in persistent atrial fibrillation (PeAF). The long-term durability of VOM-EI induced low-voltage area (LVA), might condition the success of RFCA after VOM-EI. We hypothesized that the amount of LVA after VOM-EI decreases over time. METHODS:Consecutive patients with recurrent PeAF and no history of previous ablation were enrolled in this prospective, center-cluster, case-control study. In the experimental group, RFCA was performed 1 month after VOM-EI. In the control group, VOM-EI and RFCA were performed concomitantly. The primary endpoint was the bipolar VOM-EI LVA measured immediately prior to RFCA. RESULTS:We studied 80 consecutive patients who met the inclusion criteria. The two groups did not differ in baseline characteristics. The mean bipolar VOM-EI-LVA measured before RFCA was significantly smaller in the 40 patients who underwent VOM-EI 1 month earlier than in the group of 40 patients who underwent the standard procedure (2.6 ± 2.4 vs. 10.0 ± 7.0 cm2, p = 0.012). At a mean follow-up of 19.6 ± 7.3 months, freedom from AF/AT recurrences was promisingly higher in the investigational group compared to the control group (90.0% vs. 82.5%). CONCLUSION:These data suggest that the endocardial newly-formed lesion induced by VOM-EI decreases over time, probably due to progressive resolution of perilesional oedema. These results merit larger studies testing the hypothesis that postponing RFCA 1 month after VOM-EI may increase its effectiveness in terms of fewer recurrences of atrial fibrillation.

BACKGROUND There are limited real -world data on the extended prognosis of patients with drug -induced type 1 Brugada electrocardiogram (ECG). OBJECTIVE We assessed the clinical outcomes and predictors of life -threatening arrhythmias in patients with drug -induced type 1 Brugada ECG. METHODS This multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug -induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. RESULTS A total of 606 patients (mean age 49.7 6 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0-122.4 months). Nineteen patients (3.1%) experienced life -threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life -threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. CONCLUSION In patients with drug -induced type 1 Brugada ECG, the annual risk of life -threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of “heart failure with reduced ejection fraction” (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.