Background Stereotactic arrhythmia radioablation (STAR) may represent an alternative to standard catheter ablation (CA) for treatment of refractory ventricular arrhythmias (VA). Most STAR treatments performed to date have used photon radiotherapy. However, protons have advantageous ballistic properties suitable for this application, potentially improving sparing of organs at risk (OARs). Methods ECG-gated CT scans and electroanatomical mapping were performed to reconstruct a 3D bipolar voltage map and identify ablation targets in a cohort of patients with VA candidates for CA. Three radiation treatment modalities were investigated/compared using the breath-hold technique: photon volumetric modulated arc therapy (VMAT) and proton active pencil beam scanning delivered with/without cardiac gating. When cardiac gating was applied, the diastolic phase—longer and more stable than the systolic one—was selected as the reference. Results Twenty-three patients were enrolled, and three presented multifocal ventricular arrhythmias, resulting in a total of 27 treatment targets. Both photon and proton plans achieved adequate target coverage. Compared with photon plans, proton therapy showed a statistically significant reduction in the mean maximum dose to several OARs and to important non-target cardiac structures (coronary arteries, valvular apparatus and right atrium) while maintaining comparable target coverage. These findings were consistent for proton plans with and without cardiac gating. In a subset of 14 patients, cardiac gating provided additional reductions in dose to healthy cardiac tissue. Conclusions This in-silico study suggests that STAR using proton beams may significantly reduce radiation exposure to non-target cardiac substructures and surrounding extracardiac OARs, regardless of the cardiac motion management strategy adopted.

Coronary microvascular dysfunction (CMD) is a key driver of ischemia and prognosis across several non-ischemic cardiomyopathies. This review summarizes the main tools for diagnosing microvascular dysfunction and available evidence on CMD incidence and the prognostic role in patients with cardiomyopathies. In dilated cardiomyopathy, CMD is associated with reduced myocardial blood flow, greater fibrosis, adverse remodeling, and worse outcomes. In hypertrophic cardiomyopathy, CMD is highly prevalent and multifactorial (arteriolar remodeling, reduced capillary density, extravascular compression, diastolic dysfunction, and/or left ventricular (LV) outflow obstruction), correlating with fibrosis, heart failure, and arrhythmias/sudden death. In Takotsubo syndrome, CMD appears acute and reversible, with microvascular spasms as a predominant mechanism and plausible pathophysiologic basis of the event. In arrhythmogenic right ventricular cardiomyopathy, preliminary data show a blunted hyperemic response and autonomic abnormalities that may impair microvascular vasodilation. In infiltrative and storage diseases (amyloidosis and Anderson–Fabry disease), CMD is often early, preceding hypertrophy/fibrosis, and contributes to symptoms, contractile dysfunction, and adverse outcomes; in sarcoidosis, microvascular inflammation reduces coronary flow reserve (CFR) and is associated with events. Targeted therapies remain limited; optimization of risk factors and drugs that modulate endothelial/metabolic function (statins, angiotensin converting enzyme (ACE) inhibitors, vasodilating β-blockers, calcium channel blockers, sodium glucose cotransporter 2 (SGLT2) inhibitors) yielded variable signals; device-based and nonpharmacologic strategies are under investigation. In conclusion, integrating microcirculatory assessment improves risk stratification and may furnish future therapeutic targets across cardiomyopathies.

BACKGROUND:Patients harboring pathogenic/likely pathogenic (P/LP) variants in the desmoplakin (DSP) gene are at risk of ventricular arrhythmias (VAs). In this population, a risk prediction model estimating the 5-year risk of VAs has been recently developed. OBJECTIVE:This study aimed to provide external validation of this prediction model in a new large, international, multicenter cohort and to test its reliability in patients with and without a history of myocarditis-like episodes. METHODS:All patients with a P/LP pathogenic DSP variant enrolled in the Desmoplakin Specific Effort for a Rare Disease Outcome Study Network with no sustained VA before or at first assessment and who were not used for the development of the DSP-risk score (www.DSP-risk.com) were used to test its performance. Model performance was assessed using the c-statistic in both the overall cohort and stratifying by history of myocarditis-like episodes. RESULTS:450 DSP patients from 30 centers were enrolled (mean age 42.2 ± 17.6; 40.4% female; 18.4% with previous myocarditis-like episode). Over a median of 4.3 years (1.6-10.0), 60 sustained VAs were observed. The DSP-risk score yielded good discrimination both overall (c-statistic, 0.719; 95% confidence interval [CI], 0.706-0.733) and for patients with (c-statistic, 0.719; 95% CI, 0.702-0.737) and without previous myocarditis-like episodes (c-statistic, 0.749; 95% CI, 0.740-0.759). CONCLUSION:In a large independent cohort of DSP patients, this study showed external validity of the DSP-risk score. These findings support the use of the DSP-risk score to facilitate shared decision making regarding implantable cardioverter-defibrillator implantation in the primary prevention of VAs in patients harboring DSP P/LP variants.

BACKGROUND:The management of catecholaminergic polymorphic ventricular tachycardia (CPVT) patients with drug refractory cardiac events (CEs) is challenging. OBJECTIVES:This study sought to assess the efficacy of left cardiac sympathetic denervation (LCSD) in 162 CPVT patients, focusing on those symptomatic without a high-risk genotype and compliant to therapy (main subanalysis, n = 118) of whom 41 had syncope on medical therapy. CEs included syncope, sudden cardiac arrest (SCA), sudden cardiac death (SCD), and appropriate implantable cardioverter-defibrillator (ICD) interventions. METHODS:A retrospective study including 162 CPVT patients (51% female, 80% probands, 79% RYR2 positive) who underwent LCSD worldwide. RESULTS:Most (n = 139; 85%) of the 162 patients experienced ≥1 CE before LCSD, 84 (52%) had CEs despite medical therapy, and 43 (27%) had previous SCA. Overall, 93% received a beta-blocker (nonselective in 85%), 53% both a beta-blocker and a class I antiarrhythmic drug, and 55% (89) had an ICD before LCSD. During a median of 48 months (Q1-Q3: 12-111 months) after LCSD, 28 of 162 patients (17%) had ≥1 CE, including 10 of 28 (36%) during noncompliance. Of the 118 patients (main subanalysis), 13% suffered CEs after LCSD, including 3 SCAs and 1 SCD despite an ICD (3%). Of the 41 with syncope on medical therapy, 6 (15%) experienced CEs after LCSD, including the SCD despite an ICD (3%). LCSD improved quality of life by reducing ICD shocks by 67% and electrical storms by 80%. CONCLUSIONS:Our data suggest that probably <5% of symptomatic CPVT patients compliant to medical therapy require an ICD after LCSD. ICDs do not reliably prevent SCD.

BACKGROUND AND AIMS:Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with β-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on β-blocker monotherapy. METHODS:The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator shock, sudden cardiac arrest (SCA), and sudden cardiac death. Near-fatal or fatal AEs (nf/fAEs) included all AEs except for arrhythmic syncope. Prediction models using Cox regression were developed and internally and externally validated. RESULTS:A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced ≥1 AE over a median follow-up of 5.1 [interquartile range (IQR), 7.7] and 2.4 (IQR, 4.4) years, respectively. Predictors of AE were arrhythmic syncope or SCA prior to diagnosis and age at β-blocker initiation. In the derivation and validation cohorts, the optimism-corrected C-indices of the models for AE were 0.67 [95% confidence interval (CI) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before β-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE. CONCLUSIONS:These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on β-blocker monotherapy at low and high risk for future AEs while treated with β-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.

AIMS:Long-term arrhythmic risk after myocarditis remains uncertain, and optimal management is debated. We aimed to assess the incidence and predictors of major arrhythmic events (MAEs) after myocarditis. METHODS AND RESULTS:We conducted a systematic literature review and meta-analysis including 19 observational studies on myocarditis and MAEs during follow-up. Major arrhythmic events were defined as a composite of sudden cardiac death (SCD), ventricular fibrillation (VF), aborted cardiac arrest (ACA), sustained ventricular tachycardia (sVT), and appropriate implantable cardioverter defibrillator (ICD) or wearable-cardioverter defibrillator (WCD) intervention. The primary outcome was the incidence of MAEs after discharge; secondary outcomes included occurrence of each component of MAEs and the composite of all-cause mortality or heart transplantation (HTx). Three thousand nine hundred and fifty-four patients (71% male, 67% acute, 88% complicated myocarditis) were included. At presentation, 15% had high-grade atrioventricular block (AVB), 31% heart failure, 38% MAEs. At a median follow-up of 24 months (interquartile range 19-57), 28% suffered MAEs, with a median time of presentation of 12 months. The incidence of sVT, ACA/VF, appropriate ICD/WCD intervention, and SCD were 22%, 6%, 20%, and 1%, respectively. The combined rate of all-cause mortality/HTx was 11%. At meta-regression analysis, high-grade AVB, MAEs at presentation, and fulminant myocarditis were associated with higher risk of MAEs during follow-up, while male gender resulted as a protective factor. CONCLUSION:The incidence of MAEs after a complicated acute myocarditis can be high over time. Further prospective studies are needed to better stratify high-risk patients, identify those with an underlying arrhythmogenic cardiomyopathy, and guide antiarrhythmic strategies.

Abstract Infections associated with cardiac implantable electronic devices (CIEDs) pose significant clinical challenges due to their life-threatening nature and complex management. Recent advancements in prevention, diagnosis, and treatment have been driven by landmark trials such as PADIT and WRAP-IT, alongside evolving diagnostic tools like [18 F]FDG PET/CT and updated diagnostic criteria (e.g., 2023 Duke-ISCVID). A combination of well-established approaches—such as leadless pacemakers, subcutaneous ICDs, and an antibiotic-eluting envelope—and evolving adjunctive strategies, including a taurolidine-containing antimicrobial agent, incision drapes, fascial plane blocks or double gloving, have broadened the spectrum of options to reduce and potentially mitigate the risk of CIED infection. While devices like leadless pacemakers, subcutaneous ICDs, and antibiotic envelopes are supported by randomized controlled trials, adjunctive measures such as taurolidine rely predominantly on observational data. To address this variation in the strength of available evidence, a modified Delphi consensus process was conducted, bringing together cardiologists and infectious disease experts to define experience-based best practices in areas where current guidelines offer limited or no specific recommendations. The consensus achieved strong agreement (≥ 80%) on key strategies, including mandatory double-gloving to reduce contamination, the use of validated risk models (e.g., PADIT, BLISTER) for tailored infection prevention employing an antibiotic eluting envelope, multidisciplinary decision-making for non-extractable infections and the use of taurolidine solutions as adjuncts to prevent CIED infection. Moderate consensus (60–79%) supported non-delayed reimplantation after lead-related endocarditis and single-session reimplantation in pacing-dependent patients under specific circumstances. However, no consensus was reached on mandating a minimum annual procedural volume (≥ 500 cases) for CIED centers, reflecting concerns about access and operator expertise. The findings emphasize the importance of personalized risk stratification, procedural innovations, and multidisciplinary collaboration in optimizing CIED infection outcomes. Areas requiring further research include the efficacy of iodophor-impregnated drapes, fascial plane blocks, and taurolidine solutions. This consensus provides a pragmatic framework for clinicians, highlighting evidence-informed strategies to mitigate infection risks and improve care for patients undergoing CIED procedures.

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) yields variable positivity rates. Identifying clinical predictors of positive genetic tests could improve pre-test counseling and refine expectations about diagnostic yield. Methods: We analyzed consecutive genotyped HCM probands from a contemporary multicenter cohort across four Italian tertiary centers. Genotype positivity was defined as the presence of >= 1 pathogenic or likely pathogenic variant (ACMG classes 4-5). Multivariable logistic regression identified predictors of genotype positivity. Sensitivity analyses assessed the incremental value of left atrial volume index (LAVI) >= 34 mL/m(2) and the mode of first clinical presentation. Results: Among 274 genotyped probands (median age at diagnosis 54 years; 62% male), 86 (31%) were genotype-positive (38% MYBPC3, 29% MYH7). Age at diagnosis <40 years (OR 2.38, 95%CI 1.26-4.51, p = 0.008), family history of sudden cardiac death/major ventricular arrhythmias (OR 2.34, 95%CI 1.16-4.84, p = 0.019) and family history of non-ischemic cardiomyopathy (OR 1.92, 95%CI 1.04-3.54, p = 0.038), were independently associated with genotype positivity whereas arterial hypertension was inversely associated (OR 0.42, 95%CI 0.23-0.77). Maximal left ventricular wall thickness > 20 mm and gender were not predictive of genotype positivity. Inclusion of LAVI modestly improved the model performance (AUC 0.769, p = 0.016, Delta AUC +0.024; DeLong p = 0.016) but without leading to meaningful patient reclassification. Conclusions: Genotype positivity in HCM links to earlier onset and family history; traditional severity markers and initial presentation may not independently suggest genetic causality. These findings may help shape a personalized approach to genetic counseling in HCM.

Aims Percutaneous stellate ganglion block (PSGB) is a promising treatment for refractory electrical storm (ES). However, there is a lack of solid indications regarding the optimal pharmacological regimens and combination of local anaesthetics (LAs). This study, from the multicentre STAR registry, aimed to evaluate the impact of single vs. dual LA regimen on the efficacy and safety of PSGB. Methods and results We analysed 422 PSGB procedures from 298 patients (30% single LA, 70% dual LAs). Both regimens significantly reduced the number of treated ventricular arrhythmias (VAs) in the 12 h post-PSGB. Crucially, the combination of two LAs-typically pairing a fast-acting with a long-acting agent-resulted in a significantly higher rate of complete VA suppression at 1 h (85% vs. 70%, P < 0.01) and 3 h (78% vs. 67%, P = 0.02) compared with the single LA regimen. This superior early efficacy was confirmed after propensity score matching and multivariable analysis. The total complication rate, driven by minor ones, was higher with two LAs (8% vs. 2%, P = 0.02), but this association was no longer significant after adjusting for the procedural approach (lateral vs. anterior). Conclusion The combination of two local anaesthetics for PSGB is significantly associated with a greater likelihood of early and complete ventricular arrhythmia suppression in patients with electrical storm. Despite the need for randomized ad hoc trials, the dual-LA regimen represents an optimization strategy for PSGB, offering enhanced efficacy without an increased risk of major complications.

BACKGROUND AND AIMS:Stereotactic arrhythmia radioablation (STAR) is increasingly used for refractory ventricular tachycardia (VT), yet prospective multicentre outcome data remain limited. Here, the planned interim analysis of the prospective Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) registry is reported. METHODS:STOPSTORM is a European prospective, international, multicentre registry of patients treated with STAR. The primary efficacy endpoint was the change in sustained VT episode burden comparing the 6 months before versus the 6 months after STAR. The primary safety endpoint was the occurrence of serious adverse events (SAEs) adjudicated as possibly or probably treatment-related. Overall survival was assessed using time-to-event methods. RESULTS:Across 28 centres, 193 patients were included (mean age 68±9 years; 88% male; 53% non-ischaemic cardiomyopathy). Median follow-up was 19 months. Among 107 evaluable patients with ≥6-month follow-up, the median VT episode burden was reduced by 80% after STAR. Among patients surviving ≥6 months, 72% were free from implantable cardioverter-defibrillator (ICD) shock. In the full cohort, 12 SAEs were adjudicated as possibly or probably treatment-related, including pericardial effusion, coronary events, and early post-treatment ventricular arrhythmia. Overall survival probability was 77% at 12 months. CONCLUSIONS:In the largest prospective multicentre cohort reported to date, STAR was associated with a substantial reduction in VT burden and ICD shocks, with a low frequency of possibly or probably treatment-related SAEs.

Il progressivo incremento dei pazienti affetti da scompenso cardiaco portatori di dispositivi cardiaci elettronici impiantabili (CIED) richiede l’integrazione sistematica dei dati derivanti dal telemonitoraggio continuo in un percorso assistenziale multidisciplinare orientato alla gestione proattiva della patologia. La presente rassegna valuta criticamente le evidenze relative ai più recenti algoritmi predittivi incorporati nei CIED e analizza il ruolo di infermieri/tecnici di elettrofisiologia specializzati in monitoraggio remoto e case manager, quale snodo operativo tra il paziente e il team clinico. Viene inoltre delineato un modello organizzativo che connette in modo strutturato l’ambulatorio pacemaker/defibrillatori con quello dedicato allo scompenso, con l’obiettivo di intercettare la fase subclinica della malattia e ottenere un miglioramento della qualità di vita, una diminuzione delle ospedalizzazioni e un contenimento dei costi per il sistema sanitario.

The growing number of heart failure patients with cardiac implantable electronic devices (CIEDs) requires a systematic integration of telemonitoring data into a multidisciplinary care pathway. This review critically appraises the emerging evidence on the latest predictive algorithms embedded in CIEDs and delineates the pivotal roles of nurses/technicians remote-monitoring specialists and case managers as the operational interface between the patient and the clinical team. This review also proposes an organizational model that integrates the pacemaker/device clinic with the heart failure clinic, aiming to detect the subclinical phase of the disease, improve quality of life, reduce hospitalizations, and optimize healthcare system costs.