Maria Lucia Narducci

Background: C-reactive protein (CRP) is commonly used to assess systemic inflammation, yet its prognostic value in acute myocarditis remains uncertain. Evidence is limited by heterogeneous populations, variable CRP thresholds and differing outcome definitions. We therefore aimed to evaluate whether CRP levels measured at presentation are associated with 90-day clinical outcomes in adults hospitalised with acute myocarditis. Methods: Using the TriNetX Research Network, we identified 3615 adults hospitalised with acute myocarditis between 2005 and 2025. Patients were stratified according to baseline CRP <10 mg/L (n=1001) vs ≥10 mg/L (n=2614). Propensity score matching (1:1) was performed using age, sex and race. The primary outcome was a 90-day composite of all-cause death and tachyarrhythmias (atrial fibrillation, ventricular tachycardia, ventricular fibrillation or torsades de pointes). Secondary outcomes included the individual components. Results: In the unmatched cohort, patients with CRP <10 mg/L had a numerically higher 90-day incidence of the primary composite outcome compared with those with CRP ≥10 mg/L (16.4% vs 14.0%; log-rank p=0.087; HR 1.17, 95% CI 0.98 to 1.41), driven by a borderline higher incidence of tachyarrhythmias (14.1% vs 11.7%; log-rank p=0.059; HR 1.21, 95% CI 0.99 to 1.48), while all-cause mortality was similar between groups. After propensity score matching, the 90-day incidence of the primary composite outcome was virtually identical in the CRP <10 mg/L and CRP ≥10 mg/L groups (16.4% vs 16.9%; log-rank p=0.735; HR 0.96, 95% CI 0.78 to 1.19). Individual endpoints (tachyarrhythmias and all-cause mortality) were also similar, with no statistically significant differences. Conclusion: In this large dataset analysis, elevated baseline CRP was frequent in patients with acute myocarditis and was not consistently associated with 90-day adverse outcomes. A single CRP measurement at presentation appears to have limited value for risk stratification in this setting.

Background: Atrial fibrillation (AF) is a common but often undetected cause of cryptogenic stroke (CS) and embolic stroke of undetermined source (ESUS). Implantable cardiac monitors aid in detecting subclinical AF, but their widespread use is limited by cost and logistical challenges. Several scoring systems exist to predict AF in patients with CS/ESUS, though few have been externally validated. This study was designed to externally validate 7 scoring systems for predicting incident AF in patients with CS/ESUS. Methods: In this observational study, we analyzed 132 patients with CS or transient ischemic attack who received implantable cardiac monitors. After a comprehensive literature search, 7 prediction models (Coronary Artery Disease or Chronic Obstructive Pulmonary Disease, Hypertension, Elderly, Systolic Heart Failure, Thyroid Disease [C2HEST], Brown ESUS‐AF, ESUS‐AF, Hypertension, Age, Valvular Heart Disease, Peripheral Vascular Disease, Obesity, Congestive Heart Failure, Coronary Artery Disease [HAVOC], Age, Hypercholesterolemia, Tricuspid Regurgitation, Left Ventricular End‐Diastolic Volume, Left Atrium [ACTEL], Age, Stroke Severity, National Institutes of Health Stroke Scale >5 to Find Atrial Fibrillation [AS5F], and Coronary, Heart Failure, Age, Stroke Severity, Lipidemia, Sugar, Prior Stroke [CHASE‐LESS]) were applied. The primary outcome was the discriminatory ability to detect AF. Secondary outcomes included evaluating the threshold scores and the performance of such threshold‐based criteria for predicting nonoccurrence of AF with high specificity. Results: AF was detected in 40 patients (30.3%) over a mean follow‐up of 13±12 months. Area under the receiver operating characteristic curves were C2HEST (0.704), Brown ESUS‐AF (0.755), AS5F (0.726), ESUS‐AF (0.607), HAVOC (0.661), ACTEL (0.650), and CHASE‐LESS (0.671). C2HEST, Brown ESUS‐AF, and AS5F showed acceptable predictive performance (area under the receiver operating characteristic curve >0.7). Threshold‐based criteria using these scores achieved high specificity and positive predictive value. Combining thresholds across scores improved identification of patients unlikely to develop AF. Conclusions: C2HEST, Brown ESUS‐AF, and AS5F scores reliably predicted AF in patients with CS/ESUS and may help identify low‐risk individuals, supporting more targeted use of diagnostic tools and guiding stroke prevention strategies.

Background: Epicardial mapping and ablation of ventricular tachycardia (VT) are used in different clinical situations but pericardial adhesions following prior cardiac surgery or previous epicardial procedures may limit a percutaneous approach. The objective of this case series is to evaluate the safety and feasibility of a hybrid approach with surgical epicardial access as a valid alternative when pericardial space is not accessible percutaneously. Methods: After a complete preprocedural evaluation, four patients with prior cardiac surgery underwent hybrid VT ablation under general anesthesia. Surgical subxiphoid access was performed in three cases and one patient was subjected to median resternotomy for concomitant open-heart surgery. Epicardial electroanatomic voltage maps were acquired using the CARTO 3 system (Biosense Webster) or NavX (St. Jude Medical) and VT ablations with irrigated catheters were performed. The procedural endpoint was VT non-inducibility and/or LAVA/LP abolition. Results: No serious periprocedural complications occurred after hybrid VT ablation. Three patients had no complex ventricular arrhythmias after a median follow-up of 43 months. A symptomatic sustained VT relapsed in one patient, without requiring a redo ablation procedure but responded to escalation of antiarrhythmic therapy. Conclusions: A carefully planned hybrid VT ablation with surgical epicardial access is a safe and feasible procedure in patients with epicardial scar-related re-entry circuits and pericardial adhesions that limit a percutaneous approach.

Ablation of ventricular arrhythmias (VA) relies on accurate electroanatomical mapping (EAM) to identify critical reentry circuit sites. Analysis of local peak frequency (PF) and Vector Field Disarray (VFD) may serve as useful metrics to improve EAM accuracy. We retrospectively analyzed high-density EAM data from consecutive patients who underwent VT ablation using the EnSite X System with Advisor HD Grid catheter at our institution. PF and VFD distributions were analyzed for co-localization with conventional substrate markers and activation-mapped VT isthmus sites. The diagnostic accuracy of PF for identifying VT isthmus sites was assessed using mixed-effects models and ROC analysis. Sixty maps from 34 patients (70.5 years, 52.9% ischemic) were analyzed. Within low-voltage areas, median PF was 280 Hz and VFD 60%. At baseline, VT isthmus sites had higher PF than non-isthmus sites (372 ± 96 vs. 247 ± 84 Hz, p < 0.0001), with 16% higher odds of isthmus presence per 10-Hz increase (OR 1.016, p < 0.0001, AUC 0.849). A 315 Hz threshold provided an accuracy of 78% (sensitivity 72%, specificity 84%) in identification of isthmus areas. Post-ablation PF decreased to 123 ± 42 Hz (p < 0.0001). Analysis of PF and VFD may enhance the identification of VT critical isthmus sites by improving near-field signal annotation and detecting wavefront collision zones. These metrics should be considered as a complementary tool to conventional EAM.

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. 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. 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.

Background/Objectives: Electroanatomic mapping (EAM) provides high-resolution spatial and electrogram information, but the prognostic utility of quantitative EAM features has not been systematically evaluated with contemporary artificial intelligence (AI) methods. We investigated whether an AI analysis of quantitative EAM exports from the CARTO system enhances the prediction of major arrhythmic events (MAEs). Methods: In this retrospective, multicenter cohort study, 248 consecutive patients undergoing left ventricular EAM at four tertiary electrophysiology centers were analyzed. Numerical EAM descriptors (spatial coordinates, unipolar/bipolar voltages, local activation time, impedance) were transformed into derived metrics, including local activation heterogeneity (GR), late-potential extent (LAT), bipolar–unipolar discrepancy (VLT), and low-amplitude scar extent (Scar Areas), and were spatially normalized via spherical projection. Clinical, anamnestic, and imaging variables were integrated. Machine learning and deep learning models were trained with an 80:20 train/test split and evaluated using three-fold cross-validation. Performance metrics included area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision. Results: Models incorporating both clinical and AI-processed EAM features achieved high discriminatory performance (test AUC up to 0.92; accuracy up to 0.896). Specificity was consistently high (≈0.97–0.998), whereas sensitivity remained modest (≈0.39–0.58). Among the EAM-derived features, GR was the most consistently informative predictor across algorithms and analyses; VLT, LAT, and Scar Areas also contributed substantially. Regionally, basal sub-mitral, subaortic, and posterolateral basal-to-mid zones exhibited the strongest associations with MAEs. Conclusions: AI-driven quantitative analysis of left ventricular EAM exports augments risk stratification for MAEs beyond conventional clinical and binary EAM descriptors. Reflecting local conduction heterogeneity, GR emerged as the dominant EAM predictor. Prospective validation in larger, disease-specific cohorts and real-time integration within EAM platforms are warranted.

BACKGROUND: No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS: In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS: Median age at presentation was 48 years (first to third quartile, 34–59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%–48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis–associated form (13.1%) at 3 years ( P =0.15). CONCLUSIONS: Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06447935.

Introduction: Acute myocarditis can lead to chronic inflammatory cardiomyopathy (Infl-CMP), a condition characterized by increased risk of ventricular arrhythmias (VA), left ventricular (LV) systolic dysfunction (LVSD), and heart failure (HF). Immunosuppressive therapy is generally not recommended for Infl-CMP when diagnosed non-invasively by cardiac magnetic resonance imaging (CMRI) or fluorodeoxyglucose-positron emission tomography (FDG-PET). We are assessing, in the CMP-MYTHiC trial, whether colchicine (0.5 mg in patients <70 kg or 1 mg in patients ≥70 kg), an immunomodulatory drug with a good safety profile, can reduce myocardial inflammation in patients with Infl-CMP. Study design: The CMP-MYTHiC, a multicenter investigator-initiated single-blinded randomized controlled trial, screens adult patients diagnosed with Infl-CMP by CMRI or FDG-PET within the prior 3 months at 12 Italian centres. Eligibility is further defined by the presence of VA or LVSD/HF phenotype. VA phenotype is determined by a high burden of premature ventricular complexes (PVCs) on baseline 24-h ECG ambulatory monitoring, non-sustained ventricular tachycardia (NSVT), or sustained ventricular tachycardia (SVT). The LVSD/HF phenotype is characterized by reduced LV ejection fraction (LVEF <50% on echocardiogram or 10% or new areas of oedema plus increased inflammation) worsening, and who demonstrate improvement in either imaging (reduction in oedema on CMRI or FDG uptake) or arrhythmic (PVC burden reduction ≥70% with no NSVT/SVT) outcomes at 6 months. Assuming 80% power with an overall type I error of 0.025 using one-sided Fisher's Exact test, 40 patients per group are required to demonstrate that the primary endpoint will be reached in 66% of patients in the colchicine group compared with 33% in the placebo. Twenty-nine patients were randomized since December 2023, and the conclusion is expected in 2029. Discussion: The results can define the role of colchicine in treating patients with Infl-CMP non-invasively diagnosed by CMRI or FDG-PET. Clinicaltrials.gov identifier: NCT06158698.