Giacomo Veronese

BACKGROUND: Parvovirus B19 is a DNA virus transmitted via respiratory droplets, commonly causing erythema infectiosum in children but also implicated in acute myocarditis. In 2024, an outbreak of parvovirus B19 infections was reported across Europe and the United States. Despite growing awareness, data on the clinical features and outcomes of children with parvovirus B19–associated acute myocarditis remain limited. METHODS: This multicenter retrospective observational study reviewed medical records of pediatric patients (+ ), whereas 82 with negative parvovirus B19 testing served as a comparator group (PVB19 ⁻ ). Population-based incidence trends of pediatric myocarditis were also evaluated in the Lombardy region from 2004 through 2024. RESULTS: Among PVB19 ⁺ acute myocarditis cases, 58 of 66 (87.9%) were admitted in 2024. The median age was 32 months, with 51 of 66 (77.2%) ≤7 years of age, and 36 of 66 (54.5%) were boys. Median plasma viral load was 34 411 copies/mL, whereas only 30 of 56 (53.6%) had immunoglobulin M (IgM) positivity. Among 26 of 66 (39.4%) with available histology, 23 (88.4%) had lymphocytic myocarditis, and parvovirus B19 DNA was identified in 84.0% of myocardial specimens. Among 25 of 65 (38.4%) who underwent genetic testing, none had pathogenic or likely pathogenic variants. Overall, 13 of 66 (19.7%) died, underwent heart transplantation, or received a durable left ventricular assist device (in total, there were 6 deaths, 5 durable left ventricular assist devices, and 5 transplantations) compared with 1 of 82 (1.2%) among PVB19 ⁻ acute myocarditis (one patient who received a durable left ventricular assist device and later underwent transplantation; P + cases. CONCLUSIONS: During the 2024 parvovirus B19 outbreak, pediatric PVB19 ⁺ acute myocarditis cases surged in Italy and were associated with severe outcomes. A high index of suspicion is required for diagnosis, and early virological testing is essential to guide management and potentially improve outcomes.

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.

Background: Parvovirus B19 (PVB19) has emerged as a relevant etiologic agent of paediatric myocarditis, particularly during recent epidemiological surges in Europe and the United States. Despite increasing recognition, current knowledge remains fragmented, and standardised diagnostic and therapeutic strategies are lacking.Methods: We conducted a systematic review of the literature up to May 2025, including 40 studies encompassing 53 individual case reports, 107 patients from registry‐based cohorts, and 4 tissue‐based investigations.Results: Clinical presentation was frequently fulminant, with cardiogenic shock, severe left ventricular dysfunction, and need for mechanical circulatory support in up to 47% of cases. Mortality rates ranged from 10% to 30%, with heart transplantation rates varying between 5% and 42% across cohorts. Diagnosis relied primarily on blood polymerase chain reaction (PCR), while serology showed limited diagnostic utility. Histological confirmation via endomyocardial biopsy (EMB) was variably applied across studies, and myocardial viral load quantification was reported in only one study. Case series and cohort studies confirmed early age of onset (median 16–24 months), respiratory or gastrointestinal prodromes, and poor outcomes in fulminant presentations. Tissue‐based studies revealed high myocardial PVB19 loads in acute myocarditis, particularly in infants, but also demonstrated viral persistence in asymptomatic individuals, complicating causal inference. Immunomodulatory therapy was administered in up to 58% of cases, although its clinical impact remains uncertain due to heterogeneity in treatment protocols. No antiviral treatments have been evaluated to date.Conclusion: These findings highlight the need for standardised diagnostic criteria incorporating PCR, serology, imaging, and, where appropriate, EMB and viral load assessment. Given recent epidemiologic surges and high morbidity, prospective multicentre studies and surveillance efforts are urgently required to refine clinical algorithms and improve outcomes in paediatric PVB19 myocarditis.

Veno-arterial extracorporeal life support (VA ECLS) is crucial for neonatal and paediatric patients with severe circulatory collapse but may cause left ventricular (LV) overload, affecting myocardial recovery and causing complications. Evidence on optimal LV decompression strategies in paediatric patients remains limited. We conducted a systematic review following PRISMA guidelines, including articles published between 1993 and 2024 focused on VA ECLS and LV decompression in patients under 18 years of age. The review included 11 retrospective cohorts and registry-based studies (2012–2024), totalling 1222 paediatric patients undergoing decompression. Patient demographics, initial diagnoses and VA ECLS settings were heterogeneous. The prevalence of LV decompression ranged from 46.6% in post-cardiotomy to 10.5% in non-post-cardiotomy peripheral VA ECLS cases. Most patients (57.1%) were supported with peripheral VA ECLS, and the majority (57.4%) underwent percutaneous decompression, whereas surgical approaches predominated in post-cardiotomy central VA ECLS. Balloon atrial septostomy (BAS) was the most frequent technique (50%), followed by surgically placed left atrial cannula (37.4%). Thirteen case series (70 patients) and 28 case reports (28 patients) were also reviewed. Substantial variability in LV decompression strategies exists based on age and clinical scenario. PAS-based techniques were more common in younger patients on peripheral VA ECLS while older children often underwent different strategies. Surgical approaches were preferred in central VA ECLS, particularly in the post-cardiotomy setting. Procedural safety varied by technique. While PAS-based strategies such as BAS generally showed low complication rates, adverse events like arrhythmia, bleeding and cardiac perforation were reported in 7%–9% of cases. Surgical LA cannulation was associated with higher bleeding risk. Impella use was linked to haemolysis (50%) and major bleeding (20%). Comparative data highlight that each technique carries distinct procedural risks and complication profiles. In conclusion, LV decompression during paediatric VA ECLS remains technically challenging and variably adopted. Its benefit appears more consistent in the post-cardiotomy setting, where improved survival and reduced adverse outcomes were observed. Given the lack of standardization, further prospective studies and collaborative registries are essential to guide strategy selection, timing and risk–benefit balance, particularly in such a vulnerable population.