AIMS:Eosinophilic myocarditis (EM) is a rare inflammatory heart disease often associated with eosinophilic granulomatosis with polyangiitis or hypereosinophilic syndrome. While anti-IL-5/5R and anti-IL-4/13 monoclonal antibodies (mAbs) efficacy in systemic eosinophilic diseases is established, data on EM are lacking. We aimed to (1) characterize a single-centre cohort of EM patients treated with mepolizumab, benralizumab, or dupilumab in combination with glucocorticoids and/or immunosuppressants; (2) systematically review published cases, comparing them with a contemporary cohort; and (3) evaluate myocardial response and safety of mAbs in EM, in comparison with a historical cohort treated without mAbs at our centre. METHODS AND RESULTS:Thirty-seven EM patients were included (19 from a contemporary cohort, 18 from the literature; 51% male; median age 47 years). Biologic treatments were mepolizumab (81%), benralizumab (14%), and dupilumab (5%). Median time to mAb initiation was 2.5 months; treatment duration 24 months. No EM relapses, deaths, or heart transplantations occurred. Glucocorticoids were tapered and withdrawn in 89% of cases, with no mAb discontinuations due to adverse events. In the contemporary cohort, mAb therapy was associated with improved LVEF (47%-55%, P = 0.004), TnI normalization (95%-12%, P < 0.001), and eosinophil reduction (95%-11%, P < 0.001). Compared with EM patients managed with conventional immunosuppressants alone, the mAb group had no myocarditis relapses (0% vs. 25%) and lower follow-up eosinophil counts (0.04 × 109/L vs. 0.85 × 109/L). CONCLUSION:In EM within eosinophilic disease, anti-IL-5/5R and anti-IL-4/13 mAbs showed steroid-sparing effects and favourable safety, suggesting potential benefit for disease control.

Objectives:The aim of the study was to comprehensively characterize the population of hypertrophic cardiomyopathy (HCM) patients in Poland in 2016-2021, including the analysis of annual incidence, prevalence, comorbidities, and therapeutic paths. Methods:A population-based cross-sectional study was conducted using data from the Polish National Health Fund database. The analysis included a registered annual incidence and prevalence rates, mortality, prognosis, and data on patients pathways in the healthcare system. Results:In 2016, the registered annual incidence of HCM diagnosis in Poland was 1,494 cases (3.89/100,000), decreasing to 808 cases (2.11/100,000) in 2021. Despite the decline in new diagnoses, the registered prevalence of HCM increased from 13,271 cases (34.53/100,000) in 2016 to 13,880 cases (36.23/100,000) in 2021, indicating improved patient survival. Annual mortality rose from 824 deaths (2.14/100,000) in 2016 to 1,022 deaths (2.67/100,000) in 2021, with the highest mortality observed in older adults (60+ years). Conclusion:The study highlights significant underdiagnosis of HCM in Poland. Mortality in HCM population remains high, underscoring the need for improvement in earlier detection and comprehensive care strategies in Polish healthcare system.

Cardiovascular involvement is a leading cause of morbidity and mortality in autoimmune rheumatic diseases (ARDs), arising through diverse mechanisms such as microvascular dysfunction, inflammation, fibrosis, in addition to traditional cardiovascular risk factors. Cardiac troponin (cTn), a sensitive and specific marker of myocardial injury, is increasingly investigated for its diagnostic and prognostic value. However, interpretation in ARDs is complex, as cTn elevations may reflect primary cardiac involvement, comorbidities or analytical interferences. This review explores the value of cTn as a biomarker of cardiac involvement in several ARDs, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, and idiopathic inflammatory myopathies. Articles in the PubMed database (1969-november 2025) were selected using each ARD in combination with "troponin," "cardiovascular," "myocardial involvement," "cardiac involvement," and "biomarker", as keywords. High sensitivity cTn assays can identify both overt and subclinical myocardial injury, predict major adverse cardiovascular events, and correlate with imaging findings, such as myocardial fibrosis and inflammation. Also, cTn increase can result from renal impairment, infections, anemia, or pulmonary hypertension, which frequently complicate ARDs. Further challenges arise from analytical pitfalls, including heterophilic antibodies, rheumatoid factor interference, and macrocomplexes, which may generate false results in ARDs patients. Despite growing evidence, significant knowledge gaps persist regarding the differential value of cTn isoforms, optimal thresholds in ARDs populations, and their role in guiding treatment strategies. Overall, hs-cTn represents a promising, accessible tool to refine diagnosis, risk stratification, and monitoring in ARDs, provided results are interpreted carefully in the clinical and laboratory context.

BACKGROUND AND AIMS:A previous trial of intravenous immunoglobulin therapy (IVIg) added to guideline-directed medical therapy (GDMT) in patients with dilated cardiomyopathy (DCM) and cardiac parvovirus-B19 (B19V) persistence showed no improvement of cardiac function at six months follow-up. We investigated whether IVIg confers long-term clinical benefits and analyzed its molecular and cellular effects in cardiac tissue to elucidate the immunomodulatory mechanisms underlying the observed long-term clinical improvement. METHODS:Fifty patients with DCM and cardiac B19V were blindly randomized to receive either IVIg (n=26; 2g/kg/day over 4 days) or placebo (n=24). The composite clinical endpoint-cardiac death, heart failure hospitalization, and life-threatening arrhythmia-was assessed after a median follow-up of 6.8 [5.6-10.3] years. To investigate IVIg-associated molecular changes in the heart, single-nuclear RNA sequencing (snRNA-seq) sequencing on endomyocardial biopsies (EMB) obtained at baseline (prior to treatment) and at six months after randomization was performed. RESULTS:The IVIg group experienced fewer composite endpoint events (n=1/26) than the placebo group (8/24; p=0.0075). Comparison of baseline and six-month EMBs by snRNA-seq showed that IVIg treatment reduced cardiac monocyte infiltration and, unlike placebo, prevented the expansion of injured cardiomyocytes. IVIg induced transcriptomic reprogramming across immune cells, fibroblasts, and cardiomyocytes, including diminished myeloid-to-fibroblast signaling with reduced TGFβ activity, decreased pro-fibrotic and pro-inflammatory pathways and metabolic shifts in cardiomyocytes characterized by enhanced oxidative phosphorylation. CONCLUSION:In patients with DCM and cardiac B19V persistence, IVIg added to GDMT correlated with improved long-term clinical outcome. IVIg may attenuate myeloid-driven fibrosis formation and mitigate cardiomyocyte deterioration.

Background Hypertrophic cardiomyopathy (HCM) is commonly associated with atrial fibrillation (AF), but its impact on outcomes in real-world practice is uncertain. The aim of the study was to evaluate the clinical profile and prognosis of patients with HCM and AF.Methods Overall, 1739 adult patients with HCM (40.9% women; median age: 55.5 years) were enrolled in the EURObservational Research Programme (EORP) Cardiomyopathy/Myocarditis Registry. Clinical characteristics at baseline and cardiovascular endpoints at 1 year were prospectively assessed.Results At baseline, AF was present in 478 (27.5%) patients; an additional 48 patients (2.8%) developed AF at 1-year follow-up. Oral anticoagulants (OAC) were administered at baseline in 69.5% of the patients. Patients with AF were older and more symptomatic, had higher body mass index, more prevalent cardiovascular risk factors, a history of sustained ventricular tachycardia and implantable cardioverter-defibrillator, lower left ventricular ejection fraction (LVEF), larger left atria (LA) and more advanced LV diastolic dysfunction (pp<0.001 for all). Age at enrolment (OR=1.068, p<0.001), symptom: palpitations (OR=2.191, p<0.001), LVEF (OR=0.978, p<0.001) and LA diameter (OR=1.094, p<0.001) were independent predictors of AF in HCM population. Patients with AF had a higher annual incidence of stroke/transient ischaemic attack (2.6 vs 0.9%, p=0.009) and a trend towards increased all-cause mortality in comparison to the non-AF cohort (3.4 vs 1.7%, p=0.053).Conclusions AF affects nearly one-third of patients with HCM and is associated with higher symptom burden, increased prevalence of comorbidities, myocardial remodelling and increased annual risk of cerebral ischaemic events. In spite of this, the utilisation of OAC was suboptimal.

BACKGROUND:A close link between anti phosphatidyl-serine/prothrombin antibodies (aPS/PT), Lupus Anticoagulant (LA) potency and thrombophilia detected by activated protein C Resistance (aPC-R) in triple-positive antiphospholipid syndrome (APS) patients (LA+/anticardiolipin-aCL+/aβ2-Glycoprotein I-aβ2GPI+) has been observed. Whether this interdependence is present in patients with isolated LA is not known. OBJECTIVES:This cross-sectional study evaluates aPS/PT and aPC-R in isolated LA patients in relation on how the diagnosis of the coagulation inhibitor was made. METHODS:LA was determined using the diluted Russell Viper Venom Time (dRVVT) and the Silica Clotting Time (SCT). IgG and IgM aCL, aβ2GPI and aPS/PT were measured by ELISA. APC-R was determined by thrombin generation assay. RESULTS:We studied 32 patients with isolated LA (LA+/aCL-/aβ2GPI-), 53 triple positive patients (LA+/aCL+/aβ2GPI+) and 24 controls. Total (IgG + IgM) aPS/PT antibody titer was lower and aPC-R weaker in isolated LA compared to triple-positive patients. When isolated LA was diagnosed by both coagulation positive tests (dRVVT and SCT), total aPS/PT titers were higher and aPC-R stronger than when isolated LA was diagnosed by a single positive test (either dRVVT or SCT). Total aPS/PT and aPC-R in patients positive for SCT only (dRVVT-, SCT+), were like those of control subjects. CONCLUSIONS:The relation between LA, aPS/PT and aPC-R is linked to the way the coagulation inhibitor is diagnosed. These data may be useful to clinicians when interpreting the clinical value of isolated LA.

Toxic myocarditis (TM) is rare, and no systematic evidence is available regarding its treatment or prognosis. Hydrocarbons even more rarely cause TM, and they are associated with severe extracardiac toxicity. Moreover, a pathogenic interaction between viral and toxic agents in TM has not been studied. We present the first case of biopsy-proven parvovirus B19 (B19V) viral fulminant myocarditis diagnosed after hydrocarbon exposure, along with a systematic literature review of hydrocarbon-TM cases. A systematic literature review was conducted by searching hydrocarbon-TM cases. Clinical and prognostic data were recorded. After screening of 937 records, 7 were included. All cases were male, with a median age of 24 years (IQR 23–25). Chest pain and dyspnea were the main symptoms, but arrhythmic presentation was also reported; endomyocardial biopsy (EMB) was performed in only one case. Overall, treatment was based on supportive measures, such as antiarrhythmic and/or vasoactive therapy. Our example (male, 47 years old) is the first reported fulminant biopsy-proven case diagnosed after a massive exposure to hydrocarbons, in which EMB molecular analysis unexpectedly revealed B19V with a high viral load. Hemodynamic and arrhythmic instability required percutaneous stellate ganglion blockade and temporary wearable defibrillator use. Left ventricular function spontaneously normalized at 3 months. In conclusion, we report the first fulminant B19V myocarditis case temporally associated with aromatic hydrocarbon exposure due to a coexistence of viral and toxic causes. Our case and the systematic review show that promptly performing EMB can provide a definitive diagnosis and guide treatment, especially in severe cases in which infectious agents may contribute to myocardial damage.

AIMS:Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS:Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS:Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

Background: Autoantibodies against Desmoglein-2 desmosomal protein (anti-DSG2-ab) were identified in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) by Enzyme-Linked ImmunoSorbent Assay (ELISA); anti-intercalated disk autoantibodies (AIDAs) were identified in myocarditis and (ARVC) by indirect immunofluorescence (IFL). We aim to assess: (1) anti-DSG2-ab specificity in ARVC and myocarditis, (2) accuracy of anti-DSG2-ab detection by ELISA versus AIDA by IFL, and (3) clinical correlates of anti-DSG2-ab in ARVC. Methods: We included 77 patients with ARVC, 91 with myocarditis/dilated cardiomyopathy (DCM), 27 with systemic immune-mediated diseases, and 50 controls. Anti-heart antibodies (AHAs) and AIDAs were assessed by IFL, and anti-DSG2-ab by ELISA (assessed both by optical density, OD, and U/L). Receiving operator curve (ROC) analysis was used to assess ELISA diagnostic accuracy. Results: A relevant proportion (56%) of ARVC patients was anti-DSG2-ab-positive, with higher anti-DSG2-ab levels than controls. Anti-DSG2-ab titer was not different between ARVC and myocarditis/DCM patients (48% anti-DSG-ab positive). Frequency of anti-DSG2 positivity by ELISA was higher in AIDA-positive cases by IFL than AIDA-negative cases (p = 0.039 for OD, p = 0.023 for U/L). In ARVC, AIDA-positive patients were more likely to be AHA-positive (p < 0.001), had pre-syncope (p = 0.025), and abnormalities in cardiac rhythm (p = 0.03) than ARVC AIDA-negative patients, while anti-DSG2-ab positivity did not have clinical correlates. Conclusions: Anti-DG2-ab detection in ARVC and myocarditis/DCM reflects immune-mediated pathogenesis to desmosomal proteins. Higher frequency of anti-DSG2-ab positivity by ELISA by U/L was higher in AIDA-positive cases by IFL than AIDA-negative cases, in keeping with the hypothesis that DSG2 is one of AIDA autoantigens. In ARVC, AIDA status but not anti-DSG2-ab showed distinct clinical correlates, possibly reflecting a wider AIDA autoantigenic spectrum.

The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.

Myocarditis remains an unknown disease with varying clinical manifestations, often leading to heart failure. The latest 2021 and 2022 guidelines of the European Society of Cardiology (ESC) are the first official European documents updating knowledge on the diagnosis and treatment of myocarditis since the 2013 ESC expert consensus statement. These guidelines and new studies allow standardization and improvements to the management of myocarditis. In this review, we discuss the most important aspects of myocarditis diagnosis, therapies and follow-up based on current knowledge.

Background Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). Methods Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. Results Forty-seven patients (median age 41 [30–47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients’ recovery in only 4% patients. Conclusions In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS. Graphical Abstract

Myocarditis is an inflammatory disease of the myocardium with heterogeneous etiology, clinical presentation, and prognosis; when it is associated with myocardial dysfunction, this identifies the entity of inflammatory cardiomyopathy. In the last few decades, the relevance of the immune system in myocarditis onset and progression has become evident, thus having crucial clinical relevance in terms of treatment and prognostic stratification. In fact, the advances in cardiac immunology have led to a better characterization of the cellular subtypes involved in the pathogenesis of inflammatory cardiomyopathy, whether the etiology is infectious or autoimmune/immune-mediated. The difference in the clinical course between spontaneous recovery to acute, subacute, or chronic progression to end-stage heart failure may be explained not only by classical prognostic markers but also through immune-pathological mechanisms at a cellular level. Nevertheless, much still needs to be clarified in terms of immune characterization and molecular mechanisms especially in biopsy-proven myocarditis. The aims of this review are to (1) describe inflammatory cardiomyopathy etiology, especially immune-mediated/autoimmune forms, (2) analyze recent findings on the role of different immune cells subtypes in myocarditis, (3) illustrate the potential clinical relevance of such findings, and (4) highlight the need of further studies in pivotal areas of myocarditis cellular immunology.

BACKGROUND AND AIMS:Childhood-onset cardiomyopathies are rare and poorly characterized. This study examined the baseline characteristics and 1-year follow-up of children with cardiomyopathy in the first European Cardiomyopathy Registry. METHODS:Prospective data were collected on individuals aged 1-<18 years enrolled in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis long-term registry (June 2014-December 2016). RESULTS:A total of 633 individuals aged ≤18 years with hypertrophic [HCM; n = 388 (61.3%)], dilated [DCM; n = 206 (32.5%)], restrictive [RCM; n = 28 (4.4%)], and arrhythmogenic right ventricular cardiomyopathy [ARVC; n = 11 (1.7%)] were enrolled by 23 referral centres in 14 countries. Median age at diagnosis was 4.0 [interquartile range (IQR) 0-10] years, and there was a male predominance [n = 372 (58.8%)] across all subtypes, with the exception of DCM diagnosed <10 years of age; 621 (98.1%) patients were receiving cardiac medication and 80 (12.6%) had an implantable cardioverter-defibrillator. A total of 253 patients (253/535, 47.3%) had familial disease. Genetic testing was performed in 414 (67.8%) patients with a pathogenic or likely pathogenic variant reported in 250 (60.4%). Rare disease phenocopies were reported in 177 patients (28.0%) and were most frequent in patients under 10 years [142 (30.9%) vs. 35 (19.6%); P = .003]. Over a median follow-up of 12.5 months (IQR 11.3-15.3 months), 18 patients (3.3%) died [HCM n = 9 (2.6%), DCM n = 5 (3.0%), RCM n = 4 (16.0%)]. Heart failure events were most frequent in RCM patients (36.0%). CONCLUSIONS:The findings confirm the heterogeneous aetiology of childhood cardiomyopathies and show a high frequency of familial disease. Outcomes differed by cardiomyopathy subtype, highlighting a need for disease-specific evaluation and treatment.

BACKGROUND AND AIMS:Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS:Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS:Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS:Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Abstract Background Myocarditis is an inflammatory disease of the myocardium with viral or immune-mediated/autoimmune etiology. Definite etiological diagnosis relays on endomyocardial biopsy (EMB). High titre anti-heart autoantibodies (AHA) define severe autoimmune forms. Virus-negative myocarditis may require immunosuppression (IS) to reduce progression to dilated cardiomyopathy, heart transplant or death. Prognostic stratification is incomplete and IS is not always efficacious. Animal and human studies suggest a pathogenetic role of immune cells, but little is known on their peripheral distribution or prognostic role. Purpose Characterize EMB-proven myocarditis patients’ peripheral blood to identify new non-invasive etiological and prognostic biomarkers. Methods Seventy-eight EMB-proven myocarditis patients and 9 healthy controls (HC) were enrolled according to the Declaration of Helsinki and written informed consent was collected for each participant. Peripheral blood mononuclear cells were purified by Ficoll stratification and immune cells distribution was evaluated by flow cytometry. Variables were analysed by Mann-Whitney or Kruskall-Wallis and Dunn post-hoc tests clustering patients according to clinical features, EMB and AHA results. Results Compared to HC (figure 1), plasmacytoid dendritic cells were reduced in myocarditis patients: with autoimmune/lymphocytic forms (p=0.0091); without extra cardiac autoimmune diseases (AD, p=0.0075); in those unresponsive to IS (p=0.0379) or never treated because of spontaneous healing (p=0.0015). Moreover, several immunophenotypical features discriminated myocarditis type/IS-response from HC. Viral forms were characterized by reduced CD94+ NK cells and CCR2 over-expression in intermediate monocytes (p=0.029, p=0.013). Autoimmune cases were defined by: higher CD62L+ NK cells when AHA negative (p=0.019); increased Th1 if not requiring IS (p=0.03); higher γδ-TCR+ Th17 and reduced Treg cells if without other AD (both p=0.04), or higher CD4+/IL17+ cells with concurrent AD (p=0.02) and AHA positivity (p=0.036). Moreover, ongoing IS treatment influenced peripheral cells distribution: whole blood cell counts were more frequently altered and total NK cells were reduced (p=0.007); treg cells were reduced in patients actively treated but unresponsive to IS (p=0.036). Conclusion Biopsy-proven myocarditis patients showed a skewed peripheral blood distribution of either innate or adaptive immune cells according to different histology, etiology (viral vs autoimmune) and response to IS in autoimmune forms, unveiling potential new non-invasive immunological biomarkers for myocarditis. Figure: Plasmacytoid dendritic cells (pDCs) percentage was assessed by flow-cytometry and data were showed by boxplots clustering myocarditis patients for etiology (A), EMB histological result (B), presence of extracardiac AD (C) or IS response (D). Data were analysed by Kruskall-Wallis (graph bottom) and Dunn post-hoc tests.

Background. Pericarditis has a heterogeneous clinical spectrum and rate of relapse. Data on aetiology, real-life treatment strategies, and long-term course from contemporary pericarditis cohorts are lacking. Methods. Pericarditis patients referred to the Cardioimmunology Outpatient Clinic at Padua University Hospital in 2001-2020 were retrospectively included. Kaplan-Meier method was used for recurrence-free survival probability estimation. The appropriateness of treatment was assessed based on the European Society of Cardiology guidelines. Results. One-hundred forty-four patients (57% males, mean age 50 years) followed up for 18 months (IQR 7-45) were included; of those, 52% had acute, 35% recurrent, 8% incessant, and 5% chronic pericarditis; 9% had cardiac tamponade at diagnosis. Time to pericardial effusion resolution was 53 days (IQR 16-124); median medical treatment duration was 87 days (IQR 48-148). Treatment was readjusted following the ESC guidelines for nonsteroidal anti-inflammatory drugs in 29% of the cases, steroids in 12%, and colchicine in 25%. Eleven (8%) patients were treated with anti-IL1 agents. Recurrence-free survival probability was 86% at 1st-year follow-up, and 23 patients (16%) had at least one recurrence, with a mean of two relapses per patient. Compared to patients without recurrences, they had a higher frequency of cardiac tamponade (27% vs. 6%, p = 0.006) and left bundle branch block (14% vs. 1%, p = 0.034). Out of the 144 patients, 5 (3%) were diagnosed as having constrictive pericarditis at first evaluation at our clinic, underwent successful pericardiectomy, and are currently alive and asymptomatic. Conclusions. When treated following a guideline-based approach, pericarditis has a favourable evolution. A relevant quote of cases benefits from the treatment readjustment of previously prescribed medical therapy when not in line with ESC recommendations. Cases relapsing despite treatment readjustment should receive anti-IL1 therapies.