Adler, Eric D

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.

Abstract Background The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. Purpose To ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. Methods In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV(+)), 25 with AM and negative gene testing (DGV(−)), and 36 AM patients without genetics (w/o genetics). All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance imaging (CMRI). In 86 patients CMRI changes in function and structure were re-assessed at follow-up. Results In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular (LV) ejection fraction was 56% on CMRI (p=NS vs. the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared to DGV(−) and w/o genetics patients (62.3% vs. 17.5% vs. 5.3% at 5 years respectively; p<0.0001), driven by myocarditis recurrence and ventricular arrhythmias (Figure 1A, B). At follow-up CMRI, a higher number of late-gadolinium enhanced segments was found in DGV(+) AM. Conclusions Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with AM patients without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health

Aims The outcomes of patients presenting with acute myocarditis and life‐threatening ventricular arrhythmias (LT‐VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population. Methods and results We retrospectively analysed 156 patients (median age 44 years; 77% male) discharged with a diagnosis of acute myocarditis and LT‐VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death or successfully defibrillated ventricular fibrillation, or sustained ventricular tachycardia (sVT) requiring implantable cardioverter‐defibrillator therapy or synchronized external cardioversion. Median follow‐up was 23 months [first to third quartile (Q1–Q3) 7–60]. Fifty‐eight (37.2%) patients experienced MAEs after discharge, at a median of 8 months (Q1–Q3 2.5–24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated with MAEs were presentation with sVT [hazard ratio (HR) 2.90, 95% confidence interval (CI) 1.38–6.11]; late gadolinium enhancement involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39–8.53), and absence of positive short‐tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40–4.79) at first CMR. Conclusions Among patients discharged with a diagnosis of myocarditis and LT‐VA, 37.2% had recurrences of MAEs during follow‐up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmia recurrence.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

Advanced heart failure therapies, including heart transplantation and durable mechanical circulatory support, are available to a limited number of patients because of the scarcity of donors, expense, and large burden of care. The importance of psychological and social determinants of health, including cognitive status, health literacy, psychopathology, social support, medical adherence, and substance abuse, are emphasized in advanced heart failure and further amplified in the context of mechanical circulatory support and heart transplantation. The psychosocial assessment of advanced heart failure therapy candidates remains largely subjective, requiring a multidisciplinary evaluation, which may include psychiatrists, social workers, case managers, financial coordinators, pharmacists, and clinicians. Objective tools—including the Stanford Integrated Psychosocial Assessment for Transplantation, Psychosocial Assessment of Candidates for Transplantation, and Transplant Evaluation Rating Scale—were developed and validated in limited populations to help standardize the evaluation process. Small, retrospective studies have inconsistently shown that these tools may predict clinical outcomes in the transplant population, with higher-risk scores associated with readmissions, rejection episodes, and infections. However, it has been more difficult to show that these tools can predict mortality, and their applicability to the mechanical circulatory support population is less studied. The International Society for Heart and Lung Transplantation released a consensus statement in 2018 to promote consistency of psychosocial evaluation across advanced heart failure programs, but it lacks specific recommendations given the current state of evidence. This state-of-the-art review expands on the current consensus by critically reviewing current studies supporting available objective assessment tools, proposing a psychosocial evaluation framework that uses a multidisciplinary approach and offering future directions for research.