Highlights
1. Acute eosinophilic myocarditis (EM) carries a high risk of in-hospital and midterm mortality, with a death or heart transplantation rate of approximately 15% during hospitalization.
2. Peripheral eosinophilia is absent in more than 40% of histologically proven cases, making endomyocardial biopsy essential for diagnosis.
3. Early in-hospital immunosuppressive therapy is an independent predictor of survival and improved clinical outcomes.
The Clinical Challenge of Eosinophilic Myocarditis
Acute eosinophilic myocarditis (EM) has long been perceived as a rare but potentially catastrophic form of myocardial inflammation. Characterized by the infiltration of eosinophils into the myocardium, it often manifests as fulminant heart failure or sudden cardiac death. Historically, our understanding of EM has been limited to small case series and individual reports, leading to significant gaps in our knowledge regarding its natural history, associated systemic conditions, and optimal management strategies.
One of the most significant clinical hurdles is the reliance on peripheral eosinophilia as a diagnostic marker. Clinicians often look for an elevated eosinophil count in the blood to justify a suspicion of EM. However, this study challenges that paradigm, suggesting that many patients may be misdiagnosed or diagnosed too late because they lack this classic hematologic sign. Given the high mortality rate, there is an urgent need for a systematic evaluation of EM presentation and outcomes.
Study Design and Methodology
In a comprehensive international, multicenter, retrospective cohort study, researchers from 53 centers across the globe screened 193 patients with histologically proven acute EM between 1992 and 2023. To ensure data integrity and relevance, the study employed strict inclusion criteria: symptoms had to last for 30 days or less, and histological diagnoses were subject to rigorous review. After excluding patients with insufficient data or those whose diagnosis could not be confirmed, 156 patients were included in the final analysis.
The study population was predominantly adult, with a median age of 48 years and a significant male predominance (67.3%). Pediatric cases were notably rare, representing only 1.3% of the cohort. The primary objective was to characterize the clinical presentation, identify associated systemic conditions, and evaluate the predictors of major adverse outcomes, specifically death or the need for heart transplantation (HTx).
Key Findings and Results
Clinical Presentation and the ‘Missing’ Eosinophilia
The study revealed that the most common signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Perhaps the most striking finding was that peripheral eosinophilia (defined as >500 cells/μL) was reported in only 57.4% of cases. The median cell count was a modest 630 eosinophils/μL. This suggests that in over 40% of histologically proven EM cases, the peripheral blood count would not have triggered a suspicion of the disease based on eosinophil levels alone.
Cardiac Function and Associated Disorders
Patients typically presented with severe cardiac dysfunction. The median left ventricular ejection fraction (LVEF) on admission was 32%. The study identified several distinct etiologies associated with EM:
- Idiopathic or undefined forms: 44.9%
- Eosinophilic granulomatosis with polyangiitis (EGPA): 22.4%
- Hypersensitivity forms (often drug-induced): 14.1%
- Miscellaneous causes (including infections and paraneoplastic syndromes): 18.6%
Mortality and Outcomes
Despite aggressive treatment, outcomes were sobering. In-hospital death or the need for heart transplantation occurred in 23 patients (14.7%), consisting of 22 deaths and 1 HTx. This occurred despite 43.6% of the cohort receiving temporary mechanical circulatory support and 92.3% receiving immunosuppressive agents. The estimated rates of death or HTx remained high over time, reaching 19.0% at one year and 23.8% at three years.
Predictors of Survival
Multivariable analysis identified three independent predictors of death or heart transplantation:
- Increased age at presentation.
- Decreased LVEF on admission.
- The absence of immunosuppressive therapy during the initial hospitalization.
Interestingly, while the hypersensitivity form showed a higher trend toward death/HTx (46.1%) compared to the EGPA-associated form (13.1%) at three years, this difference did not reach statistical significance (P=0.15), likely due to the rarity of the subsets.
Expert Commentary and Clinical Implications
The results of this registry provide a crucial reality check for the cardiology and critical care communities. The finding that nearly half of EM patients do not present with peripheral eosinophilia is a critical diagnostic pearl. It reinforces the current guidelines suggesting that endomyocardial biopsy (EMB) should not be delayed in cases of unexplained, rapid-onset heart failure, even if the hematologic profile appears normal.
The protective effect of in-hospital immunosuppression (largely corticosteroids) is another major takeaway. While the study was retrospective, the strong association between immunosuppression and HTx-free survival suggests that early initiation of therapy—once the diagnosis is histologically confirmed—is vital. However, the high mortality rate despite treatment highlights that ‘one-size-fits-all’ steroid therapy may not be enough. Tailored approaches, perhaps involving steroid-sparing agents or biologics targeting interleukin-5 (such as mepolizumab) in specific subsets like EGPA, require further investigation.
Clinicians must also remain vigilant about the various triggers of EM. The significant portion of hypersensitivity-related cases reminds us to meticulously review medication histories for potential drug-induced reactions, which can be life-threatening if the offending agent is not removed.
Summary and Conclusion
Acute eosinophilic myocarditis is a high-risk clinical entity that often masquerades as other forms of heart failure due to the frequent absence of peripheral eosinophilia. This international registry underscores that LVEF impairment is severe at presentation and that mortality remains high both in-hospital and in the midterm. The gold standard for diagnosis remains the endomyocardial biopsy, which should be performed early when EM is suspected. Furthermore, the administration of immunosuppressive therapy during the acute phase is strongly associated with improved survival. Future research should focus on refining diagnostic pathways and developing personalized treatment protocols to lower the burden of this devastating disease.
Funding and Registration
This study was registered at clinicaltrials.gov with the unique identifier: NCT06447935. The authors declare no specific external funding for this retrospective registry beyond institutional support.
References
Ammirati E, Palazzini M, Lehtonen J, et al. Natural History of Patients With Histologically Proven Acute Eosinophilic Myocarditis. Circulation. 2026 Mar 3;153(9):634-652. doi: 10.1161/CIRCULATIONAHA.125.074797. Epub 2026 Feb 6. PMID: 41645905.
