Natural History of Patients With Histologically Proven Acute Eosinophilic Myocarditis

Patient Information and Clinical Presentation

Acute eosinophilic myocarditis (EM) has long been considered a rare but potentially catastrophic cardiac condition. In the largest international, multicenter study to date, researchers analyzed a cohort of 156 patients with histologically proven acute EM (symptoms lasting ≤30 days) identified between 1992 and 2023 across 53 centers. The clinical profile revealed that EM primarily affects adults, with a median age of 48 years (IQR 34–59). There was a notable male predominance (67.3%), while pediatric cases (≤16 years) were exceptionally rare, representing only 1.3% of the cohort.

The clinical presentation of acute EM is often dramatic and non-specific, mimicking other forms of acute heart failure or coronary syndromes. The most common presenting symptoms include:

• Dyspnea: 75.6% of patients
• Fever: 61.3% of patients
• Chest Pain: 53.2% of patients

At the time of admission, the hemodynamic status was often severely compromised, with a median left ventricular ejection fraction (LVEF) of only 32% (IQR 25%–48%).

Diagnosis: The Diagnostic Trap of Peripheral Eosinophilia

The most striking finding of this study is the unreliability of peripheral eosinophil counts in the diagnostic workup. While the disease is defined by the infiltration of eosinophils into the myocardium, peripheral eosinophilia (defined as >500 cells/μL) was present in only 57.4% of cases. The median cell count was a modest 630 eosinophils/μL. This underscores a critical clinical lesson: the absence of elevated eosinophils in the blood does not rule out eosinophilic myocarditis.

Due to this diagnostic ambiguity, endomyocardial biopsy (EMB) remains the mandatory gold standard for diagnosis. Without histological confirmation, a significant portion of these high-risk patients would be misdiagnosed as having idiopathic giant cell myocarditis or common lymphocytic myocarditis, leading to suboptimal treatment strategies.

Differential Diagnosis and Associated Conditions

Acute EM is frequently a cardiac manifestation of a broader systemic disorder. The study categorized the patients into four primary etiological groups:

1. Idiopathic/Undefined Forms (44.9%): Cases where no clear underlying trigger or systemic disease was identified.
2. Eosinophilic Granulomatosis with Polyangiitis (EGPA) (22.4%): Formerly known as Churg-Strauss syndrome, this systemic vasculitis is a major contributor to EM.
3. Hypersensitivity Forms (14.1%): Often related to drug reactions (DRESS syndrome) or other allergic triggers.
4. Miscellaneous Causes (18.6%): Including parasitic infections, paraneoplastic syndromes, or other rare immune-mediated conditions.

Treatment and Management

The management of acute EM requires an aggressive, multi-modal approach focusing on hemodynamic support and the suppression of the inflammatory cascade. In this cohort, 43.6% of patients required temporary mechanical circulatory support (MCS), such as intra-aortic balloon pumps, ECMO, or ventricular assist devices, highlighting the severity of the initial presentation.

Pharmacological intervention was centered on immunosuppressive therapy, which was administered to 92.9% of the patients. This typically involved high-dose corticosteroids, often initiated intravenously. The study found that the use of immunosuppressive agents during hospitalization was an independent predictor of survival. In cases of hypersensitivity myocarditis, immediate cessation of the offending drug is also mandatory.

Outcome and Prognosis

The prognosis for acute EM remains guarded, particularly in the early stages of the disease. In-hospital death or the need for an urgent heart transplantation (HTx) occurred in 14.7% of the cohort (22 deaths and 1 HTx). Long-term outcomes showed that the estimated rates of death or HTx rose to 19.0% at one year and 23.8% at three years.

Independent predictors of poor outcomes (death or HTx) included:

• Increased age at presentation
• Lower LVEF on admission
• Failure to initiate immunosuppressive therapy during the hospital stay

Notably, patients with the hypersensitivity form tended to have higher mortality/HTx rates (46.1% at 3 years) compared to those with EGPA-associated EM (13.1%), although this did not reach statistical significance (P=0.15).

Discussion

This study provides definitive evidence that acute eosinophilic myocarditis is a high-mortality condition that requires a high index of clinical suspicion. The discovery that nearly half of the patients do not present with peripheral eosinophilia is a practice-changing observation. Clinicians must be prepared to perform an endomyocardial biopsy in patients presenting with unexplained acute heart failure, even if blood tests are relatively normal.

The strong association between in-hospital immunosuppression and heart-transplant-free survival suggests that early aggressive treatment can mitigate myocardial damage. However, the high midterm mortality rates even among treated patients indicate that current protocols may need further refinement. Future research should focus on tailored immunosuppressive regimens and the use of biologics (such as IL-5 inhibitors) to improve the long-term prognosis of these patients.

References

• Ammirati E, et al. Natural History of Patients With Histologically Proven Acute Eosinophilic Myocarditis. Circulation. 2026;153(9):634-652.
• Kuznetsova T, et al. Eosinophilic myocarditis: a clinical review. Heart. 2020;106(17):1294-1301.
• Caforio AL, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34(33):2636-2648.