Eosinophilic myocarditis. Characteristics, treatment and outcomes, J Am Coll Cardiol 70 (2017) 2363–75

Background

Eosinophilic myocarditis (EM) is an etiologically heterogeneous disease, which is rare in prospective biopsy-proven case series including all forms of myocarditis, but potentially life-threatening. Published studies mainly include individual case reports and small case series (1-2).

Objective

The paper by Brambatti, et al (1)  is a systematic revision of all published histologically proven cases of eosinophilic myocarditis (EM), aimed at describing the clinical presentation, treatment, and outcome of EM.

Methods

The study identified 443 papers in MEDLINE and EMBASE on cases of EM published until June 2017. The authors selected 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.

Results

Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivityand eosinophilic granulomatosis with polyangiitis (EGPA), which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n =30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n =40), with the highest occurrence in the hypersensitivity form (36.1%; p =0.026).

Conclusion

The authors conclude that EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.

Comments

Although the authors provide a diligent and useful review of published data on EM, the paper has obvious limitations, being a “meta-analysis” of case reports published over more than 3 decades, with a variable histological confirmation (ranging from endomyocardial biopsy with up to date pathology tools to diagnosis based only on the Dallas criteria, and from surgical samples taken at the time of mechanical circulatory support to post-mortem cases). Survival in EM is likely to be related, as for other myocarditis forms, to severity of biventricular dysfunction and of heart failure at diagnosis (3); the study design by Brambatti et al (1) does not permit a multivariable analysis to provide reliable estimates for the independent negative prognostic role, if any, of specific EM etiologies.  In addition, as correctly discussed by the authors and by the accompanying editorial by L. Cooper (2), it is very likely that a publication bias  has lead to an overestimation of mortality. As pointed out by the authors (1), the “red flag” in EM, e.g. peripheral hypereosinophilia, was lacking in about 25% of cases; on the other hand majority of clinically suspected EM had peripheral hypereosinophilia and unexplained troponin release and regretfully did not undergo EMB.

Therefore, prospective multicenter biopsy-proven studies including all patients with clinically suspected myocarditis defined according to a uniform clinical and diagnostic work-up, as suggested by the ESC 2013 consensus paper and criteria by the Working Group on Myocardial and Pericardial Disease, with and without “red flags” for EM, are needed to define the whole spectrum, the frequency and outcome of EM as well as of other histological forms of the disease (3). This is also the only study design that will clarify, without selection bias, the frequency of EM and of other histological forms of myocarditis in the very common pseudo-infarct presentation, mimicking MINOCA (4-5).  This diagnostic approach is also best suited to provide etiology-directed therapy both in isolated myocarditis and in myocarditis in the context of systemic immune-mediated diseases, as suggested in a recent multidisciplinary ESC consensus paper by the ESC Working Group on Myocardial and Pericardial Disease (6).