Evolution of acute myocarditis in a pediatric population: An MRI based study

Highlights

• We present data from a large multicentric cohort of pediatric patients submitted to CMR for acute myocarditis with a mean follow-up time of 745 days.

• Recover of function was attained in about 2/3 of patients and is inversely correlated with the presence of a midwall or mixed LGE pattern.

• A complete recovery from functional and tissue abnormalities found only in a third of patients.

Abstract

Background

Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis.

Methods

CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214–923) days.

Results

LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70–746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036).

Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE.

Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08–10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16–18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery.

Conclusions

In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.

Introduction

Myocarditis is defined as inflammation of the myocardial tissue [1] with an estimated incidence rate in pediatric population under 15 years of 2–3 cases/100,000 person-years [2,3]. It is, however, generally accepted that this is probably an underestimation due to an unknown yet significant proportion of sub-clinical disease. Indeed, clinical presentation is highly variable, ranging from subclinical to fulminant disease requiring mechanical circulatory support shortly after disease onset.

With current supportive therapies, clinical and echocardiographic recovery from acute myocarditis is common, attained in 52 to 66% children affected [4,5]. The remaining survivors will progress to dilated cardiomyopathy (DCM). In fact, biopsy-proven myocarditis is reported in up to 46% of children with an identified cause of DCM [6]. The progression to DCM carries significant morbidity, accounting for 12 to 15% of pediatric hospitalizations for heart failure [7]. Foerster et al. evaluated echocardiographic data at presentation, suggesting left ventricular dilatation as a negative predictor and septal thickness as a positive predictor of recovery [5]. On the other hand, Belkaya et al. elegantly suggest a genetic basis of progression to DCM [8].

An endomyocardial biopsy (EMB) with research for Dallas criteria has been considered the gold standard for diagnosis of acute myocarditis, but its current role has been largely debated and is still controversial. The risk of EMB in young children with severe left ventricular dilatation is high. Moreover, its sensitivity is poor because of the patchy nature of inflammatory process in acute myocarditis. Previous studies found no differences in outcomes in pediatric patients with biopsy-proven myocarditis vs. those with clinically diagnosed myocarditis while others did [[9], [10], [11]]. EMB is therefore infrequently performed in current clinical practice, due to its invasivity and comparable sensitivity to Cardiovascular magnetic resonance (CMR) [12].

CMR imaging allows non-invasive assessment of myocardial inflammation as defined by the Lake Louise criteria [1,9]. CMR permits tissue characterization of the entire myocardium and accurate evaluation of ventricular volumes and global and regional ventricular function. Recent CMR guidelines recommend the use of routine mapping in cases of suspected myocarditis [13], but in children data about value of mapping CMR in acute myocarditis are scarce [14] because of significant practice variability between institutions as well as technical challenges in children such as motion artifacts and heart rate variability.

Adult data also suggest a prognostic role in for CMR in acute myocarditis, with an association of septal intramyocardial late gadolinium enhancement (LGE) with worse prognosis [[15], [16], [17], [18]]. One pediatric study found a correlation between persistent dysfunction and larger left ventricular end-diastolic volume and lower left and right ventricular ejection fraction [19].

In the present study we aim to identify predictors of recovery from functional and tissue abnormalities in a large cohort of children with acute myocarditis.