Acute myocarditis can present with new-onset severe left ventricular dysfunction, and differential diagnosis with a genetic dilated cardiomyopathy should be considered. In our study, most patients from group 2 (66.6%) had a subacute clinical presentation (more than 15 days of evolution) whereas most patients from group 1 had a fulminant or acute presentation. Unlike what might be expected, the presence of a family history of genetic cardiomyopathy was infrequent. Troponin values were above the reference values in both groups, but the elevation was higher in patients with myocarditis. All the patients selected in our study had a LVEF of less than 35%. Left ventricle end-diastolic diameter was significantly higher in group 2. The presence of trabeculations that met non-compaction criteria was more common in group 2 (44.4%), but it was also seen in 2 patients (11.1%) from group 1 (p = 0.136). These 2 patients had a subacute presentation, with a history of PVB19 infection several weeks before heart failure and PVB19 PCR was positive in blood and heart samples. Genetic test was negative in both, and there was no family history of cardiomyopathy. Thus, LV trabeculations seen in these patients could be the result of a LV remodelling process. Hypertrophy of the septum or posterior wall of the LV was more frequent in patients with myocarditis (88.8% vs 33.3%, p = 0.03), and this finding is likely to be associated with myocardial oedema.
In our experience, CMR sensitivity in paediatric patients with myocarditis, is low in cardiomyopathic clinical presentation. This fact has been previously described in adult patients21. In our study, we could perform a CRM in only 14 patients due to hemodynamic instability on admission. In the myocarditis group, 7/8 patients (87.8%) met at least 1 of the Lake Louise criteria, but only 3 patients (37.5%) met 2/3, a necessary condition for making the diagnosis. Interestingly, we also found 2 out of 6 patients in group 2 (33.3%) that underwent a CMR that also met 2/3 Lake Louise criteria for myocarditis. This finding has also been recently described by Martins et al22.
The current gold standard test for the diagnosis of myocarditis is the EMB but is a risky technique4,5 in paediatric patients and is not widely used. In our experience, the rate of complications is low when performed in patients ≥ six months and ≥ 8 kg and the samples are taken from the right ventricular septum.
Suthar et al17 published a remarkably interesting study in which they assessed the utility
of non-invasive measures to distinguish myocarditis from other forms of dilated cardiomyopathy in paediatric patients. They establish the diagnosis of myocarditis based on Dallas criteria. In our experience, these criteria6 are of limited use, as only 50% of patients with myocarditis fulfilled them. Despite this, some of our results are similar. In addition, we describe the most common findings in EMB. Current immunohistology criteria8 have not been validated in the paediatric population. We observed a high rate of false positives, given that 77.8% of the patients with genetic cardiomyopathy presented ≥ 14 mononuclear cells/mm2 with ≥ 7 CD3 lymphocytes/mm2 in the EMB. One possible explanation for these findings could be that these patients had concurrent acute myocarditis. In our opinion, a more plausible explanation is that myocardial inflammation can be triggered by acute clinical decompensation with severe cardiac dysfunction in individuals with genetic cardiomyopathy. This theory has also been proposed recently by Ammirati et al. 23.
Although the number of lymphocytes/mm2 was higher in group 1 (37.5 (8- 180) vs 14 (0–24) CD3/ mm2,p = 0.1), no significant differences were found. Some patients in group 1 had a minor infiltrate, and this could be due to the patchy nature of the disease. Interestingly, a recent paper from Ukimuraet al. reported that myocarditis secondary to influenza viruses could present a clinical picture of fulminant myocarditis with very mild histological changes24. In our study, 3 cases had influenza (patients 9, 10 and 13), and all of them had very mild histological changes. If those patients were excluded from the analysis, the number of lymphocytes/mm2 would have been significantly higher in the myocarditis group (53 (8-180) CD3/mm2 vs 14 (0–24), p = 0.009). Then the differences in both groups would become statistically significant. Myocardial oedema in the EMB was observed in 66.6% of patients in group 1 and none of group 2 (p = 0.001), suggesting that it could be a specific marker of myocarditis. On the other hand, myocyte hypertrophy was more likely in patients with genetic cardiomyopathy (5.5% vs 44.4%, p = 0.03). The latter, we believe, was an unspecific finding associated with a long-standing clinical picture.
In our patients, PVB19 was the main responsible for acute myocarditis, as has been described before1,3. Despite this, myocardial PCR only had a 50% sensitivity, with a 22.2% rate of false-positive cases. The detection of viral genome in the heart of patients without cardiomyopathy has also been previously described16. The usefulness of the blood PCR was greater in younger patients (Table 1), especially in children under 5 years of age.
Mortality during the acute phase of illness was higher in patients from group 1 (16.6 % vs 0%, p = 0.021) and 55.5% required ECMO support on admission. If patients survived the initial stage, the long-term survival was excellent. Thus, 92.8% of cases of myocarditis who survived the initial stage, had a complete recovery. In the other hand, patients from group 2 had 0% acute mortality, had a non-fulminant clinical presentation. Still, recovery is rare, and only 22% were free of transplant at the end of follow-up time.