Discussion

Electrocardiogram is universally recommended as a first-line investigation for patients with suspected myocarditis. ^{Reference Caforio, Pankuweit and Arbustini1,Reference Pomiato, Perrone, Palmieri and Gagliardi2} Numerous retrospective studies have demonstrated that electrocardiogram abnormalities are detected in nearly all patients, ^{Reference Buttà, Zappia, Laterra and Roberto9,Reference Punja, Mark, McCoy, Javan, Pines and Brady11} although some studies report a subset of patients with normal electrocardiogram findings. ^{Reference Pompa, Beerman, Feingold and Arora10} However, the potential association between specific electrocardiogram patterns and a particular causative agent has not yet been studied, particularly in paediatric populations where research is limited, and sample sizes are smaller. This study is the first to present an electrocardiogram pattern that could potentially help identify PVB19 as the underlying cause of myocarditis in paediatric patients.

Previous studies examining electrocardiogram alterations during acute myocarditis have identified sinus tachycardia and repolarisation abnormalities, particularly T-wave inversion, as the most common electrocardiogram findings. ^{Reference Buttà, Zappia, Laterra and Roberto9,Reference Punja, Mark, McCoy, Javan, Pines and Brady11} In our study, repolarisation abnormalities were observed in all patients with PVB19 myocarditis, compared to 35.1% of patients with myocarditis caused by other virus. Repolarisation abnormalities have been reported in patients with myocarditis of varying severity, from non-complicated to fulminant myocarditis, with a prevalence ranging from 9 to 48%. ^{Reference Buttà, Zappia, Laterra and Roberto9,Reference Punja, Mark, McCoy, Javan, Pines and Brady11,Reference De Lazzari, Zorzi and Baritussio12}

The pathogenic link between myocardial oedema and repolarisation abnormalities remains to be fully elucidated. However, it has been proposed that regional or transmural myocyte repolarisation inhomogeneity secondary to the inflammatory process could be responsible. ^{Reference Buttà, Zappia, Laterra and Roberto9,Reference De Lazzari, Zorzi and Baritussio12} In this context, T-wave inversion may result from inflammatory or fibrotic infiltration beginning in the subepicardium, where depolarisation and repolarisation become more delayed compared to the subendocardium, leading to a transmural repolarisation gradient. ^{Reference Aimo, Milandri and Barison13} In line with this hypothesis, T-wave inversion has been independently associated with the extent of myocardial necrosis and oedema detected by MRI, with transmural oedema distribution strongly correlated with the location of T-wave inversion.^{Reference De Lazzari, Zorzi and Baritussio12}

Low QRS voltages were observed in 16 of our patients (16/20, 80%), a finding traditionally associated with pericardial effusion or extracardiac conditions such as obesity or emphysema. ^{Reference Aimo, Milandri and Barison13} However, low QRS voltages have also been documented in myocarditis independent of pericardial effusion, ^{Reference Punja, Mark, McCoy, Javan, Pines and Brady11} a finding confirmed by this study. The proposed mechanisms for low QRS voltages in this setting include expansion of extracellular spaces by oedema and fibrosis in the ventricular wall. Pulmonary or peripheral oedema can also contribute to reducing voltage amplitude by increasing impedance to electrical conduction. ^{Reference Buttà, Zappia, Laterra and Roberto9} In cardiomyopathies, low QRS voltages are observed in 3–6% of patients with dilated cardiomyopathy and in up to 41% of patients with certain forms of non-dilated left ventricular cardiomyopathy. ^{Reference Aimo, Milandri and Barison13} The markedly higher prevalence of low voltages in PVB19 myocarditis in our cohort (80%) highlights the relevance of this electrocardiogram finding in this specific aetiology.

Additionally, peaked p waves on electrocardiograms, which indicate increased atrial pressures, are often a consequence of heart failure. Concurrently, myocardial oedema can further diminish ventricular compliance, exacerbating atrial pressure by creating a restrictive filling pattern and diastolic dysfunction. The impaired ventricular contraction and relaxation can also lead to atrioventricular valve regurgitation, further exacerbating atrial volume overload and pressure elevation. ^{Reference Aimo, Milandri and Barison13}

Although electrocardiogram is widely used for the early screening of myocarditis, ^{Reference Caforio, Pankuweit and Arbustini1,Reference Ammirati, Frigerio and Adler3,Reference Pompa, Beerman, Feingold and Arora10} its sensitivity and specificity for diagnosing myocarditis remain low. ^{Reference Pomiato, Perrone, Palmieri and Gagliardi2,Reference Buttà, Zappia, Laterra and Roberto9,Reference Pompa, Beerman, Feingold and Arora10} However, once myocarditis is suspected, the presence of this specific electrocardiogram pattern in the limb leads (characterised by peaked p waves, low QRS voltages and abnormal repolarisation) should prompt consideration of PVB19 as the likely cause, with a specificity of 98%. The sensitivity of this pattern, while lower at 70%, is still noteworthy. These findings could have significant clinical implications, not only guiding the selection of appropriate diagnostic tests but also influencing therapeutic decisions.

In particular, recent studies have proposed that immunosuppressive treatment, potentially combined with interferon-beta to suppress active PVB19 transcription in the myocardium, might offer an effective strategy for managing PVB19 myocarditis. ^{Reference Krych, Jęczmyk and Jurkiewicz4,Reference Esmel-Vilomara, Dolader and Izquierdo-Blasco5,Reference He, Li and Li14} However, in the absence of definitive evidence, targeted immunosuppressive or antiviral therapy should not be initiated based solely on electrocardiogram findings without microbiological confirmation. While early empirical immunomodulatory treatment with corticosteroids may be considered in critically ill patients with cardiogenic shock or severe systolic dysfunction, particularly if this characteristic electrocardiogram pattern is present, this approach remains untested in clinical trials. ^{Reference Pomiato, Perrone, Palmieri and Gagliardi2,Reference He, Li and Li14} Current guidelines do not provide specific recommendations for empiric immunosuppression in acute myocarditis beyond standard heart failure management. ^{Reference Caforio, Pankuweit and Arbustini1,Reference Ammirati, Frigerio and Adler3}

Beyond specialised centres where endomyocardial biopsy is routinely available, this electrocardiogram pattern could serve as a practical and widely accessible tool to aid in the early identification and risk stratification of paediatric myocarditis, particularly in resource-limited settings where advanced diagnostic tools as endomyocardial biopsy or cardiac MRI are not readily available. If validated in larger multicentre studies, its application could contribute to earlier clinical suspicion, optimised diagnostic workflows, and potentially improved patient outcomes.

The primary limitation of this study is its single-centre design, which may impact the generalisability of the findings. Additionally, the small sample size of 20 patients with PVB19 myocarditis, due to the rarity of the disease, restricts the robustness of the conclusions. To validate these results and enhance clinical applicability, future prospective multicentre studies with larger, well-characterised cohorts are needed. These studies should aim to confirm the specificity and sensitivity of this electrocardiogram pattern and assess its predictive value in clinical decision-making. Furthermore, expanding the number of centres and patients would facilitate an evaluation of interobserver agreement, ensuring consistent electrocardiogram interpretation in routine practice.