Over the past decade, the boundaries between inflammatory and genetic cardiomyopathies have become increasingly permeable [1–3]. The traditional view of myocarditis as a distinct, self-limiting entity is being replaced by a more integrated concept—one that acknowledges the complex interplay between immune activation, viral infection, and myocardial vulnerability [2,3]. This intersection is especially relevant in paediatrics, where inflammatory cardiomyopathy may coexist with, often within families harbouring desmosomal or cytoskeletal variants [4]. Understanding the true aetiology of myocardial inflammation in this context requires not only advanced imaging but also histological and molecular confirmation [5,7]. It is within this evolving landscape that the study by Caforio and colleagues, published in the European Heart Journal in 2024, gains particular resonance [1].

The authors present a multicentre analysis from the European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Cardiomyopathy and Myocarditis Long-Term Registry, encompassing 581 patients—493 adults and 88 children—across 46 centres in 18 European countries [1]. Such a dataset represents one of the most comprehensive efforts to date to capture the contemporary clinical, diagnostic, and prognostic features of myocarditis across age groups. The registry’s strength lies in its prospective design, its use of standardised ESC criteria [2], and its balanced inclusion of both imaging- and biopsy-based diagnoses [1,7]. In doing so, it reflects the diversity of current European practice, from tertiary centres with advanced imaging infrastructure to centres maintaining active biopsy programmes.

Perhaps the most striking and practice-changing finding is the demonstration that endomyocardial biopsy (EMB) can be performed safely in both adult and paediatric populations [1]. The overall complication rate was below 5% in each group, with no procedure-related deaths. This observation challenges long-held apprehensions about the risks of EMB, particularly in children, where smaller cardiac chambers and limited procedural experience have often prompted diagnostic conservatism [6]. The results suggest that, when performed in experienced centres, EMB is both safe and diagnostically rewarding, providing critical tissue-level information that imaging alone cannot offer [5,7]. For paediatric cardiologists, this is especially reassuring, as it supports a more assertive diagnostic approach in cases of uncertain or atypical presentation.

The study also offers important insights into the diagnostic interplay between biopsy and cardiac magnetic resonance (CMR). In adults, a classical myocarditis pattern was detected in nearly 58% of patients, but this proportion fell to 31% among paediatric cases with biopsy-proven disease [1]. This discrepancy underscores the limitations of applying adult-derived imaging criteria, such as the Lake Louise criteria, to children [6]. Although the registry does not investigate mapping techniques, it is relevant to note—outside the scope of the present study—that normative values for T1 and T2 mapping in paediatrics remain scarce and heterogeneous. CMR guidelines emphasise that each centre should establish its own age-specific reference ranges, given the variability in scanners, sequences and myocardial developmental stages [6]. Although not addressed in the EORP dataset, these challenges likely contribute to the lower diagnostic yield of CMR in paediatric myocarditis seen in clinical practice. These considerations support viewing imaging and biopsy as complementary rather than competing modalities [5,6].

Histologically, lymphocytic myocarditis emerged as the dominant pattern, accounting for over 80% of biopsy-proven cases [1]. Notably, most samples were virus-negative on molecular testing, suggesting a predominance of immune-mediated or autoimmune processes [1–3]. This aligns with the broader shift in conceptualising myocarditis not merely as a post-viral entity but as a disease spectrum including virus-negative inflammatory and potentially genetically mediated subtypes [3]. In paediatric cohorts, inflammation may act as a disease amplifier or early marker of myocardial vulnerability, although such patterns are not analysed within the present registry.

Although the EORP registry does not include genetic testing or genotype–phenotype analyses, a broader and speculative but clinically relevant consideration is the role of underlying genetic predisposition in shaping inflammatory presentations. Increasing evidence—from studies external to the present dataset—suggests that myocarditis-like episodes may constitute an early or triggering phenotype in individuals harbouring pathogenic variants in desmosomal, cytoskeletal, or sarcomeric genes [4]. This concept is not addressed in this study, but is gaining recognition particularly in paediatric and young adult settings.

Similarly, while the registry does not pursue etiological reclassification, the findings can be viewed—purely as contextual reflection—in light of the 2023 ESC Guidelines on Cardiomyopathies, which promote an aetiology-based interpretation of myocardial disease [8]. Within that conceptual framework, myocarditis can appear as one phenotype within broader inherited cardiomyopathy spectra. This perspective does not stem from the EORP data but provides a useful lens through which clinicians might interpret complex inflammatory presentations.

Whether distinct genotypes lead to subtle differences in histopathology remains an open question. The present registry does not evaluate this, but external literature has reported myocarditis-like injury patterns in patients with DSP and other genetic variants [4,5]. These remain hypotheses and potential areas for future research integrating genetic and tissue-level characterisation.

At one year, the registry reported modest adverse outcomes: 2.7% mortality, 1.7% heart transplantation, and 3.9% implantable cardioverter-defibrillator implantation [1]. The most powerful predictors of adverse events were reduced left ventricular ejection fraction at baseline and the need for immunosuppressive therapy [1,3]. These findings reinforce the prognostic role of ventricular dysfunction and identify immunologically active forms of myocarditis as high-risk phenotypes [3]. Interestingly, only a small proportion of virus-negative cases received immunosuppression, reflecting a persistent gap between diagnostic capability and therapeutic confidence [2,3,6]. Recent paediatric and adult literature—not evaluated in the current study—has increasingly supported the use of immunomodulatory therapy in selected virus-negative cases [3,6].

Methodologically, the EORP registry has notable strengths: its multinational scope, prospective design and unified diagnostic framework [1,2] confer high generalisability. Nonetheless, limitations must be acknowledged. As an observational registry, treatment decisions were made at clinician discretion, introducing heterogeneity. The absence of centralised CMR adjudication may have contributed to variability in imaging interpretation. The one-year follow-up period limits the assessment of long-term remodelling or progression to dilated cardiomyopathy [1]. The paediatric subgroup, although invaluable, remained small, underscoring the need for larger collaborative studies focusing exclusively on children [6].

Despite these limitations, the implications of this work are substantial. It repositions EMB not as an obsolete or hazardous technique, but as a cornerstone of precision diagnostics in myocarditis [1,5,7]. In paediatric cardiology—where diagnostic uncertainty often delays definitive management—biopsy can provide decisive information shaping treatment and follow-up [6]. Beyond the scope of the study, future integration of genetic testing and histological characterisation may help disentangle the interplay between inflammation and inherited myocardial vulnerability [4,8].

For the broader cardiology community, this study is a reminder that imaging, while indispensable, cannot fully capture the biological complexity of myocardial inflammation. The ability to examine tissue directly remains uniquely powerful [5,7]. In an era increasingly defined by precision medicine, molecular diagnostics and artificial intelligence, the biopsy retains its authority—not as a relic, but as a vital tool within a modern multimodal approach.

In conclusion, the work by Caforio and colleagues reaffirms the value of endomyocardial biopsy in myocarditis and encourages its confident, evidence-based use, particularly in children [1,6]. It bridges the gap between clinical caution and diagnostic necessity, demonstrating that the benefits of biopsy outweigh its risks. As paediatric and genetic cardiomyopathy research evolves, this registry reminds us that meaningful progress often depends on revisiting established tools with renewed understanding. To see the future of myocarditis clearly, we must still, quite literally, look at the heart itself.