Myocarditis is an inflammatory disease of the myocardium, and its diagnosis remains challenging owing to a varying clinical presentation and broad spectrum of underlying aetiologies. In clinical practice, cardiovascular magnetic resonance has become an invaluable non-invasive imaging tool in the evaluation of patients with clinically suspected myocarditis, mainly thanks to its unique multiparametric tissue characterization ability. Although considered as useful, the method also has its limitations. This review aims to provide an up-to-date overview of the strengths and weaknesses of cardiovascular magnetic resonance in the diagnostic work-up of patients with clinically suspected myocarditis in a broad clinical context.

Myocarditis is a disease caused by cardiac inflammation that can progress to dilated cardiomyopathy, heart failure, and eventually death. Several etiologies, including autoimmune, drug-induced, and infectious, lead to inflammation, which causes damage to the myocardium, followed by remodeling and fibrosis. Although there has been an increasing understanding of pathophysiology, early and accurate diagnosis, and effective treatment remain challenging due to the high heterogeneity. As a result, many patients have poor prognosis, with those surviving at risk of long-term sequelae. Current diagnostic methods, including imaging and endomyocardial biopsy, are, at times, expensive, invasive, and not always performed early enough to affect disease progression. Therefore, the identification of accurate, cost-effective, and prognostically informative biomarkers is critical for screening and treatment. The review then focuses on the biomarkers currently associated with these conditions, which have been extensively studied via blood tests and imaging techniques. The information within this review was retrieved through extensive literature research conducted on major publicly accessible databases and has been collated and revised by an international panel of experts. The biomarkers discussed in the article have shown great promise in clinical research studies and provide clinicians with essential tools for early diagnosis and improved outcomes.

Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function. Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg ^–/– mice). In 9- to 10-week-old hUgcg ^–/– mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg ^–/– mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg ^–/– mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors. Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function. Cardiac glycosphingolipids are required to maintain β-adrenergic signaling and contractile capacity in cardiomyocytes and to preserve normal heart function.

Neutrophil-to-lymphocyte ratio (NLR) is an easy-to-use inflammatory biomarker. Baseline NLR is independently associated with incident cardiovascular events and all-cause mortality. However, whether this applies to acute myocarditis (AM) has not been evaluated. The present study aimed to investigate the prognostic value of NLR in patients with AM. A total of 1,150 consecutive patients with a diagnosis of AM admitted to 10 international tertiary referral cardiac centers were included in the study. The diagnosis was confirmed using cardiac magnetic resonance or endomyocardial biopsy. The primary outcome measure was a composite of all-cause mortality or heart transplantation. Patients were divided into 2 groups according to an NLR cutoff of 4 derived from spline regression analysis and 70:30 train-test split algorithm. Patients with an NLR <4 were younger and more likely to present with chest pain, and those with an NLR ≥4 were more likely to present with breathlessness and have other comorbidities. Over a median follow-up of 228 weeks, a NLR ≥4 was associated with a worse prognosis (P < 0.0001). After adjustment for prognostic variables, NLR emerged as an independent predictor of outcome (HR: 3.03 [95% CI: 1.30-7.04]; P = 0.010). Elevated NLR remained associated with worse outcomes among patients with preserved ejection fraction at baseline, who are conventionally considered to be at lower risk of adverse events (P < 0.0001). In patients with AM, elevated NLR is associated with worse prognosis and may be valuable for stratifying patients, even those conventionally considered at low risk.

Background: Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM.Method: We compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020.Results: The median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5–60.9] and 2.98 [0.6–40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001).Conclusion: GCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.