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The diagnosis and specific and causal treatment of myocarditis and inflammatory cardiomyopathy remain a major clinical challenge. Despite the rapid development of new imaging techniques, endomyocardial biopsies remain the gold standard for accurate diagnosis of inflammatory myocardial disease. With the introduction and continued development of immunohistochemical inflammation diagnostics in combination with viral nucleic acid testing, myocarditis diagnostics have improved significantly since their introduction. Together with new technologies such as miRNA and gene expression profiling, quantification of specific immune cell markers, and determination of viral activity, diagnostic accuracy and patient prognosis will continue to improve in the future. In this review, we summarize the current knowledge on the pathogenesis and diagnosis of myocarditis and inflammatory cardiomyopathies and highlight future perspectives for more in-depth and specialized biopsy diagnostics and precision, personalized medicine approaches.

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.

Background/Objectives: To assess free-breathing, dynamic radial magnetic resonance angiography (MRA) for detecting endoleaks post-endovascular aortic repair (EVAR) in cases with inconclusive computed tomography angiography (CTA). Methods: This prospective single-center study included 17 participants (mean age, 70 ± 9 years; 13 males) who underwent dynamic radial MRI (Golden-angle RAdial Sparse Parallel-Volumetric Interpolated BrEath-hold, GRASP-VIBE) after inconclusive multiphasic CT for the presence of endoleaks during the follow-up of EVAR-treated abdominal aortic aneurysms. CT and MRI datasets were independently assessed by two radiologists for image quality, diagnostic confidence, and the presence/type of endoleak. Statistical analyses included interrater and intermethod agreement, and diagnostic performance (sensitivity, specificity, area under the curve (AUC)). Results: Subjective image analysis demonstrated good image quality and interrater agreement (k ≥ 0.6) for both modalities, while diagnostic confidence was significantly higher in MRA (p = 0.03). There was significantly improved accuracy for detecting type II endoleaks on MRA (AUC 0.97 [95% CI: 0.87, 1.0]) compared to CTA (AUC 0.66 [95% CI: 0.41, 0.91]; p = 0.03). Although MRA demonstrated higher values for sensitivity, specificity, AUC, and interrater agreement, none of the other types nor the overall detection rate for endoleaks showed differences in the diagnostic performance over CT (p ≥ 0.12). CTA and MRA revealed slight to moderate intermethod concordance in endoleak detection (k = 0.3–0.64). Conclusions: The GRASP-VIBE MRA characterized by high spatial and temporal resolution demonstrates clinical feasibility with good image quality and superior diagnostic confidence. It notably enhances diagnostic performance in detecting and classifying endoleaks, particularly type II, compared to traditional multiphase CTA with inconclusive findings.

The advent of CAR T cells targeting CD19 or BCMA on B cell neoplasm demonstrated remarkable efficacy, but rapid relapses and primary refractoriness remains challenging. A leading cause of CAR T cell failure is their lack of expansion and limited persistence. Long-lived, self-renewing multipotent T memory stem cells (TSCM) and T central memory cells (TCM) likely sustain superior tumor regression, but their low frequencies in blood from cancer patients impose a major hurdle for clinical CAR T production. We designed a clinically compliant protocol for generating BCMA CAR T cells starting with increased TSCM/TCM cell input. A CliniMACS Prodigy process was combined with flow cytometry-based enrichment of CD62L+CD95+ T cells. Although starting with only 15% of standard T cell input, the selected TSCM/TCM material was efficiently activated and transduced with a BCMA CAR-encoding retrovirus. Cultivation in the presence of IL-7/IL-15 enabled the harvest of CAR T cells containing an increased CD4+ TSCM fraction and 70% TSCM cells amongst CD8+. Strong cell proliferation yielded cell numbers sufficient for clinical application, while effector functions were maintained. Together, adaptation of a standard CliniMACS Prodigy protocol to low input numbers resulted in efficient retroviral transduction with a high CAR T cell yield.