Congenital heart defects (CHDs) are the most common malformation amongst newborns, with a prevalence of approximately 0.8–2

BACKGROUND AND OBJECTIVE:Pediatric patients with myocarditis present with heterogeneous symptoms, disease courses and outcomes. Late Gadolinium Enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) is a routine diagnostic tool, but relationships between LGE patterns and patient characteristics are typically assessed qualitatively. We investigate the use of radiomic features to quantify LGE texture and location to identify signatures that stratify pediatric myocarditis cases. METHODS:We compared radiomic features in a digital phantom across different resampling strategies to address variability in patient size and imaging parameters. Non-negative matrix factorization (NMF) was applied to spatially resolved radiomic features of the left myocardium to identify distinct radiomic signatures in a pediatric cohort with confirmed myocarditis. Clinical parameters were compared across the resulting groups, and correlations between image meta-features and outcomes explored. A user-friendly software tool offers feature extraction and signature calculation on unseen data and comparison of new patients to the existing cohort. RESULTS:The phantom experiments showed improved comparability of radiomic features when resampled to uniform voxel density (voxel count per myocardial diameter) rather than uniform voxel size. After appropriate pre-processing, NMF identified four patient groups with distinct LGE signatures within 195 patients (median age 16 years, 19% female). One group separates out patients with signs of heart failure, correlating with left-ventricular ejection fraction (r=-0.38, 95% CI [-0.50,-0.25]) and log(NT-proBNP) (r=0.36,[0.21,0.50]). A second group's dominant meta-feature correlates with myocardial edema (r=0.27,[0.13,0.40]) and ventricular tachycardia (r=0.19,[0.05,0.32]); a third indicates mild presentation. The clinical relevance of the fourth remains unclear. CONCLUSIONS:Spatially resolved radiomic features from suitably resampled LGE CMR images yield quantitative LGE signatures associated with clinical characteristics in pediatric myocarditis, supporting improved stratification and personalized management in the long run.

Several studies have demonstrated the value of large-scale human exome and genome data analysis to maximise gene discovery in rare diseases. Using this approach, we have analysed the exomes of 4747 cases and 52,881 controls to identify genes which confer a substantial risk of congenital heart disease (CHD). We identified both rare loss-of-function and missense coding variants in 14 genes, which reached genome-wide significance at FDR 5%. Ten genes have been associated with CHD, whereas four genes (PBX1, KAT6B, SHOX2, HCAR1) have not been reported as genome-wide significant so far. We highlight distinct genetic contributions to syndromic and non-syndromic CHD by independently analysing probands from these two groups. In addition, by integrative analysis of exome data with single-cell transcriptomics data from human embryonic hearts, we identified cardiac-specific cells, such as neural crest cells and endothelial cells, as well as putative biological processes underlying the pathogenesis of CHD. In summary, our findings strengthen the association of known CHD genes and have identified additional novel disease genes contributing to the aetiology of CHD.

Einleitung: Nach niedrigen Inzidenzen des Parvovirus B19 (B19V) 2020–2022 gab es seit Ende 2023 europaweit eine starke B19V-Infektionswelle. Eine B19V-Infektion kann als seltene Komplikation eine Myokarditis verursachen. Im Juli 2024 wurden 4 Kinder mit fulminanter Myokarditis (Alter: 7–20 Monate) in ein Hamburger Krankenhaus aufgenommen. Drei der Kinder verstarben innerhalb von 3 Tagen. Bei allen 4 Kindern wurde B19V in unterschiedlichen Probenmaterialien nachgewiesen. Erste Ermittlungen der zuständigen Gesundheitsbehörden zeigten keine Anzeichen für nosokomiale Übertragung oder gemeinsame Expositionen. Wir intensivierten die gemeinsame Ausbruchsuntersuchung mit dem Ziel, das Ausmaß des Ausbruchs abschätzen zu können und B19V oder andere Faktoren als Ursache der Myokarditiden zu identifizieren. Ein weiteres Ziel war, zu analysieren, in wie weit die B19V-Infektionswelle diesen Myokarditis-Ausbruch erklären könnte, oder ob möglicherweise eine erhöhte Erregervirulenz eine Rolle spielen könnte.

Purpose: Myocarditis in pediatric patients can lead to severe heart failure, necessitating ventricular assist devices (VAD) which might serve as a bridge to transplant or as a temporary circulatory support until myocardial recovery. We aimed to identify differences in the clinical and diagnostic findings at initial admission between pediatric patients who could be successfully weaned from VAD and those who could not.

Background/Objectives: Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Methods: Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis “MYKKE”. Age- and sex-adjusted logistic regression and ROC analysis identified predictors of cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, atrioventricular blockage III°) and major adverse cardiac events (MACE: need for mechanical circulatory support (MCS), cardiac transplantation, and/or cardiac death). Results: Echocardiograms from 175 patients (median age 15 years, IQR 7.9–16.5 years; 70% male) across 13 centers were included. Cardiac arrhythmias occurred in 36 patients (21%), and MACE in 28 patients (16%). Impaired LV LS strongly correlated with reduced LVEF (r > 0.8). Impaired layer-specific LV LS, reduced LVEF, LV dilatation, and increased BSA-indexed LV mass, were associated with the occurrence of MACE and cardiac arrhythmias. In patients with preserved LVEF, LV LS alone predicted cardiac arrhythmias (p < 0.001), with optimal cutoff values of −18.0% for endocardial LV LS (sensitivity 0.69, specificity 0.94) and –17.0% for midmyocardial LV LS (sensitivity 0.81, specificity 0.75). Conclusions: In pediatric myocarditis, STE-derived LV LS is not only a valuable tool for assessing systolic myocardial dysfunction and predicting MACE but also identifies patients at risk for cardiac arrhythmias, even in the context of preserved LVEF.

Introduction: Multicenter studies show that demographic and CMR-based volumetrics and strain predict death, ventricular tachycardia and fibrillation (DVTF) in repaired tetralogy of Fallot (rTOF). We developed a novel deep learning method to calculate radial (RS) and circumferential strain (CS) from end-diastole (ED) to other key frames: mid systole (MS), end-systole (ES), peak flow (PF) in diastole, and mid-diastole (MD) (called ED2K), as well as from each key frame to the next (called K2K strain), for each left ventricle (LV) segment. Hypothesis: We hypothesized that: H1) ED-ES strain; H2) septal strain; and H3) diastolic strain would be additionally predictive of DVTF as compared to a traditional model. Approach: 704 patients combined from the German Competence Network and INDICATOR cohorts had ED2K and K2K strain values calculated using CMR short axis stack. We first created a 4-variable “traditional” logistic regression model including age at CMR, RVEF%, LVEF% and RVESVi. We then separately added ED2K and K2K parameters to assess increased ability to discriminate DVTF, measured by the c-statistic. Results: In univariate analyses, H1: ED to ES RS and CS; H2: multiple systolic septal and non-septal variables; and H3: overall diastolic RS and CS were significantly associated with DVTF, with c-statistics between 0.65 and 0.73 (n=56, Table 1). When added to the traditional model, H1: ED to ES CS; and H2: septal and non-septal CS slightly improved model performance (Table 2). Model calibration was adequate for all models. Conclusion: Our key-frame specific strain recapitulates the CS prediction of adverse events in rTOF, and slightly improves prediction in a multiparameter model. Future work includes external validation.

Background: The spectrum of myocarditis ranges from asymptomatic courses to severe heart failure. Cardiac arrhythmias are another feared complication. The aim of this study is to evaluate initial arrhythmias and their occurrence in the long-term course in pediatric patients with myocarditis to define certain risks.

Cardiac magnetic resonance (CMR) sequences visualise the cardiac function voxel-wise over time. Simultaneously, deep learning-based deformable image registration is able to estimate discrete vector fields which warp one time step of a CMR sequence to the following in a self-supervised manner. However, despite the rich source of information included in these 3D+t vector fields, a standardised interpretation is challenging and the clinical applications remain limited so far. In this work, we show how to efficiently use a deformable vector field to describe the underlying dynamic process of a cardiac cycle in form of a derived 1D motion descriptor. Additionally, based on the expected cardiovascular physiological properties of a contracting or relaxing ventricle, we define a set of rules that enables the identification of five cardiovascular phases including the end-systole (ES) and end-diastole (ED) without the usage of labels. We evaluate the plausibility of the motion descriptor on two challenging multi-disease, -center, -scanner short-axis CMR datasets. First, by reporting quantitative measures such as the periodic frame difference for the extracted phases. Second, by comparing qualitatively the general pattern when we temporally resample and align the motion descriptors of all instances across both datasets. The average periodic frame difference for the ED, ES key phases of our approach is $0.80\pm{0.85}$, $0.69\pm{0.79}$ which is slightly better than the inter-observer variability ($1.07\pm{0.86}$, $0.91\pm{1.6}$) and the supervised baseline method ($1.18\pm{1.91}$, $1.21\pm{1.78}$). Code and labels will be made available on our GitHub repository. https://github.com/Cardio-AI/cmr-phase-detection

BACKGROUND:Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS:Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS:From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS:Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

BackgroundMyocarditis represents one of the most common causes of Sudden Cardiac Death in children. Myocardial involvement during a viral infection is believed to be higher as a consequence of intensive exertion. Recommendations for return to sports are based on cohort and case studies only. This study aims to investigate the relationship between physical activity and myocarditis in the young.PatientEvery patient in the MYKKE registry fulfilling criteria for suspicion of myocarditis was sent a questionnaire regarding the physical activity before, during and after the onset of myocarditis.MethodThis study is a subproject within the MYKKE registry, a multicenter registry for children and adolescents with suspected myocarditis. The observation period for this analysis was 93 months (September 2013–June 2021). Anamnestic, cardiac magnetic resonance images, echocardiography, biopsy and laboratory records from every patient were retrieved from the MYKKE registry database.Results58 patients (mean age 14.6 years) were enrolled from 10 centers. Most patients participated in curricular physical activity and 36% in competitive sports before the onset of myocarditis. There was no significant difference of heart function at admission between the physically active and inactive subjects (ejection fraction of 51.8 ± 8.6% for the active group vs. 54.4 ± 7.7% for the inactive group). The recommendations regarding the return to sports varied widely and followed current guidelines in 45%. Most patients did not receive an exercise test before returning to sports.ConclusionSports before the onset of myocarditis was not associated with a more severe outcome. There is still a discrepancy between current literature and actual recommendations given by health care providers. The fact that most participants did not receive an exercise test before being cleared for sports represents a serious omission.

Purpose: Donor-derived cell-free DNA (dd-cfDNA) is utilized by some adult lung transplant (LTX) centers as a biomarker of allograft injury or dysfunction.An elevated level of dd-cfDNA may be predictive of acute cellular rejection, antibody mediated rejection (AMR), chronic lung allograft dysfunction , or acute infection.Therefore, dd-cfDNA may have a role as a surrogate test for graft surveillance versus invasive methods including bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBX).While there is an existing body of literature on the role of dd-cfDNA in adult LTX, there is limited understanding of its utility in pediatric patients.Non-invasive testing such as dd-cfDNA may be particularly helpful in young children with inherent challenges with TBBX.Methods: Our center performed three bilateral LTX in pediatric patients in which we used dd-cfDNA as an adjunctive method of graft surveillance.All were females, ranging in age from 2-11 years.We obtained dd-cfDNA levels prior to bronchoscopy, BAL and TBBX .The % dd-cfDNA was evaluated in conjunction with clinical symptoms, BAL and TBBX results, and measurements of panel reactive antibody (cPRA) and donor specific antibodies.Results: The specific diagnoses leading to transplant were interstitial lung disease related to juvenile idiopathic arthritis, post-infectious bronchiolitis obliterans, and alveolar capillary dysplasia.Results of data collected are summarized in Table 1.Conclusion: In this small cohort of pediatric LTX recipients, we found consistently elevated dd-cfDNA levels.In two patients, dd-cfDNA levels did not correlate with histological evidence of graft dysfunction.However, in one patient, sustained high dd-cfDNA values may have signaled ongoing graft injury from AMR as a precedent to the onset of symptoms, subsequent respiratory failure, and ultimate clinical demise.Further investigation into dd-cfDNA as a biomarker of allograft injury in pediatric LTX recipients is needed.

Background: Several studies described occurrence of myocarditis after SARS-CoV-2 vaccination in pediatric patients. We aimed to characterize the clinical course of myocarditis following SARS-CoV2 vaccination including follow-up data within the prospective German registry for suspected myocarditis in children and adolescents “MYKKE.”

Background: Myocarditis is an inflammatory entity of the myocardium that can lead to severe heart failure. Recently, we showed that pediatric myocarditis with dilated cardiomyopathy (DCM) phenotype is caused by pathogenic genetic variants in cardiomyopathy genes. The potential role of defects in immune disorder genes was not investigated.

Background: Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis. Methods: Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic). Results: A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased. Conclusion: Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.