Pathology of explanted pediatric hearts: An 11-year study. Population characteristics and implications for outcomes.

BACKGROUND: As more pediatric patients become candidates for heart transplantation (HT), understanding pathological predictors of outcome and the accuracy of the pretransplantation evaluation are important to optimize utilization of scarce donor organs and improve outcomes. The authors aimed to investigate explanted heart specimens to identify pathologic predictors that may affect cardiac allograft survival after HT. METHODS: Explanted pediatric hearts obtained over an 11-year period were analyzed to understand the patient demographics, indications for transplant, and the clinical-pathological factors. RESULTS: In this study, 149 explanted hearts, 46% congenital heart defects (CHD), were studied. CHD patients were younger and mean pulmonary artery pressure and resistance were significantly lower than in cardiomyopathy patients. Twenty-one died or underwent retransplantation (14.1%). Survival was significantly higher in the cardiomyopathy group at all follow-up intervals. There were more deaths and the 1-, 5- and 7-year survival was lower in patients ≤10 years of age at HT. Early rejection was significantly higher in CHD patients exposed to homograft tissue, but not late rejection. Mortality/retransplantation rate was significantly higher and allograft survival lower in CHD hearts with excessive fibrosis of one or both ventricles. Anatomic diagnosis at pathologic examination differed from the clinical diagnosis in eight cases. CONCLUSIONS: Survival was better for the cardiomyopathy group and patients >10 years at HT. Prior homograft use was associated with a higher prevalence of early rejection. Ventricular fibrosis (of explant) was a strong predictor of outcome in the CHD group. We presented several pathologic findings in explanted pediatric hearts.

Explainable synthetic image generation to improve risk assessment of rare pediatric heart transplant rejection.

Expert microscopic analysis of cells obtained from frequent heart biopsies is vital for early detection of pediatric heart transplant rejection to prevent heart failure. Detection of this rare condition is prone to low levels of expert agreement due to the difficulty of identifying subtle rejection signs within biopsy samples. The rarity of pediatric heart transplant rejection also means that very few gold-standard images are available for developing machine learning models. To solve this urgent clinical challenge, we developed a deep learning model to automatically quantify rejection risk within digital images of biopsied tissue using an explainable synthetic data augmentation approach. We developed this explainable AI framework to illustrate how our progressive and inspirational generative adversarial network models distinguish between normal tissue images and those containing cellular rejection signs. To quantify biopsy-level rejection risk, we first detect local rejection features using a binary image classifier trained with expert-annotated and synthetic examples. We converted these local predictions into a biopsy-wide rejection score via an interpretable histogram-based approach. Our model significantly improves upon prior works with the same dataset with an area under the receiver operating curve (AUROC) of 98.84% for the local rejection detection task and 95.56% for the biopsy-rejection prediction task. A biopsy-level sensitivity of 83.33% makes our approach suitable for early screening of biopsies to prioritize expert analysis. Our framework provides a solution to rare medical imaging challenges currently limited by small datasets.

NVTrans-UNet: Neighborhood vision transformer based U-Net for multi-modal cardiac MR image segmentation.

With the rapid development of artificial intelligence and image processing technology, medical imaging technology has turned into a critical tool for clinical diagnosis and disease treatment. The extraction and segmentation of the regions of interest in cardiac images are crucial to the diagnosis of cardiovascular diseases. Due to the erratically diastolic and systolic cardiac, the boundaries of Magnetic Resonance (MR) images are quite fuzzy. Moreover, it is hard to provide complete information using a single modality due to the complex structure of the cardiac image. Furthermore, conventional CNN-based segmentation methods are weak in feature extraction. To overcome these challenges, we propose a multi-modal method for cardiac image segmentation, called NVTrans-UNet. Firstly, we employ the Neighborhood Vision Transformer (NVT) module, which takes advantage of Neighborhood Attention (NA) and inductive biases. It can better extract the local information of the cardiac image as well as reduce the computational cost. Secondly, we introduce a Multi-modal Gated Fusion (MGF) network, which can automatically adjust the contributions of different modal feature maps and make full use of multi-modal information. Thirdly, the bottleneck layer with Atrous Spatial Pyramid Pooling (ASPP) is proposed to expand the feature receptive field. Finally, the mixed loss is added to the cardiac image to focus the fuzzy boundary and realize accurate segmentation. We evaluated our model on MyoPS 2020 dataset. The Dice score of myocardial infarction (MI) was 0.642 ± 0.171, and the Dice score of myocardial infarction + edema (MI + ME) was 0.574 ± 0.110. Compared with the baseline, the MI increases by 11.2%, and the MI + ME increases by 12.5%. The results show the effectiveness of the proposed NVTrans-UNet in the segmentation of MI and ME.

Cardiac involvement in Multisystem Inflammatory Syndrome in Children cases.

Multisystem Inflammatory Syndrome in Children is a rare form of COVID-19 that affects various organ systems and carries the risk of morbidity and mortality. Cardiac involvement is commonly observed in Multisystem Inflammatory Syndrome in Children cases; hence, this study was conducted to evaluate the cardiac findings of the Multisystem Inflammatory Syndrome in Children cases that were diagnosed and followed up in our hospital. MATERIALS AND METHODS: The medical histories, laboratory results, cardiac findings, and treatments of the cases that were diagnosed with Multisystem Inflammatory Syndrome in Children between December 2020 and August 2021 were evaluated retrospectively. RESULTS: Our study group consisted of 14 males and 12 females whose median age was 3.67 years. Of the 26 patients, 24 had echocardiographic findings and 12 cases had cardiac pathologies that were mostly mild. Among these, mitral valve insufficiency, coronary artery pathology, and pericardial effusion were the most common. Perivascular brightness, aortic and tricuspid insufficiency, systolic dysfunction, and tricuspid thrombosis were less common. The cardiac pathologies of all patients resolved in less than a month following treatment. CONCLUSION: Although the cardiac pathologies of Multisystem Inflammatory Syndrome in Children cases disappear fairly rapidly, the long-term cardiac effects of this disease are not known clearly. To improve our current understanding of Multisystem Inflammatory Syndrome in Children, more multi-centred studies with long-term follow-up periods should be conducted, and treatment protocols for cases of different severities should be developed to maximise the treatments' efficacy.

Cardiac Pathology in Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy affecting adults and children, is a multi-systemic disorder affecting skeletal, cardiac, and smooth muscles as well as neurologic, endocrine and other systems. This review is on the cardiac pathology associated with DM1. The heart is one of the primary organs affected in DM1. Cardiac conduction defects are seen in up to 75% of adult DM1 cases and sudden death due to cardiac arrhythmias is one of the most common causes of death in DM1. Unfortunately, the pathogenesis of cardiac manifestations in DM1 is ill defined. In this review, we provide an overview of the history of cardiac studies in DM1, clinical manifestations, and pathology of the heart in DM1. This is followed by a discussion of emerging data about the utility of cardiac magnetic resonance imaging (CMR) as a biomarker for cardiac disease in DM1, and ends with a discussion on models of cardiac RNA toxicity in DM1 and recent clinical guidelines for cardiologic management of individuals with DM1.

The ASCOD Phenotyping of Embolic Strokes of Undetermined Source.

BACKGROUND AND PURPOSE: Various pathogenesis are presumed to be involved in the etiology of embolic stroke of undetermined source (ESUS), which has a high recurrence rate, and much remains unknown about the clinical subtype of recurrent stroke. The purpose of this study was to clarify the pathogenesis of ESUS using the ASCOD classification for ESUS patients and to examine the factors involved in the recurrence of ischemic stroke. METHODS: The subjects of this study were 236 of these patients who fulfilled the criteria for ESUS. The rate of stroke recurrent, subtype of recurrent ischemic stroke, and new-onset atrial fibrillation (AF) in these patients were surveyed retrospectively, and each patient was graded for the A, S, and C categories of the ASCOD classification. RESULTS: Ischemic stroke recurred in 32 patients during the follow-up period (7 days to 12.9 years [median 54.3 months]), and new-onset AF was seen in 44 (18.6%) patients. The most subtype of recurrent ischemic stroke was ESUS again (19 patients). Multivariate analysis with a Cox proportional hazards model, the S score (hazard ratio 5.21; 95% confidence interval (CI) 2.38-11.42; P < .001) and the number of A, S, C categories (hazard ratio 1.90; 95% CI 1.14-3.10; P = .013) were factors significantly related to recurrent ischemic stroke. CONCLUSIONS: Assessment of comorbid conditions in ESUS patients based on the ASCOD classification may be useful in predicting the likelihood of recurrence of ischemic stroke.

CIRP downregulation renders cardiac cells prone to apoptosis in heart failure.

OBJECTIVES: Cold-inducible RNA binding protein (CIRP) is a stress protein which is involved in regulating multiple cellular processes. However, its role in pathological heart diseases is still unknown. Our current study was aimed at addressing the response and functional role of CIRP in heart failure. METHODS: CIRP protein level was evaluated in heart samples from patients with heart failure and mice with post-myocardial infarction (post-MI). Cardiac-derived H9C2 cells were utilized to test the effects of CIRP deficiency on cell survival and apoptosis in response to H2O2 treatment. RESULTS: Reduced expression of cardiac CIRP was observed in patients with heart failure, mice with post-MI. In addition, knockdown of CIRP exacerbated cell apoptosis and cell death in response to H2O2 treatment, suggesting a protective role of CIRP in cell apoptosis induced by oxidative stress in the heart. CONCLUSIONS: Our findings suggest that altered expression of CIRP may be involved in the pathogenesis of heart failure and downregulation of CIRP may render cardiac cells prone to apoptosis in heart failure.

Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease.

Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured in either the acute or chronic stage of infection with benznidazole. At the experimental endpoint (5 to 6 months postinfection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct T. cruzi lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine T. cruzi infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level.

Complexity of consenting for medical termination of pregnancy: prospective and longitudinal study in Paris.

BACKGROUND: We analyzed the patients' perception of prenatal diagnosis of fetal cardiac pathology, and the reasons for choosing to continue with pregnancy despite being eligible to receive a medical termination of pregnancy. We also identified the challenges, the motives interfering in decision-making, and the consequences of the decisions on pregnancy, child and mother. METHODS: This descriptive, prospective and longitudinal study was conducted in France, amongst pregnant women who wished to continue their pregnancy despite an unfavorable medical advice (incurable fetal cardiac pathologies). Socio-demographic data were collected through a questionnaire. Such questionnaire covered information assessing the parents/mother's perception of prenatal diagnosis, and medical termination of pregnancy, their interpretation of the established diagnosis and their motives for not considering pregnancy termination. RESULTS: 72 eligible patients were analyzed over one year: mean age 33 ± 6.89 years, 47 patients had already given birth to ≥1 healthy child. Mean gestational age at the detection of fetal cardiac pathologies was 30 ± 4.37 weeks of amenorrhea. Patients decided to keep the child after 3 ± 1.25 consultations. 56 (77.78%) patients made their decision with their husbands and 16 made their decision alone. Reasons for declining the medical termination were culpability and responsibility (n = 36), ideologies and convictions (n = 24), mistrust and hope (n = 12). Newborns of 67 patients died with a mean survival duration of 38 days. CONCLUSIONS: Patient informed consent should be sought before any decision in neonatology, even if conflicting with the medical team's knowledge and the pregnant mother's benefits. Decisions to accept or decline pregnancy termination depend on the patients' psychological character, ideologies, convictions, and mistrust in the diagnosis/prognosis, or hope in the fetus survival.

Repair of Partial Anomalous Pulmonary Venous Connection: A Rare Case Evaluated by Multi-Slice Computed Tomographic Angiography.

Partial anomalous pulmonary venous connection (PAPVC) is an uncommon congenital heart disease, which may be difficult to identify and often remains undiagnosed. Accurate diagnosis of major aortopulmonary collaterals and partial anomalous pulmonary venous drainage in patients with congenital heart disease is important but problematic. The goal of this publication is to present the diagnosis and surgical repair of this rare pathology in an eight-year-old boy. Atrial septal defect was found by echocardiography, but no anomalous pulmonary vein was found. However, multi-slice computed tomographic angiography (MSCTA) revealed that the isolated right superior pulmonary vein was replaced by right superior pulmonary vein 1 (RSPV1), right superior pulmonary vein 2 (RSPV2) and right superior pulmonary vein 3 (RSPV3), which connected to the superior vena cava (SVC), the orifice of SVC, and the left atrium, respectively. The patient underwent the repair of PAPVC with division of the SVC and re-implantation on the right atrial appendage to restore normal systemic venous drainage. Postoperative course was uneventful. In conclusion, PAPVC is a rare congenital cardiac pathology. MSCTA could contribute to an accurate anatomic and functional definition of this variant.

Strenuous Exercise and Cardiovascular Disease Outcomes.

PURPOSE OF REVIEW: This review summarizes several issues at the forefront of recent controversies involving the appropriate exercise dose including epidemiologic data describing mortality trends in those who engage in high levels of physical activity and recent observational data suggesting adverse cardiovascular outcomes among long-term endurance athletes. RECENT FINDINGS: The benefits of habitual and moderate levels of exercise on cardiovascular disease outcomes in the general population have been well established. However, recent data have questioned whether higher doses of physical and athletic activity are associated with adverse cardiovascular outcomes. Specifically in regard to adverse cardiovascular outcomes, the evidence and limitations of the available data associating veteran endurance athletes with an increased risk of atrial fibrillation, exercise-induced arrhythmogenic cardiac remodeling, and accelerated coronary atherosclerosis will be discussed. This review will also provide a conceptual framework in the context of the clinical management of athletic patients and will highlight key areas of future research that may resolve many of these controversial issues.

Extra-cardiac findings in cardiovascular magnetic resonance: what the imaging cardiologist needs to know.

Cardiovascular magnetic resonance (CMR) is an established non-invasive technique to comprehensively assess cardiovascular structure and function in a variety of acquired and inherited cardiac conditions. A significant amount of the neck, thorax and upper abdomen are imaged at the time of routine clinical CMR, particularly in the initial multi-slice axial and coronal images. The discovery of unsuspected disease at the time of imaging has ethical, financial and medico-legal implications. Extra-cardiac findings at the time of CMR are common, can be important and can change clinical management. Certain patient groups undergoing CMR are at particular risk of important extra-cardiac findings as several of the cardiovascular risk factors for atherosclerosis are also risk factors for malignancy. Furthermore, the presence of certain extra-cardiac findings may contribute to the interpretation of the primary cardiac pathology as some cardiac conditions have multi-systemic extra-cardiac involvement. The aim of this review is to give an overview of the type of extra-cardiac findings that may become apparent on CMR, subdivided by anatomical location. We focus on normal variant anatomy that may mimic disease, common incidental extra-cardiac findings and important imaging signs that help distinguish sinister pathology from benign disease. We also aim to provide a framework to the approach and potential further diagnostic work-up of incidental extra-cardiac findings discovered at the time of CMR. However, it is beyond the scope of this review to discuss and determine the clinical significance of extracardiac findings at CMR.

RETROSPECTIVE ANALYSIS OF ADULT-ONSET CARDIAC DISEASE IN FRANÇOIS' LANGURS (TRACHYPITHECUS FRANCOISI) HOUSED IN U.S. ZOOS.

Cardiac disease is a common condition in captive primates, and multiple cases in François' langurs ( Trachypithecus francoisi ) were noted on review of the Species Survival Plan studbook. To determine the prevalence of cardiac disease in this species, surveys were distributed to current and previous holding institutions (n = 23) for the U.S. studbook population (n = 216). After exclusion of stillbirths (n = 48), animals less than 1 yr of age (n = 8), and animals housed internationally (n = 2), a study group (n = 158) was identified for this analysis. Robust data was received for 98.7% (n = 156) of the study group and antemortem and postmortem cardiac abnormalities were reported for 25.3% (n = 40) of these animals. Eight animals were reported as medically managed for clinical cardiac disease, and three of these were alive at the time of survey. Six of 11 animals with radiographic cardiac silhouette enlargement antemortem were noted with cardiomegaly on postmortem examination. Of 102 deceased animals in the study group, four were identified with dilated cardiomyopathy, and varying degrees of myocardial fibrosis was observed in 18 animals. Langurs with cardiac fibrosis were found to be significantly older than langurs without cardiac fibrosis (P = 0.003) and more commonly were male (P = 0.036). Screening tests for cardiac disease, such as thoracic radiographs and echocardiography, are recommended to diagnose affected animals earlier, to monitor progression of disease, and to guide treatment, although they should be interpreted with caution because of apparent insensitivity when compared with pathologic results.

Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner.

YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology.

Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes.

The network for cardiac fuel metabolism contains intricate sets of interacting pathways that result in both ATP-producing and non-ATP-producing end points for each class of energy substrates. The most salient feature of the network is the metabolic flexibility demonstrated in response to various stimuli, including developmental changes and nutritional status. The heart is also capable of remodeling the metabolic pathways in chronic pathophysiological conditions, which results in modulations of myocardial energetics and contractile function. In a quest to understand the complexity of the cardiac metabolic network, pharmacological and genetic tools have been engaged to manipulate cardiac metabolism in a variety of research models. In concert, a host of therapeutic interventions have been tested clinically to target substrate preference, insulin sensitivity, and mitochondrial function. In addition, the contribution of cellular metabolism to growth, survival, and other signaling pathways through the production of metabolic intermediates has been increasingly noted. In this review, we provide an overview of the cardiac metabolic network and highlight alterations observed in cardiac pathologies as well as strategies used as metabolic therapies in heart failure. Lastly, the ability of metabolic derivatives to intersect growth and survival are also discussed.

Ultrastructural cardiac pathology: the wide (yet so very small) world of cardiac electron microscopy.

Electron microscopy (EM) was a popular diagnostic tool in the 1970s and early 80s. With the adoption of newer, less expensive techniques, such as immunohistochemistry, the role of EM in diagnostic surgical pathology has dwindled substantially. Nowadays, even in academic centers, EM interpretation is relegated to renal pathologists and the handful of (aging) pathologists with experience using the technique. As such, EM interpretation is truly arcane-understood by few and mysterious to many. Nevertheless, there remain situations in which EM is the best or only ancillary test to ascertain a specific diagnosis. Thus, there remains a critical need for the younger generation of surgical pathologists to learn EM interpretation. Recognizing this need, cardiac EM was made the theme of the Cardiovascular Evening Specialty Conference at the 2023 United States and Canadian Academy of Pathology (USCAP) annual meeting in New Orleans, Louisiana. Each of the speakers contributed their part to this article, the purpose of which is to review EM as it pertains to myocardial tissue and provide illustrative examples of the spectrum of ultrastructural cardiac pathology seen in storage/metabolic diseases, cardiomyopathies, infiltrative disorders, and cardiotoxicities.

Association of Shock Index with Echocardiographic Parameters in Cardiac Intensive Care Unit.

BACKGROUND: A high shock index (SI), the ratio of heart rate (HR) to systolic blood pressure (SBP), has been associated with unfavorable outcomes. We sought to determine the hemodynamic underpinnings of an elevated SI using 2-D and doppler Transthoracic Echocardiography (TTE) in unselected cardiac intensive care unit (CICU) patients. METHODS: We included Mayo Clinic CICU admissions from 2007 to 2018 who were in sinus rhythm at the time of TTE. The SI was calculated using HR and SBP at the time of TTE. Patients were grouped according to SI: <0.7, 4012 (64%); 0.7-0.99, 1764 (28%); and ≥ 1.0, 513 (8%). Pearson's correlation coefficient was used to assess associations between continuous variables. RESULTS: We included 6289 unique CICU patients, 58% of whom had acute coronary syndrome. The median age was 67.9 years old and 37.8% were females. The mean SI was 0.67 BPM/mmHg. As the SI increased, markers of left ventricular (LV) systolic function and forward flow decreased, including left ventricular ejection fraction (LVEF), fractional shortening, left ventricular outflow tract (LVOT) velocity time integral (VTI), stroke volume, LV stroke work index, and cardiac power output. Biventricular filling pressures increased, and markers of right ventricular function worsened with rising SI. Most TTE measurements reflecting LV function and forward flow were inversely correlated with SI, including LV stroke work index (r = -0.59) and LVOT VTI (r = -0.41), as were both systemic vascular resistance index (r = -0.43) and LVEF (r = -0.23). CONCLUSION: CICU patients with elevated SI have worse biventricular function and systemic hemodynamics, particularly decreased stroke volume and related calculated TTE parameters. The SI is an easily available marker that can be used to identify CICU patients with unfavorable hemodynamics who may require further assessment.

Blood Pressure/Heart Rate-Derived Ratios as Indices of Health and Cardiovascular Pathology.

This communication, based on a review of the relevant literature on ratios deriving from blood pressure and heart rate measurements, and their conformance/nonconformance to the mathematical golden rule (ie, 1.681), proposes that such ratios, particularly emanating from large numbers of home blood pressure and heart rate measurements obtained by the patients themselves or their caretakers, may constitute new risk markers, useful in the assessment of health and cardiovascular pathologies, prognosis of morbidity and mortality, and implementation to clinical practice and research.

Relative apical sparing in cardiac amyloidosis is not always explained by an amyloid gradient.

AIMS: Myocardial longitudinal strain (LS) by two-dimensional (2D) speckle-tracking echocardiography has a diagnostic and prognostic role in cardiac amyloidosis (CA). Typically, the apical segments of the left ventricle (LV) are less affected by LS abnormalities, a finding called relative apical sparing (RELAPS). Whether a variable burden of CA might explain the RELAPS remains unknown.We aimed to evaluate the extent, distribution, and deposition pattern of amyloid in autopsy hearts of CA patients and to correlate the histopathology findings with 2D echocardiography. METHODS AND RESULTS: This is a retrospective study of whole heart specimens of CA patients who died and underwent autopsy and 2D echocardiography. Amyloid burden quantification was assessed by histomorphometry in each segment at different LV levels. The LS analysis results were compared with the amyloid burden and the base-to-apex distribution.Histopathology investigation of 27 hearts with CA [immunoglobulin light chains (AL) 17 cases and transthyretin (ATTR) 10 cases] demonstrated an amyloid base-to-apex gradient. In 11 CA patients with 2D echocardiography, analysis of LS and histological amyloid burden allowed to identify different patterns: RELAPS (8 cases, 73%), with (2) or without (6) amyloid gradient, normal or mildly reduced LS with diffuse low amyloid (2, 18%), and severely reduced LS with diffuse high amyloid (1, 9%). CONCLUSION: The typical RELAPS pattern at echocardiography is not always explained by a base-to-apex gradient of amyloid burden at histopathology, suggesting that RELAPS might be an epiphenomenon of complex interactions among amyloid infiltration, myocardial structure, and adaptation.

Autopsy-based histopathological characterization of myocarditis after anti-SARS-CoV-2-vaccination.

Cases of myocarditis, diagnosed clinically by laboratory tests and imaging have been described in the context of mRNA-based anti-SARS-CoV-2 vaccination. Autopsy-based description of detailed histological features of vaccine-induced myocarditis is lacking. We describe the autopsy findings and common characteristics of myocarditis in untreated persons who received anti-SARS-CoV-2 vaccination. Standardized autopsies were performed on 25 persons who had died unexpectedly and within 20 days after anti-SARS-CoV-2 vaccination. In four patients who received a mRNA vaccination, we identified acute (epi-)myocarditis without detection of another significant disease or health constellation that may have caused an unexpected death. Histology showed patchy interstitial myocardial T-lymphocytic infiltration, predominantly of the CD4 positive subset, associated with mild myocyte damage. Overall, autopsy findings indicated death due to acute arrhythmogenic cardiac failure. Thus, myocarditis can be a potentially lethal complication following mRNA-based anti-SARS-CoV-2 vaccination. Our findings may aid in adequately diagnosing unclear cases after vaccination and in establishing a timely diagnosis in vivo, thus, providing the framework for adequate monitoring and early treatment of severe clinical cases.