Reductive stress induces unresolved ER stress and proteotoxic cardiomyopathy.

Chronic reductive stress (cRS), induced by constitutive activation of Nrf2 in transgenic (TG) mouse hearts leads to pathological cardiac remodeling and diastolic dysfunction. Transcriptomic analysis revealed that both pro-reductive (PR) and reductive stress (RS) conditions disrupt ER-associated gene expression in a dose-dependent manner, with pronounced dysregulation in high-expressing TG (TGH) mice. These shifts were associated with persistent activation of the unfolded protein response (UPR), impaired ER function, and redox imbalance marked by elevated glutathione and reduced ROS levels.

Electroanatomic localization of idiopathic ventricular arrhythmia origins in the left ventricular outflow tract.

Idiopathic ventricular arrhythmias (VAs) originate from endocardial and epicardial or intramural sites in the left ventricular outflow tract (LVOT). Several specialized ablation techniques such as sequential or simultaneous unipolar ablation, bipolar ablation, and anatomic ablation have been developed to treat those epicardial and intramural VAs. Because those ablation techniques eliminate VA origins across the muscle wall remotely from a different anatomic location, the anatomic sites of successful ablation do not necessarily indicate the true anatomic locations of VA origins.

Tafazzin-deficient zebrafish display mitochondrial dysfunction, neutropenia, and metabolic defects without myopathy.

Barth syndrome is an X-linked syndrome characterized by cardiomyopathy, skeletal myopathy, and neutropenia. This life-threatening disorder results from loss-of-function mutations in TAFAZZIN, which encodes a phospholipid-lysophospholipid transacylase located in the mitochondria inner membrane. Decreased cardiolipin levels and increased monolysocardiolipin levels perturb mitochondrial function.

Tafazzin-Deficient Zebrafish Display Mitochondrial Dysfunction, Neutropenia, and Metabolic Defects Without Myopathy.

Barth syndrome is an X-linked syndrome characterized by cardiomyopathy, skeletal myopathy, and neutropenia. This life-threatening disorder results from loss-of-function mutations in , which encodes a phospholipid-lysophospholipid transacylase located in the mitochondria inner membrane. Decreased cardiolipin levels and increased monolysocardiolipin levels perturb mitochondrial function.

The Cardiovascular Repository for Type 1 Diabetes (CaRe-T1D): An NIDDK Initiative to Advance Understanding of Mechanisms Underlying Cardiovascular Disease in Type 1 Versus Type 2 Diabetes.

Unlabelled: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in individuals with diabetes. Individuals with type 1 diabetes have a two- to fourfold higher risk of CVD in comparison with the general population, driven by an earlier onset and increased lifetime incidence of CVD events and mortality. Similarly, type 2 diabetes confers two- to threefold increased CVD risk, usually alongside metabolic syndrome, obesity, and hypertension.

Late Recurrent Left Atrial Mass in Patient With Patent Foramen Ovale Occluder Device.

Patent foramen ovale (PFO) closure is a widely used procedure to manage recurrent cryptogenic stroke, with most complications occurring in the early postimplantation period. Very late device-related thrombosis, especially more than a decade after placement, is a rare presentation with unique diagnostic and management challenges. We present a case of thromboembolic stroke caused by a left atrial mass of unknown origin attached to a PFO occlusion device placed 15 years prior.

Spatial Transcriptomic Approach to Understanding Coronary Atherosclerotic Plaque Stability.

Background: Coronary atherosclerotic plaques susceptible to acute coronary syndrome have traditionally been characterized by their surrounding cellular architecture. However, with the advent of intravascular imaging, novel mechanisms of coronary thrombosis have emerged, challenging our contemporary understanding of acute coronary syndrome. These intriguing findings underscore the necessity for a precise molecular definition of plaque stability.

Exercise mitigates reductive stress-induced cardiac remodeling in mice.

The endoplasmic reticulum (ER) regulates protein folding and maintains proteostasis in cells. We observed that the ER transcriptome is impaired during chronic reductive stress (RS) in cardiomyocytes. Here, we hypothesized that a prolonged moderate treadmill exercise mitigates the RS-induced ER dysfunction and cardiac remodeling in cardiac-specific constitutively active Nrf2 mice (CaNrf2-TG).

Prevalence and electrocardiographic and electrophysiological characteristics of idiopathic ventricular arrhythmias originating from the septal left ventricular summit.

Introduction: The left ventricular summit (LVS) is the highest point on the epicardial surface of the left ventricle. A part of the LVS that is located between the left coronary arteries (lateral-LVS) is one of the major sites of idiopathic ventricular arrhythmia (VA) origins. Some idiopathic epicardial VAs can be ablated at endocardial sites adjacent to the epicardial area septal to the lateral-LVS (septal-LVS).

Structurally constrained and pathology-aware convolutional transformer generative adversarial network for virtual histology staining of human coronary optical coherence tomography images.

Significance: There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions.

Aim: The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns.

Subclinical maternal autoimmune disease leading to congenital high degree atrioventricular block: Case report and review of the literature.

Maternal autoimmune disease is the most common cause of congenital heart block (CHB), a rare illness characterized by fibrosis and calcification of the fetal atrioventricular (AV) node due to maternal autoantibodies anti-SSA/Ro and anti-SSB/La. We report the full autopsy and clinical information on a female neonate with high degree AV block and calcification in the AV node, atrial approaches to the AV node, and both right and left bundle branches, born to a 27-year-old female with subclinical autoimmune disease.

A Large Postmortem Database of COVID-19 Patients Can Inform Disease Research and Public Policy Decision Making.

Context.—: Autopsies performed on COVID-19 patients have provided critical information about SARS-CoV-2's tropism, mechanisms of tissue injury, and spectrum of disease.

Objective.

The interplay between sex, time of day, fasting status, and their impact on cardiac mitochondrial structure, function, and dynamics.

Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We observed peak mitochondrial number at ZT8 in the fed state, which was dependent on the intrinsic cardiac circadian clock, as hearts from cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit different TOD responses.

Consensus statement on the processing, interpretation and reporting of temporal artery biopsy for arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists.

heterozygous pathogenic variant in an autopsy case of multiple aneurysms and right renal artery dissection: a case report.

Background: Marfan syndrome is a potentially fatal inherited autosomal dominant condition impacting the cardiovascular and the skeletal system with an estimated 25% cases caused by sporadic genetic variations. Given the genetic inheritance pattern, an autopsy of probands with Marfan syndrome-associated mortality is critical to establish the phenotypic expression and clinical implications of the particular genetic variant, especially for first-degree relatives. We present the findings of a Marfan syndrome proband decedent presenting with sudden onset abdominal pain and unexplained retroperitoneal abdominal hemorrhage.

Coronary Stent Abscess in the Setting of Arteriovenous Graft Infection following COVID-19: An Autopsy Case Report.

While rare, coronary stent infections present with significant mortality-with most infections and further complications occurring within months of percutaneous coronary intervention (PCI). Here, we discuss a post-COVID-19 patient who presented approximately one year after PCI for declotting of an arteriovenous graft (AVG). Upon admission, the patient was found to be bacteremic with multilobar pneumonia and an infection of the AVG.

Unsupervised mRNA-seq classification of heart transplant endomyocardial biopsies.

Background: Endomyocardial biopsy (EMB) is currently considered the gold standard for diagnosing cardiac allograft rejection. However, significant limitations related to histological interpretation variability are well-recognized. We sought to develop a methodology to evaluate EMB solely based on gene expression, without relying on histology interpretation.

Cardiomyocyte ZKSCAN3 regulates remodeling following pressure-overload.

Autophagy is important for protein and organelle quality control. Growing evidence demonstrates that autophagy is tightly controlled by transcriptional mechanisms, including repression by zinc finger containing KRAB and SCAN domains 3 (ZKSCAN3). We hypothesize that cardiomyocyte-specific ZKSCAN3 knockout (Z3K) disrupts autophagy activation and repression balance and exacerbates cardiac pressure-overload-induced remodeling following transverse aortic constriction (TAC).

Cardiogenic shock in a woman with a mitochondrial cardiomyopathy: a case report.

Background: Mitochondrial cardiomyopathy (MCM) is an alteration in cardiac structure and function caused by gene mutations or deletions affecting components of the mitochondrial respiratory chain. We report a case of MCM presenting as cardiogenic shock, ultimately requiring left ventricular assist device (LVAD) placement.

Case Summary: A 35-year-old woman with chronic weakness and non-ischaemic cardiomyopathy, on home dobutamine, was referred to our institution for heart transplantation evaluation.

Toward reliable calcification detection: calibration of uncertainty in object detection from coronary optical coherence tomography images.

Significance: Optical coherence tomography (OCT) has become increasingly essential in assisting the treatment of coronary artery disease (CAD). However, unidentified calcified regions within a narrowed artery could impair the outcome of the treatment. Fast and objective identification is paramount to automatically procuring accurate readings on calcifications within the artery.

Percutaneous debulking of tricuspid valve endocarditis in severe COVID-19 pneumonia after prolonged venovenous extracorporeal membrane oxygenation with right-ventricular support: a case series.

Background: Over the past 2 years, the utilization of venovenous extracorporeal membrane oxygenation (VV-ECMO) for the treatment of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) has increased. While supporting respiratory function, VV-ECMO requires large-bore indwelling venous cannulas, which risk bleeding and infections, including endocarditis.

Case Summary: We describe two adults hospitalized for COVID-19 pneumonia who developed ARDS and right-ventricular failure, requiring VV-ECMO and ProtekDuo cannulation.

Fulminating herpes simplex hepatitis.

Herpes simplex virus (HSV) is a rare cause of acute hepatitis in patients with chronic immunosuppression, including Crohn's disease. HSV hepatitis has the propensity to cause acute liver failure and death. The presenting signs and symptoms can be nonspecific, thereby causing the diagnosis to go overlooked with inadequate management, leading to a high mortality rate.

Cardiac and Pulmonary Histopathology in Baboons Following Genetically-Engineered Pig Orthotopic Heart Transplantation.

BACKGROUND Although improving, survival after pig orthotopic heart transplantation (OHTx) in baboons has been mixed and largely poor. The causes for the high incidence of early failure remain uncertain. MATERIAL AND METHODS We have carried out pig OHTx in 4 baboons.