A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.

While membrane proteins such as ion channels continuously turn over and require replacement, the mechanisms of specificity of efficient channel delivery to appropriate membrane subdomains remain poorly understood. GJA1-20k is a truncated Connexin43 (Cx43) isoform arising from translation initiating at an internal start codon within the same parent GJA1 mRNA and is requisite for full-length Cx43 trafficking to cell borders. GJA1-20k does not have a full transmembrane domain, and it is not known how GJA1-20k enables forward delivery of Cx43 hemichannels.

Cardiac Recovery: Webcast September 24 2024.

This 61-minute webcast features a conversation about "Cardiac Recovery"-the focus of Issue 20.4. Led by the issue's editors, the discussion engages the authors on emerging themes and lessons learned while researching and writing the articles.

Image quality assessment and automation in late gadolinium-enhanced MRI of the left atrium in atrial fibrillation patients.

Background: Late gadolinium-enhanced (LGE) MRI has become a widely used technique to non-invasively image the left atrium prior to catheter ablation. However, LGE-MRI images are prone to variable image quality, with quality metrics that do not necessarily correlate to the image's diagnostic quality. In this study, we aimed to define consistent clinically relevant metrics for image and diagnostic quality in 3D LGE-MRI images of the left atrium, have multiple observers assess LGE-MRI image quality to identify key features that measure quality and intra/inter-observer variabilities, and train and test a CNN to assess image quality automatically.

Predicting blood loss volume in a canine model of hemorrhagic shock using arterial waveform machine learning analysis.

Objective: To determine if the compensatory reserve algorithm validated in humans can be applied to canines. Our secondary objective was to determine if a simpler waveform analysis could predict the percentage of blood loss volume.

Methods: 6 purpose-bred, anesthetized dogs underwent 5 rounds of controlled hemorrhage and resuscitation while continuously recording invasive arterial blood pressure waveforms in this prospective, experimental study.

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.

Heart failure (HF) is a major cause of mortality and morbidity worldwide, yet with limited therapeutic options. Cardiac bridging integrator 1 (cBIN1), a cardiomyocyte transverse-tubule (t-tubule) scaffolding protein which organizes the calcium handling machinery, is transcriptionally reduced in HF and can be recovered for functional rescue in mice. Here we report that in human patients with HF with reduced ejection fraction (HFrEF), left ventricular cBIN1 levels linearly correlate with organ-level ventricular remodeling such as diastolic diameter.

Functional and Structural Remodeling as Atrial Fibrillation Progresses in a Persistent Atrial Fibrillation Canine Model.

Background: Contractile, electrical, and structural remodeling has been associated with atrial fibrillation (AF), but the progression of functional and structural changes as AF sustains has not been previously evaluated serially.

Objectives: Using a rapid-paced persistent AF canine model, the authors aimed to evaluate the structural and functional changes serially as AF progresses.

Methods: Serial electrophysiological studies in a chronic rapid-paced canine model (n = 19) prior to AF sustaining and repeated at 1, 3, and 6 months of sustained AF were conducted to measure changes in atrial conduction speed and direction.

Effective ablation settings that predict chronic scar after atrial ablation with HELIOSTAR™ multi-electrode radiofrequency balloon catheter.

Background: Radiofrequency balloon (RFB) ablation (HELIOSTAR™, Biosense Webster) has been developed to improve pulmonary vein ablation efficiency over traditional point-by-point RF ablation approaches. We aimed to find effective parameters for RFB ablation that result in chronic scar verified by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR).

Methods: A chronic canine model (n = 8) was used to ablate in the superior vena cava (SVC), the right superior and the left inferior pulmonary vein (RSPV and LIPV), and the left atrial appendage (LAA) with a circumferential ablation approach (RF energy was delivered to all electrodes simultaneously) for 20 s or 60 s.

A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease.

Background: Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

Diffuse functional and structural abnormalities in fibrosis: Potential structural basis for sustaining atrial fibrillation.

Background: Structural remodeling has been associated with increased incidence of atrial fibrillation, but how fibrotic regions allow atrial fibrillation to be sustained remains unclear.

Objective: With a novel transgenic goat model, we evaluated structural and functional differences between structurally remodeled and healthy regions of the atria.

Methods: A novel transgenic goat model with cardiac-specific overexpression of transforming growth factor β1 was used.

Amyloid-beta metabolism in age-related neurocardiovascular diseases.

Epidemiological evidence suggests the presence of common risk factors for the development and prognosis of both cardio- and cerebrovascular diseases, including stroke, Alzheimer's disease, vascular dementia, heart, and peripheral vascular diseases. Accumulation of harmful blood signals may induce organotypic endothelial dysfunction affecting blood-brain barrier function and vascular health in age-related diseases. Genetic-, age-, lifestyle- or cardiovascular therapy-associated imbalance of amyloid-beta (Aβ) peptide metabolism in the brain and periphery may be the missing link between age-related neurocardiovascular diseases.

Epigenetic regulation of cardiovascular diseases induced by behavioral and environmental risk factors: Mechanistic, diagnostic, and therapeutic insights.

Behavioral and environmental risk factors are critical in the development and progression of cardiovascular disease (CVD). Understanding the molecular mechanisms underlying these risk factors will offer valuable insights for targeted preventive and therapeutic strategies. Epigenetic modifications, including DNA methylation, histone modifications, chromatin remodeling, noncoding RNA (ncRNA) expression, and epitranscriptomic modifications, have emerged as key mediators connecting behavioral and environmental risk factors to CVD risk and progression.

Left atrial functional changes associated with repeated catheter ablations for atrial fibrillation.

Introduction: The impact of repeated atrial fibrillation (AF) ablations on left atrial (LA) mechanical function remains uncertain, with limited long-term follow-up data.

Methods: This retrospective study involved 108 AF patients who underwent two catheter ablations with cardiac magnetic resonance imaging (MRI) done before and 3 months after each of the ablations from 2010 to 2021. The rate of change in peak longitudinal atrial strain (PLAS) assessed LA function.

Are drivers recurring or ephemeral? observations from serial mapping of persistent atrial fibrillation.

Aims: Rotational re-entries and ectopic foci, or 'drivers', are proposed mechanisms for persistent atrial fibrillation (persAF), but driver-based interventions have had mixed success in clinical trials. Selective targeting of drivers with multi-month stability may improve these interventions, but no prior work has investigated whether drivers can be stable on such a long timescale.

Objective: We hypothesized that drivers could recur even several months after initial observation.

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.

Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA cycle). This reaction is thought to occur in the cytosol, with pyruvate subsequently transported into mitochondria via the mitochondrial pyruvate carrier (MPC).

The calcium transient coupled to the L-type calcium current attenuates cardiac alternans.

Cardiac action potential (AP) alternans have been linked to the development of arrhythmia. AP alternans may be driven by AP instabilities, Ca transient (CaT) instabilities, or both. The mechanisms underlying CaT driven AP alternans is well-supported experimentally, but the ionic mechanism underlying alternans driven by AP instabilities remain incompletely understood.

A repository of Ogden syndrome patient derived iPSC lines and isogenic pairs by X-chromosome screening and genome-editing.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene, encodes the enzyme NAA10, as the catalytic subunit for the N-terminal acetyltransferase A (NatA) complex, including the accessory protein, NAA15. The first human disease directly involving was discovered in 2011, and it was named Ogden syndrome (OS), after the location of the first affected family residing in Ogden, Utah, USA.

Environmental Cues Facilitate Maturation and Patterning of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Background/aims: Advances in induced pluripotent stem cell (iPSC) technology allow for reprogramming of adult somatic cells into stem cells from which patient- and disease-specific cardiomyocytes (CMs) can be derived. Yet, the potential of iPSC technology to revolutionize cardiovascular research is limited, in part, by the embryonic nature of these cells. Here, we test the hypothesis that decellularized porcine left ventricular extracellular cardiac matrix (ECM) provides environmental cues that promote transcriptional maturation and patterning of iPSC-CMs in culture.

In-hospital unfavorable outcomes of MIS-C during 2020-2022: a systematic review.

Unlabelled: Studies on the severity in multisystem inflammatory syndrome in children (MIS-C) show heterogeneous results and may not reflect a global perspective. This systematic review aims to estimate the frequency of in-hospital unfavorable outcomes in patients with MIS-C over the 3 years since the onset of the SARS-CoV-2 pandemic. A systematic search was conducted in Medline, Scopus, Embase, Cochrane, Web of Science, Scielo, and preprint repositories until December 15, 2022.

Refinement of machine learning arterial waveform models for predicting blood loss in canines.

Introduction: Hemorrhage remains a leading cause of death in civilian and military trauma. Hemorrhages also extend to military working dogs, who can experience injuries similar to those of the humans they work alongside. Unfortunately, current physiological monitoring is often inadequate for early detection of hemorrhage.

Clinical Characteristics and Outcomes of Patients Suffering Acute Decompensated Heart Failure Complicated by Cardiogenic Shock.

Background: Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes.