Right atrial pressure torsades de pointes.

A 39-year-old man with non-ischemic cardiomyopathy presented for routine right heart catheterization.

A humanized knockin mouse model of Duchenne muscular dystrophy and its correction by CRISPR-Cas9 therapeutic gene editing.

Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disease caused by mutations in the X-linked dystrophin () gene. Exon deletions flanking exon 51, which disrupt the dystrophin open reading frame (ORF), represent one of the most common types of human DMD mutations. Previously, we used clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) gene editing to restore the reading frame of exon 51 in mice and dogs with exon 50 deletions.

Long-term maintenance of dystrophin expression and resistance to injury of skeletal muscle in gene edited DMD mice.

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by mutations in the dystrophin gene. CRISPR/Cas9 genome editing has been used to correct DMD mutations in animal models at young ages. However, the longevity and durability of CRISPR/Cas9 editing remained to be determined.

Biomarkers in Duchenne Muscular Dystrophy.

Purpose Of Review: This review highlights the key studies investigating various types of biomarkers in Duchenne muscular dystrophy (DMD).

Recent Findings: Several proteomic and metabolomic studies have been undertaken in both human DMD patients and animal models of DMD that have identified potential biomarkers in DMD. Although there have been a number of proteomic and metabolomic studies that have identified various potential biomarkers in DMD, more definitive studies still need to be undertaken in DMD patients to firmly correlate these biomarkers with diagnosis, disease progression, and monitoring the effects of novel treatment strategies being developed.

Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy.

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health.

Identifying Discordance of Right- and Left-Ventricular Filling Pressures in Patients With Heart Failure by the Clinical Examination.

Background: In ≈25% of patients with heart failure and reduced left-ventricular ejection fraction, right-ventricular (RV), and left-ventricular (LV) filling pressures are discordant (ie, one is elevated while the other is not). Whether clinical assessment allows detection of this discordance is unknown. We sought to determine the agreement of clinically versus invasively determined patterns of ventricular congestion.

A consolidated AAV system for single-cut CRISPR correction of a common Duchenne muscular dystrophy mutation.

Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin gene, is a lethal neuromuscular disease. Correction of DMD mutations in animal models has been achieved by CRISPR/Cas9 genome editing using Cas9 (Cas9) delivered by adeno-associated virus (AAV). However, due to the limited viral packaging capacity of AAV, two AAV vectors are required to deliver the Cas9 nuclease and its single guide RNA (sgRNA), impeding its therapeutic application.

Ascites and Edema After Bicaval Orthotopic Heart Transplant.

IVC stenosis is a rare complication of bicaval orthotopic heart transplant. IVC stenosis can occur at either the cavo-atrial anastomosis, or the caval cannulation site, with presentations ranging from acute shock early post transplant to a more indolent course. Causes include extensive hemostatic suturing, fibrous contraction, and donor-recipient size mismatch.

In-Depth Evaluation of a Case of Presumed Myocarditis After the Second Dose of COVID-19 mRNA Vaccine.

Supplemental Digital Content is available in the text.

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization.

Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism.

Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy.

Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD.

Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function.

Parvalbumin-positive (PV ) fast-spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV interneurons imposes high-energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single-cell transcriptomic data for the mouse cortex, we identified a metabolism-associated gene with highly restricted expression to PV interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit.

Saved by the VAC: Minimally Invasive Removal of a Surely Fatal Right Heart Thrombus in a Patient with Advanced Heart Failure.

Intracardiac thrombi are associated with an increased morbidity and mortality due to their unpredictability and embolic potential. Right heart thrombus is infrequently encountered in clinical practice outside the scenario of acute pulmonary embolism with hemodynamic compromise, and even more uncommon is the presence of a massive right heart thrombus. Embolic potential is high, and historically, management has revolved around open surgical removal or systemic thrombolysis.

Enhanced CRISPR-Cas9 correction of Duchenne muscular dystrophy in mice by a self-complementary AAV delivery system.

Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disease caused by mutations in the dystrophin gene (). Previously, we applied CRISPR-Cas9-mediated "single-cut" genome editing to correct diverse genetic mutations in animal models of DMD. However, high doses of adeno-associated virus (AAV) are required for efficient in vivo genome editing, posing challenges for clinical application.

Clinical Care Recommendations for Cardiologists Treating Adults With Myotonic Dystrophy.

Myotonic dystrophy is an inherited systemic disorder affecting skeletal muscle and the heart. Genetic testing for myotonic dystrophy is diagnostic and identifies those at risk for cardiac complications. The 2 major genetic forms of myotonic dystrophy, type 1 and type 2, differ in genetic etiology yet share clinical features.

Impact of induction immunosuppression on patient survival in heart transplant recipients treated with tacrolimus and mycophenolic acid in the current allocation era.

Background: The practice of induction therapy with either rabbit anti-thymocyte globulin (r-ATG) or interleukin-2 receptor antagonists (IL-2RA) is common among heart transplant recipients. However, its benefits in the setting of contemporary maintenance immunosuppression with tacrolimus/mycophenolic acid (TAC/MPA) are unknown.

Methods: We compared post-transplant mortality among three induction therapy strategies (r-ATG vs IL2-RA vs no induction) in a retrospective cohort analysis of heart transplant recipients maintained on TAC/MPA in the Organ Procurement Transplant Network (OPTN) database between the years 2006 and 2015.

CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells.

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), which is characterized by lethal degeneration of cardiac and skeletal muscles. Mutations that delete exon 44 of the dystrophin gene represent one of the most common causes of DMD and can be corrected in ~12% of patients by editing surrounding exons, which restores the dystrophin open reading frame. Here, we present a simple and efficient strategy for correction of exon 44 deletion mutations by CRISPR-Cas9 gene editing in cardiomyocytes obtained from patient-derived induced pluripotent stem cells and in a new mouse model harboring the same deletion mutation.

Delayed febrile response with bloodstream infections in patients with continuous-flow left ventricular assist devices.

Bloodstream infections (BSIs) are common in patients with continuous-flow left ventricular assist devices (CF-LVADs). Whether CF-LVADs modulate the febrile response to BSIs is unknown. We retrospectively compared the febrile response to BSIs in patients with heart failure (HF) with CF-LVADs versus a control population of patients with HF receiving inotropic infusions.