Regulation of sarcomere formation and function in the healthy heart requires a titin intronic enhancer.

Heterozygous truncating variants in the sarcomere protein titin (TTN) are the most common genetic cause of heart failure. To understand mechanisms that regulate abundant cardiomyocyte TTN expression we characterized highly conserved intron 1 sequences that exhibited dynamic changes in chromatin accessibility during differentiation of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CMs). Homozygous deletion of these sequences in mice caused embryonic lethality while heterozygous mice demonstrated allele-specific reduction in Ttn expression.

The Prognostic Role of Pulmonary Arterial Elastance in Patients Undergoing Left Ventricular Assist Device Implantation: A Pilot Study.

: Pulmonary arterial elastance (Ea) is a helpful parameter to predict the risk of acute postoperative right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation. A new method for calculating Ea, obtained by the ratio between transpulmonary gradient and stroke volume (Ea), has been proposed as a more accurate measure than the Ea obtained as the ratio between pulmonary artery systolic pressure and stroke volume (Ea). However, the role of Ea in predicting acute RVF post-LVAD implantation remains unclear.

Assessment of cardiovascular diagnoses associated with telemedicine during and after the COVID-19 pandemic.

Background: The COVID-19 pandemic led to widespread adoption of telemedicine, which has persisted in healthcare delivery.

Objective: We aimed to characterize telemedicine use in ambulatory cardiology clinics over two years following the onset of the COVID-19 pandemic.

Methods: Retrospective cross-sectional study from 16 March 2020 to 27 June 2022 in a single-center ambulatory cardiology clinic and telemedicine visits.

Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.

Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types.

Protective role of 3-mercaptopyruvate sulfurtransferase (MPST) in the development of metabolic syndrome and vascular inflammation.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that occur concurrently and increase the risk of cardiovascular disease. 3-mercaptopyruvate sulfurtransferase (MPST) is a cysteine-catabolizing enzyme that yields pyruvate and hydrogen sulfide (HS) and plays a central role in the regulation of energy homeostasis. Herein, we seek to investigate the role of MPST/HS in MetS and its cardiovascular consequences using a mouse model of the disease.

Sex Differences in Cardiovascular-Kidney-Metabolic Syndrome: 30-Year US Trends and Mortality Risks-Brief Report.

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States.

A case report of verapamil toxicity leading to haemodynamic compromise in obstructive hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is an inherited condition characterized by left ventricular (LV) hypertrophy unexplained by increased afterload, often with concomitant outflow tract obstruction. Verapamil is commonly used to treat symptomatic patients. However, its potential for adverse effects should be recognized.

Automated Evaluation for Pericardial Effusion and Cardiac Tamponade with Echocardiographic Artificial Intelligence.

Background: Timely and accurate detection of pericardial effusion and assessment cardiac tamponade remain challenging and highly operator dependent.

Objectives: Artificial intelligence has advanced many echocardiographic assessments, and we aimed to develop and validate a deep learning model to automate the assessment of pericardial effusion severity and cardiac tamponade from echocardiogram videos.

Methods: We developed a deep learning model (EchoNet-Pericardium) using temporal-spatial convolutional neural networks to automate pericardial effusion severity grading and tamponade detection from echocardiography videos.

Implementing Precision Medicine for Dilated Cardiomyopathy: Insights from The DCM Consortium.

Background: Clinical genetic evaluation of dilated cardiomyopathy (DCM) is implemented variably or not at all. Identifying needs and barriers to genetic evaluations will enable strategies to enhance precision medicine care.

Methods: An online survey was conducted in June 2024 among cardiologist investigators of the DCM Consortium from US advanced heart failure/transplant (HF/TX) programs to collect demographics, training, program characteristics, genetic evaluation practices for DCM, and implementation needs.

Genome-wide association study reveals shared and distinct genetic architecture of fatty acids and oxylipins in the Hispanic Community Health Study/Study of Latinos.

Bioactive fatty acid-derived oxylipin molecules play key roles mediating inflammation and oxidative stress. Circulating levels of fatty acids and oxylipins are influenced by environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biology. We performed a genome-wide association study (GWAS) of 81 fatty acids and oxylipins in 11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.

Complete revascularization versus culprit-only revascularization in older adults with ST-elevation myocardial infarction: Systematic review and meta-analysis of randomized controlled trials.

Background: Randomized controlled trials (RCTs) of complete revascularization (CR) versus culprit-only revascularization (COR) in patients with ST-elevation myocardial infarction (STEMI) have shifted the recommendation for CR from class III to class I in the AHA/ACC/SCAI guidelines, but it remains unclear if the benefit of CR over COR extends to older adults, who have greater bleeding risk, comorbidity burden, and complexity of lesions. We performed a meta-analysis to place the results of the previous RCTs in the context of the recently published FIRE trial and the subgroup analysis of the COMPLETE trial in adults ≥75 years old.

Methods: We searched the literature from inception to October 21, 2023.

Mechanical loading reveals an intrinsic cardiomyocyte stiffness contribution to diastolic dysfunction in murine cardiometabolic disease.

Cardiometabolic syndromes including diabetes and obesity are associated with occurrence of heart failure with diastolic dysfunction. There are no specific treatments for diastolic dysfunction, and therapies to manage symptoms have limited efficacy. Understanding of the cardiomyocyte origins of diastolic dysfunction is an important priority to identify new therapeutics.

Artificial intelligence and digital tools for design and execution of cardiovascular clinical trials.

Recent advances have given rise to a spectrum of digital health technologies that have the potential to revolutionize the design and conduct of cardiovascular clinical trials. Advances in domain tasks such as automated diagnosis and classification, synthesis of high-volume data and latent data from adjacent modalities, patient discovery, telemedicine, remote monitoring, augmented reality, and in silico modelling have the potential to enhance the efficiency, accuracy, and cost-effectiveness of cardiovascular clinical trials. However, early experience with these tools has also exposed important issues, including regulatory barriers, clinical validation and acceptance, technological literacy, integration with care models, and health equity concerns.

Utility of Mechanistic Target of Rapamycin Inhibitors in Cardiac Sarcoidosis.

Background: Cardiac sarcoidosis is an uncommon but potentially devastating manifestation of sarcoidosis, which is a multisystem inflammatory granulomatous disease. Although corticosteroids are the mainstay of treatment, given the number of complications associated with their long-term use, there is increasing interest in the use of steroid-sparing agents. Recent basic and translational studies have suggested a role for the mechanistic target of rapamycin (mTOR) pathway in cardiac sarcoidosis.

Evolutionary loss of an antibiotic efflux pump increases quorum sensing mediated virulence .

Antibiotic resistance is one of the most pressing threats to human health, yet recent work highlights how loss of resistance may also drive pathogenesis in some bacteria. In two recent studies, we found that β-lactam antibiotic and nutrient stresses faced during infection selected for the genetic inactivation of the () antibiotic efflux pump . Unexpectedly, efflux pump mutations increased virulence during infection; however, neither the prevalence of efflux pump inactivating mutations in real human infections, nor the mechanisms driving increased virulence of efflux pump mutants are known.

Liquid Biopsy in Hepatocellular Carcinoma: Challenges, Advances, and Clinical Implications.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC.

Noninvasive pulsed radiofrequency for trigeminal neuralgia: Off the beaten path - Case series.

Trigeminal neuralgia (TN) is a debilitating condition characterized by excruciating facial pain resulting from dysfunction in the trigeminal nerve. Treatment options are limited. Noninvasive pulsed radiofrequency (PRF) therapy is an emerging promising approach to managing TN.

Enrollment of Females in Randomized Trials for Glucagon-Like Peptide 1 Receptor Agonists: A Systematic Review.

Background: Randomized controlled trials (RCTs) of glucagon-like peptide 1 receptor agonists (GLP-1RAs) form the basis for therapeutic recommendations for both males and females. Historically, females have been significantly underrepresented in RCTs.

Objectives: The authors sought to determine the trends of representation of females in GLP-1RA RCTs from 2007 to 2024.

Interplay between lifestyle factors and polygenic risk for incident coronary heart disease in a large multiethnic cohort.

Introduction: The objective of this study was to examine the interplay of polygenic risk and individual lifestyle factors (and a composite score of lifestyle) as antecedents of CHD in a large multiethnic cohort.

Methods: We used Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort participants free of CHD at baseline (n = 60,568; 67 % female; 18 % non-European). The individual and joint associations of smoking, Mediterranean diet pattern, level of physical activity and polygenic risk with incident CHD were assessed using Cox regression adjusting for genetic ancestry and non-mediating risk factors.

Transcatheter Tricuspid Valve Replacement.

Transcatheter tricuspid valve replacement (TTVR) has emerged as a promising intervention for the treatment of severe tricuspid regurgitation with complex valve morphology. This consensus document provides a comprehensive overview of the current state of orthotopic TTVR, focusing on patient selection, procedural details, and follow-up care. Clinical outcomes from initial studies and compassionate use cases are discussed, highlighting the effectiveness of TTVR in reducing tricuspid regurgitation, inducing reverse right ventricular remodeling, and enhancing patients' quality of life.