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.

Identifying mitigating strategies for endothelial cell dysfunction and hypertension in response to VEGF receptor inhibitors.

Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to endothelial cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators of VEGFRi-induced EC dysfunction and validated in primary aortic ECs, mice, and canine cancer patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) and increased markers of endothelial and renal dysfunction in mice and canine cancer patients.

MicroRNA-409-3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice.

Wound healing is facilitated by neoangiogenesis, a complex process that is essential to tissue repair in response to injury. MicroRNAs are small, noncoding RNAs that can regulate the wound healing process including stimulation of impaired angiogenesis that is associated with type-2 diabetes (T2D). Expression of miR-409-3p was significantly increased in the nonhealing skin wounds of patients with T2D compared to the non-wounded normal skin, and in the skin of a murine model with T2D.

Clinical impact of pulmonary artery catheter in patients with cardiogenic shock: A systematic review and meta-analysis.

Background: The clinical utility of the pulmonary artery catheter (PAC) for the management of cardiogenic shock (CS) remains controversial. We performed a systematic review and meta-analysis exploring the association between PAC use and mortality among patients with CS.

Methods: Published studies of patients with CS treated with or without PAC hemodynamic guidance were retrieved from MEDLINE and PubMed databases from January 1, 2000, to December 31, 2021.

Cardiometabolic deaths attributable to poor diet among Kuwaiti adults.

Background: Nutrition transition towards a Western diet is happening in parallel with the rapidly increasing rates of cardiovascular disease and its risk factors in Kuwait. The cardiometabolic deaths attributable to poor diet have not been quantified among Kuwaiti adults.

Methods: Using a Comparative Risk Assessment model that incorporated dietary intake data from Kuwait's first national nutrition survey, number of cardiometabolic deaths from the World Health Organization, and estimated associations of diet with cardiometabolic deaths from the Global Burden of Disease project, we estimated the number and proportion of cardiometabolic deaths attributable to suboptimal intake of 10 dietary factors among Kuwaiti adults ages 25+ years, and by population subgroups.

Do Patients With Non-Viable Myocardium From Ischemic Cardiomyopathy Benefit From Revascularization? A Systematic Review And Meta-Analysis.

Background: Myocardial viability assessment is used to select patients who will derive the greatest benefit from revascularization. It remains controversial whether revascularization only benefits patients with ischemic cardiomyopathy who have viable myocardium. The objective of this meta-analysis was to compare mortality between patients with ischemic cardiomyopathy and non-viable myocardium who underwent revascularization and those who underwent medical therapy alone.

Specialized Pro-Resolving Mediators Reduce Scarring After Cleft Lip Repair.

Objective: Residual scarring after cleft lip repair surgery remains a challenge for both surgeons and patients and novel therapeutics are critically needed. The objective of this preclinical experimental study was to evaluate the impact of the methyl-ester of pro-resolving lipid mediator lipoxin A (LXA-ME) on scarring in a novel rabbit model of cleft lip repair.

Methods: A defect of the lip was surgically created and repaired in eight six-week old New Zealand white rabbits to simulate human cleft lip scars.

TTR variants in patients with dilated cardiomyopathy: An investigation of the DCM Precision Medicine Study.

Purpose: The cardiac phenotype of hereditary transthyretin amyloidosis (hTTR) usually presents as a restrictive or hypertrophic cardiomyopathy, and, although rarely observed as dilated cardiomyopathy (DCM), TTR is routinely included in DCM genetic testing panels. However, the prevalence and phenotypes of TTR variants in patients with DCM have not been reported.

Methods: Exome sequences of 729 probands with idiopathic DCM were analyzed for TTR and 35 DCM genes.

Altered intercellular communication and extracellular matrix signaling as a potential disease mechanism in human hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is considered a primary disorder of the sarcomere resulting in unexplained left ventricular hypertrophy but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained. To understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease. Clustering analysis based on gene expression patterns identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression.

Validating an Idiopathic Dilated Cardiomyopathy Diagnosis Using Cardiovascular Magnetic Resonance: The Dilated Cardiomyopathy Precision Medicine Study.

Background: Coronary angiography to identify coronary artery disease has been foundational to distinguish the cause of dilated cardiomyopathy (DCM), including the assignment of idiopathic or ischemic cardiomyopathy. Late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR) has emerged as an approach to identify myocardial scar and identify etiology.

Methods: The DCM Precision Medicine Study included patients with left ventricular dilation and dysfunction attributed to idiopathic DCM, after expert clinical review excluded ischemic or other cardiomyopathies.

Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation.

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction, referred for surgical myectomy. Plasma was collected at the surgical preoperative visit, approximately one month prior to surgery and then at the post-surgical visit, approximately 3 months later.

Individualized interactomes for network-based precision medicine in hypertrophic cardiomyopathy with implications for other clinical pathophenotypes.

Progress in precision medicine is limited by insufficient knowledge of transcriptomic or proteomic features in involved tissues that define pathobiological differences between patients. Here, myectomy tissue from patients with obstructive hypertrophic cardiomyopathy and heart failure is analyzed using RNA-Seq, and the results are used to develop individualized protein-protein interaction networks. From this approach, hypertrophic cardiomyopathy is distinguished from dilated cardiomyopathy based on the protein-protein interaction network pattern.

Retrospective analysis on confirmation rates for referred positive rotavirus samples in England, 2016 to 2017: implications for diagnosis and surveillance.

BackgroundRapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.AimWe aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.

Noninvasive Epidermal Metabolite Profiling.

A buffer placed in brief contact in the skin was assayed by H NMR spectroscopy. We found that this passive extraction of the skin surface yields abundant metabolites. Metabolites of the skin surface originate from a variety of sources, including the sweat gland, which produces lactate from the glucose received from its capillary bed.

Associations between Circulating Lipids and Fat-Soluble Vitamins and Carotenoids in Healthy Overweight and Obese Men.

Inconsistent associations between lipids and circulating markers of fat-soluble vitamin and carotenoid status have been reported. The aim of this hypothesis-generating study was to examine the contribution of the LC-MS-based lipidome, characterized by lipid class, carbon count, and the number of unsaturated bonds, to the interindividual variability in circulating concentrations of retinol, carotenoids, 25-hydroxyvitamin D, α-tocopherol, γ-tocopherol, and phylloquinone in 35 overweight and obese, but healthy men. A sparse partial least-squares method was used to accomplish this aim.