Peripheral Blood DNA Methylation Changes in Response to Treatment in Aged Mice.

Alterations in epigenetic modifications, like DNA methylation, in peripheral blood could serve as a useful, minimally invasive biomarker of the effects of anti-aging interventions. This study explores this potential with a water extract of the botanical (CAW). Eighteen-month-old mice were treated with CAW in their drinking water for 5 weeks alongside vehicle-treated eighteen-month-old C57BL6 mice.

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

Importance: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration.

Objective: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration.

Design, Setting, And Participants: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023.

Cardiovascular Complications During Delivery Hospitalization in Patients With Psoriasis.

Background: Psoriasis in pregnancy is associated with adverse maternal outcomes. However, there are limited data on this subject.

Objectives: The purpose of our study was to investigate the association between psoriasis and related cardiovascular complications during delivery.

Human P2X4 receptor gating is modulated by a stable cytoplasmic cap and a unique allosteric pocket.

P2X receptors (P2XRs) are adenosine 5'-triphosphate (ATP)-gated ion channels comprising homomeric and heteromeric trimers of seven subtypes (P2X1-P2X7) that confer different rates of desensitization. The helical recoil model of P2XR desensitization proposes stability of the cytoplasmic cap sets the rate of desensitization, but timing of its formation is unclear for slow-desensitizing P2XRs. We report cryo-electron microscopy structures of full-length wild-type human P2X4 receptor in apo closed, antagonist-bound inhibited, and ATP-bound desensitized states.

New therapies to treat cardiac amyloidosis.

Purpose Of Review: Review advancements in therapies for transthyretin (ATTR-CM) and immunoglobulin light chain (AL-CM) cardiac amyloidosis.

Recent Findings: In ATTR-CM, tafamidis remains the cornerstone therapy, with Food and Drug Administration (FDA) approval for over 5 years. Acoramidis, another transthyretin stabilizer, has very recently been FDA-approved following positive results in the ATTRibute-CM trial.

Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes.

Background: The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA.

Methods And Results: In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021).

Background and design of the Physical Frailty and Symptom Monitoring and Management Behaviors in Heart Failure (PRISM-HF) study: A mixed methods study.

Background: Many adults with heart failure (HF) are physically frail and have worse outcomes. While the biological profile of physical frailty in HF has been examined, the behavioral profile remains unstudied. Physical frailty may impact self-care behaviors, particularly symptom monitoring and management (SMM), which in turn results in adverse outcomes.

Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity.

Maternal obesity puts the offspring at high risk of developing obesity and cardio-metabolic diseases in adulthood. Here, we utilized a mouse model of maternal high-fat diet (HFD)-induced obesity that recapitulates metabolic perturbations seen in humans. We show increased adiposity in the offspring of HFD-fed mothers (Off-HFD) when compared to the offspring regular diet-fed mothers (Off-RD).

How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology.

It is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography.

Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact.

Data generated using single-cell RNA-sequencing has the potential to transform understanding of the cerebral circulation and advance clinical care. However, the high volume of data, sometimes generated and presented without proper pathophysiological context, can be difficult to interpret and integrate into current understanding of the cerebral circulation and its disorders. Furthermore, heterogeneity in the representation of brain regions and vascular segments makes it difficult to compare results across studies.

Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles.

Background: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven.

Objectives: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use.

Enhanced myocardial perfusion in late gestation fetal lambs with impaired left ventricular inflow.

Robust preclinical models of asymmetric ventricular loading in late gestation reflecting conditions such as hypoplastic left heart syndrome are lacking. We characterized the morphometry and microvascular function of the hypoplastic left ventricle (LV) and remaining right ventricle (RV) in a sham-controlled late gestation fetal lamb model of impaired left ventricular inflow (ILVI). Singleton fetuses were instrumented at ∼120 days gestational age (dGA; term is ∼147 days) with vascular catheters, an aortic flow probe and a deflated left atrial balloon.

Atlas-scale single-cell DNA methylation profiling with sciMETv3.

Single-cell methods to assess DNA methylation have not achieved the same level of cell throughput per experiment compared to other modalities, with large-scale datasets requiring extensive automation, time, and other resources. Here, we describe sciMETv3, a combinatorial indexing-based technique that enables atlas-scale libraries to be produced in a single experiment. To reduce the sequencing burden, we demonstrate the compatibility of sciMETv3 with capture techniques to enrich regulatory regions, as well as the ability to leverage enzymatic conversion, which can yield higher library diversity.

Association between insurance type, clinical characteristics, and healthcare use in adults with congenital heart disease.

Introduction: Adults with congenital heart disease (CHD) represent a heterogeneous and growing population with high healthcare utilization. We sought to understand the association between insurance type, healthcare use, and outcomes among adults with CHD in Oregon.

Methods: The Oregon All Payers All Claims database from 2010 to 2017 was queried for adults aged 18-65 in 2014 with ICD-9 or 10 codes consistent with CHD; patient demographics, comorbidities, healthcare use, and disease severity were identified.

A medical assistant-facilitated transition activity in a pediatric cardiology clinic.

Background: Formal transition programs prepare pediatric patients with congenital heart disease (CHD) for successful lifelong management of their disease. Conducting transition program activities in pediatric cardiology clinics can be a challenge if there are limited resources. The purpose of this study was to test the effectiveness of a medical assistant (MA)-facilitated transition activity in increasing documentation of transition discussions and characterize staff acceptability of this intervention.

Increases in donor/recipient predicted heart mass ratios do not result in large donor right ventricles.

Pulmonary hypertension puts strain on the right ventricle (RV), leading to the widespread practice of oversizing donor hearts to mitigate complications. However, contemporary evidence for this practice is neutral. We studied the relationship between donor-recipient predicted heart mass (D/R PHM) ratios and increases in donor left ventricle (LV) and RV mass.

The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.

Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK), and high molecular weight kininogen interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients.

Relationship Between Coronary Artery Calcium Score and Vulnerability of Culprit Plaque Assessed by OCT in Patients With Established Coronary Artery Disease.

Background: Coronary artery calcium score (CACS) is widely used for risk stratification. However, in patients with established coronary artery disease, its clinical implication and relationship with plaque vulnerability are unclear. We sought to correlate the CACS and plaque vulnerability assessed by optical coherence tomography.

Impact of Length Indexing of Deformation in Echocardiographic Evaluation of Right Ventricular Function.

Background: When assessing right ventricular (RV) function by echocardiography, some discordance between the deformational indices is predicted on the basis of the influence of RV length. RV free wall longitudinal strain (RVFWS) is relatively independent of RV length, whereas tricuspid annular plane systolic excursion (TAPSE) reflects the strain-length product. Systolic annular velocity (s'; distance over time) is also likely to be influenced by length.