Hemodynamics are associated with subsequent lumen remodeling and clinical maturation of hemodialysis arteriovenous fistula.

The pathogenesis of arteriovenous fistula (AVF) maturation failure is unclear. We evaluated the associations of wall shear stress (WSS) with subsequent AVF remodeling and clinical maturation using regression models in this prospective cohort study. Participants underwent duplex ultrasound at postoperative Day 1, Week 2, and Week 6 to measure AVF blood flow rate and diameter of the draining vein and proximal artery.

Defining Echocardiographic Degrees of Right Heart Size and Function in Pulmonary Vascular Disease from the PVDOMICS Study.

Background: Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function.

Methods: We investigated 1053 study participants in the Redefining Pulmonary Hypertension through PVD Phenomics program (PVDOMICS) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance (PVR) severity.

Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.

Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status.

Association of Male Sex With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort.

Background: Sex-based differences are important in the development and progression of pulmonary arterial hypertension. However, it is not established whether these differences are generalizable to all forms of pulmonary hypertension (PH).

Research Question: What are the sex-based differences in right ventricle (RV) function and transplant-free survival in patients with PH from the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort?

Study Design And Methods: Patients with PH enrolled in the PVDOMICS cohort study underwent right heart catheterization, cardiac MRI, and echocardiography.

Clinical Implications of Pretest Probability of HFpEF on Outcomes in Precapillary Pulmonary Hypertension.

Background: Patients with group 1 pulmonary hypertension (PH) and risk factors for heart failure with preserved ejection fraction (HFpEF) demonstrate worse response to pulmonary vasodilator therapy. The mechanisms and optimal diagnostic approach to identify such patients remain unclear.

Objectives: The purpose of this study was to compare exercise capacity, cardiac function, and hemodynamic responses to provocative maneuvers among patients with group 1 PH based upon pretest probability of HFpEF.

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

Aims: The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved.

Methods And Results: We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2).

Pulmonary hypertension across the spectrum of left heart and lung disease.

Aims: Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized.

Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes.

Importance: Randomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration.

Objective: To determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes.

Design, Setting, And Participants: ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022.

Health-Related Quality of Life Across the Spectrum of Pulmonary Hypertension.

Background: Health-related quality of life (HRQOL) is frequently impaired in pulmonary arterial hypertension. However, little is known about HRQOL in other forms of pulmonary hypertension (PH).

Research Question: Does HRQOL vary across groups of the World Symposium on Pulmonary Hypertension (WSPH) classification system?

Study Design And Methods: This cross-sectional study included patients with PH from the Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort study.

Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension.

Background: Group 1 pulmonary arterial hypertension (PAH) is a progressive fatal condition characterized by right ventricular (RV) failure with worse outcomes in connective tissue disease (CTD). Obstructive sleep apnea and sleep-related hypoxia may contribute to RV dysfunction, though the relationship remains unclear.

Objectives: The aim of this study was to prospectively evaluate the association of the apnea-hypopnea index (AHI) and sleep-related hypoxia with RV function and survival.

Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension.

Understanding metabolic evolution underlying pulmonary arterial hypertension (PAH) development may clarify pathobiology and reveal disease-specific biomarkers. Patients with systemic sclerosis (SSc) are regularly surveilled for PAH, presenting an opportunity to examine metabolic change as disease develops in an at-risk cohort. We performed mass spectrometry-based metabolomics on longitudinal serum samples collected before and near SSc-PAH diagnosis, compared with time-matched SSc subjects without PAH, in a SSc surveillance cohort.

Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension.

Background: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RV functional recovery [RVFnRec]). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition.

Methods: We evaluated 63 incident patients with pulmonary arterial hypertension by right heart catheterization and cardiac magnetic resonance imaging at diagnosis and cardiac magnetic resonance imaging and invasive cardiopulmonary exercise testing following treatment (≈11 months).

Frequency of acute vasodilator response (AVR) in incident and prevalent patients with pulmonary arterial hypertension: Results from the pulmonary vascular disease phenomics study.

The prevalence of acute vasodilator response (AVR) to inhaled nitric oxide (iNO) during right heart catheterization (RHC) is 12% in idiopathic pulmonary arterial hypertension (IPAH). AVR, however, is reportedly lower in other disease-associated pulmonary arterial hypertension (PAH), such as connective tissue disease (CTD). The prevalence of AVR in patients on PAH therapy (prevalent cases) is unknown.

Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension.

Background: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RVFnRec). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition.

Methods: We evaluated 63 incident patients with PAH by right heart catheterization and cardiac MRI (CMR) at diagnosis and CMR and invasive cardiopulmonary exercise (CPET) following treatment (∼11 months).

Association of Shear Stress with Subsequent Lumen Remodeling in Hemodialysis Arteriovenous Fistulas.

Background: Blood flow-induced wall shear stress is a strong local regulator of vascular remodeling, but its effects on arteriovenous fistula (AVF) remodeling are unclear.

Methods: In this prospective cohort study, we used computational fluid dynamics simulations and statistical mixed-effects modeling to investigate the associations between wall shear stress and AVF remodeling in 120 participants undergoing AVF creation surgery. Postoperative magnetic resonance imaging data at 1 day, 6 weeks, and 6 months were used to derive current wall shear stress by computational fluid dynamic simulations and to quantify subsequent changes in AVF lumen cross-sectional area at 1-mm intervals along the proximal artery and AVF vein.

Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial.

Background: BEAR (bridge-enhanced anterior cruciate ligament [ACL] restoration), a paradigm-shifting technology to heal midsubstance ACL tears, has been demonstrated to be effective in a single-center 2:1 randomized controlled trial (RCT) versus hamstring ACL reconstruction. Widespread dissemination of BEAR into clinical practice should also be informed by a multicenter RCT to demonstrate exportability and compare efficacy with bone--patellar tendon-bone (BPTB) ACL reconstruction, another clinically standard treatment.

Purpose: To present the design and initial preparation of a multicenter RCT of BEAR versus BPTB ACL reconstruction (the BEAR: Multicenter Orthopaedic Outcomes Network [BEAR-MOON] trial).

The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.

Introduction: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity.

A New Panel-Estimated GFR, Including β-Microglobulin and β-Trace Protein and Not Including Race, Developed in a Diverse Population.

Rationale And Objective: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFR) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFR or eGFR, respectively), but the inclusion of creatinine in eGFR requires specification of a person's race. β-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is.

Study Design: Study of diagnostic test accuracy.

The effect of frequent hemodialysis on matrix metalloproteinases, their tissue inhibitors, and FGF23: Implications for blood pressure and left ventricular mass modification in the Frequent Hemodialysis Network trials.

Background: Frequent hemodialysis modifies serum phosphorus, blood pressure, and left ventricular mass (LVM). We ascertained whether frequent hemodialysis is associated with specific changes in biomarker profile among patients enrolled in the frequent hemodialysis network (FHN) trials.

Methods: This was a post hoc analysis of biomarkers among patients enrolled to the FHN trials.

GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Meta-Analysis of Treatment Effects of Randomized Controlled Trials.

Background: Surrogate end points are needed to assess whether treatments are effective in the early stages of CKD. GFR decline leads to kidney failure, but regulators have not approved using differences in the change in GFR from the beginning to the end of a randomized, controlled trial as an end point in CKD because it is not clear whether small changes in the GFR slope will translate to clinical benefits.

Methods: To assess the use of GFR slope as a surrogate end point for CKD progression, we performed a meta-analysis of 47 RCTs that tested 12 interventions in 60,620 subjects.

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial.

Background: Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week.

Mineral Metabolism Disturbances and Arteriovenous Fistula Maturation.

Background: The arteriovenous fistula (AVF) is central to haemodialysis treatment, but up to half of surgically created AVF fail to mature. Chronic kidney disease often leads to mineral metabolism disturbances that may interfere with AVF maturation through adverse vascular effects. This study tested associations between mineral metabolism markers and vein histology at AVF creation and unassisted and overall clinical AVF maturation.