Organoid single cell profiling identifies a transcriptional signature of glomerular disease.

Podocyte injury is central to many forms of kidney disease, but transcriptional signatures reflecting podocyte injury and compensation mechanisms are challenging to analyze in vivo. Human kidney organoids derived from pluripotent stem cells (PSCs), a potentially new model for disease and regeneration, present an opportunity to explore the transcriptional plasticity of podocytes. Here, transcriptional profiling of more than 12,000 single cells from human PSC-derived kidney organoid cultures was used to identify robust and reproducible cell lineage gene expression signatures shared with developing human kidneys based on trajectory analysis.

NT-proBNP Goal Achievement Is Associated With Significant Reverse Remodeling and Improved Clinical Outcomes in HFrEF.

Objectives: This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.

Background: In patients with heart failure with reduced ejection fraction (HFrEF), it is unclear if lowering natriuretic peptides reflects structural and functional changes in the heart. This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.

Sampling bias overestimates climate change impacts on forest growth in the southwestern United States.

Climate-tree growth relationships recorded in annual growth rings have recently been the basis for projecting climate change impacts on forests. However, most trees and sample sites represented in the International Tree-Ring Data Bank (ITRDB) were chosen to maximize climate signal and are characterized by marginal growing conditions not representative of the larger forest ecosystem. We evaluate the magnitude of this potential bias using a spatially unbiased tree-ring network collected by the USFS Forest Inventory and Analysis (FIA) program.

Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure.

Background: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial prospectively compared the efficacy of an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided heart failure treatment strategy (target NT-proBNP level <1,000 pg/ml) with optimal medical therapy alone in high-risk patients with heart failure and reduced ejection fraction. When the study was stopped for futility, 894 patients had been enrolled.

Objectives: The purpose of this study was to assess treatment-related quality-of-life (QOL) and economic outcomes in the GUIDE-IT trial.

Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial.

Background: Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30days post discharge.

Relationship Between Enrolling Country Income Level and Patient Profile, Protocol Completion, and Trial End Points.

Background: Globalization of clinical trials fosters inclusion of higher and lower income countries, but the influence of enrolling country income level on heart failure trial performance is unclear. This study sought to evaluate associations between enrolling country income level, acute heart failure patient profile, protocol completion, and trial end points.

Methods And Results: The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial included 7141 patients with acute heart failure from 30 countries.

Reassessing the Role of Surrogate End Points in Drug Development for Heart Failure.

With few notable exceptions, drug development for heart failure (HF) has become progressively more challenging, and there remain no definitively proven therapies for patients with acute HF or HF with preserved ejection fraction. Inspection of temporal trends suggests an increasing rate of disagreement between early-phase and phase III trial end points. Preliminary results from phase II HF trials are frequently promising, but increasingly followed by disappointing phase III results.

Dose Response of β-Blockers in Adrenergic Receptor Polymorphism Genotypes.

Background In heart failure (HF) with reduced ejection fraction, 2 clinical trials, the BEST (β-Blocker Evaluation of Survival Trial) and HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), have reported an effectiveness interaction between the ADRB1 (β-1 adrenergic receptor) Arg389Gly polymorphism and β-blockers (BBs). HF-ACTION additionally reported a dose-related interaction of unclear origin. If confirmed and pharmacogenetically resolved, these findings may have important implications for HF with reduced ejection fraction precision therapy.

Renal Function and Exercise Training in AmbulatoryHeart Failure Patients With a Reduced Ejection Fraction.

Patients with chronic kidney disease (CKD) and/or end-stage renal disease are less active and experience significant functional limitations. The impact of a structured aerobic exercise intervention on outcomes in ambulatory heart failure (HF) patients with comorbid CKD is unknown. HF-ACTION enrolled 2,331 outpatients with HF and a reduced ejection fraction (i.

Impact of exercise-based cardiac rehabilitation in patients with heart failure (ExTraMATCH II) on mortality and hospitalisation: an individual patient data meta-analysis of randomised trials.

Aims: To undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity.

Methods And Results: Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow-up or longer, providing IPD time to event on mortality or hospitalisation (all-cause or HF-specific). IPD were combined into a single dataset.

A Critical Appraisal of Short-Term End Points in Acute Heart Failure Clinical Trials.

The prevalence of heart failure continues to grow, and this is accompanied by an increase in hospitalization for acute heart failure. Hospitalization for heart failure results in a trajectory shift of the syndrome and is associated with worsening outcomes, increased mortality risk, and high costs. Numerous clinical trials over the past 2 decades have had limited success, with no single agent shown to improve mortality risk.

Relation of Volume Overload to Clinical Outcomes in Acute Heart Failure (From ASCEND-HF).

We aimed to study whether jugular venous distension (JVD) and peripheral edema were associated with worse outcomes in patients with acute heart failure in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial. Of 7,141 patients in Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure, 7,135 had complete data on baseline JVD and peripheral edema status. Patients were grouped according to baseline examination findings: (1) no JVD or peripheral edema; (2) JVD only; (3) peripheral edema only; (4) JVD and peripheral edema.

Relationship between changing patient-reported outcomes and subsequent clinical events in patients with chronic heart failure: insights from HF-ACTION.

Aims: A 5-point change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) is commonly considered to be a clinically significant difference in health status in patients with heart failure. We evaluated how the magnitude of change relates to subsequent clinical outcomes.

Methods And Results: Using data from the HF-ACTION trial of exercise training in chronic heart failure (n = 2331), we used multivariable Cox regression with piecewise linear splines to examine the relationship between change in KCCQ overall summary score from baseline to 3 months (range 0-100; higher scores reflect better health status) and subsequent all-cause mortality/hospitalization.

Loop diuretic adjustments in patients with chronic heart failure: Insights from HF-ACTION.

Background: The relationship between diuretic use or change in diuretic use and outcomes in chronic heart failure (HF) remains poorly defined. We evaluated the association between diuretic use and changes in health status, exercise capacity, and clinical events in a large randomized trial of subjects with HF.

Methods: HF-ACTION randomized 2,331 outpatients with HF and ejection fraction ≤35% to aerobic exercise training versus usual care.

Enrollment of Older Patients, Women, and Racial and Ethnic Minorities in Contemporary Heart Failure Clinical Trials: A Systematic Review.

Importance: Despite the importance of age, sex, and race/ethnicity representativeness in clinical trials, limited data exist regarding the enrollment trends of these groups in contemporary heart failure (HF) trials.

Objective: To characterize the representation of older patients, women, and racial and ethnic minorities in HF trials.

Evidence Review: We performed a systematic search of HF trials enrolling more than 400 participants published between January 2001 and December 2016 using PubMed/Medline and ClinicalTrials.

Worsening renal function during decongestion among patients hospitalized for heart failure: Findings from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial.

Introduction: Worsening renal function (WRF) can occur throughout a hospitalization for acute heart failure (HF). However, decongestion can be measured in different ways and the prognostic implications of WRF in the setting of different measures of decongestion are unclear.

Methods: Patients (N = 433) from the ESCAPE were classified by measures of decongestion during hospitalization: hemodynamic (right atrial pressure ≤8 mmHg and/or wedge pressure ≤15 mmHg at discharge), clinical (≤1 sign of congestion at discharge), hemoconcentration (any increase in hemoglobin) and estimated plasma volume using the Hakim formula (5% reduction in plasma volume).