Drug-Induced Liver Injury in Pregnancy: The U.S. Drug-Induced Liver Injury Network Experience.

There are limited data on the causative agents and characteristics of drug-induced liver injury in pregnant individuals. Data from patients with drug-induced liver injury enrolled in the ongoing multicenter Drug-Induced Liver Injury Network between 2004 and 2022 and occurring during pregnancy or 6 months postpartum were reviewed and compared with cases of drug-induced liver injury in nonpregnant women of childbearing age. Among 325 individuals of childbearing age in the Drug-Induced Liver Injury Network, 16 cases of drug-induced liver injury (5%) occurred during pregnancy or postpartum.

Impact of vasodilators on diuretic response in patients with congestive heart failure: A mechanistic trial of cimlanod (BMS-986231).

Aim: To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide.

Methods And Results: In this randomized, double-blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction <45%, increased plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion.

Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study.

Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events.

Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects.

A change of heart: Preliminary results of the US 2018 adult heart allocation revision.

In 2018, the Organ Procurement and Transplantation Network (OPTN) modified adult heart allocation to better stratify candidates and provide broader access to the most medically urgent candidates. We analyzed OPTN data that included waiting list and transplant characteristics, geographical distribution, and early outcomes 1 year before (pre: October 18, 2017-October 17, 2018) and following (post: October 18, 2018-October 17, 2019) implementation. The number of adult heart transplants increased from 2954 pre- to 3032 postimplementation.

Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial.

Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30.

Site enrollment rate, outcomes, and study drug effects in a multicenter trial. Results from RELAX-AHF.

Background: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response.

Methods And Results: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included.

Relationship between baseline systolic blood pressure and long-term outcomes in acute heart failure patients treated with TRV027: an exploratory subgroup analysis of BLAST-AHF.

Introduction: TRV027, a 'biased' ligand of the angiotensin II type 1 receptor (AT1R), did not affect a composite clinical outcome at 30 days in a phase 2b acute heart failure (AHF) trial (BLAST-AHF).

Methods: Post-hoc analyses from BLAST-AHF (n = 618) examined the effects of TRV027 by baseline systolic blood pressure (SBP) on changes in renal function and 180-day outcomes. Interactions between baseline SBP and select endpoints were identified utilizing a subpopulation treatment effect pattern plots (STEPP) analysis, then grouping of patients by SBP tertile: < 127, ≥ 127 to < 140, and ≥ 140 mmHg.

Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF).

Aims: Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation.

Day vs night: Does time of presentation matter in acute heart failure? A secondary analysis from the RELAX-AHF trial.

Background: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial.

Use of High-Sensitivity Troponin T to Identify Patients With Acute Heart Failure at Lower Risk for Adverse Outcomes: An Exploratory Analysis From the RELAX-AHF Trial.

Objectives: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes.

Background: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted.

Applying novel methods to assess clinical outcomes: insights from the TRILOGY ACS trial.

Aims: Several methods provide new insights into understanding clinical trial composite endpoints, using both conventional and novel methods. The TRILOGY ACS trial is used as a contemporary example to prospectively compare these methods side by side.

Methods And Results: The traditional time-to-first-event, Andersen-Gill recurrent events method, win ratio, and a weighted composite endpoint (WCE) are compared using the randomized, active-control TRILOGY ACS trial.