SOPRANO: Macitentan in patients with pulmonary hypertension following left ventricular assist device implantation.

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study.

Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus.

Background: Oral treprostinil is a prostacyclin analogue approved to treat pulmonary arterial hypertension (PAH) by delaying disease progression and improving exercise capacity. Higher doses of oral treprostinil correlate with increased treatment benefit. Titrations may be challenging due to common side effects of prostacyclin-class therapies.

Surveillance with dual noninvasive testing for acute cellular rejection after heart transplantation: Outcomes from the Surveillance HeartCare Outcomes Registry.

Background: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated.

Unveiling molecular insights: in silico exploration of TLR4 antagonist for management of dry eye syndrome.

Background: Dry eye disease is the most commonplace multifractional ocular complication, which has already affected millions of people in the world. It is identified by the excessive buildup of reactive oxygen species, leading to substantial corneal epithelial cell demise and ocular surface inflammation attributed to TLR4. In this study, we aimed to identify potential compounds to treat of dry eye syndrome by exploring in silico methods.

Access to durable LVAD therapy for patients with limited social support: Surveying program-specific approaches.

Racial and ethnic disparities in provision of left ventricular assist device (LVAD) therapy have been identified. These disparities may be at least partially related to socioeconomic factors, including social support networks and financial constraints. This study aimed to identify specific barriers, and variations in institutional approaches, to the provision of equitable care to underserved populations.

Computational Design of Low Melting Eutectics of Molten Salts: A Combined Machine Learning and Thermodynamic Modeling Approach.

We develop a computational framework combining thermodynamic and machine learning models to predict the melting temperatures of molten salt eutectic mixtures (). The model shows an accuracy of ∼6% (mean absolute percentage error) over the entire data set. Using this approach, we screen millions of combinatorial eutectics ranging from binary to hexanary, predict new mixtures, and propose design rules that lead to low .

A Phenomapping Tool and Clinical Score to Identify Low Diuretic Efficiency in Acute Decompensated Heart Failure.

Background: Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking.

Objectives: The authors sought to develop and externally validate a machine learning-based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency.

Predicting the functional state of protein kinases using interpretable graph neural networks from sequence and structural data.

Protein kinases are central to cellular activities and are actively pursued as drug targets for several conditions including cancer and autoimmune diseases. Despite the availability of a large structural database for kinases, methodologies to elucidate the structure-function relationship of these proteins (without manual intervention) are lacking. Such techniques are essential in structural biology and to accelerate drug discovery efforts.

Left Ventricular Assist Device and the Current State of the Art: HeartMate 3 at 5 Years.

Left ventricular assist devices (LVADs) or cardiac transplantation are the two prevailing methods of treating patients with end-stage heart failure. The availability of donor hearts is insufficient to meet the needs of patients with advanced heart failure. LVADs offer a potential alternative to transplantation for those patients who cannot wait or are otherwise unsuited for cardiac transplantation.

Clinical Outcomes With a Fully Magnetically Levitated Left Ventricular Assist Device Among Women and Men.

Background: Left ventricular assist devices (LVADs) are underused among women with advanced heart failure, but reasons remain unclear. Outcomes in women compared with men with contemporary fully magnetically levitated LVADs remain uncertain.

Objectives: The authors examined differences in characteristics, 2-year outcomes, and risk for key adverse events among women and men.

Parenteral treprostinil induction for rapid attainment of therapeutic doses of oral treprostinil.

Rationale: Oral treprostinil slows disease progression and improves exercise capacity in pulmonary arterial hypertension; however, titration can be prolonged. Published data suggests prostacyclin-naïve patients achieve total daily oral treprostinil doses of about 6 mg by Week 16, while those on prior parenteral treprostinil reach higher doses at the same timepoint.

Objectives: EXPEDITE (NCT03497689), a single-arm, multicenter study, assessed the efficacy of rapid parenteral treprostinil induction to quickly reach higher doses of oral treprostinil for the treatment of pulmonary arterial hypertension.

Implementing the EXPEDITE parenteral induction protocol: Rapid parenteral treprostinil titration and transition to oral treprostinil.

Treprostinil is a prostacyclin analogue that targets multiple cellular receptors to treat pulmonary arterial hypertension (PAH). In certain scenarios, patients may require aggressive treprostinil titration. Several studies have demonstrated that higher doses of treprostinil lead to greater clinical benefit.

Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study.

Introduction: The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD.

Methods: Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil.

Safety of macitentan for the treatment of pulmonary hypertension: Real-world experience from the OPsumit® USers Registry (OPUS) and OPsumit® Historical USers cohort (OrPHeUS).

Macitentan is an oral endothelin receptor antagonist for the management of pulmonary arterial hypertension (PAH). The OPsumit® USers Registry (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) medical chart review provide real-world data for patients newly initiating macitentan. This study aims to describe the characteristics, safety profile, and clinical outcomes of PAH patients newly treated with macitentan in the combined OPUS/OrPHeUS data set.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

Background: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices.

Disparities in Practice Patterns by Sex, Race, and Ethnicity in Patients Referred for Advanced Heart Failure Therapies.

Advanced heart failure (HF) therapies improve survival in patients with stage D HF. We sought to evaluate differences by race/ethnicity and sex in advanced HF therapy referrals and decision-making across a multicenter survey. We performed a retrospective analysis of patients referred for evaluation for advanced HF therapies at 9 centers (n = 515) across the United States.

Safety and effects of SGLT-2 inhibitor use among LVAD patients with type 2 diabetes mellitus.

SGLT-2 inhibitors have been shown to confer reduced risk of adverse cardiovascular events in patients with heart failure, and have also been studied preliminarily among heart transplant patients, with overall positive findings. Use of SGLT-2 inhibitors among patients with durable mechanical circulatory support has not been studied. Here we present our results from a combined retrospective cohort of LVAD patients on SGLT-2 inhibitors at two major academic centers, which showed a good safety profile but prompted questions for further investigation.

Implantable cardioverter-defibrillator-related procedures and associated complications in continuous flow left ventricular assist device recipients: A multicenter experience.

Background: Limited data exist regarding complication rates of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy devices (CRT-D) in patients with left ventricular assist devices (LVAD).

Objective: We describe the incidence and characteristics of ICD- and CRT-D-related procedures and complications in a multicenter LVAD cohort.

Methods: A total of 537 LVAD patients with a pre-existing ICD or CRT-D from 5 centers were included.

Impact of Race on Clinical Outcomes After Implantation With a Fully Magnetically Levitated Left Ventricular Assist Device: An Analysis From the MOMENTUM 3 Trial.

Background: Heart failure disproportionately affects Black patients. Whether differences among race influence outcomes in advanced heart failure with use of a fully magnetically levitated continuous-flow left ventricular assist device remains uncertain.

Methods: We included 515 IDE (Investigational Device Exemption) clinical trial patients and 500 Continued Access Protocol patients implanted with the HeartMate 3 left ventricular assist device in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3).