Apneas of Heart Failure and Phenotype-Guided Treatments: Part One: OSA.

Sleep-disordered breathing (SDB), including OSA and central sleep apnea, is highly prevalent in patients with heart failure (HF). Multiple studies have reported this high prevalence in asymptomatic as well as symptomatic patients with reduced left ventricular ejection fraction (HFrEF), as well as in those with HF with preserved ejection fraction. The acute pathobiologic consequences of OSA, including exaggerated sympathetic activity, oxidative stress, and inflammation, eventually could lead to progressive left ventricular dysfunction, repeated hospitalization, and excessive mortality.

Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined HF Population: The GENETIC-AF Trial.

Objectives: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF).

Background: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta-adrenergic receptor (ADRB1) Arg389Arg genotype.

Methods: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.

Phrenic nerve stimulation in patients with central sleep apnea: a single‑center experience from pilot and pivotal trials evaluating the remedē System.

Background: Patients with central sleep apnea (CSA) have recently been shown to have improved sleep metrics and quality of life (QoL) with phrenic nerve stimulation (PNS).

Aims: The aim of this study was to report the results of a partnership between cardiology, sleep medicine, and electrophysiology in a single clinical center as well as the enrollment, implantation, and follow‑up experience demonstrating both the safety and efficacy of PNS.

Methods: This analysis included data from the pilot and pivotal trials investigating the effect of PNS using an implantable transvenous system in patients with CSA.

Establishment of an induced memory response in Pseudomonas aeruginosa during infection of a eukaryotic host.

In a given habitat, bacterial cells often experience recurrent exposures to the same environmental stimulus. The ability to memorize the past event and to adjust current behaviors can lead to efficient adaptation to the recurring stimulus. Here we demonstrate that the versatile bacterium Pseudomonas aeruginosa adopts a virulence phenotype after serial passage in the invertebrate model host Galleria mellonella.

Health Status After Transcatheter Mitral-Valve Repair in Heart Failure and Secondary Mitral Regurgitation: COAPT Trial.

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) led to reduced heart failure (HF) hospitalizations and improved survival in patients with symptomatic HF and 3+ to 4+ secondary mitral regurgitation (MR) on maximally-tolerated medical therapy. Given the advanced age and comorbidities of these patients, improvement in health status is also an important treatment goal.

Objectives: The purpose of this study was to understand the health status outcomes of patients with HF and 3+ to 4+ secondary MR treated with TMVr versus standard care.

Imaging Device Therapy: Essentials for the Imager.

Treatment of patients with heart failure with reduced ejection fraction has evolved. Recently, a fully implantable remote hemodynamic monitoring sensor in the pulmonary artery was approved in the treatment of patients at risk of heart failure readmissions. Several novel devices designed to offload the left atrium by creating a small interatrial shunt are being investigated.

Glutamate Receptor Trafficking and Protein Synthesis Mediate the Facilitation of LTP by Secreted Amyloid Precursor Protein-Alpha.

Secreted amyloid precursor protein-alpha (sAPPα) has growth factor-like properties and can modulate long-term potentiation (LTP) and memory. Here, we demonstrate that exposure to sAPPα converts short-lasting LTP into protein-synthesis-dependent late LTP in hippocampal slices from male rats. sAPPβ had no discernable effect.

Cardiac Contractility Modulation and Baroreflex Activation Therapy in Heart Failure Patients.

Purpose Of Review: Despite advances in medical therapy, heart failure with reduced ejection fraction (HFrEF) is still a leading cause of mortality, hospitalizations, and healthcare costs. In this review, we describe two novel, implantable devices for the treatment of patients with HFrEF, cardiac contractility modulation (CCM), and baroreflex activation therapy (BAT), and summarize literature regarding these devices from the last 5 years.

Recent Findings: CCM improves quality of life and functional capacity as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, 6-min hall walk test (6MHWT) distance, New York Heart Association (NYHA) functional class, peak oxygen consumption (pVO), heart failure (HF) hospitalizations, and mortality.

Income Inequality and Outcomes in Heart Failure: A Global Between-Country Analysis.

Objectives: This study examined the relationship between income inequality and heart failure outcomes.

Background: The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes.

Methods: This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries.

Electrophysiological Investigation of Metabotropic Glutamate Receptor-Dependent Metaplasticity in the Hippocampus.

Metabotropic glutamate receptors (mGluRs) are one of the major types of glutamatergic receptors contributing to synaptic plasticity mechanisms such as long-term potentiation (LTP) and long-term depression. Interestingly, activation of mGluRs alone can engage metaplastic mechanisms that create a new neuronal state, facilitating the induction and maintenance of future LTP. Here we describe typical methods used to investigate mGluR-induced metaplasticity in acute hippocampal slices.

Differential Impact of Heart Failure With Reduced Ejection Fraction on Men and Women.

Background: Heart failure (HF) trials initiated in the last century highlighted many differences between men and women. Of particular concern was undertreatment of women compared with men, but much has changed during the past 20 years.

Objectives: This study sought to identify these changes, which may give a new perspective on the management of, and outcomes in, women with HF.

Design and rationale of haemodynamic guidance with CardioMEMS in patients with a left ventricular assist device: the HEMO-VAD pilot study.

Aims: We aim to study the feasibility and clinical value of pulmonary artery pressure monitoring with the CardioMEMS™ device in order to optimize and guide treatment in patients with a HeartMate 3 left ventricular assist device (LVAD).

Methods And Results: In this single-centre, prospective pilot study, we will include 10 consecutive patients with New York Heart Association Class IIIb or IV with Interagency Registry for Mechanically Assisted Circulatory Support Classes 2-5 scheduled for implantation of a HeartMate 3 LVAD. Prior to LVAD implantation, patients will receive a CardioMEMS sensor, for daily pulmonary pressure readings.

A Novel Wireless Left Atrial Pressure Monitoring System for Patients with Heart Failure, First Ex-Vivo and Animal Experience.

The V-LAP™ measures left atrial pressure (LAP) and enables bi-directional communications with an external unit, designed to monitor heart failure patients. We hereby describe the pre-clinical experience. Following an ex vivo phase, the system was implanted at the interatrial septum of 10 ovine subjects.

Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas.

Aims: Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world.

Methods And Results: We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.

Ambulatory Fontan pressure monitoring: Results from the implantable hemodynamic monitor Fontan feasibility cohort (IHM-FFC).

Background: Implantable invasive hemodynamic monitoring (IHM) using the CardioMEMS™ HF system has been shown to reduce heart failure (HF) hospitalizations. IHMs have not yet been used in congenital heart disease (CHD). We aimed to evaluate feasibility and mid-term outcomes of IHM use in the single ventricle/Fontan population.

Interatrial Shunting for Heart Failure: Early and Late Results From the First-in-Human Experience With the V-Wave System.

Objectives: This was a first-in-human study to assess the feasibility, safety, and exploratory efficacy of interatrial shunting for treating high-risk heart failure (HF) in patients with reduced and preserved ejection fraction.

Methods: A single-arm open-label study of patients with New York Heart Association functional class III or IV HF on optimal therapy was performed at 6 centers. The V-Wave shunt, an hourglass-shaped implant containing a 1-way bioprosthetic valve, was implanted by transseptal catheterization.

Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus Aureus.

During the course of our ongoing work to discover new inhibitors of biofilm formation of from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison.

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.

Circulating Plasma microRNAs are Altered with Amyloidosis in a Mouse Model of Alzheimer's Disease.

Pathological changes underlying Alzheimer's disease (AD) begin decades before the classical symptoms of memory loss become evident. As microRNAs are released from neurons and enter the bloodstream, circulating microRNAs may be reflective of AD progression and are ideal candidates as biomarkers for early-stage disease detection. Here, we provide a novel, in-depth analysis of how plasma microRNAs alter with aging, the most prominent risk factor for AD, and with development of amyloid-β (Aβ) plaque deposition.

Phrenic nerve stimulation to treat patients with central sleep apnoea and heart failure.

Aims: The presence of central sleep apnoea (CSA) is associated with poor prognosis in patients with heart failure (HF). The aim of this analysis was to evaluate if using phrenic nerve stimulation to treat CSA in patients with CSA and HF was associated with changes in HF-specific metrics.

Methods And Results: All patients randomized in the remedē System Pivotal Trial and identified at baseline with HF were included (n = 96).

Transcatheter Mitral-Valve Repair in Patients with Heart Failure.

Background: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.

Methods: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy.

Environmental enrichment increases prefrontal EEG power and synchrony with the hippocampus in rats with anterior thalamus lesions.

The anterior thalamic nuclei (ATN) are a major interface between the hippocampus and prefrontal cortex within an extended Papez circuit. Rat models suggest that the deficits caused by ATN damage, which is associated with "diencephalic amnesia", can be ameliorated by environmental enrichment (EE) through unknown mechanisms. We examined whether changes in theta rhythmicity within and between the hippocampus and prefrontal cortex are influenced by EE in rats with ATN lesions.