Congestion in acute heart failure trials and registries: a systematic review

Introduction: The term “congestion” is used to describe a broad range of clinical presentations. Congestion is a variably understood and assessed entity. Patients develop a mixture of central (pulmonary) and/or peripheral (non-pulmonary) symptoms of congestion. These are likely to have different pathophysiological mechanisms. The presence of subclinical congestion is an independent risk factor for early re-hospitalisation and morbidity. Novel techniques to assess congestion have been developed, but their clinical role is not yet established. Methods: I performed two systematic reviews of acute heart failure (AHF) trials and registries from Jan 1, 2001 to Dec 31, 2018 on EMBASE and MEDLINE to determine the methods and techniques used to assess and grade congestion. The search terms utilised were “acute heart failure”, “decompensated heart failure” and “hospitalized heart failure”. The minimum enrolment numbers were 180 patients for randomised trials and 2,000 patients for registries. Results: 18 major acute heart failure registries and 21 major trials were analysed. There are no standardised methods for assessing central or peripheral congestion. Acute heart failure trials preferentially recruited patients with pulmonary congestion (manifesting as dyspnoea at rest). In 6 of 8 trials with available data, this was mandatory for 100% of patients. By contrast, for large registry trials this rate ranged from 34 to 73%. Dyspnoea on exertion was a more predominant presentation (61 to 95%). With the exception of a chest X-ray, no trial or registry routinely utilised non-invasive (e.g. lung ultrasound) or invasive (e.g. right heart catheterisation) techniques to objectively and systematically quantify either congestion on recruitment or congestion on discharge. Conclusion: Congestion is variably assessed and defined. Internationally agreed definitions of the presence and severity of congestion are required. These definitions should include conventional symptoms and signs as well as newer methods of assessing congestion. Trials of treatments for central or peripheral congestion may have different inclusion criteria

Personalized medicine and hospitalization for heart failure: if we understand it, we may be successful in treating it

Randomized trials in patients with hospitalized heart failure (HHF) continue to frustrate the cardiology community. Promising haemodynamic, structural and biomarker findings from phase 2 studies consistently fail to deliver substantive benefits in larger outcome trials. What underlies these recurrent failures? Why are persistently high readmission and post‐discharge mortality rates not being reduced? Challenging any pre‐conceived ideas about the existence of a ‘typical’ acutely decompensated heart failure patient is fundamental, as is the adoption of a carefully personalized approach. These individuals come from a remarkably heterogeneous group. Surely precise phenotyping should translate to a more successful therapeutic approach

A comparative study of polyurethane nanofibers with different patterns and its analogous nanofibers containing MWCNTs

Tissue engineering is a multidisciplinary field that has evolved in various dimensions in recent years. One of the main aspects in this field is the proper adjustment and final compatibility of implants at the target site of surgery. For this purpose, it is desired to have the materials fabricated at the nanometer scale, since these dimensions will ultimately accelerate the fixation of implants at the cellular level. In this study, electrospun polyurethane nanofibers and their analogous nanofibers containing MWCNTs are introduced for tissue engineering applications. Since MWCNTs agglomerate to form bundles, a high intensity sonication procedure was used to disperse them, followed by electrospinning the polymer solutions that contained these previously dispersed MWCNTs. Characterization of the produced nanofibers has confirmed production of different non-woven mats, which include random, semi-aligned and mostly aligned patterns. A simultaneous and comparative study was conducted on the nanofibers with respect to their thermal stability, mechanical properties and biocompatibility. Results indicate that the mostly aligned nanofibers pattern presents higher thermal stability, mechanical properties, and biocompatibility. Furthermore, incorporation of MWCNTs among the different arrangements significantly improved the mechanical properties and cell alignment along the nanofibers

Imaging, Spectroscopy, Mechanical, Alignment and Biocompatibility Studies of Electrospun Medical Grade Polyurethane (Carbothane™ 3575A) Nanofibers and Composite Nanofibers Containing Multiwalled Carbon Nanotubes

In the present study, we discuss the electrospinning of medical grade polyurethane (Carbothane™ 3575A) nanofibers containing multi-walled-carbon-nanotubes (MWCNTs). A simple method that does not depend on additional foreign chemicals has been employed to disperse MWCNTs through high intensity sonication. Typically, a polymer solution consisting of polymer/MWCNTs has been electrospun to form nanofibers. Physiochemical aspects of prepared nanofibers were evaluated by SEM, TEM, FT-IR and Raman spectroscopy, confirming nanofibers containing MWCNTs. The biocompatibility and cell attachment of the produced nanofiber mats were investigated while culturing them in the presence of NIH 3T3 fibroblasts. The results from these tests indicated non-toxic behavior of the prepared nanofiber mats and had a significant attachment of cells towards nanofibers. The incorporation of MWCNTs into polymeric nanofibers led to an improvement in tensile stress from 11.40 ± 0.9 to 51.25 ± 5.5 MPa. Furthermore, complete alignment of the nanofibers resulted in an enhancement on tensile stress to 72.78 ± 5.5 MPa. Displaying these attributes of high mechanical properties and non-toxic nature of nanofibers are recommended for an ideal candidate for future tendon and ligament grafts

Imaging, Spectroscopic, Mechanical and Biocompatibility Studies of Electrospun Tecoflex® EG 80A Nanofibers and Composites Thereof Containing Multiwalled Carbon Nanotubes

The present study discusses the design, development and characterization of electrospun Tecoflex® EG 80A class of polyurethane nanofibers and the incorporation of multiwalled carbon nanotubes (MWCNTs) to these materials. Scanning electron microscopy results confirmed the presence of polymer nanofibers, which showed a decrease in fiber diameter at 0.5% wt. and 1% wt. MWCNTs loadings, while transmission electron microscopy showed evidence of the MWCNTs embedded within the polymer matrix. The fourier transform infrared spectroscopy and Raman spectroscopy were used to elucidate the polymer-MWCNTs intermolecular interactions, indicating that the C-N and N-H bonds in polyurethanes are responsible for the interactions with MWCNTs. Furthermore, tensile testing indicated an increase in the Young’s modulus of the nanofibers as the MWCNTs concentration was increased. Finally, NIH 3T3 fibroblasts were seeded on the obtained nanofibers, demonstrating cell biocompatibility and proliferation. Therefore, the results indicate the successful formation of polyurethane nanofibers with enhanced mechanical properties, and demonstrate their biocompatibility, suggesting their potential application in biomedical area

Low Temperature Synthesis of Superparamagnetic Iron Oxide (Fe3O4) Nanoparticles and Their ROS Mediated Inhibition of Biofilm Formed by Food-Associated Bacteria

In the present study, a facile environmentally friendly approach was described to prepare monodisperse iron oxide (Fe3O4) nanoparticles (IONPs) by low temperature solution route. The synthesized nanoparticles were characterized using x-ray diffraction spectroscopy (XRD), Raman spectroscopy, field emission scanning electron microscopy (FESEM) measurements, Fourier-Transform Infrared Spectroscopy (FTIR), and Thermogravimetric analysis (TGA) analyses. XRD patterns revealed high crystalline quality of the nanoparticles. SEM micrographs showed the monodispersed IONPs with size ranging from 6 to 9 nm. Synthesized nanoparticles demonstrated MICs of 32, 64, and 128 μg/ml against Gram negative bacteria i.e., Serratia marcescens, Escherichia coli, and Pseudomonas aeruginosa, respectively, and 32 μg/ml against Gram positive bacteria Listeria monocytogenes. IOPNs at its respective sub-MICs demonstrated significant reduction of alginate and exopolysaccharide production and subsequently demonstrated broad-spectrum inhibition of biofilm ranging from 16 to 88% in the test bacteria. Biofilm reduction was also examined using SEM and Confocal Laser Scanning Microscopy (CLSM). Interaction of IONPs with bacterial cells generated ROS contributing to reduced biofilm formation. The present study for the first time report that these IONPs were effective in obliterating pre-formed biofilms. Thus, it is envisaged that these nanoparticles with broad-spectrum biofilm inhibitory property could be exploited in the food industry as well as in medical settings to curtail biofilm based infections and losses

Natural product-inspired synthesis of coumarin–chalcone hybrids as potential anti-breast cancer agents

Twelve novel neo-tanshinlactone–chalcone hybrid molecules were constructed through a versatile methodology involving the Horner–Wadsworth–Emmons (HWE) olefination of 4-formyl-2H-benzo [h]chromen-2-ones and phosphonic acid diethyl esters, as the key step, and evaluated for anticancer activity against a series of four breast cancers and their related cell lines, viz. MCF-7 (ER + ve), MDA-MB-231 (ER-ve), HeLa (cervical cancer), and Ishikawa (endometrial cancer). The title compounds showed excellent to moderate in vitro anti-cancer activity in a range of 6.8–19.2 µM (IC50). Compounds 30 (IC50 = 6.8 µM and MCF-7; IC50 = 8.5 µM and MDA-MB-231) and 31 (IC50 = 14.4 µM and MCF-7; IC50 = 15.7 µM and MDA-MB-231) exhibited the best activity with compound 30 showing more potent activity than the standard drug tamoxifen. Compound 30 demonstrated a strong binding affinity with tumor necrosis factor α (TNF-α) in molecular docking studies. This is significant because TNFα is linked to MCF-7 cancer cell lines, and it enhances luminal breast cancer cell proliferation by upregulating aromatase. Additionally, virtual ADMET studies confirmed that hybrid compounds 30 and 31 met Lipinski’s rule; displayed high bioavailability, excellent oral absorption, favorable albumin interactions, and strong penetration capabilities; and improved blood–brain barrier crossing. Based on the aforementioned results, compound 30 has been identified as a potential anti-breast cancer lead molecule

Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial

Aims Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods and results In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2; P = 0.03) and NTG (28 ± 8 mL/m2; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e′ (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo. Conclusion In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure