Search

Aims: Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline‐directed medical therapies. The haemodynamic effects of vericiguat remain unclear. Methods and results: This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II–IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline‐recommended therapies between March and December 2022, with follow‐ups completed in June 2023. A balloon‐tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5 mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5 mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30 min after (both P < 0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P < 0.05), when vericiguat was titrated to 2.5 mg 25% (N = 3), 5 mg 50% (N = 6), and 10 mg 25% (N = 3). Conclusions: The consistent reduction in PAWP underscores the well‐tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Introduction: As well as preventing nosocomial and healthcare‐associated infections, a reliable and eco‐friendly washer for medical equipment would also be safe for the global environment. The aim of this study was to evaluate the efficacy of a newly developed automatic washing system (Nano‐washer) that uses electrolyzed water and ultrasonication without detergent for washing endoscopes. Methods: Patients who underwent laparoscopic lobectomy or laparoscopic colectomy at Nagasaki University between 2018 and 2022 were included. A total of 60 cases of endoscope use were collected and classified according to endoscope washing method into the Nano‐washer group (using no detergent) (n = 40) and the manual washing group (n = 20). Protein and bacterial residues were measured before and after washing, using absorbance spectrometry and 16S rRNA polymerase chain reaction. The effectiveness of protein and bacterial removal and endoscope surface damage after washing were compared under specular vision between the groups. Results: Nano‐washer did not use detergent unlike manual washing. There was no difference in demographic or clinical characteristics between the groups except for the presence of comorbidities in the lobectomy group (Nano‐washer, 85%; manual washing, 40%, P =.031). Compared with the manual washing group, residual protein levels in the Nano‐washer group were significantly reduced after washing (lobectomy, 0.956 mg/mL vs 0.016 mg/mL, P <.001; colectomy, 0.144 mg/mL vs 0.002 mg/mL, P =.008). Nano‐washer group showed a significant reduction in bacteria between before and after lobectomy (9437 copies/cm2 vs 4612 copies/cm2, P =.024). Conclusion: Nano‐washer is a promising, effective, and eco‐friendly automatic washing device that is safer and more efficient than manual washing. [ABSTRACT FROM AUTHOR]

Aims: The pathophysiology of pulmonary hypertension (PH) due to left‐sided heart disease (Group 2 PH) is distinct from that of other groups of PH, yet there are still no approved therapies that selectively target pulmonary circulation. The increase in pulmonary capillary pressure due to left‐sided heart disease is a trigger event for physical and biological alterations of the pulmonary circulation, including the nitric oxide (NO)–soluble guanylate cyclase–cyclic guanosine monophosphate axis. This study investigated inhaled NO vasoreactivity tests for patients with Group 2 PH and hypothesized that these changes may have a prognostic impact. Methods and results: This was a single‐centre, retrospective study with a median follow‐up of 365 days. From January 2011 to December 2015, we studied 69 patients with Group 2 PH [age, 61.5 ± 13.0 (standard deviation) years; male:female, 49:20; left ventricular ejection fraction, 50.1 ± 20.4%; mean pulmonary arterial pressure, ≥25 mmHg; and pulmonary arterial wedge pressure (PAWP), >15 mmHg]. No adverse events were observed after NO inhalation. Thirty‐four patients with Group 2 PH showed increased PAWP (ΔPAWP: 3.26 ± 2.22 mmHg), while the remaining 35 patients did not (ΔPAWP: −2.11 ± 2.29 mmHg). Multivariate analysis revealed that increased PAWP was the only significant predictor of all‐cause death or hospitalization for heart failure (HF) after 1 year (hazard ratio 4.35; 95% confidence interval, 1.27–14.83; P = 0.019). The acute response of PAWP to NO differed between HF with preserved and reduced ejection fractions. Conclusions: Patients with Group 2 PH were tolerant of the inhaled NO test. NO‐induced PAWP is a novel prognostic indicator. [ABSTRACT FROM AUTHOR]

Dual chalcogen‐bonding interactions is proposed as a novel means for the conformational control of urea derivatives. The formation of a chalcogen‐bonding interaction at both sides of the urea carbonyl group was unambiguously confirmed by X‐ray diffraction as well as computational studies including non‐covalent interaction (NCI) plot index analysis, quantum theory of atoms in molecules (QTAIM) analysis, and natural bond orbital (NBO) analysis via DFT calculations. By virtue of this dual interaction, urea derivatives that bear chalcogen atoms (X=S and Se) adopt a planar structure via the carbonyl oxygen (O) with an X⋅⋅⋅O⋅⋅⋅X arrangement on the same side of the molecule. The rigidity of the conformational lock was evaluated using the molecular arrangement in the crystal and the rotational barrier of benzochalcogenophene ring, which indicated a stronger conformational lock in benzoselenophene than in benzothiophene urea derivatives. Furthermore, the acidity of the urea derivatives increases according to the Lewis‐acidic properties of the chalcogen‐bonding interactions, whereby benzoselenophene urea is more acidic than benzothiophene urea. Tweezer‐shaped urea derivatives were prepared, and their stereostructure proved the viability of the conformational control for defining the location of the substituents on the urea framework. [ABSTRACT FROM AUTHOR]

Aims: With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super‐aged society. Methods and results: The KUNIUMI registry chronic cohort is a community‐based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P < 0.01). The prevalence of atrial fibrillation, and in particular long‐standing persistent atrial fibrillation, increased at 70 years of age (P < 0.01). The proportion of patients with heart failure with preserved ejection fraction increased to ~60% when age was over 75 years. Although ischaemic heart disease accounted for 35.0% of chronic heart failure aetiologies, valvular heart disease was the most common cause of chronic heart failure (49.8%). The major types of valvular heart disease were mitral regurgitation and tricuspid regurgitation (27.2% and 21.7%, respectively), both of which increased significantly with age (P < 0.01). The incidence of aortic valve stenosis increased markedly over the age of 85 years (P < 0.01). Atrial functional mitral regurgitation increased with age and was the major cause of mitral regurgitation in patients aged >75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long‐standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P < 0.001, respectively). Conclusions: The KUNIUMI registry chronic cohort showed a change in heart failure aetiology to valvular heart disease in a super‐aged society. Effective and comprehensive countermeasures are required to prepare for the rapid rise in heart failure incidence in a super‐aged society. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acids, such as arachidonic acid, are accumulated in brain and induce neuronal differentiation. Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) by cytochrome P450s. In this study, we found that 14,15-EET and 20-HETE-enhanced NGF-induced rat pheochromocytoma PC12 cell neurite outgrowth even at the concentration of 100 nmol L-1. LC-MS analysis revealed that 14,15-EET was effectively produced from arachidonic acid by rat CYP2C11, 2C13, and 2C23, and these P450s were expressed in PC12 cells. An inhibitor of these P450s, ketoconazole, inhibited neurite outgrowth, whereas inhibition of soluble epoxide hydrolase, which hydrolyzes EETs to their corresponding diols enhanced neurite outgrowth. To determine the mechanism of neurite formation enhancement by arachidonic acid metabolites, we focused on transient receptor potential (TRP) channels expressed in PC12 cells. The TRPV4 inhibitor HC067047, but not the TRPV1 inhibitor capsazepine, inhibited the effects of 14,15-EET on neurite outgrowth of PC12. Furthermore, 14,15-EET increased the cytosolic calcium ion concentration and this increase was inhibited by HC067047. 14,15-EET also enhanced neurite outgrowth of primary cultured neuron from rat hippocampus. This study suggests that arachidonic acid metabolites produced by P450 contribute to neurite outgrowth through calcium influx. [ABSTRACT FROM AUTHOR]

A 29-year-old male who underwent a complete tetralogy of Fallot repair at 2 years of age was referred to our hospital for treatment of sustained ventricular tachycardia (VT). The bipolar voltage map using an electroanatomical mapping system (CARTO, Biosense-Webster. during sinus rhythm revealed a low voltage area identical to the site of the right ventricular outflow tract (RVOT. patch on the anterior wall of the RVOT. During the tachycardia, the activation wavefront was found to revolve in a counterclockwise manner around the patch in the RVOT. Two radiofrequency catheter ablation (RFCA. sessions creating a line between the patch in the RVOT and pulmonary artery achieved only transient success. He underwent a pulmonary valve replacement and reconstruction of the RVOT with a transannular patch to treat the VT refractory to RFCA and severe pressure gradient in the RVOT. In postoperative electrophysiological study, a low voltage area in the RVOT connected to the pulmonary artery with the patch was observed, and produced conduction block in the reentry circuit of the VT. The patient has been free from any VT recurrence during 6 months of follow up. [Copyright &y& Elsevier]