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It is hypothesized that sodium glucose cotransporter 2 (SGLT2) inhibition, mediated by sustained glucose loss, restores mTOR cycling through nutrient-driven, nightly periods of transient mTOR inhibition (and restoration of catabolic cellular housekeeping processes) interspersed by daily periods of transient mTOR activation (and anabolism) accompanying eating. In this way, a flexible mTOR dynamic is restored, thereby preventing or even reducing the progress of AD pathology. The first study to investigate the effect of SGLT2 inhibition in patients with AD is ongoing and focuses on the impact on energy metabolism in the brain following treatment with the SGLT2 inhibitor dapagliflozin.Non-communicable diseases (NCDs) that involve neurodegenerative disorders and metabolic disease impact over 400 million individuals globally. Interestingly, metabolic disorders, such as diabetes mellitus, are significant risk factors for the development of neurodegenerative diseases. Given that current therapies for these NCDs address symptomatic care, new avenues of discovery are required to offer treatments that affect disease progression. selleck inhibitor Innovative strategies that fill this void involve the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR complex 1 (mTORC1), mTOR complex 2 (mTORC2), AMP activated protein kinase (AMPK), trophic factors that include erythropoietin (EPO), and the programmed cell death pathways of autophagy and apoptosis. These pathways are intriguing in their potential to provide effective care for metabolic and neurodegenerative disorders. Yet, future work is necessary to fully comprehend the entire breadth of the mTOR pathways that can effectively and safely translate treatments to clinical medicine without the development of unexpected clinical disabilities.Pulmonary hypertension (PH) associated with left heart disease, or Group 2 PH, includes heart failure, valvular heart diseases, and congenital heart diseases. Although it is axiomatic that in PH due to heart failure the increase in pulmonary pressure is directly related to an enhanced left atrial pressure, which is common to both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), there has been limited attention over the years on the potential differences in terms of driving mechanisms, pathophysiology, and clinical phenotypes. Major differences between HFpEF and HFrEF are the underlying causes, associated comorbidities, and cardiac remodeling. This suggests that despite similar hemodynamic profiles, there may be some disparities in PH development. A focused knowledge on the differences between the 2 syndromes has relevant implications to seek new, personalized, and timely treatments for Group 2 PH. The purpose of the present review is to highlight the mechanisms and clinical phenotypes of PH in HFpEF and HFrEF.Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor short- and long-term outcomes. There are no specific therapies to reduce mortality related to either AKI or CRS, apart from supportive care and volume status management. Acute renal replacement therapies (RRTs), including ultrafiltration, intermittent hemodialysis, and continuous RRT are used to manage complications of medically refractory AKI and CRS and may restore normal electrolyte, acid-base, and fluid balance before renal recovery. Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient selection. Despite the growing use of RRT in the cardiac intensive care unit, there are few resources for the cardiovascular specialist that integrate the epidemiology, diagnostic workup, and medical management of AKI and CRS with an overview of indications, multidisciplinary team management, and transition off of RRT.

Unlike for paroxysmal atrial fibrillation (AF), pulmonary vein isolation (PVI) alone is considered insufficient for many patients with persistent AF. Adjunctive ablation of the left atrial posterior wall (LAPW) may improveoutcomes, but is limited by both the difficulty of achieving lesion durability and concerns of damage to the esophagus-situated behind the LAPW.

This study sought to assess the safety and lesion durability of pulsed field ablation (PFA) for both PVI and LAPW ablation in persistent AF.

PersAFOne is a single-arm study evaluating biphasic, bipolar PFA using a multispline catheter for PVI and LAPW ablation under intracardiac echocardiographic guidance. A focal PFA catheter was used for cavotricuspid isthmus ablation. No esophageal protection strategy was used. Invasive remapping was mandated at 2 to 3months to assess lesion durability.

In 25 patients, acute PVI (96 of 96 pulmonary veins [PVs]; mean ablation time 22min; interquartile range [IQR] 15 to 29min) and LAPW ablation (24 of 24 pa forms of AF. (Pulsed Fields for Persistent Atrial Fibrillation [PersAFOne]; NCT04170621).

The unique safety profile of PFA potentiated efficient, safe, and durable PVI and LAPW ablation. This extends the potential role of PFA beyond paroxysmal to persistent forms of AF. (Pulsed Fields for Persistent Atrial Fibrillation [PersAFOne]; NCT04170621).

Paroxysmal and permanent atrial fibrillation (AF) are common in heart failure with preserved ejection fraction (HFpEF).

This study sought to determine the implications of left atrial (LA) myopathy and dysrhythmia across the spectrum of AF burden in HFpEF.

Consecutive patients with HFpEF (n=285) and control subjects (n=146) underwent invasive exercise testing and echocardiographic assessment of cardiac structure, function, and pericardial restraint.

Patients with HFpEF were categorized into stages of AF progression 181 (65%) had no history of AF, 49 (18%) had paroxysmal AF, and 48 (17%) had permanent AF. Patients with permanent AF were more congested with greater pulmonary vascular disease and lower cardiac output. LA volumes increased, while LA compliance, LA reservoir strain, and right ventricular function decreased with increasing AF burden. The presence of permanent AF was characterized by a distinct pathophysiology, with greater total heart volume caused by atrial dilatation, leading to elevated filling pressures through heightened pericardial restraint.