Dysregulated Autophagy and Sarcomere Dysfunction in Patients With Heart Failure With Co-Occurrence of P63A and P380S Variants.

Background: Mutations to the co-chaperone protein BAG3 (B-cell lymphoma-2-associated athanogene-3) are a leading cause of dilated cardiomyopathy (DCM). These mutations often impact the C-terminal BAG domain (residues 420-499), which regulates heat shock protein 70-dependent protein turnover via autophagy. While mutations in other regions are less common, previous studies in patients with DCM found that co-occurrence of 2 variants (P63A, P380S) led to worse prognosis.

Endoplasmic Reticulum Chemical Chaperone 3-Hydroxy-2-Naphthoic Acid Reduces Angiotensin II-Induced Vascular Remodeling and Hypertension In Vivo and Protein Synthesis In Vitro.

Background Investigations into alternative treatments for hypertension are necessary because current treatments cannot fully reduce the risk for the development of cardiovascular diseases. Chronic activation of unfolded protein response attributable to the endoplasmic reticulum stress has been proposed as a potential therapeutic target for hypertension and associated vascular remodeling. Triggered by the accumulation of misfolded proteins, chronic unfolded protein response leads to downstream signaling of cellular inflammation and dysfunction.

Genetics of BAG3: A Paradigm for Developing Precision Therapies for Dilated Cardiomyopathies.

Nonischemic dilated cardiomyopathy is a common form of heart muscle disease in which genetic factors play a critical etiological role. In this regard, both rare disease-causing mutations and common disease-susceptible variants, in the Bcl-2-associated athanogene 3 () gene have been reported, highlighting the critical role of in cardiomyocytes and in the development of dilated cardiomyopathy. The phenotypic effects of the mutations help investigators understand the structure and function of the gene.

Time-Dependent Risk of Cardiovascular Events Following an Exacerbation in Patients With Chronic Obstructive Pulmonary Disease: Post Hoc Analysis From the IMPACT Trial.

Background The association between chronic obstructive pulmonary disease exacerbations and increased cardiovascular event risk has not been adequately studied in a heterogenous population with both low and high cardiovascular risk. Methods and Results This post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (N=10 355 symptomatic patients with chronic obstructive pulmonary disease at risk of exacerbations) evaluated time-dependent risk of cardiovascular adverse events of special interest (CVAESI) following exacerbations and impact of exacerbation history, cardiovascular risk factors, and study treatment on this association. Risk (time-to-first) of CVAESI or CVAESI resulting in hospitalization or death was assessed during and 1 to 30, 31 to 90, and 91 to 365 days after resolution of moderate or severe exacerbations.

Impact of Racial Disparities in Preoperative Cardiovascular Evaluation and Surgical Outcomes in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Cohort Analysis.

Background We investigated preoperative referral patterns, rates of cardiovascular testing, surgical wait times, and postoperative outcomes in White versus Black, Hispanic, or other racial or ethnic groups of patients undergoing metabolic and bariatric surgery. Methods and Results This was a single center retrospective cohort analysis of 797 consecutive patients undergoing metabolic and bariatric surgery from January 2014 to December 2018; 86% (n=682) were Black, Hispanic, or other racial or ethnic groups. White versus Black, Hispanic, or other racial or ethnic groups had similar baseline comorbidities and were referred for preoperative cardiovascular evaluation in similar proportion (65% versus 68%, =0.

Outcomes Associated With a Strategy of Adjuvant Metolazone or High-Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis.

Background In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high-dose loop diuretics. Methods and Results Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity-adjusted analysis of all-cause mortality.