YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12.

Background And Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.

Protocatechuic acid prevents isoproterenol-induced heart failure in mice by downregulating kynurenine-3-monooxygenase.

Protocatechuic acid (3,4-dihydroxybenzoic acid) prevents oxidative stress, inflammation and cardiac hypertrophy. This study aimed to investigate the therapeutic effects of protocatechuic acid in an isoproterenol-induced heart failure mouse model and to identify the underlying mechanisms. To establish the heart failure model, C57BL/6NTac mice were given high-dose isoproterenol (80 mg/kg body weight) for 14 days.

Modified reverse shock index predicts early outcomes of heart failure with reduced ejection fraction.

Aims: Increased blood pressure (BP) and decreased heart rate (HR) are signs of stabilization in patients admitted for acute HF. Changes in BP and HR during admission and their correlation with outcomes were assessed in hospitalized patients with heart failure (HF) with reduced ejection fraction (HFrEF).

Methods: A novel modified reverse shock index (mRSI), defined as the ratio between changes in systolic BP and HR during admission, was devised, and its prognostic value in the early outcomes of acute HF was assessed using the Korean Acute HF registry.

Syringic acid mitigates isoproterenol-induced cardiac hypertrophy and fibrosis by downregulating Ereg.

Gallic acid has been reported to mitigate cardiac hypertrophy, fibrosis and arterial hypertension. The effects of syringic acid, a derivative of gallic acid, on cardiac hypertrophy and fibrosis have not been previously investigated. This study aimed to examine the effects of syringic acid on isoproterenol-treated mice and cells.

Zinc-dependent histone deacetylases: Potential therapeutic targets for arterial hypertension.

The pathogenesis of hypertension caused by various genetic and environmental factors has not been elucidated. Clinical trials have evaluated various anti-hypertensive drugs with different therapeutic mechanisms. Due to the increasing prevalence of hypertension in the aging population and appearance of adverse effects, novel anti-hypertensive drugs need be developed.

Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1.

Background: Heart failure is characterized by activation of the renin-angiotensin-aldosterone system, which is involved in the regulation of cardiac hypertrophy and hypertension. Recently, we reported that Hdac8 inhibition alleviates isoproterenol-induced and angiotensin II-induced cardiac hypertrophy or hypertension in mice. Here, the effect and regulatory mechanisms of the Hdac8 selective inhibitor PCI34051 on pressure overload-induced heart failure were examined.

Determinants of left ventricular function improvement for cardiac resynchronization therapy candidates.

Aims: A waiting period of more than 3 months is recommended for patients before undergoing cardiac resynchronization therapy (CRT). However, due to an anticipated high mortality rate, early implementation of CRT might be beneficial for some patients. We aimed to evaluate the rate and the probability of left ventricular (LV) function improvement and their predictors in patients with heart failure (HF) with indications for CRT.

Evaluation of Adherence to Guideline for Heart Failure with Reduced Ejection Fraction in Heart Failure with Preserved Ejection Fraction and with or without Atrial Fibrillation.

Background: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF).

Methods: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists.

Impact of insulin therapy on the mortality of acute heart failure patients with diabetes mellitus.

Background: Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients.

Heart failure and atrial fibrillation: tachycardia-mediated acute decompensation.

Aims: Tachycardia is a reversible event that may cause hemodynamic decompensation but may not necessarily cause direct damages to the myocardium. To evaluate the clinical outcomes of patients with heart failure (HF) and atrial fibrillation (AF), whose acute decompensation was tachycardia mediated.

Methods And Results: The Korean Acute Heart Failure registry was a prospective registry that consecutively enrolled 5625 patients with acute HF.

Selective HDAC8 Inhibition Attenuates Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis via p38 MAPK Pathway.

Histone deacetylase (HDAC) expression and enzymatic activity are dysregulated in cardiovascular diseases. Among Class I HDACs, HDAC2 has been reported to play a key role in cardiac hypertrophy; however, the exact function of HDAC8 remains unknown. Here we investigated the role of HDAC8 in cardiac hypertrophy and fibrosis using the isoproterenol-induced cardiac hypertrophy model system.

MicroRNA-212-5p and its target PAFAH1B2 suppress vascular proliferation and contraction via the downregulation of RhoA.

Vascular remodeling and contraction contribute to the development of hypertension. We investigated the role of miR-212-5p and its downstream target in vascular smooth muscle cell (VSMC) proliferation, migration, and contraction. MicroRNA microarray and PCR analyses showed that miR-212-5p expression was increased with angiotensin II treatment in vivo and in vitro.

HDAC5 inhibition reduces angiotensin II-induced vascular contraction, hypertrophy, and oxidative stress in a mouse model.

Non-specific histone deacetylase (HDAC) inhibition reduces high blood pressure in essential hypertensive animal models. However, the exact HDAC isoforms that play a critical role in controlling hypertension are not known. Here, we investigated the role of HDAC5 in vascular contraction, hypertrophy, and oxidative stress in the context of angiotensin II (Ang II)-induced hypertension.

Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation.

Background: β-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF.

Impact of successful restoration of sinus rhythm in patients with atrial fibrillation and acute heart failure: Results from the Korean Acute Heart Failure registry.

Background: Restoring and maintaining sinus rhythm (SR) in patients with atrial fibrillation (AF) failed to show superior outcomes over rate control strategies in prior randomized trials. However, there is sparse data on their outcomes in patients with acute heart failure (AHF).

Methods: From December 2010 to February 2014, 5,625 patients with AHF from 10 tertiary hospitals were enrolled in the Korean Acute Heart Failure registry, including 1,961 patients whose initial electrocardiogram showed AF.

Impact of diabetes mellitus on mortality in patients with acute heart failure: a prospective cohort study.

Background: Although more than one-third of the patients with acute heart failure (AHF) have diabetes mellitus (DM), it is unclear if DM has an adverse impact on clinical outcomes. This study compared the outcomes in patients hospitalized for AHF stratified by DM and left ventricular ejection fraction (LVEF).

Methods: The Korean Acute Heart Failure registry prospectively enrolled and followed 5625 patients from March 2011 to February 2019.

Prognostic Value of QRS Duration among Patients with Cardiogenic Shock Complicating Acute Heart Failure: Data from the Korean Acute Heart Failure (KorAHF) Registry.

Background And Objectives: Prolonged QRS duration is associated with poor outcomes in patients with chronic heart failure (HF). However, the prognostic value of QRS duration in patients with cardiogenic shock complicating acute HF remains unknown. We evaluated the hypothesis that prolonged QRS duration may be associated with short-term mortality among acute HF patients with cardiogenic shock (CS).

Neutrophil-Lymphocyte Ratio in Patients with Acute Heart Failure Predicts In-Hospital and Long-Term Mortality.

The application of a simple blood test to predict prognosis in acute heart failure (AHF) patients is not well established. Neutrophil-lymphocyte ratio (NLR) is inexpensive and easy to obtain in hospitalized patients using a routine blood test. We evaluate the prognostic implications of NLR as an independent predictor of in-hospital and long-term mortality in AHF patients.

Management and Prognosis of Heart Failure in Octogenarians: Final Report from the KorAHF Registry.

Treatment of heart failure (HF) in the elderly face many difficulties due to lack of robust evidence. We analyzed the outcome of HF in octogenarians using a nationwide HF registry. Among 5625 patients from the Korean Acute Heart Failure (KorAHF) registry, prognosis of octogenarian HF and the association of guideline-directed medical therapy (GDMT) with mortality and readmissions were analyzed.

Artificial intelligence algorithm for predicting mortality of patients with acute heart failure.

Aims: This study aimed to develop and validate deep-learning-based artificial intelligence algorithm for predicting mortality of AHF (DAHF).

Methods And Results: 12,654 dataset from 2165 patients with AHF in two hospitals were used as train data for DAHF development, and 4759 dataset from 4759 patients with AHF in 10 hospitals enrolled to the Korean AHF registry were used as performance test data. The endpoints were in-hospital, 12-month, and 36-month mortality.

Selective inhibition of histone deacetylase 8 improves vascular hypertrophy, relaxation, and inflammation in angiotensin II hypertensive mice.

Background: The dysregulation of histone deacetylase (HDAC) protein expression or its enzyme activity is implicated in a variety of diseases. Cardiac HDAC6 and HDAC8 enzyme activity induced by deoxycorticosterone acetate (DOCA) hypertension was attenuated by sodium valproate, a pan-HDAC inhibitor. However, the HDAC6-selective inhibitor, tubastatin A, did not attenuate angiotensin II-induced hypertension.

Prognostic Implication of Ventricular Conduction Disturbance Pattern in Hospitalized Patients with Acute Heart Failure Syndrome.

Background And Objectives: Conflicting data exist regarding the prognostic implication of ventricular conduction disturbance pattern in patients with heart failure (HF). This study investigated the prognostic impact of ventricular conduction pattern in hospitalized patients with acute HF.

Methods: Data from the Korean Acute Heart Failure registry were used.

Class I histone deacetylase inhibitor MS-275 attenuates vasoconstriction and inflammation in angiotensin II-induced hypertension.

Objective: Non-selective histone deacetylase (HDAC) inhibitors are known to improve hypertension. Here, we investigated the therapeutic effect and regulatory mechanism of the class I HDAC selective inhibitors, MS-275 and RGFP966, in angiotensin (Ang) II-induced hypertensive mice.

Methods And Results: MS-275 inhibited the activity of HDAC1, HDAC2, and HDAC3, while RGFP966 weakly inhibited that of HDAC3 in a cell-free system.

Gentisic acid prevents the transition from pressure overload-induced cardiac hypertrophy to heart failure.

We previously reported that gentisic acid attenuates cardiac hypertrophy and fibrosis in transverse aortic constriction (TAC)-induced cardiac hypertrophy. Here, we examined whether gentisic acid prevents the development of heart failure. Heart failure was induced in mice via chronic TAC.