Sacubitril/valsartan improves diastolic left ventricular stiffness with increased titin phosphorylation via cGMP-PKG activation in diabetic mice.

Titin, a giant sarcomeric protein, regulates diastolic left ventricular (LV) passive stiffness as a molecular spring and could be a therapeutic target for diastolic dysfunction. Sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor, has been shown to benefit patients with heart failure with preserved ejection fraction. The effect of Sac/Val is thought to be due to the enhancement of the cGMP/PKG pathway via natriuretic peptide.

Novel Q234K variant, identified in patients with long QT syndrome and epileptiform activity, induces both gain- and loss-of-function of slowly activating delayed rectifier potassium currents.

Introduction: KCNQ1 and KCNE1 form slowly activating delayed rectifier potassium currents (I). Loss-of-function of I by variants causes type-1 long QT syndrome (LQTS). Also, some variants are reported to cause epilepsy.

Validation of a Five-Year Prognostic Model Using I-metaiodobenzylguanidine Scintigraphy in Patients with Heart Failure.

: I-metaiodobenzylguanidine (MIBG) scintigraphy evaluates the severity and prognosis of patients with heart failure. A prognostic model has been proposed using a multicenter study data of I-MIBG scintigraphy. We evaluated the usefulness of the model using a database.

Empagliflozin induces the transcriptional program for nutrient homeostasis in skeletal muscle in normal mice.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve heart failure (HF) outcomes across a range of patient characteristics. A hypothesis that SGLT2i induce metabolic change similar to fasting has recently been proposed to explain their profound clinical benefits. However, it remains unclear whether SGLT2i primarily induce this change in physiological settings.

Pyothorax and Constrictive Pericarditis after Chemoradiotherapy for Esophageal Cancer.

A 75-year-old man underwent chemoradiotherapy for advanced esophageal cancer. After nine years, he was hospitalized for left pyothorax. Consequently, the patient underwent drainage and window opening surgery.

Targeted deep sequencing analyses of long QT syndrome in a Japanese population.

Long QT syndrome (LQTS) is one of the most common inherited arrhythmias and multiple genes have been reported as causative. Presently, genetic diagnosis for LQTS patients is becoming widespread and contributing to implementation of therapies. However, causative genetic mutations cannot be detected in about 20% of patients.

Short-Term Exposure to Sulfur Dioxide and Nitrogen Monoxide and Risk of Out-of-Hospital Cardiac Arrest.

Background & Aims: Over the past decades, particulate matter (PM), especially fine PM <2.5 μm in aerodynamic diameter (PM) has been a major research focus. However, the air pollutant is a mixture of gases or vapour-phase compounds, such as carbon monoxide (C), nitrogen oxides (NO), photochemical oxidants (Ox), and sulfur dioxide (SO).

Novel CACNA1C R511Q mutation, located in domain Ⅰ-Ⅱ linker, causes non-syndromic type-8 long QT syndrome.

Background: Gain-of-function mutations in CACNA1C encoding Cav1.2 cause syndromic or non-syndromic type-8 long QT syndrome (LQTS) (sLQT8 or nsLQT8). The cytoplasmic domain (D)Ⅰ-Ⅱ linker in Cav1.

Ketone body and FGF21 coordinately regulate fasting-induced oxidative stress response in the heart.

Ketone body β-hydroxybutyrate (βOHB) and fibroblast growth factor-21 (FGF21) have been proposed to mediate systemic metabolic response to fasting. However, it remains elusive about the signaling elicited by ketone and FGF21 in the heart. Stimulation of neonatal rat cardiomyocytes with βOHB and FGF21 induced peroxisome proliferator-activated receptor α (PPARα) and PGC1α expression along with the phosphorylation of LKB1 and AMPK.

Peripheral Venous Pressure-Assisted Exercise Stress Echocardiography in the Evaluation of Pulmonary Hypertension During Exercise in Patients With Suspected Heart Failure With Preserved Ejection Fraction.

Background: Identification of elevated pulmonary artery (PA) pressures during exercise may provide diagnostic, prognostic, and therapeutic implications in heart failure with preserved ejection fraction. Although widely performed, exercise stress echocardiography may underestimate true PA pressures due to the difficulty in estimating right atrial pressure (RAP) during exercise. We hypothesized that peripheral venous pressure (PVP) could allow for reliable estimation of RAP, and thus PA pressures during exercise stress echocardiography.

Impact of left atrial enlargement on image quality in coronary computed tomography angiography.

Purpose: To assess the associations between simple measurements of left atrial (LA) size and image quality of coronary computed tomography angiography (CCTA).

Materials And Methods: Four hundred and nineteen patients who underwent CCTA were retrospectively examined. Image quality was measured by coronary artery attenuation and contrast-to-noise ratio (CNR) of the proximal coronary artery (mean values of right coronary artery and left main trunk).

Cardiac Metabolism and Contractile Function in Mice with Reduced Trans-Endothelial Fatty Acid Transport.

The heart is a metabolic omnivore that combusts a considerable amount of energy substrates, mainly long-chain fatty acids (FAs) and others such as glucose, lactate, ketone bodies, and amino acids. There is emerging evidence that muscle-type continuous capillaries comprise the rate-limiting barrier that regulates FA uptake into cardiomyocytes. The transport of FAs across the capillary endothelium is composed of three major steps-the lipolysis of triglyceride on the luminal side of the endothelium, FA uptake by the plasma membrane, and intracellular FA transport by cytosolic proteins.

Reduced Fatty Acid Use from CD36 Deficiency Deteriorates Streptozotocin-Induced Diabetic Cardiomyopathy in Mice.

Cardiac dysfunction is induced by multifactorial mechanisms in diabetes. Deranged fatty acid (FA) utilization, known as lipotoxicity, has long been postulated as one of the upstream events in the development of diabetic cardiomyopathy. CD36, a transmembrane glycoprotein, plays a major role in FA uptake in the heart.

Pulmonary Artery Diameter (PAD) and the Pulmonary Artery to Aorta Ratio (PAD/AAD) as Assessed by Non-contrast Cardiac CT: The Association with Left Ventricular (LV) Remodeling and the LV Function.

Objective Dilatation of the pulmonary artery itself (PAD: pulmonary artery diameter) or in relation to the ascending aorta (PAD/AAD: pulmonary artery diameter to ascending aortic diameter ratio) has been reported to be associated with pulmonary hypertension and with a prognostic outcome of either heart failure or cardiovascular events. We herein aimed to assess the correlations between pulmonary hypertension-related parameters PAD (or PAD/AAD) and left ventricular (LV) remodeling and LV function. Methods This retrospective study included 193 patients (ages: 67±12 years) who underwent both coronary CT angiography (CCTA) and echocardiography.

Pathophysiological and diagnostic importance of fatty acid-binding protein 1 in heart failure with preserved ejection fraction.

Elevated intracardiac pressure at rest and/or exercise is a fundamental abnormality in heart failure with preserved ejection fraction (HFpEF). Fatty acid-binding protein 1 (FABP1) is proposed to be a sensitive biomarker for liver injury. We sought to determine whether FABP1 at rest would be elevated in HFpEF and would correlate with echocardiographic markers of intracardiac pressures at rest and during exercise.

Functional Tricuspid Regurgitation and Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.

Tricuspid regurgitation (TR) is common in patients with heart failure with preserved ejection fraction (HFpEF), but it has not been well characterized. We hypothesized that right atrial (RA) remodeling would be associated with TR in HFpEF, forming a type of atrial functional TR (AFTR). Echocardiography was performed in 328 patients with HFpEF.

Visual echocardiographic scoring system of the left ventricular filling pressure and outcomes of heart failure with preserved ejection fraction.

Aims: Elevated left ventricular filling pressure (LVFP) is a powerful indicator of worsening clinical outcomes in heart failure with preserved ejection fraction (HFpEF); however, detection of elevated LVFP is often challenging. This study aimed to determine the association between the newly proposed echocardiographic LVFP parameter, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, and clinical outcomes of HFpEF.

Methods And Results: We retrospectively investigated 310 well-differentiated HFpEF patients in stable conditions.

A case of a middle-aged patient with a ventricular septal defect complicated by severe pulmonary hypertension-stepwise surgical repair with pulmonary vasodilators.

We report a case of ventricular septal defect (VSD) in which we attempted to treat pulmonary arterial hypertension (PAH) with the goal of VSD closure in an adult with suspected Eisenmenger syndrome in childhood. Four years previously (age 41 years), she was referred to our department due to repeated hemoptysis requiring further treatment of PAH. We started combination therapy with several pulmonary vasodilators.

Unilateral Lung Congestion During Exercise in a Patient With a Single Pulmonary Vein Stenosis.

A 55-year-old man underwent exercise stress echocardiography for evaluation of left inferior pulmonary vein stenosis. During exercise, ultrasound B-lines developed in the left lung only. Unilateral pulmonary congestion did not lead to forward or backward failure.

Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of F-THK5351 Positron Emission Tomography: A Case Report.

In Alzheimer's disease, the apolipoprotein E gene ε2 allele is a protective genetic factor, whereas the ε4 allele is a genetic risk factor. However, both the ε2 and the ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the ε2 allele remains unknown.

Effects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction.

Purpose: The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined.

Methods: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission.