Association between Sodium-Glucose Co-Transporter-2 Inhibitor Use and Prognosis in Underweight Patients with Diabetes Mellitus and Heart Failure.

Background & Aims: It remains unclear whether sodium-glucose co-transporter-2 (SGLT2) inhibitors are effective for patients with underweight. This study aimed to elucidate the association between SGLT2 inhibitors use and prognosis in underweight patients with diabetes mellitus (DM) and HF.

Methods: This study was a post-hoc analysis of data from the Japanese Registry of Acute Decompensated Heart Failure, a prospective, multicenter, observational, nationwide registry.

Goreisan attenuates cardiac hypertrophy and diastolic dysfunction in heart failure with preserved ejection fraction induced by HFD/L-NAME via regulation of ICAT-β-catenin/ERK axis.

Heart failure with preserved ejection fraction (HFpEF), characterized by cardiac hypertrophy and diastolic dysfunction, is increasing worldwide. Goreisan (GRS) is a traditional herbal formulation; its component attenuates cardiomyocyte hypertrophy. This study aimed to investigate the effect of GRS on the pathophysiology of HFpEF.

Excessive HIF-1α driven by phospholipid metabolism causes septic cardiomyopathy through cytopathic hypoxia.

Septic cardiomyopathy, one manifestation of multiple organ dysfunction syndrome, is a challenging complication in sepsis, and cytopathic hypoxia has been proposed to have a key role in the pathophysiology of multiple organ dysfunction syndrome. However, the underlying mechanisms remain unknown. Here, we show that upregulation of hypoxia-inducible factor-1α (HIF-1α) in cardiomyocytes following lipopolysaccharide (LPS) treatment suppresses mitochondrial respiration via inducible nitric oxide synthase-dependent nitric oxide, leading to cytopathic hypoxia.

Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension.

Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR) and/or PAR. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model.

Reduction in Acetylation of Superoxide Dismutase 2 in Skeletal Muscle Improves Exercise Capacity in Mice With Heart Failure.

Background: Skeletal muscle abnormalities, including mitochondrial dysfunction, play a crucial role in decreasing exercise capacity in patients with heart failure (HF). Although enhanced reactive oxygen species (ROS) production in skeletal muscle mitochondria has been implicated in skeletal muscle abnormalities, the underlying mechanisms have not been fully elucidated to date. Superoxide dismutase 2 (SOD2), an antioxidant enzyme present in mitochondria, is modified by acetylation, which reduces its activity.

Clinical characteristics and outcomes of hospitalized patients with heart failure from the Japanese prospective registry.

Background: Recent studies showed that clinical parameters other than cardiac function, such as physical function, cognitive function, mental status, social status, and quality of life, were associated with heart failure (HF) prognosis. These parameters have not been extensively investigated in large Japanese cohorts. Furthermore, novel biomarkers to predict prognosis or treatment responses are required to provide individualized medicine.

Severe COVID-19-related Pneumonia Seven Years after Heart Transplantation.

A 67-year-old man on intense immunosuppressive therapy after heart transplantation for end-stage hypertrophic cardiomyopathy 7 years ago developed severe dyspnea and was admitted to our hospital. His serum severe acute respiratory syndrome coronavirus 2 antigen test was positive, and he was diagnosed with coronavirus disease 2019 (COVID-19)-related pneumonia. He was started on ventilatory management for severe respiratory failure and remdesivir for COVID-19, with careful adjustment of immunosuppressive drugs.

Triglyceride/high density lipoprotein cholesterol index and future cardiovascular events in diabetic patients without known cardiovascular disease.

The triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index, calculated as TG divided by HDL-C, has been suggested as a predictor of cardiovascular disease (CVD). We investigated the association between the TG/HDL-C index and CVD events in type 2 diabetes mellitus (T2DM) patients with retinopathy and hyperlipidemia but no known CVD, enrolled in the EMPATHY study, which compared intensive and standard statin therapy (targeting LDL-C levels < 70 mg/dL and ≥ 100 to < 120 mg/dL, respectively). A total of 4665 patients were divided into high (TG/HDL-C ≥ 2.

Validation of Guideline Recommendation on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy.

Background: To prevent sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM), the HCM Risk-SCD calculator and guideline recommendations are used to aid decision making for implantable cardioverter-defibrillator placement.

Objectives: The aim of this study was to assess the clinical profiles and occurrence of SCD by phenotypes of HCM and validate the performance of the current guidelines from a large-scale Japanese multicenter registry.

Methods: This was a retrospective, multicenter, observational, longitudinal cohort study that enrolled 3,611 consecutive patients with HCM.

Prognostic impact of moderate to severe anemia associated with renal dysfunction in patients with heart failure.

Moderate/severe anemia [hemoglobin (Hb) < 10 g/dL] is recommended to be treated in patients with renal anemia. However, the optimal therapeutic target for Hb levels in patients with heart failure (HF) is unknown. This study aimed to investigate the impact of severity of anemia, especially moderate/severe anemia, associated with renal dysfunction (RD: eGFR < 60 mL/min/1.

Clinical characteristics and predictive biomarkers of intensive care unit-acquired weakness in patients with cardiogenic shock requiring mechanical circulatory support.

Intensive care unit-acquired weakness (ICU-AW) is recognized as newly-acquired bilateral muscle weakness, which is a complication of critical illness in the ICU; however, there are no reports on the pathogenesis and early predictors of ICU-AW specifically associated with cardiogenic shock (CS). Therefore, this study aimed to investigate the clinical characteristics of ICU-AW in patients with CS requiring mechanical circulatory support (MCS). This study was a single-center, prospective, and observational study.

Deep learning model to diagnose cardiac amyloidosis from haematoxylin/eosin-stained myocardial tissue.

Aims: Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue.

Methods And Results: This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses.

Establishment of a HFpEF model using female Dahl salt-sensitive rats: a valuable tool for elucidating the pathophysiology of HFpEF in women.

The pathogenesis of heart failure with preserved ejection fraction (HFpEF) remains unclear, and effective treatments are limited. HFpEF is more prevalent in females, indicating potential gender differences in its pathogenesis. However, no female HFpEF model animals have been established.

Clinical and pathological characteristics of immune checkpoint inhibitor-related fulminant myocarditis.

The advent of immune checkpoint inhibitors (ICIs) has significantly improved cancer treatment. With the increasing use of ICIs, ICI-related myocarditis has been recognized. However, an evidence-based therapeutic strategy has not been established because of the limited knowledge on ICI-related myocarditis.

Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis.

Background: Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established.

Methods And Results: This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively).

Association of Multiple Nonhypertrophic Cardiomyopathy-Related Genetic Variants and Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Approximately 10% of hypertrophic cardiomyopathy (HCM) patients have left ventricular systolic dysfunction (end-stage HCM) leading to severe heart-failure; however, risk stratification to identify patients at risk of progressing to end-stage HCM remains insufficient.

Objectives: In this study, the authors sought to elucidate whether the coexistence of other cardiovascular disease (CVD)-related variants is associated with progression to end-stage HCM in patients with HCM harboring pathogenic or likely pathogenic (P/LP) sarcomeric variants.

Methods: The authors performed genetic analysis of 83 CVD-related genes in HCM patients from a Japanese multicenter cohort.

Different Impact of Immunosuppressive Therapy on Cardiac Outcomes in Systemic Versus Isolated Cardiac Sarcoidosis.

Isolated cardiac sarcoidosis (iCS) is increasingly recognized; however, its prognosis and the efficacy of immunosuppressive therapy remain undetermined. We aimed to compare the prognosis of iCS and systemic sarcoidosis including cardiac involvement (sCS) under immunosuppressive therapy.We retrospectively reviewed the clinical data of 42 patients with sCS and 30 patients with iCS diagnosed at Kyushu University Hospital from 2004 through 2022.

Effectiveness of Vericiguat on right ventricle to pulmonary artery uncoupling associated with heart failure with reduced ejection fraction.

Backgrounds: A soluble guanylyl cyclase stimulator vericiguat has been shown to reduce cardiovascular mortality or hospitalization for heart failure in patients with worsening heart failure in the VICTORIA study. However, little is known about the effects of vericiguat on biventricular structure and function.

Methods And Results: A retrospective analysis of 63 consecutive patients with heart failure with reduced ejection fraction (HFrEF) who were treated with vericiguat was performed.

Management and outcomes of heart failure hospitalization among older adults in the United States and Japan.

Aims: Despite advances in therapies, the disease burden of heart failure (HF) has been rising globally. International comparisons of HF management and outcomes may reveal care patterns that improve outcomes. Accordingly, we examined clinical management and patient outcomes in older adults hospitalized for acute HF in the United States (US) and Japan.

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect.