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Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. Methods A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. Results In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was − 1.07 (95% confidence interval [CI] − 1.29 to − 0.86; P

Abstract Subclinical leaflet thrombosis (SLT) can be one of the causes of transcatheter heart valve (THV) failure after transcatheter aortic valve implantation (TAVI). We sought to clarify the formation process of SLT and thrombogenicity during the perioperative period of TAVI. This multicenter, prospective, single-arm interventional study enrolled 26 patients treated with edoxaban for atrial fibrillation and who underwent TAVI for severe aortic stenosis between September 2018 and September 2022. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI in 18 patients and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD) (n = 11). SLT was observed in 16.7% (3/18) at 1 week, but decreased to 5.9% (1/17) at 3 months after TAVI. Patients with SLT at 1 week had a significantly decreased maximal leaflet thickness compared to those without SLT. Thrombogenicity assessed by T-TAS decreased markedly at 1 week and tended to increase at 3 months. The stagnation volume assessed by CFD was positively associated with a higher maximum leaflet thickness. This study showed the course of leaflet thrombus formation and visualization of stagnation in neo-sinus of THV in the acute phase after TAVI.

Abstract Aims There are minimal data on the prognostic impact of right atrial strain during the reservoir phase (RASr) in patients with immunoglobulin light‐chain (AL) cardiac amyloidosis. Methods and results Among 78 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from 2007 to 2022, 72 patients with sufficient two‐dimensional speckle tracking imaging data without chemotherapy before the diagnosis were retrospectively analysed. During a median follow‐up of 403 days, 31 deaths occurred. Age and the rate of male sex were not significantly different between the all‐cause death group and the survival group (age, 70.4 ± 8.8 years vs. 67.0 ± 10.0 years, P = 0.14, male sex, 65% vs. 66%, P = 0.91). The estimated glomerular filtration rate (eGFR) was significantly lower, and B‐type natriuretic peptide (BNP) and high sensitivity cardiac troponin T (hs‐cTnT) were significantly higher, in the all‐cause death group versus the survival group (eGFR, 48.2 ± 21.0 mL/min/1.73 m2 vs. 59.4 ± 24.4 mL/min/1.73 m2, P 311.2 pg/mL) had a significantly high probability of all‐cause death (both, P

Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The subjects of this study were 158 patients (68 males and 90 females, mean age 74.8 ± 11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had a significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e′, and E/e′ (p < 0.001, respectively). Multivariate logistic regression analysis revealed that higher PWV values and hypertension were significant predictors for the dependent factor (HFpEF). Arterial stiffness amplified afterload, leading to LV concentric hypertrophy and diastolic dysfunction. This study presents that arterial stiffness is a key predictor of HFpEF, and that phosphate retention is involved in the pathology of HFpEF.

Abstract Catalytic antibodies possess a dual function that enables both antigen recognition and degradation. However, their time-consuming preparation is a significant drawback. This study developed a new method for quickly converting mice monoclonal antibodies into catalytic antibodies using site-directed mutagenesis. Three mice type monoclonal antibodies targeting hemagglutinin molecule of influenza A virus could be transformed into the catalytic antibodies by deleting Pro95 in CDR-3 of the light chain. No catalytic activity was observed for monoclonal antibodies and light chains. In contrast, the Pro95-deleted light chains exhibited a catalytic activity to cleave the antigenic peptide including the portion of conserved region of hemagglutinin molecule. The affinity of the Pro95-deleted light chains to the antigen increased approximately 100-fold compared to the wild-type light chains. In the mutants, three residues (Asp1, Ser92, and His93) come closer to the appropriate position to create the catalytic site and contributing to the enhancement of both catalytic function and immunoreactivity. Notably, the Pro95-deleted catalytic light chains could suppress influenza virus infection in vitro assay, whereas the parent antibody and the light chain did not. This strategy offers a rapid and efficient way to create catalytic antibodies from existing antibodies, accelerating the development for various applications in diagnostic and therapeutic applications.

Background Mineralocorticoid receptor (MR) induces cardiac inflammation cooperatively with nuclear factor‐κB and signal transducer and activator of transcription 3 (STAT3); MR blockers exert anti‐inflammatory effects. However, the underlying mechanism remains unclear. We investigated the anti‐inflammatory effect of esaxerenone, a novel MR blocker, in experimental myocardial infarction (MI) and its underlying mechanisms. Methods and Results Male C57BL/6J mice subjected to ligation of the left anterior descending artery were randomly assigned to either the vehicle or esaxerenone group. Esaxerenone was provided with a regular chow diet. The mice were euthanized at either 4 or 15 days after MI. Cardiac function, fibrosis, and inflammation were evaluated. Esaxerenone significantly improved cardiac function and attenuated cardiac fibrosis at 15 days after MI independently of its antihypertensive effect. Inflammatory cell infiltration, inflammatory‐related gene expression, and elevated serum interleukin‐6 levels at 4 days after MI were significantly attenuated by esaxerenone. In vitro experiments using mouse macrophage‐like cell line RAW264.7 cells demonstrated that esaxerenone‐ and spironolactone‐attenuated lipopolysaccharide‐induced interleukin‐6 expression without altering the posttranslational modification and nuclear translocation of p65 and STAT3. Immunoprecipitation assays revealed that MR interacted with both p65 and STAT3 and enhanced the p65–STAT3 interaction, leading to a subsequent increase in interleukin‐6 promoter activity, which was reversed by esaxerenone. Conclusions Esaxerenone ameliorated postinfarct remodeling in experimental MI through its anti‐inflammatory properties exerted by modulating the transcriptional activity of the MR–p65–STAT3 complex. These results suggest that the MR–p65–STAT3 complex can be a novel therapeutic target for treating MI.

Background: Although the prevalence rate of valvular heart disease (VHD) is high in patients with systemic lupus erythematosus (SLE), the predictive factors of concomitant VHD have not been fully evaluated. Methods and results: Among 288 patients with SLE who underwent transthoracic echocardiography at Kumamoto University Hospital from 2016 to 2021, 241 patients with sufficient echocardiographic data were retrospectively analysed. Among them, 22 (9 %) had VHD (10 had mitral regurgitation, 3 had aortic regurgitation, 6 had tricuspid regurgitation, 1 had mitral regurgitation and tricuspid regurgitation, and 2 had a prosthetic cardiac valve). After excluding the two patients with a prosthetic cardiac valve, we divided the remaining patients into two groups: the VHD group and non-VHD group. Multivariate logistic regression analysis revealed that age and the platelet count were significantly and independently associated with having VHD (age: odds ratio, 1.06; 95 % confidence interval, 1.02–1.10; p

Pulmonary arterial hypertension associated with portal hypertension, known as portopulmonary hypertension (PoPH) is one of the important and serious pulmonary complications in patients with portal hypertension. Although there are a large number of patients with portal hypertension due to mainly liver cirrhosis, the number of cases diagnosed with PoPH are far fewer because the causes of dyspnea in patients with cirrhosis are diverse and the disease entity of PoPH is poorly recognized by clinicians. We report here the case with PoPH suggested and assessed comprehensively by dual energy computed tomography (CT) including high-resolution pulmonary CT angiography, pulmonary perfusion imaging, myocardial late iodine enhancement imaging, and myocardial extracellular volume analysis. This refined CT imaging protocol can be used in conjunction with standard chest evaluation and offers a practical and useful approach for the noninvasive “one-stop shop” evaluation of PoPH.

Background: Polypharmacy is associated with an increased risk of adverse events due to the higher number of drugs used. This is particularly notable in patients with chronic coronary syndrome (CCS), who are known to use a large number of drugs. Therefore, we investigated polypharmacy in patients with CCS, using CLIDAS, a multicenter database of patients who underwent percutaneous coronary intervention. Method and results: Between 2017 and 2020, 1411 CCS patients (71.5 ± 10.5 years old; 77.3 % male) were enrolled. The relationship between cardiovascular events occurring during the median follow-up of 514 days and the number of drugs at the time of PCI was investigated. The median number of drugs prescribed was nine. Major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke, heart failure, transient ischemic attack, or unstable angina, occurred in 123 patients, and all-cause mortality occurred in 68 patients. For each additional drug, the adjusted hazard ratios for MACE and all-cause mortality increased by 2.069 (p = 0.003) and 1.102 (p = 0.010). The adjusted hazard ratios for MACE and all-cause mortality were significantly higher in the group using nine or more drugs compared to the group using eight or fewer drugs (1.646 and 2.253, both p

Background Although tafamidis treatment improves prognosis in patients with wild‐type transthyretin amyloid cardiomyopathy, an optimal surrogate marker monitoring its therapeutic effect remains unclear. This study investigated the association between changes in cardiac biomarkers, high‐sensitivity cardiac troponin T (hs‐cTnT) and B‐type natriuretic peptide (BNP) during the first year after tafamidis treatment and clinical outcomes. Methods and Results In 101 patients with wild‐type transthyretin amyloid cardiomyopathy receiving tafamidis at our institution, change in cardiac biomarkers from baseline to 1 year after tafamidis administration and its association with composite outcomes (composite of all‐cause death and hospitalization attributable to heart failure) was assessed. During the follow‐up period (median, 17 months), 16 (16%) patients experienced composite outcomes. The hs‐cTnT level significantly decreased at 1 year after tafamidis treatment, unlike the BNP level. The frequencies of increased hs‐cTnT and BNP levels were significantly higher in those with composite outcomes than in those without (44% versus 15%; P=0.01). Kaplan‐Meier survival analysis showed that patients in whom both hs‐cTnT and BNP levels increased at 1 year after tafamidis had a higher probability of composite outcomes compared with those with decreased hs‐cTnT and BNP levels (log‐rank P