This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myocardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG).

This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suitable for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular Society (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Seattle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT.

After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly improved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT.

CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional capacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.

We retrospectively examined the feasibility of paclitaxel-coated balloon (PCB) angioplasty for de novo stenosis in large coronary vessels (LV; pre- or postprocedural reference vessel diameter ≥ 2.75 mm) in comparison with placement of drug-eluting stents (DESs).

Consecutive de novo stenotic lesions in the LV electively and successfully treated with either PCB (n = 73) or DESs (n = 81) from January 2016 to December 2018 at our center were included. The primary endpoint was the incidence of target lesion failure (TLF), including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. The impact of PCB on TLF was examined using Cox proportional hazards models by including 39 variables. The secondary endpoint, angiographic restenosis, defined as a follow-up percent diameter stenosis > 50, was examined in angiographic follow-up lesions after PCB angioplasty (n = 56) and DES placement (n = 53). This retrospective investigation was conducted in July 2022.

The mean PCB size and length were 3.23 ± 0.42 and 18.4 ± 4.3 mm, respectively. The TLF frequency in the PCB group (6.8% during the mean observational interval of 1536 ± 538 days) was not significantly different from that in the DES group (14.6%, 1344 ± 606 days, P = 0.097). PCB was not a significant predictor of TLF in the univariate analysis (hazard ratio: 0.424; 95%CI: 0.15-1.21; P = 0.108). There was no angiographic restenosis after PCB angioplasty.

The present observational single-center study showed that PCB for de novo stenosis in the LV had no significant adverse impact on TLF and had favorable angiographic outcomes.

Creation of sizable subintima during intervention for chronic total occlusions (CTO) could lead to the key selection preference of metallic stents rather than bioresorbable vascular scaffolds (BVS) and then possibly deviate the outcome comparisons in real-world studies. By including recanalized CTO with true lumen tracking, we tested if any selection preference remained and compared the outcomes between everolimus-eluting stent (EES) and BVS implantation.

Among 211 consecutive CTO interventions with true lumen tracking from August 2014 to April 2018 when BVS was available, we compared the clinical and interventional features between 28 patients with BVS and 77 patients with EES implantation. With propensity score matching and a median follow-up of 50.5 (37.3-60.3) months, we further assessed 25 patients with BVS and 25 with EES for target vessel failure (TVF: cardiac death, target vessel myocardial infarction, and target lesion revascularization).

Multivariate analyses showed that BVS was still favored in the presence of LAD CTO (odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.0-11.7) and an average scaffold/stent size ≥ 3 mm (OR = 10.5, 95% CI = 3.0-37.3). EES was preferred for lesions with a J-CTO score ≥ 3 (OR = 19.3, 95% CI = 3.4-110.8) and multivessel intervention necessary at index procedure (OR = 11.3, 95% CI = 1.9-67.3). With matched comparisons, the TVF-free survival of EES was better than that of BVS for CTO recanalization (P = 0.049 by log-rank test) at long-term follow-up.

Even with true lumen tracking techniques, selection bias remained substantial when determining either device for CTO implantation. The matched comparison of outcomes suggested the unfavorable longer-term impacts of the first generation of BVS on CTO lesions.

Patients with acute myocardial infarction (AMI) triaged as life-threatening are transferred to our emergency medical care center (EMCC). However, data on these patients remain limited. We aimed to compare the characteristics and AMI prognosis of patients transferred to our EMCC with those transferred to our cardiovascular intensive care unit (CICU) using whole and propensity-matched cohorts.

We analyzed the data of 256 consecutive AMI patients transferred from the scene to our hospital by ambulance between 2014 and 2017. The EMCC and CICU groups comprised 77 and 179 patients, respectively. There were no significant between-group age or sex differences. Patients in the EMCC group had more disease severity score and had the left main trunk identified as the culprit more frequently (12% versus 0.6%, P < 0.001) than those in the CICU group; however, the number of patients with multiple culprit vessels did not differ. The EMCC group had a longer door-to-reperfusion time (75 [60, 109] minutes versus 60 [40, 86] minutes, P< 0.001) and a higher in-hospital mortality (19% versus 4.5%, P < 0.001), especially from non-cardiac causes (10% versus 0.6%, P < 0.001), than the CICU group. However, peak myocardial creatine phosphokinase did not significantly differ between the groups. The EMCC group had a significantly higher 1-year post-discharge mortality than the CICU group (log-rank, P = 0.032); this trend was maintained after propensity score matching, although the difference was not statistically significant (log-rank, P = 0.094).

AMI patients transferred to the EMCC exhibited more severe disease and worse overall in-hospital and non-cardiac mortality than those transferred to the CICU.

We aimed to investigate the correlation between serum laminin (LN) levels and cardiac function in patients with atrial fibrillation (AF) and its predictive value for in-hospital prognosis. This study included 295 patients with AF who were admitted to the Second Affiliated Hospital of Nantong University from January 2019 to January 2021. The patients were divided into three groups according to the New York Heart Association (NYHA) functional classification (I-II, III, and IV); the LN levels increased with increasing NYHA class (P < 0.05). Spearman's correlation analysis revealed a positive correlation between LN and NT-proBNP (r = 0.527, P < 0.001). Of the patients, 36 had in-hospital major adverse cardiac events (MACEs), of whom 30 had acute heart failure, 5 had malignant arrhythmias, and one had stroke. The area under the ROC curve for predicting the in-hospital MACEs by LN was 0.815 (95% CI: 0.740-0.890, P < 0.001). Multivariate logistic regression analysis revealed that LN could be an independent predictor of in-hospital MACEs (odds ratio: 1.009, 95% confidence interval: 1.004-1.015, P = 0.001). In conclusion, LN may serve as a potential biomarker to evaluate the severity of cardiac function and predict in-hospital prognosis in AF patients.

The relationship between Holter electrocardiography (ECG) and atrial fibrillation (AF) diagnosis in the real world has not been widely evaluated in Japan.

This is a claims-based retrospective study using a health insurance claims database provided by DeSC Healthcare Corporation. We identified patients with at least one Holter for any purpose during the data period from April 2015 to November 2020 and without diagnosis of AF before the tests (n = 19,739). We obtained a whole picture of Holter and AF diagnosis after correcting for population distribution bias in the dataset. Based on this picture and the assumption that the patient had AF at the 1^st Holter whose AF was detected for the first time at the second or subsequent Holter, we estimated the number of diagnosis with AF and overlooked AF by initial Holter. We conducted sensitivity analyses changing the definition of AF, the potential detection period, and the washout period (a period required to avoid including patients who have already been diagnosed with AF or who have already undergone several Holters) to confirm the validity of the base scenario.

Among patients for analysis, 88.4% had only one Holter. The percentage of AF diagnosis by initial Holter was 7.6%. The percentage of AF overlooked by initial Holter was estimated to be 31.4% and this value did not change much by sensitivity analyses.

It was estimated that approximately 30% of AF patients were overlooked by initial Holter, and reducing the overlooked rate will be a clinical challenge.

The aim of the present single-center, nonrandomized, retrospective study was to assess the safety and long-term efficacy of percutaneous left atrial appendage closure (LAAC) procedures and to compare the different LAAC devices and therapeutic regimes in this respect.

Medical data of 136 patients (pts) (mean age, 72.5 ± 7.6 years; score for atrial fibrillation stroke risk estimation [CHA₂DS₂-VASc], 4.6 ± 1.6; and score for estimation of major bleeding risk for patients on anticoagulant therapy [HAS-BLED], 2.6 ± 0.9) who underwent percutaneous LAAC procedures in Gottsegen National Cardiovascular Center from January 2010 to January 2020 were analyzed.

The rates of outpatient cardiac mortality, ischemic brain event, and major bleeding were 3.8, 1, and 1.9/100 pt years, respectively. The rate of successful device deployment was 96.4%. There was one case of procedural mortality (0.7%), one case of device dislocation (0.7%), one case of ischemic stroke (0.7%), and one case of myocardial infarction (0.7%). Two cases of pericardial tamponades (1.5%) and four cases of major femoral complications (3%) occurred. Although the implantation success of different occluder types was similar, significant differences were found concerning procedural characteristics. Patients on single antiplatelet therapy (SAPT) in the first 3 months after the LAAC procedure did not suffer from stroke or embolic events.

The present study confirmed the safety and effectivity of percutaneous LAAC. Robust relative stroke risk reduction and less pronounced but significant bleeding risk reduction were observed. Device implantation success was high. The perioperative complication rate was relatively low. The results of long-term observations regarding ischemic events confirmed the safety of using a simplified antithrombotic regime after LAAC in pts with high bleeding risk.

Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.

This study aimed to evaluate the changes in the left ventricular (LV) myocardial work (MW) in breast cancer patients following chemotherapy by left ventricular pressure-strain loop (LVPSL).

A total of 50 patients with newly breast cancer undergoing postoperative adjuvant chemotherapy containing anthracycline were selected. Echocardiography was performed before the treatment (T0), the second (T2) and fourth (T4) cycles of chemotherapy, and 3 (P3 m) and 6 (P6 m) months after the end of chemotherapy. The standard dynamic images of the required sections were collected. After off-line analysis, the routine, global myocardial strain, and global MW parameters were obtained, and the average regional MW index (RMWI) and regional MW efficiency (RMWE) at three levels of LV were calculated.

Compared with those at T0 and T2, the global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and global longitudinal strain (GLS) gradually decreased and global wasted work (GWW) gradually increased at T4, P0, and P6 m. The mean RMWI and RMWE of the three levels of LV exhibited a gradually decreasing trend at T4, P0, and P6 m compared with those at T0 and T2. The GWI, GCW, GWE, mean RMWI, and RMWE (basal, medial, and apical) were negatively correlated with the GLS (r = −0.76, −0.66, −0.67, −0.76, −0.77, −0.66, −0.67, −0.59, and −0.61, respectively), whereas the GWW was positively correlated with the GLS (r = 0.55).

The mean RMWI and RMWE are effective parameters to reflect the cardiotoxicity of LV, and LVPSL has certain value in the evaluation of the left ventricular myocardial work (LVMW) during anthracycline treatment and follow-up in breast cancer patients.

The time-dependent changes in the simultaneous evaluation of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels during hospitalization for acute heart failure (AHF) remain obscure.

A total of 356 AHF patients were analyzed. Blood samples were collected within 15 minutes of admission (Day 1), 48-120 hours (Day 2-5) and between days 7 and 21 (Before-discharge). Plasma BNP and serum NT-proBNP were significantly decreased on Days 2-5 and Before-discharge in comparison to Day 1, but the NT-proBNP/BNP ratio was not changed. Patients were divided into 2 groups according to the median NT-proBNP/BNP (N/B) ratio on Day 2-5 (Low-N/B versus High-N/B). A multivariate logistic regression model showed that age (per 1-year increase), serum creatinine (per 1.0-mg/dL increase), and serum albumin (per 1.0-mg/dL decrease) were independently associated with High-N/B (odds ratio [OR]: 1.071, 95%confidence interval [CI]: 1.036-1.108, OR: 1.190, 95%CI: 1.121-1.264 and OR: 2.410, 95%CI: 1.121-5.155, respectively). Kaplan-Meier curve analysis showed that the High-N/B group had a significantly poorer prognosis than the Low-N/B group, and a multivariate Cox regression model revealed that High-N/B was an independent predictor of 365-day mortality (hazard ratio [HR]: 1.796, 95%CI: 1.041-3.100) and HF events (HR: 1.509, 95%CI: 1.007-2.263). The same trend in prognostic impact was significantly observed in both low and high delta-BNP cohorts (< 55% and ≥ 55% BNP value on the start date/BNP value at 2-5-days).

A high NT-proBNP/BNP ratio on Day 2-5 was associated with non-cardiac conditions and was associated with adverse outcomes even if BNP was adequately decreased by the treatment of AHF.

This study aimed to assess the association of dietary carotenoid intake with risk of depression among patients with cardiometabolic disease.

Data were obtained from the 2005 to 2014 National Health and Nutrition Examination Survey. Participants aged ≥ 20 years with any chronic cardiometabolic diseases, including diabetes, hypertension, coronary heart disease, heart failure, and stroke, were included in this cross-sectional study.

We enrolled a total of 8655 cardiometabolic disease patients in the analysis. Compared to those in the lowest tertile, patients with cardiometabolic disease in the third tertiles of dietary α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin intakes demonstrated ORs for depression risk of 0.73 (95% confidence intervals (CI): 0.62, 0.87), 0.68 (95% CI: 0.57, 0.81), 0.69 (95% CI: 0.57, 0.82), 0.77 (95% CI: 0.65, 0.91), and 0.69 (95% CI: 0.58, 0.82), respectively. The third tertiles of dietary total carotenoid intake were also associated with reduced risk of depression (odds ratios (OR): 0.72; 95% CI: 0.60, 0.85) compared to the lowest tertile. Furthermore, restricted cubic splines showed that dietary total carotenoid intake had a U-shaped association with risk of depression, indicating a positive relation when the dietary total carotenoid intake was higher than the turning point.

Overall, our study suggests the significant inverse associations of dietary α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, and total carotenoid intakes with risk of depression among patients with cardiometabolic diseases. In addition, we found a nonlinear U-shaped relationship between dietary total carotenoid intake and risk of depression among patients with cardiometabolic diseases.

Pulmonary hypertension (PH) often causes right-sided heart failure (HF), inducing organ damage. Shear wave elastography (SWE) is a novel ultrasound technique for characterizing tissue. Some studies have reported that shear wave dispersion slope (SWDS) enables the assessment of early hepatic damage in HF. This study aimed to evaluate the prognostic impact of SWDS in patients with PH.

This single-center cohort study enrolled 36 patients with PH who underwent SWE at Okayama University Hospital between March 2018 and April 2021. Patients were divided into 2 groups on the basis of the median value of SWDS: low SWDS group (SWDS < 12.4 m/second/kHz, n = 18) and high SWDS group (SWDS ≥ 12.4 m/second/kHz, n = 18). The primary endpoint was the complex of all-cause death or hospitalization for HF. During the follow-up of 391 ± 288 days, all-cause death or hospitalization for HF occurred in 8 patients. One patient died in the low SWDS group. Three patients died and 4 patients were hospitalized for HF in the high group. Kaplan-Meier analysis revealed that the event-free survival rate was significantly worse in the high SWDS group than in the low SWDS group (log-rank, P = 0.01). In univariate Cox proportional hazards analysis, high SWDS was associated with the events (hazard ratio 10.8; 95% confidence interval 1.89-202, P = 0.005).

An elevated SWDS was associated with a high rate of events in patients with PH. SWDS has the potential to predict adverse outcomes in patients with PH.

Plasma xanthine oxidoreductase (XOR) activity in patients with cardiopulmonary arrest (CPA) has not yet been studied.

A total of 1,158 patients who required intensive care and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analyzed. Blood samples were collected within 15 minutes of admission from patients in intensive care patients, which were divided into a CPA group (n = 1,053) and a no-CPA group (n = 105). Plasma XOR activity was compared between the 3 groups and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the CPA group (median, 1,030.0 pmol/hour/mL; range, 233.0-4,240.0 pmol/hour/mL) was significantly higher than in the no-CPA group (median, 60.2 pmol/hour/mL; range, 22.5-205.0 pmol/hour/mL) and control group (median, 45.2 pmol/hour/mL; range, 19.3-98.8 pmol/hour/mL). The regression model showed that out-of-hospital cardiac arrest (OHCA) (yes, odds ratio [OR]: 2.548; 95% confidence interval [CI]: 1.098-5.914; P = 0.029) and lactate levels (per 1.0 mmol/L increase, OR: 1.127; 95% CI: 1.031-1.232; P = 0.009) were independently associated with high plasma XOR activity (≥ 1,000 pmol/hour/mL). Kaplan-Meier curve analysis indicated that the prognosis, including all-cause death within 30 days, was significantly poorer in high-XOR patients (XOR ≥ 6,670 pmol/hour/mL) than in the other patients.

Plasma XOR activity was extremely high in patients with CPA, especially in OHCA. This would be associated with a high lactate value and expected to eventually lead to adverse outcome in patients with CPA.

This study aimed to assess the safety of SGLT2 inhibitors in type 2 diabetes, chronic kidney disease, and chronic heart failure considering the number needed to treat (NNT).

Methods: Data were obtained from 10 morbidity-mortality trials and were pooled to calculate the NNTs. The number needed to treat to benefit (NNTB) is used to express beneficial outcomes, whereas the number needed to treat to be harmed (NNTH) is used for harmful outcomes. The eight safety outcomes of interest were fracture, diabetic ketoacidosis, amputation, urinary tract infection, genital infection, acute kidney injury, severe hypoglycemia, and volume depletion.

A total of 10 trials involving 76319 patients were included in this meta-analysis. The mean follow-up was 2.35 years. SGLT2 inhibitors play a positive role in acute kidney injury and severe hypoglycemia, with the corresponding mean NNTBs being 157 and 561, respectively. SGLT2 inhibitors significantly increased the risk of diabetic ketoacidosis, genital infection, and volume depletion, with the corresponding mean NNTHs being 1014, 41, and 139. It was found that the safety of SGLT2 inhibitors was the same in three diseases and five SGLT2 inhibitors.

SGLT2 inhibitors have a positive impact on acute kidney injury and severe hypoglycemia, but they increase the incidence of diabetic ketoacidosis, genital infection, and volume depletion.

Atherosclerosis (AS) is the main reason for most cardiovascular diseases. Circular RNA hsa_circ_0044073 (circ_0044073) has been found to promote AS progression. However, the specific regulatory mechanism of circ_0044073 in AS progression remains unclear.

In this study, oxidized low-density lipoprotein (Ox-LDL) -stimulated human vascular smooth muscle cells (VSMCs) were used as AS cell models. The expression changes of circ_0044073 in serum samples and Ox-LDL-stimulated human VSMCs were assessed via real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, colony formation, migration, and invasion were assessed using 3- (4,5-Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EDU), colony formation, and transwell assays. Some protein levels were detected via Western blotting. The regulatory mechanism of circ_0044073 was predicted using bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays.

We observed an overt increase in circ_0044073 expression in serum samples derived from AS patients and Ox-LDL-stimulated human VSMCs. Circ_0044073 was identified as a miR-377-3p sponge. Either circ_0044073 knockdown or miR-377-3p overexpression could impair Ox-LDL-induced human VSMC proliferation, migration, invasion, and inflammation. AURKA served as a miR-377-3p target, and circ_0044073 regulated AURKA expression by adsorbing miR-377-3p. Furthermore, AURKA overexpression partly reversed the effects of circ_0044073 inhibition on Ox-LDL-induced human VSMC proliferation, migration, invasion, and inflammation.

Circ_0044073 promoted AS progression by elevating AURKA expression by functioning as a miR-377-3p sponge. Providing a proof-of-concept demonstration to support circ_0044073 might be a target for AS treatment.

Accumulating evidence suggested that aberrantly regulated circular RNA (circRNA) is a critical contributor to cardiovascular diseases, including acute myocardial infarction (AMI). However, the role and molecular mechanism of circUSP39 in AMI development remain unclear.

Candidate circRNAs were screened from the Gene Expression Omnibus (GEO) database (GSE160717) and analyzed using the GEO2R tool. Hypoxia/reoxygenation (H/R) -induced AC16 cells were used to investigate the function of circUSP39 in H/R injury of cardiomyocytes. Quantitative real-time PCR (qRT-PCR) was employed to test RNA levels in H/R-induced AC16 cells. Cell Counting Kit-8, enzyme-linked immunosorbent assay, flow cytometry, and western blot (WB) assay were used to determine cell viability, oxidative stress, inflammatory factor levels, and cell apoptosis. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were conducted to validate the interactions between circRNA ubiquitin-specific peptidase 39 (circUSP39), miR-362-3p, and tumor necrosis factor receptor-associated factor 3 (TRAF3).

In H/R-induced AC16 cells, the expression levels of circUSP39 and TRAF3 were upregulated whereas miR-362-3p expression was downregulated. CircUSP39 silencing markedly enhanced cell viability and superoxide dismutase activity but mitigated malondialdehyde level, secretion of inflammatory factors (IL-6, TNF-α, IL-1β, and MCP-1), and cell apoptosis in H/R-induced AC16 cells. CircUSP39 expedited H/R-induced AC16 cell injury by sponging miR-362-3p to increase the expression of TRAF3.

CircUSP39 could facilitate H/R-induced cardiomyocyte oxidative stress, inflammation, and apoptosis by the miR-362-3p/TRAF3 axis, elucidating that it might be a therapeutic target for AMI.

Circular RNAs (circRNAs) are a new type of regulatory RNAs, which are involved in various cardiac processes. However, the role of circRNA hsa_circ_0055440 (circ-USP39) in acute myocardial infarction regulation has not been studied yet.

This study aims to explore the effect of circ-USP39 on hypoxia-induced cardiomyocyte injury.

The head-to-tail splicing of circ-USP39 was verified by agarose gel electrophoresis. AC16 cell viability was detected using 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assays. The apoptosis of the AC16 cell was determined by flow cytometry and detection of caspase-3 activity. The levels of creatine kinase-muscle/brain and cTnl were evaluated by specific detection kits. The interactions between miR-499b-5p and circ-USP39 (or acyl-CoA synthetase long-chain family member-1 (ACSL1) ) were verified by luciferase reporter assays.

After confirming the circular characteristics of circ-USP39, we further found that the circ-USP39 expression was upregulated in hypoxia-induced cardiomyocytes and the circ-USP39 knockdown facilitated the viability of hypoxia-induced AC16, while suppressing cardiomyocyte apoptosis and injury. Importantly, circ-USP39 negatively regulated miR-499b-5p expression. As a downstream target of miR-499b-5p, ACSL1 partially counteracted the protective effect of circ-USP39 depletion on cardiomyocyte injury.

Silencing of circ-USP39 alleviates hypoxia-induced cardiomyocyte injury via the miR-499b-5p/ACSL1 axis.

Vascular endothelial insulin resistance (IR) is an important risk factor in the development of vascular complications in diabetes. Prolonged endoplasmic reticulum stress (ERS) contributes to the development and progression of endothelial IR. The current study assessed the effects and mechanism of nebivolol on vascular IR in Goto-Kakizaki (GK) rats and endothelial IR induced by high glucose (33.3 mmol/L) associated with high insulin (10⁻⁷ mol/L) in human aortic endothelial cells (HAECs). Rats were divided into Wistar, Wistar + Neb (Wistar rats treated with nebivolol, 10 mg/kg, ig), GK, and GK + Neb (GK rats treated with nebivolol, 10 mg/kg, ig). GK rats showed hyperglycemia, dyslipidemia, impaired glucose homeostasis, metabolic IR, reduced relaxation to insulin, and lower serum nitric oxide (NO) level. Treatment with nebivolol for 4 months ameliorated insulin's vasorelaxation and NO production, and relieved dyslipidemia in GK rats. Additionally, nebivolol increased glucose uptake and NO level in the endothelial IR group in vitro. Nebivolol increased aortic expressions of IRS-1/PI3K/Akt/eNOS relative proteins and GLUT4 and reduced expressions of ERS markers (ATF6, GRP78, and CHOP, p-JNK/JNK). Furthermore, both nebivolol and TUDCA (ERS inhibitor) alleviated the attenuated IRS-1PI3K/Akt/eNOS pathway and enhanced ERS in HAECs IR. Tunicamycin (ERS inducer) not only induced endothelial IR but also blocked nebivolol's alleviation on the IRS-1PI3K/Akt/eNOS pathway and ERS. Nebivolol ameliorated endothelial IR partially by inhibiting ERS and then regulating the IRS-1/PI3K/Akt/eNOS signal.

A 77-year-old female presented with loss of consciousness, blood pressure of 90/60 mmHg, and heart rate of 47 bpm. At admission, highly sensitive Trop-T and lactate were elevated, and an electrocardiogram revealed an infero-posterior ST elevation myocardial infarction. Echocardiography revealed a depressed left ventricular ejection fraction with abnormal wall motion in the infero-posterior region and hyperkinetic apical movement along with severe mitral regurgitation (MR). Coronary angiography showed a hypoplastic right coronary artery, 100% thrombotic occlusion of the dominant left circumflex (LCx) artery, and 75% stenosis in the left anterior descending (LAD) artery. Substantial hemodynamic improvement with the reduction of acute ischemic MR was achieved by the initiation of an Impella 2.5, which is a transvalvular axial flow pump, and successful percutaneous coronary intervention (PCI) was conducted with stents to the LCx. The patient was weaned off the Impella 2.5 in 5 days, received staged PCI to LAD, and was later discharged after completion of the staged PCI to LAD.

Sick sinus syndrome (SSS) is a group of syndromes characterized by pathological changes in the sinoatrial node and its adjacent tissues. Although several mutations in the SCN5A gene have been associated with early-onset SSS, pediatric patients are still less common. Here, we report a rare compound missense mutation in the SCN5A gene [c.2893C>T (p. R965C) and c.2431C>T (p. R811C) ] in two sisters with childhood-onset SSS in Chinese population. The proband (5 years and 5 months old) was the second child of a clinically normal and nonconsanguineous couple. Her elder sister was 12 years old and had been implanted with a pacemaker because of the diagnosis of SSS at another hospital one year ago. The proband was presented to the hospital with a slowed heart rate and reduced endurance exercise capacity for more than three months. After a comprehensive clinical examination, she was diagnosed with SSS and underwent pacemaker implantation. Exome and Sanger sequencing were used to determine the compound heterozygous missense mutation of [c.2893C>T (p. R965C) and c.2431C>T (p. R811C) ] in the SCN5A in the patient and her elder sister. Each healthy parent carried a different heterozygous missense mutation. The compound heterozygous mutation of c.2893C>T (p. R965C) and c.2431C>T (p. R811C) rather than the single mutation might be the primary cause of familial early-onset SSS in Chinese population. Our current findings expanded the current understanding of the SCN5A gene mutations. We further confirmed the essential role of the SCN5A gene on the diagnosis, family cascade screening, early intervention, and prognostic evaluation of SSS.

Renovascular hypertension (RVH) is a common cause of secondary hypertension. However, there have been no reports on RVH due to radiation-induced abdominal aorta stenosis after renal autotransplantation. A 27-year-old woman with a history of neuroblastoma treated by radiation therapy and RVH treated with renal autotransplantation presented with hypertension and dyspnea. At age 19, she had experienced hypertensive heart failure due to RVH from radiation-induced left renal artery stenosis and had undergone renal autotransplantation involving the extraction of her left kidney. Her systolic blood pressure (BP) was well-controlled but had increased progressively. She was diagnosed with hypertensive heart failure and admitted to hospital. Although her dyspnea soon subsided after treatment, her BP remained high. Renal artery ultrasound revealed no obvious stenosis. The ankle brachial pressure index (ABI) showed a significant bilateral decrease to 0.71/0.71 (right/left) from 0.94/0.95 eight years before. Magnetic resonance angiography and aortic angiography revealed severe stenosis in the abdominal aorta, and the systolic pressure gradient of intra-aortic blood flow, distal and proximal to a stenotic lesion, was 58 mmHg. These arterial stenoses in the irradiated area were highly suggestive of radiation-induced vasculopathy. She finally underwent an endovascular VIABAHN VBX balloon-expandable stent-graft placement for this radiation-induced abdominal aorta stenosis, which resolved the pressure gradient. After the procedure, her ABI improved to 0.91/0.88 and her BP was well-controlled. This is the first case of successful stent-graft placement for RVH after renal autotransplantation due to radiation-induced abdominal aorta stenosis as a consequence of neuroblastoma.

Cardiac paragangliomas (PGLs) are rare neuroendocrine tumors, and data regarding the features of nonfunctioning PGLs are limited. These tumors are extensively vascularized and have high risk of hemorrhage for surgery and even biopsy. Differential diagnosis including biochemical analysis of these PGLs is important for further management. In this case report, we present the clinical, laboratory, imaging, and radionuclide presentations of a rare primary nonfunctioning cardiac PGL with a coronary aneurysm. Echocardiography initially showed a large echogenic mass in the left atrioventricular groove. The mass presented a diffuse hyperenhancement pattern with a central perfusion defect on contrast echocardiography. The tumor enclosed the left coronary artery from the coronary orifice, and an aneurysm was found in the left circumflex artery, with significantly increased flow velocity. These echocardiographic features and its susceptible location are indicative of the presence of a cardiac PGL. Although all biochemical evaluations of catecholamines from blood and urine samples were negative, positron emission tomography and scintigraphy finally confirmed the diagnosis of a primary cardiac PGL. Therefore, when imaging features are indicative of the presence of PGLs, the implementation of radionuclide imaging for final diagnosis is required even if the biochemical results are negative. Recognizing these uncommon Doppler and contrast echocardiographic characteristics is important for early diagnosing these nonfunctioning PGLs.

Pulmonary arterial hypertension (PAH) is a rare and fatal disease for which some causative drugs have been developed. Qing-Dai is a Chinese herbal drug that is sometimes used as a specific treatment for ulcerative colitis in Asia, including Japan. Here, we report a case of severe Qing-Dai-induced PAH. A 19-year-old woman who has been taking Qing-Dai for 8 months was admitted for exertional dyspnea. Her mean pulmonary artery pressure dramatically improved from 72 to 18 mmHg with Qing-Dai discontinuation and PAH-specific therapy. After 6 years of onset, she had not relapsed with PAH with PAH-specific therapy.

Primary aldosteronism (PA) is a typical example of low renin hypertension, whereas renal artery stenosis (RAS) is a classic form of high renin hypertension. PA and RAS occurring simultaneously in a patient is challenging to diagnose. We report a 32-year-old woman with a 12-year history of resistant hypertension. She was identified to have elevated plasma aldosterone and renin levels with normal aldosterone/renin ratio (ARR). Imaging examinations identified bilateral adrenal thickening and subtotal occlusion of the anterior segment of the left renal artery. Adrenal venous sampling was performed and indicated the existence of unilateral aldosterone over-secretion. It may suggest that even though RAS led to non-suppressed renin, adrenal venous sampling remains to be an applicable approach to establish the diagnosis of aldosterone-producing adenomas, although the diagnostic value of ARR may be compromised due to non-suppressed renin level. The patient underwent a two-stage treatment. First, stenosis of the left renal artery was dilated by percutaneous transluminal renal balloon angioplasty. Two months later, laparoscopic complete left adrenalectomy was performed. Hematoxylin-eosin staining and CYP11B2 immunostaining suggested that this tumor was an aldosterone-producing adenoma. After the two-stage treatment, her blood pressure decreased to a normal level without antihypertensive drugs. This case report raises our awareness of the simultaneous occurrence of RAS and PA. Under this condition, ARR could lead to a false-negative PA. Adrenal venous sampling is warranted to achieve a confirmed diagnosis. For subjects with complex etiologies of secondary hypertension, multi-stage treatment may be required.

An error appeared in the article entitled "The Usefulness and Limitations of Impedance Cardiography for Cardiac Resynchronization Therapy Device Optimization" by Kojiro Ogawa, Miyako Igarashi, Akihiko Nogami, Masayoshi Yamamoto, Akinori Sugano, Yukio Sekiguchi, Kazutaka Aonuma, Masaki Ieda (Vol. 61 No.5, 896-904, 2020). The unit of the variable in Table IV on page 903 should be replaced by the following.

An error appeared in the article entitled "Patients with Moderate Non-Culprit Coronary Lesions of Recent Acute Coronary Syndrome: A Comparison of Fractional Flow Reserve and Dobutamine Stress Echocardiography" by Abdelkrim Ahres, Balázs Jablonkai, Ágnes Schrancz, Zsuzsanna Balogh, Andrea Kenessey, Tamás Baranyai, Ágnes Őze, Zsolt Szigeti, Gábor Rubóczky, Béla Nagybaczoni, Astrid Apor, Judit Simon, Bálint Szilveszter, Márton Kolossváry, Béla Merkely, Pál Maurovich-Horvat, and Péter Andrássy (Vol. 62 No.5, 952-961, 2021). The affiliation of the first author on page 952 should be replaced by the following.