International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
64 巻, 4 号
選択された号の論文の36件中1~36を表示しています
Review Article
  • Chandhu AS, Debashish Danda
    2023 年 64 巻 4 号 p. 519-534
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー
    電子付録

    Takayasu arteritis (TA or TAK) is a chronic large vessel vasculitis with predilection to affect the aorta and its branches. The new 2022 ACR/EULAR classification criteria for Takayasu arteritis incorporated imaging characteristics as an absolute requirement. ESR and CRP fails in accuracy as disease activity markers. Pentraxin 3 appears to be a relatively superior biomarker, which correlates with ITAS 2010 as per several studies. PET-CT is also increasingly being studied for assessing disease activity with variable results. The management of TAK involves use of steroids with upfront steroid sparing immunosuppressive agents. MMF is one such conventional DMARD/immunosuppressant with good efficacy and better safety profile, as reported in various cohort studies. Tocilizumab is proved to be a rapid remission inducing agent in refractory Takayasu arteritis in observational studies. TNF inhibitors in many uncontrolled studies showed good responses, and there is a need for good RCTs for confirmation. JAK inhibitors have also been used with success in a few reports.

    Editor's pick

Clinical Studies
  • A Suburban Single-Center Observational Study
    Keiichi Kohashi, Masataka Nakano, Takaaki Isshiki, Yoshio Maeno, Shuzo ...
    2023 年 64 巻 4 号 p. 535-542
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    Rapid reperfusion by primary percutaneous coronary intervention (pPCI) is an established strategy for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Pre-hospital electrocardiogram (PH-ECG) transmission by the emergency medical services (EMS) facilitates timely reperfusion in these patients. However, evidence regarding the clinical benefits of PH-ECG in individual hospitals is limited.

    This retrospective, observational study investigated the clinical efficacy of PH-ECG in STEMI patients who underwent pPCI. Of a total of 382 consecutive STEMI patients, 237 were enrolled in the study and divided into 2 groups: a PH-ECG group (n = 77) and non-PH-ECG group (n = 160). Door-to-balloon time (D2BT) was significantly shorter in the PH-ECG group (66 [52-80] min), compared to the non-PH-ECG group (70 [57-88] minutes, P = 0.01). The 30-day all-cause mortality rate was 6% in the PH-ECG group, which was significantly lower than that in the non-PH-ECG group (16%) (P = 0.037, hazard ratio [HR]: 0.38, 95% CI: 0.15-0.98). This trend was particularly evident in severely ill patients when stratified by GRACE score.

    The use of PH-ECG improved the survival rate of STEMI patients undergoing pPCI due to the improved pre-arrival preparation based on the EMS information. Coordination between EMS and PCI-capable institutes is essential for the management of PH-ECG.

  • Xiangrong Xie, Yan Chen, Weipeng Gan, Cheng Liang, Quan Zuo, Yimeng Zh ...
    2023 年 64 巻 4 号 p. 543-550
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.

    Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.

    The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.

    This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.

  • A Prospective Cohort Study
    Zhaogui Wu, Shan Zeng, Xuezhu Wang, Hangkuan Liu, Haonan Sun, Xin Zhou ...
    2023 年 64 巻 4 号 p. 551-561
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    Limited information exists regarding whether circulating microbiota could predict long-term clinical outcomes following ST-segment elevation myocardial infarction (STEMI). A total of 244 consecutive patients with STEMI were followed for 2.8 years, and 64 first major adverse cardiovascular events (MACEs) were recorded. Both microbiota abundance [Corynebacterium tuberculostearicum (HR, 1.28; 95% CI, 1.03-1.58) and Staphylococcus aureus (S. aureus) (HR, 1.16; 95% CI, 1.02-1.33) ] and microbiota clusters (Cluster 2 versus Cluster 1: HR, 1.84; 95% CI, 1.04-3.27) could independently predict MACE. Furthermore, a model based on established independent predictors alone was significantly improved by the addition of different microbiota patterns. In addition, CD14++CD16+ monocytes (Mon2) had a significant mediation effect on the microbiota patterns → MACE association. The present study demonstrated that the abundance and clusters of circulating microbiota are associated with future adverse cardiovascular events independent of traditional risk factors, which were partially mediated by an increase in Mon2.

  • Yi Zhou, Haiwei Liu, Hongfei Yang, Xiangyu Zhao, Yungen Jiao
    2023 年 64 巻 4 号 p. 562-569
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー
    電子付録

    This study aims to assess the predictive value of the apolipoprotein B (ApoB) /apolipoprotein A1 (ApoA1) ratio in acute coronary syndrome (ACS) in patients with diabetes mellitus (DM) for the rapid progression (RP) of non-culprit coronary lesions (NCCLs) after percutaneous coronary intervention (PCI) and observe the effect of the ApoB/ApoA1 ratio on major adverse cardiac events (MACE).

    A total of 175 patients with DM presenting with ACS who received a PCI and an average 13-month follow-up coronary angiography (CAG) were enrolled from January 2015 to December 2020. According to the CAG, the patients were divided into the RP group and the non-RP group. MACE was defined as a composite of death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization from unstable or progressive angina at the end of a 24-month follow-up.

    The low-density lipoprotein cholesterol (LDL-C), ApoB, ApoB/ApoA1 ratio, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio levels at baseline were significantly higher in the RP group than in the non-RP group. The ApoA1 level at baseline in the non-RP group was significantly higher than in the RP group. The predictive significance of the ApoB/ApoA1 ratio (area under the curve (AUC) = 0.712) for the RP of NCCLs was significantly higher than those of ApoA1, ApoB, LDL-C/HDL-C ratio (AUC = 0.628, AUC = 0.640, and AUC = 0.620, respectively). A higher ApoB/ApoA1 ratio and the RP of NCCLs were significantly associated with the occurrence of MACE.

    The ApoB/ApoA1 ratio was an effective clinical indicator for the RP of NCCLs after PCI in patients with DM presenting with ACS. The high ApoB/ApoA1 ratio and the RP of NCCLs were two risks for MACE.

  • Akinori Satake, Yasuhiro Uchida, Hideki Ishii, Daiki Yamashita, Jun Yo ...
    2023 年 64 巻 4 号 p. 570-576
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    The concept of complex and high-risk indicated procedures using percutaneous coronary intervention (CHIP-PCI) has recently been defined. However, few studies have investigated the prognosis of patients after CHIP-PCI. We enrolled 322 consecutive patients who underwent CHIP-PCI. CHIP-PCI was defined as a procedure satisfying at least one criterion each for both patient and procedure characteristics, as follows: patient characteristics [age ≥ 75 years old, low left ventricular ejection fraction (LVEF), diabetes mellitus, acute coronary syndrome, previous coronary artery bypass surgery, peripheral arterial disease, severe chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and severe valvular disease] and procedure characteristics [unprotected left main disease, degenerated saphenous or radial artery grafts, severely calcified lesions, last patent conduit, chronic total occlusions, multivessel disease, and use of mechanical circulatory support]. On Kaplan-Meier analysis, 1-, 2-, and 3-year survival rates following CHIP-PCI was 93.8%, 89.2%, and 85.4%, respectively. Moreover, on Cox multivariate hazard analysis, age (≥ 75 years old) (hazard ratio: 4.01, 95% confidence interval: 1.92-8.38, P < 0.01), COPD (hazard ratio: 2.95, 95% confidence interval: 1.38-6.32, P < 0.01), low LVEF (hazard ratio: 3.35, 95% confidence interval: 1.55-7.22, P < 0.01), severe CKD (hazard ratio: 3.02, 95% confidence interval: 1.44-6.36, P < 0.01), and use of mechanical circulatory support (hazard ratio: 5.97, 95% confidence interval: 2.72-13.10, P < 0.01) remained significant predictors of mortality. In conclusion, we revealed the clinical outcomes after CHIP-PCI. The presence of advanced age, COPD, low LVEF, severe CKD, and mechanical circulatory support use might lead to worse clinical outcomes.

  • Nobuaki Suzuki, Tatsuru Yokoi, Takahiro Kimura, Yoshiyuki Ikeda, Shinj ...
    2023 年 64 巻 4 号 p. 577-583
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Residual risk of atherosclerosis remains high despite the use of lipid-lowering therapy with statins. Near-infrared spectroscopy intravascular ultrasound imaging (NIRS-IVUS) can identify vulnerable plaque via the detection of lipid-rich plaque. This study aimed to reveal the clinical characteristics of patients with vulnerable plaque despite statin therapy.

    NIRS-IVUS was used to determine the maximum 4 mm Lipid Core Burden Index (MaxLCBI4 mm) values of 38 de novo culprit lesions from 32 patients with acute coronary syndrome (53%) (mean age: 73.1 ± 13.1 years) who underwent percutaneous coronary intervention after a minimum 6 months of statin therapy for primary prevention. A patient with vulnerable plaque was defined as an individual presenting at least 1 target lesion with a vulnerable plaque (MaxLCBI4 mm > 400). Overall, the average low-density lipoprotein cholesterol (LDL-C) level was 95.5 ± 27.2 mg/dL. Patients in the vulnerable plaque group were younger and had higher LDL-C, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C) levels than those in the non-vulnerable plaque group. The MaxLCBI4 mm was positively correlated with LDL-C (P = 0.0002), triglycerides (P = 0.0003), and non-HDL-C (P = 0.0001). In multivariate analysis, all 3 treatable lipid components failed to show an independent relationship with the patients with vulnerable plaque. Using receiver-operating characteristics curve analysis, the cutoff points for LDL-C, triglycerides, and non-HDL-C were determined to be 78 mg/dL, 108 mg/dL, and 111 mg/dL, respectively, at MaxLCBI4 mm > 400. In conclusion, this study supports a more comprehensive and aggressive lipid-lowering therapy for the primary prevention of coronary artery disease.

  • Daisuke Isomatsu, Akihiko Sato, Yuya Sakuma, Yuta Kurosawa, Yuki Muto, ...
    2023 年 64 巻 4 号 p. 584-589
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Living alone is associated with increased cardiac events and mortality in patients with acute myocardial infarction. However, the prognostic impact of living alone with chronic coronary syndrome (CCS) still remains unclear. In the present study, we examined the relationship between living alone and long-term mortality in patients with CCS who underwent percutaneous coronary intervention (PCI).

    Consecutive 830 patients with CCS who underwent PCI were enrolled and divided into 2 groups according to whether or not they were living alone at the time of admission (living alone group and non-living alone group). We compared the clinical characteristics between the 2 groups and followed up cardiac mortality. The living alone group was younger compared with the non-living alone group (67.5 versus 70.7 years old, P = 0.017). The prevalence of comorbidities, including coronary risk factors, atrial fibrillation, heart failure, stroke, peripheral artery disease, coronary lesion characteristics, laboratory data, and left ventricular ejection fraction, were comparable between the 2 groups. During the follow-up period (median 1,622 days), 52 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly higher in the living alone group than in the non-living alone group (24% versus 11%, P = 0.008). In the multivariable Cox proportional hazard analyses after adjusting for possible confounding factors, living alone was an independent predictor of cardiac mortality (hazard ratio, 2.426, 95% confidence interval 1.225-4.804, P = 0.011).

    Among CCS patients who underwent PCI, living alone was associated with high long-term cardiac mortality.

  • Shun Sasaki, Kenji Inoue, Masayuki Shiozaki, Chien-Chang Lee, Shuo-Ju ...
    2023 年 64 巻 4 号 p. 590-595
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー
    電子付録

    The European Society of Cardiology recommends the 0/1-hour algorithm for risk stratification of patients with suspected non-ST-elevation myocardial infarction as class I, level B; however, there are few reports on the long-term prognosis, resulting in a rule-out group. We aimed to determine whether implementation of the 0-hour/1-hour algorithm is safe and effective in emergency department (ED) patients with possible acute coronary syndrome (ACS) through a 1-year follow-up period. Our study analyzed the 1-year follow-up data from a prospective pre-post study of 1106 ED patients with possible ACS from 4 hospitals in Japan and Taiwan. Patients were 18 years or older. Accrual occurred for 1 year after implementing the 0-1-hour algorithm from November 2014 to December 2018. Overall, 520 patients were stratified into the rule-out group. Major advanced cardiovascular events (all-cause death, acute myocardial infarction [AMI], stroke, unstable angina, and revascularization) at 1-year were determined using data from health records and phone calls. The 0-1-hour algorithm stratified 47.0% of patients in the rule-out group. Over the 1-year follow-up period (follow-up rate = 86.9%), cardiovascular death and subsequent AMI did not occur in the rule-out group. Among the 27 patients who underwent the procedure within 30 days post-index visit, 3 patients (0.7%) had a stroke, 6 patients (1.3%) died of non-cardiovascular cause, and 30 patients (6.7%) underwent coronary revascularization within 1 year. At the 1-year follow-up, implementation of the 0-hour/1-hour algorithm was associated with very low rates of adverse event among patients in the rule-out group.

  • Teruhiko Imamura, Nikhil Narang, Masakazu Hori, Koichiro Kinugawa
    2023 年 64 巻 4 号 p. 596-601
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Small dense LDL-cholesterol is an established risk factor for atherosclerosis, but it is not routinely measured in clinical practice, and its measurement has not yet been reimbursed. The Sampson equation that uses triglyceride and LDL-cholesterol levels has very recently been proposed to estimate small dense LDL-cholesterol levels. We validated its accuracy in patients with acute coronary syndrome.

    Serum samples were obtained on admission from hospitalized patients with acute coronary syndrome before heparinization. Small dense LDL-cholesterol levels were measured directly and were also estimated from triglyceride and LDL-cholesterol levels using the Sampson equation. The correlation between the Sampson's equation and direct measurement was investigated.

    A total of 55 patients were enrolled. The median age was 75 (65, 84) years old, and 35 (64%) were men. There was a moderate correlation between the two methods (r = 0.76, P < 0.001). A lower level of small dense LDL-cholesterol was independently associated with a greater overestimation of the Sampson equation.

    The Sampson equation is useful for estimating small dense LDL-cholesterol levels in patients with acute coronary syndrome. However, the estimated value may be overestimated in patients with low lipid profiles.

  • Junji Morita, Yusuke Kondo, Takuya Okada, Takayuki Kitai, Yuhei Kasai, ...
    2023 年 64 巻 4 号 p. 602-605
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    The predictors of pacing capture threshold (PCT) exacerbation after leadless pacemaker implantation remain unknown. We analyzed the predictors of poor PCT by identifying risk factors using multivariate logistic regression analysis for 211 patients with leadless pacemaker implantation. Twenty patients met the criteria for elevated PCT levels and were categorized in the poor PCT group. Multivariate analyses revealed that PCT (P < 0.0001) and pacing impedance (P = 0.03) were independent predictors of PCT exacerbation. Elevated PCT levels and low pacing impedance during leadless pacemaker implantation were potential risk factors for the replacement of leadless pacemakers after the procedure.

  • Jiyi Liu, Fengzhi Sun, Jiao Sun, Yunbo Ba, Weilong Zhao, Zhipeng Zhang ...
    2023 年 64 巻 4 号 p. 606-613
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    This study aimed to evaluate the effect of circumferential pulmonary vein isolation (CPVI) on autonomic nervous function and prognosis in patients with paroxysmal atrial fibrillation (AF) with or without sinus bradycardia.

    A total of 66 patients with paroxysmal AF accompanied by sinus bradycardia and who underwent CPVI were recruited as the sinus bradycardia group. A total of 91 patients with paroxysmal AF but without sinus bradycardia and who underwent catheter ablation were selected as the control group. After surgical contraindications were eliminated, CPVI was performed by three-dimensional mapping system. 24-hour dynamic electrocardiogram was used to observe the changes of heart rate before and 2 days after surgery.

    A total of 45 (68%) and 51 (56%) patients in the sinus bradycardia and control groups, respectively, maintained sinus rhythm. There was an increase in heart rate after CPVI in both groups. The standard deviation of normal-to-normal (NN) intervals (SDNN), standard deviation of the average NN intervals (SDANN), low frequency (LF), and LF/high frequency (HF) in the sinus bradycardia and control groups decreased after CPVI (P < 0.01). Moreover, SDANN was higher in patients with sinus bradycardia treated by successful ablation than in those with recurrence (P < 0.01), while SDNN, a standard statistical measure of heart rate variability (rMSSD), LF, and HF were significantly lower in patients with sinus bradycardia (P < 0.05).

    CPVI was able to produce a significant reduction effect on vagal nerve and sympathetic activity regardless of whether patients with paroxysmal AF had sinus bradycardia. Moreover, CPVI exerted a certain influence on the success rate of AF catheter ablation.

  • Minoru Nodera, Miyako Igarashi, Kanae Hasegawa, Kazutaka Aonuma, Akihi ...
    2023 年 64 巻 4 号 p. 614-622
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    Radiofrequency catheter ablation (RFCA) to treat ventricular arrhythmias (VAs) originating below the His bundle (HB) region of the right ventricular (RV) septum could impair the atrioventricular node conduction. This study aimed to clarify the parameters of the 12-lead electrocardiography that predict successful RFCA of VAs originating from this region. This study included 20 consecutive patients (13 men; mean age, 68 ± 7 years) with monomorphic VAs in whom the earliest ventricular activation during the VA was below the HB region of the RV septum. According to the ablation results, the patients were divided into two groups: successful ablation (S-group; n = 10) and failed ablation groups (F-group; n = 10). The electrocardiographic parameters during the VAs and RFCA results were assessed. The R wave amplitudes in leads aVL (P = 0.001) and I (P = 0.010) in the S-group were both smaller than those in the F-group. In addition, the S-group had smaller negative deflection amplitudes in leads III (P = 0.002) and aVF (P = 0.003) than the F-group. According to the receiver operating characteristic curve analysis, the most useful electrocardiographic parameter for predicting successful ablation was the R wave amplitude in lead aVL (area under the curve, 0.895; P < 0.001); a cutoff value of < 1.3 mV predicted a successful RFCA with the highest accuracy (sensitivity, 90%; specificity, 80%; positive predictive value, 82%; negative predictive value, 89%). The R wave amplitude in lead aVL was the most useful parameter for predicting a successful RFCA to treat VAs originating below the HB region of the RV septum.

  • Issei Yoshimoto, Hitoshi Ichiki, Masaaki Miyata, Hiroyuki Kamada, Yuic ...
    2023 年 64 巻 4 号 p. 623-631
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Arterial stiffness has been reported to cause left atrial (LA) remodeling due to increased left ventricular filling pressure, resulting in atrial fibrillation (AF). This study aimed to evaluate the association between LA reverse remodeling (LARR) after AF ablation and cardio-ankle vascular index (CAVI), an indicator of arterial stiffness.

    This study included 333 patients with AF (171 with paroxysmal AF and 162 with nonparoxysmal AF) and LA enlargement (LA volume index ≥ 34 mL/m2) who underwent AF ablation between December 2008 and July 2021. CAVI was evaluated preoperatively during AF (n = 155, 46.5%) or sinus rhythm (n = 178, 53.5%). Participants were divided into groups with LARR (n = 133, 39.9%) and without LARR (n = 200, 60.1%) according to whether the degree of decrease in LA volume index on transthoracic echocardiography 6 months after ablation was ≥ 15% or < 15%, respectively.

    Sinus rhythm was maintained in 168 (50.5%) patients within 3-6 months after the index procedure. Univariate analysis revealed that preoperative CAVI (7.80 ± 1.22 versus 8.57 ± 1.09, P < 0.001) was significantly lower, and the maintenance of sinus rhythm (61.6% versus 43.0%, P = 0.0011) was higher in the group with LARR. Multivariate logistic regression analysis revealed that preoperative CAVI was independently associated with LARR (odds ratio, 0.60, 95% confidence interval, 0.46-0.78, P < 0.001).

    In patients with AF and LA enlargement, CAVI is independently associated with LA reverse remodeling after catheter ablation.

  • Yibo Yu, Renyuan Fang, He Jin, Binhao Wang, Fang Gao, Bin He
    2023 年 64 巻 4 号 p. 632-640
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Atrial fibrillation (AF) is the most common arrhythmia that is harmful to human health. This study aims to explore the relationship between myosin light chain 4 (MYL4) and AF recurrence after radiofrequency ablation (RFA). Patients with AF (n = 85) were enrolled, and healthy subjects (n = 90) with normal sinus rhythm and no previous history of AF were selected as controls. The serum levels of MYL4, transforming growth factor (TGF) -β1, and procollagen type-I C-terminal propeptide (PICP) were determined. The correlation between MYL4 and atrial fibrosis remodeling indicators (TGF-β1/PICP) and left atrial diameter (LAD) was analyzed. The influence of MYL4 on AF recurrence after RFA was evaluated, and the independent correlation between them was assessed. Patients with AF and the controls showed no significant differences in age, gender, body mass index, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, white blood cell count, neutrophil/lymphocyte ratio, brain natriuretic peptide, and history of smoking, drinking, hypertension, and diabetes (P > 0.05), but with increased LAD in patients with AF (P < 0.01). Serum MYL4 level was reduced in patients with AF (0.6 ± 0.2) compared with that of controls (0.1 ± 0.6) (P < 0.01), and it was negatively correlated with TGF-β1, PICP, and LAD (r = −0.2389, P < 0.05; r = −0.5174, P < 0.01; r = −0.3191; P < 0.01). Low levels of MYL4 increased the risk of AF recurrence after RFA (χ2 = 16.64; P < 0.0001). A low MYL4 level in patients with AF showed a poorer prognosis. Serum MYL4 level and AF type were independent risk factors affecting AF recurrence after RFA.

  • Makiko Nakamura, Teruhiko Imamura, Toshihide Izumida, Masaki Nakagaito ...
    2023 年 64 巻 4 号 p. 641-646
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Exercise training in addition to re-assessment of medical treatments is recommended for patients with advanced heart failure. However, the feasibility and efficacy of exercise training in patients with heart failure receiving intravenous inotropes remains uncertain.

    Clinical data were analyzed from consecutive patients with stabilized hemodynamics receiving intravenous inotropes for more than 1 week and undergoing cardiac rehabilitation at our institute between February 2020 and May 2022. All patients received re-assessment of guideline-directed medical therapy and non-pharmacological treatment, in addition to the exercise therapy. The intensity of exercise training was determined based on the results of cardiopulmonary exercise testing.

    A total of 10 patients receiving intravenous inotropes (median age 60 years, left ventricular ejection fraction 23%) were included. All patients received low-dose dobutamine and 4 patients received concomitant milrinone. Exercise training was continued for 112 days on median without any critical complications. Intravenous inotropes were continued for 41 days on median and weaned off in all patients. Plasma B-type natriuretic peptide decreased slightly from 291 (129, 526) to 177 (54, 278) pg/mL (P = 0.070) and peak oxygen consumption increased from 10.0 (8.3, 15.3) to 15.2 (10.9, 17.2) mL/kg/minute (P = 0.142) during the 6-month observational period following the initiation of exercise intervention.

    Exercise training might be feasible and effective in patients with advanced heart failure receiving low-dose intravenous inotrope support concomitant with re-assessment of medical treatment.

  • A Preliminary Study
    Yuta Nakaya, Akiyoshi Ogimoto, Hiroaki Kitaoka
    2023 年 64 巻 4 号 p. 647-653
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    Tafamidis improves the prognosis of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM). Additionally, it delays the decline in exercise tolerance, as observed in the six-minute walking test. However, the changes in cardiopulmonary function over time based on cardiopulmonary exercise tests are unclear. Thus, this preliminary study investigated the changes in exercise tolerance after one year of tafamidis treatment using cardiopulmonary exercise testing. Eight patients with ATTR-CM (average age: 77 years; male: n = 7) underwent cardiopulmonary exercise testing at baseline and after one year of tafamidis treatment. All eight patients completed a one-year follow-up. At baseline, the anaerobic threshold oxygen uptake (AT VO2: 10.9 ± 1.5) and peak VO2 (14.3 ± 3.0 mL/kg/minute) indicated relatively favorable exercise capacity; however, the minute ventilation/carbon dioxide production (VE/VCO2 slope), which indicates effective ventilation, showed poor performance (33.7 ± 12.8). One year after tafamidis treatment, frailty, as assessed by the Clinical Frailty Scale, had progressed in seven of eight patients (88%) (P < 0.01), and AT VO2 and peak VO2 were significantly reduced (19.2% and 22.3%, respectively; P < 0.05). The VE/VCO2 slope and peak O2 pulse decreased nonsignificantly by approximately 20% (P = 0.47, and P = 0.16, respectively). Further, the structure of the ventricles and atrium and the left ventricle ejection fraction on echocardiography did not change. Thus, exercise tolerance in patients with ATTR-CM was reduced after one year despite tafamidis administration. Not only ATTR-CM progression, but also frailty progression may influence this decrease in exercise tolerance. A comprehensive approach, including tafamidis administration and cardiac rehabilitation, is required for further improvement in the exercise capacity of patients with ATTR-CM.

  • Evidence from the China Kadoorie Biobank Study
    Xiaojia Sun, Ruihong Sun, Liming Zhang
    2023 年 64 巻 4 号 p. 654-662
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Associations between red meat consumption and cardio-cerebrovascular diseases (CCVDs) are mostly studied in Western populations but not in Chinese or elderly. This prospective study investigated adults ≥65 years from the China Kadoorie Biobank (CKB). Associations between red meat consumption and CCVD, ischemic stroke/transient ischemic attack (TIA), CCVD mortality, and all-cause mortality were determined by Cox regression. A total of 59,980 participants were analyzed, 14,715 (24.53%) of whom ate red meat daily, 9,843 (16.41%) ate red meat 4-6 days/week, 23,472 (39.13%) ate red meat 1-3 days/week, and 11,950 (19.92%) ate red meat less than 1 day/week. Average amount of red meat usual consumption was 38 g/day. After adjustment, per 50 g/day higher red meat consumption at baseline was significantly associated with increased incident CCVD (aHR = 1.10) among high-income subjects (≥ 10,000 RMB) and urban residents (aHR = 1.12). Per 50 g/day higher baseline red meat consumption was significantly associated with increased ischemic stroke/TIA in urban residents (aHR = 1.08) but decreased risk in rural residents (aHR = 0.84). Higher baseline red meat consumption was associated with lower CCVD mortality in the poorest (aHR = 0.78) and rural residents (aHR = 0.72) and lower all-cause mortality in the poorest (aHR = 0.82) and rural residents (aHR = 0.80). In general, among older adults in China, higher red meat intake independently predicted increased CCVD among urban and high-income individuals but not poor ones. Higher red meat intake appears to be protective against mortality in rural and low-income subjects. Socioeconomic status is a crucial modifying factor on the association between red meat consumption and adverse cardiovascular outcomes in China.

  • Yuichi Ishikawa, Hiroaki Urabe, Yuya Yamada, Kenichiro Yamamura, Katsu ...
    2023 年 64 巻 4 号 p. 663-671
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Age-related mean and reference ranges for ventricular volumes and mass, regional blood flow measurements, and T1 values using cardiovascular magnetic resonance (CMR) imaging are yet to be established for the pediatric population. Especially in infants and toddlers, no consistent flow volume sets or T1 values have been reported. The purpose of this study was to determine the relevant normal values.

    Twenty-three children (aged 0.1-15.3 years) without cardiovascular diseases were included. Comprehensive CMR imaging including cine, 2-dimensional phase-contrast, and native T1 mapping, were performed. Ventricular volumes and masses, 11 sets of regional blood flow volumes, and myocardial and liver T1 values were measured. All intraclass correlation coefficient values were > 0.94, except for the right ventricular mass (0.744), myocardial (0.868) and liver T1 values (0.895), reflecting good to excellent agreement between rates.

    Regression analysis showed an exponential relationship between body surface area (BSA) and ventricular volumes, mass, and regional blood flow volumes (normal value = a*BSAb). Left ventricular myocardial T1 values were regressed on linear regression with age (normal value = -7.39*age + 1091), and hepatic T1 values were regressed on a quadratic function of age (normal value = 0.923*age2 -18.012*age + 613).

    Comparison of the 2 different methods for the same physical quantities by Bland-Altman plot showed no difference except that the right ventricular stroke volume was 1.5 mL larger than the main pulmonary trunk flow volume.

    This study provides the normal values for comprehensive CMR imaging in Japanese children.

  • Ryusei Ohno, Hidehiro Kaneko, Kensuke Ueno, Kentaro Kamiya, Akira Okad ...
    2023 年 64 巻 4 号 p. 672-677
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Despite having a higher risk of cardiovascular disease (CVD), there are currently limited data for stratifying CVD risk among cancer survivors. The purpose of this study was to uncover the relationship of subjective gait speed with incident CVD among cancer survivors.

    This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2021 including 56,589 patients with a prior history of breast, colorectal, or stomach cancer but no history of CVD. Gait speed was evaluated using information from self-reported questionnaires collected during health checkups. The primary endpoint was composite CVD outcome, which included heart failure, myocardial infarction, angina pectoris, and stroke.

    The median (interquartile range) age was 54 (48-61) years, and 20,981 (37.1%) were male. Among them, 25,933 patients (45.8%) reported fast gait speed. During a mean follow-up period of 1002 ± 803 days, 3,221 composite CVD outcomes were recorded. In multivariate Cox regression analysis, slow gait speed was associated with a higher risk of developing CVD compared with fast gait speed (hazard ratio, 1.14, 95% confidence interval, 1.06-1.22). This association was consistent across a variety of sensitivity analyses.

    We demonstrated that subjective slow gait speed was associated with a greater risk of CVD development among cancer survivors. This suggests the potential value of gait speed assessment for the CVD risk stratification of cancer patients as well as the clinical importance of maintaining exercise capacity among patients living with cancer.

  • Hisako Tsuji, Ichiro Shiojima
    2023 年 64 巻 4 号 p. 678-683
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Although chronic liver disease has been associated with cardiovascular disease, to which metabolic syndrome might be related, intracerebral hemorrhage (ICH) generally has not been focused. Associations of chronic liver disease assessed by aspartate (AST) and alanine (ALT) aminotransferase levels with ICH deaths were examined using 15,952 subjects without a history of cardiovascular disease who underwent annual health checkups in 1997 in Japan. Proportional hazards regression analyses adjusted for age, sex, hypertension, current smoking, diabetes mellitus, drinking habits, excess body weight, and hypercholesterolemia were performed. During a mean follow-up of 18.6 ± 7.2 years, there were 227 stroke deaths (including 124 ischemic and 60 ICH deaths) and 135 coronary deaths. Elevated aminotransferase levels, defined as a serum AST or ALT level of ≥ 30 IU/L were significantly associated with ICH deaths (hazard ratio (HR) = 2.72, 95% confidence interval (CI) = 1.56-4.73, P = 0.0004). Because elevated aminotransferase levels are frequently observed in alcoholic or metabolic liver diseases, additional analyses were performed to examine the effect of drinking habits and/or metabolic syndrome on the association of elevated aminotransferase levels with ICH deaths. After exclusion of subjects with any drinking habit (n = 9,941), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 2.88, 95%CI = 1.44-5.76, P = 0.0028). After exclusion of subjects with at least one metabolic syndrome component (n = 5,672), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 6.47, 95% CI = 1.85-22.6, P = 0.0035). Elevated aminotransferase levels were not associated with ischemic stroke or coronary deaths in any models. Elevated aminotransferase levels were significantly associated with ICH deaths, independent of drinking habits, or metabolic syndrome.

  • Insights from Real-World Japanese Data
    Yuichi Tamura, Hiraku Kumamaru, Shiori Nishimura, Yasuo Nakajima, Hiro ...
    2023 年 64 巻 4 号 p. 684-692
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー
    電子付録

    Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV−) PGI2-IV.

    Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV− n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV− cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV − cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV − cohort.

    These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.

  • Pengyishi Peng, Jingsong Xu, Kun Hu, Hai Su
    2023 年 64 巻 4 号 p. 693-699
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    We aimed to explore whether the cuff/arm (C/A) circumference ratio within the suggested range (> 80%) affects the accuracy of mercury cuff blood pressure (BP) measurement (cuff BP) using intrabrachial BP (IABP) as a reference.

    A total of 253 patients aged 62.42 ± 9.70 years were included. After coronary angiography, the catheter in the right arm was gradually withdrawn toward the cubital fossa, and the IABP was continuously recorded. The cuff BP of the right arm was measured based on the artery blood flow using a special method similar to the traditional mercury method. The cuff was replaced using another C/A ratio after one minute, and the test was performed again. We used three different cuffs for each participant to meet the C/A ratios of 80%-84%, 85%-89%, and 90%-100%. We calculated the percentage deviation degree (DD) between the cuff BP and IABP values: DD = difference/IABP × 100%. The agreement between the values was evaluated using the Bland-Altman method.

    The IABP values were 138.52 ± 16.89/79.67 ± 9.81 mmHg. The DD of the systolic BP (SBP), with a ratio of 80%-84% (3.06%), was the smallest. The DD of the diastolic BP (DBP) was lowest at a ratio of 85%-89% (2.47%). Men and women had the lowest DD of the SBP at a C/A ratio of 80%-84% and the lowest DD of the DBP at a C/A ratio of 85%-89%. Regardless of whether the participants had coronary heart disease, the DD of the SBP at a C/A ratio of 80%-84% was the lowest, and the DD of the DBP at a C/A ratio of 85%-89% was the lowest.

    Even in the suggested range of > 80%, when the C/A ratio was 80%-84%, the difference in the SBP between the cuff and IABP was the lowest, but when the C/A ratio was 85%-89%, the difference in the DBP was the lowest.

  • Wenyi Gu, Jing Zhou, Yunzhu Peng, Hongyan Cai, Huawei Wang, Wen Wan, H ...
    2023 年 64 巻 4 号 p. 700-707
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー
    電子付録

    Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.

    We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.

    Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.

  • Dujuan Meng, Ruoxi Gu, Yasong Wang, Zhiqiang Zhang, Tianshu Xu, Xiaoze ...
    2023 年 64 巻 4 号 p. 708-716
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    This study aimed to investigate the short-term predictors of aortic-related adverse events in patients with acute type B aortic intramural hematoma (IMH) initially treated with optimized medical therapy.

    A total of 157 patients with acute type B IMH were included in this study. These patients were divided into worsening group (n = 45) and stable group (n = 112) based on the incidence of aortic-related adverse events. The clinical data and imaging features of the two groups were compared. Multivariate logistic regression analysis of predictors of aortic-related adverse events in type B IMH was performed. Receiver operating characteristic (ROC) curve was applied to determine the optimal cutoff value for maximum descending aorta diameter (MDAD). Kaplan-Meier survival curve was used to analyze the incidence of aortic-related adverse events.

    Worsening and stable groups were statistically significant in diuretics, abnormal D-dimer level, observation endpoint systolic blood pressure (SBP), MDAD, aortic atherosclerosis, ulcer-like projection (ULP), and thickness of hematoma (P < 0.05). Multivariate logistic regression showed that abnormal D-dimer level (OR = 12.464, P = 0.025), MDAD (OR = 1.113, P = 0.030), and ULP (OR = 5.849, P = 0.022) were powerful independent risk factors for predicting aortic-related adverse events in type B IMH, and observation endpoint SBP within 100-120 mmHg (OR = 0.225, P = 0.014) was a protective factor for predicting aortic-related adverse events in type B IMH. The cutoff value of MDAD was 35.2 mm.

    Short-term imaging is recommended for type B IMH patients with abnormal D-dimer level, MDAD > 35.2 mm, and ULP. Blood pressure should also be strictly monitored and controlled during the acute phase of IMH.

  • Yanjuan Lin, Yuanyuan Tao, Yanchun Peng, Hong Ni, Liangwan Chen
    2023 年 64 巻 4 号 p. 717-723
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Several studies have found that lactate correlates with surgical outcomes in patients with heart disease. However, the prognostic value of postoperative lactate in patients with acute type A aortic dissection (AAAD) remains unclear. This study aimed to investigate the relationship between postoperative lactate and in-hospital mortality in patients with AAAD. Patients who underwent AAAD surgery at Fujian Cardiac Medical Center from February 2020 to January 2022 were enrolled in this retrospective study. Correlations between in-hospital mortality and various parameters, including lactate, were investigated. A total of 357 patients were included in this study, 58 of which died. Multivariate logistic regression analysis revealed that body mass index (BMI) (odds ratio [OR] = 1.099, 95% confidence interval [CI]: 1.017-1.188, P = 0.017), cardiopulmonary bypass (CPB) time (OR = 1.005; 95% CI: 1.000-1.010, P = 0.039), and lactate (OR = 1.291, 95% CI: 1.182-1.409, P < 0.001) were independent risk factors for in-hospital mortality in AAAD patients. Receiver operating characteristic (ROC) curve analysis showed that lactate had a moderate power for in-hospital mortality (area under the curve [AUC] = 0.729, 95% CI: 0.647-0.810, P < 0.001). Furthermore, the combination of lactate, BMI, and CPB time showed better performance (AUC = 0.780; 95% CI: 0.706-0.854, P < 0.001) in predicting in-hospital mortality than in using these variables independently. Among patients undergoing AAAD surgery, postoperative lactate was significantly associated with in-hospital mortality. Lactate can be used as a potential predictor of in-hospital mortality. The combination of lactate, BMI, and CPB time showed better performance in predicting in-hospital mortality than using single one.

Experimental Studies
  • Amy E. Thompson, Melissa Christie, Linnea Lentz
    2023 年 64 巻 4 号 p. 724-731
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー

    The extravascular implantable cardioverter-defibrillator (EV ICD) with lead implantation in the substernal space may provide clinical advantages over transvenous and subcutaneous systems. This is the first reported examination of substernal infection in large animals implanted with the EV ICD system.

    The system was implanted in 13 large animals (canine, porcine, and ovine). The porcine were co-implanted with a transvenous cardiac resynchronization therapy with defibrillator (CRT-D) system. Infection was promoted through a cadence of immunosuppressive monitors and study interventions. The animals were monitored for clinical presentation of infection over 12-18 weeks, and cultures were collected to confirm infection. Treatment was bifurcated: 1) some infections were treated only with antibiotics ( "antibiotics only" ), whereas 2) some infections were treated with system removal and antibiotics ( "antibiotics + explant" ). Histopathology was conducted at the study closure.

    Five infections were confirmed over the course of the study, four of which involved infection of the EV ICD system and one infection of only the concomitantly implanted transvenous CRT-D system without EV ICD-related infection. Among the four EV ICD infections, two of two infections treated with antibiotics only did not resolve whereas two of two infections treated with antibiotics + explant resolved, as shown by histology. The transvenous CRT-D system infection progressed to septicemia and endocarditis, requiring early study discontinuation. No EV ICD-related infection progressed to blood stream infection, and the sternal bone did not become infected when infection was present in the substernal tissues.

    The study findings suggest that EV ICD-related infections are treatable with system removal and antibiotic therapy.

  • Di-Di Tao, Ya Li, Xiao-Jiao Tian, Xing-Juan Liao, Zhong-Qin Yu, Zhao-Y ...
    2023 年 64 巻 4 号 p. 732-740
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    To investigate the possible effect of FoxO on coxsackievirus B3 (CVB3) -induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.

    Viral myocarditis (VMC) models were establied via CVB3 infection both in vivo and in vitro. Western blotting was adopted to detect FoxO1 and TLR4 expressions in myocardial tissues and cells. Cardiomyocytes of suckling mouse were divided into the control, CVB3, CVB3 + pcDNA, CVB3 + pcDNA-FoxO1, CVB3 + TLR4 siRNA, and CVB3 + pcDNA-FoxO1 + TLR4 siRNA groups. Flow cytometry was employed to evaluate cell apoptosis. The expressions of inflammatory factors including TNF-α, IL-1β, and IL-6 were detected via quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Then, TLR4/NF-κB pathway-related proteins were determined via Western blotting.

    VMC mice had increased FoxO1 and TLR4 expressions in myocardial tissues. Cardiomyocytes with CVB3 infection also had upregulated protein expressions of p-FoxO1/FoxO1 and TLR4. Compared with those in the control group, the cardiomyocytes in the CVB3 group were increased in LDH and CK-MB levels, cell apoptosis rate and inflammatory factors (TNF-α, IL-1β and IL-6), as well as protein expressions of TLR4 and p-p65/p65. Compared with those in the CVB3 group, the cardiomyocytes in the CVB3 + pcDNA-FoxO1 group were further upregulated whereas those in the CVB3 +TLR4 siRNA group were downregulated in the aforementioned indicators. Furthermore, TLR4 siRNA can reverse the effect of pcDNA-FoxO1 on the aggravation of cardiomyocyte injury induced by CVB3 infection.

    FoxO1 can upregulate the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced VMC.

  • Jianhua Li, Mingzhu Wang, Lei Yao, Bo Lu, Mingtai Gui, Xunjie Zhou, De ...
    2023 年 64 巻 4 号 p. 741-749
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Yixin granules are medications modified from a Chinese prescription (Sheng Xian Tang) that has been used to alleviate shortness of breath. ADAM metallopeptidase with thrombospondin type 1 motif 8 (ADAMTS8) is upregulated in the myocardium of patients with dilated cardiomyopathy. Its high expression is associated with tumor necrosis factor (TNF) -α and myocardial fibrosis. This study aimed to explore the effect of Yixin granules on heart failure (HF) in rats and whether this effect is correlated with ADAMTS8 to provide new ideas for the treatment of HF.

    HF rat models were established by ligation of the left anterior descending coronary artery. Model rats were injected with adeno-associated virus vectors for the overexpression of ADAMTS8 and/or treated with Yixin granules for 4 weeks. Hematoxylin-eosin and Masson staining were used to detect myocardial injury and fibrosis, respectively. Reverse transcription polymerase chain reaction, western blotting, and/or enzyme-linked immunosorbent assay were used to detect the expression of ADAMTS8, TNF-α, interleukin (IL) -1β, IL-6, collagen I, collagen III, and α-smooth muscle actin in myocardium. The myocardial infarction area of rats was measured using 2,3,5-triphenyltetrazolium chloride staining.

    ADAMTS8 was upregulated in the myocardium of HF rats. Yixin granule treatment improved left ventricular contractility and reduced ADAMTS8 expression, myocardial injury, inflammation, and fibrosis in HF rats. ADAMTS8 overexpression aggravated myocardial injury, inflammation, and fibrosis. Moreover, ADAMTS8 overexpression counteracted the cardioprotective effects of Yixin granules.

    Yixin granules may reduce myocardial inflammation and fibrosis in HF rats by inhibiting the expression of ADAMTS8.

  • Junqi Xiao, Yang Xie, Qing Duan, Tao Liu, Rong Ye, Xunhong Duan, Zhibi ...
    2023 年 64 巻 4 号 p. 750-758
    発行日: 2023/07/29
    公開日: 2023/07/29
    ジャーナル フリー

    Endothelial-mesenchymal transition (EndMT) and endothelial cell apoptosis have been documented to have a role in atherosclerosis (AS) progression. To deepen knowledge in this aspect, our study investigated the effect of LIM homeobox 2 (LHX2) and adhesion-regulating molecule 1 (ADRM1) on EndMT and endothelial cell apoptosis in the oxidized low-density lipoprotein (ox-LDL) -stimulated AS cell model.

    Ox-LDL was utilized to treat human umbilical vein endothelial cells (HUVECs) for constructing an AS model in vitro, followed by measurement of LHX2 and ADRM1 expressions. Afterward, gain- and loss-of-function assays were performed in HUVECs, followed by detection of cell viability, invasion, migration, and apoptosis and the expression of inflammatory factors [tumor necrosis factor (TNF) -α, interleukin (IL) -1β, and IL-6], EndMT-related proteins [CD31, vascular epithelium (VE) -cadherin, vimentin, α-smooth muscle actin (SMA), Snai1, Snai2, and Twist1], and the apoptotic protein cleaved caspase-3. Interactions between LHX2 and ADRM1 were analyzed with dual-luciferase reporter gene and chromatin immunoprecipitation assays.

    High levels of LHX2 and ADRM1 were observed in ox-LDL-induced HUVECs. In ox-LDL-treated HUVECs, LHX2, or ADRM1 knockdown promoted CD31 and VE-cadherin levels, viability, invasion, and migration and reduced apoptosis and the expressions of TNF-α, IL-1β, IL-6, vimentin, α-SMA, Snai1, Snai2, Twist1, and cleaved caspase-3. Mechanistically, LHX2 bound to the ADRM1 promoter to promote ADRM1 transcription. Overexpression of ADRM1 annulled the aforementioned effects of LHX2 knockdown on ox-LDL-induced HUVECs.

    LHX2 facilitates the pathological progression of ox-LDL-stimulated AS cell models by increasing ADRM1 transcription.

  • Fei Yang, Dexiang Chen, Yi Liu, Xumiao Zhang, Yang Su, Xialing Zhang, ...
    2023 年 64 巻 4 号 p. 759-767
    発行日: 2023/07/29
    公開日: 2023/07/29
    [早期公開] 公開日: 2023/07/14
    ジャーナル フリー
    電子付録

    Deep venous thrombosis (DVT) is the third most common cardiovascular disease. Its clinical therapeutic effect is unsatisfactory due to the high rate of postthrombotic syndrome. Several studies have demonstrated the involvement of miRNAs in DVT. Therefore, we identified differentially expressed miRNAs in patients with DVT and explored their effects and underlying mechanism on endothelial cell (EC) injury.

    Differentially expressed miRNAs were identified via microRNA sequencing and verified using real-time quantitative PCR. The biological function of miR-181c-5p in human umbilical vein endothelial cell (HUVEC) injury stimulated by oxidized low-density lipoprotein (ox-LDL) was investigated. The target gene of miR-181c-5p was analyzed using bioinformatics and verified via dual-luciferase reporter assay.

    miRNA sequencing showed that miR-181c-5p was downregulated in the peripheral blood of patients with DVT. Furthermore, miR-181c-5p had a high clinical diagnostic value for DVT by receiver operating characteristic curve analysis. An in vitro cell model of EC injury, miR-181c-5p, was repressed in ox-LDL-treated HUVECs. Enhancing miR-181c-5p expression could alleviate the inhibition cell viability, cell apoptosis, raising ROS and MDA production, the reducing SOD level, and the elevated levels of thrombosis-related factor, ET-1 and vWF induced by ox-LDL. Further analysis revealed that FBJ osteosarcoma oncogene (FOS) is a target of miR-181c-5p and could antagonize the protective role of miR-181c-5p in ox-LDL-induced HUVEC injury.

    Our research demonstrated that miR-181c-5p could attenuate ox-LDL-induced EC injury and thrombosis-related factor expression by negatively regulating FOS. These findings suggest that the miR-181c-5p/FOS axis is a promising therapeutic target for DVT.

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