Exercise-induced cardiac troponin elevations and cardiac ventricular dysfunction assessed by tissue Doppler echocardiography and speckle tracking among non-elite runners in Beijing marathon.

OBJECTIVES: We aimed to identify the major determinants of cardiac troponin changes response to exercise among non-elite runners participating in the Beijing 2022 marathon, with a particular focus on the associations with the cardiac function assessed by tissue Doppler echocardiography and speckle tracking. DESIGN: A prospective study. METHODS: A total of 33 non-elite participants in the 2022 Beijing Marathon were included in the study. Echocardiographic assessment and blood sample collection were conducted before, immediately after, and two weeks after the marathon. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Echocardiography included tissue Doppler and speckle tracking echocardiography. RESULTS: Following the marathon, significant increases were observed in cardiac biomarkers, with hs-cTnI elevating from 3.1 [2.3-6.7] to 49.6 [32.5-76.9] ng/L (P < 0.0001). Over 72 % of participants had post-race hs-TnI levels surpassing the 99th percentile upper reference limit. There was a notable correlation between pre-marathon hs-cTnI levels (ß coefficient, 0.56 [0.05, 1.07]; P = 0.042), weekly average training (ß coefficient, -1.15 [-1.95, -0.35]; P = 0.009), and hs-cTnI rise post-marathon. Echocardiography revealed significant post-race cardiac function changes, including decreased E/A ratio (P < 0.0001), GWI (P < 0.0001), and GCW (P < 0.0001), with LVEF (ß coefficients, 0.112 [0.01, 0.21]; P = 0.042) and RV GLS (ß coefficients, 0.124 [0.01, 0.23]; P = 0.035) changes significantly associated with hs-TnI alterations. All echocardiographic and laboratory indicators reverted to baseline levels within two weeks. CONCLUSIONS: Baseline hs-cTnI levels and weekly average training influence exercise-induced hs-cTnI elevation in non-elite runners. Echocardiography revealed post-race changes in cardiac function, with LVEF and RV GLS significantly associated with hs-TnI alterations. These findings contribute to understanding the cardiac response to exercise and could guide training and recovery strategies.

Corrigendum: Regional myocardial work measured by echocardiography for the detection of myocardial ischemic segments: a comparative study with invasive fractional flow reserve.

[This corrects the article DOI: 10.3389/fcvm.2022.813710.].

Long-term all-cause death prediction by coronary, aortic, and valvular calcification in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: To determine the prognostic value of cumulative calcification score of coronary artery calcification (CAC), thoracic aortic calcification (TAC) and aortic valve calcification (AVC) in acute ST segment elevation myocardial infarction (STEMI) patients. METHODS: This was a retrospective, single-center cohort study. A total of 332 STEMI patients who received primary percutaneous coronary intervention (PPCI) were enrolled in this study between January 2010 to October 2018. We assessed the calcification in the left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), thoracic aorta, and aortic valve. Calcification of each part was counted as 1 point, and the cumulative calcification score was calculated as the sum of all points. The primary endpoint was all-cause mortality. Multivariate Cox proportional hazards models were used to determine association of cumulative calcification score with end points. The performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis and absolute net reclassification improvement (NRI), compared with the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: The overall population's calcification score was 2.0 ± 1.6. During a mean follow-up time of 69.8 ± 29.3 months, the all-cause mortality rate was 12.1%. Kaplan-Meier curve showed that the score was significantly associated with mortality (log-rank p < 0.001). The multivariable Cox proportional hazard analyses showed that a calcification score of 4-5 was independently associated with all-cause death in STEMI patients [hazard ratio (HR) = 2.32, 95% confidence interval (CI): 1.01-5.31, p = 0.046]. The area under the ROC curve (AUC) of the calcification score was 0.67 (95% CI: 0.61-0.72), and the AUC of the GRACE score was 0.80 (95% CI: 0.75-0.84). There was no statistical difference in the predictive value between both scores for 3-year mortality in STEMI patients after PPCI (p = 0.06). Based on the NRI analysis, the calcification score showed better risk classification compared with the GRACE score (absolute NRI = 6.63%, P = 0.027). CONCLUSION: The cumulative calcification score is independently associated with the long-term prognosis of STEMI patients after PPCI.

Machine learning-enhanced echocardiography for screening coronary artery disease.

BACKGROUND: Since myocardial work (MW) and left atrial strain are valuable for screening coronary artery disease (CAD), this study aimed to develop a novel CAD screening approach based on machine learning-enhanced echocardiography. METHODS: This prospective study used data from patients undergoing coronary angiography, in which the novel echocardiography features were extracted by a machine learning algorithm. A total of 818 patients were enrolled and randomly divided into training (80%) and testing (20%) groups. An additional 115 patients were also enrolled in the validation group. RESULTS: The superior diagnosis model of CAD was optimized using 59 echocardiographic features in a gradient-boosting classifier. This model showed that the value of the receiver operating characteristic area under the curve (AUC) was 0.852 in the test group and 0.834 in the validation group, with high sensitivity (0.952) and low specificity (0.691), suggesting that this model is very sensitive for detecting CAD, but its low specificity may increase the high false-positive rate. We also determined that the false-positive cases were more susceptible to suffering cardiac events than the true-negative cases. CONCLUSIONS: Machine learning-enhanced echocardiography can improve CAD detection based on the MW and left atrial strain features. Our developed model is valuable for estimating the pre-test probability of CAD and screening CAD patients in clinical practice. TRIAL REGISTRATION: Registered as NCT03905200 at ClinicalTrials.gov. Registered on 5 April 2019.

Noninvasive assessment of myocardial work during left ventricular isovolumic relaxation in patients with diastolic dysfunction.

BACKGROUND: This study aims to investigate the value of myocardial work (MW) parameters during the isovolumic relaxation (IVR) period in patients with left ventricular diastolic dysfunction (LVDD). METHODS: This study prospectively recruited 448 patients with risks for LVDD and 95 healthy subjects. An additional 42 patients with invasive measurements of left ventricular (LV) diastolic function were prospectively included. The MW parameters during IVR were noninvasively measured using EchoPAC. RESULTS: The total myocardial work during IVR (MWIVR), myocardial constructive work during IVR (MCWIVR), myocardial wasted work during IVR (MWWIVR), and myocardial work efficiency during IVR (MWEIVR) of these patients were 122.5 ± 60.1 mmHg%, 85.7 ± 47.8 mmHg%, 36.7 ± 30.6 mmHg%, and 69.4 ± 17.8%, respectively. The MW during IVR was significantly different between patients and healthy subjects. For patients, MWEIVR and MCWIVR were significantly correlated with the LV E/e' ratio and left atrial volume index, MWEIVR exhibited a significant correlation with the maximal rate of decrease in LV pressure (dp/dt per min) and tau, and the MWEIVR corrected by IVRT also exhibited a significant correlation with tau. CONCLUSIONS: MW during IVR significantly changes in patients with risks for LVDD, and is correlated to LV conventional diastolic indices, including dp/dt min and tau. Noninvasive MW during IVR may be a promising tool to evaluate the LV diastolic function.

Association of stress hyperglycemia ratio and in-hospital mortality in patients with coronary artery disease: insights from a large cohort study.

BACKGROUND: Stress hyperglycemia is strongly associated with poor clinical outcomes in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR) has been proposed to represent relative hyperglycemia. Studies regarding the relationship between SHR and mortality in coronary artery disease (CAD) are limited. This study aimed to clarify the association between SHR and in-hospital mortality in patients with CAD. METHODS: A total of 19,929 patients with CAD who were hospitalized in Beijing Hospital were enrolled in this study. Patients with an estimated glomerular filtration rate < 30 ml/min, cancer, or missing blood glucose/HbA1c data were excluded; therefore, 8,196 patients were included in the final analysis. The patients were divided into three groups based on tertiles of SHR: T1 group (SHR < 0.725, n = 2,732), T2 group (0.725 ≤ SHR < 0.832, n = 2,730), and T3 group (SHR ≥ 0.832, n = 2,734). The primary endpoint was in-hospital mortality. RESULTS: The overall in-hospital mortality rate was 0.91% (n = 74). After adjusting for covariates, SHR was significantly associated with in-hospital mortality in patients with CAD [odds ratio (OR) = 17.038; 95% confidence interval (CI) = 9.668-30.027; P < 0.001], and the T3 group had a higher risk of in-hospital mortality (OR = 4.901; 95% CI = 2.583-9.297; P < 0.001) compared with T1 group. In the subgroup analysis, the T3 group had an increased risk of mortality among patients with pre-diabetes mellitus (pre-DM) (OR = 9.670; 95% CI = 1.886-49.571; P = 0.007) and diabetes mellitus (DM) (OR = 5.023; 95% CI = 2.371-10.640; P < 0.001) after adjustments for covariates. The relationship between SHR and in-hospital mortality among patients with ACS and chronic coronary syndrome was consistent with the main finding. SHR and in-hospital mortality exhibited a dose-response relationship, and the risk of in-hospital mortality increased when the SHR index was above 1.20. Moreover, the area under the curve of SHR for predicting in-hospital mortality in patients with CAD was 0.741. CONCLUSION: SHR is significantly associated with in-hospital mortality in patients with CAD. SHR may be an effective predictor of in-hospital mortality in patients with CAD, especially for those with pre-DM and DM.

Association between the triglyceride-glucose index and severity of coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index, which is a reliable surrogate marker of insulin resistance (IR), has been associated with cardiovascular diseases. However, evidence of the impact of the TyG index on the severity of coronary artery disease (CAD) is limited. This study investigated the relationship between the TyG index and CAD severity of individuals with different glucose metabolic statuses. METHODS: This study enrolled 2792 participants with CAD in China between January 1, 2018 and December 31, 2021. All participants were divided into groups according to the tertiles of the TyG index as follows: T1 group, TyG index < 6.87; T2 group, TyG index ≥ 6.87 to < 7.38; and T3 group, TyG index ≥ 7.38. The glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus (pre-DM), and diabetes mellitus according to the standards of the American Diabetes Association. CAD severity was determined by the number of stenotic vessels (single-vessel CAD versus multi-vessel CAD). RESULTS: We observed a significant relationship between the TyG index and incidence of multi-vessel CAD. After adjusting for sex, age, body mass index, smoking habits, alcohol consumption, hypertension, estimated glomerular filtration rate, antiplatelet drug use, antilipidemic drug use, and antihypertensive drug use in the logistic regression model, the TyG index was still an independent risk factor for multi-vessel CAD. Additionally, the highest tertile of the TyG group (T3 group) was correlated with a 1.496-fold risk of multi-vessel CAD compared with the lowest tertile of the TyG group (T1 group) (odds ratio [OR], 1.496; 95% confidence interval [CI], 1.183-1.893; P < 0.001) in the multivariable logistic regression model. Furthermore, a dose-response relationship was observed between the TyG index and CAD severity (non-linear P = 0.314). In the subgroup analysis of different glucose metabolic statuses, the T3 group (OR, 1.541; 95% CI 1.013-2.344; P = 0.043) were associated with a significantly higher risk of multi-vessel CAD in individuals with pre-DM. CONCLUSIONS: An increased TyG index was associated with a higher risk of multi-vessel CAD. Our study indicated that TyG as an estimation index for evaluating IR could be a valuable predictor of CAD severity, especially for individuals with pre-DM.

Beneficial Effect of Edoxaban on Preventing Atrial Fibrillation and Coagulation by Reducing Inflammation via HBG1/HBD Biomarkers.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The effectiveness and mechanism of edoxaban in preventing stroke after atrial fibrillation remain unclear. Methods: The expressions of HBG1 and HBD in red blood cells were tested in AF. Sixty C57B/6J mice were randomly divided into the following groups: the control (CON) group, atrial fibrillation (AF) group, AF + edoxaban group, and AF + rivaroxaban group. H&E staining assay and reticular fiber staining were performed. Myocardial fibrosis was evaluated by the Masson staining assay, Sirius red staining assay, and immunohistochemical assay for the expressions of α-SMA and COL1A1. ELISA and RT-PCR assay were performed for the detection of inflammatory parameters (TNF-α, IL-1ß, IL-6, and IL-10). Blood lipids were detected by using the Beckman automatic biochemical analyzer. Furthermore, four items of coagulation were detected, and molecular docking among HBG1, HBD, and MASP1 (Xa) was performed by PyMOL 2.1 software. The BP neural network model, cubic spline interpolation, and support vector machine model were constructed to predict prothrombin time based on HBG1 and HBD expressions. COIP assay was performed to construct the interaction between HBG1 and HBD. The functional enrichment analysis was performed by DAVID and Metascape tools. Results: The expressions of HBG1 and HBD in red blood cells of the patients with atrial fibrillation were decreased. The results showed a lower level of hemoglobin in red blood cells with HBG1-siRNA and HBG1-siRNA. Compared with the AF group, the collagen fiber percentage in the AF + edoxaban group was decreased (p < 0.05). After using edoxaban, the expressions of TNF-α, IL-1ß, IL-6, and IL-10 were significantly decreased (p < 0.05). The LDL-C, TC, and TG levels were downregulated in the AF + edoxaban group. The PT and APTT levels in the AF + edoxaban group were more increasing than in the AF mice (p < 0.05). Compared with the AF group, the expressions of HBG1 and HBD were downregulated in the AF + edoxaban group (p < 0.05). HBG1 protein matched well with HBD and MASP1(Xa) protein surfaces. There exists a significant interaction between HBG1, HBD, and PT via the BP neural network and support vector machine. Enrichment analysis showed that HBG1 and HBD were mainly enriched in blood coagulation. Conclusion: Edoxaban could prevent atrial fibrillation and coagulation by reducing inflammation, lipids, and fibrosis via HBG1/HBD biomarkers effectively, and the effect was superior to that of rivaroxaban.

Selenium Supplementation Improved Cardiac Functions by Suppressing DNMT2-Mediated GPX1 Promoter DNA Methylation in AGE-Induced Heart Failure.

Objective: Advanced glycation end products (AGEs) are featured metabolites associated with diabetic cardiomyopathy which is characterized by heart failure caused by myocyte apoptosis. Selenium was proved cardioprotective. This study was aimed at investigating the therapeutic effects and underlying mechanisms of selenium supplementation on AGE-induced heart failure. Methods: Rats and primary myocytes were exposed to AGEs. Selenium supplementation was administrated. Cardiac functions and myocyte apoptosis were evaluated. Oxidative stress was assessed by total antioxidant capacity (TAC), reactive oxygen species (ROS) generation, and GPX activity. Expression levels of DNA methyltransferases (DNMTs) and glutathione peroxidase 1 (GPX1) were evaluated. DNA methylation of the GPX1 promoter was analyzed. Results: AGE exposure elevated intracellular ROS generation, induced myocyte apoptosis, and impaired cardiac functions. AGE exposure increased DNMT1 and DNMT2 expression, leading to the reduction of GPX1 expression and activity in the heart. Selenium supplementation decreased DNMT2 expression, recovered GPX1 expression and activity, and alleviated intracellular ROS generation and myocyte apoptosis, resulting in cardiac function recovery. DNA methylation analysis in primary myocytes indicated that selenium supplementation or DNMT inhibitor AZA treatment reduced DNA methylation of the GPX1 gene promoter. Selenium supplementation and AZA administration showed synergic inhibitory effect on GPX1 gene promoter methylation. Conclusions: Selenium supplementation showed cardioprotective effects on AGE-induced heart failure by suppressing ROS-mediated myocyte apoptosis. Selenium supplementation suppressed ROS generation by increasing GPX1 expression via inhibiting DNMT2-induced GPX1 gene promoter DNA methylation in myocytes exposed to AGEs.

Regional Myocardial Work Measured by Echocardiography for the Detection of Myocardial Ischemic Segments: A Comparative Study With Invasive Fractional Flow Reserve.

Purpose: This study is to assess the diagnostic value of noninvasive regional myocardial work (MW) by echocardiography for detecting the functional status of coronary stenosis using fractional flow reserve (FFR) as a standard criterion. Methods: A total of 84 consecutive patients were included in this study, among which 92 vessels were identified with ≥50% stenosis confirmed by invasive coronary angiography. Patients were investigated by invasive FFR and transthoracic echocardiography. Regional MW indices including myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work, and myocardial work efficiency were calculated. Results: MWI and MCW were significantly impaired in the FFR ≤ 0.75 group compared with the FFR > 0.75 group (both p < 0.01). There were significant positive associations between MWI and MCW with FFR. In total group, MWI <1,623.7 mmHg% [sensitivity, 78.4%; specificity, 72.2%; area under the curve value, 0.768 (0.653-0.883)] and MCW <1,962.4 mmHg% [77.0%; 72.2%; 0.767 (0.661-0.872)], and in single-vessel subgroup, MWI <1,412.1 mmHg% [93.5%; 63.6%; 0.808 (0.652-0.965)] and MCW <1,943.3 mmHg% [(84.8%; 72.7%; 0.800 (0.657-0.943)] were optimal to detect left ventricular segments with an FFR ≤ 0.75. MWI and MCW significantly increased after percutaneous coronary intervention in 13 cases. Conclusion: In patients with coronary artery disease, especially those with single-vessel stenosis, the regional MW measured by echocardiography exhibited a good diagnostic value in detecting significant myocardial ischemia compared to the standard FFR approach.

Joint efficacy of the three biomarkers SNCA, GYPB and HBG1 for atrial fibrillation and stroke: Analysis via the support vector machine neural network.

Atrial fibrillation (AF) is the most common type of persistent arrhythmia. Although its incidence has been increasing, the pathogenesis of AF in stroke remains unclear. In this study, a total of 30 participants were recruited, including 10 controls, 10 patients with AF and 10 patients with AF and stroke (AF + STROKE). Differentially expressed genes (DEGs) were identified, and functional annotation of DEGs, comparative toxicogenomic database analysis associated with cardiovascular diseases, and predictions of miRNAs of hub genes were performed. Using RT-qPCR, biological process and support vector machine neural networks, numerous DEGs were found to be related to AF. HBG1, SNCA and GYPB were found to be upregulated in the AF group. Higher expression of hub genes in AF and AF + STROKE groups was detected via RT-PCR. Upon training the biological process neural network of SNCA and GYPB for HBG1, only small differences were detected. Based on the support vector machine, the predicted value of SNCA and GYPB for HBG1 was 0.9893. Expression of the hub genes of HBG1, SNCA and GYPB might therefore be significantly correlated to AF. These genes are involved in the incidence of AF complicated by stroke, and may serve as targets for early diagnosis and treatment.

Myocardial Work by Speckle Tracking Echocardiography Accurately Assesses Left Ventricular Function of Coronary Artery Disease Patients.

Objective: Myocardial work (MW) is a novel non-invasive method that uses speckle tracking echocardiography (STE) to assess left ventricular (LV) function. MW incorporates the global longitudinal strain and afterload conditions. Here we aimed to use MW to assess the LV function of patients with coronary artery disease (CAD) with or without heart failure (HF). Methods: We enrolled a total of 150 individuals (50 each) with CAD and a normal LV ejection fraction (LVEF), CAD with HF, and healthy controls. Patients were divided into the hypertension (HTN) and normal blood pressure (no HTN) subgroups. MW was determined from the pressure-strain loop using STE. The relationships between MW indices and conventional echocardiographic parameters were evaluated, and the MW indices were compared among groups. Results: Univariate and multivariate analyses showed that MW indices were strongly correlated with LVEF. The global work index (GWI) was increased in the CAD with normal LVEF subgroup with HTN vs. controls (1,922.3 ± 393.1 vs. 1,639.7 ± 204.6 mmHg%, p < 0.05) and decreased in CAD patients with HF (no HTN: 940.9 ± 380.6 vs. 1,639.7 ± 204.6 mmHg%, p < 0.05; HTN: 857.3 ± 369.3 vs. 1,639.7 ± 204.6 mmHg%, p < 0.05). Global waste work was increased in all CAD subgroups vs. controls. Global constructive work had the same tendency as GWI in patients with CAD. Global MW efficiency was decreased in all patients with CAD. Conclusion: MW using STE accurately quantifies LV function in patients with CAD. It offers additional information about LV function with respect to disease progression, particularly in CAD patients with a normal LVEF.

Oxidized sulfur-rich arc magmas formed porphyry Cu deposits by 1.88 Ga.

Most known porphyry Cu deposits formed in the Phanerozoic and are exclusively associated with moderately oxidized, sulfur-rich, hydrous arc-related magmas derived from partial melting of the asthenospheric mantle metasomatized by slab-derived fluids. Yet, whether similar metallogenic processes also operated in the Precambrian remains obscure. Here we address the issue by investigating the origin, fO2, and S contents of calc-alkaline plutonic rocks associated with the Haib porphyry Cu deposit in the Paleoproterozoic Richtersveld Magmatic Arc (southern Namibia), an interpreted mature island-arc setting. We show that the ca. 1886-1881 Ma ore-forming magmas, originated from a mantle-dominated source with minor crustal contributions, were relatively oxidized (1‒2 log units above the fayalite-magnetite-quartz redox buffer) and sulfur-rich. These results indicate that moderately oxidized, sulfur-rich arc magma associated with porphyry Cu mineralization already existed in the late Paleoproterozoic, probably as a result of recycling of sulfate-rich seawater or sediments from the subducted oceanic lithosphere at that time.

Two-Dimensional Speckle Tracking Echocardiography Identifies Coronary Artery Disease in 690 Patients: A Retrospective Study from a Single Center.

BACKGROUND Two-dimensional speckle tracking echocardiography (2D-STE) is a novel and non-invasive technique for the diagnosis of coronary artery disease (CAD). This retrospective study from a single center aimed to identify myocardial ischemia using 2D-STE in CAD patients identified by angiography. MATERIAL AND METHODS From March 1 to November 30, 2019, 690 patients in Beijing Hospital were enrolled. After angiography, 346 patients were diagnosed with CAD. Reduction in vessel diameter of ≥50% by stenosis in at least 1 major coronary artery or its main branch was considered CAD. Analysis of 2D-STE was performed using EchoPAC version 201. RESULTS The global strain was significantly impaired in CAD patients (P<0.01). Global longitudinal peak strain (GLPS) was analyzed in layers. For GLPS of the epicardium, the odds ratio (OR) was 1.297 (1.217-1.382; P=0.002), the area under the curve (AUC) was 0.727, and the cut-off value was -16.95; sensitivity and specificity were 73.7% and 63.0%, respectively. For GLPS of the middle layer, the OR was 1.260 (1.192-1.333; P<0.001), the AUC was 0.732, and the cut-off value was -20.95; sensitivity and specificity were 82.4% and 56.2%, respectively. For GLPS of the endocardium, the OR was 1.193 (1.137-1.251; P<0.001), the AUC was 0.708, and the cut-off value was -22.95; sensitivity and specificity were 82.9% and 52.9%, respectively. CONCLUSIONS The findings from this study support the clinical application of 2D-STE in patient populations with suspected myocardial ischemia due to CAD. Therefore, 2D-STE combined with ECG monitoring may have a future role for early screening of CAD patients.