Biomarkers Of Myocardial Injury Research Articles

The Role of QRS Complex and ST-Segment in Major Adverse Cardiovascular Events Prediction in Patients with ST Elevated Myocardial Infarction: A 6-Year Follow-Up Study.

as a relatively high number of ST-segment elevation myocardial infarction (STEMI) patients develop major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI), our aim was to determine the significance, and possible predictive value of QRS complex width and ST-segment elevation. our patient sample included 200 PCI-treated STEMI patients, which were divided into two groups based on the following duration of symptoms: (I) less than 6 h, and (II) 6 to 12 h. For every patient, an ECG was performed at six different time points, patients were followed for up to six years for the occurrence of MACE. the mean age was 60.6 ± 11.39 years, and 142 (71%) were male. The 6-12 h group had significantly wider QRS complex, higher ST-segment elevation, lower prevalence of ST-segment resolution as well as MACE prevalence (p < 0.05). ECG parameters, QRS width, and magnitude of ST-segment elevation were proved to be independent significant predictors of MACE in all measured time points (p < 0.05). Even after controlling for biomarkers of myocardial injury, these ECG parameters remained statistically significant predictors of MACE (p < 0.05). our study highlights that wider QRS complex and a more pronounced ST-segment elevation are associated with longer total ischemic time and higher risk of long-term MACE.

MiR-92b-3p Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting MAP3K2 in a Mouse Model.

MicroRNAs are well-known RNA regulators modulating biological functions in complex signaling networks. This work aims to explore the impact of microRNA-92b-3p (miR-92b-3p) on myocardial ischemia-reperfusion (I/R) injury. The I/R model was established by left anterior descending coronary artery ligation in mice. The hemodynamic parameters were detected through a multichannel physiological recorder. Myocardial injury markers: serum cardiac troponin I, myocardial kinase isoenzyme (creatine kinase-MB), and serum inflammatory factors (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were evaluated by enzyme-linked immunosorbent assay. Cardiac tissue oxidative stress-related factors (malondialdehyde, glutathione peroxidase, total antioxidation capability, and superoxide dismutase) were assessed by colorimetry, myocardial pathology was observed by hematoxylin-eosin staining, and cardiomyocyte apoptosis was measured by triphosphate nick end-labeling staining, as well as the expression of miR-92b-3p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) in cardiac tissues were determined by reverse transcription quantitative polymerase chain reaction or western blot assay. The targeting relationship between miR-92b-3p and MAP3K2 was verified by bioinformatics, RNA immunoprecipitation, and luciferase reporter assays. miR-92b-3p was lowly expressed and MAP3K2 was highly expressed in myocardial I/R injury mice. Upregulation of miR-92b-3p improved hemodynamic indices, decreased serum levels of myocardial injury biomarkers, inhibited serum inflammatory response, alleviated cardiac tissue oxidative stress, relieved myocardial pathology, and reduced cardiomyocyte apoptosis during the myocardial I/R injury in mice. MAP3K2 was a direct target gene of miR-92b-3p. This research suggests that miR-92b-3p protects against myocardial I/R injury by inhibiting MAP3K2, which may provide novel candidates for treatment of myocardial I/R injury.

Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis

Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.

The establishment and evaluation of a swine model of deinagkistrodon acutus snakebite envenomation

ObjectiveTo establish a preclinical large-animal model of Deinagkistrodon acutus snakebite envenomation and evaluate its feasibility. MethodsThe venom of D. acutus (0 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, or 10 mg/kg) was injected into the left biceps femoris of 11 male pigs. Then, the circumferences of the limbs were regularly measured, and changes in muscle injury biomarkers, blood parameters, coagulation function, vital organ function and injury biomarkers were regularly detected. At 24 h after venom injection, the animals were euthanized, and the pathological damage to the vital organs mentioned above was evaluated. ResultsThe two pigs receiving 10 mg/kg and 5 mg/kg snake venom died at 8 h and 12 h after injection, respectively. The remaining pigs were equally divided into 0 mg/kg, 1 mg/kg, and 2 mg/kg snake venom groups, and all of them survived to 24 h after injection. Compared with the pigs receiving 0 mg/kg snake venom, the pigs receiving 1 mg/kg or 2 mg/kg snake venom exhibited significant abnormities, including limb swelling; increased muscle injury biomarker creatine kinase (CK) and coagulation function indicators prothrombin time and D-dimer; and decreased blood routine indicator platelet and coagulation function indicator fibrinogen. Moreover, significant abnormalities in myocardial and cerebral function and injury biomarkers in the heart, brain, liver, kidney and intestine were also observed. In particular, the abnormalities mentioned above were significantly obvious in those pigs receiving 2 mg/kg snake venom. Pathological evaluation revealed that the morphology of muscle, heart, brain, liver, kidney, and intestine in those pigs receiving 0 mg/kg snake venom was normal; however, pathological damage was observed in those pigs receiving 1 mg/kg and 2 mg/kg snake venom. Similarly, the pathological damage was more severe in those pigs receiving 2 mg/kg snake venom. ConclusionThe intramuscular injection of 2 mg/kg D. acutus venom seems to be an optimal dose for examining the preclinical efficacy of existing and novel therapeutics for treating D. acutus envenomation in pigs.

Fibroblast growth factor 23 during septic shock and myocardial injury in ICU patients

ObjectiveFibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular disease and is closely related to inflammation over the past decade. This study aimed to assess the relationship between FGF23 and myocardial injury in patients with sepsis. MethodsWe sequentially measured serum FGF23, Klotho, biomarkers of inflammation (CRP, IL-6 and WBC), myocardial injury (cTnI and N-terminal B-type natriuretic peptide) and sepsis (procalcitonin) at peak of intercurrent septic shock and after complete resolution or before death in a series of 29 patients with septic shock. 29 healthy adults without infections were used as controls. ResultsThere was a difference in serum FGF23 level between patients with septic shock and healthy adults (p < 0.0001), and the peak level of FGF23 in septic shock in the survivor group was higher than that after complete remission (p < 0.0001). No statistical difference was found in the level of FGF23 before and after treatment in the death group (p = 0.0947). At the peak of septic shock, FGF23 was significantly correlated with inflammatory markers, CRP (r = 0.8063, p < 0.0001), PCT (r = 0.6091, p = 0.0005) and WBC (r = 0.8312, p < 0.0001), while the correlation with IL-6 was not statistically significant (r = 0.0098, p = 0.9598). At the same time, it was found that FGF23 was significantly correlated with myocardial injury markers, cTNI (r = 0.8475, p < 0.0001) and NTproBNP (r = 0.8505, p < 0.0001). Nevertheless, FGF23 and klotho are not correlated (r = 0.2609, p = 0.1717). ConclusionIn conclusion, in patients with septic shock and myocardial injury, the exacerbation of inflammation in the septic process was accompanied by a abnormal increase of circulating FGF23 level. FGF23 also subsided after the improvement of inflammation, and the opposite was true for patients who did not survive. The up-regulation of FGF23 may be involved in the response of patients to septic shocks, and it is also speculated that FGF23 is involved in the myocardial injury of septic shock.

Correlation of Plasmatic Amyloid Beta Peptides (Aβ-40, Aβ-42) with Myocardial Injury and Inflammatory Biomarkers in Acute Coronary Syndrome.

Background/Objective: Amyloid beta (β) -40 levels increase with age and inflammation states and appear to be associated with clinical manifestations of acute coronary syndrome (ACS). We investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in patients with or without ST elevation myocardial infarction (STEMI, NSTEMI). Methods: This singe-center, cross-sectional, observational, and correlation study included 65 patients with ACS (n = 34 STEMI, 29 males, age = 58 ± 12 years; n = 31 NSTEMI, 22 males, age = 60 ± 12 years) who were enrolled in the coronary care unit within 12 h after symptom onset from February 2022 to May 2023. Aβ peptide levels and biochemical parameters were assessed. Results: NSTEMI patients had a higher prevalence of hypertension (p = 0.039), diabetes (p = 0.043), smoking (p = 0.003), and prior myocardial infarction (p = 0.010) compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI (p = 0.001) but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) (p = 0.001, p = 0.002 respectively). Conclusions: Our results show that patients with NSTEMI had a higher prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, and prior myocardial infarction). Considering these results, we propose that Aβ-42 can add value to risk stratification in NSTEMI patients.

Development and validation of cardiac diffusion weighted magnetic resonance imaging for the diagnosis of myocardial injury in small animal models

Cardiac diffusion weighted-magnetic resonance imaging (DWI) has slowly developed due to its technical difficulties. However, this limitation could be overcome by advanced techniques, including a stimulated echo technique and a gradient moment nulling technique. This study aimed to develop and validate a high-order DWI sequence, using echo-planar imaging (EPI) and second-order motion-compensated (M012) diffusion gradient applied to cardiac imaging in small-sized animals with fast heart and respiratory rates, and to investigate the feasibility of cardiac DWI, diagnosing acute myocardial injury in isoproterenol-induced myocardial injury rat models. The M012 diffusion gradient sequence was designed for diffusion tensor imaging of the rat myocardium and validated in the polyvinylpyrrolidone phantom. Following sequence optimization, 23 rats with isoproterenol-induced acute myocardial injury and five healthy control rats underwent cardiac MRI, including cine imaging, T1 mapping, and DWI. Diffusion gradient was applied using a 9.4-T MRI scanner (Bruker, BioSpec 94/20, gradient amplitude = 440 mT/m, maximum slew rate = 3440 T/m/s) with double gating (electrocardiogram and respiratory gating). Troponin I was used as a serum biomarker for myocardial injury. Histopathologic examination of the heart was subsequently performed. The developed DWI sequence using EPI and M012 provided the interpretable images of rat hearts. The apparent diffusion coefficient (ADC) values were significantly higher in rats with acute myocardial injury than in the control group (1.847 ± 0.326 * 10–3 mm2/s vs. 1.578 ± 0.144 * 10–3 mm2/s, P < 0.001). Troponin I levels were increased in the blood samples of rats with acute myocardial injury (P < 0.001). Histopathologic examinations detected myocardial damage and subendocardial fibrosis in rats with acute myocardial injury. The newly developed DWI technique has the ability to detect myocardial injury in small animal models, representing high ADC values on the myocardium with isoproterenol-induced injury.

Complexity of coronary artery disease and the release of cardiac biomarkers after CABG.

In patients with complex coronary artery disease (CAD) undergoing cardiac surgery, myocardial protection might be impaired due to microvascular obstruction, resulting in myocardial injury and subsequent biomarker release. Therefore, this study investigated the correlation between the complexity of CAD, reflected by the SYNTAX Score, and the release of cardiac biomarkers after CABG. In a consecutive series of 919 patients undergoing isolated CABG SYNTAX scores I and II were calculated to assess the complexity of CAD. Levels of high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) were routinely measured once before and serially after surgery. Patients were divided into tertiles according to their SYNTAX Scores I and II. Spearman correlations and regression models were performed to measure the degree of association between the release of hs-cTnT and CK-MB and the SYNTAX Scores. Patients with a higher SYNTAX Score I had more comorbidities reflected in a higher EuroSCORE II. Preoperatively, higher levels of cardiac biomarkers were found in patients with higher SYNTAX Score II. No correlation was observed between hs-cTnT, CK-MB and SYNTAX Score I or II. Regression models did not show any association between cardiac biomarkers and the complexity of CAD. The complexity of CAD is not associated with the release of cardiac biomarkers after CABG. Factors influencing postoperative biomarker release need to be elucidated in future trials to include postoperative biomarker release into risk stratification models predicting outcome after cardiac surgery.

Role of Biomarkers of Myocardial Injury to Predict Adverse Outcomes in Hypertrophic Cardiomyopathy.

Serum troponins and CK-MB (creatine kinase-MB) are readily detectable and reliable cardiac-specific biomarkers of subclinical myocardial injury. This study explores the roles of cTnI (cardiac troponin I) and CK-MB in hypertrophic cardiomyopathy (HCM). This study included 1045 patients with HCM who had baseline cTnI and CK-MB measurements at Fuwai Hospital between 1999 and 2019. Patients were excluded if they had undergone percutaneous coronary intervention or coronary artery bypass grafting, or had renal failure. Five end points were studied: all-cause death, cardiovascular death, noncardiovascular death, sudden cardiac death, and other cardiovascular death. Cox regression was used to assess the associations of cTnI and CK-MB levels with outcomes. Nine hundred seventy patients with available follow-up data were finally analyzed (mean age, 49.3 years; 36.4% female). During the median 4.3-year follow-up period, 87 patients reached the end points. Higher cTnI (per 0.05 ng/mL increase) and CK-MB (per 1 IU/L increase) levels were associated with increased risks of all-cause death (cTnI: adjusted hazard ratio [HR], 1.038, P<0.001; CK-MB: adjusted HR, 1.021, P=0.004), cardiovascular death (cTnI: adjusted HR, 1.040, P<0.001; CK-MB: adjusted HR, 1.025, P=0.006), and sudden cardiac death (cTnI: adjusted HR, 1.045, P<0.001; CK-MB: adjusted HR, 1.032, P=0.001). Patients with elevated levels of both cTnI and CK-MB had worse prognoses than patients with an elevated level of either biomarker alone and patients who did not have an elevated level of either biomarker. Addition of the binary indicator elevation of both cTnI and CK-MB significantly improved the discrimination and reclassification abilities of the standard HCM Risk- sudden cardiac death model (C statistics: P=0.002; net reclassification improvement, 0.652; integrated discrimination improvement, 0.064). Comprehensive evaluations of biomarkers of myocardial injury, cTnI and CK-MB, have considerable value for predicting adverse outcomes among patients with HCM. Routine cTnI and CK-MB assessments may help to guide implantable cardioverter defibrillator implantation for primary prevention in HCM.

Elucidation for the pharmacological effects and mechanism of Shen Bai formula in treating myocardial injury based on energy metabolism and serum metabolomic approaches

Ethnopharmacological relevanceShen Bai formula (SBF) is a proven effective traditional Chinese medicine for treating viral myocarditis (VMC) sequelae in clinic, and myocardial injury is the pathological basis of VMC sequelae. However, the pharmacological action and mechanism of SBF have not been systematically elucidated. Aim of the studyIn present research, the doxorubicin-induced myocardial injury rat model was used to evaluate the efficacy of SBF, and energy metabolism and metabolomics approaches were applied to elucidate the effects of SBF on myocardial injury. Materials and methodsThrough energy metabolism measurement system and UPLC-Q-TOF-MS/MS oriented blood metabolomics, directly reflected the therapeutic effect of SBF at a macro level, and identified biomarkers of myocardial injury in microcosmic, revealing its metabolomic mechanism. ResultsResults showed that SBF significantly improved the electrocardiogram (ECG), heart rate (HR), extent of myocardial tissue lesion, and ratio of heart and spleen. In addition, the serum levels of AST, CK, LDH, α-HBDH, cTnI, BNP, and MDA decreased, whereas SOD and ATP activity and content increased. Moreover, SBF increased locomotor activity and basic daily metabolism in rats with myocardial injury, restoring their usual level of energy metabolism. A total of 45 potential metabolomic biomarkers were identified. Among them, 44 biomarkers were significantly recalled by SBF, including representative biomarkers arachidonic acid (AA), 12-HETE, prostaglandin J2 (PGJ2), 15-deoxy-Δ-12,14-PGJ2, 15-keto-PGE2, 15(S)-HPETE, 15(S)-HETE, 8,11,14-eicosatrienoic acid and 9(S)-HODE, which involved AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism. ConclusionWe successfully replicated a myocardial injury rat model with the intraperitoneal injection of doxorubicin, and elucidated the mechanism of SBF in treating myocardial injury. This key mechanism may be achieved by targeting action on COX, Alox, CYP, and 15-PGDH to increase or decrease the level of myocardial injury biomarker, and then emphatically interven in AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism, and participate in regulating purine metabolism, sphingolipid metabolism, primary bile acid biosynthesis, and steroid hormone synthesis.

Biomarkers of myocardial injury in big laboratory data

Biomarkers of myocardial injury in big laboratory data

Melatonin protects against myocardial ischemia-reperfusion injury by inhibiting excessive mitophagy through the Apelin/SIRT3 signaling axis

Excessive or uncontrolled mitophagy may result in a drastic shortage of healthy mitochondrial for ATP supply after reperfusion, leading to irreversible myocardial damage. Melatonin, a hormone produced by the pineal gland, has been proven to ameliorate myocardial ischemia-reperfusion (I/R) injury via regulating mitophagy. However, its underlying mechanism has not been fully elucidated. The present study focused on the role of mitophagy in the cardioprotective effects of melatonin by using the myocardial I/R rat model. The rats were pretreated with or without the apelin inhibitor ML221, the sirtuin 3 (SIRT3) inhibitor 3-TYP and then subjected to I/R injury, with melatonin administrated 10 min before reperfusion. The effects of melatonin on myocardial infarct size, biomarkers of myocardial injury, oxidative stress, and mitochondrial function were detected, and the expression of apelin, SIRT3, and mitophagy-related proteins were also measured. Excessive mitophagy was activated after I/R injury and was correlated with oxidative stress and mitochondrial dysfunction. Melatonin pretreatment ameliorated myocardial injury by decreasing oxidative stress, restoring mitochondrial function, and inhibiting excessive mitophagy. However, ML221 or 3-TYP disrupted these beneficial effects of melatonin on I/R injury. Taken together, these results suggest that melatonin pretreatment ameliorates myocardial I/R injury through regulating the apelin/SIRT3 pathway to inhibit excessive mitophagy.

Metabolomic profiling during ex situ normothermic perfusion before heart transplantation defines patterns of substrate utilization and correlates with markers of allograft injury

PURPOSECardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex-situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substrate utilization and report on subclinical and clinical allograft dysfunction risk. METHODSMetabolomic profiling was performed on serial samples of ex-situ normothermic perfusate assaying biomarkers of myocardial injury in lactate and cardiac troponin I (TnI) as well as metabolites (66 acylcarnitines, 15 amino acids, non-esterified fatty acids (NEFA), ketones, and 3-hydroxybutyrate). We tested for change over time in injury biomarkers and metabolites, along with differential changes by recovery strategy (donation after circulatory death (DCD) v. donation after brain death (DBD)). We examined associations between metabolites, injury biomarkers, and primary graft dysfunction (PGD). Analyses were performed using linear mixed models adjusted for recovery strategy, assay batch, donor predicted heart mass, and time. RESULTSA total of 176 samples from 92 ex-situ perfusion runs were taken from donors with a mean age of 35 years (SD 11.3) years and a median total ex-situ perfusion time of 234 (IQR 84) minutes. Lactate trends over time differed significantly by recovery strategy, while TnI increased during ex-situ perfusion regardless of DCD v. DBD status. We found fuel substrates were rapidly depleted during ex-situ perfusion, most notably the branched-chain amino acids leucine/isoleucine, as well as ketones, 3-hydroxybutyrate, and NEFA (least squares (LS) mean difference from the first to last timepoint -1.7 - -4.5, FDR q<0.001). Several long-chain acylcarnitines (LCAC), including C16, C18, C18:1, C18:2, C18:3, C20:3, and C20:4 increased during the perfusion run (LS mean difference 0.42 – 0.67, q<0.001). Many LCACs were strongly associated with lactate and TnI. The change over time of many LCACs was significantly different for DCD vs. DBD, suggesting differential trends in fuel substrate utilization by ischemic injury pattern. Changes in leucine/isoleucine, arginine, C12:1-OH/C10:1-DC, and C16-OH/C14-DC were associated with increased odds of moderate-severe PGD. Neither end-of-run nor change in lactate or TnI was associated with PGD. CONCLUSIONMetabolomic profiling of ex-situ normothermic perfusion solution reveals a pattern of fuel substrate utilization that correlates with subclinical and clinical allograft dysfunction. This study highlights a potential role for interventions focused on fuel substrate modification in allograft conditioning during ex-situ perfusion to improve allograft outcomes.

Trajectories of postoperative serum troponin concentrations following pediatric heart transplantation

IntroductionTroponin is a readily measured serum biomarker of myocardial injury and death, but has not been well studied after pediatric heart transplants. The objective of this analysis is to describe the distribution and clinical determinants of serum troponin measured in the first week after pediatric heart transplantation. MethodsWe included all patients who underwent heart transplantation at Seattle Children’s Hospital between January 1, 2012 and December 31, 2016. During this period, serum Troponin-I (TnI) was measured daily in the first week after heart transplant. We described the distribution of serum TnT collected in this period. We examined the relationship between peak TnI with known pre- peri-operative risk factors for myocardial injury including etiology of heart failure, ischemia time, and donor to recipient characteristics. Logistic regression models were used to test the association between peak TnI with incidence of death or rejection and formation of donor specific antibodies within 1 year. Adjusted models included age, HF etiology, crossmatch status, and panel reactive antibodies. ResultsDuring the study period, 86 transplants were performed on 83 unique individuals. Serum TnI peaked at a median of 0.9 days after transplantation. In adjusted models, higher peak TnI was associated with death and/or rejection within 1-year post-transplant (Odds Ratio [95% confidence interval]: 1.10 [1.02, 1.19]). Higher peak TnI was not associated with de-novo DSA formation in adjusted models (OR [95%CI]: 1.01 [0.94, 1.09]). Post-transplant length of stay in the intensive care unit was positively correlated with peak TnI (r=0.36, p<0.001). ConclusionsThis study provides a description of serum TnI in the first week after pediatric heart transplant; a population for whom existing data is sparse. Post-transplant TnI reflects pre- and peri-operative factors such as ischemia time. This suggests TnI may have utility as a readily measurable biomarker of transplant-related myocardial injury. Our results serve as a basis to test the prognostic significance of higher post-transplant TnI in future studies.

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension

Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH? A total of 135 age- and BMI-matched patients with PAH and 49 control participants were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. Compared with the control participants, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8mL vs3.5 ± 0.7mL; P= .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear= .001), right ventricular end-diastolic volume index (P< .001), right ventricular cardiac output (P= .003), N-terminal pro-brain natriuretic peptide (P= .030), and the risk of clinical worsening (P= .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95%CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95%CI, 1.5-30.2) for high-level EATV in patients with PAH. Patients with PAH had a decreased EATV compared with control participants. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

CytogeneticsComparability of Beckman Coulter Access Cardiac Troponin I Assays

Abstract Cardiac troponins (cTn) are the most sensitive and specific biomarkers of myocardial injury. The rise and/or fall of cardiac troponins above the 99th percentile of the upper reference limit (URL) is required in the assessment of acute myocardial infarction. In our institution, high sensitivity troponin I (hsTnI) is performed on four Access 2 Immunoassay Systems and three DXI 800 Access Immunoassay Systems. As a regional medical center, we accept patients from outside hospitals where contemporary cardiac troponin I (cTnI) were performed. The results from different assays and platforms may disagree and lead to incorrect explanation of the results as false rise and/or fall of cTn. To harmonize results among these assays, we analyzed the variation between the two assays of cTnI and hsTnI, and the concordance of same assay hsTnI on different instruments using patient specimens. To investigate the between-method variance, 424 patient specimens with troponin levels ranging from 0-23370 ng/L were used to measure both cTnI and hsTnI on DXI 800 instruments. To investigate the within-method agreement, 43 patient specimens with troponin levels ranging from 2-114394 ng/L were used to measure hsTnI on Access 2 and DXI instruments. The between-method comparison of cTnI and hsTnI on DXI showed a slope of 1.003 with intercept of -43.31 and correlation coefficient (CC) of 0.9590. The mean bias was -5.1%, which was within the analytical imprecision range determined in our laboratory (2.2%-10.7%). However, comparison of cTnI and hsTnI in patients with troponin &amp;lt;20ng/L (n=103), the 99th percentile of the URL for males, showed the slope was 1.325 with intercept of -0.97 and CC of 0.7462. The mean bias was 1.91 (21.53%), which was much larger than the analytical imprecision. This is consistent with the fact that cTnI results are not reliable at the lower level due to the imprecision problem. Comparison of cTnI and hsTnI in patients with troponin &amp;gt;20ng/L (n=321) showed the slope was 1.006 with intercept of –60.09 and CC of 0.9576. The mean bias was -54.30 (-5.23%), which was within the analytical imprecision range. The within-method comparison of hsTnI on Access 2 and DXI 800 showed the slope was 1.138 with intercept of -633.0 and CC of 0.9888. The mean bias was 2126.4 (10.6%), within the analytical imprecision range. These data indicate that cTnI results above the 99th percentile URL are comparable with hsTnI results if both are tested on DXI 800, and hsTnI results tested on Access 2 and DXI 800 are comparable. Thus, to use the cardiac troponins assay properly, we suggest the laboratory report cardiac troponins with the assay and instrument names to reduce confusion during results comparison.

Breviscapine attenuates lead‑induced myocardial injury by activating the Nrf2 signaling pathway.

The present study investigated the therapeutic potential of breviscapine (Bre) in mitigating lead (Pb)-induced myocardial injury through activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Rat cardiomyocytes (H9C2 cells) were exposed to Pb to model Pb poisoning, and various parameters, including cell viability, apoptosis and reactive oxygen species (ROS) production, were assessed using Cell Counting Kit-8, flow cytometry and 2',7'-dichlorfluoresceindiacetate assays, respectively. Additionally, a rat model of Pb poisoning was established in which blood Pb levels were measured using a graphite furnace atomic absorption spectrophotometer, and alterations in myocardial tissue, oxidative stress markers, inflammatory indicators, protein expression related to apoptosis and the Nrf2 pathway were evaluated via histopathology, ELISA and western blotting. The results showed that Bre treatment enhanced cell viability, decreased apoptosis, and reduced ROS production in Pb-exposed H9C2 cells. Moreover, Bre modulated oxidative stress markers and inflammatory factors while enhancing the expression of proteins in the Nrf2 pathway. In a rat model, Bre mitigated the lead-induced increase in blood Pb levels and myocardial injury biomarkers, and reversed the downregulation of Nrf2 pathway proteins. In conclusion, the current findings suggested that Bre mitigates Pb-induced myocardial injury by activating the Nrf2 signaling pathway, highlighting its potential as a therapeutic agent for protecting the heart from the harmful effects of Pb exposure. Further research is required to elucidate the exact mechanisms and explore the clinical applicability of Bre in mitigating Pb-induced myocardial damage.

Bioinformatics and experimental studies jointly reveal that Sacubitril Valsartan improves myocardial oxidative stress and inflammation by regulating the MAPK signaling pathway to treat chemotherapy related cardiotoxicity

BackgroundCRC is a common but serious complication or sequela of tumor treatment, and new coping strategies are urgently needed. SV is a classic clinical cardiovascular protective drug, which has been widely used in the treatment of heart failure, hypertension and other diseases. It has good therapeutic effect in other cardiovascular diseases such as diabetes cardiomyopathy, ischemic cardiomyopathy and vascular disease, but it has not been proved by research that SV can prevent and treat CRC. MethodIn this study, DOX was used to induce a rat CRC model and evaluate the therapeutic effect of SV on it. Subsequently, R software was applied to analyze the control group, SV group, and DOX group in databases GSE207283 and GSE22369, and to screen for common differentially expressed genes. Use the DAVID website for enrichment analysis and visualization. Use STRING website to analyze and visualize protein interaction networks of key genes. Finally, experimental verification was conducted on key genes. ResultOur research results show that SV has a protective effect on DOX induced myocardial injury by alleviating Weight loss, increasing Ejection fraction, and reducing the level of biomarkers of myocardial injury. Meanwhile, SV can effectively alleviate the above abnormalities. Bioinformatics and KEGG pathway analysis showed significant enrichment of metabolic and MAPK signaling pathways, suggesting that they may be the main regulatory pathway for SV treatment of CRC. Subsequent studies have also confirmed that SV can inhibit DOX induced myocardial injury through the MAPK signaling pathway, and alleviate DOX induced oxidative stress and inflammatory states. ConclusionOur research indicates that SV is a potential drug for treating CRC and preliminarily elucidates its molecular mechanism of regulating the MAPK pathway to improve oxidative stress and inflammation.

The effects of volatile anesthetics and propofol in patients undergoing off-pump coronary artery bypass grafting: a systematic review and meta-analysis.

Studies investigating the cardioprotective effect of volatile anesthetics on cardiac troponins in off-pump coronary artery bypass grafting (OPCAB) surgery remain controversial. This current study was conducted to systematically evaluate the impact of volatile anesthetics and propofol on patients undergoing OPCAB surgery. A computerized search of electronic databases was conducted up to July 21, 2023, to identify relevant studies using appropriate search terms. The primary outcomes of interest were the levels of myocardial injury biomarkers (e.g., cTnI, cTnT), while secondary outcomes included extubation time, length of ICU stay, 30-day mortality, transfusion and thrombosis, and postoperative recovery, which were compared between two anesthesia techniques. A search of databases produced 14 relevant studies with a combined total of 703 patients. Among them, 355 were allocated to the volatile anesthetics group and 348 to the propofol group. Our study reveals a statistically significant reduction in myocardial injury biomarkers among patients who received volatile anesthetics compared to those who received propofol (P < .001). Subgroup analysis showed that patients using sevoflurane had lower postoperative cardiac troponins levels compared to propofol (P = .01). However, desflurane and isoflurane currently have no significant advantage over propofol (all P > 0.05). There was no significant difference in postoperative mechanical ventilation time, length of ICU stay, and mortality between the two groups (all P > 0.05). This study suggested that volatile anesthetics, specifically sevoflurane, in adult OPCAB surgery provide a better cardioprotective effect than propofol. PROSPERO (CRD42023444277).

Biomarkers of myocardial injury during cellular electroporation by means of pulsed-field ablation and radiofrequency of atrial fibrillation

Abstract Background Several authors implemented different biomarkers to evaluate and quantify the size of effective atrial fibrillation (AF) ablation lesions after pulmonary veins isolation (PVI) with thermal energy source. However, limited data have been reported on the effects of a new form of non-thermal energy such as electroporation obtained by means of a pulsed-field ablation (PFA, Farapulse) system. Purpose Our analysis aims to compare acute myocardial injury through different biomarkers variation after PVI performed with different technologies (PFA vs radiofrequency, RF). Methods All consecutive patients (pts) undergoing AF ablation with PFA at our center were included. A PFA protocol-directed PVI was applied using 2kV with 8 applications per vein. RF deliveries were deployed according to a wide antral lesion set around the PVs at 50W. Pre- and post-procedure samples of cardiac troponin I (hs-TnI, ng/l), creatinine kinase-MB (CK-MB, ng/dl), fibrinogen (FB, mg/dl), myoglobin (Myo, ng/ml), N-terminal (NT)-pro hormone B-type natriuretic peptide (NT-ProBNP, pg/ml) and C-reactive protein (CRP, mg/dl) values were collected before PVI and at 24h after ablation. Ablation endpoint was PVI. Results Fourty-nine pts were included (62±12 years, 63% male, 84% with paroxysmal AF). PFA cases were 35 (71.4%) whereas RF cases were 14 (28.6%). Evaluating the kinetic of each cardiac biomarker, no differences were found between baseline and 24h for both FB (363±93 at baseline vs 387±112 at 24h, p=0.4513) and NT-ProBNP (137[61-462] at baseline vs 227[157-423] at 24h, p=0.0544). On the contrary kinetics of remaining biomarkers differed and significantly increased from baseline to 24h: 61±22 to 112±101 for Myo level, p=0.0017; 0.38±0.2 to 1.45±2.2 for CRP values, p&amp;lt;0.0001; 1.5±0.7 to 19.4±14 for CK-MB level, p&amp;lt;0.0001 and 11.2±20 to 6177±5765 for hs-TnI level, p&amp;lt;0.0001. By looking at the effect of the ablation strategy on cardiac biomarkers, hs-TnI level, CRP level and CK-MB were significantly different between groups at 24h after PFA/RF (hs-TnI: 7556±6025 for PFA vs 2038±1257 for RF, p&amp;lt;0.0001; CRP: 1.6±2.3 for PFA vs 0.9±1.2 for RF, p=0.0297; CK-MB: 23.7±12 for PFA vs 6.3±9.6 for RF, p&amp;lt;0.0001). PVI was achieved in all patients (100%) using only RF or PFA. No major procedure-related adverse events were reported. Conclusion Our preliminary results showed that cardiac troponin I enzyme level, C-reactive protein and creatinine kinase-MB increased after PVI by means of both radiofrequency and pulsed-field ablation and were higher after cellular electroporation by PFA than RF.