Markers Of Myocardial Injury Research Articles

Mesenchymal Stem Cells Alleviate Mouse Sepsis-Induced Cardiomyopathy by Inhibiting the NR1D2/LCN2 Pathway.

Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis-induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and proinflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations. In this study, the author established a mouse SICM model through cecal ligation and puncture and administered MSCs through the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, enzyme-linked immunosorbent assay,, and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. In addition, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis, and multiomics association analysis, it was revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell coculture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM through inhibiting NR1D2/LCN2 pathway.

Utility of Dexmedetomidine in Paediatric Cardiac Surgery: a Systematic Review and Meta-analysis

Dexmedetomidine is a selector α 2-agonist that provides sedation with sparing respiratory depression, anxiolysis, and analgesic adjunct with opioids and benzodiazepines sparing effects, prolongs the duration of regional anesthesia and allows early tracheal extubation after pediatric cardiac surgery.[1,2,3 ] Recently, dexmedetomidine has been established as a cardioprotective agent in adult cardiac surgical patients. Some trials show significantly lower myocardial injury markers like interleukin-6 (IL-6) levels, cardiac troponin I (cTnI), and creatinine kinase-myocardial band (CK-MB), after cardiac surgery in the dexmedetomidine group.[ ] The majority of published studies have suggested that dexmedetomidine is a seemingly efficacious agent protecting against cardiac injury during CPB.[6] Its administration lowers mechanical ventilation period, ICU stay, and length of hospital stay after pediatric cardiac surgery. In addition, it is effective against postoperative shivering, refractory JET rhythm and Tet spells, and acute kidney injury (AKI) in cyanotic pediatric patients undergoing corrective surgery. However, studies on its application in pediatric heart surgery using cardiopulmonary bypass (CPB) remain limited. This systematic review aimed to provide information on the utility of dexmedetomidine in patients undergoing pediatric cardiac surgery using CPB: hemodynamic stability, cardioprotective, renal protection, neuroprotective effects, control of refractory JET, and Tet spells, and the early and late outcome.

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.

Study of Postmortem Pericardial Fluid Concentrations of Troponin T (cTnT) in Sudden Natural Death

Background: Cardiovascular diseases are the most common cause of sudden natural deaths. Cardiac troponin T is a specific biochemical marker of myocardial injury. It may help in diagnosis of early myocardial ischemia when macroscopic or microscopic evidence of necrosis is not available after autopsy. Aim of this study was to assess the effectiveness of pericardial fluid troponin T in predicting the cause of death in sudden natural death and in estimating the post mortem interval. Materials and methods: It was a pilot study. Sudden natural deaths brought to Forensic Medicine department of GMCH Nagpur for autopsy were included in this observational cross sectional study. Deaths were grouped into cardiac and non cardiac deaths. Pericardial fluid samples were collected by opening pericardial sac with sterile syringe and processed on Roche Cobas e411 autoanalyzer for estimation of levels of Troponin T. Results: There was a statistically significant difference seen for the values between the groups (p<0.05) for Trop-T (ng/ml) with higher values in Cardiac cause. There was a statistically non significant correlation between postmortem interval vs Trop T (p>0.05). Conclusion: Estimation of pericardial fluid Troponin-T may be used to predict the cause of death in sudden natural death.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway

BackgroundSepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PurposeTo investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. MethodsWe induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. ResultsTHCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. ConclusionThe effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

PLD2 deletion ameliorates sepsis-induced cardiomyopathy by suppressing cardiomyocyte pyroptosis via the NLRP3/caspase 1/GSDMD pathway

ObjectiveSepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms.MethodsThe SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry.ResultsSICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells.ConclusionPLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.

Uncoupling Protein 2 Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Cardiomyocyte Ferroptosis

Introduction: Following our recent finding that Ucp2 knockout promotes ferroptosis, we aimed to examine whether UCP2 alleviates myocardial ischemia/reperfusion injury (MI/RI) by inhibiting ferroptosis. Methods: The left anterior descending coronary arteries of wild-type and Ucp2−/− C57BL/6 mice were ligated for 30 min and reperfused for 2 h to establish an MI/RI model. The effects of UCP2 on ferroptosis and MI/RI were determined by echocardiography, 2,3,5-triphenylttrazolium chloride staining, hematoxylin-eosin staining, Masson’s trichrome staining, Sirius red staining, and analysis of myocardial injury markers and ferroptosis indicators. Ferrostatin-1 (Fer-1) and erastin (Era) were used to investigate whether UCP2 alleviated MI/RI by inhibiting ferroptosis and the molecular mechanism. Results: UCP2 was upregulated in the MI/RI model in WT mice. Deletion of Ucp2 exacerbated ferroptosis, altered the expression levels of multiple ferroptosis-related genes, and significantly exacerbated MI/RI. Knockout of Ucp2 promoted ferroptosis induced by Era and inhibited the antiferroptotic effects of Fer-1. Knockout of Ucp2 activated the p53/TfR1 pathway to exacerbate ferroptosis. Conclusion: Our results showed that UCP2 inhibited ferroptosis in MI/RI, which might be related to regulation of the p53/TfR1 pathway.

Combining anatomical and biochemical markers in the detection and risk stratification of coronary artery disease.

We aimed to test the hypothesis if combining coronary artery calcium score (Ca-score) as a quantitative anatomical marker of coronary atherosclerosis with high-sensitivity cardiac troponin as a quantitative biochemical marker of myocardial injury provided incremental value in the detection of functionally relevant coronary artery disease (fCAD) and risk stratification. Consecutive patients undergoing myocardial perfusion single-photon emission computed tomography (MPS) without prior CAD were enrolled. The diagnosis of fCAD was based on the presence of ischaemia on MPS and coronary angiography; fCAD was centrally adjudicated in the diagnostic and prognostic domain. Diagnostic accuracy was evaluated using the area under the receiver-operating characteristic curve (AUC). The composite of cardiovascular death and non-fatal acute myocardial infarction (AMI) within 730 days was the primary prognostic endpoint. Among 1715 patients eligible for the diagnostic analysis, 399 patients had fCAD. The combination of Ca-score and high-sensitivity cardiac troponin T (hs-cTnT) had good diagnostic accuracy for the diagnosis of fCAD (AUC 0.79, 95% confidence interval (CI) 0.77-0.81), but no incremental value compared with the Ca-score alone (AUC 0.79, 95% CI 0.77-0.81, P = 0.965). Similar results were observed using high-sensitivity cardiac troponin I (AUC 0.80, 95% CI 0.77-0.82) instead of hs-cTnT. Among 1709 patients (99.7%) with available follow-up, 59 patients (3.5%) suffered the composite primary prognostic endpoint (non-fatal AMI, n = 34; CV death, n = 28). Both Ca-score and hs-cTnT had independent prognostic value. Increased risk was restricted to patients with elevation in both markers. The combination of the Ca-score with hs-cTnT increases the prognostic accuracy for future events but does not provide incremental value vs. the Ca-score alone for the diagnosis of fCAD. Clinical trial registration: NCT00470587.

Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial

Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\\kg\\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients.What is Known:• Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes.• L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery.What is New:• L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group.• L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.

Relationship Between Heart Rate Variability Parameters and Short-Term Prognosis of Patients with Acute Myocardial Infarction.

To determine the link between heart rate variability (HRV) and short-term adverse outcomes (re-hospitalisation or death due to cardiac arrhythmia, recurrent myocardial infarction, heart failure, all-cause death) in acute myocardial infarction (AMI). A descriptive study. Place and Duration of the Study: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, China, from January 2018 to December 2021. Clinical data of 245 patients diagnosed with AMI were retrospectively analysed. After discharge from the hospital, patients were followed for a year and categorised into two groups based on the occurrence of adverse events: the adverse event group (n=82) and the no adverse event group (n=163). Differences in clinical characteristics were compared, independent factors influencing adverse events were analysed, and diagnostic efficacy was assessed. Univariate analysis showed age, hyperlipidaemia, specific HRV parameters (SDNN, SDANN, RMSSD, PNN50, LF/HF), and myocardial injury markers (CK-MB, cTnI, NT-proBNP) as associated with these events (all p < 0.05). Multivariable analysis revealed decreased SDNN, decreased SDANN, increased LF/HF, and elevated levels of CK-MB, cTnI, and NT-proBNP as independent influences. Both HRV parameters and myocardial injury markers were reliable predictors on ROC curve analysis. The highest diagnostic efficacy was achieved by combining these predictors. AMI patients frequently experience short-term adverse events. Both HRV parameters and myocardial injury markers, which demonstrate significant predictive efficacy, independently influence these outcomes. Acute myocardial infarction, Coronary angiography, Heart rate variability, Myocardial injury, Risk factors.

Compound SJ-12 attenuates streptozocin-induced diabetic cardiomyopathy by stabilizing SERCA2a

Heart failure (HF) is one of the major causes of death among diabetic patients. Although studies have shown that curcumin analog C66 can remarkably relieve diabetes-associated cardiovascular and kidney complications, the role of SJ-12, SJ-12, a novel curcumin analog, in diabetic cardiomyopathy and its molecular targets are unknown. 7-week-old male C57BL/6 mice were intraperitoneally injected with single streptozotocin (STZ) (160 mg/kg) to develop diabetic cardiomyopathy (DCM). The diabetic mice were then treated with SJ-12 via gavage for two months. Body weight, fast blood glucose, cardiac utrasonography, myocardial injury markers, pathological morphology of the heart, hypertrophic and fibrotic markers were assessed. The potential target of SJ-12 was evaluated via RNA-sequencing analysis. The O-GlcNAcylation levels of SP1 were detected via immunoprecipitation. SJ-12 effectively suppressed myocardial hypertrophy and fibrosis, thereby preventing heart dysfunction in mice with STZ-induced heart failure. RNA-sequencing analysis revealed that SJ-12 exerted its therapeutic effects through the modulation of the calcium signaling pathway. Furthermore, SJ-12 reduced the O-GlcNAcylation levels of SP1 by inhibiting O-linked N-acetylglucosamine transferase (OGT). Also, SJ-12 stabilized Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2a (SERCA2a), a crucial regulator of calcium homeostasis, thus reducing hypertrophy and fibrosis in mouse hearts and cultured cardiomyocytes. However, the anti-fibrotic effects of SJ-12 were not detected in SERCA2a or OGT-silenced cardiomyocytes, indicating that SJ-12 can prevent DCM by targeting OGT-dependent O-GlcNAcylation of SP1.These findings indicate that SJ-12 can exert cardioprotective effects in STZ-induced mice by reducing the O-GlcNAcylation levels of SP1, thus stabilizing SERCA2a and reducing myocardial fibrosis and hypertrophy. Therefore, SJ-12 can be used for the treatment of diabetic cardiomyopathy.

Abstract 3625: Metabolic phenotypes of doxorubicin-induced cardiotoxicity in breast cancer patients

Abstract Background. Doxorubicin (DOX) is a highly effective chemotherapy agent that is commonly used in combination with other chemotherapy regimens to treat a wide range of cancers, including 32% of breast cancer (BC) cases. Although DOX has greatly increased the number of long-term cancer survivors, some DOX recipients have experienced DOX-induced cardiotoxicity (DIC). Currently, there are no validated markers that can predict the early development of DIC. Cardiac troponin released by cardiomyocytes has been used in non-clinical studies as a marker of myocardial injury; however, the false positive rates are high, and the predictive value on cardiotoxicity is limited. Therefore, novel biomarkers of DIC are urgently needed to identify patients who are at an increased risk, allowing early detection of the cardiotoxicity before it causes permanent cardiac damage. Methods. Untargeted metabolomics profiling was performed for plasma samples from a cohort of 28 breast cancer patients who developed abnormal cardiac function (ABN) and those who maintained normal cardiac function (NML). Blood samples were collected before, during, and after DOX-containing chemotherapy. Using both baseline observations and pre-post changes, machine-learning techniques were used to identify metabolite markers that can be used as early indicators of DIC in BC patients. Area under the receiver operating characteristic curve was reported to evaluate the performance of significant metabolites, and metabolite set enrichment analysis (MSEA) and network analysis were used to extrapolate known associations between metabolites and diseases. Results. Significant separation of plasma metabolomics profiles between ABN and NML patients at baseline was observed. From 1,124 metabolites, abundance of 59 metabolites were found to differ between ABN and NML patients at baseline. Across all patients, levels of 78 metabolites changed between baseline and after the 1st chemotherapy cycle. Of the 6 metabolites identified in both baseline and pre-post data, ABN patients had higher levels of dicarboxylic acids suberate and sebacate derived from ω-oxidation of fatty acids at baseline than NML patients. Enrichment analysis on the metabolites from the pre-post analysis suggested myocardio injury and carnitine palmitoyltransferase deficiency. Network analysis of metabolite-disease interactions further suggests potential impact on neurological health after chemotherapy. Conclusion. The metabolomics phenotype identified is indicative of impaired beta-oxidation at baseline for ABN patients. In addition, our findings suggest neurotoxic effect from DOX, implicating the potential brain-heart axis involved behind the cardiotoxicity phenotype. Citation Format: Se-Ran Jun, Katherine Wallis, Reid D. Landes, Valentina K. Todorova, L. Joseph Su, Sam Makhoul, Ping-Ching Hsu. Metabolic phenotypes of doxorubicin-induced cardiotoxicity in breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3625.

Association of myocardial injury with adverse long-term survival among cancer patients.

Over time, cardiovascular disease (CVD) deaths increasingly exceed those from malignancy among cancer survivors. However, the association of myocardial injury with long-term survival (beyond three years) in cancer patients has not been previously described. The National Health and Nutrition Examination Survey high-sensitivity cardiac troponin (hs-cTn) and morbidities databases (1999-2004) were linked with the latest mortality dataset isolating records were respondents reported cancer diagnosis by a healthcare professional. Myocardial injury was then determined by elevated hs-cTn. 16,225,560 weighted records (1,058 unweighted) were included in this observational study, with myocardial injury identified in 14·2%. Those with myocardial injury had progressively worse survival at 5 (51·6% vs. 89·5%), 10 (28·3% vs. 76·0%), and 15 years (12·6% vs. 61·4%) compared to those without myocardial injury. After adjusting for baseline characteristics, those with myocardial injury had an adjusted hazard ratio (aHR) of 2·10 (95% CI 2·09-2·10, p<0·001) for all-cause mortality, 2·23 (2·22-2·24, p<0·001) for cardiovascular mortality, and 1·59 (95% CI 1·59-1·60, p<0·001) for cancer mortality compared to those without myocardial injury. Among patients with no pre-existing CVD, the hs-cTn I Ortho assay was a strong independent predictor of all cause (aHR 6·29, 95% CI 6·25-6·33, p<0·001), CVD (aHR 11·38, 95% CI 11·23-11·54, p<0·001), and cancer (aHR 5·02, 95% CI 4·96-5·07, p<0·001) mortality. As a marker for myocardial injury, hs-cTn/s were independently associated with worse long-term survival among cancer patients with a stronger relationship with all-cause, cardiovascular, and cancer mortality using hs-cTn I ortho assay.

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85

ObjectiveTo investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85.MethodsOne hundred patients (four cases excluded) aged 70–85 years, with body mass index 18–24 kg·m−2 and American Society of Anesthesiologists physical status II–III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg−1·h−1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid–binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted.ResultsCompared with group C, MAP was significantly higher at T1–T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia.ConclusionsLow-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury.Trial registrationThis study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

Early detection of anthracycline-induced cardiotoxicity using [68Ga]Ga-FAPI-04 imaging.

Anthracycline-induced cardiotoxicity (AIC), whose major manifestation is diffuse myocardial fibrosis, is an important clinical problem in cancer therapy. Therefore, early identification and treatment are clinically important. This study aims to explore the feasibility of using 68Ga-labelled fibroblast activation protein (FAP) inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for the early identification of the fibrotic process and guidance of antifibrosis therapy in AIC. An AIC rat model was induced by the intravascular administration of doxorubicin (DOX) once per week for 1, 2, 3 and 6weeks (2.5mg/kg/injection, groups 1-4), whereas intravascular saline was administered to control rats. Experimental and control groups (n = 4) underwent [68Ga]Ga-FAPI PET/CT following disease induction. Groups 5 and 6 received DOX injections for 3 and 6weeks, treated with angiotensin-converting enzyme (ACE) inhibitor starting at 3weeks, treated with enalapril (20mg/kg, gastric gavage) daily and underwent echocardiography and [68Ga]Ga-FAPI PET/CT at 3weeks after treatment. Rat hearts were subjected to haematoxylin and eosin staining, FAP immunohistochemistry, Sirius red staining and Masson's trichrome staining to investigate the pathological changes and deposition of collagen fibres. Rat blood was sampled weekly for the enzyme-linked immunosorbent assay of various markers of myocardial injury, such as plasma cardiac troponin I, B-type natriuretic peptide and angiotensin II. [68Ga]Ga-FAPI-04 uptake by the heart was significantly higher in the cardiotoxicity group than in the control group at weeks 3 (SUVmax: 1.21 ± 0.23 vs 0.67 ± 0.01, P < 0.05) and 6 (SUVmax: 1.48 ± 0.28 vs 0.67 ± 0.08, P < 0.001), whereas left ventricle ejection fraction (LVEF) did not significantly differ between normal and AIC rats at week 3. FAP+ expression began to increase starting at week 3, before irreversible fibrotic changes were detected, until week 6. After 3weeks of enalapril treatment, [68Ga]Ga-FAPI-04 accumulation decreased in groups 5 and 6 (SUVmax decreased from 1.21 ± 0.23 to 0.77 ± 0.08 and 1.48 ± 0.28 to 1.09 ± 1.06, P < 0.05). Cardiac function was preserved (LVEF was 75.7% ± 7.38% in group 3 vs 74.5% ± 2.45% in group 5, P > 0.05) and improved (LVEF increased from 51.6% ± 9.03% in group 4 to 65.2% ± 4.27% in group 6, P < 0.05), and myocardial fibrosis attenuated (from 6.5% ± 1.2% in group 4 to 4.31% ± 0.37% in group 6, P < 0.01). [68Ga]Ga-FAPI PET/CT can be used for the early detection of active myocardial fibrosis in AIC and the evaluation of the efficacy of therapeutic interventions. Early treatment guided by [68Ga]Ga-FAPI PET/CT may reduce anthracycline-induced myocardial injury and improve heart function.

Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30μg followed by placebo, or placebo followed by BNT162b2 30µg, 1month apart. A participant subset, previously unvaccinated against COVID-19, in the phase3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35ng/l; female, > 17ng/l) were assessed. Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. Among 5- to < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified.

Effect of dapagliflozin on blood glucose control, cardiac function, and myocardial injury markers in patients with type 2 diabetes and heart failure

Purpose: To investigate the impact of dapagliflozin treatment on blood glucose control, cardiac function, and myocardial injury markers in patients with type 2 diabetes and heart failure. &#x0D; Methods: In a retrospective analysis of clinical data for 132 patients with type 2 diabetes and heart failure admitted to Beijing Tongren Hospital, China from January 2020 to June 2021, these patients were stratified into two groups (66 patients each). Control group received conventional pharmacotherapy and study group received additional treatment with dapagliflozin. Both treatment courses lasted for 6 months. The levels of blood glucose control, cardiac function, and myocardial injury markers before and after 6 months of treatment were compared between the two groups, as well as safety during treatment. &#x0D; Results: After 6 months of treatment, both groups exhibited significant reductions in fasting plasma glucose (FPG), 2-h postprandial glucose (2 h PG), glycated hemoglobin (HbA1c), N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), creatine kinase-MB isoenzyme activity (CK-MB), aspartate aminotransferase (AST) levels, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, with study group showing a greater improvement (p &lt; 0.05). &#x0D; Conclusion: Dapagliflozin enhances blood glucose control and cardiac function, improving quality of life in patients with type 2 diabetes and heart failure. Furthermore, Dapagliflozin demonstrates a safe and well-tolerated profile. Future studies will require establishing the mechanism of dapagliflozin action in a larger and more diverse population.

Effect of modified Buyang huanwu decoction on hemorheology, myocardial remodeling, serum soluble CD40 ligand and serum soluble P-selectin in patients with acute myocardial infarctionafter percutaneous coronary intervention

Purpose: To investigate the effect of modified Buyang Huanwu decoction on hemorheology and myocardial remodeling in patients with acute myocardial infarction (AMI) after conventional percutaneous coronary intervention (PCI), and its relationship with serum levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-sel). &#x0D; Methods: After PCI, 80 patients seen from February 2021 to February 2022 in Shijiazhuang Fourth Hospital, China with AMI were enrolled in the study. Subjects were assigned to study and control groups. Control group received standard conventional medical treatments, while study group received modified Buyang Huanwu decoction, in addition to the same standard treatment, orally twice a day (morning and night) for 3 months). The effect of modified Buyang Huanwu decoction was determined by comparing the post-treatment clinical outcomes and levels of hemorheology indices and myocardial remodeling-associated indices (myocardial injury markers) in both groups of patients. &#x0D; Results: The clinical outcome in study group was significantly better, and the hemorheology indices were significantly improved when compared to control subjects (p &lt; 0.05). Serum levels of myocardial injury markers (cardiac troponin (cTnI), cardiac markers (CRP), and brain natriuretic peptide (BNP)), and inflammatory markers (sCD40L and sP-sel) in study group were significantly decreased to varying degrees, relative to control group (p &lt; 0.05). &#x0D; Conclusion: Modified Buyang Huanwu decoction reduces inflammatory marker levels, cardiac inflammatory response and myocardial remodeling, and improves the prognosis of AMI in patients after PCI. Therefore, it may be beneficial to develop other methods for treating acute myocardial infarction after percutaneous coronary intervention.

Efficacy of sodium creatine phosphate in pediatric viral myocarditis and cellular immune functions

Purpose: To investigate the effectiveness of sodium creatine phosphate (SCP) in pediatric viral myocarditis, and cellular immune functions. &#x0D; Methods: Clinical data of 83 children with viral myocarditis admitted to Dezhou Traditional Chinese Medicine Hospital, China between May 2019 and June 2021 were collected and randomly assigned to control (n = 41) and study groups (n = 42). Control group (CNG) received conventional treatment for 14 days, including intravenous drip of sodium fructose diphosphate, vitamin C, and ribavirin, with the addition of prednisone if necessary. Study group (SG) received SCP in addition to conventional treatment for 14 days. Clinical efficacy, cardiac function, inflammatory and immune markers, myocardial injury, and adverse effects at the end of treatment were determined. &#x0D; Results: Results indicated a significantly higher total effective rate in study group (95.24 %) compared to control group (78.05 %) (p &lt; 0.05). Study group demonstrated significantly lower heart rates and improved cardiac output, stroke volume, and left ventricular ejection fraction after 14 days of treatment compared to control group (p &lt; 0.05). Furthermore, study group exhibited significant reduction in levels of inflammatory markers (p &lt; 0.05), enhanced cellular immune markers (p &lt; 0.05), and reduced myocardial injury and remodeling markers (p &lt; 0.05). Both groups showed similar incidence of adverse reactions. &#x0D; Conclusion: Sodium creatine phosphate (SCP) is effective in treating pediatric viral myocarditis, enhances cardiac function, restores cellular immune function, reduces inflammation, and minimizes myocardial damage and remodeling. There will be need to evaluate the long-term efficacy and prognosis of SCP in treating pediatric viral myocarditis in the future.