Elevated CK-MB Levels Research Articles

Classification of 90-day mortality risk among patients with cardiogenic shock requiring advanced mechanical circulatory support

Abstract Background The SCAI shock classification aims to provide a simple and practical stratification of the severity of patients with cardiogenic shock (CS) and to immediately offer them crucial treatments such as mechanical circulatory support (MCS). Additionally, the IABP shock II risk score is designed to predict 30-day mortality in patients with CS following acute coronary syndrome (ACS), and the SAVE score can also predict in-hospital mortality for patients after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) insertion due to refractory CS. However, previous studies on SCAI staging in patients with MCS have been inconsistent, and the association with prognosis remains unclear. Purpose The aim of this study is to investigate the correlation between the SCAI shock stage and prognosis in ACS patients requiring advanced MCS, and to compare it with other prognostic scores. Methods From January 2012 to July 2023, 137 ACS patients with advanced MCS (excluding IABP) were evaluated. Upon ICU admission, patients were categorized into SCAI stages B to E. The IABP shock II score and the SAVE score were also calculated to serve as prognostic tools. The type of MCS was categorized as Impella, VA-ECMO with IABP, and ECPELLA (VA-ECMO with Impella). We compared the 90-day survival rates with the SCAI shock stage and other prognostic tools. Result The distribution for SCAI classifications stage B to E was 13 (10%), 38 (28%), 21 (15%), and 65 (47%), respectively. There were no significant differences among the groups regarding age, gender, comorbidities, the ratio of ST-elevation myocardial infarction, door-to-balloon time, and onset-to-reperfusion time. In SCAI Stage E, a significantly higher proportion of patients (86%) underwent extracorporeal cardiopulmonary resuscitation, exhibiting elevated lactate and peak CK-MB levels, along with higher IABP Shock II and lower SAVE scores, compared to other stages. A Kaplan-Meier analysis of 90-day mortality, based on the SCAI, the IABP Shock II, the SAVE categories, and the type of MCS, demonstrated that outcomes deteriorated as the stage advanced across all classifications. In the univariate Cox regression analysis for 90-day mortality, significant differences in outcomes were observed across the four classifications. However, in the multivariate Cox regression analysis that incorporated all four classifications, only the type of MCS (Impella vs. ECMO with IABP; hazard ratio [HR] 0.36; 95% confidence interval [CI], 0.16 - 0.78, p = 0.012) and the SCAI classification (stage E vs. stage C; HR 3.03; 95% CI, 1.51 - 6.08, p = 0.002) demonstrated a significant association with 90-day mortality. Conclusion The SCAI shock stage upon ICU admission suggests the potential for convenient prediction of mid-term outcomes in ACS patients who received advanced MCS.

Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation.

Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from Angelica dahurica, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25mg/kg twice weekly for 6weeks), and found that both IMP (25mg/kg and 12.5mg/kg) and dexrazoxane 12.5mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25µg/mL relieved DOX (1μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity.

Evaluation of Serum Levels of CK-MB in Heart Transplant Patients and Their Relationship with Graft Rejection Grades

Background: Heart transplant rejection is a multifactorial phenomenon routinely assessed using endomyocardial biopsy. Recently, efforts have been made to identify less invasive and cost-effective biomarkers for predicting graft rejection. Objectives: This study evaluated serum CK-MB levels in heart transplant patients and examined their relationship with the grading of graft rejection. Methods: In a prospective cohort study, 92 biopsy specimens from heart transplant patients were analyzed at Tehran's Rajaie Cardiovascular Medical and Research Center during 2022. Rejection grades, plasma CK-MB levels, and their relationship were investigated. Results: The mean age (standard deviation) of the patients was 36.70 (9.59) years, with 60.9% being male. Regarding graft rejection grades, 16.3% were grade 0R, 46.7% had Quilty effect (QE), 32.6% were grade 1R, and 4.3% were grade 2R. The mean (standard deviation) serum CK-MB levels for grades 0R, QE, 1R, and 2R were 17.14 (16.46), 12.39 (7.52), 26.77 (22.97), and 29.50 (7.94) ng/L, respectively (P = 0.046). The sensitivity of CK-MB for detecting grade 1R and 2R graft rejection was 56.7% and 75%, respectively, while its specificity for detecting grade 0R was 80%. A significant correlation was observed between increased serum CK-MB levels and transplant rejection grades (P < 0.001). Most cases of grade 0R had negative CK-MB serum levels (< 24 IU/L), with a higher frequency of positive CK-MB in grade 1R compared to grade 0R and in grade 2R compared to grade 1R. Conclusions: While elevated serum CK-MB levels in heart transplant patients may indicate graft rejection, the inconsistency of CK-MB levels with graft rejection grades suggests that endomyocardial biopsy and histopathological examination remain the gold standard for determining graft rejection grades.

Does black widow spider bite the heart?

BackgroundBlack widow spider (BWS) bites account for 0.5 % of global poisonings and 21 % of poisonings in North-East Iran. In addition to local reactions, systemic cardiovascular manifestations are likely to occur. ObjectiveThis study aims to present cases of patients who experienced cardiac symptoms after being envenomed by BWS. MethodsA descriptive retrospective cross-sectional evaluation was conducted on all patients who were bitten by a BWS in 2020 and presented with cardiac manifestations. They were referred to our tertiary pediatric cardiology center in Mashhad, Iran for evaluation. All accessible variables including history, physical examination, laboratory tests prioritizing cardiology, as well as electrocardiography and echocardiography findings, were evaluated. ResultSix patients, ranging in age from 5.5 to 13 years old, were bitten by BWS. None of the patients had a past or drug history and were admitted due to pain complaints at various bite sites that radiated in different directions. Four patients showed signs of tachycardia, and two showed hypertension, but no signs of infection were observed. Half of the patients experienced systemic complications. Upon arrival at the hospital, four patients showed elevated CKMB levels, which decreased during their hospitalization. Troponin I and N-Terminal Pro B-type Natriuretic Peptide levels were high in all patients. One patient with unstable hemodynamics showed pro-BNP over 35,000. T wave inversion was observed in six patients, ST segment depression in three patients, and ST-segment elevation in one patient, with overlap between them. ConclusionTaking notice of cardiovascular presentations after a BWS bite is considerable.

Diagnostic value of the creatine kinase-MB/creatine kinase and neutrophil/lymphocyte ratios in acute myocardial infarction

ObjectiveTo investigate the clinical significance of the creatine kinase (CK)-MB/total CK ratio, neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width in acute myocardial infarction (AMI).MethodsA retrospective analysis was conducted of 196 AMI cases from our hospital’s cardiology department; healthy people were selected over the same period as the control. The two groups’ test indexes were compared through multivariate logistic regression analysis to screen for AMI risk factors; the receiver operating characteristic (ROC) curve was used to evaluate their AMI predictive values.ResultsThe serum CK, CK-MB, CK index, neutrophils and NLR values in the AMI group were significantly higher compared with those in the control group (p < 0.05); however, the levels of serum lymphocytes were significantly lower compared with those in the control group (p < 0.05). Multivariate logistic regression analysis showed that elevated CK-MB and NLR levels were risk factors for AMI (p < 0.05). The ROC curve showed that the area under the curve of the NLR and CK levels were 0.917 and 0.594, respectively.ConclusionThe CK index and NLR have a clinical predicting value for AMI and could be used as a clinical auxiliary diagnostic index for the assessment of patients with AMI.

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.

Efficacy and Bioavailability of silymarin on Plasma S100B Level in Cardiotoxicity-induced Rats

Cardiotoxicity is a cause of death by drug overdose. Silymarin, a cytoprotective agent used in this research to protect against induced-cardiotoxic effects in Albino Wister rats; exhibited signs of heart damage, such as elevated levels of S100B, troponin I, and CK-MB. Seventy albino Wister rats of both genders were divided randomly with each group having 10 rats. Silymarin-treated, cardiotoxic-induced, and control groups were treated for ten days. The bioavailability of silymarin was assessed, and evaluation of the efficacy of silymarin on the biomarker S100B and cardiac biomarkers (Troponin I, and CK-MB), also the histopathological assessments of the heart, liver, and kidney, in addition to the coefficient correlation of the studied biomarkers were analyzed. Research’s outcome indicated that the sets subjected to silymarin presented substantial differences in rat weight and food consumption, compared to a decrease in cardiotoxic clusters. S100B plasma level was increased in cardiotoxic groups, reduced in those subjected to silymarin, and eliminated by pretreatment with silymarin. Troponin I &amp; CK-MB expressively elevated significantly in cardiotoxic prompted rats, which declined with silymarin treatment and were prohibited in pretreatment by silymarin. The shielding characteristic of silymarin detected in end organs, like the liver, kidneys, and hearts when exposed to the cardiotoxic agent clozapine was extremely significant. The consequences of the histopathological examination of this study illustrated silymarin’s cardioprotective effects. A significant positive coefficient correlation of S100B with troponin I &amp; CK-MB was recorded. In conclusion, silymarin reduces and prevents to a larger extent the cardiotoxicity brought about by clozapine and averts heart injury. The cardioprotective efficacy of silymarin is explained by its new mechanism of action as decreasing S100B, troponin I &amp; CK-MB levels with a strong significant correlation to each other. The cardioprotective efficacy of silymarin gives promise for monitoring the cardiotoxicity adverse drug reaction induced by drugs.

Pomegranate fruit peel extract improves cardiac functions via suppressing oxidative stress, fibrosis, and myocardial infarction in Long-Evans rats

The pomegranate fruit (locally known as Dalim) is a rich source of various bioactive metabolites. The cardioprotective effect was aimed to investigate on polyphenol-rich pomegranate peel extract (PPE) that were administered isoproterenol, a synthetic catecholamine used to induce cardiac stress in rats. Twenty four adult rats were taken to evaluate the effects. The selected rats were divided into four groups, serving as the control (Group I), Isoproterenol (ISO) administered (Group II), PPE with ISO treatment (Group III) and gallic acid (polyphenol) along with ISO administration (Group IV). ISO administration increased inflammatory cell infiltration, fibrosis and lipid peroxidation. However, antioxidant enzyme activities were reduced in heart tissues by using isoproterenol. The findings of the study indicate that the various detrimental effects arose on the rat’s heart tissues by ISO administration which seemed to be protected by the administration of the polyphenol-rich PPE. This protection was associated with several positive outcomes, including: reduced inflammatory cell infiltration and fibrosis, reduction in free radicals by improving antioxidant enzymes activities (SOD, catalase), suppression of oxidative stress markers (MDA, NO, APOP), and reduction in inflammatory marker (MPO). Besides, PPE treatment normalized the elevated ALT, AST, ALP, and CK-MB levels. The cardioprotective effects shown by PPE may be due to the presence of polyphenolic compounds, as determined by HPLC analysis. Overall, the outcomes recommend that polyphenol enriched PPE may protect cardiac tissues in ISO-administered rats by suppressing oxidative stress, fibrosis, and myocardial infarction as well as enhancing antioxidant enzyme functions.

Effect of Sulforaphane on cardiac injury induced by sepsis in a mouse model: Role of toll-like receptor 4.

As sepsis is associated with a 50% increase in mortality, sepsis-induced cardiomyopathy has become a critical topic. A multidisciplinary approach is required for the diagnosis and treatment of septic cardiomyopathy. This study looked at Sulforaphane, a natural product that aims to evaluate cardiac function after sepsis, and its likely mechanism of action. Twenty-four adult male Swiss albino mice were randomly divided into 4 equal groups (n=6): sham, CLP, vehicle Sulforaphane (the same amount of DMSO injected IP one hour before the CLP), and Sulforaphane group (one hour before the CLP, a 5mg/kg dose of Sulforaphane was injected). Cardiac tissue levels of toll-like receptor 4 (TLR-4), pro-inflammatory mediators, anti-inflammatory markers, oxidative stress markers, apoptosis markers, and serum cardiac damage biomarkers were assessed using ELISA. Statistical analyses, including t-tests and ANOVA tests, were performed with a significance level of 0.05 for normally distributed data. Compared to the sham group, the sepsis group had significantly elevated levels of TLR-4, IL-6, TNF-α, MIF, F2-isoprostane, caspase-3, cTn-I, and CK-MB (p<0.05). In contrast, the Sulforaphane pre-treated group demonstrated significantly lower levels of these markers (p<0.05). Additionally, Bcl-2 levels were significantly reduced (p<0.05) in the Sulforaphane group. Sulforaphane administration also significantly attenuated cardiac tissue injury (p<0.05). The findings suggest that Sulforaphane can decrease heart damage in male mice during CLP-induced polymicrobial sepsis by suppressing TLR-4/NF-kB downstream signal transduction pathways.

Aconitum carmichaelii Debx. Attenuates Heart Failure through Inhibiting Inflammation and Abnormal Vascular Remodeling

Heart failure (HF) is the most common complication following myocardial infarction, closely associated with ventricular remodeling. Aconitum carmichaelii Debx., a traditional Chinese herb, possesses therapeutic effects on HF and related cardiac diseases. However, its effects and mechanisms on HF-associated cardiac diseases are still unclear. In the present study, a water extraction of toasted Aconitum carmichaelii Debx. (WETA) was verified using UPLC-Q/TOF-MS. The heart function of HF rats was assessed by echocardiography and strain analysis, and myocardial injury was measured by serum levels of CK-MB, cTnT, and cTnI. The pathological changes of cardiac tissues were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and Masson's trichrome staining. Additionally, the levels of inflammation-related genes and proteins and components related to vascular remodeling were detected by RT-qPCR, Western blot, and immunofluorescence. WETA significantly inhibited the changes in echocardiographic parameters and the increase in heart weight, cardiac infarction size, the myonecrosis, edema, and infiltration of inflammatory cells, collagen deposition in heart tissues, and also mitigated the elevated serum levels of CK-MB, cTnT, and cTnI in ISO-induced rats. Additionally, WETA suppressed the expressions of inflammatory genes, including IL-1β, IL-6, and TNF-α and vascular injury-related genes, such as VCAM1, ICAM1, ANP, BNP, and MHC in heart tissues of ISO-induced HF rats, which were further confirmed by Western blotting and immunofluorescence. In summary, the myocardial protective effect of WETA was conferred through inhibiting inflammatory responses and abnormal vascular remodeling in ISO-treated rats.

A study to evaluate the role of biomarkers in assessing the severity of COVID-19

Objectives: COVID-19 is a systemic multiorgan disease caused by severe acute respiratory syndrome coronavirus 2, a beta-type RNA coronavirus. Different laboratory markers are implicated as an indicator of disease severity, progression, and outcome. The objectives of the study are as follows: To study the role of laboratory biomarkers in assessing the severity of COVID-19. (1) To compare the values of various biomarkers (interleukin-6 [IL-6], C-reactive proteins [CRPs], D-Dimer, S. Ferritin) in clinically categorized mild-moderate and severe COVID-19 patients. (2) To compare clinical severity with computed tomography (CT) severity score in COVID-19 patients. (3) To determine association between laboratory markers and CT severity score in COVID-19 patients. Materials and Methods: A hospital-based, retrospective, and observational study was conducted at our tertiary care center on 200 patients to assess the role of different laboratory biomarkers in COVID-19 patients. Values of laboratory markers, serum urea, serum creatinine, serum sodium, and serum potassium were compared between clinically categorized mild/moderate and severe COVID-19 patients. Non-contrast CT chest was performed and CT severity score (mild ≤ 7, moderate 8–17, and severe ≥ 18) was assessed in COVID-19 patients. Results: Levels of total leukocyte count (TLC), D-dimer, CRP, lactate dehydrogenase (LDH), S. ferritin, CK-MB, IL-6, urea, sodium, and potassium were significantly elevated in severe COVID-19 group as compared to mild/ moderate group. Chest CT Severity Score ≥18 was found in 37.1% of patients in severe group; while only in 4.2% patients in mild-to-moderate group and chest CT Severity Score and clinical severity of COVID-19 showed statistically significant agreement (P &lt; 0.001). CRP, LDH, NTPROBNP, S. Ferritin, and CPK showed statistically significant positive correlation with CT severity score whereas sodium and potassium levels showed significant negative correlation. Conclusion: Elevated levels of TLC, D-dimer, CRP, LDH, S. ferritin, CK-MB, and IL-6 were associated with severe COVID-19 cases. NTPROBNP, CRP, LDH, D-dimer, IL-6, and S. Ferritin demonstrated better ability to predict the severity of COVID-19 in comparison to other laboratory biomarkers.

Evaluation of Cardiac Biomarkers and Expression Analysis of IL-1, IL-6, IL-10, IL-17, and IL-25 among COVID-19 Patients from Pakistan.

Coronavirus disease 19 (COVID-19) is caused by viral infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where upregulation of several important biomarkers and multiple organ dysfunction occurs, this study aimed to evaluate the association of cardiac biomarkers and CS induced acute lung damage with disease severity and mortality in survival of COVID-19 patients. A total of 500 COVID-19 patients with elevated cardiac biomarkers were studied for the analysis of myocardial abnormality through cardiac enzymes, inflammatory biomarkers, and the expression analysis of various cytokines, including IL-1, IL-6, IL-10, IL-17, and IL-25 genes. The elevation of various cardiac enzymes including LDH (87%), CK (78.4%), TNI (80.4%), CK-MB (83%), and D-dimer (80.8%) were found correlated (p < 0.001) with COVID-19 infection. Cardiac enzyme elevation was highly associated with an increased level of inflammatory biomarkers such as CRP (14.2%), SAA (11.4%) and erythrocyte sedimentation rate (ESR) (7.8%) (p = 0.001 for all). The quantitative expression analysis of IL-10, 1L-17, and 1L-25 were found to be high, while those of IL-1 and IL-6 were moderately elevated. The death-to-live ratio of COVID-19 patients was 457:43 indicating that the patients having elevated levels of both CKMB, D-dimer, CK and IL-1, IL-6, IL-10 and D-dimer, Troponin, CK and IL-1, IL-10 had high fatality rate (73% and 12% respectively). The current finding concludes that the evaluation of cardiac biomarkers with cytokine storm plays a significant role in COVID-19-associated anatomical organ damage, myocardial injury, and mortality. Physicians should pay special attention to cardiac biomarkers in patients with old age, inflammation, and comorbidities among COVID-19 infections.

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Some patients with autism spectrum disorder (ASD) exhibit elevated serum creatine kinase levels, which are believed to be associated with mitochondrial dysfunction. Although a few articles have reported this situation in the past and the increase mostly ranges from 100 to 300 U/L, there is a paucity of previous study focusing on the serum creatine kinase MB isoenzyme. This article discusses a 5-year-old girl with ASD, whose serum creatine kinase and creatine kinase MB isoenzyme have been rising for nearly 2 years, fluctuating at 584–993 and 111–625 U/L respectively. Except for behavioral and language symptoms associated with ASD, the child appears normal in other aspects. The child's laboratory tests showed no abnormality, except that the serum levels of lactic acid was slightly higher than normal (1.89 mmol/L, normal 1.33–1.78 mmol/L). The child was prescribed with a traditional Chinese medicine during the process and the serum creatine kinase MB isoenzyme level decreased dramatically to 111 U/L after the treatment. This study firstly recorded the serum creatine kinase levels and the MB isoenzyme in patients with autism spectrum disorder for nearly 2 years, indicating that patients with ASD may experience long-term increases in serum creatine kinase and creatine kinase MB isoenzyme, and that the traditional Chinese medicine decoction Xinfukang can temporarily reduce the serum creatine kinase MB isoenzyme level in patients. Nevertheless, the effect is not sustained. Therefore, it is of great importance to conduct long-term longitudinal studies so as to elucidate the potential mechanism responsible for long-term elevation of serum creatine kinase level.

The neurological complications after covid-19 in children

Studies have shown that during the pandemic period, children under 5 years of age accounted for 1.8% of COVID-19 cases. After covid complications are now a major concern and represent a new disease entity known as PIMS and MIS-C. Many studies have been conducted on the pathomechanism of the virus and the clinical manifestations it causes in adults, including neurological complications.&#x0D; Symptoms are mainly associated with central and peripheral neurological disorders, ranging from mild (headache, fever, cough, pharyngitis, rhinitis and anosmia) to severe (stroke or Guillain-Barré syndrome). Dyspnoea or respiratory failure is seen in approximately 11.7% of young patients. Although SARS-CoV-2 mainly occupies the respiratory system, about 10% report gastrointestinal symptoms. CT abnormalities of the chest of children are less frequent and milder than in adults, and include opacities of frosted glass and patchy shadows. In many cases, elevated CK-MB levels have also been noted, indicating possible myocardial damage.&#x0D; Children and adolescents contribute to an increasing proportion of all Covid-19 cases. It can be due to the emergence of highly infectious variants of the virus. Many drugs have been tried in children both antiviral, antimalarial, corticosteroids and intravenous immunoglobulin or selective cytokine brokers. The only effective method of prophylaxis is two doses of BNT162b2 vaccine given 21 days apart.

Pirfenidone attenuates cardiac hypertrophy against isoproterenol by inhibiting activation of the janus tyrosine kinase-2/signal transducer and activator of transcription 3 (JAK-2/STAT3) signaling pathway

ABSTRACT Cardiovascular risk factors have attracted increasing attention in recent years with the acceleration of population aging, amongst which cardiac hypertrophy is the initiating link to heart failure. Pirfenidone is a promising agent for the treatment of idiopathic pulmonary fibrosis and has recently proven to exert inhibitory effects on the inflammatory response. This study proposes to explore the potential pharmacological action of pirfenidone in treating cardiac hypertrophy in a rodent model. Four groups of mice were used in the present study: the control, ISO (5 mg/kg/day) for 7 days, pirfenidone (200 mg/kg/day) for 14 days, and spironolactone (SPI) (200 mg/kg/day) for 14 days groups. Increased heart weight index, left ventricle (LV) weight index, LV wall thickness, declined LV volume, and elevated serum levels of CK-MB, AST, and LDH were observed in ISO-challenged mice, all of which were dramatically reversed by the administration of pirfenidone or SPI. Furthermore, an elevated cross-sectional area of cardiomyocytes in the wheat germ agglutinin (WGA) staining of heart cross-sections, upregulated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β-Myosin Heavy Chain (β-MHC), and excessively released tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in cardiac tissues were observed in the ISO group but greatly alleviated by pirfenidone or SPI. Lastly, the promoted expression levels of p-JAK-2/JAK-2 and p-STAT3/STAT-3 in the cardiac tissues of ISO-challenged mice were significantly repressed by pirfenidone or SPI. Collectively, our data reveals a therapeutic property of pirfenidone on ISO-induced cardiac hypertrophy in mice.

Risk Factors Associated with Severe Disease in COVID-19

Aim: The aim of this study was to determine the characteristics and risk factors associated with severe disease in COVID-19.&#x0D; Materials and Methods: A total of 186 adult patients (97 female) hospitalized with a diagnosis of COVID-19 (laboratory-confirmed cases, SARS-CoV-2-RNA detected with the molecular method) between March 2020-May 2020 were included in the study. The possible risk factors evaluated were age, gender, comorbidities, smoking, symptoms, and laboratory parameters at the time of admission to the hospital.&#x0D; Results: The patients comprised 97 (52.2%) females, evaluated as severe COVID-19 in 43 (23.1%) cases and non-severe COVID-19 in 143 (76.9%) cases. Multivariate logistic regression analysis identified risk factors for severe COVID-19 to be age &gt;65 years (odds ratio (OR)=5.289, 95% confidence interval (CI):1.680-16.651, p:0.004), and elevated levels of LDH (OR=8.521, 95% CI:2.445-29.702, p:0.001), ferritin (OR=7.436, 95% CI:2.171-25.468, p:0.001), D-dimer (OR=10.076, 95% CI: 2.758-36.813, p65 years, and elevated LDH, ferritin, D-dimer, CK-MB, and troponin levels are independent risk factors. Clinicians should consider these potential risk factors for progression to severe disease when treating COVID-19 patients.

Mechanism of CREB1 in cardiac function of rats with heart failure via regulating the microRNA-376a-3p/TRAF6 axis.

Heart failure (HF) is a complicated disease resulting from impaired heart function. CREB1 is a candidate target in heart-concerning diseases. This paper attempts to explore the role of CREB1 in HF. Initially, the HF rat model was established by constricted abdominal aortic surgery and the cardiac function of HF rats was assessed by ultrasonic cardiogram. Levels of CK-MB and LDH and activity of Caspase-3 and Caspase-9 in HF rats were determined. Subsequently, myocardium pathological injury and myocardium apoptosis were detected. Additionally, the interactions between CREB1 and miR-376a-3p and between miR-376a-3p and TRAF6 were verified. The roles of CREB1, miR-376a-3p, and TRAF6 in HF were evaluated. In HF rats, CREB1 and miR-376a-3p were both downregulated while TRAF6 was upregulated. Besides, HF rats had decreased values of EF and FS, elevated levels of CK-MB and LDH, inflammatory infiltration, promoted cardiomyocyte apoptosis, and elevated activity of Caspase-3 and Caspase-9, which were all reversed by CREB1. Additionally, CREB1 activated miR-376a-3p expression, and miR-376a-3p targeted TRAF6 transcription. Both miR-376a-3p knockdown and TRAF6 overexpression annulled the protective role of CREB1 overexpression in cardiac function of HF rats. CREB1 activated miR-376a-3p expression to suppress TRAF6, thereby promoting the cardiac function of HF rats.

C58. Management of Ellis Type V RV Branch Coronary Perforation Using Handmade Covered-stent: a case report

Abstract Coronary perforation is a rare but life-threatening complication of percutaneous coronary intervention (PCI) requiring urgent management including balloon inflation, thrombin, microcoils, fat embolization, autologous blood clots administration, heparin-reversing agent, covered-stent implantation, or surgery. We report a case of Ellis type V RV branch coronary artery perforation during PCI treated with a handmade covered-stent. A 69-year-old female presented with typical angina in three days. She was hemodynamically stable and no sign of congestion. Laboratory results showed leukocytosis, mild elevation of liver transaminase, elevated CK-MB level, mild hypoalbuminemia. ECG showed sinus rhythm with atrial bigeminy, late-onset inferoposterior and RV MI, and first-degree AV block. TTE revealed reduced LV systolic function (LVEF 45%), impaired LV relaxation, reduced RV function, marked LV hypokinetic in inferior, inferoseptal, apicoseptal, and inferolateral wall, and mild ischemic mitral regurgitation. DCA result showed 90 – 95% tubular stenosis in mid-LAD and total occlusion in proximal-RCA with grade V thrombus. She had an anomaly of RV branch angle that resembles the RCA so that the guidewire perforated the distal part of the RV branch artery. PCI was done using hydrophilic wire to distal RCA. Ellis type V perforation was found following multiple balloon inflation in RV branch. Perforation was managed with a handmade covered-stent using a Sirolimus-eluting stent with Tegaderm film. TIMI flow 3 was reached without thrombi or residual stenosis. In medical centers that have limited resources, handmade covered-stents can be used as an option after unsuccessful balloon inflation trial.

C58. Management of Ellis Type V RV Branch Coronary Perforation Using Handmade Covered-stent: a case report

Abstract Coronary perforation is a rare but life-threatening complication of percutaneous coronary intervention (PCI) requiring urgent management including balloon inflation, thrombin, microcoils, fat embolization, autologous blood clots administration, heparin-reversing agent, covered-stent implantation, or surgery. We report a case of Ellis type V RV branch coronary artery perforation during PCI treated with a handmade covered-stent. A 69-year-old female presented with typical angina in three days. She was hemodynamically stable and no sign of congestion. Laboratory results showed leukocytosis, mild elevation of liver transaminase, elevated CK-MB level, mild hypoalbuminemia. ECG showed sinus rhythm with atrial bigeminy, late-onset inferoposterior and RV MI, and first-degree AV block. TTE revealed reduced LV systolic function (LVEF 45%), impaired LV relaxation, reduced RV function, marked LV hypokinetic in inferior, inferoseptal, apicoseptal, and inferolateral wall, and mild ischemic mitral regurgitation. DCA result showed 90 – 95% tubular stenosis in mid-LAD and total occlusion in proximal-RCA with grade V thrombus. She had an anomaly of RV branch angle that resembles the RCA so that the guidewire perforated the distal part of the RV branch artery. PCI was done using hydrophilic wire to distal RCA. Ellis type V perforation was found following multiple balloon inflation in RV branch. Perforation was managed with a handmade covered-stent using a Sirolimus-eluting stent with Tegaderm film. TIMI flow 3 was reached without thrombi or residual stenosis. In medical centers that have limited resources, handmade covered-stents can be used as an option after unsuccessful balloon inflation trial.

Mitigation of doxorubicin-induced cardiotoxicity by dichloroacetate: potential roles of restoration of PGC-1α/SIRT3 signaling and suppression of oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective chemotherapeutic agent used in the treatment of various neoplasms. Nevertheless, its therapeutic efficacy is hampered by life-threatening heart failure. Therefore, the current study was undertaken to investigate whether dichloroacetate (DCA), a metabolic and mitochondrial modulator, when administered at a therapeutically feasible dose could potentially reverse acute DOX cardiotoxicity. Furthermore, the possible underlying mechanisms of cardioprotection were also assessed. Different techniques were performed to assess cardiac injury like echocardiography, histopathology, transmission electron microscope, biomarkers of cardiac injury, and oxidative stress markers. Further, the expression levels of mRNA and protein were quantified by PCR and immunohistochemistry, respectively. Echocardiography showed that mice that received DOX/DCA combination were protected against heart failure. Additionally, histopathology and transmission electron microscopy revealed structural damage alleviation by DOX/DCA combination, which was confirmed biochemically via significant suppression of elevated CK-MB and AST levels. Mechanistically, DOX dysregulated the expression of PGC-1α and SIRT-3 genes which are key to normal mitochondrial functioning. Of note, co-treatment with DCA effectively restored PGC-1α/SIRT-3 signaling and normalized the mitochondrial DNA index. Moreover, events downstream of DOX-triggered mitochondrial dysfunction such as oxidative stress and p53-dependent apoptosis were all abrogated by combination with DCA. The present study is the first to provide in vivo evidence that DCA is effective in protecting against acute DOX cardiotoxicity. Additionally, the study highlights the potential of administering metabolic modulators to safeguard against DOX cardiotoxicity.