Cardiac Biomarker Levels Research Articles

Changes of myocardial dysfunction and injury biomarkers over chemotherapy for multiple myeloma: difficulties in laboratory data interpretation

Aim. To study the changes of the levels of cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI)) in patients with newly diagnosed multiple myeloma (MM) during programmatic treatment with bortezomib (VCd regimen).Material and methods. This prospective pilot study included patients with a newly diagnosed MM (n=30), who were scheduled for a cycle of chemotherapy including a proteasome inhibitor (bortezomib). All patients underwent standard laboratory (complete blood count, biochemical tests, serum protein electrophoresis), electrocardiography, echocardiography, as well as the level of specific laboratory markers of myocardial dysfunction (NT-proBNP) and injury (hsTnI) was determined immediately before treatment, after 3 and 6 cycles of chemotherapy.Results. The mean age was 63,8±10 years with a slight predominance of men (56,7%, n=17). The patients initially had an increased level of NT-proBNP (316 [75,9; 602,6] pg/mL) with its decrease to 144,0 [102,3; 294,0] pg/ml after 3 cycles and to 109,2 [59,9; 344,5] pg/ml after 6 cycles of chemotherapy. At the MM onset, the mean hsTnI values were 0,06 [0,03; 0,49] ng/mL, whereas after 3 and 6 chemotherapy cycles it accounted for 0,02 [0,01-0,68] and 0,65 [0,02; 1,51] ng/ml, respectively, with the normal range of less than 0,1 ng/ml. Despite this, no statistical significance has been obtained. There were no clinical and/or laboratory signs of heart failure, ischemia, or other non-cardiac causes of elevated NT-proBNP levels in this cohort. Multivariate regression analysis revealed the following significant factors influencing the initial hsTnI level: paraprotein, hemoglobin and erythrocyte sedimentation rate (ESR). The resulting regression model was characterized by a strong correlation (r=0,702, p<0,001).Conclusion. MM and its pathogenetic features such as paraproteinemia may be challenging for NT-proBNP and hsTnI levels assessment in group of interest before treatment. An unreliable assessment of these markers before chemotherapy may lead to incorrect baseline cardiovascular risk stratification and make it difficult for a cardiologist/cardio-oncologist to choose proper management strategy.

Abstract 18264: Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Cognitive Outcomes in SPRINT

Background: Subclinical elevations in high sensitivity cardiac troponin T (hsc-TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) identifies a high-risk subgroup with reduction in cardiovascular disease in response to intensive systolic blood pressure (SBP) lowering. However, it remains unknown if these markers also identify subgroups with greater improvement in cognitive outcomes from intensive SBP lowering. Methods: We measured hs-cTnT and NT-proBNP at baseline in Systolic Blood Pressure Intervention Trial (SPRINT). Adjudicated cognitive outcomes were classified as probable dementia (PD) and mild cognitive impairment (MCI). Combined cardiac biomarker categories were defined as elevated, intermediate, and non-elevated. The association of combined biomarker categories with risk of cognitive outcomes was assessed using multivariable Cox proportional hazards models. Heterogeneity in the effect of intensive versus standard SBP lowering on the risk of cognitive outcomes across combined biomarker categories was determined. Results: Of 8,111 SPRINT participants with measured biomarkers and at least one follow-up cognitive assessment, 830 (10.2%) experienced the composite outcome of PD or MCI. After multivariable adjustment, elevated vs. non-elevated cardiac biomarker levels were independently associated with increased risk of composite outcome [HR 95% CI: 1.56 (1.26 - 1.92)]. The effect of intensive SBP lowering on the composite outcome was strongest among participants with non-elevated cardiac biomarkers (see Table). Conclusion: Elevated cardiac biomarkers were associated with higher risk for cognitive impairment. The effect of intensive SBP lowering on preventing cognitive impairment was strongest among patients with non-elevated cardiac biomarkers. This suggests that intensive SBP lowering may be more effective in preventing cognitive impairment in individuals with favorable cardiac biomarker profiles.

Ambient Temperature and Cardiac Biomarkers: A Meta-Analysis.

This study quantified the effect of cold or heat exposure of ambient temperature on the alteration of well-known cardiac markers. A meta-analysis was performed using the PRISMA guidelines. Peer-reviewed studies on ambient temperature and cardiac biomarkers were retrieved from MEDLINE, ScienceDirect and Google Scholar from January 2000 to February 2022. The pooled effect sizes of ambient temperature on cardiac biomarkers c-reactive protein, soluble-cell adhesion-molecule-1, soluble-intercellular-adhesion-molecule-1, total cholesterol, low-densitylipoprotein, interleukin-6, B-type-Natriuretic-Peptide; systolic/diastolic blood pressure were quantified using a random-effects meta-analysis. A total of 26 articles were included in the metaanalysis after screening the titles, abstracts and full texts. The pooled results for a 1°C decrease of ambient temperature showed an increase of 0.31% (95% CI= 0.26 to 0.38) in cardiac biomarkers (p=0.00; I-squared=99.2%; Cochran's Q=5636.8). In contrast, the pooled results for a 1°C increase in ambient temperature showed an increase of 2.03% (95% CI= 1.08 to 3.82) in cardiac biomarkers (p=0.00; I-squared=95.7%; Cochran's Q=235.2). In the cardiovascular (CV) population, the percent increase in cardiac biomarkers levels due to a decrease/increase in ambient temperature was greater. This study showed the decrease/increase in ambient temperature has a direct correlation with the alterations in cardiac biomarkers. These findings are useful for managing temperatureassociated cardiovascular mortality.

The use of high-sensitivity cardiac troponin I in assessing cardiac involvement and Disease prognosis in idiopathic inflammatory myopathy

ObjectivesCardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients.MethodsA total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis.ResultsHigher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962–31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis.ConclusionsSerum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis.

Single-Cell RNA Sequencing Reveals a Subset of cMAS can Aggravate RIHD through CXCL1-CXCR2 Axis

Radiation induced heart disease (RIHD) is any form of cardiac toxicity induced by radiation therapy (RT) for thoracic cancers. Our previous studies have shown that RT obviously contributed to cardiovascular diseases-specific death over 3 years while RT became protective in the short term within 2 years survival in non-small cell lung cancer patients. Here, single cell RNA sequencing (scRNA-seq) was performed to identify various cell subsets and investigate their functions and dynamics in RIHD which offered several targets for early clinical interventions to alleviate RIHD. Based on evaluation of histopathological characteristics, ejection fraction and serum levels of cardiac injury biomarkers, we have established mouse models during different stages to simulate clinical RIHD progression. Hence, we performed single cell RNA-sequencing of RIHD models to characterize the diversity within specific cell types and obtain basic information of differently expressed genes (DEGs). We investigated the role of several cell clusters and DEGs in RIHD through bioinformatics analysis and experimental verification. In vivo, mouse models were given intraperitoneal injection of CXCR2 inhibitor. Bone marrow macrophages and primary cardiac fibroblasts were extracted for in vitro experiments. RIHD processes were divided into acute injury, compensation and decompensation stage. Transcriptomes of 31769 single cells from cardiac suspension have been profiled. Analysis of scRNA-seq revealed that there were 30 cell clusters participating in RIHD. The fraction of cell populations varied greatly at three stages which indicated RIHD was a dynamic process and each cell cluster functioned differently at different stages. Notably, we observed cardiac resident macrophages (cMAS) subset accounted for the highest fraction during the compensatory period and decreased in decompensation period. Pseudotime analysis showed cMAS had a different developmental trajectory compared to myeloid derived cells. Moreover, CXCR2 was significantly expressed in cMAS cluster. Ligand-receptor interaction results suggested that CXCL1 secreted by cardiac fibroblasts bind primarily to CXCR2+ cMAS and participated in the formation of the extracellular matrix (ECM) related to cardiac fibrosis. Moreover, cardiac fibrosis of RIHD models were relieved after CXCR2 inhibitor treatment. CXCL1 expression in primary cardiac fibroblast elevated after RT. The identification of main cell clusters provided a new insight to investigate RIHD through dynamics of cell phenotypes and cell-cell communications during RIHD processes. In compensation stage, CXCR2+ cMAS could be activated by CXCL1 secreted by cardiac fibroblasts. Both were associated with ECM and contribute to the decompensation stage.

Predictors of In-Hospital Death in Patients With Acute Myocardial Infarction.

Factors such as age, vital signs, renal function, Killip class, cardiac arrest, elevated cardiac biomarker levels, and ST deviation predict survival in patients with acute myocardial infarction (AMI). However, the existing risk assessment tools lack comprehensive consideration of catheter-related factors, and short-term prognostic predictors are unknown. This study aimed to clarify in-hospital prognostic predictors in hospitalized patients with AMI. Five hundred and thirty-six patients who underwent percutaneous coronary intervention (PCI) for AMI were divided into non-survivor (n = 36) and survivor (n = 500) groups. Coronary risk factors, laboratory findings, angiographic findings, and clinical courses were compared between the two groups. Multiple logistic regression was used to analyze in-hospital death in pre- and post-PCI phases. In the pre-PCI phase, multiple logistic regression analysis revealed several predictors of in-hospital death, including systolic blood pressure [odds ratio (OR) = 0.985, p = 0.023)], Killip class ≥2 (OR = 14.051, p <0.001), and chronic kidney disease (OR = 4.859, p = 0.040). In the post-PCI phase, multiple logistic regression analysis revealed additional predictors of in-hospital death, including Killip class ≥2 (OR = 5.982, p = 0.039), presence of lesions in the left main trunk (OR = 51.381, p = 0.044), utilization of intra-aortic balloon pumps and percutaneous cardiopulmonary support (OR = 6.141, p = 0.016), and presence of multi-vessel disease (OR = 6.323, p = 0.022). Predictors of in-hospital death in AMI extend beyond conventional risk factors to include culprit lesions, mechanical support, and multi-vessel disease that manifest post-PCI.

Cardiac Biomarkers and Their Role in Identifying Increased Risk of Cardiovascular Complications in COVID-19 Patients.

Cardiovascular disease (CVD) is a global health concern, causing significant morbidity and mortality. Both lifestyle and genetics influence the development of CVD. It is often diagnosed late, when the treatment options are limited. Early diagnosis of CVD with help of biomarkers is necessary to prevent adverse outcomes. SARS-CoV-2 infection can cause cardiovascular complications even in patients with no prior history of CVD. This review highlights cardiovascular biomarkers, including novel ones, and their applications as diagnostic and prognostic markers of cardiovascular complications related to SARS-CoV-2 infection. Patients with severe SARS-CoV-2 infection were shown to have elevated levels of cardiac biomarkers, namely N-terminal pro-brain natriuretic peptide (NT-pro-BNP), creatine kinase-myocardial band (CK-MB), and troponins, indicating acute myocardial damage. These biomarkers were also associated with higher mortality rates and therefore should be used throughout COVID-19 patient care to identify high-risk patients promptly to optimize their outcomes. Additionally, microRNAs (miRNAs) are also considered as potential biomarkers and predictors of cardiac and vascular damage in SARS-CoV-2 infection. Identifying molecular pathways contributing to cardiovascular manifestations in COVID-19 is essential for development of early biomarkers, identification of new therapeutic targets, and better prediction and management of cardiovascular outcomes.

Investigation of phytotherapeutic potential of herbal mixtures and their effects on salbutamol induced cardiotoxicity and hyperlipidemia in rabbits

BackgroundCardiovascular diseases (CVDs) are the major cause of deaths all over the world. The high level of blood cholesterol and oxidative stress are major risk factors for heart diseases. The phytotherapeutics have attracted attention as potential agents for preventing and treating oxidative stress associated diseases. The objective of present study was to evaluate the synergetic cardio-protective and antilipidemic potential of medicinal plants viz. Coriandrum sativum, Piper nigrum and Cactus grandiflorus. Cardio-protective and anti-lipidemic potential of herbal mixture was evaluated against salbutamol induced cardiotoxicity in rabbits. For this purpose, rabbits were divided into six groups as normal control, salbutamol control, curative and standard drug curative.ResultsSalbutamol significantly (p < 0.05) increased the level of serum cardiac biomarkers (ALT, CK-MB, AST and LDH) and lipids (LDL, triglycerides, cholesterol) in rabbits. The prior and post administration of herbal mixture significantly (p < 0.05) lowered the elevated level of serum cardiac biomarkers and lipids equal to normal control. Gross pathological examination revealed that heart of salbutamol control animals became hardened, congested and were enlarged than preventive and curative groups. The phytotherapeutic analysis of medicinal plants revealed the presence of phenols, tannins, alkaloids and steroids.ConclusionThe results showed that this herbal mixture has strong cardio-protective and anti-lipidemic potential.

Correlation between admission red cell distribution width and GRACE risk score as an early mortality marker in patients with acute myocardial infarction

Background: Red blood cell distribution width (RDW) is a measurement of the size variation of red blood cells in circulation. The Global Registry of Acute Coronary Events (GRACE) score is the most commonly used risk-stratification scoring system to predict mortality in acute coronary syndrome for both ST- elevated myocardial infarction (STEMI), non-ST elevated myocardial infarction (NSTEMI). The aim of this study was to assess the easily determinable red blood cell distribution width (RDW) as an early mortality marker of acute myocardial infarction (MI) mortality and the correlation of RDW-CV on admission with GRACE risk score in patients with acute myocardial infarction. Methods: This hospital-based, prospective observational study included 211 patients (mean age 58.15 +/- 12.45 years, male 176) admitted with acute MI (STEMI/NSTEMI) from January 2022 to June 2022. The study population was divided into two groups basing on the 50th percentile of the admission RDW-CV value -13.7. The GRACE score was calculated on admission to predict the GRACE in hospital mortality score within 24 hours of admission. Results: The study found that the higher RDW-CV values were associated with adverse prognostic factors in acute myocardial infarction like increased age, lower systolic blood pressure, heart failure, cardiac arrest, higher cardiac biomarker levels and higher in-hospital mortality (p = 0.049, level of significance p&lt; 0.05) and this correlated with a higher GRACE score (Pearson’s correlation coefficient R= 0.47, P&lt;0.05). Conclusion: Thus, RDW can be used as a useful parameter for predicting in-hospital mortality in acute MI patients.

Effect of large volume red blood cell apheresis on cardiovascular functions in healthy donors.

Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. Thirty-two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT-proBNP, hs-TnT and CK-MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single-time, the cardiovascular functions did not change significantly compared with traditional whole blood donation.

Pretreatment with Notoginsenoside R1 attenuates high-altitude hypoxia-induced cardiac injury via activation of the ERK1/2-P90RSK-Bad signaling pathway in rats.

High-altitude cardiac injury (HACI) is one of the common tissue injuries caused by high-altitude hypoxia that may be life threatening. Notoginsenoside R1 (NG-R1), a major saponin of Panax notoginseng, exerts anti-oxidative, anti-inflammatory, and anti-apoptosis effects, protecting the myocardium from hypoxic injury. This study aimed to investigate the protective effect and molecular mechanism of NG-R1 against HACI. We simulated a 6000 m environment for 48 h in a hypobaric chamber to create a HACI rat model. Rats were pretreated with NG-R1 (50, 100 mg/kg) or dexamethasone (4 mg/kg) for 3 days and then placed in the chamber for 48 h. The effect of NG-R1 was evaluated by changes in Electrocardiogram parameters, histopathology, cardiac biomarkers, oxidative stress and inflammatory indicators, key protein expression, and immunofluorescence. U0126 was used to verify whether the anti-apoptotic effect of NG-R1 was related to the activation of ERK pathway. Pretreatment with NG-R1 can improve abnormal cardiac electrical conduction and alleviate high-altitude-induced tachycardia. Similar to dexamethasone, NG-R1 can improve pathological damage, reduce the levels of cardiac injury biomarkers, oxidative stress, and inflammatory indicators, and down-regulate the expression of hypoxia-related proteins HIF-1α and VEGF. In addition, NG-R1 reduced cardiomyocyte apoptosis by down-regulating the expression of apoptotic proteins Bax, cleaved caspase 3, cleaved caspase 9, and cleaved PARP1 and up-regulating the expression of anti-apoptotic protein Bcl-2 through activating the ERK1/2-P90RSK-Bad pathway. In conclusion, NG-R1 prevented HACI and suppressed apoptosis via activation of the ERK1/2-P90RSK-Bad pathway, indicating that NG-R1 has therapeutic potential to treat HACI.

Differentiation of Multi-system Inflammatory Syndrome Associated with COVID-19 Versus Kawasaki Disease Using Cardiac Biomarkers.

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 shares clinical similarities to Kawasaki disease (KD). We sought to determine whether cardiac biomarker levels differentiate MIS-C from KD and their association with cardiac involvement. Subjects included 38 MIS-C patients with confirmed prior CoVID-19 and 32 pre-pandemic and 38 contemporaneous KD patients with no evidence of COVID-19. Patient, clinical, echocardiographic, electrocardiographic and laboratory data timed within 72 hours of cardiac biomarker assessment were abstracted. Groups were compared, and regression analyses were used to determine associations between biomarker levels, diagnosis and cardiac involvement, adjusting for clinical factors. MIS-C patients had fewer KD clinical features, with more frequent shock, ICU admission, inotrope requirement, and ventricular dysfunction, with no difference regarding coronary artery involvement. Multivariable regression analysis showed that both higher N-terminal pro-B-type natriuretic peptide (NTproBNP) and cardiac troponin I (TnI) were associated with MIS-C versus KD, after adjusting for significant covariates. Receiver operating characteristic curves for diagnosis showed that any detectable TnI greater than 10 ng/L was predictive of MIS-C versus KD with 91% sensitivity and 76% specificity. NTproBNP >2000 ng/L predicted MIS-C versus KD with 82% sensitivity and 82% specificity. Higher TnI but not NTproBNP was associated with lower LV ejection fraction; neither biomarker was associated with coronary artery involvement. Positive TnI and higher NTproBNP may differentiate MIS-C from KD, which may become more relevant as evidence of prior COVID-19 becomes more challenging to determine. Cardiac biomarkers may have limited associations with cardiac involvement in this setting.

Right ventricular myocarditis and rapid fibrosis induced by pazopanib.

A 56-year-old woman with metastatic chondrosarcoma visited our emergency department because of chest discomfort. Treatment with oral pazopanib, a multi-targeted tyrosine kinase inhibitor that targets angiogenesis growth factor receptors, fibroblast growth factor receptors, platelet-derived growth factor receptors, and vascular endothelial growth factor receptors, was initiated 26 days previously. Electrocardiography showed new-onset significant ST elevation in the precordial leads V1–V3 and pathologic Q-waves in leads III and aVF (Panel A). The cardiac and inflammatory biomarker levels were elevated as follows: creatine kinase (CK), 705 (reference range, 32–135 IU/L); CK-myocardial band (MB) fraction, 12.5 (reference range, 0–5 ng/mL); troponin-T, 402 (reference range, 0–14 pg/mL); NT-proBNP, 11 230 (reference range, 0–287 pg/mL); and C-reactive protein, 77.3 (reference range, 0–8 mg/L). Echocardiography showed newly developed akinesia with thinning in the septum and throughout the right ventricle with markedly reduced biventricular systolic dysfunction compared with echocardiography performed 1 month ago (Panel B and Supplementary data online, Video). Luminal narrowing or thrombosis in the coronary arteries was not observed on emergency coronary angiography (Panel C). Cardiac magnetic resonance imaging performed on the second day of hospitalization showed diffuse late gadolinium enhancement in the right ventricular wall and the right side of the septum (Panel D). The nails of both hands showed hyperpigmentation and onycholysis induced by taking pazopanib (Panel E). Despite the discontinuation of pazopanib and heart failure management, she developed fatal ventricular tachycardia and cardiogenic shock (Panel F). Imaging findings show pazopanib-induced right ventricular myocarditis with subsequent rapid wall thinning and fibrosis.

Protective role of vitamin D3 in a rat model of hyperthyroid-induced cardiomyopathy.

Several studies have reported the cardioprotective effect of vitamin D. Thus, this study aimed to investigate the possible cardioprotective effect of vitamin D3 in hyperthyroid-induced cardiomyopathy rat model. Rats were divided into 3 groups: control group; hyperthyroid group, rats were administrated l-thyroxine sodium daily for 4 weeks; and hyperthyroid+vitamin D3 treated group, rats were treated with l-thyroxine sodium for 4 weeks daily, and received the vitamin D3 for the same duration. After 4 weeks, electrocardiogram (ECG) was recorded. Then, blood samples were collected for biochemical analysis. After that, the final body weight was measured, and the rats were sacrificed. Finally, the hearts were excised, weighed and were prepared for histological examination by hematoxylin and eosin, and immunohistochemistry assessment of caspase-3 and proliferating cell nuclear antigen (PCNA). Hyperthyroid rats showed significant ECG changes, increased serum levels of cardiac biomarkers, fibroblast growth factor-23 (FGF23), malondialdehyde, antioxidant enzymes, tumor necrosis factor-alpha (TNF-α) and relative heart weight compared with the control rats. Vitamin D3 coadministration with l-thyroxine resulted in significant improvement in thyroid profile, ECG parameters, significant decrease of cardiac biomarkers, FGF23, malondialdehyde, TNF-α and relative heart weight, and significant decrease of the antioxidant enzymes compared with the hyperthyroid rats. The histological study was consistent with the biochemical results. Hyperthyroid rats showed upregulation of caspase-3 and PCNA in the myocardium compared with control group. Vitamin D3 treated rats showed downregulation of caspase-3 and PCNA. Vitamin D3 provides cardioprotective effects in hyperthyroid rats.

Effect of Periprocedural Myocardial Infarction After Initial Revascularization With Left Main PCI in Patients With Recent Myocardial Infarction.

Periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) for left main coronary artery disease (LMCAD) may be particularly deleterious in patients with recent myocardial infarction (MI). We sought to determine the rates and prognostic relevance of PMI using different definitions and biomarker thresholds after PCI for LMCAD in patients with recent MI. Between January 2004 and December 2016, 442 patients underwent PCI for LMCAD at a median of 3 days after presentation with MI. A total of 350 patients presented with elevated cardiac biomarker levels (349 with serial creatine kinase-myocardial band [CK-MB] and 219 with serial cardiac troponin I (cTnI) values) that were stable or falling before the PCI. In this cohort, PMI within 48 hours of PCI was adjudicated using Society for Cardiovascular Angiography & Interventions (SCAI), Academic Research Consortium 2 (ARC-2), and fourth Universal Definition of Myocardial Infarction (UDMI) criteria. The primary and secondary end points were 3-year rates of cardiovascular (CV) and all-cause death. An incremental post-PCI rise in CK-MB starting at ≥10× the upper reference limit from baseline was significantly associated with 3-year CV death (adjusted hazard ratio [aHR], 7.96; 95% confidence interval [CI], 2.89-21.90), whereas CV death was not associated with any threshold elevation of cTnI. The frequencies of PMI according to the fourth UDMI, ARC-2, and SCAI definitions were 19.4%, 12.3%, and 8.6%, respectively. PMI by all 3 definitions was significantly associated with 3-year CV death, with the SCAI definition having the strongest relationship (aHR, 6.34; 95% CI, 2.47-16.27) compared with those of ARC-2 (aHR, 2.82; 95% CI, 1.15-6.96) and fourth UDMI (aHR, 2.65; 95% CI, 1.14-6.14). In patients with recent MI undergoing PCI for LMCAD, an incremental elevation in postprocedural CK-MB of ≥10× the upper reference limit as a stand-alone measure was strongly predictive of 3-year CV and all-cause death, whereas no cTnI elevations of any level were prognostic. All 3 contemporary PMI definitions in widespread use were associated with 3-year mortality after PCI in this high-risk cohort, with the SCAI definition having the strongest relationship with subsequent death.

Cardiac and noncardiac biomarkers in patients undergoing anthracycline chemotherapy – a prospective analysis

BackgroundBiomarkers represent a potential tool to identify individuals at risk for anthracycline-induced cardiotoxicity (AICT) prior to symptom onset or left ventricular dysfunction.MethodsThis study examined the levels of cardiac and noncardiac biomarkers before, after the last dose of, and 3–6 months after completion of doxorubicin chemotherapy. Cardiac biomarkers included 5th generation high-sensitivity cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide, growth/differentiation factor-15 (GDF-15), and soluble suppression of tumorigenesis-2 (sST2). Noncardiac biomarkers included activated caspase-1 (CASP-1), activated caspase-3, C-reactive protein, tumor necrosis factor-α, myeloperoxidase (MPO), galectin-3, and 8-hydroxy-2’-deoxyguanosine. Echocardiographic data (LVEF and LVGLS) were obtained at pre- and post-chemotherapy. Subanalysis examined interval changes in biomarkers among high (cumulative doxorubicin dose ≥ 250 mg/m2) and low exposure groups.ResultsThe cardiac biomarkers cTnT, GDF-15, and sST2 and the noncardiac biomarkers CASP-1 and MPO demonstrated significant changes over time. cTnT and GDF-15 levels increased after anthracycline exposure, while CASP-1 and MPO decreased significantly. Subanalysis by cumulative dose did not demonstrate a larger increase in any biomarker in the high-dose group.ConclusionsThe results identify biomarkers with significant interval changes in response to anthracycline therapy. Further research is needed to understand the clinical utility of these novel biomarkers.

Physiological ischemic training improves cardiac function through the attenuation of cardiomyocyte apoptosis and the activation of the vagus nerve in chronic heart failure.

This study investigated the functional outcomes of patients with chronic heart failure (CHF) after physiological ischemic training (PIT), identified the optimal PIT protocol, evaluated its cardioprotective effects and explored the underlying neural mechanisms. Patients with CHF were randomly divided into experimental group (n = 25, PIT intervention + regular treatment) and control group (n = 25, regular treatment). The outcomes included the left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) and cardiopulmonary parameters. LVEF and cardiac biomarkers in CHF rats after various PIT treatments (different in intensity, frequency, and course of treatment) were measured to identify the optimal PIT protocol. The effect of PIT on cardiomyocyte programmed cell death was investigated by western blot, flow cytometry and fluorescent staining. The neural mechanism involved in PIT-induced cardioprotective effect was assessed by stimulation of the vagus nerve and muscarinic M2 receptor in CHF rats. LVEF and VO2max increased while BNP decreased in patients subjected to PIT. The optimal PIT protocol in CHF rats was composed of five cycles of 5 min ischemia followed by 5 min reperfusion on remote limbs for 8 weeks. LVEF and cardiac biomarker levels were significantly improved, and cardiomyocyte apoptosis was inhibited. However, these cardioprotective effects disappeared after subjecting CHF rats to vagotomy or muscarinic M2 receptor inhibition. PIT improved functional outcomes in CHF patients. The optimal PIT protocol required appropriate intensity, reasonable frequency, and adequate treatment course. Under these conditions, improvement of cardiac function in CHF was confirmed through cardiomyocyte apoptosis reduction and vagus nerve activation.

The study on association of elevated cardiac biomarker in patients of acute exacerbation of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and also resulting in economic and social burden which is substantial and is significantly increasing with time. Chronic obstructive pulmonary disease is frequently associated with right ventricular loading and pulmonary hypertension. Study aimed to evaluate a possible association between cardiac biomarker levels and adverse events in hospitalized patients with Acute exacerbations of chronic obstructive pulmonary disease comorbidities are important determinants of outcome and quality of life of patients with chronic obstructive pulmonary disease. An observational, cross-sectional study was conducted on 89 patients with AECOPD admitted in the medicine emergency ward of Baba Raghav Das medical college and Nehru Hospital Gorakhpur India. Acute exacerbations of chronic obstructive pulmonary disease were diagnosed according to Global Initiative for chronic obstructive lung disease guidelines. cTnI levels were estimated at the time of admission by method based on chemiluminescence with other investigations. Levels ≥ 0.01ng/ml was taken as positive. Tabulation and statistical analysis were performed using Microsoft Excel and SPSS v.17.0 software. p –value&amp;#60; 0.05 at 95% confidence intervals taken as statistically significant. 89 patients with AECOPD were enrolled, among them mean age was 59.59±8.72. We found that cardiac biomarker elevation (cTnI≥0.01ng/ml) is significantly associated with increased mortality, duration of hospitalization, need of ventilation (both invasive or non-invasive) &amp; cardiovascular morbidity. cTnI positivity predicted increased need of ICU admission and significantly increased duration of hospital stay (P=0.0001). cTnI positivity can prognosticate need of NIV or ventilator support. It was found in our study that ventilator support necessity &amp; mortality was more in cTnI positive patients which shows statical significance (P=0.006).cTnI in AECOPD has close relation with exacerbation od disease, right ventricular dysfunction, so it can be used as prognostic marker for mechanical ventilation requirement in future.

Acute myocardial calcification in a patient with fulminant myocarditis.

Relationship with Industry: None A 38-year-old man was admitted with a 3-week history of rapid clinical deterioration. The patient presented with multisystem inflammatory syndrome associated with multi-organ failure (white blood and polynuclear cells counts at respectively 54.40 and 51.60 *109/L; C-reactive protein, Ferritin and Fibrinogen levels at respectively, 214 mg/L, 1624 μg/L, and 8.31 g/L; and creatinine and bilirubin levels at respectively 397 μmol/L (4,49 mg/dL) and 57 μMol/L (3,33 mg/dL)). Large screening and multiple testing for bacterial and viral infections remained negative in a patient with Covid-19 infection 3-months earlier without vaccination. The patient was transferred to the Intensive Care Unit necessitating mechanical ventilation, hemodialysis, and inotropic support. Rapidly, diffuse ST elevation on electrocardiogram and increased levels of high-sensitivity cardiac I troponin (hs-cTnI = 135000 ng/L) and natriuretic peptide (NT-ProBNP = 72114 ng/L) were found. Coronary angiogram showed no significant coronary disease and transthoracic echocardiography (TTE) showed reduced left ventricular ejection fraction (LVEF = 40%). Cardiac magnetic resonance imaging confirmed diffuse and extensive gadolinium uptake. Despite negative cardiac biopsies, the diagnosis of fulminant myocarditis was made and the patient underwent corticosteroids bolus and intravenous immunoglobulin therapies. Clinical evolution was deemed favourable with a progressive decrease in systemic inflammatory process associated with a decrease in cardiac biomarkers levels. However, 2 weeks later, chest X-ray (Panel A) and TTE (Panel B) showed acute and impressive left ventricular calcified remodelling process with diffuse epicardial calcification and septal patchy fibrosis (whites triangles). The positron emission tomography (PET-CT) confirmed the diffuse FDG uptakes suggesting persistent local inflammatory process (Panel C) associated with large epicardial calcified remodelling (Panel D). The patient was discharged 1 month after the index admission with optimized heart-failure therapy and planned follow-up at the Heart Failure Clinic.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n= 74) during monitoring and those without AF (n= 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.