Specific Cardiac Biomarkers Research Articles

The ameliorating effect of carotenoid rich fraction extracted from Dunaliella salina microalga against inflammation- associated cardiac dysfunction in obese rats

The carotenoid rich fraction of microalgae Dunaliella salina (crf-DS) have been receiving great attention, due to they abilities to protect and improve various disorders. The objective of this study is to explore the therapeutic efficiency of crf-DS on obesity-assciated cardiac dysfunction in the high-fat diet (HFD) treated rats. These rats were orally administered with crf-DS (150 mg /kg body weight), for six consecutive weeks in comparison with reference drug(orlistat). Specific cardiac biomarkers were examined including; adiponectin, plasminogen activator inhibitor (PAI-1), glucagon, troponin-I (cTnI). The cell adhesion molecules (VCAM and ICAM), C-reactive protein (CRP), collagen type II (Col II), collagen alpha-1 (III) chain (Col3A1), lipoxygenase activity (LOX), as well as histopathological examination of cardiac tissue were investigated. Results indicated a significant reduction(P ≤ 0.05) in adiponectin and glucagon levels in serum of obese rats. However, cTnI, PAI-1, cell adhesion molecules, CRP, Col II, and Col3A1 and LOX levels declared marked increase. Histopathological examination of cardiac tissue showed fibrosis with severe congestion in the myocardial blood vessels. On the other hand, rats medicated with a crf-DS demonstrated noticeable ameliorating effect in all the measured parameters. Beside, myocardial tissue of obese rats showed no alteration. Hence, It could be concluded that, oral supplementation with crf-DS is able to attenuate cardiac dysfunction in obese rats. Further extended work is needed to exploit, the possible application of D. salina as nutraceuticals and food additives.

Novel Invasive and Noninvasive Cardiac-Specific Biomarkers in Obesity and Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of fatality and disability worldwide regardless of gender. Obesity has reached epidemic proportions in population across different regions. According to epidemiological studies, CVD risk markers in childhood obesity are one of the significant risk factors for adulthood CVD, but have received disproportionally little attention. This review has examined the evidence for the presence of traditional cardiac biomarkers (nonspecific; lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, myoglobulin, glycogen phosphorylase isoenzyme BB, myosin light chains, ST2, and ischemia-modified albumin) and novel emerging cardiac-specific biomarkers (cardiac troponins, natriuretic peptides, heart-type fatty acid-binding protein, and miRNAs). Besides, noninvasive anatomical and electrophysiological markers (carotid intima-media thickness, coronary artery calcification, and heart rate variability) in CVDs and obesity are also discussed. Modifiable and nonmodifiable risk factors associated with metabolic syndrome in the progression of CVD, such as obesity, diabetes, hypertension, dyslipidemia, oxidative stress, inflammation, and adipocytokines are also outlined. These underlying prognostic risk factors predict the onset of future microvascular and macrovascular complications. The understanding of invasive and noninvasive cardiac-specific biomarkers and the risk factors may yield valuable insights into the pathophysiology and prevention of CVD in a high-risk obese population at an early stage.

THE GROWTH HORMONE SECRETAGOGUE RECEPTOR, GHRELIN, AND BNP IN HUMAN HEART DISEASE WITH PRESERVED EJECTION FRACTION

Heart disease (HD) diagnosis is based on clinical features, imaging, and circulating biomarkers, notably B-type natriuretic peptide (BNP), the gold standard marker of heart failure. However, a cardiac-specific biomarker detecting contractile dysfunction at early stages is lacking. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin may be cardiac-specific biomarkers. We have characterized a fluorescent analog of ghrelin, Cy5-ghrelin (1-19) that detects changes in cardiac GHSR in situ in diabetic cardiomyopathy and heart failure. We are now using this tool to map changes in regional and cellular distribution of GHSR in HD. We obtained tissue from the left ventricle (LV) and right atrium (RA) from 10 cardiac surgery patients with preserved ejection fraction (pEF) and from 10 deceased donors with no history of HD. GHSR levels were measured by quantitative fluorescence microscopy using Cy5-ghrelin(1-19). Ghrelin and BNP were measured by immunofluorescence. High-resolution images were acquired using a Nikon A1R confocal microscope and fluorescence intensities were quantified using ImageJ FIJI's built-in algorithms (Shanbhag for GHSR or RenyiEntropy for ghrelin and BNP). Values of fluorescence intensities were compared based on individual algorithms and colocalization analysis was conducted with the NIS-Elements software. Data were analysed by t-test, one-way ANOVA, and Pearson correlation coefficient (PCC) with significance set at p < 0.05. There were significantly lower levels of GHSR in RA tissue samples from cardiac surgery patients (p=0.041) and no significant differences in ghrelin or BNP expression (Figure 1). There was strong colocalization of ghrelin and BNP in both healthy (PCC=0.935) and diseased (PCC=0.856) tissue samples. In healthy tissue, colocalization appeared as large, discretely defined punctate areas near the nucleus, whereas in the tissue from cardiac surgery patients, ghrelin and BNP signals were more diffuse and contained in smaller areas surrounding the nucleus (Figure 2, arrows). We have shown expression of GHSR, ghrelin and BNP in both healthy and diseased cardiac tissue with only GHSR significantly changing in HD. This may indicate GHSR expression is decreased in HD with pEF whereas BNP (elevated in end stage HF) and ghrelin are not changed. The strong correlation between ghrelin and BNP indicates that these markers may be stored in the same intracellular compartment near the nucleus where they are released upon cellular stress induced by HD. This is the first study showing colocalization between ghrelin and BNP in human cardiac tissue. We are currently stratifying these results based on sex, type of HD, and region of the heart.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Abstract 184: Cardioprotective Effects of Brain-derived Neurotrophic Factor rs6265 Polymorphism in Duchenne Cardiomyopathy

We previously identified brain-derived neurotrophic factor (BDNF) as a putative cardiac-specific biomarker for preserved cardiac function in Duchenne Muscular Dystrophy (DMD). BDNF has cardioprotective qualities that may attenuate dilated cardiomyopathy, and a common, functional BDNF single nucleotide polymorphism rs6265 (Val66-Met) may be correlated with increased risk of cardiovascular events. We hypothesized that BDNF is protective in the setting of DMD and that BDNF’s beneficial effects are diminished in rs6265 allelic carriers. We compared circulating BDNF levels with cardiovascular and skeletal muscle functional parameters in DMD patients stratified by carrier status. Positive association of circulating BDNF with left ventricular ejection fraction in DMD patients was restricted to non-carriers of the rs6265 allele, whereas carriers exhibited worse cardiac function with increased BDNF, more fibrosis and worse skeletal muscle function. To more directly assess association of rs6265 with cardiac function, we used mice with knock-in of BDNF polymorphic Val66Met allele. RNASeq showed higher expression of extracellular matrix genes in Val66Met hearts, and there was a negative correlation of cardiac BDNF protein levels with fibrosis. Additionally, there were baseline echocardiographic and ECG differences, and isolated cardiomyocytes had decreased contractility. This overall cardiac phenotype was substantially enhanced when Val66Met mice were crossed with muscular dystrophy mice. Considered together, our results indicate that BDNF plays a protective role in the dystrophic heart and may represent a novel therapeutic candidate for DMD cardiomyopathy.

Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection

The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK−MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10–20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2= 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI.

Acute Responses of Novel Cardiac Biomarkers to a 24-h Ultra-Marathon.

The aim of the present study was to examine the acute effect of an ultra-endurance performance on N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnT), creatinine kinase-myocardial band (CK-MB), high sensitive C-reactive protein (hsCRP), ischemia modified albumin (IMA), heart-type fatty acid binding protein (H-FABP) and cardiovascular function. Cardiac biomarkers were evaluated in 14 male ultra-marathoners (age 40 ± 12 years) during a 24 h ultra-marathon at five points (i.e., Pre-race; Marathon, 12-h run, 24-h run, and 48-h post-race). All subjects underwent baseline echocardiography assessment at least 10 days prior to the ultra-marathon and 48 h post-race. The average distance covered during the race was 149.4 ± 33.0 km. Running the ultra-marathon led to a progressive increase in hsCRP and H-FABP concentrations (p < 0.001). CK-MB and cTnT levels were higher after a 24-h run compared to pre-race (p < 0.05). Diastolic function was altered post-race characterized by a reduction in peak early to late diastolic filling (p < 0.01). Running an ultra-marathon significantly stimulates specific cardiac biomarkers; however, the dynamic of secretion of biomarkers linked to myocardium ischemia were differentially regulated during the ultra-marathon race. It is suggested that both exercise duration and intensity play a crucial role in cardiovascular adaptive mechanisms and cause risk of cardiac stress in ultra-marathoners.

THE GROWTH HORMONE SECRETAGOGUE RECEPTOR, GHRELIN AND BIOCHEMICAL SIGNALING MOLECULES IN HUMAN HEART DISEASE

Diagnosis of heart disease (HD) is based on clinical features, imaging, and circulating biomarkers, such as B-type natriuretic peptide (BNP), the gold standard heart failure biomarker. However, a cardiac-specific biomarker with potential to detect and might have the potential to predict the development of contractile dysfunction is lacking. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin may be cardiac-specific biomarkers. We have characterized a fluorescent analog of ghrelin, [Ghrelin(1-19), Lys19(Sulf-cyanine5)] to detect changes in cardiac GHSR in situ in diabetic cardiomyopathy and heart failure. We are now using this tool to map changes in regional and cellular distribution of GHSR in HD. Tissue was obtained from the left ventricle (LV) and right atrium (RA) of 23 patients who had aortic valve reconstruction (AVR). Ten patients also had coronary artery bypass grafting (CABG). GHSR levels were measured by quantitative fluorescence microscopy using Cy5-ghrelin(1-19). Immunofluorescence was used to measure ghrelin, BNP, sarcoplasmic reticulum ATPase pump (SERCA, marker of contractility) and phosphorylated extracellular signal-related kinase (pERK, marker of cell metabolism). Fluorescence intensities from 4 slides per patient were quantified using ImageJ FIJI. Data were analysed by two-tailed t-test, one-way ANOVA and Tukey test, Pearson correlation and linear regression (p<0.05). A strong positive correlation (p<0.001) was noted between ghrelin and GHSR (r=0.857) or BNP (r=0.769). Ghrelin strongly correlated with SERCA2a (r=0.789, p<0.0001) and pERK (r=0.430, p<0.0319) relative to BNP (r=0.619, p=0.001 and r=0.508, p=0.0095 respectively). Regional localization analyses showed marked differences in the RA compared with the LV; there were highly significant correlations (p<0.0001) between ghrelin and BNP (r=0.802) or SERCA2a (r=0.847), and GHSR and SERCA2a (r=0.875), only in the RA. In both males and females, there was strong correlation between GHSR and ghrelin. In females BNP was more strongly correlated with ghrelin (r=0.827, p=0.0032) and GHSR (r=0.860, p=0.0014) while in males, SERCA2A was more strongly correlated with GHSR (r=0.714, p=0.0019) and ghrelin (r=0.8243, p<0.0001). Those who also underwent CABG showed significant correlations with ghrelin and BNP (r=0.792, p=0.0013) or SERCA2a (r=0.772, p=0.0033), and GHSR and SERCA2a (r=0.745, p=0.0054). GHSR expression in HD has shown differences in its sensitivity as a biomarker according to regional tissue distribution, gender and HD etiology. These results highlight the potential use of GHSR/ghrelin as a new cardiac-specific biomarker for HD detection from the RA and coronary artery disease, and also highlights the need for gender-specific biomarkers of HD.

Heart Failure Stimulates Tumor Growth by Circulating Factors.

Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer. HF was induced by inflicting large anterior myocardial infarction in APCmin mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort. The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APCmin mice (all P<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index). We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Rapid and Sensitive Detection of Cardiac Troponin I for Point-of-Care Tests Based on Red Fluorescent Microspheres.

A reliable lateral flow immunoassay (LFIA) based on a facile one-step synthesis of single microspheres in combining with immunochromatography technique was developed to establish a new point-of-care test (POCT) for the rapid and early detection of cardiac troponin I (cTnI), a kind of cardiac specific biomarker for acute myocardial infarction (AMI). The double layered microspheres with clear core-shell structures were produced using soap-free emulsion polymerization method with inexpensive compounds (styrene and acrylic acid). The synthetic process was simple, rapid and easy to control due to one-step synthesis without any complicated procedures. The microspheres are nanostructure with high surface area, which have numerous carboxyl groups on the out layer, resulting in high-efficiency coupling between the carrier and antibody via amide bond. Meanwhile, the red fluorescent dye, Nile-red (NR), was wrapped inside the microspheres to improve its stability, as well to reduce the background noise, because of its higher emission wavelength than interference from real plasma samples. The core-shell structures provided different functional areas to separate antibody and dyes, so the immunoassay has highly sensitive, wide working curves in the range of 0–40 ng/mL, low limits of detection (LOD) at 0.016 ng/mL, and limits of quantification (LOQ) at 0.087 ng/mL with coefficient of variations (CV) of 10%. This strategy suggested an outstanding platform for LFIA, with good reproducibility and stability to straightforwardly analyze the plasma samples without washing steps, thereby reducing the operating procedures for non-professionals and promoting detection efficiency. The whole detection process can be completed in less than 15 min. This novel immunoassay offers a reliable and favorable analytical result by detecting the real samples, indicating that it holds great potential as a new alternative for biomolecule detection in complex samples, for the early detection of cardiac specific biomarkers.

Biomarker and cardiovascular profiles of healthy aging, putting multiple biomarkers in perspective

Although many studies have reported age-specific changes in selected cardiovascular (CV) markers, few have analyzed the simultaneous changes that occur in the cardiac, metabolic, immune and growth factor axis with healthy aging. To assess the relationship between CV parameters and circulating biomarkers with aging. We prospectively recruited 150 healthy volunteers, of whom 44 were excluded due to reported illness on a comprehensive health questionnaire or the presence of CV disease on screening. Echocardiography and vascular Doppler were performed in all participants as per international guidelines, with Pulse Wave Velocity (PWV) calculated as the path length traveled divided by transit time of the aortic pulse wave. All cardiac-specific biomarkers, including NT-proBNP and GDF-15 were undertaken in the Abbott Core Laboratory, cytokines and growth factors were assessed using a 48-plex Luminex bead kit and comprehensive lipid profile with a Vertical Auto Profile lipid test. There was a wide age range, from 20 to 95 years, 45% females with a mean body mass index of 24.1 ± 3.1 kg/m 2 and systolic blood pressure of 118 ± 13 mmHg. Among CV ultrasound parameters, average E’ showed the highest correlation with age ( r 2 = 0.55, P < 0.001) with the highest significant correlation on each diagnostic group, as shown in Table 1 . Partial correlation mapping was used to represent the complex relationships between variables most correlated with age ( Figure 1 ). PWV, a measure of arterial stiffness appeared to be well correlated to E/A, a parameter of ventricular relaxation and GDF-15, which has been associated with CV mortality. On multivariate regression when considering the other modulating factors, insulin ( r = 0.29, P = 0.001) in addition to age ( r = 0.75, P < 0.001) explained the majority of the variance in PWV. The study presents the interactions in CV and biomarker profiles with aging, with insulin emerging as a major modulator of PWV. PWV indicates Pulse wave Velocity; GDF-15, Growth-differentiation factor-15; NT-proBNP, N-terminal pro-B-type natriuretic peptide; Gal-3, Galectin-3; CysC, Cystatin C; BUN, Blood Urea Nitrogen; HDL, high-density lipoprotein; CXCL, Chemokine (C-X-C motif) ligand; CCL, Chemokine (C-C motif) ligand.

Correlation between MYBPC3 mutation and Circulating concentrations of a marker of type I collagen metabolism on hypertrophic cardiomyopathy

Human carriers of hypertrophic cardiomyopathy associated sarcomeric mutations have abnormal collagen metabolism before overt left ventricular hypertrophy is detectable. This study investigated whether differences in collagen biomarkers were present in blood samples in positive for the MYBPC3 mutation compared with others sarcomeric mutations. 69 subjects were recruited for hypertrophic cardiomyopathy screening using echocardiography and genotyping. Circulating markers of collagen N-terminal propeptide of type III procollagen [type III collagen synthesis]), metalloproteinase (MMP3) and specific tissue inhibitor TIPM2 and cardiac biomarkers (N-terminal B-type natriuretic peptide) were measured. Correlation between concentrations of collagen biomarkers and echocardiographic variables was analyzed, and collagen biomarker concentrations were compared between MYBPC3 mutation positive and negative subjects with left ventricular hypertrophy and mutation on others sarcomeric genes. Linear regression analyses showed that mutation carriers genotype was independently associated with collagene peptide concentration and was higher (425.4 ± 122 μg/L,) than non-carriers (214.6 ± 98.5 μg/L; P = 0.0024). Collagene petide was correlated to the LV mass and left atrium volume ( r = 0.624, P = 0.001; and r = 0.588, P = 0.002). Circulating collagen peptide was higher in MYBPC3-positive subjects than negative controls and may indicate altered collagen metabolism. Further studies are necessary to determine whether alterations in circulating collagen biomarker concentration relate to an early stage of hypertrophic cardiomyopathy.

Contemporary and Future Usage of Conventional Cardiac Biomarkers: A Novel Algorithm for the Early Diagnosis of AMI and CVA

We propose a contemporary and novel algorithm using cardiac specific biomarkers for patients presenting with chest pain and other disease states associated with elevated levels of troponin T (TnT) and/or creatine kinase (CK) isoforms. We predict the implementation of this novel algorithm will differentiate between a type-I and type-II myocardial infarction (MI). We summarize advances using high-sensitivity Tn assays (hs-Tn), which include a greater sensitivity for rapid diagnosis of MI within 1-3 hours of symptom onset and is predictive of patient prognosis. We summarize the use of CK isoenzymes as a diagnostic marker for various disease states, determine myocardial infarct size, differentiate MI type, and diagnose myocardial reinfarction. We propose further studies using CK isoforms to define transient ischemic attack (TIA) and cerebrovascular accident (CVA) in order to direct treatments for acute CVA.

EXPRESSION OF THE GROWTH HORMONE SECRETAGOGUE RECEPTOR AND GHRELIN IN HUMAN HEART FAILURE

Heart failure (HF) is defined as occurring when the heart is unable to provide adequate blood flow and oxygen to organs across the body. Currently, a diagnosis of HF is made using a combination of clinical features, cardiac imaging, and detection of certain biomarkers in the circulation, notably BNP. However, a biomarker specific to cardiac tissue and that reflects the heart’s contractile state is lacking. Our group is characterizing the growth hormone secretagogue receptor (GHSR) and its ligand ghrelin as possible cardiac-specific biomarkers for HF. We have previously developed a fluorescent analog of ghrelin, Ghrelin(1-18, Lys18(Cy5), to detect GHSR in cardiac tissue in situ. We hypothesize that GHSR and ghrelin are biomarkers for the early detection of HF. We obtained samples of cardiac tissue from 10 cardiac transplant patients at the time of organ harvesting and serial post-transplant biopsies. Samples from the LV and RA of the explanted hearts, and biopsies from the newly-transplanted hearts (weekly for 4 weeks, monthly for 6 months, and 1 year post-Tx). GHSR levels were measured using Ghrelin(1-18, Lys18(Cy5) and ghrelin and BNP were measured using fluorescent antibodies. All samples were quantified using fluorescence microscopy. Fibrotic tissue was detected using Masson’s trichrome stain. Levels of all markers were compared between the explanted heart and the healthy biopsies using two-tailed t-test, one-way ANOVA and Tukey’s test and Pearson’s correlation (p < 0.05). GHSR and fibrosis levels increased and were highly variable in explanted hearts when compared to the healthy biopsies which had a much lower level of variability. Within 3 individual patients, there were significant differences (p < 0.001, p < 0.05, p < 0.01 respectively) between the explanted heart (LV and RA) and the short-term biopsies of the healthy heart (weeks 1-4) of both GHSR and ghrelin but not BNP. Within the entire transplant patient cohort (n=10), there was a strong positive correlation between both ghrelin and BNP (r2=0.575, p < 0.0001) and ghrelin and GHSR (r2=0.7033, p < 0.0001). GHSR and ghrelin showed elevated expression and significant differences in 3 of the 10 patients with end stage HF where BNP showed no significant differences indicating the increased sensitivity of GHSR and ghrelin in HF detection. Correlation between ghrelin and BNP, and ghrelin and GHSR in cardiac tissue may show evidence of a ghrelin/GHSR system working independently in the myocardium. These results indicate the potential use of ghrelin and GHSR as new cardiac-specific biomarkers that can help with the detection of HF.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Predictors of left ventricular remodeling after ST-elevation myocardial infarction

Adverse left ventricular (LV) remodeling after acute ST-elevation myocardial infarction (STEMI) is associated with morbidity and mortality. We studied clinical, biochemical and angiographic determinants of LV end diastolic volume index (LVEDVi), end systolic volume index (LVESVi) and mass index (LVMi) as global LV remodeling parameters 4 months after STEMI, as well as end diastolic wall thickness (EDWT) and end systolic wall thickness (ESWT) of the non-infarcted myocardium, as compensatory remote LV remodeling parameters. Data was collected in 271 patients participating in the GIPS-III trial, presenting with a first STEMI. Laboratory measures were collected at baseline, 2 weeks, and 6–8 weeks. Cardiovascular magnetic resonance imaging (CMR) was performed 4 months after STEMI. Linear regression analyses were performed to determine predictors. At baseline, patients were 21% female, median age was 58 years. At 4 months, mean LV ejection fraction (LVEF) was 54 ± 9%, mean infarct size was 9.0 ± 7.9% of LVM. Strongest univariate predictors (all p < 0.001) were peak Troponin T for LVEDVi (R2 = 0.26), peak CK-MB for LVESVi (R2 = 0.41), NT-proBNP at 2 weeks for LVMi (R2 = 0.24), body surface area for EDWT (R2 = 0.32), and weight for ESWT (R2 = 0.29). After multivariable analysis, cardiac biomarkers remained the strongest predictors of LVMi, LVEDVi and LVESVi. NT-proBNP but none of the acute cardiac injury biomarkers were associated with remote LV wall thickness. Our analyses illustrate the value of cardiac specific biochemical biomarkers in predicting global LV remodeling after STEMI. We found no evidence for a hypertrophic response of the non-infarcted myocardium.

Interpreting Cardiac Biomarkers in the Setting of Chronic Kidney Disease.

Chronic kidney disease (CKD) is common, particularly in those of advanced age. Because patients with CKD frequently have cardiac comorbidities and acute or chronic symptoms that may represent heart failure or an acute myocardial infarction (AMI), testing for concentrations of cardiac troponins and natriuretic peptides is frequent. Interpretation of these biomarkers can be challenging when differentiating acute from chronic processes, potentially resulting in missed opportunities to direct appropriate treatment. This review is designed to provide clinicians and laboratorians a platform to understand cardiac specific biomarker interpretation in patients with CKD by summarizing the extensive literature base that has developed specific to this population. First we review the epidemiology and unique contributions of CKD to cardiac pathophysiology. Next we consider the interpretation of cardiac troponin tests for the diagnosis AMI and the prognostic significance of chronic increases across the spectrum of CKD including those requiring renal replacement therapy. Last, we consider the caveats of interpreting natriuretic peptide results for the diagnosis of acute decompensated heart failure in addition to the short- and long-term prognostic implications of increased natriuretic peptide concentrations and CKD in a patient with heart failure. CKD is common and associated with acceleration of cardiovascular disease. Cardiac biomarker concentrations are often increased even in an absence of symptoms; typically reflecting the extent of underlying cardiovascular disease rather than impairment of renal clearance. Thoughtful interpretation of cardiac biomarkers in those with CKD can continue to provide important diagnostic and prognostic information.

Circulating Galectin-3 Levels Are Persistently Elevated After Heart Transplantation and Are Associated With Renal Dysfunction

ObjectivesThis study evaluated changes in serum levels of galectin (Gal)-3 before and after heart transplantation (HTx) and assessed the role of pre-HTx Gal-3 as a biomarker for post-HTx outcomes. BackgroundGal-3 is a novel biomarker that reflects cardiac remodeling and fibrosis. Elevated serum Gal-3 levels are associated with poor prognosis in heart failure patients. Whether Gal-3 levels change following HTx and the significance of post-HTx outcomes are unknown. MethodsSerum Gal-3 levels were measured in 62 patients at 118 days (Interquartile Range [IQR]: 23 to 798 days) before and 365 days (IQR: 54 to 767 days) post HTx. Cardiac tissue taken during routine post-HTx endomyocardial biopsy was evaluated to assess the correlation between tissue Gal-3 staining and serum Gal-3 levels and with the presence of myocardial hypertrophy and fibrosis. ResultsSerum Gal-3 levels remained significantly elevated (>17.8 ng/ml) in 35 patients (56%) post HTx. There was a significant inverse correlation between Gal-3 levels and glomerular filtration rate measured before and after HTx (p > 0.005). There was no association between Gal-3 serum level and Gal-3 staining of myocardial tissue or with the presence of myocyte hypertrophy and interstitial fibrosis post HTx. Elevated pre-HTx Gal-3 levels were associated with reduced post-HTx exercise capacity, but this association was not significant after adjustment for age, body mass index, and glomerular filtration rate. ConclusionsThis is the first study to demonstrate the fact that Gal-3 levels remain elevated in the majority of patients despite HTx and is associated with renal dysfunction. Our findings suggest Gal-3 is a systemic rather than cardiac-specific biomarker.

Concordance between cardio-protective effect on isoproterenol-induced acute myocardial ischemia and phenolic content of different extracts of Curcuma aromatica

Context: A classic traditional Chinese medicine Curcuma aromatica Salisb. (Zingiberaceae) has been reported to have favourable effects on the cardiovascular system.Objective: To research the cardio-protective effect of different C. aromatica hydroalcoholic extracts on isoproterenol (ISO)-induced acute myocardial ischemia (AMI) in rats. The total phenols in different extracts were detected simultaneously.Materials and methods: The rhizomes of C. aromatica dry powder were refluxed with 30%, 50%, 70% and 90% hydroalcoholic solvents to obtain different extracts. Rats were pretreated with four C. aromatica extracts (150 mg/kg/day, i.g.) for 9 days and then given ISO (30 mg/kg/day, s.c.) for 2 consecutive days, respectively. Heart rate, ST-segment, T-wave and serum levels of CK-MB, LDH, TAC, SOD, NO and MDA were measured. Total phenols of the different extracts were determined using the Folin-Ciocalteu assay.Results: Pretreatment with C. aromatica significantly decreased the elevated levels of serum specific cardiac injury biomarkers (CK-MB and LDH), the serum level of MDA, the ST-segment and T-wave. In addition, C. aromatica increased the heart rate, as well as the levels of TAC, SOD and NO, compared to ISO-induced controls. The total phenols in the 70% extract were higher than in the other extracts reaching 5.629 ± 0.037 mg/g, crude drug.Discussion and conclusion: Curcuma aromatica hydroalcoholic extracts exhibited remarkable cardio-protective effects against AMI in rats. The 70% extracts showed the strongest bioactivity. These results indicate that ethanol concentration in preparation of extracts of C. aromatica plays an important role in the protective effect against AMI.

Impact of moderate physical activity on the longitudinal trajectory of a cardiac specific biomarker of injury: Results from a randomized pilot study of exercise intervention

In animal models, physical activity (PA) prevents cardiac myocyte cell death. Data for PA mitigating myocyte injury in humans are limited to observational studies. Using a randomized controlled trial design, we sought to determine if introducing moderate PA to previously sedentary older adults could reduce the trajectory of myocardial injury as measured by the high-sensitive cardiac troponin T (hs-cTnT) assay. Participants (age ≥70 years) were assigned to a 1-year intervention of moderate PA or health education control. High-sensitive cTnT was measured at baseline and 1 year in the 307 of 424 subjects who had available stored serum. Changes in hs-cTnT within 1 year were compared between PA and control groups, as were differences in the proportion of subjects with a significant rise in hs-cTnT (prospectively defined as a>50% increase at follow-up from baseline). Moderate to vigorous PA in kcal/wk was estimated with the CHAMPS questionnaire. Baseline hs-cTnT levels and PA kcal/wk were similar for both groups. Activity kcal/wk increased in the PA, but not in the control group at 1 year. The median increase in hs-cTnT level from baseline was >3 times larger in the control (0.73 ng/L, interquartile range -0.64 to 2.59) vs the PA group (0.19ng/L, interquartile range -1.10 to 1.93) (P=.02). The proportion with a>50% increase in hs-cTnT was larger in the control group than in the PA group (9.3% vs 5.1%), but this difference was not statistically significant (P=.16). Initiation of moderate PA in sedentary older adults may favorably modify subclinical myocardial injury.

Anthracycline or trastuzumab-related cardiotoxicity: do we have a predictive biomarker?

Chemotherapy-induced cardiotoxicity, is a well-known and potentially serious complication strongly impacting the quality of life and overall survival of breast cancer patients. The current diagnostic approach to detect cardiac damage is the estimation of left ventricular ejection fraction by echocardiography. However, this approach exhibits less sensitivity toward early prediction of cardiomyopathy, not allowing for preventive strategies. Measurement of serum cardiac-specific biomarkers can be a valid diagnostic tool for identifying patients prone to developing cardiotoxocity and in whom closer cardiac monitoring and preventive strategies are pivotal. In this article, we review work done on biomarkers in recent years, with an emphasis on troponin and B-type natriuretic peptide, which are currently the most studied in this field. We also briefly discuss current and emerging imaging techniques for early detection of cardiomyopathy.

Serum cardiac troponin I analysis to determine the excessiveness of exercise intensity: A novel equation

Physical exertion is often promoted because of its beneficial health effects. This only holds true, however, as long as the optimal exercise intensity is not exceeded. If physical exertion becomes too strenuous or prolonged, cardiac injury or dysfunction may occur. Consequently, a significant elevation of the serum concentration of the sensitive and specific cardiac biomarker troponin I can be observed. In this article, we present the derivation of a novel equation that can be used to evaluate to what extent the intensity of conducted endurance exercise was excessive, based on a post-exercise assessment of serum cardiac troponin I. This is convenient, as exercise intensity is difficult for an athlete to quantify accurately and the currently used heart rate indices can be affected by various physiological and environmental factors. Serum cardiac troponin I, on the other hand, is a post-hoc parameter that directly reflects the actual effects on the myocardium and may therefore be a promising alternative. To our knowledge, this is the first method to determine relative exercise intensity in retrospect. We therefore believe that this equation can serve as a potentially valuable tool to objectively evaluate the benefits or harmful effects of physical exertion.