Specific Marker Of Myocardial Damage Research Articles

The Antioxidant Effect of Mitochondrially Targeted Antioxidant SkQ1 on the Isolated Rat Heart Model

Mitochondrially targeted antioxidants based on Skulachev ions (SkQ1) are extremely attractive for neutralizing reactive oxygen species directly in the mitochondrial matrix.The aim was to examine the antioxidant and cardioprotective status of the SkQ1 mitochondrially targeted antioxidant in an isolated rat heart model of ischemia and reperfusion after cold cardioplegia.Material and methods. The effects of different concentrations of SkQ1 (1200 ng/ml, 120 ng/ml, 12 ng/ml) were explored on isolated hearts of Wistar rats (n=50) during 240-min cold cardioplegia. The levels of oxidative stress, changes in myocardial damage markers (classical and highly specific) and cardiac function (coronary flow velocity, heart rate, systolic pressure) were assessed.Results. The use of SkQ1 at 12 ng/ml resulted in a significant neutralization of oxidative stress manifestations (P<0.05). The minimum concentration of NO metabolites (nitrates and nitrites) (36.2 [30.8; 39.8] µmol/ml) was maintained at pre-ischemic level throughout the 30-minute reperfusion period, while the malonic dialdehyde concentration (49.5 [41.1; 58.9] µmol/g) was lower compared with SkQ1 use at 120 ng/ml dose. Due to the «mitigation» of oxidative stress, intracellular enzymes and highly specific markers of myocardial damage rose more slowly during reperfusion, while cardiac function recovery occurred at a higher rate and showed stability upon restoration of perfusion.Conclusion. SkQ1 at 12 ng/ml concentration showed strong antioxidant and cardioprotective properties in an ex vivo study.

P0340 / #970: TROPONIN THRESHOLD FOR PREDICTING ACUTE KIDNEY INJURY AND MORTALITY IN INFANTS UNDERGOING CARDIAC SURGERY

Aims & Objectives: Acute kidney injury (AKI) occurs in up to 50% of children after cardiopulmonary bypass (CPB) and is independently associated with adverse outcomes including longer lengths of stay (LOS), prolonged mechanical ventilation and higher mortality. Cardiac troponin I (cTnI) a specific marker of myocardial damage has been found to be accurate predictor of complications and adverse clinical events after pediatric cardiac surgery. The purpose of this study was to determine a threshold value of cTnI measured immediately after pediatric open-heart surgery to predict AKI and mortality. Methods: Retrospective observational study in which data from 439 consecutive children undergoing cardiac surgery and entering to the intensive care unit (ICU) during a 10-month period were studied. Clinical, surgical y laboratory variables were evaluated. We used ROC curve to determine our postoperative cTnI threshold level and binary logistic regression to predict development of AKI and mortality. Results: 439 electronic medical records were reviewed, of which 130 met selection criteria, 54% men, mean age of 4.45 ± 4.19 years. A cTnI level of 25 ng/ml showed 94% sensibility to predict AKI. cTnI and RACHS-1 categories 3 and 4 were a strong independent predictor of AKI (p 0.001) and mortality (p 0.004). A value greater than our threshold had statistical significance for LOS 14.8±18.87 (p 0.009). Conclusions: In our study a postoperative cTnI level greater than 25ng/ml was a strong and independent biomarker predictor of AKI and mortality. Identifying these patients may allow anticipation of postoperative course and implementation of treatment strategies.

Prognostic impact of high sensitive troponin in predicting 30-day mortality among patients admitted to hospital with influenza.

BackgroundWorldwide, seasonal influenza causes significant mortality and severe infections may cause cardiac injury. High-sensitive-troponins (hsTnT) are sensitive and specific markers of myocardial damage. This study investigated the prognostic impact of hsTnT on 30-day mortality in hospitalised influenza patients.MethodsThis retrospective study included influenza patients ≥ 18 years, who had hsTnT performed during admission in two tertiary-hospitals in South Australia. Diagnosis of influenza was confirmed by polymerase–chain-reaction (PCR) test and hsTnT > 14 ng/L with a change of > 20% during admission was considered to be indicative of acute-cardiac injury. Clinical characteristics, complications and 30-day mortality were compared among four groups of patients: hsTnT unavailable, hsTnT negative, chronically elevated hsTnT and acutely elevated hsTnT. Cox-proportional hazard regression determined the hazard of death at 30-days following hospital discharge after adjustment for co-variates.ResultsBetween January 2016 -March 2020, 1828 influenza patients, mean age 66.4 years, were hospitalised. Troponin results were available for 617 (47.7%) patients, of whom, 62 (10%) had acute myocardial injury and 232 (37.6%) had chronic hsTnT elevation. Both inpatient and 30-day mortality were significantly higher among patients with acute (P < 0.001) and chronic hsTnT (P < 0.001) when compared to other groups. When compared to patients with negative hsTnT, acute but not chronic hsTnT elevation was significantly associated with 30-day mortality after adjustment for various co-variates (HR 8.30, 1.80–17.84, P value = 0.013).ConclusionsThis is the largest available analysis of cardiac-specific biomarker hsTnT in patients with influenza. An acutely elevated hsTnT was associated with 30-day mortality among hospitalised influenza patients.

Cardiac troponin I is associated with non-sustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy.

As highly sensitive and specific markers of myocardial damage, cardiac troponins were demonstrated to correlate with clinical parameters of patients with hypertrophic cardiomyopathy. However, the relationship between cardiac troponins and presence of non-sustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy remains unclear. The aim of our study was to explore the association between serum cardiac troponin I (cTNI) and presence of NSVT in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 309 HOCM patients were enrolled in our study. All participants underwent clinical evaluations, including collections of medical history, blood tests, 24-h Holter monitoring, echocardiography, and cardiac magnetic resonance imaging. There were 53 (17.2%) patients with NSVT and 256 patients without it. Compared to patients without NSVT, serum cTNI (P < 0.001) and plasma NT-proBNP (P = 0.042) were significantly higher in patients with NSVT. Moreover, cTNI and NT-proBNP were positively correlated with left atrial diameter, maximum wall thickness (MWT), left ventricular volume index and left ventricular mass index. In multivariable logistic analysis, log cTNI [odds ratio (OR) = 2.408, 95% confidence interval (CI) 1.108-5.325, P = 0.027], left ventricular end-diastole diameter (OR = 0.922, 95%CI 0.856-0.994, P = 0.034), MWT (OR = 1.131, 95%CI 1.035-1.235, P = 0.006) and left ventricular end-systole volume index (OR = 1.060, 95%CI 1.025-1.096, P = 0.001) were independent determinants of NSVT occurrence after adjustment for potential cofounders. Serum cTNI level was elevated in patients with NSVT. And it was independently associated with NSVT in patients with HOCM. Our results suggest that it may be more reasonable for HOCM patients with elevated serum cTNI to extend the time of Holter monitoring.

P1811Association between the autonomic dysfunction and biomarker levels in patients with chagas disease without evidence of structural heart disease

Abstract Background Several studies have shown autonomic dysfunction in early stages of Chagas disease (ChD). These alterations may be involved in the progression of the disease. The Valsalva Ratio (VR) is one of the most used tests to evaluate parasympathetic function, because it is easy and reproducible. On the other hand, the Higth Sensitive T troponin (HS-TnT) and the N-terminal pro B-type natriuretic peptide (NT-proBNP) are specific markers of myocardial damage and elevation of filling pressures, respectively. Both elevations are asociated with higher risk. The association between autonomic dysfunction and biomarker levels in ChD without evidence of structural heart affection, has been poorly studied. Purpose The aim of this study is to evaluate the presence of abnormal VR as an expression of disanutonomy in patients with Chagas without evidence of structural heart disease and its association with HS-TnT and NT-proBNP levels. Methods A prospective study was performed, which included outpatients with positive serology for Chagas, with electrocardiogram, ergometry, holter and Doppler echocardiogram within normal parameters. The exclusion criteria were the following: history of ischemic heart disease, neurological diseases, chronic renal failure (clearence &lt;30 ml/min), arterial hypertension and diabetes mellitus. All patients underwent a valsalva maneuver (VM), with continuous recording of the R-R interval by electrocardiogram. The VR was calculated dividing the longest RR interval after VM over the shortest RR interval during VM. Abnormal VR was considerated as a value &lt;1.1. In addition, HS-TnT and NT-proBNP were measured in all patients. Results One hundred and forty four patients were included, with 45±8 years old, 44% fameles. The VR was 1.22±0.12, HS-TnT 6.44±3.8 ng/L and the NT-proBNP was 55±44 pg/ml. Abnormal VR was found in 29.1% of patients (n=42). The abnormal VR group showed a higher level of HS-TnT (8.11±3.8 versus 5.7±3.5 ng/L, p=0.0006) and higher level of NT-proBNP (78±54 versus 45±36 pg/ml, p&lt;0.0001). In addition, the abnormal VR group presented a greater E/e'ratio (9.48±2.5 versus 7.1±1.8, p&lt;0.0001) and greater s wave (0.08±0.02 versus 0.10±0.02 cm/sec, p=0.02). In the multivariate análisis, abnormal VR was asociated with higher HS-TnT (OR 1.22 (CI 95% 1.04–1.43), p=0.01) and higher E/e'ratio (OR 1.54 (CI95% 1.17–2.02), p=0.001), but not with NT-proBNP (p=0,09). Conclusions About one third of patients with ChD without evidence of cardiopaty had autonomic dysfunction. The patients with abnormal VR had higher leves of HS-TnT and NT-proBNP, but in the multivariate analisys only the HS-TnT had associated with abnormal VR.

Cardiac enzymes activity and lactate concentration in the blood of sport horses at myocardial dystrophy

The article presents the results of research on the activity of cardiac specific enzymes and the concentration of lactate in the blood of sport horses for myocardial dystrophy of physical activity. Materials for researches were horses, used in the classical forms of equestrian sport of Ukrainian riding (n = 20), Hanoverian (n = 15) and Westphalian (n = 15) breeds. The average age of horses was 8.4 ± 0.71 years (3.5–16.0 g.), weight – 479.4 ± 8.54 kg (350–605 kg). Studies were conducted immediately before and immediately after exercise. The duration of regular training of average intensity was 1 hour: step 5 min; roaring lynx 10 minutes; step 5 min; training lynx 10 minutes; step 10 min; gallop with a transition to a step of 10 minutes; step 10 min. Blood samples from horses were taken from a jugular vein in a test tube without an anticoagulant (10 ml; Vacutest, Italy) and an anticoagulant (EDTA-K, 2.0 ml; Sarstedt, Germany). Diseases of the heart muscle are accompanied by the release of substances released from damaged cardiomyocytes, in particular, creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin. It has been established that the key to the pathogenesis of myocardial dystrophy in sport horses is the discrepancy between costs and energy recovery in the functioning structures of the heart muscle due to excessive cardiac load and significant increase in energy costs, as well as a disturbance in the balance of the electrolytes. Hyperlactatemia that occurs in horses during exercise causes changes in the permeability of cardiomyocytes and exit enzymes in the blood and can play a key role in the pathogenesis of myocardial dystrophy. Іn sporting horses, after activity in blood serum, activity of AST and LDH increases in blood serum, a tendency to increase activity of creatine kinase (CК) is observed. The cardiac isoenzyme CK (CK‒MB) was detected by a specific marker of myocardial dystrophy in sport horses, since its activity was likely to increase in the blood of all experimental groups of animals. A less specific marker of myocardial damage was the activity of hydroxybutyrate dehydrogenase (LDH‒1) in the blood, since the probable difference was established only in the Westphalian horses. Investigating the activity of AST, CK and CK-MB in horses can serve for differential diagnosis of rhabdomyolysis syndrome and damage to heart muscle cells, in particular for myocardial dystrophy.

Troponin levels in patients with stable CAD

IntroductionCardiac troponins are known as specific markers of myocardial damage. Their elevation in the serum is not always related to acute myocardial ischaemia. The increased sensitivity of diagnostic kits has resulted in an increase in the number of positive results in patients without acute coronary syndrome (ACS). Study objectivesTo determine the level of highly sensitive troponin T (hs TnT) in stable patients (without ACS) before selective coronarography (SCG) and to determine the correlation between hs TnT values and the extent of atherosclerotic damage to the coronary arteries. MethodologyWe studied a group of 251 consecutive patients with indications for SCG diagnosis. Indication criteria were stable angina pectoris, shortness of breath, newly diagnosed heart failure, syncope, and ventricular arrhythmia. Exclusion criteria were acute coronary syndrome, including unstable angina pectoris, prior cardiopulmonary resuscitation, cerebrovascular accident (CVA) within the last 6 months, and ongoing sepsis. The hs TnT value was determined before SCG (normal range, 0–0.013μg/l). Monitored parameters included coronary angiography (70% stenosis of coronary artery diameter was considered significant coronary disease), age, gender, heart rate, and serum creatinine levels. The study included 182 patients with normal renal function and 69 patients with renal insufficiency. The results were processed using STATISTICA (version 12), StatSoft©, Inc. (2013). ResultsThe average age of the studied population was 69.6±10.3 years (median, 70 years); 33% of patients were women. The serum level of hs TnT for the entire population was 0.031±0.091μg/l (0.014). A positive hs TnT was noted in 133 patients. The population study group consisted of 121 patients with normal coronary arteries or with insignificant atherosclerotic disease. Significant damage involving one or more arteries was present in 130 patients. In the subgroup with significant coronary disease, we found a significantly higher hs TnT level than in the group of patients without significant coronary disease: 0.043±0.125μg/l (0.018) vs. 0.019±0.018μg/l (0.013) (p=0.008) (Mann–Whitney test).Significantly higher troponin levels were found in the group of patients with renal insufficiency than in the subgroup with normal creatinine levels: 0.057±0.150μg/l (0.023) vs. 0.022±0.053μg/l (0.012), respectively (p<0.05) (Mann–Whitney test). ConclusionSlightly elevated serum troponin T levels are common in patients with stable coronary artery disease (CAD). We observed a significant correlation between the level of troponin and the presence of atherosclerotic damage to the coronary arteries. A significant correlation between the value of troponin and the extent of atherosclerotic damage (in terms of the number of damaged arteries) could not be demonstrated. On the basis of our findings, the absolute level of troponin T in patients with stable CAD must be interpreted with caution, especially in patients who also have renal insufficiency. Determination of basal troponin T levels in patients with stable CAD is reasonable as they may be used for comparison in case of change in a patient's clinical condition.

ABILITY OF N(2)-L-ALANYL-L-GLUTAMINE TO RESTORE THE FUNCTION OF ISCHEMIC MYOCARD

The purpose. The goal of this study was to assess the revitalizing effects of N(2)-L-alanyl-L-glutamine («Dipeptiven») on ischemic heart rate. Materials and methods. Isolated hearts of laboratory rats were perfused by Langendorff method (n=7). After global cardioplegic ischemia hearts of experimental group were perfused by standard solution with N(2)-L-alanyl-L-glutamine. Control group was excluded from the pharmaceuticals on reperfusion. Physiological indices of the hearts were fixed. Classic and highly specific markers of myocardial damage were studied by using biochemistry methods and ELISA. NADH dynamics in the myocardial tissue were also recorded. Main Results. Levels of troponin I and NO were significantly lower than baseline and control values. Changes in intracellular translocation enzymes fluctuated at low values and were not significantly different from control during reperfusion, but significantly higher than the original translocation. Level of H-FABP and formation of peroxides were significantly higher in compares with original values. Respiratory chain of both groups was overloaded by electrons during the ischemia. Conclusions . The structure of contractile proteins was stabilized by reperfusion solution with N(2)-L-alanyl-Lglutamine. However, protection of cardiomyocytes was ineffective from oxidative stress. «Dipeptiven» should be used in combination with other pharmaceuticals.

DIAGNOSTIC SIGNIFICANCE OF OPTICAL MYOCARDIAL BIOPSY TO ASSESS THE SEVERITY OF ISCHEMIC AND REPERFUSION INJURY

Purpose. To determine whether laser induced fluorescence is significant for the diagnostics of ischemic and reperfusion injury of isolated heart in a cardioplegic arrest conditions. Materials and methods. Isolated hearts (n=14) of Wistar rats (♂) were perfused by Langendorff method. The experimental and control groups included hearts with or without intracoronary injection of Neoton in reperfusion period, respectively. Continuous monitoring of the hearts was performed using the LAKK-M device. We recorded the dynamics of fluorescence of NADH, pyridoxine and flavins. We also fixed physiological indices of the hearts. By using ELISA, we studied the perfusate for release of both classic and highly specific markers of myocardial damage in coronary arteries. Results. The highest correlation coefficients were obtained between Kf of NADH and Heart-FABP, Troponin I, and the total concentration оf peroxides: r=0.76, r=0.63, r=-0.83 respectively. Neoton prevented energy shortage that contributed to the increase in shift of NAD/NADH to the right and reduction of oxidative stress. Conclusions. The optical biopsy is a promising method for diagnostics of ischemic and reperfusion injury.

Abstract 19747: The Effect of Internal vs. External Shocks on Myocardial Injury in an Animal Model of Myocardial Infarction

Introduction: ICD use early after myocardial infarction (MI) has not proven advantageous, possibly in part due to myocardial injury associated with intracardiac defibrillation shocks. Previous studies have reported myocardial injury with internal defibrillation, but external defibrillation from the wearable cardioverter defibrillator (WCD) has not been investigated. The goal of this study was to determine the acute damage to the heart caused by external defibrillation from the WCD as compared to an ICD in an animal model of myocardial infarction (MI) using typical energy levels and times to shock. Methods: Two weeks after MI creation, 20 pigs were anesthetized and induced into VF through direct current applied to the right ventricular endocardium via an implanted transvenous lead. Control animals received 20-J internal shocks from the dual-coil defibrillator lead after 30 seconds of VF, while experimental animals received 150-J external shocks from a WCD after 45 seconds of VF. Each animal received a total of five consecutive internal or external shocks. Blood samples were collected at baseline (prior to first shock), immediately after the last shock, and at 4- and 24-hours post-shocks to determine myocardial biomarkers. Animals that did not survive 24 hours, control animals that had to be rescue-defibrillated externally, or those requiring &gt;5 shocks were excluded from analysis (n=6, 3 per arm). Differences were determined using t-tests. Results: Troponin I (cTnI), a specific marker of myocardial damage, was elevated above baseline in both the ICD (n = 7) and WCD (n = 7) groups at the 4 hr and 24 hr post-shock time points (Figure). However, the cTnI at 4 hr and 24 hr was significantly higher in the ICD control group as compared to the WCD (p &lt; 0.05). Conclusions: In an animal model of myocardial injury, cardiac-specific cTnI increases are significantly greater following internal 20-J shocks than external 150-J shocks, indicating less myocardial damage with external shocks.

Clinical use of cardiac troponins in dogs.

Abstract Cardiac troponins are sensitive and specific markers of myocardial damage. They have been shown to be elevated in a number of primary cardiac and non-cardiac conditions. In cardiomyopathies, they are useful for detecting occult disease, and can provide prognostic information. They can be used to detect myocardial damage caused by the administration of doxorubicin, and have been shown to be elevated in cases of intoxication, as well as after anaesthesia. Other diseases that have been shown to increase troponin levels include gastric dilatation volvulus, pyometra and brachycephalic obstructive syndrome, as well as infectious diseases, including dirofilariasias, babesiosis and ehrlichiosis.

The Diagnostic Utility of Cardiac Biomarkers in Dialysis Patients

Mortality in dialysis patients remains high due to excessive cardiovascular disease burden from coronary artery disease, left ventricular hypertrophy, and heart failure. Thus, cardiovascular risk stratification is an important aspect in managing dialysis patients; it may enable early identification of high-risk patients to optimize therapeutic interventions that may ultimately lower their cardiovascular morbidity and mortality. In particular, serum cardiac biomarkers that are readily measured, inexpensive, reproducible with high sensitivity and specificity, may have potential for cardiovascular risk prediction and stratification. Cardiac troponin represents a highly sensitive and specific marker of myocardial damage and is a current gold standard test for diagnosing acute myocardial infarction in the general population. On the other hand, natriuretic peptides, released from the heart secondary to increased left ventricular wall stress, have emerged as a diagnostic marker for heart failure in the general population. These two biomarkers reflect unique pathology of the myocardium and are powerful prognostic markers in the dialysis population. This article reviews the diagnostic potentials of these two cardiac biomarkers and their clinical application in the dialysis population.

Troponin T levels in patients with acute heart failure: clinical and prognostic significance of their detection and release during hospitalisation

Myocardial injury during an episode of acute heart failure (AHF) may be important for patents' outcome. We hypothesised that an increase of cardiac troponin levels (cTnT) during hospitalisation, in patients with undetectable levels on admission (cTnT release), may be a more specific marker of myocardial damage. With this aim, we assessed the clinical and prognostic significance of high serum cTnT levels at the time of admission and that of cTnT release in 198 consecutive patients admitted for AHF and with no signs of acute coronary syndrome. cTnT levels were serially measured at the time of admission, and after 6 and 12 h, in 198 consecutive patients admitted for AHF and with no signs of acute coronary syndrome. cTnT was detectable (>0.01 ng/mL) in 102 patients (52 %) and positive for myocardial necrosis (>0.03 ng/mL) in 78 patients (39 %). Negative cTnT at the time of admission became positive at 6 and/or 12 h in 36 (18 %) patients. Patients with increased cTnT levels were more likely to have coronary artery disease, hypertension, diabetes, and renal dysfunction. During a median follow-up duration of 247 days (IQR 96-480 days), the detection of increased cTnT levels was associated with a higher rate of all-cause deaths and, for cTnT release, all-cause death and cardiovascular rehospitalisation rate. CTnT release was an independent predictor of all-cause death and cardiovascular rehospitalisation, along with glomerular filtration rate, and the administration of inotropic agents during the initial hospitalisation. Increased cTnT levels are a frequent finding in patients with AHF. They are more likely to occur in patients with comorbidities and are associated with poorer outcomes. cTnT release is an independent predictor of poorer outcomes.

Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in zucker diabetic fatty rats with metabolic syndrome

This study investigated whether telmisartan, a selective angiotensin type 1 (AT1) receptor antagonist and gamma peroxisome proliferator-activated receptor (PPAR-γ) partial agonist, reduces myocardial ischaemia/reperfusion (I/R) injury in an experimental model of metabolic syndrome. Zucker Diabetic Fatty (ZDF) rats were treated for 3 weeks with telmisartan at doses of 2, 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25-min occlusion of the left descending coronary artery followed by 2-h reperfusion (I/R). Telmisartan reduced the extension of the infarct size in a dose-dependent fashion and decreased the levels of plasma troponin I, a specific marker of myocardial damage. Telmisartan also caused a dose-dependent increase in adiponectin both in plasma and cardiac tissue of infarcted ZDF rats. These levels were minimally increased (p < 0.05 vs. vehicle) by telmisartan 7 mg/kg/day and reached the maximum values with the highest dose of 12 mg/kg/day (p < 0.01 vs. vehicle). In contrast, within the infarcted tissue telmisartan decreased the expression of markers of inflammation such as the transcription factor NF-κB, the toll-like receptors TLR2 and TLR4 as well as TNF-α cytokine. Nitrosative stress was maximal in vehicle-treated infarcted hearts as evidenced by increased expression of iNOS, which was almost abolished after treatement with telmisartan. Treatment of ZDF rats for 3 weeks with telmisartan, a dual angiotensin II receptor antagonist and partial PPAR-γ receptor agonist, resulted in a significant reduction of myocardial damage induced by I/R and was associated with increased adiponectin and a decrease in inflammatory markers.

Cardiac troponin I levels after cardiac surgery as predictor for in-hospital mortality☆

Troponin is a specific marker of myocardial damage. Increased troponins, however, are observed after almost all cardiac surgery. The clinical significance of this elevation is controversial. The aim of this study was to evaluate if troponin I (cTnI) measured 1 h after cardiac surgery provides additional information to identify patients at risk for hospital mortality. Nine hundred and thirty-eight patients undergoing cardiac surgery between October 2006 and June 2008 served as development set. This group included 688 isolated CABGs and 250 valvular (+CABG) operations, and cTnI levels were measured 1 h (cTnI) after surgery. Hospital mortality, defined as death occurring at the Radboud University Nijmegen Medical Centre (UMCN) at any time after surgery, is the studied outcome. To assess the value of cTnI as a predictor for hospital mortality, receiver-operator characteristic (ROC) curves were used. The Youden-index was used for identifying the best cut-off point. Five hundred and seventy-nine patients undergoing cardiac surgery between July 2008 and February 2009 served as validation set. The median cTnI level was 1.3 microg/l, 75% inter-quartile range (IQR) 0.68-2.59 microg/l. Ten patients (1.1%) died, cTnI release of the dead, median: 6.8 microg/l was significantly higher than the measured values in the group of survivors, median: 1.3 microg/l (P<0.001). Regression analysis showed a significant correlation between cTnI and hospital mortality (P<0.001). The ROC indicates a cTnI level of 4.25 microg/l with a ROC of 0.80 as optimal cut-off point for predicting hospital mortality, with a sensitivity of 70% and a specificity of 89%. Addition of type of surgery, isolated CABG vs. valve surgery, acute vs. elective surgery and EuroSCORE class did not improve the ROCs. In the validation set, the median cTnI level was 1.17 microg/l. Fifty-six patients had a cTnI level >4.25 microg/l. Of the 579 patients, 11 patients (1.8%) died, six of them had a cTnI level >4.25 microg/l. Postoperative cTnI level, measured within the first hour after cardiac surgery, can identify a subgroup of patients with increased risk for hospital mortality. These patients may benefit from better monitoring, eventually with specific diagnostic and therapeutic interventions.

Dose-Dense (dd) Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel (P) with Trastuzumab (T) and Lapatinib (L) in Early Breast Cancer (EBC); Troponin I and C-Reactive Protein as Biomarkers of Cardiotoxicity.

Abstract BackgroundThe early detection of cardiotoxicity and congestive heart failure (CHF) from anthracyclines and anti-HER2 agents is currently limited to measuring changes in left ventricular ejection fraction (LVEF) at arbitrary time points. This approach has limited sensitivity and specificity and has led to the investigation of putative biomarkers such as cardiac Troponin I (TnI), a highly specific marker of myocardial damage and C-reactive protein (CRP), a sensitive inflammatory marker. In a pre-planned analysis we investigated these as biomarkers of cardiotoxicity within a prospective study testing the feasibility of ddAC- followed by weekly P with T and L.Materials and MethodsPatients (pts) with HER2+ EBC enrolled at MSKCC and DF/HCC and received ddAC (A 60mg/m2 + C 600mg/m2) x 4 → weekly P (80mg/m2) x 12 + T + L (1000mg/day). T+L continued for a total of 1yr. At baseline pts had LVEF ≥50%. Pts with unstable angina, CHF, recent MI, uncontrolled arrhythmia, grade 3 QT prolongation were excluded. LVEF was assessed by MUGA scan at mths 0, 2, 6, 9 and 18. TnI and CRP were measured every 2 wks right before treatment (Rx) during ddAC-PTL, then at mths 6, 9 and 18. TnI was categorized as “undetectable” (&amp;lt; 0.06 ng/ml; MSKCC, &amp;lt;0.04 ng/ml; DF/HCC), “minimally elevated” (&amp;lt;0.31 ng/ml) and “elevated” (&amp;gt;0.31ng/ml). Elevated CRP was defined as (&amp;gt;0.8mg/dl; MSKCC, &amp;gt;0.3mg/dl; DF/HCC). Investigators were blinded to these results until pts completed 18mth follow-up (F/U).ResultsFrom Apr 07- Apr 08, 95 pts were enrolled; 39/95 (41%) withdrew due to PTL toxicities (incl. 3 with asymptomatic LVEF (aLVEF) declines and 3 with CHF). Final biomarker results were available in 84 pts (88%) and 11 pts (12%) continue on study. During Rx, minimal elevations in TnI occurred in 55 pts (65%). One pt had ↑TnI above normal range with AC#4; MUGA 1 wk later was unchanged (LVEF 75%), but she died from sepsis during subsequent Rx without evidence of CHF. Elevations in TnI occurred only during chemoRx and no pt had a ↑TnI during TL or at 18mth F/U. Of 55pts with elevated TnI, 25 (45%) had aLVEF declines (3 ↓ ≥16%, 10 ↓ 10-15%, 12 ↓ 5&amp;lt;10%). Of 29 pts with undetectable TnI, 7 (24%) had aLVEF declines (1 ↓ ≥16%, 4 ↓ 10-15%, 2↓ 5&amp;lt;10%). Elevations in CRP occurred in 61/84 (73%) pts during chemoRx but only in 22 (26%) during TL or at 18mth F/U. Three pts discontinued Rx for aLVEF ↓ at mths 4, 5 and 7 respectively; 2 (66%) had rises in CRP and 2 had minimal elevation in TnI. Three pts developed CHF at mths 3, 6, and 12 respectively, all had rises in CRP; 1 pt had a single ↑TnI of 0.08 ng/ml during chemoRx, and 2pts had no ↑TnIs.ConclusionsIn pts receiving ddAC-PTL fluctuations in TnI and CRP are common but do not persist after chemoRx (during TL). These biomarkers do not appear to predict for CHF. One possibility is that the timing of the drawing of these biomarkers (immediately preceding the specified treatment cycle and after Rx completion) may have been suboptimal. We plan to assess for potential biomarkers by assessing both immediately preceding and following therapy in a planned trial. Updated results will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3088.

Exercise-Induced Cardiac Troponin T Release

Cardiac troponin T (cTnT) is a highly specific marker of myocardial damage and used clinically in the diagnosis of acute myocardial infarction (AMI). Release of cTnT has been demonstrated in several small studies after endurance exercise. The purpose of this study was to explore, using a meta-analytic approach, the incidence of postexercise cTnT release after endurance exercise. Articles identified via Pubmed, SportDiscus, and Embase (1997-2006) searches using the key words cardiac troponin T, cTnT, cardiac biomarkers, and exercise; a search of bibliographies; and consultation with experts in the field were entered into a random-effects meta-analysis. We identified 26 relevant studies (1120 cases). Age, gender, and body mass of participants, as well as exercise mode and duration, were explored as possible moderator variables with meta-regressions. Postexercise cTnT levels exceeded the assay detection limit in 47% of participants (95% CI = 39-56%). The detection of postexercise cTnT after cycling events was approximately half that of running events (27 vs 52%, P = 0.042). The detection of postexercise cTnT decreased slightly as event duration increased (P = 0.022) and mean body mass decreased (P = 0.0033). Postexercise detection of cTnT was not affected by age (P= 0.309) and was only slightly higher for studies with more males in the sample (P = 0.028). Exercise-induced cTnT release is apparent in almost half of the endurance athletes who have been studied to date. Relatively heavy individuals competing in shorter endurance events, primarily running marathons, are slightly more likely to demonstrate elevated cTnT postexercise than other athletes. These data are useful for clinicians evaluating athletes with cTnT elevations after competitive endurance exercise events.

Diagnostic accuracy of cardiac markers for myocardial damage after radiofrequency catheter ablation

This study compares serum markers of myocardial damage incurred during radiofrequency catheter ablation (RFCA). Blood was sampled from 34 patients with atrial flutter (n = 16), atrioventricular nodal reentrant tachycardia (AVNRT; n = 13), and Wolff-Parkinson-White syndrome (WPW; n = 5) to measure creatine kinase MB subfraction (CK-MB), human heart-type fatty acid protein (h-FABP), and cardiac troponin T (cTnT) values at baseline and after RFCA. The controls comprised 12 patients without significant elevation of all myocardial markers during electrophysiological study (EPS) without RFCA. h-FABP values did not elevate significantly, whereas CK-MB and cTnT demonstrated significant change after RFCA (P < 0.001). Neither peak h-FABP nor CK-MB correlated with following RFCA parameters: delivery duration, number of RFCA discharges, and cumulative RFCA energy. In contrast, correlations were significant between mean peak values of cTnT and these RFCA parameters (all P < 0.05). The sensitivity (71.6%) and specificity (35.6%) of h-FABP were inferior to those of cTnT (93.3% and 89.8%, respectively). h-FABP is an insensitive and less specific marker of myocardial damage in RFCA much along the lines of CK-MB and when compared with the proven accuracy of cTnT.

Troponin I as a Biomarker of Cardiac Injury in Neonates with Idiopathic Respiratory Distress

Troponin I (TnI), an inhibitory protein complex located on the actin filament of cardiac muscle, has become a specific marker of myocardial damage. Troponin has been studied in a wide range of clinical settings. However, many questions are still unanswered, especially in preterm neonates with the most common pathology at birth, such as idiopathic respiratory distress syndrome (IRDS). The aim of this study was to establish a reference range for cardiac TnI for healthy preterm infants and serum levels in sick preterm infants with IRDS. Echocardiography was performed and TnI serum levels were measured at a median age of 62 hours of life in three groups of healthy preterm infants (n = 10), and ventilated infants with moderate (n = 15) and severe IRDS (n = 15). Ventilated infants with idiopathic moderate IRDS had significantly different cardiac parameters (R/L ejection fraction, R/L stroke volume, R/L cardiac output; p < 0.05) and significantly higher cardiac TnI levels than healthy infants (0.037 versus 0.01 microg/mL; p < 0.05). Furthermore, infants with severe IRDS had higher TnI concentrations than infants with moderate IRDS (0.26 versus 0.037 microg/mL; p < 0.05). The results of this study show that increased TnI serum levels in sick preterm infants with IRDS are explained by myocardial injury or dysfunction due to impaired arterial oxygenation or reduction in cardiac output during treatment with mechanical ventilation. These results suggest that cardiac TnI may be a useful, specific marker for myocardial damage in preterm neonates with IRDS.

Cardiac Troponins as Indicators of Acute Myocardial Damage in Dogs

Cardiac troponin I (cTnI) and T (cTnT) have a high sequence homology across phyla and are sensitive and specific markers of myocardial damage. The purpose of this study was to evaluate the Cardiac Reader, a human point‐of‐care system for the determination of cTnT and myoglobin, and the Abbott Axsym System for the determination of cTnI and creatine kinase isoenzyme MB (CK‐MB) in healthy dogs and in dogs at risk for acute myocardial damage because of gastric dilatationvolvulus (GDV) and blunt chest trauma (BCT). In healthy dogs (n = 56), cTnI was below detection limits (&lt; 0.1 μg/L) in 35 of 56 dogs (reference range 0‐0.7 μg/L), and cTnT was not measurable (&lt; 0.05 ng/mL) in all but 1 dog. At presentation, cTnI, CK‐MB, myoglobin, and lactic acid were all significantly higher in dogs with GDV (n = 28) and BCT (n = 8) than in control dogs (P &lt; .001), but cTnT was significantly higher only in dogs with BCT (P= .033). Increased cTnI or cTnT values were found in 26 of 28 (highest values 1.1–369 μg/L) and 16 of 28 dogs (0.1‐1.7 ng/mL) with GDV, and in 6 of 8 (2.3–82.4 μg/L) and 3 of 8 dogs (0.1‐0.29 ng/mL) with BCT, respectively. In dogs suffering from GDV, cTnI and cTnT increased further within the first 48 hours (P &lt; .001). Increased cardiac troponins suggestive of myocardial damage occurred in 93% of dogs with GDV and 75% with BCT. cTnI appeared more sensitive, but cTnT may be a negative prognostic indicator in GDV. Both systems tested seemed applicable for the measurement of canine cardiac troponins, with the Cardiac Reader particularly suitable for use in emergency settings.