Increase In cTnI Research Articles

148 Paediatric cardiac arrest: is there any myocardial damage in paediatric patients when adult defibrillation energies are administered?

PurposeWhen attempting defibrillation in an out-of-hospital paediatric patient, the use of a reduced energy is currently recommended in the resuscitation guidelines due to concerns surrounding potential myocardial damage. The purpose...

Ascorbic acid-mediated enhanced cardiomyocyte differentiation of mouse ES-cells involves interplay of DNA methylation and multiple-signals

Embryonic stem cells (ES-cells) provide a good model system to study lineage-specific differentiation. Though, the differentiation of ES-cells to cardiomyocytes is documented, a clear understanding of the molecular mechanism of differentiation and improved functional-differentiation efficiency are yet to be achieved. In this regard, ascorbic acid (Aa) is shown to be one of the effective cardiac inducers in ES-cells. But, its mechanism is poorly understood. We therefore, investigated the mechanism of Aa-mediated cardiomyocyte differentiation of ES-cells. Here, we describe the potential involvement of epigenetic (DNA methylation) as well as integrin- and Erk- signaling systems during cardiomyocyte differentiation. Transgenic GS-2 ES-cells and wild-type D3 ES-cells were differentiated to cardiomyocytes, in the presence or absence of Aa and with or without inhibitors of Erk-, collagen- and integrin- pathways. At specific time points, differentiated states of ES-cells were scored by gene expression analyses and the proportion of functional cTnI+ cardiomyocytes. DNA methylation changes of Isl-1, BMP-2, GATA-4 and α-MHC in cardiogenic cells, following stimulation with Aa, were analyzed by using methylation specific PCR (MSP). We observed that Aa, when applied in initial phase of ES-cell differentiation, consistently enhanced cardiac differentiation (99%) over that observed during spontaneous differentiation (70%). This was associated with enhanced expressions of cardiogenesis-associated genes. A two-fold increase in cTnI+ cells was observed, with appropriate myofibril arrangement. The observed effect of Aa was due to enhanced collagen and integrin signaling, coupled with a high p-ERK1/2 expression, downstream. Besides, the involvement of DNA methylation in regulating the expression of cardiac genes i.e., Isl-1 and α-MHC was also observed. Overall, this study, for the first time, demonstrates that Aa-mediated cardiac enhancement is brought about, mechanistically, through the interplay of epigenetic changes in DNA methylation of cardiac genes (Isl-1 and α-MHC) and integrin signaling system.

Population pharmacokinetic modelling of doxorubicin and doxorubicinol in children with cancer: is there a relationship with cardiac troponin profiles?

Anthracyclines are a mainstay of the treatment of several childhood malignancies, but their utility is limited by dose-related cardiotoxicity. This study is aimed to explore the link between exposure of paediatric cancer patients to doxorubicin and its metabolite doxorubicinol, and cardiac troponin I (cTnI). In a prospective pilot study plasma doxorubicin, doxorubicinol, and cTnI concentrations were measured in samples from children undergoing cancer chemotherapy. A mixed-effects population pharmacokinetic model for doxorubicin and doxorubicinol and in combination with a turn-over model for cTnI were developed. Seventeen patients, aged 3.4-14.7year, treated for a variety of cancers had 99 doxorubicin and 119 doxorubicinol concentrations analysed from samples drawn between 0.5 and 336h after the start of the infusion. Eleven patients had received previous doses of anthracyclines, with a median cumulative prior dose of 90mg/m2 (range 0-225mg/m2). The median administered doxorubicin dose was 30mg/m2 (range 25-75mg/m2). Doxorubicin disposition was described by a three-compartment model with first-order elimination and metabolism to doxorubicinol. Body surface area was related to all clearance and distribution parameters and age further influenced clearance (CL, 58.7L/h/1.8m2 for an average 8.4-year-old patient). Combined doxorubicin and metabolite exposure stimulated a temporary increase in cTnI in plasma, with a concentration of 11.8µg/L required to achieve half-maximal effect. Prior cumulative anthracycline dosage received by patients was predictive of an increased cTnI baseline prior to a new doxorubicin dose. Prior anthracycline exposure increased baseline cTnI in a dose-dependent manner, consistent with the known cumulative risk of anthracycline exposure-induced cardiotoxicity.

Impact of Smoking on Circulating Cardiac Troponin I Concentrations and Cardiovascular Events in the General Population: The HUNT Study (Nord-Trøndelag Health Study).

Both tobacco smoking and circulating cardiac troponin I (cTnI) levels are associated with the risk of acute myocardial infarction, heart failure, and cardiovascular death. However, whether cTnI levels differ according to smoking status and whether smoking modifies the prognostic relationship between cTnI and outcomes remain unclear. Using data from a large, population-based cohort, we assessed the association between smoking and cTnI and the impact of smoking on the associations between cTnI levels and the incidence of acute myocardial infarction, heart failure, and cardiovascular death. cTnI was measured with a high-sensitivity assay in 3824 never smokers, 2341 former smokers, and 2550 current smokers participating in the prospective observational HUNT Study (Nord-Trøndelag Health Study). All subjects were free from known prior cardiovascular disease and diabetes mellitus at baseline. The age of the participants ranged from 19 to 94 years; 55.5% were women. Current smokers exhibited significantly lower levels of cTnI (median, 2.9 ng/L; interquartile range, 2.0-4.1 ng/L) than never smokers (3.2 ng/L; interquartile range, 2.2-4.7 ng/L; P<0.001) and former smokers (3.4 ng/L; interquartile range, 2.3-5.0 ng/L; P<0.001). This association remained significant after adjustment for potential confounders (B=-0.098; 95% confidence interval, -0.129 to -0.068). We observed an association between increasing concentrations of cTnI and clinical end points in the total study cohort (adjusted hazard ratio per log unit increase in cTnI, 1.41; 95% confidence interval, 1.29-1.54). This association was attenuated for current smokers (hazard ratio, 1.17; 95% confidence interval, 0.98-1.40) and was significantly weaker than in never/former smokers (P for interaction=0.003). Prognostic accuracy, as assessed by C statistics, was significantly lower in current smokers than in never smokers (P<0.001). In addition, cTnI provided no incremental prognostic information to the Framingham Cardiovascular Disease risk score in current smokers (P=0.08). Current smoking is associated with lower concentrations of cTnI, suggesting that substances in tobacco smoke may affect cardiomyocyte injury. The association between cTnI levels and cardiovascular end points is stronger in never/former smokers than in current smokers, compatible with the theory that the detrimental cardiovascular impact of current smoking is mediated via mechanisms other than subclinical myocardial injury.

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction

Context: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes.Objective: The study examined the early release kinetics of TnTuORF.Materials and methods: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n = 31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH).Results: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18 ng/L versus 27 ng/L; cTnI median: 15 ng/L versus 25 ng/L). TnTuORF showed no variation.Discussion: We observed a significantly greater increase in cTnI compared with cTnT.Conclusion: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.

Association of chronic kidney disease with periprocedural myocardial injury after elective stent implantation: A single center prospective cohort study.

Coronary artery disease (CAD) is the leading cause of mortality in patients with chronic kidney disease (CKD). Patients with CKD who undergo percutaneous coronary intervention (PCI) may have more ischemic events than patients without CKD. The aim of our study was to determine the incidence of periprocedural myocardial injury (PMI) after elective stent implantation in patients with CKD using the Third Joint ESC/ACCF/AHA/WHF PMI definition.In a single center prospective cohort study, we enrolled 344 consecutive patients who underwent elective PCI in a period of 39 months. Serum troponin I (cTnI) concentrations were measured at baseline and at 8 and 16 hours after PCI. Periprocedural increase of cTnI, according to the most recent PMI definition, was used to define both the presence and intensity of PMI. Patients were further stratified according to the estimated glomerular filtration rate (eGFR) using 4 variable Modification of Diet in Renal Disease (MDRD) equation: control group with eGFR >90 mL/min/1.73 m2 and the CKD group with eGFR < 90 mL/min/1.73 m2, with further subdivision according to the CKD stage.We found no significant difference in the incidence as well as intensity of the PMI in the control (>90 mL/min/1.73 m2) and the CKD group (<90 mL/min/1.73 m2) both 8 and 16 hours after PCI. When the CKD patients were further subdivided according to their CKD stage, there was again no difference in the intensity or incidence of PMI compared to the control group. Further analyses of our data showed angina pectoris CCS IV, bare metal stent (BMS) implantation, and treatment with angiotensin-converting enzyme inhibitors (ACEI) as independent predictors of PMI. Furthermore, the presence of hypertension was inversely related to the occurrence of PMI.Applying the new guidelines for PMI and using the eGFR equation most suitable for our patients, we found no association between PMI and CKD. Further analyses showed other factors that could potentially influence the occurrence of PMI.

Frequency of Increase in Cardiac Troponin Levels After Peripheral Arterial Operations (Carotid Endarterectomy, Abdominal Aorta Procedure, Distal Bypass) and Their Effect on Medical Management

The utility of measuring cardiac troponins (cTn) in asymptomatic patients during the perioperative period has been controversial. In the present substudy of the Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery Trial (NCT01558596), we hypothesized that surveillance of myocardial injury with cTnI in the perioperative period would lead to initiation or intensification of medical therapies for coronary artery disease. Increases in cTnI ≥0.01μg/l in the perioperative period were considered clinically significant. Intensification of medical therapy was defined as initiation of aspirin or initiation or increases in the dose of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers, statins, or β blockers and was left to the discretion of treating physicians. From June 2011 to April 2015, a total of 185 patients (mean age 68 ± 7 years, 100% men) were enrolled in the trial. A total of 28 patients (15%) had significant increases in cTnI after vascular surgery, and 38 (20.5%) had their medical therapies intensified in the perioperative period. Among patients with increases in cTnI, 11 (39%) had intensification of medical therapy versus 27 patients (17%) with no or smaller increases in cTnI (p= 0.02). Among those patients with ΔcTnI ≥0.01μg/l, hospital readmissions at 3 to 6months were 7.6% for the intensification group versus 25% for the no intensification group (p= 0.18). Mortality rate at 6months was low in both groups (2.6% vs 0%, respectively, p= 0.13). In conclusion, among patients undergoing vascular surgery, perioperative increases in cTn were associated with initiation or intensification of medical therapies for coronary artery disease at the time of discharge.

Assessment of Cardiac Troponin I Responses in Nonhuman Primates during Restraint, Blood Collection, and Dosing in Preclinical Safety Studies.

Limited information has been published on the use of cardiac troponin I (cTnI) as a biomarker of cardiac injury in monkeys. The purpose of these studies was to characterize the cTnI response seen in cynomolgus macaques during routine dosing and blood collection procedures typically used in preclinical safety studies and to better understand the pathogenesis of this response. We measured cTnI using two different methods, the Siemens Immulite cTnI assay and the more sensitive Siemens Troponin I-Ultra assay. We were able to demonstrate that after oral, subcutaneous, or intravenous dosing of common vehicles, as well as serial chair restraint for venipuncture blood collection, that minimal to mild transient increases in cTnI could be detected in monkeys with both assays. cTnI values typically peaked at 2, 3, 4, or 6 hr after sham dosing and returned to baseline at 22 or 24 hr. In addition, marked increases in heart rate (HR) and blood pressure (BP) occurred in monkeys during the restraint procedures, which likely initiated the cTnI release in these animals. Monkeys that were very well acclimated to the chairing procedures and had vascular access ports for blood sampling did not have marked increases in HRs and BP or increases in cTnI.

Effect of remote ischemic preconditioning on myocardial injury and inflammatory response induced by ablation for atrial fibrillation: A randomized controlled trial

BackgroundRemote ischemic preconditioning (RIPC) has been suggested to reduce postoperative release of cardiac and inflammatory markers in patients undergoing cardiac surgery. This study aimed to evaluate the effect of RIPC on nonischemic myocardial damage and inflammatory response in patients undergoing radiofrequency catheter ablation for paroxysmal atrial fibrillation (AF). MethodsSeventy-two patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation were randomized into RIPC or control groups. RIPC (intermittent arm ischemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) was performed once daily on 2 consecutive days before the ablation and immediately before ablation. Cardiac troponin-I (cTnI), high-sensitive C-reactive protein (hs-CRP), and interleukin (IL)-6 levels were measured before RIPC/sham RIPC, after the ablation, and 24 and 72h later. The early recurrence of atrial fibrillation (ERAF) in the two groups was observed over the subsequent 3months. ResultsRadiofrequency ablation resulted in a significant rise in cTnI, hs-CRP, and IL-6 in both groups, which persisted for 72h. The RIPC group showed a lower increase in cTnI (P<0.001), hs-CRP (P=0.003), and IL-6 (P=0.008) than the control and tended to have a lower risk of ERAF (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.32–1.88). ConclusionsThese results show that RIPC before ablation for paroxysmal AF significantly reduces the increase in cTnI, hs-CRP, and IL-6 associated with the procedure and results in a lower risk of ERAF. These findings suggest that RIPC could provide cardioprotection against nonischemic myocardial damage.

Abstract 4639: Reproductive hormone levels modulate doxorubicin induced cardiomyopathy in female tumor-bearing spontaneously hypertensive rats

Abstract The anthracycline doxorubicin (dox) is known to cause cardiomyopathy, at least in part, through the generation of excess reactive oxygen species (ROS) in the mitochondria. Cardiomyocytes have higher concentrations of mitochondria and lower concentrations of antioxidants, making them more sensitive to excessive ROS. The incidence of dox induced cardiac stress is greater in pre-pubescent and post-menopausal females compared to age-matched males but lower in women of reproductive age. Previous studies have associated gender and age differences in cardiosensitivity with estrogen production. This is the first part of a two part study investigating the role that reproductive hormones (estrogen and progesterone) play in dox induced cardiotoxicity in female, tumor-bearing spontaneously hypertensive rats (SHRs). In this portion of the study our aim was to evaluate the effect of hormone therapy on cardioprotection from dox. Reproductively mature ovariectomized animals were implanted with time-release pellets containing a “carrier-matrix” (vehicle), 17-β-estradiol (E2), progesterone (P4), Tamoxifen (Tam) or combinations thereof. The animals were implanted with cells from an SHR-derived syngeneic breast cancer cell line (SST-2). Tumor-bearing animals were then treated with a single dose of saline or dox and monitored for 12 days. Daily vaginal cytologies were obtained to measure estrous cycle status. Serum was collected throughout the study to correlate estrous phase to E2 and P4 levels and evaluate serum protein cTnI as a biomarker for cardiac injury. In all hormone groups, dox exhibited significant anti-tumor activity and resulted in a net decrease in growth rate compared to saline controls. After 12 days exposure, animals treated with dox and implanted with Tam, Tam+E2 or vehicle pellets showed a significant increase in cTnI, indicative of cardiac damage. Dox treated animals with pellets containing E2, P4 or the combination showed a significant decrease in cTnI, demonstrating potential cardioprotection from reproductive hormone therapy. Furthermore, histopathology of cardiac sections from dox-treated groups displayed lower cardiomyopathy scores in animals that received E2, P4 or the combination of the two. We are currently evaluating additional endpoints for cardiotoxicity and cellular stress to assess the mechanism behind E2 and P4 cardioprotection from chemotherapy. Overall, our findings suggest that the hormones estrogen and progesterone reduce dox-induced cardiotoxicity. Citation Format: Kaytee L. Pokrzywinski, Elliot T. Rosen, Julia Bonanno, Thomas Biel, Delaram Moshkelani, Baikuntha Aryal, Steven Mog, V. Ashutosh Rao. Reproductive hormone levels modulate doxorubicin induced cardiomyopathy in female tumor-bearing spontaneously hypertensive rats. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4639.

Different Prognostic Significance of Cardiac Troponin at Presentation and Peak Cardiac Troponin in Patients with Non-ST Segment Elevation Myocardial Infarction

Objectives: Non-ST elevation myocardial infarction (NSTEMI) is one of the most common manifestations of acute coronary syndromes (ACS). We evaluated the prognostic role of cardiac troponin I (cTnI) at presentation and peak cardiac troponin I in patients with NSTEMI. Methods: We consecutively enrolled 215 subjects presenting with NSTEMI. Subjects were followed up for 1 year. cTnI at presentation and the peak value of cTnI were measured. The primary end point was defined as cardiovascular death, readmission to hospital with heart failure and new ACS. Results: The subjects who presented the primary end point (49 subjects) had significantly increased values of peak cTnI compared to subjects free of cardiovascular events [7.19 (2.97-21.32) vs. 4.09 (1.18-11.85) ng/l; p = 0.002]. Nevertheless, cTnI at presentation did not differ between subjects who presented the primary end point and those free of events (p = 0.39). Multivariate Cox regression analysis after adjustment for confounders revealed by the univariate analysis showed that for an increase in peak cTnI from 1 to 10 ng/l, there is a 60% anticipated increase in the relative risk to present the primary end point (p = 0.04). Conclusion: These findings documented the different prognostic significance of cTnI at presentation and peak cTnI in patients presenting with NSTEMI, and highlighted the importance of monitoring the levels of cTnI in this high-risk population.

2-Deoxy-d-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and BNP as Potential Early Cardiac Safety Biomarkers.

2-Deoxy-d-glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in rats. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity. In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed. Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials.

Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction

ObjectiveSupplemental oxygen therapy may increase myocardial injury following ST-elevation myocardial infarction (STEMI). In this study, we aimed to evaluate the effect of the dose and duration of oxygen exposure on...

Is Local Nitric Oxide Availability Responsible for Myocardial Salvage after Remote Preconditioning?

Background:Remote ischemic preconditioning (RIPC) represents an attractive therapy for myocardial protection, particularly when ischemic events can be anticipated. Although several hypothetic mechanisms have been proposed, no definite molecular pathways have been elucidated.Objective:We evaluated the effect of brachial circulation cuff occlusion on myocardial ischemic tolerance, necrosis, and nitric oxide (NO) in patients with ischemic heart disease undergoing elective percutaneous coronary interventions (PCI).Methods:46 patients were randomly allocated into two groups: control and RIPC before PCI procedures. Electrocardiographic analysis, serum concentrations of troponin I (cTn-I) were measured at baseline and 24 hours after PCI. A blood sample from the atherosclerotic plaque was drawn to determine nitrate and nitrites.Results:RIPC increased the availability of NO in the stented coronary artery. Control patients presented a small but significant increase in cTn-I, whilst it remained unchanged in preconditioned group. The preconditioning maneuver not only preserved but also enhanced the sum of R waves.Conclusions:RIPC induced an intracoronary increase of NO levels associated with a decrease in myocardial damage (measured as no increase in cTn-I) with electrocardiographic increases in the sum of R waves, suggesting an improved myocardium after elective PCI.

2015 AHA Late-Breaking Basic Science Abstracts.

### 23060 ### Validation Of Circulating MicroRnas As Biomarkers In Heart Failure In Two Large Independent Cohorts Antoni Bayes-Genis1, David Lanfear2, Maurice de Ronde3, Josep Lupon1, Joost Leenders4, Elisabet Zamora1, L. Keoki Williams2, De Antonio Marta5, Zhen Liu4, Koos Zwinderman3, Sara-Joan Pinto-Sietsma3, Yigal Pinto3; 1Universitat Autonoma de Barcelona, Barcelona, Spain; 2Henry Ford Hospital, Detroit, MI; 3Academic Med Cntr, Univ of Amsterdam, Amsterdam, Netherlands; 4Mirnext BV, Amsterdam, Netherlands; 5Germans Trias i Pujol Hosp, Badalona, Spain Background: Small studies suggested circulating microRNAs (circmiRs) as biomarkers for Heart Failure (HF). However, standardized approaches and quality assessment are not established, and results have been inconsistent, with little replication between studies. We aimed to implement quality standards to enable comparison between cohorts and assess which circmiRs may add prognostic information in HF. Methods: We measured 15 circmiRs in two independent cohorts totaling >2000 subjects. Cohort I (Barcelona) comprised of n=843 chronic HFrEF patients. Cohort II from Detroit comprised n= 1384 chronic HF patients (892 HFrEF, 492 HFpEF). Each sample was measured in duplicate, and normalized to an abundant and stable circmiR (miR-486-5p). Algorithms were installed to define each circmiR measurement as “valid”, “unmeasurable” or “invalid”. This allowed inclusion of valid low-level circmiR measurements while reducing noise from false amplification signals. Results: In general, between 20–40% of measurements were “invalid”, while miR-499a\_5p and -208a were “unmeasurable” in the majority of patients in both cohorts. Higher levels of circmiRs-133b, -1254, -622, -208a and -499a\_5p were significantly associated with risk of death in both cohorts, with hazard ratios ranging from 1.103 to 1.365 per log increase (p-values 0.001 to 0.05). However, adding these circmiRs to established predictors (age, renal function and NTproBNP) did not further augment the c-stat beyond 0.71 (cohort I) or 0.78 (cohort II). …

Abstract 11457: Surveillance of Perioperative Myocardial Injury With Cardiac Troponins Influences Medical Management at the Time of Hospital Discharge

Background: Current AHA/ACC guidelines recommend against the use of cardiac troponins (cTn) for the surveillance of perioperative myocardial injury (PMI) in asymptomatic patients. We hypothesized that surveillance of PMI with cTnI would lead to initiation or intensification of medical therapies for coronary artery disease (CAD). Methods: The Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery (CRIPES, NCT 01558596) is an ongoing prospective, randomized, sham-controlled phase 2 trial using remote ischemic preconditioning prior to elective vascular procedures. The primary efficacy end-point is the proportion with and magnitude of postoperative increases in cTnI. Cardiac troponins, measured before and after surgery, were available to treating clinicians. Increases above ≥ 0.01 μg/L in the perioperative period were considered clinically significant. Intensification of medical therapy was defined as initiation of aspirin (ASA) or initiation/increases in the dose of angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin-receptor blockers, statins, or beta-blockers. Results: Between June 2011 and April 2015, a total of 185 patients (mean age 68±7, 100% male) were enrolled in the trial. A total of 28 patients (15%) had significant increases in cTnI after vascular surgery and 38 (20.5%) had their medical therapies intensified in the perioperative period. Baseline utilization of medical therapies was high: ASA 86%, statins 75%, beta-blockers 65%, ACEI 48%. The most frequent change in medical therapy in the perioperative period was initiation of ASA (9%). Among patients with substantial increases in cTnI 11 (39%) had intensification of medical therapy versus 27 (17%) in patients with no or smaller increases in cTnI (p=0.02). Using logistic regression analysis to control for subject’s age, history of CAD, CHF, diabetes, high-risk surgery, and revised cardiac risk index, a cTnI increase &gt; 0.01 μg/L remained associated with intensification of medical therapy (odds ratio: 3.2, 95% CI: 1.3-8.3. p=0.014). Conclusions: Among patients undergoing vascular surgery, surveillance of cTn in the perioperative period has value, by altering the clinician’s decisions to either initiate or intensify medical therapies for CAD.

Abstract 16939: Reversible Myocardial Ischemia Sufficient to Produce Transient Stunning Leads to Delayed Cardiac Troponin I Release That Reflects Focal Myocyte Apoptosis in the Absence of Pathological Infarction

Introduction: The release of cardiac troponin I (cTnI) after reversible ischemia is controversial. It has been hypothesized that elevations in serum cTnI in this scenario reflect selective release from an exchangeable pool rather than cellular necrosis since irreversible injury with sarcolemmal membrane disruption does not begin until ischemia exceeds 15 minutes following a total coronary occlusion. Objective: To determine whether cTnI release occurs after a brief coronary occlusion when the duration of ischemia is insufficient to induce myocyte necrosis. Methods: Closed-chest propofol-anesthetized swine (n=10) were subjected to a 10 minute LAD occlusion. Blood sampling was performed to measure serum cTnI concentrations before, during and after ischemia. Myocardial tissue was collected either 1 hour (n=5) or 24 hours (n=5) after reperfusion for pathological assessment of infarction (TTC) and apoptosis (TUNEL). Results: Regional LAD wall thickening was 60 ± 4% at baseline and became dyskinetic during coronary occlusion (-4 ± 2%, p&lt;0.05). One hour after reperfusion, wall thickening improved but remained depressed relative to baseline, indicative of myocardial stunning (37 ± 4%, p&lt;0.05). It returned to normal after 24 hours (59 ± 2%). Serum cTnI was 0.01 ± 0.01 ng/mL at baseline and remained unchanged at the end of ischemia. A slight increase in cTnI was observed 1 hour after reperfusion (0.06 ± 0.02 ng/mL, p&lt;0.05 vs. baseline), followed by a marked elevation at 24 hours (1.02 ± 0.57 ng/mL, p&lt;0.05 vs. baseline). TTC staining demonstrated no evidence of infarction. Heart tissue collected 1 hour after reperfusion demonstrated a regional increase in apoptotic myocytes (LAD: 17.7 ± 3.7 myocytes/cm 2 vs. Remote: 3.1 ± 2.0 myocytes/cm 2 , p&lt;0.05). Myocyte apoptosis normalized 24 hours after reperfusion (LAD: 5.2 ± 2.3 myocytes/cm 2 vs. Remote: 3.6 ± 1.5 myocytes/cm 2 ) when serum cTnI remained elevated. Conclusion: A duration of reversible ischemia compatible with angina can lead to cTnI release that is similar in magnitude to that occurring with myocardial infarction. Rather than infarction or release from an exchangeable cTnI pool, the rise in serum cTnI is delayed and appears to reflect focal programmed myocyte death from apoptosis rather than myocardial necrosis.

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 Application of the Heart Rate Deceleration Capacity Test to Predict Epirubicin-induced Cardiotoxicity.

Objective:To investigate the clinical value of heart rate deceleration capacity (DC) in predicting the risk of epirubicin-induced cardiotoxicity.Methods:The CK-MB and cTnI levels and DC values of 86 patients were examined before chemotherapy and again after 2 and 4 cycles of chemotherapy. Patients were divided into low-risk group (LRG) (40 cases), medium-risk group (26 cases), and high-risk group (HRG) (20 cases) based on the calculated DC values.Results:After 4 cycles of chemotherapy, HRG showed a significantly greater increase in serum CK-MB (17.1 ± 4.9 vs. 14.6 ± 3.7) and cTnI (1.28 ± 0.38 vs. 1.0 ± 0.29) concentrations over the prechemotherapy levels when compared with LRG. After 2 and 4 cycles of chemotherapy, HRG exhibited a significantly greater increase in mean heart rate (2 cycles: 79.6 ± 6.0 vs. 77.6 ± 6.7; 4 cycles: 88.2 ± 10.2 vs. 82.4 ± 6.2) and the supraventricular (2 cycles: 68.9 ± 19.3 vs. 57.2 ± 17.6; 4 cycles: 131.1 ± 29.5 vs. 91.7 ± 16.5) and ventricular arrhythmia counts (2 cycles: 179.0 ± 20.5 vs. 162.3 ± 16.3; 4 cycles: 228.6 ± 44.8 vs. 187.4 ± 22.6) over the prechemotherapy values compared with LRG. When the supraventricular and ventricular arrhythmia counts measured after 4 cycles of chemotherapy were compared with those obtained before chemotherapy, HRG (131.1 ± 29.5 and 228.6 ± 44.8, respectively) showed the largest differences, followed by medium-risk group (107.4 ± 31.9 and 202.0 ± 29.8, respectively) and then LRG (91.7 ± 16.5 and 187.4 ± 22.6, respectively) (P < 0.01). After 4 cycles of chemotherapy, the incidence rates of ventricular arrhythmia greater than Lown's grade 3 (30% vs. 2.5%), QTc (20% vs. 0) elongation, and ST-T (40% vs. 5%) changes in HRG were significantly higher than those observed in LRG (P < 0.05).Conclusions:DC test was shown to be an effective predictor of the risk of epirubicin-induced cardiotoxicity.

Post-exercise cardiac troponin I release and clearance in normal Standardbred racehorses.

There are currently no studies detailing cardiac troponin I (cTnI) release in normal horses post-exercise using an analytically validated assay. These data are essential for selecting appropriate sampling times in equine athletes with suspected myocardial injury. To plot the magnitude and time course of cTnI release after maximal effort, using validated cTnI assays. Descriptive longitudinal study. Five clinically normal Standardbred racehorses in race training were included in the study. Horses were exercised in harness at near-race intensity. Blood samples were taken immediately pre- and post-exercise and then hourly for 24h. Samples were analysed using the validated high-sensitivity cTnI assay and a contemporary sensitivity cTnI assay. Mean resting cTnI was 1.33±0.6s.d.ng/L (range, 0.82-2.33ng/L) using assay A. All horses were below the detection limit at rest using assay B. Peak elevation occurred 2-6h post-exercise with both assays (mean, 4.6±1.7 and 4.0±2h, respectively). Mean peak increase in cTnI was 11.96±9.41ng/L (range, 1.72-23.76ng/L) using assay A. Peak concentrations were detectable in three of the horses using assay B and were between 0.039 and 0.051μg/L (mean: 0.043±0.006μg/L). All horses returned to baseline within 24h. A small (n=5) convenience sample was used as random sampling was not logistically possible. All horses experienced an increase in cTnI post-exercise, with peak occurring 2-6h post-exercise. Cardiac troponin I elevation was detected earlier using the high-sensitivity assay, which may convey a diagnostic advantage. Targeted studies are needed to determine the significance of these increases.