Baseline Troponin I Research Articles

Comparison of two anthracycline regimens for treatment of breast cancer and the incidence of cardiac injury

Abstract Background Anthracycline based breast cancer treatment regimens have evolved over time. Whether the risk of myocardial injury is different between regimens is unclear. Purpose To compare the incidence and significance of high sensitivity troponin-I (TpI) levels immediately post anthracycline therapy in women with breast cancer treated with two different anthracycline regimens. Methods We prospectively recruited women with early-stage breast cancer who received either dose-dense doxorubicin and cyclophosphamide (ddAC) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) with or without subsequent HER2 therapy. The ddAC regimen comprises 4 cycles of doxorubicin given every 2 weeks (240mg/m2), whereas FEC consists of 3 cycles of epirubicin given every 3 weeks (total epirubicin dose of 300mg/m2, which is doxorubicin equivalent dose of 240mg/m2 using a cardiovascular toxicity dose ratio of 0.80 as per the 2022 ESC Cardio-oncology guidelines). Clinical characteristics were collected and TpI levels were measured before anthracyclines and 4-6 weeks post last dose. Comprehensive echocardiograms were conducted at baseline and post-therapy. Results 236 female participants were enrolled; 103 (43.6%) received ddAC and 133 (56.4%) received FEC. Compared to FEC, patients receiving ddAC were older (mean age 58.1±10.2 vs 51.0±9.3 years; p < 0.001) received similar cumulative doxorubicin equivalent dose (237.4±23.4 vs 239.9 ± 11.9 mg/m2; p=0.30), had similar baseline LVEF (62.1 ± 4.8 vs 61.3 ± 3.6%, p=0.14), and TpI levels (median (IQR) 2.0 (2.0-2.0) vs 2 (2.0-3.0) ng/L, p=0.12) respectively. Baseline risk factors were similar (hypertension 21% vs 17%, p=0.34; diabetes 7% vs 5%, p=0.44; dyslipidemia 15% vs. 8%, p=0.12). Post-anthracycline, the ddAC group had higher TpI level compared to patients in the FEC group (median (IQR) 12 (7-29) vs 6 (4-11) ng/L; p<0.001). The proportion of patients with abnormal TpI levels (>99th percentile, >16.0 ng/L) was higher in the ddAC group (43.7% vs 15.0%; p < 0.001). In a multivariable linear regression model that included age, treatment regimen, baseline TpI, hypertension, diabetes mellitus and dyslipidemia, ddAC remained significantly associated with higher post anthracycline TpI levels (β=15.5, 95%CI: 8.7-22.3; p<0.001). There was no significant difference in the mean LVEF post-anthracycline (59.9 ± 5.1 vs 60.0 ± 3.8; p=0.91). No patients developed clinical heart failure. Conclusion Despite similar doxorubicin equivalent doses, the incidence of abnormal TpI levels was ~3 fold higher with DD-AC than FEC. Given that DD-AC is now more commonly used especially with immunotherapy this knowledge is clinically relevant. The difference in proportion with troponin elevation could be due to differences in the number of cycles (3 vs 4) and the frequency of chemotherapy administration (every 2 vs 3 weeks) between the regimens. However, this did not translate into a larger reduction in LVEF. But longer-term follow-up is needed.

The Association Between Elevated Myocardial Injury-Related Biomarker (TnI) and Increased Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome.

The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). A retrospective cohort study. Union Hospital in Wuhan, China. A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. None. In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d -dimer levels were potential risk factors for elevated TnI levels in patients with SFTS. Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.

Diagnostic accuracy of baseline troponin and troponin change for the diagnosis of myocardial infarction complicated with heart failure

BackgroundThe diagnosis of myocardial infarction (MI) in the presence of heart failure (HF) presents a clinical problem. While diagnostic algorithms using high-sensitivity cardiac troponin have been established for suspected MI,...

Low troponin I levels predict the presence of arrhythmia-induced cardiomyopathy in patients with atrial fibrillation and left ventricular systolic dysfunction.

Successful atrial fibrillation (AF) ablation can improve reduced left ventricular ejection fraction (LVEF) with AF, which is defined as arrhythmia-induced cardiomyopathy (AIC). However, it is difficult to pre-procedurally predict the presence of AIC. We aimed to explore the pre-procedural predictors of AIC in patients with AF and reduced LVEF. This study included 60 patients with a reduced LVEF (LVEF < 50%; 69.1 ± 8.8years; 45 men) who underwent successful AF ablation. Responders were defined as patients whose LVEF post-procedurally improved to the normal range (≥ 50%). Multivariate analysis revealed that the log-transformed pre-procedural troponin I (TnI) levels (odds ratio [OR] = 0.059; 95% confidence interval [CI] = 0.0052-0.42, p = 0.003) and age (OR = 0.91; 95% CI = 0.82-1.00, p = 0.044) were independent predictors of post-procedural LVEF recovery; further, low TnI levels (< 11.1pg/ml) predicted LVEF recovery (sensitivity, 79.1%; specificity, 76.5%; positive predictive value, 89.5%; and negative predictive value, 59.1%). There were no significant differences in TnI levels between the baseline and 1month after the procedure. However, four patients with high baseline TnI levels showed a > 50% reduction in the TnI levels post-procedurally, with three of these patients showing LVEF recovery. Low pre-procedural TnI levels can predict LVEF recovery after successful AF ablation in patients with reduced LVEF.

Postoperative Serum Troponin Trends in Infants Undergoing Cardiac Surgery

Troponin-I (TN-I) levels are elevated following pediatric cardiac surgery with speculation that particular patterns may have prognostic significance. There is lack of procedure-specific data regarding postoperative TN-I levels in infants undergoing cardiac surgery. We hypothesized that TN-I elevation varies with type of surgery and persistent elevation predicts poor prognosis. We prospectively measured serial TN-I levels (preoperatively, 4, 8, 12, 24, and 48 hours postoperatively) in 90 infants (age < 1 year) undergoing cardiac surgery: off cardiopulmonary bypass (CPB) (n = 15), on CPB (n = 43), and on CPB with ventricular incision (CPB with ventricular incision; n = 32). All patients had undetectable baseline TN-I levels. The area under the curve of TN-I levels over the 48-hour period was significantly different among the surgical groups (P < 0.002), and highest in patients with CPB with ventricular incision. Generally, TN-I levels peaked by 4 hours after surgery and returned to near-normal levels within 48 hours. A persistent TN-I rise beyond 8 hours after surgery was a strong predictor of postoperative hypoperfusion injury (defined as a composite endpoint of end-organ injury resulting from inadequate perfusion, odds ratio 21.5; P = 0.001) and mortality (30% in those with persistently high TN-I, compared with 3.5% in the remaining patients; P < 0.001), independent of patient age, anatomy and/or complexity of surgery, and level of postoperative support. Our data provide benchmark values for TN-I levels following cardiac surgery in infants. Extent of TN-I elevation correlates with type of surgery. Persistent TN-I elevation beyond 8 hours after surgery is strongly associated with postoperative hypoperfusion injury and mortality.

Infarct size assessment by cardiac magnetic resonance and peak troponin I after aspiration thrombectomy and intracoronary abciximab assisted primary percutaneous coronary intervention in a real-world cohort of patients with ST-segment elevation myocardial infarction: A single-center study

To assess the effect of manual thrombectomy on infarct size by cardiac magnetic resonance (CMR) and peak troponin I (TnI) levels. Use of manual thrombectomy during primary percutaneous coronary intervention (primary PCI) and its effect on infarct size is still debatable. 70 patients (30 patients with thrombectomy and 40 without) who underwent primary PCI for ST-elevation myocardial infarction (STEMI) with adjunct intracoronary abciximab between January 2007 and August 2013 and had CMR afterwards were included. No significant difference in the baseline characteristics except for a higher baseline TnI (11.6 ± 16.7 vs. 2.4 ± 7.9, P = 0.009) and more visible thrombus and or TIMI 0 flow (P = 0.04) in the thrombectomy group. No significant difference was found in infarct size assessed by CMR (18.1 ± 13.2 vs. 16.45 ± 11.7, P = 0.6) or peak TnI (75.9 ± 126 vs. 51.3 ± 50.4, P = 0.26) between the two groups. A moderate positive correlation was found between Peak as well as TnI at 24 hours (TnI-24 h) and CMR-determined infarct size (r = 0.5 and r = 0.7 respectively, P < 0.001). TnI-24 h (B = 0.152, 95.0% Confidence Interval (CI) 0.116–0.187, P < 0.001) as well as final TIMI grade (B = −10,848, 95.0% CI −15.109 to −6.587, P < 0.001) predicts infarct size. In a retrospective real world cohort of patients with STEMI, no difference was found in infarct size assessed by CMR or peak TnI between the groups with and without thrombectomy. TnI-24 h as well as final TIMI flow predicts infarct size.

Cardio- and reno-protective effect of remote ischemic preconditioning in patients undergoing percutaneous coronary intervention. A prospective, non-randomized controlled trial

Abstract Objectives This study assessed the cardio- and renoprotective effect of remote ischemic Preconditioning (PreC) in patients undergoing percutaneous coronary intervention (PCI). Background Myocyte necrosis and contrast induced nephropathy (CIN) occur frequently in PCI and are associated with subsequent cardiovascular events. Methods: Two hundred consecutive patients undergoing elective PCI with normal baseline troponin-I (cTnI) values were recruited. Subjects were systematically allocated into 2 groups: 100 patients received PreC (created by three 5 min inflations of a blood pressure cuff to 200 mmHg around the upper arm, separated by 5 min intervals of reperfusion) n = 100). Results The incidence of PCI-related myocardial infarction (MI 4a) at 24 h after PCI was lower in the PreC group compared with control group (41% vs 64%, P = 0.02). Subjects who received PreC had significant trend toward lower incidence of CIN at 72 h after contrast exposure (4 vs. 11, P = 0.05) and less chest pain during stent implantation compared to control group. At 3 months, the major adverse event rate was lower in the PreC group (6 vs. 14 events; P = 0.04). Conclusions The use of PreC

Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: Results of a prospective multicenter trial

ObjectivesWe investigated absolute and relative cardiac troponin I (TnI) delta changes, optimal sampling protocols, and decision thresholds for early diagnosis of myocardial infarction (MI). Serial cardiac biomarker values demonstrating a rise and/or fall define MI diagnosis; however the magnitude of change, timing, and diagnostic accuracy of absolute versus relative (percentage) deltas remains unsettled. MethodsWe prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent symptoms of acute coronary syndrome at 14 medical centers. Diagnosis was adjudicated by an independent central committee. ResultsElevated TnI above a threshold of 0.03ng/mL demonstrated significant diagnostic efficacy (AUC 0.96). For patients with TnI<0.03ng/mL and symptom onset≥8h, 99.1% (NPV) were diagnosed with conditions other than MI. Absolute delta performed significantly better than relative delta at 1–3h (AUC 0.84 vs 0.69), 3–6h (0.85 vs 0.73), and 6–9h (0.91 vs 0.79). Current recommendations propose ≥20% delta within 3–6h; however, results were optimized using an absolute delta of 0.01 or 0.02ng/mL. Sensitivity results for absolute delta at 1–3h and 3–6h (75.8%, 78.3%) were superior to relative delta (48.0%, 61.3%). NPV (rule out) was 99.6% when baseline TnI<0.03ng/mL and absolute delta TnI<0.01ng/mL. ConclusionsAbsolute delta performed significantly better than relative delta at all time intervals. Baseline TnI and absolute delta may be used in conjunction to estimate probability of MI. Consensus recommendations are supported for sampling on admission and 3h later, repeated at 6h in patients when clinical suspicion remains high.

Association of Contemporary Sensitive Troponin I Levels at Baseline and Change at 1 Year With Long-Term Coronary Events Following Myocardial Infarction or Unstable Angina: Results From the LIPID Study (Long-Term Intervention With Pravastatin in Ischaemic Disease)

This study sought to assess whether baseline and change in contemporary sensitive troponin I (TnI) levels predicts coronary heart disease (CHD) death and myocardial infarction (MI), and to determine the effects of pravastatin on TnI levels. The role of troponins in predicting long-term outcomes in patients with stable CHD is not clearly defined. The LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) study randomized patients with cholesterol levels of 155 to 271 mg/dl 3 to 36 months after MI or unstable angina to placebo or pravastatin 40 mg per day. TnI levels were measured at baseline and after 1 year in 7,863 patients. Median follow-up was 6 years. Change in TnI was defined as moving up or down 1 tertile or ≥50% change. Baseline TnI tertiles were<0.006 ng/ml,0.006 to <0.018 ng/ml, and≥0.018 ng/ml. TnI levels were related to CHD death and MI after adjustment for 23 risk factors and treatment (≥0.018 ng/ml vs.<0.006 ng/ml hazard ratio [HR]: 1.64; 95% CI: 1.41 to 1.90; p< 0.001). TnI levels increased in 23.0%, were unchanged in 51.3%, and decreased in 25.7% of patients. Pravastatin decreased TnI levels by 0.003 ng/ml versus placebo (p= 0.002). In landmark analyses, increases in TnI levels were associated with increased numbers of CHD death and MI (HR: 1.31; 95% CI: 1.06 to 1.62) and decreases with decreased risk (HR: 0.90; 95% CI: 0.74 to 1.09; overall p= 0.01). Data were similar with 50% change criteria. Net reclassification improvement by adding TnI to the baseline model for CHD death and MI was 4.8% (p= 0.01). Baseline TnI levels and change at 1 year are independent predictors of CHD death and MI. TnI levels are strong predictors of risk, and change modifies risk.

Evaluation of the diagnostic performance of current and next-generation assays for cardiac troponin I in the BWH-TIMI ED Chest Pain Study

Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (TnI) assay with 10-100-times greater sensitivity than current commercial assays. Among patients with non-traumatic chest pain enrolled in the BWH-TIMI ED Chest Pain Study, we measured TnI (n=381) at baseline, 4-6 h, and 12-24 h with an investigational assay (S-TnI; Singulex, detection-limit 0.0002 µg/l, 99th percentile 0.009 µg/l) and a contemporary sensitive assay (TnI-Ultra; Siemens, detection-limit 0.006 µg/l, 99th percentile 0.04 µg/l). Final diagnosis was adjudicated using all diagnostic data and local hospital-based cardiac TnI (Siemens), blinded to investigational cardiac Tn. The adjudicated diagnosis was myocardial infarction (MI) in 96 patients, unstable angina in 41, and acute non-coronary cardiovascular conditions in 50 patients. Baseline S-TnI was highly sensitive for MI (97%, 95% CI 91-99%) with specificity 81% (95% CI 76-86%) and positive predictive value 63% (95% CI 55-71%). The negative predictive value with S-TnI was 99% (95% CI 96-100%). S-TnI had better diagnostic accuracy than the local assay (area under the curve 0.976 vs. 0.916, p=0.003). Among 20 patients with negative baseline TnI and diagnosis of MI, 19 had elevated baseline S-TnI. Compared to TnI-Ultra, S-TnI trended toward higher sensitivity (97 vs. 94%, p=NS) but did not differ significantly in negative predictive value (99 vs. 98%) or area under the curve (p=0.29). Current and investigational Tn assays substantially increased clinical sensitivity and improved diagnostic accuracy for MI, despite a decline in specificity. A contemporary sensitive assay delivered similar overall accuracy to the investigational test, suggesting that we have reached a point of maximum diagnostic return with increasing analytical sensitivity.

Abstract 16968: Troponin I Is an Independent Predictor of Long-Term Coronary Events Following Myocardial Infarction or Unstable Angina: Results from the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Trial

Background The role of higher-sensitivity troponins in predicting long-term outcomes in patients with stable CHD is not clearly defined. Objective: To assess the value of a higher sensitivity troponin I (TnI) assay to predict outcomes during median follow-up of 6 years and to assess the effect of pravastatin on TnI levels and outcomes. Methods Among 9014 patients in LIPID with cholesterol levels 4.0-7.0 mmol/L randomized to placebo or pravastatin after MI or unstable angina 3-36 months previously, TnI levels (Siemens ultra, level of detection 0.006 ng/mL, 99th percentile with CV 10% 0.04 ng/mL) were measured at randomization and at 1 year. Baseline TnI levels (ng/ml) were assessed in 3 groups: not detectable (38%), 0.006-0.018 (31%), and ≥0.018 (31%), and change over 1 year defined as a change in group. Results Patients with the highest TnI levels were older, more likely to have previous MI, and to be on ACE inhibitors but less likely to be on beta-blockers. Levels of TnI at 1 year had decreased in 25%, were unchanged (51%) or increased (23%), but pravastatin had no effect on TnI levels. In a multivariable Cox regression for CHD death or nonfatal MI, HR was 2.02 (95% CI 1.66-2.45), P &lt;0.001, for levels of TnI above the reference 99th percentile (0.04 ng/mL), vs undetectable levels, adjusted for baseline risk factors. In multivariable landmark analysis of 6544 patients event-free at 12 months, baseline TnI levels and changes in TnI were both independent predictors of subsequent CHD events ( P &lt;0.001), even after adjustment for 23 traditional risk factors, including treatment. The effect of pravastatin in reducing CHD events remained highly significant in each model ( P &lt;0.02) and was independent of TnI levels. Conclusions Baseline and change to 1 year in TnI levels, additional to traditional risk factors, were independent predictors of CHD death and MI. TnI was more powerful for predicting fatal than nonfatal events (table), and the benefits of pravastatin were independent of TnI levels.

Troponin I levels in asymptomatic patients on haemodialysis using a high-sensitivity assay

Troponin I (TnI) is an effective marker for detecting myocardial injury, but the interpretation of levels in the setting of end-stage renal disease (ESRD) is still unclear. TnI levels have been noted to be increased in 5-18% of asymptomatic haemodialysis (HD) patients with standard assays, but newer-generation, high-sensitivity assays have not been examined. In addition, there is limited data on the variability of TnI levels in patients over time as well as the effect of HD on TnI levels. The aim of this study was to prospectively explore the incidence of TnI with a high-sensitivity assay, the variability of TnI levels over time and the effect of HD on levels. We enrolled 51 asymptomatic HD patients and checked TnI levels using a high-sensitivity assay. Levels were drawn pre-HD monthly for three consecutive months. As per manufacturer guidelines, levels were considered normal up to 0.034 ng/mL, indeterminate elevation (IE) if between 0.035 and 0.120 ng/mL and consistent with myocardial infarction (MI) if >0.120 ng/mL. In the third month, post-HD TnI was also drawn to determine change with dialysis. At baseline, median TnI level was 0.025 ng/mL (range, 0-0.461 ng/mL). Baseline TnI levels were normal in 63% and elevated (≥0.035 ng/mL) in 37%. Of those with elevations, 79% were in the IE range and 21% in the acute myocardial infarction range. Higher TnI levels at baseline were associated with a history of coronary artery disease, left ventricular hypertrophy, lower cardiac ejection fraction and higher serum phosphate levels. Average incidence of elevated TnI was 41% over the 3 months. Thirty-six patients had stable levels without a change in classification over 3 months. Twelve varied over time. Forty-five (94%) had no change in classification pre- and post-HD. Using a new-generation, high-sensitivity assay, over a third of asymptomatic ESRD patients have an elevated TnI. The significance of these low-level elevations is unclear at this time. TnI levels remain stable over a 3-month period in most patients. HD treatment does not appear to affect the TnI level.

Myocardial cell injury is common in children with septic shock

To determine the prevalence of myocardial cell injury in children with septic shock by estimating the levels of biochemical markers of myocardial injury, troponin I (TnI) and creatine kinase MB (CK-MB). Children aged 3 months to 16 years were admitted to paediatric intensive care unit (PICU) with septic shock. Children with sepsis without shock and children with hypovolaemic shock were enrolled as controls. Serum TnI and CK-MB levels were measured at admission and serially at 24 h, 48 h and 96 h in children with septic shock, while baseline measurement of the same markers was taken from the controls. In total, 88% (15/18) of children with septic shock had elevated TnI levels compared with 25% (5/20) with sepsis and 6.7% (1/15) with hypovolaemic shock (p < 0.001). Serial TnI levels at admission, 24 h, 48 h and 96 h were higher in the nonsurvivors. There was a positive correlation between the baseline TnI levels and the predicted mortality using the paediatric index of mortality (PIM2) scores at admission (r = 0.51, p = 0.03). A majority of children with septic shock have evidence of myocardial cell injury. The estimation of serum TnI levels may help in better prognostication of children with septic shock.

Is Phospholamban or Troponin I the “Prima Donna” in β-Adrenergic Induced Lusitropy?

See related articles, pages 377–386 In normal myocardium, acute β-adrenergic stimulation augments both systolic and diastolic performance via protein kinase A (PKA)–mediated phosphorylation of key proteins governing Ca2+ handling and the contractile machinery. Twenty-five years ago Kranias and Solaro identified troponin I (TnI) and phospholamban (PLN) as the 2 major cardiac proteins which were nearly simultaneously phosphorylated by β-adrenergic stimulation of the beating heart in synchrony with the agonist effect of augmenting contractility (inotropy) and rate of relaxation (lusitropy).1 Numerous subsequent studies have mechanistically examined the role of these proteins in inotropy and lusitropy. It is well established that enhanced Ca2+ availability during systole is the major, though perhaps not the only, driver of enhanced inotropy with β- adrenergic stimulation.2–4 The effect on Ca2+ dynamics is primarily mediated by phosphorylation of PLN, though increased ionic current through the L-type calcium channel contributes to Ca2+ loading. When PLN is phosphorylated by PKA, the “brake” imposed by PLN on sarcoplasmic reticulum (SR) Ca2+ ATPase is relieved, resulting in an increase in the activity of the latter that leads to a faster sequestration of Ca2+ into the SR, enhancing cardiac relaxation and re-loading the SR with Ca2+ to increase Ca2+ release in subsequent beats. Yet, PLN phosphorylation by PKA is not the sole mechanism implicated in enhancing relaxation. In particular, phosphorylation of TnI by PKA has long been proposed to have a role in diastole because it desensitizes the myofilament to Ca2+, increases the off rate of Ca …

Predictive Risk Factors for Upper Gastrointestinal Bleeding with Simultaneous Myocardial Injury

The aims of this study were to: (1) evaluate the epidemiology of simultaneous upper gastrointestinal bleeding (UGIB) and myocardial injury using parameters including troponin I (TnI); and (2) investigate the predictive risk factors of this syndrome. One hundred and fifty-five patients (101 men, 54 women; mean age, 64.7+/-10.4 years; range, 38-94 years) at the emergency department (ED) with the major diagnosis of UGIB were included. They underwent serial electrocardiography (ECG) and cardiac enzyme follow-up. Emergent gastroendoscopy was performed within 24 hours in most patients except for those who refused or were contraindicated. Mild myocardial injury was defined as the presence of any of the following: typical ST-T change on ECG, elevated creatine kinase-MB (CK-MB)>12 U/L, or TnI>0.2 ng/dL. Moderate myocardial injury was defined as the presence of any two of the previously mentioned conditions. In total, 51 (32.9%) and 12 (7.74%) patients developed mild and moderate myocardial injuries, respectively. Myocardial injury was more common among patients with variceal bleeding (20/25=80.0%) than those with ulcer bleeding (23/112=20.5%). It could partially be attributed to a higher baseline TnI level in cirrhotic patients. After adjusting for significant risk factors revealed by the univariate analysis, UGIB patients with a history of liver cirrhosis and more than three cardiac risk factors comprised a high-risk group for simultaneously developing myocardial injury. Other factors including age, gender, the color of nasogastric tube irrigation fluid, history of nonsteroidal anti-inflammatory drug use, vasopressin or terlipressin administration, vital signs, and creatinine recorded at the ED were not significant predictors. Those who developed myocardial injury had a longer hospital stay (mean duration, 8.73+/-6.94 vs. 6.34+/-2.66 days; p=0.03) and required transfusion of more units of packed erythrocytes.

Increase in interleukin‐6 following arterial injury is related to insulin resistance, the −174G→C polymorphism and complex plaque morphology

Interleukin-6 (IL-6) is associated with many disease states in humans. We prospectively sought to determine whether IL-6 levels increased following percutaneous coronary intervention (PCI) in the absence of myonecrosis. Additionally, we systematically assessed other clinical and anatomic factors associated with IL-6 levels in a population of patients with coronary atherosclerosis undergoing PCI. Blood samples were collected from 117 patients at baseline, 8 and 16 h following PCI. Samples were assayed for IL-6, creatine kinase-myocardial band (CK-MB), troponin-I (Tn-I), high sensitivity C-reactive protein, glucose, haemoglobin A1c, and a lipid profile. Genotyping of the -174G-->C polymorphism of the IL-6 gene was performed. IL-6 levels increased following PCI among the study group (slope = 0.4 pg/mL/h, P = 0.001). IL-6 levels increased to a similar degree in the absence of myonecrosis. Patients with the XC genotype (either having the GC or the CC allele) had higher IL-6-values at baseline compared to GG genotype patients (4.9 +/- 6.4 vs. 2.6 +/- 1.8 pg/mL, P = 0.02). Multivariable predictors of detectable baseline IL-6 levels included XC genotype (odds ratio [OR]: 4.14, 95% CI 1.58-10.82, P = 0.004), ACC/AHA type C lesion classification (OR: 4.08, 95% CI 1.54-10.84, P = 0.005), elevated baseline Tn-I (OR: 3.31, 95% CI 1.16-9.43, P = 0.025), diabetes (OR: 3.00, 95% CI 1.11-8.09, P = 0.030), and waist circumference (OR: 1.49, 95% CI 1.08-2.06, P = 0.015). Predictors of peak IL-6 following PCI included the XC genotype (estimate 1.4, 95% CI 1.06-1.87, P = 0.019), homeostasis model assessment (estimate 0.99, 95% 0.982-0.999, P = 0.042) and baseline Tn-I > upper limit of normal (estimate 0.7, 95% CI 0.50-0.96, P = 0.039). Lastly, IL-6 increased following PCI even in the absence of myonecrosis as measured by Tn-I elevation. IL-6 levels are also related to the -174G-->C polymorphism, arterial injury, lesion complexity, and insulin resistance.

Effects of tirofiban plus heparin versus heparin alone on troponin i levels in patients with acute coronary syndromes

Elevated serum troponins following an acute coronary syndrome (ACS) predict a poor clinical outcome. Glycoprotein (GP) IIb/IIIa inhibitors reduce adverse clinical outcomes in patients with ACS, although their effect on serum troponin I (TnI) in this setting has not been described. We therefore studied the effects of the GP IIb/IIIa inhibitor tirofiban on serum TnI levels in a group of patients in the Platelet Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Serial blood samples were obtained in 53 patients receiving the combination therapy of tirofiban/heparin and in 52 receiving heparin alone, and were analyzed for baseline, peak, and mean concentrations of TnI. Baseline TnI levels were not different between the combination therapy and heparin-only groups (1.6 ± 3.0 vs 3.1 ± 6.7 ng/ml, p = 0.15). The peak TnI level was significantly lower in the combination therapy group than in the heparin group (5.2 ± 8.3 vs 15.5 ± 29.1 ng/ml, p = 0.017), and mean levels over the initial 24-hour period were also significantly lower in the combination therapy group (3.2 ± 5.0 vs 8.5 ± 14.8 ng/ml, p = 0.016). In univariate analysis, combination therapy was associated with lower TnI levels, whereas in a multivariate model, the lower peak and mean TnI levels as a consequence of tirofiban/heparin compared with heparin monotherapy remained significant (peak, p = 0.029; mean, p = 0.035). Among patients with negative TnI at baseline, treatment with the combination of tirofiban/heparin compared with heparin monotherapy still resulted in significantly lower peak (2.5 ± 5.4 vs 14.6 ± 32.8 ng/ml, p = 0.024) and mean (1.2 ± 2.6 vs 6.9 ± 15.8 ng/ml, p = 0.029) TnI levels. In patients with ACS, therapy with the combination of tirofiban and heparin (compared with heparin treatment alone) resulted in lower serum TnI levels, suggesting reduced myocardial injury.

Troponin I phosphorylation and myofilament calcium sensitivity during decompensated cardiac hypertrophy.

We have measured myocyte cell shortening, troponin-I (Tn-I) phosphorylation, Ca2+ dependence of actomyosin adenosinetriphosphatase (ATPase) activity, adenosine 3',5'-cyclic monophosphate (cAMP) levels, and myofibrillar isoform expression in the spontaneously hypertensive rat (SHR) during decompensated cardiac hypertrophy (76 wk old) and in age-matched Wistar-Kyoto rat (WKY) controls. The decreased inotropic response to beta-adrenergic stimulation previously observed in myocytes from 26-wk-old SHR was further reduced at 76 wk of age. In response to beta-adrenergic stimulation, Tn-I phosphorylation was greater in the 76-wk-old SHR than in the WKY, although cAMP-dependent protein kinase A (PKA)-dependent Tn-I phosphorylation in the SHR did not increase with progression from compensated (26 wk) to decompensated (76 wk) hypertrophy. We also observed a dissociation between the increased PKA-dependent Tn-I phosphorylation and decreased cAMP levels in the 76-wk-old SHR versus WKY during beta-adrenergic stimulation. Baseline Tn-I phosphorylation was significantly reduced in 76-wk-old SHR versus WKY and was associated with decreased basal cAMP levels and increased Ca2+ sensitivity of actomyosin ATPase activity. The change in myofilament Ca2+ sensitivity during beta-adrenergic stimulation in the 76-wk-old SHR (0.65 pCa units) was over twofold greater than in the 76-wk-old WKY (0.30 pCa units). We also determined whether embryonic troponin T isoforms were reexpressed in decompensated hypertrophy and observed significant reexpression of the embryonic cardiac troponin T isoforms in the 76-wk-old SHR. The significant decrease in Ca2+ sensitivity with beta-adrenergic stimulation in 76-wk-old SHR may contribute to the severely impaired inotropic response during decompensated hypertrophy in the SHR.

Troponin I phosphorylation in spontaneously hypertensive rat heart: effect of beta-adrenergic stimulation.

We compared baseline and protein kinase A (PKA)-dependent troponin I (TnI) phosphorylation in 32Pi-labeled left ventricular myocytes from hearts of 26-wk spontaneously hypertensive rats (SHR) and Wistar-Kyoto controls (WKY). TnI phosphorylation was normalized to myosin light chain 2 phosphorylation, which was invariant. There was no difference in baseline TnI phosphorylation in SHR and WKY, but stimulation with isoproterenol, norepinephrine plus prazosin, forskolin, chloroadenosine 3',5'-cyclic monophosphate, or 3-isobutyl-1-methylxanthine caused a greater increase in TnI phosphorylation in the SHR than in the WKY. This was observed both in the presence and absence of the phosphatase inhibitor calyculin A; thus the differences in TnI phosphorylation between SHR and WKY are not due to decreased phosphatase activity in the SHR. After stimulation of the beta-adrenergic pathway, phospholamban phosphorylation was not different in SHR and WKY, indicating that the observed differences may be specific for PKA phosphorylation of TnI. The increased PKA-dependent TnI phosphorylation in the SHR resulted in decreased Ca2+ sensitivity of actomyosin adenosinetriphosphatase activity as compared with the WKY. We conclude that increased PKA-dependent TnI phosphorylation in the SHR may contribute to the impaired response to sympathetic stimulation.