Troponin I Values Research Articles

Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus

IntroductionHigh-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients.Methods and resultsWe compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 ± 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM.ConclusionThe present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up.

The concentration of troponin I is increased in patients with acute-onset atrial fibrillation

Some preliminary evidence shows that atrial fibrillation (AF) in patients admitted to the emergency department (ED) with clinical symptoms suggestive of myocardial ischemia is frequently associated with elevations of cardiospecific troponin I (TnI) [1]. Since definitive information about the frequency of troponin release during acute-onset AF (AAF) is lacking to the best our knowledge, we carried out a retrospective observational study by retrieving data from the electronic database of our hospital about all ED visits for AAF (defined as onset of symptoms within 48 hours) recorded in the year 2013. According to currently available guidelines, the definition of AAF included both first-diagnosed AF and paroxysmal AF (PAF) [2]. The ED of the Academic Hospital of Parma is a large urban facility, with approximately 90.000 visits per year. The concentration of TnI was measured in all patients with the contemporary sensitive immunoassay Beckman Coulter AccuTnI, on Unicel DxI (Beckman Coulter, Brea, CA, USA) [3]. The concentration of cTnI was also assessed, during the same period, in a population of 125 ostensibly healthy blood donors (77 males and 48 females, age range 21-54 years), who had this biomarker measured for definition of the local 99 th percentile of the upper reference limit (URL), as specified by the recommendations of the Clinical and Laboratory Standards Institute (CLSI) [4]. Results of TnI were finally expressed as median, interquartile range (IQR) and range (minimum and maximum values). The quality of TnI data was systematically validated throughout the study period by regular internal quality control (IQC) procedures and participation in an External Quality Assessment Scheme (EQAS). Differences between groups were assessed by WilcoxonMann-Whitney test (for continuous variables) and χ 2 test with Yates’ correction (for categorical variables), using Analyse-it (Analyse-it Software Ltd, Leeds, UK). The investigation was performed in accord with the Declaration of Helsinki and under the terms of all relevant local legislation. The 99th percentile URL calculated from our local population of blood donors was 0.03 µg/L. Overall, 474 cases of AAF were recorded in the ED in the year 2013. The median concentration of TnI was found to be significantly higher in patients with AAF (0.01 µg/L; IQR, <0.01 to 0.02 µg/L; range, <0.01 to 0.54 µg/L) than in controls (<0.01 µg/L; IQR, <0.01 to <0.01 µg/L; range, <0.01 to 0.03 µg/L; p<0.001) (Fig. 1). The frequency of values exceeding the 99 th URL was also significantly grater in the group of patients with AAF (86/474, 18%) than in the control population (3/125, 2%; p<0.001). The results of this study confirm the existence of an association between AAF and increased values of TnI, even when this biomarker is measured with a contemporarysensitive immunoassay in a patient population with no symptoms of myocardial ischemia. Due to a substantially increased risk of cardiovascular mortality and morbidity, AF requires an early and appropriate management. AAF represents a frequent reason for ED evaluation and the appropriate management strategy (e.g., rate-control versus rhythm control, antithrombotic therapy) should hence be based on timely risk stratification of stroke, bleeding and cardiovascular morbidity.

Late stent fracture – A potential role of left ventricular dilatation

BackgroundCoronary stent fracture is an under-recognized event but one that has been reported frequently in the drug-eluting stent era. Most reported cases of stent fracture occurred within days to two years after implantation, and are related to stent thrombosis and restenosis. Case reportPresentation of a 69-year-old male with a history of arterial hypertension and previous percutaneous coronary intervention (PCI), and with implantation of three overlapping drug-eluting stents (DES) on proximal-to-middle left anterior descending artery (LAD). At five-year outpatient evaluation, the patient was found to have a new left bundle branch block associated with mild elevation in Troponin-I value and severe left ventricular dysfunction. The patient recovered as non ST-segment elevation myocardial infarction (NSTEMI) and consequently a new coronary angiography showed total occlusion of proximal LAD with multiple stent fracture. Here we discuss the role of left ventricular dilatation as a contributing factor to late drug-eluting stent fracture. ConclusionDifferent anatomical coronary settings have been described as predisposing factors to stent fracture. Consequently, the remodeling of the left ventricle, together with the rise in diastolic pressure, may have affected the shear stress of LAD stents by increasing mechanical forces produced in the diastolic phase on the epicardial vessel. In addition, left ventricular enlargement could have increased the elongation forces on the stent frames by altering the curvature of the stent. All predisposing factors of stent fracture, including coronary and left ventricular issues, need to be considered before stent implantation to avoid stent fracture and clinical sequelae.

Association between Cardiac Troponin Level and Coronary Flow Reserve in Patients without Coronary Artery Disease: Insight from a Thermodilution Technique Using an Intracoronary Pressure Wire.

Background and ObjectivesCardiac troponins are associated with increased mortality, even among patients with no coronary artery disease. Elevated cardiac troponin levels are frequently observed in patients without significant coronary lesions, although the mechanism underlying this finding is unclear. The aim of our study was to evaluate the association between the levels of cardiac troponin and coronary flow reserve (CFR).Subjects and MethodsWe evaluated serum cardiac troponin-I in 19 patients (9 female; age 61.9±10.9 year-old). All patients had an ejection fraction >40% and angiographically normal coronary arteries. Simultaneous measurements of fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and CFR measurements using an intracoronary temperature- and pressure-sensing guidewire under basal conditions and during maximal hyperemia were performed in three vessels: the left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA).ResultsAll patients were followed for a median of 13 months. FFR, IMR, and CFR measurements were performed successfully in all subjects. Mean CFRs of LAD, LCX, and RCA were 1.98±1.20, 2.75±2.11, and 4.44±2.51, respectively. Mean IMRs of LAD, LCX and RCA were 33.28±18.78, 29.11±26.70, and 30.55±23.65, respectively. There was a poor correlation between CFR and troponin-I values in each vessel. In selecting the lowest value of CFR in each patient as the corresponding value, the lowest CFR was not associated with troponin-I levels (r=-0.219, p=0.367).ConclusionIn patients without significant coronary lesions, the correlation between CFR and troponin-I level was not significant using a thermodilution technique. Further study of a larger population with longer-term follow-up may be needed to more fully understand microvascular dysfunction.

Predictive value of high-sensitivity troponin-I for adverse cardiovascular outcomes in patients with type 2 diabetes mellitus

Predictive value of high-sensitivity troponin-I for adverse cardiovascular outcomes in patients with type 2 diabetes mellitus

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study

IntroductionCell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I)MethodsThis was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department.ResultsPlasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P < 0.001) and a plasma value of H-FBAP >6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality.Conclusionsmt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.

Pseudoischemic electrocardiography: Cardiac metastasis masquerades as myocardial infarction

A man 37 years of age was found to have chest tightness, shortness of breath, and diaphoresis during hospitalization for chemotherapy for metastatic buccal cancer (squamous cell carcinoma) on March 18, 2012. The electrocardiography (ECG) showed ST-segment elevation over V3eV5 leads (Fig. 1B), which was absent on the baseline ECG 1 year ago (Fig. 1A). Although cardiac enzymes were within normal limits, ST-segment elevation myocardial infarction was highly suspected. However, the patient hesitated about coronary angiography due to his terminal cancer status and renal insufficiency (estimated glomerular filtration rate: 29.7 ml/minute/1.73m). Follow-up ECG showed persistent ST-segment elevation without dynamic change. Cardiac enzymes showed extremely low troponin-I value (<0.04 ng/ml at 6 hours, 12

Early verification of myocardial ischemia with a novel biomarker of acute tissue damage: C-reactive protein fractional forms

BackgroundWe evaluated the utility of an independent biomarker of early ischemic cellular damage—circulating fractional forms of C-reactive protein (fracCRP), to verify the diagnostic relevance of low Troponin I (TnI) values within the context of a workup for Acute Coronary Syndrome (ACS). MethodsOn a semi-preparative scale, the molecular characteristics of fracCRP were established by electron microscopy and Western Blot, using isolates captured from patient serum on phosphorylcholine beads and purified by size exclusion high-pressure liquid chromatography (SE-HPLC). Captured on an analytical scale, the diagnostic utility of fracCRP was evaluated in first-draw plasma specimens (total CRP not exceeding 6mg/l) recovered from 300 cardiac emergency patients with final discharge diagnoses of ACS ruled out (N=132) or ruled in (N=168). ResultsAt a cutoff value chosen for 97.7% test specificity, the test metric (fracCRP×TnI) identified in the first blood draw 39.9% of all emergency patients ultimately diagnosed with ACS, and 17.9% of ultimately diagnosed patients who arrived with TnI values within the normal reference range (0.01–0.04ng/ml). ConclusionsThese findings suggest that the fracCRP test metric could serve as a rule-in test for ACS in a significant proportion of low to moderate risk emergency patients.

Serum troponin-I as an indicator of clinically significant myocardial injury in paediatric trauma patients

Myocardial injury is a cause of mortality in paediatric trauma, but it is often difficult to diagnose. The objectives of this pilot study were to (1) determine the prevalence of elevated cardiac troponin I (TnI) in paediatric trauma patients and (2) to determine whether elevated TnI correlates with clinically significant myocardial injury, defined as abnormalities on echocardiogram (ECHO) and/or electrocardiograms (ECG). To this end, we investigated a convenient sample size of 59 paediatric trauma patients with an Injury Severity Score (ISS)>12. TnI and creatine kinase-MB (CK-MB) were measured on admission, at then at regular intervals until TnI had normalized. Patients with elevated TnI levels had an ECHO performed within 24h of admission and underwent daily ECGs until TnI normalized. Elevated serum TnI was found in n=16/59 (27%; 95% CI: 18–40%) patients and was associated with elevated CK-MB in all cases. Abnormal ECHOs were seen in 4/16 patients with elevated TnI, but peak TnI values did not correlate with abnormalities on ECHO (p=0.23). Only 1 patient had a clinically significant, albeit mild, decrease in cardiac function. All ECGs were normal. Patients with elevated TnI were more likely to be intubated (p=0.04), to have higher Injury Severity Scores (p=0.02), required more resuscitation fluid (p=0.001), and to have thoracic injuries (p<0.001). Our data indicates that the prevalence of elevated TnI in paediatric trauma patients is 27%; and whilst elevated TnI reflects overall trauma severity, it is frequently elevated without a clinically significance myocardial injury. Hence, large scale studies are required to determine if an elevated threshold TnI value can be identified to accurately diagnose severe myocardial injury in paediatric trauma.

Prognostic value of cardiac troponin‐I or troponin‐T elevation following nonemergent percutaneous coronary intervention: A meta‐analysis

The aim of this meta-analysis was to assess the prevalence and prognostic value regarding mortality of cTnT or cTnI elevations after nonemergent percutaneous coronary intervention (PCI) in a large number of cohort/registry studies. Routine cardiac troponin measurement after elective PCI has been controversial among interventionalists. Recent studies have provided conflicting data in regard to predictive value of cardiac troponin-T (cTnT) and troponin-I (cTnI) elevation after non-emergent PCI. Electronic and manual searches were conducted of all published studies reporting on the prognostic impact of cTnT or cTnI elevation after elective PCI. A meta-analysis was performed with all-cause mortality at follow-up as the primary endpoint. We identified 22 studies, involving 22,353 patients, published between 1998 and 2009. Postprocedural cTnT and cTnI were elevated in 25.9% and 34.3% of patients, respectively. Follow-up period ranged from 3 to 67 months (mean: 17.7 ± 14.9 months). The results showed no heterogeneity among the trials (Q-test: 25.39; I(2) : 17%; P = 0.23). No publication bias was detected (Egger's test: P = 0.16). The long-term all-cause mortality in patients with cTnI or cTnT elevation after PCI (5.8%) was significantly higher when compared to patients without cTnI or cTnT elevation (4.4%); OR 1.45 (95% CI: 1.22-1.72), P < 0.01. In addition, the postprocedural composite adverse clinical events of all-cause mortality or myocardial infarction (MI) in patients with cTnI or cTnT elevation after PCI (9.2%) was significantly higher when compared to patients without cTnI or cTnT elevation (5.3%); OR 1.77 (95% CI: 1.48-2.11), P < 0.01. The current meta-analysis indicates that cTnI or cTnT elevation after nonemergent PCI is indicative of an increase in long-term all-cause mortality as well as the composite adverse events of all-cause mortality and MI. Efforts to routinely monitor periprocedural cTn levels along with more intensive outpatient monitoring/treatment of patients with cTn elevations may help to improve the long-term adverse outcomes in these patients following non-emergent PCI.

Unrecognized myocardial scars detected by delayed–enhanced MRI are associated with increased levels of NT-proBNP

Patients with unrecognized myocardial infarction (UMI) scars detected by delayed-enhanced magnetic resonance imaging (DE-MRI) have a decreased left ventricular ejection fraction and an increased left ventricular mass. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of heart failure, and troponin I (TnI) is a marker of myocardial injury. The primary aim of this study was to investigate whether NT-proBNP plasma levels (in addition to ejection fraction) differed in patients with UMI scars compared with normal participants. The second aim was to compare whether the TnI levels differed in those two groups. Data from the Prospective Investigation of Vasculature in Uppsala Seniors study were used. The participants who had undergone cardiac MRI were included in this study (n=248). Patients were divided into three groups depending on the existence of a myocardial infarction (MI) scar in DE-MRI and their earlier history of MI. In all the patients, a peripheral blood sample was collected and the plasma levels of NT-proBNP and TnI were determined. Patients with UMI had higher plasma levels of NT-proBNP (median 140.2 ng/l; 25th-75th percentiles: 79-225.5) than no-MI participants (median 94.9 ng/l; 25th-75th percentiles: 59.2-144.2; P=0.01) and lower levels than patients with recognized MI (median 310.4 ng/l; 25th-75th percentiles: 122.6-446.5; P=0.02). Plasma TnI values did not differ among the three groups. Patients with UMI scars detected by DE-MRI have increased plasma levels of NT-proBNP that is known to correlate with an increased risk of future cardiovascular adverse events.

An investigation of the heart rate, heart rate variability, cardiac ions, troponin-I and CK-MB in men exposed to 1.5 T constant magnetic fields

The aim of this study was to investigate heart rate (HR), heart rate variability (HRV) and other cardiac parameters in individuals who were exposed to a high static magnetic field. 30 healthy male volunteers aged between 20-30 years were included. The searching was divided into three phases: pre-magnetic field, during the magnetic field and post-magnetic field. Every phase lasted 30 minutes. Pulse, systolic and diastolic blood pressure, respiration rate and elektrocardiography (ECG), recorded for 30 minutes, in all of the individuals were measured during three phases. The men were exposed to a 1.5 T static magnetic field. The levels of Na(+), K(+), Ca(2+), Cl(-), CK-MB, troponin-I and HR and HRV parameters were investigated. There was an increase in the respiration rate, and no change in the systolic and diastolic blood pressure and pulse in the individuals exposed to the magnetic field. There was also an enhancement in the values of ions, CK-MB and troponin-I after exposure to the magnetic field. Heart rate parameters (minimum HR-I, maximum HR-I, average HR-I) were decreased and rMSSD, pNN50, power, VLF, HF, LF values increased during the magnetic field.

Predictive value of cardiac troponin-I compared to creatine kinase-myocardial band for the assessment of infarct size as measured by cardiac magnetic resonance

The estimation of infarct size by biochemical myocardial necrosis markers is used in current clinical practice, rather than the more expensive and not always available imaging techniques. However, for this purpose, the peak value of serum biomarkers can overestimate the necrotic area, especially after reperfusion. We investigated whether late release cardiac troponin I (cTnI) values could predict more precisely infarct volume measured by delayed-enhancement cardiac magnetic resonance (DE-CMR) in patients with acute myocardial infarction [ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI)] independently of reperfusion (spontaneous and provoked). Sixty patients with a first acute myocardial infarction (55 STEMI and five NSTEMI) and normal function were enrolled. Among STEMI patients, 52 underwent reperfusion. cTnI and creatine kinase-myocardial band were assessed at admission and at 6, 12, 24, 48, 72 and 96 h (+/-1 h) from symptom onset. DE-CMR (Siemens Avanto 1.5T) was performed before discharge (4 +/- 2 days). Infarct size was determined by manual delineation of the areas of delayed enhancement. Infarct volume was calculated as the sum of each slice of infarct size area multiplied by thickness. Peak cTnI was 55 +/- 59 ng/ml (range 0.3-347). The area under the curve of cTnI was 1916 +/- 2224 ng/ml. The volume of infarcted myocardium assessed by DE-CMR was 27 +/- 25 ml (range 0-134). The single value of cTnI at 72 h after symptom onset provided the most accurate estimation of predischarge infarct volume (r = 0.84, 95% confidence interval 0.75-0.91) and was significantly more accurate than creatine kinase-myocardial band value assessed at any time during the same period (r = 0.42, 95% confidence interval 0.19-0.62; P < 0.002). In patients with a first acute myocardial infarction, cTnI value assessed at 72 h from symptom onset shows the best correlation with predischarge infarct volume as assessed by DE-CMR and is superior to cTnI and creatine kinase-myocardial band peak and total values.

An atypical case of inverted Tako-Tsubo syndrome: case report and review of the literature

Dr. Vicidomini, Dr. Zanobetti, Dr. Innocenti: A 69-yearold Caucasian woman was admitted to our emergency department (ED) for an acute and initial episode of substernal chest pain radiating to the left arm, which had lasted about 1 h, associated with dyspnea and diaphoresis. She had a past medical history of depression and first stage primary biliary cirrhosis. She was taking chronic low-dose sotalol therapy (80 mg PO bid) for a prior episode of supraventricular tachycardia. She had an otherwise normal heart, and was without cardiovascular risk factors. At admission, she denied any recent emotional or stressful event. The first EKG recorded 10 min after the ED admission showed mild ST-segment depression in the precordial leads V5 and V6 (Fig. 1), without significant changes in the inferior, posterior and right precordial leads. The first blood sample analysis exhibited normal values of Troponin-I (cTn-I: 0.10 lg/L, normal range: 0–0.15 lg/L) and CK-MB (1.1 ng/ml, normal range: 0.5–3.6 ng/ml). The patient, fully asymptomatic, was admitted to our intensive observation unit. Based on our protocol, a second blood chemistry control was performed 6 h after the initial results. An elevated cTn-I value of 3.31 lg/L with normal CK-MB value (1.0 ng/ml) was observed. The EKG registered at the same time as the laboratory blood tests showed T-wave inversion in the precordial leads from V1 to V4 (Fig. 2), not present in the first tracing,and a small QT dispersion with a QT interval a bit longer than previous EKG. Trans-thoracic echocardiography showed normal left ventricular internal dimensions; the segmental wall motion analysis revealed akinesis of the basal anterior wall and the entire interventricular septum associated with hypokinesis of the inferior wall basal segments. Posterolateral basal segments and all mid-ventricular and apical segments appeared hyperkinetic.

Falsely elevated troponin I results due to outliers indicate a lack of analytical robustness

Troponin (Tn) is the preferred biochemical marker for the diagnosis of acute coronary syndrome. Spurious false Tn results (outliers) may cause significant problems with clinical management. We investigated the occurrence of outliers and whether this phenomenon could be explained by analytical imprecision. Methods and results Troponin I (TnI) was measured in duplicate with Beckman AccuTnI reagent if the first TnI result was > or =0.04 microg/L (n = 5265). All TnI requests were performed in duplicate in a subset of samples for one calendar month (n = 881). A total of 13,178 TnI requests were received during the study period. Variables were sample type, centrifugation speed and analyser. Results were identified as outliers when the difference between two results exceeded a critical difference (CD) limit defined by CD = z x square root 2 x SD(Analytical). Outliers at the 0.0005 probability level were detected in 102 of 5265 duplicate observations (1.94 +/- 0.37%). This translated into an outlier rate of 0.55 +/- 0.13% for all TnI results and 1.37 +/- 0.31% for results above 0.04 microg/L. Outliers resulted only in falsely elevated TnI values and were not dependent on the analyser, centrifugation speed or sample type. TnI outliers occurred more frequently than anticipated, could not be explained by analytical imprecision and indicated a lack of robustness in the assay. The high rate and the magnitude of the errors will complicate clinical management and carry a risk of detrimental patient outcome. The outlier rate is a useful parameter to define the robustness of assays.

Caspase Inhibition Modulates Left Ventricular Remodeling Following Myocardial Infarction Through Cellular and Extracellular Mechanisms

Myocyte death occurs by necrosis and caspase-mediated apoptosis in myocardial infarction (MI). In vitro studies suggest caspase activation causes myocardial contractile protein degradation without inducing apoptosis. Thus, caspase activation may evoke left ventricular (LV) remodeling through independent processes post-MI. The effects of caspase activation on LV geometry post-MI remain unclear. This project applied pharmacologic caspase inhibition (CASPI) to a porcine model of MI. Pigs (34 kg) were instrumented to induce 60 minutes of coronary artery occlusion followed by reperfusion and a 7-day follow-up period. Upon reperfusion, the pigs were randomized to saline (n = 12) or CASPI (n = 10, IDN6734, 6 mg/kg i.v., then 6 mg/kg/h for 24 hours). Plasma troponin-I values were reduced with CASPI compared with saline at 24 hours post-MI (133 +/- 15 vs. 189 +/- 20 ng/mL, respectively, P < 0.05). LV end-diastolic area (echocardiography) and interregional length (sonomicrometry) increased from baseline in both groups but were attenuated with CASPI by 40% and 90%, respectively (P < 0.05). Myocyte length was reduced with CASPI compared with saline (128 +/- 3 vs. 141 +/- 4 microm, respectively, P < 0.05). Plasma-free pro-matrix metalloproteinase-2 values increased from baseline with CASPI (27% +/- 6%, P < 0.05) indicative of reduced conversion to active MMP-2. Separate in vitro studies demonstrated that activated caspase species cleaved pro-MMP-2 yielding active MMP-2 forms and that MMP activity was increased in the presence of activated caspase-3. CASPI attenuated regional and global LV remodeling post-MI and altered viable myocyte geometry. Caspases increased MMP activity in vitro, whereas CASPI modified conversion of MMP-2 to the active form in vivo. Taken together, the results of the present study suggest that the elaboration of caspases post-MI likely contribute to LV remodeling through both cellular and extracellular mechanisms.

Cardiac troponin‐I as a screening tool for myocarditis in children hospitalized for viral infection

The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 microg/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 microg/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 microg/L) for two months, but decreased after that to normal levels. The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful.

Role of serum troponin-I in identifying left ventricular ejection fraction of

To determine the serum levels of troponin-I in identifying left ventricular ejection fraction (LVEF) of <or= 40% in patients with first anterior ST Elevation Myocardial Infarction (STEMI). Case series. At the Tabba Heart Institute, Karachi, from May to November 2008. Consecutive patients presenting with first anterior STEMI were studied. Troponin-I concentration was measured by MEIA (microparticle enzyme immunoassay) method and LVEF was visually assessed. Analysis of relation between troponin-I levels and LVEF by the Receiver-Operator Characteristic (ROC) curve was performed to determine the cut off values of troponin-I in identifying LVEF of <or= 40% in patients, who had received streptokinase or undergone primary Percutaneous Coronary Intervention (PCI). Out of the 90 patients studied, 50 patients received streptokinase and the remaining 40 patients underwent primary PCI. Mean age was 54.6 +/- 9 years and 82% were male. Troponin-I levels of > 63.5 ng/ml predicted LVEF of <or= 40% with a sensitivity of 94% and specificity of 97% in patients receiving streptokinase, whereas in patients undergoing primary PCI, troponin-I levels of > 87.5 ng/ml predicted LVEF < 40% with a sensitivity of 86% and specificity of 100%. Troponin-I concentration of > 63.5 ng/ml and > 87.5 ng/ml can predict LVEF <or= 40% in patients treated with either streptokinase or primary PCI respectively for first anterior STEMI. Troponin-I can be used as a non-imaging tool to identify patients with LVEF <or= 40% who need early aggressive therapy.

Low Troponin-I Levels on Admission Are Associated With Worse Prognosis in Patients With Fulminant Myocarditis

The clinical outcomes of patients with fulminant acute myocarditis (FAM) range from death to complete recovery. We sought to identify clinical, biological, and echocardiographic characteristics of prognostic value for this population. We prospectively included 185 patients with the diagnosis of acute myocarditis who were admitted to our institution between 2000 and 2007, selecting 15 who displayed FAM, namely, severe congestive heart failure or cardiogenic shock, requiring inotropic and/or mechanical circulatory support. Their mean age was 27.9 +/- 12.4 years (range, 12-52) and mean left ventricular ejection fraction (LVEF) was 22 +/- 8.4% (range, 10-35). Seven subjects had poor outcomes, defined as death (n = 4), urgent transplantation (x = 2), or persistent left ventricular dysfunction (n = 3). The other 6 individuals experienced complete recovery of ventricular function. Troponin-I values below 1 ng/mL on admission were significantly associated with greater in-hospital (P = .05) and mid-term poor outcomes (P = .001). Additionally, patients with poor outcomes showed significantly lower LVEF (17.6 +/- 6.2% vs 28.8 +/- 6.9%; P = .006). Among patients with FAM, normal or minimal elevation of troponin-I and low LVEF on admission were associated with worse in-hospital and mid-term prognosis.

Clinical Significance of Borderline Elevated Troponin I Levels Across Different Assays in Patients With Suspected Acute Coronary Syndrome

We aimed to elucidate the clinical significance of borderline troponin I (TnI) increases and see if such increases are of similar significance across different assays. Markedly increased TnI is a strong predictor of adverse cardiac events. It is not clear if borderline increases with different commercially available TnI assays provide similar prognostic information. From January 2001 to February 2004, 3 different TnI assays (Beckman Access TnI, Beckman Access AccuTnI, and Vitros ECI Troponin) were used to evaluate the peak TnI value in 1,152 consecutive patients admitted with suspected acute coronary syndrome/non-ST-elevation myocardial infarction (MI). Recommended cutoffs were used to differentiate borderline from marked increases reported as consistent with MI. Clinical data and 30-day death/new MIs were determined by chart abstraction. Demographics and cardiac risk factors were similar for the 3 groups. Frequency of borderline TnI ranged widely among assays (18.7% to 42.1%) but was significantly less with the Vitros ECI Troponin assay (p <0.0001). Prognostic significance of borderline increased TnI values also varied greatly by assay, with borderline Beckman Access AccuTnI increases being predictive of adverse 30-day outcomes (odds ratio 4.0, 95% confidence interval 1.46 to 10.97, p = 0.007), but not with the other 2 assays. Borderline increases were significantly associated with chronic renal insufficiency (CRI; serum creatine >1.5); the relation to adverse 30-day outcomes and borderline increases persisted after correcting for CRI in a multivariate logistic regression model. In conclusion, although borderline increased TnI levels are common and significantly associated with CRI, they do not all portend the same clinical prognosis. This study highlights the need for standardization of TnI levels across different assays.