Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism.

BACKGROUND: To investigate the frequency of cardiac troponin I (cTnI) increases in patients with pulmonary embolism (PE) and to assess the correlation between this finding, the clinical presentation, and outcomes. METHODS: Consecutive patients admitted to the coronary care unit with acute PE were prospectively enrolled between January 2000 and December 2001. cTnI was sequentially determined. Various cut off concentrations were analysed, but patients were categorised prospectively as having increased or no increased cTnI based on a cut off concentration of 0.6 ng/ml. The main outcome measure was in-hospital mortality. RESULTS: On admission, 14 of the 48 patients (29%) had cTnI concentrations greater than the receiver operating characteristic curve value used to diagnose acute myocardial infarction (> 0.6 ng/ml). Subsequently, six patients developed increases for an overall prevalence of 42% (20 of 42). The prevalence was higher when lower cut off concentrations were used: 73% (35 of 48) at the 99th centile and 60% (29 of 48) at the 10% coefficient of variability. Increased cTnI > 0.6 ng/ml was associated with a slower oxygen saturation (86 (7)% v 93 (4)%, p < 0.0001) and more frequent involvement of the main pulmonary arteries as assessed by spiral computed tomography (100% v 60%, p = 0.022). In-hospital mortality was 36% (5 of 14) of patients with increases > 0.6 ng/ml v 3% (1 of 42) of patients with lower concentrations (p = 0.008). Increased cTnI > 0.6 ng/ml on admission was the most powerful predictor of mortality (p = 0.046). CONCLUSIONS: In high risk patients with acute PE, cTnI was frequently detected on admission. It was the strongest independent predictor of mortality.

Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide.

High-dose cyclophosphamide (HD-CTX) is largely employed in high-dose chemotherapy (HD-CHT) protocols. HD-CTX dose-limiting toxicity expresses itself as cardiac toxicity which is fatal in a minority of patients. The pathophysiology of HD-CTX-associated cardiotoxicity is still poorly understood. Autopsy studies in patients who died from acute HD-CTX-induced cardiac toxicity revealed hemorrhagic myocardial cell death and interstitial edema. Recently troponins, in particular troponin I (cTnI), have been found to represent a uniquely sensitive and specific marker of myocyte membrane integrity and therefore to increase in response to minimal myocardial cell damage in different settings, including doxorubicin-induced cardiotoxicity. We performed a multiparametric cardiologic monitoring in 16 consecutive breast cancer patients undergoing HD-CTX by means of serial ECG registrations and cardiac enzymes (CPK, CPK-MB and cTnI) determinations plus echocardiography in order to clarify acute cardiac events following HD-CTX administration. Neither overt cardiac toxicity nor cardiac enzymes elevation were recorded. Serial ECGs revealed in six cases little and reversible reduction of QRS voltage and/or ST abnormalities. Echo monitoring showed in four cases mild and transient increase of LV diastolic/systolic diameter/volume without decrease of FS% or EF% below normal values: in two of them abnormalities of diastolic function (E/A mitral doppler ratio) were also recorded. We conclude that our protocol of HD-CTX administration does not cause myocardial cell damage as analyzed by serum cTnI levels, thus suggesting that myocyte membrane injury may not be the first direct mechanism of HD-CTX cardiotoxicity. ECG (ie QRS voltages ) and Echo (ie E/A ratio) monitoring leads us to hypothesize that slight interstitial edema with reduction of LV diastolic compliance may be initial signs of cardiac dysfunction in this clinical setting.

[Assessment of cardiotoxicity of high dose cyclophosphamide with electrocardiographic, echocardiographic, and troponin I monitoring in patients with breast tumors]. / Analisi della cardiotossicità da ciclofosfamide ad alte dosi mediante monitoraggio elettrocardiografico, ecocardiografico e della troponina I in pazienti con tumore della mammella.

BACKGROUND: High-dose cyclophosphamide is the nucleus for virtually all high-dose chemotherapy protocols. Non-hematologic dose-limiting toxicity is represented by acute cardiomyopathy, even fatal in a minority of patients. The pathophysiology of such a cardiotoxicity is still poorly understood. Postmortem studies revealed hemorrhagic myocardial cell death, endothelial damage, and interstitial edema. Recently troponins, in particular troponin I, have been found to represent uniquely sensitive and specific markers of myocyte membrane integrity, thus to increase in response to myocardial cell damage in different clinical settings. METHODS: We performed a multiparametric monitoring in 16 consecutive breast cancer patients undergoing cyclophosphamide, by means of serial ECGs, cardiac enzymes determinations (creatine phosphokinase, MB mass and troponin I) through 0 to 72 hours, and echocardiography at baseline and after 48 hours. RESULTS: Neither overt cardiac failure nor enzyme elevation were recorded. Serial ECGs revealed a reduction in QRS voltage and/or ST segment abnormalities in 6 cases. Echocardiography showed an increase in left ventricular diastolic and/or systolic diameters and volumes in 4 cases but without any decrease in fractional shortening and ejection fraction under normal values: in 2 of them abnormalities of diastolic function (E/A mitral Doppler ratio, isovolumic relaxation time and deceleration time) were also recorded. CONCLUSIONS: Our protocol of cyclophosphamide administration did not cause cardiac toxicity by myocardial cell damage, as analyzed by troponin I levels, thus suggesting that myocyte membrane injury is not the first mechanism of it. ECG (i.e. QRS voltages) and echo-Doppler (i.e. E/A ratio) monitoring lead to hypothesize that endothelial injury and interstitial edema with subsequent reduction in left ventricular diastolic compliance may be the first signs of cardiac dysfunction in this clinical setting.

Cardiac troponin I as diagnostic and prognostic marker in severe heart failure.

BACKGROUND: Cardiac cell death has been shown to occur in heart failure and has been implicated as one of the mechanisms responsible for progression of the disease. Cardiac Troponin I (cTnI) represents a highly sensitive marker for myocardial cell death. Based on previous studies reporting that cTnI may be detected in patients with heart failure, we evaluated the clinical correlates and prognostic implications of detectable cTnI in a consecutive series of patients with severe heart failure. METHODS: Thirty-four patients were examined. Upon admission, we measured serum levels of cTnI by conventional immunoenzymatic assay (Stratus Dade II). According to the results of this assay, patients were divided into 2 groups, based on the presence (cTnI+) or absence (cTnI-) of detectable cTnI. These 2 groups were compared by non-parametric analysis for their clinical characteristics, instrumental findings, and short-term outcome. RESULTS: The cTnI+ group included 10 patients (29%) with a mean serum cTnI of 0.7 +/- 0.3 ng/ml. Compared with the cTnI- group, these patients had significantly lower left ventricular ejection fractions (20% +/- 5% vs 26% +/- 7%, p = 0.023) and a trend for higher systolic pulmonary artery pressure (59 +/- 17 mm Hg vs 49 +/- 13 mm Hg, p = 0.08). In cTnI+ patients, the correlation between cTnI levels upon admission and ejection fraction was r = -0.530 (p = 0.11). We found ischemic etiology was equally present in the 2 groups, whereas we never found histologic signs of acute myocarditis. Other clinical characteristics (functional class, daily diuretic dose, need for intravenous inotropes) were not statistically different in the 2 groups. In cTnI+ patients who improved after admission, cTnI became undetectable after a few days; in patients with refractory heart failure who were hospitalized until death, cTnI persisted in detectable levels throughout the observation period. Using the Cox proportional hazard model, a positive cTnI was the most powerful predictor of mortality at 3 months (p = 0.013; hazard ratio 6.86; 95% confidence interval 1.32 to 35.4). CONCLUSIONS: These observations suggest that cTnI is detected in the blood of 25% to 33% of patients with severe heart failure; its presence may help to identify a high-risk sub-group who faces very poor short-term prognosis.

External Quality Assessment of stat test intralaboratory turnaround times. Pilot study from the Members of the Working Group for the Standardization and Promotion of Turnaround Time Control under the Auspices of the Comitato Italiano per la Standardizzazione dei Metodi Ematologici e di Laboratorio.

We describe procedures, results and prospects of a pilot program in External Quality Assessment (EQA) of the stat test intralaboratory turnaround times. Our goals are to promote quality by systematic monitoring and comparison of performances by laboratories, continuous investigation into the state of the art of the processes from receipt of sample to transmission of results and creation of a data base for standardization of measures and definition of consensus values for turnaround time. Of 30 laboratories invited to participate, 25 took part, agreeing to record times of arrival and transmission for all determinations of three analytes (blood hemoglobin, serum/plasma potassium and plasma prothrombin time) for seven consecutive days and to continue for one or more further periods of seven days as necessary if there were less than 300 determinations for each analyte. Within a preset time limit, data were sent by e-mail on an Excel file and we sent back two reports per analyte, showing: i) the graph for time vs. percentage of tests completed and several measures of turnaround time; ii) results of all laboratories in graph form, allowing each laboratory to identify only its own data. The high proportion of participating laboratories among those invited (83%) encourages us to implement the EQA program systematically, on a half-yearly basis, extending it to all laboratories wishing to participate in Italy or elsewhere in Europe.

Detectable serum troponin I in patients with heart failure of nonmyocardial ischemic origin.

Cardiac troponin I, a specific and sensitive marker of myocardial damage, was detected in the blood of 6 of 26 patients studied in our Heart Failure Clinic. In these patients functional class, ventricular function, and prognosis were significantly worse than in those without detectable troponin I. This study suggests that troponin I may represent the biochemical marker of myocardial damage occurring in severe heart failure.

[Troponin T, Troponin I and CK-MB (mass) in the detection of periprocedural myocardial damage after coronary angioplasty]. / Troponina T, troponina I e CK-MB (massa) nel riconoscimento del danno miocardico periprocedurale dopo angioplastica coronarica.

The development of methods for the detection of circulating CK-MB mass, cardiac troponin T (cTn-T) and troponin I (cTn-I) has increased the diagnostic potential in the identification of myocardial damage. Coronary angioplasty (PTCA) represents a widely accepted revascularization procedure and a clinical model of induced ischemia. Using these new biochemical markers, we evaluated the incidence and the clinico-procedural correlates of minor myocardial damage (MMD) in a series of patients treated with PTCA in our Department. In 57 consecutive patients (75% males; mean age 58 years; range 35-80) undergoing elective PTCA from March 1 to June 30, 1995, serum levels of CK-MB mass, cTn-T and cTn-I were measured at baseline and at 6, 12 and 24 hours after the procedure. Seventy-eight coronary stenoses were dilated (mean 1.4 lesion/patient), 17 of these were in infarct-related vessels; 8 were total occlusions and 2 were located in saphenous vein grafts. Twenty-two procedures were completed by coronary stenting (17 elective). cTn-T and cTn-I were considered abnormal when serum levels were > 0.2 ng/ml and > 0.6 ng/ml, respectively. CK-MB mass was also determined in all patients (abnormal > 5 ng/ml). No patients had clinical or electrocardiographic evidence of myocardial infarction after the procedure. Overall, 16 patients (28%) developed biochemical evidence of post-procedural MMD (defined as the presence of at least one abnormal sample of any among the three markers tested). Four (7%) had abnormal CK-MB mass (at least one sample), 9 (16%) abnormal cTn-T, and 15 (26%) abnormal cTn-I. When CK-MB mass was elevated, both cardiac troponins were also elevated. In patients positive for MMD and abnormal CK-MB mass, peak cTn-I was significantly higher than in patients with normal CK-MB (3.02 +/- 1.07 vs 1.02 +/- 0.11 ng/ml; p = 0.009). The difference was not evident when comparing the same groups of patients for cTn-T (0.26 +/- 0.04 vs 0.18 +/- 0.10 ng/ml; p = 0.16). Also, peak cTn-I but not peak cTn-T had a positive correlation with peak CK-MB mass (r = 0.89; p < 0.0001 and r = 0.23; p = 0.40). The elevation of either marker of MMD was not related to clinical, angiographic or procedural variables. A possible interpretation for MMD was found in 2/3 of cases: bail-out (2); late occlusion (1); minor side branch occlusion (3); distal embolization from saphenous vein grafts (2) or total occlusions (2). In our series, MMD after PTCA occurs in 28% of cases and is unrelated to clinical, angiographic and procedural variables. Both cTn-T and cTn-I increase the sensitivity of CK-MB mass in the detection of MMD after PTCA, cTn-I being the most sensitive marker. In about 1/3 of cases, the presence of MMD remains unexplained. The prognostic implications of MMD are as yet undefined.

Troponin T, troponin I and creatine kinase-MB mass after elective coronary stenting.

OBJECTIVE: To assess whether and to what extent elective coronary stenting is associated with biochemical evidence of minor myocardial damage (MMD), as defined by the detection of abnormal post-procedural serum levels of one more among the following markers of ischaemic injury: creatine kinase (CK)-MB mass, troponin T (Tn-T) and troponin I (Tn-I). METHODS: Nineteen elective procedure of coronary stenting were compared with a matched group of 25 conventional percutaneous transluminal coronary angioplasty (PTCA) procedures performed in our laboratory from March to June 1995. Cases with evolving or recent (< 2 weeks) myocardial infarction, chronic total occlusions and dilation of saphenous vein grafts were excluded. By definition, all of the patients had undergone uneventful deployment of a single palmaz-Schatz stent, with no chest pain and no persistent ECG changes after the procedure. Serum levels of CK-MB mass, Tn-T and Tn-I were determined at baseline and 6, 12 and 24 h after the procedure. The frequency of abnormal results was determined for each marker. Baseline and peak post-procedural levels in the two groups were compared and related to procedural variables. RESULTS: Baseline values were normal in all cases. The quantitative analysis showed that post-procedural levels of each marker (including total CK) were significantly higher with respect to baseline in both groups. In the stent group, two patients had positive CK-MB mass, four positive Tn-T and seven positive Tn-I. Absolute changes in Tn-T and Tn-I were closely related to changes in CK-MB mass (r = 0.76, P < 0.0001; r = 0.90, P < 0.0001), respectively). Three of these patients developed clinically silent side-branch occlusion. All of them were positive for troponins and two were positive for CK-MB. No correlation was found between procedural variables and the results of biochemical assays. In the PTCA group, three patients were positive for Tn-I, whereas the CK-MB mass and Tn-T remained constantly normal. No side-branch occlusion was observed. The peak CK-MB mass and Tn-I were significantly higher in the stent group than they were in the PTCA group (3.04 +/- 4.1 versus 1.27 +/- 1.3 ng/ml, P = 0.046; 0.78 +/- 1.17 versus 0.28 +/- 0.3 ng/ml, P = 0.046, respectively). This difference was no longer apparent when patients with side-branch occlusion were excluded. CONCLUSIONS: In our series, Tn-I measurement shows the highest ability to detect MMD, being positive in 37% of stent and 14% of PTCA cases. Elective coronary stenting associated with greater release of CK-MB mass and Tn-I than is conventional PTCA. This finding is mainly determined by cases of side branch occlusion, which account for most, but not all, periprocedural MMD in the stent group.