Beneficial impact of isoflurane during coronary bypass surgery on troponin I release.

BACKGROUND: Experimental studies indicate that isoflurane, a commonly used volatile anesthetic, mimics the cardioprotective effects of ischemic preconditioning, probably through ATP-sensitive K+ (KATP) channel activation. The aim of this study was to evaluate the impact of isoflurane during coronary bypass surgery (CABG) on troponin I release. MATERIAL AND METHODS: Forty consecutive patients with chronic stable angina and multivessel disease undergoing isolated CABG were randomized to a control (16 men and 4 women, aged 51 to 73 years, mean 62) or isoflurane (15 men and 5 women, aged 51 to 77 years, mean 65) group before aortic cross-clamping and cardioplegia. Serum levels of troponin I and creatine kinase (CK)-MB, as markers of ischemic injury, were obtained at 24 hours after CABG. Regional wall motion score and left ventricular ejection fraction (LVEF) at transthoracic echocardiography were assessed 5 days postoperatively. Comparisons between groups were performed in the entire population and, subsequently, in those patients with preoperative LVEF < 50%. RESULTS: There were no significant differences between isoflurane-treated patients and controls in cross-clamp time (49 +/- 14 vs 51 +/- 13 min, p = ns), peak values of troponin I (0.9 +/- 0.7 vs 1.4 +/- 1.3 ng/ml, p = ns) and CK-MB (62 +/- 27 vs 64 +/- 27 U/l, p = ns), or postoperative echocardiographic score (26 +/- 7 vs 22 +/- 5, p = ns) and LVEF (53 +/- 10 vs 55 +/- 7%, p = ns). When the comparisons were restricted to those patients with preoperative LVEF < 50%, at 24 hours the isoflurane-treated patients exhibited a smaller release of troponin I and of CK-MB than controls (1.1 +/- 0.7 vs 2.3 +/- 1.3 ng/ml, p = 0.03, and 39 +/- 10 vs 57 +/- 22 U/l, p = 0.04, respectively). CONCLUSIONS: Isoflurane reduces myocardial injury in patients with impaired left ventricular function undergoing CABG; thus, it can be safely used as an additional cardioprotective tool during routine CABG in high-risk patients with poor left ventricular function.     

Dynamic assessment of myocardial involvement in patients with end-stage renal disease by ultrasonic tissue characterization and serum markers of collagen metabolism

BACKGROUND: Congestive heart failure is the most common cause of mortality in patients with end-stage renal disease (ESRD). However, noninvasive assessment for cardiac involvement in ESRD has not been established. HYPOTHESIS: Assessment of ultrasonic tissue characterization and serum markers of collagen degradation is useful for defining myocardial involvement in ESRD. METHODS: Cyclic variation of ultrasonic integrated backscatter of the ventricular septum (CV-IBS) and the serum levels of free matrix metalloproteinase-I (MMP-I) and tissue inhibitor of metalloproteinase-I (TIMP-I) were measured in 30 patients with ESRD undergoing routine hemodialysis (HD) and in 40 patients with essential hypertension (HTN). RESULTS: Compared with the group with HTN, ESRD (before HD) showed larger left ventricular (LV) mass index (217 +/- 56 vs. 146 +/- 45 g/m2, p < 0.01), worse LV diastolic function (E/A, 0.6 +/- 0.2 vs. 0.9 +/- 0.3, p < 0.05), smaller CV-IBS (9.0 +/- 1.3 vs. 12.4 +/- 0.9 dB, p < 0.01), and larger TIMP-I/MMP-I (46 +/- 10 vs. 34 +/- 10, p < 0.05), in spite of the comparable ventricular wall thickness. Thus, these indices may possibly reflect myocardial interstitial fibrosis. After HD (after the improvement of myocardial interstitial edema), a negative linear relationship between CV-IBS and TIMP-I/MMP-I was observed (r= -0.52, p < 0.05). CONCLUSIONS: Noninvasive assessment of ultrasonic tissue characterization and serum markers of collagen type I degradation may be a new diagnostic tool for defining myocardial interstitial fibrosis in patients with ESRD and LV hypertrophy.     

Delayed time to peak serum myoglobin level as an indicator of cardiac dysfunction following open heart surgery

Postoperative changes in serum myoglobin levels have been studied in 47 patients undergoing open heart surgery. The patients were retrospectively divided into two groups according to the time to peak myoglobin level during reperfusion. In 38 patients, myoglobin levels increased rapidly to a peak within 3 hours after reperfusion, after which it was cleared from the blood (group 1). Contrarily, a rise in myoglobin levels was persistent for 24 hours and its time to peak was greater than 3 hours after reperfusion in nine patients (group 2). There were no differences in preoperative and early reperfusion (within 1 hour of reperfusion) values of myoglobin between the two groups. At 3, 6, and 12 hours of reperfusion, myoglobin levels were significantly greater in group 2: 448 +/- 196 vs 1,149 +/- 900 ng/ml, 359 +/- 172 vs 2,653 +/- 3,179 ng/ml, 184 +/- 95 vs 1,896 +/- 1,387 ng/ml, respectively, p less than 0.0001 in each. The maximum activities of both myoglobin and CK-MB were significantly higher in group 2 (myoglobin-max: 771 +/- 257 vs 3,221 +/- 3,024 ng/ml, p less than 0.0001; CK-MBmax: 107 +/- 60 vs 227 +/- 219 IU/L, p less than 0.005). Five of nine patients in group 2 required post-operative assistance with intra-aortic balloon pumping (p less than 0.0005 compared with one of 38 in group 1) and perioperative myocardial infarction developed in three patients (33.3 percent) in this group (p less than 0.005 compared with 0 percent in group 1). Thus, patients with a delayed peak of serum myoglobin level exhibited detrimental cardiac failure postoperatively. These findings suggest that myocardial injury accelerated by reperfusion following ischemia might progress in these patients.     

Influence of ACE inhibition on myocardial damage,the Kallikrein-Kinin system and hemostasis during cardiopulmonary bypass surgery

BACKGROUND: ACE inhibitors may have a cardioprotective effect by enhancing bradykinin levels during cardiopulmonary bypass (CPB). However, ACE inhibition could lead to unwelcome effects on the kallikrein contact phase during CPB (since reduction of kallikrein activity by aprotinin has been shown to be beneficial) and may alter the hemostasis. We examined the effects of ACE inhibitors on intraoperative myocardial damage, kallikrein contact phase and hemostasis in patients undergoing CPB. METHODS: 47 patients randomly received either 20 mg/d enalapril or placebo. Creatine kinase (CK and CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), thrombin-antithrombin III complex (TAT), fibrinogen and kallikrein-like activity were measured before surgery, during and immediately after CPB, at the end of surgery and 1, 3 and 5 days after surgery. RESULTS: No significant differences between enalapril- and placebo- treated patients concerning CK (318 +/- 38.6 U/l vs. 316 +/- 16.8 U/l), CK-MB, LDH, TnT (1.81 +/- 0.45 ng/ml vs. 1.52 +/- 0.34 ng/ml), TAT, fibrinogen and kallikrein-like-activity could be found during study period. CONCLUSIONS: Reduction of ischemic injury during CPB is not achieved with ACE inhibitors. However, treatment of patients with ACE inhibitors before and during CPB is fully feasible without side effects affecting the kallikrein contact phase or significant influence on hemostasis.     

Detection of myocardial injury during radiofrequency catheter ablation by measuring serum cardiac troponin I levels: procedural correlates.

OBJECTIVES: In the present prospective controlled study, we measured blood levels of cardiac troponin I (cTnI) in patients undergoing radiofrequency (RF) catheter ablation (RFA), and we sought to investigate the degree of myocardial injury incurred by the application of RF energy and determine its procedural correlates. BACKGROUND: Measurement of serum creatine kinase (CK) levels after RFA may underestimate the degree of myocardial injury due to its thermal inactivation by RFA. Cardiac troponin I is a newer, more specific marker of myocardial injury, which may circumvent this limitation; its use in this setting has rarely been studied. METHODS: In 118 consecutive patients, 67 men and 51 women aged 38 +/- 19 years undergoing RFA for a variety of arrhythmias, cTnI and creatine kinase isoenzyme (CK-MB) levels were measured before, immediately after and 4 to 24 h after RFA. Cardiac troponin I was also measured in 39 patients (control group) having only electrophysiologic studies (EPS) without RFA. RESULTS: All RFA procedures were uncomplicated, lasted 3.2 +/- 2.0 h and included delivery of 16 +/- 22 (median: 9) RF current applications. Baseline cTnI levels averaged 0.17 +/- 0.18 ng/ml, rose to 0.88 +/- 1.12 at the end of RFA and to 2.19 +/- 2.46 at 4-24 h later. Creatine kinase isoenzyme was found to be elevated (>6 microg/l) in 32 patients (27%), while cTnI levels were increased (> or =1 ng/ml) in 80 patients (68%) (p = 0.0001). Cardiac troponin I levels correlated with the number of RF lesions applied (r = 0.53, p < 0.0001), the site of RFA, being higher with ventricular > atrial > annular lesions (p = 0.012) and the approach to the mitral annulus (transaortic > transseptal, p = 0.004). In a control group of 39 patients undergoing EPS, all but one patient had normal cTnI or CK-MB. CONCLUSIONS: The degree of myocardial injury incurred by RFA is far more accurately assessed by cTnI levels rather than by CK-MB measurements. Cardiac troponin I levels correlate with the number of RF lesions applied, the site of RFA and the approach to the mitral annulus.     

Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery

OBJECTIVES: The aim of this study was to determine the long-term prognosis with postoperative markers of myocardial ischemia and infarction. BACKGROUND: Cardiac troponins (cTn) are superior to creatine kinase-MB fraction (CK-MB) in detecting perioperative myocardial infarction (PMI). However, their threshold levels signifying PMI and their long-term prognostic value are not yet determined. METHODS: A cohort of 447 consecutive patients who underwent 501 major vascular procedures was prospectively studied. Perioperative continuous 12-lead electrocardiogram monitoring, cardiac troponin-I (cTn-I) and/or cardiac troponin-T (cTn-T), and CK-MB levels on the first three postoperative days, and long-term survival were determined. The association of different cutoff levels of CK-MB, troponin, and ischemia duration with long-term survival was investigated. RESULTS: Between 14 (2.9%) and 107 (23.9%) of the patients sustained PMI, depending on the biochemical criteria used. Elevated postoperative CK-MB, cTn, and prolonged (>30 min) ischemia, at all cutoff levels examined, predicted long-term mortality independent of the preoperative predictors: patient's age, type of vascular surgery, previous myocardial infarction, and renal failure (Cox multivariate analysis). Both CK-MB >10% and cTn-I >1.5 ng/ml and/or cTn-T >0.1 ng/ml independently predicted a 3.75-fold and 2.06-fold increase in long-term mortality (p = 0.006 and 0.012, respectively). Similarly, both CK-MB >5% and cTn-I >0.6 ng/ml and/or cTn-T >0.03 ng/ml independently predicted a 2.15-fold and 1.89-fold increase in mortality (p = 0.018 and 0.01, respectively). Patients with both these markers elevated had a 4.19-fold increase in mortality (p < 0.001). CONCLUSIONS: Postoperative CK-MB and troponin, even at low cutoff levels, are independent and complementary predictors of long-term mortality after major vascular surgery.     

Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel-group trial

BACKGROUND: GH may be beneficial in treating patients with end-stage renal disease (ESRD). However, the efficacy and safety of GH could be compromised by the potential for accumulation in the circulation. OBJECTIVE: The objective was to investigate the pharmacokinetics and safety of GH treatment in ESRD patients. DESIGN: This was an open, nonrandomized, single-centre parallel-group study lasting 8-9 days. SUBJECTS: Eleven adult ESRD patients and 10 matched healthy individuals received recombinant human GH (50 microg/kg/day for 7 days) by subcutaneous injection; there were two dose reductions (25%) from Day 5/7. ESRD patients underwent dialysis four times. MEASUREMENTS: Serum concentrations of GH, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-I (IGFBP-I), IGFBP-III and GHBP were measured. The primary end-point was GH exposure [area-under-the-curve (AUC) calculated from the 24-h profile] on Days 7-8. RESULTS: GH AUC(0-24 h) was greater for patients (387.91 +/- 134.13 microg h/l) than healthy subjects (225.35 +/- 59.63 microg h/l) and the 90% confidence interval (CI) for the estimated patient : healthy subject ratio (1.40-2.07) was not within the acceptance interval (0.67-1.50). GH AUC(18-24 h) for patients and healthy subjects (3.03 +/- 2.71 microg h/l and 6.37 +/- 4.21 microg h/l) returned approximately to baseline (2.86 +/- 3.91 microg h/l and 1.09 +/- 1.43 microg h/l); terminal half-life (t(1/2,z)) was shorter for patients (2.28 +/- 00.43 h vs. 3.23 +/- 00.75 h). No major safety issues were identified. CONCLUSIONS: Results demonstrate a difference between patients and healthy subjects regarding GH AUC(0-24 h). However, GH concentrations for both groups were comparable to baseline by 20-22 h, thus GH was not retained in the circulation of ESRD patients.     

Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure

Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 +/- 472 micrograms/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 +/- 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 +/- 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p less than 0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.     

C-reactive protein is a marker for a complex culprit lesion anatomy in unstable angina.

BACKGROUND: The putative theory is that the clinical syndrome of unstable angina is caused by rupture of the atherosclerotic plaque with superimposed thrombus formation. It is characterized by angiographically complex coronary lesions in the majority of patients. HYPOTHESIS: This study aimed at assessing the correlation between C-reactive protein (CRP) and the complexity of culprit coronary lesions in unstable angina. METHODS: We identified culprit lesion complexity in 96 patients with unstable angina and normal creatine kinase (CK) and CK-MB mass. Serum concentrations of CRP (N < 5.0 mg/l) and cardiac troponin T (cTnT; N < 0.1 ng/ml) were measured on admission. RESULTS: There was a trend toward a higher grade of anatomical complexity of the culprit lesion in patients with elevated CRP (p = 0.007) and cTnT levels (p = 0.027). Patients who had intermediate- or high-grade lesion severity had a higher level of CRP (8.5 +/- 5.7 mg/l) and cTnT (0.118 +/- 0.205 ng/ml) on admission than those who had normal or low-grade lesions (5.7 +/- 4.0 mg/l, 0.017 +/- 0.021 ng/ml, respectively); Mann-Whitney U, p = 0.002 and p < 0.001, respectively. Furthermore, the likelihood of having intermediate- or high-grade complexity of the culprit lesion was higher when CRP levels were elevated in all patients (p = 0.007, odds ratio [OR] = 4.286; 95% confidence interval [CI] 1.492-12.310) and in those with normal cTnT levels (p = 0.025, OR = 3.876; 95% CI 1.185-12.678). Also, higher CRP levels strongly correlated with the need for revascularization interventions (p < 0.0005). CONCLUSION: Elevated CRP level on admission is a marker for anatomic complexity of culprit lesions and need for revascularization interventions in unstable angina.     

Prognostic value of serum cardiac troponin I in ambulatory patients with chronic renal failure undergoing long-term hemodialysis: a two-year outcome analysis

OBJECTIVES: We sought to evaluate the prognostic value of cardiac troponin I (cTnI) in asymptomatic, ambulatory patients with chronic renal failure treated with long-term hemodialysis. BACKGROUND: Smaller, short-term follow-up studies on this subject have given conflicting results. METHODS: A total of 126 ambulatory patients with chronic renal failure treated with long-term hemodialysis were followed for two years for all-cause mortality, cardiac mortality, all-cause hospital admissions and cardiac hospital admissions. Serum cTnI was measured before dialysis at the time of study entry. RESULTS: One hundred two patients had normal serum levels of cTnI (< or =0.03 ng/ml) and 24 patients had elevated levels (0.015 +/- 0.007 vs. 0.053 +/- 0.029 ng/ml, p < 0.0001). No significant difference in all-cause mortality (20 vs. 4 deaths), cardiac mortality (4 vs. 1 death), all-cause hospital admissions (1.74 +/- 1.72 vs. 1.25 +/- 1.19 admissions/patient) or cardiac admissions (0.52 +/- 0.89 vs. 0.33 +/- 0.76 admissions/patient) was present between the patients with normal cTnI levels and those with elevated cTnI levels. Serum cTnI was not significantly different between patients who died versus those who survived (0.022 +/- 0.019 vs. 0.022 +/- 0.021 ng/ml). Serum cTnI was not an independent predictor of all-cause mortality, cardiac mortality, all-cause admissions or cardiac admissions. Age (older) and serum albumin (lower) were independent predictors of all-cause mortality, whereas a history of myocardial infarction was an independent predictor of cardiac mortality. Serum sodium (lower) was an independent predictor of all-cause hospital admissions, whereas hypertension and previous myocardial infarction were independent predictors of cardiac admissions. The best predictors of the time to death were age (older) and serum sodium level (lower), irrespective of the serum cTnI levels. CONCLUSIONS: Cardiac troponin I has a limited role in predicting mortality and hospital admissions in asymptomatic patients with chronic renal failure treated with long-term hemodialysis.     

Cardiac troponin I in patients with acute lower limb ischemia

The presence, cause, and clinical significance of elevated cardiac troponin I in patients with acute lower limb ischemia is yet unknown. Forty-six patients (20 men [43%]; mean age 72 +/- 10 years, range 42 to 92) with acute lower limb ischemia were enrolled in this study. Serial creatine kinase (CK), CK isoenzyme MB (CK-MB), and troponin I measurements were obtained in all consecutive patients. Peak levels were evaluated for each patient. Twenty-four patients (52%) had elevated peak troponin I levels (>0.2 ng/ml) during their hospitalization. Patients were divided into 3 groups according to their peak troponin I levels: 11 patients (24%) had peak troponin I levels >1 ng/ml (the high troponin I group), 13 (28%) had levels of 0.2 to 1 ng/ml (the intermediate troponin I group), and the remaining 22 (48%) had peak troponin I levels <0.2 ng/ml (the low troponin I group). The peak CK levels were 10,263 +/- 16,513, 1,294 +/- 1,512, and 934 +/- 1,045 IU/ml (p = 0.04) in the 3 different troponin I subgroups, respectively, and the peak CK-MB levels were 143 +/- 170, 38 +/- 31, and 38 +/- 43, respectively (p = 0.04). Troponin I was positively correlated with CK (R = 0.35, p = 0.017) and CK-MB (R = 0.38, p = 0.009). The mean length of hospitalization was 8.3 +/- 6.2 days for the whole study group and did not vary among the 3 troponin I groups (10.5 +/- 10.9 vs 8.6 +/- 4.9 vs 7.2 +/- 4.0 days, p = 0.762). There were no differences in mortality during hospitalization among the 3 groups (4 of 11 vs 1 of 13 vs 4 of 22 patients, p = 0.22). In conclusion, patients with acute lower limb ischemia often have elevated cardiac troponin I levels. Elevated troponin I levels were not associated with the duration of hospitalization or with in-hospital mortality in this group of patients.     

Usefulness of myocardial necrosis triad markers for predicting 4-year mortality in patients with suspected acute coronary syndrome

OBJECTIVE: Cardiac troponins (cTn), creatine kinase-MB (CK-MB), myoglobin (MYO) are commonly used biochemical markers for risk stratification and diagnosis in patients with suspected acute coronary syndrome (ACS). The aim of the study was to analyse the prognostic implications of 3 myocardial necrosis markers measured at admission in the long-term observation. METHODS: The study group consisted of 336 consecutive patients whose concentration of cTnl, CK-MB and MYO were measured at admission. Patients were categorized into 4 groups according to the number of positive myocardial necrosis markers. RESULTS: There was a significant increase in the mean marker levels with increasing numbers of positive markers (over upper normal range): cTnl (0.02 +/- 0.06; 0.7 +/- 1.9; 3.4 +/- 8.8; 5.1 +/- 9.2 ng/ml; P < 0.001), CK-MB (1.3 +/- 1.1; 3.3 +/- 3.9; 21.9 +/- 39.4; 37.5 +/- 48.4 ng/ml; P < 0.001), MYO (39.4 +/- 16.5; 94.5 +/- 91; 202.2 +/- 172.2; 320.3 +/- 234.3 ng/ml; P < 0.001). There was a statistically significant increase in the 4-year all-cause mortality with increasing numbers of positive markers; P value for trend < 0.0001. CONCLUSIONS: All 3 marker levels at admission may be an important addition to the risk stratification of patients with suspected ACS and a potentially important target for therapy. They have prognostic implications in the long-term observation of patients with chest pain and suspected ACS.     

Leukocyte-depleted continuous blood cardioplegia for coronary artery bypass grafting

Many cardiac surgeries are performed with blood cardioplegia. However, some studies suggest that activated neutrophils form blood cardioplegia can cause reperfusion injury. In this study we assessed myocardial protection using a leukocyte-depleted cardioplegic solution. Patients undergoing elective coronary artery bypass grafting (CABG) with continuous blood cardioplegia were divided into two groups: the LD group, which received leukocyte-depleted blood cardioplegia (n = 11); and the control group, which received nonfiltered blood cardioplegia (n = 11). IL-6, IL-8, CK-MB, and troponin T were measured in the coronary sinus blood immediately after the release of the aortic cross-clamp. Cytokine concentrations were also measured upon the patient's return to the ICU. The total dopamine and dobutamine doses, hemodynamic measurements after surgery, and the leukocyte filtration rate were also measured. During antegrade cardioplegia infusion, leukocytes were almost completely removed (filtration rate: 85.8+/-4.0%). However, during terminal warm cardioplegia, leukocyte removal decreased (filtration rate: 39.9+/-7.8%). Immediately after the release of the aortic cross-clamp, plasma CK-MB and troponin T concentrations were significantly lower in the LD group (17.7+/-1.9 U/l and 0.017+/-0.002 ng/ml, respectively) than in the control group (30.3+/-3.6 U/l and 0.072+/-0.029 ng/ml, respectively). The IL-6 and IL-8 concentrations were similar in the LD group and the control group. After the return to the ICU, the CK-MB and troponin T concentrations were similar in the two groups. No significant differences were found in the total doses of dopamine or dobutamine after surgery in the two groups (99+/-77 vs 101+/-128 microg/kg/min). No significant differences were found in the hemodynamic parameters after surgery in the two groups. In patients undergoing CABG with continuous blood cardioplegia, leukocyte-depleted blood cardioplegic solution may attenuate reperfusion injury.     

Predictors of survival in patients with end-stage renal disease evaluated for kidney transplantation

Cardiovascular disease is the major cause of mortality in patients with end-stage renal disease (ESRD). This study examined the all-cause mortality in 3,698 patients with ESRD evaluated for kidney transplantation at our institution from 2001 to 2004. Mean age for the cohort was 48+/-12 years, and 42% were women. Stress myocardial perfusion imaging was done in 2,207 patients (60%) and coronary angiography in 260 patients (7%). There were 622 deaths (17%) during a mean follow-up period of 30+/-15 months. The presence and severity of coronary disease on angiography was not predictive of survival. Coronary revascularization did not impact survival (p=0.6) except in patients with 3-vessel disease (p=0.05). The best predictor of death was left ventricular ejection fraction, measured by gated myocardial perfusion imaging, with 2.7% mortality increase for each 1% ejection fraction decrease. In conclusion, left ventricular ejection fraction is a strong predictor of survival in patients with ESRD awaiting renal transplantation. Strategies to improve cardiac function or earlier renal transplantation deserve further studies.     

Cardiac troponins T and I in patients with end-stage renal disease: the relation with left ventricular mass and their prognostic value

BACKGROUND: Cardiac troponins are frequently elevated in patients with end-stage renal disease (ESRD) in the absence of acute myocardial ischemia. The cause and prognostic value of cardiac troponin elevations in such patients are controversial. HYPOTHESIS: The aims of this study were (1) to define the incidence of cTnT and cTnI elevations in patients with ESRD, (2) to evaluate the relationship between troponin elevations and left ventricular mass index (LVMI), and (3) to evaluate the prognostic value of elevations in cTnT and cTnI prospectively. METHODS: We included 129 patients with ESRD (71 men, age 44 +/- 16 years) with no clinical evidence of coronary artery disease. All patients underwent cardiac examinations, including medical history, physical examination, electrocardiogram, and transthoracic echocardiography. Left ventricular mass index was calculated and all patients were followed for 2 years. RESULTS: The cTnT concentration was > 0.03-0.1 ng/ml in 27 (20.9%) and > 0.1 ng/ml in 27 (20.9%) of the 129 patients. The cTnI concentration was > 0.5 ng/ml in 31 (24%) of 129 patients. Multiple logistic regression analysis identified LVMI (p < 0.001), diabetes (p = 0.001), and serum albumin level (p = 0.009) as a significant independent predictor for elevated cTnT. Left ventricular mass index was the only significant independent predictor for elevated cTnI (p = 0.002). There were 25 (19.4%) deaths during follow-up. Multivariable analysis showed that elevation of cTnT and cTnI did not emerge as an independent predictor for death. Serum albumin level (p < 0.001) was the strongest predictor of mortality, followed by age (p = 0.002) and LVMI (p = 0.005). CONCLUSIONS: Cardiac troponin T and I related significantly to the LVMI. The increased serum concentration of cardiac troponins probably originates from the heart; however, they are not independent predictors for prognosis.     

Perioperative myocardial infarction in coronary bypass surgery

Thirteen of 199 consecutive patients undergoing coronary artery bypass surgery revealed definite perioperative myocardial infarction (PMI) in electrocardiography (ECG). The occurrence of PMI was not higher in the group of 44 patients who had intermittent aortic cross-clamping than in those patients treated with cold chemical cardioplegia. In 83 patients serum MB isoenzyme of creatine kinase (CK) and LD1 isoenzyme of lactic dehydrogenase were determined. Patients with unchanged ECG had peak CK-MB levels of 0 to 49 U/l (mean 18.7 U/l +/- 2.6 SEM) at 18 hours postoperatively while patients with PMI showed CK-MB levels of 64-350 U/l (mean 207 +/- 53 U/l); the difference was significant (p less than 0.01). In patients with unchanged ECG, LD1 was 139 +/- 19 U/l and 594 +/- 95 U/l in those with PMI (p less than 0.01). Risk factors for PMI were: age greater than or equal to 60 years, coronary endarterectomies, or cardiopulmonary bypass time greater than or equal to 100 minutes. One patient died of PMI while the remaining patients had postoperative courses comparable to those patients without PMI.     

Comparative analysis of cardiac troponin i and creatine kinase-MB as markers of acute myocardial infarction

Background: The World Health Organization (WHO) criteria for the diagnosis of acute myocardial infarction (AMI) includes presentation of chest pain over 20 min, evolutionary changes on the electrocardiogram (ECG), and abnormal levels of cardiac enzymes. Hypothesis: A multicenter study was conducted to evaluate the efficacy of cardiac troponin I (cTnI) in detecting and ruling out AMI. Methods: The normal range for cTnI in 149 apparently healthy subjects without known history of cardiac or other diseases was 0 to 0.5 ng/ml. Cutoffs of 2.5 ng/ml for cTnI and 5.0 ng/ml for creatine kinase-MB (CK-MB) were used. Results: The diagnostic sensitivity of blood collected from 291 consecutive patients with suspicion of AMI was 95.0 and 96.4%, respectively, for samples obtained at 4–48 h after AMI onset. CK-MB was more sensitive during the early 4–8 h interval (84 vs. 74%); both had 100% sensitivity from 12–36 h. CTnI remained at 100% for 72 h, while CK-MB declined to 57%. The clinical specificity was 97.4 vs. 85.8%, respectively, on non-AMI patients with cardiac and noncardiac diseases, and those with renal disease. Conclusion: cTnI is an excellent marker for detecting and ruling out AMI, because it has better specificity and a wider diagnostic window than the accepted standard, CK-MB.     

Impact of statin therapy on coronary intervention for non-ST elevation acute coronary syndrome with decreased low-density lipoprotein cholesterol

OBJECTIVES: The benefits of treating patients with acute coronary syndrome (ACS) with statins are well established. This study investigated the effects of statins on patients who presented with low levels of low-density lipoprotein (LDL) cholesterol, were diagnosed with non-ST elevation ACS, and subsequently underwent percutaneous coronary interventions (PCI). METHODS: From 2000 to 2003, 87 patients(mean age 68 +/- 10 years, 69 males, 18 females) underwent PCI because of non-ST elevation ACS, and had low LDL cholesterol on presentation. These patients were divided into two groups: those who had been taking statins (S-group, n = 46), and those not taking statins, or controls (C-group, n = 41). Only patients whose LDL cholesterol was < 100 mg/dl at admission (average: 82 +/- 12 mg/dl) were included in the study. Troponin-T (TnT), creatine kinase (CK), CK-MB, and high-sense C reactive protein (hs-CRP) were measured before and 6 hr after PCI. The two groups were evaluated at 6 months clinical follow-up. RESULTS: There was no difference in these markers before PCI in both groups. TnT and CK-MB in the S-group at 6 hr post-PCI were significantly decreased compared to those of the C-group (0.45 +/- 1.34 vs 1.40 +/- 2.37 ng/ml, respectively, for TnT, p = 0.04; 17.2 +/- 45.5 vs 81.3 +/- 157.2 IU/l, respectively, for CK-MB, p = 0.02). Major adverse cardiac events (MACE) defined as death, myocardial infarction, congestive heart failure and target lesion revascularization were evaluated after 6 months. There was no difference in MACE between the two groups. CONCLUSIONS: Statin treatment before PCI in patients with non-ST elevation ACS demonstrated beneficial effects such as less myocardial damage, even though both groups presented with low LDL cholesterol levels. However, no significant effect on MACE was seen at 6 months after PCI.     

Interleukin 12 induces activation of fibrinolysis and coagulation in humans

Interleukin 12 (IL-12) has potential efficacy in malignant, infectious and allergic diseases. Its side-effects include activation of coagulation and fibrinolysis, as documented in chimpanzees. We assessed the coagulative and fibrinolytic response in 18 patients with renal cell carcinoma after subcutaneous injection of 0.5 microg/kg recombinant human IL-12. IL-12 induced a fibrinolytic response in 17 patients (94%): plasmin-alpha2-anti-plasmin complexes (PAPc) increased from 11.8 +/- 6.6 nmol/l (mean +/- SD) to a maximum of 18.8 +/- 7.4 nmol/l at 72 h. Baseline levels of tissue plasminogen activator (tPA) and plasminogen-activator inhibitor-I (PAI) were elevated in eight and 14 patients respectively. tPA increased from 12.6 +/- 5.2 ng/ml to a maximum of 19.0 +/- 6.7 ng/ml at 72 h. PAI decreased from 111 +/- 69 ng/ml to a minimum of 65 +/- 53 ng/ml at 8 h, thereafter remaining below baseline. Elevation of PAPc correlated with elevation of tPA and reduction of PAI. A coagulative response occurred in nine patients (50%): thrombin-anti-thrombin III complexes increased from 29 +/- 53 ng/ml to a maximum of 460 +/- 322 ng/ml at 12 h. Patients with and without a coagulative response had similar levels of recombinant human IL-12, interferon-gamma or tumour necrosis factor-alpha. We conclude that IL-12 can activate both fibrinolysis and coagulation in a significant proportion of patients with cancer. The time-frame and sequence of these activation processes differ from those known for other cytokines.