GRACE, TIMI, Zwolle and CADILLAC risk scores--do they predict 5-year outcomes after ST-elevation myocardial infarction treated invasively?

BACKGROUND: GRACE, TIMI, Zwolle, and CADILLAC are risk scores designed for predicting short-term outcome after acute coronary syndromes. The aim of our study was to test their utility for a prognosis of 5-year survival in a "real-life" population of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI). METHODS: Our registry consisted of consecutive patients with STEMI treated with pPCI. Five-year follow-up was performed with all-cause mortality as the end-point. RESULTS: Out of 505 patients (mean age 58.6±11.3 years) 32 died during the first 30 days (6.3%) and an additional 74 within 5 years (15.6%). PCI was successful in 95.2% (n=481). Prognostic values (c statistics) for predicting 5-year mortality equaled: 0.742 (CI 0.69-0.79) for the GRACE risk score, 0.727 (CI 0.67-0.78) for TIMI, 0.72 (CI 0.67-0.77) for Zwolle, and 0.687 (CI 0.63-0.74) for CADILLAC. In a univariate analysis all the scores were associated with the 5-year outcome. CONCLUSIONS: GRACE, TIMI, and Zwolle risk scores predicted well 5-year all-cause mortality in patients with STEMI treated with pPCI. Our data show that the usefulness of initial bedside risk assessment can be further extended for long-term follow-up.

Circadian variations of interleukin 6 in coronary circulations of patients with myocardial infarction.

UNLABELLED: We hypothesize that higher morbidity of patients with ST-segment elevation myocardial infarction (STEMI) in the out-of-office hours differences in outcome after myocardial infarction may depend on the concentrations of inflammatory cytokines. The aim of the study was to determine the relation between the time of percutaneous coronary intervention (PCI) and local concentration of interleukin 6 (IL-6) and its soluble receptors (sIL-6R and sgp130) in patients with STEMI. METHODS AND RESULTS: The study included 32 patients with invasively treated left anterior descending artery occlusion and no significant co-morbidities. Blood samples were drawn from coronary sinus and aorta before and after intervention. Patients admitted in the afternoon (13-20) presented significantly higher mean IL-6 levels in all samples than patients admitted in the morning. There was a positive correlation between time of intervention and concentrations of IL-6 in all samplings, but also with transcardiac IL-6 gradient at the end of procedure and IL-6 increase during PCI. We did not find any significant association between time of PCI and concentrations of sIL-6R and sgp130, time from pain to balloon, angiographic parameters or medical history. CONCLUSIONS: Coronary concentration of IL-6 in patients with STEMI is significantly higher in the afternoon than in the morning. This might be involved in increased morbidity of those patients.

Percutaneous coronary interventions affect concentrations of interleukin 6 and its soluble receptors in coronary sinus blood in patients with stable angina.

Coronary stenting may create local inflammatory reaction. Interleukin 6 effects depend on the presence of soluble receptors (sIL-6R and sgp130) that facilitate or impede interleukin 6 signal transduction. Concentrations of interleukin 6 and its soluble receptors were assessed in aorta and coronary sinus after stenting in optimally treated stable angina patients scheduled for elective stenting. Baseline levels of interleukin 6 and its soluble receptors in patients did not differ from healthy controls. Initial levels of sIL-6R in aorta were significantly higher than in coronary sinus but this difference disappeared after intervention. Stenting caused interleukin 6 concentration increase to a similar extent both in coronary sinus and in aorta. Moreover, there was significantly higher sgp130 concentration in coronary sinus than in aorta. Coronary intervention increases concentration of interleukin 6 in patients with stable angina. It affects the cardiac level of interleukin 6 soluble receptors what may influence the local inflammatory reaction.

Coronary sinus concentrations of interleukin 6 and its soluble receptors are affected by reperfusion and may portend complications in patients with myocardial infarction.

UNLABELLED: Interleukin 6 (IL-6) is a pleiotropic cytokine involved in both inflammatory reaction and myocardial response to stress. Its effects largely depend on the concentration of the soluble receptors (sIL-6R and sgp130). We investigated the production of IL-6, sIL-6R and sgp130 by the heart during ischemia and reperfusion. METHODS: The levels of IL-6 were determined in blood of 34 patients with first myocardial infarction (STEMI), left anterior descending (LAD) artery occlusion, otherwise normal coronaries, without significant co-morbidities and 16 comparable subjects with stable ischemic heart disease and lesion in LAD. Blood samples from coronary sinus (CS) and aorta (Ao) were drawn before percutaneous intervention (PCI), immediately after and at the end of the procedure. Venous blood from 30 healthy volunteers served as control. RESULTS: STEMI patients presented high IL-6 concentrations that increased further after reperfusion when its levels in CS became significantly higher than in Ao. In both groups prior to the PCI there were significantly higher concentrations of sIL-6R in Ao than in CS. This difference disappeared immediately after reperfusion. STEMI patients who experienced cardiovascular complications had higher IL-6 concentration and higher transcardiac sIL-6R gradient than patients with event-free hospitalisation. This association was confirmed in multivariate logistic regression analysis. Myocardial infarction increases concentration of IL-6 that is further elevated by reperfusion. A transcardiac gradient of sIL-6R during ischemia may indicate that large amounts of soluble IL-6 receptors are bound to the infarcted heart and thus affect signal transduction. IL-6 and initial sIL-6R gradient may portend complications in STEMI patients.

Lack of ST-segment depression normalization after PCI is a predictor of 5-year mortality in patients with ST-elevation myocardial infarction.

BACKGROUND: The significance of dynamic changes in a depressed ST-segment in the reciprocal changes after percutaneous coronary intervention (PCI) of patients with ST-elevation myocardial infarction (STEMI) is unknown, so the aim of this study was to evaluate the significance of reciprocal ST-segment depression normalization (STN) on long-term mortality in patients with STEMI treated with primary PCI. METHODS AND RESULTS: Data for 247 consecutive patients with STEMI were analyzed; 84 patients were excluded because of exclusion or incomplete inclusion criteria, so finally, 163 patients successfully treated with primary PCI were included. The study group was divided into 3 subgroups according to percentage of STN: poor STN (<30%), partial STN (30-70%), complete STN (>70%). Complete STN occurred in 63%, partial in 24% and poor in 13% of patients. STN correlated with late mortality (15% vs 28% vs 38% respectively, p=0.012). Patients who died during the follow-up period had a lower mean percentage reduction of initial ST-segment depression after PCI (50% vs 75%, p=0.001). Percentage reduction of initial ST-segment depression after PCI was a significant and independent risk factor of long-term mortality (odds ratio 1.01; 95% confidence interval: 1.00-1.02; p=0.02). CONCLUSIONS: These data revealed the use of reciprocal changes normalization as a novel tool for assessment of long-term risk of death in patients after successful primary PCI for STEMI.

Transfer with GP IIb/IIIa inhibitor tirofiban for primary percutaneous coronary intervention vs. on-site thrombolysis in patients with ST-elevation myocardial infarction (STEMI): a randomized open-label study for patients admitted to community hospitals.

AIMS: Our study aimed to compare two reperfusion strategies in patients with ST-elevation myocardial infarction (STEMI) admitted initially to a community hospital without catheterization facilities. METHODS AND RESULTS: Four hundred and one patients with STEMI admitted to community hospital (13 hospitals, radius 20-150 km from cath-lab) were randomized to on-site thrombolysis or to transport with tirofiban (10 microg/kg bolus i.v. + i.v. infusion 0.1 microg/kg/min) for primary PCI in single invasive centre. Primary endpoints were total mortality, recurrent MI (re-AMI), and stroke during 1 year follow-up. Delay to reperfusion defined as interval between admission and start of fibrinolysis or primary PCI was 35 and 145 min (P < 0.0001). Mean time of tirofiban administration to PCI in transfer group was: 122.3 +/- 35.7 min. Mortality was not different during hospitalization and at 30th-day, with trend towards lower mortality at 1 year in transport group (12.5 vs. 7.0%, P = 0.061). There were no differences in the rate of re-AMI and stroke, with trend towards lower incidence of re-AMI in transfer group at 1 year (7.5 vs. 3.5%, P = 0.073). Composite of death/re-AMI/stroke was higher in on-site group during follow-up (15.5 vs. 8.0%, P = 0.019; 21.5 vs. 11.4%, P = 0.006, respectively, at 30th-day and 1 year). CONCLUSION: Outcomes at 1 year follow-up suggest that transportation with adjunctive therapy with GP IIb/IIIa inhibitor tirofiban for primary PCI is superior to on-site thrombolysis for patient with STEMI presenting to hospital without catheterization facilities.

Is transport with platelet GP IIb/IIIa inhibition for primary percutaneous coronary intervention more efficient than on-site thrombolysis in patients with STEMI admitted to community hospitals? Randomised study. Early results.

INTRODUCTION: The advantage of primary percutaneous coronary intervention (pPCI) in the management of ST-elevation myocardial infarction (STEMI) over thrombolytic therapy has been demonstrated. However, an optimal medical treatment of STEMI patients admitted to regional hospitals without catheterisation facilities has not yet been established. Delay in initiation of pPCI resulting from transportation to the catheterisation laboratory may diminish the benefits of such therapy in comparison with thrombolysis administered in a regional hospital. Early initiation of therapy with platelet glycoprotein IIb/IIIa receptor inhibitor, which provides protection for the transportation, may be a reasonable solution to maintain the advantage of pPCI over thrombolysis alone in STEMI patients. METHODS: The studied group comprised patients with STEMI (infarct duration time <12 hours, typical clinical and electrocardiographic criteria of MI) who were randomly assigned in 13 regional hospitals located 20 to 150 km from invasive centre to one of two subgroups, either to thrombolysis in the community hospital or to transport after thrombolysis initiation with platelet GP IIb/IIIa receptor inhibitor (tirofiban; 10 mg/kg in intravenous bolus in the emergency room of the community hospital followed by continuous intravenous infusion of 0.1 mg/kg/min during transport as well as coronary procedure) in order to receive pPCI. All patients with cardiogenic shock on admission were routinely treated with PCI and were excluded from the study. RESULTS: 341 patients were included in the study (169 were randomised to receive thrombolytic therapy and 172--transport with intention to perform PCI). Mean time between onset of MI and randomisation was similar in the transport and thrombolysis groups, (139+/-133 min. vs 143+/-117 min., respectively, p=0.94). Mean infusion time of tirofiban to the beginning of PCI in the transport group was 121+/-36 min. Anterior MI was present in 42.6% of patients in the PCI group and in 41.5% in the thrombolytic group (p=0.085). Mean time from randomisation to pPCI was 158+/-60 min., and to thrombolysis initiation in 44+/-43 min. (p <0.0001). None of the patients died during transfer. In a 30-day follow-up we noted (pPCI vs thrombolytic group, respectively): mortality 3.49% vs 8.88% (p=0.04); reinfarction 1.16% vs 5.92% (p=0.02), stroke 0.58% vs 1.18% (p=0.55). In-hospital stay was significantly shorter in the transport group (9+/-3 days vs 14+/-7 days, p <0.0001). During hospitalisation, 17 (10.05%) patients initially assigned to thrombolysis alone had to be transferred to the catheterisation laboratory to undergo PCI (rescue PCI or PCI for postinfarction angina). Combined end-point (death/reinfarction/stroke) was reached more frequently in the thrombolytic group (15.98% vs 5.23%, p=0.001). CONCLUSIONS: A strategy of invasive therapy involving transport with GP IIb/IIIa receptor inhibitor and pPCI in STEMI patients admitted to hospital without catheterisation facilities was found to be more effective than thrombolytic therapy alone employed in the regional hospitals.

Does gastro-esophageal reflux provoke the myocardial ischemia in patients with CAD?

BACKGROUND: Gastro-esophageal reflux disease (GERD) may cause chest pain. The aim was to determine the correlation between ischemia and gastro-esophageal reflux in patients with CAD and to assess the influence of short-term "anti-reflux" therapy on the ischemia in patients with GERD and CAD. METHODS: Fifty patients with angiographically proven CAD underwent simultaneous 24-h continuous ECG and esophageal pH monitoring. We assessed the number of ST-segment depression episodes (ST dep.) and total duration of ischemic episodes, expressed as total ischemic burden (TIB). In pH-metry, we assessed: time percentage of pH lower than 4, total time of pH lower than 4 and the number of pathological refluxes (PR). Patients fulfilling the GERD criteria received a 7-day therapy with omeprazole 20 mg bid. On the 7th day of therapy, simultaneous Holter and esophageal pH monitoring was repeated. RESULTS: Total number of 224 PRs in 42 patients (84%) was recorded during esophageal pH-metry. GERD criteria were fulfilled in 23 patients (46%). Out of 218 episodes of ST dep., 45 (20.6%) correlated with PR. GERD patients had larger TIB and higher number of ST dep. (p<0.015 and p<0.035, respectively). The anti-reflux therapy reduced all analyzed parameters of esophageal pH monitoring (p<0.0022) as well as the number of ST dep. (p<0.012) and TIB (p<0.05). CONCLUSIONS: Gastro-esophageal reflux disease is common in patients with CAD and may provoke myocardial ischemia. Short-term proton pump inhibitors therapy that restores normal esophageal pH significantly reduces myocardial ischemia, possibly due to elimination of acid-derived esophago-cardiac reflex compromising coronary perfusion-the phenomenon known as "linked angina".

Safety and feasibility of a novel dosing regimen of tirofiban administered in patients with acute myocardial infarction with ST elevation before primary coronary angioplasty: a pilot study.

BACKGROUND: Intravenous glycoprotein GP IIb/IIIa receptor antagonists administered to patients with acute coronary syndromes limit platelet-dependent thrombus formation and vasoconstriction and lower the complication rate of PCI. The efficacy of glycoprotein IIb/IIIa inhibitors critically depends on appropriate suppression of platelet aggregation. A growing body of evidence indicates that regimen of tirofiban used in several recent trials may be suboptimal. We investigated if a novel regimen of dosage of tirofiban administered to patients with acute myocardial infarction with ST elevation (STEMI) before primary angioplasty is safe, feasible and whether such treatment improves coronary flow in infarct-related artery. METHODS: It was an open-label, non-randomized, prospective observational study. 253 consecutive patients with STEMI, qualified to PCI were included. 104 of patients (group 1) received heparin plus tirofiban at a novel regimen (10 microg/kg bolus, followed by 0.4 microg/kg/min for 30 min and then 0.1 microg/kg/min for 12-24 hours) and the remaining 149 of the patients (group 2) received a standard dose of heparin prior to PCI. Bleeding complications were recorded. The primary end point of the study was combined TIMI 1 + 2 + 3 grade flow at the time of first contrast medium injection during angiography for primary PCI. RESULTS: Heparin was administered 50.3 +/- 58.1 minutes (group 1) or 62.3 +/- 67.3 minutes (group 2) ( p = 0.205). Tirofiban was administered for an average of 14.5 +/- 14.4 minutes before TIMI assessment (group 1). In patients treated with heparin + tirofiban the rate of combined TIMI 1 + 2 + 3 coronary flow was higher (38.4% vs. 24.8%, p = 0.020) as compared to patients treated with heparin alone. The difference in the rate of TIMI > or = 2 coronary blood flow between the groups 1 and 2 (24.0% vs. 20.1%) has not reached statistical significance ( p = 0.459). At the same time the significant difference in the rate of TIMI 1 coronary blood flow between the groups 1 and 2 was noted (14.4 vs. 4.7%, p = 0.007). In hospital mortality in the groups 1 and 2 was similar (5.3 vs. 4.8%, p = 0.838). Significant difference was noted between the groups 1 and 2 with regard to minor bleeding complications (17.3 vs. 8.7%, p = 0.041). CONCLUSION: In patients undergoing primary angioplasty for acute myocardial infarction the novel regimen of tirofiban is well tolerated and feasible, and is associated with improvement in coronary blood flow in the infarct related artery. Larger studies assessing the effects of tirofiban on clinical outcomes of patients with AMI undergoing primary angioplasty seem worthwhile.

Platelet inhibition by increased tirofiban dosing during primary coronary angioplasty for ST elevation myocardial infarction.

BACKGROUND: Platelet receptor IIb/IIIa inhibition during percutaneous coronary interventions (PCI) decreases incidence of major adverse cardiac events (MACE). These effects directly result from the level of platelet inhibition. Due to existing data indicating that standard dosing of tirofiban is insufficient for optimal platelet inhibition, we proposed a novel, experimental dosing. AIM: In this study we assessed, with the use of Ultegra Rapid Platelet Function Assay (RFPA), the level of platelet inhibition with increased tirofiban dosing during primary PCI for ST elevation myocardial infarction (STEMI). METHODS: Twenty eight patients (22 males, 6 females, mean age 63 years, range 32-78 years) with STEMI were included into the study. All patients received 300 mg of aspirin, iv. heparin in a dose of 10 000 IU, which was followed by platelet receptor GP IIb/IIIa inhibitor tirofiban - 10 micro g/kg iv bolus, 0.4 micro g/kg/min for 30 min and infusion 0.1 micro g/kg/min continued for 12-24 h. Platelet function was assessed with RFPA before tirofiban administration and after 10, 30, 90 minutes as well as 8 hours from the initial dose of tirofiban. Baseline fibrinogen binding to platelet receptor IIb/IIIa was defined as PAU (platelet aggregation unit) and the effects of tirofiban on platelets were expressed as a percentage of platelet inhibition. RESULTS: During in-hospital stay, no deaths, re-infarction nor recurrences of ischaemia requiring intervention were noted. The mean total duration of tirofiban administration was 21 hours. Thrombocytopenia was not observed in any patient. Bleeding complications occurred in 5 (17.9%) patients. Blood transfusion was required in three patients. The percentages of platelet inhibition measured at the pre-specified time-points were 95%, 94%, 91% and 87%, respectively. In 32% of patients an inhibition of platelet exceeding 95%, measured 10 minutes from the onset of tirofiban infusion, was not achieved. At the same time, platelet inhibition <90% was found in only 3 (11%) patients. Eight hours from the initiation of tirofiban, platelet inhibition <70% was found in 3 (11%) patients; of them, two had platelet inhibition <95% when measured 10 minutes from the onset of therapy with tirofiban. CONCLUSIONS: 1. Increased dosing of tirofiban resulted in an enhanced platelet inhibition. 2. Optimal platelet inhibition, especially during first minutes of drug administration, was not achieved in a substantial number of patients. 3. Increased IIb/IIIa inhibitor dosing resulted in a high partial and normal baseline coronary flow in an infarct-related artery. 4. Increased tirofiban dosing resulted in a relatively high bleeding complications rate.