Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors.

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb-IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb-IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb-IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0-2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0-1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31-6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63-9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.

Gender-related differences in outcome after ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation.

Several studies have found that among patients with ST-elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is associated with a worse outcome. The aim of this study was to investigate sex-related differences in clinical and angiographic findings in patients with STEMI treated with primary angioplasty and Gp IIb-IIIa inhibitors. Our population is represented by 1662 patients undergoing primary angioplasty included in the EGYPT database. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Among 1662 patients, 379 were women (22.8%). Female sex was associated with more advanced age, higher prevalence of diabetes, hypertension, more advanced Killip class, longer ischemia time, less often smokers, with higher prevalence of preprocedural recenalization. No difference was observed in terms of postprocedural TIMI flow, myocardial perfusion and distal embolization. Similar findings were observed in terms of enzymatic infarct size and preprocedural ejection fraction. Female gender was associated with higher mortality (6.4% vs. 3.6%, HR = 1.83 [1.12-3.0], P = 0.015). However, the difference disappeared after correction for baseline confounding factors (HR = 1.01 [0.56-1.83], P = 0.98). This study shows that in patients with STEMI treated by primary angioplasty, female gender is associated with higher mortality rate in comparison with men, and this is mainly due to their higher clinical and angiographic risk profiles. In fact, female sex did not emerge as an independent predictor of mortality.

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation.

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ''cutoff'' in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2-3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 +/- 356 U/l vs. 259 +/- 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2-3 (adjusted OR [95% CI] = 3.14 [2.06-4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84-1.92], P = 0.26). At 208 +/- 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73-6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1-4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb-IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.

Association between advanced Killip class at presentation and impaired myocardial perfusion among patients with ST-segment elevation myocardial infarction treated with primary angioplasty and adjunctive glycoprotein IIb-IIIa inhibitors.

BACKGROUND: Although primary angioplasty has been shown to improve survival as compared with thrombolysis, the outcome is still unsatisfactory in subsets of patients such as those with signs of heart failure at presentation. In fact, although primary angioplasty is able to restore TIMI 3 flow in most patients, suboptimal myocardial reperfusion is observed in a relatively large proportion of patients. The aim of this study was to investigate among patients with ST-segment elevation myocardial infarction undergoing primary angioplasty the association between heart failure at presentation and myocardial perfusion and its implications in terms of survival. METHODS: Our population is represented by patients undergoing primary angioplasty who are included in the EGYPT database. Congestive heart failure was defined as Killip class >1 at admission. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Detailed data on Killip class at presentation were available in 1,427 of 1,662 patients (86% of the initial population) who represent the final population of this study. Killip class was associated with myocardial perfusion, distal embolization, enzymatic infarct size, predischarge ejection fraction, and 1-year mortality rate. Myocardial blush was an independent predictor of 1-year mortality (hazard ratio 7.44, 95% CI 1.82-30.4, P = .005) in patients with advanced Killip class at presentation. CONCLUSIONS: Our study shows that patients with heart failure complicating ST-segment elevation myocardial infarction have impaired myocardial perfusion, which accounts for the poor outcome observed in these patients. Further efforts should be aimed at improving myocardial perfusion, beyond epicardial recanalization, to further improve the outcome of these high-risk patients.

Benefits of pharmacological facilitation with glycoprotein IIb-IIIa inhibitors in diabetic patients undergoing primary angioplasty for STEMI. A subanalysis of the EGYPT cooperation.

The Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty (EGYPT) cooperation aimed at evaluating, by pooling individual patient's data of randomized trials, the benefits of pharmacological facilitation with Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. In the current study we analyze the benefits of early Gp IIb-IIIa inhibitors in diabetic patients. The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. We examined all randomized trials on facilitation by early administration of Gp IIb-IIIa inhibitors in STEMI. No language restrictions were enforced. Individual patients' data were obtained from 11 out of 13 trials, including 1,662 patients. Diabetes was present in 281 (16.9%). Early Gp IIb-IIIa inhibitors were associated with improved preprocedural TIMI 3 flow (26.0% vs. 13.1%, P = 0.006), postprocedural TIMI 3 flow (90.1% vs. 75.0%, P = 0.18), MBG 3 (40.8% vs. 30.4%, P = 0.004), and less distal embolization (11.6% vs. 20.8%, P = 0.05). However, early Gp IIb-IIIa inhibitors did not significantly reduce mortality (8.3% vs. 9.5%, P = 0.64). This meta-analysis shows that pharmacological facilitation with early administration of Gp IIb-IIIa inhibitors in STEMI patients with diabetes undergoing primary angioplasty, is associated with significant benefits in terms of preprocedural and postprocedural TIMI flow, improved myocardial perfusion, without significant benefits in mortality.

Impact of time from symptom onset to drug administration on outcome in patients undergoing glycoprotein IIb-IIIa facilitated primary angioplasty (from the EGYPT cooperation).

Contrasting data have been so far reported on facilitation with glycoprotein IIb-IIIa inhibitors (GpIIbIIIa) in patients who underwent primary percutaneous coronary intervention. However, it has been demonstrated a time-dependent composition of coronary thrombus in ST-segment elevation myocardial infarction, with more platelets in the first hours. Subsequently, the benefits of early administration of GpIIbIIIa may be affected by the time from symptoms onset to GpIIbIIIa, that therefore is the aim of this study. Our population is represented by 814 patients who underwent GpIIbIIIa facilitated primary angioplasty included in the Early glycoprotein IIb-IIIa inhibitors in primary angioplasty database. Patients were divided according to quartiles of time from symptom onset to GpIIbIIIa administration (≤65 minutes; 65 to 100 minutes; 101 to 178 minutes; and >178 minutes). Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Time from symptoms onset to GpIIbIIIa was linearly associated with hypertension, diabetes, hypercholesterolemia, and previous myocardial infarction but inversely associated with smoking. Abciximab was more often administrated later from symptoms onset. Time from symptoms onset to GpIIbIIIa was significantly associated with the rate of preprocedural recanalization (thrombolysis in myocardial infarction [TIMI] 2 to 3; p <0.001), postprocedural TIMI 3 flow (p <0.001), the rate of complete ST-segment resolution (p <0.001), and the rate of myocardial blush grade 2 to 3 (p <0.001) and inversely associated with the occurrence of distal embolization (p <0.001). Follow-up data were collected at a median (twenty-fifth to seventy-fifth) of 360 (30 to 1,095) days. A total of 52 patients had died. Time to GpIIbIIIa had a significant impact on mortality (hazard ratio [95% confidence interval] 1.46 [1.11 to 1.92], p = 0.007) that was confirmed after correction for baseline confounding factors (adjusted hazard ratio [95% confidence interval] 1.41 [1.02 to 2.21], p = 0.042). In conclusion, this study showed that in patients who underwent primary angioplasty with upstream GpIIbIIIa, time from symptoms onset to GpIIbIIIa strongly impacts on preprocedural recanalization, distal embolization, myocardial perfusion, and long-term survival.

Myocardial perfusion and angioplasty. Comparison of myocardial contrast echocardiography and scintigraphy.

OBJECTIVES: To estimate the efficacy of myocardial contrast echocardiography (MCE) by harmonic power imaging (HPI), in evaluation of perfusion in one-vessel coronary disease treated by angioplasty, using myocardial scintigraphy as gold standard. STUDY DESIGN: Prospective comparative study. SETTING: Ambulatory. POPULATION: We included 33 patients (pts), aged 53.5 +/- 9 years, 27 male. INCLUSION CRITERIA: pts with one-vessel coronary disease (> or = 70% stenosis), with indication for angioplasty; sinus rhythm; good echocardiographic window with harmonic imaging. Exclusion criterion: previous myocardial infarction. METHODS: All patients underwent myocardial scintigraphy and HPI together with stress echocardiography, both followed by angioplasty (stenting in ten). HPI and myocardial scintigraphy were repeated, in all patients, at three months after intervention. Ten patients were re-assessed by coronary angiography for ischemia on the scintigraphic study. For the HPI exam, Levovist was selected as contrast and dipyridamole as stress agent (0.56 mg/kg). Perfusion was assessed visually and classified by HPI and scintigraphy studies as: 1 (normal), 2 (reduced), or 3 (absent). For analysis, the left ventricle was divided into 16 segments. RESULTS: Of the 43 coronary angiograms performed (ten at three months after angioplasty), 38 showed 70% stenosis, none occlusive or subocclusive. We analyzed 1056 left ventricle segments, from 66 HPI and myocardial scintigraphy studies (before and after angioplasty). Analysis was impossible or doubtful in 4.9%. Baseline and stress HPI detected 216 perfusion abnormalities. Global concordance between the segmental perfusion score obtained by HPI and scintigraphy was 66.2%, which became 76.3% when two groups were considered: a) score 1 b) score 2 and 3 together. In comparison with scintigraphy, HPI sensitivity for detection of perfusion abnormalities was 79.3% (higher for anterior septum, anterior and lateral wall) and specificity was 91.4% (higher for septum, inferior wall and apical segments). HPI correctly identified the location of coronary stenosis in 73.5% of patients. CONCLUSIONS: In our study, HPI was a feasible and promising method for assessment of perfusion in one-vessel coronary disease and chronic ischemia. In comparison with myocardial scintigraphy, a high concordance for perfusion score was found, as well as high sensitivity and specificity for detection of perfusion abnormalities.

Impact of hypertension on distal embolization, myocardial perfusion, and mortality in patients with ST segment elevation myocardial infarction undergoing primary angioplasty.

Hypertension is a well-known risk factor for atherosclerosis. However, data on the impact of hypertension in patients with ST elevation myocardial infarction (STEMI) are inconsistent and mainly related to studies performed in the thrombolytic era, with very few data on patients undergoing primary angioplasty. The aim of the present study was to evaluate the impact of hypertension on distal embolization, myocardial perfusion, and mortality in patients with STEMI undergoing primary percutaneous coronary intervention. Our population is represented by 1,662 patients undergoing primary angioplasty for STEMI included in the Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty database. Myocardial perfusion was evaluated by myocardial blush grade and ST segment resolution. Follow-up data were collected within 1 year after primary angioplasty. Hypertension was observed in 700 patients (42.1%). Hypertension was associated with more advanced age (p <0.001), female gender (p <0.001), diabetes (p <0.001), hypercholesterolemia (p <0.001), previous revascularization (p <0.001), anterior myocardial infarction (p = 0.006), longer ischemia time (p = 0.03), more extensive coronary artery disease (p = 0.002), more often treated with abciximab (p <0.001), and less often smokers (p <0.001). Hypertension was associated with impaired postprocedural myocardial blush grade 2 to 3 (68.2% vs 74.2%, p = 0.019) and complete ST segment resolution (51.7% vs 61.1%, p = 0.001). By a mean follow-up of 206 ± 158 days, 70 patients (4.3%) had died. Hypertension was associated with a greater mortality (6.2% vs 2.9%, hazard ratio 2.31, 95% confidence interval 1.42 to 3.73, p <0.001), confirmed after correction for baseline confounding factors (hazard ratio 1.82, 95% confidence interval 1.03 to 3.22, p <0.001). In conclusion, this study showed that among patients with STEMI undergoing primary angioplasty, hypertension is associated with impaired reperfusion and independently predicts 1-year mortality.

Impact of preprocedural TIMI flow on myocardial perfusion, distal embolization and mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb/IIIa inhibitors.

BACKGROUND: Despite optimal epicardial recanalization, primary angioplasty for ST-elevation myocardial infarction (STEMI) is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim of the current study was to evaluate the impact of preprocedural TIMI flow on myocardial perfusion, distal embolization, and survival among STEMI patients undergoing primary angioplasty with glycoprotein (GP) IIb/IIIa inhibitors. METHODS: Our population is represented by a total of 1637 patients undergoing primary angioplasty for STEMI treated with GP IIb/IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Poor preprocedural TIMI flow (TIMI 0-1) was observed in 1039 patients (63.5%), and was associated with higher Killip class at presentation (P=.006), longer time-to-treatment (P=.03), less often with early administration of GP IIb/IIIa inhibitors (P<.001), impaired postprocedural epicardial (P=.001) and myocardial perfusion (determined by myocardial blush grade, P<.001 and/or ST-segment resolution (P<.001), and distal embolization (P=.041). At 206 ± 158 days follow-up, poor preprocedural recanalization was associated with a significantly higher mortality (adjusted odds ratio, 0.58; 95% CI, 0.34-0.96; P=.034). CONCLUSION: This study shows that among patients with STEMI undergoing primary angioplasty with GP IIb/IIIa inhibitors, poor preprocedural TIMI flow is associated with higher incidence of distal embolization and impaired epicardial and myocardial perfusion, and significantly higher mortality.

Time-related impact of distal embolisation on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation.

AIMS: Considerable interest has been focused in recent years on the role of distal embolisation as a major determinant of impaired reperfusion after primary angioplasty for STEMI. The aim of the current study was to evaluate in a large cohort of STEMI patients undergoing primary angioplasty with glycoprotein (Gp) IIb-IIIa inhibitors, whether the impact of distal embolisation on myocardial perfusion and survival may depend on time-to-treatment. METHODS AND RESULTS: Our population is represented by 1,182 patients undergoing primary angioplasty for STEMI included in the EGYPT database. Patients were grouped according to time-to-treatment (<3 hours, 3-6 hours, >6 hours). Distal embolisation was defined as an abrupt "cutoff" in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase (CK) and CK-MB. Follow-up data were collected between 30 days and one year after primary angioplasty. Distal embolisation was observed in 132 patients (11.1%) and tended to occur more frequently in late presenters (p=0.067). Patients with distal embolisation less often had post-procedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow (p<0.001), post-procedural myocardial blush grade (MBG) 2-3 (p<0.001), complete ST-segment resolution (p=0.021) and larger infarct size (p=0.012). Distal embolisation was associated with a significantly higher mortality (9.2% vs. 2.7%, heart rate [HR] [95% CI]=3.41 [1.73-6.71], p<0.0001). The impact of distal embolisation on myocardial perfusion and survival persisted for all time intervals. CONCLUSIONS: This study showed that among STEMI patients treated with Gp IIb-IIIa inhibitors, the negative impact of distal embolisation on myocardial perfusion and mortality is independent of the time from symptom onset to balloon angioplasty.

Role of abciximab in the treatment of coronary artery disease.

Glycoprotein IIb/IIIa complex is a crucial membrane receptor for platelet aggregation, binding platelets to fibrinogen and establishing interplatelet bridges. This receptor is the common end point of the multiple activation pathways of a platelet. Antiplatelet agents, such as aspirin or thienopyridines, including ticlopidine and clopidogrel, inhibit one or more but not all, of these pathways. Inhibitors of the receptor are powerful platelet antiaggregants and include two groups of agents: non-competitive receptor blockers, such as abciximab, and competitive antagonists, such as tirofiban and eptifibatide. Abciximab is a monoclonal antibody that binds to the glycoprotein IIb/IIIa complex, thus blocking the interaction with fibrinogen. It is used for treatment of coronary artery disease, being well-studied in the setting of acute coronary syndromes and percutaneous coronary intervention, in which a rapid and effective antiaggregation is clinically important.

Early administration of abciximab bolus in the emergency department improves angiographic outcome after primary PCI as assessed by TIMI frame count: results of the early ReoPro administration in myocardial infarction (ERAMI) trial.

OBJECTIVES: We assessed the safety and efficacy of early administration of abciximab prior to percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. BACKGROUND: Research suggests that platelet glycoprotein IIb/IIIa receptor inhibitors, e.g. abciximab, may improve myocardial perfusion. In particular, early administration in the emergency department, prior to PCI, may result in more effective reperfusion. METHODS: Eighty AMI patients with planned PCI were randomized in a double-blind fashion to receive a 0.25 mg/kg abciximab bolus either "early" in the emergency department or "late" in the catheterization laboratory after angiographic assessment. In total, 74 patients underwent PCI after diagnostic angiography, all of which then received an abciximab infusion of 0.125 microg/kg/min for 12 hr. RESULTS: Prior to PCI, no significant differences were observed between the two groups regarding the angiographic endpoints or ST-segment resolution. After PCI, thrombolysis in MI (TIMI) frame count (TFC) was significantly improved in patients treated early rather than in those treated late (23 +/- 10 vs. 41 +/- 35; P = 0.02). Consistent trends, also favoring early treatment, were observed for TIMI flow grade 3 (TFG 3), corrected TFC (CTFC), and TIMI myocardial perfusion grade 3 (TMPG 3). Nine deaths (4 early, 5 late) and six significant bleeds (4 early, 2 late) were observed at 30 days after randomization. CONCLUSIONS: Early administration of abciximab is both feasible and safe in patients planned for primary PCI, increasing coronary flow and myocardial reperfusion after PCI, as demonstrated by significantly decreased TFC scores and trends toward improvements in TFG, CTFC, and TMPG.