Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial).

OBJECTIVES: This prospective randomized trial evaluates the impact of early abciximab administration on angiographic and left ventricular function parameters. BACKGROUND: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. METHODS: Two-hundred ten consecutive patients with first AMI undergoing primary PCI were randomized to abciximab administration either in the emergency room (early group: 105 patients) or in the catheterization laboratory, after coronary angiography (late group: 105 patients). Primary end points were initial Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and myocardial blush grade (MBG), as well as left ventricular function recovery as assessed by serial echocardiographic evaluations. RESULTS: Angiographic pre-PCI analysis showed a significantly better initial TIMI flow grade 3 (24% vs. 10%; p = 0.01), cTFC (78 +/- 30 frames vs. 92 +/- 21 frames; p = 0.001), and MBG 2 or 3 (15% vs. 6%; p = 0.02) favoring the early group. Consistently, post-PCI tissue perfusion parameters were significantly improved in the early group, as assessed by 60-min ST-segment reduction > or =70% (50% vs. 35%; p = 0.03) and MBG 2 or 3 (79% vs. 58%; p = 0.001). Left ventricular function recovery at 1 month was significantly greater in the early group (mean gain ejection fraction 8 +/- 7% vs. 6 +/- 7%, p = 0.02; mean gain wall motion score index 0.4 +/- 0.3 vs. 0.3 +/- 0.3, p = 0.03). CONCLUSIONS: In patients with AMI treated with primary PCI, early abciximab administration improves pre-PCI angiographic findings, post-PCI tissue perfusion, and 1-month left ventricular function recovery, possibly by starting early recanalization of the infarct-related artery.

Early abciximab administration in acute myocardial infarction treated with primary coronary intervention.

BACKGROUND: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion and clinical outcomes of patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. In this prospective randomized trial, we evaluated the impact of early abciximab administration on angiographic findings, myocardial salvage and left ventricular function. METHODS AND RESULTS: Fifty-five consecutive patients with first AMI, undergoing primary PCI, were randomized to abciximab administration either in the emergency room (early group: 27 patients) or in the catheterization laboratory after coronary angiography (late group: 28 patients). The primary outcome measures were initial Thrombolysis In Myocardial Infraction (TIMI) grade flow, corrected TIMI frame count and myocardial blush grade as well as salvage index and left ventricular function recovery as assessed by serial scintigraphic scans performed at admission, and 7 days and 1 month after PCI. Angiographic analysis showed a significant difference in initial TIMI grade 3 flow, corrected TIMI frame count and myocardial blush grade favouring early group. Moreover, salvage index and left ventricular function recovery were significantly greater in the early group (P=0.007; and P=0.043, respectively). CONCLUSIONS: In patients with AMI, treated with primary PCI, early abciximab administration improves myocardial salvage and left ventricular function recovery probably by starting early recanalization of the infarct-related artery.

[Sirolimus-eluting stent for in-stent restenosis treatment: single center results in an unselected study population]. / Stent a rilascio di sirolimus nel trattamento della restenosi intrastent: esperienza di un singolo centro in una popolazione non selezionata di pazienti.

BACKGROUND: Sirolimus-eluting stents have already proved to be efficient in the prevention of restenosis in de novo lesions and have been already proposed as a potential treatment of in-stent restenosis. In the present study, we evaluated the effectiveness of sirolimus-eluting stent implantation in unselected patients with in-stent restenosis. METHODS: Fifty consecutive patients (59 lesions) were treated with sirolimus-eluting stents for instent restenosis. The incidence of major adverse cardiovascular events and restenosis was evaluated at 1-year clinical and angiographic follow-up. RESULTS: At baseline, 54% of the lesions were complex (46% proliferative and 8% total occlusions). Small vessel size (< or = 2.5 mm) was present in 30%, a long lesion (> 20 mm) in 25%, and diabetes in 42% of the patients. The angiographic follow-up was obtained in 47 patients (55 lesions). Restenosis was observed in 13% of the lesions. At the 1-year follow-up, the incidence of major adverse cardiovascular events was 16% (4% acute myocardial infarction, 12% target lesion revascularization). CONCLUSIONS: This study confirms the efficacy of sirolimus-eluting stents for the treatment of instent restenosis in an unselected population of consecutive patients at high risk of restenosis and with a broad range of morphological lesion patterns.

Effects of tirofiban plus clopidogrel versus clopidogrel plus provisional abciximab on biomarkers of myocardial necrosis in patients with non-ST-elevation acute coronary syndromes treated with early aggressive approach. Results of the CLOpidogrel, upstream TIrofiban, in cath Lab Downstream Abciximab (CLOTILDA) study.

BACKGROUND: In non-ST-elevation acute coronary syndromes (NSTE-ACS), a strong correlation between adverse clinical events and peak values of myocardial necrosis markers has been found. In this study, we evaluated whether the adjunctive treatment with upstream tirofiban reduces the peak levels of cardiac troponin I and creatine kinase-MB (CK-MB) fraction in patients with NSTE-ACS undergoing early invasive strategy and pretreated with aspirin, heparin, and clopidogrel. METHODS: A total of 300 patients were randomized to receive tirofiban (group 1) or not (group 2). Serial marker samples were collected before and after coronary angiography in all cases and after percutaneous coronary intervention (PCI) when performed. RESULTS: Between the 2 groups, no differences were observed in clinical and angiographic findings. Percutaneous coronary intervention was globally performed in 198 patients (66%). Of 99 group 2 patients, 26 (26%) received abciximab just before PCI. No significant differences between the 2 groups were observed with regard to cardiac troponin I and CK-MB values at admission and at 6, 12, and 24 hours thereafter; peak values before coronary angiography; and peak values of index event. In addition, the cumulative biomarkers release of the index event was similar between the 2 groups. Major bleeding rate was 2% in group 1 and 1% in group 2 (P = not significant). Composite incidence of death, myocardial infarction, or rehospitalization for ACS at 30 days was 9% in group 1 and 10% in group 2. CONCLUSIONS: In patients with NSTE-ACS undergoing early invasive strategy, the adjunctive administration of upstream tirofiban did not reduce the peak values and the cumulative release of myocardial necrosis markers, compared with aspirin, heparin, and clopidogrel given on admission and associated with selective use of abciximab just before PCI.

Facilitated primary coronary intervention with abciximab and very low dose of alteplase during off-hours compared with direct primary intervention during regular hours.

In patients with acute myocardial infarction (AMI), the off-hour presentation is one of the major determinants of door-to-balloon delay. Moreover, the nighttime presentation is associated with increased mortality after primary coronary intervention (PCI). The prompt starting of a therapy able to start recanalization of the infarct-related artery before intervention might improve the results of off-hour primary PCI. We compared the outcome of 212 consecutive patients with AMI undergoing either direct or facilitated PCI according to the hour of presentation. Patients arriving off-hours were pretreated with alteplase (20 mg) and abciximab and underwent facilitated PCI. Patients presenting on-hours underwent direct PCI. A basal Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 was observed in 1.0% of patients undergoing direct PCI and in 44% of patients undergoing facilitated PCI (P = 0.001). More patients starting PCI with a TIMI 3 flow achieved a postinterventional fast TIMI frame count (72.0% vs. 38.8% direct PCI group vs. 34.9% facilitated PCI group with basal TIMI 0-2; P = 0.001) and a TIMI perfusion grade 3 (66.0% vs. 38.8% direct PCI group vs. 39.7% facilitated PCI group with basal TIMI 0-2; P = 0.004). Preinterventional TIMI flow grade 3 was associated with a higher gain in left ventricular ejection fraction at 1 month (10.9% +/- 6.4% vs. 7.0% +/- 9.6% direct PCI group vs. 6.1% +/- 6.0% facilitated PCI group with basal TIMI 0-2; P = 0.005). No significant difference was observed in major bleedings, although there was a trend toward a higher risk in the facilitated PCI group. Patients in the facilitated PCI group achieving a basal TIMI 3 flow showed improved myocardial reperfusion and better left ventricular function recovery. Bleeding complications associated with combination therapy remained an important concern.

[Non-ST-elevation acute coronary syndromes: the problem of the elderly patient]. / Sindromi coronariche acute senza sopraslivellamento del tratto ST: il problema del paziente anziano.

The elderly population represents a relevant proportion of patients with non-ST-elevation acute coronary syndromes and are at increased risk because of the greater extent of coronary artery disease, a reduction in left ventricular ejection fraction, and associated comorbidities. Results from registries and post-hoc analysis of randomized clinical trials have shown that an early invasive strategy with myocardial revascularization when indicated offers a greater clinical benefit in the elderly that in younger patients despite an increased procedural risk in elderly patients.

Therapeutic strategies, immediate and mid-term outcomes in non-ST-segment elevation acute coronary syndromes with respect to age: a single-center registry of 488 consecutive patients.

BACKGROUND: Elderly patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) may receive benefit from an early invasive strategy. However, aged patients often suffer from comorbidities that may contraindicate an invasive approach and affect prognosis adversely. The impact of comorbidities on an invasive approach to NSTE-ACS in the elderly has not been fully investigated. HYPOTHESIS: This study sought to examine the outcome of an unselected population of patients with NSTE-ACS stratified according to age and treatment approach. METHODS: The feasibility and efficacy of an invasive strategy for NSTE-ACS and the 6-month outcome were assessed in 253 unselected consecutive patients > or = 70 years (elderly) and compared with those of 235 unselected consecutive patients < 70 years. RESULTS: Angiography was not performed in 69 patients (86% > or = 70 years) because of contraindications. In the whole population, the 6-month event rate was significantly higher in elderly compared with younger patients (22 vs. 14%; odds ratio 1.8, 95% confidence interval 1.1-2.9; p < 0.02). This difference was driven by the high event rate observed in the elderly with contraindications to angiography (47 vs. 16% in the elderly treated invasively; p < 0.002). On the other hand, no significant difference was observed in the 6-month event rate between elderly and younger patients undergoing an invasive approach (16 vs. 13%; p = 0.36). Contraindications to angiography-namely, creatinine > or = 1.5 mg/dl and elevated troponin I at admission--were the only independent predictors of 6-month outcome. CONCLUSIONS: The invasive approach was feasible in 77% of patients > or = 70 years. Those with contraindications to angiography showed a poor mid-term prognosis. The early invasive strategy was associated with more favorable outcomes regardless of age.

Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myocardial infarction treated with primary coronary intervention.

In this prospective randomized trial on patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI), we hypothesized that abciximab administered intracoronarily, downstream of the coronary occlusion, leads to a greater degree of myocardial salvage and better left ventricular function recovery compared with the usual abciximab administration. Forty-five consecutive patients with first AMI and infarct-related artery TIMI flow 0-1 undergoing primary PCI were enrolled. Twenty-two patients were randomly assigned to the intracoronary treatment and 23 to the usual treatment. The initial perfusion defect, final infarct size, myocardial salvage, salvage index, and left ventricular function recovery were assessed by serial scintigraphic scans performed at admission and 7 days and 1 month after PCI. Angiographic myocardial blush grade, corrected TIMI frame count, and electrocardiographic ST segment elevation reduction were also assessed as markers of myocardial reperfusion. Final infarct size was significantly smaller (P = 0.043) and salvage index significantly higher (P = 0.003) in the intracoronary treatment group as a result of a greater degree of myocardial salvage (P = 0.0001). The increase of left ventricular ejection fraction at 1 month was significantly higher in the intracoronary treatment patients (P = 0.013). The markers of myocardial reperfusion were also significantly better in the intracoronary treatment group. In patients with AMI and occluded infarct-related artery treated with primary PCI, intracoronary abciximab given just before PCI downstream of the occlusion is associated to a greater degree of myocardial salvage than the usual abciximab protocol. This benefit is mainly related to a substantial reduction in final infarct size, which leads to an improvement in left ventricular ejection fraction.

Use of 99mTc-sestamibi gated SPECT to assess the influence of anterograde flow before primary coronary angioplasty on tissue salvage and functional recovery in acute myocardial infarction.

PURPOSE: Preserved thrombolysis in myocardial infarction (TIMI) flow before percutaneous coronary intervention (PCI) in acute myocardial infarction is related to improved outcome. Gated single-photon emission computed tomography (SPECT) allows the simultaneous assessment of left ventricular perfusion and function. We evaluated the initial risk area and subsequent evolution of perfusion and function according to TIMI flow before successful primary PCI. METHODS: In 36 patients, treated with abciximab, primary PCI and stenting, 99mTc-sestamibi was injected before PCI and gated SPECT acquired thereafter. Gated SPECT was repeated 7 and 30 days later. Perfusion defect, wall motion score index, left ventricular ejection fraction and volumes were examined. RESULTS: Before PCI, 14 patients (group A) showed TIMI flow 2-3 and 22 (group B) TIMI flow 0-1, but no differences in clinical variables, initial risk area, wall motion score, ejection fraction or volumes. Perfusion defect was smaller in group A at 7 (9%+/-11% vs 19%+/-14%, p<0.02) and 30 days (7%+/-7% vs 16%+/-12%, p<0.02) and the salvage index was higher at 30 days (77%+/-22% vs 55%+/-28%, p<0.02). Wall motion score was lower in group A at 30 days (p<0.05). Ejection fraction significantly improved in both groups at 7 and 30 days. End-diastolic volume showed a trend towards a reduction in group A, whilst it was significantly increased in group B. Conversely, end-systolic volume was significantly decreased in group A but remained unchanged in group B. CONCLUSION: In the setting of optimal myocardial reperfusion for myocardial infarction, preserved TIMI flow before PCI does not limit the initial risk area but it does improve myocardial salvage and functional recovery.

Gated SPECT evaluation of the relationship between admission troponin I, myocardial salvage, and functional recovery in acute myocardial infarction treated by abciximab and early primary angioplasty.

UNLABELLED: Using gated SPECT, we evaluated the relationship between admission troponin I, risk area, and myocardial salvage in patients with a first myocardial infarction treated with abciximab and primary percutaneous coronary intervention within 6 h. METHODS: In 43 patients, (99m)Tc-sestamibi was injected before primary percutaneous coronary intervention. Gated SPECT was acquired immediately thereafter and was repeated 7 and 30 d later. The initial risk area and subsequent infarct size were expressed as a percentage of the left ventricle; salvage index was the ratio between salvaged myocardium and initial risk area; left ventricular ejection fraction was calculated using the quantitative gated SPECT software. RESULTS: On admission, 20 patients showed elevated troponin I and had a larger risk area (P < 0.03) than did the group with normal troponin I. Infarct size at 30 d (15% +/- 12% vs. 13% +/- 13%) and salvage index (0.63 +/- 0.27 vs. 0.60 +/- 0.28) were not significantly different between the 2 groups. Ejection fraction was lower in the group with high troponin I on admission (36% +/- 10% vs. 41% +/- 11%, P < 0.05) and at 7 d (41% +/- 11% vs. 48 +/- 10, P < 0.03). At 30 d, improvement was greater in the group with high troponin I, and ejection fraction became comparable. CONCLUSION: Patients with high troponin I on admission have a larger initial risk area, but if they undergo primary percutaneous coronary intervention within 6 h and are treated with abciximab, myocardial salvage and functional recovery are similar to those observed in patients with normal troponin I, and no unfavorable relationship between high troponin I values on admission and myocardial salvage is registered.

Markers of myocardial reperfusion as predictors of left ventricular function recovery in acute myocardial infarction treated with primary angioplasty.

BACKGROUND: Myocardial blush grade (MBG), corrected TIMI frame count (cTFC), and ST-segment reduction are indices of myocardial reperfusion. HYPOTHESIS: We evaluated their predictive value for left ventricular (LV) function recovery by gated single-photon emission computed tomography (SPECT) after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). METHODS: In 40 patients with AMI, gated SPECT was performed at admission and repeated 7 and 30 days after PCI. Left ventricular function recovery was defined as an increase > or = 10 points in SPECT LV ejection fraction from baseline to 1 month. The MBG, cTFC, and ST-segment elevation index 1 h after PCI were determined to evaluate reperfusion. RESULTS: Twenty-four patients (Group 1) had LV function recovery and 16 (Group 2) did not. A significant correlation was found between LV function recovery and MBG (r = 0.66; p = 0.0001), and ST-segment elevation index at 1 h (r = -0.55; p = 0.0001), but not with cTFC. Univariate predictors of LV function recovery were MBG (p = 0.0003) and ST-segment elevation index 1 h after intervention (p = 0.0026), but not cTFC. In a multivariate analysis, MBG was the only predictor of LV function recovery. Myocardial blush grade > or = 2 and ST-segment elevation index reduction had the same accuracy (88%) for predicting LV function recovery. Lower accuracy (75%) was shown by fast cTFC (< 23 frames). Myocardial blush grade > or = 2 showed the better negative likelihood ratio, and ST-segment elevation index reduction had the higher positive likelihood ratio in predicting LV function recovery. CONCLUSIONS: Myocardial blush grade was the best parameter for prediction of LV function recovery: MBG > or = 2 and ST-segment elevation index reduction showed good accuracy in predicting LV function recovery. The cTFC failed to be a significant predictor.

Low-dose dobutamine nitrate-enhanced technetium 99m sestamibi gated SPECT versus low-dose dobutamine echocardiography for detecting reversible dysfunction in ischemic cardiomyopathy.

BACKGROUND: The simultaneous assessment of perfusion and function with the use of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) is helpful for the detection of myocardial viability, but its value in comparison with more established methods is not yet defined. METHODS AND RESULTS: This study compared low-dose dobutamine (LDD) nitrate-enhanced gated SPECT with LDD echocardiography for predicting recovery of regional ventricular function after revascularization in 25 patients with ischemic cardiomyopathy. In both studies, regional function (wall motion and thickening) at rest, during inotropic stimulation, and after revascularization was scored by a 4-point scale. In LDD echocardiography, the prediction of reversible dysfunction was based on the recognition of contractile reserve in asynergic (hypokinetic or a-dyskinetic) segments. In LDD gated sestamibi SPECT, reversible dysfunction was predicted on the basis of perfusion quantification (sestamibi uptake >or= 50%) in a-dyskinetic segments and on the basis of contractile reserve in hypokinetic segments. LDD echocardiography predicted reversible dysfunction with sensitivity, specificity, and global accuracy of 57%, 85%, and 75%, respectively. The sensitivity and specificity of LDD gated SPECT for identifying dysfunctional segments capable of functional recovery were 77% and 88%, respectively, with a diagnostic accuracy of 84% (P <.02 vs LDD echocardiography). CONCLUSIONS: The combined use of 2 different markers of viability, such as cellular integrity in a-dyskinetic segments and contractile reserve in hypokinetic segments, as permitted by LDD gated sestamibi SPECT, showed higher predictive accuracy for reversible dysfunction than the assessment of contractile reserve in all asynergic segments with LDD echocardiography.

[Evaluation of the appropriateness of prescribing non-invasive cardiologic tests]. / La valutazione dell'appropriatezza della prescrizione dei test cardiologici non invasivi.

BACKGROUND: We evaluated the appropriateness of the prescription of echocardiography, exercise testing, Holter monitoring and vascular sonography for ambulatory patients, performed during 4 weeks in 21 outpatient laboratories in Tuscany and Umbria, Italy. METHODS: We collected the following data: the appropriateness of the prescription (according to the guidelines of the Italian Federation of Cardiology), the prescribing physician (cardiologist vs noncardiologist), the synthetic result (normal vs abnormal) and the clinical utility (useful vs useless) of each exam. RESULTS: We evaluated 5614 prescriptions (patients: 3027 males, 2587 females; mean age 63 years, range 14-96 years). The indication to the test was of class I (appropriate) in 45.3%, of class II (doubtfully appropriate) in 34.8% and of class III (inappropriate) in 19.9% of the cases. The test was abnormal in 58.3% of class I exams vs 17% of class III exams (p < 0.05). The test was useful in 72.4% of class I exams vs 17.1% of class III exams (p < 0.05). The test was prescribed by a cardiologist in 1882 cases (33.5%). Cardiologist-prescribed exams were of class I in 57.3%, of class II in 32.4% and of class III in 10.3% of the cases vs 39.2, 36.1 and 24.7% of non-cardiologist-prescribed exams (p < 0.05). Cardiologist-prescribed exams were abnormal in 53.4% of the cases vs 39% of those of non-cardiologists' (odds ratio 1.76, 95% confidence interval 1.58-1.97; p < 0.05). Cardiologist-prescribed exams were useful in 64.7% of the cases vs 44.4% of those of non-cardiologists' (odds ratio 2.26, 95% confidence interval 2.02-2.53; p < 0.05). CONCLUSIONS: In Tuscany and Umbria, Italy, less than half of the prescriptions for non-invasive diagnostic tests are appropriate: appropriately prescribed exams more often provide abnormal and useful results; cardiologist-prescribed exams are more often appropriate, abnormal and useful.

Usefulness of dobutamine Tc-99m sestamibi-gated single-photon emission computed tomography for prediction of left ventricular ejection fraction outcome after coronary revascularization for ischemic cardiomyopathy.

Gated single-photon emission computed tomography (SPECT) imaging allows analysis of myocardial perfusion and assessment of baseline global and regional left ventricular (LV) function and their changes during low-dose dobutamine infusion. The study examined whether the changes in LV ejection fraction induced by dobutamine and evaluated using technetium-99m sestamibi- gated SPECT predict the evolution of ejection fraction after revascularization in patients with ischemic cardiomyopathy. Thirty-seven patients underwent resting and dobutamine nitrate-enhanced sestamibi-gated SPECT before revascularization and baseline-resting sestamibi gated SPECT after intervention to assess global functional changes. A postrevascularization improvement in ejection fraction > or =5 U was defined as significant. At follow-up, ejection fraction increased significantly in 19 patients. According to receiver-operating characteristic curve analysis, an increase in ejection fraction > or =5 U during dobutamine was the optimal cutoff value for predicting a significant postrevascularization improvement, with 79% sensitivity, 78% specificity, and 78% accuracy. A significant correlation was found between dobutamine and postrevascularization ejection fraction (r = 0.85; p <0.0001). The increase in ejection fraction during dobutamine is a good predictor of an improvement in ejection fraction after revascularization. This represents another important diagnostic contribution obtained using gated SPECT imaging for the assessment of myocardial viability in patients with ischemic cardiomyopathy.