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The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted ( p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR. [ABSTRACT FROM AUTHOR]

There are very few clinical data concerning the safety of switching from clopidogrel to prasugrel in patients undergoing coronary stenting. However, in the daily activity, clinicians face the decision of switching patients at high-risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to evaluate clinical events in patients undergoing coronary stent implantation and prasugrel therapy with (SWITCH group) or without (NAÏVE group) prior clopidogrel therapy. A total of 454 patients with stable or unstable coronary artery disease, aged 70 ± 10 years, underwent non-emergent stent implantation and received prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before switching to prasugrel therapy. In 239 patients with high residual platelet reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from 72 ± 11 to 43 ± 16 % ( p < 0.001). There was no difference in in-hospital major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and NAÏVE groups as well as in mortality, acute stent thrombosis, reinfarction and stroke rates. At multivariable analysis, independent predictors of bleeding were female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27 [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed after switching propensity score adjustment ( c-statistic 0.81; Hosmer-Lemeshow test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non-emergent coronary stent implantation seems to be tolerated with no overt signs of increased bleeding. [ABSTRACT FROM AUTHOR]

Despite optimal epicardial recanalization, primary angioplasty for STEMI is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim the current study was to evaluate the impact of preprocedural TIMI flow on myocardial scintigraphic infarct size among STEMI undergoing primary angioplasty. Our population is represented by 793 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi. Poor preprocedural TIMI flow (TIMI 0-1) was observed in 645 patients (81.3 %). Poor preprocedural TIMI flow was associated with more hypercholesterolemia ( p = 0.012), and a trend in lower prevalence of diabetes ( p = 0.081). Preprocedural TIMI flow significantly affected scintigraphic and enzymatic infarct size. Similar findings were observed in the analysis restricted to patients with postprocedural TIMI 3 flow. The impact of preprocedural TIMI flow on scintigraphic infarct size was confirmed when the analysis was performed according to the percentage of patients above the median ( p < 0.001) and after adjustment for baseline confounding factors (Hypercholesterolemia and diabetes) [adjusted OR (95 % CI) for pre preprocedural TIMI 3 flow = 0.59 (0.46-0.75), p < 0.001]. This study shows that among patients with STEMI undergoing primary angioplasty, poor preprocedural TIMI flow is independently associated with larger infarct size. [ABSTRACT FROM AUTHOR]

Doxycycline has been demonstrated to reduced left ventricular (LV) remodeling, but its effect in patients with ST-elevation myocardial infarction (STEMI) and a baseline occluded [thrombolysis in myocardial infarction (TIMI) flow grade ≤1] infarct-related artery (IRA) is unknown. According to the baseline TIMI flow grade, 110 patients with a first STEMI were divided into 2 groups. Group 1: 77 patients with TIMI flow ≤1 (40 patients treated with doxycycline and 37 with standard therapy, respectively), and a Group 2: 33 patients with TIMI flow 2-3 (15 patients treated with doxycycline and 18 with standard therapy, respectively). The two randomized groups were well matched in baseline characteristics. A 2D-Echo was performed at baseline and at 6 months, together with a coronary angiography, for the remodeling and IRA patency assessment, respectively. The LV end-diastolic volume index (LVEDVi) decreased in Group 2 [−3 mL/m (IQR: −12 to 4 mL/m)], and increased in Group 1 [6 mL/m (IQR: −2 to 14 mL/m)], ( p = 0.001). In Group 2, LVEDVi reduction was similar regardless of drug therapy, while in Group 1 the LVEDVi was smaller in patients treated with doxycycline as compared to control [3 mL/m (IQR: −3 to 8 mL/m) vs. 10 mL/m (IQR: 1-27 mL/m), p = 0.006]. A similar pattern was observed also for LV end-systolic volume and ejection fraction. In STEMI patients at higher risk, as those with a baseline TIMI flow grade ≤1, doxycycline reduces LV remodeling. [ABSTRACT FROM AUTHOR]

Purpose: In acute myocardial infarction (AMI) treated by primary percutaneous coronary intervention (PCI), there is a direct relationship between myocardial damage and consequent left ventricular (LV) functional impairment. It is however unclear whether there is a safety threshold below which infarct size does not significantly affect LV ejection fraction (EF). The aim of this study was to evaluate the relationship between infarct size and LVEF in AMI patients treated by successful PCI using a specific statistical approach to identify a possible safety threshold. Methods: Among patients with recent AMI submitted to perfusion gated single photon emission computed tomography (SPECT) to define the infarct size, the data of 427 subjects with sizable infarct size were considered. The relationship between infarct size and LVEF was analysed using a simple segmented regression (SSR) model and an iterative algorithm based on robust least squares (RLS) for parameter estimation. Results: The RLS algorithm detected two break points in the SSR model, set at infarct size values of 11.0 and 51.5 %. Because the slope coefficients of the two extreme segments of the regression line were not significant, by constraining such segments to zero slope in the SSR model, the lower break point was identified at infarct size = 8 % and the upper one at 45 %. Conclusion: Using a rigorous statistical approach, it is possible to demonstrate that below a threshold of 8 % the infarct size apparently does not affect the LVEF and therefore a safety threshold could be set at this value. Furthermore, the same analysis suggests that the relationship between infarct size and LVEF impairment is lost for an infarct size > 45 %. [ABSTRACT FROM AUTHOR]

Infarct artery stenting with adjunctive abciximab therapy is widely used treatment for patients with acute myocardial infarction (AMI). However, bleeding complications have been associated with a worse clinical outcome. Randomized trials in elective patients have shown that postprocedural protamine administration is safe and associated with a significant reduction in bleeding complications. The aim of the current study was to evaluate in STEMI patients undergoing primary percutaneous coronary intervention (PCI) with abciximab and stenting whether immediate reversal of anticoagulation by protamine is safe and associated with a reduction in the occurrence of bleeding complications. From January 2004 to June 2005, 254 patients with STEMI had immediate reversal of anticoagulation by protamine administration after infarct artery stenting and received abciximab therapy without heparin infusion (Group 1). These patients were compared with a control group of 265 patients (June 2002-December 2003) treated with the standard heparin therapy: bolus in order to achieve an activated coagulation time of 250-300 s during PCI plus 12-h infusion (7 UI/kg/h; Group 2). We excluded patients undergoing IABP implantation. The two groups were similar in all baseline characteristics. There were no differences in in-hospital mortality, reinfarction, urgent target vessel revascularization, stroke or acute or subacute stent thrombosis, while Group 1 patients showed a lower incidence of major bleeding complications (ACUITY scale: 1.1 vs. 4.0%, P = 0.035) and a shorter length of hospital stay (3.5 ± 1.7 vs. 4.0 ± 1.6 days, P = 0.002) as compared with heparin treated patients. Among patients undergoing primary stenting with abciximab administration, immediate post-PCI reversal anticoagulation by protamine without associated heparin infusion is safe and associated with a significant reduction in major bleeding complications. [ABSTRACT FROM AUTHOR]

The current technique of choice for perfusion imaging is gated single-photon emission computed tomography (SPECT), which allows the simultaneous assessment of perfusion and left ventricular (LV) function. We examined the relationships of infarct size and severity with LV ejection fraction (EF) and volumes in 215 myocardial infarction patients treated with primary percutaneous coronary intervention within 6 h of symptom onset. Patients were studied with resting gated SPECT 1 month later. Infarct size was expressed as LV percent, and infarct severity as the lowest activity ratio within the defect. LVEF, end-diastolic (ED) and end-systolic (ES) volume indexes (Vi) were calculated with commercial software. There was a significant correlation between infarct size and LVEF (r=-0.68, P<0.00001), EDVi (r=0.53, P<0.00001), and ESVi (r=0.62, P<0.00001). Slightly lower correlations were demonstrated using infarct severity. LVEF and volumes were related to infarct location. A significantly higher correlation was observed between infarct size and LVEF in anterior than in non-anterior infarctions (r=-0.75 vs -0.60, P<0.05). In multivariate analysis, infarct size and infarct location were significant predictors of LVEF (R2=0.50) and ESV (R2=0.40). Infarct size and infarct severity were significant predictors of EDVi (R2=0.29). Infarct size (and severity) and LVEF (and volumes) derived from a single gated SPECT study correlate closely. Infarct location influences this relationship, with anterior infarctions showing a lower LVEF than inferior or lateral ones of the same extent. [ABSTRACT FROM AUTHOR]

Chest pain (CP) represents a frequent reason for presentation at the emergency department (ED). A large proportion of patients have non-diagnostic ECG on presentation, and in many cases several hours have elapsed since onset of symptoms. Acute rest myocardial scintigraphy (rest SPET) has been shown to have a relevant role in the detection of patients at risk for coronary events, but its sensitivity and negative predictive value are optimal only within the first 3 h following onset of symptoms. In those with delayed presentation, exercise SPET alone, as a screening approach, appears more promising, but its feasibility and diagnostic role in the ED are still unresolved. A total of 231 consecutive patients with a recent-onset (<24 h) first episode of CP had a negative first-line work-up including ECG, troponins, creatine kinase-MB and echocardiography. These patients were considered at low risk for short-term coronary events. Patients were studied with rest SPET if they presented <3 h after onset of CP and exercise SPET if they presented after ≥3 h. The end-points of the study were detection of significant coronary artery disease (CAD) by angiography and major coronary events or cardiac death at 6 months. Eighty patients (35%) underwent rest SPET, while 151 (65%) underwent exercise SPET. Two of the 159 patients with negative SPET had evidence of critical CAD at 6-month follow-up (one patient in the rest SPET group and one in the exercise SPET group; P=NS). Of the 72 patients (31%) with a positive scan, 34 (15%) had documented CAD (16 patients in the rest SPET group and 18 in the exercise SPET group; P=NS). Sensitivity, specificity, accuracy and predictive value were not statistically different between the two groups. In conclusion, the accuracy of exercise SPET in patients with CP and delayed presentation to the ED is comparable to that of validated rest SPET in patients with early presentation. Owing to the high negative predictive value (99%), exercise SPET... [ABSTRACT FROM AUTHOR]