Different clinical models of CD34 + cells mobilization in patients with cardiovascular disease.

To test the role of necrosis, ischemia or both in bone marrow cells (BMC) mobilization in patients with cardiovascular disease. We studied three groups of patients: group 1, Iatrogenic Necrosis, with pure necrosis (28 patients undergoing transcatheter radiofrequency ablation); group 2, Ischemic Necrosis (30 patients with myocardial infarction); group 3, Pure Ischemia (24 patients with unstable angina). As control groups, we studied 27 patients with stable coronary artery disease (CAD), and 20 patients without CAD undergoing angiography for valvular diseases or cardiomiopathy. CD34 + cells and cytokines were evaluated at: T(0) (baseline), 48 h and 5, 7, 10, 14 days thereafter. We observed a significant increase of CD34 + cells at T(3) and T(4) only in Iatrogenic Necrosis and Ischemic Necrosis group. The peak of mobilization was observed ten days after the necrotic event (2.8 ± 1.4 vs. 5.9 ± 1.9 in the group 1, P = 0.03; and 3 ± 1.5 vs. 5.6 ± 2 in the group 2, P = 0.04; respectively). We found a good correlation between CD34 + and vascular endothelial growth factor (VEGF) and stromal derived factor (SDF-1α) peak values (r = 0.77 and r = 0.63, respectively). At multivariable analysis, myocardial necrosis (OR 3.5, 95%CI 2.2-4.2, P < 0.01), VEGF (OR 2, 95%CI 1.1-3, P = 0.01 as above versus below median value), and SDF-1α (OR 1.6, 95%CI 1.1-2.5, P = 0.02 as above versus below median value) emerged as independent predictors of C34 + cells increase. Myocardial necrosis with simultaneous elevation of VEGF and SDF-1α causes a significant CD34 + cells mobilization in patients with cardiovascular disease.

Diagnostic performance of 16- and 64-section spiral CT for coronary artery bypass graft assessment: meta-analysis.

PURPOSE: To perform a meta-analysis to evaluate the accuracy of 16- and 64-section spiral computed tomography (CT) to help assess coronary artery bypass grafts (CABGs). MATERIALS AND METHODS: The MEDLINE, Cochrane library, and BioMed Central databases were searched for relevant original articles published up to May 2007. Major criteria for article inclusion were that it (a) used multisection CT as a diagnostic test for the assessment of significant lesions (occlusion or >50% stenosis) of CABG, (b) used a 16- or 64-section scanner, and (c) used coronary angiography as the reference standard. After data extraction, the analysis was performed according to a random-effects model. Between-study statistical heterogeneity was also assessed by using the Cochran Q chi(2) test. RESULTS: Of 158 screened articles, 15 fulfilled all inclusion criteria. Graft assessability (including distal anastomosis) ranged from 78%-100% among all included studies (mean, 92.4%; 90% with 16- and 96% with 64-section CT; P < .001). Statistical heterogeneity was observed for specificity and positive likelihood ratio (LR), justifying the use of the random-effects model. The analysis, pooled from 15 studies (723 patients, 2023 CABGs), provided the following results for the assessment of graft obstruction (occlusion and >50% stenosis): sensitivity, 97.6% (95% confidence interval [CI]: 96%, 98.6%); specificity, 96.7% (95% CI: 95.6%, 97.5%); positive predictive value, 92.7% (95% CI: 90.5%, 94.6%); negative predictive value, 98.9% (95% CI: 98.2%, 99.4%); positive LR, 23.42 (95% CI: 13.69, 40.07); negative LR, 0.045 (95% CI: 0.028, 0.071); and diagnostic odds ratio, 780.32 (95% CI: 379.12, 1606.1). CONCLUSION: Multisection CT provided high accuracy for the evaluation of CABG obstruction in assessable conduits, and might be used as a noninvasive tool for the evaluation of suspected graft dysfunction in patients who are at high risk for complications from coronary angiography.

Multislice spiral computed tomography for the evaluation of stent patency after left main coronary artery stenting: a comparison with conventional coronary angiography and intravascular ultrasound.

BACKGROUND: Surveillance conventional coronary angiography (CCA) is recommended 2 to 6 months after stent-supported left main coronary artery (LMCA) percutaneous coronary intervention due to the unpredictable occurrence of in-stent restenosis (ISR), with its attendant risks. Multislice computed tomography (MSCT) is a promising technique for noninvasive coronary evaluation. We evaluated the diagnostic performance of high-resolution MSCT to detect ISR after stenting of the LMCA. METHODS AND RESULTS: Seventy-four patients were prospectively identified from a consecutive patient population scheduled for follow-up CCA after LMCA stenting and underwent MSCT before CCA. Until August 2004, a 16-slice scanner was used (n = 27), but we switched to the 64-slice scanner after that period (n = 43). Patients with initial heart rates > 65 bpm received beta-blockers, which resulted in a mean periscan heart rate of 57 +/- 7 bpm. Among patients with technically adequate scans (n = 70), MSCT correctly identified all patients with ISR (10 of 70) but misclassified 5 patients without ISR (false-positives). Overall, the accuracy of MSCT for detection of angiographic ISR was 93%. The sensitivity, specificity, and positive and negative predictive values were 100%, 91%, 67%, and 100%, respectively. When analysis was restricted to patients with stenting of the LMCA with or without extension into a single major side branch, accuracy was 98%. When both branches of the LMCA bifurcation were stented, accuracy was 83%. For the assessment of stent diameter and area, MSCT showed good correlation with intravascular ultrasound (r = 0.78 and 0.73, respectively). An intravascular ultrasound threshold value > or = 1 mm was identified to reliably detect in-stent neointima hyperplasia with MSCT. CONCLUSIONS: Current MSCT technology, in combination with optimal heart rate control, allows reliable noninvasive evaluation of selected patients after LMCA stenting. MSCT is safe to exclude left main ISR and may therefore be an acceptable first-line alternative to CCA.

Two-by-two factorial comparison of high-bolus-dose tirofiban followed by standard infusion versus abciximab and sirolimus-eluting versus bare-metal stent implantation in patients with acute myocardial infarction: design and rationale for the MULTI-STRATEGY trial.

BACKGROUND: Current treatment standards for patients undergoing primary percutaneous coronary intervention support early infusion of abciximab, followed by bare-metal stent (BMS) implantation. Whether the use of sirolimus-eluting stent (SES) would result in a further improvement of clinical outcomes remains to be proven. Similarly, whether tirofiban administered at high-bolus dose (HBD) followed by standard infusion is a valuable alternative to abciximab in the setting of ST-segment elevation myocardial infarction remains uncertain. STUDY DESIGN: Multicentre evaluation of single high-bolus dose tirofiban versus abciximab and sirolimus-eluting versus bare metal stent in acute myocardial infarction (MULTI-STRATEGY) is a phase III, open-label, multinational investigator-driven clinical trial evaluating, with a 2-by-2 factorial design, the safety/efficacy profile of 4 interventional strategies of reperfusion: tirofiban given at HBD (bolus of 25 microg/kg over 3 minutes), followed by an infusion of 0.15 microg/kg per minute for 18 to 24 hours versus abciximab and SES, as compared to BMS implantation in primary percutaneous coronary intervention. The coprimary objectives are (i) the evaluation of the effect of SES versus BMS on the incidence of major adverse cardiac events within 8 months of the index procedure and (ii) the degree of ST-segment resolution obtained after the mechanical intervention for the comparison of HBD tirofiban versus abciximab. The protocol mandates clinical follow-up for 5 years. CONCLUSIONS: MULTI-STRATEGY will evaluate the role of SES and HBD tirofiban versus BMS and abciximab in the acute management of patients presenting with ST-segment elevation myocardial infarction.

Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events.

OBJECTIVE: We investigated in patients with ongoing myocardial infarction (MI) whether coagulation factor VII (FVII) and tissue factor (TF) levels are affected at admission by genetic components and whether they may predict subsequent cardiovascular events. METHODS AND RESULTS: 256 patients admitted for MI were evaluated for FVII and TF antigen levels before any treatment at entry, and were genotyped for FVII and TF polymorphisms. FVII gene insertions at -323, 11293 and the -402G/A change predicted FVII levels and explained 14% of variance. The -603 TF gene polymorphism failed to affect significantly TF levels (P=0.07). These variables were correlated with the incidence of death (36 patients) and reinfarction (9 patients) after a median follow-up of 397 days. Events were independently predicted by FVII (HR 2.1, 95% CI 1.2 to 5.7) and TF (HR 4.1, 95% CI 2 to 11) levels. Composite end point was significantly worse when both parameters were above the receiver-operating characteristics (ROC) values (HR 8.3, 95% CI 5 to 18, compared with FVII and TF below), and above the ROC value of TF (>630 pg/mL) it differed among FVII genotype groups. CONCLUSIONS: Admission FVII and TF antigen levels, partially predicted by polymorphisms, are independent predictors of mortality and reinfarction in patients with acute MI.

Tumor necrosis factor-alpha receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: the Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) study.

BACKGROUND: Tumor necrosis factor alpha-alpha (TNF-alpha) activation is an independent prognostic indicator of mortality in patients with heart failure (HF). Despite the recognition that several TNF family cytokines are elevated during myocardial infarction, their role in predicting subsequent prognosis in these setting remains poorly understood. METHODS AND RESULTS: We performed a systematic evaluation of TNF-alpha and its type 1 and 2 soluble receptors, together with interleukin (IL)-6, IL-1 receptor antagonist, and IL-10, in 184 patients (132 men; mean age, 64+/-12) consecutively admitted for myocardial infarction. We correlated their values to short- and long-term incidence of death and HF (primary outcome). In 10 patients, we also studied the presence of transcardiac gradients for TNF-alpha and its soluble receptors. The control group comprised 45 healthy subjects who were sex and age matched (33 men; mean age, 65+/-6 years) to the patients. All tested cytokines were increased in patients, and no transcardiac or systemic AV difference was found. After a median follow-up of 406 days (range, 346 to 696 days), 24 patients died and 32 developed HF. Univariate analysis showed that all cytokines were related to outcome, whereas after adjustment for baseline and clinical characteristics, sTNFR-1 remained the only independent predictor of death and HF (hazard ratio, 2.9; 95% CI, 1.9 to 3.8, tertile 1 versus 3), together with left ventricular ejection fraction, Killip class, and creatine kinase-MB at peak. CONCLUSIONS: sTNFR-1 is a major short- and long-term predictor of mortality and HF in patients with acute myocardial infarction.

Single-vessel versus bifurcation stenting for the treatment of distal left main coronary artery disease in the drug-eluting stenting era. Clinical and angiographic insights into the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registries.

BACKGROUND: Routine drug-eluting stent (DES) implantation has recently improved outcome in patients undergoing percutaneous treatment of left main (LM) coronary artery. However, even in the DES era, distal LM treatment remains an independent predictor of poor outcome. Whether single-vessel stenting (SVS) or bifurcation stenting (BS) should be performed to optimize treatment of such a lesion is unclear. METHODS: From April 2002 to June 2004, 94 patients affected by distal LM disease underwent percutaneous intervention at our institution either with SVS (n = 48) or BS (n = 46). The 2 groups were well balanced for all baseline characteristics but the extension of disease in the LM carina. RESULTS: After a median follow-up of 587 days (range, 328-1179), the cumulative incidence of MACE was similar between the 2 groups (31% in the BS vs 28% in SVS group, HR 0.96, 95% CI 0.46-1.49, P = .92), with no difference for the composite death/myocardial infarction or target vessel revascularization. After adjustment for confounders, the technique of stenting was not a predictor of either major adverse cardiac events or target vessel revascularization. Angiographic analysis--performed in 81% of eligible patients in SVS and 87% in the BS group--confirmed the equivalency between SVS versus BS. CONCLUSIONS: In consecutive patients undergoing catheter-based distal LM intervention, SVS or BS may perform equally under both clinical and angiographic perspective in current DES era.

Multidetector CT for visualization of coronary stents.

Whereas the clinical diagnosis of in-stent thrombosis is straightforward, that of in-stent restenosis remains a problem, because although many patients experience chest pain after coronary stent placement, that symptom is secondary to ischemia in only a few. The use of a noninvasive technique to identify such patients for early invasive intervention versus more conservative management is thus highly desirable. Multidetector computed tomography (CT) performed with 16-section scanners recently emerged as such a technique and has overtaken modalities such as electron-beam CT and magnetic resonance imaging as an alternative to conventional angiography for the assessment of in-stent restenosis. The improved hardware design of the current 64-section CT scanners allows even better delineation of stent struts and lumen. The more reliable criterion of direct lumen visualization thus may be substituted for the presence of distal runoff, which lacks specificity for a determination of in-stent patency because of the possibility of collateral pathways. However, the capability to accurately visualize the in-stent lumen depends partly on knowledge of the causes of artifacts and how they can be compensated for with postprocessing and proper image display settings. In addition, an understanding of the major stent placement techniques used in the treatment of lesions at arterial bifurcations is helpful.

Reversibility of Left Ventricle Longitudinal Strain Alterations Induced by Adjuvant Therapy in Early Breast Cancer Patients.

Left ventricular ejection fraction (LV-EF), despite its high feasibility, is not sensitive enough to detect early and subtle LV systolic dysfunction during oncologic treatments. Therefore, we used systolic global longitudinal strain (GLS) by speckle tracking echocardiography to verify whether early LV systolic dysfunction induced by adjuvant therapy in early breast cancer patients at low risk for cardiotoxicity can be reversed. Thirty patients (aged 53 ± 11 y) with no previous cardiac and oncologic disease who were receiving adjuvant trastuzumab and taxane (group HER2+, n = 15) or taxane only (group HER2-, n = 15), after treatment with anthracyclines, were studied. LV-EF and GLS were measured at baseline, after anthracyclines (end of week 7 or 8), short term after trastuzumab and/or taxane (end of week 18) and after completion of therapy. Significant LV systolic dysfunction was defined as a relative reduction in GLS of >10% with respect to baseline values. Mean and individual LV-EFs did not change significantly during the oncologic treatment and after completion of therapy, although GLS varied significantly. In particular, during the course of therapy, four patients in the trastuzumab-docetaxel HER2+ subgroup and two patients in the taxane HER2- subgroup had a relative decrease (>10%) in GLS. However, after the end of adjuvant treatment, strain modification was fully or partially reversible. Speckle tracking echocardiography is more sensitive than LV-EF in recognizing subtle myocardial impairment during adjuvant chemotherapy. However, in patients at low risk for cardiotoxicity, these alterations may be reversible and not associated with clinically significant cardiotoxicity or late development of decreased LV-EF.

CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure.

BACKGROUND: Peripheral blood CD34(+) cells and circulating endothelial progenitor cells (EPCs) increase in myocardial infarction and vascular injuries as a reflection of endothelial damage. Despite the occurrence of endothelial dysfunction in heart failure (HF), no data are available on EPC mobilization in this setting. We investigated the pattern of CD34(+) cells and EPC mobilization during HF and their correlation with the severity and origin of the disease. METHODS AND RESULTS: Peripheral blood CD34(+) cells (n=91) and EPCs (n=41), assessed both as CD34(+) cells coexpressing AC133 and vascular endothelial growth factor (VEGF) receptor-2 and as endothelial colony-forming units, were studied in HF patients (mean age 67+/-11 years) and 45 gender- and age-matched controls. Tumor necrosis factor-alpha (TNF-alpha) and its receptors (sTNFR-1 and sTNFR-2), VEGF, stromal derived factor-1 (SDF-1), granulocyte-colony stimulating factor (G-CSF), and B-type natriuretic peptide were also measured. CD34(+) cells, EPCs, TNF-alpha and receptors, VEGF, SDF-1, and B-type natriuretic peptide were increased in HF. CD34(+) cells and EPCs were inversely related to functional class and to TNF-alpha, being decreased in New York Heart Association class IV compared with class I and II and controls. No role was found for the origin of the disease. CONCLUSIONS: CD34(+) cells and EPC mobilization occurs in HF and shows a biphasic response, with elevation and depression in the early and advanced phases, respectively. This could be related to the myelosuppressive role of TNF-alpha.

Hydroxyl radical generation, levels of tumor necrosis factor-alpha, and progression to heart failure after acute myocardial infarction.

OBJECTIVES: We used acetylsalicylic acid (ASA) as a probing agent to quantify hydroxyl radical ((*)OH) in Controls and patients with coronary artery disease and to prospectively investigate (*)OH production in patients with myocardial infarction (MI) complicated by heart failure (HF). BACKGROUND: Oxidative stress status (OSS) is a mechanism for transition to HF in experimental heart injury models, but evidence for its causal role in humans is still limited. METHODS: Thirty healthy subjects (Controls), 12 patients with stable angina (Group 1), and 74 patients with ST-segment elevation MI (Group 2) were enrolled. A dose of 250 mg Flectadol was given intravenously before each blood collection to determine the 2,3-dihydroxybenzoic acid/salicylic acid (DHBA/SA) ratio. We also quantified vitamin E and coenzyme Q(10) to monitor antioxidant reserve, as well as tumor necrosis factor (TNF)-alpha, TNF-soluble receptors, interleukin (IL)-6, and IL-1ra to assess inflammatory status. All measurements were repeated at month 6 in Group 2. RESULTS: There were no differences between Controls and Group 1. Group 2 showed increased (*)OH production, peaking at 24 h, whereas vitamin E and coenzyme Q(10) progressively declined. Group 2 patients developing HF during hospitalization (Group 2Bi) presented with an increase of both (*)OH production at discharge and inflammatory status, as compared with patients without HF (Group 2Ai), persisting at month 6 in post-MI patients with HF (Group 2Bii). CONCLUSIONS: We found a distinct pattern of (*)OH generation in post-MI patients who show progression to HF. The interplay between OSS and inflammatory status should be targeted as a possible mechanism of progression to post-MI left ventricular dysfunction.

Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial.

CONTEXT: Bare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents. OBJECTIVE: To evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI. DESIGN, SETTING, AND PATIENTS: Prospective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004. INTERVENTION: Single high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88). MAIN OUTCOME MEASURES: The primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR). RESULTS: Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002). CONCLUSION: Tirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.

Persistent coronary no flow after wire insertion is an early and readily available mortality risk factor despite successful mechanical intervention in acute myocardial infarction: a pooled analysis from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials.

OBJECTIVES: These studies sought to investigate the impact on mortality of coronary flow after passage of the wire through the culprit vessel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical reperfusion. BACKGROUND: Reduced spontaneous coronary flow before percutaneous coronary intervention influences mortality in patients with STEMI. Response to vessel wiring in patients with an occluded coronary artery before intervention might further discriminate outcomes irrespective of pre- and post-intervention coronary flow. METHODS: Data from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials were pooled: of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI (Thrombolysis In Myocardial Infarction) flow determination. RESULTS: TIMI flow grade 0 was present before percutaneous coronary intervention in 59% of infarct vessels, TIMI flow grade 1 to 2 was found in 21%, whereas the remainder of infarct arteries presented with TIMI flow grade 3. In 49% of patients who showed persistent TIMI flow grade 0 after wire insertion (AWI), mortality was higher at 30 days (5.3%) and 1 year (9.4%) compared with patients in whom TIMI flow grade before percutaneous coronary intervention was either >0 (0.8%; p < 0.003 and 3.6%, p < 0.008) or improved from 0 AWI (1.5%, p < 0.04 and 3.6%, p < 0.02). After correcting for multiple imbalances, including baseline and final flow, persistent TIMI flow grade 0 AWI remained associated at 30 days to 2-fold (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 1.08 to 5.00; p = 0.038) and at 1 year to almost 3-fold increases of mortality (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008). CONCLUSIONS: STEMI patients displaying persistent no-flow AWI have a lower survival rate despite an apparently successful mechanical intervention. As an early marker for high residual mortality risk, persistent no-flow AWI may qualify STEMI patients for dedicated pharmacomechanical treatment strategies.

Plaque sealing: are the benefits outweighing the risks?

A 36-year-old man was admitted with reported short attacks of acute chest pain with small increment of troponin and CK-MB and normal ECG. The 64-slice CT coronary angiography revealed a large non-obstructing non-calcified plaque in the proximal left anterior descending artery with positive vessel remodeling. The conventional coronary angiogram was normal but the intravascular ultrasound confirmed the CT findings. A drug eluting stent was implanted to seal the plaque. During the procedure, myocardial damage had occurred. At 6-month follow-up, 64-slice CT revealed minimal in-stent hyperplasia, which was confirmed at conventional angiography.

Two-year clinical follow-up after sirolimus-eluting versus bare-metal stent implantation assisted by systematic glycoprotein IIb/IIIa Inhibitor Infusion in patients with myocardial infarction: results from the STRATEGY study.

OBJECTIVES: We sought to investigate whether the previously reported midterm clinical benefit of planned sirolimus-eluting stent (SES) implantation in patients with ST-segment elevation myocardial infarction (STEMI) was maintained over a 24-month time period. Moreover, the distribution of clinical events in relation to thienopyridine discontinuation was thoroughly investigated. BACKGROUND: No randomized data are currently available on the safety/benefit profile of SES in this subset of patients beyond 12 months. METHODS: Between March 2003 and April 2004, 175 patients with STEMI were randomly allocated to tirofiban infusion followed by SES or abciximab plus bare-metal stent (BMS). Complete follow-up information up to 720 days was available for all patients. RESULTS: The cumulative incidence of death, myocardial infarction (MI), or target vessel revascularization (TVR) remained lower in the tirofiban-SES compared with the abciximab-BMS group at 2 years (24.2% vs. 38.6%, respectively; hazard ratio [HR] 0.56 [95% confidence interval (CI) 0.33 to 0.98]; p = 0.038). The composite of death/MI was similar in the tirofiban-SES (16.1%) and the abciximab-BMS groups (20.5%, HR 0.77 [95% CI 0.38 to 1.55]; p = 0.43) while the need for TVR was markedly reduced (9.8% vs. 25.5%, respectively; HR 0.34 [95% CI 0.16 to 0.77]; p = 0.01) in the tirofiban-SES arm. The rate of confirmed, probable, or possible stent thrombosis did not differ in the 2 groups, nor the incidence of death/MI after thienopyridine discontinuation. CONCLUSIONS: The midterm clinical benefit of planned SES implantation assisted by tirofiban infusion in STEMI patients was mainly carried over after 2 years with no overall excess of late adverse events after thienopyridine discontinuation.

Use of 64-slice CT in symptomatic patients after coronary bypass surgery: evaluation of grafts and coronary arteries.

AIMS: Although previous generations of multislice computed tomography (CT) have demonstrated accurate detection of obstructive bypass graft disease, progression of coronary disease is a more frequent cause for ischaemic symptoms late after bypass graft surgery. We explored the diagnostic performance of 64-slice CT in symptomatic patients after bypass surgery, for the assessment of both grafts and native coronary arteries. METHODS AND RESULTS: The 64-slice CT angiography (Siemens Sensation 64, Germany) was performed in 52 symptomatic patients, 10 +/- 5 years after bypass surgery. Two independent, blinded observers assessed all grafts and coronary arteries for stenosis, using conventional quantitative angiography as a reference. A total of 109 grafts (182 graft segments), 123 distal coronary run-offs, and 116 non-bypassed coronary branches (288 segments) were analysed. Per-segment detection of graft disease yielded a sensitivity of 99% (71/72) and specificity of 96% (106/110). Sensitivity and specificity to detect run-off disease were 89% (8/9) and 93% (106/114), positive predictive value was 50% (8/16). In non-grafted coronary segments, CT detected significant stenosis with a sensitivity and specificity of 97% (62/64) and 86% (192/224). Overestimation occurred more frequently in calcified segments (P = 0.002). CONCLUSION: The 64-slice CT allows angiographic evaluation of grafts and coronary arteries, although overestimation of coronary obstruction occurs, particularly in the presence of calcified disease.

Non-invasive visualization of coronary atherosclerosis: state-of-art.

Coronary artery disease remains the leading cause of death in the Western world. Non-invasive coronary artery imaging challenges any diagnostic modality because the coronary arteries are small and tortuous, whereas cardiac contraction and respiration cause motion artifacts. Therefore, non-invasive coronary imaging requires high spatial and temporal resolution. This review discusses the feasible applications in coronary imaging of magnetic resonance imaging and multi-slice computed tomography (MSCT), which are currently the only non-invasive diagnostic modalities for direct coronary atherosclerosis imaging. Particular attention and focus is devoted to the potential indications and clinical impact of MSCT due to its fast development and the robust results recently reported. MSCT of the coronary arteries is a promising imaging modality for the assessment of the coronary lumen and wall.

Factor XIIIA-V34L and factor XIIIB-H95R gene variants: effects on survival in myocardial infarction patients.

It has been demonstrated recently that coagulation factor XIII (FXIII) plays an extraordinary role in myocardial healing after infarction, improving survival in a mouse model. Common FXIII gene variants (i.e. FXIIIA-V34L and FXIIIB-H95R) significantly influence the molecular activity. To evaluate whether there is a relationship between the two FXIII gene variants and survival in patients after myocardial infarction (MI), V34L and H95R were PCR-genotyped in a cohort of 560 MI cases and follow-up was monitored. Cases with ST-segment elevation MI (STEMI) were 416 (74.3%) and 374 of these were treated with primary percutaneous coronary intervention (PCI) (89.9%). The remaining 144 patients showed non-ST-segment elevation MI (NSTEMI) at enrollment. The combined endpoint was the occurrence of death, re-infarction, and heart failure. Kaplan-Meier analysis at one year yielded an overall rate for adverse events of 24.5% with a lower incidence in the L34-carriers (28.8% vs 17.1%; log-rank, P = 0.00025), similar to that of the 416 STEMI (23.8%) being (28.0% and 16.9%; VV34- and L34-carriers respectively; log-rank, P = 0.001). Primary PCI-group had a slight lower incidence (22.9%) of adverse events (26.8% and 17.1%; VV34- and L34-carriers respectively; log-rank, P = 0.009). During hospitalization, 506 patients received PCI (374 primary PCI and 132 elective PCI). Significance was conserved also in the overall PCI-group (28.6% and 17.8%; VV34- and L34-carriers respectively; log-rank, P = 0.001). Similar findings were observed at 30 days follow-up. Cases carrying both FXIII variants had improved survival rate (log-rank, P = 0.019). On the other hand, minor bleeding complications were found increased in L34-carriers (P = 0.0001) whereas major bleeding complications were not. Finally, more direct evidence on the role of FXIII molecule on survival might come from the fact that despite significant FXIII antigen reductions observed in cases after MI, regardless the FXIII genotype considered, L34-carriers kept almost normal FXIII activity (VV34- vs L34-carriers; P < 0.001). We conclude that FXIII L34-allele improves survival after MI in all the groups analyzed, possibly through its higher activity associated with assumable positive effects on myocardial healing and recovered functions. Genetically determined higher FXIII activity might influence post-MI outcome. This paves the way for using FXIII molecules to improve myocardial healing, recovery of functions, and survival after infarction.

Diagnostic performance of multislice spiral computed tomography of coronary arteries as compared with conventional invasive coronary angiography: a meta-analysis.

OBJECTIVES: This study was designed to define the current role of multislice spiral computed tomography (MSCT) for the diagnosis of coronary artery disease (CAD) using a meta-analytic process. BACKGROUND: Multislice spiral computed tomography has recently been proposed as an alternative to conventional coronary angiography (CA) for the diagnosis of CAD. METHODS: Using Medline, we identified 29 studies (2,024 patients) evaluating CAD by means of both MSCT (> or =16 slices) and conventional CA before July 2006. After data extraction the analysis was performed according to a random-effects model. RESULTS: The per-segment analysis pooled the results from 27 studies corresponding to a cumulative number of 22,798 segments. Among unassessable segments, 4.2% were excluded from the analysis and 6.4% were classified at the discretion of the investigators, underscoring the shortcomings of MSCT. With this major limitation, the per-segment sensitivity and specificity were 81% (95% confidence interval [CI] 72% to 89%) and 93% (95% CI 90% to 97%), respectively, with positive and negative likelihood ratios of 21.5 (95% CI 13.1 to 35.5) and 0.11 (95% CI 0.06 to 0.21), respectively, and positive and negative predictive values of 67.8% (95% CI 57.6% to 78.0%) and 96.5% (95% CI 94.7% to 98.3%), respectively. As expected, the per-patient analysis has shown an increased sensitivity of 96% (95% CI 94% to 98%) but a decreased specificity of 74% (95% CI 65% to 84%). CONCLUSIONS: Multislice spiral computed tomography has shortcomings difficult to overcome in daily practice and, at the more clinically relevant per-patient analysis, continues to have moderate specificity in patients with high prevalence of CAD. Studies evaluating the diagnostic performance of the newest generation of MSCT, including patients with low to moderate CAD prevalence, will be critical in establishing the clinical role of this emerging technology as an alternative to CA.

Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates.

PURPOSE: Assess the effect of heart rate on diagnostic accuracy for the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). MATERIAL AND METHODS: About 120 patients (105 males; 59+/-11 years) with suspected coronary artery disease who underwent conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA (Sensation 16, Siemens, Germany), with the following protocol: collimation 16 x 0.75 mm, gantry rotation time 420 ms, feed/rotation 3.0 mm, kV 120, mAs 400-500. The protocol for contrast material administration was 100 ml of Iodixanol (Visipaque 320 mg l/ml, Amersham, UK) at 4 ml/s and the delay was defined with a bolus tracking technique. In all patients the mean heart rate (HR) during the scan was used as a criteria to divide the population in two groups of 60 patients each. In one group (Low HR) the 60 patients with lower heart rates, and in the other group (High HR) the patients with higher heart rates. In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (>or=50% lumen reduction) was evaluated in vessels >or=2 mm of diameter using quantitative CA as reference standard. The difference in diagnostic accuracy were compared with a Chi(2) test and a p<0.05 was considered significant. RESULTS: There was no significant difference between the two groups regarding age, gender, weight, mean intravascular attenuation, and calcium score. Overall 1,310 (652 for Low HR and 658 for High HR) segments with 219 (105 for Low HR and 114 for High HR) significant lesions were available for the analysis. The average heart rate was 52+/-4 HU and 63+/-5 HU for Low HR and High HR, respectively (p<0.001). The sensitivity and specificity were 92 and 96% for Low HR and 90 and 92% for High HR (p<0.05). There were 22 vs. 44 false positives, and 8 vs. 12 false negatives in the Low HR and High HR, respectively. CONCLUSION: Increasing HR significantly deteriorates diagnostic accuracy in MSCT-CA.