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Cardiovascular (CV) diseases caused 20.5 million deaths in 2021, making up nearly one-third of global mortality. This highlights the need for practical prognostic markers to better classify patients and guide treatment, especially in ischemic heart disease (IHD), which represents one of the leading causes of CV mortality. Transthoracic echocardiography (TTE) is a key, non-invasive imaging tool widely used in cardiology for diagnosing and managing a range of CV conditions. It is the first choice for diagnosing and monitoring patients with acute coronary syndrome (ACS). Alongside well-established echocardiographic measures, new techniques have proven useful for predicting adverse events in IHD patients, such as three-dimensional (3D) and tissue Doppler imaging (TDI), and speckle tracking technology. This review aims to explore the latest echocardiographic tools that could provide new prognostic markers for patients in the acute phase and during follow-up after an acute myocardial infarction (AMI). We focus on new imaging methods like TDI, myocardial work index (MWI), speckle-tracking strain, and 3D technologies using TTE, which are easy to use and widely available at all stages of coronary artery disease (CAD)., (© 2024 Wiley Periodicals LLC.)

After a cardiac transplantation, the steering of immunosuppression requires an active search for acute cellular rejection (ACR). Surveillance with endomyocardial biopsy (EMB) is the gold standard. Given the costs and potential complications, there is growing interest in the use of non-invasive screening methods. Thus, we have conducted a systematic review and meta-analysis to evaluate the role of speckle-tracking echocardiography as a screening method for ACR. We searched PubMed (CENTRAL) and gray literature for studies presenting data on speckle tracking echocardiography in heart-transplant patients experiencing acute cellular rejection. The primary outcomes of the meta-analysis were left and right ventricular global longitudinal strain. We used random effects models for all our calculations. We pre-registered our meta-analysis with PROSPERO (CRD42024508654). By incorporating data from over 2000 biopsies included in 18 studies, we found that both left (LVGLS, MD -1.96, 95% CI -2.85 to -1.07, p < 0.0001), and right (RVGLS, MD -2.90, 95% CI -4.03 to -1.76, p < 0.00001) ventricular longitudinal strain were lower among patients without ACR. The change of LVGLS from baseline over time was also greater among patients experiencing ACR (MD -2.43, 95% CI -4.82 to -0.05, p = 0.045). Current data suggest that myocardial strain measured by speckle tracking echocardiography is affected in ACR and could potentially be used for early rejection detection as a rule-out strategy, leading to reduction of routine EMB in heart transplant follow-up., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

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., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., ((c) RSNA, 2008.)

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.

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.

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.

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.

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.

Objectives: The purpose of this study was to evaluate the value of platelet reactivity (PR) in predicting the response to treatment and outcome in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention assisted by glycoprotein (GP) IIb/IIIa inhibition., Background: There is limited prognostic information on the role of spontaneous or drug-modulated PR in STEMI patients., Methods: The PR was measured with Platelet Function Analyzer (PFA)-100 and light transmission aggregometry (LTA) using adenosine diphosphate as agonist in 70 consecutive STEMI patients at entry (PR-T0), 10 min after GP IIb/IIIa bolus (PR-T1), and discharge (PR-T2) and in 30 stable angina (SA) patients (PR-SA). Complete platelet inhibition (CPI) was based on closure time >300 s by PFA-100 and percentage inhibition of platelet aggregation >95% by LTA. Clinical, electrocardiographic, and angiographic responses to treatment during 1-year follow-up were collected., Results: According to both techniques, PR-T0 was higher than: 1) PR-T2 and PR-SA; 2) in those without CPI at T1; and 3) in patients with final Thrombolysis In Myocardial Infarction (TIMI) flow grade <3. The PR-T0 assessed with PFA-100 correlated with: 1) corrected TIMI frame count (r = -0.6, p < 0.001); 2) ST-segment resolution (r = 45, p < 0.001); and 3) creatine kinase-MB (r = -0.47, p < 0.001). At 1 year, patients with high PR-T0 showed an adjusted 5- to 11-fold increase in the risk of death, reinfarction, and target vessel revascularization (hazard ratio [HR] 11, 95% confidence interval [CI] 1.5 to 78 [p = 0.02] in PFA-100; HR 5.2, 95% CI 1.1 to 23 [p = 0.03] in LTA)., Conclusions: The PR at entry affects response to GP IIb/IIIa inhibition, mechanical treatment, and long-term outcome in STEMI patients undergoing primary intervention.

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.

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.

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.

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.

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., (Copyright RSNA, 2006.)

Objectives: This study sought to investigate whether the anatomical location of the disease carries prognostic implications in patients undergoing drug-eluting stent (DES) implantation for the left main coronary artery (LMCA) stenosis., Background: Liberal use of DES, compared with a bare metal stent (BMS), has resulted in an improved outcome in patients undergoing LMCA intervention. However, the overall event rate in this subset of patients remains high, and alternative tools to risk-stratify this population beyond conventional surgical risk status would be desirable., Methods: From April 2002 to June 2004, 130 patients received DES as part of the percutaneous intervention for LMCA stenoses in our institution. Distal LMCA disease (DLMD) was present in 94 patients. They were at higher surgical risk and presented with a greater coronary disease extent compared with patients without DLMD., Results: After a median of 587 days (range 368 to 1,179 days), the cumulative incidence of major adverse cardiac events (MACE) was significantly higher in patients with DLMD at 30% versus 11% in those without DLMD (hazard ratio [HR] 3.42, 95% confidence interval [CI] 1.34 to 9.7; p = 0.007), mainly driven by the different rate of target vessel revascularization (13% and 3%; HR 6, 95% CI 1.2 to 29; p = 0.02). After adjustment for confounders, DLMD (HR 2.79,95% CI 1.17 to 8.9; p = 0.032) and surgical risk status (HR 2.18,95% CI 1.06 to 4.5; p = 0.038) remained independent and complementary predictors of MACE., Conclusions: Distal LMCA disease carries independent prognostic implications, and it may help in selecting the most appropriate patient subset for LMCA intervention beyond the conventional surgical risk status in the DES era.

Aims: Relative plaque composition, more than its morphology alone, is thought to play a pivotal role in determining propensity to vulnerability. Thus, we investigated in vivo whether the distance from coronary ostium to plaque location independently affects plaque composition in humans. This may help explaining the recently reported non-uniform distribution of culprit lesions along the vessel in acute coronary syndromes., Methods and Results: In 51 consecutive patients (45 men), aged 38-76 years (mean age: 58+/-10), a non-culprit vessel was investigated through spectral analysis of IVUS radiofrequency data (IVUS-Virtual Histology). The study vessel was the left anterior descending artery in 23 (45%) patients; the circumflex artery in nine (18%), and right coronary artery in 19 (37%). The overall length of the region of interest, subsequently divided into 10 mm segments, was 41.5+/-13 mm long (range: 30.2-78.4). No significant change was observed in terms of relative plaque composition along the vessel with respect to fibrous, fibrolipidic, and calcified tissue, whereas the percentage of lipid core resulted to be increased in the first (median: 8.75%; IQR: 5.7-18) vs. the third (median: 6.1%; IQR: 3.2-12) (P=0.036) and fourth (median: 4.5%; IQR: 2.4-7.9) (P=0.006) segment. At multivariable regression analysis, distance from the ostium resulted to be an independent predictor of relative lipid content [beta=-0.28 (95%CI: -0.15, -0.41)], together with older age, unstable presentation, no use of statin, and presence of diabetes mellitus., Conclusion: Plaque distance from the coronary ostium, as an independent determinant of relative lipid content, is potentially associated to plaque vulnerability in humans.

Multislice computed tomography (CT) is an emerging technique for the non-invasive detection of coronary stenoses. While the diagnostic accuracy of 4-slice scanners was limited, 16-slice CT imagers showed promising results due to increased temporal and spatial resolution. These technical advances prompted us to evaluate the diagnostic performance of 64-slice CT coronary angiography in the detection of significant stenoses (defined as > or = 50% luminal diameter reduction) versus invasive quantitative coronary angiography (QCA). Thirty-five patients with stable angina pectoris underwent CT coronary angiography performed with a 64-slice scanner (gantry rotation time 330 ms, individual detector width 0.6 mm) prior to conventional coronary angiography. Patients with heart rates >70 beats/min received 100 mg metoprolol orally. One hundred millilitres of contrast agent with an iodine concentration of 400 mgl/ml were injected at a rate of 5 ml/s into the antecubital vein. The CT scan was triggered with the bolus tracking technique. The sensitivity, specificity and the positive and negative predictive values of 64-slice CT were 99%, 96%, 78% and 99%, respectively, on a per-segment basis. The values obtained on a per-patient basis were 100%, 90%, 96% and 100%, respectively. When referral to catheterisation is questionable, CT coronary angiography may identify subjects with normal angiograms and consistently decrease the number of unnecessary invasive procedures.

Objectives: The purpose of this study was to investigate the long-term clinical and angiographic profile of sirolimus-eluting stent (SES) versus paclitaxel-eluting stent (PES) in patients undergoing percutaneous intervention for left main (LM) coronary disease., Background: The long-term clinical and angiographic impact of SES as opposed to PES implantation in this subset of patients is unknown., Methods: From April 2002 to March 2004, 110 patients underwent percutaneous intervention for LM stenosis at our institution; 55 patients were treated with SES and 55 with PES. The two groups were well balanced for all baseline characteristics., Results: At a median follow-up of 660 days (range 428 to 885), the cumulative incidence of major adverse cardiovascular events was similar (25% in the SES group vs. 29%, in the PES group; hazard ratio 0.88 [95% confidence interval 0.43 to 1.82]; p = 0.74), reflecting similarities in both the composite death/myocardial infarction (16% in the SES group and 18% in the PES group) and target vessel revascularization (9% in the SES group and 11% in the PES group). Angiographic in-stent late loss (mm), evaluated in 73% of the SES group and in 77% of the PES group, was 0.32 +/- 74 in the main and 0.36 +/- 0.59 in the side branch in the SES group vs. 0.46 +/- 0.57 (p = 0.36) and 0.52 +/- 0.42 (p = 0.41) in the PES group, respectively., Conclusions: In consecutive patients undergoing percutaneous LM intervention, PES may perform closely to SES both in terms of angiographic and long-term clinical outcome.

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.

The introduction of multislice computed tomography (MSCT) has allowed non-invasive coronary angiography. Although widely applied, extensive information on technical details of the technique is lacking. This survey offers detailed information on patient preparation, data acquisition, reconstruction and interpretation. In addition, a summary of the available studies using MSCT for non-invasive angiography is provided. Based on pooled analysis of direct comparisons between MSCT and invasive angiography, the weighted mean sensitivity and specificity of current 16-slice MSCT for the detection of coronary artery disease are 88% and 96%, respectively. At present, the technique is particularly well suited for reliable exclusion of coronary artery disease. It is important to emphasise that MSCT only provides anatomical images, visualising the presence of atherosclerosis; information on the haemodynamic significance of these lesions (i.e. ischaemia) cannot be derived.

Multislice computed tomography is a rapidly emerging technique for the non-invasive visualization of coronary arteries. Over the past 5 years several scanner generation were introduced with a progressive improvement in the diagnostic accuracy in the detection of coronary artery stenosis in selected patients populations. The introduction of 64-slice technology has further improved the diagnostic performance. This technique is at the edge of clinical implementation and, even though large clinical trials are still missing, an increased demand for these type of studies is observed all over the world. We describe our experience of more than 1 year with 64-slice CT coronary angiography providing clues on reasonable clinical applications.

Aims: There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI)., Methods and Results: Twenty patients with STEMI (mean age, 61+/-10 years), of whom 14 were submitted to primary percutaneous coronary intervention, were randomized to G-CSF (5 microg/kg/day s.c. for 4 consecutive days) or placebo. At entry and then at months 3 and 6, (99m)Tc-sestamibi gated-SPECT was performed to estimate extension of perfusion defect (PD) and LV function. The study drug was well tolerated and induced a significant increase of white blood count, CD34(+) cells, and CD34(+) cells coexpressing AC133 and VEGFR-2. At follow-up, treated and placebo groups did not differ for the angiographic coronary late loss and showed a similar pattern of PD recovery, whereas in the former at 6 months LVEF and especially LVEDV tended to be relatively higher (P=0.068) and lower (P=0.054), respectively., Conclusion: G-CSF administration in acute MI patients was feasible and did not lead to any clinical or angiographic adverse events and resulted in CD34(+) and CD34(+)AC133(+)VEGFR2(+) cell mobilization.

The aim of this article is to illustrate the main technical improvements in the last generation of 64-row CT scanners and the possible applications in coronary angiography. In particular, we describe the new physical components (X-ray tube-detectors system) and the general scan and reconstruction parameters. We then define the scan protocols for coronary angiography with the new generation of 64-row CT scanners to enable radiologists to perform a CT study on the basis of the diagnostic possibilities.

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.

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.

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.

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.

Background: Primary bare metal stenting and abciximab infusion are currently considered the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus eluting stents (SES), compared to bare metal stent (BMS), greatly reduce the incidence of binary restenosis and target vessel revascularisation (TVR), but their use on a routine basis results in a significant increase in medical costs. With current European list prices, the use of tirofiban instead of abciximab would save enough money to absorb the difference between SES and BMS., Aim: To assess whether in patients with STEMI the combination of SES with high dose bolus (HDB) tirofiban results in a similar incidence of major cardiovascular events (MACE) but in a lower binary restenosis rate after six months compared to BMS and abciximab., Methods and Results: 160 patients are required to satisfy the primary composite end-point, including MACE and binary restenosis. The study is ongoing: the current paper focuses on the methodology and demography of the first 100 patients so far enrolled. Patients randomised to HDB tirofiban (n = 50, mean age: 62 +/- 12, 40 males) and abciximab (n = 50, mean age: 63 +/- 12, 38 males) do not differ for medical history, presentation profile, medications at discharge, angiographic profile and creatine-kinase MB-fraction at peak., Conclusions: The results of the trial will be available by the end of 2004: they will be crucial for the cardiologists to know whether the gold standard for AMI treatment should be reconsidered after the introduction of SES into the clinical practice.

The past two decades have highlighted the pivotal role of the endothelium in preserving vascular homeostasis. Among others, nitric oxide (NO) is currently believed to be the main component responsible for endothelium dependent vasorelaxation and therefore for endothelial function integrity. Reduced NO bioavailability causes the so-called "endothelial dysfunction," which seems to be the common molecular disorder comprising stable atherosclerotic narrowing lesions or acute plaque rupture causing unstable angina or myocardial infarction. Compelling evidence is accumulating, stressing the role of oxidative stress in causing reduced NO bioavailability and subsequently endothelial dysfunction (ED). More recently, the role of endothelial cell (EC) apoptosis as a possible final stage of ED and plaque activation has been suggested. In vitro and in vivo evidence suggests a role of oxidative stress also as a putative mechanism finally leading to plaque denudation and activation through increased EC apoptosis. Thus, oxidative stress, irrespective of atherosclerotic disease stages, seems to represent a key phenomenon in vascular disease progression and possible prevention.