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Aims: This study evaluated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) for detecting microvascular obstruction (MVO) and left ventricular (LV) remodelling revealed by DE magnetic resonance imaging after acute myocardial infarction (AMI)., Methods and Results: In 92 patients with first AMI, MDCT without iodine reinjection was performed immediately following successful percutaneous coronary intervention (PCI). Delayed-enhancement magnetic resonance imaging performed in the acute and chronic phases was used to detect MVO and LV remodelling (any increase in LV end-systolic volume at 6 months after infarction compared with baseline). Patients were divided into two groups according to the presence (n = 33) or absence (n = 59) of heterogeneous enhancement (HE). Heterogeneous enhancement was defined as concomitant presence of hyper- and hypoenhancement within the infarcted myocardium on MDCT. Microvascular obstruction and LV remodelling were detected in 49 (53%) and 29 (32%) patients, respectively. In a multivariable analysis, HE and a relative CT density >2.20 were significant independent predictors for MVO [odds ratio (OR) 13.5; 95% confidence interval (CI), 2.15-84.9; P = 0.005 and OR 12.0; 95% CI, 2.94-49.2; P < 0.001, respectively). The presence of HE and relative CT density >2.20 showed a high positive predictive value of 93%, and the absence of these two findings yielded a high negative predictive value of 90% for the predictive value of MVO. Heterogeneous enhancement was significantly associated with LV remodelling (OR 6.75; 95% CI, 1.56-29.29; P = 0.011)., Conclusion: Heterogeneous enhancement detected by MDCT immediately after primary PCI may provide promising information for predicting MVO and LV remodelling in patients with AMI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Global measures of left ventricular (LV) function, in particular LV ejection fraction (LVEF) and global myocardial strain measures, are powerful predictors of outcomes in patients with LV dysfunction, heart failure, or both. However, less is known about the relationship between regional myocardial function, especially that assessed by strain echocardiography and clinical prognosis., Methods and Results: We studied 248 patients with LV dysfunction, heart failure, or both 5 days after first myocardial infarction (MI) from the VALIANT study. We assessed peak longitudinal strain (LS) via B-mode speckle tracking in 12 segments from the apical 4- and 2-chamber views and visually assessed LV wall motion score (WMS). We related these measures of regional myocardial function to each other and to clinical outcomes over 20-month follow-up. Normal reference values for segmental LS were derived from 50 healthy controls. Regional LS (-7.7%, Q1: -11.2%, Q3: -4.9%) was worse in segments with abnormal WMS, although was significantly impaired even in segments scored as normokinetic compared with normal controls (-10.4 ± 5.2% vs. -20.0 ± 7.6%, P < 0.001). In multivariable Cox proportional hazards models, each additional abnormal LS segment was associated with an increased risk of all-cause mortality (hazard ratio: 1.42, 95% confidence interval: 1.06-1.90, P = 0.02) even after adjustment for clinical covariates, including LVEF, LV end-systolic volume, and number of abnormal segments by WMS., Conclusion: In patients with LV dysfunction, heart failure, or both after MI, regional LS is significantly depressed even in segments with normal WMS, and this measure was related to adverse outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: We evaluated coronary artery disease (CAD) extent, severity, and major adverse cardiac events (MACEs) in never, past, and current smokers undergoing coronary CT angiography (CCTA)., Methods and Results: We evaluated 9456 patients (57.1 ± 12.3 years, 55.5% male) without known CAD (1588 current smokers; 2183 past smokers who quit ≥3 months before CCTA; and 5685 never smokers). By risk-adjusted Cox proportional-hazards models, we related smoking status to MACE (all-cause death or non-fatal myocardial infarction). We further performed 1:1:1 propensity matching for 1000 in each group evaluate event risk among individuals with similar age, gender, CAD risk factors, and symptom presentation. During a mean follow-up of 2.8 ± 1.9 years, 297 MACE occurred. Compared with never smokers, current and past smokers had greater atherosclerotic burden including extent of plaque defined as segments with any plaque (2.1 ± 2.8 vs. 2.6 ± 3.2 vs. 3.1 ± 3.3, P < 0.0001) and prevalence of obstructive CAD [1-vessel disease (VD): 10.6% vs. 14.9% vs. 15.2%, P < 0.001; 2-VD: 4.4% vs. 6.1% vs. 6.2%, P = 0.001; 3-VD: 3.1% vs. 5.2% vs. 4.3%, P < 0.001]. Compared with never smokers, current smokers experienced higher MACE risk [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.4-2.6, P < 0.001], while past smokers did not (HR 1.2, 95% CI 0.8-1.6, P = 0.35). Among matched individuals, current smokers had higher MACE risk (HR 2.6, 95% CI 1.6-4.2, P < 0.001), while past smokers did not (HR 1.3, 95% CI 0.7-2.4, P = 0.39). Similar findings were observed for risk of all-cause death., Conclusion: Among patients without known CAD undergoing CCTA, current and past smokers had increased burden of atherosclerosis compared with never smokers; however, risk of MACE was heightened only in current smokers., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The efficient and reliable evaluation of patients with acute chest pain is one of the most challenging tasks in the emergency department. Coronary computed tomography (CT) angiography may play a major role, since it permits ruling out coronary artery disease with high accuracy if performed with expertise in properly selected and prepared patients. Several randomized trials have established early cardiac CT as a viable safe and potentially more efficient alternative to functional testing in the evaluation of acute chest pain. Ongoing investigations explore whether advanced anatomic and functional assessments such as high-risk coronary plaque, resting myocardial perfusion, and left ventricular function, or the simulation of the fractional coronary flow reserve will add information to the anatomic assessment for stenosis, which would allow expanding the benefits of cardiac CT from triage to treatment decisions. Especially, the combination of high-sensitive troponins and coronary computed tomography angiography may play a valuable role in future strategies for the management of patients presenting with acute chest pain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aim: The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phenotype in non-infarct-related arteries of STEMI patients undergoing primary percutaneous coronary intervention (PCI)., Methods and Results: Between September 2009 and January 2011, 103 STEMI patients underwent intravascular ultrasonography (IVUS) and radiofrequency ultrasonography (RF-IVUS) of the two non-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. Patients were treated with high-intensity rosuvastatin (40 mg/day) throughout 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS end-point was the change in per cent atheroma volume (PAV). After 13 months, low-density lipoprotein cholesterol (LDL-C) had decreased from a median of 3.29 to 1.89 mmol/L (P < 0.001), and high-density lipoprotein cholesterol (HDL-C) levels had increased from 1.10 to 1.20 mmol/L (P < 0.001). PAV of the non-IRA decreased by -0.9% (95% CI: -1.56 to -0.25, P = 0.007). Patients with regression in at least one non-IRA were more common (74%) than those without (26%). Per cent necrotic core remained unchanged (-0.05%, 95% CI: -1.05 to 0.96%, P = 0.93) as did the number of RF-IVUS defined thin cap fibroatheromas (124 vs. 116, P = 0.15)., Conclusion: High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aim: We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care., Methods and Results: We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (-0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups., Conclusion: In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials., Methods and Results: The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients., Conclusion: In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial., Clinical Trial Registration Information: Unique identifier NCT00976092 (www.clinicaltrials.gov)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography., Methods and Results: Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033)., Conclusion: In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

Aims: Diastolic dysfunction in acute myocardial infarction (MI) is associated with adverse outcome. Recently, the ratio of early mitral inflow velocity (E) to global diastolic strain rate (e'sr) has been proposed as a marker of elevated LV filling pressure. However, the prognostic value of this measure has not been demonstrated in a large-scale setting when existing parameters of diastolic function are known. We hypothesized that the E/e'sr ratio would be independently associated with an adverse outcome in patients with MI., Methods and Results: We prospectively included patients with MI and performed echocardiography with comprehensive diastolic evaluation including E/e'sr. The relationship between E/e'sr and the primary composite endpoint (all-cause mortality, hospitalization for heart failure (HF), stroke, and new onset atrial fibrillation) was analysed with Cox models. A total of 1048 patients (mean age 63 ± 12, 73% male) were included and 142 patients (13.5%) reached the primary endpoint (median follow-up 29 months). A significant prognostic value was found for E/e'sr [hazard ratio (HR) per 1 unit change: 2.36, 95% confidence interval (CI): 2.02-2.75, P < 0.0001]. After multivariable adjustment E/e'sr remained independently related to the combined endpoint (HR per 1 unit change, 1.50; CI: 1.05-2.13, P = 0.02). The prognostic value of E/e'sr was driven by mortality (HR per 1 unit change, 2.52; CI: 2.09-3.04, P < 0.0001) and HF admissions (HR per 1 unit change, 2.79; CI: 2.23-3.48, P < 0.0001)., Conclusion: Deformation-based E/e'sr contributes important information about global myocardial relaxation superior to velocity-based analysis and is independently associated with the outcome in acute MI.

Aims: Kynurenine is a potent endothelium-derived vasodilator. Its synthesis from tryptophan is stimulated by interferon γ and may represent an important compensatory pathway for the regulation of vascular function in inflammatory conditions. We assessed associations of urine kynurenine to tryptophan ratio (KTR) levels to incident major coronary events (MCEs), acute myocardial infarction (AMI), and ischaemic stroke and mortality in patients with suspected stable coronary artery disease (CAD)., Methods and Results: A total of 3224 patients (mean age 62 years, 69% men) underwent urine and blood sampling prior to elective coronary angiography and were subsequently followed up for median 55 months. A total of 8.4% experienced an MCE, 7.8% suffered an AMI, and 7.6% died. In age- and gender-adjusted analyses, the hazard ratios [HRs; 95% confidence intervals (CI)] of MCE, AMI, and all-cause mortality were 1.43 (1.29-1.59), 1.44 (1.29-1.59), and 1.38 (1.23-1.54) per standard deviation increment of the (log-transformed) urinary KTR, respectively. These estimates were only minimally attenuated after adjustment for potential confounders. The addition of the urine KTR to a model of conventional risk factors significantly improved goodness of fit, discrimination, and risk classification for these clinical endpoints. No association was seen between the urine KTR and the risk of incident ischaemic stroke., Conclusion: A novel urinary inflammation marker, KTR, is strongly associated with adverse prognosis in patients with suspected stable CAD. Underlying pathomechanisms should be further elucidated.

Aims: The optimal timing of intervention in non-ST-elevation myocardial infarction (NSTEMI) remains uncertain. The aim of this multicentre trial was to assess whether an immediate invasive approach is superior to an early invasive or a selective invasive approach with respect to reduction of large infarction., Methods and Results: Patients with NSTEMI were randomized to either an immediate (<2 h after randomization; n= 201), an early (10-48 h after randomization; n= 200), or a selective invasive approach with high invasive percentage (n= 201). The primary outcome was the peak creatine kinase (CK)-myocardial band (MB) activity during index hospitalization; key secondary clinical endpoints were the composite of (i) death and non-fatal infarction; (ii) death, non-fatal infarction, and refractory ischaemia; (iii) death, non-fatal infarction, refractory ischaemia, and rehospitalization for unstable angina within 6 months. The median time from randomization to angiography was 1.1 h in the immediate vs. 18.6 h in the early and 67.2 h in the selective invasive group (P< 0.001). There was no significant difference in the peak CK-MB activity between groups. The key secondary clinical endpoints were similar between groups at 6-month follow-up: death and infarction: 21.0 vs. 16.0 vs. 14.5%; P= 0.17; death, infarction, refractory ischaemia: 20.9 vs. 21.5 vs. 22.0%; P= 0.98; death, infarction, refractory ischaemia, rehospitalization: 26.0 vs. 26.5 vs. 24.5%; P= 0.91, respectively., Conclusions: In NSTEMI patients, an immediate invasive approach does not offer an advantage over an early or a selective invasive approach with respect to large myocardial infarctions as defined by peak CK-MB levels, which is supported by similar clinical outcomes. ClinicalTrials.gov NCT00402675.

Aims: The endothelium plays a role in regulating vascular tone. Acute and dynamic changes in low-flow-mediated constriction (L-FMC) and how it changes with regard to traditional flow-mediated dilatation (FMD) have not been described. We aimed to investigate the changes in brachial artery L-FMC following percutaneous coronary intervention (PCI) and during recovery from non-ST-segment elevation myocardial infarction (NSTEMI)., Methods and Results: FMD was performed in accordance with a previously described technique in patients before and after PCI and in the recovery phase of NSTEMI, but in addition, L-FMC data were acquired from the last 30 s of cuff inflation. About 135 scans were performed in 96 participants (10 healthy volunteers and 86 patients). Measurement of brachial L-FMC was reproducible over hours. L-FMC was greater among patients with unstable vs. stable coronary atherosclerosis (-1.33 ±1.09% vs. -0.03 ± 1.26%, P < 0.01). Following PCI, FMD reduced (4.43 ± 2.93% vs. 1.66 ± 2.16%, P < 0.01) and L-FMC increased (-0.33 ± 0.76% vs. -1.63 ± 1.15%, P = 0.02). Furthermore, during convalescence from NSTEMI, L-FMC reduced (-1.37 ± 1.19% vs. 0.01 ± 0.82%, P = 0.02) in parallel with improvements in FMD (2.54 ± 2.19% vs. 5.15 ± 3.07%, P < 0.01)., Conclusion: Brachial L-FMC can be measured reliably. Differences were observed between patients with stable and unstable coronary disease. L-FMC was acutely increased following PCI associated with reduced FMD and, in the recovery from NSTEMI, L-FMC reduced associated with increased FMD. These novel findings characterize acute and subacute variations in brachial L-FMC. The pathophysiological and clinical implications of these observations require further study.

Aims: we tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores., Methods and Results: the rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67%). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group., Conclusion: the 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.

Aims: Cardioprotective effects of erythropoietin (EPO) have been shown in experimental and smaller clinical studies. We performed a prospective, multicentre, randomized trial to assess the effects of a single high dose of EPO after primary coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Methods and results Patients with a successful PCI for a first STEMI were randomized to receive either standard medical care alone, or in combination with a single bolus with 60,000 IU i.v. of epoetin alfa within 3 h after PCI. Primary endpoint was left ventricular ejection fraction (LVEF) after 6 weeks, assessed by planar radionuclide ventriculography. Pre-specified secondary endpoints included enzymatic infarct size and major adverse cardiovascular events. A total of 529 patients were enrolled (EPO n = 263, control n = 266). At baseline (before EPO administration), groups were well-matched for all relevant characteristics. After a mean of 6.5 (± 2.0) weeks, LVEF was 0.53 (± 0.10) in the EPO group and 0.52 (± 0.11) in the control group (P = 0.41). Median area under the curve (inter-quartile range) after 72 h for creatinine kinase was 50 136 (28 212-76 664)U/L per 72 h in the EPO group and 53 510 (33 973-90 486)U/L per 72 h in the control group (P = 0.058). More major adverse cardiac events occurred in the control than in the EPO group (19 vs. 8; P = 0.032). Conclusion A single high dose of EPO after a successful PCI for a STEMI did not improve LVEF after 6 weeks. However, the use of EPO was related to less major adverse cardiovascular events and a favourable clinical safety profile., Clinical Trial Registration Information: NCT00449488; http://www.clinicaltrials.gov/ct2/show/NCT00449488?term=voors&rank=2.

Aims: To study coronary microvascular dysfunction as possible pathogenetic mechanism in Apical Ballooning Syndrome (ABS)., Methods and Results: Fifteen ABS patients (all women, 68 +/- 14 years) underwent myocardial contrast echocardiography at baseline during adenosine infusion (140 microg/kg/min) and at 1-month follow-up and compared with a group of anterior ST-elevation myocardial infarction (STEMI) patients with similar clinical characteristics. Myocardial perfusion was assessed by contrast score index (CSI) and endocardial length of contrast defect (contrast defect length, CDL), whereas myocardial dysfunction by wall motion score index (WMSI), endocardial length of contractile dysfunction (wall motion defect length, WMDL), and LV ejection fraction (LVEF). At baseline, no difference in myocardial perfusion and dysfunction were present between the two groups. During adenosine challenge, while no changes were observed in STEMI group, in ABS patients CSI, CDL, WMSI, and WMDL significantly decreased compared with baseline (P < 0.001 vs. baseline for all parameters) and LVEF significantly increased (P = 0.01 vs. baseline). At 1-month follow-up, myocardial perfusion and dysfunction completely recovered in ABS patients (P < 0.001 vs. baseline for all parameters), whereas no significant changes were observed in STEMI group., Conclusion: Our data strongly suggest that in ABS, irrespectively of its underlying aetiology, acute and reversible coronary microvascular vasoconstriction could represent a common pathophysiological mechanism.

Aims: To determine (i) the effect of perindopril on several geometric and functional parameters of the left and right ventricles assessed by echocardiography in the unique Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) population of post-acute myocardial infarction (AMI) elderly patients with preserved left ventricular (LV) function; and (ii) the prognostic predictors at pre-discharge derived from echo-Doppler measurements in the same population., Methods and Results: PREAMI included 1252 post-AMI patients (age 73 +/- 6 years, LV ejection fraction 59.1 +/- 7.7%) receiving optimal therapy after AMI, randomized to perindopril 8 mg/day (n = 631) or placebo (n = 621); n = 896 had complete echo-Doppler data. Outcome measures were clinical [death, heart failure (HF)] and standard echo-Doppler parameters. Pre-discharge LV end-diastolic volume (LVEDV) was similar: 81.1 +/- 23.1 (perindopril) and 79.6 +/- 22.7 mL (placebo). At 6 months and 1 year, LVEDV remained unchanged with perindopril (81.2 +/- 24.4 and 81.8 +/- 26.8 mL, respectively), but increased with placebo (83.0 +/- 25.3 and 83.6 +/- 25.7 mL, respectively, both P < 0.001 vs. baseline). Perindopril reduced cardiac sphericity vs. placebo (P = 0.015 at 6 months; P = 0.020 at 1 year). Classification regression tree analysis showed treatment as the most important predictor of remodelling. Multiple pre-discharge echocardiographic variables predicted the death/HF endpoint, independently of treatment (P < or = 0.05)., Conclusion: Remodelling occurs in post-AMI in elderly patients with normal LV function. Echo-Doppler variables at baseline have prognostic implications. Treatment with perindopril reduces progressive LV remodelling that can occur even in the case of small infarct size.

Aims: Myocardial reperfusion after acute myocardial infarction can be angiographically assessed by the myocardial blush grade (MBG) or TIMI Perfusion Grade. These scores are based on subjective human judgement and lead to a score of four categories. A more operator-independent way of scoring myocardial perfusion may facilitate research in this area., Methods and Results: We designed the 'Quantitative Blush Evaluator' (QuBE), a computer program which calculates a score for myocardial perfusion. This program will be freely available as open source software. The inter-observer concordance was 97.7%. We calculated values on prospectively collected angiograms in patients with acute ST-elevation myocardial infarction from the TAPAS trial. Quantitative blush evaluator values could be assessed on 790 out of 980 collected angiograms (81%). The QuBE score correlated significantly with MBG as determined by a core lab. The QuBE score predicted complete ST-elevation resolution, low enzyme levels, and 1 year survival (all P < 0.001). Quantitative blush evaluator value was an independent predictor of mortality at 1 year [OR 0.40 (0.17-0.90), P = 0.02]., Conclusion: The QuBE program provides a practical, freely available computer-assisted assessment of myocardial perfusion. The QuBE score provides a useful surrogate endpoint in trials of therapies aimed at improving myocardial reperfusion.

Aims: Few data are available on the extent and prognostic value of reverse left ventricular remodelling (r-LVR) after ST-elevation acute myocardial infarction (STEMI). We sought to evaluate incidence, major determinants, and long-term clinical significance of r-LVR in a group of STEMI patients treated with primary percutaneous coronary intervention (PPCI). In particular, the role of preserved microvascular flow within the infarct zone in inducing r-LVR has been investigated., Methods and Results: Serial echocardiograms (2DE) and myocardial contrast study were obtained within 24 h of coronary recanalization (T1) and at pre-discharge (T2) in 110 reperfused STEMI patients. Follow-up 2DE was scheduled after 6 months (T3). Two-year clinical follow-up was obtained. Reverse remodelling was defined as a reduction >10% in LV end-systolic volume (LVESV) at 6 months follow-up. r-LVR occurred in 39% of study population. At multivariable analysis, independent predictors of r-LVR were an effective microvascular reflow within the infarct zone, the in-hospital improvement of myocardial perfusion, an initial large LVESV, and a short time to reperfusion. Cox analysis identified r-LVR as the only independent predictor of 2-year event-free survival. Combined events rate was significantly higher among patients without compared to those with r-LVR (log-rank test P < 0.05)., Conclusion: r-LVR frequently occurs in STEMI patients treated with PPCI and it is an important predictor of favourable long-term outcome. A preserved microvascular perfusion within the infarct zone is the major determinant of r-LVR.

Aims: To investigate whether intracoronary transfer of bone marrow progenitor cells (BMPCs) early after reperfusion of an acute myocardial infarction improves regional myocardial function in a randomized double-blind, placebo-controlled strain rate imaging study., Methods and Results: Regional myocardial deformation was measured using velocity-derived strain rate imaging in 67 STEMI patients randomized 1:1 to intracoronary infusion of BMPC (n = 33) or placebo (n = 34). Myocardial segments were grouped into infarct (n = 232), border (n = 250), and remote (n = 526) based on MRI-delayed enhancement and the perfusion territory of the infarct-related vessel. Four months after revascularization and progenitor cell/placebo transfer, regional myocardial deformation (rate) improved significantly more in the infarct segments of BMPC patients (treatment effect on end-systolic strain: -3.7 +/- 1.0%, P = 0.0003; peak-systolic strain rate: -0.20 +/- 0.07 s(-1), P = 0.0035). These findings were confirmed by a significantly greater improvement of longitudinal mitral valve ring displacement in the infarct walls of BMPC patients (treatment effect: 0.93 mm, P = 0.034)., Conclusion: Intracoronary infusion of BMPC early after reperfusion of a STEMI improves recuperation of regional myocardial function at 4 months' follow-up. Quantitative assessment of regional systolic function might be more sensitive than global LV ejection fraction for the evaluation of BMPC therapy after STEMI.

Aims: Both contrast enhanced (CE) two-dimensional echocardiography (2DE) and three-dimensional echocardiography (3DE) have been proposed as techniques to improve the accuracy of left ventricular (LV) volume measurements. We sought to examine the accuracy of non-contrast (NC) and CE-2DE and 3DE for calculation of LV volumes and ejection fraction (EF), relative to cardiac magnetic resonance imaging (MRI)., Methods and Results: We studied 50 patients (46 men, age 63 +/- 10 year) with past myocardial infarction who underwent echocardiographic assessment of LV volume and function. All patients sequentially underwent NC-2DE followed by NC-3DE. CE-2DE and CE-3DE were acquired during contrast infusion. Resting echocardiographic image quality was evaluated on the basis of NC-2DE. The mean LV end-diastolic volume (LVEDV) of the group by MRI was 207 +/- 79 mL and was underestimated by 2DE (125 +/- 54 mL, P = 0.005), and less by CE-2DE (172 +/- 58 mL, P = 0.02) or 3DE (177 +/- 64 mL, P = 0.08), but EDV was comparable by CE-3DE (196 +/- 69 mL, P = 0.16). Limits of agreement with MRI were similar for NC-3DE and CE-2DE, with the best results for CE-3D. Results were similar for calculation of LVESV. Patients were categorized into groups of EF (< or =35, 35-50, >50%) by MRI. NC-2DE demonstrated a 68% agreement (kappa 0.45, P = 0.001), CE-2DE a 62% agreement (kappa 0.20, P = 136), NC-3DE a 74% agreement (kappa 0.39, P = 0.005) and CE-3DE an 80% agreement (kappa 0.56, P < 0.001)., Conclusion: CE-2DE is analogous to NC-3DE in accurate categorization of LV function. However, CE-3DE is feasible and superior to other NC- and CE-techniques in patients with previous infarction.

Aims: To assess the relationship between left atrial (LA) size and outcome after high-risk myocardial infarction (MI) and to study dynamic changes in LA size during long-term follow-up., Methods and Results: The VALIANT Echocardiography study prospectively enrolled 610 patients with left ventricular (LV) dysfunction, heart failure (HF), or both following MI. We assessed LA volume indexed to body surface area (LAVi) at baseline, 1 month, and 20 months after MI. Baseline LAVi was an independent predictor of all-cause death or HF hospitalization (P = 0.004). In patients who survived to 20 months, LAVi increased a mean of 3.00 +/- 7.08 mL/m(2) from baseline. Hypertension, lower estimated glomerular filtration rate, and LV mass were the only baseline independent predictors of LA remodelling. Changes in LA size were related to worsening in MR and increasing in LV volumes. LA enlargement during the first month was significantly greater in patients who subsequently died or were hospitalized for HF than in patients without events., Conclusion: Baseline LA size is an independent predictor of death or HF hospitalization following high-risk MI. Moreover, LA remodelling during the first month after infarction is associated with adverse outcome.

Aims: To evaluate the clinical impact of early administration of glycoprotein IIb/IIIa agents (IIb/IIIa agents) in the context of a dedicated hub and spoke network allowing very prompt pharmacological/mechanical interventions., Methods and Results: Using a prospective database, we conducted a cohort study of ST-elevation myocardial infarction (STEMI) patients (n = 1124) undergoing primary percutaneous coronary interventions (PPCIs) and IIb/IIIa agents administration (period, 2003-2006). Comparisons were planned between patients receiving early IIb/IIIa agents administration (in hub/spoke centre emergency departments or during ambulance transfer; early group, n = 380) or delayed administration (in the catheterization laboratory; late group, n = 744). The primary outcome measure was long-term overall mortality/re-infarction. Baseline characteristics of the two groups were largely comparable. Angiographically, early group patients more often achieved pre-PPCI TIMI Grade 2-3 and TIMI Grade 3 flow. Clinically, the early administration group experienced lower 2-year risk of unadjusted mortality/re-infarction (17 vs. 23%; P = 0.01). After adjustment for potential confounders, early administration was associated with favourable outcome in the overall population (HR = 0.71, P = 0.03) and in high-risk subgroups (TIMI risk index >25, HR = 0.64, P = 0.02; Killip class >1, HR = 0.54, P = 0.01)., Conclusion: In patients treated by PPCI within a STEMI network setting, early administration of IIb/IIIa agents may provide long-term clinical benefits. Notably, these results appeared magnified in high-risk patients.

Aims: To review existing evidence on the role of pre-hospital fibrinolysis in patients with ST-elevation myocardial infarction (MI)., Methods and Results: Overview of current guidelines and data from trials and registries on the best perfusion approach for acute MI with ST-elevation. Despite advances in the treatment of ST-elevation MI, the mortality rate before any therapy is administered is high, with half of all fatalities occurring within 2 h of symptom onset. Current treatment options, including the timely use of pre-hospital fibrinolysis, have reduced the overall 1 month mortality. Mortality can be further improved when patient characteristics, risk factors and time delays to treatment are considered., Conclusion: Time factors are essential in the success of fibrinolysis, and subsequent coronary intervention seems beneficial.

Aims: We studied the clinical, demographic, and angiographic factors associated with successful reperfusion and the relationship between angiographic indices and clinical outcomes in a subset of the APEX-AMI trial, which tested the efficacy of pexelizumab in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PCI)., Methods and Results: Among 5745 patients enrolled in the trial, 1018 underwent independent quantitative angiographic evaluation by a core laboratory. Successful epicardial reperfusion was defined as TIMI (thrombolysis in myocardial infarction) flow grade 3 or corrected TIMI frame count (cTFC) <28 frames, and successful myocardial reperfusion as TIMI myocardial perfusion grade (TMPG) 2 or 3. TIMI 3 flow after PCI occurred in 85%, cTFC < 28 in 58% (mean cTFC was 27 +/- 20), and TMPG 2 or 3 in 91%. Overall 90 day clinical outcomes were 2.7% for mortality and 8.2% for the composite of death, congestive heart failure (CHF), or shock. After adjustment for baseline characteristics, TMPG 2/3 after PCI was associated with younger age [odds ratio (OR) for 10 year increase 0.75, 95% confidence interval (CI) 0.59-0.96, P = 0.023], pre-PCI TIMI flow 2/3 (OR 3.5, 95% CI 1.7-7.1, P = 0.001), and ischaemic time [for every hour, OR 0.81 (0.69-0.96), P = 0.015]. TMPG 2/3 after PCI was significantly associated with 90 day mortality (adjusted hazard ratio 0.26, 95% CI 0.09-0.78, P = 0.013). Neither post-PCI TMPG nor TIMI flow grade was significantly associated with 90 day death/CHF/shock., Conclusion: Younger age, patent infarct-related artery at presentation, and ischaemic time predicted higher likelihood of successful myocardial perfusion, which was associated with improved survival.

Aims: To investigate the association between neutrophil count, outcomes, and benefit of clopidogrel therapy in ST-elevation myocardial infarction (STEMI)., Methods and Results: Baseline neutrophil count was measured in 2865 patients in CLARITY-TIMI 28, a randomized trial of clopidogrel vs. placebo in STEMI patients undergoing fibrinolysis. Angiography was performed at 2-8 days following enrollment. Analyses were adjusted for demographics, time from symptom onset, Killip class, peak CK-MB, and therapies received. A baseline neutrophil count in the highest quartile was independently associated with the risk of cardiovascular (CV) death [adj (adjusted) OR (odds ratio) 5.8, P < 0.001] and congestive heart failure (adj OR 3.0, P = 0.009) at 30 days. Patients with higher neutrophil counts were less likely to achieve complete ST-segment resolution (adj OR 0.76, P = 0.03) or TIMI myocardial perfusion grade 2/3 (adj OR 0.71, P = 0.017). Clopidogrel had a lesser effect on reducing the odds of a closed infarct-related artery, or death or MI before angiography, in patients with a neutrophil count above the median (adjusted OR 0.83, 0.61-1.13) vs. in those below the median (adjusted OR 0.46, 0.33-0.64) (Pinteraction = 0.008)., Conclusion: In patients with STEMI, higher baseline neutrophil count is associated with worse angiographic findings and increased CV mortality, as well as a diminished benefit of clopidogrel.

Acute myocardial infarction (AMI) continues to be a significant public health problem in industrialized countries and an increasingly significant problem in developing countries. ST elevation myocardial infarctions (STEMI) constitute approximately 40% of all AMIs with approximately 670,000 cases yearly in the United States alone. The risk of further cardiac complications such as re-infarction, sudden death, and heart failure for those who survive AMI is substantial. Thus, early assessment and risk stratification during the acute phase of STEMI is important. Furthermore, it is essential to assess the efficacy early after any initial therapeutic intervention, not only to facilitate further management, but also to enable development of new treatment algorithms/approaches to further improve the outcome. The aim of reperfusion therapy in AMI is not only to rapidly restore epicardial coronary blood flow but also to restore perfusion at the microcirculatory level. Myocardial contrast echocardiography (MCE) which utilizes microbubbles can assess myocardial perfusion in real time. Its ability to assess myocardial perfusion and function in one examination allows it to ascertain the extent of myocardial reperfusion achieved in the risk area. Furthermore, in stable patients after AMI, MCE allows assessment of LV function, residual myocardial viability, and ischaemia which are all powerful prognostic markers of outcome. Its portability, rapid acquisition and interpretation of data, and the absence of radiation exposure make it an ideal bedside technique.

Mortality rates due to coronary artery disease (CAD) have declined in recent years as result of improved prevention, diagnosis, and management. Nonetheless, CAD remains the leading cause of death worldwide with most casualties expected to occur in developing nations. Myocardial perfusion scintigraphy (MPS) provides a highly cost-effective tool for the early detection of obstructive CAD in symptomatic individuals and contributes substantially to stratification of patients according to their risk of cardiac death or nonfatal myocardial infarction. MPS also provides valuable information that assists clinical decision-making with regard to medical treatment and intervention. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.

Aims: Although impaired renal function is associated with adverse cardiovascular outcomes, it is unknown whether this association exists in young, healthy adults with normal or mildly impaired renal dysfunction. METHODS AND RESULTS We calculated the baseline creatinine clearance of young males without antecedent diabetes mellitus, coronary artery disease (CAD), or renal dysfunction, and examined their subsequent diagnosis of CAD, defined as coronary artery diameter stenosis of at least 50% and/or myocardial infarction. The 23 964 males, 32.5 +/- 5.9 years old, had a baseline estimated creatinine clearance of 107.9 +/- 0.6 mL min(-1) per 1.73 m(2) (60-150 mL min(-1) per 1.73 m(2)). During a mean follow-up of 3.5 +/- 1.9 years, 77 subjects were diagnosed with CAD. After age adjustment, there was a progressive increase in the risk for CAD as the estimated creatinine clearance decreased [hazard ratio (HR) 4.77, 95% confidence interval 3.22-7.06, P < 0.001 for comparison between the fifth and first quintiles]. This association also persisted after further adjustments for conventional and ancillary risk factors for CAD (HR 2.10, 95% confidence interval 1.40-3.14, P < 0.001). Conclusion Reduced renal function in the normal to mildly impaired range is independently associated with increased risk for CAD among young, healthy males.

Aims: In this study, we investigated the relationship between longitudinal morphology reconstructed from pre-intervention intravascular ultrasound (IVUS) images and thrombolysis in myocardial infarction (TIMI) flow grade at initial angiograms in the acute phase of acute coronary syndrome (ACS)., Methods and Results: Our patient population comprised 72 ACS patients in whom we obtained successful reconstructed longitudinal images. On the basis of the site of the maximum aperture of rupture in the longitudinally reconstructed IVUS images, patients were divided into three groups: plaques with rupture in the proximal shoulder (proximal type; n = 28), mid-portion (mid-type; n = 18), and distal shoulder (distal type; n = 26) of the plaque. There were no differences in terms of coronary risk factors or the angiographic findings. The proximal-type group more frequently showed TIMI 0 on initial angiogram (proximal type, 86%; mid-type, 50%; and distal type, 31%; P = 0.002). A multivariable logistic regression model revealed that the presence of a proximal-type rupture correlated with the presentation of ST-elevation myocardial infarction (P = 0.019; odds ratio, 8.12; 95% CI, 1.404-49.996)., Conclusions: Longitudinal morphological features in a ruptured plaque may affect the formation of obstructive thrombus in ACS. Our results suggest that longitudinal morphology may be an important determinant of coronary artery occlusion.

Aims: Mono-[(123)I]iodohypericin ([(123)I]MIH) has been reported to have high avidity for necrosis. In the present study, by using rabbit models of acute myocardial infarction, we explored the suitability of [(123)I]MIH micro single photon emission computed tomography (microSPECT) for non-invasive visualization of myocardial infarcts in comparison with [(13)N]ammonia micro positron emission tomography (microPET) imaging, postmortem histomorphometry, and [(123)I]MIH autoradiography., Methods and Results: Fourteen rabbits were divided into four groups. The left circumflex coronary artery was permanently occluded in group A (n = 3), reperfused by releasing the ligature after 15 min in group B (n = 3) or 90 min in group C (n = 6), or not occluded in group D (n = 2). Animals received [(13)N]ammonia microPET perfusion imaging 18 h after infarct induction followed by microSPECT imaging at 2-3.5, 9-11, and 22-24 h post injection (p.i.) of [(123)I]MIH. The cardiac images were assembled into polar maps for assessment of tracer uptake. Animals were sacrificed and the excised heart was sliced for autoradiography, triphenyl tetrazolium chloride, and haematoxylin-eosin staining. Using [(123)I]MIH microSPECT, infarcts were well delineated at 9 h p.i. Mean microSPECT infarct size was 38.8 and 32.7% of left ventricular area for groups A and C, respectively, whereas group B showed low uptake of [(123)I]MIH. Highest mean infarct/viable tissue activity ratio of 61/1 was obtained by autoradiography in group C animals at 24 h p.i., Conclusion: The study indicates the suitability of [(123)I]MIH for in vivo visualization of myocardial infarcts.

Aims: This study was designed to assess whether intracoronary application of adipose tissue-derived stem cells (ADSCs) compared with bone marrow-derived stem cells (BMSCs) and control could improve cardiac function after 30 days in a porcine acute myocardial infarction/reperfusion model., Methods and Results: An acute transmural porcine myocardial infarction was induced by inflating an angioplasty balloon for 180 min in the mid-left anterior descending artery. Two million cultured autologous stem cells were intracoronary injected through the central lumen of the inflated balloon catheter. Analysis of scintigraphic data obtained after 28 +/- 3 days showed that both absolute and relative perfusion defect decreased significantly after intracoronary administration of ADSCs or BMSCs (relative 30 or 31%, respectively), compared with carrier administration alone (12%, P = 0.048). Left ventricular ejection fraction after 4 weeks increased significantly more after ADSC and BMSC administration than after carrier administration: 11.39 +/- 4.62 and 9.59 +/- 7.95%, respectively vs. 1.95 +/- 4.7%, P = 0.02). The relative thickness of the ventricular wall in the infarction area after cell administration was significantly greater than that after carrier administration. The vascular density of the border zone also improved. The grafted cells co-localized with von Willebrand factor and alpha-smooth muscle actin and incorporated into newly formed vessels., Conclusion: This is the first study to show that not only bone marrow-derived cells but also ADSCs engrafted in the infarct region 4 weeks after intracoronary cell transplantation and improved cardiac function and perfusion via angiogenesis.

Aims: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk., Methods and Results: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA., Conclusion: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.

Aim: Late-acquired incomplete stent apposition (ISA) has been documented after drug-eluting stent (DES) implantation; however, its clinical role remains controversial. We sought to investigate the incidence and long-term clinical consequences of late ISA after implantation of sirolimus- (SES) or paclitaxel-eluting stent (PES) in a non-selected population., Methods and Results: From our database, we analysed 195 consecutive patients who underwent DES placement (175 with SES and 20 with PES) into native artery lesions and had serial intravascular ultrasound studies (IVUS) performed at index procedure and after 6-8 months. They were clinically followed for 29 +/- 15 months (median of 24.3 months, interquartile range 18.1-31.6 months). Late ISA was defined as separation of at least one stent strut from the vessel wall in a segment without a side-branch and where the immediate post-implantation IVUS revealed complete apposition of stent struts. We identified 10 patients (5.1%) with late ISA, three patients after PES, and seven patients after SES implantation. ISA was localized almost exclusively at body of the stents (nine out of 10 cases). Mean ISA volume and length were 44.5 +/- 41.9 mm(3) and 7.4 +/- 11 mm, respectively. There was a marked increase in vessel volume from 416.0 +/- 163.9 mm(3) at baseline to 514.4 +/- 247.9 mm(3) at follow-up (P = 0.001) with no significant change in plaque volume (232.4 +/- 52.7 at baseline and 226.4 +/- 22.3 mm(3) at follow-up, P = 0.3) in patients who presented with late-acquired ISA. During the follow-up period, one patient with SES and one patient with PES who presented late-acquired ISA had late stent thrombosis and acute myocardial infarction., Conclusion: Late-acquired ISA was observed in 5.1% of patients after DES implantation and is related to regional vessel positive remodelling. The relationship between late-acquired ISA and long-term adverse outcomes (e.g. stent thrombosis) requires further analysis.

Aims: Experimental and clinical pilot studies suggest that intracoronary progenitor cell infusion can improve left ventricular function and remodelling after acute myocardial infarction (AMI). Since progenitor cells are also known to be involved in restenosis development and atherosclerosis progression, an increased restenosis rate may be a risk of intracoronary cell therapy., Methods: We performed a retrospective study to compare quantitative angiographic measurements of the infarct target vessel in 83 patients with AMI treated with bare metal stent PCI (matched control) and in 83 patients receiving additional intracoronary progenitor cell infusion at a mean of 5 days post-AMI stent PCI and after 4 months., Results: The late loss as a measure of neointima formation was similar between the control and the cell-treated group at follow-up (0.9+/-0.8 vs. 0.9+/-0.7 mm, P=0.9). Moreover, restenosis rate was comparable in both groups (35% control vs. 27% cell-treated group, P=0.2). Multivariable analysis excluded cell therapy as an independent significant predictor of increased late loss (P=0.4), whereas acute gain (P=0.012) and diabetes mellitus (P=0.002) were independent predictors of late loss. Finally, in the cell-treated group, target vessel revascularization rate remained at 28.9% during a median of >3 years of follow-up, thus excluding an effect on atherosclerotic disease progression., Conclusion: In patients with AMI successfully treated with bare metal stent PCI, additional intracoronary progenitor cell infusion does not lead to an increased neointima formation within the implanted stent within 4 months or aggravation of atherosclerotic disease progression.

Aims: Normal exercise echocardiography predicts a good prognosis. Dobutamine stress echocardiography (DSE) is generally reserved for patients with comorbidities which preclude exercise testing. We evaluated predictors of adverse events after normal DSE., Methods and Results: We studied 3014 patients (1200 males, 68+/-12 years) with normal DSE, defined as the absence of wall motion abnormality at rest or with stress. During median follow-up of 6.3 years, all-cause mortality and cardiac events, defined as myocardial infarction and coronary revascularization, occurred in 920 (31%) and 231 (7.7%) patients, respectively. Survival and cardiac event-free probabilities were 95 and 98% at 1 year, 78 and 93% at 5 years, and 56 and 89% at 10 years, respectively. Age, diabetes mellitus, and failure to achieve 85% age-predicted maximal heart rate were independent predictors of mortality and cardiac events. Patients with all three of these characteristics had a 13% probability of cardiac events within the first year and higher risk throughout follow-up., Conclusion: Prognosis after normal DSE is not necessarily benign, but depends on patient and stress test characteristics. Careful evaluation, using clinical and stress data, is required to identify patients with normal DSE who are at increased risk of adverse outcomes during long-term follow-up.