Pre-screening to guide coronary artery calcium scoring for early identification of high-risk individuals in the general population.

AIMS: To evaluate the ability of Systematic COronary Risk Estimation 2 (SCORE2) and other pre-screening methods to identify individuals with high coronary artery calcium score (CACS) in the general population. METHODS AND RESULTS: Computed tomography-based CACS quantification was performed in 6530 individuals aged 45 years or older from the general population. Various pre-screening methods to guide referral for CACS were evaluated. Miss rates for high CACS (CACS ≥300 and ≥100) were evaluated for various pre-screening methods: moderate (≥5%) and high (≥10%) SCORE2 risk, any traditional coronary artery disease (CAD) risk factor, any Risk Or Benefit IN Screening for CArdiovascular Disease (ROBINSCA) risk factor, and moderately (>3 mg/24 h) increased urine albumin excretion (UAE). Out of 6530 participants, 643 (9.8%) had CACS ≥300 and 1236 (18.9%) had CACS ≥100. For CACS ≥300 and CACS ≥100, miss rate was 32 and 41% for pre-screening by moderate (≥5%) SCORE2 risk and 81 and 87% for high (≥10%) SCORE2 risk, respectively. For CACS ≥300 and CACS ≥100, miss rate was 8 and 11% for pre-screening by at least one CAD risk factor, 24 and 25% for at least one ROBINSCA risk factor, and 67 and 67% for moderately increased UAE, respectively. CONCLUSION: Many individuals with high CACS in the general population are left unidentified when only performing CACS in case of at least moderate (≥5%) SCORE2, which closely resembles current clinical practice. Less stringent pre-screening by presence of at least one CAD risk factor to guide CACS identifies more individuals with high CACS and could improve CAD prevention.

Multi-Modality Imaging for Prevention of Coronary Artery Disease and Myocardial Infarction in the General Population: Ready for Prime Time?

Cardiovascular disease (CVD) remains a leading cause of death and disability worldwide. Acute myocardial infarction (AMI) causes irreversible myocardial damage, heart failure, life-threatening arrythmias and sudden cardiac death (SCD), and is a main driver of CVD mortality and morbidity. To control the forecasted increase in CVD burden for both the individual and society, improved strategies for the prevention of AMI and SCD are required. Current prevention of AMI and SCD is directed towards risk-modifying interventions, guided by risk assessment using clinical risk prediction scores (CRPSs) and the coronary artery calcium score (CACS). Early detection of more advanced coronary artery disease (CAD), beyond risk assessment by CRPSs or CACS, is a promising strategy to allow personalized treatment for the improved prevention of AMI and SCD in the general population. We review evidence for further testing, beyond CRPSs and CACS, and therapies focusing on promising targets, including subclinical obstructive CAD, high-risk plaques, and silent myocardial ischemia. We also evaluate the potential of multi-modality imaging to enhance the conduction of adequately powered trials to provide high-quality evidence on the impact of add-on tests and therapies in the prevention of AMI and SCD in asymptomatic individuals. To conclude, we discuss the occurrence of AMI and SCD in individuals currently estimated to be at "low-risk" by the current strategy based on CRPSs, and methods to improve prevention of AMI and SCD in this "low-risk" population.

Association of epicardial adipose tissue with different stages of coronary artery disease: A cross-sectional UK Biobank cardiovascular magnetic resonance imaging substudy.

Objective: Increased epicardial adipose tissue (EAT) has been identified as a risk factor for the development of coronary artery disease (CAD). However, the exact role of EAT in the development of CAD is unclear. This study aims to compare EAT volumes between healthy controls and individuals with stable CAD and a history of myocardial infarction (MI). Furthermore, associations between clinical and biochemical parameters with EAT volumes are examined. Methods: This retrospective cross-sectional study included 171 participants from the United Kingdom Biobank (56 healthy controls; 60 stable CAD; 55 post MI), whom were balanced for age, sex and body mass index (BMI). EAT volumes were quantified on end-diastolic cardiac magnetic resonance (CMR) imaging short-axis slices along the left and right ventricle and indexed for body surface area (iEAT) and iEAT volumes were compared between groups. Results: iEAT volumes were comparable between control, CAD and MI cases (median [IQR]: 66.1[54.4-77.0] vs. 70.9[55.8-85.5] vs. 67.6[58.6-82.3] mL/m2, respectively (p > 0.005 for all). Increased HDL-cholesterol was associated with decreased iEAT volume (ß = -14.8, CI = -24.6 to -4.97, p = 0.003) and suggestive associations (P-value < 0.05 and ≥ 0.005) were observed between iEAT and triglycerides (ß = 3.26, CI = 0.42 to 6.09, p = 0.02), Apo-lipoprotein A (ß = -16.3, CI = -30.3 to -2.24, p = 0.02) and LDL-cholesterol (ß = 3.99, CI = -7.15 to -0.84, p = 0.01). Conclusions: No significant differences in iEAT volumes were observed between patients with CAD, MI and healthy controls. Our results indicate the importance of correcting for confounding by CVD risk factors, including circulating lipid levels, when studying the relationship between EAT volume and CAD. Further mechanistic studies on causal pathways and the role of EAT composition are warranted.

Early detection of obstructive coronary artery disease in the asymptomatic high-risk population: objectives and study design of the EARLY-SYNERGY trial.

BACKGROUND: Coronary artery disease (CAD) burden for society is expected to steeply increase over the next decade. Improved feasibility and efficiency of preventive strategies is necessary to flatten the curve. Acute myocardial infarction (AMI) is the main determinant of CAD-related mortality and morbidity, and predominantly occurs in individuals with more advanced stages of CAD causing subclinical myocardial ischemia (obstructive CAD; OCAD). Unfortunately, OCAD can remain subclinical until its destructive presentation with AMI or sudden death. Current primary preventive strategies are not designed to differentiate between non-OCAD and OCAD and the opportunity is missed to treat individuals with OCAD more aggressively. METHODS: EARLY-SYNERGY is a multicenter, randomized-controlled clinical trial in individuals with coronary artery calcium (CAC) presence to study (1.) the yield of cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) for early OCAD diagnosis and (2) whether early OCAD diagnosis improves outcomes. Individuals with CAC score ≥300 objectified in 2 population-based trials (ROBINSCA; ImaLife) are recruited for study participation. Eligible candidates are randomized 1:1 to cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) or no additional functional imaging. In the CMR-MPI arm, feedback on imaging results is provided to primary care provider and participant in case of guideline-based actionable findings. Participants are followed-up for clinical events, healthcare utilization and quality of life. CONCLUSIONS: EARLY-SYNERGY is the first randomized-controlled clinical trial designed to test the hypothesis that subclinical OCAD is widely present in the general at-risk population and that early differentiation of OCAD from non-OCAD followed by guideline-recommended treatment improves outcomes.

The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction.

Heart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 ± 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07-19.31, p = 0.001 and 1.68 (1.03-2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5-18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk.

Computational quantitative flow ratio to assess functional severity of coronary artery stenosis.

Background Computational quantitative flow ratio (QFR) based on 3-dimensional quantitative coronary angiography (3D QCA) analysis offers the opportunity to assess the significance of coronary artery disease (CAD) without using an invasive pressure wire or inducing hyperemia. This study aimed to evaluate the diagnostic performance of QFR compared to wire-based fractional flow reserve (FFR) and to validate the previously reported QFR cut-off value of >0.90 to safely rule out functionally significant CAD. Methods QFR was retrospectively derived from standard-care coronary angiograms. Correlation and agreement of fixed-flow QFR (fQFR) and contrast-flow QFR (cQFR) models with invasive wire-based FFR was calculated. Diagnostic performance of QFR was evaluated at different QFR cut-off values defining significant CAD (FFR ≤ 0.80). Results 101 vessels in 96 patients who underwent FFR were studied. Mean FFR was 0.87 ±â€¯0.08 and 21 of 101 (21%) vessels had an FFR ≤ 0.80. Correlation of fQFR and cQFR with FFR was r = 0.71 (p < 0.001) and r = 0.70 (p < 0.001), respectively. Sensitivity and specificity were 57% and 93% for fQFR and 67% and 96% for cQFR at a QFR cut-off value >0.80 defining non-significant CAD, respectively. fQFR > 0.90 was present in 34 (34%) and cQFR > 0.90 in 39 (39%) vessels. For both QFR models, none of the vessels with QFR > 0.90 had an FFR ≤ 0.80. Conclusions QFR appears to be a safe and effective gatekeeper to wire-based FFR when applying a QFR threshold of >0.90 to rule out significant CAD. Further prospective research is required to establish QFR in the real-life setting of functional CAD assessment in the catheterization laboratory.

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Computed tomography coronary angiography in patients with acute myocardial infarction and normal invasive coronary angiography.

BACKGROUND: Three to five percent of patients with acute myocardial infarction (AMI) have normal coronary arteries on invasive coronary angiography (ICA). The aim of this study was to assess the presence and characteristics of atherosclerotic plaques on computed tomography coronary angiography (CTCA) and describe the clinical characteristics of this group of patients. METHODS: This was a multicentre, prospective, descriptive study on CTCA evaluation in thirty patients fulfilling criteria for AMI and without visible coronary plaques on ICA. CTCA evaluation was performed head to head in consensus by two experienced observers blinded to baseline patient characteristics and ICA results. Analysis of plaque characteristics and plaque effect on the arterial lumen was performed. Coronary segments were visually scored for the presence of plaque. Seventeen segments were differentiated, according to a modified American Heart Association classification. Echocardiography performed according to routine during the initial hospitalisation was retrieved for analysis of wall motion abnormalities and left ventricular systolic function in most patients. RESULTS: Twenty-five patients presented with non ST-elevation myocardial infarction (NSTEMI) and five with ST-elevation myocardial infarction (STEMI). Mean age was 60.2 years and 23/30 were women. The prevalence of risk factors of coronary artery disease (CAD) was low. In total, 452 coronary segments were analysed. Eighty percent (24/30) had completely normal coronary arteries and twenty percent (6/30) had coronary atherosclerosis on CTCA. In patients with atherosclerotic plaques, the median number of segments with plaque per patient was one. Echocardiography was normal in 4/22 patients based on normal global longitudinal strain (GLS) and normal wall motion score index (WMSI); 4/22 patients had normal GLS with pathological WMSI; 3/22 patients had pathological GLS and normal WMSI; 11/22 patients had pathological GLS and WMSI and among them we could identify 5 patients with a Takotsubo pattern on echo. CONCLUSIONS: Despite a diagnosis of AMI, 80 % of patients with normal ICA showed no coronary plaques on CTCA. The remaining 20 % had only minimal non-obstructive atherosclerosis. Patients fulfilling clinical criteria for AMI but with completely normal ICA need further evaluation, suggestively with magnetic resonance imaging (MRI).

Hemodynamic significance of coronary stenosis by vessel attenuation measurement on CT compared with adenosine perfusion MRI.

PURPOSE: We assessed the association between corrected contrast opacification (CCO) based on coronary computed tomography angiography (cCTA) and inducible ischemia by adenosine perfusion magnetic resonance imaging (APMR). METHODS: Sixty cardiac asymptomatic patients with extra-cardiac arterial disease (mean age 64.4 ± 7.7 years; 78% male) underwent cCTA and APMR. Luminal CT attenuation values (Hounsfield Units) were measured in coronary arteries from proximal to distal, with additional measurements across sites with >50% lumen stenosis. CCO was calculated by dividing coronary CT attenuation by descending aorta CT attenuation. A reversible perfusion defect on APMR was considered as myocardial ischemia. RESULTS: In total, 169 coronary stenoses were found. Seven patients had 8 perfusion defects on APMR, with 11 stenoses in corresponding vessels. CCO decrease across stenoses with hemodynamic significance was 0.144 ± 0.112 compared to 0.047 ± 0.104 across stenoses without hemodynamic significance (P=0.003). CCO decrease in lesions with and without anatomical stenosis was similar (0.054 ± 0.116 versus 0.052 ± 0.101; P=0.89). Using 0.20 as preliminary CCO decrease cut-off, hemodynamic significance would be excluded in 82.9% of anatomical stenoses. CONCLUSIONS: CCO decrease across coronary stenosis is associated with myocardial ischemia on APMR. CCO based on common cCTA data is a novel method to assess hemodynamic significance of anatomical stenosis.

Neutrophil/Lymphocyte ratio is associated with non-calcified plaque burden in patients with coronary artery disease.

BACKGROUND: Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potential marker of both CAD severity and cardiovascular prognosis. OBJECTIVES: The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD. METHODS: Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls. RESULTS: Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09-0.44) vs 0.11(0.00-0.25), p<0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden. CONCLUSIONS: Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.

Time of symptom onset and value of myocardial blush and infarct size on prognosis in patients with ST-elevation myocardial infarction.

In patients with ST-segment elevation myocardial infarction (STEMI), the time of onset of ischemia has been associated with myocardial infarction (MI) size. Myocardial blush grade (MBG) reflects myocardial response to ischemia/reperfusion injury, which may differ according to time of the day. The aim of our study was to explore the 24-hour variation in MBG and MI size in relation to outcomes in STEMI patients. A retrospective multicenter analysis of 6970 STEMI patients was performed. Time of onset of STEMI was divided into four 6-hour periods. STEMI patients have a significant 24-hour pattern in onset of symptoms, with peak onset around 09:00 hour. Ischemic time was longest and MI size, estimated by peak creatine kinase concentration, was largest in patients with STEMI onset between 00:00 and 06:00 hours. Both MBG and MI size were independently associated with mortality. Time of onset of STEMI was not independently associated with mortality when corrected for baseline and procedural factors. Interestingly, patients presenting with low MBG between 00:00 and 06:00 hours had a better prognosis compared to other groups. In conclusion, patients with symptom onset between 00:00 and 06:00 hours have longer ischemic time and consequently larger MI size. However, this does not translate into a higher mortality in this group. In addition, patients with failed reperfusion presenting in the early morning hours have better prognosis, suggesting a 24-hour pattern in myocardial protection.

Comparison of the relation between the calcium score and plaque characteristics in patients with acute coronary syndrome versus patients with stable coronary artery disease, assessed by computed tomography angiography and virtual histology intravascular ultrasound.

A considerable number of patients with an acute coronary syndrome (ACS) who present with a 0 or low calcium score (CS) still demonstrate coronary artery disease (CAD) and significant stenosis. The aim of the present study was to evaluate the relation between the CS and the degree and character of atherosclerosis in patients with suspected ACS versus patients with stable CAD obtained by computed tomography angiography and virtual histology intravascular ultrasound (VH IVUS). Overall 112 patients were studied, 53 with ACS and 59 with stable CAD. Calcium scoring and computed tomography angiography were performed and followed by VH IVUS. On computed tomography angiography each segment was evaluated for plaque and classified as noncalcified, mixed, or calcified. Vulnerable plaque characteristics on VH IVUS were defined by percent necrotic core and presence of thin-cap fibroatheroma. If the CS was 0, patients with ACS had a higher mean number of plaques (5.0 ± 2.0 vs 2.0 ± 1.9, p <0.05) and noncalcified plaques (4.6 ± 3.5 vs 1.3 ± 1.9, p <0.05) on computed tomography angiography than those with stable CAD. If the CS was 0, VH IVUS demonstrated that patients with ACS had a larger amount of necrotic core area (0.58 ± 0.73 vs 0.22 ± 0.43 mm(2), p <0.05) and a higher mean number of thin-cap fibroatheromas (0.6 ± 0.7 vs 0.1 ± 0.3, p <0.05) than patients with stable CAD. In conclusion, even in the presence of a 0 CS, patients with ACS have increased plaque burden and increased vulnerability compared to patients with stable CAD. Therefore, absence of coronary calcification does not exclude the presence of clinically relevant and potentially vulnerable atherosclerotic plaque burden in patients with ACS.

Diagnostic performance of non-invasive multidetector computed tomography coronary angiography to detect coronary artery disease using different endpoints: detection of significant stenosis vs. detection of atherosclerosis.

AIMS: The positive predictive value of multidetector computed tomography angiography (CTA) for detecting significant stenosis remains limited. Possibly CTA may be more accurate in the evaluation of atherosclerosis rather than in the evaluation of stenosis severity. However, a comprehensive assessment of the diagnostic performance of CTA in comparison with both conventional coronary angiography (CCA) and intravascular ultrasound (IVUS) is lacking. Therefore, the aim of the study was to systematically investigate the diagnostic performance of CTA for two endpoints, namely detecting significant stenosis (using CCA as the reference standard) vs. detecting the presence of atherosclerosis (using IVUS as the reference of standard). METHODS AND RESULTS: A total of 100 patients underwent CTA followed by both CCA and IVUS. Only those segments in which IVUS imaging was performed were included for CTA and quantitative coronary angiography (QCA) analysis. On CTA, each segment was evaluated for significant stenosis (defined as ≥ 50% luminal narrowing), on CCA significant stenosis was defined as a stenosis ≥ 50%. Second, on CTA, each segment was evaluated for atherosclerotic plaque; atherosclerosis on IVUS was defined as a plaque burden of ≥ 40% cross-sectional area. CTA correctly ruled out significant stenosis in 53 of 53 (100%) patients. However, nine patients (19%) were incorrectly diagnosed as having significant lesions on CTA resulting in sensitivity, specificity, positive, and negative predictive values of 100, 85, 81, and 100%. CTA correctly ruled out the presence of atherosclerosis in 7 patients (100%) and correctly identified the presence of atherosclerosis in 93 patients (100%). No patients were incorrectly classified, resulting in sensitivity, specificity, positive, and negative predictive values of 100%. Conclusions The present study is the first to confirm using both CCA and IVUS that the diagnostic performance of CTA is superior in the evaluation of the presence or the absence of atherosclerosis when compared with the evaluation of significant stenosis.

Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.

BACKGROUND: administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. METHODS AND RESULTS: a total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (P=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P=0.786). CONCLUSIONS: in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size.

Assessment with multi-slice computed tomography and gray-scale and virtual histology intravascular ultrasound of gender-specific differences in extent and composition of coronary atherosclerotic plaques in relation to age.

Data evaluating gender- and age-specific differences in plaque observations on multislice computed tomography (MSCT) are scarce. Accordingly, the aim of this study was to evaluate coronary plaque patterns in men and women in relation to age using MSCT. The findings were compared to observations on grayscale intravascular ultrasound (IVUS) and virtual histology (VH) IVUS. In total, 93 patients (59 men, 34 women) underwent 64-slice MSCT followed by conventional coronary angiography with IVUS. Plaque extent and composition were assessed on MSCT, grayscale IVUS, and VH IVUS. Coronary plaque patterns were compared between men and women in 2 age groups (<65 and >or=65 years old). In patients aged <65 years, more plaques were observed on MSCT in men (6 +/- 4 vs 2 +/- 2 in women, p <0.001). Also, a larger plaque burden was observed on grayscale IVUS in men (45.7 +/- 11.4% vs 36.3 +/- 11.6% in women, p <0.001). Similarly, more mixed plaques were observed in men (3 +/- 3 vs 1 +/- 1 in women, p = 0.003), whereas a larger arc of calcium was detected on grayscale IVUS in men (91.7 +/- 93.5 degrees vs 25.7 +/- 51.0 degrees in women, p <0.001). On VH IVUS, the prevalence of thin-cap fibroatheroma was higher in men (31% vs 0%) compared to women. In patients aged >or=65 years old, no important differences in plaque patterns were observed between men and women. In conclusion, more extensive atherosclerosis and more calcified lesions were observed in men than in women. These differences were predominantly present in patients aged <65 years and were lost in those aged >or=65 years.

Comparison of non-invasive multi-slice computed tomography coronary angiography versus invasive coronary angiography and fractional flow reserve for the evaluation of men with known coronary artery disease.

Multislice computed tomographic coronary angiography (MSCT) can accurately detect the presence of atherosclerosis noninvasively. However, a discrepancy has been observed between MSCT and noninvasive functional imaging. The purpose of the present study was to evaluate the correlation between MSCT and invasive fractional flow reserve (FFR) in men with known coronary artery disease. Thirty-three patients (mean age 57 +/- 11 years) clinically referred for coronary angiography underwent MSCT and FFR analysis. Coronary angiography and MSCT were evaluated for nonsignificant (30% to 50% luminal narrowing) and significant (>50% luminal narrowing) stenosis. Abnormal FFR was defined as < or =0.75. A total of 36 vessels were evaluated for FFR, with 8 (22%) showing reduced FFR. Results on MSCT were normal (completely normal or <30% luminal narrowing in 11 vessesl [31%], nonsignificant lesions in 13 vessels [36%], and significant stenoses in 12 vessels [33%]). Abnormal FFR was observed in only 58% of vessels with lesions >50% on MSCT. Nevertheless, the agreement between normal results on MSCT and normal FFR was excellent; FFR was normal in all 11 vessels with normal results on MSCT. In conclusion, significant stenoses on MSCT frequently do not result in reduced FFR. Normal results on MSCT, however, can accurately rule out the presence of hemodynamically significant lesions in men with known coronary artery disease.

Incremental prognostic value of multi-slice computed tomography coronary angiography over coronary artery calcium scoring in patients with suspected coronary artery disease.

AIMS: The purpose of this study was to assess the relationship between calcium scoring (CS) and multi-slice computed tomography coronary angiography (MSCTA) and to determine if MSCTA has an incremental prognostic value to CS. METHODS AND RESULTS: In 432 patients (59% male, age 58 +/- 11 years) referred for cardiac evaluation owing to suspected coronary artery disease (CAD), CS and 64-slice MSCTA were performed. The following events were combined in a composite endpoint: all-cause mortality, non-fatal infarction, and unstable angina requiring revascularization. CS was 0 in 147 (34%) patients, CS 1-99 was present in 122 (28%), CS 100-399 in 75 (17%), CS 400-999 in 56 (13%), and CS > or = 1000 in 32 (7%). MSCTA was normal in 133 (31%) patients, MSCTA 30-50% stenosis was observed in 190 (44%), and MSCTA > or =50% stenosis in 109 (25%). During follow-up [median 670 days (25th-75th percentile: 418-895)], an event occurred in 21 patients (4.9%). After multivariate correction for CS, MSCTA > or = 50% stenosis, the number of diseased segments, obstructive segments, and non-calcified plaques were independent predictors with an incremental prognostic value to CS. CONCLUSION: MSCTA provides additional information to CS regarding stenosis severity and plaque composition. This additional information was shown to translate into incremental prognostic value over CS.