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.

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).

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.

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.

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.

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.

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.

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.

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.

Type 2 diabetes is associated with more advanced coronary atherosclerosis on multislice computed tomography and virtual histology intravascular ultrasound.

BACKGROUND: Data on coronary plaque observations on multi-slice computed tomography (MSCT) in patients with type 2 diabetes are scarce. METHODS AND RESULTS: In total, 60 patients (19 with diabetes) underwent 64-slice MSCT, followed by conventional coronary angiography with intravascular ultrasound (IVUS). Non-invasively, the extent of coronary atherosclerosis and 3 plaque types (non-calcified, calcified, mixed) were visually evaluated on MSCT. Invasively, plaque burden was assessed on gray-scale IVUS. Plaque composition was evaluated on virtual histology intravascular ultrasound (VH IVUS). Concerning geometrical plaque data, diabetic patients showed more plaques on MSCT (7.1 +/- 3.2 vs 4.9 +/- 3.2 in non-diabetic patients, P = .01). On gray-scale IVUS, diabetes was associated with a larger plaque burden (48.7 +/- 10.7% vs 40.0 +/- 12.1%, P = .003). Concerning plaque composition, diabetes was associated with more calcified plaques on MSCT (52% vs 24%). Relatively more fibrocalcific plaques in diabetic patients (29% versus 9%) were observed on VH IVUS. Moreover, these plaques contained more necrotic core (10.8 +/- 5.9% vs 8.6 +/- 5.2%, P = .01). CONCLUSION: A higher plaque extent and more calcified lesions were observed in diabetic patients on MSCT. The findings were confirmed on gray-scale and VH IVUS. Thus, MSCT may potentially be used to explore patterns of coronary atherosclerosis in diabetic patients.

Multi-slice computed tomography coronary angiography for ruling out suspected coronary artery disease: what is the prevalence of a normal study in a general clinical population?

AIMS: To assess the prevalence of a normal multi-slice computed tomography (MSCT) in patients with suspected coronary artery disease (CAD) and to relate these observations to clinical presentation and pre-test likelihood of CAD. METHODS AND RESULTS: In total, 340 consecutive patients (182 men, 55 +/- 12 years) without a history of CAD who were referred for MSCT angiography were included in the study. Based on patient characteristics and the referral reason for MSCT angiography, patients were classified as having a low, intermediate, or high pre-test likelihood of CAD. Patients were evaluated for the presence of coronary artery calcium as well as the presence of atherosclerosis. Overall, 157 (46%) patients did not have coronary artery calcium and 133 (40%) patients had a completely normal MSCT angiogram. In 58% of the patients with low pre-test likelihood, no coronary atherosclerosis was observed when compared with 33 and 17% of the patients with intermediate and high pre-test likelihood, respectively. CONCLUSION: MSCT ruled out coronary atherosclerosis in 40-46% of patients without known CAD who were referred for MSCT. Accordingly, in patients with low-to-intermediate pre-test likelihood, MSCT may be an attractive modality to exclude coronary atherosclerosis and may prevent unnecessary additional functional testing or invasive angiography.

Evaluation of plaque characteristics in acute coronary syndromes: non-invasive assessment with multi-slice computed tomography and invasive evaluation with intravascular ultrasound radiofrequency data analysis.

AIMS: Atherosclerotic plaque characteristics play an important role in the development of coronary events. We investigated coronary plaque characteristics on multi-slice computed tomography (MSCT) and virtual histology intravascular ultrasound (VH IVUS) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). METHODS AND RESULTS: Fifty patients (25 with ACS, 25 with stable CAD) underwent 64-slice MSCT followed by VH IVUS in 48 (96%) patients. In ACS patients, 32% of plaques were non-calcified on MSCT and 59% were mixed [corresponding odds ratio (95% confidence intervals): 3.9 (1.6-9.5), P = 0.003 and 3.4 (1.6-6.9), P = 0.001, respectively]. In patients with stable CAD, completely calcified lesions were more prevalent (61%). On VH IVUS, the percentage of necrotic core was higher in the plaques of ACS patients (11.16 +/- 6.07 vs. 9.08 +/- 4.62% in stable CAD, P = 0.02). In addition, thin cap fibroatheroma was more prevalent in ACS patients (32 vs. 3% in patients with stable CAD, P < 0.001) and was most frequently observed in mixed plaques on MSCT. Plaque composition both on MSCT and VH IVUS was identical between culprit and non-culprit vessels of ACS patients. CONCLUSION: On MSCT, differences in plaque characterization were demonstrated between patients with ACS and stable CAD. Plaques of ACS patients showed features of vulnerability to rupture on VH IVUS. Potentially, MSCT may be useful for non-invasive identification of atherosclerotic plaque patterns associated with higher risk.

Image quality of 16-slice computed tomography coronary angiography in patients with complete left bundle branch block.

OBJECTIVE: Noninvasive diagnosis of coronary artery disease in patients with left bundle branch block is challenging. Multislice computed tomography can be useful in this population; however, quality of images depends on the patterns of myocardial contractions. We investigated the influence of left bundle branch block on image quality of multislice computed tomography coronary angiography. MATERIALS AND METHODS: Multislice computed tomography coronary angiography was performed in 30 patients with left bundle branch block and 30 patients without conduction disturbances. Image quality of each coronary segment was visually assessed and rated on a five-point scale (1=highest quality). RESULTS: Average image quality score in the best cardiac cycle phase did not differ significantly between groups (1.71+/-0.59 in the left bundle branch block group vs. 1.60+/-0.57 in the control group, P=0.46). In the left bundle branch block group, a significantly lower image quality score was observed in end-systolic cardiac phase (2.67+/-0.6 vs. 2.22+/-0.65 in the control group, P=0.007), whereas no difference was demonstrated in mid-diastolic phase (1.73+/-0.6 vs. 1.69+/-0.66 in the control group, P=0.81). After image assessment in multiple cardiac phases, an increase in image quality score was higher in the left bundle branch block than in the control group (0.2+/-0.17 vs. 0.11+/-0.14, P=0.003). A negative correlation was observed between image quality score and both the heart rate and heart rate variability in both groups (P<0.001). CONCLUSION: A nonsignificantly lower overall image quality of multislice computed tomography coronary angiography was demonstrated in the left bundle branch block group. In the presence of left bundle branch block, image quality in the end-systolic phase was significantly lower. Image assessment in multiple phases increased overall image quality and is therefore advisable in patients with left bundle branch block. Increased heart rate and heart rate variability worsened image quality in both groups.

Anatomic correlates of a normal perfusion scan using 64-slice computed tomographic coronary angiography.

Both myocardial perfusion imaging (MPI) and multislice computed tomography (MSCT) are currently used to detect coronary artery disease (CAD). However, MSCT permits early detection of atherosclerosis while myocardial perfusion is still normal. In addition, MPI results can be normal despite the presence of high-risk CAD (left main and balanced 3-vessel CAD). In this study, the range of anatomic findings using MSCT in patients with normal MPI results was evaluated. In 180 patients presenting with chest pain, MPI (with gated single-photon emission computed tomography) and 64-slice MSCT were performed. In patients with normal MPI results, prevalences of completely normal coronary arteries, nonobstructive CAD, and obstructive CAD were determined using MSCT. The occurrence of high-risk CAD, including left main and 3-vessel disease, was also evaluated. Normal MPI and adequate MSCT findings were obtained in 97 patients (54%; 50% women; average age 58 +/- 12 years; 5% with known CAD). A total of 38 patients (39%) showed normal coronary anatomy, whereas nonsignificant and significant CAD were observed in 37 (38%) and 18 patients (19%), respectively. Importantly, only 4 patients (4%) presented with high-risk CAD using 64-slice MSCT, 2 with left main and 2 with 3-vessel disease. In conclusion, a normal MPI result can be associated with a wide range of anatomic observations and cannot exclude the presence of both nonobstructive and obstructive CAD. However, importantly, the prevalence of high-risk CAD was rare.

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.

Impact of coronary calcium score on diagnostic accuracy of multislice computed tomography coronary angiography for detection of coronary artery disease.

BACKGROUND: The impact of the coronary calcium score on the diagnostic accuracy of multislice computed tomography (MSCT) to detect obstructive coronary stenoses remains controversial. METHODS AND RESULTS: We examined 41 patients (mean Agatston score, 340 +/- 530 [range, 0-2546]) with coronary artery disease with 16-slice MSCT and 60 patients (mean Agatston score, 446 +/- 877 [range, 0-6264]) with 64-slice MSCT. MSCT scans were analyzed with invasive coronary angiography (CA) as the standard of reference. Lesions with luminal narrowing of 50% or greater were considered obstructive. In total, 9% and 2% of uninterpretable segments were excluded from analysis in patients examined with 16- and 64-slice MSCT, respectively. On a segment basis, the percentage of false-negative segments in the groups with Agatston scores of 0 to 100, 101 to 400, and greater than 400 with 16-slice MSCT were 0%, 5.3%, and 2.9% (P = .0005), respectively; other comparisons of false-positive and false-negative segments were not significant. The sensitivity and specificity on a vessel and patient basis with 16- and 64-slice MSCT were not significantly different in different calcium score groups. CONCLUSIONS: A slight impact of coronary calcium was observed on the diagnostic accuracy of 16-slice MSCT CA on a segment basis, with no significant impact on a vessel and patient basis. No significant impact of coronary calcium was observed on the diagnostic accuracy of 64-slice MSCT CA on a segment, vessel, or patient basis.

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.

Diagnostic accuracy of 64-slice multislice computed tomography in the noninvasive evaluation of significant coronary artery disease.

The purpose of the present study was to determine the diagnostic accuracy of current 64-slice multislice computed tomography (MSCT) in the detection of significant coronary artery disease, using conventional coronary angiography as the gold standard. In 61 patients scheduled for conventional coronary angiography, 64-slice MSCT was performed and evaluated for the presence of significant (>or=50% luminal narrowing) stenoses. One patient had to be excluded because of a heart rate>90 beats/min during data acquisition. In the remaining 60 patients (46 men, 14 women; average age 60+/-11 years), 854 segments were available for evaluation. Of these segments 842 (99%) were of sufficient image quality. Conventional coronary angiography identified 73 lesions, of which 62 were detected by MSCT. The corresponding sensitivity and specificity were 85% and 97%, respectively. On a patient-per-patient analysis, sensitivity, specificity, and positive and negative predictive values were 94%, 97%, 97%, and 93%, respectively. In conclusion, the present study confirms that 64-slice MSCT enables the accurate and noninvasive evaluation of significant coronary artery stenoses.

Advances in the noninvasive evaluation of coronary artery disease with multislice computed tomography.

Current noninvasive detection of coronary artery disease (CAD) is based on the demonstration of ischemia using stress-rest imaging, which is an indirect way of identifying CAD by demonstration of the hemodynamic consequences, rather than direct visualization of the obstructive lesions in the coronary arteries. Multislice computed tomography (MSCT) has recently emerged as an extremely rapidly developing noninvasive imaging modality, which allows anatomical imaging of the coronary arteries or noninvasive coronary angiography. In addition, total plaque burden, plaque morphology and (to some extent) plaque constitution can be assessed by MSCT. The technique also provides information on resting left ventricular systolic function, and possibly resting perfusion. Ideally, stress function and perfusion should also be evaluated, since this would allow detection of ischemia and would complete the picture of CAD. However, this is not routinely performed, since sequential acquisitions are associated with high radiation doses and thus pose a limitation for cardiovascular applications of MSCT. It is anticipated that, with a reduction in radiation, MSCT may become an important player in the diagnostic and prognostic work-up of patients with known or suspected CAD.