Augustin Delago

Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial.

OBJECTIVES The purpose of this study was to evaluate the diagnostic accuracy of electrocardiographically gated 64-multidetector row coronary computed tomographic angiography (CCTA) in individuals without known coronary artery disease (CAD). BACKGROUND CCTA is a promising method for detection and exclusion of obstructive coronary artery stenosis. To date, no prospective multicenter trial has evaluated the diagnostic accuracy of 64-multidetector row CCTA in populations with intermediate prevalence of CAD. METHODS We prospectively evaluated subjects with chest pain at 16 sites who were clinically referred for invasive coronary angiography (ICA). CCTAs were scored by consensus of 3 independent blinded readers. The ICAs were evaluated for coronary stenosis based on quantitative coronary angiography (QCA). No subjects were excluded for baseline coronary artery calcium score or body mass index. RESULTS A total of 230 subjects underwent both CCTA and ICA (59.1% male; mean age: 57 +/- 10 years). On a patient-based model, the sensitivity, specificity, and positive and negative predictive values to detect > or =50% or > or =70% stenosis were 95%, 83%, 64%, and 99%, respectively, and 94%, 83%, 48%, 99%, respectively. No differences in sensitivity and specificity were noted for nonobese compared with obese subjects or for heart rates < or =65 beats/min compared with >65 beats/min, whereas calcium scores >400 reduced specificity significantly. CONCLUSIONS In this prospective multicenter trial of chest pain patients without known CAD, 64-multidetector row CCTA possesses high diagnostic accuracy for detection of obstructive coronary stenosis at both thresholds of 50% and 70% stenosis. Importantly, the 99% negative predictive value at the patient and vessel level establishes CCTA as an effective noninvasive alternative to ICA to rule out obstructive coronary artery stenosis. (A Study of Computed Tomography [CT] for Evaluation of Coronary Artery Blockages in Typical or Atypical Chest Pain; NCT00348569).

Age- and Sex-Related Differences in All-Cause Mortality Risk Based on Coronary Computed Tomography Angiography Findings Results From the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 Patients Without Known Coronary Artery Disease

OBJECTIVES We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA). BACKGROUND Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes. METHODS We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models. RESULTS At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men. CONCLUSIONS Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis.

Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention

CONTEXT Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. OBJECTIVES To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. DESIGN, SETTING, AND PARTICIPANTS The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. INTERVENTIONS Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. MAIN OUTCOME MEASURES One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. RESULTS At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P =.02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P =.23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P =.051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P =.07). CONCLUSIONS Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.

Prevalence and Severity of Coronary Artery Disease and Adverse Events Among Symptomatic Patients With Coronary Artery Calcification Scores of Zero Undergoing Coronary Computed Tomography Angiography Results From the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) Registry

OBJECTIVES The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA). BACKGROUND The frequency and clinical relevance of CAD in patients without CAC are unclear. METHODS We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed. RESULTS Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84). CONCLUSIONS In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA.

Mortality Risk in Symptomatic Patients With Nonobstructive Coronary Artery Disease: A Prospective 2-Center Study of 2,583 Patients Undergoing 64-Detector Row Coronary Computed Tomographic Angiography

OBJECTIVES We examined mortality risk in relation to extent and composition of nonobstructive plaques by 64-detector row coronary computed tomographic angiography (CCTA). BACKGROUND The prognostic significance of nonobstructive coronary artery plaques by CCTA is poorly understood. METHODS We prospectively evaluated consecutive adults from 2 centers undergoing 64-detector row CCTA without prior documented coronary artery disease (CAD) and without obstructive (≥50%) CAD by CCTA. Luminal diameter stenosis severity was classified for each segment as none (0%) or mild (1% to 49%), and plaque composition was classified as noncalcified, calcified, or mixed. RESULTS During 3.1 ± 0.5 years, 54 intermediate-term (≥90 days) deaths occurred among 2,583 patients (2.09%), with 4 early (<90 days) deaths. Adjusted for CAD risk factors, the presence of any nonobstructive plaque was associated with higher mortality (hazard ratio [HR]: 1.98, 95% confidence Interval [CI]: 1.06 to 3.69, p = 0.03), with the highest risk among those exhibiting nonobstructive CAD in 3 epicardial vessels (HR: 4.75, 95% CI: 2.10 to 10.75, p = 0.0002) or ≥5 segments (HR: 5.12, 95% CI: 2.16 to 12.10, p = 0.0002). Higher mortality for nonobstructive CAD was observed even among patients with low 10-year Framingham risk (3.4%, p < 0.0001) as well as those with no traditional, medically treatable CAD risk factors, including diabetes mellitus, hypertension, and dyslipidemia (6.7%, p < 0.0001). No independent relationship between plaque composition and incident mortality was observed. Importantly, patients without evident plaque experienced a low rate of incident death during follow-up (0.34%/year). CONCLUSIONS The presence and extent of nonobstructive plaques augment prediction of incident mortality beyond conventional clinical risk assessment.

Coronary Computed Tomographic Angiography and Risk of All-Cause Mortality and Nonfatal Myocardial Infarction in Subjects Without Chest Pain Syndrome From the CONFIRM Registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)

Background— The predictive value of coronary computed tomographic angiography (cCTA) in subjects without chest pain syndrome (CPS) has not been established. We investigated the prognostic value of coronary artery disease detection by cCTA and determined the incremental risk stratification benefit of cCTA findings compared with clinical risk factor scoring and coronary artery calcium scoring (CACS) for individuals without CPS. Methods and Results— An open-label, 12-center, 6-country observational registry of 27 125 consecutive patients undergoing cCTA and CACS was queried, and 7590 individuals without CPS or history of coronary artery disease met the inclusion criteria. All-cause mortality and the composite of all-cause mortality and nonfatal myocardial infarction were measured. During a median follow-up of 24 months (interquartile range, 18–35 months), all-cause mortality occurred in 136 individuals. After risk adjustment, compared with individuals without evidence of coronary artery disease by cCTA, individuals with obstructive 2- and 3-vessel disease or left main coronary artery disease experienced higher rates of death and composite outcome (P<0.05 for both). Both CACS and cCTA significantly improved the performance of standard risk factor prediction models for all-cause mortality and the composite outcome (likelihood ratio P<0.05 for all), but the incremental discriminatory value associated with their inclusion was more pronounced for the composite outcome and for CACS (C statistic for model with risk factors only was 0.71; for risk factors plus CACS, 0.75; for risk factors plus CACS plus cCTA, 0.77). The net reclassification improvement resulting from the addition of cCTA to a model based on standard risk factors and CACS was negligible. Conclusions— Although the prognosis for individuals without CPS is stratified by cCTA, the additional risk-predictive advantage by cCTA is not clinically meaningful compared with a risk model based on CACS. Therefore, at present, the application of cCTA for risk assessment of individuals without CPS should not be justified.

Coronary Computed Tomographic Angiography as a Gatekeeper to Invasive Diagnostic and Surgical Procedures : Results From the Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) Registry

OBJECTIVES This study sought to examine patterns of follow-up invasive coronary angiography (ICA) and revascularization (REV) after coronary computed tomography angiography (CCTA). BACKGROUND CCTA is a noninvasive test that permits direct visualization of the extent and severity of coronary artery disease (CAD). Post-CCTA patterns of follow-up ICA and REV are incompletely defined. METHODS We examined 15,207 intermediate likelihood patients from 8 sites in 6 countries; these patients were without known CAD, underwent CCTA, and were followed up for 2.3 ± 1.2 years for all-cause mortality. Coronary artery stenosis was judged as obstructive when ≥50% stenosis was present. A multivariable logistic regression was used to estimate ICA use. A Cox proportional hazards model was used to estimate all-cause mortality. RESULTS During follow-up, ICA rates for patients with no CAD to mild CAD according to CCTA were low (2.5% and 8.3%), with similarly low rates of REV (0.3% and 2.5%). Most ICA procedures (79%) occurred ≤3 months of CCTA. Obstructive CAD was associated with higher rates of ICA and REV for 1-vessel (44.3% and 28.0%), 2-vessel (53.3% and 43.6%), and 3-vessel (69.4% and 66.8%) CAD, respectively. For patients with <50% stenosis, early ICA rates were elevated; over the entirety of follow-up, predictors of ICA were mild left main, mild proximal CAD, respectively, or higher coronary calcium scores. In patients with <50% stenosis, the relative hazard for death was 2.2 (p = 0.011) for ICA versus no ICA. Conversely, for patients with CAD, the relative hazard for death was 0.61 for ICA versus no ICA (p = 0.047). CONCLUSIONS These findings support the concept that CCTA may be used effectively as a gatekeeper to ICA.

Optimized Prognostic Score for Coronary Computed Tomographic Angiography: Results From the CONFIRM Registry (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry)

OBJECTIVES The aim of this study was to analyze the predictive value of coronary computed tomography angiography (CCTA) and to model and validate an optimized score for prognosis of 2-year survival on the basis of a patient population with suspected coronary artery disease (CAD). BACKGROUND Coronary computed tomography angiography carries important prognostic information in addition to the detection of obstructive CAD. But it is still unclear how the results of CCTA should be interpreted in the context of clinical risk predictors. METHODS The analysis is based on a test sample of 17,793 patients and a validation sample of 2,506 patients, all with suspected CAD, from the international CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry. On the basis of CCTA data and clinical risk scores, an optimized score was modeled. The endpoint was all-cause mortality. RESULTS During a median follow-up of 2.3 years, 347 patients died. The best CCTA parameter for prediction of mortality was the number of proximal segments with mixed or calcified plaques (C-index 0.64, p < 0.0001) and the number of proximal segments with a stenosis >50% (C-index 0.56, p = 0.002). In an optimized score including both parameters, CCTA significantly improved overall risk prediction beyond National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) score as best clinical score. According to this score, a proximal segment with either a mixed or calcified plaque or a stenosis >50% is equivalent to a 5-year increase in age or the risk of smoking. CONCLUSIONS In CCTA, both plaque burden and stenosis, particularly in proximal segments, carry incremental prognostic value. A prognostic score on the basis of this data can improve risk prediction beyond clinical risk scores.

Differences in Prevalence, Extent, Severity, and Prognosis of Coronary Artery Disease Among Patients With and Without Diabetes Undergoing Coronary Computed Tomography Angiography: Results from 10,110 individuals from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes): an InteRnational Multicenter Registry

OBJECTIVE We examined the prevalence, extent, severity, and prognosis of coronary artery disease (CAD) in individuals with and without diabetes (DM) who are similar in CAD risk factors. RESEARCH DESIGN AND METHODS We identified 23,643 consecutive individuals without known CAD undergoing coronary computed tomography angiography. A total of 3,370 DM individuals were propensity matched in a 1-to-2 fashion to 6,740 unique non-DM individuals. CAD was defined as none, nonobstructive (1–49% stenosis), or obstructive (≥50% stenosis). All-cause mortality was assessed by risk-adjusted Cox proportional hazards models. RESULTS At a 2.2-year follow-up, 108 (3.2%) and 115 (1.7%) deaths occurred among DM and non-DM individuals, respectively. Compared with non-DM individuals, DM individuals possessed higher rates of obstructive CAD (37 vs. 27%) and lower rates of having normal arteries (28 vs. 36%) (P < 0.0001). CAD extent was higher for DM versus non-DM individuals for obstructive one-vessel disease (19 vs. 14%), two-vessel disease (9 vs. 7%), and three-vessel disease (9 vs. 5%) (P < 0.0001 for comparison), with higher per-segment stenosis in the proximal and mid-segments of every coronary artery (P < 0.001 for all). Compared with non-DM individuals with no CAD, risk of mortality for DM individuals was higher for those with no CAD (hazard ratio 3.63 [95% CI 1.67–7.91]; P = 0.001), nonobstructive CAD (5.25 [2.56–10.8]; P < 0.001), one-vessel disease (6.39 [2.98–13.7]; P < 0.0001), two-vessel disease (12.33 [5.622–27.1]; P < 0.0001), and three-vessel disease (13.25 [6.15–28.6]; P < 0.0001). CONCLUSIONS Compared with matched non-DM individuals, DM individuals possess higher prevalence, extent, and severity of CAD. At comparable levels of CAD, DM individuals experience higher risk of mortality compared with non-DM individuals.

Does coronary CT angiography improve risk stratification over coronary calcium scoring in symptomatic patients with suspected coronary artery disease? Results from the prospective multicenter international CONFIRM registry

AIMS The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied. METHODS AND RESULTS We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D-F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index-accounting for stenosis severity, plaque distribution, and plaque location-was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17-40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D-F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D-F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001). CONCLUSION In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI.