Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

AIM: Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown. METHODS AND RESULTS: From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0-10, 11-100, 101-400, 401-1000, >1000. For CCTA analysis, the number of obstructive vessels-as defined by the per-patient presence of a ≥50% luminal stenosis-was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) χ(2), C-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th-75th percentile, 17-30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LRχ(2), 25.34; increment in C-statistic, 0.24; NRI, 0.62, all P < 0.001), but not among those with CACS ≤100 (all P > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS. CONCLUSION: Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.

Diuretic response in acute heart failure-an analysis from ASCEND-HF.

BACKGROUND: Diuretic unresponsiveness often occurs during hospital admission for acute heart failure (AHF) and is associated with adverse outcome. This study aims to investigate determinants, clinical outcome, and the effects of nesiritide on diuretic response early after admission for AHF. METHODS: Diuretic response, defined as weight loss per 40 mg of furosemide or equivalent, was examined from hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial. As an additional analysis, a urinary diuretic response metric was investigated in 5,268 patients using urine volume from hospital admission to 24 hours per 40 mg of furosemide or equivalent. RESULTS: Mean diuretic response was -0.42 kg/40 mg of furosemide (interquartile range -1.0, -0.05). Poor responders had lower blood pressure, more frequent diabetes, long-term use of loop diuretics, poorer baseline renal function, and lower urine output (all P < .01). Randomized nesiritide treatment was not associated with diuretic response (P = .987). Good diuretic response was independently associated with a significantly decreased risk of 30-day all-cause mortality or heart failure rehospitalization (odds ratio 0.44, 95% CI 0.29-0.65, highest vs lowest quintile, P < .001). Diuretic response based on urine output per 40 mg of furosemide showed similar results in terms of clinical predictors, association with outcome, and the absence of an effect of nesiritide. CONCLUSIONS: Poor diuretic response early after hospital admission for AHF is associated with low blood pressure, renal impairment, low urine output, and an increased risk of death or rehospitalization early after discharge. Nesiritide had a neutral effect on diuretic response.

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.

Performance of the traditional age, sex, and angina typicality-based approach for estimating pretest probability of angiographically significant coronary artery disease in patients undergoing coronary computed tomographic angiography: results from the multinational coronary CT angiography evaluation for clinical outcomes: an international multicenter registry (CONFIRM).

BACKGROUND: Guidelines for the management of patients with suspected coronary artery disease (CAD) rely on the age, sex, and angina typicality-based pretest probabilities of angiographically significant CAD derived from invasive coronary angiography (guideline probabilities). Reliability of guideline probabilities has not been investigated in patients referred to noninvasive CAD testing. METHODS AND RESULTS: We identified 14048 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography. Angina typicality was recorded with the use of accepted criteria. Pretest likelihoods of CAD with ≥ 50 diameter stenosis (CAD50) and ≥ 70 diameter stenosis (CAD70) were calculated from guideline probabilities. Computed tomographic angiography images were evaluated by ≥ 1 expert reader to determine the presence of CAD50 and CAD70. Typical angina was associated with the highest prevalence of CAD50 (40 in men, 19 in women) and CAD70 (27 men, 11 women) compared with other symptom categories (P<0.001 for all). Observed CAD50 and CAD70 prevalences were substantially lower than those predicted by guideline probabilities in the overall population (18 versus 51 for CAD50, 10 versus 42 for CAD70; P<0.001), driven by pronounced differences in patients with atypical angina (15 versus 47 for CAD50, 7 versus 37 for CAD70) and typical angina (29 versus 86 for CAD50, 19 versus 71 for CAD70). Marked overestimation of disease prevalence by guideline probabilities was found at all participating centers and across all sex and age subgroups. CONCLUSION: In this multinational study of patients referred for coronary computed tomographic angiography, determination of pretest likelihood of angiographically significant CAD by the invasive angiography-based guideline probabilities greatly overestimates the actual prevalence of disease.

Diagnostic accuracy of fractional flow reserve from anatomic CT angiography.

CONTEXT: Coronary computed tomographic (CT) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia. In contrast, fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFR(CT)) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date. OBJECTIVE: To assess the diagnostic performance of FFR(CT) plus CT for diagnosis of hemodynamically significant coronary stenosis. DESIGN, SETTING, AND PATIENTS: Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFR(CT) between October 2010 and October 2011. Computed tomography, ICA, FFR, and FFR(CT) were interpreted in blinded fashion by independent core laboratories. Accuracy of FFR(CT) plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFR(CT) of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA. MAIN OUTCOME MEASURES: The primary study outcome assessed whether FFR(CT) plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95% confidence interval of this estimate exceeded 70%. RESULTS: Among study participants, 137 (54.4%) had an abnormal FFR determined by ICA. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR(CT) plus CT were 73% (95% CI, 67%-78%), 90% (95% CI, 84%-95%), 54% (95% CI, 46%-83%), 67% (95% CI, 60%-74%), and 84% (95% CI, 74%-90%), respectively. Compared with obstructive CAD diagnosed by CT alone (area under the receiver operating characteristic curve [AUC], 0.68; 95% CI, 0.62-0.74), FFR(CT) was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001). CONCLUSION: Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy, use of noninvasive FFR(CT) plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference standard.

Incremental prognostic significance of left ventricular dysfunction to coronary artery disease detection by 64-detector row coronary computed tomographic angiography for the prediction of all-cause mortality: results from a two-centre study of 5330 patients.

AIMS: Early reports indicate a prognostic value of coronary artery disease (CAD) detection by coronary computed tomographic angiography (CCTA), although studies have been limited by small samples in single centres. Coronary computed tomographic angiographic measures of left ventricular ejection fraction (LVEF) to add incremental prognostic value beyond CAD detection have not been examined. METHODS AND RESULTS: We evaluated 5330 consecutive patients without known CAD undergoing CCTA at two centres. Stenosis severity by CCTA was graded as none (0%), mild (1-49%), moderate (50-69%), or obstructive (> or = 70%). Left ventricular ejection fraction was graded as normal (>50%) or reduced (< or = 50%). About 2.3 +/- 0.6 year follow-up of patients for all-cause mortality was performed using multivariate and Cox proportional hazards models; 100 deaths occurred (1.9%). Detection of obstructive CAD correlated with mortality [hazards ratio (HR) 2.44, 95% confidence interval (CI) 1.61-3.72, P < 0.001]. Compared with those without obstructive CAD, individuals with increasing numbers of vessels with obstructive CAD experienced increased risk of death: 1-vessel (HR 2.23, 95% CI 1.34-3.72), 2-vessel (HR 3.29, 95% CI 1.62-6.71), or 3-vessel (HR 7.35, 95% CI 3.79-14.29) (P < 0.001 for all). Compared with those with LVEF >50%, those with LVEF < or = 50% exhibited higher rates of death (HR 1.56, 95% CI 1.04-2.36, P = 0.03). Annualized mortality rates in those with non-obstructive CAD and LVEF >50% were low (0.51%) and increased accordingly for non-obstructive CAD and LVEF < or = 50% (0.74%), obstructive CAD and LVEF >50% (1.76%), and obstructive CAD and LVEF < or = 50% (3.97%) (log-rank test P < 0.001). CONCLUSION: In a large two-centre cohort of patients without known CAD, obstructive CAD detection by CCTA was related to incident death by the absolute presence of as well as increasing numbers of vessels with obstructive CAD. The addition of LVEF by CCTA enhanced risk correlation for death.

Improved 5-year prediction of all-cause mortality by coronary CT angiography applying the CONFIRM score.

AIMS: To investigate the long-term performance of the CONFIRM score for prediction of all-cause mortality in a large patient cohort undergoing coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Patients with a 5-year follow-up from the international multicentre CONFIRM registry were included. The primary endpoint was all-cause mortality. The predictive value of the CONFIRM score over clinical risk scores (Morise, Framingham, and NCEP ATP III score) was studied in the entire patient population as well as in subgroups. Improvement in risk prediction and patient reclassification were assessed using categorical net reclassification index (NRI) and integrated discrimination improvement (IDI). During a median follow-up period of 5.3 years, 982 (6.5%) of 15 219 patients died. The CONFIRM score outperformed the prognostic value of the studied three clinical risk scores (c-indices: CONFIRM score 0.696, NCEP ATP III score 0.675, Framingham score 0.610, Morise score 0.606; c-index for improvement CONFIRM score vs. NCEP ATP III score 0.650, P < 0.0001). Application of the CONFIRM score allowed reclassification of 34% of patients when compared with the NCEP ATP III score, which was the best clinical risk score. Reclassification was significant as revealed by categorical NRI (0.06 with 95% CI 0.02 and 0.10, P = 0.005) and IDI (0.013 with 95% CI 0.01 and 0.015, P < 0.001). Subgroup analysis revealed a comparable performance in a variety of patient subgroups. CONCLUSIONS: The CONFIRM score permits a significantly improved prediction of mortality over clinical risk scores for >5 years after CCTA. These findings are consistent in a large variety of patient subgroups.

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA. METHODS: From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA. RESULTS: Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3-4.9) and 2.2 (95% CI 1.6-3.0), respectively]. CONCLUSIONS: Patients without luminal narrowing but with CAC experience greater risk of 5-year mortality. Patients with CAC score ≥100 and no coronary luminal narrowing experience death rates similar to those with non-obstructive CAD.

Effectiveness of a low contrast load CT angiography protocol in octogenarians and nonagenarians being evaluated for transcatheter aortic valve replacement.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) typically requires computed tomographic angiography (CTA) for aortoiliofemoral assessment to determine feasibility of a transfemoral approach, although many candidates being considered for TAVR are at increased risk of contrast-induced nephropathy (CIN). OBJECTIVE: To determine the feasibility and safety of a load contrast load CTA protocol in octogenarians and nonagenarians at risk of CIN. APPROACH: We evaluated 54 consecutive octogenarians and nonagenarians considered for TAVR who underwent CTA using a standard contrast protocol (n=21) versus a protocol incorporating low-dose contrast in patients at risk of CIN (n=33). We compared clinical characteristics, CTA image quality (score 1-4) and interpretability, and clinical outcomes, including CIN and vascular complications. RESULTS: The mean age was 88.5±4.0 years, 37% were male, and chronic renal insufficiency was common in both the standard and low-dose contrast cohorts (57% vs. 70%, P=.39). The low-dose contrast protocol was associated with a significantly less contrast volume compared to standard contrast protocol (127±18 ml vs 76±55 ml, P<.001). Individuals imaged using low-dose (n=16) versus standard (n=17) contrast protocols received 80% less contrast volume (23±10 vs. 125±23 ml, P<.001). There was similar graded image quality (3.8±0.4 vs. 3.9±0.3, P=.76) and interpretability (100% for each, P=1.0) between standard and low-dose contrast protocol groups. There was no significant difference in rates of CIN after CTA between standard and low-dose contrast protocol groups (10% vs. 3%, P=.55), with no CIN events in those imaged by low-dose CTA. There were no major vascular injuries associated with TAVR or pigtail insertion, no major bleeding for CTA, and no noninterpretable studies in all patients. CONCLUSION: In this proof-of-principle study, a low-dose contrast protocol appears feasible and safe in octogenarians and nonagenarians undergoing screening for TAVR, and results in significant reduction in contrast load as compared to a standard contrast protocol without observed differences in image quality or safety.

Coronary dominance and prognosis in patients undergoing coronary computed tomographic angiography: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry.

AIMS: Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. METHODS AND RESULTS: The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9 ± 12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD (HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. CONCLUSION: In our study population, survival after 5 years of follow-up did not differ significantly between patients with left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations.

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.

Impact of an automated multimodality point-of-order decision support tool on rates of appropriate testing and clinical decision making for individuals with suspected coronary artery disease: a prospective multicenter study.

OBJECTIVES: This study sought to evaluate the impact of a multimodality-appropriate use criteria decision support tool (AUC-DST) on rates of appropriate testing and clinical decision making. BACKGROUND: AUC have been developed to guide utilization of noninvasive imaging for individuals with suspected coronary artery disease (CAD). The effect of a point-of-order AUC-DST on rates of appropriateness and clinical decision making has not been examined. METHODS: We performed a prospective multicenter cohort study evaluating physicians who ordered CAD imaging tests for consecutive patients insured by 1 large private payer. During an 8-month study period, each study site was granted exemption from prior authorization requirements by radiology benefits managers. An AUC-DST was employed to determine appropriateness ratings for myocardial perfusion scintigraphy (MPS), stress echocardiography (STE), or coronary computed tomographic angiography (CCTA), as well as intended downstream testing and therapy. RESULTS: One hundred physicians used the AUC-DST for 472 patients (age 55.6 ± 9.6 years, 61% male, 52% prior known CAD) over 8 months for MPS (72%), STE (24%), and CCTA (5%). The AUC-DST required an average of 137 ± 360 s to determine the appropriateness category that, by American College of Cardiology AUC, was considered appropriate in 241 (51%), uncertain in 96 (20%), inappropriate in 85 (18%), and not addressed in 50 (11%). For tests ordered in the first 2 months compared with the last 2 months, appropriate tests increased from 49% to 61% (p = 0.02), whereas inappropriate tests decreased from 22% to 6% (p < 0.001). During this period, intended changes in medical therapy increased from 11% to 32% (p = 0.001). CONCLUSIONS: A point-of-order AUC-DST enabled rapid determination of test appropriateness for CAD evaluation and was associated with increased and decreased testing for appropriate and inappropriate indications, respectively. These changes in test ordering were associated with greater intended changes in post-test medical therapy.

Noninvasive fractional flow reserve derived from computed tomography angiography for coronary lesions of intermediate stenosis severity: results from the DeFACTO study.

BACKGROUND: Fractional flow reserve derived from computed tomography angiography (FFRCT) is a noninvasive method for diagnosis of ischemic coronary lesions. To date, the diagnostic performance of FFRCT for lesions of intermediate stenosis severity remains unexamined. METHODS AND RESULTS: Among 407 vessels from 252 patients at 17 centers who underwent CT, FFRCT, invasive coronary angiography, and invasive FFR, we identified 150 vessels of intermediate stenosis by CT, defined as 30% to 69% stenosis. FFRCT, FFR, and CT were interpreted in blinded fashion by independent core laboratories. FFRCT and FFR ≤0.80 were considered hemodynamically significant, whereas CT stenosis ≥50% was considered obstructive. Diagnostic performance of FFRCT versus CT was assessed for accuracy, sensitivity, specificity, positive predictive values, and negative predictive values. Area under the receiver operating characteristic curve and net reclassification improvement were evaluated. For lesions of intermediate stenosis severity, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFRCT were 71%, 74%, 67%, 41%, and 90%, whereas accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT stenosis were 63%, 34%, 72%, 27%, and 78%. FFRCT demonstrated superior discrimination compared with CT stenosis on per-patient (area under the receiver operating characteristic curve, 0.81 versus 0.50; P=0.0001) and per-vessel basis (area under the receiver operating characteristic curve, 0.79 versus 0.53; P<0.0001). FFRCT demonstrated significant reclassification of CT stenosis for lesion-specific ischemia (net reclassification improvement, 0.45; 95% confidence interval, 0.25-0.65; P=0.01). CONCLUSIONS: FFRCT possesses high diagnostic performance for diagnosis of ischemic for lesions of intermediate stenosis severity. Notably, the high sensitivity and negative predictive value suggest the ability of FFRCT to effectively rule out intermediate lesions that cause ischemia.

Predictive value of cardiac computed tomography and the impact of renal function on all cause mortality (from Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes).

Patients with chronic kidney disease have a worse cardiovascular prognosis than those without. The aim of this study was to determine the incremental prognostic value of coronary computed tomographic angiography in predicting mortality across the entire spectrum of renal function in patients with known or suspected coronary artery disease (CAD). A large international multicenter registry was queried, and patients with left ventricular ejection fraction (LVEF) and creatinine data were screened. National Cholesterol Education Program Adult Treatment Panel III risk was calculated. Coronary computed tomographic angiographic results were evaluated for CAD severity (normal, nonobstructive, or obstructive) and an LVEF <50%. Patients were followed for the end point of all-cause mortality. Among 5,655 patients meeting the study criteria, follow-up was available for 5,572 (98.9%; median follow-up duration 18.6 months). All-cause mortality (66 deaths) significantly increased with every 10-unit decrease in renal function (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.07 to 1.41). All-cause mortality occurred in 0.33% of patients without coronary atherosclerosis, 1.82% of patients with nonobstructive CAD, and 2.43% of patients with obstructive CAD. Multivariate Cox proportional-hazards models revealed that impaired renal function (HR 2.29, 95% CI 1.65 to 3.18), CAD severity (HR 1.81, 95% CI 1.31 to 2.51), and an abnormal LVEF (HR 4.16, 95% CI 2.45 to 7.08) were independent predictors of all-cause mortality. In conclusion, coronary computed tomographic angiographic measures of CAD severity and the LVEF provide effective risk stratification across a wide spectrum of renal function. Furthermore, renal dysfunction, CAD severity, and the LVEF have additive value for predicting all-cause death in patients with suspected obstructive CAD.

Usefulness of noninvasive fractional flow reserve computed from coronary computed tomographic angiograms for intermediate stenoses confirmed by quantitative coronary angiography.

Coronary lesions of intermediate severity often cause ischemia, and fractional flow reserve (FFR)-guided revascularization for these coronary lesions is safe and effective. FFR derived from coronary computed tomography (FFR(CT)) is a noninvasive method for diagnosis of lesion-specific ischemia, but its performance for intermediate stenoses has not been examined to date. We examined the performance of FFR(CT) versus FFR at the time of invasive angiography in 66 vessels of 60 patients who were identified as having an intermediate stenosis, defined by quantitative coronary angiographic percent diameter stenosis 40% to 69%. Ischemia for FFR(CT) and FFR was defined as ≤0.80. Diagnostic performance of FFR(CT) was determined compared to an invasive FFR standard. Mean age of the study group was 63.5 ± 8.1 years (81% men). Thirty-one patients (47%) demonstrated ischemia with an FFR ≤0.80, with 2 of 16 (12.5%), 21 of 37 (56.8%), and 8 of 13 (61.5%) lesions of 40% to 49%, 50% to 59%, and 60% to 69% stenosis causal of ischemia, respectively. At an FFR ≤0.80 cutoff for lesion-specific ischemia, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR(CT) were 86.4%, 90.3%, 82.9%, 82.4%, and 90.6%, respectively, with an area under the receiver operator characteristics curve of 0.95 (p <0.001) and good correlation to FFR (0.60, p <0.0001). No biases between FFR(CT) and FFR were noted by Bland-Altman analysis (0.03 ± 0.12, p = 0.054). In conclusion, FFR(CT) is a novel noninvasive method for diagnosis of lesion-specific ischemia of coronary lesions of intermediate stenosis severity.

Cardiologist concordance with the American College of Cardiology appropriate use criteria for cardiac testing in patients with coronary artery disease.

The American College of Cardiology Appropriate Use Criteria (AUC) were developed to guide use of myocardial perfusion single-photon emission computed tomography (MPS), stress echocardiography, and cardiac computed tomographic angiography (CCTA). To date, cardiologist application of AUC from a patient-based multiprocedure perspective has not been evaluated. A Web-based survey of 15 clinical vignettes spanning a wide spectrum of indications for MPS, STE, and CCTA in coronary artery disease was administered to cardiologists who rated the ordered test as appropriate, inappropriate, or uncertain by AUC application and suggested a preferred alternative imaging procedure, if any. In total 129 cardiologists responded to the survey (mean age 49.5 years, board certification for MPS 65%, echocardiography 39%, CCTA 32%). Cardiologists agreed with published AUC ratings 65% of the time, with differences in all categories (appropriate, 50% vs 53%; inappropriate, 42% vs 20%; uncertain, 9% vs 27%, p <0.0001 for all comparisons). Physician age, practice type, or board certification in MPS or echocardiography had no effect on concordance with AUC ratings, with slightly higher agreement for those board certified in CCTA (68% vs 64%, p = 0.04). Cardiologist procedure preference was positively associated with active clinical interpretation of MPS and CCTA (p = 0.03 for the 2 comparisons) but not for ownership of the respective imaging equipment. In conclusion, cardiologist agreement with published AUC ratings is generally high, although physicians classify more uncertain indications as inappropriate. Active clinical interpretation of a procedure contributes most to increased procedure preference.

Coronary CT angiography versus myocardial perfusion imaging for near-term quality of life, cost and radiation exposure: a prospective multicenter randomized pilot trial.

BACKGROUND: Clinical outcomes and resource utilization after coronary computed tomography angiography (CTA) versus myocardial perfusion single-photon emission CT (MPS) in patients with stable angina and suspected coronary artery disease (CAD) has not been examined. OBJECTIVE: We determined the near-term clinical effect and resource utilization after cardiac CTA compared with MPS. METHODS: We randomly assigned 180 patients (age, 57.3 ± 9.8 years; 50.6% men) presenting with stable chest pain and suspected CAD at 2 sites to initial diagnostic evaluation by coronary CTA (n = 91) or MPS (n = 89). The primary outcome was near-term angina-specific health status; the secondary outcomes were incident medical and invasive treatments for CAD, CAD health care costs, and estimated radiation dose. RESULTS: No patients experienced myocardial infarction or death with 98.3% follow-up at 55 ± 34 days. Both arms experienced comparable improvements in angina-specific health status. Patients who received coronary CTA had increased incident aspirin (22% vs 8%; P = 0.04) and statin (7% vs -3.5%; P = 0.03) use, similar rates of CAD-related hospitalization, invasive coronary angiography, noninvasive cardiac imaging tests, and increased revascularization (8% vs 1%; P = 0.03). Coronary CTA had significantly lower total costs ($781.08 [interquartile range (IQR), $367.80-$4349.48] vs $1214.58 [IQR, $978.02-$1569.40]; P < 0.001) with no difference in induced costs. Coronary CTA had a significantly lower total estimated effective radiation dose (7.4 mSv [IQR, 5.0-14.0 mSv] vs 13.3 mSv [IQR, 13.1-38.0 mSv]; P < 0.0001) with no difference in induced radiation. CONCLUSION: In a pilot randomized controlled trial, patients with stable CAD undergoing coronary CTA and MPS experience comparable improvements in near-term angina-related quality of life. Compared with MPS, coronary CTA evaluation is associated with more aggressive medical therapy, increased coronary revascularization, lower total costs, and lower effective radiation dose.

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.

Periprocedural safety of 64-detector row coronary computed tomographic angiography: results from the prospective multicenter ACCURACY trial.

BACKGROUND: Coronary computed tomographic angiography (CCTA) requires iodinated contrast and often atrioventricular nodal blocking agents and nitroglycerin for heart rate lowering and coronary vasodilation, respectively. To date, the periprocedural safety of CCTA is unknown. OBJECTIVES: The purpose of this study was to evaluate the periprocedural safety of CCTA. METHODS: We prospectively evaluated 232 patients with symptomatic chest pain without preexisting renal insufficiency at 16 sites who underwent CCTA as part of the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY) trial. Patients received iodinated contrast, ß-blockers, and nitroglycerin as part of a predefined CCTA protocol. We assessed the rates of adverse events (AEs) related to these agents. RESULTS: As measured by serum creatinine and creatinine clearance, no significant change was observed in renal function from baseline (1.00 ± 0.19 mg/dL; modification of diet in renal disease [MDRD]: 76.91 ± 17.96 mL/min/1.73 m(2)) to 48 hours (1.0 ± 0.2 mg/dL; P = 1.00; MDRD change: 0.2 ± 12.4 mL/min/1.73 m(2); P = 0.83) or at 30 days (1.0 ± 0.2 mg/dL; P = 0.52; MDRD change: -0.9 ± 16.9 mL/min/1.73 m(2); P = 0.77). Mean systolic blood pressure decreased from baseline (133 ± 19 mm Hg) at 1 hour (125 ± 17 mm Hg; P < 0.001) and rebounded at 48 hours (133 ± 17 mm Hg). Mean heart rate decreased from baseline (65 ± 10 beats/min) at 1 hour (60 ± 7 beats/min) but rose at 48 hours (69 ± 11 beats/min; P < 0.001. All patients were asymptomatic from baseline to follow-up. CONCLUSIONS: The performance of CCTA is safe with low rates of AEs.

What is the optimal number of readers needed to achieve high diagnostic accuracy in coronary computed tomographic angiography? A comparison of alternate reader combinations.

BACKGROUND: Coronary computed tomographic angiography (CCTA) possesses high accuracy to detect coronary artery disease (CAD), although studies have reported differences in diagnostic performance. Prior trials used different numbers of interpreters, and the optimal number to detect CAD is unknown. OBJECTIVE: We compared the diagnostic performance of 1, 2, 3, and 5 randomly selected interpreters for CCTA. METHODS: We evaluated 50 patients randomly selected from 2 multicenter studies with both 64-detector CCTA and invasive quantitative coronary angiography (QCA). Five blinded, experienced readers independently interpreted CCTA and assessed for obstructive CAD (≥ 50% stenosis) and high-risk CAD (left main, proximal left anterior descending, or 3-vessel stenoses). A core laboratory performed QCA. For each patient, different random combinations of readers were selected; the accuracy of 1, 2, and 5 readers was compared with 3 readers. RESULTS: Obstructive and high-risk CAD were observed in 20 of 50 (40%) and 6 of 50 (12%) patients, respectively. With combinations of 1, 2, 3, or 5 readers, there was a range of per-patient diagnostic performance (sensitivity, 100% each; specificity, 67%-90%; accuracy, 80%-94%; P = NS), per-segment diagnostic performance (sensitivity, 67%-83%; specificity, 87%-93%; accuracy, 87%-92%; P < .001 for 1 vs 3 and 2 vs 3 readers), and detection of high-risk CAD (sensitivity, 83%-100%; specificity, 73%-80%; accuracy, 76%-82%; P = NS). The highest diagnostic accuracy was observed with 3 readers for each comparison. CONCLUSION: The diagnostic performance of CCTA to detect obstructive or high-risk CAD is generally high irrespective of the number of readers. Consensus interpretation by ≥ 3 readers provides the highest diagnostic accuracy.