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Background: It is unclear how patients hospitalized for acute heart failure (HF) who are long-term chronic HF survivors differ from those with more recent HF diagnoses., Objectives: The goal of this study was to evaluate the influence of HF chronicity on acute HF patient profiles and outcomes., Methods: The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 hospitalized patients with acute HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. The present analysis compared patients according to duration of HF diagnosis before index hospitalization by using pre-specified cutoffs (0 to 1 month [i.e., "recently diagnosed"], >1 to 12 months, >12 to 60 months, and >60 months)., Results: Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis (recently diagnosed, n = 1,536; >1 to 12 months, n = 1,020; >12 to 60 months, n = 1,653; and >60 months, n = 1,532). Across HF duration groups, mean age ranged from 64 to 66 years, and mean ejection fraction ranged from 29% to 32%. Compared with patients with longer HF duration, recently diagnosed patients were more likely to be women with nonischemic HF etiology, higher baseline blood pressure, better baseline renal function, and fewer comorbidities. After adjustment, compared with recently diagnosed patients, patients with longer HF duration were associated with more persistent dyspnea at 24 h (>1 to 12 months, odds ratio [OR]: 1.20; 95% confidence interval [CI]: 0.97 to 1.48; >12 to 60 months, OR: 1.34; 95% CI: 1.11 to 1.62; and >60 months, OR: 1.31; 95% CI: 1.08 to 1.60) and increased 180-day mortality (>1 to 12 months, hazard ratio [HR]: 1.89; 95% CI: 1.35 to 2.65; >12 to 60 months, HR: 1.82; 95% CI: 1.33 to 2.48; and >60 months, HR: 2.02; 95% CI: 1.47 to 2.77). The influence of HF duration on mortality was potentially more pronounced among female patients (interaction p = 0.05), but did not differ according to age, race, prior ischemic heart disease, or ejection fraction (all interactions, p ≥ 0.23)., Conclusions: In this acute HF trial, patient profile differed according to duration of the HF diagnosis. A diagnosis of HF for ≤1 month before hospitalization was independently associated with greater early dyspnea relief and improved post-discharge survival compared to patients with chronic HF diagnoses. The distinction between de novo or recently diagnosed HF and worsening chronic HF should be considered in the design of future acute HF trials. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD)., Methods: From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality., Results: Patient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not., Conclusion: CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To develop a clinical cardiac risk algorithm for stable patients with suspected coronary artery disease based upon angina typicality and coronary artery disease risk factors., Methods: Between 2004 and 2011, 14,004 adults with suspected coronary artery disease referred for cardiac imaging were followed: 1) 9093 patients for coronary computed tomography angiography (CCTA) followed for 2.0 years (CCTA-1); 2) 2132 patients for CCTA followed for 1.6 years (CCTA-2); and 3) 2779 patients for exercise myocardial perfusion scintigraphy (MPS) followed for 5.0 years. A best-fit model from CCTA-1 for prediction of death or myocardial infarction was developed, with integer values proportional to regression coefficients. Discrimination was assessed using C-statistic. The validated model was tested for estimation of the likelihood of obstructive coronary artery disease, defined as ≥50% stenosis, as compared with the method of Diamond and Forrester. Primary outcomes included all-cause mortality and nonfatal myocardial infarction. Secondary outcomes included prevalent angiographically obstructive coronary artery disease., Results: In CCTA-1, best-fit model discriminated individuals at risk of death or myocardial infarction (C-statistic 0.76). The integer model ranged from 3 to 13, corresponding to 3-year death risk or myocardial infarction of 0.25% to 53.8%. When applied to CCTA-2 and MPS cohorts, the model demonstrated C-statistics of 0.71 and 0.77, respectively. Both best-fit (C = 0.76; 95% confidence interval [CI], 0.746-0.771) and integer models (C = 0.71; 95% CI, 0.693-0.719) performed better than Diamond and Forrester (C = 0.64; 95% CI, 0.628-0.659) for estimating obstructive coronary artery disease., Conclusions: For stable symptomatic patients with suspected coronary artery disease, we developed a history-based method for prediction of death and obstructive coronary artery disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Studies examining coronary computed tomographic angiography (CCTA) have demonstrated increased mortality related to coronary artery disease (CAD) severity but are limited to relatively nondiverse ethnic populations. The aim of this study was to evaluate the prognostic significance of CAD on CCTA according to ethnicity for patients without previous CAD in a prospective international CCTA registry of 11 sites (7 countries) who underwent 64-slice CCTA from 2005 to 2010. CAD was defined as any coronary artery atherosclerosis and obstructive CAD as ≥50% stenosis. All-cause mortality and nonfatal myocardial infarction (MI) were assessed by ethnicity using Kaplan-Meier and Cox proportional hazards, controlling for baseline risk factors, medications, and revascularization. A total of 16,451 patients of mean age 58 years (55% men) were followed over a median of 2.0 years (interquartile range 1.4 to 3.2). Patients were 60.1% Caucasian, 34.4% East Asian, and 5.5% African. Death or MI occurred in 0.5% (38 of 7,109) among patients with no CAD, 1.6% (91 of 5,600) among those with nonobstructive CAD, and 3.8% (142 of 3,742) among those with ≥50% stenosis (p <0.001 among all groups). The annualized incidence of death or MI comparing obstructive to no obstructive CAD among Caucasians was 2.2% versus 0.7% (adjusted hazard ratio [aHR] 2.77, 95% confidence interval [CI] 1.73 to 4.43, p <0.001), among Africans 4.8% versus 1.1% (aHR 6.25, 95% CI 1.12 to 34.97, p = 0.037), and among East Asians 0.8% versus 0.1% (aHR 4.84, 95% CI 2.24 to 10.9, p <0.001). Compared to other ethnicities, East Asians had fewer than expected events (aHR 0.25, 95% CI 0.16 to 0.38, p <0.001). In conclusion, the presence and severity of CAD visualized by CCTA predict death or MI across 3 large ethnicities, whereas normal results on CCTA identify patients at very low risk., (Published by Elsevier Inc.)

Objectives: We sought to determine the incremental prognostic value of 64 multi-slice coronary computed tomography angiography (CCTA) in coronary artery bypass graft (CABG) patients., Background: Prognostication in CABG patients can be difficult. Anatomical assessment of native coronary artery disease and graft patency might provide useful information, but the utility of CCTA in the assessment of CABG patients is unknown., Methods: Six hundred fifty-seven CABG patients with all-cause mortality follow-up were identified from a multicenter CCTA registry, of 10,628 patients from 5 CCTA centers. Clinical risk was profiled with modified logistic and additive EuroSCOREs (European Systems for Cardiac Operative Risk Evaluations). The CCTA defined coronary anatomy. Patients were classified by unprotected coronary territory (UCT) or a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS)., Results: Forty-four deaths occurred during a mean follow-up of 20 months. Left ventricular ejection fraction, creatinine, age, severity of native vessel disease, UCT, CAPS, and EuroSCOREs were univariate predictors of mortality (p < 0.001). In multivariate analysis with additive EuroSCORE, UCT (p = 0.004) and CAPS were predictive of events (p < 0.001). In comparison with additive EuroSCORE, CAPS score was associated with a 27% net reclassification index., Conclusions: Coronary computed tomography angiography provides incremental anatomical data to clinical risk assessment to help determine the prognosis of patients after CABG. The CAPS evaluation with CCTA might help identify those patients at highest risk., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Large multicenter studies validating the prognostic value of coronary computed tomographic angiography (CCTA) and left ventricular ejection fraction (LVEF) are lacking. We sought to confirm the independent and incremental prognostic value of coronary artery disease (CAD) severity measured using 64-slice CCTA over LVEF and clinical variables., Methods and Results: A large international multicenter registry (CONFIRM Registry) was queried, and CCTA patients with LVEF data on CCTA were screened. Patients with a history of myocardial infarction, coronary revascularization, or cardiac transplantation were excluded. The National Cholesterol Education Program-Adult Treatment Panel III risk was calculated for each patient, and CCTA was evaluated for CAD severity (normal, nonobstructive, non-high-risk, or high-risk CAD) and LVEF <50%. Patients were followed for an end point of all-cause mortality; 27 125 patients underwent CCTA at 12 participating centers, with a total of 14 064 patients meeting the analysis criteria. Follow-up was available for 13 966 (99.3%) patients (mean follow-up of 22.5 months; 95% confidence interval, 22.3 to 22.7 months). All-cause mortality (271 deaths) occurred in 0.65% of patients without coronary atherosclerosis, 1.99% of patients with nonobstructive CAD, 2.90% of patients with non-high-risk CAD, and 4.95% for patients with high-risk CAD. Multivariable analysis confirmed that LVEF <50% (hazard ratio, 2.74; 95% confidence interval, 2.12 to 3.51) and CAD severity (hazard ratio,1.58; 95% confidence interval, 1.42 to 1.76) were predictors of all-cause mortality, and CAD severity had incremental value over LVEF and clinical variables., Conclusions: Our results demonstrate that CCTA measures of CAD severity and LVEF have independent prognostic value. Incorporation of CAD severity provides incremental value for predicting all-cause death over routine clinical predictors and LVEF in patients with suspected obstructive CAD.

ObjectivesThis study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS).BackgroundCurrent risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification.MethodsA total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971).ResultsThe mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort.ConclusionsThe new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/).

AimsCoronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults.Methods and resultsOf 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value

ObjectivesThis study sought to assess clinical outcomes associated with the novel Coronary Artery Disease-Reporting and Data System (CAD-RADS) scores used to standardize coronary computed tomography angiography (CTA) reporting and their potential utility in guiding post-coronary CTA care.BackgroundClinical decision support is a major focus of health care policies aimed at improving guideline-directed care. Recently, CAD-RADS was developed to standardize coronary CTA reporting and includes clinical recommendations to facilitate patient management after coronary CTA.MethodsIn the multinational CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, 5,039 patients without known coronary artery disease (CAD) underwent coronary CTA and were stratified by CAD-RADS scores, which rank CAD stenosis severity as 0 (0%), 1 (1% to 24%), 2 (25% to 49%), 3 (50% to 69%), 4A (70% to 99% in 1 to 2 vessels), 4B (70% to 99% in 3 vessels or ≥50% left main), or 5 (100%). Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality or myocardial infarction (MI). Receiver-operating characteristic (ROC) curves were used to compare CAD-RADS to the Duke CAD Index and traditional CAD classification. Referrals to invasive coronary angiography (ICA) after coronary CTA were also assessed.ResultsCumulative 5-year event-free survival ranged from 95.2% to 69.3% for CAD-RADS 0 to 5 (p < 0.0001). Higher scores were associated with elevations in event risk (hazard ratio: 2.46 to 6.09; p < 0.0001). The ROC curve for prediction of death or MI was 0.7052 for CAD-RADS, which was noninferior to the Duke Index (0.7073; p = 0.893) and traditional CAD classification (0.7095; p = 0.783). ICA rates were 13% for CAD-RADS 0 to 2, 66% for CAD-RADS 3, and 84% for CAD-RADS ≥4A. For CAD-RADS 3, 58% of all catheterizations occurred within the first 30 days of follow-up. In a patient subset with available medication data, 57% of CAD-RADS 3 patients who received 30-day ICA were either asymptomatic or not receiving antianginal therapy at baseline, whereas only 32% had angina and were receiving medical therapy.ConclusionsCAD-RADS effectively identified patients at risk for adverse events. Frequent ICA use was observed among patients without severe CAD, many of whom were asymptomatic or not taking antianginal drugs. Incorporating CAD-RADS into coronary CTA reports may provide a novel opportunity to promote evidence-based care post-coronary CTA.

BackgroundLeft ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking.Methods and results1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry (54.5% males, mean age 53.1 ± 12.4 years, range: 18-92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD (>50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6 ± 7.7% vs. 64.6 ± 8.1%, P < 0.001). This gender-difference in overall LVEF was caused by a significantly higher LVEF in women ≥70 years when compared with men ≥70 years (69.95 ± 8.89% vs. 65.50 ± 9.42%, P = 0.004). Accordingly, a significant increase in LVEF was observed with age (P = 0.005 for males and P < 0.001 for females), which was more pronounced in females (5.21%) than in males (2.6%). LV end-diastolic volume decreased in females from 122.48 ± 27.87 (70 years; P < 0.001) and in males from 155.22 ± 35.07 (70 years; P < 0.001).ConclusionOur findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values.

AimsTo identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA).Methods and resultsWe examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11-0.47) and 5 years (HR 0.31, 95% CI 0.18-0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22-0.93) but not 5 years (HR 0.63, 95% CI 0.33-1.20). For low-risk CAD, there was no survival benefit at either time point.ConclusionsEarly revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD.

Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events.

AimsTo 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 resultsPatients 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.ConclusionsThe 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.

ObjectivesThis study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD).BackgroundAlthough current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy.MethodsRetrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort.ResultsThe risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (

AimPrior 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 resultsFrom 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.ConclusionCoronary 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.

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥ 64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n = 690) were matched 1:1:1 to those with 1 component (n = 690) and 2 components (n = 690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p < 0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p > 0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p = 0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p = 0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

PurposeTo determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution.Materials and methodsInstitutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (

BackgroundCoronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD.MethodsFrom the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (0% but

AimsPrior studies evaluating the prognostic utility of cardiac CT angiography (CCTA) have been largely constrained to an all-cause mortality endpoint, with other cardiac endpoints generally not reported. To this end, we sought to determine the relationship of extent and severity of coronary artery disease (CAD) by CCTA to risk of incident major adverse cardiac events (MACEs) (defined as death, myocardial infarction, and late revascularization).Methods and resultsWe identified subjects without prior known CAD who underwent CCTA and were followed for MACE. CAD by CCTA was defined as none (0% luminal stenosis), mild (1-49% luminal stenosis), moderate (50-69% luminal stenosis), or severe (≥70% luminal stenosis), and ≥50% luminal stenosis was considered as obstructive. CAD severity was judged on per-patient, per-vessel, and per-segment basis. Time to MACE was estimated using univariable and multivariable Cox proportional hazards models. Among 15 187 patients (57 ± 12 years, 55% male), 595 MACE events (3.9%) occurred at a 2.4 ± 1.2 year follow-up. In multivariable analyses, an increased risk of MACE was observed for both non-obstructive [hazard ratio (HR) 2.43, P < 0.001] and obstructive CAD (HR: 11.21, P < 0.001) when compared with patients with normal CCTA. Risk-adjusted MACE increased in a dose-response relationship based on the number of vessels with obstructive CAD ≥50%, with increasing hazards observed for non-obstructive (HR: 2.54, P < 0.001), obstructive one-vessel (HR: 9.15, P < 0.001), two-vessel (HR: 15.00, P < 0.001), or three-vessel or left main (HR: 24.53, P < 0.001) CAD. Among patients stratified by age

Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value= 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. [ABSTRACT FROM AUTHOR]

Aims Patients hospitalized for heart failure (HF) are at high risk for 30-day readmission. This study sought to examine the timings and causes of readmission within 30 days of an HF hospitalization. Methods and results Timing and cause of readmission in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure) trial were assessed. Early and late readmissions were defined as admissions occurring within 0-7 days and 8-30 days post-discharge, respectively. Patients who died in hospital or remained hospitalized at day 30 post-randomization were excluded. Patients were compared by timing and cause of readmission. Logistic and Cox proportional hazards regression analyses were used to identify independent risk factors for early vs. late readmission and associations with 180-day outcomes. Of the 6584 patients (92%) in the ASCEND-HF population included in this analysis, 751 patients (11%) were readmitted within 30 days for any cause. Overall, 54% of readmissions were for non-HF causes. The median time to rehospitalization was 11 days (interquartile range: 6-18 days) and 33% of rehospitalizations occurred by day 7. Rehospitalization within 30 days was independently associated with increased risk for 180-day all-cause death [hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.93-2.94; P <0.001]. Risk for 180-day all-cause death did not differ according to early vs. late readmission (HR 0.99, 95% CI 0.67-1.45; P =0.94). Conclusions In this hospitalized HF trial population, a significant majority of 30-day readmissions were for non-HF causes and one-third of readmissions occurred in the first 7 days. Early and late readmissions within the 30-day timeframe were associated with similarly increased risk for death. Continued efforts to optimize multidisciplinary transitional care are warranted to improve rates of early readmission. [ABSTRACT FROM AUTHOR]