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Background: Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina.Objectives: This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD.Methods: We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long-term clinical outcomes.Results: At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01).Conclusions: Angina does not predict all-cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Background: Patients with left bundle branch block (LBBB) often respond to cardiac resynchronization therapy (CRT) with left ventricular ejection fraction (LVEF) improvement. Guideline-directed medical therapy (GDMT), not CRT, is first-line therapy for patients with reduced LVEF with LBBB. However, there are little data on how patients with reduced LVEF and LBBB respond to GDMT.Objectives: This study examined patients with cardiomyopathy and sought to assess rates of LVEF improvement for patients with LBBB compared to other QRS morphologies.Methods: Using data from the Duke Echocardiography Laboratory Database, the study identified patients with baseline electrocardiography and LVEF ≤35% who had a follow-up LVEF 3 to 6 months later. The study excluded patients with severe valve disease, a cardiac device, left ventricular assist device, or heart transplant. QRS morphology was classified as LBBB, QRS duration <120 ms (narrow QRS duration), or a wide QRS duration ≥120 ms but not LBBB. Analysis of variance testing compared mean change in LVEF among the 3 groups with adjustment for significant comorbidities and GDMT.Results: There were 659 patients that met the criteria: 111 LBBB (17%), 59 wide QRS duration ≥120 ms but not LBBB (9%), and 489 narrow QRS duration (74%). Adjusted mean increase in LVEF over 3 to 6 months in the 3 groups was 2.03%, 5.28%, and 8.00%, respectively (p < 0.0001). Results were similar when adjusted for interim revascularization and myocardial infarction. Comparison of mean LVEF improvement between patients with LBBB on GDMT and those not on GDMT showed virtually no difference (3.50% vs. 3.44%). The combined endpoint of heart failure hospitalization or mortality was highest for patients with LBBB.Conclusions: LBBB is associated with a smaller degree of LVEF improvement compared with other QRS morphologies, even with GDMT. Some patients with LBBB may benefit from CRT earlier than guidelines currently recommend. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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 &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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 &y& Elsevier]

Objectives: The aim of this study was to determine the diagnostic performance of a new method for quantifying fractional flow reserve (FFR) with computational fluid dynamics (CFD) applied to coronary computed tomography angiography (CCTA) data in patients with suspected or known coronary artery disease (CAD). Background: Measurement of FFR during invasive coronary angiography is the gold standard for identifying coronary artery lesions that cause ischemia and improves clinical decision-making for revascularization. Computation of FFR from CCTA data (FFR(CT)) provides a noninvasive method for identifying ischemia-causing stenosis; however, the diagnostic performance of this new method is unknown. Methods: Computation of FFR from CCTA data was performed on 159 vessels in 103 patients undergoing CCTA, invasive coronary angiography, and FFR. Independent core laboratories determined FFR(CT) and CAD stenosis severity by CCTA. Ischemia was defined by an FFR(CT) and FFR ≤0.80, and anatomically obstructive CAD was defined as a CCTA with stenosis ≥50%. Diagnostic performance of FFR(CT) and CCTA stenosis was assessed with invasive FFR as the reference standard. Results: Fifty-six percent of patients had ≥1 vessel with FFR ≤0.80. On a per-vessel basis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 84.3%, 87.9%, 82.2%, 73.9%, 92.2%, respectively, for FFR(CT) and were 58.5%, 91.4%, 39.6%, 46.5%, 88.9%, respectively, for CCTA stenosis. The area under the receiver-operator characteristics curve was 0.90 for FFR(CT) and 0.75 for CCTA (p = 0.001). The FFR(CT) and FFR were well correlated (r = 0.717, p < 0.001) with a slight underestimation by FFR(CT) (0.022 ± 0.116, p = 0.016). Conclusions: Noninvasive FFR derived from CCTA is a novel method with high diagnostic performance for the detection and exclusion of coronary lesions that cause ischemia. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the diagnostic performance of a new method for quantifying fractional flow reserve (FFR) with computational fluid dynamics (CFD) applied to coronary computed tomography angiography (CCTA) data in patients with suspected or known coronary artery disease (CAD). Background: Measurement of FFR during invasive coronary angiography is the gold standard for identifying coronary artery lesions that cause ischemia and improves clinical decision-making for revascularization. Computation of FFR from CCTA data (FFRCT) provides a noninvasive method for identifying ischemia-causing stenosis; however, the diagnostic performance of this new method is unknown. Methods: Computation of FFR from CCTA data was performed on 159 vessels in 103 patients undergoing CCTA, invasive coronary angiography, and FFR. Independent core laboratories determined FFRCT and CAD stenosis severity by CCTA. Ischemia was defined by an FFRCT and FFR ≤0.80, and anatomically obstructive CAD was defined as a CCTA with stenosis ≥50%. Diagnostic performance of FFRCT and CCTA stenosis was assessed with invasive FFR as the reference standard. Results: Fifty-six percent of patients had ≥1 vessel with FFR ≤0.80. On a per-vessel basis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 84.3%, 87.9%, 82.2%, 73.9%, 92.2%, respectively, for FFRCT and were 58.5%, 91.4%, 39.6%, 46.5%, 88.9%, respectively, for CCTA stenosis. The area under the receiver-operator characteristics curve was 0.90 for FFRCT and 0.75 for CCTA (p = 0.001). The FFRCT and FFR were well correlated (r = 0.717, p < 0.001) with a slight underestimation by FFRCT (0.022 ± 0.116, p = 0.016). Conclusions: Noninvasive FFR derived from CCTA is a novel method with high diagnostic performance for the detection and exclusion of coronary lesions that cause ischemia. (The Diagnosis of ISChemia-Causing Stenoses Obtained Via NoninvasivE FRactional FLOW Reserve; NCT01189331) [ABSTRACT FROM AUTHOR]