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Purpose: Contrast-induced acute kidney injury is a prominent complication following cardiac catheterization, though the risk has progressively decreased in recent times with appropriate risk stratification and use of safer contrast agents. Despite data supporting further lowering of risk with the iso-osmolar agent, iodixanol, uptake has lagged, perhaps due to increased upfront cost of this agent. We undertook an economic analysis to estimate the cost-effectiveness of a strategy utilizing iodixanol compared to using a low-osmolar contrast agent., Methods: We created a Markov model to evaluate the two strategies, and included a differential relative risk of contrast-induced acute kidney injury, based on a systematic review of the literature. Downstream clinical events, including need for dialysis and mortality, were modeled using data from existing published literature. A third-party payer perspective was utilized for the analysis and presentation of the primary economic analysis., Results: The strategy of using iodixanol dominated in both the low-risk and high-risk base case analyses. However, the difference was quite small in the low-risk scenario (lifetime cost: C$678,034 vs. C$678,059 and life expectancy: 19.80 vs. 19.72 years). The difference was more marked (life expectancy 15.65 vs. 14.15 years and cost C$680,989 vs. C$682,023) in the high-risk case analysis. This was robust across most of the variables tested in sensitivity analyses., Conclusion: The use of iodixanol, compared with low-osmolar contrast agents, for cardiac catheterization, results in a small benefit clinical outcomes, and in a savings in direct healthcare costs. Overall, our analysis supports the use of iodixanol for cardiac catheterization, especially in patients at high risk of acute kidney injury.

Noninvasive cardiac imaging is widely used for the diagnosis and management of cardiac patients. The increasing demand for cardiac imaging begins to exceed the number of available interpreting physicians, leaving less time to interpret studies. In addition, the busy clinician is facing the increasingly daunting task of keeping abreast of current medical advancements and the ongoing changes in disease diagnosis and therapy. Committing to memory and recalling such large volumes of information is challenging and is responsible for difficulties in adopting the rapid changes in imaging practice, and is likely partially responsible for errors in patient diagnosis and management. Diagnostic errors rank high in the cause of death in the United States, and are more common than any other medical error and are responsible for most malpractice claims. Most of these errors are related to cognitive errors. The use of artificial intelligence systems that can serve as complementary methods to assist humans with decision making can potentially prevent these errors. The past decades witnessed the development and integration of these tools, which can assist physicians with image interpretation. These tools work to optimize image quality for better visualization and accompany all imaging modalities, starting from patient selection for the appropriate test, patient preparation, image acquisition, processing, and finally interpretation. Current and future directions for technologies that support cardiac imaging physicians are discussed in this review., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Heart disease continues to be the leading cause of death, and the prevalence of coronary artery disease is expected to increase as the population ages. It is important to understand the clinical utility of medical tests, or its lack thereof, in the aging population. The objective of this study was to understand the incremental prognostic value of positron emission tomographic (PET) myocardial perfusion imaging in the elderly (≥85 years of age)., Methods and Results: A total of 3343 patients enrolled in a multicenter observational PET registry were analyzed. Participants were initially divided into 3 age categories: 65 to 74.9, 75 to 84.9, and ≥85 years of age and followed for all-cause death. Median follow-up time was 3 years. Of the total patient population, 248 patients (49% men) were ≥85 years old. When compared with younger patients, individuals ≥85 years had a higher prevalence of hypertension (79%) and a lower incidence of dyslipidemia (54%) and diabetes mellitus (24%). On multivariable analysis, %left ventricular stress defect and %left ventricular ischemia were predictors of patient outcome for those <85 years of age but was not statistically significant in those ≥85 years of age. The prognostic value of PET (%left ventricular stress defect and %left ventricular ischemia) appeared to decrease with advancing age., Conclusions: The elderly is a high-risk population irrespective of PET myocardial perfusion imaging results, and incremental prognostic value of PET myocardial perfusion imaging appears to wane in those ≥85 years of age. Although PET myocardial perfusion imaging may be diagnostically useful in the elderly, its prognostic value in this population requires further evaluation., (© 2018 American Heart Association, Inc.)

Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden., Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS., Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA-evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs)., Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm 3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm 3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP., Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden., (Published by Elsevier Inc.)

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: 18-41 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 <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.

Introduction: Machine learning (ML) is a field in computer science that demonstrated to effectively integrate clinical and imaging data for the creation of prognostic scores. The current study investigated whether a ML score, incorporating only the 16 segment coronary tree information derived from coronary computed tomography angiography (CCTA), provides enhanced risk stratification compared with current CCTA based risk scores., Methods: From the multi-center CONFIRM registry, patients were included with complete CCTA risk score information and ≥3 year follow-up for myocardial infarction and death (primary endpoint). Patients with prior coronary artery disease were excluded. Conventional CCTA risk scores (conventional CCTA approach, segment involvement score, duke prognostic index, segment stenosis score, and the Leaman risk score) and a score created using ML were compared for the area under the receiver operating characteristic curve (AUC). Only 16 segment based coronary stenosis (0%, 1-24%, 25-49%, 50-69%, 70-99% and 100%) and composition (calcified, mixed and non-calcified plaque) were provided to the ML model. A boosted ensemble algorithm (extreme gradient boosting; XGBoost) was used and the entire data was randomly split into a training set (80%) and testing set (20%). First, tuned hyperparameters were used to generate a trained model from the training data set (80% of data). Second, the performance of this trained model was independently tested on the unseen test set (20% of data)., Results: In total, 8844 patients (mean age 58.0 ± 11.5 years, 57.7% male) were included. During a mean follow-up time of 4.6 ± 1.5 years, 609 events occurred (6.9%). No CAD was observed in 48.7% (3.5% event), non-obstructive CAD in 31.8% (6.8% event), and obstructive CAD in 19.5% (15.6% event). Discrimination of events as expressed by AUC was significantly better for the ML based approach (0.771) vs the other scores (ranging from 0.685 to 0.701), P < 0.001. Net reclassification improvement analysis showed that the improved risk stratification was the result of down-classification of risk among patients that did not experience events (non-events)., Conclusion: A risk score created by a ML based algorithm, that utilizes standard 16 coronary segment stenosis and composition information derived from detailed CCTA reading, has greater prognostic accuracy than current CCTA integrated risk scores. These findings indicate that a ML based algorithm can improve the integration of CCTA derived plaque information to improve risk stratification., (Published by Elsevier Inc.)

Cardiac computed tomography angiography (CCTA) is a noninvasive imaging technique that has been rapidly adopted into clinical practice. Over the past decade, technological advances have improved CCTA accuracy, and there is an increasing amount of data supporting its prognostic value in the assessment of coronary artery disease. Recently, "appropriate use criteria" has been used as a tool to minimize inappropriate testing and reduce patient exposure to unnecessary risk and inconclusive studies. This review will summarize the appropriate uses of CCTA in patients before and after cardiac surgery. Although the most common indication for CCTA is assessment of patency of native coronary arteries, other potential perioperative uses (eg, assessment of congenital heart disease, valvular heart disease, pericardial disease, myocardial disease, cardiac anatomy, bypass grafts, aortic disease, and cardiac masses) will be reviewed.

Background: Prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) is well established. There is paucity of data on how the prognostic value of PET relates to the hemodynamic response to vasodilator stress. We hypothesize that inadequate hemodynamic response will affect the prognostic value of PET MPI., Methods and Results: Using a multicenter rubidium (Rb)-82 PET registry, 3406 patients who underwent a clinically indicated rest/stress PET MPI with a vasodilator agent were analyzed. Patients were categorized as, "responders" [increase in heart rate ≥ 10 beats per minute (bpm) and decrease in systolic blood pressure (SBP) ≥10 mmHg], "partial responders" (either a change in HR or SBP), and "non-responders" (no change in HR or SBP). Primary outcome was all-cause death (ACD), and secondary outcome was cardiac death (CD). Ischemic burden was measured using summed stress score (SSS) and % left ventricular (LV) ischemia. After a median follow-up of 1.68 years (interquartile range = 1.17- 2.55), there were 7.9% (n = 270) ACD and 2.6% (n = 54) CD. Responders with a normal PET MPI had an annualized event rate (AER) of 1.22% (SSS of 0-3) and 1.58% (% LV ischemia = 0). Partial and non-responders had higher AER with worsening levels of ischemic burden. In the presence of severe SSS ≥12 and LV ischemia of ≥10%, partial responders had an AER of 10.79% and 10.36%, compared to non-responders with an AER of 19.4% and 12.43%, respectively. Patient classification was improved when SSS was added to a model containing clinical variables (NRI: 42%, p < 0.001) and responder category was added (NRI: 61%, p < 0.001). The model including clinical variables, SSS and hemodynamic response has good discrimination ability (Harrell C statistics: 0.77 [0.74-0.80])., Conclusion: Hemodynamic response during a vasodilator Rb-82 PET MPI is predictive of ACD. Partial and non-responders may require additional risk stratification leading to altered patient management.

Aim: The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown., Methods and Results: From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all)., Conclusions: Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

Purpose: Cardiac imaging expenditures have come under scrutiny, and a focus on appropriate use criteria (AUC) has arisen to ensure cost-effective resource utilization. Although AUC has been developed by clinical experts, it has not undergone rigorous quality assurance testing to ensure that inappropriate indications for testing yield little clinical benefit. The objective of the study was to evaluate the potential incremental prognostic value of coronary computed tomographic angiography (CCTA) in the different AUC categories., Materials and Methods: Consecutive patients enrolled into a cardiac CT Registry were collated. Patient indications were reviewed and based on the 2010 AUC (appropriate, uncertain, and inappropriate). Patients were followed-up for death, myocardial infarction (MI), and late revascularization, with the primary composite endpoint being cardiac death, nonfatal MI, and late revascularization. The prognostic value of CCTA over clinical variables in each of the AUC categories was assessed., Results: Indications for CCTA were appropriate, uncertain, and inappropriate in 1284 (66.5%), 312 (16.2%), and 334 (17.3%) patients, respectively. Rates of all-cause of death, cardiac death, nonfatal MI, and late revascularization were similar across patients with appropriate, uncertain, and inappropriate indications for CCTA. Moreover, in each AUC category, CCTA had incremental prognostic value over a routine clinical risk score (National Cholesterol Education Program) with hazard ratios of 9.98, 7.39, and 5.61., Conclusions: CCTA has incremental prognostic value in all AUC categories, even when the reason for the study was deemed "inappropriate." This suggests that CCTA may still have clinical value in "inappropriate" indications and that further quality assurance AUC studies are needed.

Background: Contrast-induced acute kidney injury (CI-AKI) is defined as worsening of renal function after the administration of iodinated contrast material. In patients with cardiovascular disease, kidney disease, and/or diabetes, renin-angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics, and metformin can increase the risk of CI-AKI when undergoing contrast imaging. Despite CI-AKI being the leading iatrogenic cause of acute kidney injury, there is a lack of sufficient scientific evidence supporting which drugs should be stopped, when they should be stopped, and when they should be resumed. The purpose of this systematic review is to assess (1) the effect of withholding medication before contrast procedures on the risk of CI-AKI and other clinical outcomes and (2) the incidence of adverse events occurring after withholding these drugs prior to contrast procedures. This protocol has been registered with PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display&#95;record.asp?ID=CRD42016033178 ., Methods: An information specialist will assist in searching MEDLINE, Embase, and the Cochrane Library databases to identify randomized controlled trials, observational studies, case reports, and case series. Relevant abstracts from professional society meetings and web-based registries of clinical trials will also be included. Studies included will compare patients aged ≥ 18 years instructed to continue taking the drugs of interest and those advised to stop taking them before undergoing contrast procedures. If these drugs are not withheld prior to contrast procedures, the studies must compare patients who are administered these drugs and those who are not before undergoing contrast procedures. Two reviewers will independently screen the titles and abstracts of the studies obtained from the search using pre-defined inclusion criteria and will then extract data from the full texts of selected studies. The quality of the studies will be assessed by two independent reviewers using the Cochrane Risk of Bias 2.0 tool for randomized trials and the Newcastle-Ottawa Scale for observational studies., Discussion: This systematic review will provide a synthesis of current evidence on the discontinuation of drugs prior to contrast procedures and its effect on CI-AKI and other clinical outcomes. These findings will provide clinicians with guidelines and serve as a strong research base for future studies in this field., Systematic Review Registration: PROSPERO CRD42016033178.

Background: Infective endocarditis (IE) is a serious, potentially life-threatening condition. Currently, the modified Duke criteria is used to assist with the diagnosis of IE, but it can still remain difficult. Growing data supports the potential use of molecular imaging to assist in the diagnosis of IE. Our objective was to understand the potential utility of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography-computed tomography (PET-CT), 67 Ga citrate and radiolabeled white blood cell (WBC) scintigraphy in the diagnosis of IE., Methods and Results: A systematic review of the literature and meta-analysis on the use of all 3 modalities in IE was conducted. The literature search identified 2753 articles. A total of 14 studies met the inclusion criteria (10 for 18 F-FDG, 3 for WBC and 1 for both modalities). No 67 Ga citrate study met the inclusion criteria. Pooled sensitivity of 18 F-FDG studies with adequate cardiac preparation for the diagnosis of IE was 81% (95% CI, 73%-86%) and pooled specificity was 85% (95% CI, 78%-91%). There was good overall accuracy with an area under the curve (AUC) of 0.897. Pooled sensitivity of WBC for the diagnosis of IE was 86% (95% CI, 77%-92%) and pooled specificity was 97% (95% CI, 92%-99%). The overall accuracy of WBC was excellent with an AUC of 0.957., Conclusions: Both 18 F-FDG and WBC have good sensitivity, specificity and accuracy for the diagnosis of IE. Both modalities are useful in the investigation of IE, and should be considered in cases where the diagnosis is uncertain., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: The identification of coronary artery calcification (CAC) detected coincidentally on chest CT exams could assist in cardiovascular risk assessment but may not be reported consistently on clinical studies. Cardiovascular risk factor stratification is important to predict short term cardiac events during cancer therapy and long term cardiac event free survival in cancer patients. We sought to determine the prevalence of CAC and clinical reporting rates in a cohort of cancer patients at high risk of cancer therapy related cardiac events., Methods: 408 Breast cancer patients who were referred to a cardiac oncology clinic were screened. Inclusion criteria included having had a CT chest and the absence of known coronary disease. Among those screened 263 patients were included in the study., Results: CAC was identified in 70 patients (26%). CAC was reported in 18% of studies. The reporting rates of CAC increased with the extent of coronary calcification ( p  < 0.01) and increased during the period of the study ( p  < 0.05)., Conclusions: CAC was commonly detected on chest CT studies in this observational study of breast cancer patients at high risk of cardiac oncology events. The presence of CAC was often not reported clinically but reporting rates have increased over time. Recent SCCT/STR guidelines recommend reporting the presence of CAC on routine chest CT scans in recognition of the importance of CAC as a predictor of cardiovascular events. Reporting of CAC on chest CTs may help to further risk stratify breast cancer patients and improve cardiovascular outcomes in this vulnerable population.

Objectives: This 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., Background: Clinical 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., Methods: In 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., Results: Cumulative 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., Conclusions: CAD-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., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A drop in blood pressure (BP) or blunted BP response is an established high-risk marker during exercise myocardial perfusion imaging (MPI); however, data are sparse regarding the prognostic value of BP response in patients undergoing vasodilator stress rubidium-82 (Rb-82) Positron Emission Tomography (PET) MPI., Methods and Results: From the PET Prognosis Multicenter Registry, a cohort of 3413 patients underwent vasodilator stress Rb-82 PET MPI with dipyridamole or adenosine. We used multivariable Cox proportional hazard regression to analyze the association with mortality of four BP variables: stress minus rest systolic BP (∆SBP), stress minus rest diastolic BP (∆DBP), resting systolic BP (rSBP), and resting diastolic BP (rDBP). Covariates that had univariate P values <.10 were entered into the multivariable model. After median 1.7 years follow-up, 270 patients died. In univariate analyses, ∆SBP (P = .082), rSBP (P = .008), and rDBP (P < .001) were of potential prognostic value (P < .10), but ∆DBP was not (P = .96). After adjustment for other clinical and MPI variables, ∆SBP no longer independently predicted mortality (P = .082); only lower rSBP (P = .026) and lower rDBP (P = .045) remained independently prognostic., Conclusions: In patients undergoing vasodilator stress MPI, only lower resting BP is an independent predictor of mortality along with other clinical and MPI variables; BP response does not appear to add to risk stratification in these patients.

Opinion Statement: Acute coronary syndromes are most often the result of vulnerable atherosclerotic plaque events. Plaques events occur when intimal fibroatheroma in the coronary artery wall becomes vulnerable to erosion or rupture. Such vulnerable plaques can be distinguished from quiescent atheroma by features that have been defined through histopathology and invasive imaging. A challenge for coronary CT angiography has been to identify vulnerable plaques non-invasively. Were this possible, CT angiography could offer comprehensive vessel assessment including stenosis severity and plaque characteristics with the hope of reducing acute coronary events through timely intervention. Over the past decade, advances in invasive imaging techniques have enabled unstable coronary plaques to be accessed more readily. In this fashion it has been possible to correlate invasive appearances to CT angiographic findings in an unprecedented manner. Several CT defined plaque characteristic have now been described to reliably identify unstable plaques. Retrospective studies have demonstrated the utility of these plaque features to predict future acute coronary events. If these can be confirmed in prospective studies, the intrinsic benefits of non-invasive imaging will position coronary CT angiography firmly in our armamentarium to image coronary arteries and help prevent acute coronary events.

Background: Appropriate Use Criteria (AUC) guidelines for cardiac computed tomography (CCT) were developed to limit testing to reasonable clinical settings. However, significant testing is still done for inappropriate indications. This study investigates the impact of AUC on evaluability of CCT to determine if inappropriate tests result in a greater proportion of nondiagnostic results., Methods: Investigators reviewed the medical records of 2417 consecutive patients who underwent CCT at the University of Ottawa Heart Institute. We applied the 2010 AUC and classified them as appropriate, inappropriate, or uncertain. Unclassifiable tests, as well as those with uncertain appropriateness, were excluded from the final analysis. Cardiac computed tomography results were classified as diagnostic if (1) all coronary segments were visualized, evaluable, and without obstructive stenosis; or (2) obstructive coronary artery disease with greater than 50% diameter stenosis in at least 1 coronary artery. All other test results were considered nondiagnostic., Results: Of the 1984 patients included in the final analysis, 1522 patients (76.7%) had indications that were appropriate, whereas the remaining 462 (23.3%) were inappropriate. Inappropriate tests resulted in a higher rate of nondiagnostic results compared with appropriate CCT (9.0% vs 6.2%, P = 0.034). Inappropriate tests also had significantly more studies with nonevaluable segments than appropriate tests (24.5% vs 16.4%, P < 0.001) and were more likely to reveal obstructive coronary disease than appropriate CCT (50.5% vs 32.7%, P < 0.001)., Conclusions: Cardiac computed tomography done for inappropriate indications may be associated with lower diagnostic yield and could impact future downstream resource utilization and health care costs.

Background: Coronary artery disease is a leading killer of women. Arterial stiffness predicts myocardial infarction, and postmenopausal women have lower arterial compliance (AC) than men. We hypothesized that lower AC would be associated with greater burden of coronary artery plaque and calcification, and that these associations would be stronger in women than men., Methods and Results: We evaluated 3639 consecutive adults without coronary artery disease history who had coronary computed tomography between 2006 and 2014. Coronary artery calcification was calculated using the Agatston method. Plaque extent was assessed by the number of arterial segments with visible plaque divided by the number of visualized segments ×100 (percent plaque score). Indexed AC was calculated as stroke volume index/central pulse pressure. We used step-wise multivariable linear regression to assess associations of log indexed AC with log (percent plaque score+1) and log (coronary artery calcification+1). Sex-specific models were performed if the interaction sex×AC was significant. Mean age was 57±11 years, 53% were men, and 71% were hypertensive. Interaction term sex×AC was significant for both models ( P =0.008 for percent plaque score and 0.022 for coronary artery calcification). Lower indexed AC was associated with higher percent plaque score and coronary artery calcification in women (β±SE: -0.231±0.113, P =0.042 and -0.334±0.166, P =0.044, respectively), but not in men (β±SE: -0.062±0.104, P =0.551 and 0.114±0.173, P =0.510, respectively)., Conclusions: Lower AC is associated with greater burden of coronary artery plaque and calcification in women, but not in men. Our findings highlight low AC as a correlate of more-advanced coronary artery disease and as a potential link to the worse cardiovascular outcomes in women., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined., Methods and Results: In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P <0.0001); men (24.6% versus 18.2%; P <0.0001). A significant interaction existed between sex and LM status for the composite outcome ( P =0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P =0.005) but not in men (adjusted hazard ratio, 0.98, P =0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P =0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque., Conclusion: Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts., (© 2017 American Heart Association, Inc.)

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., (© 2017 American Heart Association, Inc.)

Background: The segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (CTA). We sought to evaluate by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD)., Methods: Electronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models., Results: Eleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I 2  = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I 2  = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I 2  = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I 2  = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I 2  = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I 2  = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I 2  = 89.8%, p = 0.029), respectively., Conclusion: Despite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Ticagrelor is a P2Y 12 receptor inhibitor used in acute coronary syndromes to reduce platelet activity and to decrease thrombus formation. Ticagrelor is associated with a reduction in mortality incremental to that observed with clopidogrel, potentially related to its non-antiplatelet effects. Evidence from animal models indicates that ticagrelor potentiates adenosine-induced myocardial blood flow (MBF) increases. We investigated MBF at rest and during adenosine-induced hyperemia in patients with stable coronary artery disease treated with ticagrelor versus clopidogrel., Methods and Results: This randomized double-blinded crossover study included 22 patients who received therapeutic interventions of ticagrelor 90 mg orally twice a day for 10 days and clopidogrel 75 mg orally once a day for 10 days, with a washout period of at least 10 days between the treatments. Global and regional MBF and myocardial flow reserve were measured using rubidium 82 positron emission tomography/computed tomography at baseline and during intermediate- and high-dose adenosine. Global MBF was significantly greater with ticagrelor versus clopidogrel (1.28±0.55 versus 1.13±0.47 mL/min per gram, P =0.002) at intermediate-dose adenosine and not different at baseline (0.65±0.19 versus 0.60±0.15 mL/min per gram, P =0.084) and at high-dose adenosine (1.64±0.40 versus 1.61±0.19 mL/min per gram, P =0.53). In regions with impaired myocardial flow reserve (<2.5), MBF was greater with ticagrelor compared with clopidogrel during intermediate and high doses of adenosine ( P <0.0001), whereas the differences were not significant at baseline., Conclusions: Ticagrelor potentiates global and regional adenosine-induced MBF increases in patients with stable coronary artery disease. This effect may contribute to the incremental mortality benefit compared with clopidogrel., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01894789., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aims: To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA)., Methods and Results: We 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., Conclusions: Early 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., (© The Author 2017 Published on behalf of the European Society of Cardiology.)

Background The accuracy of coronary computed tomography angiography (CCTA) is sub-optimal in patients with coronary stents. Methods that can increase its diagnostic accuracy are desirable. Objective A proof-of-concept study was undertaken to determine if corrected coronary opacification (CCO) differences can improve the accuracy of CCTA in stented coronary arteries. Methods PCI patients who underwent both CCTA and invasive coronary angiography (ICA) within 3 months were analyzed. Coronary luminal attenuation values (normalized to the aorta) were measured proximally and distally to coronary stents. CCO differences were evaluated for ability to predict (i) stenosis on invasive angiography, (ii) abnormal resting coronary flow as measured by the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), and (iii) the combination of abnormal resting flow and significant stenosis on invasive angiography. Results Twenty-nine stented coronary arteries (n = 25, mean age =61.4 years, men =80.0%) were assessed. In stented coronary vessels, CCO identified stenosis (≥ 70%) with an area under the curve of 0.767 (P = 0.021). CCO predicted abnormal resting coronary flow with high accuracy (AUC =0.867, P = 0.002). Combined CCTA/CCO identified both abnormal cTFC and stenosis ≥70% on ICA (functionally significant stenosis) with diagnostic accuracy of 92.3%. In contrast, CCTA visual assessment alone had lower diagnostic accuracy of 66.7% for identifying functionally significant stenosis. Conclusion CCO differences are predictive of abnormal resting flow and consequently, in-stent restenosis. Incorporation of this technique may improve the specificity of CCTA in PCI patients.

Background: Downstream resource utilization and its impact on outcomes after a canceled CCTA have not been well studied. We sought to understand downstream resource utilization and patient outcomes after canceled CCTA., Methods and Results: Consecutive patients were prospectively enrolled into an institutional cardiac CT registry. Patients who had the CCTA study canceled because of severe coronary calcification were followed for downstream resource utilization and the composite of all-cause mortality and non-fatal myocardial infarction (MI). 463 patients had their CCTA canceled due to severe coronary calcification and follow-up was available for 453 (97.8%) patients (median follow-up=36.0months). There were a total of 62 events (41 all-cause deaths and 21 non-fatal MI) with an annualized event rate of 4%. Three hundred and twenty patients underwent downstream CAD (ICA or MPI or EST) investigations. Age, NCEP/ATP III risk, beta-blocker use, Agatston and downstream CAD testing were associated with the primary outcome. There were fewer events in those that received downstream CAD testing (30 (9.7%) versus 32 (22.4%)). The annualized event rates for those who did and did not receive downstream CAD testing were 2.8% and 6.2%, respectively. Multivariable analysis confirmed that downstream CAD testing was an independent predictor of event-free survival and that the absence of additional CAD testing was associated with worse outcome (HR: 2.58 (95% CI: 1.54-4.31))., Conclusions: Patients with canceled CCTA due to severe and/or extensive CAC have high rates of death and non-fatal MI. The use of additional CAD testing appears to be associated with improved outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Cardiac sarcoidosis (CS) is a cause of conduction system disease (CSD). (18)F-Fluorodeoxyglucose-positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) are used for detection of CS. The relative diagnostic value of these has not been well studied. The aim was to compare these imaging modalities in this population., Methods: We recruited steroid-naive patients with newly diagnosed CSD due to CS. All CS patients underwent both imaging studies within 12 weeks of each other. Patients were classified into two groups: group A with chronic mild CSD (right bundle branch block and/or axis deviation), and group B with new-onset atrioventricular block (AVB, Mobitz type II or third-degree AVB)., Results: Thirty patients were included. Positive findings on both imaging studies were seen in 72 % of patients (13/18) in group A and in 58 % of patients (7/12) in group B. The remainder (28 %) of the patients in group A were positive only on CMR. Of the patients in group B, 8 % were positive only on CMR and 33 % were positive only on FDG PET. Patients in group A were more likely to be positive only on CMR, and patients in group B were more likely to be positive only on FDG PET (p = 0.02). Patients in group B positive only on FDG PET underwent CMR earlier relative to their symptomatology than patients positive only on CMR (median 7.0, IQR 1.5 - 34.3, vs. 72.0, IQR 25.0 - 79.5 days; p = 0.03)., Conclusion: The number of positive FDG PET and CMR studies was different in patients with CSD depending on their clinical presentation. This study demonstrated that CMR can adequately detect cardiac involvement associated with chronic mild CSD. In patients presenting with new-onset AVB and a negative CMR study, FDG PET may be useful for detecting cardiac involvement due to CS.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)