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Background: Sexual dimorphism in the manifestation of coronary artery disease (CAD) has unleashed a call to reconsider cardiovascular risk assessment. Alterations of bone mineral density (BMD) have been associated with congestive heart failure and appear to be modified by sex. However, the sex-specific association between BMD, myocardial perfusion, and cardiovascular outcomes is currently unknown., Methods: A total number of 491 patients (65.9 ± 10.7 years, 32.4% women) underwent 13 N-ammonia positron emission tomography/computed tomography for evaluation of CAD, and were tracked for major adverse cardiac events (MACEs)., Results: Event-free survival (median follow-up time of 4.3 ± 2.0 years) was significantly reduced in patients with low (≤ 100 Hounsfield units) compared to those with higher BMD (log-rank P = .037). Accordingly, reduced BMD was chosen as significant predictor of MACE in a fully adjusted proportional hazards regression model (P = .015). Further, a first-order interaction term consisting of sex and BMD was statistically significant (P = .007). BMD was significantly lower in patients with abnormal myocardial perfusion or impaired left ventricular ejection fraction (P < .05). This difference, however, was noticed in men, but not in women., Conclusions: The association between low BMD and cardiovascular disease is sex dependent. Our data suggest that quantification of BMD during myocardial perfusion imaging for evaluation of CAD may be particularly useful in men.

Objectives: To evaluate the diagnostic performance of a deep learning algorithm for automated detection of small 18 F-FDG-avid pulmonary nodules in PET scans, and to assess whether novel block sequential regularized expectation maximization (BSREM) reconstruction affects detection accuracy as compared to ordered subset expectation maximization (OSEM) reconstruction., Methods: Fifty-seven patients with 92 18 F-FDG-avid pulmonary nodules (all ≤ 2 cm) undergoing PET/CT for oncological (re-)staging were retrospectively included and a total of 8824 PET images of the lungs were extracted using OSEM and BSREM reconstruction. Per-slice and per-nodule sensitivity of a deep learning algorithm was assessed, with an expert readout by a radiologist/nuclear medicine physician serving as standard of reference. Receiver-operator characteristic (ROC) curve of OSEM and BSREM were assessed and the areas under the ROC curve (AUC) were compared. A maximum standardized uptake value (SUV max )-based sensitivity analysis and a size-based sensitivity analysis with subgroups defined by nodule size was performed., Results: The AUC of the deep learning algorithm for nodule detection using OSEM reconstruction was 0.796 (CI 95%; 0.772-0.869), and 0.848 (CI 95%; 0.828-0.869) using BSREM reconstruction. The AUC was significantly higher for BSREM compared to OSEM (p = 0.001). On a per-slice analysis, sensitivity and specificity were 66.7% and 79.0% for OSEM, and 69.2% and 84.5% for BSREM. On a per-nodule analysis, the overall sensitivity of OSEM was 81.5% compared to 87.0% for BSREM., Conclusions: Our results suggest that machine learning algorithms may aid detection of small 18 F-FDG-avid pulmonary nodules in clinical PET/CT. AI performed significantly better on images with BSREM than OSEM., Key Points: • The diagnostic value of deep learning for detecting small lung nodules (≤ 2 cm) in PET images using BSREM and OSEM reconstruction was assessed. • BSREM yields higher SUV max of small pulmonary nodules as compared to OSEM reconstruction. • The use of BSREM translates into a higher detectability of small pulmonary nodules in PET images as assessed with artificial intelligence.

Coronary computed tomography angiography (CCTA) provides critical prognostic information on plaque burden and stenosis severity of coronary arteries. We aimed to investigate the long-term prognostic value of coronary artery volume per myocardial mass as a potential new imaging parameter. Consecutive patients with suspected coronary artery disease (CAD) were included. Coronary artery volume index (CAVi) was defined as volume over myocardial mass. Additionally, obstructive CAD (≥ 70% stenosis) and segment severity score (SSS: sum of all segments scored according to lesion severity with 0 = no lesion, 1 = narrowing < 50%, 2 = stenosis 50-69% and 3 = stenosis ≥ 70%) were evaluated. Major adverse cardiovascular events (MACE) were defined as cardiac death, non-fatal myocardial infarction or revascularization. The association of CAVi with MACE was evaluated using Cox regression hazards ratios (HR) and Kaplan Meier curves. In a total of 325 patients, 36 (11.1%) patients experienced MACE during the mean follow-up of 5.4 ± 1.7 years. Patients with low-CAVi (< 27.9 mm 3 /g) experienced more MACE than patients with high-CAVI (17.2% versus 4.5%, p < 0.001, Kaplan Meier curve p = 0.001). SSS, obstructive CAD and low-CAVi were all significant predictors of MACE in univariable analysis (HR 1.14, 95% CI 1.09-1.19, p < 0.001; HR 5.51, 95% CI 2.86-10.60, p < 0.001; and HR 3.79, 95% CI 1.66-8.65, p = 0.002, respectively). CAVi maintained significant association with MACE when adjusted to SSS (CAVi HR 2.43, 95% CI 1.02-5.75, p = 0.04) or obstructive CAD (CAVi HR 2.4, 95% CI 1.002-5.75, p = 0.049). CAVi could further risk stratify patients without obstructive CAD when stratifying patients according to obstructive CAD (Kaplan-Meier curve p = 0.049). CAVi is a novel CCTA-derived imaging parameter, yielding independent prognostic value over stenosis and plaque burden.

Objective: The purpose of this study was to quantify the reduction in radiation dose achievable by using the optimal z-axis coverage in coronary computed tomography (CT) angiography (CCTA) on a latest-generation 256-slice scanner., Methods: A total of 408 scans were reviewed that were performed on a wide-range detector scanner allowing up to 16-cm z-axis coverage (adjustable in 2-cm increments). For each CCTA study, we assessed the radiation dose (ie, dose-length product and volume CT dose index) and measured the minimum z-axis coverage necessary to cover the complete cardiac anatomy. We calculated the potential radiation dose savings achievable through reduction of the z-axis coverage to the minimum necessary., Results: The majority of the CCTA scans were performed with a z-axis coverage of 16 cm (n = 285, 69.9%), followed by 14 cm (n = 121, 29.7%) and 12 cm (n = 2, 0.5%). In the group that was scanned with a collimation of 16 cm, radiation dose could have been reduced by 12.5% in 55 patients, 25% in 195 patients, and 37.5% in 33 patients when using optimal z-axis coverage for CCTA. In the group that was scanned with a collimation of 14 cm, radiation dose could have been reduced by 14.3% in 90 patients, and 28.6% in 30 patients, whereas in the group that was scanned with a collimation of 12 cm, dose could have been reduced by 16.7% in 2 patients., Conclusions: Using correct z-axis coverage in CCTA on a latest-generation 256-slice scanner yields average dose reductions of 22.0% but may be as high as 37.5%.

Background: In light of growing cardiovascular mortality rates observed in young women, sexual dimorphism in cardiac autonomic nervous control is gaining increasing attention. Heart rate responses to adenosine mirror autonomic activity and may carry important prognostic information., Methods and Results: Hemodynamic changes during adenosine stress were retrospectively analysed in a propensity-matched cohort of 1932 consecutive patients undergoing myocardial perfusion single-photon-emission computed tomography (MPI-SPECT). Heart rate (HR) and systolic blood pressure (SBP) increased during adenosine infusion (P < 0.001). The increase in SBP and HR (heart rate reserve, HRR), was significantly more pronounced in women compared with men (P < 0.05). Patients ≤ 55 years had a higher HRR compared with patients > 55 years (46.8% vs 37.5%, P = 0.015). Women ≤ 55 years with a reversible perfusion defect on MPI-SPECT exhibited the highest HRR (89.2%), while age-matched men showed a blunted HR response to adenosine (26.4%, P = 0.01). Accordingly, age and an interaction term of female sex and increased HRR were identified as significant predictors of myocardial ischemia in a multiple regression analysis (OR 1.4, 95% CI 1.02-1.9, P = 0.038)., Conclusion: HRR during adenosine infusion is influenced by age and sex. Our data suggest a stronger, sympathetic-driven, hemodynamic response to adenosine in younger women with myocardial ischemia.

Background: The applicability of ultra-low-dose computed tomography (CT) for attenuation correction (AC) of single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) remains elusive., Methods and Results: One-hundred patients underwent one-day 99m Tc-tetrofosmin stress-rest MPI and non-contrast enhanced cardiac CT with 120, 80, and 70 kilovolt peak (kVp) tube voltage and tube current of 200 milliamperes for creation of AC maps. Normalized percent myocardial uptake from SPECT-MPI using 80 kVp scans for AC showed excellent correlation vs AC from 120 kVp scans for stress [intraclass correlation (ICC) = 0.988, 95% CI = 0.986-0.989, P < .001] and rest (ICC = 0.985, 95% CI = 0.983-0.987, P < .001) with narrow Bland-Altman limits of agreement (BA-LA) (- 5.3% to 4.5% and - 5.4% to 4.4%, respectively) and minimal bias (- 0.4% and - 0.5%, respectively). Correlation of AC SPECT-MPI based on 70 vs 120 kVp scans was excellent for stress (ICC = 0.988, 95% CI = 0.986-0.989, P < .001) and rest (ICC = 0.986, 95% CI = 0.984-0.987, P < .001) with narrow BA-LA (- 5.3% to 4.4% and - 5.2% to 4.5%, respectively) and small bias (- 0.4% and - 0.3%, respectively). Mean effective radiation dose for the 120, 80 and 70 kVp scans were 0.58 ± 0.07, 0.19 ± 0.02, and 0.12 ± 0.01 mSv, respectively., Conclusions: Attenuation maps for MPI obtained from ultra-low radiation dose CT scans are interchangeable with attenuation maps from standard-dose CT while offering a substantial reduction in radiation dose exposure.

Background: The arterial switch operation (ASO) for repair of transposition of the great arteries (TGA) requires transection of the great arterial trunks and re-implantation of the coronary arteries into the neoaortic root resulting in cardiac sympathetic denervation which may affect myocardial blood flow (MBF) regulation. The aims of the present study were to evaluate sympathetic (re-)innervation in young adults after ASO and its impact on MBF., Methods: Twelve patients (age 22.5 ± 2.6 years) after ASO for TGA in the neonatal period and ten healthy controls (age 22.0 ± 1.7 years) were included. Positron emission tomography (PET) was used for measuring cardiac sympathetic innervation with [ 11 C]meta-hydroxyephedrine (mHED) and MBF with [ 15 O]H 2 O PET at rest, during adenosine stimulation, and during sympathetic stimulation with cold pressor test. Cold pressor-induced MBF response capacity was calculated as maximal global MBF over peak rate-pressure product multiplied by 10'000., Results: Global [ 11 C]mHED uptake was significantly lower in patients compared to controls (7.0 ± 2.3 versus 11.8 ± 2.1%/min, p < 0.001). Global MBF was lower in patients compared to controls at rest and during adenosine-induced hyperemia (0.66 ± 0.08 versus 0.82 ± 0.15 ml/min/g, p = 0.005; 2.23 ± 1.19 versus 3.36 ± 1.04 ml/min/g, p = 0.030, respectively). Interestingly, MBF during cold pressor test did not differ between patients and controls (0.99 ± 0.20 versus 1.07 ± 0.16 ml/min/g, p = 0.330). However, cold pressor-induced MBF response capacity was significantly lower for patients as compared to controls (1.09 ± 0.35 versus 1.44 ± 0.39 ml/g/10,000 mmHg, p = 0.040)., Conclusions: With only partial sympathetic re-innervation of the coronary arteries, maximal dilator capacity of the coronary microvasculature and cold pressor-induced MBF response capacity remain substantially impaired in young adults after ASO compared to healthy controls., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the industrialized countries. Assessment of symptomatic patients with suspected obstructive CAD is a common reason for a clinical visit. Noninvasive anatomical and functional imaging are established tools to rule-in and rule-out CAD, to assess the severity of disease and to determine the potential risk of future cardiovascular events. In this review, we discuss the updated Guidelines from the European Society of Cardiology on Chronic Coronary Syndromes and explore the different imaging modalities used in current clinical practice for the noninvasive assessment of CAD. The pros and cons of each method, especially comparing anatomical and functional testing, are presented. Furthermore we we address the practical clinical aspects in the selection of the optimal noninvasive tests according to clinical need.

Purpose: The human pathophysiology of stunned, hibernating and scarred myocardium in ischemic cardiomyopathy is a subject of controversy. While the "smart heart" theory postulates that reduced myocardial blood flow (MBF) at rest is responsible for myocytes switching to a state of hibernation, other theories suggest that a reduced myocardial flow reserve (MFR) may be the cause., Methods: We included 110 patients with ischemic cardiomyopathy. Based on quantitative myocardial perfusion assessment and viability imaging with 13 N-NH3 and 18 F-FDG positron emission tomography, respectively, as well as wall motion assessment from echocardiography, myocardial tissue was characterized as remote (i.e., normal myocardium), stunned (i.e., dysfunctional but viable myocardium with normal rest perfusion), hibernating (i.e., dysfunctional but viable myocardium with impaired rest perfusion), or scarred myocardium (i.e., non-viable myocardium)., Results: Compared to remote myocardium, dysfunctional but viable myocardium (including stunned and hibernating) had reduced rest MBF (0.89 mL/min/g vs. 0.79 and 0.76 mL/min/g, respectively; p < 0.001) and MFR (1.53 vs. 1.27 and 1.17; p < 0.001). Between stunned and hibernating myocardium, however, rest MBF and MFR did not differ (p = 0.40). In scarred myocardium, rest MBF was lowest (0.66 mL/min/g; p < 0.001) but, in contrast to the other myocardial states, k2 (i.e., tracer washout) was increased (0.199/min vs. 0.178/min to 0.181/min; all p < 0.05 in pairwise comparison)., Conclusions: In patients with ischemic cardiomyopathy, impaired MFR is associated with stunning and hibernation. These states of dysfunctional but viable myocardium have lower rest MBF compared to remote myocardium. At the end of the continuum, rest MBF is lowest in scar tissue and linked to increased rate of tracer washout.

The detection, quantification and characterization of coronary atherosclerotic plaques has a major effect on the diagnosis and treatment of coronary artery disease (CAD). Different studies have reported and evaluated the noninvasive ability of Computed Tomography Coronary Angiography (CTCA) to identify coronary plaque features. The identification of calcified plaques (CP) and non-calcified plaques (NCP) using CTCA has been extensively studied in cardiovascular research. However, NCP detection remains a challenging problem in CTCA imaging, due to the similar intensity values of NCP compared to the perivascular tissue, which surrounds the vasculature. In this work, we present a novel methodology for the identification of the plaque burden of the coronary artery and the volumetric quantification of CP and NCP utilizing CTCA images and we compare the findings with virtual histology intravascular ultrasound (VH-IVUS) and manual expert's annotations. Bland-Altman analyses were employed to assess the agreement between the presented methodology and VH-IVUS. The assessment of the plaque volume, the lesion length and the plaque area in 18 coronary lesions indicated excellent correlation with VH-IVUS. More specifically, for the CP lesions the correlation of plaque volume, lesion length and plaque area was 0.93, 0.84 and 0.85, respectively, whereas the correlation of plaque volume, lesion length and plaque area for the NCP lesions was 0.92, 0.95 and 0.81, respectively. In addition to this, the segmentation of the lumen, CP and NCP in 1350 CTCA slices indicated that the mean value of DICE coefficient is 0.72, 0.7 and 0.62, whereas the mean HD value is 1.95, 1.74 and 1.95, for the lumen, CP and NCP, respectively., (Copyright © 2019. Published by Elsevier Ltd.)

Background Increasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart-brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease. Methods and Results The association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor-18-deoxyglucose positron emission tomography and 99m Tc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor-18-deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P =0.047, P =0.022, and P =0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P =0.010, P =0.013, and P =0.016, respectively). In a sex-stratified analysis, these differences were observed in men, but not in women. A first-order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P =0.015 for brainstem; myocardial ischemia: P =0.004, P =0.018, and P =0.003 for callosal, caudate, or brainstem metabolism, respectively). Conclusions Myocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems.

Aim: Amongst patients with coronary artery disease (CAD), women experience relatively worse outcomes as compared to men. Evidence to date has failed to explore unique female imaging targets as major determinants of cardiovascular risk. We sought to assess the prognostic value of epicardial (EFV) and intrathoracic fat volume (IFV) quantification in women and men with suspected and known CAD., Methods and Results: Intrathoracic fat volume and EFV were calculated from non-contrast CT and analyzed in a propensity-matched cohort of 190 patients (95 women, mean age 62.5 ± 11.3 years) undergoing myocardial perfusion imaging (MPI) and coronary computed tomography angiography (CCTA) for evaluation of CAD. IFV and EFV were significantly lower in women as compared to men (198.2 ± 78.4 vs 293.2 ± 114.7 cm 3 and 105.6 ± 48.9 vs 135.8 ± 60.9 cm 3 , p < 0.001) and showed a strong association with coronary artery calcium score (CACS) and obstructive CAD in women (p < 0.05), but not in men. Fat volumes were not related to abnormal MPI in either population (p = NS). During a median follow-up of 2.8 years, high IFV was associated with reduced event free survival (log rank = 0.019 vs low IFV) in women, but not in men. Accordingly, a multivariate Cox regression model adjusted for cardiovascular risk factors, CACS, CCTA, and MPI findings selected IFV as a significant predictor of major adverse cardiovascular events (MACE) in women (HR 1.32, 95%CI 1.18-1.55, p = 0.001)., Conclusion: Quantification of IFV provides incremental prognostic value for MACE in women, beyond that provided by traditional risk factors and imaging findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Although women with cardiovascular disease experience relatively worse outcomes as compared to men, substantial knowledge gaps remain regarding the unique female determinants of cardiovascular risk. Heart rate (HR) responses to vasodilator stress mirror autonomic activity and may carry important long-term prognostic information in women., Methods and Results: Hemodynamic changes during adenosine stress were recorded in a total of 508 consecutive patients (104 women) undergoing clinically indicated 13 N-ammonia Positron-Emission-Tomography (PET) at our institution. Following propensity matching, 202 patients (101 women, mean age 61.3 ± 12.6 years) were analyzed. During a median follow-up of 5.6 years, 97 patients had at least one cardiac event, including 17 cardiac deaths. Heart rate reserve (% HRR) during adenosine infusion was significantly higher in women as compared to men (23.8 ± 19.5 vs 17.3 ± 15.3, p = 0.009). A strong association between 10-year cardiovascular endpoints and a blunted HRR was observed in women, while this association was less pronounced in men. Accordingly, in women, but not in men, reduced HRR was selected as a strong predictor for adverse cardiovascular events in a Cox regression model fully adjusted for imaging findings and traditional risk factors (HR 2.41, 95% CI 1.23-4.75, p = 0.011). Receiver operating characteristics (ROC) curves revealed that a blunted HRR <21% was a powerful predictor for MACE in women with a sensitivity of 77% and a specificity of 68%., Conclusion: Blunted HRR to adenosine stress adds incremental prognostic value for long-term cardiovascular outcomes in women beyond that provided by traditional risk factors and imaging findings.

Background:  Inflammation plays a fundamental role in mediating all stages of atherosclerosis. Given the higher prevalence of inflammatory rheumatologic conditions in women and the female propensity towards worse cardiovascular outcomes, refined strategies are needed to better identify the high-risk female cardiovascular phenotype., Objectives:  This article aims to assess sex-specific links between inflammatory processes and the development and progression of ischemic heart disease., Patients and Methods:  The relationship between vertebral bone marrow metabolism-a marker of inflammation-and myocardial injury was retrospectively assessed in 294 patients (28.6% women, mean age: 66.9 ± 10.0 years) who underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) and 99m Tc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI)., Results:  A significant increase in 18 F-FDG bone marrow uptake was observed in women with impaired myocardial perfusion (SPECT-MPI) as compared to women with normal myocardial perfusion (standardized uptake value [SUV]: 2.2 ± 1.2 vs. 1.7 ± 0.5, p  = 0.013), while no such difference was observed in men (SUV: 1.6 ± 0.8 vs. 1.6 ± 0.4, p  = 0.372). Furthermore, a significant inverse correlation between left ventricular ejection fraction (LVEF) and bone marrow metabolism was seen in women ( r  = -0.229, p  = 0.037), but not in men ( r  = -0.075, p  = 0.289). Accordingly, in women, but not in men, bone marrow activity was identified as an independent predictor of both, reduced LVEF ( β -coefficient, -4.537; p  = 0.040) and impaired myocardial perfusion (β-coefficient, 0.138; p  = 0.014)., Conclusion:  A strong link between bone marrow metabolism and impaired myocardial function and perfusion was observed in women, but not in men. Our data suggest that novel biomarkers of inflammation might help to identify women at risk for ischemic cardiomyopathy and to tailor disease management to the female cardiovascular phenotype., Competing Interests: All authors have the following to disclose: The University Hospital of Zurich holds a research contract with GE Healthcare. C.G. has received research grants from the Novartis Foundation, Switzerland., (Georg Thieme Verlag KG Stuttgart · New York.)

Given the current increase in the incidence of coronary artery disease in younger women as well as the high lifetime risk of developing an x-ray-induced malignancy in this population, we aimed at assessing chest radiation in 206 women ≤55 years old undergoing coronary calcium scoring (CACS) by using a Monte Carlo simulation tool. Our data indicate that the simulated radiation dose of the female breast during CACS depends substantially on the starting position of the x-ray tube, with an almost 2 times excess of breast radiation exposure being measured during anterior-posterior tube positioning. Thus, an additional technical feature taking into account the position of the x-ray tube when acquisition is triggered might be an important tool to reduce radiation exposure of the female breast during CACS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Evidence to date has failed to adequately explore determinants of cardiovascular risk in women with coronary microvascular dysfunction (CMVD). Heart rate responses to adenosine mirror autonomic activity and may carry important prognostic information for the diagnosis of CMVD., Methods: Hemodynamic changes during adenosine stress were analyzed in a propensity-matched cohort of 404 patients (202 women, mean age 65.9 ± 11.0) who underwent clinically indicated myocardial perfusion 13 N-ammonia Positron-Emission-Tomography (PET) at our institution between September 2013 and May 2017., Results: Baseline heart rate (HR) was significantly higher in patients with abnormal coronary flow reserve (CFR, p < 0.001 vs normal CFR). Accordingly, a blunted HR response to adenosine (=reduced heart rate reserve, %HRR) was seen in patients with abnormal CFR, with a most pronounced effect being observed in female patients free of myocardial ischemia (45.9 ± 34.9 vs 26.5 ± 18.0, p < 0.001 in women and 29.1 ± 16.9 vs 24.3 ± 21.7, p = 0.15 in men). Hence, a fully-adjusted multivariate logistic regression model identified HRR as the strongest negative predictor of reduced CFR in women free of myocardial ischemia, but not in men. Accordingly, receiver operating characteristics (ROC) curves for the presence of reduced CFR revealed that a %HRR <35 was a powerful predictor for abnormal CFR with a sensitivity of 81% and a specificity of 60% in women., Conclusion: A blunted HRR <35% is associated with abnormal CFR in women. Taking into account HR responses during stress test in women may help to risk stratify the heterogeneous female population of patients with non-obstructive coronary artery disease (CAD).

Aims: Cardiovascular outcomes of women with coronary artery disease (CAD) are perceived as relatively worse when compared to men. Amygdalar metabolic activity has recently been shown to independently predict cardiovascular events in patients without known cardiovascular disease. Given that traditional algorithms for risk prediction perform worse in women than in men, we sought to assess sex-specific associations between amygdalar metabolic activity and cardiac dysfunction with suspected or known CAD., Methods and Results: This retrospective study included 302 patients (mean age 66.8 ± 10.2 years, 29.1% women) selected for evaluation of CAD, malignant, or inflammatory disease. All patients had undergone both, myocardial perfusion imaging by single photon emission computed tomography (MPI-SPECT) and whole-body fluoro-18-deoxyglucose (18F-FDG) positron emission tomography (PET), within 6 months. 18F-FDG resting amygdalar uptake was significantly increased in women with abnormal MPI scans (standardized uptake value 33.4 ± 6.5 vs. 30.4 ± 4.7, P = 0.043), while no such difference was observed in men (P = 0.808). In women, but not in men, a negative association between 18F-FDG resting amygdalar activity and left ventricular ejection fraction (LVEF) was observed (Pearson r = -0.308, P = 0.004). Accordingly, either LVEF [B-coefficient (standard error, SE) = -0.232 (0.109), P = 0.045] or abnormal MPI [B-coefficient (SE) = 8.264 (2.449), P = 0.003] were selected as significant predictors of high amygdalar 18F-FDG uptake in a fully adjusted linear regression model in women, and a first order interaction term consisting of sex and LVEF or sex and abnormal MPI was significant (P = 0.035 and P = 0.001, respectively)., Conclusion: Resting amygdalar metabolic activity is associated with abnormal cardiac function and perfusion in women, suggesting a link between emotional stress and cardiovascular disease in women., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Enhanced sympathetic nervous system activity is associated with increased mortality in many cardiac conditions including heart failure and coronary artery disease (CAD). To ensure adequate image quality of coronary CT angiography (CCTA), pre-scan β-adrenergic blockers (BB) are routinely administered. It is currently unknown whether sensitivity to sympathicolytic compounds is associated with severity of CAD. A total of 2633 consecutive patients (1733 [65.8%] men and 900 [34.2%] women, mean age 56.7 ± 11.5 years) undergoing CCTA for exclusion of significant CAD at our department between 06/2013 and 12/2016 were evaluated. Acute heart rate (HR) responses to BB administration were recorded in all patients. Coronary plaque burden as indicated by segment severity score (SSS), segment involvement score (SIS), and significant CAD (i.e. > 50% luminal narrowing) was higher in weak responders to BB as compared to strong responders to BB (p = 0.001 for SSS and SIS, and p = 0.021 for significant CAD). Accordingly, in a multiple linear regression model adjusted for known risk factors of CAD such as smoking, hypertension, diabetes and dyslipidaemia, as well as age, sex, body mass index (BMI), glomerular filtration rate, and HR during CCTA scan, a strong response to BB was selected as a significant independent negative predictor of coronary plaque burden (beta coefficient - 0.08, p = 0.001). We demonstrate that individuals with a weak acute response to BB administration encounter an increased risk of severe CAD. Taking into account sensitivity to sympatho-inhibition may add complementary information in patients undergoing CCTA for evaluation of CAD.

Background: To assess the functional relevance of a coronary artery stenosis, corrected coronary opacification (CCO) decrease derived from coronary computed tomography angiography (CCTA) has been proposed. The present study aims at validating CCO decrease with quantitative 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI)., Methods and Results: This retrospective study consists of 39 patients who underwent hybrid CCTA/PET-MPI. From CCTA, attenuation in the coronary lumen was measured before and after a stenosis and corrected to the aorta to calculate CCO and its decrease. Relative flow reserve (RFR) was calculated by dividing the stress myocardial blood flow (MBF) of a vessel territory subtended by a stenotic coronary by the stress MBF of the reference territories without stenoses. RFR was abnormal in 11 vessel territories (27%). CCO decrease yielded a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for prediction of an abnormal RFR of 73%, 70%, 88%, 47%, and 70%, respectively., Conclusions: CCTA-derived CCO decrease has moderate diagnostic accuracy to predict an abnormal RFR in PET-MPI. However, its high negative predictive value to rule out functional relevance of a given lesion may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis.

Acute coronary events, the dreaded manifestation of coronary atherosclerosis, remain one of the main contributors to mortality and disability in the developed world. The majority of those events are associated with atherosclerotic plaques-related thrombus formation following an acute disruption, that being rupture or erosion, of an event-prone lesion. These historically termed vulnerable plaques have been the target of numerous benchtop and clinical research endeavors, yet to date without solid results that would allow for early identification and potential treatment. Technological leaps in cardiovascular imaging have provided novel insights into the formation and role of the event-prone plaques. From intracoronary optical coherence tomography that has enhanced our understanding of the pathophysiological mechanisms of plaque disruption, over coronary computed tomography angiography that enables non-invasive serial plaque imaging, and positron emission tomography poised to be rapidly implemented into clinical practice to the budding field of plaque imaging with cardiac magnetic resonance, we summarize the invasive and non-invasive imaging modalities currently available in our armamentarium. Finally, the current status and potential future imaging directions are critically appraised.

Aims: To determine if tube-adapted thresholds for coronary artery calcium (CAC) scoring by computed tomography at 80 kilovolt-peak (kVp) tube voltage and 70-kVp yield comparable results to the standard 120-kVp protocol., Methods and Results: We prospectively included 103 patients who underwent standard scanning with 120-kVp tube voltage and additional scans with 80 kVp and 70 kVp. Mean body mass index (BMI) was 27.9 ± 5.1 kg/m2. For the lowered tube voltages, we applied novel kVp-adapted thresholds for calculation of CAC scores and compared them with standard 120-kVp scans using intraclass correlation and Bland-Altman (BA) analysis. Furthermore, risk-class (CAC score 0/1-10/11-100/101-400/>400) changes were assessed. Median CAC score from 120-kVp scans was 212 (interquartile range 25-901). Thirteen (12.6%) patients had zero CAC. Using the novel kVp-adapted thresholds, CAC scores derived from 80-kVp scans showed excellent correlation (r = 0.994, P < 0.001) with standard 120-kVp scans with BA limits of agreement of -235 (-39.5%) to 172 (28.9%). Similarly, for 70-kVp scans, correlation was excellent (r = 0.972, P < 0.001) but with broader limits of agreement of -476 (-85.0%) to 270 (48.2%). Only 2 (2.8%) reclassifications were observed for the 80-kVp scans in patients with a BMI <30 kg/m2 (n = 71), and 2 (6.1%) for the 70-kVp scans in patients with a BMI <25 kg/m2 (n = 33). Mean effective radiation dose was 0.60 ± 0.07 millisieverts (mSv), 0.19 ± 0.02 mSv, and 0.12 ± 0.01 mSv for the 120-kVp, 80-kVp, and 70-kVp scans, respectively., Conclusion: The present study suggests that CAC scoring with reduced peak tube voltage is accurate if kVp-adapted thresholds for calculation of CAC scores are applied while offering a substantial further radiation dose reduction.

Purpose: Evidence to date on the unique female determinants of cardiovascular risk is inadequate. Positron Emission Tomography (PET) is considered to have the highest accuracy for the assessment of myocardial perfusion in patients with suspected coronary artery disease (CAD), but its long-term prognostic accuracy in women has not been established., Methods: A total of 619 consecutive patients (138 women, mean age 60.0 ± 11.8 years) underwent clinically indicated 13 N-ammonia PET at our institution and were followed up (median 5.7 years) for major adverse cardiovascular events (MACE) including cardiac death, nonfatal myocardial infarction, hospitalization for any cardiac reason and late revascularization., Results: During follow-up, 271 patients had at least one cardiac event, including 64 cardiac deaths and 33 nonfatal myocardial infarctions. In both women and men, abnormal myocardial perfusion was associated with reduced event-free survival (log rank p < 0.001). In women, abnormal myocardial perfusion was associated with a higher risk of a worse outcome than in men (adjusted HR 4.1, 95% CI 1.8-9.0 in women; HR 2.4, 95% CI 1.5-3.8 in men; p interaction  < 0.001). In contrast, abnormal coronary flow reserve (CFR) was a significant predictor of 10-year MACE in men (p = 0.006) but not in women (p = NS). Accordingly, an interaction term of sex and abnormal myocardial perfusion or CFR was significant (p < 0.001)., Conclusion: While perfusion findings in 13 N-ammonia PET provide effective risk stratification in women and men, CFR adds incremental prognostic value for long-term cardiac outcomes only in men. Refined strategies in noninvasive imaging are needed in women to improve CAD risk prediction.

Purpose To determine the value of cardiac hybrid imaging, performed by combining SPECT myocardial perfusion imaging (MPI) with coronary CT angiography, as a long-term predictor for major adverse cardiac events (MACEs) (death, myocardial infarction [MI], unstable angina requiring hospitalization, coronary revascularization). Materials and Methods For this retrospective single-center study, 428 patients referred between May 2005 and December 2008 were classified according to hybrid imaging findings into the following groups: (a) those with stenosis of 50% or greater (at coronary CT angiography) with ischemia (at SPECT) in subtended territory (matched), (b) those with coronary CT angiography and/or SPECT findings in unrelated territories (unmatched), and (c) those with normal findings at coronary CT angiography and SPECT. End points were all-cause death or MI ("hard events") and a composite of MACEs. The Kaplan-Meier method was used to identify survival free of MACEs, and Cox proportional hazard regression analysis was used to determine independent predictors for MACE. Results During a median follow-up of 6.8 years, a total of 160 MACEs, including 45 deaths, were observed in the final study population (mean age, 62 years ± 11 [standard deviation]; 132 women). The annual hard event rate was more than fivefold higher for patients with matched findings (n = 46 [7.0%]) and was threefold higher for patients with unmatched findings (n = 113 [3.7%]) compared with that for patients with normal findings (1.2%; n = 216 [1.2%]; P < .001). The MACE rates were 21.8%, 9.0%, and 2.4% for matched, unmatched, and normal findings, respectively. A matched finding was an independent predictor for MACE and hard events. Conclusion In patients evaluated for coronary artery disease, cardiac hybrid imaging is an excellent long-term predictor of adverse cardiac events. A matched hybrid finding is associated with a high annual cardiac event rate. © RSNA, 2018.

Background: Sexual dimorphism in cardiac sympathetic outflow has recently gained attention in the context of Takotsubo cardiomyopathy. Previous studies suggest that there are sex- and age-dependent differences in peripheral autonomic control, however, data on cardiac-specific sympathetic activation in aged women and men are lacking., Methods and Results: Regional quantitative analysis of cardiac fluorine-18 (18F)- Dihydroxyphenylalanine (DOPA) uptake was retrospectively performed in 133 patients (69 females, mean age 52.4±17.7 years) referred for assessment of neuroendocrine tumours (NET) by Positron-Emission-Tomography. Cardiac 18F-DOPA uptake was significantly higher in women as compared to men (1.33±0.21 vs. 1.18±0.24, p<0.001). This sex-difference was most pronounced in the apical region of the left ventricle (LV, 1.30±0.24 in women vs. 1.13±0.25 in men, p<0.001) and in individuals >55 years of age (1.39±0.25 in women vs. 1.09±0.24 in men, p<0.001). Women showed a prominent increase in myocardial 18F-DOPA uptake with age with the strongest increase seen in the LV apical region (r = 0.34, p = 0.004). Accordingly, sex and age were selected as significant predictors of LV apical 18F-DOPA uptake in a stepwise linear regression model. No age-dependent changes of cardiac 18F-DOPA uptake were observed in men or in the right ventricular region., Conclusion: Our study suggests that aging is related to sex-specific changes in regional cardiac sympathetic activity. Future studies will have to assess whether the increase in LV apical 18F-DOPA uptake with age in women is of pathogenic relevance for the higher susceptibility of postmenopausal women to conditions associated with increased sympathetic activity., Competing Interests: We declare that the authors received research grants from the Swiss National Science Foundation (SNSF), the Olga Mayenfisch Foundation, Switzerland, the OPO Foundation, Switzerland, the Novartis Foundation, Switzerland, the Helmut Horten Foundation, Switzerland, and the Swissheart Foundation (all to Catherine Gebhard). These funding organizations did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support only in the form of salaries (CG, SB, AH, MM) and research materials. The specific roles of these authors are articulated in the ‘author contributions’ section. We further declare that the affiliation to these funding agencies does not alter our adherence to PLOS ONE policies on sharing data and materials.

It is unclear whether non-invasive screening of asymptomatic diabetic patients for coronary artery disease (CAD) may improve cardiac outcomes. Thus, we performed a systematic literature review and meta-analysis of randomised controlled trials (RCT's) on this topic. We searched appropriate RCT's in five online databases (PubMed/MEDLINE, Cochrane Library, Embase, Scopus, and Web of Science) from January 2000 to November 2017 and in 41 recent reviews. Two investigators independently extracted and assessed study data using standardised forms. Additional unpublished data were obtained from trial authors. The primary endpoint 'any cardiac event' was a composite of cardiac death, non-fatal myocardial infarction (MI), unstable angina (UA), or heart failure (HF) hospitalisation. We performed a meta-analysis of relative risks (RRs) with 95% confidence intervals (CI) using the Mantel-Haenszel method. We included five RCT's with 3299 patients, of which 189 (5.7%) experienced any cardiac event on follow-up (weighted mean 4.1 years). Non-invasive CAD screening significantly reduced any cardiac event by 27% [RR 0.73 (95% CI 0.55-0.97), P = 0.028, number needed to screen 56]. This result was driven by important, albeit non-significant decreases in non-fatal MI [RR 0.65 (95% CI 0.41-1.02), P = 0.062] and HF hospitalisation [RR 0.61 (95% CI 0.33-1.10), P = 0.100]. Non-invasive CAD screening did not significantly affect cardiac death [RR 0.92 (95% CI 0.53-1.60), P = 0.77] and UA [RR 0.73 (95% CI 0.41-1.31), P = 0.29]. Compared with the standard care, non-invasive CAD screening reduced cardiac events by 27% in asymptomatic diabetic patients, largely through reductions in non-fatal MIs, and HF hospitalisations. The present results justify larger, appropriately powered trials to potentially revisit current recommendations.

Background: Although randomized trials have provided evidence for invasive fractional flow reserve to guide revascularization, evidence for non-invasive imaging is less well established. The present study investigated whether hybrid coronary computed tomography (CCTA)/single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) can identify patients who benefit from early revascularization compared to medical therapy., Methods: This retrospective study consists of 414 patients referred for evaluation of known or suspected coronary artery disease (CAD) with CCTA/SPECT hybrid imaging. CCTA categorized patients into no CAD, non-high-risk CAD and high-risk CAD. In patients with CAD (n = 329), a matched finding (n = 75) was defined as a reversible perfusion defect in a territory subtended by a coronary artery with CAD. All other combinations of pathologic findings were classified as unmatched (n = 254). Death, myocardial infarction, unstable angina requiring hospitalization, and late coronary revascularization were defined as major adverse cardiac events (MACE). Cox hazards models included covariates age, male gender, more than two risk factors, previous CABG, high-risk CAD and early revascularization., Results: During median follow-up of 6.0 years, 112 patients experienced a MACE (27%). Early revascularization (n = 50) was independently associated with improved outcome among patients with a matched finding (p < 0.001). There was no benefit among patients with an unmatched finding (p = 0.787), irrespective of presence (p = 0.505) or absence of high-risk CAD (p = 0.631)., Conclusions: Early revascularization is associated with an outcome benefit in CAD patients with a matched finding documented by cardiac hybrid imaging while no benefit of revascularization was observed in patients with an unmatched finding., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Iterative reconstruction (IR) algorithms allow for a significant reduction in radiation dose of coronary computed tomography angiography (CCTA). We performed a head-to-head comparison of adaptive statistical IR (ASiR) and model-based IR (MBIR) algorithms to assess their impact on quantitative image parameters and diagnostic accuracy for submillisievert CCTA., Methods and Results: CCTA datasets of 91 patients were reconstructed using filtered back projection (FBP), increasing contributions of ASiR (20, 40, 60, 80, and 100%), and MBIR. Signal and noise were measured in the aortic root to calculate signal-to-noise ratio (SNR). In a subgroup of 36 patients, diagnostic accuracy of ASiR 40%, ASiR 100%, and MBIR for diagnosis of coronary artery disease (CAD) was compared with invasive coronary angiography. Median radiation dose was 0.21 mSv for CCTA. While increasing levels of ASiR gradually reduced image noise compared with FBP (up to - 48%, P < 0.001), MBIR provided largest noise reduction (-79% compared with FBP) outperforming ASiR (-59% compared with ASiR 100%; P < 0.001). Increased noise and lower SNR with ASiR 40% and ASiR 100% resulted in substantially lower diagnostic accuracy to detect CAD as diagnosed by invasive coronary angiography compared with MBIR: sensitivity and specificity were 100 and 37%, 100 and 57%, and 100 and 74% for ASiR 40%, ASiR 100%, and MBIR, respectively., Conclusion: MBIR offers substantial noise reduction with increased SNR, paving the way for implementation of submillisievert CCTA protocols in clinical routine. In contrast, inferior noise reduction by ASiR negatively affects diagnostic accuracy of submillisievert CCTA for CAD detection., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Objectives: Recommendations regarding sports restriction are lacking for middle-aged athletes with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS)., Methods: Sixty-three patients with ACAOS were subdivided into ACAOS with (n = 38) or without (n = 25) an interarterial course (IAC). Sports behavior, either competitive (COMP) or recreational (REC), was evaluated at the time of diagnosis and after a median follow-up of 4.2 years., Results: Mean age was 56 ± 11 years and 48 (76.2%) patients were engaged in sports. Three individuals (4.8%) were surgically corrected after diagnosis. Thirty-eight (60.3%) patients were aware of their diagnosis at follow-up and 12 (19.0%) were counseled by their physician about sports restrictions. Sports behavior at the time of diagnosis and at follow-up did not differ significantly, neither in patients engaged in COMP (17.5 vs. 12.7%, p = 0.619) nor those engaged in REC (58.7 vs. 61.9%, p = 0.856). Sport-related symptoms were not significantly different between ACAOS patients with and without IAC. No athlete had died at follow-up., Conclusions: The majority of middle-aged individuals with ACAOS were involved in sports activities at the time of diagnosis and at follow-up. Awareness and counseling about ACAOS diagnosis had no significant effect on sports behavior. IAC did not have an impact on sport-related symptoms, and outcomes were favorable in all athletes, regardless of surgical correction., (© 2018 S. Karger AG, Basel.)

Objectives: To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering., Methods: We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions., Results: Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001)., Conclusion: Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries., Key Points: • Coronary CT angiography (CCTA) has an excellent long-term prognostic performance. • CCTA can accurately stratify cardiac risk according to coronary lesion severity. • A normal CCTA predicts freedom from cardiac events for >6 years. • Patients with a coronary calcium score of 0 may experience cardiac events. • CCTA allows for reclassification of cardiac risk compared with ESC SCORE.

Background: Estimation of hemodynamic relevance of a coronary stenosis from coronary computed angiography (CCTA) has raised substantial interest. Recently, the corrected coronary opacification (CCO) decrease and the transluminal attenuation gradient (TAG) have been suggested as faster alternatives to the FFR CT . The aim of the study was to evaluate whether the diagnostic accuracy of CCO decrease and TAG translates into an added prognostic value in patients evaluated for coronary artery disease (CAD)., Methods: This retrospective study consists of 162 consecutive patients referred for evaluation of known or suspected CAD by CCTA. CCO decrease was defined as difference of mean luminal coronary attenuation normalized to aorta attenuation proximal-distal of a stenosis. To calculate TAG, mean attenuation was measured at 5-mm intervals from the ostium to a distal segment with a minimal cross-sectional area of 2.0mm 2 . Death, myocardial infarction, unstable angina requiring hospitalization, and coronary revascularization were defined as major adverse cardiac events (MACE). Multivariate analysis included covariates age, sex, ≥3 cardiovascular risk factors and stenosis severity., Results: Follow-up was completed in 154 patients, CAD was found in 72. During median follow-up of 6.1years (interquartile range, 5.8-6.9years), 55 patients experienced a MACE. Among CAD patients, the presence of an abnormal CCO decrease (p<0.05) but not TAG (p=0.894) was associated with a worse MACE-free survival. In multivariate analysis, CCO decrease was an independent predictor of MACE (HR, 2.27; 95% CI, 1.14-4.52; p=0.02) while TAG was not predictive (p=0.895)., Conclusion: In CAD patients, CCO decrease adds long-term prognostic value over clinical characteristics and stenosis severity while TAG does not., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Aims: Anomalous origin of a coronary artery from the opposite sinus (ACAOS) has been associated with adverse cardiac events in the young. It remains unknown whether this holds true for middle-aged patients with uncorrected ACAOS as well. We assessed the outcome in middle-aged patients with newly diagnosed ACAOS by coronary computed tomography angiography (CCTA) compared with a matched cohort., Methods and Results: We retrospectively identified 68 consecutive patients with ACAOS documented by CCTA. ACAOS with a course of the anomalous vessel between the aorta and pulmonary artery were classified as interarterial course (IAC). Each patient with ACAOS was matched to two controls without ACAOS. Major adverse cardiac events (i.e. myocardial infarction, revascularization and cardiac death) were recorded for all patients and controls. Two (3%) patients were lost to follow-up. Thus, 66 patients with ACAOS were included in the final analysis and matched with 132 controls. Mean age of patients was 56 ± 11 years, 73% were male and the mean follow-up was 49 months. Forty (65%) patients were classified as having ACAOS with IAC. The annual event rate of ACAOS vs. controls was 4.9 and 4.8%, the hazard ratio (HR) 0.94 (0.39-2.28, P = 0.89). The annual event rate of ACAOS with IAC compared with their matched controls was 5.2 and 4.3%, and the HR 1.01 (95% CI 0.39-2.58, P = 0.99)., Conclusions: In middle-aged individuals with newly diagnosed ACAOS mid-term outcome is not statistically different to a matched control cohort without coronary artery anomalies, regardless of whether ACAOS with or without IAC variants are present., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Precise definition of the mitral valve plane (VP) during segmentation of the left ventricle for SPECT myocardial perfusion imaging (MPI) quantification often requires manual adjustment, which affects the quantification of perfusion. We developed a machine learning approach using support vector machines (SVM) for automatic VP placement. Methods: A total of 392 consecutive patients undergoing 99m Tc-tetrofosmin stress (5 min; mean ± SD, 350 ± 54 MBq) and rest (5 min; 1,024 ± 153 MBq) fast SPECT MPI attenuation corrected (AC) by CT and same-day coronary CT angiography were studied; included in the 392 patients were 48 patients who underwent invasive coronary angiography and had no known coronary artery disease. The left ventricle was segmented with standard clinical software (quantitative perfusion SPECT) by 2 experts, adjusting the VP if needed. Two-class SVM models were computed from the expert placements with 10-fold cross validation to separate the patients used for training and those used for validation. SVM probability estimates were used to compute the best VP position. Automatic VP localizations on AC and non-AC images were compared with expert placement on coronary CT angiography. Stress and rest total perfusion deficits and detection of per-vessel obstructive stenosis by invasive coronary angiography were also compared. Results: Bland-Altman 95% confidence intervals (CIs) for VP localization by SVM and experts for AC stress images (bias, 1; 95% CI, -5 to 7 mm) and AC rest images (bias, 1; 95% CI, -7 to 10 mm) were narrower than interexpert 95% CIs for AC stress images (bias, 0; 95% CI, -8 to 8 mm) and AC rest images (bias, 0; 95% CI, -10 to 10 mm) ( P < 0.01). Bland-Altman 95% CIs for VP localization by SVM and experts for non-AC stress images (bias, 1; 95% CI, -4 to 6 mm) and non-AC rest images (bias, 2; 95% CI, -7 to 10 mm) were similar to interexpert 95% CIs for non-AC stress images (bias, 0; 95% CI, -6 to 5 mm) and non-AC rest images (bias, -1; 95% CI, -9 to 7 mm) ( P was not significant [NS]). For regional detection of obstructive stenosis, ischemic total perfusion deficit areas under the receiver operating characteristic curve for the 2 experts (AUC, 0.79 [95% CI, 0.7-0.87]; AUC, 0.81 [95% CI, 0.73-0.89]) and the SVM (0.82 [0.74-0.9]) for AC data were the same ( P = NS) and were higher than those for the unadjusted VP (0.63 [0.53-0.73]) ( P < 0.01). Similarly, for non-AC data, areas under the receiver operating characteristic curve for the experts (AUC, 0.77 [95% CI, 0.69-0.89]; AUC, 0.8 [95% CI, 0.72-0.88]) and the SVM (0.79 [0.71-0.87]) were the same ( P = NS) and were higher than those for the unadjusted VP (0.65 [0.56-0.75]) ( P < 0.01). Conclusion: Machine learning with SVM allows automatic and accurate VP localization, decreasing user dependence in SPECT MPI quantification., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To evaluate the impact of a low-dose (LD) and an ultra-LD (ULD) contrast protocol for coronary CT angiography on qualitative and quantitative image parameters in a clinical setting., Methods: We scanned 120 consecutive patients with a 256-slice CT scanner applying a LD (60 patients, 35-55 ml) or ULD (60 patients, 25-45 ml) contrast protocol adapted to the body mass index. Visually assessed image quality and attenuation measured in each coronary segment were retrospectively compared in 20 consecutive patients scanned with a normal-dose (ND, 40-105 ml) contrast protocol., Results: Visually assessed image quality did not differ significantly among protocols. By contrast, attenuation obtained from the ULD protocol (median contrast volume 35 ml) differed significantly from the LD (median 45 ml) and ND (median 70 ml) protocols in the coronary segments (316 ± 52 vs 363 ± 60 and 359 ± 52 HU, p < 0.001). Attenuation did not differ significantly between the LD and ND protocol. The proportion of patients with inadequate coronary vessel attenuation was significantly higher (p < 0.001) in the ULD protocol (37%) than in the ND (5%) and LD (10%) protocols but did not differ significantly between the ND and LD protocols., Conclusion: In a clinical setting, a LD contrast protocol with a median volume of 45 ml is feasible for the latest generation 256-slice coronary CT angiography as it yields attenuation comparable to a ND protocol. By contrast, the implementation of an ULD protocol remains challenging. Advances in knowledge: Although not perceived by the naked eye, an ULD contrast protocol in a clinical setting yields attenuation below a threshold for diagnostic image quality.

Background: Anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS) are associated with adverse cardiac events. Discrimination between ACAOS and coronary artery disease (CAD)-related perfusion defects may be difficult. The aim of the present study was to investigate the value of hybrid coronary computed tomography angiography (CCTA)/SPECT-MPI in patients with ACAOS and possible concomitant CAD., Methods: We retrospectively identified 46 patients (mean age 56 ± 12 years) with ACAOS revealed by CCTA who underwent additional SPECT-MPI. ACAOS with an interarterial course were classified as malignant, whereas all other variants were considered benign. CCTA/SPECT-MPI hybrid imaging findings (ischemia or scar) were analyzed according to the territory subtended by an anomalous vessel or a stenotic coronary artery., Results: Twenty-six (57%) patients presented with malignant ACAOS. Myocardial ischemia or scar was found only in patients who had concomitant obstructive CAD in the vessel matching the perfusion defect as evidenced by hybrid CCTA/SPECT imaging., Conclusion: Hybrid CCTA/SPECT-MPI represents a valuable non-invasive tool to discriminate the impact of ACAOS from concomitant CAD on myocardial ischemia. Our results suggest that in a middle-aged population myocardial ischemia due to ACAOS per se may be exceedingly rare and is more likely attributable to concomitant CAD.

Objective: To provide data on the value of fused cardiac hybrid imaging with coronary computed tomography angiography (CCTA) and positron emission tomography myocardial perfusion imaging (PET-MPI) in patients with complex coronary artery anomalies (CCAA)., Design/setting: This is a retrospective, single-center study., Patients: Seven consecutive patients with CCAA (mean 57 ± 7 y, 86% were male) who underwent clinically indicated hybrid CCTA/PET-MPI between 2005 and 2015 in our clinic were included. The findings from both modalities and fused cardiac hybrid imaging were evaluated in these patients., Results: Out of the seven patients with CCAA, two patients had Bland-White-Garland anomaly, two patients showed a coronary artery fistula, two patients showed a "single right," and one patient showed a "single left" coronary artery. Semiquantitative fused hybrid CCTA/PET-MPI depicted inferolateral scar matching the territory of a nonanomalous vessel with significant concomitant coronary artery disease (CAD) in one patient only. In contrast, analysis of quantitative myocardial blood flow (MBF) as assessed by fused hybrid CCTA/PET-MPI revealed abnormally reduced flow capacities in the territories subtended by the anomalous vessels in 4 patients., Conclusions: In this case series of middle-aged patients with CCAA, perfusion defects as assessed by semiquantitative PET-MPI were rare and attributable to concomitant CAD rather than to the anomalous vessel itself. By contrast, impaired MBF as assessed by quantitative hybrid CCTA/PET-MPI was revealed in the majority of patients in the vessel territories subtended by the anomalous coronary artery itself. Fused hybrid CCTA/PET-MPI incorporating information on morphology and on semiquantitative and quantitative myocardial perfusions may provide added value for the management of patients with CCAA., (© 2016 Wiley Periodicals, Inc.)

Aims: To assess the impact of respiratory phase matching between single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) and low-dose computed tomography (CT) for attenuation correction (AC)., Methods and Results: Forty patients underwent 1-day 99m Tc-tetrofosmin pharmacological stress/rest SPECT-MPI using a cadmium-zinc-telluride gamma camera. Low-dose CT for AC was performed at deep-inspiration breath-hold. SPECT-MPI was acquired once with free-breathing (FB) and repeated at deep-inspiration breath-hold (BH) to match the respiratory phase of AC. From these acquisitions we reconstructed four data sets: free-breathing SPECT-MPI without AC (non-corrected; FB-NC), breath-hold SPECT-MPI without AC (non-corrected; BH-NC), free-breathing SPECT-MPI with AC (FB-AC), and breath-hold SPECT-MPI with AC (BH-AC), the latter representing respiratory-phase-matched AC SPECT-MPI. We compared semi-quantitative segmental tracer uptake, visual diagnosis, inter-observer agreement, and image quality. Compared with FB-NC, deep-inspiration BH-NC increases inferior and lateral uptake, but decreases septal uptake. Addition of AC to FB increases inferior and septal uptake, but decreases anterolateral uptake. Combining breath-hold MPI with breath-hold CT AC (BH-AC) increases inferior, inferolateral, and septal uptake, but reduces apical uptake, without affecting anterolateral uptake, with significant differences to all other protocols. Frequency of normal scans increases across protocols: 10% with FB-NC, 21% with BH-NC, 38% with FB-AC, and 51% with BH-AC. Image quality and inter-observer agreement were highest for BH-AC among all protocols., Conclusion: Compared with non-corrected breath-hold SPECT-MPI and with free-breathing AC SPECT-MPI, respiratory-phase-matched AC SPECT-MPI significantly affects segmental semi-quantitative uptake, increases the frequency of normal scans, yields the best inter-observer agreement, and significantly improves image quality. These findings suggest a potential role of respiratory triggered SPECT-MPI in clinical routine., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objective: The clinical utility of a latest generation iterative reconstruction algorithm (adaptive statistical iterative reconstruction [ASiR-V]) has yet to be elucidated for coronary computed tomography angiography (CCTA). This study evaluates the impact of ASiR-V on signal, noise and image quality in CCTA., Methods: Sixty-five patients underwent clinically indicated CCTA on a 256-slice CT scanner using an ultralow-dose protocol. Data sets from each patient were reconstructed at 6 different levels of ASiR-V. Signal intensity was measured by placing a region of interest in the aortic root, LMA, and RCA. Similarly, noise was measured in the aortic root. Image quality was visually assessed by 2 readers., Results: Median radiation dose was 0.49 mSv. Image noise decreased with increasing levels of ASiR-V resulting in a significant increase in signal-to-noise ratio in the RCA and LMA (P < 0.001). Correspondingly, image quality significantly increased with higher levels of ASiR-V (P < 0.001)., Conclusions: ASiR-V yields substantial noise reduction and improved image quality enabling introduction of ultralow-dose CCTA.

Rationale and Objectives: The aim of the study was to evaluate the impact of the latest coronary computed tomography angiography (CCTA) techniques allowing a radiation- and contrast-sparing protocol on image quality in unselected patients referred for exclusion of suspected coronary artery disease (CAD)., Materials and Methods: This prospective study was approved by the local ethics committee, and all patients provided written informed consent. Between March and June 2015, 89 consecutive patients (61% male; mean age 55 ± 11 years) referred for exclusion of CAD by 256-slice CCTA using prospective electrocardiogram triggering were included. Tube voltage (80-120 kVp), tube current (180-310 mA) as well contrast agent volume (25-45 mL) and flow rate (3.5-5 mL/s) were adapted to body mass index. Signal intensity was measured by placing a region of interest in the aortic root, the left main artery, and the proximal right coronary artery. Image noise was measured in the aortic root. Two independent blinded readers semi-quantitatively assessed the image quality regarding motion, noise, and contrast on a 4-point scale., Results: Median contrast agent volume and median effective radiation dose were 35 mL (interquartile range, 30-40 mL) and 0.5 mSv (interquartile range, 0.4-0.6 mSv), respectively. Mean attenuation in the aortic root was 412 ± 89 Hounsfield units. Diagnostic image quality was obtained in 1050 of 1067 (98.4%) coronary segments and, on an intention-to-diagnosis basis, in 85 of 89 (95.5%) patients. Below a cut-off heart rate of 67 beats/min, only 1 of 974 (0.1%) coronary segments was nondiagnostic., Conclusion: A radiation- and contrast-sparing protocol for CCTA on a latest generation 256-slice computed tomography scanner yields diagnostic image quality in patients referred for CAD exclusion in daily clinical routine., (Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Aims: To compare the predictive value of epicardial and intrathoracic fat volume (EFV, IFV), coronary artery calcium (CAC) score, and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for major adverse cardiac events (MACE)., Methods and Results: Follow-up was obtained in 275 patients with known or suspected coronary artery disease (CAD), who underwent SPECT-MPI including non-contrast cardiac computed tomography (CT) for attenuation correction to evaluate ischaemic heart disease and in whom EFV, IFV, and CAC score were calculated from non-contrast CT. Associations between fat volume, traditional cardiovascular risk factors, CAC score, and SPECT-MPI results were assessed and MACE predictors identified by Cox proportional hazard regression and global χ(2) statistics. After a median follow-up of 2.9 years, MACE were recorded in 38 patients. In univariate Cox regression analysis, EFV and IFV were predictors of MACE (P = 0.013 and P = 0.004, respectively). In multivariate analysis, EFV and IFV provided incremental predictive value beyond traditional cardiovascular risk factors (P < 0.05 and P < 0.01). However, after adjustment for CAC score and SPECT-MPI results, EFV and IFV fell short of statistical significance as independent outcome predictors., Conclusion: Quantification of EFV and IFV is associated with MACE and may improve risk stratification beyond traditional cardiovascular risk factors. However, once CAC score and/or SPECT-MPI results are known, EFV and IFV do not provide any added clinically relevant prognostic value. Further studies may identify the subpopulation with the largest relative merit of EFV and IFV as an adjunct to SPECT-MPI and CAC score., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)