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The authors sought to investigate whether a patient-specific implantation technique during transcatheter aortic valve replacement (TAVR) can result in a safe and reproducible neo-commissural alignment of self-expanding transcatheter heart valves (THVs).To date, little attention has been paid to neo-commissural alignment during TAVR.A fluoroscopy-based, patient- and valve-specific TAVR implantation technique was applied in 60 patients treated with 3 different self-expanding THV platforms (Evolut R/PRO, Medtronic; ACURATE neo2, Boston Scientific; and Portico, Abbott-20 patients in each group). Post-TAVR cardiac computed tomography was used to assess THV neo-commissural alignment.Considering all 60 patients, ≤mild commissural misalignment (CMA 30°) was obtained in 53 patients (88%) using this modified TAVR implantation technique-in 36 patients (60%), optimal commissural alignment (15°) was obtained. In 2 patients, cardiac computed tomography revealed severe CMA (45°) with overlap between the coronary ostia and THV commissures. Using the ACURATE neo2 platform, operators succeeded in avoiding ≥moderate CMA in all 20 cases. When analyzing those cases in which the optimal amount of THV rotation could be assessed and applied before THV expansion (n = 52; 87%), the success rate of TAVR with ≤mild CMA was 98%. No procedure- or valve-related complications occurred in this study cohort.A patient-specific TAVR implantation technique aiming to obtain neo-commissural alignment is feasible and safe, and aides to prevent THV implantations with overlap between the coronary ostia and THV commissures. Optimized TAVR devices and design may further improve the success rate of TAVR with neo-commissural alignment.

Aims Little is known about the prevalence of aortic aneurysms among people living with HIV (PLWH). We investigated whether HIV status is independently associated with having aortic aneurysms. Furthermore, we determined risk factors associated with aortic aneurysms in PLWH. Methods and results PLWH aged ≥40 years (n = 594) were recruited from the Copenhagen Comorbidity in HIV Infection study and matched for age and sex with uninfected controls (n = 1188) from the Copenhagen General Population Study. Aortic dimensions were assessed using contrast enhanced computed tomography. Aortic aneurysms were defined according to the European Society of Cardiology guidelines, i.e. an aortic dilation of ≥50% or an infrarenal aortic diameter of ≥30 mm. Among PLWH and uninfected controls, the median (interquartile range) age was 52 (47–60) and 52 (48–61) and 88% and 90% were male, respectively. We found 46 aneurysms in 42 (7.1%) PLWH and 31 aneurysms in 29 (2.4%) uninfected controls (P Conclusion PLWH had four-fold higher odds of aortic aneurysms compared to uninfected controls, and HIV status was independently associated with aortic aneurysms. Among PLWH, age, obesity and hepatitis B co-infection were associated with higher odds of aortic aneurysms. Our findings suggest that increased attention to aortic aneurysms in PLWH may be beneficial.

Aims The role of atherosclerosis in the pathogenesis of aortic enlargement is uncertain. We aimed to evaluate the relationship between the diameters of the ascending, descending and abdominal aorta, and coronary artery calcification. Methods and results Individuals in the Copenhagen General Population Study underwent thoracic and abdominal computed tomography. Maximal aortic diameters were measured in each aortic segment and coronary artery calcium scores (CACS) were calculated. Participants were stratified into five predefined groups according to CACSs and compared to aortic dimensions. The relation between aortic diameter and CACS was adjusted for risk factors for aortic dilatation in a multivariable model. A total of 2678 eligible individuals were included. In all segments of the aorta, aortic diameter was associated to CACSs, with mean increases in aortic diameters ranging from 0.7 to 3.5 mm in individuals with calcified coronary arteries compared to non-calcified subjects (P-value < 0.001). After correction for risk factors, individuals with CACS above 400 had larger ascending, descending and abdominal aortic diameter than the non-calcified reference group (P-value < 0.01). Conclusion Enlarged thoracic and abdominal aortic vascular segments are associated with co-existing coronary artery calcification in the general population.

Objective: In complex and high-risk aortic root disease, the porcine Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, Minn) is an important surgical treatment option. We aimed to determine prevalence and clinical effect of structural and functional abnormalities after full-root Freestyle implantation.Methods: Our cross-sectional 2-center study combined with clinical follow-up included 253 patients with full-root Freestyle bioprostheses implanted from 1999 to 2017. Patients underwent transthoracic echocardiography (TTE) and contrast-enhanced, electrocardiogram-gated 4-dimensional cardiac computed tomography (4DCT) at median age 70 (interquartile range, 62-75) years. After 4DCT, clinical follow-up continued throughout 2018. Median follow-up was 3.3 years before 4DCT and 1.4 years after.Results: We identified abnormalities in 46% of patients, including pseudoaneurysms (n = 32; 13%), moderate or severe coronary ostial stenosis (n = 54; 21%), and moderate-severe leaflet thickening or reduced leaflet motion (n = 51; 20%). TTE only identified 1 patient with pseudoaneurysm. After 4DCT, the unadjusted hazard ratio for surgical reintervention among patients with abnormal 4DCT was 4.2 (95% confidence interval, 1.2-15.3), in all, 10% required a reintervention. 4DCT abnormalities were associated with a statistically nonsignificant increased risk of death, stroke, or myocardial infarction (hazard ratio obtained using Cox proportional hazards regression analysis, 2.4; 95% confidence interval, 0.7-7.6). In all, 4.0% died, 3.6% had a myocardial infarction, and 2.0% had a stroke.Conclusions: Structural and functional abnormalities of the aortic root are frequent after Freestyle implantation and TTE appears to be insufficient for follow-up. Abnormalities might be associated with increased risk of reintervention and potentially adverse clinical outcomes. Longer follow-up and larger study populations are needed to further clarify the clinical implications of abnormalities identified with 4DCT. Objective: In complex and high-risk aortic root disease, the porcine Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, Minn) is an important surgical treatment option. We aimed to determine prevalence and clinical effect of structural and functional abnormalities after full-root Freestyle implantation.Methods: Our cross-sectional 2-center study combined with clinical follow-up included 253 patients with full-root Freestyle bioprostheses implanted from 1999 to 2017. Patients underwent transthoracic echocardiography (TTE) and contrast-enhanced, electrocardiogram-gated 4-dimensional cardiac computed tomography (4DCT) at median age 70 (interquartile range, 62-75) years. After 4DCT, clinical follow-up continued throughout 2018. Median follow-up was 3.3 years before 4DCT and 1.4 years after.Results: We identified abnormalities in 46% of patients, including pseudoaneurysms (n = 32; 13%), moderate or severe coronary ostial stenosis (n = 54; 21%), and moderate-severe leaflet thickening or reduced leaflet motion (n = 51; 20%). TTE only identified 1 patient with pseudoaneurysm. After 4DCT, the unadjusted hazard ratio for surgical reintervention among patients with abnormal 4DCT was 4.2 (95% confidence interval, 1.2-15.3), in all, 10% required a reintervention. 4DCT abnormalities were associated with a statistically nonsignificant increased risk of death, stroke, or myocardial infarction (hazard ratio obtained using Cox proportional hazards regression analysis, 2.4; 95% confidence interval, 0.7-7.6). In all, 4.0% died, 3.6% had a myocardial infarction, and 2.0% had a stroke.Conclusions: Structural and functional abnormalities of the aortic root are frequent after Freestyle implantation and TTE appears to be insufficient for follow-up. Abnormalities might be associated with increased risk of reintervention and potentially adverse clinical outcomes. Longer follow-up and larger study populations are needed to further clarify the clinical implications of abnormalities identified with 4DCT.

OBJECTIVES In patients with arterial hypertension (AH), hypertension-mediated organ damage may be manifested by cardiac chamber enlargement and/or remodeling. Cardiac computed tomography imaging has emerged as an important method for morphological assessment of cardiac chambers. We tested the hypothesis that prevalence of cardiac chamber abnormalities is specifically related to clinical categories of AH in the general population. METHODS We studied 4747 individuals, mean age was 60 years (range: 40-93), 46% were men, undergoing 320-detector computed tomography in the Copenhagen General Population Study. Clinical categories of AH were: normotensive (n = 2484), untreated hypertensive (n = 1301), treated controlled hypertensive (n = 412) and treated uncontrolled hypertensive (n = 550). Chamber abnormalities in the form of left ventricular (LV) concentric remodeling, LV eccentric hypertrophy, LV concentric hypertrophy or left atrial enlargement were assessed, in addition to LV or right ventricular enlargement. RESULTS Chamber abnormalities were present in 23% of all individuals. Combined LV and left atrial abnormalities were rare (

Background Patients with chronic kidney disease (CKD) and arterial calcification are considered at increased risk of adverse cardiovascular outcomes. However, the optimal site for measurement of arterial calcification has not been determined. The primary aim of this study was to examine the pattern of arterial calcification in different stages of CKD. Methods This was an observational, cross-sectional study that included 580 individuals with CKD stages 1–5 (no dialysis) from the Copenhagen CKD Cohort. Calcification of the carotid, coronary and iliac arteries, thoracic and abdominal aorta was assessed using non-contrast multidetector computed tomography scans and quantified according to the Agatston method. Based on the distribution of Agatston scores in the selected arterial region, the subjects were divided into calcium score categories of 0 (no calcification), 1–100, 101–400 and > 400. Results Participants with CKD stages 3–5 had the highest prevalence of calcification and the highest frequency of calcium scores > 400 in all arterial sites. Calcification in at least one arterial site was present in > 90% of patients with CKD stage 3. In all five CKD stages prevalence of calcification was greatest in both the thoracic and abdominal aorta, and in the iliac arteries. These arterial sites also showed the highest calcium scores. High calcium scores (> 400) in all five arterial regions were independently associated with prevalent cardiovascular disease. In multivariable analyses, after adjusting for cardiovascular risk factors, declining creatinine clearance was associated with increasing calcification of the coronary arteries (p = 0.012) and the thoracic aorta (p = 0.037) only. Conclusions Arterial calcification is highly prevalent throughout all five CKD stages and is most prominent in both the thoracic and abdominal aorta, and in the iliac arteries. Follow-up studies are needed to explore the potential of extracardiac calcification sites in prediction of cardiovascular events in the CKD population.

Background People with human immunodeficiency virus (PWH) may be at risk of nonalcoholic fatty liver disease. We compared the prevalence of moderate-to-severe hepatic steatosis (M-HS) in PWH with human immunodeficiency virus (HIV)-uninfected controls and determined risk factors for M-HS in PWH. Methods The Copenhagen Co-Morbidity in HIV Infection study included 453 participants, and the Copenhagen General Population Study included 765 participants. None had prior or current viral hepatitis or excessive alcohol intake. Moderate-to-severe hepatic steatosis was assessed by unenhanced computed tomography liver scan defined by liver attenuation ≤48 Hounsfield units. Adjusted odds ratios (aORs) were computed by adjusted logistic regression. Results The prevalence of M-HS was lower in PWH compared with uninfected controls (8.6% vs 14.2%, P Conclusions Moderate-to-severe hepatic steatosis is less common in PWH compared with demographically comparable uninfected controls. Besides BMI and ALT, integrase inhibitor exposure was associated with higher prevalence of steatosis in PWH.

Aims Left ventricular (LV) myocardial crypts are considered a subtle marker of hypertrophic cardiomyopathy. However, crypts have also been observed in seemingly healthy individuals and it is unknown whether myocardial crypts are associated with adverse outcome. Methods and results Myocardial crypts were defined as invaginations traversing >50% of the myocardial wall and assessed using contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. Number of crypts, location, shape, penetrance, and volume were assessed. The endpoint was a composite of major adverse cardiovascular events and defined as death, myocardial infarction, heart failure, or stroke. Cox regression models were adjusted for clinical variables, medical history, electrocardiographic parameters, and cardiac chamber sizes. A total of 1199 LV myocardial crypts were identified in 915 (9.1%) individuals. Seven hundred (6.9%) had one crypt and 215 (2.1%) had multiple crypts. During a median follow-up of 4.0 years (interquartile range 1.5–6.7), major adverse cardiovascular events occurred in 619 individuals. Individuals with one or multiple crypts had a hazard ratio for major adverse cardiovascular events of 1.00 [95% confidence interval (CI): 0.72–1.40; P = 0.98] and 0.90 (95% CI: 0.47–1.75; P = 0.76), respectively, compared with those with no crypts. No specific pattern of crypt location, shape, penetrance, or volume was associated to an increased hazard ratio for major adverse cardiovascular events. Conclusion LV myocardial crypts are frequent in the general population and are not associated with intermediate-term major adverse cardiovascular events.

Background Chest computed tomography (CT) findings in well-treated people with HIV infection (PWH) remain poorly characterized. Methods Cross-sectional analysis examining interstitial chest CT findings in PWH (n = 754) and uninfected controls (n = 470). Results HIV infection was independently associated with 1.82 (95% CI, 1.18–2.88) and 5.15 (95% CI, 1.72–22.2) higher adjusted odds of any interstitial lung abnormality and findings suspicious for interstitial lung disease, respectively. Conclusions HIV infection was independently associated with interstitial lung abnormalities and findings suspicious for interstitial lung disease. Whether these abnormalities develop into more recognizable disease states over time is unknown but warrants further investigation.

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known.METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed.RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively).CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).

Background Although the descending aortic diameter is larger in smokers, data about thoracic aortic growth is missing. Our aim is to present the distribution of thoracic aortic growth in smokers and to compare it with literature of the general population. Methods Current and ex-smokers aged 50–70 years from the longitudinal Danish Lung Cancer Screening Trial, were included. Mean and 95th percentile of annual aortic growth of the ascending aortic (AA) and descending aortic (DA) diameters were calculated with the first and last non-contrast computed tomography scans during follow-up. Determinants of change in aortic diameter over time were investigated with linear mixed models. Results A total of 1987 participants (56% male, mean age 57.4 ± 4.8 years) were included. During a median follow-up of 48 months, mean AA and DA growth rates were comparable between males (AA 0.12 ± 0.31 mm/year and DA 0.10 ± 0.30 mm/year) and females (AA 0.11 ± 0.29 mm/year and DA 0.13 ± 0.27 mm/year). The 95th percentile ranged from 0.42 to 0.47 mm/year, depending on sex and location. Aortic growth was comparable between current and ex-smokers and aortic growth was not associated with pack-years. Our findings are consistent with aortic growth rates of 0.08 to 0.17 mm/years in the general population. Larger aortic growth was associated with lower age, increased height, absence of medication for hypertension or hypercholesterolemia and lower Agatston scores. Conclusions This longitudinal study of smokers in the age range of 50–70 years shows that ascending and descending aortic growth is approximately 0.1 mm/year and is consistent with growth in the general population.

Using four-dimensional (4D) cardiac computed tomography (CCT) scans at rest and immediately after exercise, we examined the right heart chamber sizes and systolic function and its association with exercise capacity in left ventricular assist device (LVAD) recipients. Fifteen patients with HeartMate (HM) II or 3 underwent echocardiography and maximal cardiopulmonary exercise test. Subsequently, contrast-enhanced CCT scans were performed at rest and immediately after two minutes of supine 25 Watt ergometer bike exercise. Patients were (60 ± 12 years of age) 377 ± 347 days postimplant. Peak oxygen uptake (pVO2) was 15 ± 5 ml/kg/min. LV ejection fraction measured by echocardiography was 15 ± 9%. Pump speed was 9500 ± 258 in HM II and 5518 ± 388 rpm in HM 3 recipients. Resting right atrial ejection fraction (RAEF) was 18 ± 9%, and right ventricular ejection fraction (RVEF) was 36 ± 8%. During stress, RAEF was 19 ± 10%, and RVEF was 37 ± 8%. RAEF and RVEF did not correlate significantly with pVO2 at rest or during stress. Resting-RAEF and stress RAEF correlated significantly: r = 0.87, p < 0.01 as did resting RVEF and stress RVEF: r = 0.76, p < 0.01. In conclusion, resting-EF predicted stress-EF for both RA and RV in patients with an LVAD. Neither RVEF nor RAEF correlated with pVO2.

AIMS The study assessed 4-year outcomes of intramyocardial injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic heart failure. METHODS AND RESULTS The MSC-HF trial was a randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to intramyocardial injections of MSCs or placebo. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography. Sixty patients aged 30-80 years with ischaemic heart failure, New York Heart Association class II-III, left ventricular ejection fraction (LVEF)

Background The optimal timing of invasive examination and treatment of high‐risk patients with non–ST‐segment–elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard‐care invasive coronary angiography on the risk of all‐cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non–ST‐segment–elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48–72 hours) invasive strategy. The primary outcome of the present study was all‐cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow‐up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16–3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63–1.10]) ( P interaction =0.006). Conclusions In patients with non–ST‐segment–elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high‐risk and low‐risk patients with non–ST‐segment–elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02061891.

Background Liver fibrosis is associated with poor liver-related outcomes and mortality. People with human immunodeficiency virus (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls. Methods This was a cross-sectional cohort study comparing 342 PWH with 2190 population controls aged 50–70 years. Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6 kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were computed by logistic regression. Results The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%; P < .01). Human immunodeficiency virus (HIV) infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR, 1.84 [95% CI, 1.17–2.88]; P < .01); higher age (per decade: aOR, 3.34 [95% CI, 1.81–6.18]; P < .01); alanine aminotransferase (ALT) (per 10 IU/L: aOR, 1.25 [95% CI, 1.05–1.49]; P < .01); body mass index (BMI) (per 1 kg/m2: aOR, 1.17 [95% CI, 1.05–1.29]; P < .01), and previous exposure to didanosine (per year: aOR, 2.26 [95% CI, 1.01–5.06]; P = .04). Conclusions The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine, and positive HIV status were independently associated with higher odds of elevated LSM.

Women with angina and no obstructive coronary artery disease (CAD) have worse cardiovascular prognosis than asymptomatic women. Limitation in myocardial perfusion caused by coronary microvascular dysfunction (CMD) is one of the proposed mechanisms contributing to the adverse prognosis. The aim of this study was to assess myocardial perfusion in symptomatic women with no obstructive CAD suspected for CMD compared with asymptomatic sex-matched controls using static CT perfusion (CTP). We performed a semi-quantitative assessment of the left ventricular myocardial perfusion and myocardial perfusion reserve (MPR), using static CTP with adenosine provocation, in 105 female patients with angina and no obstructive CAD (

Computed tomography derived fractional flow reserve (FFRCT) and computed tomography stress myocardial perfusion imaging (CTP) are techniques to assess haemodynamic significance of coronary stenosis. To compare the diagnostic performance of FFRCT and static rest/stress CTP in detecting fractional flow reserve (FFR) defined haemodynamically-significant stenosis (FFR ≤ 0.8). Fifty-one patients (96 vessels) with suspected coronary artery disease from a single institution planned for elective invasive-angiography prospectively underwent research indicated 320-detector-CT-coronary-angiography (CTA) and adenosine-stress CTP and invasive FFR. Analyses were performed in separate core-laboratories for FFRCT and CTP blinded to FFR results. Myocardial perfusion was assessed visually and semi-quantitatively by transmural perfusion ratio (TPR). Invasive FFR ≤ 0.8 was present in 33% of vessels and 49% of patients. FFRCT, visual CTP and TPR analysis was feasible in 96%, 92% and 92% of patients respectively. Overall per-vessel sensitivity, specificity and diagnostic accuracy for FFRCT were 81%, 85%, 84%, for visual CTP were 50%, 89%, 75% and for TPR were 69%, 48%, 56% respectively. Receiver-operating-characteristics curve analysis demonstrated larger per vessel area-under-curve (AUC) for FFRCT (0.89) compared with visual CTP (0.70; p

Background Patient preference is pivotal for widespread adoption of tests in clinical practice. Patient preferences for invasive versus other noninvasive tests for coronary artery disease are not known. Purpose To compare patient acceptance and preferences for noninvasive and invasive cardiac imaging in North and South America, Asia, and Europe. Materials and Methods This was a prospective 16-center trial in 381 study participants undergoing coronary CT angiography with stress perfusion, SPECT, and invasive coronary angiography (ICA). Patient preferences were collected by using a previously validated questionnaire translated into eight languages. Responses were converted to ordinal scales and were modeled with generalized linear mixed models. Results In patients in whom at least one test was associated with pain, CT and SPECT showed reduced median pain levels, reported on 0-100 visual analog scales, from 20 for ICA (interquartile range [IQR], 4-50) to 6 for CT (IQR, 0-27.5) and 5 for SPECT (IQR, 0-25) (P < .001). Patients from Asia reported significantly more pain than patients from other continents for ICA (median, 25; IQR, 10-50; P = .01), CT (median, 10; IQR, 0-30; P = .02), and SPECT (median, 7; IQR, 0-28; P = .03). Satisfaction with preparation differed by continent and test (P = .01), with patients from Asia reporting generally lower ratings. Patients from North America had greater percentages of "very high" or "high" satisfaction than patients from other continents for ICA (96% vs 82%, respectively; P < .001) and SPECT (95% vs 79%, respectively; P = .04) but not for CT (89% vs 86%, respectively; P = .70). Among all patients, CT was preferred by 54% of patients, compared with 18% for SPECT and 28% for ICA (P < .001). Conclusion For cardiac imaging, patients generally favored CT angiography with stress perfusion, while study participants from Asia generally reported lowest satisfaction. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Woodard and Nguyen in this issue.

Aims Accurate echocardiographic assessment of left ventricular outflow tract (LVOT) and the aortic root is necessary for risk stratification and choice of appropriate treatment in patients with pathologies of the aortic valve and aortic root. Conventional 2D transthoracic echocardiographic (TTE) assessment is based on the assumption of a circular shaped LVOT and aortic root, although previous studies have indicated a more ellipsoid shape. 3D TTE and multidetector computed tomography (MDCT) applies planimetry and are not dependent on geometrical assumptions. The aim was to test accuracy, feasibility, and reproducibility of 3D TTE compared to 2D TTE assessment of LVOT and aortic root areas, with MDCT as reference. Methods and results We examined 51 patients with 2D/3D TTE and MDCT at the same day. All patients were re-examined with 2D/3D TTE on a different day to evaluate 2D and 3D re-test variability. Areas of LVOT, aortic annulus, and sinus were assessed using 2D, 3D TTE, and MDCT. Both 2D/3D TTE underestimated the areas compared to MDCT; however, 3D TTE areas were significantly closer to MDCT-areas. 2D vs. 3D mean MDCT-differences: LVOT 1.61 vs. 1.15 cm2, P = 0.019; aortic annulus 1.96 vs. 1.06 cm2, P Conclusion Estimation of LVOT and aortic root areas using 3D TTE is feasible, more precise and more accurate than 2D TTE.

Type 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes.This was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/mPersons with and without CAN had mean ± SD age of 57 ± 7 and 50 ± 8 years (p 0.001) and diabetes duration of 36 ± 11 and 32 ± 9 years (p 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (-0.5, 95% CI -1.0 to -0.0, p 0.05) and trend towards larger left (-0.4, 95% CI -0.8-0.0, p 0.1) ventricular volumes in multivariable linear regression.Our results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure.

Objectives To develop and evaluate a fully automatic method to measure diameters of the ascending and descending aorta on non-ECG-gated, non-contrast computed tomography (CT) scans. Material and methods The method combines multi-atlas registration to obtain seed points, aorta centerline extraction, and an optimal surface segmentation approach to extract the aorta surface around the centerline. From the extracted 3D aorta segmentation, the diameter of the ascending and descending aorta was calculated at cross-sectional slices perpendicular to the extracted centerline, at the level of the pulmonary artery bifurcation, and at 1-cm intervals up to 3 cm above and below this level. Agreement with manual annotations was evaluated by dice similarity coefficient (DSC) for segmentation overlap, mean surface distance (MSD), and intra-class correlation (ICC) of diameters on 100 CT scans from a lung cancer screening trial. Repeatability of the diameter measurements was evaluated on 617 baseline-one year follow-up CT scan pairs. Results The agreement between manual and automatic segmentations was good with 0.95 ± 0.01 DSC and 0.56 ± 0.08 mm MSD. ICC between the diameters derived from manual and from automatic segmentations was 0.97, with the per-level ICC ranging from 0.87 to 0.94. An ICC of 0.98 for all measurements and per-level ICC ranging from 0.91 to 0.96 were obtained for repeatability. Conclusion This fully automatic method can assess diameters in the thoracic aorta reliably even in non-ECG-gated, non-contrast CT scans. This could be a promising tool to assess aorta dilatation in screening and in clinical practice. Key Points • Fully automatic method to assess thoracic aorta diameters. • High agreement between fully automatic method and manual segmentations. • Method is suitable for non-ECG-gated CT and can therefore be used in screening. Electronic supplementary material The online version of this article (10.1007/s00330-018-5931-z) contains supplementary material, which is available to authorized users.

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1–4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78–1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67–1.01; P value for interaction=0.023). Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Background Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis to non-alcoholic steatohepatitis with or without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far there has been scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate–severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD. Methods Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen CKD Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density Results The prevalence of moderate–severe hepatic steatosis was 7.9 and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled dataset from both cohorts, adjusted odds ratios for moderate–severe hepatic steatosis among persons with diabetes, overweight and obesity were 3.1 [95% confidence interval (CI) 1.6–5.9], 14.8 (95% CI 4.6–47.9) and 42.0 (95% CI 12.9–136.6), respectively. Conclusions In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate–severe hepatic steatosis as assessed by CT scan.

Background and Aims Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and is characterised by hepatic accumulation of lipids. NAFLD represents a wide spectrum ranging from mild steatosis over non-alcoholic steatohepatitis with and without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far, there is scarce evidence of the prevalence of NAFLD among patients with CKD. The aim of this study was to investigate the prevalence of moderate to severe steatosis in a cohort with patients with different stages of CKD not on dialysis. Method A total of 291 patients from the Copenhagen Chronic Kidney Disease Study were included. For comparison, 866 participants with normal kidney function from the Copenhagen General Population Study were identified as controls. Blood samples, clinical demographics, information about smoking and alcohol were collected. Hepatic liver fat fraction was evaluated in all participants by computed tomography (CT). Liver attenuation density Results The prevalence of moderate to severe steatosis was 7.9% and 10.7% among patients with CKD and controls, respectively. Data of the continuous Hounsfield Units showed lower values among patients with CKD compared with the control group. No significant association between liver fat fraction and CKD stage was found. Pooled data from both cohorts showed that adjusted odds ratios (OR) for steatosis were strongly significant among persons with diabetes (OR 3.1, 95% confidence interval (CI) 1.6-5.9), overweight (OR 14.8, 95% CI 4.6-47.9) and obesity (OR 42.0, 95% CI 12.9-136.6), respectively. Conclusion In the present cohort of 291 patients with CKD, kidney function was not associated with the prevalence of hepatic steatosis as assessed by CT scan.

Background and Aims The relation between chronic kidney disease and adverse cardiovascular events is well-established. It is also known that traditional risk factors of cardiovascular disease such as smoking, low-density lipoprotein (LDL) cholesterol and increased blood pressure, cannot fully explain the increased cardiovascular burden observed in patients with chronic kidney disease. In addition, patients with chronic kidney disease do not demonstrate typical clinical symptoms of cardiovascular disease. Thus, good biomarkers for identifying patients at risk and a better understanding of the pathophysiology leading to cardiovascular disease in patients with chronic kidney disease are needed. The objective of the present study was to investigate associations between plasma metabolites and prevalent cardiovascular disease, as well as subclinical cardiovascular disease measured as coronary artery calcification score (CACS), in patients with chronic kidney disease. Method More than 200 metabolic biomarkers, including subclasses of lipoproteins as well as the lipid composition of these, were quantified using nuclear magnetic resonance spectroscopy in 725 patients and 174 controls from the Copenhagen Chronic Kidney Disease Cohort, a single-centre prospective, observational study of non-dialysis patients with stage 1-5 chronic kidney disease. Associations between metabolites and prevalent cardiovascular disease and between metabolites and CACS were determined using multivariable logistic regression and linear regression, respectively. The statistical models were adjusted for traditional cardiovascular risk factors and multiple testing. CACS was determined by CT-scannning and calcium scores were subsequently divided into categories of 0 (no calcification), 1-100, 101-400 and > 400. Results When comparing metabolite concentrations in patients with controls, patients presented with the expected pattern of dyslipidaemia in CKD. We found that they had increased plasma triglyceride concentrations, mainly due to an increase in the triglyceride concentration in very low-density lipoprotein (VLDL) particles, while the concentration of cholesterol in high-density lipoprotein (HDL) particles was decreased. Overall, 85 metabolites were significantly associated with prevalent cardiovascular disease in a model adjusted for eGFR, age and sex (p < 0.001). After further adjusting for diabetes, body mass index, smoking and cholesterol-lowering medication, the significance was lost for all but six metabolites (p < 0.001). The consistent inverse associations with metabolites were primarily involved in HDL metabolism (e.g. ApoA-1, HDL-C and HDL-2). This also applied to the concentration of total lipids in large HDL particles, the concentration of phospholipids in large HDL particles and the the ratio of phospholipids to total lipids in very small VLDL particles. Of the 84 metabolites associated with prevalent cardiovascular disease, 71 were also associated with CACS in a similar pattern. Yet, in the model adjusted for all seven cardiovascular risk factors, only plasma glucose levels as well as the triglyceride content of larger LDL particles remained significant. Conclusion In this study we identified metabolites associated with prevalent cardiovascular disease and subclinical cardiovascular disease (CACS) in patients with CKD. For prevalent cardiovascular disease associations were mainly found for HDL associated metabolites, while CACS was associated with an increase in the triglyceride content of LDL particles and glucose. Further work needs to be done to establish whether these associations are merely a consequence of the cardiovascular burden or whether there is a causal relation.

Background and Aims Chronic kidney disease (CKD) accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPT max) was increased in patients with CKD stage 3 compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. Method The study group consisted of 200 patients with CKD stage 3 from the Copenhagen CKD Cohort and 121 age- and sex-matched controls. cPT max was assessed by ultrasound and arterial calcification by computed tomography scanning. Results Carotid plaques were present in 58% of patients (n=115) compared with 40% of controls (n=48), P=0.002. Among participants with plaques, cPT max (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4-2.3) versus 1.5 (1.2-1.8) mm, P=0.001. Cardiovascular disease was present in 9.4% of patients without plaques (n=85), 23.2% of patients with cPT max 1.0-1.9 mm (n=69) and 34.8% of patients with cPT max >1.9 mm (n=46), P=0.001. Carotid and coronary calcium scores >400 were present in 0.0% and 4.0%, respectively, of patients with no carotid plaques, in 19.1% and 24.2% of patients with cPT max 1.0-1.9 mm, and in 47.5% and 52.6% of patients with cPT max >1.9 mm, P Conclusion This is the first study showing that cPT max is increased in patients with CKD stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

Background Liver transplantation is the only curative treatment for patients with end-stage liver disease. Short-term survival has improved due to improved surgical techniques and greater efficacy of immunosuppressive drugs. However, long-term survival has not improved to the same extent as the short-term survival, and the 10-year survival after liver transplantation is 60%. In addition to liver- and transplant-related causes, comorbidities such as cardiovascular, pulmonary, renal, and metabolic diseases have emerged as leading causes of morbidity and mortality in liver transplant recipients. The objective of this study is to assess the burden of comorbidities and identify both liver- and transplant-related risk factors as well as traditional risk factors that contribute to the pathogenesis of comorbidity in liver transplant recipients. Methods/design The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study is an observational, longitudinal study. We aim to include all adult liver transplant recipients in Denmark (n = approx. 600). Participants will be matched by sex and age to controls from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). Physical and biological measures including blood pressure, ankle–brachial index, spirometry, exhaled nitric oxide, electrocardiogram, transthoracic echocardiography, computed tomography (CT) angiography of the heart, unenhanced CT of chest and abdomen and blood samples will be collected using uniform protocols in participants in DACOLT, CGPS, and CCHS. Blood samples will be collected and stored in a research biobank. Follow-up examinations at regular intervals up to 10 years of follow-up are planned. Discussion There is no international consensus standard for optimal clinical care or monitoring of liver transplant recipients. This study will determine prevalence, incidence and risk factors for comorbidity in liver transplant recipients and may be used to provide evidence for guidelines on management, treatment and screening and thereby contribute to improvement of the long-term survival. Trial registration ClinicalTrials.gov: NCT04777032; date of registration: March 02, 2021.

Background Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS). Objectives This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. Methods The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non–high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. Results Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non–high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). Conclusions Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891 )

Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08–2.28] per decade older), being underweight (RR: 5.79 [1.70–19.71]), current smoking (RR: 2.34 [1.06–5.16]), diabetes (RR: 3.89 [1.72–8.80]) and protease inhibitor use (RR: 2.45 [1.27–4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH. Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08–2.28] per decade older), being underweight (RR: 5.79 [1.70–19.71]), current smoking (RR: 2.34 [1.06–5.16]), diabetes (RR: 3.89 [1.72–8.80]) and protease inhibitor use (RR: 2.45 [1.27–4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH.

Background Chronic kidney disease accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPTmax) was increased in patients with chronic kidney disease compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. Methods The study group consisted of 200 patients with chronic kidney disease stage 3 from the Copenhagen Chronic Kidney Disease Cohort and 121 age- and sex-matched controls. cPTmax was assessed by ultrasound and arterial calcification by computed tomography scanning. Results Carotid plaques were present in 58% of patients (n = 115) compared with 40% of controls (n = 48), p = 0.002. Among participants with plaques, cPTmax (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4–2.3) versus 1.5 (1.2–1.8) mm), p = 0.001. Cardiovascular disease was present in 9% of patients without plaques (n = 85), 23% of patients with cPTmax 1.0–1.9 mm (n = 69) and 35% of patients with cPTmax >1.9 mm (n = 46), p = 0.001. Carotid and coronary calcium scores >400 were present in 0% and 4%, respectively, of patients with no carotid plaques, in 19% and 24% of patients with cPTmax 1.0–1.9 mm, and in 48% and 53% of patients with cPTmax >1.9 mm, p Conclusions This is the first study showing that cPTmax is increased in patients with chronic kidney disease stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

OBJECTIVES The aim of this study was to assess coronary accessibility after transcatheter aortic valve replacement (TAVR)-in-TAVR using multidetector computed tomography. BACKGROUND Expanding TAVR to patients with longer life expectancy may involve more frequent bioprosthetic valve failure and need for redo TAVR. Coronary access after TAVR-in-TAVR may be challenging, particularly as the leaflets from the initial transcatheter heart valve (THV) will form a neo-skirt following TAVR-in-TAVR. METHODS In 45 patients treated with different combinations of CoreValve and Evolut (CV/EV) THVs with supra-annular leaflet position and SAPIEN THVs with intra-annular leaflet position, post-TAVR-in-TAVR multidetector computed tomographic scans were analyzed to examine coronary accessibility. RESULTS After TAVR-in-TAVR, the coronary arteries originated below the top of the neo-skirt in 90% of CV/EV-first cases compared with 67% of SAPIEN-first cases (p = 0.009). For these coronary arteries originating below the top of the neo-skirt, the distance between the THV and the aortic wall was

Background Noninvasive evaluation of patients with stable angina is preferable over invasive testing if it leads to similar patient outcome. The combination of coronary angiography and vasodilator challenge myocardial perfusion imaging by computed tomography allows fast, comprehensive assessment of patients with suspected coronary heart disease. Purpose To compare the long-term prognostic value of combined computed tomography angiography (CTA) and myocardial CT perfusion imaging (CTP) with invasive coronary angiography (ICA) and single photon emission tomography (SPECT) in patients with suspected hemodynamically significant coronary heart disease. Methods At 16 centres, 381 patients were followed for major adverse cardiac events (MACE) for the CORE320 study. All patients underwent coronary CTA, CTP, and SPECT before ICA. Prognostic performance according binary results (normal/abnormal) was assessed by 5-year major cardiovascular events (MACE) free survival and area under the receiver-operating-characteristic curve (AUC). Results Follow up beyond 2-years was available in 323 patients. MACE-free survival rate was greater among patients with normal combined CTA/CTP findings compared to ICA/SPECT: 85 vs. 80% (95% confidence interval [CI] for difference 0.1, 11.3) though event-free survival time was similar (4.54 vs. 4.37 years, 95% CI for difference: 0.03, 0.36). Abnormal results by combined CTA/CTP was associated with 3.83 years event-free survival vs. 3.66 years after abnormal combined ICA/SPECT (95% CI for difference: 0.05, 0.39, CI −1.0, 11.1) (Figure). Predicting MACE by AUC also was similar: 65 vs. 65 (difference 0.1; 95% CI: −4.6, 4.9). When MACE was restricted to death, myocardial infarction, or stroke, AUC for CTA/CTP was 66 vs. 61 by ICA/SPECT (difference 5.1; 95% CI: −7.1, 12.9). Conclusions Combined CTA/CTP yield similar 5-year prognostic performance as joined ICA/SPECT assessment in patients presenting with suspected coronary heart disease and thus may represent a fast, non-invasive alternative to the traditional diagnostic approach. Figure 1. 5-year event-free survival Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Institutes of Health

Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD.From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale.Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type.Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.Clinicaltrials.gov, NCT02400229.

OBJECTIVES People living with HIV (PLWH) have increased risk of cardiovascular diseases compared with uninfected populations. We assessed structural cardiac abnormalities and their associated risk factors in well-treated PLWH and uninfected controls using multidetector computed tomography (MDCT). METHODS People living with HIV and age- and sex-matched uninfected controls underwent MDCT to determine left atrial volume (LAV), left ventricular diastolic volume (LVDV), right ventricular diastolic volume (RVDV) and left ventricular mass (LVM). All outcomes were indexed to body surface area (BSA) (LAVi, LVDVi, RVDVi and LVMi). RESULTS A total of 592 PLWH and 1184 uninfected controls were included in the study. PLWH had smaller mean (SD) LAVi [40 (8) vs. 41 (9) mL/m2 ; P = 0.002] and LVDVi [61 (13) vs. 65 (14) mL/m2 ; P

To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67–0.78) but improved after excluding patients with known CAD (AUC range 0.73–0.86, p

Aims Prominent left ventricular trabeculations is a phenotypic trait observed in cardiovascular diseases. In the general population, the extent of left ventricular trabeculations is highly variable, yet it is unknown whether increased trabeculation is associated with adverse outcome. Methods and results Left ventricular trabeculated mass (g/m2) was measured with contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. The primary endpoint was a composite of major adverse cardiovascular events and defined as death, heart failure, myocardial infarction, or stroke. The secondary endpoints were the individual components of the primary endpoint. Cox regression models were adjusted for clinical parameters, medical history, electrocardiographic parameters, and cardiac chamber sizes. The mean trabeculated mass was 19.1 g/m2 (standard deviation 4.9 g/m2). During a median follow-up of 4.0 years (interquartile range 1.5–6.7), 710 major adverse cardiovascular events occurred in 619 individuals. Individuals with a left ventricular trabeculated mass in the highest quartile had a hazard ratio for major adverse cardiovascular events of 1.64 [95% confidence interval (CI) 1.30–2.08; P Conclusion Increased left ventricular trabeculation is independently associated with an increased rate of major adverse cardiovascular events in the general population.

Background Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls. Methods PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of >1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta. Results In total, 900 PWH were included, and 44 (5%) had a pulmonary artery–aorta ratio (PA:A) >1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76–10.65; P = .001) and injection drug use (IDU) (4.90; 1.00–18.46; P = .03) were associated with higher odds of having a PA:A >1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A >1 (adjusted odds ratio, 1.89; 95% confidence interval, .92–3.85; P = .08). Conclusions A PA:A >1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU.

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality., Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. In this Consensus Statement, the authors summarize the use of SPECT, PET, MRI, echocardiography, CT and invasive coronary flow and pressure measurement, and describe the relative strengths and weaknesses of each modality.

Background Low bone mineral density (BMD) has been described in people living with HIV (PLWH). We examined the prevalence of low BMD measured by quantitative computed tomography (QCT), a method that allows 3-dimensional volumetric density measures at the thoracic spine, in well-treated PLWH and uninfected controls and assessed risk factors for reduced BMD. Methods Cross-sectional study including 718 PLWH from the Copenhagen Co-Morbidity in HIV infection (COCOMO) study and 718 uninfected controls matched on age and sex from the Copenhagen General Population Study (CGPS). Trabecular BMD was determined by QCT. Results Median BMD was 144.2 mg/cm in PLWH vs. 146.6 mg/cm in controls (P = 0.580). HIV status was not associated with BMD in univariable or multivariable linear analyses. However, a higher prevalence of very low BMD (T-score ≤ -2.5) was found in PLWH (17.2% vs. 11.0% in controls, P = 0.003). In unadjusted analysis, HIV was associated with very low BMD (odds ratio 1.68 [95% confidence interval: 1.24-2.27], P = 0.001), but this association was not significant after adjusting for age, sex, smoking, alcohol, body mass index, physical activity, and ethnicity. Previous AIDS-defining disease was associated with lower BMD, but no other associations with HIV-specific variables were identified. Conclusion Using QCT, we found a higher prevalence of very low BMD in PLWH than in controls. However, HIV status was not independently associated with BMD indicating that traditional risk factors contribute to the difference in prevalence of very low BMD. Focus on improvement of lifestyle factors, especially in PLWH with previous AIDS-defining disease, may prevent very low BMD in PLWH.

Background: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD.Methods: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale.Results: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p p p Conclusions: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.Trial registration: Clinicaltrials.gov, NCT02400229.

The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone.Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease.Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization.Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups.A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2-Myocardial CT Perfusion [CATCH2]; NCT02014311).

Aims Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. Methods and results A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129–166) mm3, 257 (224–295) mm3, and 407 (363–457) mm3, respectively, P Conclusion Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.

Combined coronary CT angiography and CT perfusion (CTP) is a novel, non-invasive, 'one-stop' diagnostic tool to rule out ischaemia in patients suspected for coronary artery disease (CAD). However, the normal myocardial perfusion pattern by static CTP in humans is poorly described. We aimed to investigate global and regional myocardial perfusion during rest and adenosine-induced hyperaemia in asymptomatic women without history of coronary heart disease (CHD).Using a 320-row CT scanner with a static protocol, semi-quantitative assessment of rest and stress CTP was performed in 34 asymptomatic middle-aged women without obstructive CAD (50% stenosis) or history of CHD, and with normal exercise stress test and left ventricular (LV) function. Using a 16-segment model, we assessed global and regional values of LV myocardial perfusion reserve (MPR) and transmural perfusion ratio (TPR).Mean±SD age was 56 ± 13 years. Resting and hyperaemic myocardial perfusion was heterogeneously distributed throughout the LV myocardium. During hyperaemia, global MPR increased by median (IQR) 158% (144-176) with the highest increase in the right coronary artery territory (171%; P0.02). Rest and stress segmental TPR values ranged between 0.93-1.26 and 0.99-1.13, respectively, with the lowest values detected in the inferoseptal segments. No differences in perfusion parameters were found between participants with normal epicardial arteries and participants with non-significant epicardial atheromatosis (all P0.05). Global perfusion parameters were not associated with age or menopausal status (all P0.05).This descriptive study presents data on global and regional myocardial perfusion in a cohort of healthy middle-aged women.

The aim of this study was to assess the commissural alignment between bioprosthetic and native aortic valve leaflets following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) and to investigate its impact on valvular function and coronary filling.Expansion and geometry have been shown to affect leaflets of implanted transcatheter aortic bioprosthesis, but commissural alignment has not been studied.Pre- and post-procedural multidetector computed tomography (MDCT) of 28 SAVR patients and 212 TAVR patients were analyzed. Commissural alignment between the bioprosthetic (post) and native (pre) aortic valves was categorized as aligned (0° to 15° angle deviation) or as mild (15° to 30°), moderate (30° to 45°), or severe (45° to 60°) commissural misalignment (CMA).With SAVR, 27 of 28 cases (96%) were aligned and 1 had mild CMA. For all types of transcatheter heart valves (THVs), there was random valve implantation with regard to commissural alignment: 22% of THVs were aligned, 25% had mild CMA, 22% had moderate CMA, and 31% had severe CMA. The degree of commissural alignment was not associated with a difference in transvalvular gradient, paravalvular aortic regurgitation, or simulated coronary filling. However, there was a significantly higher rate of mild central aortic regurgitation in those THVs with moderate or greater CMA compared with those THV with mild or less CMA (7.8% vs. 1.1%; p = 0.03).Commissural alignment is excellent in case of SAVR but random in case of TAVR. There is no association between CMA and transvalvular gradient or coronary filling; however, there is a significantly higher rate of mild central aortic regurgitation in case of moderate or greater CMA.

BackgroundIncreased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors.MethodsPersons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography.ResultsA total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10–23; P ConclusionsHuman immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population.

Background: This study aimed to compare different pre-procedural left atrial appendage (LAA) imaging modalities and analyze the anatomical adaptation of the LAA to the closure device at 3-month mul...

Aims In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results In a cohort study of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2.41 (1.28-4.51)(P-trend = 0.004). The corresponding OR for IHD in individuals with vs. without NAFLD was 1.65 (1.34-2.04)(P = 3×10-6). PNPLA3 I148M was associated with a stepwise increase in liver fat content of up to 28% in MM vs. II-homozygotes (P-trend = 0.0001) and with ORs of 2.03 (1.52-2.70) for NAFLD (P = 3×10-7), 3.28 (2.37-4.54) for cirrhosis (P = 4×10-12), and 0.95 (0.86-1.04) for IHD (P = 0.46). In agreement, in meta-analysis (N = 279 013/IHD = 71 698), the OR for IHD was 0.98 (0.96-1.00) per M-allele vs. I-allele. The OR for IHD per M-allele higher genetically determined liver fat content was 0.98 (0.94-1.03) vs. an observational estimate of 1.05 (1.02-1.09)(P for comparison = 0.02). Conclusion Despite confirming the known observational association of liver fat content and NAFLD with IHD, lifelong, genetically high liver fat content was not causally associated with risk of IHD. These results suggest that the observational association is due to confounding or reverse causation.

AIMS This study aimed to assess the potential relationship between subclinical leaflet thickening and stent frame geometry in patients who underwent aortic valve replacement with a self-expanding transcatheter heart valve (THV). METHODS AND RESULTS Seventy-five patients with a self-expanding THV were studied with 4D-computed tomography and analysed for leaflet thickening. There was no difference in THV size, overall THV expansion, eccentricity or implantation depth between patients with and those without leaflet thickening. Moderate-to-severe regional THV underexpansion (≤90°) more frequently occurred at the non-coronary and right coronary cusps with a significantly higher incidence of leaflet thickening than in cases of full regional THV expansion (24% vs. 3%, p

Aims Four-dimensional volume-rendered computed tomography (4DCT) has demonstrated instances of hypo-attenuating leaflet thickening (HALT) with or without hypo-attenuation affecting motion (HAM) after transcatheter and surgical aortic valve implantation (TAVI, SAVR). The temporal pattern of evolution of these phenomena is uncertain. Methods and results The SAVORY registry enrolled patients treated by TAVI (n = 75) or SAVR (n = 30) with two 4DCT scans fully interpretable for HALT and HAM as well as unchanged anti-thrombotic medication between the scans. Logistic regression analysis was performed to examine the evolution of HALT and HAM while accounting for demographic and baseline variables, timing of both CT scans, valve type and antithrombotic therapy. The analysis population consisted of 84 patients, in whom first and second CT scans were performed at 140 ± 152 days and 298 ± 141 days after valve implantation, respectively. Hypo-attenuating leaflet thickening was noted in 32 patients (38.1%), with HAM in 17 (20.2%). Both findings were dynamic, showing progression in 13 (15.5%) and regression and 9 (10.7%) patients. Compared with antiplatelet therapy, progression was less likely among patients on oral anticoagulation with vitamin-K antagonists or non-VKA oral anticoagulants (odds ratio: 0.014, P = 0.036). Maintenance on chronic oral anticoagulation was not a significant predictor of regression. These findings were similar for both transcatheter and surgical bioprosthetic aortic valves. No patients developed symptoms of valve dysfunction and leaflet thickening was not clearly associated with any clinical events. Conclusions Subclinical leaflet thrombosis is a common finding after TAVI and SAVR, and may progress from normal leaflet over HALT to the more severe HAM. The phenomenon can develop and regress at variable intervals after valve implantation. Anticoagulants may have a protective effect against the development of HALT, but HALT can also regress without anticoagulation therapy. Registered at clinicaltrials.gov NCT02426307.