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BackgroundCardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement.MethodsThe DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a non-apical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and non-planned HF hospitalization. Patients are followed for a minimum of two years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024.ConclusionsThe DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or non-planned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. Background: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. Methods: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. Conclusions: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. ClinicalTrials.gov identifier: NCT03280862.

Background Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites. Methods This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1–100, 101–400 and >400. Results During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, hypertension, diabetes mellitus, hypercholesterolemia and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, at 0.21 [95% confidence interval (CI) 0.16%–0.26%, P Conclusions The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.

INTRODUCTION We aimed to determine the prevalence of coronary artery disease (CAD) in persons with HIV (PWH) and investigate if inflammatory markers including interleukin (IL)-6, IL-1β, and high sensitivity C-reactive protein (hsCRP) were associated with CAD. METHODS From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH with a coronary CT angiography. Any atherosclerosis was defined as >0% stenosis and obstructive CAD was defined as ≥50% stenosis. RESULTS Among 669 participants (mean age 51 (±11) years, 89% men), 300 (45%) had atherosclerosis, and obstructive CAD was present in 119 (18%). Risk factors including age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use were associated with any atherosclerosis and with obstructive CAD. IL-6 and hsCRP > 2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses, but not after adjusting for traditional risk factors. IL-1β was not associated with CAD. CONCLUSIONS In a large population of PWH without viral replication, almost half had angiography-verified atherosclerosis. High concentrations of IL-6 and hsCRP were univariably associated with CAD but adjusting for cardiovascular risk factors attenuated the association suggesting that inflammation may mediate the association between traditional risk factors and CAD.

Women with previous preeclampsia have an increased risk of coronary artery disease later in life.This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population.Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score0 in case of a nondiagnostic coronary CTA.A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/mYounger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

BACKGROUND: An inferoposterior transseptal puncture (TSP) is generally recommended for percutaneous left atrial appendage (LAA) closure. However, the LAA is a highly variable anatomical structure. This may have an impact on the preferred TSP site. AIMS: This study aimed to determine the optimal TSP site for percutaneous LAA closure in different LAA morphologies. METHODS: In this prospective study, 182 patients undergoing percutaneous LAA closure were included. The spatial relationship of the LAA to the fossa ovalis and its consequence for TSP was assessed at preprocedural cardiac computed tomography (CCT). RESULTS: Based on CCT analysis, it was predicted that coaxial alignment between the delivery sheath and the LAA would be obtained by an inferoposterior, inferocentral, or inferoanterior TSP in 75%, 16% and 8% of cases, respectively. This was also confirmed by procedural LAA angiogram in 175 cases (96%) with

Background The aim of the study was to investigate the association between human immunodeficiency virus (HIV)-related gut microbiota changes, alterations in the kynurenine (Kyn) pathway of tryptophan (Trp) metabolism, and visceral adipose tissue in the context of HIV infection. Methods Three hundred eighty-three people with HIV (PWH) were included from the Copenhagen comorbidity in HIV infection (COCOMO) study. Gut microbiota composition was analyzed by 16S ribosomal ribonucleic acid sequencing. Plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by single-slice computed tomography (CT) scan (4th lumbar vertebra). Results The HIV-related gut microbiota alterations were associated with lower Trp (β −.01; 95% confidence interval [CI], −0.03 to −0.00) and higher Kyn-to-Trp ratio (β 0.03; 95% CI, 0.01–0.05), which in turn was associated with higher VAT-to-SAT ratio (β 0.50; 95% CI, 0.10–0.90) and larger VAT area (β 30.85; 95% CI, 4.43–57.28). In mediation analysis, the Kyn-to-Trp ratio mediated 10% (P = .023) of the association between the VAT-to-SAT ratio and HIV-related gut microbiota. Conclusions Our data suggest HIV-related gut microbiota compositional changes and gut microbial translocation as potential drivers of high Kyn-to-Trp ratio in PWH. In turn, increased activity in the Kyn pathway of Trp metabolism was associated with larger visceral adipose tissue area. Taken together, our findings suggest a possible role for this pathway in the gut-adipose tissue axis in the context of HIV infection.

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.

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.

Bleeding is known to influence the prognosis in patients with acute coronary syndromes. In this predefined secondary outcome analysis of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial, we investigated whether a very early invasive coronary angiography (ICA), compared with one performed within 48 to 72 hours (standard care), was associated with fewer serious bleedings. Furthermore, we tested the association between demographic data including GRACE score and serious bleedings as well as bleedings and mortality. In the 2,147 patients included in the main study, bleedings within 30 days of admission were assessed based on Thrombolysis In Myocardial Infarction and Bleeding Academic Research Consortium criteria. Differences were calculated by cumulative incidence methods and Grays test. Variables associated with bleeding and mortality were estimated by Cox proportional hazard models. Serious (Bleeding Academic Research Consortium 3abc) bleeding rates were low (15 [1.4%, standard] vs 12 [1.2%, early], p = 0.56). There were no fatal bleedings or serious bleedings before ICA in either group. By multivariate analysis, there was no difference in bleedings between the 2 groups. Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 6.4; p = 0.02), anemia (HR 7.0, 95% CI 2.8 to 17.0; p 140 was not (HR 1.03, 95% CI 0.4 to 2.9; p = 0.96). In conclusion, serious bleedings were few, and there were none before ICA in either group. A very early invasive strategy did not reduce serious bleedings within 30 days, which was associated with female gender, increasing blood pressure, and anemia.

Background Studies on the pulmonary consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are impeded by limited access to pre–SARS-CoV-2 examinations. Methods We invited Copenhagen General Population Study participants with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) test during the first and second coronavirus disease 2019 waves in Denmark for a repeat chest computed tomography (CT) scan. Paired CT scans were independently assessed for interstitial and noninterstitial abnormalities by 2 trained radiologists. A semiquantitative CT score (ranging from 0 to 20) was used to quantify the extent of interstitial abnormalities. Results Of 111 SARS-CoV-2–infected individuals, 102 (91.2%) experienced symptoms and 12 (11.2%) were hospitalized. Follow-up examination was performed at median of 5.4 (interquartile range, 4.1–7.8) months after a positive SARS-CoV-2 PCR test. Of 67 individuals with paired CT scans, ground glass opacities and reticulation were present in 31 (46.3%) individuals post–SARS-CoV-2 compared to 23 (34.1%) pre–SARS-CoV-2 (mean CT score, 3.0 vs 1.3; P = .011). Results were similar for nonhospitalized individuals. We did not detect development of bronchiectasis, emphysema, or nodules. Conclusions SARS-CoV-2 infection in predominantly nonhospitalized individuals with mild disease was associated with a small increase in only interstitial lung abnormalities.

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 and aims: We tested the hypotheses (i) that elevated lipoprotein(a) is causally associated with both mitral and aortic valve calcification and disease, and (ii) that aortic valve calcification mediates the effect of elevated lipoprotein(a) on aortic valve stenosis. Methods: From the Copenhagen General Population study, we included 12,006 individuals who underwent cardiac computed tomography to measure mitral and aortic valve calcification and 85,884 to examine risk of heart valve disease. Participants had information on plasma lipoprotein(a) and genetic instruments associated with plasma lipoprotein(a) to investigate potential causality. Results: At age 70–79 years, 29% and 54% had mitral and aortic valve calcification, respectively. For 10-fold higher lipoprotein(a) levels, multifactorially adjusted odds ratios for mitral and aortic valve calcification were 1.26 (95% confidence interval: 1.13–1.41) and 1.62 (1.48–1.77). For mitral and aortic valve stenosis, corresponding hazard ratios were 0.93 (95%CI:0.40–2.15, 19 events) and 1.54 (1.38–1.71, 1158 events), respectively. For ≤23 versus ≥36 kringle IV type 2 number of repeats, the age and sex adjusted odds ratios for mitral and aortic valve calcification were 1.53 (1.18–1.99) and 2.23 (1.81–2.76). For carriers versus non-carriers of LPA rs10455872, odds ratios for mitral and aortic valve calcification were 1.33 (1.13–1.57) and 1.86 (1.64–2.13). For aortic valve stenosis, 31% (95%CI:16%–76%) of the effect of lipoprotein(a) was mediated through calcification. Conclusions: Elevated lipoprotein(a) was genetically and observationally associated with mitral and aortic valve calcification and aortic valve stenosis. Aortic valve calcification mediated 31% of the effect of elevated lipoprotein(a) on aortic valve stenosis.

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.

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.

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.

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.

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.

Objectives: Cardiovascular disease is often associated with COPD. Lung density quantification of images obtained from cardiac computed tomography (CT) scans would allow simultaneous evaluation of emphysema and coronary artery calcification score and provide further mechanistic insight into the relationship between these syndromes.Patients and methods: We assessed the agreement between lung density indices obtained by cardiac and full-lung CT scans. Paired cardiac and chest CT scans were assessed in 156 individuals with and without airflow limitation. Quantitative threshold indices of low attenuation area (LAA) and 15th percentile density index (PD15) were compared in terms of precision using Spearman’s correlation coefficient, accuracy using concordance correlation coefficient (CCC), and relative accuracy using P15 and P30. We also assessed the relationship between visually and quantitatively determined emphysema and used receiver operating characteristic curves to evaluate the ability of lung density indices to discriminate airflow limitation.Results: Correlation coefficients between lung density indices obtained from cardiac and chest CT scans were 0.49 for percent LAA (%LAA)-950 and 0.71 for PD15. Corresponding values for CCC, P15, and P30 were 0.33, 3.2, and 5.1, respectively, for %LAA-950, and 0.34, 17.3, and 37.8, respectively, for PD15. For both cardiac and chest CT scans, visually determined emphysema was associated with higher %LAA-950 and lower PD15, and the ability of %LAA-950 and PD15 to discriminate airflow limitation were comparable.Conclusion: Although chest CT imaging is preferable, cardiac CT imaging may also be used for lung emphysema quantification where association measures are of primary interest. Objectives: Cardiovascular disease is often associated with COPD. Lung density quantification of images obtained from cardiac computed tomography (CT) scans would allow simultaneous evaluation of emphysema and coronary artery calcification score and provide further mechanistic insight into the relationship between these syndromes.Patients and methods: We assessed the agreement between lung density indices obtained by cardiac and full-lung CT scans. Paired cardiac and chest CT scans were assessed in 156 individuals with and without airflow limitation. Quantitative threshold indices of low attenuation area (LAA) and 15th percentile density index (PD15) were compared in terms of precision using Spearman’s correlation coefficient, accuracy using concordance correlation coefficient (CCC), and relative accuracy using P15 and P30. We also assessed the relationship between visually and quantitatively determined emphysema and used receiver operating characteristic curves to evaluate the ability of lung density indices to discriminate airflow limitation.Results: Correlation coefficients between lung density indices obtained from cardiac and chest CT scans were 0.49 for percent LAA (%LAA)-950 and 0.71 for PD15. Corresponding values for CCC, P15, and P30 were 0.33, 3.2, and 5.1, respectively, for %LAA-950, and 0.34, 17.3, and 37.8, respectively, for PD15. For both cardiac and chest CT scans, visually determined emphysema was associated with higher %LAA-950 and lower PD15, and the ability of %LAA-950 and PD15 to discriminate airflow limitation were comparable.Conclusion: Although chest CT imaging is preferable, cardiac CT imaging may also be used for lung emphysema quantification where association measures are of primary interest.

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 )