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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.

BackgroundThe ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid cCTA analysis may be limited by extensive coronary artery calcification. In addition, the effect of very early invasive coronary angiography (ICA) with possible revascularisation is debated.MethodsThis is a posthoc analysis of patients ≥75 years included in the Very Early vs Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial. cCTA was performed prior to the ICA. The diagnostic accuracy of cCTA was investigated. Presence of a coronary artery stenosis ≥50% by subsequent ICA was used as reference. Patients were randomised to a very early (within 12 hours of diagnosis) or a standard ICA (within 48–72 hours of diagnosis). The primary composite endpoint was 5-year all-cause mortality, non-fatal recurrent myocardial infarction or hospital admission for refractory myocardial ischaemia or heart failure.ResultsOf 452 (21%) patients ≥75 years, 161 (35.6%) underwent cCTA. 19% of cCTAs excluded significant CAD. The negative predictive value (NPV) of cCTA was 94% (95% CI 79 to 99) and the sensitivity 98% (95% CI 94 to 100). No significant differences in the frequency of primary endpoints were seen in patients randomised to very early ICA (at 5-year follow-up, n=100 (46.9%) vs 122 (51.0%), log-rank p=0.357).ConclusionIn patients ≥75 years with NSTEACS, cCTA before ICA showed a high NPV. A very early ICA

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.

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).

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.

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.

Background Dynamic myocardial CT perfusion (CTP) has emerged as a potential strategy to combine anatomical and functional evaluation in a single modality. However, this method results in a high radiation dose. Methods Dynamic CTP was performed in 56 patients with suspected or known ischemic heart disease of whom 48 had complete CT-data. Datasets with reduced sampling rate of 2- and 3 RR-intervals (2RR and 3RR) were constructed post hoc. Myocardial blood flow (MBF) estimates from the 2RR and 3RR datasets were compared with estimates based on the full dataset (1RR) using the two one-sided test of equivalence for paired samples. Results Significant equivalence was found for rest MBFLV (p ​ Conclusion MBF can be quantitated with dynamic CTP using a sampling strategy of one volume for every second heartbeat. This strategy could lead to a significant reduction in radiation dose.

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.

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.

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)

The relationship between chronic kidney disease (CKD) and cardiovascular events is well-established. Clinically recognised risk factors of cardiovascular disease cannot fully explain this association. The objective of the present cross-sectional study was to investigate associations between serum metabolites and prevalent cardiovascular disease, as well as subclinical cardiovascular disease measured as coronary artery calcium score (CACS) in patients with CKD.More than 200 preselected metabolites were quantified using nuclear magnetic resonance spectroscopy in 725 patients and 174 controls from the Copenhagen CKD Cohort. CACS was determined by computed tomography.Mean age of patients was 57.8 years, and 444 (61.3%) were men. Most of patients had hypercholesterolemia, and 133 (18.3%) had type 2 diabetes. Overall, 85 metabolites were significantly associated with prevalent cardiovascular disease in a model adjusted for eGFR, age, and sex, as well as Bonferroni correction for multiple testing (p 0.001). After further adjusting for diabetes, BMI, smoking, and cholesterol-lowering medication, the significance was lost for all but six metabolites (concentration of ApoA-1, cholesterol in total HDL and HDL2, total lipids and phospholipids in large HDL particles, and the ratio of phospholipids to total lipids in smaller VLDL particles). Of the 85 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 serum glucose levels and the ratio of triglycerides to total lipids in larger LDL particles remained significant.In patients with CKD, associations with prevalent cardiovascular disease were mainly found for HDL-related metabolites, while CACS was associated with glucose levels and increased triglycerides to total lipids ratio in LDL particles.

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.

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 (

Purpose Quantitative computed tomography (QCT) may be useful in detecting high-risk patients with coronary atherosclerosis. Assessment of plaque composition using fixed Hounsfield unit (HU) thresholds is influenced by luminal contrast density. A method using adaptive HU thresholds has therefore been developed. This study investigates agreement between plaque volumes derived using fixed and adaptive HU thresholds and the influence of luminal contrast density on the determination of plaque composition. Methods We performed QCT in 260 patients with recent acute-onset chest pain without acute coronary syndrome. Plaque volumes of necrotic core (NC), fibrous fatty (FF), fibrous (FI) and dense calcium (DC) tissue were measured in 1161 coronary segments. Agreement between plaque volumes using fixed and adaptive HU thresholds was tested using the Bland-Altman method. Additionally, patients were stratified into tertiles of ascending aortic luminal contrast density and plaque volumes were compared. Results Bland-Altman plots revealed that fixed HU thresholds underestimated FI and FF plaque volumes and overestimated NC and DC plaque volumes compared to adaptive HU thresholds. Volumes of dense calcium plaque differed with increasing tertiles of luminal contrast density when using fixed HU thresholds but not when using adaptive HU thresholds: DC for fixed HU thresholds (mm3, median (95%CI)): 7.73 (5.17;12.31), 9.83 (6.55;13.57), 12.02 (8.26;16.24); DC for adaptive HU thresholds (mm3, median (95%CI)): 7.34 (5.12;12.03), 7.78 (5.40;12.61), 8.56 (5.22;12.69). Conclusions Plaque volumes by fixed and adaptive HU thresholds differed. Plaque volumes by adaptive HU thresholds were more independent of luminal contrast density for higher attenuation tissues compared to fixed HU thresholds.

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