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Aims Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. Methods and results A total of 82 healthy individuals (46 women) aged 45–78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. Conclusion MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP. [ABSTRACT FROM AUTHOR]

Background Plasma (p-)activin A is elevated in chronic kidney disease–mineral and bone disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined whether p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality and CKD-MBD complications in CKD patients. Methods The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with estimated glomerular filtration rate (eGFR), coronary and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen–Johansen or Kaplan–Meier estimator, with subsequent multiple Cox regression analyses. Results P-activin A was increased by CKD stage 3 (124–225 pg/mL, P  < .001) and correlated inversely with eGFR (r = −0.53, P  < 0.01). P-activin A was associated with all-cause mortality [97 events, hazard ratio 1.55 (95% confidence interval 1.04; 2.32), P  < 0.05] after adjusting for age, sex, diabetes mellitus (DM) and eGFR. Median follow-up was 4.36 (interquartile range 3.64–4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM and eGFR. No association with MACE, vascular calcification or BMD was demonstrated. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 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 who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as >0% stenosis, and obstructive CAD as ≥50% stenosis. Results Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels >2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1β was not associated with CAD. Conclusions In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD. [ABSTRACT FROM AUTHOR]

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  < .001], 0.26 (95% CI 0.22%–0.3%, P  < .001) and 0.20 (95% CI 0.16%–0.24%, P  < .001), respectively. This trend also applied to all-cause mortality. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 <48 HU was used as a cut-off value for moderate–severe hepatic steatosis. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Aims  Prominent left ventricular trabeculations is a phenotypic trait observed in cardiovascular diseases. In the general population, the extent of left ventricular trabeculations is highly variable, yet it is unknown whether increased trabeculation is associated with adverse outcome. Methods and results  Left ventricular trabeculated mass (g/m2) was measured with contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. The primary endpoint was a composite of major adverse cardiovascular events and defined as death, heart failure, myocardial infarction, or stroke. The secondary endpoints were the individual components of the primary endpoint. Cox regression models were adjusted for clinical parameters, medical history, electrocardiographic parameters, and cardiac chamber sizes. The mean trabeculated mass was 19.1 g/m2 (standard deviation 4.9 g/m2). During a median follow-up of 4.0 years (interquartile range 1.5–6.7), 710 major adverse cardiovascular events occurred in 619 individuals. Individuals with a left ventricular trabeculated mass in the highest quartile had a hazard ratio for major adverse cardiovascular events of 1.64 [95% confidence interval (CI) 1.30–2.08; P  < 0.001] compared to those in the lowest quartile. Corresponding hazard ratios were 2.08 (95% CI 1.38–3.14; P  < 0.001) for death, 2.63 (95% CI 1.61–4.31; P  < 0.001) for heart failure, 1.08 (95% CI 0.56–2.08; P  = 0.82) for myocardial infarction, and 1.07 (95% CI 0.72–1.57; P  = 0.74) for stroke. Conclusion  Increased left ventricular trabeculation is independently associated with an increased rate of major adverse cardiovascular events in the general population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors. Methods Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography. Results A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10–23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, −6 to −25; P  = .002) lower pericardial adipose tissue volume. Conclusions Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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  <   0.001]. Plaque composition differed significantly across cohorts, P  <   0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P  <   0.01. Conclusion Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation. [ABSTRACT FROM AUTHOR]

Aims Accurate assessment of aortic dimensions can be achieved using contrast-enhanced computed tomography. The aim of this study was to define normal values and determinants of aortic dimensions throughout multiple key anatomical landmarks of the aorta in healthy individuals from the Copenhagen General Population Study. Methods and results The study group consisted of 902 healthy subjects selected from 3000 adults undergoing cardiovascular thoracic and abdominal computed tomography-angiography (CTA), where systematic measurements of aortic dimensions were performed retrospectively. Individuals included were without any of the following predefined cardiovascular risk factors: (i) self-reported angina pectoris; (ii) hypertension; (iii) hypercholesterolaemia; (iv) taking cardiovascular prescribed medication including diuretics, statins, or aspirin; (v) overweight (defined as body mass index ≥30 kg/m2); (vi) diabetes mellitus (self-reported or blood glucose >8 mmol/L); and (vii) chronic obstructive pulmonary disease. Maximal aortic diameters were measured at seven aortic regions: sinuses of Valsalva, sinotubular junction, ascending aorta, mid-descending aorta, abdominal aorta at the diaphragm, abdominal aorta at the coeliac trunk, and infrarenal abdominal aorta. Median age was 52 years, and 396 (40%) were men. Men had significantly larger aortic diameters at all levels compared with women (P  <   0.001). Multivariable analysis revealed that sex, age, and body surface area were associated with increasing aortic dimensions. Conclusion Normal values of maximal aortic dimensions at key aortic anatomical locations by contrast-enhanced CTA have been defined. Age, sex, and body surface area were significantly associated with these measures at all levels of aorta. Aortic dimensions follow an almost identical pattern throughout the vessel regardless of sex. [ABSTRACT FROM AUTHOR]

Aims To compare the diagnostic performance of a reduced-order computed tomography-derived fractional flow reserve (CT-FFR) technique derived from luminal deformation and static CT stress myocardial perfusion (CTP). Methods and results Forty-six patients (84 vessels) with suspected coronary artery disease from a single institution planned for elective coronary angiography prospectively underwent research indicated invasive fractional flow reserve (FFR) and 320-detector CT coronary angiography (CTA) and static CTP. Analyses were performed in separate blinded core laboratories for CT-FFR and CTP. CT-FFR was derived using a reduced-order model with dedicated software on a standard desktop computer. CTP was assessed visually and quantitatively by transmural perfusion ratio (TPR). Invasive FFR was significant in 33% (28/84) of vessels. Overall per-vessel sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for CT-FFR were 81%, 84%, 71%, 90%, and 83%, respectively, those of visual CTP were 54%, 92%, 79%, 77%, and 78%, respectively, and TPR were 64%, 48%, 42%, 70%, and 54%, respectively. Per-vessel receiver operator curve analysis demonstrated a significantly larger area under the curve (AUC) for CT-FFR (0.89) with that for visual CTP (0.72; P  = 0.016), TPR (0.55; P  < 0.0001), and CTA (0.76; P  = 0.04). The addition of CT-FFR to CTA provided superior improvement in performance (AUC 0.93; P  < 0.0001) compared with CTA alone, a combination of CTA with visual CTP (AUC 0.82; P  = 0.007) and CTA with TPR (AUC 0.78; P  = 0.0006). Conclusion Based on this selected cohort of patients, a reduced-order CT-FFR technique is superior to visual and quantitatively assessed static CTP in detecting haemodynamically significant coronary stenosis as assessed by invasive FFR. [ABSTRACT FROM AUTHOR]

Aims Myocardial infarction (MI) and gallstone disease (GSD) are intrinsically linked via cholesterol metabolism. We tested the hypothesis that genetic variants in the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, are associated with risk of MI and GSD in the general population. Methods and results We performed tests of association between lipid levels and eight rare non-synonymous mutations and two common variants, rs2081687 and rs3808607, in CYP7A1 in 100 149 individuals from the general population. We further tested whether weighted allele scores for rs2081687 and rs3808607, which were associated with increased plasma levels of low-density lipoprotein (LDL) cholesterol, were associated with an increased risk of both MI and symptomatic GSD. During a mean follow-up of 7 years (0-23 years), MI developed in 2326 individuals and GSD in 2007. For rare mutations, CYP7A1 allele count was associated with an increase in LDL cholesterol of 12% (0.4 mmol/L) for individuals with the highest vs. the lowest allele count (P for trend = 3x10-4). For common variants, CYP7A1 weighted allele scores in individuals with a score >0.04 vs. ≤ 0 were associated with stepwise increases in LDL cholesterol of up to 2.4% (0.08 mmol/L), and with corresponding multifactorially adjusted hazard ratios of 1.25 [95% confidence interval (CI) 1.10-1.41] for MI and 1.39 (95% CI 1.22-1.59) for GSD (P for trend = 5x10-4 and 2x10-7, respectively). Results were similar in meta-analyses including publicly available data from large consortia. [ABSTRACT FROM AUTHOR]

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

Aims Normal values of left ventricular mass (LVM) and cardiac chamber sizes are prerequisites for the diagnosis of individuals with heart disease. LVM and cardiac chamber sizes may be recorded during cardiac computed tomography angiography (CCTA), and thus modality specific normal values are needed. Methods and results We studied 569 healthy subjects undergoing 320-detector CCTA as a part of the Copenhagen General Population Study. LVM as well as ventricular and atrial volumes was assessed with semi-automated software stratified by gender and age decades and indexed by body surface area (BSA). Mean age was 55 (range: 40-84) years, and 188 (33%) were men. BSA-indexed 97.5th percentile cut-off values: LVM = 80 and 65 gr/m², left ventricular volume = 97 and 83 mL/m², right ventricular volume = 120 and 102 mL/m², left atrial volume = 60 and 57 mL/m², and right atrial volume = 85 and 73 mL/m² for men and women, respectively. Men had greater absolute and indexed LVM and chamber volumes than women. For both genders, indexed ventricular volumes declined, whereas indexed atrial volumes increased in advancing age groups. For men, indexed LVM declined in advancing age groups. In multivariate analyses, gender, BSA, systolic blood pressure, and hard physical activity accounted for 63% of variance in LVM. Conclusion In this cross-sectional general population study, men have greater indexed LVM and chamber volumes than women, and cardiac indexed volumes vary between age groups in both genders. These findings demonstrate the need for age- and gender-specific normal values for clinical diagnostic purposes. [ABSTRACT FROM AUTHOR]

Aims Regenerative treatment with mesenchymal stromal cells (MSCs) has been promising in patients with ischaemic heart failure but needs confirmation in larger randomized trials. We aimed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe ischaemic heart failure. Methods and results The MSC-HF trial is a randomized, double-blind, placebo-controlled trial. Patients were randomized 2 : 1 to intra-myocardial injections of MSC or placebo, respectively. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography at 6 months follow-up. Sixty patients aged 30-80 years with severe ischaemic heart failure, New York Heart Association (NYHA) classes II-III, left ventricular ejection fraction (LVEF) <45% and no further treatment options were randomized. Fifty-five patients completed the 6-month follow-up (37 MSCs vs. 18 placebo). At 6 months, LVESV was reduced in the MSC group: -7.6 (95% CI -11.8 to -3.4) mL (P = 0.001), and increased in the placebo group: 5.4 (95% CI -0.4 to 11.2) mL (P = 0.07). The difference between groups was 13.0 (95% CI 5.9-20.1) mL (P = 0.001). Compared with placebo, there were also significant improvements in LVEF of 6.2% (P<0.0001), stroke volume of 18.4 mL (P < 0.0001), and myocardial mass of 5.7 g (P = 0.001). No differences were found in NYHA class, 6-min walking test and Kansas City cardiomyopathy questionnaire. No side effects were identified. Conclusion Intra-myocardial injections of autologous culture expanded MSCs were safe and improved myocardial function in patients with severe ischaemic heart failure. [ABSTRACT FROM AUTHOR]

Aims To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). Methods and results We conducted a multicentre study to evaluate the accuracy of integrated CTA–CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA–CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA–SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA–CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84–0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87–0.94) and in patients without prior CAD the AUC for combined CTA–CTP was 0.93 (95% CI: 0.89–0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72–86), 74% (68–80), 65% (58–72), and 86% (80–90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. Conclusions The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI. [ABSTRACT FROM PUBLISHER]

Objective: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. Methods: Forty-five consecutive patients with a mean duration of ischemic heart symptoms of 9 years and LV ejection fraction (EF) <45% referred for CABG were included and LV extent of viable myocardium was measured preoperatively by glucose metabolism–blood flow positron emission tomography imaging and dobutamine stress echocardiography. Symptoms, exercise-capacity and LV function were evaluated before and 7 months after surgery in event-free survivors. Results: LV extent of myocardial viability was <30% in most patients. In event-free survivors, LVEF decreased from 31±7 to 26±8% 7 months after CABG. The decrease in LVEF was correlated to the LV extent of myocardial metabolism–blood flow reverse mismatch. Most of the patients experienced an improvement in their angina pectoris, heart failure symptoms and exercise capacity after CABG; the overall 3-year survival was 77%. Conclusions: Patients with chronic ischemic heart disease and impairment of LV function, in whom an initial long-standing conservative treatment has been practiced, benefit from CABG, despite a lack of LV functional reserve. [Copyright &y& Elsevier]

Objective: [2-18F] 2-fluorodeoxyglucose (FDG) is widely used to trace glucose metabolism for cardiac imaging with positron emission tomography. Because the transport and phosphorylation rates differ for glucose and FDG, a lumped constant (LC) is used to correct for these differences. The effects of ischemia and reperfusion on the LC in vivo are unknown. To determine the validity of FDG as a tracer of glucose metabolism in post-ischemic myocardium in vivo, the relationship between glucose uptake (GU) and FDG metabolic rate (FDG-MR) was assessed early post-reperfusion following a transient ischemic event. Methods: FDG metabolic rate, measured with FDG and PET, was compared to invasive measurements of substrate metabolism in reperfused and global myocardium of dogs subjected to 25 min ischemia and 2 h reperfusion. Results: The FDG metabolic rate was decreased 20±4% in reperfused relative to remote myocardium. Glucose oxidation and lactate uptake were also decreased in reperfused relative to global myocardium, by 26±6% and 60±8% respectively. Glucose uptake did not differ significantly between reperfused and global myocardium. A linear correlation between FDG metabolic rate and glucose uptake was found in both reperfused and remote myocardium. Estimates of the LC from the slopes of the regression lines were similar in reperfused and remote myocardium, 1.25 and 1.44 respectively, and did not differ significantly from the LC determined in control dogs, 1.1. Conclusions: We conclude that the FDG metabolic rate continues to correlate well with glucose metabolism in reperfused myocardium. While FDG metabolic rate was modestly decreased in the absence of a significant change in glucose uptake, large alterations in the LC are not found 2 h post-reperfusion in vivo. [ABSTRACT FROM PUBLISHER]

Objective: Myocardial reperfusion following brief periods of ischaemia is associated with prolonged, reversible periods of metabolic dysfunction. As the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is inhibited in vitro by reactive oxygen species, we hypothesized that production of reactive oxygen species during reperfusion would lead to inhibition of GAPDH in post-ischaemic myocardium. Methods: Anaesthetized closed-chest dogs were subjected to 20 min balloon occlusion of the left anterior descending coronary artery. Biopsy samples were taken after 3 and 24 h of reperfusion, to determine the activity of GAPDH and the concentrations of glycolytic intermediates in post-ischaemic and remote, non-ischaemic territories. Results: A significant reduction in GAPDH activity was observed in post-ischaemic relative to remote tissue after 3 h reperfusion (4.8 ± 0.5 vs. 2.9 ± 0.2 μmol/min/mg protein; P < 0.01). Western blotting revealed no reduction in the levels of GAPDH protein. Analysis of enzyme kinetics showed the loss of activity to be associated with decreased Vmax (5.9 ± 0.5 vs. 3.2 ± 0.2 μmol/min/mg protein; P < 0.01) with no significant change in the Km for glyceraldehyde-3-phosphate (GAP). Incubation of the inhibited enzyme under both mild and strong reducing conditions failed to reactivate the enzyme. The acute reduction in enzyme activity in post-ischaemic tissue was accompanied by regional differences in glycolytic intermediates, notably a twofold accumulation of GAP (P < 0.05), and a reduction in the glucose metabolic rate (GMR) determined by positron emission tomography and [18F]2-fluorodeoxyglucose. By 24 h reperfusion, no regional differences in GAPDH activity, reaction Vmax or Km, GAP concentrations or GMR were detectable. Conclusions: These results suggest that inhibition of GAPDH activity may represent an important point at which glycolysis is limited during reperfusion, and further, that the mechanisms of enzyme inhibition do not involve simple oxidation or S-thiolation of critical active site thiol groups. [ABSTRACT FROM PUBLISHER]