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The article reports that Baumann et al. say correctly that symptom relief at follow-up in the DISCHARGE trial may be attributable to medical treatment after ana tomical assessment by CT. We agree that there is a need to investigate imaging techniques beyond coronary angiography to detect and quantify microvascular angina or coronary vasospasm.

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. Materials and methods: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). Results: Of 3445 randomised patients with smoking data (mean age 59.1 years + / − 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. Conclusion: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. Clinical relevance statement: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. Trial registration: ClinicalTrials.gov NCT02400229. Key Points: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required—moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health. [Display omitted] • Early-stage subclinical atherosclerosis can be identified in young individuals, but evidence-based strategies are needed to prevent progression of disease and clinical events. • Precision medicine using imaging and circulating biomarkers could facilitate early identification of atherosclerosis and the development of curative interventions. • A paradigm shift based on these principles could reduce the global burden of CVD with enormous implications for population health. [ABSTRACT FROM AUTHOR]

Background: Women with previous preeclampsia have an increased risk of coronary artery disease later in life.Objectives: This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population.Methods: 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 score >0 in case of a nondiagnostic coronary CTA.Results: 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/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity.Conclusions: Younger 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). [ABSTRACT FROM AUTHOR]

In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P=0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229 [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]

OBJECTIVE: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS: This prespecified analysis of the multicenter DISCHARGE trial (NCT02400229) in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications). RESULTS: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22–0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 – 0.63]). CONCLUSIONS: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications. [ABSTRACT FROM AUTHOR]

Background & Aims: Fatty liver disease has been associated with higher all‐cause as well as liver‐related, ischemic heart disease (IHD)‐related and extrahepatic cancer‐related mortality in observational epidemiological studies. We tested the hypothesis that fatty liver disease is a causal risk factor for higher mortality. Methods: We genotyped seven genetic variants known to be associated with fatty liver disease (in PNPLA3, TM6SF2, HSD17B13, MTARC1, MBOAT7, GCKR, and GPAM) in 110 913 individuals from the Danish general population. Hepatic steatosis was measured by hepatic computed tomography in n = 6965. Using a Mendelian randomization framework, we tested whether genetically proxied hepatic steatosis and/or elevated plasma alanine transaminase (ALT) was associated with liver‐related mortality. Results: During a median follow‐up of 9.5 years, 16 119 individuals died. In observational analyses, baseline elevated plasma ALT was associated with higher all‐cause (1.26‐fold), liver‐related (9‐fold), and extrahepatic cancer‐related (1.25‐fold) mortality. In genetic analyses, the risk alleles in PNPLA3, TM6SF2, and HSD17B13 were individually associated with higher liver‐related mortality. The largest effects were seen for the PNPLA3 and TM6SF2 risk alleles, for which homozygous carriers had 3‐fold and 6‐fold, respectively, higher liver‐related mortality than non‐carriers. None of the risk alleles, individually or combined into risk scores, were robustly associated with all‐cause, IHD‐related, or extrahepatic cancer‐related mortality. In instrumental variable analyses, genetically proxied hepatic steatosis and higher plasma ALT were associated with liver‐related mortality. Conclusions: Human genetic data support that fatty liver disease is a causal driver of liver‐related mortality. [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]

A hypercoagulable state has, in observational studies, been associated with increased risk of thromboembolic events. The aim of this trial was to study whether dual antiplatelet therapy (DAPT) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions, thromboembolic events, and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery. A total of 1683 patients were screened for eligibility, among which 165 patients were randomized and 133 patients underwent multislice computed tomography scan to evaluate their grafts. Thrombelastography (TEG) and multiplate aggregometry were performed before and after surgery, and again at three months follow up. TEG hypercoagulability was defined as the maximum amplitude above 69 mm. At three months follow up, 17 out of 66 (25.7%) DAPT patients and 15 of 67 (22.4%) aspirin patients had significant graft stenosis or occlusions (p= 0.839). Saphenous vein grafts (SVGs) were stenosed or occluded in 15 (22.7%) patients in the DAPT group and 7 (10.4%) in the aspirin group (p= 0.167). Thromboembolic events and death after the second postoperative day (when clopidogrel was started) were numerically, but not statistically, lower in the DAPT group, 3 (3.8%) vs. 8 (9.9%),p= 0.211. In univariate logistic regression analysis, only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion, OR 1.020 [1.002–1.039],p= 0.033. This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients. Due to the low enrollment and high loss to follow up, our results can only be viewed as hypothesis generating. We found a high rate of graft occlusions in this patient population. Our results were not suggestive of that DAPT improved saphenous vein graft patency. A trend was observed in patients on DAPT toward fewer MI and deaths. Postoperative response to aspirin therapy was found to be associated with early SVG occlusion. [ABSTRACT FROM AUTHOR]

Background: We sought to assess predictability of excessive bleeding using thrombelastography (TEG), multiplate impedance aggregometry, and conventional coagulation tests including fibrinogen in patients undergoing coronary artery bypass graft (CABG) surgery.Methods: A total of 170 patients were enrolled in this prospective observational study. TEG, Multiplate aggregometry, and coagulation tests were sampled on the day before surgery. Excessive bleeding was defined as >1000 mL over 18 hours.Results: Multiplate-adenosine diphosphate (ADP) measurements were significantly lower in patients with excessive bleeding, 85.5AU ± 32.8 versus 108.5AU ± 30.0, p = 0.012. Bivariate analysis revealed body mass index, myocardial infarction, and multiplate-ADP as predictors of bleeding. In multivariable linear regression analysis, multiplate-ADP remained a significant predictor of bleeding (β: -6.2 [confidence interval: -12.0 to -0.3], p = 0.035). The lowest interval of multiplate-ADP (<50 AUC) was associated with significantly more bleeding and need for platelet concentrate transfusion. Fibrinogen levels <2.5 g/L were also found to be associated with excess bleeding (p = 0.020).Conclusions: Multiplate impedance aggregometry identified patients at risk for excessive bleeding after CABG. Low fibrinogen levels were associated with increased bleeding. Neither routine TEG parameters nor conventional coagulation tests were correlated with bleeding. [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]

A correction to the article "Computed Tomography Versus Invasive Coronary Angiography in Patients With Diabetes and Suspected Coronary Artery Disease" in the Diabetes Care (date) issue is presented which includes the addition of the clinical trial number.

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. [Display omitted] • 85 metabolites were associated with cardiovascular disease (CVD). • 84 metabolites were associated with coronary artery calcium score (CACS). • After risk factor adjustment CVD was associated with HDL-related metabolites. • CACS was associated with glucose and triglycerides in larger LDL particles. • Metabolites other than LDL cholesterol may contribute to CVD in chronic kidney disease (CKD). [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]

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. 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. 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. 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. [Display omitted] • More than 12,000 individuals were CT scanned for heart valve calcification. • More than 85,000 individuals were followed in nationwide registries. • Lipoprotein(a) is causally associated with mitral valve calcification. • Lipoprotein(a) causes aortic valve stenosis but not mitral valve regurgitation. • Aortic valve calcification mediates 31% lipoprotein(a) effect on aortic stenosis. [ABSTRACT FROM AUTHOR]

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

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

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: 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]

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

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) <45% and no further treatment options were randomized. Patients were followed clinically for 12 months and in addition 4-year data of hospitalizations and survival were retrieved. After 12 months, LVESV was significantly reduced in the MSC group and not in the placebo group, with difference between groups of 17.0 ± 16.2 mL (95% confidence interval 8.3-25.7, P = 0.0002). There were also significant improvements in LVEF of 6.2% (P < 0.0001), stroke volume of 16.1 mL (P < 0.0001) and myocardial mass (P = 0.009) between groups. A significant dose-response effect was also observed. Moreover, a significant reduction in the amount of scar tissue and quality of life score in the MSC group but not in the placebo group was observed. After 4 years, there were significantly fewer hospitalizations for angina in the MSC group and otherwise no differences in hospitalizations or survival. No side effects were identified.Conclusions: Intramyocardial injections of autologous bone marrow-derived MSCs improved myocardial function and myocardial mass in patients with ischaemic heart failure. [ABSTRACT FROM AUTHOR]

Background: Low bone mineral density (BMD) has been described in people living with HIV (PLWH). We examined the prevalence of low BMD measured by quantitative computed tomography (QCT), a method that allows 3-dimensional volumetric density measures at the thoracic spine, in well-treated PLWH and uninfected controls and assessed risk factors for reduced BMD. Methods: Cross-sectional study including 718 PLWH from the Copenhagen Co-Morbidity in HIV infection (COCOMO) study and 718 uninfected controls matched on age and sex from the Copenhagen General Population Study (CGPS). Trabecular BMD was determined by QCT. Results: Median BMD was 144.2 mg/cm³ in PLWH vs. 146.6 mg/cm³ in controls (P = 0.580). HIV status was not associated with BMD in univariable or multivariable linear analyses. However, a higher prevalence of very low BMD (T-score ≤ 22.5) was found in PLWH (17.2% vs. 11.0% in controls, P = 0.003). In unadjusted analysis, HIV was associated with very low BMD (odds ratio 1.68 [95% confidence interval: 1.24-2.27], P = 0.001), but this association was not significant after adjusting for age, sex, smoking, alcohol, body mass index, physical activity, and ethnicity. Previous AIDS-defining disease was associated with lower BMD, but no other associations with HIV-specific variables were identified. Conclusion: Using QCT, we found a higher prevalence of very low BMD in PLWH than in controls. However, HIV status was not independently associated with BMD indicating that traditional risk factors contribute to the difference in prevalence of very low BMD. Focus on improvement of lifestyle factors, especially in PLWH with previous AIDS-defining disease, may prevent very low BMD in PLWH. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • In current and ex-smokers, the ascending and descending aorta grows on average 0.1 mm/year • Aortic growth was comparable between current and ex-smokers and was not associated with pack-years • Thoracic aortic growth in smokers is consistent with cross-sectional data from the general population • Annual growth did not statistically significantly differ between males and females • Based on 95th percentiles, aortic growth of 0.5 mm/year can be considered the upper limit of normal [ABSTRACT FROM AUTHOR]

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.). [ABSTRACT FROM AUTHOR]

The Agatston score (AS) is the gold standard CT calcium scoring method in clinical practice. However, the AS is an indirect method of determining calcium amount, whereas atomic absorption spectroscopy (AAS) can directly measure the calcium amount. Our primary aim was to investigate the association between the AS and the coronary calcium amount measured by AAS. Furthermore, we compared our outcome to the macroscopic and histological coronary calcification and stenosis assessment, thus allowing us to infer a clinical coronary artery status based on post-mortem findings. Deceased individuals were examined with a 64-slice multidetector CT scanner, and the AS was determined. At autopsy, the degree of CAC and stenosis was determined, and the coronary arteries were excised and weighed. The coronary arteries were decalcified in a solution that was examined using AAS to measure the calcium amount. The degree of CAC and stenosis was also assessed by a histological examination. One hundred thirty-two coronary arteries were examined, and AS was highly correlated to the coronary calcium amount, measured by AAS, (r2 = 0.72, Pearson 0.85, p < 0.0001). In cases with AS 0, AAS measurements showed zero or very low calcium amounts. AS was also correlated to macroscopic and histological calcification assessments (Spearman's rho 0.68, p < 0.0001, Spearman's rho 0.82, p < 0.0001). Furthermore, an underestimation of subclinical atherosclerosis was seen and AS 0 could not rule out stenosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background The association between low bone mineral density (BMD) and the presence of coronary artery calcium (CAC) as a marker of atherosclerosis is unclear. The aim of this study was to assess the potential relationship between volumetric thoracic bone mineral density and coronary calcification in a large population of men and women. Methods Participants from the Copenhagen General Population Study underwent multidetector computed tomography. Volumetric thoracic BMD and CAC were assessed in the same scan. CAC was measured using calibrated mass score (cMS). cMS was dichotomized as cMS = 0 or cMS > 0. The association between BMD and cMS was analyzed using multiple logistic regression in men, premenopausal and postmenopausal women. The model was adjusted for age, BMI, hypertension, hypercholesterolemia, diabetes, known cardiovascular disease and smoking. Results Of 2548 eligible participants, 1163 men and 1385 women, mean age 61 ± 10 were included in the study. Mean BMD was 138 ± 46 mg/cm3 for men and 151 ± 49 mg/cm3 women. In 696 men (67%) and 537 women (41%) cMS was found to be above zero. For men, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.49 for cMS > 0 (95% confidence interval: 1.04–2.13, P = 0.03). In postmenopausal women, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.47 for MS > 0 (95% confidence interval: 1.04–2.08, P = 0.03). For premenopausal women, no significant association was found between BMD and cMS (odds ratio = 0.74, 95% confidence interval: 0.36–1.52, P = 0.4). Conclusion Bone mineral density and coronary calcification are inversely related in both men and postmenopausal women, supporting the hypothesis that a direct relation between bone loss and development of atherosclerosis exists irrespective of gender. Highlights • Bone mineral density and coronary calcification can be measured in a single CT scan. • An inverse relation between bone loss and atherosclerosis exist regardless of gender. • It may only be detected using calibrated mass scoring and not the Agatston score. [ABSTRACT FROM AUTHOR]

Aims: Type 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes.Methods: This was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by >1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/m2 or g/m2).Results: Persons with and without CAN had mean ± SD age of 57 ± 7 and 50 ± 8 years (p < 0.001) and diabetes duration of 36 ± 11 and 32 ± 9 years (p < 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (-0.5, 95% CI -1.0 to -0.0, p < 0.05) and trend towards larger left (-0.4, 95% CI -0.8-0.0, p < 0.1) ventricular volumes in multivariable linear regression.Conclusions: Our results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS. Methods: Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen’s kappa. Results: A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64–0.66, 0.69–0.76, 0.46–0.48, and 0.41–0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile. Conclusions: Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcification (CAC) is commonly assessed with Agatston score (AS). A higher sensitivity and precision for the detection of CAC has been demonstrated with calibrated mass score (cMS). We hypothesized that cMS would detect low-level CAC not detectable with AS in a large asymptomatic background population.Methods: Participants (N = 2985) from the Copenhagen General Population Study were evaluated for CAC using both conventional AS and cMS. The population was grouped according to number of traditional risk factors and heart score was used to assess the risk of event for those with no CAC, those with only cMS > 0 and those with both AS and cMS > 0.Results: In participants with an AS = 0, 11% had cMS > 0. The risk profile of this cMS-only group was between that of the CAC-negative participants and those with AS > 0 and cMS > 0. Overall, 6% of the population belonged to the cMS-only group independent of the number of risk factors.Conclusion: In individuals with AS = 0, a fraction was found to have cMS > 0. Based on traditional risk factors, this group has a higher 10-year risk than individuals with both AS = 0 and cMS = 0; cMS might offer very early cardiovascular risk assessment in asymptomatic individuals.Key Points: • In individuals with AS=0, a fraction has CAC with highly sensitive cMS. • This fraction has a higher 10-year risk of cardiovascular disease. • Regardless of risk factors, 6% has CAC detectable only with cMS. • cMS might offer very early cardiovascular risk assessment in asymptomatic individuals. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Objective: Ankle–brachial index is an excellent tool for diagnosing peripheral artery disease (PAD). We aimed to determine the prevalence and risk factors for PAD in people living with HIV (PLWH) compared with uninfected controls. We hypothesized that prevalence of PAD would be higher among PLWH than among controls independent of traditional cardiovascular disease (CVD) risk factors. Methods: PLWH aged 40 years and older were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study. Sex- and age-matched uninfected controls were recruited from the Copenhagen General Population Study. We defined PAD as ankle–brachial index ≤0.9 and assessed risk factors for PAD using logistic regression adjusting for age, sex, smoking status, dyslipidemia, diabetes, hypertension, and high-sensitivity C-reactive protein. Results: Among 908 PLWH and 11,106 controls, PAD was detected in 112 [12% confidence interval: (95% 10 to 14)] and 623 [6% (95% 5 to 6)], respectively (P < 0.001), odds ratio = 2.4 (95% 1.9 to 2.9), and adjusted odds ratio = 1.8 (95% 1.3 to 2.3, P < 0.001). Traditional CVD risk factors, but not HIV-related variables, were associated with PAD. The strength of the association between PAD and HIV tended to be higher with older age (P = 0.052, adjusted test for interaction). Conclusions: Prevalence of PAD is higher among PLWH compared with uninfected controls, especially among older persons, and remains so after adjusting for traditional CVD risk factors. Our findings expand the evidence base that PLWH have excess arterial disease to also include PAD. The exact biological mechanisms causing this excess risk remain to be elucidated. Until then, focus on management of modifiable traditional risk factors is important. [ABSTRACT FROM AUTHOR]

Objectives: Diagnostic accuracy of conventional coronary CT angiography (CCTAconv) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTAsub) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTAsub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTAconv.Methods: In this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTAconv, and CCTAsub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTAsub reconstruction process, in which case evaluation was omitted. CCTAsub and CCTAconv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTAconv versus CCTAsub to identify > 50% coronary stenosis by ICA on a per-segment level.Results: After exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTAconv to 33% (CI:25-42%) in CCTAsub, at the expense of 7% (CI:3-14%) false negatives in CCTAsub.Conclusions: In severely calcified coronary arteries or stents, CCTAsub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTAconv. Nevertheless, misregistration artifacts are frequent in CCTAsub.Key Points: • A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT. • These patients would normally need an invasive angiogram for diagnosis. • In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations. • Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing. [ABSTRACT FROM AUTHOR]

Aims: Coronary artery calcium (CAC) is associated with cardiovascular (CV) disease and progression of CAC is an independent predictor of mortality. Type 1 diabetes is associated with increased CV risk, especially in persons with cardiovascular autonomic neuropathy (CAN). This study aimed to examine whether short-term progression of CAC is increased in persons with type 1 diabetes compared to matched controls and if CAN increases risk of CAC progression.Methods: Fifty-three normoalbuminuric persons with long-term type 1 diabetes (20 with CAN) were matched in a 1:2 ratio with 106 controls without diabetes according to age, sex and baseline CAC. All were examined twice with cardiac computed tomography scans. Progression of CAC was defined as a value ≥2.5 between the square root-transformed values of follow-up and baseline CAC volume scores.Results: The participants were examined median (interquartile range) of 25 (23-27) months (type 1 diabetes) and 29 (25-33) months (controls) apart. In multivariable logistic regression, participants with type 1 diabetes had an odds ratio of 3.3 (95% CI 1.3-8.2, p = 0.01) for CAC progression. CAN did not increase progression of CAC (p = 0.64).Conclusions: Progression of CAC was increased in well-treated, normoalbuminuric persons with type 1 diabetes compared to matched controls without diabetes, suggesting that type 1 diabetes is a risk factor for short-term progression. This finding could explain some of the increased morbidity and mortality observed in persons with type 1 diabetes, but it does not specifically explain the increased CV risk in persons with CAN. [ABSTRACT FROM AUTHOR]

Background. Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems and cryopreserved as an off-the-shelf product ready to use. Study Design. A multicentre, double-blind, placebo-controlled phase II study with direct intramyocardial injections of allogeneic CSCC_ASC in patients with chronic IHF. A total of 81 patients will be randomised at 2 : 1 to CSCC_ASC or placebo. There is no HLA tissue type matching needed between the patients and the donors. Methods. The treatment will be delivered by direct injections into the myocardium. The primary endpoint is change in the left ventricle endsystolic volume at 6-month follow-up. Secondary endpoints are safety and changes in left ventricle ejection fraction, myocardial mass, stroke volume, and cardiac output. Other secondary endpoints are change in clinical symptoms, 6-minute walking test, and the quality of life after 6 and 12 months. Conclusion. The aim of the present study is to demonstrate safety and the regenerative efficacy of the allogeneic CSCC_ASC product from healthy donors in a double-blind, placebo-controlled, multicentre study in patients with IHF. [ABSTRACT FROM AUTHOR]

Background: Subclinical leaflet thrombosis of bioprosthetic aortic valves after transcatheter valve replacement (TAVR) and surgical aortic valve replacement (SAVR) has been found with CT imaging. The objective of this study was to report the prevalence of subclinical leaflet thrombosis in surgical and transcatheter aortic valves and the effect of novel oral anticoagulants (NOACs) on the subclinical leaflet thrombosis and subsequent valve haemodynamics and clinical outcomes on the basis of two registries of patients who had CT imaging done after TAVR or SAVR.Methods: Patients enrolled between Dec 22, 2014, and Jan 18, 2017, in the RESOLVE registry, and between June 2, 2014, and Sept 28, 2016, in the SAVORY registry, had CT imaging done with a dedicated four-dimensional volume-rendered imaging protocol at varying intervals after TAVR and SAVR. We defined subclinical leaflet thrombosis as the presence of reduced leaflet motion, along with corresponding hypoattenuating lesions shown with CT. We collected data for baseline demographics, antithrombotic therapy, and clinical outcomes. We analysed all CT scans, echocardiograms, and neurological events in a masked fashion.Findings: Of the 931 patients who had CT imaging done (657 [71%] in the RESOLVE registry and 274 [29%] in the SAVORY registry), 890 [96%] had interpretable CT scans (626 [70%] in the RESOLVE registry and 264 [30%] in the SAVORY registry). 106 (12%) of 890 patients had subclinical leaflet thrombosis, including five (4%) of 138 with thrombosis of surgical valves versus 101 (13%) of 752 with thrombosis of transcatheter valves (p=0·001). The median time from aortic valve replacement to CT for the entire cohort was 83 days (IQR 33-281). Subclinical leaflet thrombosis was less frequent among patients receiving anticoagulants (eight [4%] of 224) than among those receiving dual antiplatelet therapy (31 [15%] of 208; p<0·0001); NOACs were equally as effective as warfarin (three [3%] of 107 vs five [4%] of 117; p=0·72). Subclinical leaflet thrombosis resolved in 36 (100%) of 36 patients (warfarin 24 [67%]; NOACs 12 [33%]) receiving anticoagulants, whereas it persisted in 20 (91%) of 22 patients not receiving anticoagulants (p<0·0001). A greater proportion of patients with subclinical leaflet thrombosis had aortic valve gradients of more than 20 mm Hg and increases in aortic valve gradients of more than 10 mm Hg (12 [14%] of 88) than did those with normal leaflet motion (seven [1%] of 632; p<0·0001). Although stroke rates were not different between those with (4·12 strokes per 100 person-years) or without (1·92 strokes per 100 person-years) reduced leaflet motion (p=0·10), subclinical leaflet thrombosis was associated with increased rates of transient ischaemic attacks (TIAs; 4·18 TIAs per 100 person-years vs 0·60 TIAs per 100 person-years; p=0·0005) and all strokes or TIAs (7·85 vs 2·36 per 100 person-years; p=0·001).Interpretation: Subclinical leaflet thrombosis occurred frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. Anticoagulation (both NOACs and warfarin), but not dual antiplatelet therapy, was effective in prevention or treatment of subclinical leaflet thrombosis. Subclinical leaflet thrombosis was associated with increased rates of TIAs and strokes or TIAs. Despite excellent outcomes after TAVR with the new-generation valves, prevention and treatment of subclinical leaflet thrombosis might offer a potential opportunity for further improvement in valve haemodynamics and clinical outcomes.Funding: RESOLVE (Cedars-Sinai Heart Institute) and SAVORY (Rigshospitalet). [ABSTRACT FROM AUTHOR]

Aims: The third isotype of beta adrenergic receptors (β3 ARs) has distinctly different effects on cardiomyocytes compared with β1 and β2 ARs. Stimulation of β3 ARs may reduce cardiomyocyte Na+ overload and reduce oxidative stress in heart failure (HF). We examined if treatment with the β3 AR agonist mirabegron increases LVEF in patients with HF.Methods and Results: In a double-blind trial we randomly assigned 70 patients with NYHA class II-III HF and LVEF <40% at screening-echocardiography to receive mirabegron or placebo for 6 months as add-on to optimized standard therapy. The primary endpoint was an increase in LVEF after 6 months as measured by computed tomography (CT). Changes in LVEF after 6 months between treatment groups were not significantly different (0.4%, -3.5 to 3.8%, P = 0.82). In an exploratory analysis, based on an expectation that the pathophysiological substrate targeted with treatment is dependent on the baseline LVEF, patients with LVEF <40% by CT given mirabegron had a significant increase in LVEF while no increase was seen in patients given placebo. The changes were significantly different between groups (5.5%, 0.6-10.4%, P < 0.03). Additionally, there was interaction between baseline LVEF and change in LVEF in the entire group of patients treated with mirabegron (R2  = 0.40, β  = -0.63, P < 0.001), but not in the placebo group (R2  = 0.00, β  = -0.01, P = 0.95). Treatment was generally well tolerated. Three patients in each group had fatal or life-threatening events.Conclusions: The primary endpoint was not reached. Exploratory analysis indicated that β3 AR stimulation by mirabegron increased LVEF in patients with severe HF. Treatment appeared safe. Additional studies in severe HF are needed.Trial Registration: NCT01876433. [ABSTRACT FROM AUTHOR]

Aims The third isotype of beta adrenergic receptors (β3 ARs) has distinctly different effects on cardiomyocytes compared with β1 and β2 ARs. Stimulation of β3 ARs may reduce cardiomyocyte Na+ overload and reduce oxidative stress in heart failure (HF). We examined if treatment with the β3 AR agonist mirabegron increases LVEF in patients with HF. Methods and results In a double-blind trial we randomly assigned 70 patients with NYHA class II-III HF and LVEF <40% at screening-echocardiography to receive mirabegron or placebo for 6 months as add-on to optimized standard therapy. The primary endpoint was an increase in LVEF after 6 months as measured by computed tomography (CT). Changes in LVEF after 6 months between treatment groups were not significantly different (0.4%, -3.5 to 3.8%, P = 0.82). In an exploratory analysis, based on an expectation that the pathophysiological substrate targeted with treatment is dependent on the baseline LVEF, patients with LVEF <40% by CT given mirabegron had a significant increase in LVEF while no increase was seen in patients given placebo. The changes were significantly different between groups (5.5%, 0.6-10.4%, P < 0.03). Additionally, there was interaction between baseline LVEF and change in LVEF in the entire group of patients treated with mirabegron (R² =0.40, β =-0.63, P < 0.001), but not in the placebo group (R2 =0.00, β =-0.01, P = 0.95). Treatment was generally well tolerated. Three patients in each group had fatal or life-threatening events. Conclusions The primary endpoint was not reached. Exploratory analysis indicated that β3 AR stimulation by mirabegron increased LVEF in patients with severe HF. Treatment appeared safe. Additional studies in severe HF are needed. [ABSTRACT FROM AUTHOR]

Objective: Population studies have shown coronary calcium score to improve risk stratification in subjects suspected for cardiovascular disease. The aim of this work was to assess the validity of multidetector computed tomography (MDCT) for measurement of calibrated mass scores (MS) in a phantom study, and to investigate inter-scanner variability for MS and Agaston score (AS) recorded in a population study on two different high-end MDCT scanners.Materials and Methods: A calcium phantom was scanned by a first (A) and second (B) generation 320-MDCT. MS was measured for each calcium deposit from repeated measurements in each scanner and compared to known physical phantom mass. Random samples of human subjects from the Copenhagen General Population Study were scanned with scanner A (N=254) and scanner B (N=253) where MS and AS distributions of these two groups were compared.Results: The mean total MS of the phantom was 32.9±0.8mg and 33.1±0.9mg (p=0.43) assessed by scanner A and B respectively - the physical calcium mass was 34.0mg. Correlation between measured MS and physical calcium mass was R2=0.99 in both scanners. In the population study the median total MS was 16.8mg (interquartile range (IQR): 3.5-81.1) and 15.8mg (IQR: 3.8-63.4) in scanner A and B (p=0.88). The corresponding median total AS were 92 (IQR: 23-471) and 89 (IQR: 40-384) (p=0.64).Conclusion: Calibrated calcium mass score may be assessed with very high accuracy in a calcium phantom by different generations of 320-MDCT scanners. In population studies, it appears acceptable to pool calcium scores acquired on different 320-MDCT scanners. [ABSTRACT FROM AUTHOR]

Objectives: To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease.Design: The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed.Results: CCTA detects significant (>50%) coronary artery diameter stenosis with a sensitivity, specificity, and positive and negative predictive value of 99%, 81%, 96% and 95%, respectively. CCTA was used to triage patients into guideline defined treatment groups of "no or medical treatment", "referral to percutaneous coronary intervention" or to "coronary artery bypass graft surgery" and was compared to the index ICA. CCTA correctly triaged patients in 86% of cases. During a median follow-up of 50 months, the presence of an occluded artery by CCTA was associated with adverse outcome.Conclusion: CCTA has high diagnostic and prognostic value in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population. [ABSTRACT FROM AUTHOR]

Background: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI.Methods: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408.Findings: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups.Interpretation: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population.Funding: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research. [ABSTRACT FROM AUTHOR]

Background: Left atrial volume (LAV) estimation with 3D echocardiography has been shown to be more accurate than 2D volume calculation. However, little is known about the possible effect of respiratory movements on the accuracy of the measurement.Methods: 100 consecutive patients admitted with chest pain were examined with 3D echocardiography and LAV was quantified during inspiratory breath hold, expiratory breath hold and during free breathing.Results: Of the 100 patients, only 65 had an echocardiographic window that allowed for 3D echocardiography in the entire respiratory cycle. Mean atrial end diastolic volume was 45.4 ± 14.5 during inspiratory breath hold, 46.4 ± 14.8 during expiratory breath hold and 45.6 ± 14.3 during free respiration. Mean end systolic volume was 17.6 ± 7.8 during inspiratory breath hold, 18.8 ± 8.0 during expiratory breath hold and 18.3 ± 8.0 during free respiration. No significant differences were seen in any of the measured parameters.Conclusions: The present study adds to the feasibility of 3D LAV quantitation. LAV estimation by 3D echocardiography may be performed during either end-expiratory or end-inspiratory breath-hold without any significant difference in the calculated volume. Also, the LAV estimation may be performed during free breathing. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of disease-modifying treatments in hypertrophic cardiomyopathy (HCM). The aim of this randomised, placebo-controlled study was to assess if losartan could improve or ameliorate deterioration of cardiac function and exercise capacity.Methods: Echocardiography, exercise test and MRI or CT were performed at baseline and after 12 months in 133 patients (52±13 years, 35% female) randomly allocated to losartan (100 mg/day) or placebo.Results: Losartan had no effect on systolic function compared with placebo (mean difference for left ventricular ejection fraction (LVEF) 0% (95% CI -3% to 4%), p=0.84 or global longitudinal strain 0.7% (95% CI -0.2% to 1.6%), p=0.13). Neither Doppler measures of diastolic function, left atrial volume (mean difference 2 mL/m(2) (95% CI -4 to 8 mL/m(2)) p=0.53) nor exercise capacity (mean difference -0.3 metabolic equivalents (METS) (95% CI -1.0 to 0.3 METS), p=0.28) differed between the treatment groups. At follow-up, there was further progression of disease, with the most prominent impairment being an increase in left atrial volume of 6 mL/m(2) (95% CI 3 to 9 mL/m(2), p<0.0001) in both groups combined. LVEF decreased (mean change -2%, (95% CI -3% to -1%), p=0.037) and 4% of patients had end-stage HCM with a LVEF of less than 50% at the end of the study.Conclusion: Treatment with losartan had no effect on cardiac function or exercise capacity compared with placebo. Losartan fail to improve myocardial performance and failed to alter the progression of the disease. These findings do not support the use of angiotensin II receptor blockers as disease modifiers in adult patients with overt HCM.Trial Registration Number: NCT01447654-results. [ABSTRACT FROM AUTHOR]