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

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

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

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

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)

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 = 3 × 10-4). 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 = 5 × 10-4 and 2 × 10-7, respectively). Results were similar in meta-analyses including publicly available data from large consortia. Conclusion Genetic variants in CYP7A1 which are associated with increased levels of LDL cholesterol, are associated with an increased risk of both MI and GSD.

Purpose: The purpose of this study was to evaluate whether adenosine-stress myocardial CT perfusion (CTP) in addition to CT angiography (CTA) improves the positive predictive value (PPV) of CT for diagnosing significant coronary artery stenoses in patients with recent acute-onset chest pain. Methods: Consecutive patients hospitalised with acute chest pain, but normal electrocardiogram and cardiac biomarkers were scheduled for CTP on top of CTA. Among patients referred for invasive coronary angiography (ICA), a per patient and per vessel analysis for the detection of coronary stenoses by CTA and reversible perfusion defects by CTP was performed. ICA including fractional flow reserve (FFR) for intermediate stenosis was used as a reference method. For the per vessel analysis, PPV was evaluated for intermediate (50-70%) and severe (>70%) coronary lesions as defined by CTA, and negative predictive value (NPV) for mild (0-49%) coronary lesions. Results: Both CTA and CTP were performed in 34 patients scheduled for ICA. ICA found significant coronary stenoses in 21 patients (62%) and per patient PPV was 76% for CTA increasing to 90% for combined CTA+CTP. Area under the curve (AUC) was 0.72 for CTA and 0.88 for CTA+CTP (p=0.02). In the per vessel analysis significant coronary stenoses were found on ICA in 32 vessels (31%), and PPV for CTA was 69% increasing to 97% for CTA+CTP. AUC was 0.88 for CTA and 0.96 for CTA+CTP (p=0.006). Of 102 vessels, CTA found mild coronary lesions in 56 vessels (55%), intermediate lesions in 15 vessels (15%) and severe lesions in 31 vessels (30%). In intermediate lesions by CTA, ICA/FFR confirmed a significant stenosis in 2/15 vessels (PPV= 13%), and for CTA+CTP PPV increased to 75%. In severe lesions by CTA, ICA confirmed a significant stenosis in 30/31 vessels (PPV=97%) and for CTA+CTP PPV was 100%. NPV was 98% for mild CTA lesions, without any additional contribution of CTP. Conclusion: In patients with recent acute-onset chest pain myocardial CT perfusion has incremental diagnostic value in addition to CT-angiography for diagnosing significant coronary stenoses. CT perfusion appears to be most beneficial in the assessment of intermediate coronary stenoses.