Publications by authors named "Anders Junker"

60 Publications

Coronary Artery Healing Process after Bioresorbable Scaffold in Patients with Non-ST-Segment Elevation Myocardial Infarction: Rationale, Design, and Methodology of the HONEST Study.

Cardiology 2021 Feb 1:1-11. Epub 2021 Feb 1.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Background: Bioresorbable scaffolds (BRSs) is a relatively new approach in treating coronary artery stenosis. The initial results of the first commercially available scaffolds consisting of a backbone of poly-L-lactide raised safety concerns related to delayed resorption and healing. The magnesium alloy-based scaffold degrades via bio-corrosion within months, whereas it often takes several years for polymer scaffolds to degrade. The aim of the study was to assess the healing stage by optical coherence tomography (OCT) after 6 months in patients with non-ST-segment elevation myocardial infarct (NSTEMI) randomized to OCT or angiography-guided percutaneous coronary intervention with implantation of a magnesium sirolimus-eluting Magmaris scaffold (Magmaris; Biotronik, Bülach, Switzerland).

Methods: We analyzed the healing process by comparing OCT at baseline and after 6 months. Five stages of healing were defined with stage 1 being the least healed and stage 5 demonstrating complete resorption and healing with no visible scaffold/remnant. The primary end point is a calculated healing score that is based on 5 subtypes of healing stage: (1) malapposed, (2) uncovered with no detection of smooth surface tissue on top of struts or remnants, (3) covered protruding, (4) covered embedded, and (5) complete healing with a smooth neointimal surface and no sign of struts or visible remnants assessed by OCT 6 months after the index procedure.

Results: The impact of OCT-guided compared to angiography-guided scaffold implantation will be illuminated.

Conclusion: The present study will provide new information on midterm healing properties of the magnesium BRS in patients with NSTEMI.
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http://dx.doi.org/10.1159/000512417DOI Listing
February 2021

Referral Patterns for Patients with Nonalcoholic Fatty Liver Disease.

J Clin Med 2021 Jan 21;10(3). Epub 2021 Jan 21.

Gastro Unit, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark.

The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. This study evaluates the referral pattern of patients with NAFLD. A cohort study evaluating all patients with NAFLD referred to a single Gastroenterology Department from January 2017 to June 2020. Electronic patient referral letters were reviewed, and patients with NAFLD were diagnosed using standardized tests as part of a prospective cohort study. Predictors of nonalcoholic steatohepatitis (NASH) with significant (≥F2) fibrosis were evaluated in logistic regression analyses. In total, 323 (18.6%) of 1735 patients referred to the Gastro Unit during the study period were diagnosed with NAFLD. Patients were referred from general practitioners (62.5%) or other hospital departments (37.5%). Most referral letters included information suggesting a possible diagnosis of NAFLD (patient history, blood tests, or diagnostic imaging) or used the nonspecific general diagnosis suspected disease (Z.038). Out of 110 patients referred for a liver biopsy, 71 (22%) had NASH with significant fibrosis (F2 = 39, F3 = 19, F4 = 13). Thirty-nine of these patients were referred from the primary sector. A logistic regression analysis (adjusted for age and gender) including all 323 patients showed that type 2 diabetes was the only significant independent predictor of NASH with fibrosis.
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http://dx.doi.org/10.3390/jcm10030404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866077PMC
January 2021

No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect.

Endocr Connect 2020 Dec;9(12):1221-1232

Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes (T2D), possibly by modulation of incretin action. In this study, we evaluated the effect of the TCF7L2 rs7903146 T allele on the incretin effect and other glucometabolic parameters in normal glucose tolerant individuals (NGT) and participants with T2D. The rs7903146 variant was genotyped in cohorts of 61 NGT individuals (23 were heterozygous (CT) or homozygous (TT) T allele carriers) and 43 participants with T2D (20 with CT/TT). Participants were previously examined by an oral glucose tolerance test (OGTT) and a subsequent isoglycemic intravenous glucose infusion (IIGI). The incretin effect was assessed by quantification of the difference in integrated beta cell secretory responses during the OGTT and IIGI. Glucose and hormonal levels were measured during experimental days, and from these, indices of beta cell function and insulin sensitivity were calculated. No genotype-specific differences in the incretin effect were observed in the NGT group (P = 0.70) or the T2D group (P = 0.68). NGT T allele carriers displayed diminished glucose-dependent insulinotropic polypeptide response during OGTT (P = 0.01) while T allele carriers with T2D were characterized by lower C-peptide AUC after OGTT (P = 0.04) and elevated glucose AUC after OGTT (P = 0.04). In conclusion, our findings do not exclude that this specific TCF7L2 variant increases the risk of developing T2D via diminished incretin effect, but genotype-related defects were not detectable in these cohorts.
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http://dx.doi.org/10.1530/EC-20-0471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774769PMC
December 2020

Culprit lesion morphology in patients with ST-segment elevation myocardial infarction assessed by optical coherence tomography.

Coron Artery Dis 2020 12;31(8):671-677

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Aims: This study sought to evaluate the incidence of ruptured plaques and nonruptured plaques (NRP) and to compare patient characteristics and detailed plaque morphology features between the two culprit types in ST-segment elevation myocardial infarction (STEMI) patients, using optical coherence tomography (OCT).

Methods And Results: Using OCT, the culprit lesions in patients with STEMI were assessed prior to stent implantation. The culprit lesion was categorized as ruptured plaques or NRP, and the plaque components were evaluated. Fifty-two patients (69.3%) presented with ruptured plaques and 23 (30.7%) with NRP. Patients with NRP were younger (58.0 ± 10.4 vs 64.7 ± 9.9 years, P = 0.01) and more often smokers (72.7% vs 37.1%, P = 0.001), compared to ruptured plaques. NRP contained significantly more fibrotic plaque (20.0% [interquartile range (IQR) 13.7-29.8] vs 11.3% [IQR 6.9-18.1], P = 0.005), but less lipidic plaque (44.0% ± 13.7 vs 59.3% ± 13.6, P < 0.001), less superficial [5.0% (IQR 2.8-7.5) vs 8.1% (IQR 5.7-11.0), P = 0.005] and profound macrophages [0.9% (IQR 0.0-1.7) vs 2.2% (IQR 0.9-4.7), P = 0.003]. The prevalence, numbers and lengths of thin-cap fibroatheroma (TCFA) were significantly lower in NRP, compared to ruptured plaques [47.8% vs 88.5%, 0 (IQR 0-1) vs 1 (IQR 1-2) and 0 mm (IQR 0-2.7) vs 4.5 mm (IQR 2.3-7.7), P < 0.001].

Conclusions: One-third of STEMI patients had culprit lesions without an OCT-detectable ruptured plaque. Culprit lesions with NRP contained less vulnerable plaque components, such as lipid plaque, TCFAs and macrophages compared to ruptured plaques.
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http://dx.doi.org/10.1097/MCA.0000000000000957DOI Listing
December 2020

Experience from a COVID-19 first-line referral clinic in Greater Copenhagen.

Dan Med J 2020 Aug 7;67(9). Epub 2020 Aug 7.

Introduction: Due to the coronavirus disease 2019 (COVID-19) exposure in Denmark, first-line referral centres were established to handle all patients suspected of COVID-19 or other upper respiratory tract infection. Here we report the first experiences from a first-line referral centre from Amager-Hvidovre Hospital, situated on the outskirts of Copenhagen.

Methods: A retrospective quality assessment was performed with collection of symptom patterns and COVID-19 status.

Results: During the first 24 days, a total of 3,551 patients were referred for assessment of symptoms of upper respiratory tract infection and COVID-19. A total of 2,048 patients were assessed as having mild symptoms and referred for COVID-19 testing alone, whereas 337 patients were assessed clinically by a physician. Thirty-seven were positive for COVID-19 infection, 286 were negative. The most common symptoms reported were fever, coughing and dyspnoea. Fever was an independent predictor of COVID-19 infection (odds ratio (OR) = 2.25 (95% confidence interval (CI): 1.08-5.04); p = 0.037); whereas sore throat was not (OR = 0.40 (95% CI: 0.15-0.92); p = 0.045). Only a small number of patients reported loss of taste or anosmia. In total, 113 patients were admitted to hospital, the majority of patients were discharged within 24 hours with mild symptoms of upper respiratory tract infections. Three of the COVID-19-positive patients developed a severe infection and two had a fatal outcome.

Conclusions: The present study is the first to report the experiences and symptom patterns of a COVID-19 first-line referral centre with efficient triage of patients in need of hospitalisation.

Funding: none.

Trial Registration: not relevant.
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August 2020

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

Circulation 2020 06 21;141(25):2052-2063. Epub 2020 May 21.

Department of Cardiology, Aarhus University Hospital, Skejby Hospital, Denmark (M.M., L.J., S.D.K., S.C., C.J.T., H.E.B., T.T., A.E., E.H.C.).

Background: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention.

Methods: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021.

Results: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; =0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; <0.0001).

Conclusions: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040241DOI Listing
June 2020

Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature.

World J Clin Cases 2020 May;8(9):1642-1650

Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark.

Background: Cholesteryl ester storage disease (CESD) is a rare genetic disease. Its symptoms and severity are highly variable. CESD is a systemic disease that can lead to the accumulation of fat and inflammation in the liver, as well as gastrointestinal and cardiovascular disease. The majority of patients require liver transplantation due to decompensated cirrhosis. Enzyme replacement therapy has been approved based on a randomized trial. Our study aims to clinically and genetically evaluate two siblings with CESD who underwent liver transplantation, as well as their first-degree family members.

Case Summary: The siblings were compound heterozygous for the missense variant in exon 8, c.894G>A, (p.Gln298Gln) and a single base pair deletion, c.482del (p.Asn161Ilefs*19). Analyses of single nucleotide polymorphisms showed variants with an increased risk of fatty liver disease and fibrosis for both patients. Clinically, both patients show signs of recurrence of CESD in the liver after transplantation and additional gastrointestinal and cardiovascular signs of CESD. Three family members who were heterozygous had a lysosomal acid lipase activity below the reference value. One of these carriers, a seven-year-old boy, was found to have severe dyslipidemia and was subsequently treated with statins.

Conclusion: Our study underlines that CESD is a multi-organ disease, the progression of which may occur post-liver transplantation. Our findings underline the need for monitoring of complications and assessment of possible further treatment.
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http://dx.doi.org/10.12998/wjcc.v8.i9.1642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211528PMC
May 2020

O-Water Positron Emission Tomography of Myocardial Ischemia in Patients Referred for Percutaneous Coronary Intervention.

Cardiovasc Revasc Med 2020 Oct 7;21(10):1237-1243. Epub 2020 Mar 7.

Department of Cardiology, Odense University Hospital, Odense, Denmark. Electronic address:

The diagnostic accuracy of non-invasive diagnostic methods for detecting coronary artery disease has increased in recent years. This study aimed to assess the diagnostic performance of O-water positron emission tomography (PET) in terms of stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with single-vessel disease referred for percutaneous coronary intervention (PCI), using fractional flow reserve (FFR) value of ≤0.80 as the reference for a significant stenosis. We also assessed the influence of the index of microcirculatory resistance (IMR) on the diagnostic performance of PET. O-water PET FFR and IMR were measured before PCI in 26 patients with single-vessel disease. Stress MBF < 2.5 ml/min/g (95% confidence interval [CI]) had sensitivity 78% (95% CI: 52%-94%), specificity 50% (95% CI: 16%-84%), positive predictive value (PPV) 78% (95% CI: 63%-88%), negative predictive value (NPV) 50% (95% CI: 25%-75%), and accuracy 69% (95% CI: 48%-86%). MFR < 2.5 had sensitivity 72% (95% CI: 47%-90%), specificity 75% (95% CI: 35%-97%), PPV 87% (95% CI: 65%-96%), NPV 55% (95% CI: 34%-74%), and accuracy 73% (95% CI: 52%-88%). In patients with IMR > 24, stress MBF correlated with FFR (r = 0.651; p = 0.016) whereas stress MBF did not correlate with FFR in patients with IMR < 24. In conclusion, stress MBF and MFR had modest diagnostic performance compared to invasive FFR measurements in patients with single-vessel disease.
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http://dx.doi.org/10.1016/j.carrev.2020.03.010DOI Listing
October 2020

Diagnosis and Treatment of Genetic -Hemochromatosis: The Danish Aspect.

Gastroenterology Res 2019 Oct 4;12(5):221-232. Epub 2019 Oct 4.

Department of Blood Center and Medical Biochemistry, Innlandet Hospital Trust, Lillehammer, Norway.

This paper outlines the Danish aspects of -hemochromatosis, which is the most frequent genetic predisposition to iron overload in the five million ethnic Danes; more than 20,000 people are homozygous for the C282Y mutation and more than 500,000 people are compound heterozygous or heterozygous for the -mutations. The disorder has a long preclinical stage with gradually increasing body iron overload and eventually 30% of men will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease and diabetes. Subsequently the disease may progress into irreversible arthritis, liver cirrhosis, cardiomyopathy, pancreatic fibrosis and osteoporosis. The effective standard treatment is repeated phlebotomies, which in the preclinical and early clinical stages ensures a normal survival rate. Early detection of the genetic predisposition to the disorder is therefore important to reduce the overall burden of clinical disease. Population screening seems to be cost-effective and should be considered.
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http://dx.doi.org/10.14740/gr1206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785287PMC
October 2019

Everolimus-Eluting Versus Biolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus.

Am J Cardiol 2019 09 6;124(5):671-677. Epub 2019 Jun 6.

Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

Diabetes mellitus is associated with a higher risk of target lesion revascularization after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus, treated with everolimus-eluting stents (EES; Synergy; Boston Scientific, Marlborough, Massachusetts) or biolimus-eluting stents (BES; BioMatrix NeoFlex; Biosensors Interventional Technologies Pte Ltd., Singapore). In total, 2,764 patients were randomized to stent implantation with EES (n = 1,385, diabetes: n = 250) or the BES (n = 1,379, diabetes: n = 262), stratified by gender and diabetes. The primary end point, target lesion failure (TLF), was a composite of cardiac death, target-lesion myocardial infarction, or target lesion revascularization at 12 months. Secondary end points included individual components of TLF, all-cause death, and stent thrombosis. TLF was 2.1% lower in the EES versus the BES groups in patients with diabetes (3.6% vs 5.7%; rate ratios 0.61, 95% confidence interval [CI] 0.27 to 1.41) and similar in patients without diabetes (4.1% vs 4.0%; rate ratios 0.99, 95% CI 0.66 to 1.51). In patients with diabetes, the point estimates of the individual components of TLF also favored the EES but CIs were wide. No interaction between stent type and presence of diabetes was found. The current subgroup analysis found that a thin-strut EES as compared with a thicker strut BES had a numerically lower TLF rate in patients with diabetes, but the subgroup analysis was underpowered for definite conclusions.
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http://dx.doi.org/10.1016/j.amjcard.2019.05.060DOI Listing
September 2019

Rationale and design of DanGer shock: Danish-German cardiogenic shock trial.

Am Heart J 2019 08 6;214:60-68. Epub 2019 May 6.

Heart Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Objective: The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far.

Methods: The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies.

Results: As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%).

Conclusion: The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.
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http://dx.doi.org/10.1016/j.ahj.2019.04.019DOI Listing
August 2019

Influence of Ezetimibe on Plaque Morphology in Patients with ST Elevation Myocardial Infarction Assessed by Optical Coherence Tomography: An OCTIVUS Sub-Study.

Cardiovasc Revasc Med 2020 Nov 24;21(11):1417-1424. Epub 2019 Apr 24.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Aims: The aim of the trial was to examine the influence of ezetimibe on plaque morphology in patients with ST-segment Elevation Myocardial Infarction (STEMI) with respect to fibrous cap thickness (FCT) and arcs of lipid plaque, calcific plaque, and macrophages using Optical Coherence Tomography (OCT).

Methods And Results: In 87 statin naïve patients with STEMI treated with primary percutaneous intervention, a non-culprit study plaque in a non-infarct related coronary artery was assessed with OCT at baseline and after 12 months. Patients were treated with atorvastatin 80 mg and randomized (1:1) to ezetimibe 10 mg (n = 43) or placebo (n = 44). An increase in median FCT (ezetimibe 200 (140-260) μm to 240 (190-305) μm (p = 0.002) vs. placebo 205 (135-260) μm to 230 (180-270) μm (p < 0.001), between groups p = ns), a reduction in lipid arc (ezetimibe 1728.5 (1022.5-3904.7)° to 1164.5 (736.6-2580.1)° (p = 0.001) vs. placebo 1671.6 (978.3-2868.7)° to 1373.7 (791.2-2267.3)° (p = 0.019), between groups p = ns), and macrophage arc (ezetimibe 1730.3 (965.7-2984.4)° to 1324.8 (819.0-2819.7)° (p < 0.05) vs. placebo 1570.5 (794.7-3016.8)° to 1418.9 (584.1-2501.1)° (p < 0.01), between groups p = ns) were observed.

Conclusion: Aggressive LDL-lowering resulted in changes in OCT assessed plaque composition by increased FCT thickness and a reduction in lipid content and macrophage infiltration. Addition of ezetimibe 10 mg to atorvastatin 80 mg resulted in further LDL reduction, but no additional change in plaque composition was found.
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http://dx.doi.org/10.1016/j.carrev.2019.04.021DOI Listing
November 2020

Everolimus-Eluting Versus Biolimus-Eluting Stents With Biodegradable Polymers in Unselected Patients Undergoing Percutaneous Coronary Intervention: A Randomized Noninferiority Trial With 1-Year Follow-Up (SORT OUT VIII Trial).

JACC Cardiovasc Interv 2019 04;12(7):624-633

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Objectives: The aim of this study was to compare the thin-strut biodegradable-polymer everolimus-eluting platinum-chromium stent (EES) with the biodegradable-polymer biolimus-eluting stainless-steel stent (BES).

Background: Currently available drug-eluting coronary stents have been refined to reduce the risk for coronary events following implantation.

Methods: This randomized, multicenter, all-comers, noninferiority trial was undertaken at 3 sites in western Denmark. Patients with clinical indications for percutaneous coronary intervention were eligible for inclusion. Patients were randomly assigned (1:1) to either EES or BES. The primary endpoint, target lesion failure, was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a nontarget lesion) and efficacy (target lesion revascularization) at 12 months, analyzed using intention-to-treat principles. The trial was powered to assess target lesion failure noninferiority of the EES compared with the BES with a predetermined noninferiority margin of 3%.

Results: A total of 1,385 patients were assigned to treatment with EES and 1,369 patients to treatment with BES. The analysis showed that 55 patients (4.0%) assigned to the EES and 60 (4.4%) assigned to the BES met the primary endpoint (absolute risk difference 0.4%; upper limit of 1-sided 95% confidence interval: 1.7%; p < 0.001).

Conclusions: At 1-year follow-up, the EES was found to be noninferior to the BES with respect to target lesion failure. (Everolimus-eluting SYNERGY Stent Versus Biolimus-Eluting Biomatrix NeoFlex Stent-SORT-OUT VIII; NCT02093845).
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http://dx.doi.org/10.1016/j.jcin.2018.12.036DOI Listing
April 2019

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.

Mol Syst Biol 2019 03 1;15(3):e8793. Epub 2019 Mar 1.

Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP, and LAP3, all of which are up-regulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, plasma proteome profiling can identify potential biomarkers and drug targets in liver disease.
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http://dx.doi.org/10.15252/msb.20188793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396370PMC
March 2019

[Genetic HFE-haemochromatosis].

Ugeskr Laeger 2018 Dec;180(51)

HFE-haemochromatosis is the most frequent genetic disposition for iron overload in ethnic Danes: 20,000 persons are homozygous for the C282Y mutation. The disorder has a long preclinical phase with increasing body iron overload, and 30% of males will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease, diabetes and liver disease, later progressing into cirrhosis, cardio-myo-pathy, pancreatic fibrosis and osteoporosis. Treatment consists of phlebotomies, which in the preclinical and early clinical phases ensure normal survival.
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December 2018

Fractional Flow Reserve Versus Angiographically-Guided Coronary Artery Bypass Grafting.

J Am Coll Cardiol 2018 12;72(22):2732-2743

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Background: The value of fractional flow reserve (FFR) evaluation of coronary artery stenosis in coronary artery bypass grafting (CABG) is uncertain, and stenosis assessments usually rely on visual estimates of lesion severity.

Objectives: This randomized clinical trial evaluated graft patency and clinical outcome after FFR-guided CABG versus angiography-guided CABG.

Methods: A total of 100 patients referred for CABG were randomly assigned to FFR-guided or angiography-guided CABG. Based on the coronary angiogram, a heart team made a graft plan for all patients, and FFR evaluations were performed. In FFR-guided CABG, coronary lesions with FFR >0.80 were deferred, and a new graft plan was designed accordingly, whereas the surgeon was blinded to the FFR values in patients who underwent angiography-guided CABG. The primary endpoint was graft failure in the percentage of all grafts after 6 months.

Results: Angiographic follow-up at 6 months was available for 72 patients (39 vs. 33 in the FFR-guided and angiography-guided groups, respectively). Graft failures of all grafts were similar in both groups (16% vs. 12%; p = 0.97). Rates of death, myocardial infarction, and stroke were also similar in the study groups, and no difference was seen in revascularization before angiographic follow-up. After 6 months, deferred lesions (n = 24) showed a significant reduction in mean FFR from index to follow-up (0.89 ± 0.05 vs. 0.81 ± 0.11; p = 0.002). Index FFR did not influence graft patency.

Conclusions: FFR-guided CABG had similar graft failure rates and clinical outcomes as angiography-guided CABG. However, FFR was reduced significantly after 6 months in deferred lesions. (Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization [FARGO]; NCT02477371).
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http://dx.doi.org/10.1016/j.jacc.2018.09.043DOI Listing
December 2018

Impact of diabetes on clinical outcomes after revascularization with sirolimus-eluting and biolimus-eluting stents with biodegradable polymer from the SORT OUT VII trial.

Catheter Cardiovasc Interv 2019 03 23;93(4):567-573. Epub 2018 Sep 23.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Objectives: In this substudy of the SORT OUT VII trial, the clinical outcomes among patient with diabetes mellitus treated with Orsiro sirolimus-eluting stent (O-SES; Biotronik, Bülach, Switzerland) or Nobori biolimus-eluting stent (N-BES; Terumo, Tokyo, Japan) were compared.

Background: Diabetes is associated with increased risk of target lesion failure (TLF) after percutaneous coronary intervention.

Methods: In total, 2525 patients were randomized to stent implantation with O-SES (n = 1261, diabetes: n = 236) or N-BES (n = 1264, diabetes: n = 235). The primary endpoint, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 2 years.

Results: At 2 year, TLF did not differ between O-SES vs N-BES in diabetic (9.3% vs 9.4%; RR 0.98, 95% CI 0.54-1.78) patients. The individual components of the primary endpoint did not differ among stent type. In diabetics, cardiac death occurred in 3% of O-SES-treated and in 3.8% of N-BES-treated patients (RR 0.77, 95% CI 0.29-2.08), MI occurred in 3.0% of O-SES-treated and in 3.8% of N-BES-treated patients (RR 0.76, 95% CI 0.28-2.06) and TLR occurred in 5,5% of O-SES-treated and in 6.0% of N-BES-treated patients (RR 0.91, 95% CI 0.43-1.95).

Conclusion: TLF did not differ between O-SES- and N-BES-treated diabetic patients.
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http://dx.doi.org/10.1002/ccd.27891DOI Listing
March 2019

Ten-year clinical outcome of patients treated with a drug-eluting stent in the proximal left anterior descending artery segment compared with patients stented in other non-left main coronary segments.

EuroIntervention 2018 Sep;14(7):764-771

Department of Cardiology, Zealand University Hospital, Roskilde, Denmark.

Aims: The aim of the study was to determine whether patients treated with drug-eluting stents in the proximal left anterior descending artery (LAD) carried a different long-term prognosis from patients treated in other coronary artery segments.

Methods And Results: Ten-year clinical outcome expressed as all-cause mortality and major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, or target vessel revascularisation) was determined for 1,479 patients with a single non-left main coronary stenosis treated with a first-generation drug-eluting stent in the SORT OUT II trial. The outcome of patients treated with stents in the proximal LAD (n=365) was compared with that of patients treated in a non-proximal LAD segment (n=1,114). Follow-up was 99.3% complete. All-cause mortality was 24.9% in the proximal LAD group vs. 26.3% in the non-proximal LAD group (p=0.60). MACE occurred less frequently in the proximal LAD group, 24.6% vs. 31.0% with a hazard ratio of 0.77 (95% confidence interval [CI]: 0.61-0.97, p=0.024). After multivariate analysis which included baseline characteristics that were unevenly distributed between the groups, the hazard ratio for MACE was 0.82 (95% CI: 0.65-1.03, p=0.09).

Conclusions: Patients treated with a drug-eluting stent in the proximal LAD have similar, if not better, long-term clinical outcome compared with patients stented in other coronary artery segments.
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http://dx.doi.org/10.4244/EIJ-D-18-00396DOI Listing
September 2018

Prospective Comparison of FFR Derived From Coronary CT Angiography With SPECT Perfusion Imaging in Stable Coronary Artery Disease: The ReASSESS Study.

JACC Cardiovasc Imaging 2018 11 13;11(11):1640-1650. Epub 2018 Jun 13.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Objectives: This study sought to compare the per-patient diagnostic performance of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFR) with that of single-photon emission computed tomography (SPECT), using a fractional flow reserve (FFR) value of ≤0.80 as the reference for diagnosing at least 1 hemodynamically significant stenosis in a head-to-head comparison of patients with intermediate coronary stenosis as determined by coronary CTA.

Background: No previous study has prospectively compared the diagnostic performance of FFR and myocardial perfusion imaging by SPECT in symptomatic patients with intermediate range coronary artery disease (CAD).

Methods: This study was conducted at a single-center as a prospective study in patients with stable angina pectoris (N = 143). FFR and SPECT analyses were performed by core laboratories and were blinded for the personnel responsible for downstream patient management. FFR ≤0.80 distally in at least 1 coronary artery with a diameter ≥2 mm classified patients as having ischemia. Ischemia by SPECT was encountered if a reversible perfusion defect (summed difference score ≥2) or transitory ischemic dilation of the left ventricle (ratio >1.19) were found.

Results: The per-patient diagnostic performance for identifying ischemia (95% confidence interval [CI]), FFR versus SPECT, were sensitivity of 91% (95% CI: 81% to 97%) versus 41% (95% CI: 29% to 55%; p < 0.001); specificity of 55% (95% CI: 44% to 66%) versus 86% (95% CI: 77% to 93%; p < 0.001); negative predictive value of 90% (95% CI: 82% to 98%) versus 68% (95% CI: 59% to 77%; p = 0.001); positive predictive value of 58% (95% CI: 48% to 68%) versus 67% (95% CI: 51% to 82%; p = NS); and accuracy of 70% (95% CI: 62% to 77%) versus 68% (95% CI: 60% to 75%; p = NS) respectively.

Conclusions: In patients with stable chest pain and CAD as determined by coronary CTA, the overall diagnostic accuracy levels of FFR and SPECT were identical in assessing hemodynamically significant stenosis. However, FFR demonstrated a significantly higher diagnostic sensitivity than SPECT.
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http://dx.doi.org/10.1016/j.jcmg.2018.05.004DOI Listing
November 2018

Bone Turnover Markers in Patients With Nonalcoholic Fatty Liver Disease and/or Type 2 Diabetes During Oral Glucose and Isoglycemic Intravenous Glucose.

J Clin Endocrinol Metab 2018 05;103(5):2042-2049

Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Hellerup, Denmark.

Context: Nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes (T2D) and vice versa, and both conditions are associated with an increased risk of fractures and altered bone turnover. Although patients with NAFLD typically suffer from decreased bone mineral density (BMD), T2D is associated with normal to high BMD. The pathophysiology is uncertain but may involve the gut-bone axis.

Objective: We investigated the influence of the gut on glucose-induced changes in plasma bone turnover markers in healthy controls and patients with T2D and/or biopsy-verified NAFLD.

Design: Cross-sectional cohort study.

Patients: Patients with NAFLD with normal glucose tolerance, patients with NAFLD and T2D, patients with T2D without liver disease, and healthy controls.

Interventions: Four-hour 50-g oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI).

Main Outcome Measures: Collagen type 1 C-telopeptide (CTX), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and parathyroid hormone.

Results: Plasma glucose levels achieved during OGTTs were successfully matched on corresponding IIGI days. Patients with NAFLD and T2D exhibited similar CTX suppression during the two glucose challenges (P = 0.46) and pronounced suppression of P1NP during IIGI compared with OGTT. Conversely, remaining groups showed greater (P < 0.05) CTX suppression during OGTT and similar suppression of bone formation markers during IIGI and OGTT.

Conclusions: OGTT-induced CTX suppression seems to be impaired in patients with NAFLD and T2D, but preserved in patients with either NAFLD or T2D, suggesting that coexistence of T2D and NAFLD may affect gut-bone axis.
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http://dx.doi.org/10.1210/jc.2018-00176DOI Listing
May 2018

One-year rehospitalisation after percutaneous coronary intervention: a retrospective analysis.

EuroIntervention 2018 Oct;14(8):926-934

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Aims: The aim of the study was to evaluate the incidence and causes of rehospitalisation within one year after percutaneous coronary intervention (PCI) in a country where the National Health Service provides universal tax-supported healthcare, guaranteeing residents free hospital access.

Methods And Results: Between January 2010 and September 2014, 17,111 patients were treated with PCI in two University Hospitals in Western Denmark. Patients who were readmitted within one year after PCI were identified. The overall one-year readmission rate was 50.4%. The cause was angina/myocardial infarction (MI) in 4,282 patients (49.7%), and other reasons in 4,334 (50.3%). Predictors of angina/MI-related readmissions were female gender (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.07-1.25), diabetes (OR 1.14, 95% CI: 1.04-1.26), age (per 10-year increase) (OR 0.86, 95% CI: 0.83-0.88), and indication for index PCI (stable angina pectoris as reference): ST-segment elevation myocardial infarction (OR 1.34, 95% CI: 1.23-1.47) and non-ST-segment elevation myocardial infarction (OR 1.18, 95% CI: 1.08-1.29). Predictors for other readmissions were female gender (OR 1.09, 95% CI: 1.01-1.18), diabetes (OR 1.29, 95% CI: 1.18-1.42), age (OR 1.30, 95% CI: 1.26-1.34) and Charlson comorbidity index ≥3 (OR 3.03, 95% CI: 2.71-3.27).

Conclusions: In an unselected patient cohort treated with PCI, half of the patients were rehospitalised within one year, highlighting the impact of comorbidity in patients with ischaemic heart disease.
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http://dx.doi.org/10.4244/EIJ-D-17-00800DOI Listing
October 2018

Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes.

Am J Physiol Gastrointest Liver Physiol 2018 01 28;314(1):G91-G96. Epub 2017 Sep 28.

Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high-performance liquid chromatography, in obese, middle-aged individuals with I) normal glucose tolerance (NGT) and NAFLD, II) T2D and NAFLD, III) T2D without liver disease, and IV) NGT and no liver disease. Elevated levels of total amino acids were observed in participants with NAFLD and NGT compared with NGT controls (1,310 ± 235 µM vs. 937 ± 281 µM, P = 0.03) and in T2D and NAFLD compared with T2D without liver disease (1,354 ± 329 µM vs. 511 ± 235 µM, P < 0.0001). Particularly amino acids with known glucagonotropic effects (e.g., glutamine) were increased. Plasma levels of total amino acids correlated to plasma levels of glucagon also when adjusting for body mass index (BMI), glycated hemoglobin (Hb), and cholesterol levels (β = 0.013 ± 0.007, P = 0.024). Elevated plasma levels of total amino acids associate with hyperglucagonemia in NAFLD patients independently of glycemic control, BMI or cholesterol - supporting the potential importance of a "liver-α-cell axis" in which glucagon regulates hepatic amino acid metabolism. Fasting hyperglucagonemia as seen in T2D may therefore represent impaired hepatic glucagon action with increasing amino acids levels. NEW & NOTEWORTHY Hypersecretion of glucagon (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia may depend on hepatic steatosis rather than type 2 diabetes.
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http://dx.doi.org/10.1152/ajpgi.00216.2017DOI Listing
January 2018

Randomized clinical trial: the impact of gastrointestinal risk factor screening and prophylactic proton pump inhibitor therapy in patients receiving dual antiplatelet therapy.

Eur J Gastroenterol Hepatol 2017 Oct;29(10):1118-1125

Departments of aMedical Gastroenterology bCardiology, Odense University Hospital cDepartment of Public Health, University of Southern Denmark, Odense dDepartment of Cardiology, Aarhus University Hospital, Skejby eDepartment of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Objective: Dual antiplatelet therapy reduces the risk of ischemic complications after acute coronary syndrome, but increases the risk of bleeding including upper gastrointestinal bleeding (UGIB).The aim of this study was to examine the effect of screening for risk of UGIB and prophylactic proton pump inhibitor (PPI) treatment in dual-antiplatelet-treated patients at risk of UGIB and to assess the significance of dual antiplatelet therapy compliance for cardiovascular events.

Patients And Methods: In a register-based randomized-controlled trial, 2009 patients were included at the time of first percutaneous coronary intervention and randomized to either screening or control. Screened high-risk patients were prescribed pantoprazole 40 mg during the 1-year after percutaneous coronary intervention.

Results: The incidence of UGIB was 0.8 versus 1.3% in screened patients and controls, respectively (P=0.381).Significantly fewer screened patients (5.4%) than controls (8.0%) underwent upper gastrointestinal endoscopy (P=0.026). Screened patients (2.9%) had significantly fewer events of unstable angina pectoris than controls (4.7%) (P=0.036) and a higher compliance to dual antiplatelet therapy (88.3 vs. 85.0%) (P=0.035), but no statistically difference was observed in the incidences of myocardial infarction and all-cause mortality (1.0 vs. 1.5%) (P=0.422).

Conclusion: Screening for risk factors for UGIB and subsequent prophylactic PPI treatment did not significantly reduce the incidence of UGIB. Prescription of PPI was associated with a higher compliance with dual antiplatelet therapy and decreases the risk of recurrent cardiovascular events.
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http://dx.doi.org/10.1097/MEG.0000000000000934DOI Listing
October 2017

The role of incretin hormones and glucagon in patients with liver disease.

Dan Med J 2017 May;64(5)

Non-alcoholic fatty liver disease (NAFLD) is defined as hepatic steatosis exceeding 5% of hepatocytes with no other reason for hepatic fat accumulation. The association between NAFLD and type 2 diabetes is strong. Accordingly, up to 70% of obese patients with type 2 diabetes have NAFLD. The spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis with variable degrees of fibrosis and cirrhosis. Cirrhosis is the end-stage of chronic liver disease and is characterised by diffuse fibrosis and nodular regeneration of hepatocytes. Alcoholic liver disease and NAFLD are the most common aetiologies of cirrhosis. The WHO estimates that 70% of patients with cirrhosis have impaired glucose tolerance and 30% have manifest diabetes. The latter is termed hepatic diabetes and is associated with increased complications to cirrhosis and hepatocellular carcinoma. The objective of this thesis was to study the impact of liver dysfunction on incretin and glucagon (patho)physiology in relation to glucose metabolism. We hypothesised that NAFLD patients with normal glucose tolerance would develop reduced incretin effect and that NAFLD would worsen the incretin effect in patients with existing type 2 diabetes. Thus, in study I, we investigated the incretin effect and glucagon secretion in patients with NAFLD with and without type 2 diabetes compared to controls. We also hypothesised that the incretin effect would be disturbed in non-diabetic patients with more severe liver disease. Hence, the objective of study II was to investigate the incretin effect in patients with cirrhosis. Finally, the hypothesis in study III was that an impaired glucagonostatic effect of GLP-1 contributes to the hyperglucagonaemia of patients with liver disease. We therefore explored the glucagonostatic properties of GLP-1 in non-diabetic patients with NAFLD. The results of study I show that patients with NAFLD have normal secretion of GLP-1 and GIP and a reduced incretin effect. The groups with type 2 diabetes have the lowest incretion effect. We also find that NAFLD patients have high fasting glucagon concentrations regardless of their glucose (in)tolerance. We further demonstrated that patients with normal glucose tolerance and NAFLD have preserved glucagon suppression to both oral and intravenous glucose.  In study II, we find that non-diabetic patients with cirrhosis have elevated concentrations of GLP-1 and GIP and a reduced incretin effect. Patients with cirrhosis also have fasting hyperglucagonaemia, but show intact glucagon suppression during both oral and intravenous glucose administration. Finally, study III demonstrates that normal glucose tolerant NAFLD patients had preserved glucagonostatic effect of GLP-1. In conclusion, our studies offer important information regarding the pathophysiology of glucose intolerance in patients with liver disease. We demonstrate that patients with NAFLD, in spite of normal glucose tolerance, have reduced incretin effect that is further aggravated by type 2 diabetes. We also find fasting hyperglucagonaemia in NAFLD patients, independently of type 2 diabetes. We show that cirrhosis is associated with impaired handling of oral glucose and reduced incretin effect. Finally, we find a preserved glucagonostatic effect of GLP-1 in patients with NAFLD, in spite of their hyperglucagonaemia. In light of our findings, the insulinotropic and glucagonostatic effects of GLP-1 receptor agonists might prove beneficial in patients with liver disease.
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May 2017

Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: 3-Year Clinical Outcomes in the Randomized SORT OUT VI Trial.

JACC Cardiovasc Interv 2017 02 18;10(3):255-264. Epub 2017 Jan 18.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Objectives: The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients.

Background: Biodegradable-polymer biolimus-eluting stents are superior to first-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking.

Methods: The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target lesion revascularization); the individual endpoints of MACE; all-cause mortality; any myocardial infarction; target vessel revascularization; and definite or probable stent thrombosis at 36 months.

Results: From March 2011 to August 2012, 2,999 patients were randomly assigned (1:1) to receive either the zotarolimus-eluting (1,502 patients) or the biolimus-eluting (1,497 patients) stent. At 3-year follow-up, MACE occurred in 128 (8.6%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 144 (9.6%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.36). Occurrence of cardiac death (2.7% vs. 3.4%), myocardial infarction not clearly attributable to a non-target lesion (2.7% vs. 2.5%), and target lesion revascularization (5.4% vs. 5.5%) did not differ significantly between the 2 groups. Definite very late stent thrombosis occurred in 6 (0.4%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 10 (0.7%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.33).

Conclusions: At 3-year follow-up, the durable-polymer zotarolimus-eluting stent and the biodegradable-polymer biolimus-eluting stent were similar in clinical outcome, with no significant difference in safety and efficacy outcomes, including stent thrombosis.
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http://dx.doi.org/10.1016/j.jcin.2016.11.007DOI Listing
February 2017

Lipid-core burden response to stent implantation assessed with near-infrared spectroscopy and intravascular ultrasound evaluation in patients with myocardial infarction.

Cardiovasc Revasc Med 2017 Apr - May;18(3):182-189. Epub 2016 Dec 27.

Department of Cardiology, Odense University Hospital, Denmark. Electronic address:

Introduction: Near-infrared spectroscopy (NIRS) is a new method to identify lipid core plaque (LCP). The LCP and vascular response were assessed with NIRS to examine whether LCP was compressed or redistributed during percutaneous coronary intervention with stent implantation.

Methods: In 25 patients with non-ST segment elevation myocardial infarction (NSTEMI) NIRS acquisition was performed after predilation, stent implantation with nominal pressure and high-pressure post-dilation with a non-compliant balloon. The intravascular ultrasound (IVUS) measures included volumes of external elastic membrane (EEM), lumen and plaque+media. The NIRS measures included lipid core burden index (LCBI) and maximum value of LCBI for any of the 4-mm segment (maxLCBI).

Results: From predilation to stent implantation and post-dilation EEM volume increased from 337±124mm to 369±136mm and to 397±144mm (p<0.001), while plaque volume decreased from 225±84mm to 202±85mm and to 192±81mm (p<0.001). Plaque shift to the proximal reference segment was found in 40% of the lesions. The maxLCBI decreased significantly from predilation to stent implantation (492±235 to 208±193 (p<0.001), whereas post dilation did not cause any further significant reduction. Also LCBI decreased significantly from predilation to stent implantation (173±103 to 68±67, p<0.001), without any further significant reduction during post-dilation. The LCBI did neither in the proximal nor in the distal reference segments change significantly during stent implantation or post-dilation.

Conclusion: Lumen enlargement was caused by vessel expansion, plaque compression and longitudinally plaque redistribution. Lipid-core burden at the stented segment was decreased.
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http://dx.doi.org/10.1016/j.carrev.2016.12.018DOI Listing
December 2017

Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial: Intravascular ultrasound with iMap: the OCTIVUS trial.

Cardiovasc Revasc Med 2017 Mar 28;18(2):110-117. Epub 2016 Nov 28.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Background: The aim of this study was to examine the influence of ezetimibe in addition to atorvastatin on plaque composition in patients with first-time ST-segment Elevation Myocardial Infarction treated with primary percutaneous intervention.

Methods: Eighty-seven patients were randomized (1:1) to ezetimibe 10mg or placebo in addition to Atorvastatin 80mg. Intravascular ultrasound with iMap was performed at baseline and after 12months in a non-infarct-related artery. Primary endpoint was change in necrotic core (NC). Secondary endpoints were total atheroma volume (TAV) and percentage atheroma volume (PAV).

Results: NC did not change significantly: ezetimibe group 24.9 (11.9, 51.3) mm to 24.9 (15.3, 54.5) mm, p=0.76, placebo group 29.4 (16.3, 78.5) mm to 32.0 (16.0, 88.7) mm, p=0.30, (p=0.35 between groups). TAV was reduced in the ezetimibe group only: ezetimibe (200.0 (135.6, 311.9) mm to 189.3 (126.4, 269.1) mm, p<0.001) compared to placebo group (218.4 (163.5, 307.9) mm to 212.2 (149.9, 394.8) mm, p=0.07) (p=0.56 between groups). PAV was reduced in the ezetimibe group only (40.1±8.6% to 39.2±9.0%, p=0.036) compared to placebo group (43.3±9.4% to 42.2±10.7%, p=0.07), p=0.91 between groups.

Conclusions: Ezetimibe in addition to atorvastatin therapy did not influence NC content, but was associated with regression of coronary atherosclerosis.
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http://dx.doi.org/10.1016/j.carrev.2016.11.010DOI Listing
March 2017

Optical coherence tomography assessment of incidence, morphological characteristics, and spontaneous healing course of edge dissections following percutaneous coronary intervention with stent implantation in patients with non-ST segment elevation myocardial infarction.

Int J Cardiol 2016 Nov 14;223:466-474. Epub 2016 Aug 14.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Background: Stenting-induced edge dissections (ED) can be assessed in detail by optical coherence tomography (OCT). This study sought to investigate the incidence, morphological characteristics, and spontaneous healing course of OCT-identified EDs following drug-eluting stent (DES) implantation in a non-ST segment elevation myocardial infarction (NSTEMI) patient-population.

Methods: Acute vessel wall injury at the 5-mm stent adjacent distal and proximal reference segments was assessed by post-procedure OCT and intravascular ultrasound (IVUS) in n=97 NSTEMI-patients (n=97 lesions). Six months OCT follow-up was available in 82 patients (including 35 untreated post-procedure EDs).

Results: The overall incidence of post-procedure OCT-detected ED was 38 per 97 patients (39.2%), and 47 per 182 stent edges (25.8%). None of the EDs were angiographically visualizable, while 10 (21.3%) were visible on concomitant IVUS-analysis. Morphologically, there was a significant difference in plaque type present at ED-edges vs. non-ED-edges when assessed with OCT; (1) lipid-rich and calcified plaques: 80.9% vs. 57.0%, (2) fibrous plaques: 17.0% vs. 26.7%, and (3) normal coronary vessels: 2.1% vs. 16.3%, p<0.01. Plaqueburden, assessed by IVUS, was substantially larger at ED-containing borders: 54.5±10.0% vs. 43.7±11.6%, p=0.01. Three dissections (8.6%) were incompletely healed at 6-month OCT follow-up. None of the EDs caused cardiac events during the 6-month follow-up, however, 1 ED-patient had target lesion revascularization with PCI and DES-implantation in extension of the scheduled OCT-control.

Conclusions: OCT-detected EDs were frequent after stent implantation due to NSTEMI, and the majority of these EDs healed without leading to an adverse prognosis at 6months.
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http://dx.doi.org/10.1016/j.ijcard.2016.08.245DOI Listing
November 2016

Randomized Comparison of a Biodegradable Polymer Ultrathin Strut Sirolimus-Eluting Stent With a Biodegradable Polymer Biolimus-Eluting Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT VII Trial.

Circ Cardiovasc Interv 2016 07;9(7)

From the Department of Cardiology, Odense University Hospital, Denmark (L.O.J., P.T., A.J., K.T.V., K.N.H., H.S.H.); Department of Cardiology, Aarhus University Hospital, Skejby, Denmark (M. Maeng, L.R.K., C.J.T., A.K., S.D.K., H.E.B., J.F.L., E.H.C.); Department of Cardiology, Aalborg University Hospital, Denmark (J.R., B.R., A.B.V., H.-H.T., J.A., S.E.J.); and Department of Clinical Epidemiology, Aarhus University, Denmark (M. Madsen, K.B.).

Background: Coronary drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy.

Methods And Results: The Scandinavian Organization for Randomized Trials With Clinical Outcome (SORT OUT) VII trial-a large-scale registry-based randomized, multicenter, single-blind, 2-arm, noninferiority trial-compared 2 biodegradable polymer drug-eluting stents: the thin-strut cobalt-chromium sirolimus-eluting Orsiro stent and the stainless steel biolimus-eluting Nobori stent in an all-comer patient population. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 1 year, analyzed by intention to treat (noninferiority margin of 3.0%). Clinically driven event detection based on Danish registries was used. A total of 1261 patients were assigned to receive the sirolimus-eluting stent (1590 lesions) and 1264 patients to the biolimus-eluting stent (1588 lesions). At 1 year, the composite end point target lesion failure occurred in 48 patients (3.8%) in the sirolimus-eluting group and in 58 patients (4.6%) in the biolimus-eluting group (absolute risk difference, -0.78% [upper limit of 1-sided 95% confidence interval, 0.61%]; P<0.0001). Rates of definite stent thrombosis occurred in 5 (0.4%) of the sirolimus-eluting group compared with 15 (1.2%) biolimus-eluting stent-treated patients (rate ratio, 0.33; 95% confidence interval, 0.12-0.92; P=0.034), which largely was attributable to a lower risk of subacute definite stent thrombosis: 0.1% versus 0.6% (rate ratio, 0.12; 95% confidence interval, 0.02-1.00; P=0.05).

Conclusions: The thin-strut sirolimus-eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent in unselected patients for target lesion failure at 1 year.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01879358.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.115.003610DOI Listing
July 2016

Safety and Efficacy of Everolimus- Versus Sirolimus-Eluting Stents: 5-Year Results From SORT OUT IV.

J Am Coll Cardiol 2016 Feb;67(7):751-62

Department of Cardiology, Aarhus University Hospital, Skejby Hospital, Aarhus, Denmark.

Background: Long-term safety and efficacy for everolimus-eluting stents (EES) versus those of sirolimus-eluting stents (SES) are unknown.

Objectives: This study compared 5-year outcomes for EES with those for SES from the SORT OUT IV (Scandinavian Organization for Randomized Trials with Clinical Outcome) trial.

Methods: Five-year follow-up was completed for 2,771 patients (99.9%). Primary endpoint was a composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), and definite stent thrombosis.

Results: At 5-years, MACE occurred in 14.0% and 17.4% in the EES and SES groups, respectively (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.66 to 0.97; p = 0.02). The MACE rate did not differ significantly within the first year (HR: 0.96, 95% CI: 0.71 to 1.19; p = 0.79), but from years 1 through 5, the MACE rate was lower with EES (HR: 0.71, 95% CI: 0.55 to 0.90; p = 0.006; p interaction = 0.12). Definite stent thrombosis was lower with EES (0.4%) than with SES (2.0%; HR: 0.18, 95% CI: 0.07 to 0.46), with a lower risk of very late definite stent thrombosis in the EES group (0.2% vs. 1.4%, respectively; HR: 0.16, 95% CI: 0.05 to 0.53). When censoring the patients at the time of stent thrombosis, we found no significant differences between the 2 stent groups for MACE rates (HR: 0.89, 95% CI: 0.73 to 1.08; p = 0.23), target lesion revascularization (HR: 0.90, 95% CI: 0.64 to 1.27; p = 0.55), and MI (HR: 0.93, 95% CI: 0.64 to 1.36; p = 0.72).

Conclusions: At 5-year follow-up, MACE rate was significantly lower with EES- than with SES-treated patients, due largely due to a lower risk of very late definite stent thrombosis. (Randomized Clinical Comparison of the Xience V and the Cypher Coronary Stents in Non-selected Patients With Coronary Heart Disease [SORT OUT IV]; NCT00552877).
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http://dx.doi.org/10.1016/j.jacc.2015.11.051DOI Listing
February 2016