Erik Harald Øie

• Caglar, Harun; Holmager, Therese; Kristensen, Anna Meta Dyrvig; Bakken, Arnhild; Rykind-Eriksen, Frida & Deeg, Peter Stefan [Show all 12 contributors for this article] (2026). Risk-Score Guided Estimation of Absolute Benefit From Beta-blockers after Myocardial Infarction in Patients Without Heart Failure. European Heart Journal - Quality of Care and Clinical Outcomes. ISSN 2058-5225. doi: 10.1093/ehjqcco/qcag142. Full text in Research Archive Show summary

  Abstract Aims To assess whether a modified clinical risk-score can stratify baseline risk and estimate expected absolute benefit from beta-blocker therapy in post-MI (myocardial infarction) patients with LVEF (left ventricular ejection fraction) ≥40%. Methods This substudy of the BETAMI-DANBLOCK trial included patients with a recent MI and LVEF ≥40% who were randomized to beta-blocker or no beta-blocker therapy. A modified Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) was constructed, and patients were categorized as low-, intermediate-, or high-risk. The primary outcome was a composite of all-cause mortality, new-MI, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmia. Treatment effects across TRS-2P strata were estimated using Cox proportional hazards and Fine-Gray subdistribution hazard models. Three-year absolute risk reduction (ARR) and number needed to treat (NNT) were calculated for each risk stratum. Results Among 5558 patients, 38.4% were classified as low-risk, 52.8% as intermediate-risk, and 8.8% as high-risk. Event rates increased stepwise with higher modified TRS-2P, with no evidence of heterogeneity in the relative treatment effects across risk-strata (hazard ratios: 0.88, 0.81 and 0.88, respectively). However, the score translated the modest relative effects into clinically distinct absolute benefits: Three-year ARR was 1.4% (NNT=72 [95% CI: 41 to 361]) in low-risk, 2.1% (NNT=47 [95% CI: 27 to 239]) in intermediate-risk, and 3.6% (NNT=28 [95% CI: 16 to 140]) in high-risk patients. Conclusions The modified TRS-2P stratified baseline risk and provided estimates of absolute beta-blocker benefit, supporting further evaluation of individualized, risk-guided treatment after MI in patients with LVEF ≥40%.

• Bruun, Lina Dorthea; Andersen, Geir Øystein; Myhre, Peder Langeland; Halvorsen, Sigrun; Kringen, Marianne Kristiansen & Hansen, Charlotte Holst [Show all 8 contributors for this article] (2026). Prognostic relevance of β1-adrenergic receptor polymorphisms on cardiovascular outcome in patients treated with metoprolol after acute myocardial infarction - an observational study. European Journal of Clinical Pharmacology. ISSN 0031-6970. 82(7). doi: 10.1007/s00228-026-04091-x. Full text in Research Archive
• Vinge, Leif Erik & Øie, Erik Harald (2025). Perikarditt. Hjerteforum. ISSN 0802-1465. 24(3), p. 46–55. Full text in Research Archive
• Munkhaugen, John; Kristensen, Anna Meta D.; Halvorsen, Sigrun; Holmager, Therese; Olsen, Michael Hecht & Bakken, Arnhild [Show all 64 contributors for this article] (2025). Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. New England Journal of Medicine. ISSN 0028-4793. 393(19), p. 1901–1911. doi: 10.1056/nejmoa2505985. Full text in Research Archive Show summary

  Background: The evidence supporting beta-blocker therapy after myocardial infarction was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies. Methods: In an open-label, randomized trial with blinded end-point evaluation, conducted in Denmark and Norway, we assigned patients who had had a myocardial infarction and who had a left ventricular ejection fraction of at least 40%, in a 1:1 ratio, to receive long-term beta-blocker therapy within 14 days after the event or no beta-blocker therapy. The primary end point was a composite of death from any cause or major adverse cardiovascular events (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias). Results: A total of 5574 patients underwent randomization and were included in the main analyses - 2783 in the beta-blocker group and 2791 in the no-beta-blocker group. After a median follow-up of 3.5 years (interquartile range, 2.2 to 4.6), a primary end-point event had occurred in 394 patients (14.2%) in the beta-blocker group and in 454 patients (16.3%) in the no-beta-blocker group (hazard ratio, 0.85; 95% confidence interval [CI], 0.75 to 0.98; P = 0.03). Death from any cause occurred in 4.2% of the patients in the beta-blocker group and in 4.4% of those in the no-beta-blocker group; myocardial infarction occurred in 5.0% and 6.7%, respectively (hazard ratio, 0.73; 95% CI, 0.59 to 0.92), unplanned coronary revascularization in 3.9% and 3.9%, ischemic stroke in 1.6% and 1.3%, heart failure in 1.5% and 1.9%, and malignant ventricular arrhythmias in 0.5% and 0.6%. No apparent differences in safety outcomes were observed between the groups. Conclusions: Among patients with a myocardial infarction and a left ventricular ejection fraction of at least 40%, beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events than no beta-blocker therapy

• Bruun, Lina Dorthea; Andersen, Geir Øystein; Kringen, Marianne K.; Myhre, Peder Langeland; Halvorsen, Sigrun & Hansen, Charlotte Holst [Show all 8 contributors for this article] (2025). Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study. European Journal of Clinical Pharmacology. ISSN 0031-6970. 81(4), p. 551–560. doi: 10.1007/s00228-025-03806-w. Full text in Research Archive Show summary

  Purpose The clinical benefit of up-titration of metoprolol to a guideline-recommended target dose after myocardial infarction (MI) is unknown. Our aim was to investigate whether variation in metoprolol exposure determined by cytochrome p450 enzyme 2D6 (CYP2D6) influences the occurrence of major adverse cardiovascular events (MACE) and cardiovascular death (CV death) among patients treated with metoprolol after MI. Method This Mendelian randomization study was performed using individual-level data from 1554 patients treated with metoprolol after an acute MI. CYPD26 genotype was applied as a binary genetic instrument assigning patients into two metoprolol exposure groups: CYP2D6 normal metabolizers (NM) (low exposure) and CYP2D6 intermediate and poor metabolizers (IM + PM) (high exposure). The null hypothesis of no association between the CYP2D6 metabolizer subgroup and MACE or CV death was tested using the Cox proportional hazards model. All-cause mortality and individual components of MACE were included as secondary outcomes. Results In total, 879 (56.6%) patients were classified as NM and 675 (43.4%) as IM + PM. During the 3-year follow-up, 56 patients (6.4%) in the NM group had an outcome of MACE, and 24 (2.7%) patients died from CV disease. Corresponding frequency in the IM + PM group was 47 (7.0%) and 22 (3.3%), respectively. There was no association between genotype and MACE [unadjusted HR 1.12 (CI 0.76, 1.65)] or CV death [unadjusted HR 1.20 (CI 0.67, 2.14)], or between the CYP2D6 group and any of the secondary outcomes. Conclusion In patients treated with metoprolol after MI, variation in metoprolol exposure determined by CYP2D6 did not impact the occurrence of cardiovascular events.

• Nymoen, Lisbeth Damlien; Pettersen, Julie Leonora Samdal; Flatebø, Trude Eline; Øie, Erik Harald & Viktil, Kirsten Kilvik (2024). Drug-related emergency department visits: external validation of an assessment tool in a general emergency department population. International Journal of Clinical Pharmacy. ISSN 2210-7703. 46, p. 1327–1334. doi: 10.1007/s11096-024-01760-8. Full text in Research Archive
• Berg, Erlend; Tegn, Nicolai Kloumann; Abdelnoor, Michael; Røysland, Kjetil; Ryalen, Pål Christie & Aaberge, Lars [Show all 14 contributors for this article] (2023). Long-Term Outcomes of Invasive vs Conservative Strategies for Older Patients With Non–ST-Segment Elevation Acute Coronary Syndromes. Journal of the American College of Cardiology. ISSN 0735-1097. 82(21), p. 2021–2030. doi: 10.1016/j.jacc.2023.09.809. Full text in Research Archive Show summary

  Background Non–ST-segment elevation acute coronary syndrome (NSTE-ACS) is a frequent cause of hospital admission in older people, but clinical trials targeting this population are scarce. Objectives The After Eighty Study assessed the effect of an invasive vs a conservative treatment strategy in a very old population with NSTE-ACS. Methods Between 2010 and 2014, the investigators randomized 457 patients with NSTE-ACS aged ≥80 years (mean age 85 years) to an invasive strategy involving early coronary angiography with immediate evaluation for revascularization and optimal medical therapy or to a conservative strategy (ie, optimal medical therapy). The primary endpoint was a composite of myocardial infarction, need for urgent revascularization, stroke, and death. The long-term outcomes are presented. Results After a median follow up of 5.3 years, the invasive strategy was superior to the conservative strategy in the reduction of the primary endpoint (incidence rate ratio: 0.76; 95% CI: 0.63-0.93; P = 0.0057). The invasive strategy demonstrated a significant gain in event-free survival of 276 days (95% CI: 151-400 days; P = 0.0001) at 5 years and 337 days (95% CI: 123-550 days; P = 0.0001) at 10 years. These results were consistent across subgroups of patients with respect to major cardiovascular prognostic factors. Conclusions In patients aged ≥80 years with NSTE-ACS, the invasive strategy was superior to the conservative strategy in the reduction of composite events and demonstrated a significant gain in event-free survival. (The After Eighty Study: a randomized controlled trial; NCT01255540)

• Schwartz, Thomas; Hoornstra, Dieuwertje; Øie, Erik Harald; Hovius, Joppe & Quarsten, Hanne (2023). Case report: First case of Borrelia miyamotoi meningitis in an immunocompromised patient in Norway. IDCases. 33. doi: 10.1016/j.idcr.2023.e01867. Full text in Research Archive
• Sørensen, Eivind; Myrstad, Marius; Solberg, Magnar Gangås; Øie, Erik; Platonov, Pyotr G. & Carlson, Jonas [Show all 8 contributors for this article] (2023). Left atrial dyssynchrony in veteran endurance athletes with and without paroxysmal atrial fibrillation. Echocardiography. ISSN 0742-2822. doi: 10.1111/echo.15634. Full text in Research Archive Show summary

  Background Prolonged endurance exercise increase the risk of atrial fibrillation (AF) in men. Functional parameters may help separate physiological from pathological atrial remodeling in athletes. LA mechanical dispersion (LA MD) is associated with AF in the general population, but the associations between prolonged exercise, LA MD and AF are not known. Purpose To describe LA MD in veteran athletes with and without paroxysmal AF (pAF) and to investigate LA MD's ability to identify veteran athletes with pAF. Methods Two hundred and ninety-three men, skiers with (n = 57) and without (n = 87) pAF, and controls with (n = 61) and without pAF (n = 88) underwent an echocardiographic exam in sinus rhythm. LA reservoir strain (LASr) was measured, and LA MD defined as the standard deviation of time-to-peak strain (SD-TPS). Results Skiers (mean age 70.7 ± 6.7 years) reported an average of 40–50 years of endurance exercise. LA volumes were associated with pAF and athletic status (p < .001). SD-TPS was associated with pAF (p < .001) but not athletic status (p = .173). We found no significant trend between years of exercise and SD-TPS in individuals without AF (p = .893). SD-TPS did not add incremental value in identifying athletes with pAF in addition to clinical markers, QRS width, LA volume, and LASr (p = .056). Conclusion LA MD was associated with pAF regardless of athletic status but not related to years of endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in athletes. However, we found no incremental value of LA MD identifying athletes with pAF when LASr was included in the model.

• Sørensen, Eivind; Myrstad, Marius; Solberg, Magnar Gangås; Øie, Erik; Tveit, Arnljot & Aarønæs, Marit (2022). Right Heart Structure and Function in Lifelong Recreational Endurance Athletes with and without Paroxysmal Atrial Fibrillation. Journal of the American Society of Echocardiography. ISSN 0894-7317. doi: 10.1016/j.echo.2022.06.008. Full text in Research Archive
• Nymoen, Lisbeth Damlien; Flatebø, Trude Eline; Moger, Tron Anders; Øie, Erik; Molden, Espen & Viktil, Kirsten Kilvik (2022). Impact of systematic medication review in emergency department on patients’ postdischarge outcomes—A randomized controlled clinical trial. PLOS ONE. 17:e0274907(9), p. 1–19. doi: 10.1371/journal.pone.0274907. Full text in Research Archive Show summary

  Introduction The main objective of this study was to investigate whether systematic medication review conducted by clinical pharmacists can impact clinical outcomes and post-discharge outcomes for patients admitted to the emergency department. Method This parallel group, non-blinded, randomized controlled trial was conducted in the emergency department, Diakonhjemmet Hospital, Oslo, Norway. The study was registered in ClinicalTrials.gov, Identifier: NCT03123640 in April 2017. From April 2017 to May 2018, patients ≥18 years were included and randomized (1:1) to intervention- or control group. The control group received standard care from emergency department physicians and nurses. In addition to standard care, the intervention group received systematic medication review including medication reconciliation conducted by pharmacists, during the emergency department stay. The primary outcome was proportion of patients with an unplanned contact with hospital within 12 months from inclusion stay discharge. Results In total, 807 patients were included and randomized, 1:1, to intervention or control group. After excluding 8 patients dying during hospital stay and 10 patients lacking Norwegian personal identification number, the primary analysis comprised 789 patients: 394 intervention group patients and 395 control group patients. Regarding the primary outcome, there was no significant difference in proportion of patients with an unplanned contact with hospital within 12 months after inclusion stay discharge between groups (51.0% of intervention group patients vs. 53.2% of control group patients, p = 0.546). Conclusion As currently designed, emergency department pharmacist-led medication review did not significantly influence clinical- or post-discharge outcomes. This study did, however pinpoint important practical implementations, which can be used to design tailored pharmacist-led interventions and workflow regarding drug-related issues in the emergency department setting.

• Nymoen, Lisbeth Damlien; Björk, Malin; Flatebø, Trude Eline; Nilsen, Merethe; Godø, Aasmund & Øie, Erik [Show all 7 contributors for this article] (2022). Drug-related emergency department visits: prevalence and risk factors. Internal and Emergency Medicine. ISSN 1828-0447. doi: 10.1007/s11739-022-02935-9. Full text in Research Archive
• Kolden, Mathias Øie; Nymo, Ståle Haugset & Øie, Erik (2022). Impact of neighbourhood-level socioeconomic status, traditional coronary risk factors, and ancestry on age at myocardial infarction onset: A population-based register study. BMC Cardiovascular Disorders. 22(1), p. 447–447. doi: 10.1186/s12872-022-02880-7. Full text in Research Archive
• Sørensen, Eivind; Myrstad, Marius; Solberg, Magnar Gangås; Øie, Erik; Tveit, Arnljot & Aarønæs, Marit (2022). Left atrial function in male veteran endurance athletes with paroxysmal atrial fibrillation. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 23(1), p. 137–146. doi: 10.1093/ehjci/jeab248. Full text in Research Archive Show summary

  Abstract Aims To assess left atrial (LA) function in sinus rhythm in veteran athletes with a history of paroxysmal atrial fibrillation (AF) exposed to prolonged endurance exercise compared with veteran athletes without AF and controls with and without paroxysmal AF from a non-athletic population. Methods and results Three hundred and two male participants from four groups, veteran recreational skiers with paroxysmal AF (n = 62), veteran skiers without AF (n = 89), and controls from a non-athletic population with (n = 62) and without paroxysmal AF (n = 89) underwent an echocardiographic examination in sinus rhythm to evaluate LA anatomy and function. The skiers (mean age 70.8±6.7 years) reported an average exposure to regular endurance exercise for 40–50 years. LA maximum and minimum volumes were larger in skiers (P &lt; 0.001). LA volumes differed within the athletic and non-athletic groups with larger volumes in the AF groups ( P &lt; 0.001). We observed a considerable overlap in LA volumes among non-athletes with AF and athletes without AF. LA reservoir strain (33.6% ± 4.8% vs. 28.3% ± 6.7% P &lt; 0.001) and contractile strain (18.3% ± 4.0% vs. 15.0% ± 5.2% P &lt; 0.001) were lower in both AF groups regardless of athletic status. LA reservoir strain was superior to volumetric measurements at identifying participants with AF (area under the curve 0.740 ±0.041). Conclusion Male veteran athletes had significantly larger LA volumes than non-athletes. In contrast, LA strain values were similar in athletes and non-athletes with paroxysmal AF, and significantly lower than in subjects without AF.

• Nymoen, Lisbeth Damlien; Tran, Therese Thanh Tu; Walter, Scott R; Lehnbom, Elin; Tunestveit, Ingrid Kinne & Øie, Erik [Show all 7 contributors for this article] (2021). Emergency department physicians' distribution of time in the fast paced-workflow-a novel time-motion study of drug-related activities. International Journal of Clinical Pharmacy. ISSN 2210-7703. doi: 10.1007/s11096-021-01364-6. Full text in Research Archive Show summary

  Background In the emergency department physicians are forced to distribute their time to ensure that all admitted patients receive appropriate emergency care. Previous studies have raised concerns about medication discrepancies in patient’s drug lists at admission to the emergency department. Thus, it is important to study how emergency department physicians distribute their time, to highlight where workfow redesign can be needed.<p><p> Aim to quantify how emergency department physicians distribute their time between various task categories, with particular focus on drug-related tasks. Method Direct observation, time-motion study of emergency department physicians at Diakonhjemmet Hospital, Oslo, Norway. Physicians’ activities were categorized in discrete categories and data were collected with the validated method of Work Observation Method By Activity Timing between October 2018 to January 2019. Bootstrap analysis determined 95% confidence intervals for proportions and interruption rates.<p> <p>Results During the observation time of 91.4 h, 31 emergency department physicians were observed. In total, physicians spent majority of their time gathering information (36.5%), communicating (26.3%), and documenting (24.2%). Further, physicians spent 17.8% (95% CI 16.8%, 19.3%) of their time on drug-related tasks. On average, physicians spent 7.8 min (95% CI 7.2, 8.6) per hour to obtain and document patients’ drug lists.<p> <p>Conclusion Emergency department physicians are required to conduct numerous essential tasks and distributes a minor proportion of their time on drug-related tasks. More efcient information fow regarding drugs should be facilitated at transitions of care. The presence of healthcare personnel dedicated to obtaining drug lists in the emergency department should be considered.

• Tazmini, Kiarash; Fraz, Mai; Nymo, Ståle Haugset; Stokke, Mathis Korseberg; Louch, William Edward & Øie, Erik (2020). Potassium infusion increases the likelihood of conversion of recent-onset atrial fibrillation- A single-blinded, randomized clinical trial. American Heart Journal. ISSN 0002-8703. 221, p. 114–124. doi: 10.1016/j.ahj.2019.12.014. Full text in Research Archive Show summary

  Background The optimal antiarrhythmic management of recent-onset atrial fibrillation (ROAF) or atrial flutter is controversial and there is a considerable variability in clinical treatment strategies. It is not known if potassium infusion has the potential to convert ROAF or atrial flutter to sinus rhythm (SR). Therefore, we aimed to investigate if patients with ROAF or atrial flutter and plasma-potassium levels ≤4.0 mmol/L have increased probability to convert to SR if the plasma-potassium level is increased towards the upper reference range (4.1-5.0 mmol/L). Methods In a placebo-controlled, single-blinded trial, patients with ROAF or atrial flutter and plasma-potassium ≤4.0 mmol/L presenting between April 2013 and November 2017 were randomized to receive potassium chloride (KCl) infusion (n = 60) or placebo (n = 53). Patients in the KCl group received infusions at one of three different rates: 9.4 mmol/h (n = 11), 12 mmol/h (n = 19), or 15 mmol/h (n = 30). Results There was no statistical difference in the number of conversions to SR between the KCl group and placebo [logrank test, P = .29; hazard ratio (HR) 1.20 (CI 0.72-1.98)]. However, KCl-infused patients who achieved an above-median hourly increase in plasma-potassium (>0.047 mmol/h) exhibited a significantly higher conversion rate compared with placebo [logrank P = .002; HR 2.40 (CI 1.36-4.21)] and KCl patients with below-median change in plasma-potassium [logrank P < .001; HR 4.41 (CI 2.07-9.40)]. Due to pain at the infusion site, the infusion was prematurely terminated in 10 patients (17%). Conclusions Although increasing plasma-potassium levels did not significantly augment conversion of ROAF or atrial flutter to SR in patients with potassium levels in the lower-normal range, our results indicate that this treatment may be effective when a rapid increase in potassium concentration is tolerated and achieved.

• Anstensrud, Anne Kristine; Molden, Espen; Haug, Hans Jørgen; Qazi, Rehman Ul-Haq; Muriq, Hysen & Fosshaug, Linn Elisabeth Lillerud [Show all 8 contributors for this article] (2020). Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction – a prospective observational study. European Journal of Clinical Pharmacology. ISSN 0031-6970. 76, p. 673–683. doi: 10.1007/s00228-020-02832-0. Full text in Research Archive Show summary

  Purpose The β-1 adrenergic receptor blocker metoprolol is primarily metabolized by the polymorphic enzyme cytochrome P 450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Our purpose was to investigate the impact of CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction (MI). Methods We included 136 patients with MI discharged on treatment with metoprolol with a recommendation to the general practitioner (GP) to increase the metoprolol dose up to 200 mg/day within 2 months if possible. At follow-up, metoprolol dosage after up-titration, metoprolol steady-state trough plasma concentrations, hemodynamic parameters, potential metoprolol-induced adverse drug reactions and number of visits to the GP were measured. CYP2D6 genotyping including the reduced-function variant alleles CYP2D6*9, CYP2D6*10 and CYP2D6*41 was performed after end of follow-up. Results According to the genotype-defined CYP2D6 phenotypes, 30% of the patients were metoprolol extensive metabolizers (EMs), 55% intermediate metabolizers (IMs) and 13% poor metabolizers (PMs; carriers of non-coding and reduced-function variant included). Dose-adjusted metoprolol trough concentrations were significantly higher in IM (2-fold) and PM (6.2-fold) groups vs. the EM group (p < 0.001). Only 35% of patients in the PM group achieved the primary end point, i.e. reaching at least 85% of the expected maximum heart rate (HR) during exercise, compared with 78% in the EM group (p < 0.01), and maximum observed HR at exercise was significantly lower in the PM group vs. the EM group (129 ± 5 vs. 142 ± 2 bpm, p < 0.007). In contrast, metoprolol maintenance dose, blood pressure, exercise capacity, number of visits at the GP and frequency and severity of self-reported potential metoprolol-related adverse drug reactions were not significantly different between the groups. Conclusion Using a comprehensive CYP2D6 genotyping panel, the present study demonstrates a > 6-fold increase of dose-adjusted plasma metoprolol trough concentration in CYP2D6 PMs vs. EMs with a parallel lower increase in achieved maximum HR during exercise but without association between genotype and frequency or severity of self-reported adverse drug effects. This may indicate that CYP2D6 PMs potentially could benefit of the increased plasma concentration per dose in a naturalistic setting.

• Børretzen, Mari Naumann; Romarheim, Synnøve Andrea; Danielsen, Tore Kristian; Leren, Ida Skrinde & Øie, Erik (2020). Infeksiøs endokarditt - egne data og internasjonale anbefalinger. Hjerteforum. ISSN 0802-1465. 33(4), p. 19–30. Full text in Research Archive
• Tazmini, Kiarash; Frisk, Michael; Lewalle, Alexandre; Laasmaa, Martin; Morotti, Stefano & Lipsett, David Bruce [Show all 16 contributors for this article] (2020). Hypokalemia promotes arrhythmia by distinct mechanisms in atrial and ventricular myocytes. Circulation Research. ISSN 0009-7330. 126(7), p. 889–906. doi: 10.1161/CIRCRESAHA.119.315641. Full text in Research Archive Show summary

  Rationale: Hypokalemia occurs in up to 20% of hospitalized patients and is associated with increased incidence of ventricular and atrial fibrillation. It is unclear whether these differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia on cardiomyocytes. Objective: To investigate proarrhythmic mechanisms of hypokalemia in ventricular and atrial myocytes. Methods and Results: Experiments were performed in isolated rat myocytes exposed to simulated hypokalemia conditions (reduction of extracellular [K+] from 5.0 to 2.7 mmol/L) and supported by mathematical modeling studies. Ventricular cells subjected to hypokalemia exhibited Ca2+ overload and increased generation of both spontaneous Ca2+ waves and delayed afterdepolarizations. However, similar Ca2+-dependent spontaneous activity during hypokalemia was only observed in a minority of atrial cells that were observed to contain t-tubules. This effect was attributed to close functional pairing of the Na+-K+ ATPase and Na+-Ca2+ exchanger proteins within these structures, as reduction in Na+ pump activity locally inhibited Ca2+ extrusion. Ventricular myocytes and tubulated atrial myocytes additionally exhibited early afterdepolarizations during hypokalemia, associated with Ca2+ overload. However, early afterdepolarizations also occurred in untubulated atrial cells, despite Ca2+ quiescence. These phase-3 early afterdepolarizations were rather linked to reactivation of nonequilibrium Na+ current, as they were rapidly blocked by tetrodotoxin. Na+ current-driven early afterdepolarizations in untubulated atrial cells were enabled by membrane hyperpolarization during hypokalemia and short action potential configurations. Brief action potentials were in turn maintained by ultra-rapid K+ current (IKur); a current which was found to be absent in tubulated atrial myocytes and ventricular myocytes. Conclusions: Distinct mechanisms underlie hypokalemia-induced arrhythmia in the ventricle and atrium but also vary between atrial myocytes depending on subcellular structure and electrophysiology.

• Fosshaug, Linn Elisabeth Lillerud; Colas, Romain A.; Anstensrud, Anne Kristine; Gregersen, Ida; Nymoen, Ståle H. & Sagen, Ellen [Show all 15 contributors for this article] (2019). Early increase of specialized pro-resolving lipid mediators in patients with ST-elevation myocardial infarction. EBioMedicine. 46, p. 264–273. doi: 10.1016/j.ebiom.2019.07.024. Full text in Research Archive Show summary

  Background Termination of acute inflammation is an active process orchestrated by lipid mediators (LM) derived from polyunsaturated fatty acids, referred to as specialized pro-resolving mediators (SPM). These mediators also provide novel therapeutic opportunities for treating inflammatory disease. However, the regulation of these molecules following acute myocardial infarction (MI) remains of interest. Methods In this prospective observational study we aimed to profile plasma levels of SPMs in ST-elevation MI (STEMI) patients during the first week following MI. Plasma LM concentrations were measured in patients with STEMI (n = 15) at three time points and compared with stable coronary artery disease (CAD; n = 10) and healthy controls (n = 10). Findings Our main findings were: (i) Immediately after onset of MI and before peak troponin T levels, STEMI patients had markedly increased levels of SPMs as compared with healthy controls and stable CAD patients, with levels of these mediators declining during follow-up. (ii) The increase in SPMs primarily reflected an increase in docosapentaenoic acid- and docosahexaenoic acid-derived protectins. (iii) Several individual protectins were correlated with the rapid increase in neutrophil counts, but not with CRP. (iv) A shift in 5-LOX activity from the leukotriene B4 pathway to the pro-resolving RvTs was observed. Interpretation The temporal regulation of SPMs indicates that resolution mechanisms are activated early during STEMI as part of an endogenous mechanism to initiate repair. Thus strategies to boost the activity and/or efficacy of these endogenous mechanisms may represent novel therapeutic opportunities for treatment of patients with MI.

• Tazmini, Kiarash; Nymo, Ståle Haugset; Louch, William Edward; Ranhoff, Anette Hylen & Øie, Erik (2019). Electrolyte imbalances in an unselected population in an emergency department: A retrospective cohort study. PLOS ONE. 14(4). doi: 10.1371/journal.pone.0215673. Full text in Research Archive Show summary

  Background: Although electrolyte imbalances (EIs) are common in the emergency department (ED), few studies have examined the occurrence of such conditions in an unselected population. Objectives: To investigate the frequency of EI among adult patients who present to the ED, with regards to type and severity, and the association with age and sex of the patient, hospital length of stay (LOS), readmission, and mortality. Methods: A retrospective cohort study. All patients ≥18 years referred for any reason to the ED between January 1, 2010, and December 31, 2015, who had measured blood electrolytes were included. In total, 62 991 visits involving 31 966 patients were registered. Results: EIs were mostly mild, and the most common EI was hyponatremia (glucose-corrected) (24.6%). Patients with increasing severity of EI had longer LOS compared with patients with normal electrolyte measurements. Among all admitted patients, there were 12928 (20.5%) readmissions within 30 days from discharge during the study period. Hyponatremia (glucose-corrected) was associated with readmission, with an adjusted odds ratio (OR) of 1.25 (95% CI, 1.18–1.32). Hypomagnesemia and hypocalcemia (albumin-corrected) were also associated with readmission, with ORs of 1.25 (95% CI, 1.07–1.45) and 1.22 (95% CI, 1.02–1.46), respectively. Dysnatremia, dyskalemia, hypercalcemia, hypermagnesemia, and hyperphosphatemia were associated with increased in-hospital mortality, whereas all EIs except hypophosphatemia were associated with increased 30-day and 1-year mortality. Conclusions: EIs were common and increasing severity of EIs was associated with longer LOS and increased in-hospital, 30-days and 1-year mortality. EI monitoring is crucial for newly admitted patients, and up-to-date training in EI diagnosis and treatment is essential for ED physicians.

• Berge, Torkil; Bull-Hansen, Bente; Solberg, Erik Ekker; Heyerdahl, Else Resser; Jørgensen, Kjetil Nordbø & Vinge, Leif Erik [Show all 9 contributors for this article] (2019). Screening for symptomer på depresjon og angst ved en hjertemedisinsk avdeling. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(14). doi: 10.4045/tidsskr.18.0570. Full text in Research Archive
• Eek, Anne Katrine; Øie, Erik & Granås, Anne Gerd (2017). Prescribing of NOACs has outnumbered warfarin: exploring how physicians choose anticoagulant treatments. European Journal of Clinical Pharmacology. ISSN 0031-6970. 74(3), p. 323–330. doi: 10.1007/s00228-017-2374-4. Full text in Research Archive
• Berge, Torkil; Finset, Arnstein; Fjerstad, Elin; Henriksen, Lise Søvde; Hyldmo, Ingrid & Lang, Nina [Show all 8 contributors for this article] (2017). Kartlegging av depressive symptomer ved hjertesykdom : hjertesykdom øker risikoen for depresjon. Hvordan kan man best fange opp deprimerte hjertepasienter? Sykepleien Forskning. ISSN 1890-2936. 2017, p. 1–8. doi: 10.4220/Sykepleienf.2017.60372. Full text in Research Archive
• Halvorsen, Sigrun; Jortveit, Jarle; Hasvold, Pål; Thuresson, Marcus & Øie, Erik (2016). Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction. BMC Cardiovascular Disorders. 16(115). doi: 10.1186/s12872-016-0283-6. Full text in Research Archive
• Fosshaug, Linn Elisabeth Lillerud; Dahl, Christen Peder; Risnes, Ivar; Bohov, Pavol; Berge, Rolf Kristian & Nymo, Ståle Haugset [Show all 12 contributors for this article] (2015). Altered Levels of Fatty Acids and Inflammatory and Metabolic Mediators in Epicardial Adipose Tissue in Patients With Systolic Heart Failure. Journal of Cardiac Failure. ISSN 1071-9164. 21(11), p. 916–923. doi: 10.1016/j.cardfail.2015.07.014. Full text in Research Archive
• Hommerstad, Anders; Hall, Kirsten Sundby; Bjerkehagen, Bodil; Eskild, Trond H.; Geiran, Odd & Øie, Erik (2014). En kvinne i 50-årene med tungpustethet og hypotensjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(18), p. 1758–1761. doi: 10.4045/tidsskr.13.1110. Full text in Research Archive
• Ueland, Thor; Svardal, Asbjørn M.; Øie, Erik; Askevold, Erik Tandberg; Nymoen, Ståle H. & Bjørndal, Bodil [Show all 10 contributors for this article] (2013). Disturbed carnitine regulation in chronic heart failure - Increased plasma levels of palmitoyl-carnitine are associated with poor prognosis. International Journal of Cardiology. ISSN 0167-5273. 167(5), p. 1892–1899. doi: 10.1016/j.ijcard.2012.04.150. Full text in Research Archive
• Øie, Erik; Berge, Rolf Kristian; Ueland, Thor; Dahl, Christen Peder; Edvardsen, Thor & Beitnes, Jan Otto [Show all 9 contributors for this article] (2013). Tetradecylthioacetic Acid Increases Fat Metabolism and Improves Cardiac Function in Experimental Heart Failure. Lipids. ISSN 0024-4201. 48(2), p. 139–154. doi: 10.1007/s11745-012-3749-z. Full text in Research Archive
• Yndestad, Arne; Finsen, Alexandra; Ueland, Thor; Husberg, Cathrine; Dahl, Christen Peder & Øie, Erik [Show all 19 contributors for this article] (2012). The Homeostatic Chemokine CCL21 Predicts Mortality and May Play a Pathogenic Role in Heart Failure. PLOS ONE. 7(3). doi: 10.1371/journal.pone.0033038. Full text in Research Archive Show summary

  Background: CCL19 and CCL21, acting through CCR7, are termed homeostatic chemokines. Based on their role in concerting immunological responses and their proposed involvement in tissue remodeling, we hypothesized that these chemokines could play a pathogenic role in heart failure (HF). Methodology/Principal Findings: Our main findings were: (i) Serum levels of CCL19 and particularly CCL21 were markedly raised in patients with chronic HF (n = 150) as compared with healthy controls (n = 20). A CCL21 level above median was independently associated with all-cause mortality. (ii) In patients with HF following acute myocardial infarction (MI; n = 232), high versus low CCL21 levels 1 month post-MI were associated with cardiovascular mortality, even after adjustment for established risk factors. (iii). Explanted failing human LV tissue (n = 29) had markedly increased expression of CCL21 as compared with non-failing myocardium (n = 5). (iv) Our studies in CCR7−/− mice showed improved survival and attenuated increase in markers of myocardial dysfunction and wall stress in post-MI HF after 1 week, accompanied by increased myocardial expression of markers of regulatory T cells. (v) Six weeks post-MI, there was an increase in markers of myocardial dysfunction and wall stress in CCR7 deficient mice. Conclusions/Significance: High serum levels of CCL21 are independently associated with mortality in chronic and acute post-MI HF. Our findings in CCR7 deficient mice may suggest that CCL21 is not only a marker, but also a mediator of myocardial failure. However, while short term inhibition of CCR7 may be beneficial following MI, a total lack of CCR7 during long-term follow-up could be harmful.

• Sikkeland, Liv Ingunn Bjoner; Dahl, Christen Peder; Ueland, Thor; Andreassen, Arne K.; Gude, Einar & Edvardsen, Thor [Show all 12 contributors for this article] (2012). Increased levels of inflammatory cytokines and endothelin-1 in alveolar macrophages from patients with chronic heart failure. PLOS ONE. 7(5:e36815). doi: 10.1371/journal.pone.0036815. Full text in Research Archive
• Astrup, Elisabeth; Lekva, Tove; Davi, Giovanni; Otterdal, Kari; Santilli, Francesca & Øie, Erik [Show all 13 contributors for this article] (2012). A Complex Interaction between Rickettsia conorii and Dickkopf-1-Potential Role in Immune Evasion Mechanisms in Endothelial Cells. PLOS ONE. 7(9). doi: 10.1371/journal.pone.0043638. Full text in Research Archive Show summary

  The pathophysiological hallmark of spotted fever group rickettsioses comprises vascular inflammation. Based on the emerging importance of the wingless (Wnt) pathways in inflammation and vascular biology, we hypothesized that Dickkopf-1 (DKK-1), as a major modulator of Wnt signaling, could be involved in the pathogenesis in rickettsial infections. Our major findings were: (i) While baseline concentration of DKK-1 in patients with R. conorii infection (n = 32) were not different from levels in controls (n = 24), DKK-1 rose significantly from presentation to first follow-up sample (median 7 days after baseline). (ii) In vitro experiments in human umbilical vein endothelial cells (HUVECs) showed that while heatinactivated R. conorii enhanced the release of interleukin-6 (IL-6) and IL-8, it down-regulated the release of endothelialderived DKK-1 in a time- and dose-dependent manner. (iii) Silencing of DKK-1 attenuated the release of IL-6, IL-8 and growth-related oncogene (GRO)a in R. conorii-exposed HUVECs, suggesting inflammatory effects of DKK-1. (iv) Silencing of DKK-1 attenuated the expression of tissue factor and enhanced the expression of thrombomodulin in R. conorii-exposed HUVECs suggesting pro-thrombotic effects of DKK-1. The capacity of R. conorii to down-regulate endothelial-derived DKK-1 and the ability of silencing DKK-1 to attenuate R. conorii-induced inflammation in endothelial cells could potentially reflect a novel mechanism by which R. conorii escapes the immune response at the site of infection.

• Beitnes, Jan Otto; Øie, Erik; Shahdafar, Aboulghassem; Karlsen, Tommy Aleksander; Müller, Regine & Aakhus, Svend [Show all 8 contributors for this article] (2012). Intramyocardial Injections of Human Mesenchymal Stem Cells Following Acute Myocardial Infarction Modulate Scar Formation and Improve Left Ventricular Function. Cell Transplantation. ISSN 0963-6897. 21(8), p. 1697–1709. doi: 10.3727/096368911X627462. Full text in Research Archive
• Røsjø, Helge; Stridsberg, Mats; Florholmen, Geir; Stensløkken, Kåre-Olav; Ottesen, Anett Hellebø & Sjaastad, Ivar [Show all 12 contributors for this article] (2012). Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties. PLOS ONE. 7(5). doi: 10.1371/journal.pone.0037401. Full text in Research Archive
• Andersen, Geir Øystein; Knudsen, Eva Cecilie; Aukrust, Pål; Yndestad, Arne; Øie, Erik & Muller, Carl [Show all 8 contributors for this article] (2011). Elevated serum osteoprotegerin levels measured early after acute ST-elevation myocardial infarction predict final infarct size. Heart. ISSN 1355-6037. 97(6), p. 460–465. doi: 10.1136/hrt.2010.206714. Full text in Research Archive
• Lillerud, Linn Elisabeth; Berge, Rolf Kristian; Beitnes, Jan Otto; Berge, Kjetil; Vik, Hogne & Aukrust, Pål [Show all 9 contributors for this article] (2011). Krill oil attenuates left ventricular dilatation after myocardial infarction in rats. Lipids in Health and Disease. 10. doi: 10.1186/1476-511X-10-245. Full text in Research Archive Show summary

  Background: In the western world, heart failure (HF) is one of the most important causes of cardiovascular mortality. Supplement with n-3 polyunsaturated fatty acids (PUFA) has been shown to improve cardiac function in HF and to decrease mortality after myocardial infarction (MI). The molecular structure and composition of n-3 PUFA varies between different marine sources and this may be of importance for their biological effects. Krill oil, unlike fish oil supplements, contains the major part of the n-3 PUFA in the form of phospholipids. This study investigated effects of krill oil on cardiac remodeling after experimental MI. Rats were randomised to pre-treatment with krill oil or control feed 14 days before induction of MI. Seven days post-MI, the rats were examined with echocardiography and rats in the control group were further randomised to continued control feed or krill oil feed for 7 weeks before re-examination with echocardiography and euthanization. Results: The echocardiographic evaluation showed significant attenuation of LV dilatation in the group pretreated with krill oil compared to controls. Attenuated heart weight, lung weight, and levels of mRNA encoding classical markers of LV stress, matrix remodeling and inflammation reflected these findings. The total composition of fatty acids were examined in the left ventricular (LV) tissue and all rats treated with krill oil showed a significantly higher proportion of n-3 PUFA in the LV tissue, although no difference was seen between the two krill oil groups. Conclusions: Supplement with krill oil leads to a proportional increase of n-3 PUFA in myocardial tissue and supplement given before induction of MI attenuates LV remodeling.

• Ahmed, Muhammad Shakil; Gravning, Jørgen A.; Martinov, Vladimir Nikolkaev; Lueder, Thomas Gero von; Edvardsen, Thor & Czibik, Gabor Tamas [Show all 11 contributors for this article] (2011). Mechanisms of novel cardioprotective functions of CCN2/CTGF in myocardial ischemia-reperfusion injury. American Journal of Physiology. Heart and Circulatory Physiology. ISSN 0363-6135. 300(4), p. H1291–H1302. doi: 10.1152/ajpheart.00604.2010. Full text in Research Archive
• Øie, Erik; Ueland, Thor; Dahl, Christen Peder; Bohov, Pavol; Berge, Christ & Yndestad, Arne [Show all 9 contributors for this article] (2011). Fatty acid composition in chronic heart failure: low circulating levels of eicosatetraenoic acid and high levels of vaccenic acid are associated with disease severity and mortality. Journal of Internal Medicine. ISSN 0954-6820. 270(3), p. 263–272. doi: 10.1111/j.1365-2796.2011.02384.x. Full text in Research Archive
• Røsjø, Helge; Husberg, Cathrine; Dahl, Mai Britt; Stridsberg, Mats; Sjaastad, Ivar & Finsen, Alexandra [Show all 10 contributors for this article] (2010). Chromogranin B in Heart Failure A Putative Cardiac Biomarker Expressed in the Failing Myocardium. Circulation: Heart Failure. ISSN 1941-3289. 3(4), p. 503–511. doi: 10.1161/CIRCHEARTFAILURE.109.867747. Full text in Research Archive
• Breland, Unni Mathilde; Michelsen, Annika; Skjelland, Mona; Folkersen, L; Krohg-Sørensen, Kirsten & Russell, David [Show all 14 contributors for this article] (2010). Raised MCP-4 levels in symptomatic carotid atherosclerosis: an inflammatory link between platelet and monocyte activation. Cardiovascular Research (CVR). ISSN 0008-6363. 86(2), p. 265–273. doi: 10.1093/cvr/cvq044. Full text in Research Archive
• Bergestuen, Deidi Ann; Gravning, Jørgen Amundsen; Haugaa, Kristina; Sahakyan, LG; Aakhus, Svend & Thiis-Evensen, Espen [Show all 10 contributors for this article] (2010). Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors. BMC Cancer. 10. doi: 10.1186/1471-2407-10-6. Full text in Research Archive Show summary

  Background Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. Methods Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. Results Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3). Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR). Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3). There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function had higher plasma CCN2 levels than those with normal or mildly reduced RV function (p < 0.001). Plasma CCN2 ≥ 77 μg/L was an independent predictor of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88% sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was elevated in patients with mild or greater TR/PR compared to those with no or minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe TR/PR (p = 0.03). Conclusions Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.

• Bergestuen, Deidi Ann; Edvardsen, Thor; Aakhus, Svend; Ueland, Thor; Øie, Erik & Vatn, Morten H [Show all 8 contributors for this article] (2010). Activin A in Carcinoid Heart Disease: A Possible Role in Diagnosis and Pathogenesis. Neuroendocrinology. ISSN 0028-3835. 92(3), p. 168–177. doi: 10.1159/000318014. Full text in Research Archive
• Øie, Erik; Sandberg, Wiggo Johan; Ahmed, Muhammad Shakil; Yndestad, Arne; Lærum, Ole Didrik & Attramadal, Håvard [Show all 8 contributors for this article] (2010). Activation of Notch signaling in cardiomyocytes during post-infarction remodeling. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 44(6), p. 359–366. doi: 10.3109/14017431.2010.511256. Full text in Research Archive
• Michelsen, Annika; Rathcke, CN; Skjelland, Mona; Holm, Sverre; Ranheim, Trine & Krohg-Sørensen, Kirsten [Show all 12 contributors for this article] (2010). Increased YKL-40 expression in patients with carotid atherosclerosis. Atherosclerosis. ISSN 0021-9150. 211(2), p. 589–595. doi: 10.1016/j.atherosclerosis.2010.02.035. Full text in Research Archive
• Øie, Erik; Ahmed, Muhammad Shakil; Ueland, Thor; Sikkeland, Liv Ingunn Bjoner; Dahl, Christen Peder & Hagelin, Else Marie Valbjørn [Show all 14 contributors for this article] (2010). Adrenomedullin is increased in alveolar macrophages and released from the lungs into the circulation in severe heart failure. Basic Research in Cardiology. ISSN 0300-8428. 105(1), p. 89–98. doi: 10.1007/s00395-009-0070-y. Full text in Research Archive
• Yndestad, Arne; Neurauter, Christine Gran; Øie, Erik; Johansen, Rune Forstrøm; Vinge, Leif Erik & Eide, Lars [Show all 9 contributors for this article] (2009). Up-regulation of myocardial DNA base excision repair activities in experimental heart failure. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. ISSN 0027-5107. 666(1-2), p. 32–38. doi: 10.1016/j.mrfmmm.2009.03.008. Full text in Research Archive
• Dahl, Christen Peder; Husberg, Cathrine; Gullestad, Lars; Wæhre, Anne; Damås, Jan Kristian & Vinge, Leif Erik [Show all 15 contributors for this article] (2009). Increased Production of CXCL16 in Experimental and Clinical Heart Failure: A Possible Role in Extracellular Matrix Remodeling. Circulation: Heart Failure. ISSN 1941-3289. 2(6), p. 624–632. doi: 10.1161/CIRCHEARTFAILURE.108.821074. Full text in Research Archive
• Ueland, Thor; Otterdal, Kari; Lekva, Tove; Halvorsen, Bente; Gabrielsen, A & Sandberg, Wiggo Johan [Show all 13 contributors for this article] (2009). Dickkopf-1 Enhances Inflammatory Interaction Between Platelets and Endothelial Cells and Shows Increased Expression in Atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 29(8), p. 1228–1234. doi: 10.1161/ATVBAHA.109.189761. Full text in Research Archive
• Yndestad, Arne; Larsen, Karl-Otto; Øie, Erik; Ueland, Thor; Smith, Camilla & Halvorsen, Bente [Show all 14 contributors for this article] (2009). Elevated levels of activin A in clinical and experimental pulmonary hypertension. Journal of applied physiology. ISSN 8750-7587. 106(4), p. 1356–1364. doi: 10.1152/japplphysiol.90719.2008. Full text in Research Archive
• Yndestad, A; Landrø, Linn; Ueland, Thor; Dahl, CP; Flo, Trude Helen & Vinge, Leif Erik [Show all 15 contributors for this article] (2009). Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. European Heart Journal. ISSN 0195-668X. 30(10), p. 1229–1236. doi: 10.1093/eurheartj/ehp088. Full text in Research Archive Show summary

  Aims: Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2) is a glycoprotein with bacteriostatic properties. Growing evidence suggests that NGAL may also be involved in cell survival, inflammation, and matrix degradation. We therefore aimed to investigate the role of NGAL in heart failure (HF). Methods and results: Our main findings were (i) patients with acute post-myocardial infarction (MI) HF (n = 236) and chronic HF (n = 150) had elevated serum levels of NGAL (determined by enzyme immunoassay), significantly correlated with clinical and neurohormonal deterioration, (ii) in patients with HF following acute MI, elevated NGAL levels of at baseline were associated with adverse outcomes (median of 27 months follow-up), (iii) in a rat model of post-MI HF, NGAL/lipocalin-2 gene expression was increased in the non-ischaemic part of the left ventricle primarily located to cardiomyocytes, (iv) strong NGAL immunostaining was found in cardiomyocytes within the failing myocardium both in experimental and clinical HF, (v) interleukin-1β and agonists for toll-like receptors 2 and 4, representing components of the innate immune system, were potent inducers of NGAL/lipocalin-2 in isolated neonatal cardiomyocytes. Conclusion: Our demonstration of enhanced systemic and myocardial NGAL expression in clinical and experimental HF further support a role for innate immune responses in the pathogenesis of HF.

• Sandberg, Wiggo Johan; Halvorsen, Bente; Yndestad, Arne; Smith, Camilla; Otterdal, Kari & Brosstad, Frank Roger [Show all 13 contributors for this article] (2009). Inflammatory Interaction Between LIGHT and Proteinase-Activated Receptor-2 in Endothelial Cells. Potential Role in Atherogenesis. Circulation Research. ISSN 0009-7330. 104(1), p. 60–U192. doi: 10.1161/CIRCRESAHA.108.188078. Full text in Research Archive Show summary

  The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells. We also found that LIGHT acted synergistically with PAR-2 activation to promote enhanced release of the proatherogenic chemokines interleukin-8 and monocyte chemoattractant protein-1, underscoring that the interaction between LIGHT and PAR-2 is biologically active, promoting potent inflammatory effects. We showed that the LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways. A LIGHT-mediated upregulation of PAR-2 mRNA levels was also found in human monocytes when these cells were preactivated by tumor necrosis factor {alpha}. We have previously demonstrated increased plasma levels of LIGHT in unstable angina patients, and here we show a similar pattern for PAR-2 expression in peripheral blood monocytes. We also found that LIGHT, LIGHT receptors, and PAR-2 showed enhanced expression, and, to some degree, colocalization in endothelial cells and macrophages, in the atherosclerotic plaques of ApoE–/– mice, suggesting that the inflammatory interaction between LIGHT and PAR-2 also may be operating in vivo within an atherosclerotic lesion. Our findings suggest that LIGHT/PAR-2–driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder.

• Sandberg, Wiggo Johan; Otterdal, Kari; Gullestad, Lars; Halvorsen, Bente; Ragnarsson, Asgrimur & Frøland, Stig Sophus [Show all 11 contributors for this article] (2009). The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis. Thrombosis and Haemostasis. ISSN 0340-6245. 102(4), p. 704–710. doi: 10.1160/TH08-10-0665. Full text in Research Archive
• Breland, Unni Mathilde; Halvorsen, Bente; Hol, Johanna; Øie, Erik; Paulsson-Berne, G & Yndestad, Arne [Show all 17 contributors for this article] (2008). A potential role of the CXC chemokine GRO alpha in atherosclerosis and plaque destabilization - Downregulatory effects of statins. Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 28. doi: 10.1161/ATVBAHA.108.162305. Full text in Research Archive
• Handberg, Aase; Skjelland, Mona; Michelsen, Annika; Sagen, Ellen Lund; Krohg-Sørensen, Kirsten & Russell, David [Show all 11 contributors for this article] (2008). Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability. Stroke. ISSN 0039-2499. 39, p. 3092–3095. doi: 10.1161/STROKEAHA.108.517128. Full text in Research Archive
• Husberg, Cathrine; Nygård, Ståle; Finsen, Alexandra; Damås, Jan Kristian; Frigessi, Arnoldo & Øie, Erik [Show all 11 contributors for this article] (2008). Cytokine expression profiling of the myocardium reveals a role for CX3CL1 (fractalkine) in heart failure. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 45, p. 261–269. doi: 10.1016/j.yjmcc.2008.05.009. Full text in Research Archive
• Smith, Camilla; Halvorsen, Bente; Otterdal, Kari; Wæhre, Torgun; Yndestad, Arne & Fevang, Børre [Show all 13 contributors for this article] (2008). High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in coronary artery disease: down-regulatory effects of statins. Cardiovascular Research (CVR). ISSN 0008-6363. 79, p. 195–203. doi: 10.1093/cvr/cvn071. Full text in Research Archive
• Pleger, ST; Harris, DM; Shan, CG; Vinge, Leif Erik; Chuprun, JK & Berzins, B [Show all 17 contributors for this article] (2008). Endothelial S100A1 modulates vascular function via nitric oxide. Circulation Research. ISSN 0009-7330. 102. doi: 10.1161/CIRCRESAHA.108.172031. Full text in Research Archive
• Dahl, Christen Peder; Gullestad, Lars; Fevang, Børre; Holm, Are Martin; Landrø, Linn Aina Ysland & Vinge, Leif Erik [Show all 15 contributors for this article] (2008). Increased expression of LIGHT/TNFSF 14 and its receptors in experimental and clinical heart failure. European Journal of Heart Failure. ISSN 1388-9842. 10, p. 352–359. doi: 10.1016/j.ejheart.2008.02.010. Full text in Research Archive
• Aukrust, Pål; Otterdal, K; Yndestad, Arne; Sandberg, Wiggo Johan; Smith, Camilla & Ueland, Thor [Show all 10 contributors for this article] (2008). The complex role of T-cell-based immunity in atherosclerosis. Current Atherosclerosis Reports. ISSN 1523-3804. 10, p. 236–243. Full text in Research Archive
• Otterdal, Kari; Andreassen, Arne K.; Yndestad, Arne; Øie, Erik; Sandberg, Wiggo Johan & Dahl, Christen Peder [Show all 12 contributors for this article] (2008). Raised LIGHT Levels in Pulmonary Arterial Hypertension - Potential Role in Thrombus Formation. American Journal of Respiratory and Critical Care Medicine. ISSN 1073-449X. 177, p. 202–207. doi: 10.1164/rccm.200703-506OC. Full text in Research Archive
• Aukrust, Pål; Halvorsen, Bente; Yndestad, Arne; Ueland, Thor; Øie, Erik & Otterdal, Kari [Show all 8 contributors for this article] (2008). Chemokines and cardiovascular risk. Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 28(11), p. 1909–1919. doi: 10.1161/ATVBAHA.107.161240. Full text in Research Archive
• Halvorsen, Bente; Otterdal, K; Dahl, TB; Skjelland, Mona; Gullestad, Lars & Øie, Erik [Show all 7 contributors for this article] (2008). Atherosclerotic Plaque Stability-What Determines the Fate of a Plaque? Progress in cardiovascular diseases. ISSN 0033-0620. 51(3), p. 183–194. doi: 10.1016/j.pcad.2008.09.001. Full text in Research Archive
• Aukrust, Pål; Yndestad, Arne; Damås, Jan Kristian; Ueland, Thor; Øie, Erik & Gullestad, Lars (2007). Potential mechanisms of benefit with thalidomide in chronic heart failure. American Journal of Cardiovascular Drugs. ISSN 1175-3277. 7, p. 127–134. Full text in Research Archive

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• Øie, Erik Harald (2025). Norsk lærebok i ekkokardiografi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145. doi: 10.4045/tidsskr.25.0399. Full text in Research Archive
• Nome, Ragnhild Veline; Amundsen, Erik Koldberg; Tvedt, Tor Henrik Anderson; Fenstad, Mona H. & Øie, Erik (2023). Hvor ofte bør man gjenta blodprøver? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(1). doi: 10.4045/tidsskr.22.0658. Full text in Research Archive
• Kolden, Mathias Øie; Nymo, Ståle Haugset & Øie, Erik (2022). Correction: Impact of neighbourhood-level socioeconomic status, traditional coronary risk factors, and ancestry on age at myocardial infarction onset: A population-based register study (BMC Cardiovascular Disorders, (2022), 22, 1, (447), 10.1186/s12872-022-02880-7). BMC Cardiovascular Disorders. 22(1). doi: 10.1186/s12872-022-02938-6. Full text in Research Archive
• Øie, Erik (2016). E. Øie svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(16), p. 1325–1325. doi: 10.4045/tidsskr.16.0688. Full text in Research Archive
• Øie, Erik (2016). Over 80 år og hjerteinfarkt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(12/13), p. 1058–1058. doi: 10.4045/tidsskr.16.0458. Full text in Research Archive
• Tazmini, Kiarash; Frisk, Michael; Lipsett, David Bruce; Aronsen, Jan Magnus; Sjaastad, Ivar & Øie, Erik [Show all 7 contributors for this article] (2016). Pro-arrhythmic consequences of hypokalemia in atrial cardiomyocytes. Full text in Research Archive
• Tazmini, Kiarash; Frisk, Michael; Aronsen, Jan Magnus; Sjaastad, Ivar; Øie, Erik & Louch, William Edward (2014). Pro-arrhythmic consequences of hypokalemia in atrial cardiomyocytes. Full text in Research Archive
• Hommerstad, Anders; Hall, Kirsten Sundby; Bjerkehagen, Bodil; Eskild, Trond H.; Geiran, Odd & Øie, Erik (2014). Kvinne i 50-årene med tungpustethet og hypotensjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. p. 1758–1761. doi: 10.4045/tidsskr.13.1110. Full text in Research Archive
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• Bergestuen, Deidi Ann; Edvardsen, Thor; Aakhus, Svend; Ueland, Thor; Øie, Erik & Vatn, Morten H [Show all 8 contributors for this article] (2012). Activin A in Carcinoid Heart Disease: A Possible Role in Diagnosis and Pathogenesis. Pancreas. ISSN 0885-3177. 41(2), p. 339–339. Full text in Research Archive
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• Ottesen, Anett Hellebø; Louch, William Edward; Carlson, Cathrine Rein; Landsverk, Ole J. B.; Høiseth, Arne Didrik & Stridsberg, Mats [Show all 10 contributors for this article] (2011). Secretoneurin, a peptide associated with mortality in heart failure, modulates cardiomyocyte calcium homeostasis. Full text in Research Archive
• Ottesen, Anett Hellebø; Louch, William Edward; Carlson, Cathrine Rein; Landsverk, Ole J. B.; Høiseth, Arne Didrik & Stridsberg, Mats [Show all 10 contributors for this article] (2011). Secretoneurin, a peptide associated with mortality in heart failure, modulates cardiomyocyte calcium homeostasis. Circulation. ISSN 0009-7322. 124. Full text in Research Archive
• Røsjø, Helge; Stridsberg, M.; Florholmen, Geir; Stensløkken, Kåre-Olav; Sjaastad, Ivar & Husberg, Cathrine [Show all 10 contributors for this article] (2010). Secretoneurin is a novel peptide increased in the myocardium and circulation in heart failure with cardioprotective properties. European Heart Journal. ISSN 0195-668X. 31, p. 314–314. Full text in Research Archive
• Øie, Erik; Ueland, Thor; Dahl, Christen Peder; Bohov, Pavol; Berge, Christ & Yndestad, Arne [Show all 9 contributors for this article] (2010). Low circulating eicosatetraenoic acid and high vaccenic acid are associated with disease severity and predict mortality in heart failure. European Heart Journal. ISSN 0195-668X. 31(suppl 1), p. 570–570. Full text in Research Archive
• Røsjø, Helge; Stridsberg, M; Florholmen, Geir; Stensløkken, Kåre-Olav; Sjaastad, Ivar & Husberg, Cathrine [Show all 10 contributors for this article] (2010). Secretoneurin: a novel protective agent increased in the myocardium and circulation in heart failure. Hjerteforum. ISSN 0802-1465. 23(1), p. 101–102. Full text in Research Archive
• Bergestuen, Deidi Ann; Gravning, Jørgen A.; Haugaa, Kristina; Sahakyan, Laura G.; Aakhus, Svend & Carlsen, Espen [Show all 10 contributors for this article] (2010). Plasma CCN2/Connective Tissue Growth Factor is Associated with Right Ventricular Dysfunction in Patients with Neuroendocrine Tumors. Neuroendocrinology. ISSN 0028-3835. 92(1), p. 19–19. Full text in Research Archive
• Beitnes, Jan Otto; Øie, Erik; Shahdafar, Aboulghassem; Karlsen, Tommy Aleksander; Aakhus, Svend & Brinchmann, Jan E. (2010). Mesenchymal stem cells from skeletal muscle and adipose tissue improve LV function after myocardial infarction, but do not differentiate into cardiomyocytes. European Heart Journal. ISSN 0195-668X. 31, p. 397–397. Full text in Research Archive
• Røsjø, Helge; Stridsberg, Mats; Florholmen, Geir; Stensløkken, Kåre-Olav; Sjaastad, Ivar & Husberg, Cathrine [Show all 10 contributors for this article] (2010). Secretoneurin is a novel peptide increased in the myocardium and circulation in heart failure with cardioprotective properties. Full text in Research Archive
• Dahl, Christen Peder; Husberg, Cathrine; Gullestad, Lars; Wæhre, Anne; Damås, Jan Kristian & Vinge, Leif Erik [Show all 15 contributors for this article] (2009). Increased production of CXCL16 in experimental and clinical heart failure; a possible role in extracellular matrix remodeling. Hjerteforum. ISSN 0802-1465. 22(2), p. 113–114. Full text in Research Archive
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• Røsjø, Helge; Husberg, Cathrine; Dahl, Mai Britt; Stridsberg, Mats; Sjaastad, Ivar & Øie, Erik [Show all 8 contributors for this article] (2009). Chromogranin B is regulated in the myocardium and circulation during heart failure development; a novel marker of cardiac disease. European Journal of Heart Failure. Supplements. ISSN 1567-4215. 8. Full text in Research Archive
• Dahl, Christen Peder; Husberg, Cathrine; Gullestad, Lars; Halvorsen, Bente; Aukrust, Pål & Øie, Erik [Show all 8 contributors for this article] (2009). Increased production of CXCL16 in experimental and clinical heart failure; a possible role in extracellular matrix remodeling. European Journal of Heart Failure. Supplements. ISSN 1567-4215. 8. Full text in Research Archive
• Dahl, Christen Peder; Sikkeland, Liv Ingunn Bjoner; Andreassen, Arne K.; Gude, Einar; Gullestad, Lars & Kongerud, Johny [Show all 8 contributors for this article] (2009). Increased levels of cytokines, vasoactive peptides, and growth factors in alveolar macrophages in heart failure. Full text in Research Archive
• Dahl, Christen Peder; Husberg, Cathrine; Gullestad, Lars; Wæhre, Torgun; Finsen, Alexandra & Halvorsen, Bente [Show all 10 contributors for this article] (2009). Increased production of CXCL16 in experimental and clinical heart failure; a possible role in extracellular matric remodeling. Full text in Research Archive
• Øie, Erik; Sandberg, Wiggo Johan; Ahmed, MS; Vinge, Leif Erik; Gullestad, Lars & Attramadal, Håvard [Show all 8 contributors for this article] (2009). Activation of notch signalling in cardiomyocytes during post-infarction myocardial remodelling. Full text in Research Archive
• Dahl, Christen Peder; Husberg, Cathrine; Gullestad, Lars; Halvorsen, Bente; Aukrust, Pål & Øie, Erik [Show all 8 contributors for this article] (2009). Increased production of CXCL16 in experimental and clinical heart failure, a possible role in extracellular matrix remodeling. Full text in Research Archive
• Røsjø, Helge; Husberg, Cathrine; Dahl, Mai Britt; Stridsberg, Mats; Sjaastad, Ivar & Finsen, Alexandra [Show all 10 contributors for this article] (2009). The chromogranins A and B are regulated differently in the myocardium and circulation during heart failure development; complimentary cardiac biomarkers? European Heart Journal, Supplement. ISSN 1520-765X. 30, p. 134–134. Full text in Research Archive
• Røsjø, Helge; Stridsberg, Mats; Husberg, Cathrine; Dahl, Mai Britt; Sjaastad, Ivar & Øie, Erik [Show all 8 contributors for this article] (2009). Secretogranin II is closely regulated in the murine myocardium and increased in the circulation of heart failure patients. Circulation. ISSN 0009-7322. 120, p. S858–S858. Full text in Research Archive
• Røsjø, Helge; Husberg, Cathrine; Dahl, Mai Britt; Stridsberg, Mats; Sjaastad, Ivar & Finsen, Alexandra [Show all 10 contributors for this article] (2009). Chromogranin B: a novel myocardium-regulated biomarker in experimental and clinical heart failure. Hjerteforum. ISSN 0802-1465. 22, p. 107–107. Full text in Research Archive
• Øie, Erik; Sikkeland, Liv Ingunn Bjoner; Dahl, Christen Peder; Andreassen, Arne K.; Gude, Einar & Gullestad, Lars [Show all 8 contributors for this article] (2009). Increased levels of cytokines, vasoactive peptides, and growth factors in alveolar macrophages in heart failure. Full text in Research Archive
• Røsjø, Helge; Husberg, Cathrine; Dahl, Mai Britt; Stridsberg, M; Sjaastad, I & Øie, Erik [Show all 8 contributors for this article] (2009). Chromagranin B is regulated in the myocardium and circulation during heart failure development - a novel marker of cardiac disease. Full text in Research Archive
• Breland, Unni Mathilde; Halvorsen, Bente; Hol, Johanna; Øie, Erik; Yndestad, Arne & Smith, Camilla [Show all 16 contributors for this article] (2008). Enhanced expression of the chemokine CXCL1 in atherosclerotic disorders, down-regulatory effects of statin. Full text in Research Archive
• Dahl, Christen Peder; Husberg, Cathrine; Gullestad, Lars; Wæhre, Anne; Finsen, Alexandra & Halvorsen, Bente [Show all 10 contributors for this article] (2008). Increased production of CXCL16 in heart failure; a role in extracellular matrix remodeling. Full text in Research Archive
• Dahl, Christen Peder; Gullestad, Lars; Øie, Erik; Damås, Jan Kristian; Aukrust, Pål & Yndestad, Arne (2007). The TNF superfamily cytokine LIGHT – a new inflammatory mediator in heart failure. Full text in Research Archive
• Dahl, Christen Peder; Gullestad, Lars; Øie, Erik; Fevang, Børre; Holm, Are Martin & Damås, Jan Kristian [Show all 8 contributors for this article] (2007). The TNF superfamily cytokine LIGHT: a new inflammatory mediator in heart failure. Full text in Research Archive
• Yndestad, Arne; Finsen, Alexandra; Husberg, Cathrine; Øie, Erik; Lipp, M. & Gullestad, Lars [Show all 8 contributors for this article] (2007). The homeostatic chemokines CCL19 and CCL21 are elevated in heart failure and may regulate myocardial hypertrophy. Full text in Research Archive

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