Bjørn Bendz

• Huse, Camilla; Murphy, Sarah Louise Mikalsen; Yang, Kuan; Balzer, Nora Reka; Stokke, Mathis Korseberg & Anstensrud, Anne Kristine [Show all 27 contributors for this article] (2025). The effects of interleukin-6-receptor inhibition on monocytes in STEMI: a substudy of the ASSAIL-MI trial. EBioMedicine. 121, p. 105960–105960. doi: 10.1016/j.ebiom.2025.105960. 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

• Lippert, Matthias; d’Albenzio, Gabriella; Suther, Lene Kathrine R; Dumont, Karl-Andreas; Palomar, Rafael & Odland, Hans Henrik [Show all 9 contributors for this article] (2024). HoloPatch: improving intracardiac patch fit through holographically modelled templates. European Heart Journal – Imaging Methods and Practice (EHJ-IMP). 2(3). doi: 10.1093/ehjimp/qyae103. Full text in Research Archive Show summary

  Aims Structural heart defects, including congenital ventricular septal defect closure or intracardiac rerouting, frequently require surgical reconstruction using hand-cut patch materials. Digitally modelled patch templates may improve patch fit and reduce outflow tract obstruction, residual defect risk, and conduction system damage. In this study, we benchmarked mixed-reality and a desktop application against a digitalized model of a real implanted patch. Methods and results Ten patients scheduled for the repair of various defects consented to prospective inclusion in the study. After surgery, a digital model of the implanted patch was created from the residual material. Five clinical experts created 10 digital patches, 1 per patient, both in mixed-reality and desktop application, for comparison with the reference measurements, including the digitalized model of the real patch used during the surgery. Subjective residual shunt risk prediction was performed using both modalities. Digital patches created in mixed-reality closely matched the surgical material, whereas those created using desktop applications were significantly smaller. Different evaluators showed varying preferences for the application of the residual shunt risk and area. Conclusion Digitally created patches can assist surgeons in preoperatively sizing of patch implants, potentially reducing post-operative complications.

• Rubino, Francesca; Pompei, Graziella; Mills, Gregory B.; Kotanidis, Christos P.; Laudani, Claudio & Bendz, Bjørn [Show all 16 contributors for this article] (2024). Older women with non-ST-elevation acute coronary syndrome undergoing invasive or conservative management: an individual patient data meta-analysis. European Heart Journal Open (EHJ Open). 4(6). doi: 10.1093/ehjopen/oeae093. Full text in Research Archive Show summary

  Aims Women and older patients are underrepresented in randomized controlled trials (RCTs) investigating treatment strategies following acute coronary syndrome. This study aims to evaluate the benefit of invasive vs. conservative strategy of older women with non-ST-elevation acute coronary syndrome (NSTEACS). Methods and results This analysis from an individual patient data meta-analysis included six RCTs comparing an invasive management with a conservative management in older NSTEACS patients. The primary endpoint was the composite of all-cause mortality or myocardial infarction (MI). Secondary endpoints included all-cause mortality, cardiovascular death, MI, urgent revascularization, and stroke. Follow-up time was censored at 1 year. In total, 717 women [median age 84.0 (interquartile range 81.0–87.0) years] were included. The primary endpoint occurred in 21.0% in the invasive strategy vs. 27.8% in the conservative strategy [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.52–1.13, P = 0.160 using random effect] at 1-year follow-up. The invasive management was associated with reduced risk of MI (HR 0.49, 95% CI 0.32–0.73, P < 0.001) and urgent revascularization (HR 0.44, 95% CI 0.20–0.98, P = 0.045). No significant differences were identified in the risk of all-cause mortality, cardiovascular death, and stroke. Among males, there was no significant association between the treatment strategy and primary or secondary endpoints. Conclusion An invasive strategy compared with a conservative strategy did not reduce the composite outcome of all-cause mortality or MI in older NSTEACS women at 1-year follow-up. An invasive strategy reduced the individual risk of MI and urgent revascularization. Our results support the beneficial role of the invasive strategy in older NSTEACS women. Registration This meta-analysis is registered with PROSPERO (CRD42023379819).

• Lippert, Matthias; Dumont, Karl-Andreas; Birkeland, Sigurd; Nainamalai, Varatharajan; Solvin, Håvard Bjerkeseth & Suther, Lene Kathrine R [Show all 9 contributors for this article] (2024). Cardiac anatomic digital twins: findings from a single national centre. The European Heart Journal – Digital Health (EHJ-DH). 5(6), p. 725–734. doi: 10.1093/ehjdh/ztae070. Full text in Research Archive
• Kotanidis, Christos P.; Mills, Gregory B.; Bendz, Bjørn; Berg, Erlend; Hildick-Smith, David & Hirlekar, Geir [Show all 16 contributors for this article] (2024). Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome: individual patient data meta-analysis. European Heart Journal. ISSN 0195-668X. 45(23), p. 2052–2062. doi: 10.1093/eurheartj/ehae151. Full text in Research Archive Show summary

  Background and Aims Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients. Methods MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819). Results Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63–1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44–0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18–0.95; P = .037). There was no significant difference in mortality. Conclusions No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.

• Pettersen, Trond Røed; Schjøtt, Jan Didrik; Allore, Heather; Bendz, Bjørn; Borregaard, Britt & Fridlund, Bengt [Show all 14 contributors for this article] (2024). Discharge Information About Adverse Drug Reactions Indicates Lower Self-Reported Adverse Drug Reactions and Fewer Concerns in Patients After Percutaneous Coronary Intervention. Heart, Lung and Circulation. ISSN 1443-9506. 33(3), p. 350–361. doi: 10.1016/j.hlc.2023.12.005. Full text in Research Archive Show summary

  Aim There are discrepancies between the information patients desire about adverse drug reactions (ADRs) and the information they receive from healthcare providers; this is an impediment to shared decision-making. This study aimed to establish whether patients received information about ADRs resulting from prescribed pharmacotherapy, before hospital discharge, after percutaneous coronary intervention (PCI) and to determine whether receiving information about ADRs was associated with incidence of self-reported ADRs or concerns related to prescribed pharmacotherapy. Methods CONCARDPCI, a prospective multicentre cohort study including 3,417 consecutive patients after PCI, was conducted at seven high-volume referral PCI centres in two Nordic countries. Clinical data were collected from patients’ medical records and national quality registries. Patient-reported outcome measures were registered 2 months (T1), 6 months (T2), and 12 months (T3) after discharge. Covariate-adjusted logistic regression yielded adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results At discharge, 38% of participants had been informed about potential ADRs. For these patients, the incidence of self-reported ADRs was significantly lower at T1 (aOR 0.61, 95% CI 0.50–0.74; p<0.001), T2 (aOR 0.60, 95% CI 0.49–0.74; p<0.001), and T3 (aOR 0.57, 95% CI 0.46–0.71; p<0.001). Those who were not informed reported higher levels of concern about prescribed pharmacotherapy at all measuring points (p<0.001 for all comparisons). Those living alone (aOR 0.73, 95% CI 0.57–0.92; p=0.008), who were female (aOR 0.57, 95% CI 0.44–0.72; p<0.001), and with three or more versus no comorbidities (aOR 0.61, 95% CI 0.44–0.84; p=0.002) were less likely to receive information. Conclusion A substantial proportion of patients were not informed about potential ADRs from prescribed pharmacotherapy after PCI. Patients informed about ADRs had lower incidences of self-reported ADRs and fewer concerns about prescribed pharmacotherapy.

• Kelham, Matthew; Vyas, Rohan; Ramaseshan, Rohini; Rathod, Krishnaraj; Winter, Robbert J. de & Winter, Ruben W. de [Show all 17 contributors for this article] (2024). Non-ST-elevation acute coronary syndromes with previous coronary artery bypass grafting: a meta-analysis of invasive vs. conservative management. European Heart Journal. ISSN 0195-668X. 45(27), p. 2380–2391. doi: 10.1093/eurheartj/ehae245. Full text in Research Archive Show summary

  Background and Aims A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Eligible studies were RCTs of routine invasive vs. a conservative or selective invasive strategy in patients presenting with NSTE-ACS that included patients with previous CABG. Summary data were collected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results Summary data were obtained from 11 RCTs, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477 routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5–10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97–1.29), cardiac mortality (RR 1.05, 95% CI 0.70–1.58), myocardial infarction (RR 0.90, 95% CI 0.65–1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78–1.40). Conclusions This is the first meta-analysis assessing the effect of a routine invasive strategy in patients with prior CABG who present with NSTE-ACS. The results confirm the under-representation of this patient group in RCTs of invasive management in NSTE-ACS and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered RCT.

• Holm, Marianne Sætrang; Fålun, Nina Britt; Pettersen, Trond Røed; Bendz, Bjørn; Nilsen, Roy Miodini & Langørgen, Jørund [Show all 10 contributors for this article] (2024). Appropriateness and outcomes of hospitalized patients telemetry monitored for cardiac arrhythmias in accordance with the American Heart Association Practice Standards–A multicenter study. Heart & Lung. ISSN 0147-9563. 68, p. 217–226. doi: 10.1016/j.hrtlng.2024.07.005. Full text in Research Archive Show summary

  Background To the best of our knowledge, no prospective research studies have compared clinical practice to the American Heart Association (AHA) updated practice standards for in-hospital telemetry monitoring. Objectives Our aims were therefore (1) to investigate how patients were assigned to telemetry monitoring in accordance with the AHA's updated practice standards, (2) to determine the number and type of arrhythmic events, and (3) to describe subsequent changes in clinical management. Methods This prospective multicenter study included 1154 patients at three university hospitals in Norway. Data were collected 24/7 over a four-week period, with follow-up measurements from telemetry admission until hospital discharge. Results Of patients assigned to telemetry, 67 % (n = 767) met practice standards, corresponding to AHA Class I or II. Patients were predominantly men (65 %, n = 748), and the mean age was 65 years (SD ±16). The study included both patients with cardiac and non-cardiac diagnoses from various medical and surgical departments throughout the hospitals. Ninety-one percent of the patients in Class III were monitored based on indications that were reclassified from Class II to Class III (not indicated) in the updated practice standards (patients admitted with chest pain or post-percutaneous coronary intervention (PCI) without complications). Overall, arrhythmic events occurred in 37 % (n = 424) of patients, and they occurred in all classes. Eighteen percent (n = 59) of arrhythmic events occurred in Class III. Of all arrhythmias, 3 % (n = 14) were life threatening, and all of them occurring within Class I. Telemetry monitoring led to changes in clinical management in 22 % (n = 257) of patients due to clinical alarms, of which 71 % (n = 182) were related to medication management. Conclusions Most patients were appropriately monitored according to the AHA practice standards, meeting Class I and II. Arrhythmias occurred in all classes, but life-threatening arrhythmias only occurred in patients in Class I. However, a daily re-assessment of each patient's telemetry indication is warranted.

• Instenes, Irene; Fridlund, Bengt Gotthard Anton; Borregaard, Britt; Larsen, Alf Inge; Allore, Heather & Bendz, Bjørn [Show all 10 contributors for this article] (2024). 'When age is not a barrier': an explorative study of nonagenarian patients' experiences of undergoing percutaneous coronary intervention. European Journal of Cardiovascular Nursing. ISSN 1474-5151. 23(6), p. 608–617. doi: 10.1093/eurjcn/zvad132. Full text in Research Archive Show summary

  Aims The recent rise in the number of nonagenarians (age ≥ 90 years) undergoing percutaneous coronary intervention (PCI) has revealed gaps in research, in particular on patients’ experiences. Therefore, the aim of the study was to explore and describe nonagenarians’ internal resources and their experiences of the in-hospital pathway. Methods and results Nineteen nonagenarian patients (women n = 9), mean age 91 years, 9 acutely, and 10 electively treated, were consecutively enrolled from a tertiary university hospital from June 2021 to February 2023. In-depth interviews were conducted during hospitalization, audiotaped and transcribed. The interviews were analysed using qualitative content analysis. Three sub-themes emerged from the nonagenarians’ experiences with the PCI treatment trajectory: (i) Taking lifelong responsibility for own physical and mental health describes a population striving to live a healthy life and to stay independent. Physical and mental activities including healthy food choices had been an integral aspect of their lives from early childhood. (ii) Individual internal resources influenced the PCI pathway describes how their internal resources were used, from actively engaging in the decision-making process to withstanding discomfort during the PCI procedure. (iii) The post-PCI pathway was multifaceted describes a short stay at the cardiac ward with individual post-procedural experiences, close monitoring, and preparation for discharge including cardiac rehabilitation. Conclusion Nonagenarians undergoing PCI demonstrated a personal incentive to stay healthy and independent. Their internal resources of independence, stoicism, and resilience were used during their in-hospital stay contributing to a successful PCI procedure. Individual cardiac rehabilitation strategies were highlighted after discharge from hospital.

• Woxholt, Sindre; Ueland, Thor; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar & Tøllefsen, Ingvild Maria [Show all 20 contributors for this article] (2023). Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab. Open heart. 10(2), p. 1–8. doi: 10.1136/openhrt-2023-002301. Full text in Research Archive Show summary

  Background Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size. Methods STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24–36, 72–168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months. Results Repeated measures analysis of variance showed significant (p<0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=−0.29, –0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=−0.09,–0.14, respectively). Conclusions Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients.

• 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)

• Holm, Marianne Sætrang; Fålun, Nina Britt; Bendz, Bjørn; Fridlund, Bengt Gotthard Anton; Langørgen, Jørund & Pettersen, Trond Røed [Show all 8 contributors for this article] (2023). The patient experience of in-hospital telemetry monitoring: a qualitative analysis. European Journal of Cardiovascular Nursing. ISSN 1474-5151. 23(3), p. 258–266. doi: 10.1093/eurjcn/zvad082. Full text in Research Archive Show summary

  Aims In-hospital telemetry monitoring has been an integrated part of arrhythmia monitoring for decades. A substantial proportion of patients require arrhythmia monitoring during stays in non-intensive care units. However, studies exploring patients’ experiences of telemetry monitoring are scarce. Therefore, the aim was to explore and describe patients’ experiences of in-hospital telemetry monitoring in a non-intensive care setting. Methods and results Twenty face-to-face, semi-structured interviews were conducted. Interviews were conducted before discharge at two university hospitals in Norway. The patients were purposively sampled, resulting in a well-balanced population comprising 11 men and nine women, mean age 62 years (range 25–83). Average monitoring time was 9 days (range 3–14). Data were audiotaped, transcribed verbatim, and coded using NVivo software. Qualitative content analysis using an inductive approach was performed. Patients expressed a need for individualized information during telemetry monitoring. Their feelings of safety were related to responses from nurses from the central monitoring station when alarms from the telemetry were triggered. Despite perceived physical restrictions and psychological limitations associated with telemetry monitoring, they found monitoring to be beneficial because it facilitated the diagnosis of arrhythmia. Moreover, they expressed a need for improvements in wearable monitoring equipment. Patients expressed ambivalent feelings about discontinuing the telemetry and their readiness for discharge. Conclusion Patients need individualized information about the results of their telemetry monitoring in order to better understand the arrhythmia management and to increase their experience of safety after discharge. The limitations patients experienced should be taken into consideration in further upgrades of telemetry monitoring equipment.

• Dodgson, Christopher Alexander Steele; Beitnes, Jan Otto; Kløve, Sophie Foss; Herstad, Jon; Opdahl, Anders & Undseth, Ragnhild Marie [Show all 13 contributors for this article] (2023). An investigator-sponsored pragmatic randomized controlled trial of AntiCoagulation vs AcetylSalicylic Acid after Transcatheter Aortic Valve Implantation: Rationale and design of ACASA-TAVI. American Heart Journal. ISSN 0002-8703. 265, p. 225–232. doi: 10.1016/j.ahj.2023.08.010. Full text in Research Archive Show summary

  Background The optimal antithrombotic therapy after transcatheter aortic valve implantation (TAVI) is unknown. Bioprosthetic valve dysfunction (BVD) is associated with adverse outcomes and may be prevented by anticoagulation therapy. A dedicated randomized trial comparing monotherapy NOAC to single antiplatelet therapy has not been performed previously. We hypothesize that therapy with any anti-factor Xa NOAC will reduce BVD compared to antiplatelet therapy, without compromising safety. Methods ACASA-TAVI is a multicenter, prospective, randomized, open-label, blinded endpoint, all-comers trial comparing a monotherapy anti-factor Xa NOAC strategy (intervention arm) with a single antiplatelet therapy strategy (control arm) after successful TAVI. Three-hundred and sixty patients without indication for oral anticoagulation will be randomized in a 1:1 ratio to either apixaban 5 mg twice per day, edoxaban 60 mg daily, or rivaroxaban 20 mg daily for 12 months followed by acetylsalicylic acid 75 mg daily indefinitely, or to acetylsalicylic acid 75 mg daily indefinitely. The 2 co-primary outcomes are (1) incidence of Hypo-Attenuated Leaflet Thickening (HALT) on 4-dimensional cardiac CT at 12 months, and (2) a Safety Composite of VARC-3 bleeding events, thromboembolic events (myocardial infarction and stroke), and death from any cause, at 12 months. Results The first 100 patients had a mean age of 74 ± 3.6 years, 33% were female, the average body-mass index was 27.9 ± 4.4 kg/m2, and 15% were smokers. A balloon-expanded valve was used in 82% and a self-expandable valve in 18%. Conclusions The trial is planned, initiated, funded, and conducted without industry involvement.

• Rafique, Muzammil; Solberg, Ole Geir; Gullestad, Lars; Bendz, Bjørn; Murbræch, Klaus & Nytrøen, Kari [Show all 8 contributors for this article] (2023). Effects of high-intensity interval training on cardiac remodelling, function and coronary microcirculation in de novo heart transplant patients: a substudy of the HITTS randomised controlled trial. BMJ Open sport & exercise medicine. 9(3). doi: 10.1136/bmjsem-2022-001331. Full text in Research Archive Show summary

  Objectives High-intensity interval training (HIT) improves peak oxygen consumption (VO2peak) in de novo heart transplant (HTx) recipients. It remains unclear whether this improvement early after HTx is solely dependent on peripheral adaptations, or due to a linked chain of central and peripheral adaptations. The objective of this study was to determine whether HIT results in structural and functional adaptations in the cardiovascular system. Methods Eighty-one de novo HTx recipients were randomly assigned to participate in either 9 months of supervised HIT or standard care exercise-based rehabilitation. Cardiac function was assessed by echocardiogram and the coronary microcirculation with the index of microcirculatory resistance (IMR) at baseline and 12 months after HTx. Results Cardiac function as assessed by global longitudinal strain was significantly better in the HIT group than in the standard care group (16.3±1.2% vs 15.6±2.2%, respectively, treatment effect = –1.1% (95% CI –2.0% to –0.2%), p=0.02), as was the end-diastolic volume (128.5±20.8 mL vs 123.4±15.5 mL, respectively, treatment effect=4.9 mL (95% CI 0.5 to 9.2 mL), p=0.03). There was a non-significant tendency for IMR to indicate improved microcirculatory function (13.8±8.0 vs 16.8±12.0, respectively, treatment effect = –4.3 (95% CI –9.1 to 0.6), p=0.08). Conclusion When initiated early after HTx, HIT leads to both structural and functional cardiovascular adaptations.

• Instenes, Irene; Breivik, Kyrre; Borregaard, Britt; Larsen, Alf Inge; Allore, Heather & Bendz, Bjørn [Show all 9 contributors for this article] (2023). Phenotyping Self-Reported Health Profiles in Octogenarians and Nonagenarians After Percutaneous Coronary Intervention: A Latent Profile Analysis. Heart, Lung and Circulation. ISSN 1443-9506. doi: 10.1016/j.hlc.2023.09.004. Full text in Research Archive Show summary

  Background Little is known about self-reported health in octogenarians (≥80 years) and nonagenarians (≥90 years) following percutaneous coronary intervention (PCI), including characteristics of different health outcomes. This study aimed to phenotype latent health profiles of self-reported health in older adults 2 months post-PCI. Methods A prospective, multicentre, real-world study (CONCARDPCI) of 270 octogenarians and nonagenarians was performed with five validated and standardised measures of self-reported health at 2 months post-PCI. Latent profile analysis was used to identify health profiles, and multinomial logistic regression analyses were used to investigate the associations between patient characteristics and health profiles. Results Three latent health profiles were identified: The Poor health profile included 29%, the Moderate health profile included 39%, and the Good health profile included 32% of the participants. Older adults who were frail (OR 2.50, 95% CI 1.17–5.33), had a low exercise level (OR 0.49, 95% CI 0.39–0.95), and low alcohol intake (OR 0.61, 95% CI 0.39–0.95) were more likely to belong to the Poor health profile relative to the Good health profile. Furthermore, older age (OR 1.19, 95% CI 1.03–1.37) and lower exercise level (OR 0.64, 95% CI 0.43–0.97) were associated with belonging to the Moderate health profile relative to the Good health profile. Conclusion Two months after PCI, most participants displayed having Moderate to Good health profiles. Those with a Poor health profile were more likely to be frail and less active. These findings highlight that follow-up care has to be patient-centred and tailored to improve the health status of older adults.

• Pettersen, Trond Røed; Schjøtt, Jan Didrik; Allore, Heather G.; Bendz, Bjørn; Borregaard, Britt & Fridlund, Bengt Gotthard Anton [Show all 11 contributors for this article] (2022). Perceptions of generic medicines and medication adherence after percutaneous coronary intervention: a prospective multicentre cohort study. BMJ Open. 12(9). doi: 10.1136/bmjopen-2022-061689. Full text in Research Archive Show summary

  Objective: To determine patient perceptions of generic medicines 2 and 6 months after percutaneous coronary intervention (PCI), and to determine whether these perceptions moderate medication adherence. Design: Prospective multicentre cohort study with repeated measures of perceptions of generic medicines and medication adherence. Setting: The CONCARDPCI study conducted at seven large referral PCI centres in Norway and Denmark between June 2017 and May 2020. Participants: A total of 3417 adults (78% men), using both generic and brand name medicines, with a mean age of 66 years (SD 11) who underwent PCI were followed up 2 and 6 months after discharge from hospital. Main outcome measures: Perceptions of generic medicines were the main outcome. The secondary outcome was medication adherence. Results: Perceptions of generic medicines were significantly more negative at 2 than at 6 months (1.10, 95% CI 0.41 to 1.79, p=0.002). Female sex (−4.21, 95% CI −6.75 to −1.71, p=0.001), older age (−0.12, 95% CI −0.23 to −0.02, p=0.020), lower education level (overall p<0.001), ethnicity (overall p=0.002), Norwegian nationality (10.27, 95% CI 8.19 to 12.40, p<0.001) and reduced self-reported health status (0.19, 95% CI 0.09 to 0.41, p=0.003) were significantly associated with negative perceptions of generic medicines. There was no evidence to suggest that perceptions of generic medicines moderate the association between sociodemographic and clinical variables and medication adherence (p≥0.077 for all covariates). Moreover, self-reported medication adherence was high, with 99% scoring at or above the Medication Adherence Report Scale midpoint at both time points. There were no substantial correlations between negative perceptions of generic medicines and medication non-adherence at 2 months (r=0.041, 95% CI 0.002 to 0.081, p=0.037) or 6 months (r=0.038, 95% CI −0.005 to 0.081, p=0.057). Conclusions: Mistrust and uncertainty about the safety and efficacy of generic medicines remains in a sizeable proportion of patients after PCI. This applies especially to those of lower socioeconomic status, older age, female sex, immigrants and those with poorer mental health. However, this study demonstrated a shift towards more positive perceptions of generic medicines in the longer term.

• Okuno, Taishi; Dangas, George D.; Hengstenberg, Christian; Sartori, Samantha; Herrmann, Howard C. & Winter, Robert de [Show all 30 contributors for this article] (2022). Two-year clinical outcomes after successful transcatheter aortic valve implantation with balloon-expandable versus self-expanding valves: A subanalysis of the GALILEO trial. Catheterization and cardiovascular interventions. ISSN 1522-1946. 100(4), p. 636–645. doi: 10.1002/ccd.30370. Full text in Research Archive
• Norum, Ingvild Billehaug; Otterstad, Jan Erik; Ruddox, Vidar; Bendz, Bjørn & Edvardsen, Thor (2022). Novel regional longitudinal strain by speckle tracking to detect significant coronary artery disease in patients admitted to the emergency department for chest pain suggestive of acute coronary syndrome. Journal of Echocardiography. ISSN 1349-0222. 20(3), p. 166–177. doi: 10.1007/s12574-022-00568-7. Full text in Research Archive Show summary

  Background Global longitudinal strain has shown variable results in detecting ischemia in patients admitted to the emergency department with chest pain, but without other clear evidence of coronary artery disease (CAD). Our aim was to investigate whether assessment of regional longitudinal myocardial function could assist in detecting significant CAD in these patients. Methods Clinical evaluation, electrocardiogram, echocardiogram and troponin T were evaluated in 126 patients admitted with chest pain. A subsequent invasive coronary angiography divided patients into two groups: significant CAD (CAD+) or non-significant CAD (CAD−). Global and regional myocardial function were evaluated by speckle tracking echocardiography. Regional longitudinal strain was defined as the highest longitudinal strain values in four adjacent left ventricular segments and termed 4AS. Results CAD+ was found in 37 patients (29%) of which 51% had elevated troponin. Mean 4AS was − 13.1% (± 3.5) in the CAD+ and − 15.2% (± 2.7) (p = 0.002) in the CAD− group. Predictors for CAD+ were age [OR 1.06 (1.01–1.11, p = 0.026)], smoking [OR 3.39 (1.21–9.51, p = 0.020)], troponin [OR 3.32 (1.28–8.60, p = 0.014)) and 4AS (OR 1.24 (1.05–1.46, p = 0.010)]. A cutoff for 4AS of > − 15% showed the best diagnostic performance with event-reclassification of 0.41 (p < 0.001), non-event-reclassification of − 0.34 (p < 0.001) and net reclassification improvement 0.07 (p = 0.60). Conclusion Decreased myocardial function in four adjacent LV segments assessed by strain has the potential to detect significant CAD in patients admitted with chest pain and negative/slightly elevated initial troponin.

• Nordeng, Jostein; Schandiz, Hossein Khalkhali; Solheim, Svein; Åkra, Sissel; Hoffmann, Pavel & Roald, Borghild [Show all 10 contributors for this article] (2022). TIMP-1 expression in coronary thrombi associate with myocardial injury in ST-elevation myocardial infarction patients. Coronary Artery Disease. ISSN 0954-6928. 33(6), p. 446–455. doi: 10.1097/MCA.0000000000001128. Full text in Research Archive Show summary

  Background  Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are considered important both in atherosclerosis and remodeling after acute myocardial infarction (AMI). We aimed to study genetic expression and presence of MMP-2, MMP-9, TIMP-1, TIMP-2 and the extracellular MMP-inducer (EMMPRIN) in coronary thrombi. Circulating levels and genetic expression in circulating leukocytes were also assessed, and relations to degree of myocardial injury measured by troponin T and time from symptom to PCI were explored. Expression of cell markers were also analyzed, indicating relations to cell types. Methods  Intracoronary thrombi were aspirated from 33 patients with ST-elevation myocardial infarction (STEMI). Blood samples with Pax-gene tubes were drawn at end of PCI and the next day. RNA was isolated from thrombi and leukocytes, and genes were relatively quantified by RT-PCR. Each thrombus was preserved for histology and immunohistochemistry analyzes. Results  Genes coding for the five markers were present in 84–100% of thrombi and immunohistochemically stained in 96–100%. Expression of TIMP-1 in thrombi and in leukocytes correlated significantly to peak troponin T (r = 0.393 P = 0.026, r = 0.469 P = 0.006, respectively). No significant correlations between genes expressed in thrombi and time from symptom to PCI were observed. TIMP-1 was connected mainly to monocytes/macrophages in the thrombi. Conclusion  MMP-2, MMP-9, TIMP-1, TIMP-2 and EMMPRIN were highly expressed in human coronary thrombi. The correlation between troponin T and the expression of TIMP-1 both in thrombi and in leukocytes at time of PCI indicates that TIMP-1 plays a role in myocardial damage early post-MI.

• Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar & Woxholt, Sindre [Show all 29 contributors for this article] (2022). Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial. EBioMedicine. 80(104013). doi: 10.1016/j.ebiom.2022.104013. Full text in Research Archive Show summary

  We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69). Findings (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. Interpretation Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage.

• Nordeng, Jostein; Solheim, Svein; Åkra, Sissel; Schandiz, Hossein Khalkhali; Hoffmann, Pavel & Roald, Borghild [Show all 10 contributors for this article] (2022). Gene expression of fibrinolytic markers in coronary thrombi. Thrombosis Journal. 20. doi: 10.1186/s12959-022-00383-1. Full text in Research Archive Show summary

  Background The fibrinolytic system plays an important role in coronary artery atherothrombosis, and especially circulating plasminogen-activator inhibitor (PAI) type 1 (PAI-1) associates with increased mortality, infarct size and heart failure in patients with myocardial infarction (MI). In a cross-sectional study, we aimed to study whether genes encoding tissue plasminogen activator (tPA), urinary-type plasminogen activator (uPA), PAI-1 and PAI-2 are expressed in coronary thrombi from acute ST-elevation MI (STEMI) patients. Any relations to myocardial injury measured by peak troponin T, time from symptom onset to Percutaneous Coronary Intervention (PCI), and to different cell types present in the thrombi were also explored. Methods Intracoronary thrombi were aspirated from 33 STEMI patients treated with primary PCI. The thrombi were snap-frozen for gene expression analyses, relatively quantified by RT PCR. Peripheral blood samples were drawn. Correlations were performed by Spearmans rho. Results The genes were present in 74–94% of the thrombi. Median peak troponin T was 3434 μ/L and median ischemic time 152 min. There were no significant correlations between the measured genes and troponin T, or ischemic time. Genes encoding tPA, u-PA, PAI-1 and PAI-2 all correlated significantly to the presence of monocytes/macrophages (CD68) in the thrombi (p = 0.028, p < 0.001, p = 0.003, p < 0.001). PAI-1 and PAI-2 also correlated to endothelial cells (CD31) (p = 0.002, p = 0.016). uPA associated with neutrophil granulocytes (CD 66b) (p = 0.019). Conclusion Genes encoding tPA, uPA, PAI-1 and PAI-2 were highly expressed in human coronary thrombi from STEMI patients, indicating fibrinolytic regulators playing active roles in the thrombi, although not related to myocardial injury. All markers related to the presence of monocytes/macrophages, indicating connection to local inflammatory cells. Trial registration The study is registered at clinicaltrials.gov with identification number NCT02746822.

• Alm-Kruse, Kristin; Sørensen, Gro; Osbakk, Svein Are; Sunde, Kjetil; Bendz, Bjørn & Andersen, Geir Øystein [Show all 9 contributors for this article] (2021). Outcome in refractory out-of-hospital cardiac arrest before and after implementation of an ECPR protocol. Resuscitation. ISSN 0300-9572. doi: 10.1016/j.resuscitation.2021.01.038. Full text in Research Archive Show summary

  Aim To compare the outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) fulfilling the criteria for extracorporeal cardiopulmonary resuscitation (ECPR) before and after implementation of an ECPR protocol, whether the patient received ECPR or not. Methods We compared cardiac arrest registry data before (2014–2015) and after (2016–2019) implementation of the ECPR protocol. The ECPR criteria were presumed cardiac origin, witnessed arrest with ventricular fibrillation, bystander CPR, age 18–65, advanced life support (ALS) within 15 min and ALS > 10 min without return of spontaneous circulation (ROSC). The primary outcome was 30-day survival; the secondary outcomes were sustained ROSC, neurological outcome and the proportion of patients transported with ongoing ALS. Results There were 1086 and 3135 patients in the pre- and post-implementation sample; 48 (4%) and 100 (3%) met the ECPR criteria, respectively. Of these, 21 (44%) vs. 37 (37%) were alive after 30 days, p = 0.4, and 30 (63%) vs. 50 (50%) achieved sustained ROSC, p = 0.2. All survivors in the pre-implementation sample had cerebral performance category 1–2 vs. 30 (81%) in the post-implementation sample, p = 0.03. Of the patients fulfilling the ECPR criteria, 7 (15%) and 26 (26%), p = 0.1, were transported with ongoing ALS in the pre- and post-implementation sample, respectively. Conclusions There were no differences in 30-day survival or prehospital ROSC in patients with refractory OHCA before and after initiation of an ECPR protocol.

• Nordeng, Jostein; Schandiz, Hossein Khalkhali; Solheim, Svein; Åkra, Sissel; Hoffmann, Pavel & Roald, Borghild [Show all 10 contributors for this article] (2021). The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI. Mediators of Inflammation. ISSN 0962-9351. 2021, p. 1–12. doi: 10.1155/2021/5525917. Full text in Research Archive Show summary

  Background. The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Methods. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1β (IL1-β), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Results. Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T (, ), as did NLRP3 (, ). Troponin T correlated with expression in circulating leukocytes of TLR4 (, ), NLRP3 (, ), and IL-1β (, ). IL-6R expression in thrombi correlated significantly to troponin T (, ), whereas gp130 was inversely correlated (, ). IL-6 in circulating leukocytes correlated inversely to troponin T (, ). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. Conclusions. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822.

• Otterstad, Jan Erik; Norum, Ingvild Billehaug; Ruddox, Vidar; Le, An Chau Maria; Bendz, Bjørn & Munkhaugen, John [Show all 8 contributors for this article] (2021). Prognostic impact of non-improvement of global longitudinal strain in patients with revascularized acute myocardial infarction. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 37, p. 3477–3487. doi: 10.1007/s10554-021-02349-2. Full text in Research Archive Show summary

  Global longitudinal strain (GLS) is a more sensitive prognostic factor than left ventricular ejection fraction (LVEF) in various cardiac diseases. Little is known about the clinical impact of GLS changes after acute myocardial infarction (AMI). The present study aimed to explore if non-improvement of GLS after 3 months was associated with higher risk of subsequent composite cardiovascular events (CCVE). Patients with AMI were consecutively included at a secondary care center in Norway between April 2016 and July 2018 within 4 days following percutaneous coronary intervention. Echocardiography was performed at baseline and after 3 months. Patients were categorized with non-improvement (0 to − 100%) or improvement (0 to 100%) in GLS relative to the baseline value. Among 214 patients with mean age 65 (± 10) years and mean LVEF 50% (± 8) at baseline, 50 (23%) had non-improvement (GLS: − 16.0% (± 3.7) to − 14.2% (± 3.6)) and 164 (77%) had improvement (GLS: − 14.0% (± 3.0) to − 16.9% (± 3.0%)). During a mean follow-up of 3.3 years (95% CI 3.2 to 3.4) 77 CCVE occurred in 52 patients. In adjusted Cox regression analyses, baseline GLS was associated with all recurrent CCVE (HR 1.1, 95% CI 1.0 to 1.2, p < 0.001) whereas non-improvement versus improvement over 3 months follow-up was not. Baseline GLS was significantly associated with the number of CCVE in revascularized AMI patients whereas non-improvement of GLS after 3 months was not. Further large-scale studies are needed before repeated GLS measurements may be recommended in clinical practice.

• Broch, Kaspar; Anstensrud, Anne Kristine; Woxholt, Sindre; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria & Bendz, Bjørn [Show all 23 contributors for this article] (2021). Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction. Journal of the American College of Cardiology. ISSN 0735-1097. 77(15), p. 1845–1855. doi: 10.1016/j.jacc.2021.02.049. Full text in Research Archive Show summary

  Background - Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. Objectives - This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. Methods - The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days. Results - We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups. Conclusions - Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703)

• Rafique, Muzammil; Solberg, Ole Geir; Gullestad, Lars; Bendz, Bjørn; Holm, Niels Ramsing & Neghabat, Omeed [Show all 10 contributors for this article] (2021). A randomized clinical study using optical coherence tomography to evaluate the short-term effects of high-intensity interval training on cardiac allograft vasculopathy: a HITTS substudy. Clinical Transplantation. ISSN 0902-0063. 36:e14488, p. 1–10. doi: 10.1111/ctr.14488. Full text in Research Archive Show summary

  Cardiac allograft vasculopathy (CAV) remains a leading cause of long-term mortality after heart transplantation. Both preventive measures and treatment options are limited. This study aimed to evaluate the short-term effects of high-intensity interval training (HIT) on CAV in de novo heart transplant (HTx) recipients as assessed by optical coherence tomography (OCT). The study population was a subgroup of the 81-patient HITTS study in which HTx recipients were randomized to HIT or moderate intensity continuous training (MICT) for nine consecutive months. OCT images from baseline and 12 months were compared to assess CAV progression. The primary endpoint was defined as the change in the mean intima area. Paired OCT data were available for 56 patients (n = 23 in the HIT group and n = 33 in the MICT group). The intima area in the entire study population increased by 25% [from 1.8±1.4 mm2 to 2.3±2.0 mm2, P < .05]. The change was twofold higher in the MICT group (.6±1.2 mm2) than in the HIT group (.3±.6 mm2). However, the treatment effect of HIT was not significant (treatment effect = –.3 mm2, 95% CI [–.825 to .2 mm2] P = .29). These results suggest that early initiation of HIT compared with MICT does not attenuate CAV progression in de novo HTx recipients.

• Helseth, Ragnhild; Kleveland, Ola; Ueland, Thor; Wiseth, Rune; Damås, Jan Kristian & Broch, Kaspar [Show all 11 contributors for this article] (2021). Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction. Open heart. 8(1). doi: 10.1136/openhrt-2020-001492. Full text in Research Archive Show summary

  Objective Beyond reducing inflammation and troponin T (TnT) release, the interleukin-6 receptor antagonist tocilizumab reduces neutrophil counts in patients with non-ST segment elevation myocardial infarction (NSTEMI). It is unclear if this is related to formation of neutrophil extracellular traps (NETs), carrying inflammatory and thrombotic properties. Methods In a placebo-controlled trial, 117 patients with NSTEMI were randomised to a single dose of tocilizumab (n=58) or placebo (n=59) before coronary angiography. The NETs related markers double-stranded DNA (dsDNA), myloperoxidase–DNA (MPO–DNA) and citrullinated histone 3 (H3Cit) were measured at five consecutive time points during hospitalisation (days 1–3). Results Our major findings were: (1) H3Cit levels were significantly higher in the tocilizumab compared with the placebo group at all time points (all p<0.05), and H3Cit area under the curve (AUC) was 2.3 fold higher in the tocilizumab compared with placebo group (p<0.0001). (2) MPO–DNA and dsDNA did not differ between the groups. (3) In both treatment arms, dsDNA AUC was associated with TnT AUC. (4) Neutrophil count AUC correlated inversely to H3Cit AUC (p=0.015) in the total population. Conclusions In patients with NSTEMI, treatment with tocilizumab is associated with increased circulating H3Cit levels, suggesting that tocilizumab enhances NETosis. Further studies should clarify whether NETosis is a relevant side effect of tocilizumab. Regardless of tocilizumab, dsDNA associated with TnT release, indicating a link between extracellular nuclear material and myocardial injury.

• Samuelsen, Per-Jostein; Eggen, Anne Elise; Steigen, Terje; Wilsgaard, Tom; Kristensen, Andreas & Skogsholm, Anne [Show all 12 contributors for this article] (2021). Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT). PLOS ONE. 16(3). doi: 10.1371/journal.pone.0247358. Full text in Research Archive Show summary

  Introduction Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). Materials and methods NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008–11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3–5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models. Results The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15). Conclusions The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. Clinical trial registration Unique identifier NCT00811772; http://www.clinicaltrial.gov.

• Norekvål, Tone Merete; Allore, Heather G; Bendz, Bjørn; Bjorvatn, Cathrine; Borregaard, Britt & Brørs, Gunhild [Show all 20 contributors for this article] (2020). Rethinking rehabilitation after percutaneous coronary intervention: a protocol of a multicentre cohort study on continuity of care, health literacy, adherence and costs at all care levels (the CONCARDPCI). BMJ Open. 10(2), p. e031995–e031995. doi: 10.1136/bmjopen-2019-031995. Full text in Research Archive Show summary

  Introduction Percutaneous coronary intervention (PCI) aims to provide instant relief of symptoms, and improve functional capacity and prognosis in patients with coronary artery disease. Although patients may experience a quick recovery, continuity of care from hospital to home can be challenging. Within a short time span, patients must adjust their lifestyle, incorporate medications and acquire new support. Thus, CONCARDPCI will identify bottlenecks in the patient journey from a patient perspective to lay the groundwork for integrated, coherent pathways with innovative modes of healthcare delivery. The main objective of the CONCARDPCI is to investigate (1) continuity of care, (2) health literacy and self-management, (3) adherence to treatment, and (4) healthcare utilisation and costs, and to determine associations with future short and long-term health outcomes in patients after PCI. Methods and analysis This prospective multicentre cohort study organised in four thematic projects plans to include 3000 patients. All patients undergoing PCI at seven large PCI centres based in two Nordic countries are prospectively screened for eligibility and included in a cohort with a 1-year follow-up period including data collection of patient-reported outcomes (PRO) and a further 10-year follow-up for adverse events. In addition to PROs, data are collected from patient medical records and national compulsory registries. Ethics and dissemination Approval has been granted by the Norwegian Regional Committee for Ethics in Medical Research in Western Norway (REK 2015/57), and the Data Protection Agency in the Zealand region (REG-145-2017). Findings will be disseminated widely through peer-reviewed publications and to patients through patient organisations.

• Tegn, Nicolai Kloumann; Eek, Christian; Abdelnoor, Michael; Aaberge, Lars; Endresen, Knut & Skårdal, Rita [Show all 9 contributors for this article] (2020). Patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris randomised to an invasive versus conservative strategy: angiographic and procedural results from the After Eighty study. Open heart. doi: 10.1136/openhrt-2020-001256. Full text in Research Archive
• Bjørnstad, Johannes; Khan, Adil Mahboob; Røed-Undlien, Henriette; Bendz, Bjørn; Nygård, Ståle & Nilsen-Hoel, Tom [Show all 7 contributors for this article] (2020). Operative survival in patients with acute aortic disease in the era of newer oral anticoagulants. Open heart. 7:e001278(2), p. 1–9. doi: 10.1136/openhrt-2020-001278. Full text in Research Archive Show summary

  The aim of this study was the analysis of the risk associated with direct oral anticoagulants (DOACs) in patients undergoing non-elective operations on the proximal aorta due to aortic disease.Methods and resultsData from the department’s register of cardiac surgery was analysed retrospectively with emphasis on operative mortality. 135 non-elective operations for proximal aortic disease (October 2016 to 2018) were identified, of which 19 died during the first 90 days. DOAC use was the top-ranked risk factor in the univariate analysis with a HR of 9.6 (3.1 to 29), p=0.00007. Using a Cox proportional hazards model including the most relevant risk factors, the risk associated with DOAC use remained significant with a HR of 6.1 (1.4 to 26.3), p=0.015. We did not find increased risk associated with warfarin use.In patients undergoing non-elective operations on the proximal aorta due to aortic disease, the use of DOAC is associated with increased operative mortality.

• Otterstad, Jan Erik; Norum, Ingvild Billehaug; Ruddox, Vidar; Bendz, Bjørn; Haugaa, Kristina & Edvardsen, Thor (2020). The impact of semi-automatic versus manually adjusted assessment of global longitudinal strain in post-myocardial infarction patients. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 36(7), p. 1283–1290. doi: 10.1007/s10554-020-01826-4. Full text in Research Archive Show summary

  There are unresolved questions related to the proper use of editing the region of interest (ROI) for measurements of global longitudinal strain (GLS). The purpose of the present study was to compare the semi-automatic default GLS value by the vendor's software with manually adjusted GLS and test the impact on GLS measures with different ROI widths. We selected 25 patients post myocardial infarction treated with PCI who had excellent echocardiographic recordings after 2-5 days and 3 months. The different GLS values were assessed from these 50 analyses in three steps. The semi-automatically GLS by default ROIs was compared with manually adjusted ROIs widths selected by an expert and then with manual adjustments, but with fixed ROIs being narrow, medium and wide. Their mean age was 64 (+/- 12) years, 52% had ST elevation MI and mean LVEF was 52 (+/- 4)%. Mean default GLS was - 15.3 (+/- 2.5)% with the widest ROI level selected semi-automatically in 78% of all widths. The mean expert GLS with manually adjusted ROI was - 14.7 (+/- 2.4)%, and the medium ROI level was selected by the expert in 85% of all examinations. The mean adjusted GLS, but with fixed ROIs widths was - 15.0 (+/- 2.5%)% with narrow ROI, - 14.7 (+/- 2.6)% with medium and - 13.5 (+/- 2.3)% with wide ROI width (p < 0.001 vs. default GLS). The Intra Class Coefficient Correlation between default and manually adjusted expert GLS was 0.93 (p < 0.001). The difference between the default and the manually adjusted expert GLS was neglectable. These findings may represent a simplification of the assessment of GLS that might increase its use in clinical practice. The GLS measurements with a fixed wide ROIs were significantly different from the expert measurements and indicate that a wide ROI should be avoided

• Lunde, Ngoc Dieu Nguyen; Gregersen, Ida; Ueland, Thor; Shetelig, Christian; Holm, Sverre & Kong, Xiang Yi [Show all 31 contributors for this article] (2019). Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages. Atherosclerosis. ISSN 0021-9150. p. 1–9. doi: 10.1016/j.atherosclerosis.2019.12.008. Full text in Research Archive Show summary

  Background and aims We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events. Methods Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting were used to study expression, while localization was visualized by immunohistochemistry. Results In the SUMMIT Malmö cohort (n = 339 with or without type 2 diabetes and/or cardiovascular disease [CVD], and 64 healthy controls), the levels of circulating legumain were associated with the presence of CVD in non-diabetics, with no relation to outcome. In symptomatic carotid plaques and in samples from both coronary and intracerebral thrombi obtained during acute cardiovascular events, legumain was co-localized with macrophages in the same regions as platelets. In vitro, legumain was shown to be present in and released from platelets upon activation. In addition, THP-1 macrophages exposed to releasate from activated platelets showed increased legumain expression. Interestingly, primary peripheral blood mononuclear cells stimulated with recombinant legumain promoted anti-inflammatory responses. Finally, in a STEMI population (POSTEMI; n = 272), patients had significantly higher circulating legumain before and immediately after percutaneous coronary intervention compared with healthy controls (n = 67), and high levels were associated with improved outcome. Conclusions Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.

• Munkhaugen, John; Ruddox, Vidar; Halvorsen, Sigrun; Dammen, Toril; Fagerland, Morten & Hernæs, Kjersti Helene [Show all 23 contributors for this article] (2019). BEtablocker Treatment After acute Myocardial Infarction in revascularized patients without reduced left ventricular ejection fraction (BETAMI): Rationale and design of a prospective, randomized, open, blinded end-point study. American Heart Journal. ISSN 0002-8703. 208, p. 37–46. doi: 10.1016/j.ahj.2018.10.005. Full text in Research Archive Show summary

  Background - Current guidelines on the use of β-blockers in post–acute myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF) are based on studies before the implementation of modern reperfusion and secondary prevention therapies. It remains unknown whether β-blockers will reduce mortality and recurrent MI in contemporary revascularized post-MI patients without reduced LVEF. Design - BETAMI is a prospective, randomized, open, blinded end point multicenter study in 10,000 MI patients designed to test the superiority of oral β-blocker therapy compared to no β-blocker therapy. Patients with LVEF ≥40% following treatment with percutaneous coronary intervention or thrombolysis and/or no clinical signs of heart failure are eligible to participate. The primary end point is a composite of all-cause mortality or recurrent MI obtained from national registries over a mean follow-up period of 3 years. Safety end points include rates of nonfatal MI, all-cause mortality, ventricular arrhythmias, and hospitalizations for heart failure obtained from hospital medical records 30 days after randomization, and from national registries after 6 and 18 months. Key secondary end points include recurrent MI, heart failure, cardiovascular and all-cause mortality, and clinical outcomes linked to β-blocker therapy including drug adherence, adverse effects, cardiovascular risk factors, psychosocial factors, and health economy. Statistical analyses will be conducted according to the intention-to-treat principle. A prespecified per-protocol analysis (patients truly on β-blockers or not) will also be conducted. Conclusions - The results from the BETAMI trial may have the potential of changing current clinical practice for treatment with β-blockers following MI in patients without reduced LVEF. EudraCT number 2018-000590-75.

• Anstensrud, Anne Kristine; Woxholt, Sindre; Sharma, Kapil Kishore; Broch, Kaspar; Bendz, Bjørn & Aakhus, Svend [Show all 19 contributors for this article] (2019). Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI). Open heart. 6(2), p. 1–9. doi: 10.1136/openhrt-2019-001108. Full text in Research Archive Show summary

  Introduction Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the ASSessing the effect of Anti-IL-6 treatment in MI (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI). Methods and analysis The ASSAIL-MI trial is a randomised, double blind, placebo-controlled trial, conducted at three high-volume percutaneous coronary intervention (PCI) centres in Norway. 200 patients with first-time STEMI presenting within 6 hours of the onset of chest pain will be randomised to receive tocilizumab or matching placebo prior to PCI. The patients are followed-up for 6 months. The primary endpoint is the myocardial salvage index measured by cardiac MRI (CMR) 3–7 days after the intervention. Secondary endpoints include final infarct size measured by CMR and plasma markers of myocardial necrosis. Efficacy and safety assessments during follow-up include blood sampling, echocardiography and CMR. Ethics and dissemination Based on previous experience the study is considered feasible and safe. If tocilizumab increases myocardial salvage, further endpoint-driven multicentre trials may be initiated. The ASSAIL-MI trial has the potential to change clinical practice in patients with STEMI. Registration Clinicaltrials.gov, identifier NCT03004703.

• Kvisvik, Brede Alexander; Aagaard, Erika Nerdrum; Mørkrid, Lars; Røsjø, Helge; Lyngbakken, Magnus & Smedsrud, Marit Kristine [Show all 11 contributors for this article] (2019). Mechanical dispersion as a marker of left ventricular dysfunction and prognosis in stable coronary artery disease. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 35, p. 1265–1275. doi: 10.1007/s10554-019-01583-z. Full text in Research Archive Show summary

  Assessment of global longitudinal strain (GLS) is superior to ejection fraction (EF) in the evaluation of left ventricular (LV) function in patients with stable coronary artery disease (CAD). However, the role of mechanical dispersion (MD) in this context remains unresolved. We aimed to evaluate the potential role of MD as a marker of LV dysfunction and long-term prognosis in stable CAD. EF, GLS and MD were assessed in 160 patients with stable CAD, 1 year after successful coronary revascularization. Serum levels of high-sensitivity cardiac troponin I (hs-cTnI) and amino-terminal pro B-type natriuretic peptide (NT-proBNP) were quantified as surrogate markers of LV dysfunction. The primary endpoint was defined as all-cause mortality, the secondary endpoint was defined as the composite of all-cause mortality and hospitalization for acute myocardial infarction or heart failure during follow-up. Whereas no associations between EF and the biochemical markers of LV function were found, both GLS and MD correlated positively with increasing levels of hs-cTnI (R = 0.315, P < 0.001 and R = 0.442, P < 0.001, respectively) and NT-proBNP (R = 0.195, P = 0.016 and R = 0.390, P < 0.001, respectively). Median MD was 46 ms (interquartile range [IQR] 37–53) and was successfully quantified in 96% of the patients. During a median follow-up of 8.4 (IQR 8.2–8.8) years, 14 deaths and 29 secondary events occurred. MD was significantly increased in non-survivors, and provided incremental prognostic value when added to EF and GLS. NT-proBNP was superior to the echocardiographic markers in predicting adverse outcomes. MD may be a promising marker of LV dysfunction and adverse prognosis in stable CAD.

• Bendz, Bjørn; Gude, Einar; Ragnarsson, Asgrimur; Endresen, Knut; Aaberge, Lars & Geiran, Odd [Show all 7 contributors for this article] (2019). Intra-aortic balloon pump in acute chest pain and cardiogenic shock - a long-term follow-up. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 53(6), p. 337–341. doi: 10.1080/14017431.2019.1657938. Full text in Research Archive
• Buer, Øystein; Kalfoss, Mary; Weisæth, Lars; Stifoss-Hanssen, Hans & Bendz, Bjørn (2018). Near- Death Experience Features During Various Phases Related to Unconsciousness: An Exploratory Study of Norwegian Hospital Patients. Journal of Near-Death Studies. ISSN 0891-4494. 36(4), p. 219–231. doi: 10.17514/JNDS-2018-36-4-p219-231. Full text in Research Archive
• Kleveland, Ola; Ueland, Thor; Kunszt, Gabor; Bratlie, Marte; Yndestad, Arne & Broch, Kaspar [Show all 18 contributors for this article] (2018). Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction. International Journal of Cardiology. ISSN 0167-5273. 271, p. 1–7. doi: 10.1016/j.ijcard.2018.04.136. Full text in Research Archive Show summary

  Aim To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI). Methods 117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive points in time during hospitalisation, and at follow-up after 3 and 6 months. Cytokines (n = 27) were analysed with a multiplex cytokine assay. Results Using a mixed between-within subjects analysis of variance, we observed a significant (p < 0.001) between-group difference in changes for interferon gamma-inducible protein (IP-10) and macrophage inflammatory protein-1β (MIP-1β), due to significant increases in the tocilizumab group during hospitalisation (i.e., IP-10 median change from baseline during hospitalisation (mΔ), placebo: 3 (−60, 68) pg/ml vs tocilizumab: 209 (69, 335) pg/ml; MIP-1β mΔ, placebo: 5 (−2, 12) pg/ml vs tocilizumab: 39 (24, 63) pg/ml). MIP-1β was inversely correlated to troponin T(r = −0.28, p < 0.05) and neutrophils (r = −0.32, p < 0.05) in the tocilizumab group. In contrast, tocilizumab had only modest or no effects on the other examined cytokines. Conclusions Tocilizumab led to a selective and substantial increase in IP-10 and MIP-1β during the acute phase of NSTEMI, with no or only minor effects on the other measured cytokines. ClinicalTrials.gov, NCT01491074.

• Hauge, Karoline Kråkmo; Dahle, Gry; Bendz, Bjørn; Halvorsen, Per Steinar; Abdelnoor, Michael & Mollnes, Tom Eirik [Show all 7 contributors for this article] (2018). Reduced inflammatory response by transcatheter, as compared to surgical aortic valve replacement. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 52(1), p. 43–50. doi: 10.1080/14017431.2017.1416157. Full text in Research Archive Show summary

  Objectives. The inflammatory response to on-pump cardiac surgery is well known. Systemic inflammatory response syndrome after transcatheter valve implantation (TAVI) has been reported. The objective of this study was to study the inflammatory response during TAVI, and compare with the response during surgical aortic valve replacement. Methods. Eighteen patients undergoing transcatheter implantation, either by a transfemoral (n = 9) or transaortal (n = 9) approach were compared with eighteen patients admitted for surgical replacement. Blood samples per- and postoperatively were analysed for C3bc, terminal complement complex, myeloperoxidase, macrophage inflammatory protein-1β, monocyte chemo-attractant peptide-1, eotaxin, IL-6 and troponin-T. All markers were measured at defined time points and the areas under the curve were compared. Results. Activation of complement, granulocytes, monocytes and eosinophils were significantly lower in the transcatheter group as compared to the surgical group (<0.01). There was no difference in generation of troponin T and IL-6. A small difference in complement activation was observed between the transfemoral and transaortal placement of TAVI. There was no significant difference in clinical outcomes between the TAVI and surgical groups. Discussion. Activation and release of inflammatory markers was significantly less during with TAVI as compared to SAVR, particularly for markers associated with extracorporeal circulation. TAVI and SAVR generated the same degree of IL-6 and troponin T, indicating that the burden on the myocardial tissue was the same.

• Orrem, Hilde Lang; Nilsson, Per; Pischke, Søren Erik; Kleveland, Ola; Yndestad, Arne & Ekholt, Karin [Show all 18 contributors for this article] (2018). IL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarction. Frontiers in Immunology. 9. doi: 10.3389/fimmu.2018.02035. Full text in Research Archive Show summary

  Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. Materials and Methods: NSTEMI patients were randomized to one dose of tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, n = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, n = 21) and ST-elevation myocardial infarction (STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively. Results: Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (p < 0.001) and substantially (>50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (p < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (p < 0.05) and C3aR in the NSTE-ACS group (p < 0.05). Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients.

• Pettersen, Trond Røed; Fridlund, Bengt Gotthard Anton; Bendz, Bjørn; Nordrehaug, Jan Erik; Rotevatn, Svein & Schjøtt, Jan [Show all 7 contributors for this article] (2018). Challenges adhering to a medication regimen following first-time percutaneous coronary intervention: A patient perspective. International Journal of Nursing Studies. ISSN 0020-7489. 88, p. 16–24. doi: 10.1016/j.ijnurstu.2018.07.013. Full text in Research Archive Show summary

  Background Percutaneous coronary intervention is the most common therapeutic intervention for patients with narrowed coronary arteries due to coronary artery disease. Although it is known that patients with coronary artery disease often do not adhere to their medication regimen, little is known about what patients undergoing percutaneous coronary interventions find challenging in adhering to their medication regimen after hospital discharge. Objectives To explore patients’ experiences in adhering to medications following early post-discharge after first-time percutaneous coronary intervention. Design An abductive qualitative approach was used to conduct in-depth interviews of patients undergoing first-time percutaneous coronary intervention. Settings Participants were recruited from a single tertiary university hospital, which services a large geographical area in western Norway. Patients fulfilling the inclusion criteria were identified through the Norwegian Registry for Invasive Cardiology. Participants Participants were patients aged 18 years or older who had their first percutaneous coronary intervention six to nine months earlier, were living at home at the time of study inclusion, and were prescribed dual antiplatelet therapy. Patients who were cognitively impaired, had previously undergone cardiac surgery, and/or were prescribed anticoagulation therapy with warfarin or novel oral anticoagulants were excluded. Purposeful sampling was used to include patients of different gender, age, and geographic settings. Twenty-two patients (12 men) were interviewed between December 2016 and April 2017. Methods Face-to-face semi-structured interviews were conducted, guided by a set of predetermined open-ended questions to gather patient experiences on factors relating to medication adherence or non-adherence. Transcribed interviews were analysed by qualitative content analysis. Findings Patients failed to adhere to their medication regimen for several reasons; intentional and unintentional reasons, multifaceted side effects from heart medications, scepticism towards generic drugs, lack of information regarding seriousness of disease after percutaneous coronary intervention, psychological impact of living with coronary artery disease, and these interacted. There were patients who felt that the medication information they received from physicians and nurses was uninformative and inadequate. Side effects from heart medications were common, ranging from minor ones to more disabling side effects, such as severe muscle and joint pain and fatigue. Patients found well established medication taking routines and aids to be necessary, and these improved adherence. Conclusion Patients undergoing first-time percutaneous coronary intervention face multiple, interacting challenges in trying to adhere to prescribed medications following discharge. This study highlights the need for a more structured follow-up care in order to improve medication adherence and to maximise their self-care abilities.

• Tegn, Nicolai Kloumann; Abdelnoor, Michael; Aaberge, Lars; Ranhoff, Anette Hylen; Endresen, Knut & Gjertsen, Erik [Show all 9 contributors for this article] (2018). Health-related quality of life in older patients with acute coronary syndrome randomised to an invasive or conservative strategy. The After Eighty randomised controlled trial. Age and Ageing. ISSN 0002-0729. 47(1), p. 42–47. doi: 10.1093/ageing/afx121. Full text in Research Archive
• Ruddox, Vidar; Otterstad, Jan Erik; Atar, Dan; Bendz, Bjørn & Edvardsen, Thor (2018). In Current Clinical Practice, after Percutaneous Coronary Intervention for Acute Myocardial Infarction, Are β-Blockers Prescribed for Heart Failure or as Secondary Prevention? A Pilot Study. Cardiology. ISSN 0008-6312. 140(3), p. 152–154. doi: 10.1159/000490656. Full text in Research Archive
• Holte, Espen; Kleveland, Ola; Ueland, Thor; Kunszt, Gabor; Bratlie, Marte & Broch, Kaspar [Show all 14 contributors for this article] (2017). Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction. Heart. ISSN 1355-6037. 103(19), p. 1521–1527. doi: 10.1136/heartjnl-2016-310875. Full text in Research Archive
• Yardley, Marianne; Gullestad, Lars; Bendz, Bjørn; Bjørkelund, Elisabeth; Rolid, Katrine & Arora, Satish [Show all 7 contributors for this article] (2017). Long-term effects of high-intensity interval training in heart transplant recipients: A 5-year follow-up study of a randomized controlled trial. Clinical Transplantation. ISSN 0902-0063. 31(1). doi: 10.1111/ctr.12868. Full text in Research Archive
• Kvisvik, Brede Alexander; Mørkrid, Lars; Røsjø, Helge; Småstuen, Milada Cvancarova; Rowe, Alexander D. & Eek, Christian [Show all 9 contributors for this article] (2017). High-Sensitivity Troponin T vs I in Acute Coronary Syndrome: Prediction of Significant Coronary Lesions and Long-term Prognosis. Clinical Chemistry. ISSN 0009-9147. 63(2), p. 552–562. doi: 10.1373/clinchem.2016.261107. Full text in Research Archive
• Kvisvik, Brede Alexander; Mørkrid, Lars; Røsjø, Helge; Småstuen, Milada C; Rowe, Alexander D. & Eek, Christian [Show all 9 contributors for this article] (2017). Troponinas de alta sensibilidad T vs I en Sindrome Coronario Agudo: Prediccion de lesiones coronarias significativas y pronostico a largo plazo. Acta Bioquimica Clinica Latinoamericana. ISSN 0325-2957. 51(3), p. 395–407. Full text in Research Archive
• Auensen, Andreas; Hussain, Amjad; Bendz, Bjørn; Aaberge, Lars; Falk, Ragnhild Sørum & Walle-Hansen, Marte [Show all 12 contributors for this article] (2017). Morbidity outcomes after surgical aortic valve replacement. Open heart. 4(1). doi: 10.1136/openhrt-2017-000588. Full text in Research Archive Show summary

  Objective In patients with mild to moderate operative risk, surgical aortic valve replacement (SAVR) is still the preferred treatment for patients with severe symptomatic aortic stenosis (AS). Aiming to broaden the knowledge of postsurgical outcomes, this study reports a broad set of morbidity outcomes following surgical intervention. Methods Our cohort comprised 442 patients referred for severe AS; 351 had undergone SAVR, with the remainder (91) not operated on. All patients were evaluated using the 6-minute walk test (6MWT), were assigned a New York Heart Association class (NYHA) and Canadian Cardiovascular Society class (CCS), with additional scores for health-related quality of life (HRQoL), cognitive function (Mini-Mental State Examination (MMSE)) and myocardial remodelling (at inclusion and at 1-year follow-up). Adverse events and mortality were recorded. Results Three-year survival after SAVR was 90.0%. SAVR was associated with an improved NYHA class, CCS score and HRQoL, and provoked reverse ventricular remodelling. The 6MWT decreased, while the risks of major adverse cardiovascular events (death, non-fatal stroke/transient ischaemic attack or myocardial infarction) and all-cause hospitalisation (incidence rate per 100 patient-years) were 13.5 and 62.4, respectively. The proportion of cognitive disability measured by MMSE increased after SAVR from 3.2% to 8.8% (p=0.005). Proportion of patients living independently at home, having attained NYHA class I, was met by 49.1% at 1 year. Unoperated individuals had a poor prognosis in terms of any outcome. Conclusion This study provides knowledge of outcomes beyond what is known about the mortality benefit after SAVR to provide insight into the morbidity burden of modern-day SAVR.

• Eidet, Jo; Dahle, Gry; Bugge, Jan F; Bendz, Bjørn; Rein, Kjell Arne & Aaberge, Lars [Show all 10 contributors for this article] (2016). Intraoperative improvement in left ventricular peak systolic velocity predicts better short-term outcome after transcatheter aortic valve implantation. Interactive Cardiovascular and Thoracic Surgery. ISSN 1569-9293. 22(1), p. 5–12. doi: 10.1093/icvts/ivv277. Full text in Research Archive
• Tegn, Nicolai Kloumann; Abdelnoor, Michael; Aaberge, Lars; Endresen, Knut; Smith, Pål & Aakhus, Svend [Show all 11 contributors for this article] (2016). Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): An open-label randomised controlled trial. The Lancet. ISSN 0140-6736. 387(10023), p. 1057–1065. doi: 10.1016/S0140-6736(15)01166-6. Full text in Research Archive
• Bønaa, Kaare; Mannsverk, Jan Torbjørn; Wiseth, Rune; Aaberge, Lars; Myreng, Yngvar & Nygård, Ottar [Show all 25 contributors for this article] (2016). Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease. New England Journal of Medicine. ISSN 0028-4793. 375(13), p. 1242–1252. doi: 10.1056/NEJMoa1607991. Full text in Research Archive
• Eidet, Jo; Dahle, Gry; Bugge, Jan F; Bendz, Bjørn; Rein, Kjell Arne & Aaberge, Lars [Show all 10 contributors for this article] (2016). Long-term outcomes after transcatheter aortic valve implantation: The impact of intraoperative tissue Doppler echocardiography. Interactive Cardiovascular and Thoracic Surgery. ISSN 1569-9293. 23(3), p. 403–409. doi: 10.1093/icvts/ivw159. Full text in Research Archive
• Kleveland, Ola; Kunszt, Gabor; Bratlie, Marte; Ueland, Thor; Broch, Kaspar & Holte, Espen [Show all 15 contributors for this article] (2016). Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial. European Heart Journal. ISSN 0195-668X. 37(30), p. 2406–2413. doi: 10.1093/eurheartj/ehw171. Full text in Research Archive Show summary

  Aims Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia–reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI). Methods and results In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated with percutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up. Conclusion Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients.

• Eidet, Jo; Dahle, Gry; Bugge, Jan F; Bendz, Bjørn; Rein, Kjell Arne & Fosse, Erik [Show all 8 contributors for this article] (2015). Transcatheter aortic valve implantation and intraoperative left ventricular function: A myocardial tissue Doppler imaging study. Journal of Cardiothoracic and Vascular Anesthesia. ISSN 1053-0770. 29(1), p. 115–120. doi: 10.1053/j.jvca.2014.10.016. Full text in Research Archive
• Smedsrud, Marit Kristine; Gravning, Jørgen A.; Omland, Torbjørn; Eek, Christian; Mørkrid, Lars & Skulstad, Helge [Show all 10 contributors for this article] (2015). Sensitive cardiac troponins and N-terminal pro-B-type natriuretic peptide in stable coronary artery disease: correlation with left ventricular function as assessed by myocardial strain. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 31(5), p. 967–973. doi: 10.1007/s10554-015-0646-6. Full text in Research Archive
• Halvorsen, Bente; Smedbakken, Linda Merete; Michelsen, Annika; Skjelland, Mona; Bjerkeli, Vigdis & Sagen, Ellen Lund [Show all 12 contributors for this article] (2014). Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of CXCL13. Atherosclerosis. ISSN 0021-9150. 234(2), p. 352–359. doi: 10.1016/j.atherosclerosis.2014.03.021. Full text in Research Archive
• Aakre, Kristin; Rotevatn, Svein; Hagve, Tor-Arne; Bendz, Bjørn; Landaas, Sverre & Trovik, Thor (2013). Nasjonale anbefalinger for tolkning av troponinverdier ved diagnostikk av akutt hjerteinfarkt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.13.0647. Full text in Research Archive
• Gullestad, Lars; Ørn, Stein; Dickstein, Kenneth; Eek, Christian; Edvardsen, Thor & Aakhus, Svend [Show all 14 contributors for this article] (2013). Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction. International Journal of Cardiology. ISSN 0167-5273. 168(1), p. 212–218. doi: 10.1016/j.ijcard.2012.09.092. Full text in Research Archive Show summary

  BACKGROUND: Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function. METHODS: Sixty-two patients with acute MI treated by percutaneous coronary intervention, with depressed LV ejection fraction (LVEF) were randomized in a double-blinded fashion to IVIg as induction therapy and thereafter as monthly infusions or placebo for 26weeks. The primary end point was changes in LVEF from baseline to 6months as assessed by MRI. RESULTS: Our main findings were: (i) LVEF increased significantly from 38±10 (mean±SD) to 45±13% after IVIg and from 42±9 to 49±12% after placebo with no difference between the groups. (ii) The scar area decreased significantly by 3% and 5% in the IVIg and placebo group, respectively, with no difference between the groups. (iii) During the induction therapy (baseline to day 5), IVIg induced both inflammatory (e.g., increase in tumor necrosis factor α and monocyte chemoattractant protein-1) and anti-inflammatory (e.g., increase in interleukin-10 and decrease in leukocyte counts) variables, but during maintenance therapy there were no differences in changes of inflammatory mediators between IVIg and placebo. CONCLUSIONS: IVIg therapy after ST elevation MI managed by primary PCI does not affect LV remodeling or function. This illustrates the challenges of therapeutic intervention directed against the cytokine network, to prevent post-MI remodeling.

• Sarvari, Sebastian Imre; Haugaa, Kristina; Zahid, Wasim; Bendz, Bjørn; Aakhus, Svend & Aaberge, Lars [Show all 7 contributors for this article] (2013). Layer-Specific Quantification of Myocardial Deformation by Strain Echocardiography May Reveal Significant CAD in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. Journal of the American College of Cardiology. ISSN 0735-1097. 6(5), p. 535–544. doi: 10.1016/j.jcmg.2013.01.009. Full text in Research Archive
• Gravning, Jørgen A.; Smedsrud, Marit Kristine; Omland, Torbjørn; Eek, Christian; Skulstad, Helge & Aaberge, Lars [Show all 10 contributors for this article] (2013). Sensitive troponin assays and N-terminal pro-B-type natriuretic peptide in acute coronary syndrome: Prediction of significant coronary lesions and long-term prognosis. American Heart Journal. ISSN 0002-8703. 165(5), p. 716–724. doi: 10.1016/j.ahj.2013.02.008. Full text in Research Archive
• Meen, Øystein; Brosstad, Frank Roger; Liestøl, Knut; Kunszt, Gabor; Bendz, Bjørn & Wettergreen, Marianne [Show all 9 contributors for this article] (2012). Sequential ADP-stimulated light transmission and multiple electrode aggregometry in patients taking aspirin and clopidogrel after non ST-elevation myocardial infarction. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 72(4), p. 318–325. doi: 10.3109/00365513.2012.666565. Full text in Research Archive
• Erikssen, Gunnar; Liestøl, Knut; Gullestad, Lars; Haugaa, Kristina; Bendz, Bjørn & Amlie, Jan Peder (2012). The Terminal Part of the QT Interval (T peak to T end): A Predictor of Mortality after Acute Myocardial Infarction. Annals of Noninvasive Electrocardiology. ISSN 1082-720X. 17(2), p. 85–94. doi: 10.1111/j.1542-474X.2012.00493.x. Full text in Research Archive
• Arora, Satish; Ueland, Thor; Wennerblom, Bertil; Sigurdadottir, Vilborg; Eiskjær, Hans & Bøtker, Hans Erik [Show all 16 contributors for this article] (2011). Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial. Transplantation. ISSN 0041-1337. 92(2), p. 235–243. doi: 10.1097/TP.0b013e31822057f1. Full text in Research Archive
• Aasheim, Anders; Bendz, Bjørn; Mangschau, Arild; Wik, Lars; Steen, Petter Andreas & Braarud, Anne-Cathrine (2003). Prehospitalt EKG forkorter tiden til utblokking ved akutt hjerteinfarkt i Oslo. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. Full text in Research Archive

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• Pettersen, Trond Røed; Schjøtt, Jan Didrik; Allore, Heather; Bendz, Bjørn; Borregard, Britt & Fridlund, Bengt [Show all 14 contributors for this article] (2023). Sex differences in incidence of self-reported adverse drug reactions after percutaneous coronary intervention. European Heart Journal. ISSN 0195-668X. 44. Full text in Research Archive
• Aarskog, Nikolai Ravn; Iuell, Ragnhild Skari; Dunlop, Oona Borghild; Sevre, Knut; Bendz, Bjørn & Rostrup, Morten (2023). Neuropsychological function is associated with hypocapnia at simulated high altitude. Acta Physiologica. ISSN 1748-1708. doi: 10.1111/apha.13949. Full text in Research Archive
• Pettersen, Trond Røed; Schjøtt, Jan Didrik; Allore, Heather; Bendz, Bjørn; Fridlund, Bengt & Larsen, Alf Inge [Show all 10 contributors for this article] (2022). Informing patients about potential adverse drug reactions after percutaneous coronary intervention reduces the occurrence of self-reported adverse drug reactions. Full text in Research Archive
• Pettersen, Trond Røed; Allore, Heather; Bendz, Bjørn; Borregaard, Britt; Fridlund, Bengt & Ghaderi, Sara [Show all 13 contributors for this article] (2021). Communication of Potential Adverse Drug Reactions in Patients Undergoing Percutaneous Coronary Intervention. Circulation. ISSN 0009-7322. 144. Full text in Research Archive
• Pettersen, Trond Røed; Schjøtt, Jan Didrik; Bendz, Bjørn; Borregaard, Britt; Fridlund, Bengt & Larsen, Alf Inge [Show all 10 contributors for this article] (2021). Perceptions of efficacy and safety of generic medicines in patients after percutaneous coronary intervention. European Heart Journal. ISSN 0195-668X. 42. doi: 10.1093/eurhaertj/ehab724.3020. Full text in Research Archive
• Bjørnstad, Johannes & Bendz, Bjørn (2020). Periprocedural myocardial injury in the EXCEL trial. European Heart Journal. ISSN 0195-668X. 41(17), p. 1703–1703. doi: 10.1093/eurheartj/ehaa182. Full text in Research Archive
• Pettersen, Trond Røed; Schjøtt, Jan; Allore, Heather; Bendz, Bjørn; Larsen, Alf Inge & Nordrehaug, Jan E [Show all 9 contributors for this article] (2019). Patients’ Perceptions of Generic Drugs After Percutaneous Coronary Intervention: A Multicentre Cohort Study. Circulation. ISSN 0009-7322. 140. Full text in Research Archive
• Pettersen, Trond Røed; Schjøtt, Jan; Bendz, Bjørn; Fridlund, Bengt; Nordrehaug, Jan Erik & Rotevatn, Svein [Show all 7 contributors for this article] (2018). Discontinuation of drug treatment due to side effects after first-time percutaneous coronary intervention: a patient perspective. Full text in Research Archive
• Buer, Øystein; Kalfoss, Mary; Weisæth, Lars & Bendz, Bjørn (2016). Kartlegging av nær døden-opplevelser. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(23/24), p. 1968–1969. doi: 10.4045/tidsskr.16.0953. Full text in Research Archive
• Tegn, Nicolai Kloumann; Abdelnoor, Michael; Aaberge, Lars; Endresen, Knut; Gullestad, Lars & Bendz, Bjørn (2016). Re: Over 80 år og hjerteinfarkt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(16), p. 1324–1325. doi: 10.4045/tidsskr.16.0685. Full text in Research Archive
• Tegn, Nicolai Kloumann; Abdelnoor, Michael; Aaberge, Lars; Endresen, Knut & Bendz, Bjørn (2016). Invasive strategy in acute coronary syndrome - Authors' reply. The Lancet. ISSN 0140-6736. 387(10037), p. 2504–2504. doi: 10.1016/S0140-6736(16)30673-0. Full text in Research Archive
• Aaberge, Lars; Bendz, Bjørn; Beitnes, Jan Otto & Busund, Rolf (2015). TAVI - kateterbasert behandling av aortastenose. In Wiseth, Rune; Forfang, Kolbjørn & Istad, Helge (Ed.), Kardiologi, Klinisk veileder. Gyldendal Akademisk. ISSN 9788205484580. p. 265–271. Full text in Research Archive

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