Peder Langeland Myhre

• Walser, Amely; Clerc, Olivier F.; Mork, Constantin; Flammer, Andreas J.; Myhre, Peder Langeland & Schwotzer, Rahel [Show all 10 contributors for this article] (2026). Automated echocardiographic measurements for longitudinal monitoring of ATTR cardiomyopathy: agreement and repeatability analysis. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. doi: 10.1007/s10554-026-03835-1. Full text in Research Archive
• Helseth, Ragnhild Merckoll; BADROUCHI, SAMARRA; CRUZ-SOLBES, ANA SOFIA; MARTI-CASTELLOTE, PABLO; CLAGGETT, BRIAN L. & YOUNG, MICHELLE [Show all 15 contributors for this article] (2026). Large Language Model Recommendations for Heart Failure Therapy. Journal of Cardiac Failure. ISSN 1071-9164. p. 1–6. doi: 10.1016/j.cardfail.2026.08.004. Full text in Research Archive
• Bruun, Lina Dorthea; Andersen, Geir Øystein; Myhre, Peder Langeland; Halvorsen, Sigrun; Kringen, Marianne Kristiansen & Hansen, Charlotte Holst [Show all 8 contributors for this article] (2026). Prognostic relevance of β1-adrenergic receptor polymorphisms on cardiovascular outcome in patients treated with metoprolol after acute myocardial infarction - an observational study. European Journal of Clinical Pharmacology. ISSN 0031-6970. 82(7). doi: 10.1007/s00228-026-04091-x. Full text in Research Archive
• Hage, Camilla; Mang, Annika; Daubert, Jean Claude; Donal, Erwan; Myhre, Peder Langeland & Linde, Cecilia [Show all 7 contributors for this article] (2026). Novel biomarkers distinguish heart failure with preserved vs reduced ejection fraction. ESC Heart Failure. 13(3). doi: 10.1093/eschf/xvaf011. Full text in Research Archive
• Hage, Camilla; Mang, Anika; Daubert, Jean Claude; Donal, Erwan; Myhre, Peder Langeland & Linde, Cecilia [Show all 7 contributors for this article] (2026). Total NT-proBNP in heart failure with preserved vs reduced ejection fraction. International Journal of Cardiology. ISSN 0167-5273. 458. doi: 10.1016/j.ijcard.2026.134554. Full text in Research Archive
• Braanaas, Karoline Svensen; Dammen, Toril; Fagerland, Morten; Husebye, Einar; Leinaas, Amund & Schirmer, Henrik [Show all 10 contributors for this article] (2026). Individually tailored monitoring at home after hospitalization for HEART failure (IT-HEART): design and baseline characteristics of a randomized clinical trial. Heart Failure Reviews. ISSN 1382-4147. 31(1). doi: 10.1007/s10741-026-10635-1. Full text in Research Archive Show summary

  Telemonitoring has emerged as a promising alternative to conventional heart failure (HF) management, but randomized trials show conflicting results, and data from high-risk populations with frailty, is scarce. The Individually Tailored monitoring at home after HEART failure (IT-HEART) trial evaluates whether a non-invasive multi-component telemonitoring program improves outcomes in HF patients after HF-hospitalization. The aim of this study is to describe flow of patients and baseline characteristics of the IT-HEART trial population. This multicenter, open-label, blinded-endpoint trial randomized HF patients to either written information and a standardized self-treatment plan (Control) or HF education, a personalized self-treatment plan, and three months of home telemonitoring (Intervention). The primary endpoint is the total number of HF hospitalizations or cardiovascular death. Of 1016 consecutively screened patients, 200 (19.7%) were randomized. At baseline, median age was 78 (IQR 70–83) years, and 29.5% were women. Participants were multimorbid (median 6 diagnoses) with a median Clinical Frailty Scale score 4 (IQR 4–5). Median score of the European Heart Failure Self-care Behaviour Scale was 53 (IQR 35–67), and 75.5% had inadequate self-care. Self-rated knowledge on HF management was 3 (IQR 0–7) on a 0–10 Likert scale. Only 35.5% (n = 71) weighed themselves weekly whereas 1% (n = 2) reported having a self-care plan. In conclusion, patients enrolled after a recurrent HF hospitalization were multimorbid and frail, and scored low on self‑care and health literacy. The IT-HEART intervention is targeted to these factors and has the potential to improve clinical and patient‑reported outcomes, and costs.

• Abramov, Dmitry; Minhas, Abdul Mannan Khan; Alexy, Tamas; Guimaraes, Patricia Oliveira; Lainscak, Mitja & Myhre, Peder Langeland (2026). You evaluation of the PARACHUTE-HF trial: role of sacubitril/valsartan compared to enalapril on outcomes in patients with heart failure from Chagas’ disease. Heart Failure Reviews. ISSN 1382-4147. 31(1). doi: 10.1007/s10741-026-10617-3. Full text in Research Archive
• Kobayashi, Masatake; Bozkurt, Biykem; Myhre, Peder Langeland; Azor, Juan Carlos Lopez; Guzik, Mateusz & Iwanek, Gracjan [Show all 15 contributors for this article] (2025). Urinary markers in heart failure – types, timing and thresholds. European Journal of Heart Failure expert consensus document. European Journal of Heart Failure. ISSN 1388-9842. 27(11), p. 2372–2396. doi: 10.1002/ejhf.70079. Full text in Research Archive Show summary

  Several urinary markers reflect disease severity and have the potential to support the management of heart failure (HF). Collecting urine samples is easy and inexpensive, and urine sample composition can be altered not only by underlying kidney impairments (i.e. filtration barrier damage and tubular injury) but also via neurohormonal and inflammatory activation, ageing, comorbidities, other medical conditions and pharmacological interventions. For instance, urinary sodium may help to predict the response to loop diuretic therapy in acute HF, while albuminuria is used as a risk marker and therapeutic target for the progression of cardiovascular and kidney diseases in chronic HF, especially when accompanied by kidney disease. However, these markers remain underutilized in clinical practice. This review paper underscores the role of urinary markers in HF, with a specific focus on: (i) the pathophysiologic mechanisms underlying urinary marker excretion, (ii) the prognostic values of urinary markers across diverse HF phenotypes and non-cardiovascular comorbidities (i.e. chronic kidney disease and diabetes), (iii) the impact of medical therapies on urinary markers, and (iv) existing knowledge gaps that challenge their implementation in clinical practice. The recommendations are aligned with current guidelines, evidence, and expert consensus.

• Jortveit, Jarle; Myhre, Peder L; Andersen, Geir Øystein & Halvorsen, Sigrun (2025). Cardiogenic shock as a complication of acute myocardial infarction: a nationwide cohort study. European Heart Journal: Acute Cardiovascular Care. ISSN 2048-8726. p. 1–11. doi: 10.1093/ehjacc/zuaf118. Full text in Research Archive Show summary

  Abstract Aims Cardiogenic shock (CS) is a life-threatening complication of acute myocardial infarction (AMI). This study aimed to assess real-world incidence, characteristics, and outcomes in relation to age among patients with AMI complicated by CS (AMI-CS) compared with those without CS in a nationwide cohort. Methods and results Cohort study of all patients <85 years with AMI registered in the Norwegian Myocardial Infarction Registry 2013–2022. Outcomes were short- and long-term all-cause mortality. Mortality was assessed by Kaplan-Meier survival curves, Life Tables, and multivariable Cox regression models. Among 86 730 AMI patients (40% women), 1645 (2.7%) patients <75 years and 969 (3.9%) patients 75–84 years developed CS. Regardless of age, patients with AMI-CS were more likely to have previous heart failure, diabetes, renal failure, and ST-elevation AMI compared with patients without CS. In-hospital mortality was 47.5% in AMI-CS patients <75 years and 71.4% in patients 75–84 years, and the estimated one year cumulative mortality rates were 54.7% (95% CI: 52.3–57.1%) and 79.8% (95% CI: 77.2–82.3), respectively. Patients with AMI-CS who survived to hospital discharge remained at a higher long-term mortality risk compared with patients without CS (<75 years: adjusted HR 1.91 (95% CI 1.67–2.18), 75–84 years: adjusted HR 1.65 (95% CI: 1.41–1.93)). Conclusion The in-hospital mortality rates for AMI-related CS remain high, especially in patients ≥75 years. However, long-term mortality in CS patients surviving to hospital discharge was only moderately higher compared with AMI patients without CS.

• Myhre, Peder Langeland; Grenne, Bjørnar Leangen; Asch, Federico M.; Delgado, Victoria; Khera, Rohan & Lafitte, Stéphane [Show all 11 contributors for this article] (2025). Artificial intelligence-enhanced echocardiography in cardiovascular disease management. Nature Reviews Cardiology. ISSN 1759-5002. 23, p. 164–182. doi: 10.1038/s41569-025-01197-0. Full text in Research Archive
• Johannessen, Øyvind; Espersen, Caroline; Platz, Elke; Skaarup, Kristoffer Grundtvig; Lassen, Mats Christian Højbjerg & Davidovski, Filip Soeskov [Show all 16 contributors for this article] (2025). Predictors of B-line count in hospitalized patients with COVID-19. Frontiers in Cardiovascular Medicine. 12. doi: 10.3389/fcvm.2025.1618919. Full text in Research Archive Show summary

  Background B-lines on lung ultrasound (LUS) are nonspecific signs of increased lung density, which can be secondary to pulmonary congestion, pneumonia, or fibrosis. While its use is recommended in acute heart failure (HF), its value in non-HF populations is less clear. Methods We prospectively analyzed hospitalized non-ICU patients ≥18 years old with confirmed laboratory diagnoses of COVID-19. We aimed to identify associations between 8-zone LUS findings and clinical, laboratory, and echocardiographic data, and 30-day mortality using trend and regression analyses. Results Among 270 patients (mean age 69 ± 14 years, 58% male, and 11% with prior HF) the median time from hospital admission to LUS was 4 days [interquartile range (IQR) 2–8]. In total, 263 (97%) had ≥1 B-line [median B-line number 13 (IQR 9–22)], and the median left ventricular ejection fraction (LVEF) was 59 (IQR 54–63). In adjusted models, having more B-lines was associated with higher levels of C-reactive protein, with an incidence rate ratio (IRR) of 16% (95%CI: 8%–24%) per log-unit increase ( P  < 0.001) and higher Early Warning Score [IRR 5% (95%CI: 2%–8%) per point, P  = 0.003]. Higher tricuspid regurgitation gradient was associated with more B-lines: IRR 2% (95%CI: 1%–3%) per mmHg, P  = 0.001). However, left ventricular function measures and NT-proBNP concentrations showed no significant association with B-lines. Furthermore, B-lines were not associated with 30-day mortality. Conclusions Among patients with COVID-19, B-lines on LUS are associated with markers of infectious disease severity and pulmonary hypertension, but not with markers of left-sided HF.

• Mecinaj, Albulena; Vinje, Victoria; Ngo, Doan T. M.; Sverdlov, Aaron L. & Myhre, Peder Langeland (2025). The SARAH trial: more evidence on the role of neurohormonal blockers in prevention of anthracycline-induced cardiotoxicity. Heart Failure Reviews. ISSN 1382-4147. 30(3), p. 627–631. doi: 10.1007/s10741-025-10495-1. Full text in Research Archive Show summary

  This mini-review highlights the results of the SARAH trial, which evaluated the efficacy of sacubitril/valsartan in preventing subclinical cardiac dysfunction in patients undergoing anthracycline-based chemotherapy. The trial demonstrated a significant reduction in GLS decline in the treatment group compared to placebo. The findings are discussed in context with other trials investigating neurohormonal blockade for the prevention of cancer therapy-related cardiac dysfunction.

• Desai, Milind Y.; Okushi, Yuichiro; Jadam, Shada; Olivotto, Iacopo; Owens, Anjali & Nissen, Steven E. [Show all 187 contributors for this article] (2025). Echocardiographic Changes With Mavacamten in Nonobstructive Hypertrophic Cardiomyopathy: Exploratory Insights From the ODYSSEY-HCM Trial. Journal of the American College of Cardiology. ISSN 0735-1097. 86(24), p. 2434–2449. doi: 10.1016/j.jacc.2025.08.019. Full text in Research Archive
• Ikdahl, Eirik; Kerola, Anne; Myhre, Peder Langeland; Sollerud, Eli & Semb, Anne Grete (2025). Similar myocardial infarction characteristics and short-term outcomes in patients with and without inflammatory joint diseases: A nationwide Norwegian study. Seminars in Arthritis & Rheumatism. ISSN 0049-0172. 73, p. 152760–152760. doi: 10.1016/j.semarthrit.2025.152760. Full text in Research Archive
• Myhre, Peder Langeland; Grupper, Avishay; Mebazaa, Alexandre; Davison, Beth; Edwards, Christopher & Takagi, Koji [Show all 32 contributors for this article] (2025). Changes in Liver Function Tests, Congestion, and Prognosis After Acute Heart Failure: The STRONG-HF Trial. JACC: Advances. 4(3). doi: 10.1016/j.jacadv.2025.101607. Full text in Research Archive Show summary

  Background Elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (tBil) may reflect congestion and liver dysfunction in acute heart failure (AHF), while lower ALT also associates with sarcopenia. Objectives The purpose of this study was to assess ALT, AST, and tBil levels in AHF patients during high-intensity care (HIC) vs usual care (UC) follow-up. Methods ALT, AST, and tBil were measured 1 to 2 days predischarge in 1,062 AHF patients, and again after 90 days of either HIC or UC according to the STRONG-HF (Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP testinG, of Heart Failure therapies) protocol. The primary endpoint was 180-day all-cause death or HF hospitalization. Results Median (Q1-Q3) baseline ALT, AST, and tBil were 21 (15-32) U/L, 23 (17-32) U/L, and 14(10-21) umol/L, respectively. Patients with lower ALT had lower body mass index. Patients with lower ALT, but not tBil or AST, were more likely to have edema, elevated jugular venous pressure, and orthopnea, and use more diuretics prerandomization. A nonsignificant inverse association between ALT and the primary outcome (HR: 0.82 [95% CI: 0.66-1.01] per log-unit, P = 0.06) was observed. Greater reductions of ALT, AST, and tBil to 90 days were associated with greater improvement of edema, rales, NYHA functional class, and N-terminal pro-B-type natriuretic peptide. After 90 days, the HIC group had a greater reduction in AST and tBil than the UC group, while nonsignificant for ALT. The treatment effect of HIC over UC on the primary outcome was consistent across the baseline ALT, AST, and tBil range (all P interaction >0.10), but patients with lower ALT experienced greater health status improvement from HIC. Conclusions Lower ALT was associated with lower body mass index and more congestion in AHF, supporting previous studies suggesting ALT as a sarcopenia marker. The beneficial effect of HIC on health status was greater in low baseline ALT patients. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies [STRONG-HF]; NCT03412201)

• Berge, Kristian; Janssen, Sylvan L.J.E.; Velthuis, Birgitta K.; Myhre, Peder Langeland; Mosterd, Arend & Omland, Torbjørn [Show all 8 contributors for this article] (2025). Predictors of coronary atherosclerosis in middle-aged and older athletes: the MARC-2 study. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 26(3), p. 461–470. doi: 10.1093/ehjci/jeae317. Full text in Research Archive Show summary

  Aims Exercise improves cardiovascular health, but high-volume high-intensity exercise is associated with increased coronary artery calcification (CAC). We aimed to identify predictors of CAC in athletes. Methods and results We assessed the association of traditional and non-traditional cardiovascular risk factors with CAC using linear and logistic regression. A total of 289 male athletes from the MARC-2 study were included, with a median age of 60 (Q1–3 56–66) years, lifelong weekly training load of 26 (17–35) metabolic equivalent of task hours, body mass index of 24.5 (22.9–26.6) kg/m2, systolic blood pressure of 139 ± 18 mmHg, and reported 0.0 (0.0–8.0) smoking pack years. Thirty-one per cent had a CAC score > 100 and 13% > 400. Among traditional cardiovascular risk factors, higher age, systolic blood pressure, smoking pack years, and family history of coronary artery disease independently predicted greater CAC scores, while body mass index, low-density lipoprotein cholesterol, and diabetes mellitus did not. Among non-traditional risk factors, higher training loads, serum phosphate, and lower adjusted energy intake and fat percentage of energy intake independently predicted greater CAC scores. The full model with all traditional and non-traditional risk factors had higher accuracy in predicting CAC > 100 [receiver operating characteristic area under the curve 0.76, 95% confidence interval (0.70–0.82)] and CAC > 400 [0.85 (0.77–0.92)] than traditional cardiovascular risk factors alone [0.72 (0.65–0.78), P = 0.012, and 0.81 (0.74–0.90), P = 0.038, respectively]. Conclusion Non-traditional risk factors, including training load, dietary patterns, and serum phosphate, were independently associated with CAC in aging male athletes. Prediction accuracy for CAC increased when including these variables in a prediction model with traditional risk factors.

• Øvrebotten, Tarjei; Tholin, Birgitte; Berge, Kristian; Myhre, Peder Langeland & Stavem, Knut (2025). Cardiac events and procedures following COVID-19 compared with other pneumonias: a national register study. Open heart. 12(1). doi: 10.1136/openhrt-2024-002914. Full text in Research Archive Show summary

  Background Studies have shown an increased risk of cardiac disease following COVID-19, but how it compares to pneumonia of other etiologies is unclear. Aims To determine the incidence and HRs of cardiac disease in patients hospitalised with COVID-19 compared with other viral or bacterial pneumonias. Methods Using nationwide registry data, we estimated the incidence of cardiac events after hospitalisation with COVID-19 (n=2082) in February to November 2020 vs hospitalisation with viral (n=9018) or bacterial (n=29 339) pneumonia in 2018–2019. We defined outcomes using ICD-10 codes for incident myocarditis, acute myocardial infarction, atrial fibrillation/flutter, heart failure, ischaemic heart disease, other cardiac disease and total cardiac disease (any heart condition). We used Cox regression and logistic regression for analysis. Results Patients with COVID-19 had a mean (SD) age of 60 (18) years, compared with 69 (19) years for viral and 72 (17) years for bacterial pneumonia. Those with COVID-19 were more often male and had fewer comorbidities and fewer prior hospitalisations. Patients with COVID-19 had a lower hazard of new-onset cardiac disease compared with viral (HR 0.79 [95%CI 0.66 to 0.93]) and bacterial pneumonia (HR 0.66 [95%CI 0.57 to 0.78]), adjusted for age, sex, comorbidity, hospital admission prior year and respiratory support. Results were similar when including recurrent events. Conclusion Patients hospitalised with COVID-19 had a lower hazard of new-onset cardiac disease during the first 9 months after hospitalisation compared with patients with other viral or bacterial pneumonias after adjusting for multiple possible confounders. However, there may still be residual confounding from other or unknown factors.

• Berge, Kristian; Schirmer, Henrik; Øvrebotten, Tarjei; Nahoui, Hamza; Gullestad, Lars & Ingul, Charlotte Ingeborg Björk [Show all 13 contributors for this article] (2025). Improvements in medical therapy and prognosis for patients with HFrEF following the 2021 ESC HF guidelines. ESC Heart Failure. 12(5), p. 3343–3352. doi: 10.1002/ehf2.15337. Full text in Research Archive Show summary

  Aims The guideline-directed medical therapy (GDMT) sequencing strategy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) underwent a paradigm shift with the 2021 ESC HF guidelines, from stepwise escalation to rapid simultaneous initiation of quadruple therapy. We aimed to assess the temporal trends in the use of GDMT and prognosis for patients with HFrEF. Methods and results Through the Norwegian HF Registry, we obtained data on patients treated at HF outpatient clinics with left ventricular ejection fraction ≤40% from 2016 through 2023 (n = 13 992), including GDMT, HF hospitalisations and mortality. Since 2016, >90% of patients have been treated with beta-blockers and renin-angiotensin-system-inhibitors, with angiotensin receptor-neprilysin inhibitors (ARNI) utilisation increasing from 4% in 2016 to 54% in 2023. Mineralocorticoid-receptor-antagonists (MRA) utilisation was at 36% in 2016, increased by 3% per year to 54% in 2021, and thereafter increased by 12% per year to 78% in 2023. Sodium-glucose cotransporter-2-inhibitors (SGLT2i) utilisation increased rapidly from 3% in 2020 to 85% in 2023. The utilisation of ≥50% of target dose followed similar trends. From 2016 to 2021, the crude 6-month mortality rate remained at 2.7%, followed by a decline of approximately 0.5% per year to 1.8% in 2023. HF hospitalisations declined steadily from 12.9% in 2016 to 8.2% in 2021, with a further decline to 6.8% in 2023. Conclusions The utilisation of GDMT in Norwegian HF clinics has increased markedly since 2016, with a fourfold acceleration in MRA and a substantial increase in SGLT2i use following the 2021 ESC HF guidelines. HF hospitalisations have consistently declined, while mortality rates first declined after 2021.

• Jortveit, Jarle; Myhre, Peder Langeland; Berge, Kristian & Halvorsen, Sigrun (2025). Survival after myocardial infarction according to left ventricular function and heart failure symptoms. ESC Heart Failure. 12(4), p. 2528–2539. doi: 10.1002/ehf2.15265. Full text in Research Archive
• Bruun, Lina Dorthea; Andersen, Geir Øystein; Kringen, Marianne K.; Myhre, Peder Langeland; Halvorsen, Sigrun & Hansen, Charlotte Holst [Show all 8 contributors for this article] (2025). Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study. European Journal of Clinical Pharmacology. ISSN 0031-6970. 81(4), p. 551–560. doi: 10.1007/s00228-025-03806-w. Full text in Research Archive Show summary

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

• Myhre, Peder Langeland; Tromp, Jasper; Ouwerkerk, Wouter; Ting, Daniel T W; Docherty, Kieran F & Gibson, C Michael [Show all 7 contributors for this article] (2024). Digital tools in heart failure: addressing unmet needs. The Lancet Digital Health. 6(10), p. e755–e766. doi: 10.1016/S2589-7500(24)00158-4. Full text in Research Archive Show summary

  This Series paper provides an overview of digital tools in heart failure care, encompassing screening, early diagnosis, treatment initiation and optimisation, and monitoring, and the implications these tools could have for research. The current medical environment favours the implementation of digital tools in heart failure due to rapid advancements in technology and computing power, unprecedented global connectivity, and the paradigm shift towards digitisation. Despite available effective therapies for heart failure, substantial inadequacies in managing the condition have hindered improvements in patient outcomes, particularly in low-income and middle-income countries. As digital health tools continue to evolve and exert a growing influence on both clinical care and research, establishing clinical frameworks and supportive ecosystems that enable their effective use on a global scale is crucial.

• Shah, Amil M.; Myhre, Peder Langeland; Arthur, Victoria; Dorbala, Pranav; Rasheed, Humaira & Buckley, Leo F. [Show all 22 contributors for this article] (2024). Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development. Nature Communications. 15(1). doi: 10.1038/s41467-023-44680-3. Full text in Research Archive Show summary

  Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.

• Myhre, Peder Langeland; Gaibazzi, Nicola; Tuttolomondo, Domenico; Sartorio, Daniele; Ugolotti, Pietro Tito & Covani, Marco [Show all 8 contributors for this article] (2024). Concordance of left ventricular volumes and function measurements between two human readers, a fully automated AI algorithm, and the 3D heart model. Frontiers in Cardiovascular Medicine. 11. doi: 10.3389/fcvm.2024.1400333. Full text in Research Archive Show summary

  Background: Echocardiography is essential in cardiovascular medicine for screening, diagnosis, and monitoring. Artificial intelligence (AI) has the potential to improve echocardiography by reducing variability and analysis time. While 3D echocardiography is becoming more accurate, 2D imaging still dominates clinical care. We aimed to evaluate agreement in measures of left ventricular (LV) volumes and function between human readers, a fully automated AI 2D algorithm, and the 3D Heart Model. Methods: A retrospective analysis was conducted on 109 patients who underwent 2D and 3D transthoracic echocardiography. LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and ejection fraction (LVEF) were measured by two operators, a commercially available AI algorithm (US2ai), and the 3D Heart Model. Global longitudinal strain (GLS) was measured by the integrated semi-automated software and the AI algorithm. Outcomes included measures of agreement [bias, limit of agreement and Pearson's correlation (R)] Results: For LV volume measurements, the AI algorithm was strongly correlated with the average of the human operators (r = 0.89 for LVEDV and r = 0.92 for LVESV), which was higher than between the operators (r = 0.74 and r = 0.84, respectively, p < 0.01). The same trend was seen for measures of reliability with respect to LVEDV, but not LVESV. AI demonstrated comparable performance to human operators in measuring LVEF, while the 3D Heart Model had a weaker correlation and reliability compared with human operators and AI measurements. The correlation between human operators and AI for GLS was only moderate. Conclusion: This study demonstrates AI-based echocardiography as a promising tool for accurately assessing LV volumes and LVEF in clinical practice. AI-based measures demonstrated a significantly lower inter-operator variability, thereby improving the consistency and reliability of these assessments. Moreover, AI may prove particularly effective for conducting retrospective bulk analyses, offering a valuable tool for comprehensive evaluations of past data.

• Neuen, Brendon L.; Vaduganathan, Muthiah; Claggett, Brian L.; Beldhuis, Iris; Myhre, Peder Langeland & Desai, Akshay S. [Show all 14 contributors for this article] (2024). Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction. JACC. Heart failure. ISSN 2213-1779. 13(1), p. 28–39. doi: 10.1016/j.jchf.2024.08.009. Full text in Research Archive
• Røsjø, Helge Rørvik; Solberg, Ole Geir; Aaberge, Lars; Bosse, Gerhard; Omland, Torbjørn & Stavem, Knut [Show all 7 contributors for this article] (2024). Trans-Cardiac Gradient of Secretoneurin in Patients with Takotsubo Syndrome. Cardiology. ISSN 0008-6312. 149(5), p. 466–471. doi: 10.1159/000539094. Full text in Research Archive
• Sharma, Archana; Birkeland, Kåre Inge; Nermoen, Ingrid; Sommer, Christine; Qvigstad, Elisabeth & Lee-Ødegård, Sindre [Show all 11 contributors for this article] (2024). N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus. Cardiovascular Diabetology. 23(1). doi: 10.1186/s12933-024-02349-1. Full text in Research Archive Show summary

  Background Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? Methods We examined 162 South Asian and 107 Nordic women in Norway 1–3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. Results The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15–38)  vs. 42 (22–66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1–4.4) vs. 1.2 (0.3–4.2) mg/L), IL-6 (2.3 (1.5–3.2) vs. 1.5 (1.5–2.5) pg/mL), leptin (1647 (1176–2480) vs. 1223 (876–2313) pmol/L), and lower adiponectin levels (7.2 (5.3–9.3) vs. 10.0 (7.2–13.5) mg/L) and Matsuda ISI (2.4 (1.7–3.7) vs. 4.2 (2.9–6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. Conclusions NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

• Myhre, Peder Langeland; Claggett, Brian; Ballantyne, Christie M; Hoogeveen, Ron C.; Selvin, Elizabeth & Matsushita, Kunihiro [Show all 10 contributors for this article] (2024). NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study. Circulation. ISSN 0009-7322. 150(23), p. 1847–1857. doi: 10.1161/CIRCULATIONAHA.124.069735. Full text in Research Archive
• Myhre, Peder Langeland; Hung, Chung-Lieh; Frost, Matthew J.; Jiang, Zhubo; Ouwerkerk, Wouter & Teramoto, Kanako [Show all 18 contributors for this article] (2024). External validation of a deep learning algorithm for automated echocardiographic strain measurements. The European Heart Journal – Digital Health (EHJ-DH). 5(1), p. 60–68. doi: 10.1093/ehjdh/ztad072. Full text in Research Archive Show summary

  Aims Echocardiographic strain imaging reflects myocardial deformation and is a sensitive measure of cardiac function and wall-motion abnormalities. Deep learning (DL) algorithms could automate the interpretation of echocardiographic strain imaging. Methods and results We developed and trained an automated DL-based algorithm for left ventricular (LV) strain measurements in an internal dataset. Global longitudinal strain (GLS) was validated externally in (i) a real-world Taiwanese cohort of participants with and without heart failure (HF), (ii) a core-lab measured dataset from the multinational prevalence of microvascular dysfunction-HF and preserved ejection fraction (PROMIS-HFpEF) study, and regional strain in (iii) the HMC-QU-MI study of patients with suspected myocardial infarction. Outcomes included measures of agreement [bias, mean absolute difference (MAD), root-mean-squared-error (RMSE), and Pearson’s correlation (R)] and area under the curve (AUC) to identify HF and regional wall-motion abnormalities. The DL workflow successfully analysed 3741 (89%) studies in the Taiwanese cohort, 176 (96%) in PROMIS-HFpEF, and 158 (98%) in HMC-QU-MI. Automated GLS showed good agreement with manual measurements (mean ± SD): −18.9 ± 4.5% vs. −18.2 ± 4.4%, respectively, bias 0.68 ± 2.52%, MAD 2.0 ± 1.67, RMSE = 2.61, R = 0.84 in the Taiwanese cohort; and −15.4 ± 4.1% vs. −15.9 ± 3.6%, respectively, bias −0.65 ± 2.71%, MAD 2.19 ± 1.71, RMSE = 2.78, R = 0.76 in PROMIS-HFpEF. In the Taiwanese cohort, automated GLS accurately identified patients with HF (AUC = 0.89 for total HF and AUC = 0.98 for HF with reduced ejection fraction). In HMC-QU-MI, automated regional strain identified regional wall-motion abnormalities with an average AUC = 0.80. Conclusion DL algorithms can interpret echocardiographic strain images with similar accuracy as conventional measurements. These results highlight the potential of DL algorithms to democratize the use of cardiac strain measurements and reduce time-spent and costs for echo labs globally.

• Myhre, Peder Langeland; Kleiven, Øyunn; Berge, Kristian; Grundtvig, Morten; Gullestad, Lars & Ørn, Stein (2024). Changes in 6-min walk test is an independent predictor of death in chronic heart failure with reduced ejection fraction. European Journal of Heart Failure. ISSN 1388-9842. 26(12), p. 2608–2615. doi: 10.1002/ejhf.3391. Full text in Research Archive Show summary

  Aims Functional capacity provides important clinical information in patients with heart failure (HF) and reduced ejection fraction (HFrEF). The 6-min walk test (6MWT) is a simple and inexpensive tool for assessing functional capacity and risk. Although change in 6MWT is frequently used as a surrogate outcome in HF trials, the association with mortality is unclear. We aimed to assess the prognostic importance of changes in 6MWT. Methods and results Patients with chronic HFrEF referred to HF outpatient clinics in Norway completed a 6MWT at the first visit (baseline) and at a stable follow-up visit after treatment optimization (follow-up). Absolute and relative changes in 6MWT were analysed in association with mortality risk using Cox regression models and flexible cubic splines. The study included 3636 HFrEF patients aged 67.3 ± 11.6 years, 23% women, with left ventricular ejection fraction 30 ± 7%. At baseline, mean 6MWT was 438 ± 125 m, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1574 (732–3093) ng/L, and 27% had New York Heart Association (NYHA) class III/IV. After optimization of guideline-directed medical therapy (median 147 [86–240] days), 6MWT increased by mean 40 ± 74 m, NT-proBNP decreased by median 425 (14–1322) ng/L, and NYHA class improved in 38% of patients. Patients with greater improvements in 6MWT were younger, with greater improvements in NYHA class (r = 0.27, p < 0.001) and larger reductions in NT-proBNP concentrations (r = 0.19, p < 0.001). After mean 845 ± 595 days, 419 (11.5%) patients were dead. Both absolute and relative changes in 6MWT were non-linearly associated with survival, attenuating as 6MWT increased. A 50 m increase in 6MWT was associated with a 17% lower mortality risk (hazard ratio 0.84, 95% confidence interval 0.77–0.90, p < 0.001) in the fully adjusted model, including changes in NYHA class, NT-proBNP concentrations, and other established risk factors. The associations were more pronounced in patients with lower baseline 6MWT and higher age. Conclusion Improvement in 6MWT in patients with HFrEF is associated with increased survival, independent of changes in NT-proBNP and NYHA class. These findings support 6MWT change as a surrogate outcome in HF trials.

• Øvrebotten, Tarjei; Mecinaj, Albulena; Stavem, Knut; Ghanima, Waleed; Brønstad, Eivind & Durheim, Michael Thomas [Show all 14 contributors for this article] (2024). Trajectory of cardiac troponin T following moderate-to-severe COVID-19 and the association with cardiac abnormalities. BMC Cardiovascular Disorders. 24(1). doi: 10.1186/s12872-024-03854-7. Full text in Research Archive Show summary

  Background COVID-19 has been associated with cardiac troponin T (cTnT) elevations and changes in cardiac structure and function, but the link between cardiac dysfunction and high-sensitive cardiac troponin T (hs-cTnT) in the acute and convalescent phase is unclear. Objective To assess whether hs-cTnT concentrations are associated with cardiac dysfunction and structural abnormalities after hospitalization for COVID-19, and to evaluate the performance of hs-cTnT to rule out cardiac pathology. Methods Patients hospitalized with COVID-19 had hs-cTnT measured during the index hospitalization and after 3-and 12 months, when they also underwent an echocardiographic study. A subset also underwent cardiovascular magnetic resonance imaging (CMR) after 6 months. Cardiac abnormalities were defined as left ventricular hypertrophy or dysfunction, right ventricular dysfunction, or CMR late gadolinium. Results We included 189 patients with hs-cTnT concentrations measured during hospitalization for COVID-19, and after 3-and 12 months: Geometric mean (95%CI) 13 (11–15) ng/L, 7 (6–8) ng/L and 7 (6–8) ng/L, respectively. Cardiac abnormalities after 3 months were present in 45 (30%) and 3 (8%) of patients with hs-cTnT ≥ and < 5 ng/L at 3 months, respectively (negative predictive value 92.3% [95%CI 88.5–96.1%]). The performance was similar in patients with and without dyspnea. Hs-cTnT decreased from hospitalization to 3 months (more pronounced in intensive care unit-treated patients) and remained unchanged from 3 to 12 months, regardless of the presence of cardiac abnormalities. Conclusion Higher hs-cTnT concentrations in the convalescent phase of COVID-19 are associated with the presence of cardiac pathology and low concentrations (< 5 ng/L) may support in ruling out cardiac pathology following the infection.

• Sourour, Nur; Riveland, Egil Aarstad; Næsgaard, Patrycja; Kjekshus, Harald; Larsen, Alf Inge & Røsjø, Helge Rørvik [Show all 8 contributors for this article] (2024). Associations Between Biomarkers of Myocardial Injury and Systemic Inflammation and Risk of Incident Ventricular Arrhythmia. JACC: Clinical Electrophysiology. ISSN 2405-500X. 10(9), p. 2021–2032. doi: 10.1016/j.jacep.2024.04.017. Full text in Research Archive
• Tveit, Sjur Hansen; Myhre, Peder Langeland & Omland, Torbjørn (2023). The clinical importance of high-sensitivity cardiac troponin measurements for risk prediction in non-cardiac surgery. Expert Review of Molecular Diagnostics. ISSN 1473-7159. 23(6), p. 535–544. doi: 10.1080/14737159.2023.2211267. Full text in Research Archive Show summary

  Introduction The global healthcare burden associated with surgery is substantial, with many patients experiencing perioperative complications. Cardiac troponin I and T measured with high-sensitivity assays are cardiac specific biomarkers that associate closely with adverse outcomes in most patient populations. Perioperative physiological stress can induce troponin release from cardiomyocytes, a condition known as perioperative myocardial injury (PMI). PMI is associated with increased risk of poor short- and long-term outcomes, and current European guidelines recommend screening for PMI in at-risk individuals undergoing non-cardiac surgery. Areas covered In this review we summarize current knowledge of the prognostic attributes of cardiac troponins, as well as the challenges associated with their application as biomarkers in the perioperative phase. Expert opinion Measurement of circulating levels of cardiac troponins identify individuals at increased risk of poor postoperative outcomes. Systematic screening of at-risk individuals undergoing non-cardiac surgery will result in a large proportion of patients in need of further diagnostic workup to establish the exact nature of their PMI. The lack of concrete evidence of clinical benefit and the increased cost associated with such a strategy is concerning and underscore the need for further research.

• Hamidi, Fardin; Anwari, Elaaha; Spaulding, Christian; Hauw-Berlemont, Caroline; Vilfaillot, Aurélie & Viana-Tejedor, Ana [Show all 21 contributors for this article] (2023). Early versus delayed coronary angiography in patients with out-of-hospital cardiac arrest and no ST-segment elevation: a systematic review and meta-analysis of randomized controlled trials. Clinical Research in Cardiology. ISSN 1861-0684. doi: 10.1007/s00392-023-02264-7. Full text in Research Archive Show summary

  Abstract Background Recent randomized controlled trials did not show benefit of early/immediate coronary angiography (CAG) over a delayed/selective strategy in patients with out-of-hospital cardiac arrest (OHCA) and no ST-segment elevation. However, whether selected subgroups, specifically those with a high pretest probability of coronary artery disease may benefit from early CAG remains unclear. Methods We included all randomized controlled trials that compared a strategy of early/immediate versus delayed/selective CAG in OHCA patients and no ST elevation and had a follow-up of at least 30 days. The primary outcome of interest was all-cause death. Odds ratios (OR) were calculated and pooled across trials. Interaction testing was used to assess for heterogeneity of treatment effects. Results In total, 1512 patients (67 years, 26% female, 23% prior myocardial infarction) were included from 5 randomized controlled trials. Early/immediate versus delayed/selective CAG was not associated with a statistically significant difference in odds of death (OR 1.12, 95%-CI 0.91–1.38), with similar findings for the composite outcome of all-cause death or neurological deficit (OR 1.10, 95%-CI 0.89–1.36). There was no effect modification for death by age, presence of a shockable initial cardiac rhythm, history of coronary artery disease, presence of an ischemic event as the presumed cause of arrest, or time to return of spontaneous circulation (all P-interaction &gt; 0.10). However, early/immediate CAG tended to be associated with higher odds of death in women (OR 1.52, 95%-CI 1.00–2.31, P = 0.050) than in men (OR 1.04, 95%-CI 0.82–1.33, P = 0.74; P-interaction 0.097). Conclusion In OHCA patients without ST-segment elevation, a strategy of early/immediate versus delayed/selective CAG did not reduce all-cause mortality across major subgroups. However, women tended to have higher odds of death with early CAG. Graphical abstract

• Sourour, Nur; Riveland, Egil Aarstad; Næsgaard, Patrycja; Kjekshus, Harald; Larsen, Alf Inge & Omland, Torbjørn [Show all 8 contributors for this article] (2023). N-terminal pro-B-type natriuretic peptide for prediction of ventricular arrhythmias: Data from the SMASH study. Clinical Cardiology. ISSN 0160-9289. 46(8), p. 989–996. doi: 10.1002/clc.24074. Full text in Research Archive Show summary

  Background Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict heart failure (HF) and mortality, but whether NT-proBNP predicts ventricular arrhythmias (VA) is not clear. Hypothesis We hypothesize that high NT-proBNP concentrations associate with the risk of incident VA, defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia. Methods In a prospective, observational study of patients treated with implantable cardioverter defibrillator (ICD), we analyzed NT-proBNP concentrations at baseline and after mean 1.4 years in association to incident VA. Results We included 490 patients (age 66 ± 12 years, 83% men) out of whom 51% had a primary prevention ICD indication. The median NT-proBNP concentration was 567 (25–75 percentile 203–1480) ng/L and patients with higher concentrations were older with more HF and ICD for primary prevention. During mean 3.1 ± 0.7 years, 137 patients (28%) had ≥1 VA. Baseline NT-proBNP concentrations were associated with the risk of incident VA (hazard ratio [HR]: 1.39, 95% confidence interval [95% CI]: 1.22–1.58, p < .001), HF hospitalizations (HR: 3.11, 95% CI: 2.53–3.82, p < .001), and all-cause mortality (HR: 2.49, 95% CI: 2.04–3.03, p < .001), which persisted after adjusting for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction. The association with VA was stronger in secondary versus primary prevention ICD indication: HR: 1.59 (95% CI: 1.34–1.88 C-statistics 0.71) versus HR: 1.24, 95% CI: 1.02–1.51, C-statistics 0.55), p-for-interaction = 0.06. Changes in NT-proBNP during the first 1.4 years did not associate with subsequent VA. Conclusions NT-proBNP concentrations are associated with the risk of incident VA after adjustment for established risk factors, with the strongest association in patients with a secondary prevention ICD indication.

• Warlo, Ellen Mathea Kirsch; Kalstad, Are; Myhre, Peder Langeland; Solheim, Svein; Arnesen, Harald & Tveit, Arnljot [Show all 9 contributors for this article] (2023). von Willebrand factor, ADAMTS-13, and thrombospondin 1 in relation to clinical outcomes in elderly patients with a recent myocardial infarction. Research and Practice in Thrombosis and Haemostasis (RPTH). 7(4). doi: 10.1016/j.rpth.2023.100164. Full text in Research Archive Show summary

  Background von Willebrand factor (VWF) multimers are cleaved by A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) into less active fragments. Thrombospondin 1 (TSP-1) competes with VWF’s cleavage site, protecting it from degradation. Low ADAMTS-13 and high VWF have been associated with cardiovascular disease and atrial fibrillation (AF). Objectives We aimed to investigate whether VWF, ADAMTS-13, and TSP-1 are associated with clinical outcome. Methods Elderly patients with a recent myocardial infarction (MI) (n = 1027) were followed for 2 years. Blood was collected 2 to 8 weeks after the MI for ADAMTS-13, VWF, and TSP-1 measures. The primary endpoints (major adverse cardiovascular events; n = 210) included the first event of MI, stroke, heart failure hospitalization, coronary revascularization, and all-cause death. Total mortality was also registered (n = 56). The secondary endpoint was new-onset AF (n = 43). Results Concentrations of VWF, ADAMTS-13, and TSP-1 did not intercorrelate. The risk of major adverse cardiovascular events was altered in patients with VWF ≥ median (hazard ratio [HR], 1.4; 95% CI, 1.0-1.8; P = .03) and ADAMTS-13 ≥ median (HR, 0.7; 95% CI, 0.5-0.9; P = .02); however, it was not significant in adjusted models. VWF and ADAMTS-13 were significantly associated with total mortality, with a HR of 2.7 (95% CI, 1.6-4.6; P < .001) for VWF (Q4 vs. Q1-Q3) and HR of 0.3 (95% CI, 0.2-0.5; P < .001) for ADAMTS-13 (Q2-4 vs. Q1). The associations persisted in multivariable analysis, but the significance disappeared for VWF after correcting for high-sensitivity C-reactive protein. The risk of new-onset AF was lower in patients with VWF ≥ median (HR, 0.5; 95% CI, 0.3-1.0; P = .04]), and this was still significant after adjustments. Conclusion Although low ADAMTS-13 predicted death, the cardiovascular risk associated with VWF and ADAMTS-13 was weaker than previously reported. Low VWF is associated with new-onset AF and needs further research.

• Nilsen, Dennis WT; Myhre, Peder Langeland; Solheim, Svein; Tveit, Sjur Hansen; Kalstad, Are & Laake, Kristian [Show all 8 contributors for this article] (2023). Total Bilirubin Yields Prognostic Information Following a Myocardial Infarction in the Elderly. Antioxidants. 12(6). doi: 10.3390/antiox12061157. Full text in Research Archive Show summary

  Total bilirubin consists of an unconjugated form, solubilized by its binding to albumin, and a conjugated form representing a minor part of the circulating bilirubin. As total bilirubin in physiological concentrations is a powerful antioxidant, its concentration gradient may reflect the health status of an individual, and serve as a prognostic indicator of outcome in primary and secondary cardiovascular disease prevention. The aim of this study was to assess the association between total bilirubin and incident cardiovascular events following a myocardial infarction. Total bilirubin in serum was measured at baseline 2–8 weeks after hospitalization for an MI in 881 patients, aged 70 to 82 years, included in the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) study, where patients were followed-up for up to 2 years. The first major adverse clinical event (MACE) was the primary endpoint and consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. As total bilirubin was non-normally distributed, log-transformed values and quartiles of bilirubin were analyzed using Cox regression models. The median (Q1, and Q3) baseline concentration of bilirubin was 11 (9, and 14) µmol/L, and higher log-transformed concentrations were associated with male sex, lower New York Heart Association (NYHA) class and non-smoking. MACE occurred in 177 (20.1%) patients during the follow-up. Higher concentrations of bilirubin were associated with a lower risk of MACE: HR 0.67 (95%CI 0.47–0.97) per log-unit increase, p = 0.032. Patients in the lowest quartile of bilirubin (<9 µmol/L) had the highest risk with HR 1.61 (95%CI 1.19–2.18), p = 0.002, compared to quartiles 2–4. This association remained significant even after adjusting for age, sex, body mass index (BMI), smoking status, NYHA class and treatment allocation: HR 1.52 (1.21–2.09), p = 0.009. Low concentrations of bilirubin (<9 µmol/L) are associated with increased nonfatal cardiovascular events or death in elderly patients with a recent myocardial infarction.

• Johannessen, Øyvind; Reite, Fride Uthaug; Bhatnagar, Rahul; Øvrebotten, Tarjei; Einvik, Gunnar & Myhre, Peder Langeland (2023). Lung Ultrasound to Assess Pulmonary Congestion in Patients with Acute Exacerbation of COPD. The International Journal of Chronic Obstructive Pulmonary Disease. ISSN 1176-9106. 18, p. 693–703. doi: 10.2147/COPD.S396855. Full text in Research Archive Show summary

  Purpose: Heart failure (HF) often coexists with chronic obstructive pulmonary disease (COPD) and is associated with worse outcomes. We aimed to assess the feasibility of detecting vertical artifacts (B-lines) on lung ultrasound (LUS) to identify concurrent HF in patients hospitalized with acute exacerbation of COPD (AECOPD). Second, we wanted to assess the association between B-lines and the risk of rehospitalization for AECOPD or death. Patients and Methods: In a prospective cohort study, 123 patients with AECOPD underwent 8-zone bedside LUS within 24h after admission. A positive LUS was defined by ≥ 3 B-lines in ≥ 2 zones bilaterally. The ability to detect concurrent HF (adjudicated by a cardiologist committee) and association with events were evaluated by logistic- and Cox regression models. Results: Forty-eight of 123 patients with AECOPD (age 75± 9 years, 57[46%] men) had concurrent HF. Sixteen (13%) patients had positive LUS, and the prevalence of positive LUS was similar between patients with and without concurrent HF (8[17%] vs 8[11%], respectively, p=0.34). The number of B-lines was higher in concurrent HF: median 10(IQR 6– 16) vs 7(IQR 5– 12), p=0.03. The sensitivity and specificity for a positive LUS to detect concurrent HF were 17% and 89%, respectively. Positive LUS was not associated with rehospitalization and mortality: Adjusted HR: 0.93(0.49– 1.75), p=0.81. Conclusion: LUS did not detect concurrent HF or predict risk in patients with AECOPD.

• Prebensen, Christian Haugland; Lefol, Yohan Pierre; Myhre, Peder Langeland; Lüders, Torben; Jonassen, Christine M & Blomfeldt, Anita [Show all 9 contributors for this article] (2023). Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19. Scientific Reports. 13(1). doi: 10.1038/s41598-023-37606-y. Full text in Research Archive Show summary

  Abstract A maladaptive inflammatory response has been implicated in the pathogenesis of severe COVID-19. This study aimed to characterize the temporal dynamics of this response and investigate whether severe disease is associated with distinct gene expression patterns. We performed microarray analysis of serial whole blood RNA samples from 17 patients with severe COVID-19, 15 patients with moderate disease and 11 healthy controls. All study subjects were unvaccinated. We assessed whole blood gene expression patterns by differential gene expression analysis, gene set enrichment, two clustering methods and estimated relative leukocyte abundance using CIBERSORT. Neutrophils, platelets, cytokine signaling, and the coagulation system were activated in COVID-19, and this broad immune activation was more pronounced in severe vs. moderate disease. We observed two different trajectories of neutrophil-associated genes, indicating the emergence of a more immature neutrophil phenotype over time. Interferon-associated genes were strongly enriched in early COVID-19 before falling markedly, with modest severity-associated differences in trajectory. In conclusion, COVID-19 necessitating hospitalization is associated with a broad inflammatory response, which is more pronounced in severe disease. Our data suggest a progressively more immature circulating neutrophil phenotype over time. Interferon signaling is enriched in COVID-19 but does not seem to drive severe disease.

• Sourour, Nur; Riveland, Egil Aarstad; Omland, Torbjørn; Kjekshus, Harald; Larsen, Alf Inge & Røsjø, Helge Rørvik [Show all 7 contributors for this article] (2023). Re: Detailed association between B-type natriuretic peptide levels and ventricular tachyarrhythmia. Clinical Cardiology. ISSN 0160-9289. 46(12), p. 1604–1605. doi: 10.1002/clc.24145. Full text in Research Archive
• Myhre, Peder Langeland; Berge, Trygve; Kalstad, Are; Tveit, Sjur Hansen; Laake, Kristian & Schmidt, Erik B. [Show all 10 contributors for this article] (2023). Omega-3 fatty acid supplements and risk of atrial fibrillation and ‘micro-atrial fibrillation’: A secondary analysis from the OMEMI trial. Clinical Nutrition. ISSN 0261-5614. 42(9), p. 1657–1660. doi: 10.1016/j.clnu.2023.07.002. Full text in Research Archive Show summary

  Background & aims Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. We aimed to assess risk and potential mediators of AF and ‘micro-AF’ from n-3 PUFA in post-myocardial infarction (MI) patients. Methods In the OMEMI trial, 70–82 y. o. patients with a recent MI were randomized to 1.8 g/day of eicosapentaenoic-/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF and ‘micro-AF’ was recorded by clinical detection and by screening with Zenicor thumb-ECG (adjudicated by blinded investigators). Serum EPA and DHA were measured at baseline and study end. Results At baseline, 759 of 1014 (75%) patients had no AF history. These patients were aged 75 ± 4 years and 71% were male. During follow-up, 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or ‘micro-AF’. In the n-3 PUFA group 46 (11.9%) had AF/’micro-AF’ (28 AF, 18 ‘micro-AF’) and in the placebo group 24 (6.5%) had AF/micro-AF (15 AF, 9 micro-AF); HR 1.90 (95%CI 1.16–3.11), P = 0.011. Changes in serum EPA (but not DHA) mediated the effect from n-3 PUFA on AF risk, explaining 65% of the association. Conclusion Supplementation of n-3 PUFA post MI increases the risk of ‘micro-AF’ and AF, and increases in EPA seems to be an important mediator of the treatment effect from n-3 PUFA on the risk of AF.

• Berge, Trygve; Myhre, Peder Langeland; Kalstad, Are; Laake, Kristian; Tveit, Sjur Hansen & Onarheim, Sophia [Show all 10 contributors for this article] (2023). Screen-Detected Atrial Fibrillation and "micro-Atrial Fibrillation" and Risk of Cardiovascular Events after Myocardial Infarction in Elderly Patients. Cardiology. ISSN 0008-6312. 148(1), p. 72–77. doi: 10.1159/000528726. Full text in Research Archive
• Lam, Carolyn S. P.; Docherty, Kieran F.; Ho, Jennifer E; McMurray, John J. V.; Myhre, Peder Langeland & Omland, Torbjørn (2023). Recent successes in heart failure treatment. Nature Medicine. ISSN 1078-8956. 29(10), p. 2424–2437. doi: 10.1038/s41591-023-02567-2. Full text in Research Archive Show summary

  Remarkable recent advances have revolutionized the field of heart failure. Survival has improved among individuals with heart failure and a reduced ejection fraction and for the first time, new therapies have been shown to improve outcomes across the entire ejection fraction spectrum of heart failure. Great strides have been taken in the treatment of specific cardiomyopathies such as cardiac amyloidosis and hypertrophic cardiomyopathy, whereby conditions once considered incurable can now be effectively managed with novel genetic and molecular approaches. Yet there remain substantial residual unmet needs in heart failure. The translation of successful clinical trials to improved patient outcomes is limited by large gaps in implementation of care, widespread lack of disease awareness and poor understanding of the socioeconomic determinants of outcomes and how to address disparities. Ongoing clinical trials, advances in phenotype segmentation for precision medicine and the rise in technology solutions all offer hope for the future.

• Myhre, Peder Langeland; Liu, Yuxi; Kulac, Ian J.; Claggett, Brian L.; Prescott, Margaret F. & Felker, G. Michael [Show all 14 contributors for this article] (2023). Changes in mid-regional pro-adrenomedullin during treatment with sacubitril/valsartan. European Journal of Heart Failure. ISSN 1388-9842. 25(8), p. 1396–1405. doi: 10.1002/ejhf.2957. Full text in Research Archive Show summary

  Aims Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment. Methods and results Mid-regional pro-adrenomedullin (MR-proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12 months in the HFrEF cohort. Median (Q1–Q3) baseline MR-proADM concentrations were 0.80 (0.59–0.99) nmol/L in HFrEF and 0.88 (0.68–1.20) nmol/L in HFpEF. After 12 weeks of treatment with Sac/Val, MR-proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan-treated patients (median 2%). Greater increases in MR-proADM were associated with higher Sac/Val doses. Changes in MR-proADM correlated weakly with changes in N-terminal pro-B-type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR-proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status. Conclusions MR-proAD concentrations rise substantially following treatment with Sac/Val, in contrast to no change from valsartan. Change in MR-proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of heart failure.

• Riccardi, Mauro; Myhre, Peder Langeland; Zelniker, Thomas A.; Metra, Marco; Januzzi, James L. & Inciardi, Riccardo M. (2023). Soluble ST2 in Heart Failure: A Clinical Role beyond B-Type Natriuretic Peptide. Journal of Cardiovascular Development and Disease (JCDD). 10(11). doi: 10.3390/jcdd10110468. Full text in Research Archive Show summary

  Soluble (s)ST2 has been proposed as a useful biomarker for heart failure (HF) patient management. Myocardial damage or mechanical stress stimulate sST2 release. ST2 competes with a membrane bound receptor (ST2 ligand, or ST2L) for interleukin-33 (IL-33) binding, inhibiting the effects induced by the ST2L/IL-33 interaction so that excessive sST2 may contribute to myocardial fibrosis and ventricular remodeling. Compared to natriuretic peptides (NPs), sST2 concentration is not substantially affected by age, sex, body mass index, kidney function, atrial fibrillation, anemia, or HF etiology, and has low intra-individual variation. Its prognostic role as an independent marker is well reported in the literature. However, there is a gap on its use in combination with NPs, currently the only biomarkers recommended by European and American guidelines for HF management. Reflecting the activation of two distinct biological systems, a benefit from the use of sST2 and NP in combination is advocated. The aim of this review is to report the current scientific knowledge on sST2 in the acute and chronic HF settings with a particular attention to its additive role to natriuretic peptides (NPs).

• Bork, Christian S.; Myhre, Peder Langeland & Schmidt, Erik B. (2023). Do omega-3 fatty acids increase risk of atrial fibrillation? Current opinion in clinical nutrition and metabolic care. ISSN 1363-1950. 26(2), p. 78–82. doi: 10.1097/MCO.0000000000000907. Full text in Research Archive
• Øvrebotten, Tarjei; Heck, Siri Lagethon; Skjørten, Ingunn; Einvik, Gunnar; Stavem, Knut & Ingul, Charlotte Ingeborg Björk [Show all 8 contributors for this article] (2023). Minor Myocardial Scars in Association with Cardiopulmonary Function after COVID-19. Cardiology. ISSN 0008-6312. 148(4), p. 300–306. doi: 10.1159/000530942. Full text in Research Archive Show summary

  Background: Myocardial scars detected by cardiovascular magnetic resonance (CMR) imaging after COVID-19 have caused concerns regarding potential long-term cardiovascular consequences. Objective: The objective of this study was to investigate cardiopulmonary functioning in patients with versus without COVID-19-related myocardial scars. Methods: In this prospective cohort study, CMR was performed approximately 6 months after moderate-to-severe COVID-19. Before (∼3 months post-COVID-19) and after (∼12 months post-COVID-19) the CMR, patients underwent extensive cardiopulmonary testing with cardiopulmonary exercise tests, 24-h ECG, and echocardiography. We excluded participants with overt heart failure. Results: Post-COVID-19 CMR was available in 49 patients with cardiopulmonary tests at 3 and 12 months after the index hospitalization. Nine (18%) patients had small late gadolinium enhancement-detected myocardial scars. Patients with myocardial scars were older (63.2 ± 13.2 vs. 56.2 ± 13.2 years) and more frequently men (89% vs. 55%) compared to those without scars. Cardiorespiratory fitness was similar in patients with and without scars, i.e., peak oxygen uptake: 82.1 ± 11.5% versus 76.3 ± 22.5% of predicted, respectively (p = 0.46). The prevalence of ventricular premature contractions and arrhythmias was low and not different by the presence of myocardial scar. Cardiac structure and function assessed by echocardiography were similar between the groups, except for a tendency of greater left ventricular mass in those with scars (75 ± 20 vs. 62 ± 14, p = 0.02 and p = 0.08 after adjusting for age and sex). There were no significant associations between myocardial scar and longitudinal changes in cardiopulmonary function from 3 to 12 months. Conclusion: Our findings imply that the presence of minor myocardial scars has limited clinical significance with respect to cardiopulmonary function after COVID-19.

• Øvrebotten, Tarjei; Myhre, Peder Langeland; Grimsmo, Jostein; Mecinaj, Albulena; Trebinjac, Divna & Nossen, Magnus Berger [Show all 12 contributors for this article] (2022). Changes in cardiac structure and function from 3 to 12 months after hospitalization for COVID-19. Clinical Cardiology. ISSN 0160-9289. 45(10), p. 1044–1052. doi: 10.1002/clc.23891. Full text in Research Archive Show summary

  Background Cardiac function may be impaired during and early after hospitalization for COVID-19, but little is known about the progression of cardiac dysfunction and the association with postacute COVID syndrome (PACS). Methods In a multicenter prospective cohort study, patients who had been hospitalized with COVID-19 were enrolled and comprehensive echocardiography was performed 3 and 12 months after discharge. Twenty-four-hour electrocardiogram (ECG) was performed at 3 and 12 months in patients with arrhythmias at 3 months. Results In total, 182 participants attended the 3 and 12 months visits (age 58 ± 14 years, 59% male, body mass index 28.2 ± 4.2 kg/m2). Of these, 35 (20%) had severe COVID-19 (treatment in the intensive care unit) and 74 (52%) had self-reported dyspnea at 3 months. From 3 to 12 months there were no significant overall changes in any measures of left or right ventricle (LV; RV) structure and function (p > .05 for all), including RV strain (from 26.2 ± 3.9% to 26.5 ± 3.1%, p = .29) and LV global longitudinal strain (from 19.2 ± 2.3% to 19.3 ± 2.3%, p = .64). Changes in echocardiographic parameters from 3 to 12 months did not differ by COVID-19 severity or by the presence of persistent dyspnea (p > .05 for all). Among patients with arrhythmia at 3 months, there was no significant change in arrhythmia burden to 12 months. Conclusion Following COVID-19, cardiac structure and function remained unchanged from 3 to 12 months after the index hospitalization, irrespective of COVID-19 severity and presence of persistent dyspnea. These results suggest that progression of cardiac dysfunction after COVID-19 is rare and unlikely to play an important role in PACS.

• Myhre, Peder Langeland; Claggett, Brian L.; Shah, Amil M.; Prescott, Margaret F.; Ward, Jonathan H. & Fang, James C. [Show all 9 contributors for this article] (2022). Changes in cardiac biomarkers in association with alterations in cardiac structure and function, and health status in heart failure with reduced ejection fraction: the EVALUATE-HF trial. European Journal of Heart Failure. ISSN 1388-9842. 24(7), p. 1200–1208. doi: 10.1002/ejhf.2541. Full text in Research Archive Show summary

  Aims N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status. Methods and results Patients in the EVALUATE-HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12-week open-label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 weeks of treatment, NT-proBNP, sST2 and cTnT decreased by median (Q1, Q3) −31% (−55%, +6%), −6% (−19%, +8%) and − 3% (−13%, +8%), respectively (all p < 0.001). Decreases in NT-proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in left ventricular mass, but not with changes in left ventricular function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There was no effect modification from treatment on the associations investigated (p for interaction >0.05) Conclusion In HFrEF, serial changes in NT-proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes in NT-proBNP, cTnT and sST2. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02874794.

• Myhre, Peder Langeland; Kalstad, Are; Tveit, Sjur Hansen; Laake, Kristian; Schmidt, Erik B. & Smith, Pål [Show all 11 contributors for this article] (2022). Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial. Journal of Internal Medicine. ISSN 0954-6820. 291(5), p. 637–647. doi: 10.1111/joim.13442. Full text in Research Archive Show summary

  Background The cardiovascular benefit from n-3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear. Objectives To assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events. Methods In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all-cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new-onset atrial fibrillation (AF). Results EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on-treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high-density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on-treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75–0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07–1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66–1.06] for MACE and 1.39 [0.90–2.13] for AF). Conclusion Greater on-treatment increases in EPA were associated with lower risk of MACE and higher risk of new-onset AF. These data suggest that the cardiovascular effects of increasing n-3 PUFA levels through supplements are complex, involving both potential benefits and harm.

• Sourour, Nur; Riveland, Egil Aarstad; Rømo, Terje; Næsgaard, Patrycja; Kjekshus, Harald & Larsen, Alf Inge [Show all 9 contributors for this article] (2022). QRS fragmentation is associated with increased risk of ventricular arrhythmias in high-risk patients; Data from the SMASH 1 Study. Annals of Noninvasive Electrocardiology. ISSN 1082-720X. 27(5). doi: 10.1111/anec.12985. Full text in Research Archive Show summary

  Introduction QRS fragmentation (fQRS), defined as the presence of additional spikes within the QRS complex, has been associated with myocardial conduction abnormalities and arrhythmogenicity. Objective We aimed to assess whether fQRS is associated with incident ventricular arrhythmias (VA) in high-risk patients treated with implantable cardioverter-defibrillator (ICD) for primary and secondary prevention. Methods In a prospective observational multicenter study, we included 495 patients treated with ICD. fQRS was analyzed according to previously validated criteria, by two physicians blinded for outcome data. Incident VA were obtained from ICD recordings. Results ECG recordings interpretable for fQRS were available in 459 patients (93%), aged 66 ± 12 years with left ventricular ejection fraction 40% ± 13%. fQRS was present in 52 patients (11%) with comparable baseline characteristics to patients without fQRS, except higher age, higher prevalence of coronary artery disease (CAD), lower prevalence of cardiomyopathy, and more frequently a secondary prevention ICD indication. Among patients with native QRS, those with fQRS had similar QRS duration and axis to those without fQRS. During 3.1 ± 0.7 years follow-up, 126 patients (28%) had ≥1 VA . fQRS was associated with increased risk of VA (HR 3.41 [95% CI 2.27–5.13], p < .001), which persisted after adjusting for age, gender, sex, BMI, CAD, heart failure, renal function, ICD indication, QRS duration, QRS axis, Q waves, and bundle branch block. fQRS was more strongly associated with VA in patients with a primary (HR 6.05 [95% CI 3.16–11.60]) versus secondary (HR 2.39 [95% CI 1.41–4.04]) ICD indication (p-for-interaction = .047). Conclusions fQRS is associated with threefold increased risk of VA in high-risk patients, independent of established risk factors.

• Johannessen, Øyvind; Myhre, Peder Langeland; Claggett, Brian; Lindner, Moritz; Lewis, Eldrin F. & Rivero, Jose [Show all 8 contributors for this article] (2022). Left atrial inflow propagation velocity derived by color M-mode Doppler in acute heart failure. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 38(10), p. 2155–2165. doi: 10.1007/s10554-022-02614-y. Full text in Research Archive Show summary

  Left atrial (LA) inflow propagation velocity from the pulmonary vein (LAIF-PV) has been proposed as a novel measure of LA reservoir function and is associated with pulmonary capillary wedge pressure in critically ill patients. However, data on LAIF-PV in acute heart failure (AHF) are lacking. We sought to examine the feasibility of measuring LAIF-PV and evaluate clinical and echocardiographic correlates of LAIF-PV in AHF. In a prospective cohort study of adults hospitalized for AHF, we used color M-mode Doppler of the pulmonary veins to obtain LAIF-PV in systole. Among 142 patients with appropriate images and no more than moderate mitral regurgitation, LAIF-PV measures were feasible in 76 patients (54%) aged 71 ± 14 years, including 68% men with left ventricular ejection fraction (LVEF) 38% ± 13. Mean LAIF-PV was 24.2 ± 5.9 cm/s. In multivariable regression analysis adjusted for age, sex, systolic blood pressure, heart rate, body mass index, New York Heart Association class, LA volume and LVEF, the only independent echocardiographic predictors of LAIF-PV were right ventricular (RV) S’ [ß 0.46 cm/s per cm/s (95% CI 0.01–0.91), p = 0.045] and tricuspid annular plane systolic excursion (TAPSE) [ß 0.28 cm/s per mm (95% CI 0.02–0.54), p = 0.039]. Notably, LAIF-PV was not significantly correlated with measures of LV function, LA function or E/e’. In conclusion, LAIF-PV was measurable in 54% of patients with AHF, and lower values were associated with measures of impaired RV systolic function but not LV or LA function.

• Myhre, Peder Langeland; Røsjø, Helge Rørvik; Sarvari, Sebastian; Ukkonen, Heikki; Rademakers, Frank & Engvall, Jan E. [Show all 14 contributors for this article] (2022). Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome. International Journal of Cardiology. ISSN 0167-5273. 361, p. 14–17. doi: 10.1016/j.ijcard.2022.05.027. Full text in Research Archive Show summary

  Background Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. Methods Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. Results We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73–294) versus 87 (44–192) ng/L and 10 (6–13) versus 7 (4–11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%–73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. Conclusion cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

• Myhre, Peder Langeland; Claggett, Brian; Yu, Bing; Skali, Hicham; Solomon, Scott D. & Røsjø, Helge Rørvik [Show all 13 contributors for this article] (2022). Sex and Race Differences in N-Terminal Pro-B-type Natriuretic Peptide Concentration and Absolute Risk of Heart Failure in the Community. JAMA cardiology. ISSN 2380-6583. 7(6), p. 623–631. doi: 10.1001/jamacardio.2022.0680. Full text in Research Archive
• Myhre, Peder Langeland; Prescott, Margaret F.; Claggett, Brian; Felker, G Michael; Butler, Javed & Piña, Ileana L. [Show all 11 contributors for this article] (2022). Comparative Effect of Angiotensin Receptor Neprilysin Inhibition on B-type Natriuretic Peptide Levels Measured by Three Different Assays: The PROVE-HF Study. Clinical Chemistry. ISSN 0009-9147. 68(11), p. 1391–1398. doi: 10.1093/clinchem/hvac148. Full text in Research Archive Show summary

  Abstract Background Several different B-type natriuretic peptide (BNP) assays are used clinically for diagnostic and prognostic evaluation of heart failure (HF). BNP binds weakly to neprilysin and is cleaved in multiple areas adjacent to the binding sites for the antibodies used in these immunoassays. We assessed the changes in BNP following neprilysin inhibition as measured by 3 immunoassays that recognize different epitopes. Methods Among 130 participants with HF with reduced ejection fraction, blood was collected prior to treatment with sacubitril/valsartan (sac/val) and then repeatedly measured through 52 weeks of treatment. BNP concentrations were measured with 3 widely used BNP assays (Siemens, Abbott, and Quidel). Results Study participants had a mean age of 65 ± 13 years and 76% were men. The median BNP concentration at baseline was 133 ng/L by the Siemens assay, 127 ng/L by the Abbott assay, and 141 ng/L by the Quidel assay. Following initiation of sac/val, there were significantly greater declines in BNP measured by Quidel and Abbott (P = 0.009 and P &amp;lt; 0.001), respectively (both with N-terminal capture antibodies), compared to Siemens (with C-terminal capture antibodies). The difference from baseline was not statistically significant until after week 12 (mean –10.1% for Quidel and –14.3% for Abbott) compared to non-significant differences before 12 weeks (mean –4.5% for Quidel and –6.0% for Abbott). Conclusions Following initiation of sac/val, BNP measurements may modestly differ depending on the assay method used, particularly after a few months of treatment. Whether these differences relate to neprilysin-mediated degradation of antibody binding sites deserves further study. Study registration PROVE-HF ClinicalTrials.gov Identifier: NCT02887183.

• Myhre, Peder Langeland; Vaduganathan, Muthiah; Claggett, Brian L.; Miao, Zi Michael; Jhund, Pardeep S. & Boer, Rudolf A. de [Show all 18 contributors for this article] (2022). Influence of NT-proBNP on Efficacy of Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JACC. Heart failure. ISSN 2213-1779. 10(12), p. 902–913. doi: 10.1016/j.jchf.2022.08.007. Full text in Research Archive Show summary

  Background N-terminal pro–B-type natriuretic peptide (NT-proBNP) is used for diagnostic and prognostic evaluation in heart failure (HF). Previous clinical trials in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) have shown potential heterogeneity in the treatment response by baseline NT-proBNP levels. Objectives The purpose of this study was to assess the treatment effect of dapagliflozin across baseline levels of NT-proBNP among patients with HFmrEF or HFpEF. Methods This was a post hoc analysis from DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure), a randomized, placebo-controlled trial of dapagliflozin in patients with HFmrEF or HFpEF. Elevated NT-proBNP was part of the inclusion criteria (≥300 ng/L for non–atrial fibrillation or flutter [AFF]; ≥600 ng/L for AFF). Baseline NT-proBNP was categorized in quartiles and additionally analyzed continuously. The primary composite outcome was cardiovascular death or worsening HF events. Results Among the 6,262 included patients (mean: 71.7 years and 3,516 [56%] men), the median baseline concentration of NT-proBNP was 716 (Q1-Q3: 469-1,280) ng/L and 1,399 (Q1-Q3: 962-2,212) ng/L for non-AFF and AFF, respectively. Higher NT-proBNP levels were linearly associated with a greater risk of the primary outcome (adjusted HR for log2NTpro-BNP was 1.53 [95% CI: 1.46-1.62] and Q4 vs Q1: 3.46 [95% CI: 2.48-4.22]; P < 0.001), with consistent results regardless of AFF status. The clinical benefit of dapagliflozin was present irrespective of baseline NT-proBNP concentration (P value for interaction = 0.40 by quartiles and = 0.19 continuously for the primary outcome) and the absolute risk reduction was, therefore, greater with higher NT-proBNP concentrations. The effect on health status and safety of dapagliflozin was similarly consistent across NT-proBNP quartiles. Conclusions Dapagliflozin is safe and improves outcomes irrespective of baseline NT-proBNP concentrations in HFmrEF or HFpEF, with the greatest absolute benefit likely seen in patients with higher NT-proBNP concentrations. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213)

• Myhre, Peder Langeland; Prescott, Margaret F.; Murphy, Sean P.; Fang, James C.; Mitchell, Gary F. & Ward, Jonathan H. [Show all 10 contributors for this article] (2022). Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF. JACC. Heart failure. ISSN 2213-1779. 10(2), p. 119–128. doi: 10.1016/j.jchf.2021.09.007. Full text in Research Archive Show summary

  Objectives This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. Background Through inhibition of neprilysin, Sac/Val may increase BNP concentrations. Methods In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. Results Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [−30% to +41%]; P = 0.36) or week 12 (+1% [−36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by −30% (−50% to −8%) and −32% (−54% to −1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [−34% to +115%]), unchanged (+34% [−15% to +205%]), or increased (+57% [−12% to +14%]). Conclusions In this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

• Tveit, Sjur Hansen; Myhre, Peder Langeland; Hanssen, Tove Aminda; Forsdahl, Signe Helene; Iqbal, Amjid & Omland, Torbjørn [Show all 7 contributors for this article] (2022). Cardiac troponin I and T for ruling out coronary artery disease in suspected chronic coronary syndrome. Scientific Reports. 12. doi: 10.1038/s41598-022-04850-7. Full text in Research Archive Show summary

  To compare the performance of high-sensitivity cardiac troponin I and T (hs-cTnI; hs-cTnT) in diagnosing obstructive coronary artery disease (CAD₅₀) in patients with suspected chronic coronary syndrome (CCS). A total of 706 patients with suspected CCS, referred for Coronary Computed Tomography Angiography, were included. cTn concentrations were measured using the Singulex hs-cTnI (limit of detection [LoD] 0.08 ng/L) and Roche hs-cTnT (LoD 3 ng/L) assays. Obstructive coronary artery disease (CAD₅₀) was defned as ≥ 50% coronary stenosis. Cardiovascular risk was determined by the NORRISK2-score. Median age of the patients was 65 (range 28–87) years, 35% were women. All patients had hs-cTnI concentrations above the LoD (median 1.9 [Q1-3 1.2–3.6] ng/L), 72% had hs-cTnT above the LoD (median 5 [Q1-3 2–11] ng/L). There was a graded relationship between hs-cTn concentrations and coronary artery calcium. Only hs-cTnI remained associated with CAD₅₀ in adjusted analyses (OR 1.20 95% Confdence Interval [1.05–1.38]), p = 0.009). The C-statistics for hs-cTnI and hs-cTnT were 0.65 (95% CI [0.60–0.69]) and 0.60 (0.56–0.64). The highest specifcity and negative predictive values for CAD₅₀ were in the lowest NORRISK2-tertile. hs-cTn concentrations provide diagnostic information in patients with suspected CCS, with superior performance of hs-cTnI compared to hs-cTnT in regard to CAD₅₀. The diagnostic performance appeared best in those with low cardiovascular risk.

• Kalstad, Are; Myhre, Peder L.; Laake, Kristian; Opstad, Trine B.; Tveit, Arnljot & Solheim, Svein [Show all 8 contributors for this article] (2021). Biomarkers of ageing and cardiac remodeling are associated with atrial fibrillation. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 55(4), p. 213–219. doi: 10.1080/14017431.2021.1889653. Full text in Research Archive Show summary

  Objectives. Ageing is one of the strongest risk factors for atrial fibrillation (AF), and additional risk factors are also closely related to ageing. Remodeling is part of the pathophysiology of AF, and a possible common denominator of ageing and other AF risk factors. The aim of this study was to investigate any association between the presence of AF and the ageing biomarkers, leukocyte telomere length (LTL) and sirtuin-1 (SIRT-1), and the cardiac remodeling biomarkers Galectin-3 and sST2 in elderly myocardial infarction (MI) patients. Design. Patients were included after admission for MI. Diagnosis of AF was retrieved from medical records and classified as either history of AF before MI or new onset from admission to study inclusion. SIRT-1, sST2 and Galectin-3 were analyzed by ELISAs and LTL by qPCR. Results. In total, 299 patients were included, median age 75 years, 70.2% male. A history of AF was recorded in 38 patients and 30 patients experienced new onset AF. Higher levels of SIRT-1 were associated with lower risk of having a history of AF (OR = 0.46 (95% CI 0.26, 0.81), p = 0.007), whereas higher sST2 levels were associated with higher risk of AF (OR = 4.13 (95% CI 1.69, 10.13), p = 0.002). Results remained significant after adjustment for other AF risk factors. No significant associations with AF were found for Galectin-3 or LTL. None of the biomarkers associated with new onset AF. Conclusion. In elderly patients with MI, higher ST2 and lower SIRT-2 levels were associated with higher prevalence of AF, possibly reflecting both ageing and the remodeling phenomena in AF.

• Myhre, Peder Langeland; Heck, Siri Lagethon; Skranes, Julia Brox; Prebensen, Christian Haugland; Jonassen, Christine M & Berge, Trygve [Show all 15 contributors for this article] (2021). Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity. American Heart Journal. ISSN 0002-8703. 242, p. 61–70. doi: 10.1016/j.ahj.2021.08.001. Full text in Research Archive Show summary

  Background Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. Methods Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. Results Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. Conclusions CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. Trial Registration COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232

• Myhre, Peder L.; Prebensen, Christian; Jonassen, Christine Monceyron; Berdal, Jan Erik & Omland, Torbjørn (2021). Sars-cov-2 viremia is associated with inflammatory, but not cardiovascular biomarkers, in patients hospitalized for covid-19. Journal of the American Heart Association (JAHA). 10(9), p. 1–5. doi: 10.1161/JAHA.120.019756. Full text in Research Archive Show summary

  Background COVID‐19 may present with a variety of cardiovascular manifestations, and elevations of biomarkers reflecting myocardial injury and stress are prevalent. SARS‐CoV‐2 has been found in cardiac tissue, and myocardial dysfunction post‐COVID‐19 may occur. However, the association between SARS‐CoV‐2 RNA in plasma and cardiovascular biomarkers remains unknown. Methods and Results COVID MECH (COVID‐19 Mechanisms) was a prospective, observational study enrolling consecutive, hospitalized patients with laboratory‐confirmed infection with SARS‐CoV‐2 and symptoms of COVID‐19. Biobank plasma samples used to measure SARS‐CoV‐2 RNA and cardiovascular and inflammatory biomarkers were collected in 123 patients at baseline, and in 96 patients (78%) at day 3. Patients were aged 60±15 (mean ± SD) years, 71 (58%) were men, 68 (55%) were White, and 31 (25%) received mechanical ventilation during hospitalization. SARS‐CoV‐2 RNA was detected in plasma from 48 (39%) patients at baseline. Patients with viremia were more frequently men, had more diabetes mellitus, and lower oxygen saturation. Patients with viremia had higher concentrations of interleukin‐6, C‐reactive protein, procalcitonin, and ferritin (all <0.001), but comparable levels of cTnT (cardiac troponin T; P=0.09), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; P=0.27) and D‐dimer (P=0.67) to patients without viremia. SARS‐CoV‐2 RNA was present in plasma at either baseline or day 3 in 50 (52%) patients, and these patients experienced increase from baseline to day 3 in NT‐proBNP and D‐dimer concentrations, while there was no change in cTnT. Conclusions SARS‐CoV‐2 viremia was associated with increased concentrations of inflammatory, but not cardiovascular biomarkers. NT‐proBNP and D‐dimer, but not cTnT, increased from baseline to day 3 in patients with viremia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04314232.

• Nilsen, Dennis W.T.; Myhre, Peder Langeland; Kalstad, Are; Schmidt, Erik B.; Arnesen, Harald & Seljeflot, Ingebjørg (2021). Serum levels of dihomo-gamma (γ)-linolenic acid (dgla) are inversely associated with linoleic acid and total death in elderly patients with a recent myocardial infarction. Nutrients. 13(10), p. 1–13. doi: 10.3390/nu13103475. Full text in Research Archive Show summary

  Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid (PUFA) derived from linoleic acid (LA). The LA:DGLA ratio reflects conversion from LA to DGLA. Low levels of DGLA in serum have been related to poor outcome in myocardial infarction (MI) patients. Aims: To assess the association of DGLA and LA:DGLA with total death as a primary aim and incident cardiovascular events as a secondary objective. Methods: Baseline samples from 1002 patients, aged 70 to 82 years, included 2–8 weeks after an MI and followed for 2 years, were used. Major adverse clinical events (MACE) consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. Cox regression analysis was used to relate serum n-6 PUFA phospholipid levels (%wt) to the risk of MACE, adjusting for the following: (1) age, sex and body mass index (BMI); (2) adding baseline cod liver oil supplementation; (3) adding prevalent hypertension, chronic kidney disease and diabetes mellitus. Results: Median DGLA level in serum phospholipids was 2.89 (Q1–Q3 2.43–3.38) %wt. DGLA was inversely related to LA and LA:DGLA ratio. There were 208 incident cases of MACE and 55 deaths. In the multivariable analysis, the hazard ratio (HR) for the total death in the three higher quartiles (Q2–4) of DGLA as compared to Q1 was 0.54 (0.31–0.95), with p = 0.03 (Model-1), 0.50 (0.28–0.91), with p = 0.02 (Model-2), and 0.47 (0.26–0.84), with p = 0.012 (Model-3), and non-significant for MACE. Risk of MACE (Model 3) approached borderline significance for LA:DGLA in Q2–4 vs. Q1 [HR 1.42 (1.00–2.04), p = 0.052]. Conclusions: Low levels of DGLA were related to a high LA:DGLA ratio and risk of total death in elderly patients with recent MI.

• Myhre, Peder Langeland; Lyngbakken, Magnus Nakrem; Berge, Trygve; Røysland, Ragnhild; Aagaard, Erika Nerdrum & Pervez, Mohammad Osman [Show all 13 contributors for this article] (2021). Diagnostic Thresholds for Pre-Diabetes Mellitus and Diabetes Mellitus and Subclinical Cardiac Disease in the General Population: Data From the ACE 1950 Study. Journal of the American Heart Association (JAHA). 10(11). doi: 10.1161/JAHA.120.020447. Full text in Research Archive Show summary

  Background Diabetes mellitus (DM) is associated with left ventricular remodeling and incident heart failure, but the association between glycated hemoglobin A1c (HbA1c) and subclinical cardiac disease is not established. We aimed to determine the associations between HbA1c and (1) echocardiographic measures of left ventricular structure and function, and (2) cardiovascular biomarkers: cardiac troponin T, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), and CRP (C‐reactive protein). Methods and Results Participants (n=3688) born in 1950 from the population‐based ACE (Akershus Cardiac Examination) 1950 Study were classified as DM (HbA1c≥6.5% or self‐reported DM), pre‐DM (HbA1c 5.7%–6.5%), and no‐DM (HbA1c<5.7%). DM, pre‐DM, and no‐DM were classified in 380 (10%), 1630 (44%), and 1678 (46%) participants, respectively. Mean age was 63.9±0.7 years, mean body mass index was 27.2±4.4 kg/m2, and 49% were women. Higher HbA1c was associated with worse left ventricular systolic (ejection fraction and global longitudinal strain) and diastolic (E/e'‐ratio) function, myocardial injury (cardiac troponin T), inflammation (CRP), and impaired neurohormonal homeostasis (NT‐proBNP) (P<0.001 in unadjusted and P<0.01 in adjusted analysis for all). The associations between HbA1c and cardiovascular biomarkers were independent of the echocardiographic variables, and vice versa. Associations were nonlinear (P<0.05 for nonlinearity) and appeared stronger in the pre‐DM range of HbA1c than the no‐DM and DM range. Conclusions HbA1c was associated with indexes of subclinical cardiovascular disease, and this was more pronounced in pre‐DM. Our results suggest that cardiovascular preventive measures should be considered also in subjects with hyperglycemia and HbA1c below the established DM cutoff. Registration clinicaltrials.gov. Identifier: NCT01555411.

• Johannessen, Øyvind; Myhre, Peder Langeland & Omland, Torbjørn (2021). Assessing congestion in acute heart failure using cardiac and lung ultrasound - a review. Expert Review of Cardiovascular Therapy. ISSN 1477-9072. 19(2), p. 165–176. doi: 10.1080/14779072.2021.1865155. Full text in Research Archive
• Beldhuis, Iris E.; Myhre, Peder Langeland; Bristow, Michael; Claggett, Brian; Damman, Kevin & Fang, James C. [Show all 17 contributors for this article] (2021). Spironolactone in Patients With Heart Failure, Preserved Ejection Fraction, and Worsening Renal Function. Journal of the American College of Cardiology. ISSN 0735-1097. 77(9), p. 1211–1221. doi: 10.1016/j.jacc.2020.12.057. Full text in Research Archive
• Myhre, Peder Langeland; Ottesen, Anett Hellebø; Faaren, Arne L.; Tveit, Sjur Hansen; Springett, Jon & Pyylampi, Johanna [Show all 11 contributors for this article] (2021). Performance of a Novel Research-Use-Only Secretoneurin ELISA in Patients with Suspected Acute Coronary Syndrome: Comparison with an Established Secretoneurin Radioimmunoassay. Cardiology. ISSN 0008-6312. 146(5), p. 566–574. doi: 10.1159/000517444. Full text in Research Archive Show summary

  Background: Circulating secretoneurin (SN) concentrations, as measured by established radioimmunoassay (RIA), risk stratify patients with cardiovascular disease. We now report data for a recently developed research-use-only SN enzyme-linked immunosorbent assay (ELISA) in patients with suspected acute coronary syndrome (ACS). Methods: SN ELISA was developed according to industry standards and tested in 401 unselected chest pain patients. Blood samples were drawn <24 h from admission, and we adjudicated all hospitalizations as ACS or non-ACS. The mean follow-up was 6.2 years. Results: SN ELISA with 2 monoclonal sheep anti-SN antibodies has a measuring range of 10–250 pmol/L and demonstrates excellent analytical precision and accuracy across the range of SN concentrations. SN measured by ELISA and RIA correlated in the chest pain patients: rho = 0.39, p < 0.001. SN concentrations were higher in ACS patients (n = 161 [40%]) than in non-ACS patients (n = 240) for both assays, with an area under the curve (AUC) of 0.66 (95% CI: 0.61–0.71) for ELISA and 0.59 (0.54–0.65) for RIA. SN concentrations were also higher in nonsurvivors (n = 65 [16%]) than survivors, with an AUC of 0.72 (0.65–0.79) for ELISA versus 0.64 (0.56–0.72) for RIA, p = 0.007, for difference between assays. Adjusting for age, sex, blood pressure, previous myocardial infarction, atrial fibrillation, and heart failure in multivariable analysis, SN concentrations as measured by ELISA, but not RIA, remained associated with mortality, with a hazard ratio of 1.71 (1.03–2.84), p = 0.038. Conclusions: The novel SN ELISA has excellent performance, higher AUC for diagnosis, and superior prognostic accuracy compared to the established RIA in chest pain patients.

• Omland, Torbjørn; Prebensen, Christian Haugland; Jonassen, Christine M; Svensson, My Hanna Sofia; Berdal, Jan-Erik & Seljeflot, Ingebjørg [Show all 7 contributors for this article] (2021). Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19. Open heart. 8(2), p. 1–7. doi: 10.1136/openhrt-2021-001884. Full text in Research Archive Show summary

  Objective Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. Methods We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. Results Concentrations of sST2 at baseline was median 48 (IQR 37–67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36–59) ng/mL; ICU 67 (39–104) ng/mL and non-survivors 107 (72–116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . Conclusions sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19.

• Myhre, Peder Langeland; Selvaraj, Senthil & Solomon, Scott D. (2021). Management of hypertension in heart failure with preserved ejection fraction: is there a blood pressure goal? Current Opinion in Cardiology. ISSN 0268-4705. 36(4), p. 413–419. doi: 10.1097/HCO.0000000000000852. Full text in Research Archive
• Prebensen, Christian; Myhre, Peder Langeland; Jonassen, Christine M; Rangberg, Anbjørg; Blomfeldt, Anita & Svensson, My Hanna Sofia [Show all 8 contributors for this article] (2020). Severe Acute Respiratory Syndrome Coronavirus 2 RNA in Plasma Is Associated with Intensive Care Unit Admission and Mortality in Patients Hospitalized with Coronavirus Disease 2019. Clinical Infectious Diseases. ISSN 1058-4838. 73(3). doi: 10.1093/cid/ciaa1338. Full text in Research Archive
• Myhre, Peder Langeland; Grundvold, Irene; Paulsen, Trine Hessevik; Omland, Torbjørn & Schirmer, Henrik (2020). Cardiovascular Hospitalizations, Influenza Activity, and COVID-19 Measures. Circulation. ISSN 0009-7322. 142(13), p. 1302–1304. doi: 10.1161/CIRCULATIONAHA.120.049118. Full text in Research Archive
• Tveit, Sjur Hansen; Cwikiel, Joanna; Myhre, Peder Langeland; Omland, Torbjørn; Berge, Eivind & Seljeflot, Ingebjørg [Show all 7 contributors for this article] (2020). Differential associations of cardiac troponin T and cardiac troponin I with coronary artery pathology and dynamics in response to short-duration exercise. Clinical Biochemistry. ISSN 0009-9120. p. 1–7. doi: 10.1016/j.clinbiochem.2020.11.005. Full text in Research Archive Show summary

  Background We aimed to assess the associations between cardiac troponin (cTn) T and I concentrations, physical exercise and the presence and severity of angiographic coronary artery disease (CAD) in patients evaluated for suspected chronic coronary syndrome (CCS). Methods and results All patients performed an exercise stress test on a bicycle ergometer and underwent invasive coronary angiography with weighted anatomical evaluation using the Gensini score. Blood samples were collected before and after exercise and analysed with high-sensitivity (hs) cTnT and cTnI assays. Of 297 patients (median age 62 (Quartile [Q]1–3 56–69) years, 35% female), 46% were categorized as “severe CAD” (Gensini score ≥ 20). Resting hs-cTnT and hs-cTnI concentrations were detectable in 88% and 100% of patients, with medians of 6 (Q1-3 4–9) ng/L and 1.5 (0.9–2.4) ng/L, respectively. In adjusted normalized linear regression analyses, higher resting concentrations were associated with increasing Gensini score (hs-cTnT: B 0.19, 95% Confidence Interval [CI] [0.09–0.41], p < 0.001; hs-cTnI: B 0.18, [0.06–0.30], p = 0.002). The area under the receiver operating characteristics curve for predicting severe CAD was 0.72 (95% CI [0.66–0.78]) and 0.68 (0.62–0.74) for resting hs-cTnT and hs-cTnI, p = 0.11 for difference. The median (Q1-3) relative increase in hs-cTnT and hs-cTnI concentrations were 5 (0–12) % and 13 (3–27) %, respectively, with no significant associations with CAD severity. Conclusions In patients with suspected CCS, higher hs-cTn concentrations at rest were associated with increasing angiographic severity of CAD, without any significant differences between the troponin isotypes. Post-exercise hs-cTn concentrations did not have discriminatory power for CAD.

• Berge, Kristian; Lyngbakken, Magnus; Myhre, Peder Langeland; Brynildsen, Jon; Røysland, Ragnhild & Strand, Heidi [Show all 10 contributors for this article] (2020). High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in acute heart failure: Data from the ACE 2 study. Clinical Biochemistry. ISSN 0009-9120. p. 1–7. doi: 10.1016/j.clinbiochem.2020.11.009. Full text in Research Archive Show summary

  Background To assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea. Methods We measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Results In the total population, median age was 73 (quartile [Q] 1–3 63–81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22–75) vs. 13 (4–25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73–0.86) for hs-cTnT, 0.79 (0.73–0.86) for NT–proBNP, and 0.83 (0.76–0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07–1.58), p = 0.009. Conclusion hs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea.

• Kalstad, Are; Myhre, Peder Langeland; Laake, Kristian; Tveit, Sjur Hansen; Schmidt, Erik Berg & Smith, Pål [Show all 12 contributors for this article] (2020). Effects of n-3 fatty acid supplementations in elderly patients after myocardial infarction: A randomized controlled trial. Circulation. ISSN 0009-7322. 143(6), p. 528–539. doi: 10.1161/CIRCULATIONAHA.120.052209. Full text in Research Archive Show summary

  Background: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after myocardial infarction, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. Methods: The OMEMI trial (Omega-3 Fatty acids in Elderly with Myocardial Infarction) is an investigator-initiated, multicenter, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg eicosapentaenoic acid and 660 mg docosohexaenoic acid) versus placebo (corn oil) daily to standard of care in patients aged 70 to 82 years with recent (2–8 weeks) AMI. The primary endpoint was a composite of nonfatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after 2 years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. Results: In total, 1027 patients were randomized. Follow-up data were available for 1014 patients who were included in the intention-to-treat analysis. Mean±SD age was 75±3.6 years, 294 (29%) were female, and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA versus 102 (20.0%) on placebo (hazard ratio, 1.08 [95% CI, 0.82–1.41]; P=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA versus 15 (4.0%) on placebo (1.84 [0.98–3.45]; P=0.06). Median changes in eicosapentaenoic acid and docosahexaenoic acid were +87% and +16% for n-3 PUFA versus −13% and −8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (P=0.87). Similar results were found in per-protocol analysis (n=893). Conclusions: We could not detect reduction in clinical events in our elderly patients with recent AMI who were treated with 1.8 g n-3 PUFAs daily for 2 years.

• Omland, Torbjørn; Prebensen, Christian; Røysland, Ragnhild; Søvik, Signe; Sørensen, Vibecke & Røsjø, Helge [Show all 9 contributors for this article] (2020). Established Cardiovascular Biomarkers Provide Limited Prognostic Information in Unselected Patients Hospitalized with COVID-19. Circulation. ISSN 0009-7322. 19, p. 1878–1880. doi: 10.1161/CIRCULATIONAHA.120.050089. Full text in Research Archive
• Myhre, Peder Langeland; Prebensen, Christian; Strand, Heidi; Røysland, Ragnhild; Jonassen, Christine M. & Rangberg, Anbjørg [Show all 12 contributors for this article] (2020). Growth Differentiation Factor-15 Provides Prognostic Information Superior to Established Cardiovascular and Inflammatory Biomarkers in Unselected Patients Hospitalized with COVID-19. Circulation. ISSN 0009-7322. doi: 10.1161/CIRCULATIONAHA.120.050360. Full text in Research Archive

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• Rolland, J; Ovrebotten, T; Berge, Kristian; Nahoui, Hamza; Bjorkelund, O A & Broch, Kaspar [Show all 15 contributors for this article] (2026). Contemporary post-discharge management in heart failure at home (STRONG@HOME). European Journal of Heart Failure. ISSN 1388-9842. 28(Supplement_2). doi: 10.1093/ejhf/xuag193.1424. Full text in Research Archive Show summary

  Abstract Background The post-discharge period after heart failure (HF) hospitalisation is associated with high-risk, and the uptake of guideline-directed medical therapy (GDMT) remains suboptimal. In the STRONG-HF trial, an intensive strategy of rapid GDMT up-titration and close follow-up after an acute HF admission reduced the risk of all-cause mortality and HF readmissions compared to usual care. Based on the STRONG-HF results, this strategy received a Class IB recommendation in the 2023 Focused Update of the ESC HF Guidelines, but requires substantial resources and may offer logistical challenges. Whether follow-up visits can safely be performed virtually at home and still achieve the same degree of GDMT without excess adverse events remains unknown. Objectives This abstract describes the design and methodological framework of STRONG@HOME. This trial evaluates whether patients discharged after hospitalisation for acute HF can safely achieve the same level of GDMT via digital follow-up at home as compared to hospital visits, according to the STRONG-HF strategy. Methods STRONG@HOME is a randomised, multicentre, open-label, parallel group trial. In total, 462 patients hospitalised for acute HF will be randomised in a 1:1 ratio to receive digital (experimental arm) or in-person (control arm) follow-up at 1-, 2-, 3- and 6-weeks post-discharge (See Figure). Patients in the control arm are followed at outpatient HF clinics, while patients in the experimental arm are followed up via video consultations and telemonitoring. The dual primary outcomes (Bonferroni corrected with 0.025 as significance level) are assessed for non-inferiority after 90 days at the final follow-up visit. Efficacy is measured by the GDMT-score (0-9), based on four drug classes. Safety is assessed as treatment-emergent adverse events, including eGFR &lt;30 mL/min/1.73 m², systolic BP &lt;95 mm Hg, heart rate &lt;50 bpm, and serum potassium &gt;5.5 mmol/L. The expected median GDMT-score in the control arm is 7 (SD 2.5). With a 10% non-inferiority margin, a sample size of 404 is needed for 80% power and a significance level of 0.025. For safety, a 51% expected adverse events rate requires a sample size of 416. At an expected 10% dropout rate, the final overall target sample size is 462. Per January 1, 2026, 83 patients have been enrolled, and all sites are activated. Conclusion STRONG@HOME is the first study to assess if patients with acute HF can safely achieve the same level of GDMT through digital home follow-up as through hospital visits, using the STRONG-HF strategy. This approach could enable broader implementation of guideline-recommended post-discharge management at reduced cost, improve accessibility for patients in rural or underserved areas, and alleviate capacity constraints at specialised HF clinics. Digital follow-up may also enhance patient convenience and adherence while maintaining clinical outcomes, potentially transforming post-discharge HF care delivery at scale.Strong@Home flow chartFor image description, please refer to the figure legend and surrounding text.

• Braanaas, Karoline Svensen; Dammen, Toril; Fagerland, Morten; Husebye, Einar; Leinaas, A & Schirmer, Henrik [Show all 10 contributors for this article] (2026). Individually Tailored monitoring at home after hospitalization for HEART failure (IT-HEART): Design and baseline characteristics of a randomized clinical trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(2). doi: 10.1093/eurjpc/zwag249.461. Full text in Research Archive Show summary

  Abstract Background Telemonitoring has emerged as a promising alternative to conventional heart failure (HF) management. Despite its potential, evidence from randomized controlled trials remains inconclusive, and data from high-risk populations with frailty, is scarce. The Individually Tailored remote monitoring at home after HEART failure (IT-HEART) trial evaluates whether a non-invasive telemonitoring program improves clinical, patient reported, and health economic outcomes in HF patients after a recurrent hospitalization. Purpose To describe flow of patients and baseline characteristics of the IT-HEART study population. Methods This multicentre, open-label, blinded-endpoint trial randomized HF patients to either written information and a self-management plan (Control) or HF education, a personalized self-management plan, and three months of home telemonitoring (Intervention). The primary endpoint is the total number of HF hospitalizations or cardiovascular death. Secondary endpoints include hospitalizations and outpatient visits, adherence the intervention, patient reported outcomes, and health economic measures. End of follow-up will be in October 2026. Results Of 1027 consecutively screened patients, 200 (19.5%) were randomized. Median age was 78 (IQR (70-83) years, and 29.5% were women. At baseline, participants had substantial multimorbidity with median Clinical Frailty Scale score 4, median Charlson Comorbidity Index score 6, and symptom burden was high (Table). Median self-rated HF management knowledge was 3 (IQR 0-7) on a 0-10 Likert scale. Only 35.5% weighed themselves weekly whereas 1 % (n=2) reported having a formal self-care plan at baseline. In the intervention arm (N=100), 64 participants used a digital telemonitoring platform and 36 received telephone-based monitoring. Conclusion Patients enrolled after a recurrent HF hospitalization were older, multimorbid, and frail, with high symptom burden, and low self-care and health literacy. The IT-HEART telemonitoring intervention is targeted to these modifiable deficits and has the potential to improve clinical and patient-reported outcomes.For image description, please refer to the figure legend and surrounding text.

• Myrstad, Marius; Skaar, Elisabeth & Myhre, Peder Langeland (2026). Addressing the gaps in heart failure treatment for frail older adults: challenges, evidence, and future directions. ESC Heart Failure. 13(2). doi: 10.1093/eschf/xvag084. Full text in Research Archive Show summary

  This viewpoint examines gaps in evidence and practical challenges in treating heart failure (HF) among people living with frailty. Our aim is not to argue that guideline-directed medical therapy (GDMT) should be universally applied or withheld. Rather, we (i) highlight limitations in current randomized trial evidence for frail and multimorbid patients, (ii) offer person-centred approaches for decision-making when trial data are incomplete, and (iii) propose realistic research and implementation priorities to improve safety and outcomes for this vulnerable population. Frailty is highly prevalent in older patients with HF, yet individuals living with frailty—especially those living with severe frailty, cognitive impairment, or substantial multimorbidity—are underrepresented in HF trials. While recent pharmacological advances [e.g. neprilysin inhibition and sodium–glucose cotransporter-2 (SGLT2) inhibition) have reduced HF-related events and improved symptoms, the balance between benefits and harms remains uncertain when extrapolated to patients living with severe frailty. Frailty magnifies vulnerability to adverse effects, polypharmacy harms, and functional decline, and conversely, many patients with frailty derive large symptom and function benefits from appropriate HF therapy. Moreover, treatment goals for frail patients may place relatively greater emphasis on symptom control and quality of life than on mortality benefits.

• Myhre, Peder Langeland & Vaduganathan, Muthiah (2026). Does the Mechanism of Weight Loss Matter for Cardiovascular Protection? Journal of the American College of Cardiology. ISSN 0735-1097. 85(5), p. 501–503. doi: 10.1016/j.jacc.2024.12.020. Full text in Research Archive
• Moen, Oda Klavestad; Johannessen, Øyvind; Myhre, Peder Langeland; Heck, Siri Lagethon; Corbett, Rebecca Aure & Windstad, Vilde Malo [Show all 10 contributors for this article] (2025). Pre-test probability (PTP) for coronary artery disease (CAD) is enhanced by incorporating risk factors and coronary artery calcium (CAC) score. European Society of Cardiology. Full text in Research Archive
• Færevik, Hilde; Fretland, Signe Øien & Myhre, Peder Langeland (2025). Industri og klinikere møttes under ESC-kongressen i Madrid. Full text in Research Archive Show summary

  - Vi setter aldri spørsmålstegn ved kvaliteten på data fra kliniske studier i Norge og Norden, men god kvalitet alene er ikke nok. Det må også leveres raskt og effektivt.

• Myhre, Peder L; Hoff, Nils Jakob S & Lund, Lars H (2025). Potential role of repeated Valsalva manoeuvres in atrial fibrillation risk among elite rowers. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehaf969. Full text in Research Archive
• Dahl, Tuva Børresdatter; Aftab, Friha; Prebensen, Christian Haugland; Berdal, Jan-Erik; Ueland, Thor & Barratt-Due, Andreas [Show all 15 contributors for this article] (2025). Imidazole propionate is increased in severe COVID-19 and correlates with cardiac involvement. Journal of Infection. ISSN 0163-4453. 90(6). doi: 10.1016/j.jinf.2025.106494. Full text in Research Archive
• Myhre, Peder Langeland; Berge, Kristian & Ørn, Stein (2024). Reply to the letter regarding the article ‘Changes in 6-min walk test is an independent predictor of death in chronic heart failure with reduced ejection fraction’. European Journal of Heart Failure. ISSN 1388-9842. doi: 10.1002/ejhf.3448. Full text in Research Archive
• Myhre, Peder Langeland & Lam, Carolyn S.P. (2024). Angiotensin Receptor Neprilysin Inhibition Across Ejection Fraction and Acuity Spectra in Heart Failure. JACC. Heart failure. ISSN 2213-1779. doi: 10.1016/j.jchf.2023.11.021. Full text in Research Archive
• Myhre, Peder Langeland; Omland, Torbjørn & Shah, Amil M. (2024). Ongoing Enigma of NT-proBNP in HFpEF: Insights from Proteomics. Circulation: Heart Failure. ISSN 1941-3289. 17(2), p. 126–128. doi: 10.1161/CIRCHEARTFAILURE.123.011428. Full text in Research Archive
• Lam, Carolyn S. P. & Myhre, Peder Langeland (2023). Left ventricular ejection fraction in women: when normal isn't normal. Heart. ISSN 1355-6037. doi: 10.1136/heartjnl-2023-322924. Full text in Research Archive
• Prebensen, Christian Haugland; Lefol, Yohan Pierre; Myhre, Peder Langeland; Lüders, Torben; Jonassen, Christine M & Blomfeldt, Anita [Show all 9 contributors for this article] (2023). Author Correction: Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19 (Scientific Reports, (2023), 13, 1, (10368), 10.1038/s41598-023-37606-y). Scientific Reports. 13(1). doi: 10.1038/s41598-023-39872-2. Full text in Research Archive
• Skoie, Inger Marie; Skogås, Jan Gunnar; Langø, Thomas; Myhr, Kjell-Morten; Myhre, Peder Langeland & Goll, Rasmus [Show all 8 contributors for this article] (2023). Nye sentre skal gi flere kliniske studier i Norge. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(2). doi: 10.4045/tidsskr.22.0722. Full text in Research Archive Show summary

  Seks NorTrials-sentre for behandlingsforskning er etablert ved universitetssykehusene. Målet er å øke antallet kliniske studier og forbedre pasientbehandlingen.

• Mohebi, Reza; liu, Yuxi; Myhre, Peder Langeland; Felker, G. Michael; Prescott, Margaret F. & Pina, Ileana [Show all 10 contributors for this article] (2023). Heart Failure Phenotypes According to Natriuretic Peptide Trajectory Following Initiation of Sacubitril/Valsartan. JACC. Heart failure. ISSN 2213-1779. 11(7), p. 855–858. doi: 10.1016/j.jchf.2023.03.006. Full text in Research Archive
• Myhre, Peder Langeland & Omland, Torbjørn (2023). Fine-Tuning Risk Stratification in Heart Failure: Does It Improve Patient Care? JACC. Heart failure. ISSN 2213-1779. 11(6), p. 675–677. doi: 10.1016/j.jchf.2023.02.004. Full text in Research Archive
• Nilsen, Dennis W.T.; Myhre, Peder Langeland; Kalstad, Are; Schmidt, EB; Arnesen, Harald & Seljeflot, Ingebjørg (2021). Circulation 2021 (Nov. 8); 144 (Suppl. 1): A9147. Reduced delta-6-desaturase activity may be associated with major adverse cardiac events during 2 years follow up in elderly patients with a recent myocardial infarction. Full text in Research Archive Show summary

  Background: Low levels of dihomo-gamma linolenic acid (DGLA) have been related to a bad outcome in patients with acute coronary syndromes. Reduced levels of DGLA may result from reduced conversion of its precursor linoleic acid (LA). An increase in the ratio of LA to DGLA (LA:DGLA) has been shown to reflect reduced delta-6-desaturase activity. Aim: To evaluate the association between the LA:DGLA ratio, reflecting delta-desaturase activity, and the risk of major adverse cardiovascular event (MACE, comprising nonfatal myocardial infarction (MI), unscheduled revascularization, stroke, hospitalization for heart failure, or all-cause death), in patients with a recent MI. Methods: Baseline samples from the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) trial* in which a total of 1027 patients, age 70 to 82 years, were included 2-8 weeks after an MI and followed up for 2 years, were used. FAs were measured in serum phospholipids, and the LA:DGLA ratio was calculated at baseline and related to incident MACE by univariate and multivariable Cox regression analyses, adjusted for age, sex, body mass index, omega-3 supplementation at baseline and hypertension. Results: A total of 208 patients experienced MACE during follow-up. The univariate hazard ratio (HR) for MACE in the fourth quartile (Q4) of LA:DGLA compared to the lowest quartile (Q1) was 1.49 (95% confidence interval (CI), 1.00-2.23), p=0.005. After adjustment, the HR for Q4 was weakened [1.47 (0.97-2.25), p=0.072]. The HR for Q2-4 combined as compared to Q1 was borderline significant [1.42 (0.99-2.03)], p=0.055. Although the number of total deaths were more than two-fold higher in Q4 as compared to Q1 [HR 2.30 (1.04-5.06), p=0.038], this did not reach significance in the adjusted models [HR 2.26 (0.95-5.37), p=0.065], and remained non-significant when comparing Q2-4 combined to Q1 [HR 1.74 (0.80-3.77), p=0.16]. Conclusion: Higher levels of LA:DGLA ratio were found to be associated with MACE in elderly patients with a recent MI, suggesting a mechanism to why low levels of DGLA may be associated with increased adverse events. * Circulation 2021; 143(6): 528-39.

• Nilsen, Dennis W.T.; Myhre, Peder Langeland; Kalstad, Are; Schmidt, EB; Arnesen, Harald & Seljeflot, Ingebjørg (2021). Circulation 2021 (Nov. 8); 144 (Suppl. 1): A9098. The relationship between linoleic acid (LA) and dihomo-gamma-linoleic acid (DGLA) as indicator of delta-6-desaturase activity.. Full text in Research Archive Show summary

  Introduction: Low levels of dihomo-gamma-linolenic acid (DGLA) have been shown to predict total death in patients hospitalized with an acute coronary syndrome. DGLA is converted from gamma-linolenic acid (GLA) by the enzyme elongase, following a slower and rate-limiting conversion from linoleic acid (LA) to GLA by the action of delta-6-desaturase. This would suggest that DGLA levels are (strongly) associated with delta-6-desaturase activity. Furthermore, a high ratio of LA to DGLA (LA:DGLA) has been claimed to reflect reduced delta-6-desaturase activity. Hypothesis/Aim: To evaluate the relationship between LA:DGLA ratio and DGLA levels in patients with a recent myocardial infarction (MI). Methods: Baseline samples from the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) trial* in which a total of 1027 patients, aged 70 to 82 years, were included 2-8 weeks after an MI, were obtained. The total fatty acid profile was determined in serum phospholipids and relative concentrations (wt%) of LA, GLA and the LA:DGLA ratio (used as a surrogate for delta-6-desaturase activity) were evaluated across quartiles of concentrations of DGLA. Results: Levels of GLA were low compared to other n-6 fatty acids and followed the same trend as DGLA, consistent with a rapid turnover from GLA (Table 1). Furthermore, there was a steady decrease in the LA:DGLA ratio across the quartiles of DGLA, with approximately 50% lower levels in the highest compared to the lowest quartile of DGLA. Conclusion: We found a strong inverse relationship between DGLA and the LA:DGLA ratio in patients with a recent MI, indicating that the LA:DGLA ratio may serve as a measure of delta-6-desaturase activity. * Circulation 2021; 143(6): 528-39.

• Cunningham, Jonathan W. & Myhre, Peder Langeland (2021). NT-proBNP Response to Heart Failure Therapies: An Imperfect Surrogate. Journal of the American College of Cardiology. ISSN 0735-1097. 78(13), p. 1333–1336. doi: 10.1016/j.jacc.2021.07.045. Full text in Research Archive
• Myhre, Peder Langeland; Vaduganathan, Muthiah & Solomon, Scott D. (2021). Neprilysin and Corin: It Takes Two to Tango. JACC. Heart failure. ISSN 2213-1779. 9(2), p. 96–99. doi: 10.1016/j.jchf.2020.08.018. Full text in Research Archive
• Nilsen, Dennis W.T.; Myhre, Peder Langeland; Kalstad, Are; Schmidt, Erik Berg; Arnesen, Harald & Seljeflot, Ingebjørg (2021). Low levels of dihomo-gamma-linolenic acid are associated with all-cause death in elderly patients with a recent myocardial infarction. Full text in Research Archive Show summary

  European Heart Journal 2021;42 (Supplement):2498. Background: In a previous study*, low levels of the omega-6 fatty acid (FA) dihomo-gamma (γ)-linolenic acid (DGLA; C20:3w6), were independently associated with poor 7-year outcome in elderly patients after acute coronary syndrome. Aim: In order to further evaluate DGLA as a predictor of outcome, we measured n-6 FAs including DGLA in serum samples from elderly subjects with a recent acute myocardial infarction (AMI). Methods: Baseline samples from the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) trial* in which a total of 1027 patients, aged 70 to 82 years, were included 2–8 weeks after an MI, were used. The pre-specified primary outcome during 2 years follow-up was major adverse cardiac events (MACE), which consisted of nonfatal MI, unscheduled coronary revascularization, stroke, all-cause death, or hospitalization for heart failure. Cox regression analysis was used to relate serum n-6 FA levels, measured by gas chromatography and reported as % weight of total FA (%wt) to the risk of incident cardiovascular events. Three models were employed in the multivariable analysis, adjusting for: 1) age, sex and body mass index; 2) + baseline omega-3 FA supplementation; 3) + prevalent hypertension. Results: Median DGLA levels at baseline (n=1.002) were 2.89 (Q1–Q3 2.43–3.38) %wt. After 2 years follow-up, 152 patients experienced incident MACE, including n=55 all-cause death. The univariate hazard ratio (HR) for MACE, employing continuous DGLA values was 0.89 (95% CI 0.72–1.08) per %wt increase in DGLA, p=0.24, and for all-cause death 0.72 (95% CI 0.48–1.07), p=0.11. In the multivariable Cox regression models for MACE, concentrations of DGLA did not reach statistical significance; p=0.12, 0.09 and p=0.07 in Models 1, 2 and 3, respectively. In univariate analysis, HR for total death in the three higher quartiles of DGLA as compared to the lowest quartile was 0.51 (95% CI 0.30–0.80), p=0.016. Results remained statistically significant in all the multivariable models. Model 1: HR 0.54 (0.31–0.95), p=0.03; Model 2: HR 0.50 (0.28–0.91) p=0.02; Model 3: HR 0.49 (0.27–0.88), p=0.017. Conclusion: Low serum levels of DGLA were associated with increased risk of all-cause death after AMI in elderly patients, thus, suggesting DGLA to be protective.

• Myhre, Peder Langeland; Seljeflot, Ingebjørg & Arnesen, Harald (2021). Omega-3-tilskudd forebygger ikke hjertesykdom. doi: 10.4045/tidsskr.21.0033. Full text in Research Archive
• Myhre, Peder Langeland; Lyngbakken, Magnus Nakrem; Røsjø, Helge Rørvik & Omland, Torbjørn (2020). Removing stable and adding precision to chronic coronary artery disease. International Journal of Cardiology. ISSN 0167-5273. 316, p. 54–56. doi: 10.1016/j.ijcard.2020.04.063. Full text in Research Archive
• Tveit, Sjur Hansen; Myhre, Peder Langeland; Røsjø, Helge Rørvik & Omland, Torbjørn (2020). Reply: The complementary role of cardiac troponin I and cardiac troponin T. Clinical Biochemistry. ISSN 0009-9120. 78, p. 42–42. doi: 10.1016/j.clinbiochem.2020.02.011. Full text in Research Archive
• Januzzi, James L. & Myhre, Peder Langeland (2020). The Challenges of NT-proBNP Testing in HFpEF: Shooting Arrows in the Wind. JACC. Heart failure. ISSN 2213-1779. 8(5), p. 382–385. doi: 10.1016/j.jchf.2020.03.003. Full text in Research Archive
• Slind, Eva Kjøl; Lægran, Marianne; Ingul, Charlotte Ingeborg Björk; Eriksen-Volnes, Torfinn Kirknes; Blindheimsvik, Martin Andre Brevik & Myhre, Peder Langeland [Show all 13 contributors for this article] (2022). Norsk hjertesviktregister : Årsrapport 2021 : Med plan for forbedringstiltak. Norsk hjerteviktregister. Full text in Research Archive

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