Selfreported health status, treatment decision and survival in asymptomatic and symptomatic patients with aortic stenosis in a Western Norway population undergoing conservative treatment: a cross-sectional study with 18 months follow-up

Objectives: To investigate symptoms and self-reported health of patients conservatively treated for aortic stenosis (AS) and to identify factors associated with treatment decision and patient outcomes. Design: A cross-sectional survey with an 18-month follow-up. Setting: One tertiary university hospital in Western Norway. Participants: In all, 1436 patients were diagnosed with AS between 2000 and 2012, and those 245 still under conservative treatment in 2013 were included in this study. Primary and secondary outcome measures: Primary outcome measures were symptoms and self-reported health status. Secondary outcomes were treatment decision and patient survival after 18 months. Results: A total of 136 patients with mean (SD) age 79 (12) years, 52% men responded. Among conservatively treated patients 77% were symptomatic. The symptom most frequently experienced was dyspnoea. Symptomatic patients reported worse physical and mental health compared with asymptomatic patients (effect size 1.24 and 0.74, respectively). In addition, symptomatic patients reported significantly higher levels of anxiety and depression compared with asymptomatic patients. However, symptom status did not correlate with haemodynamic severity of AS. After 18 months, 117 (86%) were still alive, 20% had undergone surgical aortic valve replacement (AVR) and 7% transcatheter aortic valve implantation (TAVI). When adjusting for age, gender, symptomatic status, severity of AS and European system for cardiac operative risk evaluation (EuroSCORE), patients with severe AS had more than sixfold chance of being scheduled for AVR or TAVI compared with those with moderate AS (HR 6.3, 95% CI 1.9 to 21.2, p=0.003). Patients with EuroSCORE ≥11 had less chance for undergoing AVR or TAVI compared with those with EuroSCORE ≤5 (HR 0.06, 95% CI 0.01 to 0.46, p=0.007). Conclusions: Symptoms affected both physical and mental health in conservatively treated patients with AS. Many patients with symptomatic severe AS are not scheduled for surgery, despite the recommendations in current guidelines. The referral practice for AVR is a path for further investigation.publishedVersio

Analyses of Increased Mortality in New and Known Diabetes in Patients with Coronary Disease Enrolled in the NORSTENT Randomized Study

Background: NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention with drug-eluting stents (DES) or bare-metal stents (BMS) with a 5-year follow-up. Among the patients, 5,512 had measured either fasting glucose level or percent glycated hemoglobin (HbA1c) at the index procedure. That cohort constitutes the present study population analyzing mortality and evaluating treatment heterogeneity of randomized stent in diabetic versus nondiabetic subgroups. Results: The cohort consisted of 4,174 (75.7%) patients without diabetes, 716 (13.0%) with known diabetes, and 622 (11.3%) with no diabetes in history but elevated fasting glucose level >7.0 mmol/L or HbA1c >6.5% and therefore defined as new diabetes. Patients with known diabetes had a significantly increased all-cause (hazard ratio [HR] 1.99, 95% CI 1.51–2.62, p < 0.001), cardiac (subhazard ratio [SHR] 2.47, 95% CI 1.55–3.93, p < 0.001), and noncardiac (SHR 1.74, 95% CI 1.23–2.44, p = 0.002) mortality after adjustment for baseline variables. In the follow-up of 5 years, patients with new diabetes, however, had a marginally increased all-cause (HR 1.40, 95% CI 1.01–1.93, p = 0.043) and significantly increased noncardiac mortality (SHR 1.52, 95% CI 1.06–2.20, p = 0.025), but no increase in cardiac mortality (SHR 1.06, 95% CI 0.53–2.12, p = 0.86) after the same adjustment. The majority of the mortality was cardiac in the first 1–2 years after intervention; thereafter, noncardiac mortality dominated. However, the time period for when noncardiac mortality became the dominating cause varied considerably and significantly between the groups. There was no heterogeneity in mortality in response to randomized stent between diabetics and nondiabetics. Conclusion: Known diabetes has increased cardiac and noncardiac mortality in contrast to new diabetes which is only associated with increased noncardiac mortality during the 5-year follow-up. Diabetic and nondiabetic patients have the same response to the treatment with BMS or DES.acceptedVersio

Quality of life in female myocardial infarction survivors: a comparative study with a randomly selected general female population cohort

Background: A substantial burden associated with MI has been reported. Thus, how survivors experience their quality of life (QOL) is now being given increasing attention. However, few studies have involved women and a comparison with the general population. The aims of this study were to determine the QOL of female MI survivors, to investigate whether their QOL differed from that of the general population, and to evaluate the clinical significance of the findings. Methods: Two cross-sectional surveys were performed; on female MI survivors and the general Norwegian population. The MI survey included women aged 62–80 years, three months to five years after their MI. One hundred and forty-five women responded, yielding a response rate of 60%. A subset of women in the same age range (n = 156) was drawn from a study of 1893 randomly selected Norwegian citizens. QOL was measured in both groups with the World Health Organization Quality of Life Instrument Abbreviated (WHOQOL-BREF). Results: The majority (54%) of the female MI survivors presented with ST-elevation in their ECG, 31% received thrombolysis, and 38% had reduced left ventricular ejection fraction. Female MI survivors reported significantly lower satisfaction with general health (p = 0.020) and overall QOL (p = 0.017) than women from the general population. This was also the case for the physical and environmental QOL domains (p < 0.001), but not for the psychological and social relationship domains. Estimated effect sizes between the two groups of participants ranged from 0.1 to -0.6. Conclusion: The burden of MI significantly affects the physical health of elderly women. Still, female MI survivors fare as well as the general female population on psychosocial QOL domains. Action should be taken not only to support women's physical needs but also to reinforce their strengths in order to maintain optimal QOL

The effect of drug-eluting stents on target lesion revascularization in native coronary arteries: Results from the NORSTENT randomized study

This is the accepted manuscript version of an article published by S. Karger AG in Cardiology, 2020;145(6):333-341, available at https://doi.org/10.1159/000506042. Background: The NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) or bare-metal stent (BMS) with 5-year follow-up. No difference was found in the composite primary outcome of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularizations, which were reduced by DES. We report the occurrence of target lesion revascularization (TLR) in time and across demographic and clinical subgroups in patients with lesions in native coronary arteries (n = 8,782). Results: Clinically driven TLR was performed on 488 (5.6%) of the 8,782 patients during 5 years of follow-up. Male gender, older age, visible thrombus in the lesion, and larger stent diameter were associated with less TLR; multivessel disease and longer stents were associated with a higher risk of TLR. There was a substantial and highly significant reduction of the risk of any TLR after 5 years in the DES group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.36–0.52], p Conclusion: DES have a time-limited effect on the rate of TLR, but with a substantial and highly significant reduction in the first 2 years after the procedure. This effect was found to be consistent across all important clinical subgroups

Thrombus characteristics evaluated by acute optical coherence tomography in ST elevation myocardial Infarction

Aims ST elevation myocardial infarction (STEMI) is caused by an occlusive thrombosis of a coronary artery. We wanted to assess if the thrombus can be characterized according to erythrocyte content and age using intravascular optical coherence tomography (OCT) in a clinical setting. Methods and results We performed manual thrombus aspiration in 66 STEMI patients. OCT was done of the thrombus remnants after aspiration. A light intensity ratio was measured through the thrombus. Forty two of the aspirates had thrombus which could be analyzed histomorphologically for analysis of erythrocyte and platelet content, and to determine the age of thrombus as fresh, lytic or organized. There were 11 red, 21 white and 10 mixed thrombi. Furthermore, 36 aspirates had elements of fresh, 7 of lytic and 8 of organized thrombi. There was no correlation between colour and age. OCT appearance could not predict erythrocyte or platelet content. The light intensity ratios were not significantly different in fresh, lytic or organized thrombi. Conclusion OCT could not differentiate between red and white thrombi, nor determine thrombus age.publishedVersio

Continuity of care and its associations with self-reported health, clinical characteristics and follow-up services after percutaneous coronary intervention

Aims Complexity of care in patients with coronary artery disease is increasing, due to ageing, improved treatment, and more specialised care. Patients receive care from various healthcare providers in many settings. Still, few studies have evaluated continuity of care across primary and secondary care levels for patients after percutaneous coronary intervention (PCI). This study aimed to determine multifaceted aspects of continuity of care and associations with socio-demographic characteristics, self-reported health, clinical characteristics and follow-up services for patients after PCI. Methods This multi-centre prospective cohort study collected data at baseline and two-month follow-up from medical records, national registries and patient self-reports. Univariable and hierarchical regressions were performed using the Heart Continuity of Care Questionnaire total score as the dependent variable. Results In total, 1695 patients were included at baseline, and 1318 (78%) completed the two-month follow-up. Patients stated not being adequately informed about lifestyle changes, medication and follow-up care. Those experiencing poorer health status after PCI scored significantly worse on continuity of care. Patients with ST-segment elevation myocardial infarction scored significantly better on informational and management continuity than those with other cardiac diagnoses. The regression analyses showed significantly better continuity (P ≤ 0.034) in patients who were male, received written information from hospital, were transferred to another hospital before discharge, received follow-up from their general practitioner or had sufficient consultation time after discharge from hospital. Conclusion Risk factors for sub-optimal continuity were identified. These factors are important to patients, healthcare providers and policy makers. Action should be taken to educate patients, reconcile discharge plans and organise post-discharge services. Designing pathways with an interdisciplinary approach and shared responsibility between healthcare settings is recommended.publishedVersio

Krill oil reduces plasma triacylglycerol level and improves related lipoprotein particle concentration, fatty acid composition and redox status in healthy young adults - a pilot study

Background: Lipid abnormalities, enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders. Krill oil (RIMFROST Sublime®) is a phospholipid-rich oil with eicosapentaenoic acid (EPA): docosahexaenoic acid (DHA) ratio of 1.8:1. In this pilot study we determined if krill oil could favourable affect plasma lipid parameters and parameters involved in the initiation and progression of atherosclerosis. Methods: The study was conducted as a 28 days intervention study examining effect-parameters of dietary supplementation with krill oil (832.5 mg EPA and DHA per day). 17 healthy volunteers in the age group 18–36 (mean age 23 ± 4 years) participated. Plasma lipids, lipoprotein particle sizes, fatty acid composition in plasma and red blood cells (RBCs), plasma cytokines, antioxidant capacity, acylcarntines, carnitine, choline, betaine, and trimethylamine-N-oxide (TMAO) were measured before and after supplementation. Results: Plasma triacylglycerol (TAG) and large very-low density lipoprotein (VLDL) & chylomicron particle concentrations decreased after 28 days of krill oil intake. A significant reduction in the TAG/HDL cholesterol resulted. Krill oil supplementation decreased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio both in plasma and RBCs. This was due to increased EPA, DHA and docosapentaenoic acid (DPA) and reduced amount of arachidonic acid (AA). The increase of n-3 fatty acids and wt % of EPA and DHA in RBC was of smaller magnitude than found in plasma. Krill oil intake increased the antioxidant capacity, double bond index (DBI) and the fatty acid anti-inflammatory index. The plasma atherogenicity index remained constant whereas the thrombogenicity index decreased. Plasma choline, betaine and the carnitine precursor, γ-butyrobetaine were increased after krill oil supplementation whereas the TMAO and carnitine concentrations remained unchanged. Conclusion: Krill oil consumption is considered health beneficial as it decreases cardiovascular disease risk parameters through effects on plasma TAGs, lipoprotein particles, fatty acid profile, redox status and possible inflammation. Noteworthy, no adverse effects on plasma levels of TMAO and carnitine were found.publishedVersio

The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease

Background: Vorapaxar has been shown to reduce cardiovascular mortality in postmyocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. Aim: This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days’ FU and beyond, in patients with coronary heart disease. Methods: Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at–80°C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and -2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). Results: A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1-month FU (p ¼ 0.034). Angiopoietin-like 4 increased (p ¼ 0.028) and plasminogen activator inhibitor-2 decreased (p ¼ 0.025) in favor of vorapaxar at final FU. In postMI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p ¼ 0.029. Also, a short-term increase in von Willebrand factor (p ¼ 0.032) favoring vorapaxar was noted in NSTEMI patients. Conclusion: Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients.publishedVersio

The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease

Abstract Background: Vorapaxar has been shown to reduce cardiovascular mortality in postmyocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. Aim: This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days’ FU and beyond, in patients with coronary heart disease. Methods: Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at–80°C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and -2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). Results: A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1-month FU (p ¼ 0.034). Angiopoietin-like 4 increased (p ¼ 0.028) and plasminogen activator inhibitor-2 decreased (p ¼ 0.025) in favor of vorapaxar at final FU. In postMI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p ¼ 0.029. Also, a short-term increase in von Willebrand factor (p ¼ 0.032) favoring vorapaxar was noted in NSTEMI patients. Conclusion: Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients