Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium - positive effects on thyroid hormones, cardiovascular mortality, and quality of life.

BACKGROUND: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL). METHODS: Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses. RESULTS: In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group. CONCLUSIONS: Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden.

PURPOSE: Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. METHODS: Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. RESULTS: In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (ß = 0.74; p < 0.001) and myocardium (ß = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. CONCLUSION: Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.

Increased cardiovascular mortality in females with the a/a genotype of the SNPs rs1478604 and rs2228262 of thrombospondin-1.

BACKGROUND: Cardiovascular diseases are still the major cause of death in the Western world, with different outcomes between the two genders. Efforts to identify those at risk are therefore given priority in the handling of health resources. Thrombospondins (TSP) are extracellular matrix proteins associated with cardiovascular diseases. The aim of this study was to investigate variations in single nucleotide polymorphisms (SNPs) of TSP-1 and plasma expression, and associations with mortality from a gender perspective. METHODS: A population of 470 community-living persons were invited to participate. The participants were followed for 7.9 years and underwent a clinical examination and blood sampling. SNP analyses of TSP-1 rs1478604 and rs2228262 using allelic discrimination and plasma measurement of TSP-1 using ELISA were performed, RESULTS: During the follow-up period, 135 (28.7%) all-cause and 83 (17.7%) cardiovascular deaths were registered. In the female population, the A/A genotype of rs2228262 and the T/T genotype of rs1478604 exhibited significantly more cardiovascular deaths compared with the A/G and G/G, or the T/C and C/C genotypes amalgamated (rs2228262: 13.7% vs 2.0%; Χ2:5.29; P = 0.02; rs1478604:17.7% vs 4.7%; Χ2:9.50; P = 0.002). Applied in a risk evaluation, the A/A, or T/T genotypes exhibited an increased risk of cardiovascular mortality (rs2228262: HR: 7.1; 95%CI 1.11-45.8; P = 0.04; rs1478604: HR: 3.18; 95%CI 1.35-7.50; p = 0.008). No differences among the three genotypes could be seen in the male group. CONCLUSION: In this study the female group having the A/A genotype of rs2228262, or the T/T genotype of rs1478604 of TSP-1 exhibited higher cardiovascular mortality after a follow-up of almost 8 years. No corresponding genotype differences could be found in the male group. Genotype evaluations should be considered as one of the options to identify individuals at risk. However, this study should be regarded as hypothesis-generating, and more research in the field is needed.

Biomarker dynamics in cardiac surgery: a prospective observational study on MR-proADM, MR-proANP, hs-CRP and sP-selectin plasma levels in the perioperative period.

Background: For many biomarkers in cardiac surgery, there is a lack of knowledge regarding the normal dynamics of plasma levels during the perioperative course. The aim of this study was to investigate the perioperative dynamics of MR-proADM, MR-proANP, hs-CRP and sP-selectin in cardiac surgery.Method: A prospective observational pilot study with 20 patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB). Plasma samples were taken for each patient and biomarker during the pre-, per- and postoperative period until Day 6 postoperatively.Results: MR-proADM increased significantly from 0.62 [IQR; 0.54-0.93] nmol/L preoperatively to 1.20 [1.04-1.80] nmol/L postoperative Day 1. MR-proANP increased significantly from 125 [77-152] pmol/L preoperatively to 198 [168-307] pmol/L on weaning from CPB. hs-CRP increased significantly from 2.5 mg/L [0.4-12] preoperatively to peak at 208 mg/L [186-239] postoperative Day 3. The preoperative level of sP-selectin at 23.0 [21.3-26.3] ng/mL initially fell at weaning from CPB, followed by a significant peak of 25.5 [22.7-27.7] ng/mL 8 h postoperatively.Conclusions: The findings in this study may help to understand the physiology of the biomarkers analysed and their response to cardiac surgical trauma including CPB. Furthermore, these findings will guide us in further research on the clinical usefulness of these biomarkers.

Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status.

PURPOSE: Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 µg/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. METHODS: In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. RESULTS: The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. CONCLUSION: In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.

Higher blood pressure in elderly hypertensive females, with increased arterial stiffness and blood pressure in females with the Fibrillin-1 2/3 genotype.

BACKGROUND: Elderly patients have a relatively high cardiovascular risk due to increased arterial stiffness, elevated blood pressure and decreased amounts of elastin in the arteries. The composition of the media layer in the arterial wall, comprising elastin, collagen, smooth muscle cells, proteoglycans, fibronectin and fibrillin-1, influences its mechanical properties. Mutations in the fibrillin-1 gene leads to increased aortic stiffness, elevated pulse pressure and aortic root dilatation. This study investigates whether there is a sex difference among hypertensive elderly patients regarding blood pressure, arterial stiffness and fibrillin-1 genotypes. METHODS: A total of 315 hypertensive subjects (systolic blood pressure > 140 mmHg) were included in this study (155 men and 160 women aged 71-88 years). Aortic pulse wave velocity and augmentation index were determined using SphygmoCor, and brachial blood pressure was measured using an oscillometric technique. Fibrillin-1 was genotyped by polymerase chain reaction and with a capillary electrophoresis system. RESULTS: Females showed a significantly higher peripheral mean arterial pressure (females; 107.20 mmHg, males 101.6 mmHg, p = 0.008), central mean arterial pressure (females; 107.2 mmHg, males 101.6 mmHg p = 0.008), central systolic blood pressure (females; 148.1 mmHg, males 139.2 mmHg, p <  0.001) and central pulse pressure (females; 68.9 mmHg, males 61.6 mmHg, p = 0.035) than males. Females with the Fibrillin-1 2/3 genotype showed a significantly higher augmentation index (FBN1 2/3; 39.9%, FBN1 2/2 35.0%, FBN1 2/4 35.8, p = 0.029) and systolic blood pressure (FBN1 2/3; 174.6 mmHg, FBN1 2/2168.9 mmHg, FBN1 2/4169.9 mmHg, p = 0.025) than females with the 2/2 and 2/4 genotypes. CONCLUSION: The findings of this study may indicate that hypertensive elderly females, especially elderly females with Fibrillin-1 2/3, have increased systolic blood pressure and arterial stiffness.

Copeptin Release in Cardiac Surgery-A New Biomarker to Identify Risk Patients?

OBJECTIVE: To describe the dynamics of copeptin in open cardiac surgery during the perioperative course. DESIGN: Prospective cohort study. SETTING: Single tertiary hospital. PARTICIPANTS: Twenty patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB). INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: Copeptin concentrations were measured pre-, peri-, and postoperatively until day 6 after surgery. Patients were analyzed as a whole cohort (n = 20) and in a restricted "normal cohort" consisting of patients with normal preoperative copeptin concentration (<10 pmol/L) and perioperative uneventful course (n = 11). In the whole cohort, preoperative copeptin concentration was 7.0 pmol/L (interquartile range: 3.1-11 pmol/L). All patients had an early rise of copeptin, with 80% having peak copeptin concentration at weaning from CPB or upon arrival in the intensive care unit. Patients in the "normal cohort" had copeptin concentration at weaning from CPB of 194 pmol/L (98-275), postoperative day 1, 27 pmol/L (18-31); and day 3, 8.9 pmol/L (6.3-12). CONCLUSIONS: Regardless of cardiac surgical procedure and perioperative course, all patients had an early significant rise of copeptin concentrations, generally peaking at weaning from CBP or upon arrival in the intensive care unit. Among patients with normal copeptin concentration preoperatively and uneventful course, the postoperative copeptin concentrations decreased to normal values within 3-to-4 days after cardiac surgery. Furthermore, the restricted "normal cohort" generally tended to display lower levels of copeptin concentration postoperatively. Further studies may evaluate whether copeptin can be a tool in identifying risk patients in cardiac surgery.

Sex-Specific Associations Between Self-reported Sleep Duration, Cardiovascular Disease, Hypertension, and Mortality in an Elderly Population.

BACKGROUND: Both short and long sleep durations have been associated to increased mortality. Knowledge about sex-specific differences among elderly regarding associations between sleep duration, cardiovascular health, and mortality is sparse. OBJECTIVE: The aims of this study are to examine the association between self-reported sleep duration and mortality and to investigate whether this association is sex specific and/or moderated by cardiovascular morbidity, and also to explore potential mediators of sleep duration effects on mortality. METHODS: A population-based, observational, cross-sectional design with 6-year follow-up with mortality as primary outcome was conducted. Self-rated sleep duration, clinical examinations, echocardiography, and blood samples (N-terminal fragment of proBNP) were collected. A total of 675 persons (50% women; mean age, 78 years) were divided into short sleepers (≤6 hours; n = 231), normal sleepers (7-8 hours; n = 338), and long sleepers (≥9 hours; n = 61). Data were subjected to principal component analyses. Cardiovascular disease (CVD) and hypertension factors were extracted and used as moderators and as mediators in the regression analyses. RESULTS: During follow-up, 55 short sleepers (24%), 68 normal sleepers (20%), and 21 long sleepers (34%) died. Mediator analyses showed that long sleep was associated with mortality in men (hazard ratio [HR], 1.8; P = .049), independently of CVD and hypertension. In men with short sleep, CVD acted as a moderator of the association with mortality (HR, 4.1; P = .025). However, when using N-terminal fragment of proBNP, this effect became nonsignificant (HR, 3.1; P = .06). In woman, a trend to moderation involving the hypertension factor and short sleep was found (HR, 4.6; P = .09). CONCLUSION: Short and long sleep duration may be seen as risk markers, particularly among older men with cardiovascular morbidity.

Sex-specific associations between self-reported sleep duration, depression, anxiety, fatigue and daytime sleepiness in an older community-dwelling population.

PURPOSE: The purpose of this study was to explore whether associations between self-reported sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness differed in older community-dwelling men and women. DESIGN: Cross-sectional. METHODS: A community-dwelling sample of 675 older men and women (mean age 77.7 years, SD 3.8 years) was used. All participants underwent a clinical examination by a cardiologist. Validated questionnaires were used to investigate sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness. Subjects were divided into short sleepers (≤6 hours), n = 231; normal sleepers (7-8 hours), n = 338; and long sleepers (≥9 hours), n = 61. ancovas were used to explore sex-specific effects. RESULTS: Depressive symptoms were associated with short sleep in men, but not in women. Fatigue was associated with both short and long sleep duration in men. No sex-specific associations of sleep duration with daytime sleepiness or anxiety were found. CONCLUSION: Nurses investigating sleep duration and its correlates, or effects, in clinical practice need to take sex into account, as some associations may be sex specific. Depressive symptoms and fatigue can be used as indicators to identify older men with sleep complaints.

PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men.

BACKGROUND: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. METHODS: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. RESULTS: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. CONCLUSION: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.

PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease. MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed. RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups. CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices.

Treatment strategies in Alzheimer's disease: a review with focus on selenium supplementation.

Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aß) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aß production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aß plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

Can BNP-guided therapy improve health-related quality of life, and do responders to BNP-guided heart failure treatment have improved health-related quality of life? Results from the UPSTEP study.

BACKGROUND: To investigate whether B-type natriuretic peptide (NP)-guided treatment of heart failure (HF) patients improved their health related quality of life (Hr-QoL) compared to routine HF treatment, and whether changes in Hr-QoL differed depending on whether the patient was a responder to NP-guided therapy or not. METHODS: A secondary analysis of the UPSTEP-study, a Scandinavian multicentre study using a prospective, randomized, open, blinded evaluation design on patients with HF with New York Heart Association (NYHA) class II-IV. NP-guiding was aimed to reduce BNP <150 ng/L if < 75 years or BNP < 300 ng/L if > 75 years. A responder was defined as a patient with a BNP < 300 ng/L and/or a decrease in BNP of at least 40% in week 16 compared to study start. Short form-36 (SF-36) was used to measure Hr-QoL. At the study start, 258 patients presented evaluable SF-36 questionnaires, 131 in the BNP group and 127 in the control group. At the study end 100 patients in the NP-guided group and 98 in the control group, presenting data from both the study start and the study end. RESULTS: There were no significant differences in Hr-QoL between NP-guided HF treatment and control group; however significant improvements could be seen in four of the eight domains in the NP-guided group, whereas in the control group improvements could be seen in six of the domains. Among the responders improvements could be noted in four domains whereas in the non-responders improvements could be seen in only one domain evaluating within group changes. CONCLUSIONS: Improved Hr-QoL could be demonstrated in several of the domains in both the NP-guided and the control group. In the responder group within group analyses showed more increased Hr-QoL compared to the non-responder group. However, all groups demonstrated increase in Hr-QoL.

Gender difference in adiponectin associated with cardiovascular mortality.

BACKGROUND: It is important to identify cardiovascular diseases in patients at high risk. To include genetics into routine cardiological patients has therefore been discussed recently. We wanted to evaluate the association between high-molecular weight adiponectin and cardiovascular risk, and secondly in the same population evaluate if specific genotype differences regarding risk could be observed, and thirdly if gender differences could be seen. METHOD: Four hundred seventy-six elderly participants recruited from a rural community were included. All participants underwent a clinical examination, echocardiography, and blood sampling and the single nucleotide polymorphism (SNP) (rs266729) of adiponectin was analysed. Follow-up time was 6.7 years. RESULTS: Those with high serum concentration of adiponectin had a more 2 fold increased cardiovascular risk, and it might be that females exhibits even higher risk where a more than 5 fold increased risk could be seen. The result could be demonstrated even in a multivariate model adjusting for well-known clinical risk factors. However, as the sample size was small the gender differences should be interpreted with caution. In the genotype evaluation the C/C carriers of the female group had a more than 9-fold increased risk of cardiovascular mortality, however the confidence interval was wide. Such genotype difference could not be found in the male group. CONCLUSION: High level of adiponectin was associated with increased cardiovascular risk. Also a gender difference in the genotype evaluation could be seen where the C/C carriers obtained higher risk in the female group but not in the male group. Thus, in order to identify patients at risk early, genetic analyses may add to the armamentarium used in the clinical routine. However, information should be regarded as hypothesis generating as the sample size was small and should stimulate further research in individualized cardiovascular prevention and treatment.

Imaging Congestion With a Pocket Ultrasound Device: Prognostic Implications in Patients With Chronic Heart Failure.

BACKGROUND: Venous congestion is common in patients with chronic heart failure (HF). We used a pocket-sized ultrasound imaging device (PID) to assess the patients' congestive status and related our findings to prognosis. METHODS AND RESULTS: One hundred four consecutive outpatients from an HF outpatient clinic were studied. Interstitial lung water (ILW), pleural effusion (PE), and the diameter of the inferior vena cava (VCI) were assessed with the use of a PID. ILW was assessed by demonstration of B-lines (comet tail artifact (CTA). Out of the 104 patients, 28 had CTA and 8 had PE. Median VCI diameter was 18 mm (interquartile range 14-22 mm). Each of these parameters correlated weakly (r = 0.26-0.37; P < .05) with the HF biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). During the median follow-up time of 530 days, 18 hospitalizations and 14 deaths were registered. Findings of CTA, PE, or both increased the risk of death or hospitalization (hazard ratio 3-4; P < .05). After adjustment for age, cardiac systolic function, and NT-proBNP, this difference remained significant for CTA alone and CTA + PE combined, but not for PE alone. CONCLUSIONS: With the use of a handheld ultrasound device, signs of pulmonary congestion could be demonstrated. When found, these had a significant prognostic impact in clinically stable HF.

Atlas-based analysis of 4D flow CMR: automated vessel segmentation and flow quantification.

BACKGROUND: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. METHODS: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at locations of interest. The method was applied on 4D flow CMR datasets obtained from 11 healthy volunteers and 10 patients with heart failure. Evaluation of the method was performed visually, and by comparison of net flow volumes in the ascending aorta obtained automatically (using the proposed method), and semi-automatically. Further evaluation was done by comparison of net flow volumes obtained automatically at different locations in the aorta, pulmonary artery, and caval veins. RESULTS: Visual evaluation of the generated segmentations resulted in good outcomes for all the major vessels in all but one dataset. The comparison between automatically and semi-automatically obtained net flow volumes in the ascending aorta resulted in very high correlation (r (2)=0.926). Moreover, comparison of the net flow volumes obtained automatically in other vessel locations also produced high correlations where expected: pulmonary trunk vs. proximal ascending aorta (r (2)=0.955), pulmonary trunk vs. pulmonary branches (r (2)=0.808), and pulmonary trunk vs. caval veins (r (2)=0.906). CONCLUSIONS: The proposed method allows for automatic analysis of 4D flow CMR data, including vessel segmentation, assessment of flow volumes at locations of interest, and 4D flow visualization. This constitutes an important step towards facilitating the clinical utility of 4D flow CMR.

Gender, underutilization of cardiac resynchronization therapy, and prognostic impact of QRS prolongation and left bundle branch block in heart failure.

AIMS: It has been suggested that cardiac resynchronization therapy (CRT) is less utilized, dyssynchrony occurs at narrower QRS, and CRT is more beneficial in women compared with men. We tested the hypotheses that (i) CRT is more underutilized and (ii) QRS prolongation and left bundle branch block (LBBB) are more harmful in women. METHODS AND RESULTS: We studied 14 713 patients (28% women) with left ventricular ejection fraction (LVEF) <40% in the Swedish Heart Failure Registry. In women vs. men, CRT was present in 4 vs. 7% (P < 0.001) and was absent but with indication in 30 vs. 31% (P = 0.826). Next, among 13 782 patients (28% women) without CRT, 9% of women and 17% of men had non-specific intraventricular conduction delay (IVCD) and 27% of women and 24% of men had LBBB. One-year survival with narrow QRS was 85% in women and 88% in men, with IVCD 74 and 78%, and with LBBB 84 and 82%, respectively. Compared with narrow QRS, IVCD had a multivariable hazard ratio of 1.24 (95% CI 1.05-1.46, P = 0.011) in women and 1.30 (95% CI 1.19-1.42, P < 0.001) in men, and LBBB 1.03 (95% CI 0.91-1.16, P = 0.651) in women and 1.16 (95% CI 1.07-1.26, P < 0.001) in men, P for interaction between gender and QRS morphology, 0.241. CONCLUSIONS: While the proportion with CRT was lower in women, CRT was equally underutilized in both genders. QRS prolongation with or without LBBB was not more harmful in women than in men. Efforts to improve CRT implementation should be directed equally towards women and men.

Responder to BNP-guided treatment in heart failure. The process of defining a responder.

OBJECTIVES: B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value. DESIGN: In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period. RESULTS: The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders. CONCLUSIONS: Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization.

Sleep disordered breathing, hypoxia and inflammation: associations with sickness behaviour in community dwelling elderly with and without cardiovascular disease.

BACKGROUND: Inflammation can induce a cluster of symptoms, referred to as sickness behaviour (e.g., depressive symptoms, sleep disturbances, pain and fatigue). Cardiovascular disease (CVD) and sleep disordered breathing (SDB) are common in older adults. CVD is associated with an increased inflammatory activity and in SDB, hypoxia can also increase inflammation. The purpose of this study is to explore if SDB-related hypoxia is associated differently with inflammation and the presence of sickness behaviour in older adults with and without CVD. METHODS: Three hundred and thirty-one older adults, whose mean age is 78 years, underwent one-night polygraphic recording to measure SDB and hypoxia. CVD was established by a clinical investigation. Questionnaires were used to measure sickness behaviour and depressive symptoms. High sensitivity C-reactive protein was used as a marker of inflammation. RESULTS: Structural Equation Modelling showed that SDB-related hypoxia was associated with inflammation (ß > 0.40) which mediated indirect associations with sickness behaviour (ß = 0.19) and depressive symptoms (ß = 0.11), but only in those with CVD (n = 119). In this model, inflammation had a direct effect on sickness behaviour (ß = 0.43) and an indirect effect on depressive symptoms (ß = 0.24). Hypoxia had the strongest effect (i.e., ß = 0.41; significant) on inflammation, whereas the AHI or ODI had weak and non-significant effects (ß = 0.03 and ß = 0.15). CONCLUSIONS: Older adults with CVD and SDB are at a particular risk of developing sickness behaviour and depressive symptoms. The effect of SDB was mainly caused by hypoxia, suggesting that hypoxia is an important marker of SDB severity in older adults with CVD.