Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers

[EN] Cardiac resynchronization therapy (CRT) is an effective treatment for those patients with severe heart failure. Regrettably, there are about one third of CRT "non-responders", i.e. patients who have undergone this form of device therapy but do not respond to it, which adversely affects the utility and cost-effectiveness of CRT. In this paper, we assess the ability of a novel surface ECG marker to predict CRT response. We performed a retrospective exploratory study of the ECG previous to CRT implantation in 43 consecutive patients with ischemic (17) or non-ischemic (26) cardiomyopathy. We extracted the QRST complexes (consisting of the QRS complex, the S-T segment, and the T wave) and obtained a measure of their energy by means of spectral analysis. This ECG marker showed statistically significant lower values for non-responder patients and, joint with the duration of QRS complexes (the current gold-standard to predict CRT response), the following performances: 86% accuracy, 88% sensitivity, and 80% specificity. In this manner, the proposed ECG marker may help clinicians to predict positive response to CRT in a non-invasive way, in order to minimize unsuccessful procedures.This work was supported by MINECO under grants MTM2013-43540-P and MTM2016-76647-P.Ortigosa, N.; Pérez-Roselló, V.; Donoso, V.; Osca Asensi, J.; Martínez-Dolz, L.; Fernández Rosell, C.; Galbis Verdu, A. (2018). Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers. Medical & Biological Engineering & Computing. 56(4):611-621. https://doi.org/10.1007/s11517-017-1711-1S611621564Boggiatto P, Fernández C, Galbis A (2009) A group representation related to the stockwell transform. 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Heart Rhythm 12(5):1071–1079Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW et al (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370:1694–1701He H, Bai Y, Garcia EA, Li S (2008) ADASYN: adaptive synthetic sampling approach for imbalanced learning. In: International joint conference on neural networks, pp 1322–1328Jacobsson J, Borgguist R, Reitan C, Ghafoori E, Chatterjee NA et al (2016) Usefulness of the sum absolute QRST integral to predict outcomes in patients receiving cardiac resynchronization therapy. J Cardiovasc Electrophysiol 118(3):389–395McMurray JJ (2010) Clinical practice. Systolic heart failure. N Engl J Med 3623:228–238Meyer CR, Keiser HN (1977) Electrocardiogram baseline noise estimation and removal using cubic splines and state-space computation techniques. Comput Biomed Res 10:459–470Ortigosa N, Giménez VM (2014) Raw data extraction from electrocardiograms with portable document format. 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Elongase Reactions as Control Points in Long-Chain Polyunsaturated Fatty Acid Synthesis

Extent: 9p.Background: Δ6-Desaturase (Fads2) is widely regarded as rate-limiting in the conversion of dietary α-linolenic acid (18:3n-3; ALA) to the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (22:6n-3; DHA). However, increasing dietary ALA or the direct Fads2 product, stearidonic acid (18:4n-3; SDA), increases tissue levels of eicosapentaenoic acid (20:5n-3; EPA) and docosapentaenoic acid (22:5n-3; DPA), but not DHA. These observations suggest that one or more control points must exist beyond ALA metabolism by Fads2. One possible control point is a second reaction involving Fads2 itself, since this enzyme catalyses desaturation of 24:5n-3 to 24:6n-3, as well as ALA to SDA. However, metabolism of EPA and DPA both require elongation reactions. This study examined the activities of two elongase enzymes as well as the second reaction of Fads2 in order to concentrate on the metabolism of EPA to DHA. Methodology/Principal Findings: The substrate selectivities, competitive substrate interactions and dose response curves of the rat elongases, Elovl2 and Elovl5 were determined after expression of the enzymes in yeast. The competitive substrate interactions for rat Fads2 were also examined. Rat Elovl2 was active with C20 and C22 polyunsaturated fatty acids and this single enzyme catalysed the sequential elongation reactions of EPA→DPA→24:5n-3. The second reaction DPA→24:5n-3 appeared to be saturated at substrate concentrations not saturating for the first reaction EPA→DPA. ALA dose-dependently inhibited Fads2 conversion of 24:5n-3 to 24:6n-3. Conclusions: The competition between ALA and 24:5n-3 for Fads2 may explain the decrease in DHA levels observed after certain intakes of dietary ALA have been exceeded. In addition, the apparent saturation of the second Elovl2 reaction, DPA→24:5n-3, provides further explanations for the accumulation of DPA when ALA, SDA or EPA is provided in the diet. This study suggests that Elovl2 will be critical in understanding if DHA synthesis can be increased by dietary means.Melissa K. Gregory, Robert A. Gibson, Rebecca J. Cook-Johnson, Leslie G. Cleland and Michael J. Jame

Supplementation of diet with krill oil protects against experimental rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis.</p> <p>Methods</p> <p>Collagen-induced arthritis susceptible DBA/1 mice were provided <it>ad libitum </it>access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1α, IL-1β, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-β were determined by a Luminex™ assay system.</p> <p>Results</p> <p>Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1α and IL-13.</p> <p>Conclusions</p> <p>The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis.</p

Perceived barriers for treatment of chronic heart failure in general practice; are they affecting performance?

BACKGROUND: The aim of this study is to determine to what extent barriers perceived by general practitioners (GPs) for prescribing angiotensin-converting enzyme inhibitors (ACE-I) in chronic heart failure (CHF) patients are related to underuse and underdosing of these drugs in actual practice. METHODS: Barriers were assessed with a semi-structured questionnaire. Prescribing data were extracted from GPs' computerised medical records for a random sample of their CHF patients. Relations between barriers and prescribing behaviour were assessed by means of Spearman rank correlation and multivariate regression modelling. RESULTS: GPs prescribed ACE-I to 45% of their patients and had previously initiated such treatment in an additional 3.5%, in an average standardised dose of 13.5 mg. They perceived a median of four barriers in prescribing ACE-I or optimising ACE-I dose. Many GPs found it difficult to change treatment initiated by a cardiologist. Furthermore, initiating ACE-I in patients already using a diuretic or stable on their current medication was perceived as barrier. Titrating the ACE-I dose was seen as difficult by more than half of the GPs. No significant relationships could be found between the barriers perceived and actual ACE-I prescribing. Regarding ACE-I dosing, the few GPs who did not agree that the ACE-I should be as high as possible prescribed higher ACE-I doses. CONCLUSION: Variation between GPs in prescribing ACE-I for CHF cannot be explained by differences in the barriers they perceive. Tailor-made interventions targeting only those doctors that perceive a specific barrier will therefore not be an efficient approach to improve quality of care

Neck Pain and Disability Scale and the Neck Disability Index: reproducibility of the Dutch Language Versions

The first aim of this study was to translate the Neck Pain and Disability Scale (NPAD) from English into Dutch producing the NPAD–Dutch Language Version (DLV). The second aim was to analyze test–retest reliability and agreement of the NPAD–DLV and the Neck Disability Index (NDI)–DLV. The NPAD was translated according to established guidelines. Thirty-four patients (mean age 37.5 years, 68% female) with chronic neck pain (CNP), within an outpatient rehabilitation setting, participated in this study. The NPAD–DLV and the NDI–DLV were filled out twice with a mean test–retest interval of 18 days. The intraclass correlation coefficient of the NPAD–DLV was 0.76 (95% confidence interval (CI) 0.57–0.87) and of the NDI–DLV 0.84 (95% CI 0.69–0.92). The limits of agreement of the NPAD–DLV and the NDI–DLV were, respectively, ±20.9 (scale 0–100) and ±6.5 (scale 0–50). The reliability of the NPAD–DLV and the NDI–DLV was acceptable for patients with CNP. The variation (‘instability’) in the NPAD–DLV total scores was relatively large and larger than the variation of the NDI–DLV

Monounsaturated fats and immune function

Animal studies suggest that olive oil is capable of modulating functions of cells of the immune system in a manner similar to, albeit weaker than, fish oils. There is some evidence that the effects of olive oil on immune function in animal studies are due to oleic acid rather than to trace elements or antioxidants. Importantly, several studies have demonstrated effects of oleic acid-containing diets on in vivo immune responses. In contrast, consumption of a monounsaturated fatty acid (MUFA)-rich diet by humans does not appear to bring about a general suppression of immune cell functions. The effects of this diet in humans are limited to decreasing aspects of adhesion of peripheral blood mononuclear cells, although there are trends towards decreases in natural killer cell activity and proliferation. The lack of a clear effect of MUFA in humans may be attributable to the higher level of monounsaturated fat used in the animal studies, although it is ultimately of importance to examine the effects of intakes which are in no way extreme. The effects of MUFA on adhesion molecules are potentially important, since these molecules appear to have a role in the pathology of a number of diseases involving the immune system. This area clearly deserves further exploration

Role of Right Ventricular Global Longitudinal Strain in Predicting Early and Long-Term Mortality in Cardiac Resynchronization Therapy Patients.

BACKGROUND: Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT. DESIGN: We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months. RESULTS: RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0-12.8) vs. 19.5 (15.0-23.9) %, p<0.0001] and RVFWS (RV free wall strain) [15.6 (10.0-19.3) vs. 17.4 (10.5-22.2) %, p = 0.04], improved 6 months after CRT implantation. Increasing baseline RVGLS and RVFWS predicted survival independent of other parameters at 6 months [hazard ratio (HR) = 0.37 (0.15-0.90), p = 0.02 and HR = 0.42 (0.19-0.89), p = 0.02; per 1 standard deviation increase, respectively]. RVGLS proved to be a significant independent predictor of mortality at 24 months [HR = 0.53 (0.32-0.86), p = 0.01], and RVFWS showed a strong tendency [HR = 0.64 (0.40-1.00), p = 0.05]. The 24-month survival was significantly impaired in patients with RVGLS below 10.04% before CRT implantation [area under the curve = 0.72 (0.60-0.84), p = 0.002, log-rank p = 0.0008; HR = 5.23 (1.76-15.48), p = 0.003]. CONCLUSIONS: Our findings indicate that baseline RV dysfunction is associated with poor short-term and long-term prognosis after CRT implantation

Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation

Introduction: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. Methods: Two specific n-3 compounds were tested, namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), each at 0.1, 1 and 10 μM. Full thickness bovine cartilage explants, 5 mm in diameter, were cultured for 5 days with or without IL-1β and in the presence or absence of each n-3 compound. The media were replaced every 24 hours and assayed for sGAG content using the 1,9-dimethylmethylene blue (DMB) method. Chondrocyte viability was determined at the end of the culture period using fluorescence microscopy to visualise cells labelled with calcein AM and ethidium homodimer. Results: Treatment with IL-1β (10 ng.ml-1) produced a large increase in sGAG release compared to untreated controls, but with no effect on cell viability, which was maintained above 80% for all treatments. In the absence of IL-1β, both n-3 compounds induced a mild catabolic response with increased loss of sGAG, particularly at 10 μM. By contrast, in the presence of IL-1β, both EPA and DHA at 0.1 and 1 μM significantly reduced IL-1β-mediated sGAG loss. The efficacy of the EPA treatment was maintained at approximately 75% throughout the 5-day period. However, at the same concentrations, the efficacy of DHA, although initially greater, reduced to approximately half that of EPA after 5 days. For both EPA and DHA, the highest dose of 10 μM was less effective. Conclusions: The results support the hypothesis that n-3 compounds are anti-inflammatory through competitive inhibition of the arachidonic acid oxidation pathway. The efficacy of these compounds is likely to be even greater at more physiological levels of IL-1β. Thus we suggest that n-3 PUFAs, particularly EPA, have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory joint disease

A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain

<p>Abstract</p> <p>Background</p> <p>Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.</p> <p>Methods</p> <p>Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.</p> <p>Results</p> <p>Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.</p> <p>Conclusions</p> <p>This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00566930">NCT00566930</a></p

Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults

<p>Abstract</p> <p>Background</p> <p>The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies.</p> <p>Methods</p> <p>We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires.</p> <p>Results</p> <p>Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, <it>p </it>= .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, <it>p </it>= .007, respectively). VEG reported significantly lower mean intakes of EPA (<it>p </it>< .001), DHA (<it>p </it>< .001), as well as the omega-6 fatty acid, arachidonic acid (AA; <it>p </it>< .001), and reported higher mean intakes of shorter-chain α-linolenic acid (<it>p </it>< .001) and linoleic acid (<it>p </it>< .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (<it>p </it>< 0.05), DHA (<it>p </it>< 0.05), and AA (<it>p </it>< 0.05), and inversely related to intakes of ALA (<it>p </it>< 0.05), and LA (<it>p </it>< 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood.</p> <p>Conclusions</p> <p>The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.</p