Postoperative atrial fibrillation (POAF) has been associated with an inflammatory response to the surgical procedure. n-3 long-chain polyunsaturated fatty acids (LC-PUFA) have been proposed for the ...prevention of POAF. We investigated the relationship between the plasma concentration of inflammatory mediators, levels of n-3 LC-PUFA in red blood cell (RBC) membrane lipids, and the risk of POAF after coronary artery bypass grafting (CABG).
A total of 125 patients who underwent CABG were studied. Inflammatory mediators in plasma and the content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in RBC membranes were assessed.
Sixty-two patients (49.6%) developed POAF. The POAF group had higher RBC levels of total n-3 LC-PUFA and DHA than did patients remaining in sinus rhythm (p < 0.05). Of the inflammatory mediators, only postoperative interleukin-6 levels differed, being higher in the POAF group (p < 0.05). Inflammatory mediators were not independent predictors of POAF by multivariable logistic regression analysis. Higher levels of DHA and total n-3 LC-PUFA in RBC membranes, measured immediately prior to CABG and on postoperative day 3, were linearly associated with an increased risk of POAF (p < 0.05).
Our findings suggest that inflammatory mediators are not associated with the occurrence of POAF. Interestingly, high n-3 LC-PUFA levels in RBC membranes appear to increase the risk of POAF.
Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is ...commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders.
Approach and Results: We whole-genome sequenced 49 962 Icelanders and imputed the identified variants into an overall sample of 166 281 chip-genotyped Icelanders. We identified 20 FH mutations in LDLR, APOB, and PCSK9 with combined prevalence of 1 in 836. Monogenic FH was associated with severely elevated LDL-C levels and increased risk of premature coronary disease, aortic valve stenosis, and high burden of coronary atherosclerosis. We used a modified version of the Dutch Lipid Clinic Network criteria to screen for the clinical FH phenotype among living adult participants (N=79 058). Clinical FH was found in 2.2% of participants, of whom only 5.2% had monogenic FH. Mutation-negative clinical FH has a strong polygenic basis. Both individuals with monogenic FH and individuals with mutation-negative clinical FH were markedly undertreated with cholesterol-lowering medications and only a minority attained an LDL-C target of <2.6 mmol/L (<100 mg/dL; 11.0% and 24.9%, respectively) or <1.8 mmol/L (<70 mg/dL; 0.0% and 5.2%, respectively), as recommended for primary prevention by European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines.
Conclusions: Clinically defined FH is a relatively common phenotype that is explained by monogenic FH in only a minority of cases. Both monogenic and clinical FH confer high cardiovascular risk but are markedly undertreated.
Studies indicate a poorer quality of life (QoL) for implantable cardioverter defibrillator (ICD) patients than for the general population. However, studies comparing the QoL of ICD patients with that ...of patients with other implantable cardiac devices are scarce. We hypothesized that ICD patients had a poorer QoL than pacemaker patients.
All ICD patients living in Iceland at the beginning of 2002 (44 subjects), and a comparison group of 81 randomly selected patients with pacemakers were invited to participate. The Icelandic Quality of Life Questionnaire (IQL), the General Health Questionnaire (GHQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were submitted to measure QoL, psychiatric distress, and symptoms of anxiety and depression. The ICD and pacemaker groups did not differ on IQL, BAI, BDI, or GHQ scores. ICD patients were as a group more fearful of death (P = 0.056) and showed more concerns about returning to work (P = 0.072), although these items fell just short of statistical significance.
Contrary to our expectations, ICD patients had a comparable QoL with pacemaker recipients and were not more likely to suffer from anxiety, depression, or general psychiatric distress. These findings are encouraging in view of expanding ICD indications.
Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into ...cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.
Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.
Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
Entrainment can be a useful method to identify reentry as a mechanism of ventricular tachycardia (VT). In this study, we evaluated the effect of gradually decreasing cycle lengths of overdrive pacing ...for stable VT induced in a canine model 1-3 h after coronary occlusion. Intact dogs underwent anterior descending coronary artery occlusion after instrumentation of the risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Overdrive pacing was attempted if the animals had sustained hemodynamically stable VT, looking for evidence of entrainment. Subsequent three-dimensional mapping determined the mechanism of VT. Fifteen of the 21 dogs studied demonstrated entrainment with overdrive pacing by progressive QRS fusion alone (1), the first nonpaced QRS entrained to the paced cycle length only (7), or both (7). Five of these 15 dogs also had postpacing acceleration of the VT at a subsequent faster pacing cycle length. The mechanism of acceleration in four was a change to a VT with a focal origin. The prepacing mechanism in all 15 dogs was subsequently mapped to reentry. Regarding the six VTs, which demonstrated no evidence for entrainment, the site of earliest activity was mapped to a focal origin in all. These data showing entrainment of inducible reentrant VTs and lack of such for focal VTs support that the focal VTs seen in this study are unlikely the result of microreentry but possibly a mechanism as triggered activity.
Previous studies have indicated that the endocardium may be responsible for a large portion of ventricular tachycardia (VT) seen with reperfusion of ischemic myocardium. To evaluate the role of the ...Purkinje system in nonreentrant VT arising from the endocardium after reperfusion, the anterior descending coronary artery was occluded for 20 min and then reperfused in 23 dogs after instrumentation of the risk zone with 21 multipolar plunge needles. VT with focal Purkinje origin was defined as a focal endocardial VT with Purkinje potentials recorded before the earliest endocardial myopotential. A total of 19 VTs (mean cycle length 214 +/- 2 ms) were observed with 11 (58%) having focal Purkinje origin. Fifty-eight percent of the VTs degenerated to ventricular fibrillation, with occurrences of two or more independent foci per complex (seen in 7 of 11 compared with 1 of 8 nonsustained VTs). In conclusion, these data show that Purkinje tissue may be important in the genesis of reperfusion VT.
The Icelandic health care system ranks favourably in international comparison but patients' experience of interaction with the health service has not been well studied. The goal of this study was to ...examine the satisfaction of patients admitted to the Acute Cardiac Unit (ACU) at Landspitali - The National University Hospital of Iceland.
A questionnaire based on the Patient Satisfaction Questionnaire III was mailed to patients admitted to the ACU between 1 January and 29 February 2012. Questions were presented as statements and participants asked to respond how strongly on a scale from 1 to 5 they agreed or disagreed with each statement. Data analysis was performed using descriptive statistics, Cronbach´s alpha for internal consistency of scales and principal components analysis, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for comparison of groups and Pearson and Spearman correlation coefficients for correlation between variables.
The questionnaire was mailed to 485 individuals of whom 275 (57%) responded. The median age of the participants was 62 (range, 19-95) years and 132 (48%) were women. Internal consistency of the scales was mostly high (Cronbach's alpha 0.62-0.91) and principal components analysis revealed one main factor. The mean score of the questionnaire was 6.8 ±1.0 and 91%, and 86% of the participants were pleased with their interaction with physicians and nurses, respectively. Similarly, 88% were pleased with the care they recieved but 25% felt they received insufficient explanations of their symptoms or that follow-up care was lacking.
Patients of the ACU generally appear to be satisfied with their care. However, our results suggest that improvement is needed in several areas, including information provided at discharge and follow-up care.
Background: During warfarin treatment rapid fluctuations occur in the traditional prothrombin time (PT) as a result of the short half-life of factor (F) VII which has little effect on the ...antithrombotic activity of warfarin, contrary to FII and FX. Such confounding INR fluctuations influence dosing and, hence also the variability of FII and FX. The new Fiix-PT measures only the activity of the longer half-life FII and FX leading to less variability of anticoagulation as shown in the Fiix-trial.
Objectives: To assess if stability of warfarin anticoagulation monitored by PT and Fiix-PT was affected differently by gender.
Methods: This study is a subgroup analysis of the prospective, randomized, double-blind Fiix-trial. A subgroup of 815 atrial fibrillation patients on long-term warfarin monitored with Fiix-PT (Fiix-warfarin patients) or PT (PT-warfarin patients) were assessed in an intention-to-monitor manner by comparing surrogate anticoagulation indicators such as dose and dose frequency, time in therapeutic range (TTR, Rosendaal method) and variance growth rate of the INR (VGR; an indicator of INR fluctuation size).
Results: Baseline parameters between the 396 Fiix-warfarin and 419 PT-warfarin patients did not differ. The median observation time was 1.4 years. Fiix-warfarin patients had more tests within therapeutic range (66% vs 63%, p=0.0019) and fewer tests below range (19% vs 21%, p=0.0061) than PT-warfarin patients. The test-in-range improvement observed with Fiix-warfarin over that with PT-warfarin was mainly explained by an improvement observed in women, i.e. the fraction of monitoring tests within range was higher (64% vs 59%, p=0.0001) and the fraction below range was lower (20% vs 24%, p=0.0002) in women on Fiix-warfarin. Likewise, with Fiix-warfarin TTR was higher (81% compared with 79%) and this was mainly explained by higher TTR in women on Fiix-warfarin (80%) than in women on PT-warfarin (75%; p=0.0401). Little difference was observed in TTR in men. The INR varied less with Fiix-warfarin than with PT-warfarin (VGRB1 0.20 vs 0.24, p=0.0810). There was significantly more variation in VGR in women than in men. Thus, Fiix-warfarin men vs women had a VGRB1 of 0.18 vs 0.25, p=0.0372, and PT-warfarin men vs women had VGRB1 0.21 vs 0.30, p=0.0056. A trend for fewer annual dose changes with Fiix-warfarin than with PT-warfarin was observed (5.6 vs 6.2 annually, p=0.0822) and this was mainly explained by 20% fewer annual dose changes with Fiix-warfarin than with PT-warfarin in women (6.0 vs 7.4, p=0.0342). Also, there were fewer dose changes per monitoring test in Fiix warfarin women (0.27 vs 0.32, p=0.0292). Finally, women treated with Fiix-warfarin used a lower median daily warfarin dose than women treated with PT-warfarin (3.4 vs 4.2 mg, p=0.0029).
Conclusions: Monitoring warfarin with the Fiix-PT improved the stability of warfarin anticoagulation and reduced the daily dose significantly in women. A non-significant but consistent smaller effect in the same direction was seen in men.
Gudmundsdottir:Fiix Diagnostics Ltd.: Equity Ownership, Patents & Royalties: Patent pending for Fiix prothrombin time. Onundarson:Fiix Diagnostics Ltd: Equity Ownership, Patents & Royalties: Patent pending status for Fiix prothrombin time.
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