Benefits of an open access echocardiography service: a Dutch prospective cohort study

Background

Open access echocardiography has been evaluated in the United Kingdom, but hardly in the Netherlands. The echocardiography service of the SHL-Groep in Etten-Leur was set up independently from the regional hospitals. Cardiologists not involved in the direct care of the participating patients evaluated the echocardiograms taken by ultrasound technicians.

Aims

We estimated the reduction in the number of referrals to regional cardiologists, the adherence of the general practitioners (GPs) to the advice of the evaluating cardiologist, GPs’ opinion on the benefit of the echocardiography service and GPs’ adherence to the diagnostic protocol advocated in the Dutch clinical guideline for heart failure.

Methods

A prospective cohort study was performed. Patients were included from April 2011 to April 2012 (N = 155). Data from application forms (N = 155), echocardiography results (N = 155) and telephone interviews with GPs (N = 138) were analysed.

Results

GPs referred less patients to the cardiologist than they would have done without echocardiography available (92 % vs. 34 %, p < 0.001). They treated more patients by themselves (62 % vs. 10 %, p < 0.001). Most GPs (81 %) followed the advice presented on the echocardiogram result. Most GPs (82 %) found the service had clinical benefit for the patient. Sixty two percent of echocardiography requests met the criteria of the Dutch clinical guideline for heart failure.

Conclusion

Open access echocardiography saved referrals to the cardiology department, saved time, and enabled GPs to treat more patients by themselves. Adherence to diagnostic guidelines for heart failure was suboptimal.     

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

Introduction

Rheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor γ agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.

Methods

In a single-center, randomized, double-blind, placebo-controlled crossover study patients with RA (N = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for eight weeks. This was followed by a four-week washout period and alternative treatment for eight weeks. Outcomes included change in Disease Activity Score in 28 joints (DAS28) score, individual components of the DAS28 score and homeostatic model assessment for insulin resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models were used.

Results

Patients had a mean (±SD) age of 51 (±14.2) years, 82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28-CRP) was 4.58 (±1.1) units. Addition of pioglitazone was associated with a 9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P = 0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28-ESR) (P = 0.92). There was a 10.7mm (95% CI = 0.4 to 20.9 mm) improvement in patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to 63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in insulin resistance as measured by HOMA (P = 0.025), but no significant reduction in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema was more common during pioglitazone treatment (16%) than placebo (0%).

Conclusion

Addition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28-CRP and two of its components, including patient-reported global health and CRP, but not DAS28-ESR or ESR.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT00763139","term_id":"NCT00763139"}}NCT00763139     

Predicting translational diffusion of evolutionary conserved RNA structures by the nucleotide number

Ribonucleic acids are highly conserved essential parts of cellular life. RNA function is determined to a large extent by its hydrodynamic behaviour. The presented study proposes a strategy to predict the hydrodynamic behaviour of RNA single strands on the basis of the polymer size. By atom-level shell-modelling of high-resolution structures, hydrodynamic radius and diffusion coefficient of evolutionary conserved RNA single strands (ssRNA) were calculated. The diffusion coefficients D of 17–174 nucleotides (nt) containing ssRNA depended on the number of nucleotides N with D = 4.56 × 10⁻¹⁰ N^−0.39 m² s⁻¹. The hydrodynamic radius R_H depended on N with R_H = 5.00 × 10⁻¹⁰ N^0.38 m. An average ratio of the radius of gyration and the hydrodynamic radius of 0.98 ± 0.08 was calculated in solution. The empirical law was tested by in solution measured hydrodynamic radii and radii of gyration and was found to be highly consistent with experimental data of evolutionary conserved ssRNA. Furthermore, the hydrodynamic behaviour of several evolutionary unevolved ribonucleic acids could be predicted. Based on atom-level shell-modelling of high-resolution structures and experimental hydrodynamic data, empirical models are proposed, which enable to predict the translational diffusion coefficient and molecular size of short RNA single strands solely on the basis of the polymer size.     

Clinical outcome of ablation for long-standing persistent atrial fibrillation with or without defragmentation

Objective

To assess the outcome and associated risks of atrial defragmentation for the treatment of long-standing persistent atrial fibrillation (LSP-AF).

Methods

Thirty-seven consecutive patients (60.4 ± 7.3 years; 28 male) suffering from LSP-AF who underwent pulmonary vein isolation (PVI) and linear ablation were compared. All patients were treated with the Stereotaxis magnetic navigation system (MNS). Two groups were distinguished: patients with (n = 20) and without (n = 17) defragmentation. The primary endpoint of the study was freedom of AF after 12 months. Secondary endpoints were AF termination, procedure time, fluoroscopy time and procedural complications. Complications were divided into two groups: major (infarction, stroke, major bleeding and tamponade) and minor (fever, pericarditis and inguinal haematoma).

Results

No difference was seen in freedom of AF between the defragmentation and the non-defragmentation group (56.2 % vs. 40.0 %, P = 0.344). Procedure times in the defragmentation group were longer; no differences in fluoroscopy times were observed. No major complications occurred. A higher number of minor complications occurred in the defragmentation group (45.0 % vs. 5.9 %, P = 0.009). Mean hospital stay was comparable (4.7 ± 2.2 vs. 3.4 ± 0.8 days, P = 0.06).

Conclusion

Our study suggests that complete defragmentation using MNS is associated with a higher number of minor complications and longer procedure times and thus compromises efficiency without improving efficacy.     

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature

Background

Coronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders.

Materials and methods

Two adult patients with CBFs are described and a PubMed search was performed using the keywords “coronary bronchial artery fistulas” in the period from 2008 to 2013.

Results

Twenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19 %), chest pain (n = 17) was frequently present followed by haemoptysis (n = 7) and dyspnoea (n = 5). Concomitant disorders were bronchiectasis (44 %), diabetes (33 %) and hypertension (28 %). Multimodality and single-modality diagnostic strategies were applied in 56 % and 44 %, respectively. The origin of the CBFs was the left circumflex artery in 61 %, the right coronary artery in 36 % and the left anterior descending artery in 3 %. Management was conservative (22 %), surgical ligation (11 %), percutaneous transcatheter embolisation (30 %), awaiting lung transplantation (7 %) or not reported (30 %).

Conclusions

CBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.     

Long-term Clinical Outcome and MIBI SPECT Parameters in Percutaneous Coronary Interventions

Background and Aim

Primary percutaneous coronary intervention (PCI) is the preferred treatment option for acute myocardial infarction (MI). Off-site PCI reduces time-to-treatment, which could potentially lead to enhanced clinical outcomes. Therefore, we investigated whether off-site PCI improves 5-year clinical outcomes compared with on-site PCI and whether this is related to in-hospital ^99mTc-sestamibi single photon emission computed tomography (MIBI SPECT) parameters.

Methods

We describe the 5-year follow-up for a combined endpoint of death or re-infarction in 128 patients with acute MI who were randomly assigned to undergo primary PCI at the off-site centre (n = 68) or to transferral to an on-site centre (n = 60). Three days after PCI, MIBI SPECT was performed to estimate infarct size. A multivariate Cox regression model was created to study the relation between MIBI SPECT parameters and long-term clinical outcomes.

Results

After a mean follow-up of 5.8 ± 1.1 years, 25 events occurred. Off-site PCI significantly reduced door-to-balloon time compared with on-site PCI (94 ± 54 versus 125 ± 59 min, p = 0.003). However, infarct size (17 ± 15 versus 14 ± 12%, p = 0.34) and 5-year death or infarct rate (21% versus 18%, p = 0.75) were comparable between treatment centres. With multivariate analysis, only Killip class ≥2 and Q wave MI, but not scintigraphic data, predicted long-term clinical outcomes.

Conclusion

Off-site PCI reduced door-to-balloon time with a comparable 5-year death or infarct rate. Parameters from resting MIBI SPECT on day 3 after MI did not predict long-term clinical outcomes.     

Feasibility of TEE-guided stroke risk assessment in atrial fibrillation—background, aims, design and baseline data of the TIARA pilot study

Background

Antithrombotic management in atrial fibrillation (AF) is currently based on clinical characteristics, despite evidence of potential fine-tuning with transoesophageal echocardiography (TEE). This open, randomised, multicentre study addresses the hypothesis that a comprehensive strategy of TEE-based aspirin treatment in AF patients is feasible and safe.

Methods

Between 2005 and 2009, ten large hospitals in the Netherlands enrolled AF patients with a moderate risk of stroke. Patients without thrombogenic TEE characteristics were randomised to aspirin or vitamin K antagonists (VKA). The primary objective is to show that TEE-based aspirin treatment is safe compared with VKA therapy. The secondary objective tests feasibility of TEE as a tool to detect echocardiographic features of high stroke risk. This report compares randomised to non-randomised patients and describes the feasibility of a TEE-based approach.

Results

In total, 310 patients were included. Sixty-nine patients were not randomised because of non-visualisation (n = 6) or TEE risk factors (n = 63). Compared with non-randomised patients, randomised patients (n = 241) were younger (65 ± 11 vs. 69 ± 9 years, p = 0.004), had less coronary artery disease (9 vs. 20%, p = 0.018), previous TIA (1.7 vs. 7.2%, p = 0.029), AF during TEE (25 vs. 54%, p < 0.001), mitral incompetence (55 vs. 70%, p = 0.038), VKA use (69 vs. 82%, p = 0.032), had a lower mean CHADS₂ score (1.2 ± 0.6 vs. 1.6 ± 1.0, p = 0.004), and left ventricular ejection fraction (59 ± 8 vs. 56 ± 8%, p = 0.016).

Conclusions

This study shows that a TEE-based approach for fine-tuning stroke risk in AF patients with a moderate risk for stroke is feasible. Follow-up data will address the safety of this TEE-based approach.     

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R = 0.5908, P = 0.0024; R = 0.4877, P = 0.0134, respectively) and the number of malformations per fetus (R = 0.6103, P = 0.0015; R = 0.4875, P = 0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R = 0.3887, P = 0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R = 0.3999, P = 0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes.     

Prodrugs of Theophylline Incorporating Ethyleneoxy Groups in the Promoiety: Synthesis, Characterization, and Transdermal Delivery

Two different types of derivatives of theophylline (Th-H) incorporating ethyleneoxy groups into the promoiety have been synthesized. One is a soft alkyl type where N-methyl-N-methoxyethyleneoxycarbonylaminomethyl chlorides have been used to alkylate Th-H in the 7 position. The other is in an acyl type where methoxyethyleneoxycarbonyl chlorides have been used to acylate Th-H in the 7 position. All of the prodrugs were more soluble in the lipid isopropyl myristate (IPM) than Th-H, and three were more soluble in water (AQ) than Th-H. The most water-soluble prodrug gave the highest maximum delivery of total species containing Th-H through hairless mouse skin from IPM (maximum flux, J_MMIPM)—more than seven times that of Th-H, while the other two gave more than three times that of Th-H. The acyl-type prodrugs delivered only Th-H, while the soft alkyl types delivered 60–70% Th-H plus intact prodrug. The Roberts–Sloan equation was able to predict the best performer for each type with an average of the absolute difference between the experimental log J_MMIPM and calculated log J_MMIPM (Δlog J_MMIPM) of 0.253 log units. The values for the present prodrugs and previously reported prodrugs that had not been previously included in the Roberts–Sloan data base (n = 23) were included in the previous n = 71 data base to give n = 94. New coefficients for the Roberts–Sloan equation have been obtained.KEY WORDS: ethyleneoxy groups, lipid solubility, maximum flux, Roberts–Sloan equation, theophylline, water solubility     

CFH, VEGF, and PEDF genotypes and the response to intravitreous injection of bevacizumab for the treatment of age-related macular degeneration

We determined whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and the response to treatment with a single intravitreous injection of bevacizumab for age-related macular degeneration (AMD). Eighty-three patients with exudative AMD treated by bevacizumab injection were genotyped for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, three SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and four SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay. The CT genotype (heterozygous) of CFH-rs1061170 was more frequently represented in nonresponders in vision than TT genotypes (nonrisk allele homozygous) at the time points of 1 and 3 months, while there was no CC genotype (risk allele homozygous) in our study cohort (p = 7.66 × 10⁻³, 7.83 × 10⁻³, respectively). VEGF-rs699947 was also associated with vision changes at 1 month and PEDF-rs1136287 at 3 months (p = 5.11 × 10⁻³, 2.05 × 10⁻², respectively). These variants may be utilized for genetic biomarkers to estimate visual outcomes in the response to intravitreal bevacizumab treatment for AMD.     

Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE.     

Is a sedentary lifestyle an independent predictor for hospital and early mortality after elective cardiac surgery?

Objective

This study evaluates whether a sedentary lifestyle is an independent predictor for increased mortality after elective cardiac surgery.

Methods

Three thousand one hundred fifty patients undergoing elective cardiac surgery between January 2007 and June 2012 completed preoperatively the Corpus Christi Heart Project questionnaire concerning physical activity (PA). Based on this questionnaire, 1815 patients were classified as active and 1335 patients were classified as sedentary. The endpoints of the study were hospital mortality and early mortality.

Results

The study population had a mean age of 69.7 ± 10.1 (19–95) years and a mean logistic EuroSCORE risk of 5.1 ± 5.6 (0.88–73.8). Sedentary patients were significantly older (p = 0.001), obese (p = 0.001), had a higher EuroSCORE risk (p = 0.001), and a higher percentage of complications. Hospital mortality (1.1 % versus 0.4 % (p = 0.014)) and early mortality (1.5 % versus 0.6 % (p = 0.006)) were significantly higher in the sedentary group compared with the active group. However, a sedentary lifestyle was not identified as an independent predictor for hospital mortality (p = 0.61) or early mortality (p = 0.70).

Conclusion

Sedentary patients were older, obese and had a higher EuroSCORE risk. They had significantly more postoperative complications, higher hospital mortality and early mortality. Despite these results, sedentary behaviour could not be identified as an independent predictor for hospital or early mortality.     

Design and development of topoisomerase inhibitors using molecular modelling studies

Topoisomerase inhibitors are used as anticancer and antibacterial agents. A series of novel 2,4,6-tri-substituted pyridine derivatives reported as topoisomerase inhibitors were used for quantitative structure–activity relationship (QSAR) study. In order to understand the structural requirement of these topoisomerase inhibitors, a ligand-based pharmacophore and atom-based 3D-QSAR model have been developed. A five-point pharmacophore with one hydrophobic group (H4), four aromatic rings (R5, R6, R7 and R8) was obtained. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least-square (PLS) statistic results. The training set correlation is characterized by PLS factors (r² = 0.7892, SD = 0.2948, F = 49.9, P = 1.379). The test set correlation is characterized by PLS factors (q² = 0.7776, root mean squared error = 0.2764, Pearson R = 0.8926). The docking study revealed the binding orientations of these inhibitors at active site amino acid residues of topoisomerases enzyme. The results of pharmacophore hypothesis and 3D-QSAR provided the detail structural insights as well as highlighted the important binding features of novel 2,4,6-tri-substituted pyridine derivatives and can be developed as potent topoisomerase inhibitors.

Figure

Open in a separate windowKey structural requirement for topoisomerase activity     

Simple Chromatographic Method for Simultaneous Analyses of Phosphatidylcholine, Lysophosphatidylcholine, and Free Fatty Acids

This study describes a simple chromatographic method for the simultaneous analyses of phosphatidylcholine (PC) and its hydrolytic degradation products: lysophosphatidylcholine (LPC) and free fatty acids (FFA). Quantitative determination of PC, LPC, and FFA is essential in order to assure safety and to accurately assess the shelf life of phospholipid-containing products. A single-run normal-phase high-performance liquid chromatography (HPLC) with evaporative light scattering detector has been developed. The method utilizes an Allsphere silica analytical column and a gradient elution with mobile phases consisting of chloroform: chloroform–methanol (70:30%, v/v) and chloroform–methanol–water–ammonia (45:45:9.5:0.5%, v/v/v/v). The method adequately resolves PC, LPC, and FFA within a run time of 25 min. The quantitative analysis of PC and LPC has been achieved with external standard method. The free fatty acids were analyzed as a group using linoleic acid as representative standard. Linear calibration curves were obtained for PC (1.64–16.3 μg, r² = 0.9991) and LPC (0.6–5.0 μg, r² = 0.9966), while a logarithmic calibration curve was obtained for linoleic acid (1.1–5.8 μg, r² = 0.9967). The detection and quantification limits of LPC and FFA were 0.04 and 0.1 μg, respectively. As a means of validating the applicability of the assay to pharmaceutical products, PC liposome was subjected to alkaline hydrolytic degradation. Quantitative HPLC analysis showed that 97% of the total mass balance for PC could be accounted for in liposome formulation. The overall results show that the HPLC method could be a useful tool for chromatographic analysis, stability studies, and formulation characterization of phospholipid-based pharmaceuticals.KEY WORDS: evaporative light scattering detection, free fatty acid, lysophosphatidylcholine, phosphatidylcholine     

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

Objective

Traditionally, oestrogens were considered to be protective for the cardiovascular system for premenopausal women. Therefore, we conducted a retrospective case–control study to examine the association between endogenous oestrogens and acute myocardial infarction (AMI) risk among postmenopausal women.

Methods

A case–control study was performed among 30 primary AMI patients and 60 control subjects. Baseline characteristics data was collected and endogenous sex hormones levels were determined using chemoluminescence and radioimmunoassay methods. Conditional logistic regression models were developed with adjustment for confounders.

Results

Compared with controls, the circulating oestrone, oestradiol, androstenedione and testosterone levels were significantly higher in AMI patients (P < 0.05) while the sex hormone binding globulin (SHBG) level was lower (P < 0.05). Spearman correlation coefficients showed oestradiol was positively correlated with body mass index (BMI) and waist-to-hip ratio (WHR) in cases, but not in controls. In univariable conditional logistic regression models, oestrone, oestradiol, testosterone, WHR, BMI, diabetes and hypertension were all found to be positively associated with AMI (P < 0.05). After adjusting for these factors, oestradiol (odds ratio (OR) = 4.75; 95 % confidence interval (CI) = 1.07–21.10; P = 0.04) and WHR (OR = 6.46; 95 % CI = 1.09–38.39; P = 0.04) continued to demonstrate strong positive associations with AMI.

Conclusions

A higher level of oestradiol was potentially associated with primary AMI risk among postmenopausal women.     

Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population

Age-related macular degeneration (AMD) is a common cause of blindness in the elderly. Caucasian patients are predominantly affected by the dry form of AMD, whereas Japanese patients have predominantly the wet form of AMD and/or polypoidal choroidal vasculopathy (PCV). Although genetic association in the 10q26 (ARMS2/HTRA1) region has been established in many ethnic groups for dry-type AMD, typical wet-type AMD, and PCV, the contribution of the 1q32 (CFH) region seem to differ among these groups. Here we show a single nucleotide polymorphism (SNP) in the ARMS2/HTRA1 locus is associated in the whole genome for Japanese typical wet-type AMD (rs10490924: , OR = 4.16) and PCV (rs10490924: , OR = 2.72) followed by CFH (rs800292: , OR = 2.08; , OR = 2.00), which differs from previous studies in Caucasian populations. Moreover, a SNP (rs2241394) in complement component C3 gene showed significant association with PCV (, OR = 3.47). We conclude that dry-type AMD, typical wet-type AMD, and PCV have both common and distinct genetic risks that become apparent when comparing Japanese versus Caucasian populations.

Electronic supplementary material

The online version of this article (doi:10.1007/s12177-009-9047-1) contains supplementary material, which is available to authorized users.     

Exercise reduces cellular stress related to skeletal muscle insulin resistance

This study sought to evaluate the effects of a single session of exercise on the expression of Hsp70, of c-jun N-terminal kinase (JNK), and insulin receptor substrate 1 serine 612 (IRS^ser612) phosphorylation in the skeletal muscle of obese and obese insulin-resistant patients. Twenty-seven volunteers were divided into three experimental groups (eutrophic insulin-sensitive, obese insulin-sensitive, and obese insulin-resistant) according to their body mass index and the presence of insulin resistance. The volunteers performed 60 min of aerobic exercise on a cycle ergometer at 60 % of peak oxygen consumption. M. vastus lateralis samples were obtained before and after exercise. The protein expressions were evaluated by Western blot. Our findings show that compared with paired eutrophic controls, obese subjects have higher basal levels of p-JNK (100 ± 23 % vs. 227 ± 67 %, p = 0.03) and p-IRS-1^ser612 (100 ± 23 % vs. 340 ± 67 %, p < 0.001) and reduced HSP70 (100 ± 16 % vs. 63 ± 12 %, p < 0.001). The presence of insulin resistance results in a further increase in p-JNK (460 ± 107 %, p < 0.001) and a decrease in Hsp70 (46 ± 5 %, p = 0.006), but p-IRS-1^ser612 levels did not differ from obese subjects (312 ± 73 %, p > 0.05). Exercise reduced p-JNK in obese insulin-resistant subjects (328 ± 33 %, p = 0.001), but not in controls or obese subjects. Furthermore, exercise reduced p-IRS-1^ser612 for both obese (122 ± 44 %) and obese insulin-resistant (185 ± 36 %) subjects. A main effect of exercise was observed in HSP70 (p = 0.007). We demonstrated that a single session of exercise promotes changes that characterize a reduction in cellular stress that may contribute to exercise-induced increase in insulin sensitivity.     

Out-of-hospital cardiac arrest: the prospect of E-CPR in the Maastricht region

Aim

The current outcome of out-of-hospital cardiac arrest (OHCA) patients in the Maastricht region was analysed with the prospect of implementing extracorporeal cardiopulmonary resuscitation (E-CPR).

Methods

A retrospective analysis of adult patients who were resuscitated for OHCA during a 24-month period was performed.

Results

195 patients (age 66 [57–75] years, 82 % male) were resuscitated for OHCA by the emergency medical services and survived to admission at the emergency department. Survival to hospital discharge was 46.2 %. Notable differences between non-survivors and survivors were observed and included: age (70 [58–79] years) vs. (63 [55–72] years, p = 0.01), chronic heart failure (18 vs. 7 %, p = 0.02), shockable rhythm (67 vs. 99 %, p < 0.01), and return of spontaneous circulation (ROSC) at departure from the site of the arrest (46 vs. 99 %, p < 0.01) and on arrival to the emergency department (43 vs. 98 %, p < 0.01), respectively. Acute coronary syndrome was diagnosed in 32 % of non-survivors vs. 59 % among survivors, p < 0.01. Therapeutic hypothermia was provided in non-survivors (20 %) vs. survivors (43 %), p < 0.01. Percutaneous coronary intervention (PCI) was performed in 14 % of non-survivors while 52 % of survivors received PCI (p < 0.01). No statistical significance was observed in terms of gender, witnessed arrest, bystander CPR, or automated external defibrillator deployed among the cohort. At hospital discharge, moderately severe neurological disability was present in six survivors.

Conclusion

These observations are compatible with the notion that a shockable rhythm, ROSC, and post-arrest care improve survival outcome. Potentially, initiating E-CPR in the resuscitation phase in patients with a shockable rhythm and no ROSC might serve as a bridge to definite treatment and improve survival outcome.     

Low efficacy of cardioversion of persistent atrial fibrillation with the implantable cardioverter-defibrillator

Aims

Atrial fibrillation (AF) and heart failure are conditions that often coexist. Consequently, many patients with an implantable cardioverter-defibrillator (ICD) present with AF. We evaluated the effectiveness of internal cardioversion of AF in patients with an ICD.

Methods

Retrospectively, we included 27 consecutive ICD patients with persistent AF who underwent internal cardioversion using the ICD. When ICD cardioversion failed, external cardioversion was performed.

Results

Patients were predominantly male (89 %) with a mean (SD) age of 65 ± 9 years and left ventricular ejection fraction of 36 ± 17 %. Only nine (33 %) patients had successful internal cardioversion after one, two or three shocks. The remaining 18 patients underwent external cardioversion after they failed internal cardioversion, which resulted in sinus rhythm in all. A smaller left atrial volume (99 ± 36 ml vs. 146 ± 44 ml; p = 0.019), a longer right atrial cycle length (227 (186–255) vs. 169 (152–183) ms, p = 0.030), a shorter total AF history (2 (0–17) months vs. 40 (5–75) months, p = 0.025) and dual-coil ICD shock (75 % vs. 26 %, p = 0.093) were associated with successful ICD cardioversion.

Conclusion

Internal cardioversion of AF in ICD patients has a low success rate but may be attempted in those with small atria, a long right atrial fibrillatory cycle length and a short total AF history, especially when a dual-coil ICD is present. Otherwise, it seems reasonable to prefer external over internal cardioversion when it comes to termination of persistent AF.     

The risk of ventricular arrhythmias in a Dutch CRT population: CRT-defibrillator versus CRT-pacemaker

Background

Patients eligible for cardiac resynchronisation therapy (CRT) have an indication for primary prophylactic implantable cardioverter defibrillator (ICD) therapy. However, response to CRT might influence processes involved in arrhythmogenesis and therefore change the necessity of ICD therapy in certain patients.

Method

In 202 CRT-defibrillator patients, the association between baseline variables, 6-month echocardiographic outcome (volume response: left ventricular end-systolic volume decrease < ≥15 % and left ventricular ejection fraction (LVEF) ≤ >35 %) and the risk of first appropriate ICD therapy was analysed retrospectively.

Results

Fifty (25 %) patients received appropriate ICD therapy during a median follow-up of 37 (23–52) months. At baseline ischaemic cardiomyopathy (hazard ratio (HR) 2.0, p = 0.019) and a B-type natriuretic peptide level > 163 pmol/l (HR 3.8, p < 0.001) were significantly associated with the risk of appropriate ICD therapy. After 6 months, 105 (52 %) patients showed volume response and 51 (25 %) reached an LVEF > 35 %. Three (6 %) patients with an LVEF > 35 % received appropriate ICD therapy following echocardiography at ± 6 months compared with 43 patients (29 %) with an LVEF ≤ 35 % (p = 0.001). LVEF post-CRT was more strongly associated to the risk of ventricular arrhythmias than volume response (LVEF > 35 %, HR 0.23, p = 0.020).

Conclusion

Assessing the necessity of an ICD in patients eligible for CRT remains a challenge. Six months post-CRT an LVEF > 35 % identified patients at low risk of ventricular arrhythmias. LVEF might be used at the time of generator replacement to identify patients suitable for downgrading to a CRT-pacemaker.