Altered embryotrophic capacities of the bovine oviduct under elevated free fatty acid conditions: an in vitro embryo--oviduct co-culture model.

Maternal metabolic stress conditions are of growing importance in both human and dairy cattle settings as they can have significant repercussions on fertility. Upregulated lipolysis is a common trait associated with metabolic disorders and results in systemically elevated concentrations of non-esterified fatty acids (NEFAs). The effects of high NEFA concentrations on the follicular environment, oocyte and embryo development is well documented. However, knowledge on the effects of NEFAs within the oviduct, representing the initial embryonic growth environment, is currently lacking. Therefore, the experiments outlined here were designed to obtain fundamental insights into both the direct and indirect interactions between NEFAs, bovine oviductal cells and developing zygotes. Hence, zygotes were co-cultured with NEFA-pre-exposed bovine oviductal cells or subjected to simultaneous NEFA exposure during the co-culture period. The outcome parameters assessed were embryo development with cleavage (48h post insemination (pi)), morula (120-126h pi) and blastocyst (192h pi) rates, as well as morula intracellular lipid content and blastocyst quality using Bodipy and differential staining respectively. Our data suggest a direct embryotoxicity of NEFAs as well as impaired embryo development through a reduced oviductal ability to support and protect early embryo development.

A clinical approach to arrhythmias revisited in 2018 : From ECG over noninvasive and invasive electrophysiology to advanced imaging.

Understanding arrhythmias and their treatment is not always easy. The current straightforward approach with catheter ablation and device therapy is an amazing achievement, but does not make management of underlying or other cardiac disease and pharmacological therapy unnecessary. The goal of this paper is to describe how much of the knowledge of the 1980s and early 1990s can and should still be applied in the modern treatment of patients with arrhythmias. After an introduction, this review will focus on paroxysmal atrial fibrillation and a prototype of 'idiopathic' ventricular arrhythmias, two diseases with a striking similarity, and will discuss the arrhythmogenesis. The ECG continues to play an important role in diagnostics. Both diseases are associated with a structurally normal heart; the autonomic nervous system plays an important role in triggering arrhythmias at both the atrial and ventricular level.

Maternal metabolic stress may affect oviduct gatekeeper function.

We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24-h treatments at Day 9: (1) control (0 µM NEFA + 0% EtOH), (2) solvent control (0 µM NEFA + 0.45% EtOH), (3) basal NEFA (720 µM NEFA + 0.45% EtOH in the basal compartment) and (4) apical NEFA (720 µM NEFA + 0.45% EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment and related to transepithelial electric resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA uptake were studied using Bodipy 493/503 and immunolabelling of FA transporters (FAT/CD36, FABP3 and CAV1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that apical NEFA reduced relative TER increase (46.85%) during treatment and increased FITC-albumin flux (27.59%) compared to other treatments. In basal NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased respectively 56.0 and 33.5% of initial FA concentrations. Apical NEFA allowed no FA transfer, but induced LD accumulation and upregulated FA transporter expression (↑CD36, ↑FABP3 and ↑CAV1). Gene expression in apical NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA) and FA uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function-specific gene expression (OVGP1, ESR1 and FOXJ1). Overall, elevated NEFAs affected BOEC metabolism and barrier function differently depending on NEFA exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions.

Differential effects of high and low glucose concentrations during lipolysis-like conditions on bovine in vitro oocyte quality, metabolism and subsequent embryo development.

Lipolytic metabolic conditions are traditionally associated with elevated non-esterified fatty acid (NEFA) concentrations, but may also be accompanied by hyperglycaemia in obesity or by hypoglycaemia during a negative energy balance status. Elevated NEFA concentrations disrupt oocyte and embryo development and quality, but little is known about whether the effects of lipolytic conditions on oocyte developmental competence are modulated by glucose availability. To answer this, bovine cumulus-oocyte complexes (COCs) were matured under different conditions: physiological NEFA (72µM) and normal glucose (5.5mM), pathophysiologically high NEFA (420µM) and normal glucose, high NEFA and high glucose (9.9mM), high NEFA and low glucose (2.8mM). Developmental potential, cumulus expansion and metabolism of COCs exposed to high NEFA and low glucose were affected to a greater extent compared with COCs matured under high NEFA and high glucose conditions. High NEFA and high glucose conditions caused a moderate increase in oocyte reactive oxygen species compared with their high NEFA and low glucose or control counterparts. Blastocyst metabolism and the transcriptome of metabolic and oxidative stress-related genes were not affected. However, both lipolytic conditions associated with hyper- or hypoglycaemia led to surviving embryos of reduced quality with regards to apoptosis and blastomere allocation.

ICDs at higher age and clinical risk factors.

BACKGROUND: The implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death. However, in elderly patients (aged 75 years or older) the role of ICDs is still not well-defined and controversial. METHODS: We retrospectively analysed all clinical and survival data of all ICD patients who were ≥75 years at the date of implantation in the Erasmus MC, Rotterdam, the Netherlands and the University Hospital, Basel, Switzerland. Kaplan-Meier survival analysis was performed, and mortality predictors were identified. Mortality of the cohort was compared with a random sample of patients aged 60-70 years originating from the same database and to an age- and sex-matched cohort of Dutch persons. RESULTS: The study cohort consisted of 179 patients aged 75 years or older who were implanted between February 1999 and July 2008. The median follow-up time was 2.0 (IQR 2.8) years. Survival rates after 1, 2 and 3 years were 87, 82, 75 %, respectively. Survival was similar for primary and secondary prevention. Mortality in this study population could be predicted by combining four clinical risk factors: QRS duration >120 ms, NYHA class > II, renal failure and atrial fibrillation (AF). Survival was worse compared with the group of ICD patients aged 60-70 years and to the age- and sex-matched group of elderly persons. However, survival was not significantly worse when comparing elderly ICD patients without additional risk factors to the general population. CONCLUSIONS: Elderly patients still have an acceptable survival probability independent of prevention indication, certainly if there are no additional clinical risk factors. The presence or absence of additional clinical risk factors should be taken into account when making the decision for implantation, since they strongly correlate with survival.

Long-term performance of the St Jude Riata 1580-1582 ICD lead family.

OBJECTIVE: Safety concerns about the Riata ICD shock lead were recently raised, with insulation failure due to conductor externalisation. Its incidence and presentation were assessed, and predictors of insulation failure and lead survival of the Riata 1580-1582 were studied, retrospectively, before the official recall. METHODS: All 374 patients at the Erasmus Medical Center between July 2003 and December 2007 with a 1580, 1581 or 1582 shock lead. RESULTS: The majority of the patients were male (78 %), with a median age of 60 years (IQR 52-70); primary prevention in 61 %. Median follow-up was 60.3 months (IQR 35.5-73.2), with 117 (31 %) patients dying. Electrical abnormalities (mainly noise, 65 %) were observed in 20/257 patients (7.8 %). Definite conductor externalisation was confirmed with fluoroscopy or chest X-ray in 16 patients, and in one after extraction. One patient presented with a drop in the high-voltage impedance trend with a short circuit of the ICD system during defibrillation testing, and needed to be shocked externally. In 8 more patients, conductor externalisation was found during an elective procedure. No predictors of externalisation could be found, except for the use of single coil (p = 0.02). Median time to conductor externalisation was 5 years (IQR 3.1-6.2). Lead externalisation was observed in 5.4 % (95 % CI 3.1-9.3) at 5 years and 22.7 % (95 % CI 13.6-36.6) at 8 years. CONCLUSION: A high incidence of insulation defects associated with conductor externalisation in the Riata ICD lead family is observed. The mode of presentation is diverse. This type of insulation failure can lead to failure of therapy delivery.

Quality of life and symptoms in patients selected for ablation of ventricular extrasystoles: a prospective study.

PURPOSE: Evaluation of the impact of catheter ablation for ventricular extrasystoles (VES) in structurally normal hearts on quality of life (QOL) and symptomatology. METHODS: Symptom analysis assessed with a disease-specific questionnaire, EHRA score for AF, and QOL analysis at baseline and 1 year after ablation. RESULTS: The study enrolled 39 patients between April 2016 and November 2019. Two patients were excluded from further analysis. At baseline, palpitations were reported in 31/37 (84%); syncope in 12/37 (32%); other cardiac symptoms in 33/37 (89%) of patients. The EHRA score was 3 or 4 in 13 patients (35%). With the modified arrhythmia-specific questionnaire (MASQ) psychological and physical scores were 46 and 39%. The overall perception of health in the SF-36 was 56 ± 16%. Ablation was performed in 35/37 (95%). At regular follow-up, symptoms were reported in 14/37 (38%) patients. ECG suggested a good procedural outcome in 65% with VES burden on Holter < 1% in 68%. At follow-up, palpitations were reported in 61% (P < 0.07); syncope in only 1 patient (P < 0.05). The EHRA score was 3 or 4 in only one patient (P < 0.05). MASQ scores improved to 62 and 60% (both p < 0.001). The overall perception of health in the SF-36 became 64 ± 17% (P < 0.02). CONCLUSIONS: Patients with VES suffer from a wide variety of symptoms and have a low quality of life, as demonstrated by the EHRA score and conventional questionnaires. After catheter ablation, palpitations are still reported, but become less frequently present. Syncope becomes rare. Quality of life improves significantly from all perspectives.

Paradoxical effects of interatrial conduction delay in a hypertrophic cardiomyopathy patient in the long-term: time is a great healer.

We present a unique case where early proarrhythmic and late antiarrhythmic characteristics of interatrial conduction delay were observed during the long-term progression of HCM. Occurrence of AT constantly increased as the interatrial conduction delay became more prominent, while the P-wave width in sinus rhythm and the AT cycle length both showed an instantaneous increase in parallel. As the interatrial delay reached a critical point, the right and left atrial P-wave became virtually separated, as demonstrated by the findings of ECGs and echocardiography. This phenomenon resulted in the complete cessation of tachycardias.

Antiarrhythmic drugs management in patients with atrial fibrillation: the new guidelines.

Antiarrhythmic drug therapy will continue to play an important role in the treatment of atrial fibrillation (AF). Pharmacological therapy is focused on AF symptom relief and on prevention of tachycardiomyopathy. The choice between the various anti-arrhythmic drugs available, either for rate or rhythm control, mainly depends on the underlying cardiac disease, type of AF and possible side-effects. New anti-arrhythmic drugs in the guidelines vernakalant and dronedarone are promising, but further research is required to explore their role in treatment of patients with AF. In this review, we will discuss the role of antiarrhythmic drugs in management of patients with AF according to the new AF guidelines of the European Society of Cardiology.

Baffle puncture guided by transoesophageal echocardiography in a patient with dextrocardia and Mustard correction.

A baffle puncture is a challenging procedure but can be safely done using direct visualization of the region of interest. To our knowledge, however, it has never been performed in a patient with dextrocardia. We present a 62-year-old male with dextrocardia, right isomerism, congenitally corrected transposition of the great arteries, persistent left-sided superior and inferior caval veins, atrial septum defect, and pulmonary valve stenosis. The atrial septum defect was surgically closed with a Teflon patch, a variant Mustard operation was performed, and also a prosthetic tricuspid valve was implanted. The patient developed multiple episodes of atrial tachycardia leading to acute heart failure on many occasions. An electrophysiological study was undertaken in order to create a bi-atrial electro-anatomical map. Owing to the presence of a prosthetic tricuspid valve, the femoral venous access was used and a baffle puncture was performed using continuous monitoring with fluoroscopy and transoesophageal echocardiography (TEE). The baffle puncture was successful and the tachycardia was ablated in the systemic venous atrium. To our knowledge, we present the very first case report demonstrating a successful baffle puncture in a patient with dextrocardia and Mustard correction. Direct imaging using TEE seems to be a very useful tool for guiding the puncture.

Usefulness of remote magnetic navigation for ablation of ventricular arrhythmias originating from outflow regions.

Monomorphic ventricular tachycardia (VT) and symptomatic monomorphic PVCs originating from the region of the right and left outflow tracts are increasingly treated by radiofrequency (RF) catheter ablation. Technical difficulties in catheter manipulation to access these outflow tract areas, very accurate mapping and reliable catheter stability are key issues for a successful treatment in this vulnerable region. VT ablation from the aortic sinus cusp (ASC) in particular carries a significant risk of perforation, of creating left coronary artery injury and of damage to the aorta and the aortic valve.This case series describes RF ablation of VT originating in the outflow region using the remote magnetic navigation system (MNS). Potential advantages of the MNS are catheter flexibility, steering accuracy and reproducibility to navigate to a desired location with a low probability of perforating the myocardium. This report supports the idea of using advanced MNS technology during RF ablation in regions which are difficult to reach and thin walled, such as parts of the outflow tract and the ASC. (Neth Heart J 2009;17:245-9.).

Acute success and short-term follow-up of catheter ablation of isthmus-dependent atrial flutter; a comparison of 8 mm tip radiofrequency and cryothermy catheters.

OBJECTIVES: To compare the acute success and short-term follow-up of ablation of atrial flutter using 8 mm tip radiofrequency (RF) and cryocatheters. METHODS: Sixty-two patients with atrial flutter were randomized to RF or cryocatheter (cryo) ablation. Right atrial angiography was performed to assess the isthmus. End point was bidirectional isthmus block on multiple criteria. A pain score was used and the analgesics were recorded. Patients were followed for at least 3 months. RESULTS: The acute success rate for RF was 83% vs 69% for cryo (NS). Procedure times were similar (mean 144+/-48 min for RF, vs 158+/-49 min for cryo). More applications were given with RF than with cryo (26+/-17 vs. 18+/-10, p<0.05). Fluoroscopy time was longer with RF (29+/-15 vs. 19+/-12 min, p<0.02). Peak CK, CK-MB and CK-MB mass were higher, also after 24 h in the cryo group. Troponin T did not differ. Repeated transient block during application (usually with cryoablation) seemed to predict failure. Cryothermy required significantly less analgesia (p<0.01), and no use of long sheaths (p<0.005). The isthmus tended to be longer in the failed procedures (p=0.117). This was similar for both groups, as was the distribution of anatomic variations. Recurrences and complaints in the successful patients were similar for both groups, with a very low recurrence of atrial flutter after initial success. CONCLUSIONS: In this randomized study there was no statistical difference but a trend to less favorable outcome with 8 mm tip cryocatheters compared to RF catheters for atrial flutter ablation. Cryoablation was associated with less discomfort, fewer applications, shorter fluoroscopy times and similar procedure times. The recurrence rate was very low. Cryotherapy can be considered for atrial flutter ablation under certain circumstances especially when it has been used previously in the same patient, such as in an AF ablation.

Recurrence of cardiac arrest after 14 years without ICD interventions: a VF cluster immediately after delivery.

One day after childbirth, a 29-year-old woman had several episodes of polymorphic ventricular tachycardia and ventricular fibrillation. She was rescued by an internal cardioverter defibrillator (ICD) which she had received 14 years ago, after out-of-hospital cardiac arrest, without recurrences until now. The electrocardiogram showed a normal QT interval, and ventricular premature beats, which seemed to arise from the same site. This case report illustrates that, even after years with freedom of ICD therapy, depleted devices still have to be replaced. (Neth Heart J 2008;16:242-5.).

Remote monitoring in implantable defibrillator therapy.

The major device manufacturers have introduced systems for remote patient monitoring. These remote monitoring systems promise more efficient patient management, especially in today's clinical setting with the growing number of defibrillator implantations. The aim of this article is to present the role of remote patient monitoring in implantable cardioverter-defibrillator follow-up, its potential benefits and its barriers to widespread diffusion. (Neth Heart J 2008;16:53-6.).

Transvenous radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia and its pitfalls: a rationale for cryoablation?

Today, radiofrequency (RF) catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT) is accompanied by a high success, a low recurrence, and a low complication rate. Despite the fact that over the years this technique has been refined, several shortcomings still remain. In this overview, the most important pitfalls in the treatment of AVNRT with RF energy are discussed. Cryotherapy has the ability to overcome some of them. Both ice mapping and cryo-adherence are important characteristics of this energy source to study prospective ablation sites before a definitive and irreversible lesion is created. Theoretically, this could lead to less applications with less tissue damage and abolish the risk for permanent conduction disturbances. The early experience with this technique will be described. Until now, it still has to be proven that in a large cohort of patients, cryotherapy is at least as effective, and safer than RF.

Coronary risk factors and inflammation in patients with coronary artery disease and internal cardioverter defibrillator implants.

BACKGROUND: The internal cardioverter defibrillator (ICD) is increasingly used to treat ventricular tachyarrhythmias in patients with coronary artery disease (CAD). The burden of coronary risk factors and inflammation is however not well studied in these high risk patients. STUDY AIMS: The aim of the present study was to describe the prevalence of coronary risk factors (including lipid values) and inflammation (including high sensitive-C-reactive protein, hs-CRP) in patients with CAD and ICD implants. METHODS: Baseline clinical characteristics and laboratory results of all eligible patients for the Cholesterol Lowering and Arrhythmias Recurrences after Internal Defibrillator Implantation trial (CLARIDI trial) were used. All patients had documented CAD, an ICD implant and were not yet treated with statins. Coronary risk factors, lipid values, glycated haemoglobin (HbA(1c)) and hs-CRP levels were determined. RESULTS: In the 110 included patients (mean age 68+/-9 years, LVEF 40+/-17%, NYHA class II-III in 47%), a high prevalence of coronary risk factors was documented: current smoking in 18%, body mass index > or =30 kg/m(2) in 16%, blood pressure > or =140/90 mm Hg in 40%, history of diabetes in 12%, and HbA(1c) > or =6% in 16% of patients not known with diabetes. A total cholesterol >175 mg/dl was found in 76% of patients and an LDL cholesterol >100 mg/dl in 83%. Finally, median hs-CRP was 4.8 mg/l (interquartile range 2.5-13.9 mg/l). Hs-CRP values > or =2 mg/l were noted in 83% of all patients and in 68% of patients who had an ICD implant more than 6 months before inclusion. CONCLUSION: In CAD patients with ICD implants, the burden of coronary risk factors is high, often unrecognized and/or under-treated. Persistent inflammation is found in the majority of these patients.

Magnetic assisted navigation in electrophysiology and cardiac resynchronisation: a review.

Magnetic assisted navigation is a new innovation that may prove useful in catheter ablation of cardiac arrhythmias and cardiac resynchronization therapy. The ability to steer extremely floppy catheters and guidewires may allow for these to be positioned safely in previously inaccessible areas of the heart. The integration of other new technology, such as image integration and electroanatomic mapping systems, should advance our abilities further. Although studies have shown the technology to be feasible, with the advantage to the physician of decreased radiation exposure, studies need to be performed to show additional benefit over standard techniques.