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.

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.

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.

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.

Elevated non-esterified fatty acid concentrations hamper bovine oviductal epithelial cell physiology in three different in vitro culture systems.

Elevated non-esterified fatty acids (NEFAs) have been recognized as an important link between lipolytic metabolic conditions and impaired fertility in high-yielding dairy cows. However, NEFA effects on the oviductal micro-environment currently remain unknown. We hypothesize that elevated NEFAs may contribute to the complex pathology of subfertility by exerting a negative effect on bovine oviductal epithelial cell (BOEC) physiology. Therefore, the objectives of this study were to elucidate direct NEFA effects on BOEC physiology in three different in vitro cell culture systems. Bovine oviductal epithelial cells (four replicates) were mechanically isolated, pooled, and cultured as conventional monolayers, as explants, and in a polarized cell culture system with Dulbecco's modified Eagle's medium/F12-based culture medium. Bovine oviductal epithelial cells were exposed to an NEFA mixture of oleic, stearic, and palmitic acids for 24 hours at both physiological and pathologic concentrations. A control (0 µM NEFA) and a solvent control (0 µM NEFA + 0.45% ethanol) group were implemented. Bovine oviductal epithelial cells physiology was assessed by means of cell number and viability, a sperm binding assay, transepithelial electric resistance (TER), and a wound-healing assay. Bovine oviductal epithelial cell morphology was assessed by scanning electron microscopy on cell polarity, presence of microvilli and cilia, and monolayer integrity. Bovine oviductal epithelial cell number was negatively affected by increasing NEFAs, however, cell viability was not. Sperm binding affinity significantly decreased with increasing NEFAs and tended (P = 0.051) to be more affected by the direction of NEFA exposure in the polarized cell culture system. The absolute TER increase after NEFA exposure in the control (110 ± 11 Ω.cm(2)) was significantly higher than that in all the other treatments and was also different depending on the exposure side. Bidirectional exposed monolayers were even associated with a significant TER reduction (-15 ± 10 Ω.cm(2); P < 0.05). Cell proliferation capacity showed a decreased cell migration with increasing NEFA concentrations but was irrespective of the exposure side. Bovine oviductal epithelial cell morphology was not affected. In conclusion, in an in vitro setting, NEFAs exert a negative effect on BOEC physiology but not morphology. Ultimately, these physiological alterations in its microenvironment may result in suboptimal development of the pre-implantation embryo and a reduced reproductive outcome in dairy cattle.

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.

Adenosine testing after cryoballoon pulmonary vein isolation improves long-term clinical outcome.

BACKGROUND: Adenosine infusion after pulmonary vein isolation (PVI) with radiofrequency energy reveals dormant muscular sleeves and predicts atrial fibrillation (AF) recurrence. The aim of our study was to determine whether adenosine could reveal dormant PV sleeves after cryoballoon isolation and study its effect on long-term recurrence of AF. METHODS: Patients with paroxysmal AF underwent cryoballoon PVI. After PVI, adenosine 25 mg was infused to test for dormant muscular sleeves in each vein. If reconnection under adenosine was shown, further cryoballoon ablation was performed until no more reconnection occurred. Follow-up was performed with ECG, 24-h Holter recording, and a symptom questionnaire at three monthly intervals. Transtelephonic Holter monitoring was performed for 1 month before and 3 months after PVI. Patients who underwent cryoballoon PVI without adenosine administration were used as controls for comparison. RESULTS: In the study group (n = 34, 24 males), adenosine revealed dormant sleeves in 9/132 (8 %) veins, and 7/34 (21 %) patients. All but one vein was further treated until the dormant sleeves were isolated. During a mean follow-up of 520 ± 147 days, 23/34 (68 %) patients were free of AF without antiarrhythmic drugs (AADs). In the control group (n = 65, 46 males), 29/65 (46 %) were free of AF without AADs. There were significantly less AF recurrences in the study group (p = 0.04). CONCLUSIONS: Adenosine administration after cryoballoon PVI reveals dormant muscular sleeves in 21 % of patients. Clinical follow-up shows that adenosine testing is effective in reducing AF recurrence after cryoballoon ablation.

Use of remote monitoring in the management of system-related complications in implantable defibrillator patients.

Remote monitoring of implantable defibrillators (ICDs) is designed to minimise regular follow-up visits and to facilitate early detection of adverse events. With the increased rate of ICD implantations in today's clinical setting and multiple device advisories, which pose management challenges, this approach becomes very attractive. The aim of this article is to present the role of remote monitoring in the detection of system-related complications, its potential benefits and its barriers in the outpatient management of ICD patients.

Health care utilisation after defibrillator implantation for primary prevention according to the guidelines in 2 Dutch academic medical centres.

BACKGROUND: The benefit of implantable defibrillators (ICDs) for primary prevention remains debated. We analysed the implications of prophylactic ICD implantation according to the guidelines in 2 tertiary hospitals, and made a healthcare utilisation inventory. METHODS: The cohort consisted of all consecutive patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) receiving a primary prophylactic ICD in a contemporary setting (2004-2008). Follow-up was obtained from hospital databases, and mortality checked at the civil registry. Additional data came from questionnaires sent to general practitioners. RESULTS: There were no demographic differences between the 2 centres; one had proportionally more CAD patients and more resynchronisation therapy (CRT-D). The 587 patients were followed over a median of 28 months, and 50 (8.5%) patients died. Appropriate ICD intervention occurred in 123 patients (21%). There was a small difference in intervention-free survival between the 2 centres. The questionnaires revealed 338 hospital admissions in 52% of the responders. Device-related admissions happened on 68 occasions, in 49/276 responders. The most frequently reported ICD-related admission was due to shocks (20/49 patients); for other cardiac problems it was mainly heart failure (52/99). Additional outpatient visits occurred in 19%. CONCLUSION: Over a median follow-up of 2 years, one fifth of prophylactic ICD patients receive appropriate interventions. A substantial group undergoes readmission and additional visits. The high number of admissions points to a very ill population. Overall mortality was 8.5%. The 2 centres employed a similar procedure with respect to patient selection. One centre used more CRT-D, and observed more appropriate ICD interventions.

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.

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.

Migraine accompagnée after transseptal puncture.

Migraine has never been reported as a complication of transseptal puncture for ablation of atrial fibrillation. We studied its incidence before and after such procedures after observing some striking new migraine in several patients. A total of 8% of procedures for pulmonary vein isolation with a 15 Fr sheath used for transseptal puncture were associated with new headache with ocular symptoms or migraine within three months. Exacerbation of pre-existing migraine was reported in another 7% of procedures. More complaints were seen in redo procedures. The questionnaires were performed at three months after the intervention and there was no more evidence of persisting flow over the atrial septum at that time, when most complaints had already disappeared. This has important implications for follow-up after ablation for atrial fibrillation. (Neth Heart J 2010;18:374-5.).

An in vivo comparison of radiofrequency cardiac lesions formed by standard and magnetically steered 4 mm tip catheters.

Background. In vivo comparison of cardiac radiofrequency ablation lesions between standard and magnetically steered 4 mm tip catheters has never been reported.Methods. High and low right atrium (RA) free wall, isthmus, right ventricle (RV) free wall and outflow tract lesions were studied macroscopically and microscopically five days after lesion formation in seven pigs. Shape, size, thrombus formation, and ablation parameters were compared. The effect of minimal, medium and high wall contact was assessed by a contact measurement utility for magnetic catheters.Results. All 14 RA free wall lesions were transmural with a similar epicardial and endocardial surface area. In the RV, the epicardial area usually appeared to be smaller than the endocardial area with standard catheters. Isthmus lesions were difficult to assess transmurality. There was no difference in endocardial area: standard 39 mm(2) (range 16 to 82 mm(2)) vs. magnetic 36 mm(2) (range 23 to 111 mm(2)). If the catheter tip was perpendicular to the tissue, magnetic lesions were more often round or oval, while standard lesions were more often elongated (p<0.05). When the catheter tip was parallel to tissue, lesions always tended to be elongated. Microscopic characteristics were similar. The contact utility was not useful. Average impedance (p<0.0001) and energy delivered (p<0.05) were less with magnetic catheters.Conclusion. Lesions from magnetically steered catheters are transmural of similar size, but with less variability than standard catheter lesions when the tip is perpendicular to the tissue. Magnetic lesions are associated with lower impedance and energy delivery. This suggests a more stable tip-to-tissue contact. (Neth Heart J 2010;18:66-71.).