Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

High incidence of (ultra)low oesophageal temperatures during cryoballoon pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Low oesophageal temperatures (OTs) during cryoballoon pulmonary vein isolation (PVI) have been associated with complications. This study assessed the incidence of low OT in clinical practice during cryoballoon PVI and verified possible predictive values for low OT. METHODS: Consecutive patients who underwent PVI using the second-generation cryoballoon were retrospectively included. The distance from the oesophagus to the different pulmonary veins (PVs) (OP distance), body mass index (BMI), sex, age, balloon temperature and application time were studied as potential predictors of low OTs. Computed tomography was performed before the procedure to determine the OP distance. OT was measured using an oesophageal temperature probe. Applications were ended prematurely if the OT reached <16 °C. Low and ultralow OT were defined as OT <20 and <16 °C respectively. RESULTS: Two hundred and four patients were included. Low OT was observed in 54 patients (26%) and 27 patients (13%) reached ultralow OTs. OP distance was the only predictor of low OTs after multivariate analysis. A cut-off value of 19 mm showed 96.2% sensitivity and 37.8% specificity in predicting low OTs. No clinically relevant relation was found between low OTs and BMI, age, sex, balloon temperature or application duration. CONCLUSIONS: The incidence of low OT was 26% for cryoballoon PVI. OP distance was the only predictor of low OTs. Since an OP distance <19 mm was present in all patients in at least one PV, we recommend routine OT measurement during PVI cryoballoon therapy to prevent oesophagus-related complications.

Use of three-dimensional computed tomography overlay for real-time cryoballoon ablation in atrial fibrillation reduces radiation dose and contrast dye.

AIMS: Cryoballoon pulmonary vein (PV) isolation in patients with atrial fibrillation has proven to be effective in short-term and long-term follow-up. To visualise the PV anatomy, pre-ablation contrast pulmonary venography is commonly performed. Three-dimensional (3D) computed tomography (CT) overlay is a new technique creating a live 3D image of the left atrium by integrating a previously obtained CT scan during fluoroscopy. To evaluate the benefits of 3D CT overlay during cryoballoon ablation, we studied the use of 3D CT overlay versus contrast pulmonary venography in a randomised fashion in patients with paroxysmal atrial fibrillation undergoing cryoballoon PV isolation. METHODS AND RESULTS: Between October 2012 and June 2013, 30 patients accepted for PV isolation were randomised to cryoballoon PV isolation using either 3D CT overlay or contrast pulmonary venography. All patients underwent a pre-procedural cardiac CT for evaluation of the anatomy of the left atrium (LA) and the PVs. In the 3D CT overlay group, a 3D reconstruction of the LA and PVs was made. An overlay of the CT reconstruction was then projected over live fluoroscopy. Patients in the contrast pulmonary venography group received significantly more contrast agent (77.1 ± 21.2 cc vs 40.1 ± 17.6 cc, p < 0.001) and radiation (43.0 ± 21.9 Gy.cm2 vs 28.41 ± 11.7 Gy.cm2, p = 0.04) than subjects in the 3D CT overlay group. There was no difference in total procedure time, fluoroscopy time and the amount of cryoapplications between the two groups. CONCLUSION: The use of 3D CT overlay decreases radiation and contrast dye exposure and can assist in guiding cryoballoon-based PV isolation.

Optimisation of cardiac resynchronization therapy in clinical practice during exercise.

AIMS: Although cardiac resynchronisation therapy (CRT) is an established treatment to improve cardiac function, a significant amount of patients do not experience noticeable improvement in their cardiac function. Optimal timing of the delay between atrial and ventricular pacing pulses (AV delay) is of major importance for effective CRT treatment and this optimum may differ between resting and exercise conditions. In this study the feasibility of haemodynamic measurements by the non-invasive finger plethysmographic method (Nexfin) was used to optimise the AV delay during exercise. METHODS AND RESULTS: Thirty-one patients implanted with a CRT device in the last 4 years participated in the study. During rest and in exercise, stroke volume (SV) was measured using the Nexfin device for several AV delays. The optimal AV delay at rest and in exercise was determined using the least squares estimates (LSE) method. Optimisation created a clinically significant improvement in SV of 10 %. The relation between HR and the optimal AV delay was patient dependent. CONCLUSION: A potential increase in SV of 10 % can be achieved using Nexfin for optimisation of AV delay during exercise. A considerable number of patients showed benefit with lengthening of the AV delay during exercise.

A challenging lead endocarditis.

Pacemaker/implantable cardioverter-defibrillator (ICD) lead endocarditis remains a challenging diagnosis in cardiology. Several parameters can be involved in the clinical path leading to the definite diagnosis. Clinical appearance and physical findings, together with transoesophageal echocardiography and serum levels of inflammatory parameters, are necessary in the workup towards the diagnosis. It is highly unlikely that ICD-lead vegetation is accompanied by positive blood cultures solely. We describe a case of ICD-infected endocarditis with positive blood cultures for Staphylococcus epidermidis without any physical findings or raised inflammatory parameters in serum plasma levels. In this case, three-dimensional echocardiography demonstrated an added value to two-dimensional echocardiography.

Venous graft perforation leading to cardiac tamponade.

We describe a cardiac tamponade after venous graft perforation due to stent inflation. The complications and therapeutic options are discussed.

A dancing thrombus in the right atrium going hand-in-hand with the electrocardiogram.

A 69-year old male with a large pulmonary embolism is described before and after thrombolytic treatment. The echocardiographic and electrocardiographic hallmarks of right ventricular pressure overload and dilatation are illustrated.

[Proposal for a treatment law based on the Scottish model]. / Voorstel voor een behandelwet naar Schots model.

Even after recent amendments and proposed modifications, the Dutch law on special admissions to psychiatric hospitals ('Bopz') is still primarily a law on admissions, whereas what psychiatry and society in general urgently require is a law on treatment. In October, 2005, in Scotland a new law concerning the care and treatment of psychiatric patients came into force: the Mental Health (Care and treatment) Act 2003 ('Act'). This new law can in fact be designated a treatment law. In this article the Scottish Act is compared to the Bopz. The comparison shows that Scotland has in fact developed a law which may provide an answer to the inadequacies of the Bopz.

[On the way to a treatment law?]. / Op weg naar een behandelwet?

Under the current Dutch law on special admissions to psychiatric hospitals (Bopz) it is possible to detain a patient who is a danger to himself and others. The Bopz, however, makes hardly any provisionfor compulsory treatment. Many psychiatrists regard this as an inherent shortcoming of the law. Members of the public, too, are becoming increasingly concerned by the fact that a seriously ill patient can, subject to strict criteria, be detained compulsorily but cannot thereafter be compelled to undergo treatment. The legislature has recently made some amendments to the Bopz law. The main goals is to widen its scope, making the law more flexible with regard to compulsory admission and compulsory treatment. In this article we discuss these amendments and new developments and by referring to case law we investigate whether these changes increase the possibilitiesfor compulsory treatment. We conclude that at the moment they do not.

Chronic amiodarone evokes no torsade de pointes arrhythmias despite QT lengthening in an animal model of acquired long-QT syndrome.

BACKGROUND: Amiodarone is an effective antiarrhythmic drug rarely associated with torsade de pointes arrhythmias (TdP). The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired long-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment. METHODS AND RESULTS: Amiodarone (n=7, 40 mg. kg(-1). d(-1)) and dronedarone (n=8, 20 mg/kg BID) were started at 6 weeks of CAVB (baseline). Six dogs served as controls. Surface ECGs and endocardially placed monophasic action potential catheters in the left (LV) and right (RV) ventricles were recorded to assess QTc time, action potential duration (APD), interventricular dispersion (DeltaAPD=LV APD minus RV APD), early afterdepolarizations (EADs), ectopic beats, and TdP. Both amiodarone (+21%) and dronedarone (+31%) increased QTc time. Amiodarone showed no increase in DeltaAPD in 4 of 7 dogs, whereas dronedarone augmented DeltaAPD in 7 of 8 animals. After dronedarone, TdP occurred in 4 of 8 dogs with the highest DeltaAPD (105+/-20 ms). TdP was never seen with amiodarone, not even in the dogs that had DeltaAPD values comparable to those with dronedarone. Furthermore, a difference existed in EADs and ectopic activity incidence (dronedarone 3 of 8; amiodarone 0 of 7), which was also seen during an epinephrine challenge. CONCLUSIONS: In the CAVB dog model, both amiodarone and dronedarone prolong QT time (class III effect). The absence of TdP with amiodarone seems to be related to homogeneous APD lengthening in the majority of dogs and the lack of EADs and/or ventricular ectopic beats in all.

Electrophysiologic parameters and predisposing factors in the generation of drug-induced Torsade de Pointes arrhythmias.

When a new (cardiovascular) drug shows signs of QT interval prolongation on the ECG (delay in repolarization time), the regulatory agencies demand screening of its possible proarrhythmic potential before approving it for clinical practice. In this review, identified predisposing factors have been related to specific electrophysiological parameters, allowing quantification of their contribution to Torsade de Pointes arrhythmias. In addition, arrhythmogenic mechanisms involved in the initiation and perpetuation of drug-induced Torsade de Pointes are discussed.

Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block.

BACKGROUND: The dog model of chronic complete AV-block (CAVB) demonstrates a considerable incidence of (witnessed) sudden death (16/117 dogs). In this study we tried to: (1) elucidate the mechanisms of sudden death using an ECG telemetry device and (2) identify retrospectively the risk parameters indicative of this arrhythmogenic death. METHODS: Between 1994 and 1998, 78 anesthetized dogs underwent an extensive electrophysiological study including: (1) left- (LV) and right ventricular (RV) monophasic action potential (MAP) recordings to assess Delta MAPD (LV APD minus RV APD) and (2) pacing protocols (PES) to induce torsade de pointes arrhythmias (TdP) at 4--6 weeks CAVB. Eight animals experienced sudden cardiac death (SCD) during the follow-up period (mean 7+/-3 weeks CAVB). Since the response of the CAVB dog to class III drugs is not uniform we also made comparisons among the SCD group, TdP drug responders and non-responders. For this purpose we selected all animals which (1) received almokalant (n=15, 0.12 mg/kg/5 min) or ibutilide (n=9, 0.025 mg/kg/5 min) as an additional challenge to induce TdP and (2) had a follow-up period of at least 4 weeks. RESULTS: Six out of eight SCD dogs showed inducible TdP at baseline. Two of eight dogs had telemetric ECG surveillance and both revealed polymorphic VT as the cause of SCD. Baseline Delta MAPD of the SCD (90+/-15 ms) was significantly higher than the non-SCD group (n=70, 60+/-30 ms). Of the 24 dogs which received class III drugs, 12 belonged to the TdP responder group. Delta MAPD of the TdP responder group (80+/-15 ms) was similar to the SCD group and significantly higher compared to the non-responder group (n=12, 40+/-25 ms). QT-time and cycle length of idioventricular rhythm were not different. CONCLUSION: In the CAVB dog model, SCD is (1) most probably related to TdP while (2) inducible TdP and the measure of Delta MAPD at baseline indicate susceptibility to SCD.

Azimilide and dofetilide produce similar electrophysiological and proarrhythmic effects in a canine model of Torsade de Pointes arrhythmias.

Torsade de Pointes arrhythmias are a feared proarrhythmic effect of (antiarrhythmic) drugs. In dogs with chronic complete AV-block bradycardia-induced volume overload leads to electrical remodeling, which includes increased susceptibility to drug-induced Torsade de Pointes arrhythmias. The IKr channel blocker, dofetilide (Tikosyn, 0.025 mg/kg/5 min), and the less specific ion channel blocker, azimilide (5 mg/kg/5 min), were compared in nine anesthetized dogs at 4 and 6 weeks of AV-block in a randomized cross-over design. Dosages were based on our own dose-dependence studies and on anti-arrhythmic dosages reported in the literature. Monophasic action potential catheters were placed endocardially in both the left and right ventricle to measure action potential duration, visualize early afterdepolarizations, and to assess interventricular dispersion of repolarization (i.e. left ventricular monophasic action potential duration (at 100%) minus right ventricular monophasic action potential duration (at 100%). Cycle length of idioventricular rhythm, QT-time and the occurrence of drug-induced Torsade de Pointes arrhythmias were determined using the surface electrocardiogram (ECG). Before drug administration, the electrophysiological parameters were identical at 4 and 6 weeks. Both azimilide and dofetilide increased monophasic action potential duration, cycle length of idioventricular rhythm, and QT-time. Dissimilar lengthening of left ventricular and right ventricular monophasic action potential duration increased the interventricular dispersion significantly from 55 to 110 ms for both drugs. All dogs had early afterdepolarizations, while, in the majority, ectopic ventricular beats developed (dofetilide 8/9 and azimilide 7/9). Torsade de Pointes arrhythmias incidence was comparable for dofetilide (6/9) and azimilide (5/9). In conclusion, azimilide and dofetilide show similar electrophysiological and proarrhythmic effects in our canine model with a high incidence of Torsade de Pointes arrhythmias.

A rare case of disseminated actinomycosis caused by Actinomyces meyeri.

A case of disseminated actinomycosis caused by Actinomyces meyeri in a 43-year-old man is described. The patient presented with signs of pericarditis, weight loss, dry cough, and subsequently an inferior vena cava syndrome. Diagnosis of thoracic as well as abdominal actinomycosis was made 4 months after admission. This article stresses the importance of considering the diagnosis of the disease. Cure was achieved by administering penicillin for several months.

The electromechanical window is no better than QT prolongation to assess risk of Torsade de Pointes in the complete atrioventricular block model in dogs.

BACKGROUND AND PURPOSE: The electromechanical window (EMW), the interval between the end of the T-wave and the end of the left ventricular pressure (LVP) curve, has recently been proposed as a predictor of risk of Torsade de Pointes (TdP) in healthy animals, whereby a negative EMW (mechanical relaxation earlier than repolarization) after drug administration indicates an increased TdP risk. The aims of this study were to assess (i) the effect of the ventricular remodelling in the canine chronic, complete atrioventricular block (CAVB) model on EMW; (ii) the effect of the I(Kr) -blocker dofetilide on EMW; and (iii) the correlation of EMW with TdP inducibility. EXPERIMENTAL APPROACH: Our 11 year database of experiments of CAVB in dogs under general anaesthesia was reviewed and experiments included if ECG and LVP were recorded simultaneously at spontaneous rhythm. In total, 89 experiments in 44 dogs were appropriate and were analysed. KEY RESULTS: During normally conducted sinus rhythm or acute atrioventricular block, EMW was positive. During CAVB, EMW was decreased to negative values. Dofetilide further reduced EMW before inducing repetitive TdP in 82% of the experiments. However, subclassification into inducible and non-inducible dogs revealed no difference in EMW. Analysis of the components of EMW revealed that the observed changes in EMW were solely caused by QT prolongation. CONCLUSIONS AND IMPLICATIONS: In the canine CAVB model, ventricular remodelling and I(Kr) block by dofetilide are associated with negative EMW values, but this reflects QT prolongation, and implies that the EMW lacks specificity to predict dofetilide-induced TdP.

Continuation of vitamin K antagonists as acceptable anticoagulation regimen in patients undergoing pulmonary vein isolation.

BACKGROUND: Recent studies have demonstrated that radiofrequency isolation of the pulmonary veins (PVI) is an effective treatment for symptomatic atrial fibrillation. Based on these positive results, non- pharmacological therapy has been incorporated in the guidelines for drug refractory atrial fibrillation, resulting in an increased popularity. The prevention of thromboembolic complications remains an important issue. METHODS: In January 2010, we adopted an anticoagulation strategy based on continuation of vitamin K antagonists (VKAs) and selective use of transoesophageal echocardiogram (TEE). We retrospectively analysed the results of this strategy in all patients referred for PVI treatment. VKAs were started for all patients 2 months prior to treatment. Discontinuation of oral anticoagulation was considered 3 months after treatment based on thromboembolic and bleeding risk profile. Bleeding and thromboembolic complications were registered during outpatient clinic follow-up up until 3 months. RESULTS: We performed 151 PVI procedures from January 2010 to March 2011. All patients were seen 6 weeks after discharge. No transient ischaemic accidents or ischaemic cerebrovascular incidents occurred pre-, peri- or postprocedure. Four (2.7%) procedures were complicated by tamponade requiring pericardiocentesis. CONCLUSIONS: Our data support the increasing evidence for continuation of periprocedural administration of VKAs complemented by a selective TEE approach as a safe therapy for thromboembolic complications.