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Objectives This multicenter registry aimed to assess the reproducibility and safety of intentional coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial ac...

We see an increasing number of patients with amiodarone-induced thyrotoxicosis. This condition can be treated pharmacologically, but treatment over several months may give rise to adverse reactions. In most cases we recommend that amiodarone therapy be continued despite newly detected thyrotoxicosis. Particularly in cases of heart failure, one should not wait too long before considering thyroidectomy. Treatment of amiodarone-induced thyrotoxicosis must be delivered with close collaboration between endocrinologist and cardiologist.

Background Amiodarone may be used against ventricular arrhythmias to reduce ICD-shocks, and for rhythm control in patients with atrial fibrillation. The 2020 ESC atrial fibrillation guidelines upgraded the recommendation for amiodarone in rhythm control to class I, level of evidence A, although still with a caution to consider other antiarrhythmic drugs first. Amiodarone is the most potent antiarrhythmic drug in clinical use, but it has frequent and potentially severe side effects affecting several organ systems. We have seen an increasing number of patients with amiodarone-induced thyrotoxicosis. Purpose We wanted to study the prescription rate of amiodarone in Norway, which indications were most prevalent, and whether there had been any changes over time. Methods From the Norwegian Prescription Registry, we have collected data on how many patients had received amiodarone, and the number of defined daily doses delivered (DDDs), related to various reimbursement categories. Results From 2010 to 2019, the number of individuals receiving amiodarone from a pharmacy in Norway increased from 5359 to 7789 (45% increase), and the number of DDDs delivered from 994905 to 1412796 (42% increase) (Figure). With an atrial fibrillation-related reimbursement code, we found during the same period an increase of individuals from 3616 to 5776 (60% increase) and number of DDDs from 661531 to 1061601 (60% increase). The dispenses for ventricular arrhythmia-related reimbursement codes were close to unchanged during the same period of years (Figure). The fraction of amiodarone use related to atrial fibrillation increased from 66% in 2009 to 75% in 2019. Conclusion We observed a 42–45% increase in the total use of amiodarone over 10 years, and almost the whole increase was related to atrial fibrillation. In 2019, atrial fibrillation-related diagnoses accounted for 75% of the total amount of amiodarone dispensed in Norway. Due to the several side effects of amiodarone, we are concerned if the threshold for use of amiodarone diminishes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Norwegian Institute of Public HealthOslo University Hospital, Rikshospitalet Number of patientsNumber of DDDs

BACKGROUND Athletes with an implantable cardioverter-defibrillator (ICD) may require unique optimal device-based tachycardia programming. OBJECTIVE The purpose of this study was to assess the association of tachycardia programming characteristics of ICDs with occurrence of shocks, transient loss-of-consciousness, and death among athletes. METHODS A subanalysis of a prospective, observational, international registry of 440 athletes with ICDs followed for a median of 44 months was performed. Programming characteristics were divided into groups for rate cutoff (very high, high, or low) and detection (long-detection interval [> nominal] or nominal). Endpoints included total, appropriate, and inappropriate shocks, transient loss-of-consciousness, and mortality. RESULTS In this cohort, 62% were programmed with high-rate cutoff and 30% with long detection. No athlete died of an arrhythmia (related or unrelated) to ICD shocks. Three patients had sustained ventricular tachycardia below programmed detection rate, presenting as palpations and/or dizziness. ICD shocks were received by 98 athletes (64 appropriate, 32 inappropriate); 2 patients received both. Programming a high-rate cutoff was associated with decreased risk of total (P = .01) and inappropriate (P = .04) shocks overall and during competition or practice. Programming long-detection intervals was associated with fewer total shocks. Single-vs dual-chamber devices and the number of zones were unrelated to risk of shock. Transient loss-of-consciousness, associated with 27 appropriate shocks, was not related to programming characteristics. CONCLUSION High-rate cutoff and long- detection duration programming of ICDs in athletes at risk for sudden death can reduce total and inappropriate ICD shocks without affecting survival or the incidence of transient loss-of-consciousness.

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.Objectives: To determine the effec...

We see an increasing number of patients with amiodarone-induced thyrotoxicosis. This condition can be treated pharmacologically, but treatment over several months may give rise to adverse reactions. In most cases we recommend that amiodarone therapy be continued despite newly detected thyrotoxicosis. Particularly in cases of heart failure, one should not wait too long before considering thyroidectomy. Treatment of amiodarone-induced thyrotoxicosis must be delivered with close collaboration between endocrinologist and cardiologist.

Background There is strong evidence for an association between atrial fibrillation (AF) and sleep apnea (SA). Purpose We aimed to examine the effect of treatment with continuous positive airway pressure (CPAP) on the burden of AF. Methods After a run-in period for CPAP-tolerance, we randomly assigned 108 eligible patients between 18–75 years, who had paroxysmal AF and moderate-to-severe obstructive SA (apnea-hypopnea index (AHI)≥15), to receive either CPAP treatment (n=54) plus usual care or usual care alone (n=54) for five months. An implanted loop recorder measured time in AF continuously. The primary endpoint was the difference in change of AF burden (% of time in AF) between CPAP treatment and usual care from baseline (one month prior to randomization) to the last three months of the intervention period. Secondary endpoints were changes in quality of life assessed by the Short Form-36 (SF-36), Epworth Sleepiness Scale (ESS), and the Functional Outcomes of Sleep Questionnaire (FOSQ). Results Mean (SD) age was 62.4 (7.7) years, BMI 29.4 (4.2) kg/m2, ESS 7.9 (3.2), and 76.1% were men. In the intervention group, the mean duration of adherence to CPAP therapy was 4.3 hours/night. During treatment mean AHI decreased from 27.6 events/hour at baseline to 2.3 events/hour during follow-up. Mean time in AF decreased from 5.0%-4.3% in the control group and from 5.6%-4.1% in the CPAP group, but the difference in change was not significant (p=0.52). Sub-analysis of those using CPAP> Conclusion This is the first randomized controlled trial to assess the effect of treatment of SA on the burden of AF, and did not detect a difference between those treated with CPAP compared to usual care alone. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Oslo University Hospital is the main funding Source. ResMed Science Center provided an unrestricted grant.

There is strong evidence for an association between atrial fibrillation (AF) and sleep apnea (SA). We aimed to examine the effect of treatment with continuous positive airway pressure (CPAP) on the burden of AF. We randomly assigned 108 patients between 18-75 years, who had paroxysmal AF and moderate-to-severe obstructive SA (apnea-hypopnea index (AHI)≥15) to receive either CPAP treatment (n=54) plus usual care or usual care alone (n=54) for five months. An implanted loop recorder measured time in AF continuously. The primary endpoint was the difference in change of AF burden (% of time in AF) between CPAP treatment and usual care from baseline (one month pre randomization) to the last three months of the intervention period. Secondary endpoints were changes in quality of life assessed by the Short Form-36 (SF-36), Epworth Sleepiness Scale (ESS) and the Functional Outcomes of Sleep Questionnaire (FOSQ) Mean (SD) age was 62.4 (7.7) years, BMI 29.4 (4.2) kg/m², ESS 7.9 (3.2), and 76.1% were men. In the intervention group, the mean duration of adherence to CPAP therapy was 4.3 hours/night. During treatment mean AHI decreased from 27.6 events/hour at baseline to 2.3 events/hour during follow-up. Mean time in AF decreased from 5.0%-4.3% in the control group and from 5.6%-4.1% in the CPAP group, but the difference in change was not significant (p=0.52). Subanalysis of those using CPAP> This is the first randomized controlled trial to assess the effect of treatment of SA on the burden of AF, and did not detect a difference between those treated with CPAP compared to usual care alone.

This multicenter registry aimed to assess the reproducibility and safety of intentional coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial access in the setting of ventricular tachycardia ablation.Epicardial ablation for ventricular tachycardia is not a widespread technique due to the significant potential complications associated with subxiphoid puncture. The first experience in 12 patients showed that intentional coronary vein exit and carbon dioxide insufflation was technically feasible.A branch of the coronary sinus was cannulated by means of a diagnostic JR4 coronary catheter. Intentional perforation at the distal portion of that branch was performed with a high tip load 0.014-inch angioplasty wire. A microcatheter was advanced over the wire into the pericardial space. Carbon dioxide was then insufflated into the pericardial space, allowing direct visualization of the anterior pericardial space to facilitate subxiphoid puncture.Intentional coronary vein exit was attempted in 102 consecutive patients in 16 different centers and successfully completed in 101 patients. Significant pericardial adhesions were confirmed in 3 patients, preventing carbon dioxide insufflation and epicardial ablation. None of the punctures were complicated with inadvertent right ventricular puncture or damage to a coronary artery. Significant bleeding (80 ml) due to coronary vein exit occurred in 5 patients, without hemodynamic compromise. None of the patients required surgery.Coronary vein exit and carbon dioxide insufflation can be safely and reproducibly achieved to facilitate subxiphoid pericardial access in the setting of ventricular tachycardia ablation.

Aims We aimed to explore the burden of frequent premature ventricular contractions (PVCs) associated with myocardial dysfunction in patients with outflow tract arrhythmia (OTA). We hypothesized that this threshold is lower than the previously suggested threshold of 24 000 PVCs/24 h (24%PVC) when systolic function is assessed by strain echocardiography. Furthermore, we aimed to characterize OTA patients with malignant arrhythmic events. Methods and results We included 52 patients referred for OTA ablation (46 ± 12 years, 58% female). Left ventricular global longitudinal strain (GLS) and mechanical dispersion were assessed by speckle tracking echocardiography. A subset underwent cardiac magnetic resonance imaging. PVC burden (%PVC) was assessed by Holter recording. Sinus rhythm QRS duration and PVC QRS duration were recorded from electrocardiogram, and the ratio was calculated (PVC QRS duration / sinus rhythm QRS duration). Median %PVC was 7.2 (0.2–60.0%). %PVC correlated with GLS (R = 0.44, P = 0.002) and with mechanical dispersion (R = 0.48, P

We used sleep monitoring data from a study that investigated the prevalence, characteristics, risk factors and type of sleep apnea (SA) in 579 patients with paroxysmal atrial fibrillation. Most patients were screened for two nights, resulting in 1,043 sleep recordings that each contained data from one night. SA was diagnosed using the Nox T3 portable sleep monitor. An experienced sleep specialist scored the recordings manually using Noxturnal software. A total of 157 women (27%) and 422 men (73%) were examined; 477 (82.7%) had an apnea–hypopnea index (AHI) ≥ 5/hr, whereas moderate to severe SA (AHI ≥ 15/hr) was diagnosed in 243 patients (42.1%). The AHI derived from automatic and manual scoring showed a good agreement (Pearson's r coefficient of 0.96). The median difference in AHI was very small (i.e., 0.72 [mean difference, 1.06]), but was statistically significant (p < .0001). Automatic scoring classified sleep recordings with more than 90% accuracy into SA categories of mild (AHI ≥ 5/hr), moderate (AHI ≥ 15/hr) and severe (AHI ≥ 30/hr). We found a minor (11%–21%) mis‐estimation of the number of recordings right above and below the boundary separating mild and moderate SA. The accuracy of automatic scoring differed from recording to recording, especially regarding the sensitivity of detecting disrupted breathing events. We found low to moderate agreement for the duration of disrupted breathing events (r = .53), for which the automatic scoring led to a statistically significant overestimation by 5.22 s (p < .0001).

Background: The association between sleep apnea (SA) and atrial fibrillation (AF) is strong. SA is probably underdiagnosed in AF patients. Polysomnography (PSG) is time consuming and costly and a valid screening tool is warranted. Aims and Objectives: The aim was to determine if the Berlin Questionnaire (BQ) and the STOP-Bang Questionnaire (SBQ) can be used as a screening tool in patients with paroxysmal atrial fibrillation (PAF). Methods: We prospectively studied 565 PAF patients. Risk for sleep apnea was assessed with the BQ and the SBQ. SA was defined as an apnea-hypopnea index (AHI) ≥15/h obtained by polygraphy (PG) two nights at home. Sleep studies were analyzed by an experienced specialist, using standard American Academy of Sleep Medicine definitions. A BQ high risk subject was defined as ≥2 of 3 risk factors: (I) snoring; (II) daytime somnolence; and (III) hypertension or a body mass index (BMI) > 30 kg/m². A SBQ high risk subject was defined as ≥5 affirmative answers to the 8 STOP-Bang items. Results: Mean age was 60 (9) years and mean BMI 29 (4) kg/m². 238 (42%) had an AHI ≥ 15/h. According to SBQ low, intermediate and high risk of SA was 7%, 14% and 21% respectively. The SBQ score ≥3 was 84% sensitive and 45 % specific for diagnosis of SA. For those with low risk and high risk according to the BQ score 19% and 23% had SA, respectively. The BQ performed with 56% sensitivity and 70% specificity. Conclusions: Of two commonly used questionnaires to screen for SA, neither the SBQ nor the BQ questionnaire discriminated well between those with or without SA in patients with PAF. Until better screening tools are available PG or PSG needs to be used to detect SA in these patients.

Background: Recent studies have suggested a strong association between sleep apnea (SA) and atrial fibrillation (AF). Aims and Objectives: In this study we aimed to examine clinical predictors to identify SA and the prevalence and type of SA in patients with paroxysmal AF. Methods: We prospectively studied 578 patients with paroxysmal AF. SA was diagnosed using portable polygraphy two nights at home. Sleep studies were analyzed by an experienced specialist, using standard American Academy of Sleep Medicine definitions. The degree of subjective daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS). Body composition data were collected using a body composition analyzer (Tanita BC-545N). We calculated differences in variables between SA categories by Chi-Square Test or ANOVA as appropriate. Results: 158 women (27 %) and 420 men (73%) were enrolled. Mean age (SD) was 60 (10) years and mean BMI 29 (4) kg/m². 477 (83%) of the patients had an apnea-hypopnea index (AHI) ≥ 5/h, while moderate/severe SA (AHI ≥ 15/h) was diagnosed in 243 patients (42%). The type of SA was predominantly obstructive, with mean AHI 15.3/h (12) (range 0.4/h-85.8/h). Mean central apnea index was 0.8/h (2). AHI increased with age, BMI, weight, neck-and waist circumference, body fat, visceral fat and metabolic age. Mean ESS score was 7 (4). There was no association between ESS and AHI/h, r=0.08. Conclusions: In our AF population the prevalence of SA (AHI ≥ 5/h) was 83 %, which is several times higher than in the general population (16%). The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. We found a positive correlation between body composition and SA severity.

Background In the ICD Sports Safety Registry, death, arrhythmia- or shock-related physical injury did not occur in athletes who continue competitive sports after implantable cardioverter-defibrillator (ICD) implantation. However, data from non-competitive ICD recipients is lacking. This report describes arrhythmic events and lead performance in intensive recreational athletes with ICDs enrolled in the European recreational arm of the Registry, and compares their outcome with those of the competitive athletes in the Registry. Methods The Registry recruited 317 competitive athletes ≥ 18 years old, receiving an ICD for primary or secondary prevention (234 US; 83 non-US). In Europe, Israel and Australia only, an additional cohort of 80 ‘auto-competitive’ recreational athletes was also included, engaged in intense physical activity on a regular basis (≥2×/week and/or ≥ 2 h/week) with the explicit aim to improve their physical performance limits. Athletes were followed for a median of 44 and 49 months, respectively. ICD shock data and clinical outcomes were adjudicated by three electrophysiologists. Results Compared with competitive athletes, recreational athletes were older (median 44 vs. 37 years; p = 0.0004), more frequently men (79% vs. 68%; p = 0.06), with less idiopathic ventricular fibrillation or catecholaminergic polymorphic ventricular tachycardia (1.3% vs. 15.4%), less congenital heart disease (1.3% vs. 6.9%) and more arrhythmogenic right ventricular cardiomyopathy (23.8% vs. 13.6%) ( p Conclusions Participants in recreational sports had less frequent appropriate and inappropriate shocks during physical activity than participants in competitive sports. Shocks did not cause death or injury. Recreational athletes with ICDs can engage in sports without severe adverse outcomes unless other reasons preclude continuation.

Atrial fibrillation is associated with increased mortality as well as morbidity. There is strong evidence for an association between atrial fibrillation and sleep apnea. It is not known whether treatment of sleep apnea with continuous positive airway pressure (CPAP) will reduce the burden of atrial fibrillation.The Treatment of Sleep Apnea in Patients with Paroxysmal Atrial Fibrillation study will investigate the effects of CPAP in patients with paroxysmal atrial fibrillation and sleep apnea.The trial has a dual center, randomized, controlled, open-label, parallel design.Two centers will enroll a total of 100 patients with both paroxysmal atrial fibrillation and sleep apnea (apnea-hypopnea index [AHI] ≥ 15 events/h) who are scheduled for catheter ablation. Patients will be randomized in a 1:1 ratio to CPAP or control group (50 patients in each arm). The effects of CPAP treatment on atrial fibrillation will be determined using an implanted loop recorder (Reveal LINQ™, Medtronic) that detects all arrhythmia episodes. The primary endpoint is a reduction of the total burden of atrial fibrillation in the intervention group, after 5 months' follow-up (preablation). Reduction in the arrhythmia recurrence rate after ablation is the main secondary endpoint. All patients will be followed up for 12 months after ablation.This study is the first randomized controlled trial that will provide data on the effects of CPAP therapy in patients with paroxysmal atrial fibrillation and sleep apnea. The results are expected to improve our understanding of the interaction between paroxysmal atrial fibrillation and sleep apnea. ClinicalTrials.gov Identifier. NCT02727192.

Aims We aimed to explore the burden of frequent premature ventricular contractions (PVCs) associated with myocardial dysfunction in patients with outflow tract arrhythmia (OTA). We hypothesized that this threshold is lower than the previously suggested threshold of 24 000 PVCs/24 h (24%PVC) when systolic function is assessed by strain echocardiography. Furthermore, we aimed to characterize OTA patients with malignant arrhythmic events. Methods and results We included 52 patients referred for OTA ablation (46 ± 12 years, 58% female). Left ventricular global longitudinal strain (GLS) and mechanical dispersion were assessed by speckle tracking echocardiography. A subset underwent cardiac magnetic resonance imaging. PVC burden (%PVC) was assessed by Holter recording. Sinus rhythm QRS duration and PVC QRS duration were recorded from electrocardiogram, and the ratio was calculated (PVC QRS duration / sinus rhythm QRS duration). Median %PVC was 7.2 (0.2–60.0%). %PVC correlated with GLS (R = 0.44, P = 0.002) and with mechanical dispersion (R = 0.48, P

Aims We evaluated if right ventricular (RV) mechanical dispersion by strain was related to ventricular arrhythmias (VT/VF) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and if mechanical dispersion was increased in so far asymptomatic mutation carriers. Methods and results We included 69 patients, 42 had symptomatic ARVC and 27 were mutation positive asymptomatic family members. Forty healthy individuals served as controls. Myocardial strain was assessed in 6 RV and 16 left ventricular (LV) segments. Contraction duration (CD) in 6 RV and 16 LV segments were measured as the time from onset R on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of CD was defined as mechanical dispersion. Mechanical dispersion was more pronounced in ARVC patients with arrhythmias compared with asymptomatic mutation carriers and healthy individuals in RV [52(41,63) vs. 35(23,47) vs. 13(9,19)ms, P < 0.001]. Mechanical dispersion was more pronounced in asymptomatic mutation carriers compared with healthy individuals ( P < 0.001). Right ventricular mechanical dispersion predicted VT/VF in a multivariate logistic regression analysis [odds ratio (OR), 1.66 (95% confidence interval (CI) 1.06–2.58), P < 0.03]. Right ventricular and LV function by strain were reduced in symptomatic ARVC patients and correlated significantly ( R = 0.81, P < 0.001). Right ventricular and LV strain were reduced in asymptomatic mutation carriers compared with healthy individuals ( P < 0.001). Conclusion Right ventricular mechanical dispersion was pronounced in patients with ARVC with VT/VF. Right ventricular mechanical dispersion was present in asymptomatic mutation carriers and may be helpful in risk stratification. Right ventricular and LV function correlated in ARVC patients implying that ARVC is a biventricular disease.

Background: This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. Methods: After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. Results: Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. Conclusions: AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.

Background CPVT (catecholaminergic polymorphic ventricular tachycardia) is a condition characterized by syncopes and cardiac arrest that was first described in 1975. CPVT has later been classified as a genetic disease with a great risk for life-threatening arrhythmias that are mainly caused by mutations in the ryanodine receptor 2 gene. Starting with a case report, we present an overview of CPVT. Material and methods The literature reviewed was identified through a non-systematic search in PubMed. Results Diagnosing CPVT may be difficult, as resting ECG is normal and the syncopes may be misdiagnosed as epilepsy. Information about syncopes related to physical or emotional stress and occurrence of unexplained syncopes or cardiac arrest among family members, is important in the diagnostic evaluation. An exercise stress test often reveals the classical pattern of ventricular arrhythmias at heart rates above 100 beats/min. The diagnosis can be confirmed by genetic testing. By beta-blocker treatment and, if necessary, an ICD (implantable cardioverter defibrillator) the prognosis can be improved. Interpretation CPVT is a serious disease with a poor prognosis when left untreated. It is a rare but important differential diagnosis in young individuals with syncopes or cardiac arrest. Genetic screening of relatives has made it possible to identify mutation carriers in affected families in order to provide them with preventive therapy.

SUMMARY Purpose: To investigate the comparative effectsof carbamazepine (CBZ) and lamotrigine (LTG)on electrocardiography (ECG) parameters inelderlypatientswithnewlydiagnosedepilepsy.Methods: ThestudywasconductedintheNorwe-gian subcohort (n = 108) of an international ran-domized double-blind 40-week trial, whichcompared the efficacy and tolerability of LTG andsustained-release CBZ in patients aged 65 andolder with newly diagnosed epilepsy. Target main-tenance doses were 400 mg/day for CBZ and100 mg/day for LTG, with adjustments based onclinical response.Patientswithsignificantunpacedatrioventricular (AV) conduction defect wereexcluded. Resting 12-lead ECG recordings weremade under standardized conditions at pretreat-ment (baseline) and at the 40-week study visit(treatment visit). Changes in QRS interval (pri-mary endpoint), heart rate (HR), PQ, and QTc(HR-corrected QT) intervals were assessed andcomparedbetweengroups.Results: Of the 108 patients randomized, 33 dis-continued prematurely because of adverse events(n = 24, none of which was cardiac) or other rea-sons (n = 9), and 15 were nonevaluable due toincomplete ECG data. None of the assessed ECGparameters differed significantly between groupsat baseline. No significant ECG changes wererecorded between baseline and treatment visitfor QRS duration and QTc intervals, whereas HRfell and PQ intervals increased slightly on bothtreatments. However, there were no differencesbetween groups in changes from baseline totreatmentvisit.Therewerenosignificantrelation-ships between individual ECG changes and serumdrug concentrations, except for QTc intervals,which decreased slightly with increasing CBZ con-centrations. The proportion of patients with ECGparameters outside the normal range at treat-mentvisitwassimilartothatrecordedatbaseline.Discussion: Clinically significant ECG changes arenot common during treatment with CBZ or LTGin elderly patients with no preexisting significantAVconductiondefects.KEY WORDS: Lamotrigine, Carbamazepine,Epilepsy,Elderly,ECG,Heart,Cardiacfunction.Adverse cardiac effects are a relatively uncommoncomplication of antiepileptic drug (AED) therapy, andhave been reported mostly with carbamazepine (CBZ).In particular, CBZ has been implicated in various disor-ders of impulse generation and conduction, resulting in avariety of bradyarrhythmias (Ladefoged & Mogelvang

AIMS: We aimed at examining the acetylcholine-dependent inward-rectifier current (IKAch) as a target for the management of atrial fibrillation (AF). METHODS AND RESULTS: The investigative agents AZD2927 and A7071 concentration-dependently blocked IKACh in vitro with minimal off-target activity. In anaesthetized dogs (n = 17) subjected to 8 weeks of rapid atrial pacing (RAP), the left atrial effective refractory period (LAERP) was maximally increased by 50 ± 7.4 and 50 ± 4.8 ms following infusion of AZD2927 and A7071. Ventricular refractoriness and the QT interval were unaltered. During sustained AF, both drugs significantly reduced AF frequency and effectively restored sinus rhythm. AZD2927 successfully restored sinus rhythm at 10/10 conversion attempts and A7071 at 14/14 attempts, whereas saline converted 4/17 episodes only (PThis work was supported by AstraZeneca R&D, CVMD Innovative Medicine, Molndal, Sweden.

Hemostatic Activation during RF Ablation. Introduction: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients. Methods and Results: We studied the activation of coagulation (prothrombin fragment 1+2 [PFl+2]). platelets (β-thromboglobulin [β-TG])) and fibrinolysis (plasmin-antiplasmin complexes [PAP) and D-dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously alter the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PFl+2 (r = 0.83, P < 0.001) and (b) the increase of PFI+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PFl+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16). or (c) RF current duration (range 46 to 687 sec). Plasma β-TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D-dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01. respectively). All parameters were normal the next morning. Conclusion: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.

Background: Radiofrequency catheter ablation of atrial flutter, atrial fibrillation or ventricular tachycardia may be favoured by large lesions. We compared lesions created in unipolar mode using 10-mm/8 F electrodes with those of 4-mm/7 F catheters. Methods: Ablations were first performed in porcine hearts in vitro (70°C, 60 s, tangential catheter tip-tissue orientation). Anaesthetized pigs were thereafter ablated with 10- or 4-mm catheters in the right atrial free wall (RAFW), inferior vena cava-tricuspid valve (IVC-TV) isthmus and left ventricle (LV). Results: In vitro, lesion length doubled and lesion volume tripled using the 10-mm catheter. Average power supply was 69 (SD12) (10-mm tip) versus 26 (SD7) W (4-mm tip). In vivo, lesion length increased by 50% and lesion volume fivefold. Charring at the lesion surface or sudden impedance rises were not observed in vivo. Histologically, coagulation necrosis and minor haemorrhages were found. One RAFW lesion (10-mm) showed a dissection approaching the epicardium. Fibrinous platelet clots or overt thromboses covered the endocardial surface in half of all lesions. Three 10-mm electrode isthmus lesions extended to the right descending posterior artery and one LV lesion to the left anterior descending artery, but there was no damage to the arterial walls. Following six ablations with the 10-mm electrode and two with the 4-mm tip, injury to the adjacent lung tissue of 0.5 to 6.0 mm depth was found (p = 0.22). Conclusion: RF ablation using 10-mm/8 F electrodes created significantly larger lesions. 10-mm electrodes appeared safe in the porcine IVC-TV isthmus and LV, but not in the RAFW.

Holes drilled in rats' skull, iliac crest, and tibia were filled with beeswax or with a new, wax-like, bioerodible polyorthoester (Alzamer®). Empty drill-holes served as controls. In addition, beeswax and polyorthoester were deposited between the left and the right oblique abdominal muscles, respectively. In muscle, both the beeswax and polyorthoester elicited a transient foreign body reaction. The beeswax was not resorbed in bone or muscle, whereas the polyorthoester was. Bone healing was inhibited in the iliac crest and the tibiae filled with beeswax, whereas holes filled with polyorthoester healed readily.

CPVT (catecholaminergic polymorphic ventricular tachycardia) is a condition characterized by syncopes and cardiac arrest that was first described in 1975. CPVT has later been classified as a genetic disease with a great risk for life-threatening arrhythmias that are mainly caused by mutations in the ryanodine receptor 2 gene. Starting with a case report, we present an overview of CPVT.The literature reviewed was identified through a non-systematic search in PubMed.Diagnosing CPVT may be difficult, as resting ECG is normal and the syncopes may be misdiagnosed as epilepsy. Information about syncopes related to physical or emotional stress and occurrence of unexplained syncopes or cardiac arrest among family members, is important in the diagnostic evaluation. An exercise stress test often reveals the classical pattern of ventricular arrhythmias at heart rates above 100 beats/min. The diagnosis can be confirmed by genetic testing. By beta-blocker treatment and, if necessary, an ICD (implantable cardioverter defibrillator) the prognosis can be improved.CPVT is a serious disease with a poor prognosis when left untreated. It is a rare but important differential diagnosis in young individuals with syncopes or cardiac arrest. Genetic screening of relatives has made it possible to identify mutation carriers in affected families in order to provide them with preventive therapy.

Aim Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of β-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening. Methods and results Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of β-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13–288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On β-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 ± 17 vs. 135 ± 34 beats/min, P = 0.02) but at similar workload ( P = 0.78). β-Blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up. Conclusion Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. β-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.

Activin A, a member of the transforming growth factor (TGF)-β superfamily, is involved in regulation of tissue remodeling and inflammation. Herein, we wanted to explore a role for activin A in pulmonary hypertension (PH). Circulating levels of activin A and its binding protein follistatin were measured in patients with PH ( n = 47) and control subjects ( n = 14). To investigate synthesis and localization of pulmonary activin A, we utilized an experimental model of hypoxia-induced PH. In mouse lungs, we also explored signaling pathways that can be activated by activin A, such as phosphorylation of Smads, which are mediators of TGF-β signaling. Possible pathophysiological mechanisms initiated by activin A were explored by exposing pulmonary arterial smooth muscle cells in culture to this cytokine. Elevated levels of activin A and follistatin were found in patients with PH, and activin A levels were significantly related to mortality. Immunohistochemistry of lung autopsies from PH patients and lungs with experimental PH localized activin A primarily to alveolar macrophages and bronchial epithelial cells. Mice with PH exhibited increased pulmonary levels of mRNA for activin A and follistatin in the lungs, and also elevated pulmonary levels of phosphorylated Smad2. Finally, we found that activin A increased proliferation and induced gene expression of endothelin-1 and plasminogen activator inhibitor-1 in pulmonary artery smooth muscle cells, mediators that could contribute to vascular remodeling. Our findings in both clinical and experimental studies suggest a role for activin A in the development of various types of PH.

Long QT syndrome is characterised by inherited long QT interval on the ECG and increased risk for syncope and sudden death caused by arrhythmias. For Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome DNA based diagnostics are available.This paper is a summary of our experience with DNA-based diagnostics of LQTS since the autumn of 2003. The diagnostic analyses are performed by sequencing the exons of five genes, KCNQ1, HERG, SCN5A, minK and MiRP1.As of mid-January 2005, 56 probands with long QT syndrome have been referred for genetic testing. We have identified an underlying mutation in 64% of the patients. Mutations in the KCNQ1 gene are most frequent in Norwegian long QT syndrome patients, as 61% of the patients have their mutation in this gene. The detection of a mutation in the probands has led to genetic testing of 215 relatives; 99 out of these are heterozygous for the mutation present in the family. Heterozygous patients have been referred to a cardiologist. Of the 43 that have been referred to follow up at the department of cardiology at Rikshospitalet, 35 have started treatment with beta blockers to reduce the risk of arrhythmias. Thus, DNA-based diagnostics has clinical significance leading to prophylactic treatment of long QT syndrome patients. Compared to evaluation of ECG, which is negative in 30% of mutation carriers, the sensitivity of DNA-based diagnostics of relatives of probands with a known mutation, is close to 1.

Inherited arrhythmogenic disorders are a group of genetically determined diseases characterised by ventricular tachyarrhythmias sometimes leading to sudden death. The molecular bases of these disorders are mutations in genes coding for various cardiac ion channels. The most common cardiac ion channel disease is the long QT syndrome. This syndrome is rare, but probably more common in Norway than previously expected. We have recently started genetic testing for cardiac ion channel disorders at Rikshospitalet University Hospital in Oslo. This review describes the current understanding of the etiology, prognosis and management of cardiac ion channel disorders, based on literature and our own clinical experience.Cardiac ion channel disorders may lead to sudden cardiac death. Prophylactic and life-saving therapies are available for many of these disorders. Therapy and risk stratification depend on the clinical presentation, the ECG pattern, and which gene is mutated. Genetic testing offers the opportunity to exclude individual family members as mutation carriers.

Aims: To discuss the diagnosis of giant coronary aneurysms. Methods and results: We describe three patients in whom initial echocardiographic findings suggested cardiac tumors in the right atrium. Additional examination proved the tumor-like structures to be giant atherosclerotic coronary aneurysms of either the right coronary artery or its saphenous vein coronary bypass graft. Conclusion: Giant coronary aneurysms are an important differential diagnosis for cardiac tumors.

ANFINSEN, O.-G., et al.: Implantable Cardioverter Defibrillator Dysfunction During and After Magnetic Resonance Imaging. This report describes a patient in whom a MRI of the brain was performed without realizing that an ICD had been implanted 8 days previously. Electromagnetic noise induced during the MRI was detected as ventricular fibrillation and nearly caused inappropriate shocks. Charge time during MRI was prolonged. The battery indicator switched to “end of life,” but this was reversed by capacitor reformation. These problems could have been avoided by inactivating the ICD prior to MRI. Three months later, the pacing threshold increased from 0.4 V per 0.5 ms at implantation to 2.8 V per 0.5. It is still uncertain whether radiofrequency current heating at the electrode tip caused the increased pacing threshold or if this would have occurred independently of the MRI. MRI of patients with an active ICD may cause life-threatening complications, and it is unknown if MRI may be safely performed if the ICD is inactivated. Therefore, MRI of patients with an ICD remains contraindicated.

RF catheter ablation is complicated by thromboembolism in about 1% of patients. Limited knowledge exists concerning when and how to use anticoagulation or antithrombotic treatment. We studied the activation of coagulation (prothrombin fragment 1 + 2 [PF1 + 2] and D-dimer), platelets (beta-thromboglobulin [beta-TG]) and fibrinolysis (plasmin-antiplasmin complexes [PAP]) during RF ablation of accessory pathways in 30 patients. They were randomized to receive heparin (100 IU/kg, intravenously) (1) immediately after introduction of the femoral venous sheaths (group I) or (2) after the initial electrophysiological study, prior to the delivery of RF current (groups II and III). Group II additionally received saline irrigation of all femoral sheaths. After the initial bolus, 1,000 IU of heparin was supplied hourly in all groups. Within groups II and III, median plasma values of PF1 + 2 and beta-TG more than tripled (P < or = 0.007) during the diagnostic study and gradually declined during heparin administration despite RF current delivery. Median D-dimer tripled (P = 0.005) and PAP doubled (NS) before heparin administration; then both remained around the upper reference values. In the early heparin group, however, PF1 + 2, D-dimer, and PAP did not rise at all, and beta-TG showed only a slight increase towards the end of the procedure. The differences between group I versus groups II and III were statistically significant prior to the first RF current delivery (PF1 + 2, D-dimer, and beta-TG) and by the end of the procedure (PF1 + 2, D-dimer, and PAP). In conclusion, "late" heparin administration allows hemostatic activation during the initial catheterization and diagnostic study. By administering intravenous heparin immediately after introduction of the venous sheaths, hemostatic activation is significantly decreased. Saline irrigation of the venous sheaths added nothing to late heparin administration.

Aims Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. Methods and Results In vitro, confluent lesions were reliably created by a ‘dielectrode’ catheter (energy delivered simultaneously (in parallel) from two 4mm electrodes spaced 1mm apart, towards an indifferent electrode), and a ‘bipolar’ catheter (energy delivered (in series) between two 4mm electrodes spaced 5mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30s duration (70°C) were administered to the inferior vena cava–tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length×width×depth measured 7·4 (2·4)×5·4 (2·2)×2·8 (0·8)mm in the standard unipolar mode, 10·2 (1·4)×6·3 (0·7)×3·3 (1·1)mm in the dielectrode mode and 14·0 (3·6)×6·0 (1·7)×3·8 (1·2)mm in the bipolar mode. Thus lesion length increased significantly through the three groups ( P

Interruption of atrial flutter and fibrillation by RF catheter ablation may be favored by large, elongated lesions. We administered RF current in unipolar and bipolar mode in porcine right atrium. Bipolar ablation was performed between the tip electrodes of two serially coupled catheters. With 4-mm tip electrodes in vitro, lesion length increased from a mean (SD) of 7.9 (1.2) mm at 3 mm-interelectrode distance (IED) to 13.3 (3.3) mm at 9-mm IED, but decreased at 12-mm IED due to nonconfluent lesions (P < 0.0001), With 4 mm distal electrodes and 8 mm IED, bipolar lesions were 65% longer than corresponding unipolar ablations. Switching to bipolar mode increased the lesion length more than increasing electrode tip length to 6 mm in unipolar mode. Power and temperature controlled ablation created equally sized lesions. Twelve anesthetized pigs were randomized to unipolar or two catheter bipolar temperature controlled ablation of the right atrial free wall. Bipolar ablation created confluent lesions with endocardial length × width of 13.5 (5.8) × 7.3 (3.7) mm, unipolar ablation 6.4 (2.8) × 4.6 (1.4) mm (P < 0.001 when comparing length and P = 0.013 for lesion width). The atrial lesions in both groups were transmural and extended into hilar lung lesions with maximal depth of 3.0 (1.1) and 2.6 (1.0) mm, respectively (P = 0.44). Five bipolarly and four unipolarly ablated pigs developed right diaphragmal paresis. We conclude that bipolar ablation may be preferable in situations where large, elongated lesions are favorable. The two catheter technique is feasible in porcine right atrium. Both bipolar and unipolar ablation of the porcine right atrial free wall may frequently be complicated by injury to the phrenic nerve and adjacent lung tissue.