Atrial Research Articles

Antiplatelet and Anti-Coagulation Therapy for Left-Sided Catheter Ablations: What Is beyond Atrial Fibrillation?

Aim: International guidelines on the use of anti-thrombotic therapies in left-sided ablations other than atrial fibrillation (AF) are lacking. The data regarding antiplatelet or anticoagulation strategies after catheter ablation (CA) procedures mainly derive from AF, whereas for the other arrhythmic substrates, the anti-thrombotic approach remains unclear. This survey aims to explore the current practices regarding antithrombotic management before, during, and after left-sided endocardial ablation, not including atrial fibrillation (AF), in patients without other indications for anti-thrombotic therapy. Material and Methods: Electrophysiologists were asked to answer a questionnaire containing questions on antiplatelet (APT) and anticoagulation therapy for the following left-sided procedures: accessory pathway (AP), atrial (AT), and ventricular tachycardia (VT) with and without structural heart disease (SHD). Results: We obtained 41 answers from 41 centers in 15 countries. For AP, before ablation, only four respondents (9.7%) used antiplatelets and two (4.9%) used anticoagulants. At discharge, APT therapy was prescribed by 22 respondents (53.7%), and oral anticoagulant therapy (OAC) only by one (2.4%). In patients with atrial tachycardia (AT), before ablation, APT prophylaxis was prescribed by only four respondents (9.7%) and OAC by eleven (26.8%). At discharge, APT was recommended by 12 respondents (29.3%) and OAC by 24 (58.5%). For VT without SHD, before CA, only six respondents (14.6%) suggested APT and three (7.3%) suggested OAC prophylaxis. At discharge, APT was recommended by fifteen respondents (36.6%) and OAC by five (12.2%). Regarding VT in SHD, before the procedure, eight respondents (19.5%) prescribed APT and five (12.2%) prescribed OAC prophylaxis. At discharge, the administration of anti-thrombotic therapy depended on the LV ejection fraction for eleven respondents (26.8%), on the procedure time for ten (24.4%), and on the radiofrequency time for four (9.8%), with a cut-off value from 1 to 30 min. Conclusions: Our survey indicates that the management of anti-thrombotic therapy surrounding left-sided endocardial ablation of patients without other indications for anti-thrombotic therapy is highly variable. Further studies are necessary to evaluate the safest approach to these procedures.

One Heart, Two Problems: Cardiomyopathy and CPVT Secondary to RYR2 Mutation

<h3>Introduction</h3> RYR2 mutations are known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disorder with risk for life threatening atrial (AT) and ventricular (VT) arrhythmias. Individuals with RYR2 mutation less commonly exhibit arrhythmogenic right ventricular cardiomyopathy (ARVC). We report the first case of a pediatric patient with RYR2 mutation, manifesting with CPVT, ARVC, and severe dysfunction requiring heart transplant (HTx). <h3>Case Report</h3> A 4.5 year old male with developmental delay presented after multiple syncopal episodes both at rest and with activity. A Holter showed AT, and he was started on a beta adrenergic antagonist with decreased frequency of syncopal episodes. He then developed sinus bradycardia with marked sinus pauses, prompting dual chamber pacemaker placement at age 6 years. He later exhibited bidirectional VT and whole exome sequencing identified a de novo, likely pathogenic variant in RYR2. He was medically managed until 16 years of age when he had syncope with exercise and was found to have both frequent AT and moderately depressed ventricular function with an ejection fraction of 45%. Given recurrent syncope with exercise, he underwent uncomplicated sympathectomy and optimization of his medical antiarrhythmic management. Over the next few months, he developed progressive heart failure symptoms and was admitted with worsening biventricular dysfunction and tachyarrhythmias. During his admission, he had a cardiac arrest with initial monitoring demonstrating VT, and was placed on extracorporeal membrane oxygenation support. He was transitioned to a durable left ventricular assist device (VAD), and was eventually listed for HTx. His VAD course was complicated by RV dysfunction needing PDE5 inhibitor; his arrhythmia burden was managed on flecainide, sotalol, and nadolol. After 80 days of VAD support, he underwent HTx. Pathology of his explanted heart revealed biventricular fibrofatty myocardial replacement consistent with ARVC with prominent LV involvement. <h3>Summary</h3> This case highlights an expanded spectrum of RYR2 mutation related disease which may include prominent atrial arrhythmias, ARVC, and developmental delay. Patients with CPVT and RYR2 mutation warrant close monitoring for ventricular dysfunction, especially if there is a significant arrhythmia burden.

B-AB08-04 IVABRADINE FOR TREATMENT OF TACHYARRHYTHMIAS IN PEDIATRIC AND CONGENITAL HEART DISEASE PATIENTS: INITIAL RESULTS OF A PACES MULTICENTER REGISTRY

Case series have suggested a role for ivabradine in treatment of automatic tachyarrhythmias. There are few pediatric data on efficacy and safety of this emerging pharmacologic strategy. To evaluate outcomes of ivabradine therapy in the pediatric and congenital heart disease (CHD) population. Subjects with CHD or age ≤ 21 years treated with ivabradine for tachyarrhythmia were eligible for inclusion in a multicenter registry. Demographics, arrhythmia diagnosis, and anti-arrhythmic therapies were recorded. Arrhythmias were categorized as acute post-operative (post-op) or not, and as junctional (JT) or atrial (AT). The primary outcome was occurrence of drug-related adverse events (AE), including rhythm and hemodynamic effects. As a secondary outcome, efficacy was graded as complete or partial rhythm or rate control, and positive response to ivabradine was defined by at least partial control. Data on 40 subjects from 4 centers were analyzed: 50% CHD, 20% cardiomyopathy. Targeted arrhythmias included post-op JT in 8, post-op AT in 9, non-post-op JT in 5, non-post-op AT in 16, and other in 2. Ivabradine was used as monotherapy in 11 and in combination in 29 (Table 1). AE occurred in 1 subject (pauses on ivabradine and sotalol), prompting discontinuation. Positive response to ivabradine was observed in 65% of all cases (n=26) and in 45% (n=5) as monotherapy. In responders, median number of doses to first effect was 2 (range 1-4). Ivabradine is a safe and moderately effective therapy for automatic tachyarrhythmias in pediatric and CHD patients. Further data are needed to confirm safety and define ivabradine-responsive substrates.

Extended state observer-based control of heartbeat described by heterogeneous coupled oscillator model

In this paper, a novel framework to investigate the effect of external electrical signals on cardiac rhythm dynamics using the extended state observer-based control (ESOBC) is proposed. Heterogeneous coupled oscillator model (HCOM) is adopted for the generation of P, Ta, QRS, and T waves, and the realistic synthetic electrocardiogram (ECG) due to its capacity for simulating cardiac muscles response. Sinoatrial (SA) and atrioventricular (AV) nodes and His–Purkinje system are described by modified Van der Pol-type (MVDP) equations connected with time-delay velocity coupling. The electrical responses resulted from depolarization (De) and repolarization (Re) of cardiac muscles are separately presented by modified FitzHugh–Nagumo (MFHN) model. The SA and HP pacemakers are coupled with atrial (AT) and ventricles (VT) muscles, respectively, through the stimulation currents. To satisfy the integral chain form of ESO, and deal with the complex structure of the model, including the large number of parameters, and the coupling between the oscillators and interdependent states, three steps are considered. Firstly, a coordinate transformation is proposed for AT and VT responses described by MFHN model to handle mismatched condition. Following this, the nonlinearity of MFHN and the coupling between cardiac muscles and pacemakers are considered as lumped disturbances. Lastly, an extended state observer is designed to compensate the nonlinearity and estimate the unmeasured system states and handle the lumped disturbances. The stability of the closed-loop system is proved, and the effectiveness of the proposed framework for suppressing well-known rhythm disorder, i.e., sinus tachycardia is demonstrated. The framework presented in this work can be easily extended for a wide range of arrhythmia, and serve as an approach to investigate the effect of external stimulation to the heart muscles.

Meditation for Improved Clinical Outcomes in Patients with Implantable Defibrillators for Heart Failure- Pilot Study.

Sympathetic activation is associated with congestive heart failure (CHF) and leads to adverse clinical events.We hypothesized that meditation by reducing emotional reactivity would have beneficial effect in reducing arrhythmias compared to control patients. Patients known to have CHF and implantable cardioverter defibrillators (ICD) were randomized to Vipassana meditation or usual care control group. Meditation group underwent meditation classes three times during the first week, thereafter every once two weeks. They were encouraged to practice meditation at least once everyday. The ICD was followed by clinic/ remote visits. Atrial (AA) and ventricular arrhythmias (VA) as well cardiac events were assessed in follow up. Chi square test was used to compare nominal variables and t test for continuous variables. Patients (n=25, 65% male, mean LVEF 25%, HTN 38%, Diabetes 12%, coronary artery disease 38%, NYHA class 2.2) were followed for 79 + 36 months. Comparing meditation vs control, survival was higher (88%vs 67%); there was less cumulative sustained AF episodes (mean 0.9, IQR 0-1 vs 2.5, IQR 2-4, p=0.045), sustained VT occurred (25% vs 55%, amiodarone use (none vs 44%), and VT ablation in 6.6% vs 33% in the meditation group. In this first pilot study of meditation in CHF patients with ICD, during long term follow up, there is a trend for improved survival and reduced arrhythmias in patients randomized to meditation.

203 Catheter Ablation for Focal Atrial and Ventricular Tachycardia Using the High Density Grid Mapping Catheter

The AdvisorTM high density grid (HDG) catheter is a novel 16 electrode mapping catheter which allows for bipole recordings parallel and perpendicular to its splines. This facilitates high density mapping with minimal catheter induced ectopy for focal atrial (AT) and ventricular tachycardia (VT). To describe and compare the clinical and procedural features from a consecutive patient cohort who underwent catheter ablation (CA) for focal AT and VT using the HDG catheter with an age and case matched cohort using conventional point by point (PBP) mapping. Consecutive patients undergoing CA for AT and VT between 2018 -2019 using the HDG were compared with a case control cohort using PBP mapping over a similar time period. 46 patients (23 in HDG vs 23 in conventional mapping) underwent CA, with focal AT (5 RA, 5 LA) and VT (8 RVOT, 4 LVOT, 1 multi-focal) in each group. There was no significant difference between cohorts in baseline characteristics. The HDG group had significantly earlier electrograms (37+/-16 ms vs 32+/-10 ms; p=0.02), shorter procedural duration (132 mins vs 157 mins, p=0.05), more electroanatomic mapping (EAM) points collected (1908 vs 133, p<0.01), & less proportion of points utilised (35% vs 81%, p<0.01). There was no significant difference in fluoroscopy times, procedural success, and arrhythmia recurrence. Multipolar mapping with the HDG catheter for focal tachycardias identified earlier activation times and was associated with shorter procedure duration with equivalent success to PBP mapping.

Clinical impact of newly developed atrial fibrillation complicated with longstanding ventricular fibrillation during left ventricular assist device support: A case report

BackgroundContinuous-flow left ventricular assist devices (LVADs) improve survival and morbidity in patients with stage D heart failure. Management of LVADs for longer durations is necessary in some clinical settings, and a better understanding of the hemodynamics of patients using LVADs is warranted. Arrhythmia, including atrial (AA) and ventricular (VAs) arrhythmias, is a modifying factor of hemodynamics that is highly prevalent among patients with LVADs. However, the clinical impact of arrhythmias in various clinical settings in patients with LVAD, in which the hemodynamic load is likely to present as worsening of right heart failure, remains to be completely elucidated.Case presentationWe describe the case of a patient under sustained ventricular fibrillation for extraordinarily long duration who was stabilized using LVAD support and in whom newly developed atrial fibrillation led to a significant worsening of right heart failure while using an LVAD.ConclusionThis case demonstrates the substantial clinical impact of AAs in the management of right heart failure using an LVAD.

The Red Kangaroo pericardium as a material source for the manufacture of percutaneous heart valves

The kangaroo pericardium might be considered to be a good candidate material for use in the manufacture of the leaflets of percutaneous heart valves based upon the unique lifestyle. The diet consists of herbs, forbs and strubs. The kangaroo pericardium holds an undulated structure of collagen. A Red Kangaroo was obtained after a traffic fatality and the pericardium was dissected. Four compasses were cut from four different sites: auricular (AUR), atrial (ATR), sternoperitoneal (SPL) and phrenopericardial (PPL). They were investigated by means of scanning electron microscopy, light microscopy and transmission electron microscopy. All the samples showed dense and wavy collagen bundles without vascularisation from both the epicardium and the parietal pericardium. The AUR and the ATR were 150±25μm thick whereas the SPL and the PPL were thinner at 120±20μm. The surface of the epicardium was smooth and glistening. The filaments of collagen were well individualized without any aggregation, but the banding was poorly defined and somewhat blurry. This detailed morphological analysis of the kangaroo pericardium illustrated a surface resistant to thrombosis and physical characteristics resistant to fatigue. The morphological characteristics of the kangaroo pericardium indicate that it represents an outstanding alternative to the current sources e.g., bovine and porcine. However, procurement of tissues from the wild raises supply and sanitary issues. Health concerns based upon sanitary uncertainty and reliability of supply of wild animals remain real problems.

Long-term seizure outcomes in patients with drug resistant epilepsy

PurposeDespite the availability of a broad range of treatments for epilepsy, a significant proportion of patients have ongoing seizures.This study aims to characterize the drug resistant population and to report long-term outcomes of patients undergoing different types of pharmacological and surgical treatment. MethodsAdult patients with drug resistant epilepsy (DRE) were identified from a largely retrospective database of 900 consecutive patients with epilepsy, recruited from two reference centers for DRE in Belgium. We report treatment trajectories and long-term seizure outcomes in the different treatment groups. Results640 patients had DRE. 249 (38.9%) underwent presurgical assessment, followed by surgical treatment in 197 (30.8%), resulting in seizure freedom in 86 (13.4%). 443 patients (69.2%) were treated only with further AED trials, of which 163 (25.5%) became seizure free. In the 391 patients with ongoing seizures (61.1%), mean age was 43.2 years, mean disease duration 23 years and mean number of AED trials 6.9. 291 (74.4%) had tonic-clonic seizures, and 43 (11.0%) had one or more episodes of status epilepticus. Patients with hippocampal sclerosis were significantly more likely to be seizure free, while patients with malformation of cortical development and those with temporal lobe epilepsy of unknown etiology were more likely to have ongoing seizures. ConclusionOur findings demonstrate that – even with adequate access to surgical treatment and further AED trials – 61.1% of patients with DRE had ongoing seizures. This illustrates that there is a scope for ongoing development of novel treatments for DRE.

Cardiac Propagation Pattern Mapping With Vector Field for Helping Tachyarrhythmias Diagnosis With Clinical Tridimensional Electro-Anatomical Mapping Tools.

Ventricular (VT) and atrial (AT) tachycardias are some of the most common clinical cardiac arrhythmias. For ablation of tachycardia substrates, two clinical diagnosis methods are used: invasive electroanatomical mapping for an accurate diagnosis using electrograms (EGMs) acquired with intracardiac catheters, and localized on the surface mesh of the studied cavities; and noninvasive electrocardiographic imaging (ECGi) for a global view of the arrhythmia, with EGMs mathematically reconstructed from body surface electrocardiograms using 3-D cardio-thoracic surface meshes obtained from CT-scans. In clinics, VT and AT are diagnosed by studying activation time maps that depict the propagation of the activation wavefront on the cardiac mesh. Nevertheless, slow conduction areas-a well-known proarrhythmic feature for tachycardias-and tachycardia specific propagation patterns are not easily identifiable with these maps. Therefore, local characterization of the activation wavefront propagation can be helpful for improving VT and AT diagnoses. The purpose of this study is to develop a method to locally characterize the activation wavefront propagation for clinical data. For this, a conduction velocity vector field is estimated and analyzed using divergence and curl mathematical operators. The workflow was first validated on a simulated database from computer models, and then applied to a clinical database obtained from ECGi to improve AT diagnosis. The results show the relevancy and the efficacy of the proposed method to guide ablation of tachyarrhythmias.

Wake up to sleep: The effects of lacosamide on daytime sleepiness in adults with epilepsy

ObjectiveThe objective of the study was to investigate the effects of lacosamide (LCM) on daytime sleepiness ascertained by the Epworth Sleepiness Scale (ESS) in adults with focal epilepsy in a randomized, controlled design. MethodsSubjects taking ≤2 AEDs for ≥4weeks underwent polysomnography with EEG followed by the maintenance of wakefulness test (MWT) and completed the ESS and other patient-reported outcomes (PROs) at baseline, LCM 200mg/day, and LCM 400mg/day (Visit 4; V4). Primary endpoint was ESS change (V4 to baseline) between LCM and placebo. Noninferiority test on ESS used a one-sided t-test based on a hypothesized difference of 4-point change between groups. Superiority test used a two-sided t-test to investigate the difference in change in PROs and MWT mean sleep latency (MSL) between groups. Fifty-five subjects provided 80% power to show noninferiority of LCM assuming 10% dropout. ResultsFifty-two subjects (mean age: 43.5±13.2years, 69% female, median monthly seizure frequency: 1 [0, 4.0]) participated. Baseline group characteristics including age, sex, ethnicity, standardized AED dose, seizure frequency, and ESS were similar. Abnormal baseline ESS scores were found in 35% of subjects. Noninferiority test found a ≤4-point increase in ESS (mean [95% CI]) in LCM subjects vs. placebo (−1.2 [−2.9, 0.53] vs. −1.1 [−5.2, 3.0], p=0.027) at V4. No significant difference in change in PROs, MSL, seizure frequency, or AED standardized dose was observed between groups. SignificanceOur interventional trial found that LCM is not a major contributor to daytime sleepiness based on subjective and objective measures. Inclusion of sleepiness measures in AED trials is warranted given the high prevalence of sleep–wake complaints in people with epilepsy.

Peculiarities of ultrastructural organization and metabolism of reactive forms of oxygen and nitrogen in a cardiovascular system for permanent effects of ionizing radiation in low doses

Determination of the peculiarities of ultrastructural changes and metabolism of reactive forms of oxy gen and nitrogen in the tissues of the myocardium, aorta and portal vein of the radiosensitive BALB/c mice due long term exposure to the complex of radionuclides of Chоrnobyl fallout (ejection) and low intensity low dose γ irradiation. Experimental studies were performed on 60 mice female radiosensitive lines BALB/c with a body weight of 20-22 g, which were divided into 3 groups: I group (control) animals age 6-9 months which were born and lived their lives in Kyiv vivarium under conditions natural radioactive background; ІІ - animals age 6 months, which were born and lived in the Chornobyl exclusion zone throughout their lives; ІІІ - animals, which from 3 months of age for 6 months were constantly located in cages with flat ionizing radiation sources and exposed to external γ irradiation in a total dose of 0.43 Sv. Animals of II and III groups were kept in the vivarium of the Institute for Safety Problems of Nuclear Power Plants of the National Academy of Sciences of Ukraine (Chornobyl). Mice of the BALB/c lines are sensitive to radiation: for males LD 50/30 < 5.7 Gy, for females - 5.85 Gy. The peculiarities of structural and functional changes in the organs of the cardiovascular system (CVS) and mechanisms of the development of oxidative and nitrosatitative stress due long term exposure to the complex of radionuclides of the Chornobyl fallout (ejection) and low intensity low dose γ radiation based on the study of ultrastructural organization and metabolism of reactive oxygen species (ROS) and nitrogen (NRS) of the atri al cardiomyocytes (CMC), the aortic endothelium and portal vein of the BALB/c mice. Found that the permanent expo sure to low doses of radiation changes occur, including the dominant mechanism is to run a CMC apoptosis and endothelial cells of the aorta and portal vein. It is shown that the development of oxidative stress accompanied by increased activity of ROS metabolism that occurs due to activation of nucleotide and lipid superoxide generators. Found that under these conditions the development of nitrosative stress is due to the activation of inducible NO syn thesis enzyme iNOS and inhibit its synthesis constitutive eNOS enzyme. High levels of simultaneous generation of superoxide and NO, bindting, lead to the formation of toxic peroxynitrite, which initiates the process of apoptosis.

Lennox-Gastaut syndrome. Management update.

Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3Hz) spike wave discharges on electroencephalography. Atonic seizures result in dangerous drop attacks with risks of injury and impairment of the quality of life. The seizures are frequently resistant to multiple antiepileptic (AED) drugs. Newer AEDs, such as rufinamide, are now available. When multiple AED trials fail, non-pharmacological treatments such as the ketogenic diet, vagus nerve stimulation, and epilepsy surgery, should be considered. The aim of this review is to present an updated outline of LGS and the available treatments. Although the prognosis for complete seizure control remains poor, the addition of newer therapies provides an improved hope for some of these patients and their families. Further long term randomized controlled trials are required to compare different therapeutic interventions in terms of efficacy and tolerability.

Impact of Cardiac Resynchronization Therapy on Clinical Outcomes in Patients With Continuous-Flow Left Ventricular Assist Devices

BackgroundImplantable cardioverter-defibrillators (ICDs) can improve survival in left ventricular assist device (LVAD) recipients. However, the impact of cardiac resynchronization therapy (CRT-D) on outcomes in continuous-flow left ventricular assist device (CF-LVAD) patients is not known. We sought to determine if CRT-D improved clinical outcomes in CF-LVAD patients compared with ICDs alone. Methods and ResultsSixty-one consecutive CF-LVAD patients with an ICD or CRT-D were evaluated. Impacts of CRT-D on mortality, all-cause hospitalization, and incidence of atrial (AA) and ventricular (VA) arrhythmias after LVAD implantation was compared with patients with ICD alone. Of the 61 LVAD patients, 31 (age 59.8 ± 16 years, 84% male) had CRT-D and 30 (age 57.2 ± 13 years, 74% male) had ICD. Before LVAD implantation, no significant differences were noted between the groups in demographic and clinical characteristics, LVAD indications, and incidence of AA and VA. Over 682 ± 45 days of LVAD support, 8 patients (25.8%) died in the CRT-D arm versus 5 (16.7%) in the ICD arm (P = .35). No differences were noted between the CRT-D and ICD groups in all-cause (96.8 vs 93.3%; P = .63) and HF (19.4 vs 26.7%; P = .78) hospitalizations, left ventricular (LV) end-diastolic diameter (6.4 ± 1.5 vs 6.2 ± 1.1 cm, P = .47), and incidence of AA (35.4% vs 33.3%; P = .80), VA (29% vs 26.6%; P = .86), and ICD shocks (22.6% vs 16.7%; P = .93). Beta-blocker and antiarrhythmic drug use after LVAD implantation was similar in both groups. ConclusionsIn patients with refractory HF who received CF-LVADs, CRT-D, compared with ICD, did not significantly improve mortality, all-cause hospitalization, LV dimensions, and incidence of AA and VA.

Chronic epilepsy due to low grade temporal lobe tumors and due to hippocampal sclerosis: Do they differ in post-surgical outcome?

Chronic seizures as a presenting feature of low grade temporal lobe gliomas and hippocampal sclerosis (HS) are reported to have similar outcomes although the prognostic indicators may not be the same. This study seeks to identify the variables that are associated with poor surgical outcome in both conditions. A retrospective analysis from our epilepsy data base was performed. All low-grade temporal lobe gliomas were selected and relevant variables were compared to the same variables in HS patients. There were 34 tumors (out of 233 cases of chronic temporal lobe epilepsy = 14.6 %) with a mean age of onset of 19 years, and the preoperative duration was 12.3 years. When compared to 120 HS patients both of these factors were significantly different (p < 0.001). Age at the time of surgery for tumors was 31.08 (p = 0.5). Tumors were left sided in 20 patients. In tumor cases amygdala resection was complete in 75 %, for hippocampus 24 % were complete and 39 % partial. Astrocytoma, ganglioglioma and oligodendroglioma constituted 80 % of tumor cases. Good outcome (Engel's Class I) was achieved in 88.2 % of tumor cases and 71 % of HS cases while poor outcome (Class III + IV) was seen in 5.9 and 16.7 % respectively. The follow up period for the two groups was not significantly different. In multivariate logistic regression analysis, the groups differed significantly in preoperative delay (between diagnosis and surgery) and in epilepsy outcome. Chronic temporal lobe epilepsy due to low-grade tumors had significantly better surgical outcome with considerably less preoperative delay. The age of onset of seizures was younger in HS patients but a delay in surgical treatment was significantly longer. Given that the diagnosis of treatment-resistant TLE secondary to HS can be established after two failed AED trials at optimal doses, shortening the interval between diagnosis and surgery may improve epilepsy outcome.

AED Trials in Newly Diagnosed Patients: Out with the Old versus New, in with the New versus New

AED Trials in Newly Diagnosed Patients: Out with the Old versus New, in with the New versus New

Adjunctive Therapy with Lacosamide for Older Epilepsy Patients (P06.115)

Objective: To examine the outcome of adjunctive therapy with lacosamide (LCS) in older epilepsy patients. Background As only 18 elderly patients were enrolled in the LCS partial-onset clinical trials, the effectiveness for this cohort is relatively unknown. Also, the pharmacokinetics differ (20% higher AUC and C max values are observed in healthy elderly vs. younger controls), but the clinical significance has not been determined. LCS can rarely induce conduction abnormalities (asymptomatic 1 st degree AV block in epilepsy trials and atrial fibrillation/flutter in diabetic neuropathy trials). Older patients with these comorbidities may be at higher risk. Design/Methods: A retrospective chart review identified patients > 50 yo on LCS. Relevant clinical factors were collected for those with documented pre-treatment and post-treatment seizure frequencies. Total mean seizure frequency 3 mo before initiation and at last follow-up were calculated, and the 50% responder rates were determined. Reason for discontinuation was classified as due to ineffectiveness or AE. Results: Thirty subjects with mean seizure onset/LCS start of 30.79 yrs (0-82) and 61.3 yrs (50-84) were included. Epilepsy syndrome was partial for all but one. Twenty-seven had failed > 2 past AED trials. Two had coronary artery disease and one diabetes. In the last 3 treatment months, 18 (60%) had > 50% total seizure reduction and 9 (30%) were seizure-free. Mean treatment duration/mean dose was 12.8 mo and 219 mg. Fourteen (47%) had AE9s: CNS-related were most common (dizziness/sedation). Seven (23%) withdrew: 4 (13%) due to AE9s (none cardiac-related). Conclusions: LCS was effective in this sample and comparable to previous studies. Although CNS-related AE9s were common, the rate of withdrawal due to AE9s was no higher than previous studies. No cardiac AE9s occurred. Combination with a sodium channel blocker (SCB) or LEV was not associated with treatment outcome as previously seen. Additional study in a larger sample is warranted. Disclosure: Dr. Fertig has nothing to disclose. Dr. Fleming has nothing to disclose. Dr. Feoli has nothing to disclose. Dr. Ghacibeh has received personal compensation for activities with UCB Pharma as a speaker. Dr. Laban has received personal compensation for activities with UCB Pharmaceuticals as a speaker. Dr. Lambrakis has nothing to disclose. Dr. Mesad has nothing to disclose. Dr. Politsky has received personal compensation for activities with UCB, Novartis, GlaxoSmithKline, Ortho-McNeill, and Eisai as a speaker and consultant.Dr. Politsky has received research support from UCB Pharmaceuticals, Cyberonics, Glaxo-Smith-Kline, and Neuropace Inc. Dr. Lancman has received research support from UCB Pharmaceuticals.

187 Incidental extracardiac findings on cardiac computed tomography performed before radiofrequency ablation of atrial fibrillation

Radiofrequency ablation has became a validated technique to cure symptomatic refractory atrial fibrillation (AF). Cardiac computed tomography (CT) is used to evaluate the left atrial (AT) anatomy in order to improve the ablation technique. The analysis of non-cardiac structures during cardiac CT may identify clinically significant incidental findings (IF). The objective of this study was to determine the prevalence of IF in patients undergoing AF catheter ablation. Between February 2006 and March 2010, patients undergoing a procedure of AF or left atrial tachycardia (LAT) ablation were enrolled and underwent a cardiac CT scan. Extracardiac IF were considered to be present if an abnormality was identified without previous clinical suspicion or known disease. 250 patients (55.2 ± 9.6 years of age, 82.4% men) were enrolled (133 paroxysmal, 43 persistent, 58 permanent AF and 16 LAT). Fifty-eight patients (23.2%) had a total of 76 IF. Patients with IF were significantly older (59.5 ± 8.2 vs 53.8 ± 9.7 years old, p<0.001). No relationship exist between the type of arrhythmia and the existence of IF. The majority of IF were pulmonary (50%). Two lung cancers were discovered. Cardiac CT scan is a useful tool to evaluate LA and pulmonary veins morphology before AF ablation. However, as a considerable prevalence of IF was found in our study, extracardiac structures should be routinely analyzed to detect unknown diseases. Organ Incidental findings n Lungs (n = 38) Emphysema 12 Atelectasis 6 Bronchic syndrome 6 Bronchectasis 5 Fibrosis 2 Pleural effusion 2 Lung cancer 2 Interstitial Pneumonia 1 Pleural calcifications 1 Asbestosis 1 Mediastinum (n = 15) Adenopathy 15 Vasculature (n = 11) Aorta dilation 9 Aorta ulceration 1 Pulmonary arteries anomalies 1 Liver (n = 5) Nodule 3 Cyst 2 Coronary arteries (n = 2) Congenital coronary arteries anomalies 2 Other (n = 5) Hiatal hernia 2 Kidney cyst 1 Pericardial calcifications 1 Thymus relicate 1

Usefulness of telemetry monitoring in patients with cardiac amyloidosis undergoing stem cell transplant

19543 Background: Stem cell transplant (SCT) for systemic amyloidosis with cardiac involvement includes high-dose melphalan and stem cell infusions, with resulting fluid overload, electrolyte disturbances, and infections which likely contribute to atrial (AA) and ventricular (VA) arrhythmias that are seen during SCT. However, the incidence of significant arrhythmias during SCT or the utility of telemetry monitoring (TM) has never been defined. Methods: Records from 17 consecutive patients with systemic AL amyloidosis with cardiac involvement who underwent SCT and TM were retrospectively reviewed. There were 12 men (71%) and five women, median age 53 years. The median number of AA and VA events per patient was calculated. The arrhythmia events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0 8/9/06). Results: Mean length of hospital stay was 24.4 days with no in-hospital mortality. There were 121 AA events and 201 VA events (median number of AA and VA events per patient = 4 and 10, respectively. The most common arrhythmia was non-sustained ventricular tachycardia (NSVT): 159 total events, median number of patient NSVT events = 7. All 17 patients had at least one episode of NSVT (Table). Thirteen patients (76.5%) had VA of Grade 2 (CTCAE) or higher and needed medical therapy that included initiation or increase in the dose of beta-blocker or amiodarone. One patient developed sustained ventricular tachycardia and required defibrillator placement. Another patient became hemodynamically unstable during an episode of rapid atrial fibrillation and required urgent cardioversion. Conclusions: Patients with cardiac amyloidosis undergoing SCT have a high incidence of AA and VA requiring treatment. In two of 17 patients, life-threatening arrhythmias were detected and treated. Therefore, concurrent TM is warranted and contributes to patient safety during SCT. Patient grading: Maximal severity of arrhythmia events during SCT. Arrhythmia Grading (CTCAE v 3.0) AA N=patients VA N=patients VA or AA N=patients Grade 1. Asymptomatic, intervention not indicated 11 4 12 Grade 2. Non-urgent medical intervention indicated 5 12 14 Grade 3. Symptomatic, incompletely controlled medically, or controlled with device 0 0 0 Grade 4. Life-threatening 1 1 2 No significant financial relationships to disclose.

Unified rate-dependent atrioventricular nodal function: Consistent recovery and fatigue properties revealed with S 1S 2S 3 protocols and different recovery indexes

Rate-dependent nodal properties are commonly assessed with premature protocols performed at different basic rates. Because characteristics of responses differ with recovery time index, the true nature of nodal rate-dependent properties is elusive. The purpose of this study was to reveal consistent nodal rate-dependent properties regardless of selected recovery index. With S(1)S(2)S(3) protocols, we independently varied basic and pretest cycle lengths and thereby distinguished cumulative from noncumulative effects of rate on nodal conduction time in rabbit heart preparations. Nodal responses to 30 basic and pretest cycle length combinations (five with identical basic and pretest cycles as in standard protocols) were analyzed using both atrial (AA) and His-atrial (HA) intervals as recovery index. AA and HA curves had an identical shape for any of 30 steady-state conditions. When assessed with constant pretest cycle lengths, cumulative effects (fatigue) of shortened basic cycle lengths were also independent of recovery index. Shortening of pretest cycle length at fixed basic rates led to apparent inhibitory and facilitatory effects when assessed with AA and HA curves, respectively. These effects vanished when a single long cycle was inserted after the pretest cycle. In all responses including those obtained with standard protocols, combined effects of basic and pretest cycle lengths set nodal conduction time. S(1)S(2)S(3) protocols reveal consistent nodal recovery and fatigue properties regardless of recovery index used. Changes in nodal function curves arising from the use of different recovery indexes mainly depend on pretest effects. This study provides a new approach to a unified interpretation of nodal recovery and fatigue properties.