Rapid Atrial Fibrillation Research Articles

Basic Science

Purpose: Experimental studies showed that local capture of atrial fibrillation (AF) by rapid pacing was possible in humans. However, contradictory observations were reported on its effect at distant atrial sites. The present model-based study investigated the effect of rapid pacing on the paced and the non-paced atria. Methods: A biophysical model of AF based on a geometry from human MRI and a membrane kinetics model was used. Rapid AF pacing was applied during 30s in right atrial (RA) free wall or left atrial (LA) appendage at optimal pacing cycle lengths based on previous studies (RA:76 ms, LA:77ms). The pacing effect was characterized by measuring 256 electrograms evenly located in RA and LA, from which the following values were computed: AF cycle length (AFCL), number of wavefronts (#WF), percentage of excited tissue (ET) and AF organization index (OI) assessing spectral regularity and ranging from 0 to 1. Results: Pacing successfully induced local AF capture in the paced atrium with an AFCL close to the pacing cycle length. Local capture was accompanied by a significant (p<0.001) reduction in #WF and increase in ET and OI in the paced atrium. In the non-paced atrium, AFCL only slightly decreased while the effect on #WF was the opposite to what was observed in the paced atrium (increase) and ET did not change. Interestingly, the effect on OI was different when pacing from the LA (decrease in the non-paced atrium compared to no pacing) or the RA (increase). Conclusions: The effect of AF rapid pacing on the non-paced atrium showed an acceleration of AF with an increased number of wavefronts. However, the effect on AF organization was dependent on the pacing site, which could explain the contradictory results reported in humans.

215 Is it necessary to indicate another electrophysiological study in patients previously studied for a preexcitation syndrome?

Accessory pathway (AP) refractory period (RP) increases from the youth to the elderly. The large indications of AP ablation have changed the natural follow-up. The purpose of the study was to report the clinical and electrophysiological data of pts with a Wolff-Parkinson White syndrome (WPW), studied within 1 to 20 years of one another to evaluate the changes of these data. 2 baseline EPS were performed within 1 to 20 years (y) of one another (mean 9 y ± 4) in 61 pts, 37 males and 24 females, aged initially from 10 to 67 y (30 ± 14), with a patent WPW. First electrophysiological study (EPS) was indicated for syncope (n = 6), atrioventricular reentrant tachycardias (AVRT) (n = 34), atrial fibrillation (AF) (n = 5) or for asymptomatic preexcitation (n = 16). The protocol was similar: the higher rate conducted through AP was measured and programmed atrial stimulation with 1 and 2 ES performed in control state (CS) and after isoproterenol. At 2 nd study, among pts studied for syncope at study 1, 1 has still syncope, 2 have AVRT, 1 has rapid AF, and 2 are asymptomatic. Among pts with AVRT at study 1, 25 have AVRT, 7 are asymptomatic and 2 have AF. Among pts with AF, 4 have still AF and 1 is asymptomatic. Among asymptomatic pts 3 have a spontaneous malignant form, 7 remain asymptomatic, 3 have AVRT, 1 has syncope and 1 has AF. All AVRT or AF occurred in pts with inducible AVRT or AF at EPS 1. The higher rate conducted by AP was significantly lower in CS and after isoproterenol at study 2 (157 ± 95 b/min, 193 ± 113) than at study 1 (199 ± 65, 257 ± 65). AP has lost anterograde conduction properties in 17 pts aged from 17 to 67 years (47 ± 15); all of them but one had initially 1/1 conduction through AP 170/min. However 8 of them had still AVRT. Among pts with initially rapid conduction through AP (250/min), all but one have a rapid conduction at EPS 2; 3 of them which were asymptomatic developed rapid AF. The study confirms that a benign form of WPW without inducible AVRT or AF remains benign. Pts with AVRT and AP and long refractory period become asymptomatic in 20% of cases. Pts with inducible rapid AF remain at high risk of events in most cases.

326 Elevated troponin in acute ischaemic stroke: prevalence, predictive factors, mortality and applicability of cardiac magnetic resonance imaging

Elevated troponin is frequent in acute ischaemic stroke but its clinical implication remain unclear. The aim of this study is to describe prevalence, predictive factors and prognosis of patients with troponin elevation in acute ischaemic stroke. A second end point was to diagnose a potential ischaemic heart disease with cardiac magnetic resonance imaging (MRI) performed in ten days after stroke. 146 consecutive patients admitted for acute ischaemic stroke in our stroke unit were prospectively enrolled between july and november 2009. The blood troponin Ic was measured in the first two days after admission. Clinical and biological data, stroke severity attested by national institute of health stroke scale (NHISS) and in-hospital mortality were compared between the two groups with and without troponin elevation. A cardiac MRI was performed during hospitalization if troponin was positive. Serum troponin was elevated in 23 patients (15,7%). After multivariate analysis, 6 independent factors were associated with troponin elevation: diabetes, 2 or more prior cardiovascular events, thrombolysis, multiple localization of stroke, SGOT elevation and creatinin >120 μmol/L. Moreover, the 3 factors associated with in-hospital mortality after logistic regression were troponin elevation (OR = 2,56 [1,11+6,02] p = 0,031), prior myocardial infarction (OR = 2,94 [1,16–7,95] p = 0,002) and severe NIHSS at admission (OR = 3,07 [1,35–7,39] p = 0,007) Only 2 cardiac MRI have been readable because other patients were died before the exam or were unable to have this exam because of stroke severity, confusion or rapid atrial fibrillation. One of these patients had an acute myocardial infarction diagnosed by cardiac MRI but a normal coronarography. Elevated troponin in acute ischaemic stroke is an independent factor of in-hospital mortality. A troponin rise is more frequent in patients with diabetes or prior cardiovascular events that's why a screening of ischaemic heart disease should be performed. Cardiac MRI can’t be widely performed at the early stage of stroke, however it has been decisive for one patient in this study.

High Incidence of Inappropriate ICD Therapies in Young Patients with Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction: We present three young patients with inappropriate shocks of implantable cardioverter defibrillator (ICD) therapies that were performed for the treatment of ventricular arrhythmias due to catecholaminergic polymorphic ventricular tachycardia (CPVT). Case Presentations: Case 1: a 4 year-old boy, CPVT with syncope occurred during swimming. He was treated with an ICD because he complained of syncope repeatedly and administered oral beta-blocker. During follow-up, he had inappropriate shocks due to rapid paroxysmal atrial fibrillation (PAF) during exercise. The PAF was disappeared with an additional flecainide, oral antiarrhythmic agent. Case 2: a 16 year-old boy, CPVT resulting in cardiopulmonary arrest occurred during exercise. He was treated with an ICD and prescribed oral beta-blocker. After that, inappropriate shocks were delivered under his awareness due to the occurrence of rapid PAF. With additional administration of flecainide, inappropriate shocks were decreased. Case 3: a 21 year-old man, an ICD was implanted for CPVT with syncope. He had repeatedly inappropriate shocks due to the occurrence of atrial flutter (AFL). Catheter ablation were performed for eliminating his AFL. Conclusions: In young patients with CPVT, inappropriate ICD therapies easily occur with atrial tachyarrhythmias even if a dual chamber ICD was used. An additional antiarrhythmic drug therapy or catheter ablation should be considered to inhibit such an inappropriate shock.

Abstract 12516: Changes of Electrophysiological Data Through the Life in the Preexcitation Syndrome

Background: The number of accessory pathway (AP) ablations has dramatically increased and the natural follow-up of Wolff-Parkinson White syndrome (WPW) becomes not possible. Changes of electrophysiological data were reported. The purpose of the study was to report the clinical and electrophysiological data of patients with a WPW, studied within 1 to 20 years of one another to evaluate the changes of the data. Methods: 2 baseline EPS were performed within 1 to 20 years of one another (mean 9 y ± 4) in 62 patients, 37 males and 25 females, aged initially from 10 to 67 y (31±15), with a patent WPW. First electrophysiological study (EPS) was indicated for syncope (n=7), atrioventricular reentrant tachycardias (AVRT) (n=34), atrial fibrillation (AF) (n=5) or for asymptomatic preexcitation (n= 16). The protocol was similar: the higher rate conducted through AP was measured and programmed atrial stimulation with 1 and 2 ES performed in control state (CS) and after isoproterenol. Results: At 2 nd study, among patients studied for syncope at study 1, 2 have still syncope, 2 have AVRT, 1 has rapid AF, and 2 are asymptomatic. Among patients with AVRT at study 1, 25 have AVRT, 7 are asymptomatic and 2 have AF. Among patients with AF, 4 have still AF and 1 is asymptomatic. Among asymptomatic patients, 3 have a spontaneous malignant form, 7 remain asymptomatic, 3 have AVRT, 1 has syncope and 1 has AF. All AVRT's or AF's occurred in patients with inducible AVRT or AF at EPS 1. The higher rate conducted by AP was significantly lower in CS and after isoproterenol at EPS 2 (157±95 b/min, 193±113) than at EPS 1 (199±65, 257±65). AP has lost anterograde conduction properties in 18 patients aged from 17 to 67 years (47±15); 16 of them had initially 1/1 conduction through AP ≤ 170/min; however 8 had still AVRT. Among 24 patients with initially rapid conduction through AP (≥ 240/min), 17 have a rapid conduction at EPS 2; 3 of them, which were asymptomatic developed rapid AF, but 2 became asymptomatic with a benign form. Conclusions: The study confirms that a benign form of WPW without inducible AVRT or AF remains benign and that AP ablation is not indicated. Patients with AVRT and AP with a long refractory period become asymptomatic in 20 % of cases. Patients with inducible rapid AF have still a malignant form in 71 % of cases.

Distinct restitution properties in vagally mediated atrial fibrillation and six-hour rapid pacing-induced atrial fibrillation

The atrial potential duration (APD) restitution has been suggested to play an important role in ventricular fibrillation; however, its role in atrial fibrillation (AF) has not been determined. This study sought to investigate the APD restitution properties in two different AF models: vagally mediated AF and 6-h rapid atrial pacing-induced AF. Twenty anaesthetized open-chest dogs were assigned to Group I, vagally mediated AF (n= 8) or Group II, 6-h rapid atrial pacing-induced AF (n= 12). In both groups, the monophasic APD was subsequently recorded at multiple pulmonary vein and atrial sites. The APD restitution curve was constructed using a dynamic pacing protocol and determined by plotting each APD(90) against the preceding diastolic interval at incremental atrial pacing rates at eight sites. In Group I, vagal stimulation significantly shortened the APD(90), flattened the APD restitution curve (slopes <1), and suppressed the APD alternans at each site, while increasing the AF inducibility and duration (P<0.05 for all). In Group II, 6-h rapid pacing-induced APD shortening steepened the restitution curves (slopes >1), facilitated the APD alternans, and also increased the incidence and duration of AF (P< 0.05 for all). The spatial dispersion of APD restitution was significantly increased in both groups. This study showed distinct atrial APD restitution properties in vagally mediated AF and 6-h rapid pacing-induced AF, indicating specific restitution kinetics in different mechanisms of AF.

Flash pulmonary edema in patients with renal artery stenosis – The Pickering Syndrome

Aim. We report the prevalence of flash pulmonary edema in patients consecutively referred for balloon angioplasty of unior bilateral renal artery stenosis (PTRA), and describe the characteristics of this special fraction of the patients. We further report two unusual cases. Methods and material. Review of medical records from 60 patients consecutively referred for unior bilateral PTRA from 2004–2005 in Copenhagen County. Results. Eight out of 60 patients had one or more episodes of flash pulmonary edema before PTRA. Compared with the remaining patients, they had a higher prevalence of bilateral stenosis (50% vs 27%) and coronary artery disease (75% vs 28%). However, only one of eight had severe systolic dysfunction of the left ventricle. After PTRA, two recurrences of flash pulmonary edema were observed. One was caused by severe restenosis and did not recur after aorto-renal bypass surgery. The other one was caused by rapid atrial fibrillation and did not recur after pacemaker and medical treatment. Conclusion. Flash pulmonary edema can be observed in patients with unilateral as well as bilateral stenosis. The prognosis is usually excellent upon treatment of the stenoses. Recurrences are rare unless restenosis occurs, and therefore, regular control, e.g. by Doppler-ultrasound examination is recommended.

Classifying fractionated electrograms in human atrial fibrillation using monophasic action potentials and activation mapping: Evidence for localized drivers, rate acceleration, and nonlocal signal etiologies

Complex fractionated electrograms (CFAEs) detected during substrate mapping for atrial fibrillation (AF) reflect etiologies that are difficult to separate. Without knowledge of local refractoriness and activation sequence, CFAEs may represent rapid localized activity, disorganized wave collisions, or far-field electrograms. The purpose of this study was to separate CFAE types in human AF, using monophasic action potentials (MAPs) to map local refractoriness in AF and multipolar catheters to map activation sequence. MAP and adjacent activation sequences at 124 biatrial sites were studied in 18 patients prior to AF ablation (age 57 ± 13 years, left atrial diameter 45 ± 8 mm). AF cycle length, bipolar voltage, and spectral dominant frequency were measured to characterize types of CFAE. CFAE were observed at 91 sites, most of which showed discrete MAPs and (1) pansystolic local activity (8%); (2) CFAE after AF acceleration, often with MAP alternans (8%); or (3) nonlocal (far-field) signals (67%). A fourth CFAE pattern lacked discrete MAPs (17%), consistent with spatial disorganization. CFAE with discrete MAPs and pansystolic activation (consistent with rapid localized AF sites) had shorter cycle length (P <.05) and lower voltage (P <.05) and trended to have higher dominant frequency than other CFAE sites. Many CFAEs, particularly at the septa and coronary sinus, represented far-field signals. CFAEs in human AF represent distinct functional types that may be separated using MAPs and activation sequence. In a minority of cases, CFAEs indicate localized rapid AF sites. The majority of CFAEs reflect far-field signals, AF acceleration, or disorganization. These results may help to interpret CFAE during AF substrate mapping.

E0714 Autonomic nerve remodelling of prolonged rapid atrial pacing-induced atrial fibrillation and reversal effect of propranolol

BackgroundLimited study disclosed atrial heterogeneous sympathetic innervation in atrial fibrillation recently. But the changes of vagal nerve and the effect of medicine on neural remodelling are not clear.Methods and ResultsTwelve...

Accuracy of dual-source computed tomography to identify significant coronary artery disease in patients with atrial fibrillation: comparison with coronary angiography

It has been previously reported that the sensitivity and specificity of multislice computed tomography (CT) for detecting significant coronary artery disease (CAD) is high. However, regular sinus rhythm has been considered a prerequisite for an adequate examination, even though atrial fibrillation (AF) is common among patients evaluated for the presence of coronary heart disease. In this study, we investigated the sensitivity and specificity of dual-source CT (DSCT) to detect and rule out significant coronary stenoses in patients with AF referred for invasive coronary angiography. One hundred and ten consecutive patients with AF who were admitted for a first diagnostic coronary angiogram were screened for participation. Out of these, 50 patients were excluded either due to renal insufficiency, inability to maintain an adequate breath hold or due to rapid AF non-responsive to β-blocker therapy (heart rate > 100 b.p.m.). Sixty remaining patients (mean age 71 ± 7 years) were included and subjected to CT angiography using DSCT within 24 h before invasive coronary angiography. A contrast-enhanced volume data set was acquired (330 ms gantry rotation, collimation 2 × 64 × 0.6 mm, retrospective electrocardiogram gating). Data sets were evaluated concerning the presence or absence of significant coronary stenoses and validated against invasive coronary angiography. A significant stenosis was assumed if the diameter reduction was ≥50%. Mean heart rate during CT was 70 ± 15 b.p.m. (range 32-107 b.p.m.). On a per-patient basis, the sensitivity and specificity for DSCT to detect significant coronary stenoses in vessels >1.5 mm diameter was 100% [14/14, 95% confidence interval (CI) 77-100] and 85% (39/46, 95% CI 71-94), respectively, with a negative predictive value (NPV) of 100% (39/39, 95% CI 91-100) and a positive predictive value (PPV) of 67% (14/21, 95% CI 43-85). On a per-artery basis, 240 vessels were evaluated (left main, left anterior descending, left circumflex, and right coronary artery in 60 patients, with 3 non-assessable vessels due to either severe calcification or motion artefacts which were considered positive for stenoses) with a sensitivity of 95% (21/22, 95% CI 77-100) and specificity of 94% (204/218, 95% CI 89-97); NPV was 99% (204/205, 95% CI 96-100), and PPV was 60% (21/35, 95% CI 38-80). Our study demonstrates high sensitivity, specificity, and NPV of DSCT to detect significant CAD in selected patients with rate controlled AF.

Conduction System Disease

Scenario:A 59-year-old woman had brief episodes of rapid atrial fibrillation and bradycardia several months ago. It was not recurrent or sustained, so she was not treated with invasive or pharmacological interventions but followed up with occasional clinic visits. She was instructed to continue taking her beta blocker, which she had done for 10 years without side effects. She has a history of hypertension and a significant family history; her mother and grandmother had hypertension and heart failure, and both died of cerebral vascular accidents. The patient is now in the emergency department with complaints of chest “discomfort” and shortness of breath. She had the rhythm below (lead II), which was only captured because the patient’s daughter, a nurse, pushed the record button on the bedside monitor. A regular feature of the American Journal of Critical Care, the ECG Puzzler addresses electrocardiogram (ECG) interpretation for clinical practice. To send an eLetter or to contribute to an online discussion about this article, visit www.ajcconline.org and click “Respond to This Article” on either the full-text or PDF view of the article. We welcome letters regarding this feature.

Troponin I and NT-proBNP (N-terminal pro-Brain Natriuretic Peptide) Do Not Predict 6-Month Mortality in Frail Older Patients Undergoing Orthopedic Surgery

To determine if troponin I and NT-proBNP were predictors of 6-month mortality after emergency orthopedic-geriatric surgery in a frail population. Prospective observational study. Orthopedic-geriatric unit of a metropolitan hospital in Australia. A total of 383 patients were screened; 44 were eligible for this study of which 33 patients consented who were receiving high-level care or had severe dementia or an illness with a prognosis of less than 12 months. Troponin I and NT-proBNP were tested on one preoperative sample and at least one postoperative blood sample. Cardiac events were defined as acute myocardial infarction, congestive cardiac failure, new onset or rapid atrial fibrillation, major arrhythmia, or cardiac arrest. The mean age of the patients was 85.8 +/- 9.6 years and 93.9% had a fractured neck of femur. Premorbid cardiac conditions were common (24.2% had ischemic heart disease and 21.2% congestive cardiac failure). A third of patients had a preoperative troponin elevation and 60.6% had a postoperative elevation. The mortality within 30 days of surgery was 15.2% (5/33 patients), rising to 39.4% (13/33) at 6 months with 46.2% (6/13) dying of a cardiac cause. The Kaplan-Meier survival curve was not significantly different between patients with and without a troponin elevation. A third of patients sustained a cardiac event at 6 months. The median preoperative NT-proBNP was 1651.50 pg/L, range 25 to 31,227, and median postoperative NT-proBNP was 3038.50pg/L, range 44 to 27,348. Troponin I and NT pro-BNP did not predict 6-month mortality or cardiac complications. Predictors of 6-month mortality using univariate analysis were number of comorbidities OR 2.0 (95% CI 1.1-3.8, P = .033) and premorbid atrial fibrillation OR 7.7 (95% CI 1.2-47.8, P = .028). Troponin I and NT-proBNP were not predictors of 6-month mortality or cardiac events in an older frailer population of patients undergoing orthopedic surgery. These patients sustained substantial cardiac morbidity and mortality at 6 months after surgery. The control of symptoms, rather than prolongation of life with cardiological intervention, may be more appropriate for this patient group.

Low-dose diltiazem in atrial fibrillation with rapid ventricular response

Objectives Diltiazem is one of the most commonly used medications to control the rapid ventricular response in atrial fibrillation (AF). The recommended starting dose is an intravenous bolus of 0.25 mg/kg over 2 minutes. To avoid hypotension, we have empirically used a lower dose of diltiazem. We compared the efficacy and safety of different doses of diltiazem in rapid AF. Methods A retrospective chart review was undertaken in patients who presented to the emergency department with rapid AF. Patients were divided into 3 groups according to diltiazem dosage: low dose (≤0.2 mg/kg), standard dose (>0.2 and ≤0.3 mg/kg), and high dose (>0.3 mg/kg). We compared the rates of therapeutic response (adequate rate control) and complications (such as hypotension). Multivariate regression analysis was used to determine the effect of diltiazem dose on the occurrence of complications. Results A total of 180 patients were included in the analysis. There were no significant differences in the rates of therapeutic response for the low-, standard-, and high-dose groups (70.5%, 77.1%, and 77.8%; P = .605). The rates of hypotension in the low-, standard-, and high-dose groups were 18%, 34.9%, and 41.7%, respectively. After adjusting confounding variables, the rate of hypotension was significantly lower in the low-dose group in comparison with the standard-dose group (adjusted odds ratio, 0.39; 95% confidence interval, 0.16-0.94). Conclusions Low-dose diltiazem might be as effective as the standard dose in controlling rapid AF and reduce the risk of hypotension.

Takotsubo cardiomyopathy following dipyridamole pharmacologic stress

This study is about an elderly female patient who presented with rapid atrial fibrillation. Pharmacologic stress myocardial perfusion imaging with dipyridamole for the assessment of myocardial ischemia resulted in transient abnormalities on electrocardiogram, wall motion and perfusion defects with complete resolution 1 month later, suggestive of Takotsubo cardiomyopathy. We believe that our case report is the first to describe this finding after dipyridamole stress.

Cardiac resynchronization therapy after atrioventricular node ablation for rapid atrial fibrillation in a heart transplant recipient with late allograft dysfunction

We report the successful use of cardiac resynchronization therapy in an orthotopic heart transplant recipient with late graft dysfunction, severe heart failure, and atrial fibrillation requiring atrioventricular node ablation. This case highlights the potential role for cardiac resynchronization therapy in orthotopic heart transplant recipients with systolic dysfunction and heart failure, especially in the setting of forced right ventricular pacing. Despite potentially different mechanisms of left ventricular dysfunction, biventricular pacing should be considered for allograft recipients with conventional indications for cardiac resynchronization therapy.

Safety of atrial fibrillation ablation with novel multi-electrode array catheters on uninterrupted anticoagulation—a single-center experience

A recent single-center report indicated that the performance of atrial fibrillation ablation in patients on uninterrupted warfarin using a conventional deflectable tip electrode ablation catheter may be as safe as periprocedural discontinuation of warfarin and bridging with heparin. Novel multi-electrode array catheters for atrial fibrillation ablation are currently undergoing clinical evaluation. While offering the possibility of more rapid atrial fibrillation ablation, they are stiffer and necessitate the deployment of larger deflectable transseptal sheaths, and it remains to be determined if they increase the risk of cardiac perforation and vascular injury. Such potential risks would have implications for a strategy of uninterrupted periprocedural anticoagulation. We audited the safety outcomes of our atrial fibrillation ablation procedures using multi-electrode array ablation catheters in patients on uninterrupted warfarin (CHADS2 score>or=2) and in patients not on warfarin (uninterrupted aspirin). Two bleeding complications occurred in 49 patients on uninterrupted warfarin, both of which were managed successfully without longterm sequelae, and no bleeding complication occurred in 32 patients not on warfarin (uninterrupted aspirin). There were no thromboembolic events or other complication with either anticoagulant regimen. Despite the larger diameter and increased stiffness of multi-electrode array catheters and their deflectable transseptal sheaths, their use for catheter ablation in patients with atrial fibrillation on uninterrupted warfarin in this single-center experience does not appear to be unsafe, and thus, an adequately powered multicenter prospective randomized controlled trial should be considered.

315 Indications of radiofrequency ablation of accessory pathway in the young population

Radiofrequency (RF) ablation of accessory pathway (AP) is widely used in Wolff-Parkinson-White syndrome (WPW), but the indications remain controversial in children and teenagers. The purpose of the study was to evaluate the clinical and electrophysiological factors associated with the indications of AP ablation in the youth. 133 children and teenagers aged from 5 to 18 years (13.5±3) were admitted for a WPW and electrophysiological study (EPS) either for tachycardia, syncope or they were asymptomatic. EPS was performed in control state and after isoproterenol. Then RF ablation was proposed in case of recurrent tachycardias or induction of rapid atrial fibrillation (AF). AP ablation was indicated in 51 children (38%), several years after initial evaluation in 5 of them (group I), and was not performed in 82 children (group II). The indications did not differ significantly from the adult population (232/504, 46%). Clinical and electrophysiological data of groups I and II were compared. Group I was older than group II (15±2 vs 13±4) (p<0.001); male sex was more frequent in group I (72.5%) than in group II (56%) (p<0.05); group I was less frequently asymptomatic (27%) than group II (55%) (p< 0.01) and had more frequently spontaneous reentrant tachycardias than group II (49% vs 28%) (p< 0.05). Syncope was as frequent in group I (21.5%) as II (18%). At EPS, group I had a more rapid conduction through AP than group II, in control state (208±68 b/min vs 176±53, p< 0.001), but not after isoproterenol (245±74 vs 230±63, NS). Reentrant tachycardia was induced more frequently in group I (70.5%) than II (37.5%) (p< 0.001). AF was induced more frequently in group I 35%) than in group II (11%). Malignant forms (rapid AF) were more frequent in group I (31%) than in group II (5%) (p< 0.001). Failures of ablation were as frequent in children (8%) as in adults (2.5%) (NS). The indications of AP ablation in the young population are based on recommended data and are similar to those of adults, with a similar risk of failure; they concern symptomatic or high risk children. The boys are referred more frequently than girls for the ablation.

Efficacy of a Brief, Cyclophosphamide-Intensive Regimen for Older Patients with Newly Diagnosed Burkitt's or Atypical Burkitt's Lymphoma/Leukemia.

Abstract 2685Poster Board II-661 Background:Although standard therapies cure most adolescents and young adults with Burkitt's lymphoma/leukemia (BL), older patients (pts) have an inferior prognosis with an estimated 1-year survival of 50%. The inferior outcome is attributable to both insufficient efficacy and excess toxicity. Cyclophosphamide (Cy) has long been recognized to be arguably the most active agent in BL. Prior work at our institution showed that high-dose Cy, equivalent to transplantation doses, could be given without stem cell rescue with minimal toxicity even in older pts. Patients and Methods:A phase II trial for pts age ≥ 30, based on intensive Cy and incorporating rituximab but no anthracycline, was developed with a primary endpoint of 1-year overall survival. Entry requirements included newly diagnosed BL or atypical BL; any performance status (PS); HIV negative; and no significant cardiac dysfunction. Renal failure, even if necessitating dialysis, was permitted if it was acute. Treatment consisted of 3 cycles, with successive cycles beginning on day 15 or when ANC was ≥ 500/μL. Cycles 1 and 2 consisted of Cy 1500 mg/m2 IV day 1; vincristine 1.4 mg/m2 (2 mg cap) day 1; prednisone 100 mg days 1-5; rituximab 375 mg/m2 IV days 1 and 8; methotrexate 3 g/m2 IV day 8 with leucovorin rescue; cytarabine 100 mg intrathecally days 1, 4, and 11; and filgrastim. Cycle 3 consisted of rituximab 375 mg/m2 IV day 1; high-dose Cy (50 mg/kg IV days 2, 3, 4, and 5) with uroprotection; filgrastim; and rituximab 375 mg/m2 IV weekly for 4 weeks once ANC was ≥ 1000/μL. Eligibility for cycle 3 included ECOG PS < 4; no disease progression or uncontrolled meningeal disease; not on dialysis; and transaminases ' 5X upper limit of normal. Results:A prespecified interim analysis of the first 12 of a planned 20 evaluable pts is presented. Diagnosis was BL in 8 and atypical BL/unclassifiable high-grade lymphoma with features intermediate between BL and diffuse large B-cell lymphoma in 4. Median age was 56 (range 34 – 75), 8/12 (67%) had Ann Arbor stage III/IV disease, and all were high-risk by Magrath's criteria. PS ranged from 0 to 4. Two pts received hemodialysis on presentation. For all pts, actuarial event-free survival and overall survival (Figure) are 66% and 75%, respectively, at both 1 year and 2 years after treatment initiation. Three pts died during cycle 1: tumor lysis syndrome on day 1, neutropenic sepsis on day 8, multiorgan failure on day 46 after respiratory arrest on day 20. All of the other 9 pts completed protocol therapy: 8 (89%) achieved anatomic CR/CRu as well as a complete metabolic response by PET, and are event-free at a median of 29 months (range < 1 – 44 months) after therapy completion. The remaining pt had residual marrow disease followed by progression and is in remission 1 year after myeloablative allogeneic BMT. Adverse events in these 9 pts included 7 neutropenic fevers; 1 non-neutropenic bacteremia; and 1 self-limited episode of pericarditis with rapid atrial fibrillation. Grade 3 peripheral neuropathy was limited to 2 pts. The planned dose intensity was achievable: median time to cycle 2 was 15 days (14 – 21), and median time from start of cycle 1 to start of cycle 3 was 31 days (28 – 35). Median time to neutrophil recovery after the last dose of Cy was 16 days (10 – 21); median time to platelets ≥ 20,000/μL, without transfusion in the preceding week, was 22 days (0 – 30). Early stopping criteria for response or all-cause mortality have not been met. [Display omitted] Conclusion:A very short regimen based on intensive Cy without anthracycline produces a high rate of durable CR's in older, poorer-risk pts with BL or atypical BL. Disclosures:Kasamon:Genentech: Research Funding. Swinnen:Genentech: Consultancy, Research Funding; Enzon: Consultancy; Abbot: Consultancy, Research Funding.

Anti-apoptotic Effects of a Calpain Inhibitor on Cardiomyocytes in a Canine Rapid Atrial Fibrillation Model

This study was designed to evaluate the effects of a calpain inhibitor on cardiac muscle apoptosis in rapid pacing canine atrial fibrillation (AF) models. Twenty one dogs were divided into three groups: a sham operation group, a control AF group and a calpain inhibitor group. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute. N-Acetyl-Leu-Leu-Met (1.0 mg/kg/day) was administered in the calpain inhibitor group for three weeks. The activity of calpain I and cardiomyocyte apoptosis were measured by fluorometry and TUNEL assay, respectively. Protein expression of caspase-3 was detected by Western blot. The localizations of caspase-3, caspase-8, bcl-2 and ARC were assessed by immunohistochemistry. In comparison to the sham operation group, the activity of calpain I was significantly increased in the control AF group (2.3 fold, p < 0.001), and decreased in the calpain inhibitor group (1.1 fold, p < 0.005). The calpain activity correlated with the apoptosis index (r = 0.9, p < 0.05). The apoptosis index was 1.0 +/- 0.2%, 11.8 +/- 6.8% and 3.5 +/- 2.1% in the sham operation group, control AF group and calpain inhibitor group, respectively. In the sham operation group, control AF group and calpain inhibitor group, the expressions of caspase-3 (13.0 +/- 1.9%, 52.8 +/- 4.3% and 33.6 +/- 3.7%), caspase-8 (40.1 +/- 5.3%, 92.6 +/- 6.5% and 55.3 +/- 5.9%), bcl-2 (65.8 +/- 6.1%, 52.0 +/- 5.7% and 69.9 +/- 5.3%) and ARC (70.2 +/- 8.6%, 68.8 +/- 7.3% and 81.5 +/- 8.8%) were calculated as immunohistochemical indexes, respectively. The calpain inhibitor N-Acetyl-Leu-Leu-Met attenuated apoptosis through a complicated network of apoptosis-related proteins, which may result in improvement of structural remodeling in atrial fibrillation.

Takotsubo Cardiomyopathy: A Nurse’s Guide

Takotsubo Cardiomyopathy: A Nurse’s Guide