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Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death especially in times of increased sympathetic tone, for example, during sports, which have been confirmed by nuclear imaging studies. However, the underlying biochemical pathways remain to be delineated. Therefore, we investigated the expression levels of proteins of the signaling cascade in patients with ARVC. Methods During diagnostic work-up, right ventricular endomyocardial biopsies (EMBs) were sampled from 15 consecutive male ARVC patients (52 ± 14 years). Tissue levels of key proteins of the signaling cascade were analyzed. Results were compared to those obtained from EMBs of 10 patients with idiopathic right ventricular outflow-tract tachycardia (RVOT; 41 ± 14 years) and of five control subjects without identifiable structural heart disease (42 ± 13 years; P = ns). Results Among the proteins analyzed, only tissue levels of norepinephrine (NE; P < 0.04) and cyclic adenosine-3´,5´-monophospate (cAMP; P < 0.01) were significantly lower in ARVC when compared to RVOT patients. When compared to controls, mean cAMP levels were lower in patients with ARVC but did not reach statistical significance. No differences in cAMP were observed between RVOT and controls. Conclusions The current findings confirm and expand the concept of adrenergic dysfunction in ARVC: the reduction of NE in ARVC could lead to an impaired stimulation of β-adrenoceptor subsequent signaling pathways with potential implication for cardiac fibrosis and arrhythmogenesis.

Background: In patients with Brugada syndrome (BrS), life-threatening ventricular tachyarrhythmias predominantly occur during vagal stimulation at rest or during sleep. Previous imaging studies displayed an impaired autonomic function in BrS patients. However, it remains unclear whether these alterations primarily stem from a reduction of synaptic release of norepinephrine (NE) or an enhanced presynaptic reuptake. Both conditions could lead to reduced NE concentrations in the synaptic cleft. Therefore, we analyzed key components of the sympathoadrenergic signaling pathways in patients with BrS. Methods and Results: Endomyocardial biopsies were obtained from eight BrS patients (seven male; age 49 ± 15 years) and five controls (three male; age 43 ± 13 years; P = ns). The concentrations of NE, epinephrine (Epi), NE transport (NET) carrier protein, cyclic adenosine 5′monophosphate (cyclic adenosine monophosphate [cAMP]), inhibitory G-proteins (Gi1,2α), troponin-I (TNI), and phosphorylated TNI were analyzed. Levels of NET, Gi1,2α, TNI, Epi, and phosphorylated TNI were comparable between the groups. Compared to controls, patients with BrS showed reduced cAMP and NE concentrations. Conclusions: The current findings expand the concept of adrenergic dysfunction in BrS: the reduction of NE in BrS could lead to an impaired stimulation of β-adrenoceptors resulting in a reduction of cAMP and alterations of the subsequent signaling pathway with potential implication for arrhythmogenesis. (PACE 2011; 34:1147–1153)

Aim: This study investigated the value of epicardial mapping immediately before CABG in the differentiation of hibernating from scarred myocardium in correlation to the noninvasive gold standard 18F-FDG PET. Methods and Results: In 35 patients with CAD, myocardial perfusion (99mTc-Tetrofosmin-SPECT), viability (18F-FDG-PET), and function (LVangiography) were assessed before CABG. 102 bipolar epicardial electrograms per patient (n = 3570 electrograms) were recorded simultaneously with a ventricular jacket array. Based on the scintigraphic and LV angiographic data at the site of each electrode with good myocardial contact (n = 1963), segments (n = 492, 14.1 ± 5.6 per patient; mean ± SD) were classified into three groups: hibernating (n = 139), scarred (n = 104), and control (n = 249). Regional mean bipolar voltage values were calculated for Receiver Operating Characteristic (ROC) analysis. Mean bipolar voltage was significantly lower in scarred when compared to hibernating myocardium. ROC curve analysis (area under the curve of O.92 ± 0.47, mean ± SE) for mean bipolar voltage to discriminate between hibernating and scarred myocardium revealed a sensitivity of 94% with a specificity of 83% at a cut-off value of 8.75 mV. Conclusion: Hibernating myocardium can be differentiated correctly from scarred myocardium by direct epicardial mapping. In the future, hibernating myocardium may be detectable by body surface mapping techniques using inverse solutions. A.N.E. 2002;7(4):349–356

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disease characterized by peculiar right ventricular involvement and electrical instability that precipitates ventricular arrhythmias and sudden death. The purpose of the present consensus report of the Study Group of the European Society of Cardiology and the Scientific Council on Cardiomyopathies of the World Heart Federation is to review the considerable progress in our understanding of the etiopathogenesis, morbid anatomy, and clinical presentation of ARVD/C since its first description in 1977. This article will focus on the important hut still unanswered issues, mostly regarding risk stratification, clinical outcome, and management of affected patients. Because ARVD/C is relatively uncommon and any one center may have experience with only a few patients, an international registry is being established to accumulate information and enhance the numbers of patients that can be analyzed to answer the pending questions. The registry also will facilitate pathologic, molecular, and genetics research on the etiology and pathogenesis of the disease. Furthermore, availability of an international database will enhance awareness of this largely unrecognized condition among the medical community. Physicians are encouraged to enroll patients in the International Registry of ARVD/C.

Introduction In the present report, the electrophysiologic findings in patients with different types of variants of preexcitation, i.e., atriofascicular, nodofascicular, and fasciculoventricular fibers, and the results of radiofrequency catheter ablation using different target sites are described. Methods and results Twelve patients (mean age 36 +/- 17 years) with variants of the preexcitation syndromes underwent electrophysiologic study and radiofrequency catheter ablation. The atrial origin of atriofascicular pathways remote from the normal AV node was assessed by application of late atrial extrastimuli that advanced ("reset") the timing of the next QRS complex without anterograde penetration into the AV node. In patients with atriofascicular pathways, ablation of the accessory pathway or the retrograde fast AV node pathway was attempted. Ablation of the atriofascicular pathways was guided by a stimulus-delta wave interval mapping in the first five patients and by recording of atriofascicular pathway activation potentials in the next five patients. A nodofascicular pathway was suggested if VA dissociation occurred during tachycardia and if atrial extrastimuli failed to reset the tachycardia without anterograde penetration into the AV node. A fasciculoventricular connection was suggested if the proximal insertion of the accessory pathway was found to arise from the His bundle or bundle branches. The PR interval was expected within normal limits during sinus rhythm and the QRS complex to be slightly prolonged with a discrete slurring of the R wave, suggesting a small delta wave. Ten of the 12 patients had evidence for atriofascicular pathways and one patient each for a nodofascicular and fasciculoventricular pathway. In six patients, the atriofascicular pathways were successfully ablated, and in two patients, the retrograde fast AV node pathway. In one patient, a concealed right posteroseptal accessory AV pathway served as the retrograde limb and was successfully ablated. The nodofascicular pathway was shown to be a bystander during AV node reentrant tachycardia. After successful fast AV node pathway ablation resulting in marked PR prolongation, no preexcitation was present during sinus rhythm because of the proximal insertion of the nodofascicular pathway distal to the delay producing parts of the AV node. The proximal insertion of the fasciculoventricular pathway was suggested to arise distal to the AV node at the site of the penetrating AV bundle. The earliest ventricular activation at the His-bundle recording site indicated the ventricular insertion of this accessory connection into the ventricular summit. The fasciculoventricular connection gave rise to a fixed ventricular preexcitation and served as a bystander during orthodromic AV reentrant tachycardia incorporating a left-sided accessory AV pathway. Conclusion The majority of patients with variants of the preexcitation syndrome present with specialized atriofascicular pathways that seem to originate from remnants of the specialized AV ring tissue. Nodofascicular and fasciculoventricular pathways exist and may give rise to preexcitation, although their functional role in participation of clinical arrhythmias still needs to be elucidated. In the present study, both a fasciculoventricular pathway and a nodofascicular pathway acted as a bystander.

Ablation with Temperature-Controlled 5-French Catheters. Introduction: In the present study, we assessed the feasibility of radiofrequency (RF) ablation of accessory pathways and AV nodal reentrant tachycardias with novel 5-French catheters with 4-mm tip electrodes using established mapping criteria and temperature-controlled power output control. Methods and Results: In this prospective study, 60 consecutive adult patients (mean age 36 ± 20 years) with accessory pathways (n = 37; 24 left-sided) or AV nodal reentrant tachycardia (n = 23) underwent RF catheter ablation. A 5-French catheter with a 4-mm tip electrode and an embedded thermistor was used for RF application. The surface of the tip electrodes was 26 mm2 compared to 38 mm2 of 7-French catheters with 4-mm tip electrodes from the same catheter series. Power output was automatically and continuously adjusted according to the preset catheter tip temperature of 60° to 70°C. Pulse duration was 90 seconds. For left-sided accessory pathways, the retrograde route via the femoral artery was used. After removing the 5-French sheaths, only 4 hours of bed rest were advised. For ablation of AV nodal reentrant tachycardia, the so-called slow pathway was targeted for ablation. Acute success was achieved in 34 (92%) of 37 patients with accessory pathways and 23 (100%) of 23 patients with AV nodal reentrant tachycardia. A mean of 3 ± 4 RF pulses (median 2 pulses; range 1 to 20 pulses) was applied. The mean fluoroscopy time was 26 ± 21 minutes. No complete AV block or other procedure-related complications were observed. Recurrences occurred in 2 patients with accessory pathways and in 2 patients with AV nodal reentrant tachycardia during a follow-up of 9 ± 4 months. Conclusions: Temperature-controlled RF ablation of accessory pathways and AV nodal reentrant tachycardia in adults using 5-French catheters is feasible, effective, and safe. Ablation with 5-French catheters might help to reduce the complication rate of catheter ablation techniques.

KOTTKAMP, H., et.al.: Idiopathic Left Ventricular Tachycardia: New Insights into Electrophysiological Characteristics and Radiofrequency Catheter Ablation. Objectives: This study was performed to investigate the electrophysiological characteristics of idiopathic left ventricular tachycardia and to determine the feasibility of radiofrequency catheter ablation for nonpharmacological cure. Background: The underlying electrophysiological mechanism of idiopathic left ventricular tachycardia with right bundle branch block morphology and left-axis deviation is presently not known. Additionally, only limited data describing the results of radiofrequency catheter ablation for treatment of idiopathic left ventricular tachycardia so far exist. Methods: Electrophysiological studies and radiofrequency catheter ablation were performed in 5 patients (3 male and 2 female, mean age 31 ± 10 years) with idiopathic left ventricular tachycardia (cycle length 376 ± 72 msec). The patients had a history of recurrent palpitations of 4 ± 1 years and had been treated unsuccessfully with 2 ± 1 antiarrhythmic drugs. Sustained ventricular tachycardia with right bundle branch block morphology and left- or right-axis deviation was documented in all patients. Results: Inducibility with critically timed ventricular extrastimuli, inverse relationships of the coupling interval of the initiating extrastimulus and the interval to the first beat of the tachycardia, continuous diastolic or mid-diastolic electrical activity during ventricular tachycardia, and fragmented late potentials during sinus rhythm suggested reentrant activation as the underlying mechanism in three patients. On the other hand, induction dependent on isoproterenol infusion and rapid ventricular pacing and exercise inducibility indicated different electrophysiological characteristics in the remaining two patients. During electrophysiological study, intravenous verapamil terminated ventricular tachycardia in all patients, whereas ventricular tachycardia did not respond to intravenous adenosine, autonomic maneuvers, or intravenous β-blocking agent esmolol. Catheter mapping revealed earliest endocardial activation during ventricular tachycardia in different areas of the left ventricular septum being distributed from the base to the midapical portion of the septum in all patients. In 4 of 5 patients, radiofrequency catheter ablation (median number of pulses 4, range 1–9) resulted in complete abolition of idiopathic left ventricular tachycardia during a follow-up of 4–43 months (median 10) without antiarrhythmic drugs. Successful target sites for catheter ablation included continuous diastolic or mid-diastolic electrical activity during ventricular tachycardia and late potentials during sinus rhythm (2 patients), polyphasic fragmented presystolic potentials during ventricular tachycardia (1 patient), and pace mapping with identical QRS morphology compared to the ventricular tachycardia and “earliest” detectable activity during tachycardia (1 patient). No procedure related complications occurred. Conclusions: Two different patterns of electrophysiological properties of idiopathic left ventricular tachycardia were observed, indicating that this arrhythmia entity does not represent a homogeneous group. The “origin” of the tachycardias as identified by successful radiofrequency catheter ablation was located in different areas of the left ventricular septum and was distributed from the base to the mid-apical region. Radiofrequency catheter ablation was an effective and safe treatment modality in most of these patients. Distinct target site characteristics for successful catheter ablation including polyphasic diastolic activity during tachycardia and fragmented late potentials during sinus rhythm could be identified.