Cardiac arrhythmias in patients with Danon disease.

AIMS: Different cardiac arrhythmias have been suggested to be associated with Danon disease, e.g. Wolff-Parkinson-White syndrome. However, a systematic electrophysiological investigation of patients with Danon disease is lacking thus far. METHODS AND RESULTS: Seven patients with Danon disease (4 males, 35.8 ± 10.8 years; 3 females, 51.3 ± 19.9 years) from 3 different families were studied. In all patients, the presence of Danon disease was confirmed by western blot of biopsy material or genetic testing. The patients were characterized by 12-lead electrocardiogram (ECG), Holter ECG, echocardiography, and serial implantable cardioverter defibrillator (ICD) interrogations (in ICD recipients). All male patients underwent electrophysiological investigation (EP study). Asymptomatic ventricular tachyarrhythmias were documented in six of the seven patients. Moreover, 5 of the 7 patients suffered from atrial fibrillation (AF), with 1 of them experiencing thromboembolic stroke at the age of 30 years. In male patients, the initial QRS complex was characterized by a slurring upstroke and shortened PQ interval mimicking ventricular pre-excitation. One male patient showed initial QRS complex slurring with prolonged PR interval. However, the presence of an accessory pathway was excluded by an EP study in all patients. In female patients, initial QRS complex slurring was significantly less distinct. In four patients, ICD implantation was performed for primary prevention of sudden cardiac death. However, sustained ventricular arrhythmias were not documented in any of the patients. CONCLUSIONS: The present study indicates that the distinct surface ECG pattern in Danon disease is not associated with ventricular pre-excitation. Atrial fibrillation is frequently observed in these patients and may be associated with thromboembolic events in the young, while sustained ventricular arrhythmias occur less frequently than previously reported.

Primary Persistent Atrial Fibrillation: A Distinct Arrhythmia Subentity of an Ablation Population.

INTRODUCTION: Persistent atrial fibrillation (persAF) can occur either as a sustained arrhythmia that has progressed from initially paroxysmal AF or as primary persAF without a history of any spontaneously terminated episode. There is a paucity of data differentiating between the 2 different persAF entities. Thus, we prospectively evaluated baseline characteristics, electrophysiological features, and ablation outcome in these 2 patient cohorts. METHODS AND RESULTS: A total number of 154 consecutive persAF patients (63 ± 10 years, f = 42, longstanding persAF = 60) were characterized in terms of having primary persAF (P-persAF group) or persAF that secondarily progressed from paroxysmal AF (S-persAF group). All patients underwent de novo catheter ablation using the stepwise approach. PersAF entities were characterized by detailed patient history, sequential Holter monitoring, and reports of documented modes of AF conversion, respectively. The P-persAF group had a higher number of young patients (<50 years), a shorter AF history, and a higher number of congestive heart failure. The HATCH score did not differ between the groups. Procedural AF termination rate was significantly higher in S-persAF than in P-persAF patients (n = 55 [81%] vs. n = 58 [68%], P = 0.043). At 1-year follow-up, the arrhythmia-free survival after a single procedure was significantly lower in patients with P-persAF (26% vs. 43%, P = 0.016). Categorization to P-persAF was the strongest independent predictor of arrhythmia recurrence. CONCLUSIONS: P-persAF seems to be a specific arrhythmia entity that is associated with a lower AF-termination rate and a worse outcome after catheter ablation as compared to S-persAF.

[Surface ECG characteristics of right and left atrial flutter]. / Oberflächen-EKG-Charakteristika von rechts- und linksatrialem Vorhofflattern.

INTRODUCTION: Atrial tachycardia in virtually all areas of both atria has become more important in the clinical management of patients with previous complex atrial fibrillation ablation. Accurate interpretation of surface electrocardiogram (ECG) characteristics is of paramount importance to localize the origin of atrial tachycardia, particularly for planning interventional treatment. This article highlights the ECG features of different types of right and left atrial tachycardia. DEFINITION: Typical right atrial flutter through the cavotricuspid isthmus conducts septally in a cranial direction and demonstrates sawtooth-like flutter waves which start negative in II, III and aVF and then show a steep slope upwards to the isoelectric line. The flutter rate typically ranges between 240-250 beats/min. In contrast, right atrial flutter in a clockwise rotation, flutter around the vena cava inferior or superior and around a scar (e.g. after cardiac surgery) show positive or biphasic flutter waves (lower or upper loop reentry). Left atrial flutter waves (e.g. around the mitral valve or around the pulmonary veins) are very heterogeneous and are typically positive in V1 as the left atrium is located in the posterior mediastinum. CONCLUSION: Specific knowledge of flutter wave morphology in surface ECG facilitates planning and performance of the ablation strategy.

Arrhythmia Termination Versus Elimination of Dormant Pulmonary Vein Conduction as a Procedural End Point of Catheter Ablation for Paroxysmal Atrial Fibrillation: A Prospective Randomized Trial.

BACKGROUND: Pulmonary vein isolation (PVI) is still associated with a substantial number of arrhythmia recurrences in paroxysmal atrial fibrillation (AF). This prospective, randomized study aimed to compare 2 different procedural strategies. METHODS AND RESULTS: A total of 152 patients undergoing de novo ablation for paroxysmal AF were randomized to 2 different treatment arms. The procedure in group A consisted of PVI exclusively. In this group, all isolated PVs were challenged with adenosine to reveal and ablate dormant conduction. In group B, PVI was performed with the patient either in spontaneous or in induced AF. If AF did not terminate with PVI, ablation was continued by targeting extra-PV AF sources with the desired procedural end point of termination to sinus rhythm. Primary study end point was freedom from arrhythmia during 1-year follow-up. In group A, adenosine provoked dormant conduction in 31 (41%) patients with a mean of 1.6±0.8 transiently recovered PVs per patient. Termination of AF during PVI was observed in 31 (65%) patients, whereas AF persisted afterward in 17 (35%) patients. AF termination occurred in 13 (76%) patients by AF source ablation. After 1-year follow-up, significantly more group B patients were free of arrhythmia recurrences (87 versus 68%; P=0.006). During redo ablation, the rate of PV reconduction did not differ between both groups (group A: 55% versus group B: 61%; P=0.25). CONCLUSIONS: Elimination of extra-PV AF sources after PVI is superior to sole PV isolation with the adjunct of abolishing potential dormant conduction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02238392.

The Incidence of Audible Steam Pops Is Increased and Unpredictable With the ThermoCool® Surround Flow Catheter During Left Atrial Catheter Ablation: A Prospective Observational Study.

INTRODUCTION: Open irrigated radiofrequency (RF) ablation catheters with a porous tip (56 holes, TC-SF) permit delivering RF energy in a temperature-controlled mode without temperature rise. This prospective observational study investigated the association of different catheter parameters on the occurrence of audible steam pops during left atrial (LA) ablation. METHODS AND RESULTS: A total of 226 patients underwent TC-SF catheter ablation for atrial fibrillation. RF power delivery, impedance and catheter tip temperature were continually recorded throughout the ablation. Pulmonary vein isolation was performed with a maximum of 27 W and LA electrogram-guided or linear ablation with a maximum of 30 W. A total of 59 audible steam pops occurred, 2 of them resulting in pericardial tamponade. In the initial 89 patients, with an irrigation flow rate of 10 mL/min, 18 steam pops with one tamponade occurred in 12 (14%) patients. Subsequently, the irrigation flow rate was increased to 20 mL/min in the following 137 patients, resulting in the occurrence of 41 steam pops including one case of tamponade in a total of 30 (22%) patients. The maximal power was significantly higher in RF applications associated with a pop than those that did not. In only 12 (20%) steam pops, a significant impedance change occurred immediately before pop occurrence (4 [7%] impedance rise >10 ohm, 8 [13%] impedance drop >15 ohm). CONCLUSIONS: The TC-SF catheter does not provide sufficient feedback from the ablated tissue to prevent steam popping.

Body surface potential mapping for mapping and treatment of persistent atrial fibrillation.

Techniques facilitating individual mapping and ablation of arrhythmogenic substrates are desired to enhance our understanding of persistent atrial fibrillation (persAF) mechanisms as a prerequisite to increasing the success rates of single procedure persAF catheter ablation. The technique of body surface potential mapping (BSM) involves the use of multiple electrodes to collect the potentials over a large body surface area and, with the use of a computed tomography scan, it facilitates their correlation to a 3D model of the atrial structures. During AF,the visualization and localization of AF driver activity, both reentrant and focal wavefronts, is possible with this technique. The ECVUE system from CardioInsight was examined for this indication in clinical studies and showed a termination rate of persAF of 63 % in a large multicenter trial (AFACART) with a promising low recurrence rate during follow-up. From our initial experience, the system appears to be effective in persAF patients who have continuous AF for less than 1 year. However, the utility of the system for highly challenging cases like long-standing persistent AF and patients with very short AF cycle length remains to be explored. Further studies are needed to confirm these data and answer the multitude of open questions in this field.

Reduction of ICD shock burden by eliminating back-up pacing induced ventricular tachyarrhythmias.

INTRODUCTION: Implantable cardioverter defibrillators (ICD) may have the capacity to provoke or worsen ventricular tachyarrhythmias (VT). It has been reported that ICD shocks by itself can increase mortality. This study aimed to determine the role of back-up pacing-induced VT (PIT) in the overall ICD shock burden by avoiding pause-related ventricular back-up pacing. METHODS AND RESULTS: A population of 550 single-chamber ICD patients was studied. Of them, 17 (3%, 69 ± 16 years, 14 male) patients had documented episodes of PIT. A total of 431 VT episodes were documented including 89 (21%) due to PIT. In 3 patients, VT events were exclusively PITs. After ≥2 documented PITs, the pacing output for VVI pacing was set to a subthreshold level resulting in noncapturable ventricular back-up pacing. All other device parameters remained unchanged to prove a potential proarrhythmic effect of pause related back-up pacing. During a follow-up of 99 ± 39 months after reducing the pacing output to a subthreshold level, no further episodes of PIT were observed (P < 0.001). Moreover, with the prevention of PITs, the ICD shock burden decreased significantly (pre: 150 vs. post: 18, P < 0.001). However, a single event of pause-induced VT occurred due to missing back-up pacing. CONCLUSIONS: PIT is a frequent mechanism of VTs in ICD patients resulting in a substantially increased shock burden. Elimination of pause-related back-up pacing by subthreshold pacing output effectively abolishes PIT and thus significantly reduces ICD shock burden.

Cross-inhibition of interferon-induced signals by GM-CSF through a block in Stat1 activation.

We investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on biologic signals induced by interferon-alpha (IFN-alpha) and IFN-gamma. In hematopoietic cell lines, IFN-induced signaling was investigated by Western blotting, electrophoretic mobility shift assays (EMSA), flow cytometry, protein-tyrosine phosphatase (PTP) assays, and RT-PCR. GM-CSF inhibited IFN-alpha-induced and IFN-gamma-induced Stat1 tyrosine phosphorylation in a time-dependent manner. EMSA showed that GM-CSF inhibited IFN-alpha-induced and IFN-gamma-induced IFN-gamma activator sequence (GAS) binding activity. As a consequence, IFN-induced transcription of the early response gene, IFN-stimulated gene 54 (ISG54), was inhibited. The expression of IFN regulatory factor-1 (IRF-1) and MHC class I antigens was downregulated at protein levels in hematopoietic cell lines (U937, THP1). In contrast to GM-CSF, granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) did not influence the IFN-induced Stat1 activation. To explore the molecular mechanism of suppression of Stat1 tyrosine phosphorylation, we investigated the induction and activation of cytokine-inducible SH2-containing protein/suppressor of cytokine signaling (CIS/SOCS) molecules and phosphatases on GM-CSF treatment. In contrast to G-CSF and IL-3, GM-CSF strongly induced the expression of CIS1 and SOCS2 at mRNA levels, but overexpression of CIS1 or SOCS2 in HEK293 cells did not show inhibition of Stat1 tyrosine phosphorylation upon IFN treatment. In PTP assays, on GM-CSF incubation, no enhanced src homology 2 domain tyrosine phosphatase 1 and 2 (SHP1 and SHP2) activity was detectable. However, GM-CSF-induced downregulation of Tyk2 and Jak1 tyrosine phosphorylation as well as Tyk2 protein levels likely contributed to the reduced Stat1 tyrosine phosphorylation. In hematopoietic cells, GM-CSF antagonizes IFN-induced signals by a block in Stat1 activation.