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.

Leukocyte-platelet aggregates-a phenotypic characterization of different stages of peripheral arterial disease.

The formation of monocyte-platelet aggregates and neutrophil-platelet aggregates (MPA and NPA, respectively) is influenced by inflammation, but also might contribute to an exacerbation of inflammatory responses in atherosclerotic plaque. The purpose of this study was to analyze MPA and NPA proportions in regard to different stages of peripheral arterial disease (PAD). Forty-five patients with intermittent claudication (IC) (3 groups: Rutherford (R)-1, R-2, and R-3; each n = 15), 20 patients with critical limb ischemia (CLI) (Rutherford 5 (40%) and 6 (60%)), and 20 healthy controls were studied. Analyses of monocyte (Mon) subpopulations (CD14++CD16- (classical) Mon1, CD14++CD16+ (intermediate) Mon2, CD14+CD16++ (non-classical) Mon3), MPA, and NPA was performed from whole blood by flow cytometry. Controls showed an increased proportion of the Mon1 subpopulation (p < 0.001), whereas CLI patients showed a significant increase of the Mon2 subpopulation compared to controls, R-1, or R-2 patients (p < 0.0001). For the Mon3 subpopulation, CLI and R-3 patients showed an increased proportion (p < 0.05). MPA formation with the proinflammatory Mon2 and Mon3 subpopulations was increased in CLI patients (both p < 0.01). Similarly, NPA was significantly increased in CLI patients (p < 0.05). Serological markers of inflammation and procoagulation (fibrinogen [r = 0.459, p < 0.001], soluble triggering receptor expressed on myeloid cells (sTREM-1) [r = 0.237, p < 0.05] and P-Selectin [r = 0.225, p < 0.05]) correlated directly with MPA formation on the Mon2 subpopulation. We found an association of inflammatory and procoagulatory markers with increased formation of MPA on the Mon2 subpopulation. Since R-3 patients also had significantly increased MPA, one can speculate that the inflammatory burden might promote an aggravation of the disease.

Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia.

BACKGROUND: Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells. METHODS: Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months. RESULTS: In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = −0.266; p < 0.01) (EPC: r = −0.297; p < 0.001)], CRP (TEM: r = −0.283; p < 0.01) (EPC: r = −0.260; p < 0.01). CONCLUSIONS: We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.

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.

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.

Prognostic role of subsequent atrial tachycardias occurring during ablation of persistent atrial fibrillation: a prospective randomized trial.

BACKGROUND: The role of subsequent atrial tachycardias (AT) in the context of persistent atrial fibrillation (AF) remains undetermined. This study evaluated the prognostic role of subsequent ATs for arrhythmia recurrences after catheter ablation of persistent AF. METHODS AND RESULTS: A total of 110 patients with persistent AF (63±9 years; 22 women; 61 long-lasting persistent AF) underwent pulmonary vein isolation followed by electrogram-guided ablation. After AF terminated to AT, patients were separated by the randomization protocol to receive either direct cardioversion (group A) or further ablation of subsequent ATs to sinus rhythm (group B). After a mean follow-up of 20.1±13.3 months after the first procedure, significantly more group B patients were in sinus rhythm as compared with patients in group A (30 [57%] versus 18 [34%]; P=0.02). Moreover, recurrences of AF were significantly less frequent of group B than in group A patients (10 [19%] versus 26 [49%]; P=0.001). After the last procedure (follow-up, 34.0±6.4 months), significantly more group B patients were free of AF as compared with patients of group A (49 [92%] versus 39 [74%]; P=0.01). The proportion of AT recurrences did not differ between the 2 groups after the first and final procedures. The strongest predictor for an arrhythmia-free survival after a single procedure was randomization to the procedural end point of termination to sinus rhythm by elimination of subsequent ATs (P=0.004). CONCLUSIONS: Catheter ablation of subsequent ATs increases freedom from AF but not AT, suggesting a contributing role of subsequent ATs in the mechanisms of persistent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01896570.

Long-term single- and multiple-procedure outcome and predictors of success after catheter ablation for persistent atrial fibrillation.

BACKGROUND: Stepwise ablation is an effective treatment for persistent atrial fibrillation (AF), although it often requires multiple procedures to eliminate recurrent arrhythmias. OBJECTIVE: This study evaluated single- and multiple-procedure long-term success rates and potential predictors of a favorable single-procedure outcome of stepwise ablation for persistent AF. METHODS: This study comprised 395 patients with persistent AF (duration 16 months) undergoing de novo catheter ablation using the stepwise approach. Procedural success was defined as the absence of any arrhythmia recurrence. Patient characteristics and electrophysiological parameters were analyzed with respect to single- and multiple-procedure outcomes. RESULTS: After a follow-up of 27 ± 7 months, 108 (27%) patients were free of arrhythmia recurrences with a single procedure. After 2.3 ± 0.6 procedures, 312 (79%) patients were free of arrhythmia with concomitant antiarrhythmic treatment in 38% (23% on ß-blocker). Female gender, duration of persistent AF, and congestive heart failure were predictive for the outcome after first ablation. However, the strongest predictors for single-procedure success were longer baseline AF cycle length (CL) and procedural AF termination. Moreover, procedural AF termination during the index procedure also predicted a favorable outcome after the last procedure, while the existence of congestive heart failure was associated with an increased risk for eventual arrhythmia recurrences. CONCLUSIONS: Single-procedure long-term success is anticipated in approximately a quarter of patients undergoing de novo ablation of persistent AF. Baseline AFCL emerged as the strongest predictor of single-procedure success, while AF termination during index ablation predicts the overall outcome. However, an overall success rate of 79% is achievable with multiple procedures.

Atrial fibrillation cycle length is a sole independent predictor of a substrate for consecutive arrhythmias in patients with persistent atrial fibrillation.

BACKGROUND: Termination of persistent atrial fibrillation (AF) can be achieved through ablation, with the majority of patients terminating to an atrial tachycardia (AT) and fewer directly to sinus rhythm (SR). We aimed to identify potential predictors for the existence of a substrate for AT on termination to SR. METHODS AND RESULTS: We assessed 95 persistent AF patients (age, 60+/-10 years) who underwent catheter ablation to the end point of AF termination. Forty patients terminated directly to SR (SRterm) and 55 to ATs (ATterm). Compared with the ATterm group, the SRterm group were younger (56+/-10 versus 63+/-9 years, P=0.001), had shorter durations of AF before ablation (9+/-26 versus 14+/-20 months, P<0.001), smaller left atrial diameters (41+/-5 versus 45+/-5 mm, P=0.015), and longer baseline AF cycle lengths (178+/-23 versus 159+/-31 ms, P=0.005). However, AF cycle length was the sole independent predictor of direct termination to SR. The most frequent AF termination site in SRterm patients was the pulmonary veins (53%), whereas in ATterm patients this was within the left atrium (58%). After follow-up of 12+/-6 months, there was a trend toward a greater proportion of patients in SR among those who terminated directly to SR after a single procedure. The most frequent type of recurrence was paroxysmal AF in SRterm patients and AT in ATterm patients. CONCLUSIONS: Patients who terminate to SR through ablation without an intermediate AT are characterized by a less altered arrhythmogenic substrate. Baseline AF cycle lengths emerged as a sole independent predictor of a substrate for consecutive arrhythmias.

Characterization, mapping, and catheter ablation of recurrent atrial tachycardias after stepwise ablation of long-lasting persistent atrial fibrillation.

BACKGROUND: Atrial tachycardias (AT) often occur after ablation of long-lasting persistent AF (CAF) and are difficult to treat conservatively. This study evaluated mechanisms and success rates of conventional mapping and catheter ablation of recurrent ATs occurring late after stepwise ablation of CAF. METHODS AND RESULTS: A total of 320 patients underwent de novo ablation of CAF using a stepwise ablation approach in 2006 to 2007 at our institution. This study comprised patients who presented with recurrent ATs at their first redo procedure after initial de novo CAF ablation. All procedures were guided by conventional mapping techniques exclusively. Sixty-one patients (63+/-10 years, 14 women) presented with their clinical AT at their redo procedure 7.7+/-4.4 months after initial de novo CAF ablation. A total of 133 ATs (2.2+/-0.9 per patient) were mapped. Forty-four (72%) were due to reentry; 17 (28%) were focal ATs. Reentry ATs were mainly characterized as roof and perimitral flutter (43% and 34%, respectively). Focal ATs mainly originated from the great thoracic veins (pulmonary veins: 41%, coronary sinus: 23%). Forty-five (74%) patients had conduction recovery of at least 1 pulmonary vein (mean, 1.2+/-0.8). Overall, 124 (93%) ATs could be ablated successfully. The mean procedure duration was 181+/-59 minutes, with a mean fluoroscopy time of 45+/-21 minutes. After a mean follow-up of 21+/-4 months, 50 (82%) patients were free of any arrhythmia recurrences after a single redo procedure. CONCLUSIONS: Although late recurrent ATs may have complex mechanisms, catheter ablation guided exclusively by conventional techniques is highly effective with excellent acute and long-term success rates.