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Mechanisms of Pulmonary Vein Reconnection After Radiofrequency Ablation of Atrial FibrillationIntroduction Pulmonary vein reconnection (PVR) is an important cause of AF recurrence after ablation. With the advent of force sensing catheters, catheter–tissue contact can be determined quantitatively. Since contact force (CF) plays a major role in determining the characteristics of RF lesion, we prospectively assessed the mechanisms of PVR with regard to catheter-contact and lesion distances in patients undergoing AF ablation. Methods and Results Forty symptomatic AF patients underwent wide circumferential PV isolation (PVI) with SmartTouch™ CF catheter. The exact locations of acute PVI and spontaneous or adenosine-provoked PVR were annotated on CARTO. One thousand nine hundred and twenty-six RF lesions isolated 153 PVs. PVR occurred in 35 (23%) PVs: 22 (63%) adenosine-provoked and 13 (37%) spontaneous. CF was significantly lower at PVR versus PVI sites for RF lesions within 6 mm from these sites: mean CF 5 versus 11 g (P < 0.0001) and force–time integral (FTI) 225 versus 415 gs (P < 0.0001); 86% of PVR occurred with a mean CF < 10 g (FTI < 400 gs); and the remaining 14% occurred at ablation sites with a long interlesion distance (≥5 mm) despite mean CF ≥ 10 g. Eighty percent of PVR sites were located anteriorly. There were no significant differences in regard to arrhythmia freedom between the patients without (69%) versus with PVR (67%; P = 1.0). Conclusions Acutely durable PVI can be achieved when RF lesions are delivered with a mean CF ≥ 10 g and an interlesion distance

Objectives This study prospectively evaluated the role of a novel 3-dimensional, noninvasive, beat-by-beat mapping system, Electrocardiographic Mapping (ECM), in facilitating the diagnosis of atrial tachycardias (AT). Background Conventional 12-lead electrocardiogram, a widely used noninvasive tool in clinical arrhythmia practice, has diagnostic limitations. Methods Various AT (de novo and post-atrial fibrillation ablation) were mapped using ECM followed by standard-of-care electrophysiological mapping and ablation in 52 patients. The ECM consisted of recording body surface electrograms from a 252-electrode-vest placed on the torso combined with computed tomography–scan-based biatrial anatomy (CardioInsight Inc., Cleveland, Ohio). We evaluated the feasibility of this system in defining the mechanism of AT—macro–re-entrant (perimitral, cavotricuspid isthmus-dependent, and roof-dependent circuits) versus centrifugal (focal-source) activation—and the location of arrhythmia in centrifugal AT. The accuracy of the noninvasive diagnosis and detection of ablation targets was evaluated vis-a-vis subsequent invasive mapping and successful ablation. Results Comparison between ECM and electrophysiological diagnosis could be accomplished in 48 patients (48 AT) but was not possible in 4 patients where the AT mechanism changed to another AT (n = 1), atrial fibrillation (n = 1), or sinus rhythm (n = 2) during the electrophysiological procedure. ECM correctly diagnosed AT mechanisms in 44 of 48 (92%) AT: macro–re-entry in 23 of 27; and focal-onset with centrifugal activation in 21 of 21. The region of interest for focal AT perfectly matched in 21 of 21 (100%) AT. The 2:1 ventricular conduction and low-amplitude P waves challenged the diagnosis of 4 of 27 macro–re-entrant (perimitral) AT that can be overcome by injecting atrioventricular node blockers and signal averaging, respectively. Conclusions This prospective multicenter series shows a high success rate of ECM in accurately diagnosing the mechanism of AT and the location of focal arrhythmia. Intraprocedural use of the system and its application to atrial fibrillation mapping is under way.

Enhanced Efficiency of a Novel Porous Tip Irrigated RF Ablation Catheter Introduction Irrigated tip radiofrequency (RF) catheter ablation is the most frequently used technology for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficiency and the safety of 2 different open irrigated tip RF ablation catheters. Methods and Results A total of 160 patients with symptomatic AF (29% persistent, 68% male, 61 ± 10 years) were randomized to circumferential PVI using 2 different irrigated tip catheters: (1) the novel Thermocool SF® with a porous tip (56 holes) or (2) the Thermocool® catheter with 6 irrigation holes at the distal tip in both power- and temperature-controlled modes. PVI procedural time and RF duration were significantly shorter with SF® versus Thermocool® catheter: 104.5 versus 114 minutes (P = 0.023) and 35.4 minutes versus 39.9 minutes (P < 0.001), respectively. Similarly, the total fluoroscopy time and dose were shorter with SF® versus. Thermocool® catheter: 21 minutes versus 24 minutes (P = 0.02) and 1014.5 μGy*m2 versus 1377 μGy*m2 (P < 0.0001), respectively. Irrigation volume was lower with SF®: 600 mL versus 1100 mL, (P < 0.0001) and the rates of complications were not significantly different (0.6% vs 0.49%, P = 0.66). At 20.5 ± 7.5 months follow-up, there were no significant differences with regard to arrhythmia freedom between SF® (59.2%) and TC® groups (59.3%), (P = 0.61). Conclusions Using the novel irrigated tip SF catheter, PVI is achieved within a shorter ablation and procedural durations. The underlying mechanisms and potential differences in RF lesion size remain to be elucidated.

This article reviews the literature on various techniques in the ablation of persistent AF, with the aim of highlighting the role of intraprocedural arrhythmia termination, defined as conversion to sinus rhythm or intermediate atrial tachycardia, in the predictability of arrhythmia recurrence. Because arrhythmia termination is not observed universally as a procedural end point, only those studies wherein it has been specifically reported, and its predictive role in arrhythmia recurrence is considered, are described.

This article reviews the literature on various techniques in the ablation of persistent AF, with the aim of highlighting the role of intraprocedural arrhythmia termination, defined as conversion to sinus rhythm or intermediate atrial tachycardia, in the predictability of arrhythmia recurrence. Because arrhythmia termination is not observed universally as a procedural end point, only those studies wherein it has been specifically reported, and its predictive role in arrhythmia recurrence is considered, are described.

To evaluate the safety and outcomes of mitral isthmus (MI) linear ablation with temporary spot occlusion of the coronary sinus (CS). Background: CS blood flow cools local tissue precluding transmurality and bidirectional block across MI lesion.

Ablation data are currently limited to a small, select population of patients with refractory ventricular fibrillation (VF) storm with medium duration of follow-up. It might be too early to recommend against the implantation of implantable cardioverter-defibrillators in patients with successfully ablated medically refractory index VF storm. Further study is needed to define the role of ablation in cases that are not medically refractory.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is responsible for the highest number of rhythm-related disorders and cardioembolic strokes worldwide. Intracardiac signal analysis during the onset of paroxysmal AF led to the discovery of pulmonary vein as a triggering source of AF, which has led to the development of pulmonary vein ablation — an established curative therapy for drug-resistant AF. Complex, multicomponent and rapid electrical activity widely involving the atrial substrate characterizes persistent/permanent AF. Widespread nature of the problem and complexity of signals in persistent AF reduce the success rate of ablation therapy. Although signal processing applied to extraction of relevant features from these complex electrograms has helped to improve the efficacy of ablation therapy in persistent/permanent AF, improved understanding of complex signals should help to identify sources of AF and further increase the success rate of ablation therapy.

Background— The remote magnetic navigation system (MNS) has been used with a nonirrigated magnetic catheter for atrial fibrillation (AF) ablation. The objective of this study was to evaluate the feasibility and efficiency of the newly available irrigated tip magnetic catheter for index pulmonary vein isolation (PVI) in patients with paroxysmal AF (PAF). Methods and Results— Between January 2008 and June 2009, 30 consecutive patients with drug-resistant PAF underwent circular mapping catheter-guided PVI with MNS (MNS group). The outcomes were compared retrospectively with those of a conventional hand-controlled ablation technique during the same period in 44 consecutive patients (manual group). All 4 pulmonary veins were successfully isolated in both groups except in 4 patients in the MNS group. Radiofrequency and procedure duration were higher in the MNS group (60±27 versus 43±16 minutes; P =0.0019) than in the manual group (246±50 versus 153±51 minutes; P P =0.0002). At 12-month follow-up after a single procedure, 69.0% of the patients in MNS group and 61.8% of patients in manual group were free of atrial tachyarrhythmia without antiarrhythmic drugs. There was no significant difference in the atrial tachyarrhythmia-free survival between the 2 groups ( P =0.961). Cardiac tamponade occurred in 1 patient in the manual group. Conclusions— In patients with PAF, MNS-guided PVI with the newly available irrigated tip magnetic catheter backed up with manual ablation whenever required is feasible. However, it requires longer ablation, fluoroscopy, and procedural times than the conventional approach in the early experience stage.

p21 Cip1 (p21) controls cell cycle progression and apoptosis in mature endothelial cells (ECs) and regulates size and cycling of the hematopoietic progenitor cell pool. Because circulating endothelial progenitor cells (EPCs) contribute to postnatal neovascularization in addition to mature ECs, we investigated the regulation of ECs and EPCs in p21-deficient mice. Mature aortic EC proliferation was increased in homozygous p21 −/− and heterozygous p21 +/− mice, in which p21 protein levels are reduced to one third of wild-type (WT). In contrast, apoptosis sensitivity was increased by 3.5-fold only in p21 −/− , but not in p21 +/− mice. Consistently, in vivo apoptosis of ECs within areas of neovascularization was elevated in p21 −/− but not in p21 +/− mice. EPC numbers were elevated 2-fold in p21 −/− mice compared with WT ( P −/− mice ( P +/− mice. As the integrative endpoint, in vivo neovascularization reflecting all p21-affected parameters was increased over WT only in p21 +/− ( P −/− mice. In conclusion, reduced p21 protein levels of mice lacking one p21 allele are associated with increased proliferation of ECs and EPCs, whereas survival of ECs to apoptotic stimuli in vitro and in vivo is not impaired. Under these conditions, neovascularization was increased. In contrast, complete p21 deficiency did not result in an increased neovascularization despite increased mature EC and EPC proliferation. This may be due to the sensitization of ECs against apoptosis.

Pulmonary vein reconnection (PVR) is an important cause of AF recurrence after ablation. With the advent of force sensing catheters, catheter-tissue contact can be determined quantitatively. Since contact force (CF) plays a major role in determining the characteristics of RF lesion, we prospectively assessed the mechanisms of PVR with regard to catheter-contact and lesion distances in patients undergoing AF ablation.Forty symptomatic AF patients underwent wide circumferential PV isolation (PVI) with SmartTouch™ CF catheter. The exact locations of acute PVI and spontaneous or adenosine-provoked PVR were annotated on CARTO. One thousand nine hundred and twenty-six RF lesions isolated 153 PVs. PVR occurred in 35 (23%) PVs: 22 (63%) adenosine-provoked and 13 (37%) spontaneous. CF was significantly lower at PVR versus PVI sites for RF lesions within 6 mm from these sites: mean CF 5 versus 11 g (P 0.0001) and force-time integral (FTI) 225 versus 415 gs (P 0.0001); 86% of PVR occurred with a mean CF 10 g (FTI 400 gs); and the remaining 14% occurred at ablation sites with a long interlesion distance (≥5 mm) despite mean CF ≥ 10 g. Eighty percent of PVR sites were located anteriorly. There were no significant differences in regard to arrhythmia freedom between the patients without (69%) versus with PVR (67%; P = 1.0).Acutely durable PVI can be achieved when RF lesions are delivered with a mean CF ≥ 10 g and an interlesion distance 5 mm. The majority of PVR occur anteriorly due to inadequate CF or long interlesion distances.

Transseptal puncture (TP) is a prerequisite for LA ablations. LA access can be gained by catheter probing in case of PFO (trans-PFO method) or puncture of the interatrial septum (IAS) using a transseptal needle. A 2nd access can again be gained via PFO, a 2nd TP or catheter probing of the previous puncture site (probe-TS method). This study investigates the risk factors and complications related to the mode of transseptal access.From August 2010 to August 2012, a total of 544 LA ablations, were performed. The mode of LA access was either a double TP or a single TP followed by the probe-TS or the trans-PFO method, respectively. TP was always guided by TEE and was successfully performed without complications in all cases. In contrast, 6/410 patients (1.5%) in whom catheter probing was performed (probe-TS, n = 4, trans-PFO, n = 2) had a dissection of the superior IAS originating from inside the oval fossa (n = 5) or perforation above the oval fossa (n = 1). Perforation into the pericardial space occurred in 4/6 patients, leading to one cardiac tamponade. In 5/6 patients, LA ablation was successfully completed, after repeated TP, despite effective anticoagulation. Patients with complications had the following characteristics: LA size 46 ± 4 mm, persistent AF (5/6), a repeat transseptal procedure (3/6) and a right-sided pouch (RSP, 5/6).Interatrial septum dissection/perforation, occasionally with perforation into the pericardial space, is an unreported complication of TP, especially with the catheter-probing techniques. An RSP is an unrecognized risk factor in this context and can be visualized by TEE.

Irrigated tip radiofrequency (RF) catheter ablation is the most frequently used technology for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficiency and the safety of 2 different open irrigated tip RF ablation catheters.A total of 160 patients with symptomatic AF (29% persistent, 68% male, 61 ± 10 years) were randomized to circumferential PVI using 2 different irrigated tip catheters: (1) the novel Thermocool SF(®) with a porous tip (56 holes) or (2) the Thermocool(®) catheter with 6 irrigation holes at the distal tip in both power- and temperature-controlled modes. PVI procedural time and RF duration were significantly shorter with SF(®) versus Thermocool(®) catheter: 104.5 versus 114 minutes (P = 0.023) and 35.4 minutes versus 39.9 minutes (P0.001), respectively. Similarly, the total fluoroscopy time and dose were shorter with SF(®) versus. Thermocool(®) catheter: 21 minutes versus 24 minutes (P = 0.02) and 1014.5 μGy*m(2) versus 1377 μGy*m(2) (P0.0001), respectively. Irrigation volume was lower with SF(®): 600 mL versus 1100 mL, (P0.0001) and the rates of complications were not significantly different (0.6% vs 0.49%, P = 0.66). At 20.5 ± 7.5 months follow-up, there were no significant differences with regard to arrhythmia freedom between SF(®) (59.2%) and TC® groups (59.3%), (P = 0.61).Using the novel irrigated tip SF catheter, PVI is achieved within a shorter ablation and procedural durations. The underlying mechanisms and potential differences in RF lesion size remain to be elucidated.

International audience; MDCT/MRI Fusion for the Guidance of VT Ablation. Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar-related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D-mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation.Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D-mapping systems and registered to high-density endocardial and epicardial maps. Low-voltage areas (

Background— Complex fractionated atrial electrograms (CFAE) are targets of atrial fibrillation (AF) ablation. Serial high-density maps were evaluated to understand the impact of activation direction and rate on electrogram (EGM) fractionation. Methods and Results— Eighteen patients (9 persistent) underwent high-density, 3-dimensional, left-atrial mapping (>400 points/map) during AF, sinus (SR), and CS-paced (CSp) rhythms. In SR and CSp, fractionation was defined as an EGM with ≥4 deflections, although, in AF, CFE-mean 1.0 mV) at all sites. During AF, the EGM voltage was higher at continuous CFAE sites than at non-CFAE sites (0.53 mV (Q1, Q3: 0.33 to 0.83) versus 0.30 mV (Q1, Q3: 0.18 to 0.515), P P Conclusions— The distribution of fractionated EGMs is highly variable, depending on direction and rate of activation (SR versus CSp versus AF). Fractionation in SR and CSp rhythms mostly resulted from wave collision. All sites with continuous fractionation in AF displayed normal voltage in SR, suggesting absence of structural scar. Thus, many fractionated EGMs are functional in nature, and their sites dynamic.

BACKGROUND: J waves are the hallmark of both inferolateral early repolarization (ER) and Brugada syndrome. While ajmaline a class 1a antiarrhythmic drug accentuates the J wave in Brugada syndrome its effect on ER is unreported. OBJECTIVE: To describe the effect of ajmaline on the electrocardiogram in ER. METHODS: We analyzed electrocardiograms before and after the administration of intravenous ajmaline (1 mg/kg) in 31 patients with ER 21 patients with Brugada type 1 electrocardiogram (Br) and 22 controls. ER was defined as J point elevation of =1 mm with QRS slurring or notching in =2 inferolateral leads (I aVL II III aVF V4 V6). RESULTS: Ajmaline decreased mean J wave amplitude in the ER group from 0.2 ± 0.15 mV at baseline to 0.08 ± 0.09 mV (P < .001). The QRS width prolonged significantly in all 3 groups but the prolongation was significantly less in the ER group (+21 ms) than in the Br group (+36 ms; P < .001) or controls (+28 ms; P = .010). Decrease in mean inferolateral R wave amplitude was similar in all the groups (ER group 0.14 mV; Br group 0.11 mV; controls 0.13 mV; P = ns) but mean inferolateral S wave amplitude increased significantly less in the ER group (ER group +0.14 mV; Br group +16 mV; controls +0.20 mV; P < .001). CONCLUSIONS: Ajmaline significantly decreases the J wave amplitude in ER and prolongs the QRS width significantly less than in patients with Br. This indicates a different pathogenesis for both disorders. The altered terminal QRS vector probably is responsible for the decrease in the J wave amplitude in ER although a specific effect of ajmaline on J waves cannot be excluded.

Background— Achievement of complete conduction block across left mitral isthmus (MI) is challenging. Anticipation of perimitral conduction time (PMCT) associated with MI block may expedite this procedure. We evaluated the relationship between the preprocedural variables and the quantum of PMCT in patients with bidirectionally blocked MI. Methods and Results— We reviewed clinical and echocardiographic parameters in 290 consecutive patients with confirmed bidirectional MI block during atrial fibrillation (AF) ablation. PMCT was defined as the temporal delay to the latest of the double potentials on the line of block while pacing posteroseptal to it in the left atrium (LA). LA size and type of AF significantly influenced PMCT in multivariate analysis. A cumulative score based on LA size (0≦45 mm; 1>45 mm) and type of AF (0: paroxysmal; 1=nonparoxysmal) ranged from 0 to 2. PMCT was directly correlated to the cumulative score (0: 169 ms; n=78; 95% confidential interval, 156 to 181); 1: 187 ms; n=103; 95% confidential interval, 178 to 196; 2: 209 ms; n=109; 95% confidential interval, 200 to 217). In 61 patients who underwent AF ablation twice, the difference between 2 PMCT values was 173 ms predicted bidirectional block with an accuracy of 86%. Conclusions— LA size and AF type significantly influence PMCT in patients undergoing successful MI ablation. These parameters can be used to predict the time value associated with MI block, preprocedurally.

Atrial fibrillation (AF) is the most common heart rhythm problem and a leading cause of morbidity and mortality. Serious complications associated with this disorder include cardioembolic stroke, heart failure, and death. The worldwide prevalence of AF is rapidly increasing owing to aging of the population. Abnormal impulse formation in the pulmonary veins is known to trigger paroxysmal AF and radiofrequency isolation of these veins is recommended in drug-refractory AF. Active pharmacological research is directed towards selectively targeting the culprit venous cells. Persistent AF is more likely to be an atrial disease. Intrinsic and extrinsic stressors are believed to cause electrostructural alterations in the atrial tissue leading to profibrillatory state. Further research will elucidate the role of stressors and help develop biomarkers to guide early management of AF. An ideal therapy for AF aims at prevention of onset and progression of AF and reduction of AF-related symptoms, hospitalization, stroke, and mortality.

A 65-year-old man with a 1-year clinical history of recurrent flush and diarrhoea was admitted to our hospital for severe right-sided heart failure. Abdominal computed tomography scan showed carcinoid tumour originating from gut with hepatic metastases. Chemotherapy with octreotid and arterial chemo-embolization of the hepatic metastases was initiated. Transthoracic echocardiography revealed severe tricuspid and pulmonary valve regurgitation …

A 19-year-old girl was referred to our cardiology department for catheter ablation (isolation of the pulmonary veins) of paroxysmal atrial fibrillation (AF). The diagnosis was made upon a 12-lead ECG of the arrhythmia documented in the emergency room. The ECG showed an irregular tachycardia without wide QRS complexes. Careful assessment revealed the irregularity of the rhythm was a sweep artifact due to a mechanic failure of the ECG-machine to advance the article smoothly. During EP study a concealed anteroseptal accessory pathway causing an orthodromic AV reentrant tachycardia was eliminated by radio-frequency ablation. This example emphasizes the need for careful assessment of an ECG tracing, including printed legends and technical data.

The protein kinase Akt is activated by growth factors and promotes cell survival and cell cycle progression. Here, we demonstrate that Akt phosphorylates the cell cycle inhibitory protein p21(Cip1) at Thr 145 in vitro and in intact cells as shown by in vitro kinase assays, site-directed mutagenesis, and phospho-peptide analysis. Akt-dependent phosphorylation of p21(Cip1) at Thr 145 prevents the complex formation of p21(Cip1) with PCNA, which inhibits DNA replication. In addition, phosphorylation of p21(Cip1) at Thr 145 decreases the binding of the cyclin-dependent kinases Cdk2 and Cdk4 to p21(Cip1) and attenuates the Cdk2 inhibitory activity of p21(Cip1). Immunohistochemistry and biochemical fractionation reveal that the decrease of PCNA binding and regulation of Cdk activity by p21(Cip1) phosphorylation is not caused by altered intracellular localization of p21(Cip1). As a functional consequence, phospho-mimetic mutagenesis of Thr 145 reverses the cell cycle-inhibitory properties of p21(Cip1), whereas the nonphosphorylatable p21(Cip1) T145A construct arrests cells in G(0) phase. These data suggest that the modulation of p21(Cip1) cell cycle functions by Akt-mediated phosphorylation regulates endothelial cell proliferation in response to stimuli that activate Akt.