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.

A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study.

AIMS: Endothelial dysfunction and plaque formation are features of atherosclerosis. Inhibition of L-type calcium channels or HMG-CoA pathway improves endothelial function and reduces plaque size. Thus, we investigated in stable coronary artery disease (CAD) the effects of a calcium antagonist on coronary endothelial function and plaque size. METHODS AND RESULTS: In 454 patients undergoing PCI, acetylcholine (10(-6) to 10(-4) M) was infused in a coronary segment without significant CAD. Changes in coronary diameter were measured and an intravascular ultrasound examination (IVUS) was performed. On top of statin therapy, patients were randomized in a double-blind fashion to placebo or nifedipine GITS 30-60 mg/day and followed for 18-24 months. Blood pressure was lower on nifedipine than on placebo by 5.8/2.1 mmHg (P < 0.001) as was total and LDL cholesterol (4.8 mg/dL; P = 0.495), while HDL was higher (3.6 mg/dL; P = 0.026). In the most constricting segment, nifedipine reduced vasoconstriction to acetylcholine (14.0% vs. placebo 7.7%; P < 0.0088). The percentage change in plaque volume with nifedipine and placebo, respectively, was 1.0 and 1.9%, ns. CONCLUSION: The ENCORE II trial demonstrates in a multi-centre setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function on top of statin treatment, but did not show an effect of nifedipine on plaque volume.

Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: results of the CEZAR study.

BACKGROUND: Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction. METHODS AND RESULTS: Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80 mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7+/-3.0% (post vs. pre p<0.001), A10E10+0.6+/-2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7+/-4.6%, A10E10+0.7+/-3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group. CONCLUSIONS: The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD.

The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial.

BACKGROUND: Crataegus preparations have been used for centuries especially in Europe. To date, no proper data on their efficacy and safety as an add-on-treatment are available. Therefore a large morbidity/mortality trial was performed. AIM: To investigate the efficacy and safety of an add-on treatment with Crataegus extract WS 1442 in patients with congestive heart failure. METHODS: In this randomised, double-blind, placebo-controlled multicenter study, adults with NYHA class II or III CHF and reduced left ventricular ejection fraction (LVEF< or =35%) were included and received 900 mg/day WS 1442 or placebo for 24 months. Primary endpoint was time until first cardiac event. RESULTS: 2681 patients (WS 1442: 1338; placebo: 1343) were randomised. Average time to first cardiac event was 620 days for WS 1442 and 606 days for placebo (event rates: 27.9% and 28.9%, hazard ratio (HR): 0.95, 95% CI [0.82;1.10]; p=0.476). The trend for cardiac mortality reduction with WS 1442 (9.7% at month 24; HR: 0.89 [0.73;1.09]) was not statistically significant (p=0.269). In the subgroup with LVEF> or =25%, WS 1442 reduced sudden cardiac death by 39.7% (HR 0.59 [0.37;0.94] at month 24; p=0.025). Adverse events were comparable in both groups. CONCLUSIONS: In this study, WS 1442 had no significant effect on the primary endpoint. WS 1442 was safe to use in patients receiving optimal medication for heart failure. In addition, the data may indicate that WS 1442 can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.

A new algorithm for concealed accessory pathway localization using T-wave-subtracted retrograde P-wave polarity during orthodromic atrioventricular reentrant tachycardia.

INTRODUCTION: AP localization can be predicted by analyzing the polarity of the delta wave, QRS polarity, and R/S ratio in patients with Wolff-Parkinson-White syndrome. However, the estimation of AP location is limited in patients with concealed pathways during atrioventricular reentrant tachycardias (AVRT). Thus, we analyzed retrograde P-wave polarity during orthodromic AVRT and developed an algorithm to predict the localization of concealed accessory pathways (AP). METHODS AND RESULTS: A total number of 131 patients with a single AP and inducible orthodromic AVRT were included. The initial 61 patients were analyzed retrospectively for algorithm development, whereas 70 patients were evaluated prospectively. The retrograde P-wave polarity was analyzed by subtracting the superimposing T-wave during orthodromic AVRT using custom-designed software. Four leads of the surface electrocardiogram (ECG) were identified to accurately distinguish AP locations assigned to four different regions around each AV annulus: I, aVR, aVL, and V(1). Lead V(1) was used to differentiate right (negative or isoelectric) from left (solely positive) APs. Retrograde P-wave in lead I was negative in left posterior APs exclusively and became more positive with an AP location shifting towards right anterior. P-wave polarity in lead aVR demonstrated a shift from a positive polarity from left APs to isoelectric in right APs. The opposite direction (shift from positive to isoelectric) was observed for lead aVL. The subsequently developed algorithm for concealed AP localization using these surface ECG leads demonstrated a high sensitivity, specificity, and positive predictive value particularly for common AP localizations (left posterior and inferior, and right septal) when applied in a prospective fashion. CONCLUSION: Concealed AP localization can be accurately predicted by the analysis of retrograde P-wave polarity during orthodromic AVRT using the algorithm derived from the presented study.

Stable and unstable ventricular tachycardias in patients with previous myocardial infarction: a clinically oriented strategy for catheter ablation.

OBJECTIVE: Catheter ablation of ventricular tachycardia (VT) after myocardial infarction (MI) can be complex and time-consuming. We only targeted the previously documented VTs and those with similar or longer cycle lengths. METHODS: 30 patients with VTs after MI were included in the study. Voltage mapping was performed using an electro-anatomic mapping system (CARTOT). Stable VTs were mapped during tachycardia and unstable VTs during sinus rhythm. RESULTS: Clinical VTs were stable in 16 (53%) and unstable in 14 (47%) patients, and ablation was successful in 11 (69%) and 9 patients (64%), respectively (p = 0.42). During follow-up (14 +/- 6 months), 4 patients (25%) treated for stable and 6 (43%) for unstable VTs had recurrences (p = 0.82); ablation was successful in none and 2 (33%) of them, respectively. Non-target VTs were inducible in 11 (55%) of 20 patients after successful ablation and non-inducible in 9 (45%). During follow-up, inducibility of non-target VTs did not predict recurrences (9 vs. 11%, p = 0.88). CONCLUSIONS: Catheter ablation of VTs after MI can be successfully performed. Acute success rates seem to be similar for stable and unstable VTs. VTs faster than those documented clinically exert a minor effect on VT recurrences during follow-up.

Substrate modification combined with pulmonary vein isolation improves outcome of catheter ablation in patients with persistent atrial fibrillation: a prospective randomized comparison.

AIMS: To investigate the effectiveness of additional substrate modification (SM) by left atrial (LA) linear lesions as compared with pulmonary vein isolation (PVI) alone in patients with persistent atrial fibrillation (AF) in a prospective randomized study. Percutaneous PVI has evolved as an accepted treatment for paroxysmal AF but seemed to be less effective in patients with persistent AF. The benefit of PVI alone and additional linear lesions has not been validated in a randomized study so far. METHODS AND RESULTS: Sixty-two patients with persistent AF (median duration 7, range 1-18 months) were randomly assigned to either PVI alone (n = 30) or additional SM (n =32) consisting of a roof line connecting both left superior and right superior PV and LA isthmus ablation between left inferior PV and mitral annulus. Procedures including SM were performed using a three-dimensional mapping system (EnSite NavX, St Jude Medical, St Paul, MN, USA). Anti-arrhythmic drugs were discontinued within 8 weeks after ablation in both groups. Follow-up included daily trans-telephonic ECG transmitted irrespective of the patient's symptoms. PVI was successful in 98% of all targeted veins in both groups. Additional SM did not increase fluoroscopy time (72.1+/-18.7 vs. 72.9+/-17.3 min, P=0.92) because of the use of three-dimensional navigation in the PVI+SM group. AF recurrences within the first 4 weeks following ablation were more common after PVI alone (77%) than additional SM (44%, P=0.002). After a follow-up time of 487 (429-570) days, only 20% of patients undergoing stand alone PVI remained in sinus rhythm when compared with 69% following PVI combined with SM (P=0.0001). Two patients assigned to PVI+SM experienced procedure-related complications (cardiac tamponade and minor stroke) which resolved without sequelae. CONCLUSION: PVI alone is insufficient in the treatment of persistent AF. However, additional left linear lesions increase the success rate significantly. Early AF-relapses are associated with a negative outcome after PVI alone but not following additional SM.

Efficacy and safety of radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia in the elderly.

INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common regular supraventricular tachycardia in the general population as well as in elderly patients. The purpose of the study was to investigate the success and complication rate particularly regarding the induction of an atrioventricular (AV) block by radiofrequency (RF) ablation in elderly patients with and without a preexisting AV block. METHODS AND RESULTS: Between February 1998 and July 2004, all patients with symptomatic AVNRT referred for slow-pathway ablation in our institution were included and divided into two groups: group 1 patients younger than 75 years (n = 508) and group 2 patients > or =75 years (n = 70). A preexisting prolonged PR interval was present in 17 (3.3%) patients of group 1 and in 26 (37%, P < 0.0001) patients of group 2. Following successful slow-pathway ablation (follow-up time group 1: 37 +/- 22, group 2: 37 +/- 24 months) no induction of an AV block was observed in group 2 but in four patients of group 1 (0.79%) a complete heart block was induced requiring a pacemaker implantation. In group 1, 15 (2.95%) patients with a recurrence of AVNRT were readmitted for a repeat ablation procedure. No recurrences occurred in group 2. CONCLUSION: Despite a higher incidence of preexisting prolonged PR intervals slow-pathway ablation in elderly patients is both effective and safe and should be considered as the first line therapy also in this patient population.

Sub-threshold stimulation in variants of atrioventricular nodal re-entrant tachycardia: electrophysiological effects and impact for guidance of slow pathway ablation.

AIM: Sub-threshold stimulation (STS) applied during atrioventricular nodal re-entrant tachycardia (AVNRT) of the common (slow-fast) type has been shown to effectively characterise target sites suitable for slow pathway (SP) ablation but has not been investigated in the setting of fast-slow and slow-slow variants. METHODS AND RESULTS: Seventeen consecutive patients (52+/-16 years, 12 female) with sustained uncommon type AVNRT (fast-slow: n = 13, slow-slow: n = 4) were investigated. Mapping of the SP was started postero-septally close to the coronary sinus ostium and continued toward mid-septal sites, if required. Target sites for STS were selected according to established criteria including the recording of the earliest retrograde atrial activation during AVNRT. Long duration (5 s) constant current STS during AVNRT variants was performed in a stepwise manner (max 5 mA) at each site eligible for SP ablation until termination or capture occurred. Radiofrequency current (RFC) was delivered following successful STS termination of tachycardia (65 degrees C, 60 s) and exclusion of catheter dislodgement. Uncommon AVNRT with a mean cycle length of 405+/-70 ms was induced without spontaneous termination in all patients. Interruption of AVNRT variants due to selective STS-induced block of the retrograde (n = 12) or anterograde (n =2) SP occurred without capture in 14/17 (82%) patients. This was exclusively observed at sites with successful subsequent RFC application. AVNRT was rendered non-inducible in all patients after a median of 1 (1-11) RFC pulses without complications. CONCLUSIONS: Uncommon AVNRT can be interrupted by STS delivered at subsequently successful target sites for SP ablation in most patients (82%). The high positive and negative concordance between the effects of STS and following RFC application indicates that STS-mapping is also useful in the setting of AVNRT variants.

Dissociated activity and pulmonary vein fibrillation following functional disconnection: impact for the arrhythmogenesis of focal atrial fibrillation.

The present study sought to investigate the electrophysiological properties of isolated pulmonary veins following successful radiofrequency (RF) catheter ablation in patients with paroxysmal atrial fibrillation (PAF). Overall, 71 pulmonary veins in 37 consecutive patients (age: 56 +/- 9 years) with recurrent PAF were targeted for RF ablation at the ostial region in order to achieve a complete functional block. Following disconnection, the incidence of dissociated pulmonary vein (PV) activity and its response to orciprenalin were studied. RF ablation abolished conduction in 67 (94%) of 71 potentially arrhythmogenic PVs after a mean of 10.7 +/- 6.4 RF applications for each PV. After ablation, spontaneous dissociated automatic activity (9 to 52 beats/min, median 27) was found in 6 out of 67 isolated PVs (left superior: n = 1, left inferior: n = 1, right superior: n = 2, common left PV: n = 2). Slight acceleration (13 to 68 beats/min, median 29) of dissociated PV activity was observed during infusion of orciprenalin. Following isolation, initiation of sustained or nonsustained local fibrillation was recorded in only two cases of the common left sided PV with preceding automatic activity. In one patient PV fibrillation occurred during orciprenalin infusion following a repetitive response to a dissociated automatic rhythm with increasing duration as well as destabilization. In the other patient, PV fibrillation occurred immediately after the occurrence of PV automaticity. Slow dissociated automatic rhythms are detectable within 9% of disconnected PVs. The unique anatomic substrate of common left PVs seem to favor the occurrence of local fibrillation following isolation. The initiation pattern of fibrillation within the isolated PV has pathophysiological implications and underlines the contribution of multiple factors to the onset and sustenance of PAF.

Nebivolol prevents vascular NOS III uncoupling in experimental hyperlipidemia and inhibits NADPH oxidase activity in inflammatory cells.

OBJECTIVE: Nebivolol, in contrast to other selective beta1-adrenergic receptor antagonists like atenolol, improves endothelial function in patients with oxidative stress within vascular tissue. With the present studies we sought to determine whether beta receptor blockade with nebivolol may improve endothelial function in hyperlipidemia and whether this is attributable to reductions in vascular oxidative stress. METHODS AND RESULTS: Watanabe heritable hyperlipidemic rabbits (WHHL) were treated with nebivolol (10 mg/kg per day for 8 weeks). New Zealand white rabbits (NZWR) served as controls. Nebivolol improved endothelial function, reduced vascular superoxide and vascular macrophage infiltration, and prevented NO synthase uncoupling in WHHL. Nebivolol treatment did not modify the expression of sGC or cGK-I but improved cGK-I activity (assessed by the phosphorylation state of the VAsodilator Stimulated Phosphoprotein at serine239, P-VASP). NAD(P)H oxidase activity in whole blood and isolated neutrophils was dose-dependently inhibited by nebivolol, whereas atenolol, metoprolol, and carvedilol were markedly less effective. CONCLUSIONS: Nebivolol therapy effectively prevents NO synthase III uncoupling and prevents activation of the neutrophil NAD(P)H oxidase and infiltration of inflammatory cells. These novel antioxidative stress actions of this compound may explain partly the beneficial effects on endothelial function in patients with enhanced vascular oxidative stress.

Atrial premature beats in patients with focal atrial fibrillation: incidence at baseline and impact of provocative maneuvers.

This study evaluated the incidence of atrial premature beats (APBs) and the impact of various provocative maneuvers in patients with focally initiated AF. Fifty patients (39 men, 57 +/- 0.4 years) with focally initiated, paroxysmal AF underwent Holter recording and a standardized protocol of provocative maneuvers: vagomechanical stimulation, adenosine 12 mg i.v., esmolol 500 ng/kg i.v., orciprenaline i.v. 5 mg/50 mL saline 0.9%, and atropine 0.01 mg/kg i.v. A surface ECG was recorded for 20 minutes at baseline and following each part of the protocol. High focal activity was defined as > or = 1 APB/minute. During Holter ECG, 29 (58%) patients had an amount of < 200 APBs, 12 (24%) patients < 700 > or = 200, and 9 (18%) patients > or = 700 APBs. Less than 1 hour of high focal activity was observed in 34 (68%) of the 50 patients. Before starting provocative maneuvers 15 (30%) patients had high focal activity whereas 35 (70%) presented < 1 APB/minute. In 29 (58%) patients APBs increased by > or = 1/min during provocative maneuvers: by vagomechanical stimulation in 11 patients, after adenosine in 15, esmolol in 12, orciprenaline in 15, and after atropine in 9 patients. In all patients with > or = 1 APB/min at baseline, focal activity decreased or disappeared during some single provocative maneuvers. AF occurred in eight patients under provocative maneuvers. No predictive factors of a successful provocative maneuver were detected with regard to the baseline patients characteristics and Holter results. In conclusion, patients with focally initiated AF have a low incidence of spontaneous APBs. Various provocative maneuvers successfully increase APBs in more than half of the patients; orciprenaline had the highest efficacy. Some provocative maneuvers may suppress APBs in the setting of high focal activity at baseline.

Adverse effects of nitroglycerin treatment on endothelial function, vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits.

OBJECTIVE: With the present studies we sought to determine how treatment with nitroglycerin (NTG) affects endothelial function, oxidative stress and nitric oxide (NO)-downstream signaling in Watanabe heritable hyperlipidemic rabbits (WHHL). BACKGROUND: In vitro experiments have demonstrated potent antiatherosclerotic effects of NO suggesting that treatment with NO-donors such as NTG could compensate for the diminished availability of endothelial NO. Nitric oxide may, however, not only be scavenged by reaction with endothelium-derived superoxide but also form the potent oxidant and inhibitor of vascular function, peroxynitrite (ONOO(-)). METHODS: Watanabe heritable hyperlipidemic rabbits were treated for three days with NTG patches. Normolipidemic New Zealand White rabbits (NZWR) served as controls. Endothelial function was assessed ex vivo with organ chamber experiments and vascular superoxide was quantified using lucigenin (5 and 250 microM) and CLA-enhanced chemiluminescence. Vascular ONOO(-) formation was determined using nitrotyrosine antibodies. The activity of the cGMP-dependent kinase (cGK-I) was assessed by determining the phosphorylation of vasodilator-stimulated phosphoprotein VASP (P-VASP). RESULTS: Nitroglycerin treatment caused endothelial dysfunction in NZWR and WHHL, associated with an increase in superoxide and ONOO(-) production and a substantial drop in cGK-I activity. In vivo NTG-treatment decreased lipophilic antioxidants (alpha- and beta-carotene) in NZWR and WHHL. Treatment of NZWR with NTG also decreased plasma extracellular superoxide dismutase (EC-SOD)-activity. CONCLUSIONS: Nitroglycerin treatment of WHHL with exogenous NO worsens rather than improves endothelial dysfunction secondary to increased formation of superoxide and/or peroxynitrite leading to decreased cGK-I activity. The decrease in plasma levels of alpha- and beta-carotene may be at least in part due to a decrease in EC-SOD activity.

Functional disconnection of arrhythmogenic pulmonary veins in patients with paroxysmal atrial fibrillation guided by combined electroanatomical (CARTO) and conventional mapping.

BACKGROUND: Isolation of arrhythmogenic pulmonary veins (PVs) by radiofrequency current (RF) application has been introduced as a curative treatment for patients (pts) with paroxysmal atrial fibrillation (AF). The present study sought to investigate the feasibility and efficacy of this approach guided by conventional and electroanatomical mapping (CARTO). METHODS: Twenty pts (13 male; 57 +/- 8 years) with recurrent documented focally triggered idiopathic AF refractory to multiple antiarrhythmic drugs were prospectively included. Atrial premature beats were present at baseline in 9 pts and could be provoked in further 8 pts. Empirical ablation of both superior PVs was performed in 3 pts with no focal activity. After transseptal puncture selective angiography of all PVs was obtained. Thirty-six PVs (left superior: n = 18, right superior: n = 10, left inferior: n = 8) were targeted for RF ablation. A complete left atrial CARTO-map including the left atrial (LA) to pulmonary vein (PV) junction was obtained during sinus rhythm and/or coronary sinus pacing. RF was initially applied at the PV-LA junction at areas with the shortest left atrial- to PV potential interval (target 50 degrees C, max. 30 W, duration 60 sec). Isolation was confirmed by the complete disappearance of specific PV potentials. RF lesions were analyzed with respect to the number of segment-quarters covering the PV ostium. RESULTS: Functional isolation could be achieved in 35 out of 36 PVs following 10 +/- 5 RF applications for each PV. RF applications covered 2 or less quarter segments of the overall PV circumference in 29 (80%) PVs. Total session duration was 6.5 +/- 1.6 h with a mean fluoro-time of 54 +/- 18 minutes. For CARTO mapping and ablation a mean fluoro time of 34 +/- 6 min was required. During a mean follow up period of 8.3 +/- 2.5 months AF relapsed in 9 pts (46%). A second approach was performed in 5 pts. and demonstrated either new foci (n = 2) or recurrence of previously isolated PV (n = 8). The second RF ablation procedure led to stable sinus rhythm in 3 out 5 pts. Thus, the overall success rate including the second procedure was 70%. CONCLUSIONS: CARTO guided functional isolation of presumed arrhythmogenic PVs by RF lesions covering 2 or less segments of the PV ostium in most patients is feasible. However, repeat procedures are often warranted to permanently treat paroxysmal atrial fibrillation.