Adverse Clinical Events during Long-Term Follow-Up After Catheter Ablation of Atrial Fibrillation.

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.

Impact of Sinus Node Recovery Time after Long-Standing Atrial Fibrillation Termination on the Long-Term Outcome of Catheter Ablation.

Atrial electrical and structural remodeling is related to the perpetuation of atrial fibrillation (AF) subsequent to sinus node dysfunction. We investigated the relationship between AF recurrence after catheter ablation and sinus node dysfunction in long-standing persistent AF patients using the sinus node recovery time (SNRT) after defibrillation.Fifty-one consecutive patients who underwent a first ablation for long-standing persistent AF were enrolled. Intracardiac cardioversion was applied before ablation in the absence of any antiarrhythmic drugs, and the power required to defibrillate, number, and SNRT after defibrillation were measured. All patients underwent the same designed radiofrequency catheter ablation procedure.No patient required permanent pacemaker implantation due to sinus dysfunction after the ablation. During the follow-up period of 28.4 months (3.6-43.7), 35 out of 51 patients (69%) experienced an AF recurrence. The AF recurrence was significantly associated with an older age (60 ± 11 versus 52 ± 12 years in the non-recurrence group, P = 0.0196), longer SNRT after defibrillation (1722 [1410-2656] versus 1295 [676-1651] msec, P = 0.0125), and larger left atrial (LA) volume (59 ± 25 versus 41 ± 15 mL, P = 0.0119). There were no significant differences in the AF duration, AF cycle length, and right and total atrial conduction times between the 2 groups. A longer SNRT after defibrillation (adjusted HR 2.13, 95%CI 1.16-3.71, P = 0.0152) and larger LA volume (adjusted HR 1.03, 95%CI 1.01-1.04, P = 0.0054) were independent predictors of AF recurrence after ablation.Assessment of the SNRT after defibrillation may help to predict a successful ablation in patients with long-standing persistent AF.

Influence of balloon temperature and time to pulmonary vein isolation on acute pulmonary vein reconnection and clinical outcomes after cryoballoon ablation of atrial fibrillation.

BACKGROUND: Limited data exist on indicators of durable pulmonary vein isolation (PVI) undergoing cryoballoon ablation (CBA) for atrial fibrillation (AF). We investigated whether balloon temperature and time to PVI can be used to predict early PV reconduction (EPVR), including residual PV conduction and adenosine triphosphate-induced dormant conduction and the relation between touch-up ablation of EPVR sites and mid-term recurrence of AF. METHODS: We obtained procedural and outcome data from the records of 130 consecutive patients who underwent CBA and followed up for 13.4 months. RESULTS: EPVR was identified in 86 (17%) PVs of 61 (47%) patients. Balloon temperatures during 30 seconds (-27 ± 5.7°C vs -31 ± 5.5°C), 60 seconds (-36 ± 5.6°C vs -41 ± 5.4°C), and at the nadir point (-41 ± 7.4°C vs -49 ± 7.0°C) were significantly higher, and the time to PVI was longer (90 ± 50 seconds vs 52 ± 29 seconds) in PVs with EPVR than in those without (P < 0.0001 for all). Among PVs without EPVR, the time to PVI was longer and balloon temperature was lower for the left superior pulmonary vein/ right inferior pulmonary vein (LSPV/RIPV) than for the right superior pulmonary vein/left inferior pulmonary vein (RSPV/LIPV) (time: 60 ± 25/73 ± 37 seconds vs 41 ± 31/45 ± 20 seconds, P < 0.0001) (temp: -39.2 ± 11.3/-39.4 ± 8.3°C vs -33.8 ± 10.6/-33.6 ± 6.8°C, P = 0.0023). AF recurrence rates were equivalent between patients with and without EPVR (13% [8/69] vs 15% [9/61], P = 0.845). CONCLUSIONS: Cryoballoon temperature and time to PVI appear to be useful in predicting durable PVI, that is, prevention of EPVR, but the balloon temperature and time required for PVI differ between PVs. Although EPVR does not predict AF recurrence, high success rates can be expected when touch-up ablation of EPVR sites is performed.

No association between dormant conduction sites and pulmonary vein reconnection sites in late atrial fibrillation recurrence after catheter ablation.

OBJECTIVE: Despite use of provocation testing to unmask dormant left atrium (LA)-PV conduction after index pulmonary vein isolation (PVI) for atrial fibrillation (AF), AF recurrence still occurs, with PV reconnection as the main cause. In an effort to answer the question whether freedom from AF recurrence can be achieved by ablation that targets sites of dormant conduction, we compared sites of dormant conduction against sites of PV reconnection identified at the time of repeat ablation for AF recurrence. MATERIALS AND METHODS: The study group comprised 46 patients (30 men/16 women, aged 58.7±10.3 years) with AF (paroxysmal: n=37, persistent: n=9) who underwent repeat ablation for AF recurrence 12.3 (7.4-29.7) months after the index ablation procedure. Ipsilateral PVs were divided into 8 segments each (736 total segments), and the relation between dormant conduction sites and PV reconnection sites was determined per segment. RESULTS: Dormant LA-PV conduction was unmasked and ablated in 22 (47.8%) of the 46 patients at sites within 43 (5.8%) of the 736 PV segments. Late PV reconnection was found within 122 (17%) of the 736 PV segments at the time of re-ablation for AF recurrence. Only 22 (18%) of these 122 PV segments corresponded to dormant conduction sites identified during the index procedure. CONCLUSION: Although additional ablation to eliminate dormant PV conduction unmasked during the index ablation procedure is performed, the majority of PVs that show reconduction at the time of treatment for clinical AF recurrence are PVs that have not shown dormant conduction.

Left atrial remodeling: Regional differences between paroxysmal and persistent atrial fibrillation.

BACKGROUND: The mechanisms underlying self-perpetuation of persistent atrial fibrillation (AF) are not well understood. To gain insight into these mechanisms, we conducted a study comparing left atrial (LA) electroanatomic maps obtained during sinus rhythm between patients with paroxysmal AF (PAF) and patients with persistent AF (PerAF). METHODS: The study included 23 men with PAF (age, 56.3±12.1 years) and 13 men with PerAF (age, 54.3±13.4 years). LA voltage mapping was performed during sinus rhythm. The clinical and electroanatomic characteristics of the two groups were evaluated and analyzed statistically. RESULTS: The bipolar voltages at the LA septum, roof, and posterior wall, right superior pulmonary vein (PV) and its antrum, right superior PV carina, and right inferior PV antrum were significantly lower in patients with PerAF than in those with PAF. The bipolar voltages in other parts of the LA did not differ statistically between the two groups. CONCLUSION: PAF and PerAF seem to be characterized by differences in the regional voltage in the LA and PVs. The LA structural remodeling of PerAF may initiate from the right PVs and their antra and LA septum, roof, and posterior wall.

Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs.

The purpose of the present study was to comparatively evaluate human HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. Various concentrations of 14 different drugs were initially evaluated in terms of their relative potency to block I(HERG) in stably transfected human embryonic kidney cells. Four general categories of drugs were identified: high-potency blockers (IC50 < 0.1 microM) included lidoflazine, terfenadine, and haloperidol; moderate-potency blockers (0.1 microM < IC50 < 1 microM) included sertindole, thioridazine, and prenylamine; low-potency blockers (IC50 > 1 microM) included propafenone, loratadine, pyrilamine, lovastatin, and chlorpheniramine; and ineffective blockers (IC50 > 300 microM) included cimetidine, pentamidine, and arsenic trioxide. All measurements were performed using similar conditions and tested acute drug effects only (<30 min of drug exposure per measurement). Since two of the drugs that were ineffective I(HERG) blockers, arsenic trioxide and pentamidine, have been associated with cardiac repolarization delays (QT interval lengthening) and torsades de pointes ventricular arrhythmias in patients, we chose to evaluate them further using the isolated perfused rabbit heart model. Neither arsenic trioxide nor pentamidine had any significant effect on QT intervals in this model, even at relatively high (micromolar) concentrations. Similar results were obtained for loratadine in this model. When the hearts were challenged with a known torsadogenic drug such as cisapride, significant QT lengthening was rapidly induced. These results demonstrate that arsenic trioxide and pentamidine are essentially devoid of direct acute effects on cardiac repolarization or inhibition of I(HERG).

Differential rate responses to nicotine in rat heart: evidence for two classes of nicotinic receptors.

Nicotinic acetylcholine receptors are pentameric, typically being composed of two or more different subunits. To investigate which receptor subtypes are active in the heart, we initiated a series of experiments using an isolated perfused rat heart (Langendorff) preparation. Nicotine administration (100 microM) caused a brief decrease (-7 +/- 2%) followed by a much larger increase (17 +/- 5%) in heart rate that slowly returned to baseline within 10 to 15 min. The nicotine-induced decrease in heart rate could be abolished by an alpha7-specific antagonist, alpha-bungarotoxin (100 nM). In contrast, the nicotine-induced increase in heart rate persisted in the presence of alpha-bungarotoxin. These results suggest that the nicotinic acetylcholine receptors (nAChRs) that mediate the initial decrease in heart rate probably contain alpha7 subunits, whereas those that mediate the increase in heart rate probably do not contain alpha7 subunits. To investigate which subunits may contribute to the nicotine-induced increase in heart rate, we repeated our experiments with cytisine, an agonist at nAChRs that contain beta4 subunits. The cytisine results were similar to those obtained with nicotine, thereby suggesting that the nAChRs on sympathetic nerve terminals in the heart probably contain beta4 subunits. Thus, the results of this study show that pharmacologically distinct nAChRs are responsible for the differential effects of nicotine on heart rate. More specifically, our results suggest that alpha7 subunits participate in the initial nicotine-induced heart rate decrease, whereas beta4 subunits help to mediate the subsequent nicotine-induced rise in heart rate.

Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts.

We have previously shown that targeted disruption of the mouse Kcnq1 gene produces a long QT phenotype in vivo that requires extracardiac factors for manifestation (Casimiro et al., 2001). In the present study, we explore the hypothesis that autonomic neuroeffector transmission represents the "extra cardiac" stimulus that induces a long QT phenotype in mouse hearts lacking Kcnq1. Using the isolated perfused (Langendorff) mouse heart preparation, we challenged wild-type (Kcnq1+/+) and mutant (Kcnq1-/-) mouse hearts with nicotine, an autonomic stimulant. ECGs were recorded continuously, and QT intervals were compared at baseline and peak nicotine-induced heart rates. No significant differences in QT or any other ECG parameters were observed in Kcnq1+/+ versus Kcnq1-/- hearts at baseline. In the presence of nicotine, however, the JT, QT, and rate-corrected QT (QTc) intervals were significantly prolonged in Kcnq1-/- hearts relative to Kcnq1+/+ hearts (e.g., QTc = 92 +/- 11 ms versus 66 +/- 2 ms, respectively, p < 0.01). Similar findings were obtained when the hearts were challenged with either epinephrine or isoproterenol (0.1 microM each), thereby suggesting that sympathetic stimulation drives the long QT phenotype in Kcnq1-deficient hearts. This idea is supported by in vivo ECG data obtained from unrestrained conscious mice using radiotelemetry recording techniques. Again, no significant ECG differences were observed in Kcnq1-/- versus Kcnq1+/+ mice at baseline, but handling/injection stress led to significant QTc increases in Kcnq1-/- mice relative to wild-type controls (11 +/- 3 versus -1 +/- 1%, respectively, p < 0.05). These data suggest that sympathetic stimulation induces a long QT phenotype in Kcnq1-deficient mouse hearts.