Relationship between sodium channel function and clinical phenotype in SCN5A variants associated with Brugada syndrome.

The identification of a pathogenic SCN5A variant confers an increased risk of conduction defects and ventricular arrhythmias (VA) in Brugada syndrome (BrS). However, specific aspects of sodium channel function that influence clinical phenotype have not been defined. A systematic literature search identified SCN5A variants associated with BrS. Sodium current (INa ) functional parameters (peak current, decay, steady-state activation and inactivation, and recovery from inactivation) and clinical features (conduction abnormalities [CA], spontaneous VA or family history of sudden cardiac death [SCD], and spontaneous BrS electrocardiogram [ECG]) were extracted. A total of 561 SCN5A variants associated with BrS were identified, for which data on channel function and clinical phenotype were available in 142. In the primary analysis, no relationship was found between any aspect of channel function and CA, VA/SCD, or spontaneous BrS ECG pattern. Sensitivity analyses including only variants graded pathogenic or likely pathogenic suggested that reduction in peak current and positive shift in steady-state activation were weakly associated with CA and VA/SCD, although sensitivity and specificity remained low. The relationship between in vitro assessment of channel function and BrS clinical phenotype is weak. The assessment of channel function does not enhance risk stratification. Caution is needed when extrapolating functional testing to the likelihood of variant pathogenicity.

Changes in quality of life, cognition and functional status following catheter ablation of atrial fibrillation.

OBJECTIVE: To investigate changes in quality of life (QoL), cognition and functional status according to arrhythmia recurrence after atrial fibrillation (AF) ablation. METHODS: We compared QoL, cognition and functional status in patients with recurrent atrial tachycardia (AT)/AF versus those without recurrent AT/AF in the AXAFA-AFNET 5 clinical trial. We also sought to identify factors associated with improvement in QoL and functional status following AF ablation by overall change scores with and without analysis of covariance (ANCOVA). RESULTS: Among 518 patients who underwent AF ablation, 154 (29.7%) experienced recurrent AT/AF at 3 months. Patients with recurrent AT/AF had higher mean CHA2DS2-VASc scores (2.8 vs 2.3, p<0.001) and more persistent forms of AF (51 vs 39%, p=0.012). Median changes in the SF-12 physical (3 (25th, 75th: -1, 8) vs 1 (-5, 8), p=0.026) and mental scores (2 (-3, 9) vs 0 (-4, 5), p=0.004), EQ-5D (0 (0,2) vs 0 (-0.1, 0.1), p=0.027) and Karnofsky functional status scores (10 (0, 10) vs 0 (0, 10), p=0.001) were more favourable in patients without recurrent AT/AF. In the overall cohort, the proportion with at least mild cognitive impairment (Montreal Cognitive Assessment <26) declined from 30.3% (n=157) at baseline to 21.8% (n=113) at follow-up. ANCOVA identified greater improvement in Karnofsky functional status (p<0.001) but not SF-12 physical (p=0.238) or mental scores (p=0.065) in those without recurrent AT/AF compared with patients with recurrent AT/AF. CONCLUSIONS: Patients without recurrent AT/AF appear to experience greater improvement in functional status but similar QoL as those with recurrent AT/AF after AF ablation.

Early experience of thoracoscopic vs. catheter ablation for atrial fibrillation.

AIMS: Video-assisted thoracoscopic surgery (VATS) ablation has been advocated as a treatment option for non-paroxysmal atrial fibrillation (AF) in recent guidelines. Real-life data on its safety and efficacy during a centre's early experience are sparse. METHODS AND RESULTS: Thirty patients (28 persistent/longstanding persistent AF) underwent standalone VATS ablation for AF by an experienced thoracoscopic surgeon, with the first 20 cases proctored by external surgeons. Procedural and follow-up outcomes were collected prospectively, and compared with 90 propensity-matched patients undergoing contemporaneous catheter ablation (CA). Six (20.0%) patients undergoing VATS ablation experienced ≥1 major complication (death n = 1, stroke n = 2, conversion to sternotomy n = 3, and phrenic nerve injury n = 2). This was significantly higher than the 1.1% major complication rate (tamponade requiring drainage n = 1) seen with CA (P < 0.001). Twelve-month single procedure arrhythmia-free survival rates without antiarrhythmic drugs were 56% in the VATS and 57% in the CA cohorts (P = 0.22), and 78% and 80%, respectively given an additional CA and antiarrhythmic drugs (P = 0.32). CONCLUSION: During a centre's early experience, VATS ablation may have similar success rates to those from an established CA service, but carry a greater risk of major complications. Those embarking on a programme of VATS AF ablation should be aware that complication and success rates may differ from those reported by selected high-volume centres.

Pulmonary Vein Re-Isolation as a Routine Strategy Regardless of Symptoms: The PRESSURE Randomized Controlled Trial.

OBJECTIVES: The goal of this study was to determine whether a strategy of early re-isolation of pulmonary vein (PV) reconnection in all patients, regardless of symptoms, would reduce the recurrence of atrial fibrillation (AF) and improve quality of life. BACKGROUND: Lasting pulmonary vein isolation (PVI) remains elusive. PV reconnection is strongly linked to the recurrence of arrhythmia. METHODS: A total of 80 patients with paroxysmal AF were randomized 1:1 after contact force-guided PVI to receive either standard care or undergo a repeat electrophysiology study after 2 months regardless of symptoms (repeat study). At the initial procedure, PVI was demonstrated by entrance/exit block and adenosine administration after a minimum 20-min wait. At the repeat study, all sites of PV reconnection were re-ablated. Patients recorded electrocardiograms daily and whenever symptomatic for 12 months using a handheld monitor. Recurrence was defined as ≥30 s of atrial tachyarrhythmia (AT) after a 3-month blanking period. The Atrial Fibrillation Effect on Quality-of-Life Questionnaire was completed at baseline and at 6 and 12 months. RESULTS: All 40 patients randomized to repeat study attended for this after 62 ± 6 days, of whom 25 (62.5%) had reconnection of 41 (26%) PVs. There were no complications related to these procedures. Subjects recorded a total of 32,203 electrocardiograms (380 [335 to 447] per patient) during 12.6 (12.2 to 13.2) months of follow-up. AT recurrence was significantly lower for the repeat study group (17.5% vs. 42.5%; p = 0.03), as was AT burden (p = 0.03). Scores on the Atrial Fibrillation Effect on Quality-of-Life Questionnaire were higher in the repeat study group at 6 months (p < 0.001) and 12 months (p = 0.02). CONCLUSIONS: A strategy of routine repeat assessment with re-isolation of PV reconnection improved freedom from AT recurrence, AT burden, and quality of life compared with current standard care. (The Effect of Early Repeat Atrial Fibrillation [AF] on AF Recurrence [PRESSURE]; NCT01942408).

Ablation index, a novel marker of ablation lesion quality: prediction of pulmonary vein reconnection at repeat electrophysiology study and regional differences in target values.

AIMS: Force-Time Integral (FTI) is commonly used as a marker of ablation lesion quality during pulmonary vein isolation (PVI), but does not incorporate power. Ablation Index (AI) is a novel lesion quality marker that utilizes contact force, time, and power in a weighted formula. Furthermore, only a single FTI target value has been suggested despite regional variation in left atrial wall thickness. We aimed to study AI's and FTI's relationships with PV reconnection at repeat electrophysiology study, and regional threshold values that predicted no reconnection. METHODS AND RESULTS: Forty paroxysmal atrial fibrillation patients underwent contact force-guided PVI, and the minimum and mean AI and FTI values for each segment were identified according to a 12-segment model. All patients underwent repeat electrophysiology study at 2 months, regardless of symptoms, to identify sites of PV reconnection. Late PV reconnection was seen in 53 (11%) segments in 25 (62%) patients. Reconnected segments had significantly lower minimum AI [308 (252-336) vs. 373 (323-423), P < 0.0001] and FTI [137 (92-182) vs. 228 (157-334), P < 0.0001] compared with non-reconnected segments. Minimum AI and FTI were both independently predictive, but AI had a smaller P value. Higher minimum AI and FTI values were required to avoid reconnection in anterior/roof segments than for posterior/inferior segments (P < 0.0001). No reconnection was seen where the minimum AI value was ≥370 for posterior/inferior segments and ≥480 for anterior/roof segments. CONCLUSION: The minimum AI value in a PVI segment is independently predictive of reconnection of that segment at repeat electrophysiology study. Higher AI and FTI values are required for anterior/roof segments than for posterior/inferior segments to prevent reconnection.

Long-term outcomes after ablation of persistent atrial fibrillation: an observational study over 6†years.

OBJECTIVES: To address the limited long-term outcome data for catheter ablation (CA) of persistent atrial fibrillation (PeAF), we analysed consecutive ablations performed at our centre from 1 January 2008 to 31 December 2010 and followed patients prospectively until January 2014. METHODS: Both arrhythmia recurrence and symptom relief were assessed. Follow-up data were collected from hospital records, supplemented by data from general practitioners and referring hospitals. At the end of the follow-up period, all patients were contacted by phone to determine their up-to-date clinical condition. RESULTS: 188 consecutive patients with PeAF (157 male, mean age 57.3±9.7 years, 20% with long-standing PeAF) underwent a mean of 1.75 procedures (range 1-4). Telephone follow-up was achieved for 77% of surviving patients. Over a mean follow-up of 46±16 months (range 4-72), 139 (75%) patients experienced arrhythmia recurrence after a single procedure and 90 (48%) after their final procedure. Median time to first recurrence was 210 days (range 91-1850). 71% of recurrences were within the first year following ablation and 91% within 2 years. At final follow-up, 82% of patients reported symptomatic improvement. 7 (2.3%) major complications occurred, and there was no procedure-related death or stroke. CONCLUSIONS: CA for PeAF is safe with a low rate of complications. Over a follow-up period of up to 6 years, a large majority of patients experience significant symptomatic improvement but recurrence after the initial procedure is the norm rather than the exception. 2 years' follow-up is sufficient to observe 90% of AF recurrences, but recurrence can occur even after 5 years' remission.

Reablated Sites of Acute Reconnection After Pulmonary Vein Isolation Do Not Predict Sites of Late Reconnection at Repeat Electrophysiology Study.

INTRODUCTION: Acute reconnection of pulmonary veins (PVs) is frequently seen in the waiting period following pulmonary vein isolation (PVI). There are concerns that reablation at these sites may not be durably effective due to tissue edema caused by the initial ablation. We aimed to prospectively study the relationship between acute and late reconnection. METHODS AND RESULTS: Wide-area circumferential PVI was performed in 40 paroxysmal AF patients. Spontaneous reconnection was assessed after a minimum 20-minute waiting period, with adenosine administered to unmask dormant reconnection. All sites of acute reconnection were ablated to reisolate the PV. All 40 patients then underwent repeat electrophysiology study after 2 months, regardless of symptoms, to identify late reconnection. Sites of acute and late reconnection were compared according to a 12-segment PVI model. Acute reconnection was seen in 28 (6%) PVI segments in 20 (50%) patients, affecting 24/160 (15%) PVs. All were successfully reisolated. At repeat electrophysiology study, 51 (11%) PVI segments were reconnected in 25 (62%) patients, affecting 41 (25%) PVs. The proportion of PVI segments with and without acute reconnection exhibiting late reconnection at repeat study was no different (14% vs. 10%, P = 0.524). There was also no difference in late reconnection between PVI circles or patients with and without acute reconnection. CONCLUSION: Most PVI segments that undergo further ablation for acute reconnection show persistent isolation at repeat electrophysiology study, and the rate of late reconnection for these segments is no different to that for segments that did not acutely reconnect. This implies that effective reablation is delivered at these sites.

Radiofrequency ablation of the interventricular septum to treat outflow tract gradients in hypertrophic obstructive cardiomyopathy: a novel use of CARTOSound® technology to guide ablation.

AIMS: Septal reduction is needed for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow tract (LVOT) gradients and symptoms despite medication. Myectomy cannot be performed in all. Alcohol septal ablation cannot be performed in 5-15% due to technical difficulties. A method of delivering percutaneous tissue damage to the septum that is not reliant on coronary anatomy is desirable. To directly ablate the interventricular septum at the mitral valve (MV) systolic anterior motion (SAM)-septal contact point using radiofrequency (RF) energy guided by CARTOSound. METHODS AND RESULTS: Five patients underwent RF ablation (RFA); we describe follow-up at 6 months in four patients. Intracardiac echocardiography (ICE) images are merged with CARTO to create a shell of the cardiac chambers. The SAM-septal contact area is marked from ICE images and mapped on to the CARTO shell; this becomes the target for RF delivery. Conduction tissue is mapped and avoided where possible. Twenty-eight to 42 min of RF energy was delivered to the target area using retrograde aortic access and SmartTouch catheters. Resting LVOT gradient improved from 64.2 (±50.6) to 12.3 (±2.5) mmHg. Valsalva/exercise-induced gradient reduced from 93.5 (±30.9) to 23.3 (±8.3) mmHg. Three patients improved New York Heart Association status from III to II, one patient improved from class III to I. Exercise time on bicycle ergometer increased from 612 to 730 s. Cardiac magnetic resonance shows late gadolinium enhancement up to 8 mm depth at LV target myocardium. One patient died following a significant retroperitoneal haemorrhage. CONCLUSION: Radiofrequency ablation using CARTOSound(®) guidance is accurate and effective in treating LVOT gradients in HOCM in this preliminary group of patients.

Management of patients with ventricular tachycardia in Europe: results of the European Heart Rhythm Association survey.

The purpose of this European Heart Rhythm Association (EHRA) survey was to assess clinical practice in the management of ventricular tachycardia (VT). The data are based on an electronic questionnaire sent to the members of the EHRA Research Network. Responses were received from 31 centres in 16 countries. The results of the survey show that the management of VT is in general in accordance with guidelines. Antiarrhythmic drugs are still frequently used for VT treatment. In patients at high risk of sudden cardiac death, an implantable cardioverter-defibrillator is routinely recommended, while the treatment options vary for patients with moderate or low risk. A discreet attitude is adopted for catheter ablation in high-risk patients as demonstrated by a relatively low rate of catheter ablation.

Recurrence of atrial tachyarrhythmia during the second month of the blanking period is associated with more extensive pulmonary vein reconnection at repeat electrophysiology study.

BACKGROUND: Current guidelines recommend a 3-month blanking period after pulmonary vein isolation (PVI) as early recurrence of atrial tachyarrhythmia (ERAT) may be due to transient proarrhythmic factors. However, studies have suggested that these factors resolve by 1 month. PV reconnection (PVrc) is strongly associated with postblanking AT recurrence in paroxysmal atrial fibrillation. We hypothesized that ERAT occurring beyond 4 weeks after PVI is associated with PVrc at repeat electrophysiology study. METHODS AND RESULTS: Forty patients with paroxysmal atrial fibrillation underwent mandatory repeat electrophysiology study 2 months after PVI, regardless of symptoms, to document the number of reconnected PVs. Antiarrhythmic drugs, including ß-blockers, were discontinued 4 weeks after PVI. Patients were instructed to record a 30-second ECG everyday between the 2 procedures using a portable monitor, with additional recordings for symptoms. ERAT was defined as ≥30 seconds of AT. Patients recorded a total of 3293 ECGs. Four (10%) patients had ERAT in the first 4 weeks (M1) only, 2 (5%) in month 2 (M2) only, and 11 (28%) in both. PVrc of 1 PV was identified in 12 (30%) patients and of >1 PV in 13 (32%) patients. ERAT in M2 was associated with PVrc, whereas M1 was not (11/13 [85%] versus 0/4 [0%]; P=0.006). M2 ERAT was strongly associated with PVrc of >1 PV (10/13 [77%] versus 3/27 [11%] without M2 ERAT; P<0.0001). CONCLUSIONS: ERAT occurring beyond 4 weeks after PVI is associated with PVrc and particularly of PVrc of >1 PV. ERAT confined to M1 is unrelated to underlying PVrc. The relationship between ERAT beyond 4 weeks after PVI and postblanking AT recurrence merits further investigation.

A novel marker to predict early recurrence after atrial fibrillation ablation: the ablation effectiveness quotient.

INTRODUCTION: Inability to predict clinical outcome despite acutely successful pulmonary vein isolation (PVI) remains the Achilles' heel of atrial fibrillation ablation (AFA). Arrhythmia recurrence is frequently due to recovery of radiofrequency (RF) ablation lesions believed to be complete at the original procedure. OBJECTIVES: We hypothesized that a high ratio between post-AFA levels of serum high sensitivity cardiac troponin T (HScTnT), a highly specific marker of acute myocardial injury, and duration of RF application (the ablation effectiveness quotient, AEQ) would indicate effective ablation and correlate with early clinical success. METHODS: We prospectively measured HScTnT levels in 60 patients (42 [70%] male, 22 [37%] with paroxysmal AF [PAF], mean age 62.5 ± 10.6 years) 12-18 hours after AFA and calculated the AEQ for each. Patients were followed-up with ECGs and Holter monitors for recurrence of atrial tachyarrhythmia (AT). RESULTS: Early recurrence of AT within 6 months occurred in 22 (37%). AT recurrence was not significantly related to left atrial size or comorbidities, nor to RF time or HScTnT level. Mean AEQ was significantly lower in those with recurrence than those without (0.35 ± 0.14 ng/L/s vs. 0.45 ± 0.18 ng/L/s), P = 0.02. Subgroup analysis showed this finding was due to patients with PAF in whom early significance was maintained to one year, with an AEQ >0.4 ng/L/s having 75% sensitivity and 90% specificity in predicting freedom from AT. CONCLUSION: A high AEQ correlates well with freedom from AT in patients with PAF in both the short and medium term. If confirmed in further studies, AEQ may become a useful marker of risk of AT post-AFA.

Improving safety in catheter ablation for atrial fibrillation: a prospective study of the use of ultrasound to guide vascular access.

INTRODUCTION: The most frequent complications of AF ablation (AFA) are related to vascular access, but there is little evidence as to how these can be minimized. METHODS: Consecutive patients undergoing AFA at a high-volume center received either standard care (Group S) or routine ultrasound-guided vascular access (Group U). Vascular complications were assessed before hospital discharge and by means of postal questionnaire 1 month later. Outcome measures were BARC 2+ bleeding complications, postprocedural pain, and prolonged bruising. RESULTS: Patients in Group S (n = 146) and U (n = 163) were well matched at baseline. Follow-up questionnaires were received from 92.6%. Patients in Group U were significantly less likely to have a BARC 2+ bleed, 10.4% versus 19.9% P = 0.02, were less likely to suffer groin pain after discharge (27.1% vs. 42.8%; P = 0.006) and were less likely to experience prolonged local bruising (21.5% vs. 40.4%; P = 0.001). Multivariable logistic regression analysis revealed a significant association of vascular complications with nonultrasound guided access (OR 3.12 95%CI 1.54-5.34; P = 0.003) and increasing age (OR 1.05 95%CI 1.01-1.09; P = 0.02). CONCLUSION: Routine use of ultrasound-guided vascular access for AFA is associated with a significant reduction in bleeding complications, postprocedural pain, and prolonged bruising when compared to standard care.

The European Heart Rhythm Association symptom classification for atrial fibrillation: validation and improvement through a simple modification.

AIMS: To validate the European Heart Rhythm Association (EHRA) symptom classification in atrial fibrillation (AF) and test whether its discriminative ability could be improved by a simple modification. METHODS AND RESULTS: We compared the EHRA classification with three quality of life (QoL) measures: the AF-specific Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire; two components of the EQ-5D instrument, a health-related utility which can be used to calculate cost-effectiveness, and the visual analogue scale (VAS) which demonstrates patients' own assessment of health status. We then proposed a simple modification [modified EHRA (mEHRA)] to improve discrimination at the point where major treatment decisions are made. quality of life data and clinician-allocated EHRA class were prospectively collected on 362 patients with AF. A step-wise, negative association was seen between the EHRA class and both the AFEQT and the VAS scores. Health-related utility was only significantly different between Classes 2 and 3 (P < 0.001). We developed and validated the mEHRA score separating Class 2 (symptomatic AF not limiting daily activities), based on whether the patients were 'troubled by their AF' (Class 2b) or not (Class 2a). This produced two distinct groups with lower AFEQT and VAS scores and, importantly, both clinically and statistically significant lower health utility (Δutility 0.9, P = 0.01) in Class 2b than Class 2a. CONCLUSION: Based on patients' own assessment of their health status and the disease-specific AFEQT, the EHRA score can be considered a useful semi-quantitative classification. The mEHRA score has a clearer separation in health utility to assess the cost efficacy of interventions such as ablation, where Class 2b symptoms appear to be the appropriate treatment threshold.

Current periprocedural management of ablation for atrial fibrillation in Europe: results of the European Heart Rhythm Association survey.

The purpose of this EP Wire survey was to assess clinical practice in periprocedural management of atrial fibrillation ablation. This survey is based on an electronic questionnaire sent to the European Heart Rhythm Association Research Network members. Responses were received from 78 centres in 20 countries. The results of the survey have shown that periprocedural management is generally in accordance with guidelines and consensus recommendations on ablation for atrial fibrillation ablation, although there are some areas of variation. Differences between high- and low-volume centres are observed with respect to patient selection, antiarrhythmic drug management, and heparin bridging.

United Kingdom national experience of entirely subcutaneous implantable cardioverter-defibrillator technology: important lessons to learn.

AIMS: The aim of this study was to describe the early phase United Kingdom (UK) clinical experience with a novel entirely subcutaneous implantable cardioverter-defibrillator (S-ICD). METHODS AND RESULTS: A questionnaire was sent to all UK hospitals implanting S-ICDs. Nineteen of 25 (76%) hospitals responded with the details of 111 implanted patients [median 5/hospital (range 1-18)]. Mean duration of follow-up was 12.7 ± 7.1 months. Median patient age was 33 years (range 10-87 years). Underlying pathology was primary electrical disease in 43%, congenital heart disease 12%, hypertrophic cardiomyopathy 20%, ischaemic cardiomyopathy 14%, idiopathic dilated cardiomyopathy 5%, and other cardiomyopathies 7% patients. Nineteen (17%) patients required 20 re-operations, including permanent device explantation in 10 (9%). Twenty-four appropriate shocks were delivered in 13 (12%) patients, including 10 for ventricular fibrillation. One patient suffered arrhythmic death, but there were no failures to detect or terminate ventricular arrhythmias above the programmed detection rate. Fifty-one inappropriate shocks were delivered in 17 (15%) patients. Forty-one (80%) were for T-wave over-sensing and 1 (2%) for atrial flutter-wave over-sensing. The 11 patients who received inappropriate shocks due to T-wave over-sensing were significantly younger than patients who did not (24 ± 10 vs. 37 ± 19 years; P = 0.02). CONCLUSION: The S-ICD is an important innovation in ICD technology. However, these data indicate that adverse event rates are significant during early clinical adoption. Important lessons in patient selection, implant technique, and device programming can be learnt from this experience.

Does treatment with ACE inhibitors or angiotensin II receptor antagonists prevent atrial fibrillation after dual chamber pacemaker implantation?

AIMS: A retrospective observational study was performed to test the hypothesis that a lower incidence of atrial fibrillation (AF) would be observed in patients treated with either angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (AIIRAs) than those without these drugs, 1-year following implantation of a dual chamber pacemaker for all indications. METHODS: One hundred and sixty consecutive patients who underwent implantation of a dual chamber pacemaker between January and August 2002 were identified and their case notes were retrospectively analysed. The primary endpoint was the presence of persistent AF (confirmed by 12-lead ECG recorded from the visit to the pacemaker clinic) at 12-month follow-up. RESULTS: Overall, 8% patients developed new onset persistent AF at 1-year follow-up. The incidence of AF at 1-year was 4% in patients treated with ACE inhibitors, 8% in patients taking AIIRAs or 5% on either drug. Although a trend towards a higher incidence of AF was observed at 1-year (10%) in patients not receiving either of these drugs, this was not statistically significant (P = 0.21, drug vs. no drug). The incidence of AF in patients with a previous history of paroxysmal AF or cardioversion was significantly higher (23%) than those patients without (5%), P < 0.0001. An odds ratio (95% CI) of 7.9 (2.3-27.8) was obtained. CONCLUSION: To confirm these interesting initial results and to investigate this important relationship further, larger prospective randomised controlled studies are required.

Repetitive 4-week periods of atrial electrical remodeling promote stability of atrial fibrillation: time course of a second factor involved in the self-perpetuation of atrial fibrillation.

BACKGROUND: Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability thought to be due to a so-called "second factor." The aim of this study was to quantify the effects and time course of such a factor on AF stability in the chronic goat model. METHODS AND RESULTS: AF was maintained in 6 goats by burst atrial pacing for 3 consecutive 4-week periods separated a mean of 6+/-2.1 days of sinus rhythm. Six days of sinus rhythm was just sufficient for refractoriness changes to reverse fully in all goats. Atrial effective refractory period, AF inducibility, and duration of individual episodes of AF were assessed at regular intervals. There was a progressive reduction from month 1 to 2 to 3 in the mean duration of burst pacing required to induce individual episodes of AF of 60 seconds (178+/-251, 110+/-102, and 21+/-30 hours), 1 hour (229+/-224, 136+/-104, and 68+/-51 hours), and 24 hours (277+/-218, 192+/-190, and 102+/-75 hours; P<0.03). The frequency with which AF was induced during extrastimulus pacing increased progressively from 16.7% in month 1 to 31.7% in month 2 and 46.9% in month 3 (P<0.001). CONCLUSIONS: Sequential 4-week periods of atrial fibrillation result in a progressive increase in AF stability independent of baseline atrial refractory period. This finding suggests the presence of a second factor in the self-perpetuation of AF with a time course comparable to that of AF-induced ultrastructural changes in the atria.

Role of the posterior left atrium and pulmonary veins in human lone atrial fibrillation: electrophysiological and pathological data from patients undergoing atrial fibrillation surgery.

BACKGROUND: Surgery can eliminate atrial fibrillation (AF), but data confirming the rationale for specific lesion sets are lacking. We used postoperative electrophysiological studies to test the rationale and effects of operative pulmonary venous isolation. METHODS AND RESULTS: Fourteen patients undergoing surgical pulmonary venous isolation for drug-refractory lone AF were studied. Successful isolation was confirmed postoperatively in 13 of 14 patients. Spontaneous sustained AF was recorded from the isolated pulmonary venous region (PVR) in 4 and was induced by extrastimulus testing in another. The remaining atrial region (RAR) was in sinus rhythm in 13 patients and nonsustained AF in 1. Atrial extrastimulus testing and burst pacing in the RAR failed to induce sustained AF. In follow-up, 1 patient developed paroxysmal AF, and electrical continuity between the PVR and RAR was confirmed. Isolation was achieved with radiofrequency ablation with no further AF. Another patient developed typical atrial flutter that required ablation. AF has not recurred in any patient at 25.1+/-11.9 months (range, 6 to 56 months) after surgery. Atrial histopathology was consistent with tachycardia-induced changes. CONCLUSIONS: Total electrical isolation of the PVR controlled AF with excellent clinical outcome and appeared necessary for success. The isolated PVR can sustain spontaneous or induced AF, whereas the considerably larger RAR does not. These data provide a sound rationale for PVR in eliminating AF.

Effect of amiodarone on dispersion of atrial refractoriness and cycle length in patients with atrial fibrillation.

INTRODUCTION: Amiodarone is effective in preventing the recurrence of atrial fibrillation (AF) after cardioversion (CV). Dispersion of atrial refractoriness may be relevant to the generation of AF. We designed a study to determine the electrophysiologic effects of amiodarone in patients with previous early recurrence of AF after CV. METHODS AND RESULTS: Fifteen patients with previous AF recurrence (without antiarrhythmic drugs) after CV (CV1) were selected for amiodarone therapy and repeat CV (CVamio). Prior to CV1, mean AF cycle length (AFCL) had been recorded at four atrial sites (right atrial appendage [RAA], distal coronary sinus [DCS], right atrial lateral wall [LAT], and interatrial septum [IAS]) and dispersion of AFCL had been calculated. These patients were treated with amiodarone and, prior to CVamio, AFCL was recorded at the four atrial sites as for CV1. Between CV1 and CVamio, AFCL increased at all atrial sites: 153 +/- 13 msec to 179 +/- 14 msec at RAA, 144 +/- 12 msec to 174 +/- 18 msec at DCS, 158 +/- 13 msec to 182 +/- 16 msec at LAT, and 161 +/- 18 msec to 181 +/- 17 msec at IAS. Dispersion of AFCL decreased from 24 +/- 10 msec at CV1 to 15 +/- 11 msec at CVamio (P = 0.01). The median time in sinus rhythm increased from 3.12 hours post CV1 to 28 days post CVamio, (P < 0.02). CONCLUSION: Amiodarone causes a reduction in the dispersion of AFCL. This action may be relevant to the beneficial effects of amiodarone in patients with AF.