Cardiac magnetic resonance for early atrial lesion visualization post atrial fibrillation radiofrequency catheter ablation.

BACKGROUND: Incomplete atrial lesions resulting in pulmonary vein-left atrium reconnection after pulmonary vein antrum isolation (PVAI), are related to atrial fibrillation (AF) recurrence. Unfortunately, during the PVAI procedure, fluoroscopy and electroanatomic mapping cannot accurately determine the location and size of the ablation lesions in the atrial wall and this can result in incomplete PVAI lesions (PVAI-L) after radiofrequency catheter ablation (RFCA). AIM: We seek to evaluate whether cardiac magnetic resonance (CMR), immediately after RFCA of AF, can identify PVAI-L by characterizing the left atrial tissue. METHODS: Ten patients (63.1 ± 5.7 years old, 80% male) receiving a RFCA for paroxysmal AF underwent a CMR before (<1 week) and after (<1 h) the PVAI. Two-dimensional dark-blood T2-weighted short tau inversion recovery (DB-STIR), Three-dimensional inversion-recovery prepared long inversion time (3D-TWILITE) and three-dimensional late gadolinium enhancement (3D-LGE) images were performed to visualize PVAI-L. RESULTS: The PVAI-L was visible in 10 patients (100%) using 3D-TWILITE and 3D-LGE. Conversely, On DB-STIR, the ablation core of the PAVI-L could not be identified because of a diffuse high signal of the atrial wall post-PVAI. Microvascular obstruction was identified in 7 (70%) patients using 3D-LGE. CONCLUSION: CMR can visualize PVAI-L immediately after the RFCA of AF even without the use of contrast agents. Future studies are needed to understand if the use of CMR for PVAI-L detection after RFCA can improve the results of ablation procedures.

Five-year safety and efficacy of leadless pacemakers in a Dutch cohort.

BACKGROUND: Adequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical benefit of leadless pacing. OBJECTIVE: The purpose of this study was to evaluate the long-term safety and efficacy of LP therapy in a real-world cohort. METHODS: In this retrospective cohort study, all consecutive patients with a first LP implantation from December 21, 2012, to December 13, 2016, in 6 Dutch high-volume centers were included. The primary safety endpoint was the rate of major procedure- or device-related complications (ie, requiring surgery) at 5-year follow-up. Analyses were performed with and without Nanostim battery advisory-related complications. The primary efficacy endpoint was the percentage of patients with a pacing capture threshold ≤2.0 V at implantation and without ≥1.5-V increase at the last follow-up visit. RESULTS: A total of 179 patients were included (mean age 79 ± 9 years), 93 (52%) with a Nanostim and 86 (48%) with a Micra VR LP. Mean follow-up duration was 44 ± 26 months. Forty-one major complications occurred, of which 7 were not advisory related. The 5-year major complication rate was 4% without advisory-related complications and 27% including advisory-related complications. No advisory-related major complications occurred a median 10 days (range 0-88 days) postimplantation. The pacing capture threshold was low in 163 of 167 patients (98%) and stable in 157 of 160 (98%). CONCLUSION: The long-term major complication rate without advisory-related complications was low with LPs. No complications occurred after the acute phase and no infections occurred, which may be a specific benefit of LPs. The performance was adequate with a stable pacing capture threshold.

Cardiac magnetic resonance-guided cardiac ablation: a case series of an early experience.

Radiofrequency (RF) catheter ablation has become a widely used therapeutic approach. However, long-term results in terms of arrhythmia recurrence are still suboptimal. Cardiac magnetic resonance (CMR) could offer a valuable tool to overcome this limitation, with the possibility of targeting the arrhythmic substrate and evaluating the location, depth, and possible gaps of RF lesions. Moreover, real-time CMR-guided procedures offer a radiation-free approach with an evaluation of anatomical structures, substrates, RF lesions, and possible complications during a single procedure. The first steps in the field have been made with cavotricuspid isthmus ablation, showing similar procedural duration and success rate to standard fluoroscopy-guided procedures, while allowing visualization of anatomic structures and RF lesions. These promising results open the path for further studies in the context of more complex arrhythmias, like atrial fibrillation and ventricular tachycardias. Of note, setting up an interventional CMR (iCMR) centre requires safety and technical standards, mostly related to the need for CMR-compatible equipment and medical staff's educational training. For the cardiac imagers, it is fundamental to provide correct CMR sequences for catheter tracking and guide RF delivery. At the same time, the electrophysiologist needs a rapid interpretation of CMR images during the procedures. The aim of this paper is first to review the logistic and technical aspects of setting up an iCMR suite. Then, we will describe the experience in iCMR-guided flutter ablations of two European centres, Policlinico Casilino in Rome, Italy, and Haga Teaching Hospital in The Hague, the Netherlands.

The jugular approach for leadless pacing: A novel and safe alternative.

AIMS: To evaluate safety of leadless pacemaker implantation through the internal jugular vein in a larger cohort with longer follow-up. Moreover, feasibility of non-apical pacing as well as relation between pacing site and QRS duration were assessed. METHODS: Eighty Two consecutive patients, who received a leadless pacemaker though the internal jugular vein, were included. Electrical parameters were measured at regular follow-up and any complications were registered. Paced QRS interval was compared for three pacing sites, RVOT, RV mid septum, and RV apical septum. RESULTS: In all patients, the leadless pacemaker was implanted successfully. In 69 patients, the device was implanted in a non-apical position. In 71% of cases, the device could be deployed at first attempt. The median fluoroscopy time was 4.4 min (range 0.9-51) The paced QRS interval was significantly narrower for non-apical pacing sites compared to apical pacing si 156  vs. 179 ms. p = .04, respectively. During mean follow-up of 16 months (range 0-43 months), electrical parameters remained stable. Two complications occurred, which could be resolved during the implant procedure. There were no access site related complications. CONCLUSION: The jugular approach for leadless pacemaker implantation is feasible and may avoid vascular complications. It facilitates non-apical positioning of leadless pacemakers leading to a narrower paced QRS interval. The jugular approach allows for immediate post procedural ambulation.

Leadless pacemaker implant with concomitant atrioventricular node ablation: Experience with the Micra transcatheter pacemaker.

BACKGROUND: The feasibility and outcomes of concomitant atrioventricular node ablation (AVNA) and leadless pacemaker implant are not well studied. We report outcomes in patients undergoing Micra implant with concomitant AVNA. METHODS: Patients undergoing AVNA at the time of Micra implant from the Micra Transcatheter Pacing (IDE) Study, Continued Access (CA) study, and Post-Approval Registry (PAR) were included in the analysis and compared to Micra patients without AVNA. Baseline characteristics, acute and follow-up outcomes, and electrical performance were compared between patients with and without AVNA during the follow-up period. RESULTS: A total of 192 patients (mean age 77.4 ± 8.9 years, 72% female) underwent AVNA at the time of Micra implant and were followed for 20.4 ± 15.6 months. AVNA patients were older, more frequently female, and tended to have more co-morbid conditions compared with non-AVNA patients (N = 2616). Implant was successful in 191 of 192 patients (99.5%). The mean pacing threshold at implant was 0.58 ± 0.35 V and remained stable during follow-up. Major complications within 30 days occurred more frequently in AVNA patients than non-AVNA patients (7.3% vs. 2.0%, p < .001). The risk of major complications through 36-months was higher in AVNA patients (hazard ratio: 3.81, 95% confidence interval: 2.33-6.23, p < .001). Intermittent loss of capture occurred in three AVNA patients (1.6%), all were within 30 days of implant and required system revision. There were no device macrodislodgements or unexpected device malfunctions. CONCLUSION: Concomitant AVN ablation and leadless pacemaker implant is feasible. Pacing thresholds are stable over time. However, patient comorbidities and the risk of major complications are higher in patients undergoing AVNA.

Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation.

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously. METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (<36 hours), symptomatic atrial fibrillation in the emergency department to be treated with a wait-and-see approach (delayed-cardioversion group) or early cardioversion. The wait-and-see approach involved initial treatment with rate-control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The primary end point was the presence of sinus rhythm at 4 weeks. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10. RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively. CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

Leadless pacing: Going for the jugular.

BACKGROUND: Leadless pacing is generally performed from a femoral approach. However, the femoral route is not always available. Until now, data regarding implantation using a jugular approach other than a single-case report were lacking. METHODS: The case records of all patients who underwent internal jugular venous (IJV) leadless pacemaker implantation (Micra, Medtronic, Dublin, Ireland) at our center were analyzed retrospectively. RESULTS: Nineteen patients underwent IJV leadless pacemaker implantation, nine females, mean age of 77.5 ±9.6  years; permanent atrial fibrillation in all patients with normal left ventricular ejection fraction. Implant indication was atrioventricular conduction disturbance in 10, pre-AV node ablation in seven, and replacement of a conventional VVI pacemaker in two (infection in one and lead malfunction in the other). The device was positioned at the superior septum in seven patients, apicoseptal in seven patients, and midseptal in five patients. In 12 patients, a sufficient device position was obtained at the first attempt, in three at the second, in one at the third, in one at the fourth, and in two at the sixth attempt. The mean pacing threshold was 0.56 ± 0.39V at 0.24-ms pulse width, sensed amplitude was 9.1 ± 3.2 mV, mean fluoroscopy duration was 3.1 ± 1.6 min. There were no vascular or other complications. At follow-up, electrical parameters remained stable in 18 of 19 patients. CONCLUSION: Although experience is minimal, we suggest that the IJV approach is safe and may be considered in patients where the femoral approach is contraindicated.

Acute cardioversion vs a wait-and-see approach for recent-onset symptomatic atrial fibrillation in the emergency department: Rationale and design of the randomized ACWAS trial.

BACKGROUND: Current standard of care for patients with recent-onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait-and-see approach with rate-control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost-effective as compared with current standard of care and to lead to a higher quality of life. DESIGN: The ACWAS trial (NCT02248753) is an investigator-initiated, randomized, controlled, 2-arm noninferiority trial that compares a wait-and-see approach to the standard of care. Consenting adults with recent-onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait-and-see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12-lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost-effectiveness for 1 year. CONCLUSIONS: The ACWAS trial aims at providing evidence for the use of a wait-and-see approach for patients with recent-onset symptomatic AF in the emergency department.

Feasibility and Accuracy of Cardiac Magnetic Resonance Imaging-Based Whole-Heart Inverse Potential Mapping of Sinus Rhythm and Idiopathic Ventricular Foci.

BACKGROUND: Inverse potential mapping (IPM) noninvasively reconstructs cardiac surface potentials using body surface potentials. This requires a volume conductor model (VCM), usually constructed from computed tomography; however, computed tomography exposes the patient to harmful radiation and lacks information about tissue structure. Magnetic resonance imaging (MRI) is not associated with this limitation and might have advantages for mapping purposes. This feasibility study investigated a magnetic resonance imaging-based IPM approach. In addition, the impact of incorporating the lungs and their particular resistivity values was explored. METHODS AND RESULTS: Three volunteers and 8 patients with premature ventricular contractions scheduled for ablation underwent 65-electrode body surface potential mapping. A VCM was created using magnetic resonance imaging. Cardiac surface potentials were estimated from body surface potentials and used to determine the origin of electrical activation. The IPM-defined origin of sinus rhythm corresponded well with the anatomic position of the sinus node, as described in the literature. In patients, the IPM-derived premature ventricular contraction focus was 3-dimensionally located within 8.3±2.7 mm of the invasively determined focus using electroanatomic mapping. The impact of lungs on the IPM was investigated using homogeneous and inhomogeneous VCMs. The inhomogeneous VCM, incorporating lung-specific conductivity, provided more accurate results compared with the homogeneous VCM (8.3±2.7 and 10.3±3.1 mm, respectively; P=0.043). The interobserver agreement was high for homogeneous (intraclass correlation coefficient 0.862, P=0.003) and inhomogeneous (intraclass correlation coefficient 0.812, P=0.004) VCMs. CONCLUSION: Magnetic resonance imaging-based whole-heart IPM enables accurate spatial localization of sinus rhythm and premature ventricular contractions comparable to electroanatomic mapping. An inhomogeneous VCM improved IPM accuracy.

Non-invasive focus localization, right ventricular epicardial potential mapping in patients with an MRI-conditional pacemaker system - a pilot study.

BACKGROUND: With the advent of magnetic resonance imaging (MRI) conditional pacemaker systems, the possibility of performing MRI in pacemaker patients has been introduced. Besides for the detailed evaluation of atrial and ventricular volumes and function, MRI can be used in combination with body surface potential mapping (BSPM) in a non-invasive inverse potential mapping (IPM) strategy. In non-invasive IPM, epicardial potentials are reconstructed from recorded body surface potentials (BSP). In order to investigate whether an IPM method with a limited number of electrodes could be used for the purpose of non-invasive focus localization, it was applied in patients with implanted pacing devices. Ventricular paced beats were used to simulate ventricular ectopic foci. METHODS: Ten patients with an MRI-conditional pacemaker system and a structurally normal heart were studied. Patient-specific 3D thorax volume models were reconstructed from the MRI images. BSP were recorded during ventricular pacing. Epicardial potentials were inversely calculated from the BSP. The site of epicardial breakthrough was compared to the position of the ventricular lead tip on MRI and the distance between these points was determined. RESULTS: For all patients, the site of earliest epicardial depolarization could be identified. When the tip of the pacing lead was implanted in vicinity to the epicardium, i.e. right ventricular (RV) apex or RV outflow tract, the distance between lead tip position and epicardial breakthrough was 6.0 ± 1.9 mm. CONCLUSIONS: In conclusion, the combined MRI and IPM method is clinically applicable and can identify sites of earliest depolarization with a clinically useful accuracy.

Computing volume potentials for noninvasive imaging of cardiac excitation.

BACKGROUND: In noninvasive imaging of cardiac excitation, the use of body surface potentials (BSP) rather than body volume potentials (BVP) has been favored due to enhanced computational efficiency and reduced modeling effort. Nowadays, increased computational power and the availability of open source software enable the calculation of BVP for clinical purposes. In order to illustrate the possible advantages of this approach, the explanatory power of BVP is investigated using a rectangular tank filled with an electrolytic conductor and a patient specific three dimensional model. METHODS: MRI images of the tank and of a patient were obtained in three orthogonal directions using a turbo spin echo MRI sequence. MRI images were segmented in three dimensional using custom written software. Gmsh software was used for mesh generation. BVP were computed using a transfer matrix and FEniCS software. RESULTS: The solution for 240,000 nodes, corresponding to a resolution of 5 mm throughout the thorax volume, was computed in 3 minutes. The tank experiment revealed that an increased electrode surface renders the position of the 4 V equipotential plane insensitive to mesh cell size and reduces simulated deviations. In the patient-specific model, the impact of assigning a different conductivity to lung tissue on the distribution of volume potentials could be visualized. CONCLUSION: Generation of high quality volume meshes and computation of BVP with a resolution of 5 mm is feasible using generally available software and hardware. Estimation of BVP may lead to an improved understanding of the genesis of BSP and sources of local inaccuracies.

Noninvasive imaging of cardiac excitation: current status and future perspective.

Noninvasive imaging of cardiac excitation using body surface potential mapping (BSPM) data and inverse procedures is an emerging technique that enables estimation of myocardial depolarization and repolarization. Despite numerous reports on the possible advantages of this imaging technique, it has not yet advanced into daily clinical practice. This is mainly due to the time consuming nature of data acquisition and the complexity of the mathematics underlying the used inverse procedures. However, the popularity of this field of research has increased and noninvasive imaging of cardiac electrophysiology is considered a promising tool to complement conventional invasive electrophysiological studies. Furthermore, the use of appropriately designed electrode vests and more advanced computers has greatly reduced the procedural time. This review provides descriptive overview of the research performed thus far and the possible future directions. The general challenges in routine application of BSPM and inverse procedures are discussed. In addition, individual properties of the biophysical models underlying the inverse procedures are illustrated.

Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry.

AIMS: To collect information on the use of the Reveal implantable loop recorder (ILR) in the patient care pathway and to investigate its effectiveness in the diagnosis of unexplained recurrent syncope in everyday clinical practice. METHODS AND RESULTS: Prospective, multicentre, observational study conducted in 2006-2009 in 10 European countries and Israel. Eligible patients had recurrent unexplained syncope or pre-syncope. Subjects received a Reveal Plus, DX or XT. Follow up was until the first recurrence of a syncopal event leading to a diagnosis or for ≥1 year. In the course of the study, patients were evaluated by an average of three different specialists for management of their syncope and underwent a median of 13 tests (range 9-20). Significant physical trauma had been experienced in association with a syncopal episode by 36% of patients. Average follow-up time after ILR implant was 10±6 months. Follow-up visit data were available for 570 subjects. The percentages of patients with recurrence of syncope were 19, 26, and 36% after 3, 6, and 12 months, respectively. Of 218 events within the study, ILR-guided diagnosis was obtained in 170 cases (78%), of which 128 (75%) were cardiac. CONCLUSION: A large number of diagnostic tests were undertaken in patients with unexplained syncope without providing conclusive data. In contrast, the ILR revealed or contributed to establishing the mechanism of syncope in the vast majority of patients. The findings support the recommendation in current guidelines that an ILR should be implanted early rather than late in the evaluation of unexplained syncope.

Cx40 polymorphism in human atrial fibrillation.

UNLABELLED: Previous studies have shown that two linked polymorphisms within regulatory regions of the gene for connexin40 (Cx40), at nucleotides -44 (G --> A) and +71 (A --> G) occur in about 7% of the general population. Cx40 is abundant in the atrium, and homozygosity for the linked polymorphisms combined with an SCN5A mutation appeared to be responsible for familial atrial standstill. We hypothesized that these polymorphisms are associated with the atrial electrophysiologic substrate favoring reentrant mechanisms for initiation of atrial fibrillation (AF). Reentry is promoted by spatial dispersion of refractoriness that can be expressed as a coefficient of dispersion (CD). METHODS: CD was calculated from the standard deviation of 12 local mean fibrillatory intervals recorded at right atrial sites during induced AF in 30 patients without structural heart disease (14 sporadic AF episodes, 16 no AF history). CD

Mechanism of propensity to atrial fibrillation in patients undergoing isthmus ablation for typical atrial flutter.

UNLABELLED: Mechanism of propensity to atrial fibrillation. BACKGROUND: Patients undergoing isthmus ablation for atrial flutter (AFL) may reveal postablation atrial fibrillation (AF). The electrophysiological mechanism is unclear. In patients with idiopathic AF, enhanced spatial dispersion of right atrial refractoriness was the substrate for the initiation of AF. We hypothesize that dispersion of right atrial refractoriness in patients undergoing AFL ablation is the major cause of postablation AF. METHODS: Consecutive patients (n=42) undergoing isthmus ablation for typical AFL were included. Twelve right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol, starting with one extrastimulus, followed by more aggressive pacing until AF was induced. Mean fibrillatory intervals were used to assess local refractoriness of each recording site. Spatial dispersion of right atrial refractoriness was calculated as the coefficient of dispersion (CD-value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). A CD-value of 3.0 or less was defined as normal, whereas CD-value greater than 3.0 was considered enhanced dispersion. PES and refractoriness analysis were followed by isthmus ablation. RESULTS: Of the 42 patients, 29 had CD-value of 3.0 or less. In these 29 patients, AF was induced with 1 extrastimulus in only 1 patient, with 2 extrastimuli in 4 patients and burst pacing was required to induce AF in 24 of these 29 patients. Prior to the procedure, 5 of 29 patients had AF episodes, after ablation 6 of 29 patients. Of the 42 patients, 13 had CD-value greater than 3.0, AF was induced with a single extrastimulus in 11 patients, with 2 extrastimuli in the remaining 2 patients. Of the 13 patients, 11 had AF episodes both before and after ablation (P<0.001). CONCLUSION: Enhanced spatial dispersion of right atrial refractoriness may be the substrate for propensity to AF in patients with AFL. The substrate was associated with enhanced inducibility of atrial fibrillation.

Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation.

Alterations in distribution, density, and properties of cardiac gap junctions, which mediate electrical coupling of cardiomyocytes, are considered potentially arrhythmogenic. We recently reported 2 linked polymorphisms within regulatory regions of the gene for the atrial gap junction protein connexin40 (Cx40) at nucleotides -44 (G-->A) and +71 (A-->G), which were associated with familial atrial standstill. The present study examined whether these Cx40 polymorphisms were associated with increased atrial vulnerability in vivo and arrhythmia susceptibility. In 30 subjects without structural heart disease, of whom 14 had documented sporadic paroxysmal atrial fibrillation (AF) and 16 had no AF history, inducibility of AF was assessed using an increasingly aggressive atrial stimulation protocol. Coefficient of spatial dispersion of refractoriness (CD) was calculated. CD was defined as the SD of 12 local mean fibrillatory intervals recorded at right atrial sites, expressed as a percentage of the overall mean fibrillatory interval. Cx40 genotypes were determined by direct DNA sequencing. Subjects were stratified according to normal or increased CD with a cutoff value of 3.0, because CD >3.0 was previously shown to be strongly associated with enhanced atrial vulnerability. The prevalence of the minor Cx40 allele (-44A) and -44AA genotype was significantly higher in subjects with increased dispersion (n=13) compared with those with CD < or =3.0 (n=17; P=0.00046 and P=0.025; odds ratios of 6.7 and 7.4) and a control population (n=253; P=0.00002 and P=3.90x10(-7)). Carriers of -44AA genotype had a significantly higher CD compared with those with -44GG genotype (6.37+/-1.21 versus 2.38+/-0.39, P=0.018), whereas heterozygotes had intermediate values (3.95+/-1.38, NS). All subjects with increased CD had a history of idiopathic AF compared with only 1 subject with normal CD. The -44A allele and -44AA genotype were significantly more frequent in subjects with prior AF than in those without (P=0.0019 and P=0.031; odds ratios 5.3 and 6.2). This study provides strong evidence linking Cx40 polymorphisms to enhanced atrial vulnerability and increased risk of AF. The full text of this article is available online at http://circres.ahajournals.org.

On the atrial response to focal discharges in man.

INTRODUCTION: Triggers and vulnerability are key factors for the occurrence of atrial fibrillation (AF). The aim of this study was to assess spatial dispersion of atrial refractoriness and vulnerability in response to both focal discharges as well as programmed electrical stimulation in patients undergoing ablation of atrial arrhythmogenic foci. METHODS AND RESULTS: Twenty-nine patients were studied, and 12 right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol that started with one extrastimulus, followed by more aggressive pacing until AF was obtained. Mean fibrillatory intervals were used to assess the local refractoriness of each recording site. Spatial dispersion of refractoriness was calculated as the coefficient of dispersion (CD value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). Based on our previous study, a CD value 3.0 was considered enhanced spatial dispersion of refractoriness. Fifteen of 29 patients had normal dispersion of refractoriness (mean CD value 1.65 +/- 0.43), and AF was inducible with burst pacing only. These patients had focal discharges causing rapid atrial tachycardia with a focal activation pattern. Activation mapping of focal activity was possible in 14 of 15 patients. Focal triggering of AF occurred in only 1 of 15 patients. Fourteen of 29 patients had enhanced dispersion (mean CD value 4.2 +/- 0.72). AF was inducible with a single extrastimulus in 11 of 14 patients (P < 0.001). Focal triggering of AF occurred in all 14 patients. CONCLUSION: Spatial dispersion of atrial refractoriness determines whether focal atrial discharges trigger AF with disorganized activity or, alternatively, only rapid atrial tachycardia.