The effect of electrode density on the interpretation of atrial activation patterns in epicardial mapping of human persistent atrial fibrillation.

BACKGROUND: Mechanisms sustaining human persistent atrial fibrillation (AF) remain debated, with significant differences between high-density epicardial and global endocardial mapping studies. A key difference is the density of recording electrodes. OBJECTIVE: We aimed to determine the differences in the prevalence of different atrial activation patterns, and specifically in the prevalence of rotational activations, with varying densities of bipolar electrodes. METHODS: Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded using a triangular plaque (6.75 cm(2) area; 117 bipoles; 2.5-mm inter-bipole spacing) applied to the left atrial posterior wall or right atrial free wall. Dynamic wavefront mapping based on the timing of atrial electrograms was applied to 2 discrete 10-second AF segments. The spacing between bipolar electrode locations was increased from 2.5 × 3.5 mm in the horizontal and oblique directions to 5.0 × 3.5, 5.0 × 7.1, and 7.5 × 10.6 mm, with wavefront mapping repeated at each density. RESULTS: As density reduced, there was a significant change in relative proportions of the various activation patterns (F=3.69; P < .001). Simple broad wavefront activations became more prevalent (20% ± 8% to 54% ± 8%; P < .05) and complex patterns became less prevalent (48% ± 8% to 9% ± 8%; P < .05) with reducing density. The prevalence of rotational activity declined with bipole density, from median 5.0% (range 0.9%-12.1%) to 0% (range 0%-1.5%) (P = .03). The largest change occurred between inter-bipole spacings of 5.0 × 3.5 and 5.0 × 7.1 mm. CONCLUSION: Apparent activation patterns in persistent AF vary significantly with electrode density. Low density underestimates the prevalence of complex and rotational patterns. The largest difference occurs between an inter-bipole spacing of 5.0 × 3.5 and a spacing of 5.0 × 7.1 mm. This may have important implications for mapping technology design.

Temporal Stability of Rotors and Atrial Activation Patterns in Persistent Human Atrial Fibrillation: A High-Density Epicardial Mapping Study of Prolonged Recordings.

OBJECTIVES: This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. BACKGROUND: The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. METHODS: Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm2; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n = 9) and the right atrial free wall (n = 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. RESULTS: The dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. CONCLUSIONS: In patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with short CL activity, and, when recurrent, demonstrate anatomical determinism.

Acute atrial stretch results in conduction slowing and complex signals at the pulmonary vein to left atrial junction: insights into the mechanism of pulmonary vein arrhythmogenesis.

BACKGROUND: The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch is an important stimulus to AF. We aimed to characterize the response of the junction to acute stretch, hypothesizing that stretch would result in electrophysiological changes predisposing to re-entry. METHODS AND RESULTS: Fifteen participants undergoing cardiac surgery underwent evaluation of the right superior PV-LA junction using an epicardial mapping plaque. In 10, this was performed before and after atrial stretch imposed by rapid volume expansion, and in 5, it was performed with an intervening observation period. Activation was characterized by conduction slowing and electrogram fractionation transversely across the PV-LA junction, with lines of block also demonstrated perpendicular to the junction. Conduction was decremental (plaque activation time 135.8 ± 46.8 ms with programmed extra stimuli at 10 ms above effective refractory period versus 66.1 ± 22.9 ms with pacing at 400 ms; P<0.001) and percentage fractionation was greater with programmed extra stimuli at 10 ms above (33.5%± 15.3% versus 20.7%± 14.0%, P=0.001). Right atrial pressure increased by 2.5 ± 1.8 mm Hg (P=0.002) with volume expansion. Stretch resulted in conduction slowing across the PV-LA junction (increase in activation time 10.9 ± 14.6 ms in acute stretch group versus -0.1 ± 4.5 ms in control group; P=0.002). Conduction slowing was more marked with programmed extra stimuli at 10 ms above effective refractory period than with stable pacing (13.4 ± 16.5 ms versus 1.7 ± 5.4 ms; P=0.003). Stretch resulted in a significant increase in fractionated electrograms (7.9%± 7.0% versus -0.4 ± 3.3; P=0.004). CONCLUSIONS: Acute stretch results in conduction slowing across the PV-LA junction, with a greater degree of signal complexity. This substrate may be important in AF initiation and maintenance by promoting re-entry.

Absence of gender-based differences in the atrial and pulmonary vein substrate: a detailed electroanatomic mapping study.

BACKGROUND: Gender-based differences in the clinical nature of cardiac arrhythmias such as atrial fibrillation (AF) are well established. OBJECTIVE: The purpose of this study was to identify any such gender-based differences in the underlying pulmonary vein and atrial substrate. METHODS AND RESULTS: Thirty-eight patients with no history of AF undergoing catheter ablation for supraventricular tachycardia (SVT) and 55 with paroxysmal or persistent AF undergoing catheter ablation of AF underwent detailed electroanatomic mapping of the pulmonary veins and atria. Refractory periods in multiple locations, sinus node function, endocardial bipolar voltage, pulmonary vein and atrial conduction, and bipolar electrogram complexity were analyzed. There were no significant between-gender differences in age or other clinical variables known to impact on the atrial or pulmonary vein substrate. In neither the AF nor the non-AF cohorts were there any significant differences in atrial or pulmonary vein refractoriness, sinus node function, any measure of PV electrophysiology, or any measure of atrial electrophysiology. CONCLUSION: No systematic between-gender differences were observed in the PV or atrial substrate either in those with or without a history of AF, with a similar prevalence of the cardiovascular comorbidities frequently associated with atrial remodeling and AF seen in both male and female groups.

Relationship between the electrocardiographic atrial fibrillation cycle length and left atrial remodeling: a detailed electroanatomic mapping study.

BACKGROUND/OBJECTIVE: The purpose of this study was to characterize the association between the extent of left atrial electroanatomic remodeling in atrial fibrillation and the atrial fibrillation cycle length derived from lead V1 of the surface ECG (V1AFCL). METHODS: Twenty-three patients in atrial fibrillation (AF) who presented for AF ablation underwent detailed electroanatomic mapping of the left atrium. The digital 12-lead ECG was exported for offline analysis, with signal filtering and QRST subtraction used to reveal the fibrillatory baseline in lead V1. Mean V1AFCL was determined by direct annotation of the fibrillatory baseline, and the corresponding dominant V1AFCL was determined by Fourier transformation to derive the dominant frequency from the frequency power spectrum. The simultaneous AFCL from proximal and distal coronary sinus recordings was determined using the same methods. The strength of the association between various left atrial remodeling variables and V1AFCL was determined. RESULTS: The 2 methods of deriving V1AFCL and intracardiac AFCL were found to produce highly equivalent results. V1AFCL showed significant correlation with intracardiac AFCL derived from both proximal and distal coronary sinus recordings. A longer V1AFCL was associated with slower left atrial conduction velocity and greater signal complexity but not with other remodeling variables, including left atrial size, atrial refractoriness, and mean endocardial voltage. CONCLUSION: A longer atrial fibrillatory cycle length in surface ECG lead V1 is significantly associated with parameters of more advanced left atrial electroanatomic remodeling, specifically slower atrial conduction and more extensive electrogram fractionation.

Catheter-tissue contact force determines atrial electrogram characteristics before and lesion efficacy after antral pulmonary vein isolation in humans.

INTRODUCTION: Electrogram (EGM) characteristics are used to infer catheter-tissue contact. We examined if (a) atrial EGM characteristics predicted CF and (b) compared the value of CF versus other surrogates for predicting lesion efficacy. METHODS AND RESULTS: Twelve paroxysmal AF patients underwent pulmonary vein isolation using radiofrequency (RF) ablation facilitated by a novel CF-sensing catheter. Operators were blinded to CF. EGM amplitude, width, and morphology were measured pre- and post-RF. At each RF site, average CF, force-time integral (FTI), impedance fall, time to impedance plateau, maximum power, catheter tip temperature, and total energy delivered were recorded. An effective lesion was defined based on previously validated EGM criteria for transmural lesions. There was a moderate correlation between CF and EGM amplitude (r = 0.19) and EGM width (r = -0.22). Pre-RF, EGM amplitude, and width had modest to poor discriminative capacity for identifying preablation CF (e.g., EGM amplitude identified CF>20 g with sensitivity and specificity of 67% and 60%, respectively). Preablation CF, FTI, and total energy delivered during RF were the only independent predictors of effective lesion formation. Neither pre-RF EGM amplitude/width nor power, temperature, and impedance changes during RF predicted effective lesion formation. An average CF >16 g or FTI >404 g*s had excellent sensitivity and specificity (>80%) for identifying an effective lesion. CONCLUSIONS: EGM characteristics do not reliably predict either CF before the onset of RF, nor do they predict the likelihood of an effective lesion. CF parameters were superior to power, temperature, and impedance changes during RF in predicting lesion efficacy.

Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity.

OBJECTIVES: To characterize the nature of atrial fibrillation (AF) activation in human persistent AF (PerAF) using modern tools including activation, directionality analyses, complex-fractionated electrogram, and spectral information. BACKGROUND: The mechanism of PerAF in humans is uncertain. METHODS AND RESULTS: High-density epicardial mapping (128 electrodes/6.75 cm(2)) of the posterior LA wall (PLAW), LA and RA appendage (LAA, RAA), and RSPV-LA junction was performed in 18 patients with PerAF undergoing open heart surgery. Continuous 10 s recordings were analysed offline. Activation patterns were characterized into four subtypes (i) wavefronts (broad or multiple), (ii) rotational circuits (≥2 rotations of 360°), (iii) focal sources with centrifugal activation of the entire mapping area, or (iv) disorganized activity [isolated chaotic activation(s) that propagate ≤3 bipoles or activation(s) that occur as isolated beats dissociated from the activation of adjacent bipole sites]. Activation at a total of 36 regions were analysed (14 PLAW, 3 RSPV-LA, 12 LAA, and 7 RAA) creating a database of 2904 activation patterns. In the majority of maps, activation patterns were highly heterogeneous with multiple unstable activation patterns transitioning from one to another during each recording. A mean of 3.8 ± 1.6 activation subtypes was seen per map. The most common patterns seen were multiple wavefronts (56.2 ± 32%) and disorganized activity (24.2 ± 30.3%). Only 2 of 36 maps (5.5%) showed a single stable activation pattern throughout the 10-s period. These were stable planar wavefronts. Three transient rotational circuits were observed. Two of the transient circuits were located in the posterior left atrium, while the third was located on the anterior surface of the LAA. Focal activations accounted for 11.3 ± 14.2% of activations and were all short-lived (≤2 beats), with no site demonstrating sustained focal activity. CONCLUSION: Human long-lasting PerAF is characterized by heterogeneous and unstable patterns of activation including wavefronts, transient rotational circuits, and disorganized activity.

Characterization of catheter-tissue contact force during epicardial radiofrequency ablation in an ovine model.

BACKGROUND: Contact force (CF) during radiofrequency ablation (RFA) is an important determinant of endocardial lesion size with limited data on epicardial RFA and CF. We evaluated CF characteristics using irrigated RFA on the epicardium in an ovine model. METHODS AND RESULTS: In 12 sheep, a 7-F irrigated RFA catheter with CF sensor was introduced via a pericardial incision onto/in parallel with ventricular epicardium. RFA (30 W per 30 second duration) was applied at 5g, 10g, 20g, 40g, and 70g: (1) over left and right ventricular myocardium with or without fat, (2) either directly over or adjacent to a coronary artery, or directly over the phrenic nerve. Force-time integral, lesion dimensions, and coronary artery/phrenic nerve injury were recorded. Lesion size, volume, and force-time integral progressively increased with higher CF (P<0.05). Steam pops occurred with high CF. Epicardial fat had an attenuating effect on RF penetration into myocardium (P<0.05); however, myocardial RF lesions could be created at sites with >3.5 mm epicardial fat. At sites with epicardial fat, each 10g increment in CF led to a 0.6 mm increase in lesion depth, whereas each 1 mm of fat reduced lesion depth into underlying myocardium by 0.7 mm. Extent of acute coronary injury with direct and indirect RFA and phrenic nerve palsy occurrence was proportional to CF. CONCLUSIONS: CF is a determinant of epicardial RF lesion size, steam pops, acute coronary artery injury, and phrenic nerve injury. Although epicardial fat limits lesion size, RFA with high CF can produce small myocardial RF lesions at sites of thick epicardial fat.

Predictive value of impedance changes for real-time contact force measurements during catheter ablation of atrial arrhythmias in humans.

BACKGROUND: Catheter-tissue contact force (CF) determines radiofrequency (RF) ablation lesion size. Impedance changes during RF delivery are used as surrogate markers for CF. The relationship between impedance and real-time CF in humans remains unknown. OBJECTIVES: To determine whether impedance changes have predictive value for real-time CF during catheter ablation of atrial arrhythmias. METHODS: Real-time CF, force-time integral, and impedance were measured in 2265 RF lesions for atrial fibrillation or flutter in 34 patients. Operators were blinded to CF measurements. Impedance preablation, at 5-second intervals for 30 seconds after the RF onset, maximal impedance fall and time to impedance plateau during RF were correlated with CF. Average CF was divided into low (≤20 g), intermediate (21-60 g), and high (>60 g) categories. RESULTS: Preablation impedance poorly correlated with preablation CF (R = .07). Maximal impedance fall modestly correlated with average CF and force-time integral (R = .32 and .37, respectively). There was a large degree of overlap in impedance fall between different CF categories. A maximal impedance fall of 10 Ω could predict average CF of >20 g, with a sensitivity and specificity of 71% and 53% and a positive and negative predictive value of 51% and 49%, respectively. Impedance fall was only able to differentiate between different CF categories ≥15 seconds after the RF onset. Higher CFs moderately correlated with delayed plateau in impedance (R = .41). CONCLUSIONS: Impedance measurements (both baseline and impedance fall) are, at best, moderately efficacious as surrogate markers for predicting real-time catheter-tissue CF. These findings highlight the importance of real-time CF measurements, rather than impedance changes to optimize ablation efficacy.

Prospective characterization of catheter-tissue contact force at different anatomic sites during antral pulmonary vein isolation.

BACKGROUND: Catheter-tissue contact is critical for effective lesion creation. We characterized the contact force (CF) at different anatomic sites during antral pulmonary vein (PV) isolation for atrial fibrillation. METHODS AND RESULTS: Two experienced operators performed PV isolation in 22 patients facilitated by a novel CF-sensing ablation catheter in a blinded fashion. Average CF and force-time integral data from 1602 lesions were analyzed. The left and right PV antra were divided into the following: carina, superior, inferior, anterior, and posterior quadrants for analysis. There was significant variability in CF within and between different PV quadrants (P<0.05). Lowest CF of all left PV sites was at the carina and anterior quadrant, whereas highest CF was at the superior and inferior quadrants (P<0.05). Lowest CF of all right PV sites was at the carina, whereas highest CF was at the anterior and inferior quadrants (P<0.05). When comparing similar PV quadrants on the left versus right (eg, left carina versus right carina), CF was always higher in the right PVs (P<0.05), except at the superior quadrant where CF was similar in the left and right PVs (P=0.19). There was no specific pattern of anatomic distribution of excess CF (P=0.39). CONCLUSIONS: Monitoring of catheter-tissue CF during PV isolation demonstrates significant variability in CF within and between different PV antral sites. Sites of lowest CF were the carina and anterior left PVs and the carina of the right PVs. This information may be important for improving ablation efficacy and clinical outcomes during PV isolation.

Esophageal hematoma after atrial fibrillation ablation: incidence, clinical features, and sequelae of esophageal injury of a different sort.

BACKGROUND: Esophageal hematoma recently has been reported as a form of esophageal injury after atrial fibrillation (AF) ablation, attributed to the use of transesophageal echocardiography (TEE). We sought to determine the incidence, clinical features, and sequelae of this form of esophageal injury. METHODS AND RESULTS: This was a prospective series of 1110 AF ablation procedures performed under general anesthesia (GA) over 9 years. TEE was inserted after induction of GA to exclude left atrial appendage thrombus, define cardiac function, and guide transseptal puncture. The procedural incidence of esophageal hematoma was 0.27% (3/1110 procedures, mortality 0%). Odonyphagia, regurgitation, and hoarseness were the predominant symptoms, with an onset within 12 hours. There was absence of fever and neurological symptoms. Chest computed tomography excluded atrio-esophageal fistula and was diagnostic of esophageal hematoma localized to either the upper esophagus or extending the length of the mid and lower esophagus; endoscopy confirmed the diagnosis. Management was conservative in all cases comprising of ceasing oral intake and anticoagulation. Long term sequelae included esophageal stricture formation requiring dilatation, persistent esophageal dysmotility (mid esophageal hematoma), and vocal cord paralysis, resulting in hoarse voice (upper esophageal hematoma). CONCLUSIONS: Esophageal hematoma is a rare but important differential diagnosis for esophageal injury after TEE-guided AF ablation under GA, and can result in significant patient morbidity. Key clinical features differentiate presentation of esophageal hematoma from that of an atrio-esophageal fistula.

Atrial fibrillation inducibility in the absence of structural heart disease or clinical atrial fibrillation: critical dependence on induction protocol, inducibility definition, and number of inductions.

BACKGROUND: Inducibility of atrial fibrillation (AF) after pulmonary vein isolation has been used to guide additional left atrial ablation in paroxysmal AF. The sensitivity and specificity of AF induction in this setting remains uncertain. We examined the incidence and characteristics of inducible AF in patients without structural heart disease or clinical AF and the effect of different induction protocols on AF inducibility. METHODS AND RESULTS: In 44 patients with supraventricular tachycardia with no history of AF or risk factors for AF, atrial refractoriness and conduction were measured, followed by AF induction attempts (10/patient). Each induction was performed after a waiting time that exceeded twice the duration of induced AF from the preceding induction. AF≥1 minute was considered inducible, and ≥5 minutes as sustained. Burst pacing (at 200 ms for 10 seconds) was compared to decremental pacing (from 200 ms to shortest cycle length, resulting in 1:1 atrial capture for 10 seconds). After 10 inductions, AF was inducible in 49.5%, and sustained in 29.5% of patients. The incidence of both inducible and sustained AF increased with each induction. Apart from male gender, no clinical or electrophysiological features were associated with sustained AF. Decremental pacing was associated with a higher incidence of sustained AF (41.2% versus 14.8%, P=0.049), longer duration of AF (P=0.006), and shorter mean AF cycle length (P<0.001) compared with burst pacing. CONCLUSIONS: Inducible and sustained AF is common in patients in the absence of structural heart disease or clinical AF, and its incidence varies according to gender, method of induction, and number of inductions. There is a direct relationship between AF persistence and number of inductions, which has not reached a plateau after 10 inductions.

Effect of respiration on catheter-tissue contact force during ablation of atrial arrhythmias.

BACKGROUND: Catheter-tissue contact is important for effective lesion creation. OBJECTIVE: To assess the effect of respiration on contact force (CF) during atrial fibrillation and cavotricuspid isthmus (CTI)-dependent atrial flutter ablation. METHODS: Patients undergoing CTI ablation alone (n = 15) and pulmonary vein (PV) isolation alone (n = 12) under general anesthesia were recruited. Lesions were delivered under ventilation (30 seconds) alternating with lesions delivered under apnea (30 seconds) at an adjacent anatomical site at CTI or PV antra. The average force (F(av)), force-time integral (FTI), and force variability were measured in a region-specific manner by using a novel CF-sensing ablation catheter. Operators were blinded to CF data. RESULTS: F(av) and FTI were higher with apnea than with ventilation in all CTI and PV segments (P <.05), an effect attributed to drop in CF with each respiratory swing, resulting in greater force variability during ventilation (P <.05). Low FTI lesions (<500 g) were strongly associated with longer ablation time to achieve bidirectional CTI block (r(2) = .81; P <.001), left PVI (r(2) = .65; P = .009), and right PVI (r(2) = .41; P = .05). Sites with transient CTI block were associated with lower F(av) and FTI than were sites with persistent CTI block (P <.05). Sites of acute PV reconnection were associated with lower F(av) and FTI compared with non-reconnected sites (P <.001). CONCLUSIONS: Catheter-tissue CF is critically influenced by respiration; greater CF is observed with ablation during apnea. Poor CF is implicated in longer ablation time to achieve CTI block or PV isolation and in acute reconnection.

Atrial electrical and structural remodeling associated with longstanding pulmonary hypertension and right ventricular hypertrophy in humans.

INTRODUCTION: Pulmonary hypertension (PH) is common to a range of cardiopulmonary conditions and is associated with atrial arrhythmias. However, little is known of the isolated atrial effects of PH and right atrial dilatation (RA) in humans. To avoid the confounding effects of PH-associated disease states, we performed detailed electrophysiological (EP) and electroanatomic (EA) mapping of the RA in patients with idiopathic PH. METHODS AND RESULTS: Eight PH patients (mean pulmonary arterial [PA] pressure 39.0 ± 15.8 mmHg) and 16 age-matched controls (mean PA pressure 11.5 ± 4.1 mmHg, P < 0.0001) were studied. Corrected sinus node recovery times (cSNRT), atrial effective refractory periods (ERPs), conduction delay at the crista terminalis (CT), and inducibility of atrial fibrillation (AF) were evaluated. EA mapping (pacing cycle length 600 and 300 milliseconds) was performed to determine RA global and regional voltage, conduction velocities, atrial activation times, fractionated electrograms and double potentials. Patients with PH demonstrated a prolongation in cSNRT without significant change in atrial ERP and an increase in AF inducibility. PH was associated with lower tissue voltage (1.8 ± 0.4 mV in PH vs 2.2 ± 0.4 mV in controls, P = 0.02), increased low voltage areas (13.7 ± 8.2% in PH vs 6.2 ± 3.7% in controls, P < 0.01) and the presence of electrically silent areas. Conduction velocities were slower (global 67.3 ± 5.6 cm/s vs 92.8 ± 4.0 cm/s, P < 0.001) and fractionated electrograms and double potentials were more prevalent (14.7 ± 4.4% vs 6.3 ± 4.1, P < 0.01) in PH compared with controls, respectively. CONCLUSION: Idiopathic PH is associated with RA remodeling characterized by: generalized conduction slowing with marked regional abnormalities; reduced tissue voltage; and regions of electrical silence. These changes provide important insights into the isolated effects of PH fundamental to a range of clinical conditions associated with AF.

Electroanatomic remodeling of the left atrium in paroxysmal and persistent atrial fibrillation patients without structural heart disease.

INTRODUCTION: The nature of the atrial substrate thought to contribute toward maintaining atrial fibrillation (AF) outside the pulmonary veins remains poorly defined. Therefore, our objective was to determine whether patients with paroxysmal and persistent AF have an abnormal electroanatomic substrate within the left atrium (LA). METHODS AND RESULTS: Thirty-one patients with AF (17 paroxysmal AF and 14 persistent AF) were compared with 15 age-matched controls with left-sided supraventricular tachycardia (SVT). High-density 3-dimensional electroanatomic maps were created and the LA was divided into 8 segments for regional analysis. Bipolar voltage, conduction, and effective refractory periods (ERPs) of the posterior LA, left atrial appendage (LAA), and distal coronary sinus (CSd) and percentage complex signals were assessed. In the majority of LA regions, compared with controls, AF patients had: (1) lower mean voltage and a higher percentage low voltage; (2) slower conduction; and (3) more prevalent complex signals. Many of these changes were more marked in the persistent than the paroxysmal AF group. CONCLUSIONS: Patients with AF have lower regional voltage, increased proportion of low voltage, slowed conduction, and increased proportion of complex signals compared to controls. Many of these changes are more pronounced in persistent AF patients, suggesting there may be a progressive nature to the changes. Differences occurred in the absence of structural heart disease. These substrate abnormalities provide further insight into the progressive nature of atrial remodeling and the mechanisms involved in maintenance of AF.

Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation.

BACKGROUND: Whether curative ablation can prevent progression of the atrial electroanatomic remodeling associated with atrial fibrillation (AF) is not known. OBJECTIVE: The purpose of this study was to determine whether successful radiofrequency ablation (RFA) of AF can prevent progression of the atrial substrate associated with AF. METHODS: Detailed right atrial electroanatomic maps from 11 patients without apparent structural heart disease undergoing RFA of AF at baseline and ≥6 months following successful RFA were compared to 11 control patients undergoing electrophysiologic evaluation of supraventricular tachycardia. Bipolar voltage, conduction, effective refractory periods (ERPs), and signal complexity were assessed. RESULTS: At baseline compared with the control group, the AF group demonstrated (1) lower voltage (P <.001); (2) slowed conduction (P = .005); (3) more prevalent complex signals (P <.001); (4) prolonged regional refractoriness (P <.05), and (5) left atrial dilation (P = .01). At 10 ± 13 month follow-up, the AF group demonstrated the following compared to baseline: (1) lower voltage (P <.05); (2) either no improvement or further slowing of conduction; (3) further prolongation of regional refractoriness (P <.05); and (4) reversal of left atrial dilation (P <.05). CONCLUSION: Patients with lone AF demonstrate evidence of an abnormal atrial substrate at baseline compared to control patients without AF. This substrate does not appear to reverse even after successful catheter ablation. These findings may have implications for long-term outcomes of ablation and for timing of ablative intervention.

High-density epicardial mapping of the pulmonary vein-left atrial junction in humans: insights into mechanisms of pulmonary vein arrhythmogenesis.

BACKGROUND: The pulmonary veins (PVs) and the PV-LA (left atrium) junction are established sources of triggers initiating atrial fibrillation. In addition, they have been implicated in the maintenance of arrhythmia. OBJECTIVE: To undertake high-density electrophysiological characterization of the right superior PV-LA junction in humans. METHODS: Mapping was performed in 18 patients without a history of atrial fibrillation undergoing cardiac surgery. A high-density epicardial plaque was positioned at the anterior right superior pulmonary vein covering 3 regions: LA, PV-LA junction, and the PV. Isochronal maps were created during (1) sinus rhythm (SR); (2) LA pacing (LA-Pace); (3) PV pacing (PV-Pace); (4) LA programmed electrical stimulation (LA-PES); and (5) PV programmed electrical stimulation (PV-PES). Regional differences in conduction slowing/conduction block (CS/CB) and the prevalence of fractionated signals (FS) and double potentials (DPs) were assessed. RESULTS: A region of isochronal crowding representing CS/CB developed at the PV-LA junction in 84% of the maps. Three distinct activation patterns were seen. Pattern 1: Uniform SR activation without CS/CB. LA-Pace and PES caused 1 to 2 lines of isochronal crowding (CS/CB) at the PV-LA junction. Pattern 2: CS/CB occurred at the PV-LA junction in SR. LA/PV-Pace and LA/PV-PES caused an increase in CS/CB at the PV-LA junction with widely split DPs and FS. Pattern 3: A single incomplete line of CS at the PV-LA junction in SR. With LA/PV pacing and LA/PV-PES, multiple lines (≥3) of CS/CB developed at the PV-LA junction with evidence of circuitous activation and a marked increase in DPs and FS. CONCLUSION: High-density epicardial mapping of the right superior pulmonary vein demonstrates marked functional conduction delay and circuitous activation patterns at the PV-LA junction, creating the substrate for reentry.

Electroanatomic remodelling of the pulmonary veins associated with age.

AIMS: Increasing age is a significant risk factor for developing atrial fibrillation (AF). Pulmonary vein (PV) triggers are critical in the mechanism of AF, but little is known of the substrate changes that occur within the PVs with ageing. Therefore, we sought to identify whether ageing is associated with electroanatomic changes within the pulmonary veins. METHODS AND RESULTS: Twenty-five patients undergoing ablation for left-sided supraventricular tachycardia had high-density 3D electroanatomic maps of all four PVs created. Patients were divided into two groups: group 1 aged <50 years and group 2 aged >50 years. Mean-voltage (MV), % low-voltage (LV < 0.5 mV), conduction, signal complexity, and PV muscle sleeve length and diameter were assessed. Age was 33 ± 8 vs. 66 ± 8 years for groups 1 and 2, respectively (P < 0.001). Group 2 demonstrated: (i) lower MV within the PVs (1.66 ± 1.1 vs. 1.88 ± 1.1 mV, P < 0.001); (ii) increased % LV (5.0 vs. 1.1%, P < 0.001), and increased voltage heterogeneity within the PVs (65 ± 14 vs. 55 ± 8%, P < 0.05); (iii) regional and global conduction slowing in the PVs; and (iv) increased % complex signals within the PVs (1.4 vs. 0.4%, P = 0.009). There was no difference in PV sleeve length or diameter. CONCLUSION: Increasing age is associated with PV electroanatomic changes characterized by a significant reduction in PV voltage, conduction slowing, and increasing signal complexity. These observations provide new insights into the potential mechanisms behind the increased prevalence of AF with advancing age.

Atrial electrical and structural changes associated with longstanding hypertension in humans: implications for the substrate for atrial fibrillation.

UNLABELLED: INTRODUCTION: Hypertension (HT) is the most common modifiable risk factor for atrial fibrillation (AF), yet little is known of the atrial effects of chronic HT in humans. We aimed to characterize the electrophysiologic (EP) and electroanatomic (EA) remodeling of the right atrium (RA) in patients with chronically treated systemic HT and left ventricular hypertrophy (LVH) without a history of AF. METHODS AND RESULTS: Twenty patients with (systolic BP 145 ± 10 mmHg) and without (BP 119 ± 11 mmHg, P < 0.01) systemic HT underwent detailed conventional EP and EA voltage and activation mapping. We measured RA refractoriness at the coronary sinus and high septum at cycle lengths (CLs) 600 and 450 ms, and RA conduction velocities, activation times, and voltages at a global and regional level at CLs 600 ms and 300 ms. HT was associated with slowing of global (73 ± 17 cm/s vs 96 ± 12 cm/s in controls, P < 0.01) and regional conduction velocity particularly in the posterior RA (70 ± 17 cm/s vs 96 ± 12 cm/s in controls, P < 0.01) at the crista terminalis (fractionation and double potentials in HT 72%± 4 vs 43%± 23 in controls, P = 0.04). Mean RA voltage was similar between the 2 groups, however HT was associated with an increase in areas of low voltage (<0.5 mV; HT 13% vs controls 9%, P = 0.04). Sustained AF was induced in 30% HT patients and no controls. CONCLUSION: Chronically treated systemic HT with LVH is accompanied by atrial remodeling characterized by: (i) global conduction slowing, (ii) regional conduction delay particularly at the crista terminalis, and (iii) increased AF inducibility. These changes may in part be responsible for the increased propensity to AF associated with systemic HT.

Electroanatomic properties of the pulmonary veins: slowed conduction, low voltage and altered refractoriness in AF patients.

INTRODUCTION: Rapid PV activity is critical in initiating and maintaining AF. The underlying substrate responsible for this remains uncertain. We sought to identify if patients with paroxysmal (PAF) and persistent atrial fibrillation (PeAF) have an abnormal substrate within the pulmonary veins (PVs). METHODS AND RESULTS: Thirty-nine patients with AF (21 PAF, 18 PeAF) were compared with 15 age-matched controls with left-sided accessory pathways (AVRT). High-density 3D electroanatomic maps of the PVs were created. PV voltage, conduction, PV muscle sleeve length, effective refractory periods (ERPs) of the PVs, posterior left atrium (PLA), left atrial appendage (LAA) and distal coronary sinus (CSd), and signal complexity were assessed. Compared with controls, the PVs of AF patients had (1) lower mean-voltage and a higher % low-voltage; (2) shorter PV muscle sleeves; (3) slower conduction; (4) shorter ERP; and (5) more prevalent complex signals. Compared with the PAF group, the PeAF group had (1) higher % low voltage; (2) slower conduction; and (3) more complex signals. In PAF patients, the PLA and LAA ERPs were longer than controls and the PV ERP was shorter than controls; in PeAF patients PLA and LAA ERPs were reduced, but to a lesser extent than in the PVs. AF induction occurred during PV ERP testing in both AF groups, but not controls. CONCLUSIONS: PAF and PeAF patients demonstrate electrical and electroanatomic remodeling of the PVs compared to control patients without prior AF. Some of these changes were more marked in PeAF.