Pawel Kuklik

Outcomes of long-standing persistent atrial fibrillation ablation: A systematic review

BACKGROUND Ablation of long-standing persistent atrial fibrillation (AF) is highly variable, with differing techniques and outcomes. OBJECTIVE The purpose of this study was to undertake a systematic review of the literature with regard to the impact of ablation technique on the outcomes of long-standing persistent AF ablation. METHODS A systematic search of the contemporary English scientific literature (from January 1, 1990 to June 1, 2009) in the PubMed database identified 32 studies on persistent/long-standing persistent or long-standing persistent AF ablation (including four randomized controlled trials). Data on single-procedure, drug-free success, multiple procedure success, and pharmaceutically assisted success at longest follow-up were collated. RESULTS Four studies performed pulmonary vein isolation alone (21%-22% success). Four studies performed pulmonary vein antrum ablation with isolation (PVAI; n = 2; 38%-40% success) or without confirmed isolation (PVA; n = 2; 37%-56% success). Ten studies performed linear ablation in addition to PVA (n = 5; 11%-74% success) or PVAI (n = 5; 38%-57% success). Three studies performed posterior wall box isolation (n = 3; 44%-50% success). Five studies performed complex fractionated atrial electrogram ablation (n = 5; 24%-63% success). Six studies performed complex fractionated atrial electrogram ablation as an adjunct to PVA (n = 2; 50%-51% success), PVAI (n = 3; 36%-61% success), or PVAI and linear (n = 1; 68% success) ablation. Five studies performed the stepwise ablation approach (38%-62% success). CONCLUSION The variation in success within and between techniques suggests that the optimal ablation technique for long-standing persistent AF is unclear. Nevertheless, long-standing persistent AF can be effectively treated with a composite of extensive index catheter ablation, repeat procedures, and/or pharmaceuticals.

Long‐term Outcomes of Catheter Ablation of Atrial Fibrillation: A Systematic Review and Meta‐analysis

Background In the past decade, catheter ablation has become an established therapy for symptomatic atrial fibrillation (AF). Until very recently, few data have been available to guide the clinical community on the outcomes of AF ablation at ≥3 years of follow‐up. We aimed to systematically review the medical literature to evaluate the long‐term outcomes of AF ablation. Methods and Results A structured electronic database search (PubMed, Embase, Web of Science, Cochrane) of the scientific literature was performed for studies describing outcomes at ≥3 years after AF ablation, with a mean follow‐up of ≥24 months after the index procedure. The following data were extracted: (1) single‐procedure success, (2) multiple‐procedure success, and (3) requirement for repeat procedures. Data were extracted from 19 studies, including 6167 patients undergoing AF ablation. Single‐procedure freedom from atrial arrhythmia at long‐term follow‐up was 53.1% (95% CI 46.2% to 60.0%) overall, 54.1% (95% CI 44.4% to 63.4%) in paroxysmal AF, and 41.8% (95% CI 25.2% to 60.5%) in nonparoxysmal AF. Substantial heterogeneity (I2>50%) was noted for single‐procedure outcomes. With multiple procedures, the long‐term success rate was 79.8% (95% CI 75.0% to 83.8%) overall, with significant heterogeneity (I2>50%).The average number of procedures per patient was 1.51 (95% CI 1.36 to 1.67). Conclusions Catheter ablation is an effective and durable long‐term therapeutic strategy for some AF patients. Although significant heterogeneity is seen with single procedures, long‐term freedom from atrial arrhythmia can be achieved in some patients, but multiple procedures may be required.

Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation.

BACKGROUND There is a known association between obstructive sleep apnea (OSA) and atrial fibrillation (AF); however, how OSA affects the atrial myocardium is not well described. OBJECTIVE To determine whether patients with OSA have an abnormal atrial substrate. METHODS Forty patients undergoing ablation of paroxysmal AF and in sinus rhythm (20 with OSA [apnea-hypopnea index ≥ 15] and 20 reference patients with no OSA [apnea-hypopnea index < 15] by polysomnography) were studied. Multipolar catheters were positioned at the lateral right atrium (RA), coronary sinus, crista terminalis, and RA septum to determine the effective refractory period at 5 sites, conduction time along linear catheters at the RA and the coronary sinus, conduction at the crista terminalis, and sinus node function (corrected sinus node recovery time). Biatrial electroanatomic maps were created to determine the voltage, conduction, and distribution of complex electrograms (duration ≥ 50 ms). RESULTS The groups had no differences in the prevalence of established risk factors for AF. Patients with OSA had the following compared with those without OSA: no difference in effective refractory period (P = .9), prolonged conduction times along the coronary sinus and RA (P = .02), greater number (P = .003) and duration (P = .03) of complex electrograms along the crista terminalis, longer P-wave duration (P = .01), longer corrected sinus node recovery time (P = .02), lower atrial voltage (RA, P <.001; left atrium, P <.001), slower atrial conduction velocity (RA, P = .001; left atrium, P = .02), and more widespread complex electrograms in both atria (RA, P = .02; left atrium, P = .01). CONCLUSION OSA is associated with significant atrial remodeling characterized by atrial enlargement, reduction in voltage, site-specific and widespread conduction abnormalities, and longer sinus node recovery. These features may in part explain the association between OSA and AF.

Obesity results in progressive atrial structural and electrical remodeling: implications for atrial fibrillation

BACKGROUND Obesity is associated with atrial fibrillation (AF); however, the mechanisms by which it induces AF are unknown. OBJECTIVE To examine the effect of progressive weight gain on the substrate for AF. METHODS Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were sampled at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor β1, and connective tissue growth factor. RESULTS Increasing weight was associated with increasing left atrial volume (P = .01), fibrosis (P = .02), inflammatory infiltrates (P = .01), and lipidosis (P = .02). While there was no change in the effective refractory period (P = .2), there was a decrease in conduction velocity (P<.001), increase in conduction heterogeneity index (P<.001), and increase in inducible (P = .001) and spontaneous (P = .001) AF. There was an increase in atrial cardiomyocyte endothelin-A and -B receptors (P = .001) and endothelin-1 (P = .03) with an increase in adiposity. In association, there was a significant increase in atrial interstitial and cytoplasmic transforming growth factor β1 (P = .02) and platelet-derived growth factor (P = .02) levels. CONCLUSIONS Obesity is associated with atrial electrostructural remodeling. With progressive obesity, there were changes in atrial size, conduction, histology, and expression of profibrotic mediators. These changes were associated with spontaneous and more persistent AF.

Electrical remodelling of the left and right atria due to rheumatic mitral stenosis

AIMS To characterize the atrial remodelling in mitral stenosis (MS). METHODS AND RESULTS Twenty-four patients with severe MS undergoing commissurotomy and 24 controls were studied. Electrophysiological evaluation was performed in 12 patients in each group by positioning multi-electrode catheters in both atria to determine the following: effective refractory period (ERP) at 10 sites at 600 and 450 ms; conduction time; conduction delay at the crista terminalis (CT); and vulnerability for atrial fibrillation (AF). P-wave duration (PWD) was determined on the surface ECG. In the remaining 12 patients in each group, electroanatomic maps of both atria were created to determine conduction velocity and identify regions of low voltage and electrical silence. Patients with MS had larger left atria (LA) (P < 0.0001); prolonged PWD (P = 0.0007); prolonged ERP in both LA (P < 0.0001) and right atria (RA) (P < 0.0001); reduced conduction velocity in the LA (P = 0.009) and RA (P < 0.0001); greater number (P < 0.0001) and duration (P< 0.0001) of bipoles along the CT with delayed conduction; lower atrial voltage in the LA (P < 0.0001) and RA (P < 0.0001); and more frequent electrical scar (P = 0.001) compared with controls. Five of twelve with MS and none of the controls developed AF with extra-stimulus (P = 0.02). CONCLUSION Atrial remodelling in MS is characterized by LA enlargement, loss of myocardium, and scarring associated with widespread and site-specific conduction abnormalities and no change or an increase in ERP. These abnormalities were associated with a heightened inducibility of AF.

High-Density Mapping of Atrial Fibrillation in Humans: Relationship Between High-Frequency Activation and Electrogram Fractionation

Introduction: Sites of complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) have been implicated in maintaining atrial fibrillation (AF); however, their relationship is poorly understood.

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation: Implications for Ablation of Atrial Fibrillation

Background—The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results—Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions—ShEn is a mechanistically based tool that may assist AF rotor mapping.Background— The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results— Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions— ShEn is a mechanistically based tool that may assist AF rotor mapping.

Left atrial remodeling in patients with atrial septal defects

BACKGROUND Information regarding left atrial (LA) substrate in conditions predisposing to atrial fibrillation (AF) is limited. OBJECTIVE This study sought to characterize the left atrial remodeling that results from chronic atrial stretch caused by atrial septal defect (ASD). METHODS Eleven patients with hemodynamically significant ASDs and 12 control subjects were studied. The following were evaluated using multipolar catheters: effective refractory period (ERP) at 7 sites, P-wave duration (PWD), conduction time, and inducibility of AF. LA electroanatomic maps were created to determine atrial activation, and regional conduction and voltage abnormalities. RESULTS Patients with ASDs showed significant LA enlargement (P <0.001), unchanged or prolonged atrial ERPs, increase in LA conduction times (P = 0.03), prolonged PWD (P <0.001), regional conduction slowing (P <0.001), greater number of double potentials or fractionated electrograms (P <0.0001), reduced atrial voltage (P <0.001), and more frequent electrical scar (P = 0.005) compared with control subjects. In addition, patients with ASDs showed a greater propensity for sustained AF with single extrastimuli (4 of 11 vs. 0 of 12, P = 0.04). CONCLUSION ASDs are associated with chronic left atrial stretch, which results in remodeling characterized by LA enlargement, loss of myocardium, and electrical scar that results in widespread conduction abnormalities but with no change or an increase in ERP. These abnormalities were associated with a greater propensity for sustained AF.

The Effect of Electrogram Duration on Quantification of Complex Fractionated Atrial Electrograms and Dominant Frequency

Introduction: Sites of complex fractionated atrial electrograms (CFAEs) and highest dominant frequency (DF) have been proposed as critical regions maintaining atrial fibrillation (AF). This study aimed to determine the minimum electrogram recording duration that accurately characterizes CFAE or DF sites for ablation without unduly lengthening the procedure.

Reverse Remodeling of the Atria After Treatment of Chronic Stretch in Humans: Implications for the Atrial Fibrillation Substrate

OBJECTIVES The aim of this report was to study the effect of chronic stretch reversal on the electrophysiological characteristics of the atria in humans. BACKGROUND Atrial stretch is an important determinant for atrial fibrillation. Whether relief of stretch reverses the substrate predisposed to atrial fibrillation is unknown. METHODS Twenty-one patients with mitral stenosis undergoing mitral commissurotomy (MC) were studied before and after intervention. Catheters were placed at multiple sites in the right atrium (RA) and sequentially within the left atrium (LA) to determine: effective refractory period (ERP) at 10 sites (600 and 450 ms) and P-wave duration (PWD). Bi-atrial electroanatomic maps determined conduction velocity (CV) and voltage. In 14 patients, RA studies were repeated >or=6 months after MC. RESULTS Immediately after MC, there was significant increase in mitral valve area (2.1 +/- 0.2 cm(2), p < 0.0001) with decrease in LA (23 +/- 7 mm Hg to 10 +/- 4 mm Hg, p < 0.0001) and pulmonary arterial pressures (38 +/- 16 mm Hg to 27 +/- 12 mm Hg, p < 0.0001) and LA volume (75 +/- 20 ml to 52 +/- 18 ml, p < 0.0001). This was associated with reduction in PWD (139 +/- 19 ms to 135 +/- 20 ms, p = 0.047), increase in CV (LA: 1.3 +/- 0.3 mm/ms to 1.7 +/- 0.2 mm/ms, p = 0.006; and RA: 1.0 +/- 0.1 mm/ms to 1.3 +/- 0.3 mm/ms, p = 0.002) and voltage (LA: 1.7 +/- 0.6 mV to 2.5 +/- 1.0 mV, p = 0.005; and RA: 1.8 +/- 0.6 mV to 2.2 +/- 0.7 mV, p = 0.09), and no change in ERP. Late after MC, mitral valve area remained at 2.1 +/- 0.3 cm(2) (p = 0.7) but with further decrease in PWD (113 +/- 19 ms, p = 0.04) and RA ERP (at 600 ms, p < 0.0001), with increase in CV (1.0 +/- 0.1 mm/ms to 1.3 +/- 0.2 mm/ms, p = 0.006) and voltage (1.8 +/- 0.7 mV to 2.8 +/- 0.6 mV, p = 0.002). CONCLUSIONS The atrial electrophysiologic and electroanatomic abnormalities that result from chronic stretch due to MS reverses after MC. These observations suggest that the substrate predisposing to atrial arrhythmias might be reversed.