Pulsed field ablation with the pentaspline catheter compared with cryoablation for the treatment of paroxysmal atrial fibrillation in the UK NHS: a cost-comparison analysis.

OBJECTIVES: Pulsed field ablation (PFA) is a promising new ablation modality for the treatment of atrial fibrillation (AF) that has recently become available in the UK National Health Service (NHS). We provide the first known economic evaluation of the technology. METHODS: A cost-comparison model was developed to compare the expected 12-month costs of treating AF using the pentaspline PFA catheter compared with cryoablation for a single hypothetical patient. Model parameters were based on a recent cost-effectiveness analysis by the National Institute for Health and Care Excellence where possible or published literature otherwise. Deterministic sensitivity, scenario and threshold analyses were conducted. RESULTS: Costs for a single patient treated with PFA were -3% (-£343) less over 12 months than those who received treatment with cryoablation. PFA was associated with 16% higher catheter costs but repeat ablation costs were over 50% less, driven by a reduction in repeat ablations required. Costs of managing complications were -£211 less in total for PFA compared with cryoablation. CONCLUSIONS: Routine adoption of PFA with the pentaspline PFA catheter looks to be as affordable for the NHS as current treatment alternative cryoablation.

Safety, Feasibility and Economic Impact of Same-Day Discharge Following Atrial Fibrillation Ablation.

BACKGROUND: The widely accepted model for atrial fibrillation (AF) ablation involves overnight hospital stay post-procedure. Day case AF ablation has been carried out at Royal Papworth Hospital (RPH) since early 2017. We evaluated the feasibility, safety and efficacy of day case AF ablation at RPH. METHOD: This was a retrospective, single-centre study of consecutive AF ablations at RPH between March 2017 and April 2018. Demographic, procedural and outcome data were analysed. RESULTS: Over the study period, 452 AF ablations were performed in 448 patients. One hundred and twenty-nine (129) (28.5%) were planned day cases; of these 128 were discharged on the same day. Two hundred and eighty-three (283) procedures resulted in at least one night admission. There was no significant difference in age or sex between the groups. Of note, day case procedures were significantly shorter, more likely to commence in the morning and less likely to require general anaesthetic than overnight stays. Patients listed as day cases also had less far to travel. The overall complication rate was 3.3%, with no significant difference between groups. Follow-up data was available for 448 cases (99.1%). Procedural success rates were comparable between groups. The overall cost saving attributable to providing AF ablation as a day case was £67,200 over the 13-month period. CONCLUSIONS: Day case AF ablation is efficacious and associated with a low event rate, even without strict standardisation of patient selection or procedural protocols, in a high-volume centre. Substantial reduction in health care expenditure can be achieved with more widespread implementation of outpatient AF ablation.

Targeting Nonpulmonary Vein Sources in Persistent Atrial Fibrillation Identified by Noncontact Charge Density Mapping: UNCOVER AF Trial.

Background Identification and elimination of nonpulmonary vein targets may improve clinical outcomes in patients with persistent atrial fibrillation (AF). We report on the use of a novel, noncontact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measures timing and density of dipolar, ionic activation (ie, charge density) across the myocardium to guide ablation of atrial arrhythmias. Methods The prospective, nonrandomized UNCOVER AF trial (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) was conducted at 13 centers across Europe and Canada. Patients with persistent AF (>7 days, <1 year) aged 18 to 80 years, scheduled for de novo catheter ablation, were eligible. Before pulmonary vein isolation, AF was mapped and then iteratively remapped to guide each subsequent ablation of charge density-identified targets. AF recurrence was evaluated at 3, 6, 9, and 12 months using continuous 24-hour ECG monitors. The primary effectiveness outcome was freedom from AF >30 seconds at 12 months for a single procedure with a secondary outcome being acute procedural efficacy. The primary safety outcome was freedom from device/procedure-related major adverse events. Results Between October 2016 and April 2017, 129 patients were enrolled, and 127 underwent mapping and catheter ablation. Acute procedural efficacy was demonstrated in 125 patients (98%). At 12 months, single procedure freedom from AF on or off antiarrhythmic drugs was 72.5% (95% CI, 63.9%-80.3%). After 1 or 2 procedures, freedom from AF was 93.2% (95% CI, 87.1%-97.0%). A total of 29 (23%) retreatments because of arrhythmia recurrence were performed with average time from index procedure to first retreatment being 7 months. The primary safety outcome was 98% with no device-related major adverse events reported. Conclusions This novel ultrasound imaging and charge density mapping system safely guided ablation of nonpulmonary vein targets in persistent AF patients with 73% single procedure and 93% second procedure freedom from AF at 12 months. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02825992 EU/NCT02462980 CN.

Ablation of Complex Fractionated Electrograms Improves Outcome in Persistent Atrial Fibrillation of Over 2 Year's Duration.

AIM: There is controversy and sparse data on whether substrate based techniques in addition to pulmonary vein isolation (PVI) confer benefit in the catheter ablation of persistent atrial fibrillation (AF), especially if long standing. We performed an observational study to assess whether substrate based ablation improved freedom from atrial arrhythmia. METHODS: A total of 286 patients undergoing first ablation procedures for persistent AF with PVI only(n = 79), PVI plus linear ablation(n = 85), or PVI plus complex fractionated electrogram (CFAE) and linear ablation(n = 107) were followed. Primary end point was freedom from atrial arrhythmia at one year. RESULTS: Mean duration of pre-procedure time in AF was 28+/-27 months.There were no differences in baseline characteristics between groups except a higher proportion of patients with a severely dilated LA in those receiving PVI+CFAEs+lines. Freedom from atrial arrhythmia was higher with a PVI+CFAE+lines strategy then for PVI alone (HR 1.56, 95% CI: 1.04-2.34, p=0.032) but was not higher with PVI+lines. Benefit of substrate modification was conferred for preprocedure times in AF of over 30 months. The occurrence of atrial tachycardia was higher when lines were added to the ablation strategy (HR 0.08, 95% CI: 0.01-0.59, p=0.014). Freedom from atrial arrhythmia at 1 year was higher with lower patient age, use of general anaesthetic (GA), normal or mildly dilated left atrium and decreasing time in AF. CONCLUSIONS: In patients with long standing persistent AF of over 30 months duration,CFAE ablation resulted in improved freedom from atrial arrhythmia. Increased freedom from atrial arrhythmia occurs in patients who are younger and have smaller atria, and with GA procedures. Linear ablation did not improve outcome and resulted in a higher incidence of atrial tachycardia.

Improved outcome and cost effectiveness in ablation of persistent atrial fibrillation under general anaesthetic.

Aims: Outcome of persistent atrial fibrillation (AF) ablation remains suboptimal. Techniques employed to reduce arrhythmia recurrence rate are more likely to be embraced if cost-effectiveness can be demonstrated. A single-centre observational study assessed whether use of general anaesthesia (GA) in persistent AF ablation improved outcome and was cost-effective. Methods and results: Two hundred and ninety two patients undergoing first ablation procedures for persistent AF under conscious sedation or GA were followed. End points were freedom from listing for repeat ablation at 18 months and freedom from recurrence of atrial arrhythmia at 1 year. Freedom from atrial arrhythmia was higher in patients who underwent ablation under GA rather than sedation (63.9% vs. 42.3%, hazard ratio (HR) 1.87, 95% confidence interval (CI): 1.23-2.86, P = 0.002). Significantly fewer GA patients were listed for repeat procedures (29.2% vs. 42.7%, HR 1.62, 95% CI: 1.01-2.60, P = 0.044). Despite GA procedures costing slightly more, a saving of £177 can be made per patient in our centre for a maximum of two procedures if all persistent AF ablations are performed under GA. Conclusions: In patients with persistent AF, it is both clinical and economically more effective to perform ablation under GA rather than sedation.

Glucagon-like peptide-1 protects against ischemic left ventricular dysfunction during hyperglycemia in patients with coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM). METHODS: In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)-one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments. RESULTS: In study 1, the HHC (compared with control) increased glucose (13.0 ± 1.9 versus 4.8 ± 0.5 mmol/l, p < 0.0001) and insulin (1,212 ± 514 versus 114 ± 47 pmol/l, p = 0.01) concentrations, and reduced FFA levels (249 ± 175 versus 1,001 ± 333 µmol/l, p < 0.0001), but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global (ejection fraction, 77.5 ± 5.0 versus 71.3 ± 4.3%, p = 0.004) and regional (peak systolic strain -18.1 ± 6.6 versus -15.5 ± 5.4%, p < 0.0001) myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia. CONCLUSIONS: In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM. TRIAL REGISTRATION: http://www.isrctn.org . Unique identifier ISRCTN69686930.

A minimal or maximal ablation strategy to achieve pulmonary vein isolation for paroxysmal atrial fibrillation: a prospective multi-centre randomized controlled trial (the Minimax study).

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF). The intervenous ridge (IVR) may be incorporated into ablation strategies to achieve PVI; however, randomized trials are lacking. We performed a randomized multi-centre international study to compare the outcomes of (i) circumferential antral PVI (CPVI) alone (minimal) vs. (ii) CPVI with IVR ablation to achieve individual PVI (maximal). METHODS AND RESULTS: Two hundred and thirty-four patients with paroxysmal AF underwent CPVI and were randomized to a minimal or maximal ablation strategy. The primary outcome of recurrent atrial arrhythmia was assessed with 7-day Holter monitoring at 6 and 12 months. PVI was achieved in all patients. Radiofrequency ablation time was longer in the maximal group (46.6 ± 14.6 vs. 41.5 ± 13.1 min; P < 0.01), with no significant differences in procedural or fluoroscopy times. At mean follow-up of 17 ± 8 months, there was no difference in freedom from AF after a single procedure between a minimal (70%) and maximal ablation strategy (62%; P = 0.25). In the minimal group, ablation was required on the IVR to achieve electrical isolation in 44%, and was associated with a significant reduction in freedom from AF (57%) compared with the minimal group without IVR ablation (80%; P < 0.01). CONCLUSION: There was no statistically significant difference in freedom from AF between a minimal and maximal ablation strategy. Despite attempts to achieve PVI with antral ablation, IVR ablation is commonly required. Patients in whom antral isolation can be achieved without IVR ablation have higher long-term freedom from AF (the Minimax study; ACTRN12610000863033).

Cardiac resynchronisation therapy: pacemaker versus internal cardioverter-defibrillator in patients with impaired left ventricular function.

OBJECTIVE: Studies have shown beneficial effects of cardiac resynchronisation therapy (CRT) on mortality among patients with heart failure. However the incremental benefits in survival from CRT with a defibrillator (CRT-D) are unclear. The choice of appropriate device remains unanswered. METHOD: This is a single-centre observational study in a tertiary cardiac centre. Patients (n=500) implanted with a CRT device with pacing alone (CRT-P) (n=354) and CRT-D (n=146) were followed for at least 2 years (mean 29 months, SD 14 months). The primary end point was all-cause mortality. RESULTS: A total of 116 deaths (23.2%) were recorded: 88 (24.8%) and 28 (19.2%), in the CRT-P and CRT-D groups, respectively. At 1 year there was a trend favouring CRT-D (HR 0.54, 95% CI 0.27 to 1.07, p=0.08) but this was attenuated by the 2nd year and became insignificant at the end of follow-up (HR 0.76, 95% CI 0.50 to 1.170, p=0.21). There was no survival benefit from having an internal cardioverter-defibrillator if patients were deemed non-responders to CRT. 27% of the CRT-P patients with ischaemic cardiomyopathy met indications for potential internal cardioverter-defibrillator implantation for primary prevention. These were older patients with poorer baseline function in comparison with CRT-D patients with devices for primary prevention. Once these differences were adjusted for, there was no difference in outcome between the groups. CONCLUSIONS: CRT-D did not offer additional survival advantage over CRT-P at longer-term follow-up, as the clinical benefit of a defibrillator attenuated with time. Further work is needed to define which subset of patients benefit from CRT-D.

Atrial fibrillation in heart failure in the older population.

Atrial fibrillation (AF) is an important and often-underrecognized cause of cardiovascular morbidity and mortality. It is an arrhythmia that is commonly seen in the older patient; the median age of patients with AF in early studies was 75 years. Heart failure (HF) is also more frequently seen in the older patient with an approximate doubling of HF prevalence with each decade of life. There is clear interaction between AF and HF, with evidence that HF can lead to AF and AF exacerbates HF. This review focuses on the specific aspect of AF management in elderly patients with HF.

Effects of high dose intravenous fish oil on human atrial electrophysiology: implications for possible anti- and pro-arrhythmic mechanisms in atrial fibrillation.

BACKGROUND: Intravenous omega-3 polyunsaturated fatty acids (ω-3 PUFAs) may prevent atrial fibrillation (AF) inducibility and perpetuation in animal models. We examined the effect of high dose IV ω-3 PUFAs on human atrial electrophysiology. METHODS AND RESULTS: We randomised 88 patients with no structural heart disease to receive saline (control group) or high dose IV ω-3 PUFA infusion prior to detailed atrial electrophysiologic evaluation. Biologically active components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured in total lipids, free fatty acid and phospholipid (membrane incorporated) fraction pre and post infusion. Compared to pre-infusion values, EPA and DHA increased significantly in the total lipids and free fatty acid but were unchanged in the phospholipid fraction. IV ω-3 did not alter atrial refractory periods, however it slowed right, left and global atrial conduction (P<.05). Inducible AF was significantly less likely in ω-3 patients compared to controls (AF ≥ 5 min, 20% vs. 58%, P = .02) and was non-sustained (mean AF duration: 14s vs. 39 s, P<.001), however inducible and sustained atrial flutter was more common (≥ 5 min: 28% vs. 0%, P = .01). Organisation of AF into flutter was observed in a greater proportion of inductions in the ω-3 group (8.5% vs. 0.6%, P<.001). CONCLUSIONS: IV ω-3 PUFAs (as free fatty acids) cause acute atrial conduction slowing, suppress AF inducibility, organise AF into atrial flutter and enhance atrial flutter inducibility. These findings provide a novel insight into potential anti and pro-arrhythmic mechanisms of fish oils in human AF.

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.

Coronary collaterals provide a constant scaffold effect on the left ventricle and limit ischemic left ventricular dysfunction in humans.

Coronary collaterals preserve left ventricular (LV) function during coronary occlusion by reducing myocardial ischemia and may directly influence LV compliance. We aimed to re-evaluate the relationship between coronary collaterals, measured quantitatively with a pressure wire, and simultaneously recorded LV contractility from conductance catheter data during percutaneous coronary intervention (PCI) in humans. Twenty-five patients with normal LV function awaiting PCI were recruited. Pressure-derived collateral flow index (CFI(p)): CFI(p) = (P(w) - P(v))/(P(a) - P(v)) was calculated from pressure distal to coronary balloon occlusion (P(w)), central venous pressure (P(v)), and aortic pressure (P(a)). CFI(p) was compared with the changes in simultaneously recorded LV end-diastolic pressure (ΔLVEDP), end-diastolic volume, maximum rate of rise in pressure (ΔLVdP/dt(max); systolic function), and time constant of isovolumic relaxation (ΔLV τ; diastolic function), measured by a LV cavity conductance catheter. Measurements were recorded at baseline and following a 1-min coronary occlusion and were duplicated after a 30-min recovery period. There was significant LV diastolic dysfunction following coronary occlusion (ΔLVEDP: +24.5%, P < 0.0001; and ΔLV τ: +20.0%, P < 0.0001), which inversely correlated with CFI(p) (ΔLVEDP vs. CFI(p): r = -0.54, P < 0.0001; ΔLV τ vs. CFI(p): r = -0.46, P = 0.0009). Subjects with fewer collaterals had lower LVEDP at baseline (r = 0.33, P = 0.02). CFI(p) was inversely related to the coronary stenosis pressure gradient at rest (r = -0.31, P = 0.03). Collaterals exert a direct hemodynamic effect on the ventricle and attenuate ischemic LV diastolic dysfunction during coronary occlusion. Vessels with lesions of greater hemodynamic significance have better collateral supply.

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.

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.

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.

Relationship among complex signals, short cycle length activity, and dominant frequency in patients with long-lasting persistent AF: a high-density epicardial mapping study in humans.

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) and regions of high dominant frequency (DF) both may identify sites critical to the maintenance of atrial fibrillation (AF). CFAEs may be defined by either (1) complex multicomponent electrograms (EGMs) and/or continuous electrical activity (multicomponent/continuous EGM) or (2) discrete high-frequency EGMs. OBJECTIVE: The purpose of this study was to test if the 2 definitions of CFAE identify the same arrhythmia substrate and determine the relationship of CFAE to areas of high DF. METHODS: High-density epicardial mapping of the posterior left atrium was performed in 10 patients with long-lasting persistent AF. Point-by-point analysis was performed to determine the spatial distribution and correlation of CFAE defined as either (1) multicomponent/continuous-EGMs or (2) AF cycle length <120 ms. Additionally, spatial analysis was performed to determine the relationship of high DF sites to CFAE sites defined by each of the 2 definitions. RESULTS: The percentage of sites deemed CFAE varied markedly between patients and was different depending on the definition of CFAE adopted. There was a poor correlation between CFAE defined by multicomponent/continuous EGMs and AF cycle length <120 ms (r = 0.18). High DF sites were arranged in clusters evenly distributed throughout the posterior left atrium, with 4.2 ± 1.0 high DF clusters per patient. Although there was poor point-by-point correlation between multicomponent/continuous EGMs and high DF sites (r = 0.107), spatial analysis revealed that 96% of multicomponent/continuous EGMs were found adjacent to and partially surrounding (≤5 mm) high DF sites. CONCLUSION: There is poor anatomic overlap between CFAE defined by multicomponent/continuous EGMs and CFAE defined by AF cycle length <120 ms. Multicomponent/continuous EGMs are found adjacent to and surrounding sites of high DF. Further studies are needed to determine the mechanisms responsible for these different signals.

The relationship between complex fractionated electrograms and atrial low-voltage zones during atrial fibrillation and paced rhythm.

AIMS: Mapping of atrial fibrillation (AF) involves identification of low-voltage regions associated with complex fractionated electrograms (CFE) which theoretically represent abnormal substrate and targets for ablation. Whether low-voltage CFE areas also identify abnormal substrate during paced rhythm is unknown. METHODS AND RESULTS: Twelve patients with persistent AF undergoing ablation of AF had high-density three-dimensional electroanatomic maps created during AF and paced rhythm (24 maps) and the mean voltage during AF and paced rhythm was compared for eight segments of the left atrium (LA). The following were correlated during AF and paced rhythm: regional mean voltage; %low voltage (defined as <0.5 mV); and extent of CFE. In addition, the relationship between the extent of CFE in AF: (i) %low voltage and (ii) conduction during paced rhythm were determined. Mean voltage was lower during AF than paced rhythm for all regions and globally (0.7 ± 0.2 mV vs. 2.1 ± 0.6 mV, P < 0.001). The regional and overall %low voltage of the LA was greater during AF than paced rhythm (53 ± 19% vs. 9 ± 2%, P < 0.001). There was no correlation between mean voltage or %low voltage during AF and paced rhythm. Complex fractionated electrograms were prevalent throughout all regions during AF, but did not correlate with %low voltage, fractionation, or slowed conduction during paced rhythm. CONCLUSION: Areas of CFE and low voltage recorded during AF frequently demonstrate normal atrial myocardial characteristics (normal conduction, electrograms, and voltage) during sinus rhythm. Therefore, AF CFE sites do not necessarily identify regions of an abnormal atrial substrate. However, this does not exclude the possibility that CFE might identify a focal driver or source occurring in a region of normal atrial myocardium.