The Study On Optimization Of Catheter Ablation Strategy Of Persistent Atrial Fibrillation

Background and ObjectivePulmonary vein isolation (PVI) alone is considered insufficient to eliminate the maintaining substrates of persistent or long-standing AF, leading to a significantly lower success rate of that method. Therefore, more aggressive ablation strategies targeting the substrate were then developed. However, the reproducibility of those techniques was inconsistent and the curative value remained controversial. The present study reports the follow-up outcomes in a large cohort of 169 patients with symptomatic persistent AF who were referred for catheter ablation using a sequential ablation approach, and aimed to evaluate the efficacy of linear and defragmentation ablation techniques in such patients.Further studies are needed to explore the true eletrophysiological substrates perpetuating AF for patients with persistent AF. The left atrium (LA) electrophysiologic abnormalities in AF patients detected during sinus rhythm which reflect electrophysiological and histological remodeling and AF substrates as well remain poorly defined. Our hypothesis is that high density electroanatomic mapping during sinus rhythm in the LA could detect electrophysiologic abnormalities that are reflected by changes in the voltage amplitude, electrogram complexity and the LA activation time. These electrophysiologic abnormalities may not only reflect the extent of LA fibrosis, but also characterize the electrophysiological substrates that promote the persistence of AF.Further, the progressive LA histological and electrophysiological remodeling with the progression of AF could also be demonstrated by comparing the mapping results of paroxysmal, persistent and longstanding AF patients.Base on finding of our research and in order to improve outcomes, we should seek specific properties of the underlying atrial substrate which can be defined. The elimination of substrate would be the major ablation end point. It may move from empiric ablation lesions to a customized ablation strategy based on atrial electrophysiology substrate.Methods and ResultsPart ⅠA cohort of 169 patients with persistent AF was studied. Ablation was performed following a sequential strategy comprised of circumferential pulmonary vein isolation (CPVI), LA roof linear ablation, posterior mitral area, coronary sinus and cavotricuspid isthmus, and complex fractionated electrograms ablation. Results following:1.During a mean follow-up of 15±8 months after a single procedure,84(50%) patients were in sinus rhythm,34 (20%) had an AF recurrence and 51(30%) developed atrial tachycardias (ATs). Repeat procedures were performed in 24 recurrent AF and 46 AT patients. A total of 81 different ATs were mapped and ablated in 46 AT patients, characterized as focal for 45 and macroreentry for 36 ATs.2. Most of the ATs were likely to be attributed to the previous lesions by an analysis of substrate and activation mapping in the redo procedure and a review of the lesions placed in the initial procedure. Overall,75 (93%) ATs were ablated successfully.3.Procedural complications occurred in 11 of the 239 procedures, and almost severe complications generated during linear and CFE ablation.4. After a mean follow-up of 20±9 months,128 (76%) patients were free of arrhythmias after the final procedure.Part IIEighty patients with AF (30 paroxysmal AF,22 persistent AF and 28 long-standing AF), and 20 age and sex matched patients with left-sided accessory pathway were enrolled in the study. High-density 3-dimensional electroanatomic mapping was performed during sinus rhythm in LA which was divided into six segments for regional analysis. Mean bipolar voltage, low voltage zone (LVZ) distribution, LA activation time and electrogram complexity were assessed. Results following:1. The cutoff values of bipolar voltage of LA to define dense scar (0.1 mV), LVZ (0.4mV) and transitional zone (0.4mV-1.3mV) which was rich in complex electrograms were established.2. With the progress of AF, there was a gradual reduction of overall LA mean voltage, prolongation of LA activation time, higher incidence of LVZ detection, increased prevalence of complex electrogram and coeffient of variation of LA voltage (dispersion). The overall LA mean voltage were 3.67±0.68mV in none AF,2.16±0.63 mV in paroxysmal AF,1.81±0.36 mV in persistent AF and 1.48±0.34 mV in long-standing AF patients(p<0.05-0.001).The LA activation time were 75.3±5.4 ms, 89.7±12.3 ms,104.9±6.1ms and 115.6±12.1ms, respectively (all p<0.001).The index of low voltage were 7.05±2.52%,21.96±12.70%,25.48±11.09% and 33.66±12.28% in four different groups, respectively (p<0.05-0.001 expect for paroxysmal AF vs persistent AF); The incidence rate of complex electrograms were 2.28±1.06%, 5.61±3.06%,7.7±2.49% and 13.63±9.65%, respectively (all p<0.001). The coeffient of variation of LA voltage were 0.78±0.10,0.95±0.20,0.98±0.16 and 1.11±0.19 in four different groups, respectively (p<0.05 expect for paroxysmal AF vs persistent AF).3.95% of points with complex electrogram were distributed in the areas with the bipolar voltage≤1.3 mV in persistent and long-standing AF patients.4. The between LA activation time and LA mean bipolar voltage (r=-0.820, p<0.001), index of low voltage(r=0.762, p<0.001), LA diameter(r=0.681, p<0.001) and incidence rate of complex electrograms (r=0.675, p<0.001)have a significant correlation, respectively.5.The correlation between the duration of AF and LA mean bipolar voltage (r=-0.405, p=0.003), LA activation time (r=0.499, p<0.001),the area of LVZ (r=0.399, p=0.004), LA diameter (r=0.627, p<0.001) and the incidence rate of complex electrograms (r=0.475, p<0.001) have a obviously correlation in persistent and longstanding AF group, respectively.Part IIIThe process and theoretical evidence of the catheter ablation strategy of persistent AF based on substrate mapped during sinus rhythm will be explained in this study. Base on findings in front of our research, we have sought specific properties of the underlying atrial substrate which can be defined. The elimination of substrate would be the major ablation end point. The LVZ (≤0.4mV) and transitional area (0.4-1.3mV) of very complex electrograms in LA mapped during sinus rhythm may pose appropriate targets for substrate based AF ablation. The substrate modification include following procedures:the LVZ should be ablated to dense scar, and the complex eletrograms in transition zone should be eliminated, the potential channel of reentrant tachycardia should be closed based on LVZ distribution.ConclusionCPVI supplemented by linear ablation and defragmentation does not seem to improve the overall success rate of persistent AF. The efficacy of linear ablation and defragmention might be diluted by their proarrhythmic effects. Patients with AF have abnormal electrophysiologic substrates characterized by lower mean bipolar voltage, more prevalent complex electrograms and longer LA activation time. These substrates which can be detected during sinus rhythm are progressive with the time course of AF and reversely render AF persistency. The LVZ and regions of very complex electrograms in LA mapped during sinus rhythm may shed some light on the true substrate perpetuating AF and may pose appropriate targets for substrate based AF ablation. The catheter ablation strategy of persistent AF based on substrate mapped during sinus rhythm need clinical studies to verify.