Insight To The Mechanism Of Artial Fibrillation Initiation And Ablation Strategy

Part one: Mechanism of Action Potential Alternans in A Swine Model of Pacing induced Acute Atrial Fibrillation.Background: Initiation of atrial fibrillation (AF) in the setting of rapid atrial pacing or supraventricular tachycardia is commonly observed. However, the changes in the atrial electrical properties that allow for the degeneration of a rapid organized rhythm into AF remain poorly understood. Recently study showed that the onset of AF is associated with MAP alternans in swine model of pacing induced AF. However, the mechanism of MAP alternans has not been fully elucidated.Methods: Monophasic action potentials (MAP) were recorded simultaneously from two sites, one in the anterolateral and the other in the posterior right atrium in 15 closed-chest pigs. An additional catheter was placed in RV.We defined alternans threshold as the longest pacing cycle length that led to MAP alternans at either one of the two atrial recording sites during overdrive pacing. The MAP alternans thresholds with atrial overdrive alone, ATAOD, and with atrioventricular sequential pacing at a fixed AV delay of 100 msec, ATAV, were determined. Each pacing period was 20 second in duration. Recordings during the first 10 seconds of pacing were excluded from analysis. We defined atrial fibrillation threshold as the longest atrial pacing cycle length that induced atrial fibrillation.Atrial programmed stimulation with single extrastimulus was performed at multiple basic drive cycle lengths (DCL) with AV sequential pacing (AV delay: 100 msec), starting at 500 ms with 20-50msec decrement till DCLreached 10 - 20ms above the alternans threshold. The stimulation strength was set two times the diastolic threshold that was determined at each DCL. The coupling interval of the extrastimulus was initially set at 10 msec below the DCL with 5-10 msec decrements until atrial effective refractory period (ERP) was reached.We defined the atrial relative refractory period (RRP) defined as the longest coupling interval that led to intraatrial conduction delay. We derived electrical restitution curve by plotting the percentage shortening in MAP80 against the coupling interval. We defined critical coupling interval (CCI) as the shortest coupling interval that failed to shorten of MAPD80 after the extrastimulus.Results:1. Effects of AV sequential pacing on alternans threshold: MAP alternans disappeared when the pacing mode was switched from AOD to AV sequential pacing. ATAV associated with atrial fibrillation threshold. ATAOD: 257.78±23.90 msec; ATAV : 196.67±8.66 msec; Atrial fibrillation threshold: 181.11±7.82 msec. MAP alternans thresholds correlated with AF threshold. Alternans threshold correlated with AV sequential pacing, ATAV, correlated with atrial fibrillation threshold (r=0.80) whereas the alternans threshold during atrial overdrive alone, ATAOD, did not (r=0.08). ATAOD correlated with the pacing cycle length that led to 2:1 AV block (r= 0.80).2. Differential effects of DCL on MAP80, ERP, CCI and RRP: As we decreased DCL from 500 msec to 20 msec above ATAV, atrial ERP decreased from 168±22 to 154±14 msec (p=0.008) but RRP remained unchanged (216±19 vs. 219±19 msec, p=0.39) such that the difference between RRP and ERP increased from 48±26 to 66±20 msec (p=0.019), suggesting a widened vulnerability window. CCI also decreased significantly (340±45.5 to 258±34.9, p=0.0005). Repetitive atrial response or AF was induced only when the coupling interval fell between RRP and ERP. CCI was always longer than RRP.3. Effects of DCL on the slope of electric restitution curve (ERC): We determine the slope of the ERC by a single exponential regression model. A smaller time constant (ι) indicates a steeper slope. In all six pigs,ιdecreased as the DCL was shortened (p<0.001).4. Relationship between CCI and alternans threshold: The ratio of CCI to DCL (CCI:DCL ratio) increased at shorter DCLs. We attempted to test the hypothesis that MAP alternans occurs as the CCI:DCL ratio approaches unity because stable MAP could no longer be maintained. Using a polynomial regression model, we calculated the alternans threshold, ATcal, as the DCL when CCI:DCL ratio reaches unity. The calculated alternans threshold was 190±11msec and the observed alternans threshold was197±9 msec. The correlation coefficient was 0.75 (p=0.033).Conclusions: Atrial MAP alternans threshold could be affected by the presence of AV block. In order to accurately assess the effects of rapid atrial pacing on MAP alternans, sequential AV pacing must be used. Changes in MAP duration or repolarization in response to premature extrastimulus precede intraatrial conduction delay, suggesting such conduction delay may be caused by encroachment of refractory period. MAP alternans induced by rapid pacing appears to be associated with an increased CCI:DCL ratio. MAP alternans may occur as the ratio approaches unity. However, the causal relationship between the two phenomena requires further investigation. Alternatively, rapid pacing may lead to MAP alternans because of a steeper restitution curve slope at shorter DCL that may allow for perpetuation of alteration in MAP duration. Such alternation in MAP duration may increase the repolarization gradient and predispose the atria to atrial fibrillation.Part two: Insight to the Effectiveness of Single Atrium-Vein Electrical Isolation to Patients with Paroxysmal Atrial FibrillationPurpose : To analyze the electrophysiological characteristics of paroxysmal atrial fibrillation (PAF) originating from pulmonary vein (PV) or superior vena cava (SVC) and evaluate the effectiveness of electrical- isolation of single PV or SVC which triggered PAF.Methods : Fourteen patients among ninety consecutive in-patients (male 10, female 4), 39-64(51±10)years old, with frequent drug refractory daily paroxysmal symptomatic atrial fibrillation, were involved in the study. After dual transeptal punctures, two LASSO catheters were positioned at PVs to identify the conduction state of PV to left atrium and trying to find out the trigger sources of each atrial fibrillation firing. Activation mapping was performed in lateral right atrium, right superior PV, left superior PV, left inferior PV or SVC. After retrograded angiograph of PV. Segmental ablation was given at the targeted PVs till reach a endpoint of completely PV-atrium conduction block and no atrial fibrillation episode during 30 minutes observation. Success criterion was that there is no atrial fibrillation, atrial tachycardia or atrial flutter during follow-up without antiarrhythmic drug therapy.Results : Single one PV/SVC triggered PAF was successfully electrical-isolated in all 14 patients. PAF reoccurred in 5 patients. 3 patients among the five patients accepted second electrophysiology study and more PVs that triggered PAF were found and successfully electro-isolation was given. During a 314.6±214.9 days following-up, 11 patients were symptom free without anti-arrhythmias medicine. There was no PAF recurrence in the five patients who accepted SVC electrical isolation. Total success rate is 78.6%(11/14)Conclusion:Electro-isolation of PV or SVC that triggered PAF could reach a good success rate of eliminating atrial fibrillation. How to identify the triggers and elucidate electrical remodeling is the key point of success.Part three: Evaluation of Pulmonary Vein Isolation in Patients with Recurred Atriial Fibrillation after Circumferential Ablation of Pulmonary Vein OstiaPurpose : To analysis the electrophysiological characteristic of recurred paroxysmal atrial fibrillation (PAF) after circumferential ablation of pulmonary vein ostia (PVO), and evaluated the effectiveness of PV isol- ation.Methods:45 patients, with frequent drug refractory daily paroxysmal symptomatic atrial fibrillation, were involved in this study. Male 33 and female 12, with mean age 59±11.4(38-72)years old. The mean history of atrial fibrillation is 6±3.5(1-25)years. After dual transeptal punctures, a LASSO catheter was positioned at each PV to identify the conduction state of PV to left atrium. A CARTO catheter was introduced to left atrium by a 8.5F sheath. After retrograded angiograph of PV. Electro-anatomy map was constructed. Two circles ablation at each side PVs was given till reach a endpoint of completely PV-atrium conduction block and no atrial fibrillation episode during 30 minutes observation. Success criterion was that there is no atrial fibrillation, atrial tachycardia or atrial flutter during follow-up without antiarrhythmic drug therapy.Results: After the first procedures 29 patients were atrial fibrillation free. While there were frequently atrial fibrillation episodes in 16 (35%) patients. 12 of them accepted secondary electrophysiology study and ablation. PV-atrium conduction recurred in all 12 patients. Additional ablation along the circle of PVs was given at necessary spots and reach a complete conduction block again. There was no complications occurred. Total success rates was 89%(4 patients refused redo ablation and 1 atrial fibrillation remained) during 15.3±4.4 months following-up.Conclusion:Trigger activaties were the main mechanism of paroxysmal atrial fibrillation. PV isolation should be the true endpoint of the procedure. The reason of blocked conduction recurring and how toprevent it remain unknown. Further investigation need to do to identify if all paroxysmal atrial fibrillation was companied with actively triggers and how long that atrial fibrillation persist will cause a unreversible electrical remodeling which cost a vast ablation of left atrium.