scholarly journals Association of ZFHX3 Genetic Polymorphisms and Extra-Pulmonary Vein Triggers in Patients With Atrial Fibrillation Who Underwent Catheter Ablation

2022 ◽  
Vol 12 ◽  
Author(s):  
Inseok Hwang ◽  
Oh-Seok Kwon ◽  
Myunghee Hong ◽  
Song-Yi Yang ◽  
Je-Wook Park ◽  
...  

Background: The ZFHX3 gene (16q22) is the second most highly associated gene with atrial fibrillation (AF) and is related to inflammation and fibrosis. We hypothesized that ZFHX3 is associated with extra-pulmonary vein (PV) triggers, left atrial (LA) structural remodeling, and poor rhythm outcomes of AF catheter ablation (AFCA).Methods: We included 1,782 patients who underwent a de novo AFCA (73.5% male, 59.4 ± 10.8 years old, 65.9% paroxysmal AF) and genome-wide association study and divided them into discovery (n = 891) and replication cohorts (n = 891). All included patients underwent isoproterenol provocation tests and LA voltage mapping. We analyzed the ZFHX3, extra-PV trigger-related factors, and rhythm outcomes.Result: Among 14 single-nucleotide polymorphisms (SNPs) of ZFHX3, rs13336412, rs61208973, rs2106259, rs12927436, and rs1858801 were associated with extra-PV triggers. In the overall patient group, extra-PV triggers were independently associated with the ZFHX3 polygenic risk score (PRS) (OR 1.65 [1.22–2.22], p = 0.001, model 1) and a low LA voltage (OR 0.74 [0.56–0.97], p = 0.029, model 2). During 49.9 ± 40.3 months of follow-up, clinical recurrence of AF was significantly higher in patients with extra-PV triggers (Log-rank p < 0.001, HR 1.89 [1.49–2.39], p < 0.001, model 1), large LA dimensions (Log-rank p < 0.001, HR 1.03 [1.01–1.05], p = 0.002, model 2), and low LA voltages (Log-rank p < 0.001, HR 0.73 [0.61–0.86], p < 0.001, model 2) but not the ZFHX3 PRS (Log-rank p = 0.819).Conclusion: The extra-PV triggers had significant associations with both ZFHX3 genetic polymorphisms and acquired LA remodeling. Although extra-PV triggers were an independent predictor of AF recurrence after AFCA, the studied AF risk SNPs intronic in ZFHX3 were not associated with AF recurrence.

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
T Hwang ◽  
M Yoon ◽  
M Kim ◽  
I Kim ◽  
H Yu ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Extra-pulmonary vein (PV) triggers play significant roles in atrial fibrillation (AF) recurrence after AF catheter ablation (AFCA). Purpose We explore the clinical and electrophysiological characteristics of extra-PV triggers in de novo and repeat-AFCA procedure. Methods We included 2,151 patients who had de novo AFCA and 319 repeat AFCA (female 28.0%, 59.1 ± 10.8 years old, paroxysmal AF 65.1%) those underwent post-procedural isoproterenol (ISO) provocation tests. We analysed the clinical, electrophysiological, and procedure-related factors associated with extra-PV triggers. Results Extra-PV triggers were documented in 11.9% (1.19 ± 0.42 foci) after de novo-AFCA and 27.0% (1.37 ± 0.65 foci) after repeat-AFCA (p = 0.004). LA volume index (OR 1.02 [1.01-1.03], p = 0.004), history of vascular disease (OR 0.55[0.31-0.91], p = 0.028) and Lead I amplitude of electrocardiogram (OR <0.01 [<0.01-0.62], p = 0.032) were independently associated with the existence of extra-PV triggers in de-novo procedure. Women (OR 1.84 [1.03-3.25], p = 0.037) and LA appendage volume (OR 1.04 [1.01-1.07] p = 0.027) were independently associated with extra-PV triggers during the redo-mapping procedure. Septum (28.4%), coronary sinus (24.0%), and superior vena cava (19.6%) were common extra-PV foci, and septal foci were more commonly found in repeat mapping (38.4% vs. 25.0%, p = 0.025). Among 65 patients who showed extra-PV at the repeat procedures, 19 (29.2%) matched with previous focal or empirical extra-PV ablation sites and 9 (13.8%) were multiple or unmappable sites. AF recurrence rates were significantly higher in both patients with extra-PV triggers after de novo procedures (Log-rank P <0.001; HR 1.93 [1.58-2.36], p= <0.001) and repeat procedures (Log-rank P <0.001, HR 1.87 [1.29-2.70], p= <0.001). Conclusion ISO provoked extra-PV triggers commonly found in AF patients with significant remodelling and previous empirical or focal extra-PV ablations. Existence of extra-PV triggers were independently associated with poorer rhythm outcome after both de novo and repeat AFCA. Denovo AF ablation outcome OverallExtra-PV triggers (-)Extra-PV triggers (+)p-value(n = 2151)(n = 1895)(n = 256)Age, yrs58.98 ± 10.9558.73 ± 11.0360.76 ± 10.200.006Male, (%)1550 ( 72.1)1389 ( 73.3)161 ( 62.9)0.001Follow up duration, month50.30 (37.71)51.65 (37.95)40.71 (34.58)<0.001Early recurrence (%)579 ( 27.8)455 ( 24.9)124 ( 48.4)<0.001Clinical recurrence (%)699 ( 33.6)584 ( 32.0)115 ( 44.9)<0.001Abstract Figure. AF free survival according to Extra PVT


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
T Hwang ◽  
M Kim ◽  
H Yu ◽  
T Kim ◽  
J Uhm ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by grants [HI18C0070] and [HI19C0114] from the Korea Health 21 R&D Project, Ministry of Health and Welfare, and a grant [NRF-2020R1A2B01001695] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF). Background Although extra-pulmonary vein (PV) left atrial (LA) linear ablation has been performed during catheter ablation (CA) of persistent atrial fibrillation (PeAF), the long-term efficacy and safety of this procedure have not yet been verified. Purpose We investigated whether an anterior line (AL) and posterior box ablation (POBA) in addition to circumferential PV isolation (CPVI) improves the rhythm without worsening the LA function in PeAF patients. Methods We retrospectively compared the additional AL + POBA and CPVI alone groups in 604 patients with PeAF who underwent regular rhythm follow-ups (16.9%; males 79.3%, 58.5 ± 10.7 years of age) after propensity score matching. The primary endpoint was AF recurrence after single procedures and secondary endpoints were the cardioversion rate, response to anti arrhythmic drugs, LA changes, and re-conduction rates of the de-novo ablation lesion set. Results After a mean follow-up of 45.2 ± 33.6 months, the clinical recurrence rate did not significantly differ between the two groups (log-rank p = 0.554) despite longer procedure times in the AL + POBA group (p < 0.001). Atrial tachycardia recurrences (p = 0.001) and the cardioversion rates after ablation (p < 0.001) were higher in the AL + POBA group than CPVI group. AL + POBA was associated with better rhythm outcomes in patients with large anterior LA volume indices (p for interaction 0.037) and low mean LAA(left atrial appendage) voltages (p for interaction 0.019). In repeat procedures, the LA pulse pressure elevation was significant after the AL + POBA. Conclusion In patients with PeAF, an AL + POBA in addition to the CPVI did not improve the rhythm outcomes nor influence the long-term safety, and lead to more extended procedures. Procedure outcomes OverallAL + POBACPVIp-value(n = 604)(n = 302)(n = 302)Procedure time, min190.8 ± 62.6226.9 ± 49.4154.6 ± 52.8<0.001Ablation time, sec5079 ± 19566420 ± 13723738± 1475<0.001Overall complications24 (4.0)13 (4.3)11 (3.6)0.835Early recurrence, n (%)277 (45.9)129 (42.7)148 (49.0)0.142Recurrence type AT, n (% in early recur)77 (27.8)51 (39.5)26 (17.6)<0.001Clinical recurrence within 1-year, n(%)116 (19.2)52 (17.2)65 (21.5)0.256Recurrence type AT, n (% in clinical recur)60 (23.1)46 (30.7)14 (12.7)0.001Cardioversion, n (% in total recur/ % overall)105 (40.4/17.4)74 (49.3/24.5)31 (28.1/10.3)<0.001POBA, posterior box ablation; AL, anterior line; CPVI, circumferential pulmonary vein isolation; AT, atrial tachycardia;Abstract Figure. Long term ablation outcome


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tae-Hoon Kim ◽  
Jae-Sun Uhm ◽  
Boyoung Joung ◽  
Moon-Hyoung Lee ◽  
Hui-Nam Pak

Introduction: Long-lasting pulmonary vein isolation (PVI) has been shown to be the key determinants for clinical outcome in both patients with paroxysmal and persistent atrial fibrillation (AF). Hypothesis: Although reconnected PV potential (PVP) has been regarded as a main mechanism of AF recurrence after catheter ablation, PVIs are well preserved in some patients at redo-procedure after recurrence. Therefore, we explored the characteristics and clinical outcome of the patients with negative PVP at redo-procedure. Methods: Among 1522 patients with AF who underwent catheter ablation, 143 patients (79.0% male, 56.1±10.0 years old, 65.0% paroxysmal AF) refractory to antiarrhythmic drug underwent redo-procedure. PVP was not shown in 52 patients (PVP- group, 36.4%), but remaining 91 patients showed PVP (PVP+ group, 234/364 (64.3%) of PVs). We mapped triggers with isoproterenol infusion in both groups (after PVI in PVP+ group). Depending on mapping finding, we ablated non-PV foci and added linear ablation or complex fractionated atrial electrogram (CFAE)-guided ablation. Results: 1. PVP- group was independently associated with female gender (OR 2.64 95%CI 1.13~6.21, p=0.026) and later de novo clinical recurrence timing (OR 1.02 95% CI 1.00~1.04, p=0.047). 2. Additional linear ablations were more likely to be performed in PVP- group (92.2% vs. 61.5%, p<0.001), but total ablation time (2411.3±1082.8 vs. 3144.8 ± 1412.5 sec, p=0.003) and procedure time (164.2± 51.4 vs. 144.2±47.1 min, p=0.027) were shorter in PVP- group than in PVP+ group. 3. During 18.4±10.2 months follow-up after redo-ablation, PVP- group showed significantly higher clinical recurrence rate than PVP+ group regardless of redo-ablation strategies (Kaplan Meier, Log Rank p=0.011). The presence of recurred PV connection (PVP+) was independently associated with lower recurrence of AF after repeat ablation (HR 0.46, 95% CI 0.21 - 0.98, p=0.043). Conclusions: AF patients with well-preserved PVI recurred later timing after de novo ablation, but showed poor clinical outcome after redo-ablation procedure, suggesting a potential AF progression.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
kiyotake Ishikawa ◽  
Yukihiko Yoshida ◽  
Sumio Morita ◽  
Kenji Furusawa ◽  
Noriyoshi Kanemura ◽  
...  

Background: Left atrium (LA) dilation plays an important role in development and persistence of atrial fibrillation (AF). Some cases show structural reverse remodeling of LA after catheter ablation of AF. The aim of this study was to assess the clinical significance of LA reverse remodeling. Method and Results: Echocardiographic data before and after ablation was obtained in 173 cases who underwent pulmonary vein isolation from January 2006 to April 2008 (74.0% men, 61.0±11 years old; paroxysmal AF 114, persistent AF 34, permanent AF 25). Mean atrial diameter before ablation was 39.0±6.1mm (paroxysmal 37.7±5.6mm, persistent 40.7±5.3mm, and permanent 43.0±6.8mm) and LA reverse remodeling was defined as 10% decrement of LA transverse diameter. Half of the cases were taking anti-arrhythmic drugs after ablation, and AF recurrence occurred in 16.8% (29/173) during mean follow up period of 8.5±6.3 months. Reverse remodeling of LA was seen in 34.1% (59/173) and AF recurrence rate in this group was 11.9% (7/59), whereas 19.3% (22/114) without reverse remodeling (P=0.29). However, limited in patients with LA diameter over 40mm (44.5%; 77/173), 3.2% (1/31) of AF recurrence was seen in those with reverse remodeling, while 21.7% (10/46) without reverse remodeling (P=0.04). LA reverse remodeling was observed significantly frequent in patients without history of hypertension(41.5% without hypertension vs 25.6% with hypertension, P=0.036). Conclusion: LA reverse remodeling after catheter ablation of AF in dilated LA patient is a simple and useful predictor for non-recurrence of AF. Hypertension could be a disturbance for LA reverse remodeling.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Laurent Macle ◽  
Atul Verma ◽  
Paul Novak ◽  
Paul Khairy ◽  
Mario Talajic ◽  
...  

Recurrences of atrial fibrillation (AF) after catheter ablation are frequently associated with recovery of conduction between the pulmonary veins (PV) and the atrium. The recovery of PV conduction could be explained by the presence of dormant conduction between the PV and the atrium. Adenosine can be used during AF ablation procedures to reveal transient re-conduction of the isolated pulmonary vein (dormant PV conduction). We prospectively evaluate the utility of iv adenosine to guide elimination of dormant PV conduction by additional radiofrequency (RF) applications during AF ablation procedures. Thirty-four consecutive patients (30 male; age 51+/−8 years) referred for catheter ablation of drug-refractory AF (Paroxysmal 31/Persistent 3) were studied. Electrical PV isolation (PVI) was performed using Irrigated-tip radiofrequency (RF) ablation and was guided by a circular mapping catheter. After PVI, the presence of dormant conduction in each vein was assessed by injection of 12 mg of adenosine. If dormant conduction was present, additional RF energy was delivered at sites of transient re-conduction. Abolition of the dormant conduction was then demonstrated by repeated injections of adenosine. The recurrence rate of arrhythmia after one procedure was evaluated. The results were compared to an historical control group comprising the previous 34 consecutive patients who underwent PVI without the use of adenosine. Electrical PVI was achieved in 100% of PV’s and all 34 patients underwent the adenosine evaluation. Dormant PV conduction was observed in 17/34 patients and could be eliminated in all by additional RF delivery. Procedural and fluoroscopy times were 163±30 and 49±13 minutes, respectively. After a mean follow-up of 8.0±3.1 months, 6/34 (18%) patients experienced AF recurrence with 28/34 (82%) remaining free of arrhythmia without the use of antiarrhythmic drugs. When compared to the 14/34 patients (41%) from the historical control group who had AF recurrence, a significant reduction was observed (P<0.01). The use of adenosine to guide elimination of dormant PV conduction increases the success rate of AF ablation procedures. This needs to be evaluated in a randomized multicenter trial.


2019 ◽  
Vol 83 (2) ◽  
pp. 304-312 ◽  
Author(s):  
Je-Wook Park ◽  
Hee Tae Yu ◽  
Tae-Hoon Kim ◽  
Jae-Sun Uhm ◽  
Jong-Youn Kim ◽  
...  

Author(s):  
Samuel K. Sørensen ◽  
Arne Johannessen ◽  
René Worck ◽  
Morten L. Hansen ◽  
Jim Hansen

Background - Recurrent paroxysmal atrial fibrillation (PAF) after catheter ablation is presumably caused by failure to achieve durable pulmonary vein isolation (PVI). The primary methods of PVI are radiofrequency (RF) and cryoballoon (CRYO) catheter ablation, but these methods have not been directly compared with respect to PVI durability and the effect thereof on AF burden (% of time in AF). Methods - Accordingly, we performed a randomized trial including 98 patients (68% male, 61 [55-67] years) with PAF assigned 1:1 to PVI by contact-force sensing, irrigated RF catheter or second-generation CRYO catheter. Implantable cardiac monitors were inserted ≥1 month before PVI for assessment of AF burden and recurrence, and all patients, irrespective of AF recurrence, underwent a second procedure 4-6 months after PVI to determine PVI durability. Results - In the second procedure, 152/199 (76%) pulmonary veins (PVs) were found durably isolated after RF and 161/200 (81%) after CRYO (NS), corresponding to durable isolation of all veins in 47% of patients in both groups (NS). Median AF burden before PVI was 5.4% (interquartile range: 0.5-13.0%) vs. 4.0% (0.6-18.1%), RF vs. CRYO, and reduced to 0.0% (0.0-0.1%) and 0.0% (0.0-0.5%), respectively - a reduction of 99.9% (92.9-100.0%) and 99.3% (85.9-100.0%) (all NS). AF burden after PVI significantly correlated to the number of durably isolated PVs (p < 0.01), but 9/45 (20%) patients with durable isolation of all veins had recurrence of AF within 4-6 months after PVI (excluding a 3-month blanking period). Conclusions - PVI by RF and CRYO catheter ablation produce similar moderate to high PVI durability. Both treatments lead to marked reductions in AF burden, which is related to the number of durably isolated PVs. However, for one fifth of PAF patients, complete and durable PVI was not sufficient to prevent even short-term AF recurrence.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
T-E Hunt ◽  
GM Traaen ◽  
L Aakeroy ◽  
C Bendz ◽  
B Oeverland ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority OnBehalf OUH Background Obstructive sleep apnea (OSA) is common in patients with atrial fibrillation (AF). Studies have reported an association between OSA and increased AF burden, as well as increased recurrence of AF after catheter ablation. However, whether treatment with positive airway pressure (CPAP) can reduce the risk of AF recurrence after pulmonary vein isolation has still not been established. Purpose This is the first randomized study evaluating the effect of CPAP treatment on AF recurrence after pulmonary vein isolation in patients with AF and OSA. Methods Consecutive patients with AF referred for catheter ablation were included after being screened positive for OSA (apnea-hypopnea index [AHI] ≥ 15 events/h). All patients received an implantable loop recorder 6 months prior to ablation to quantify the arrhythmia burden. Patients were randomized to CPAP treatment or no treatment of OSA during five months before and 12 months after ablation. The primary end point was AF recurrence, defined as one episode of AF lasting longer than 30 seconds after catheter ablation, with an initial 90-day blanking period. We also compared AF burden measured in percent of time in AF and assessed five months before and 3-12 months after catheter ablation. Results We included 83 patients (65% male, age 61 ± 7.3 years), of which 37 patients were treated with CPAP and 46 controls. The mean baseline AHI in patients with CPAP was 26.7 ± 14.7 and in patients with usual care 26.3 ± 12.3. AF-burden prior to catheter ablation expressed as median [IQR] percent of time was 2.7 [0.9-9.1] in the CPAP-group compared to 1.8 [0.2-6.4] in the control group (p = 0.24). There was no signal to a difference in AF recurrence rate between patients with or without CPAP treatment. As shown in figure, we found overlapping curves with a final 21 patients [57%] vs. 26 patients (57%) presenting at least 30 seconds of AF. After catheter ablation and blanking period, patients with CPAP treatment had an AF burden of 0.0 [0.0-0.3] % compared to 0.0 [0.0-0.3] % in patients without CPAP (p = 0.64). Conclusion In this randomized study concomitant treatment with CPAP on top of pulmonary vein isolation had no added effect on the risk of AF recurrence in patients with OSA. Although several patients revealed at least 30 seconds of AF 3-12 months after ablation, there was a great reduction in percent AF burden after catheter ablation independent of CPAP treatment. Abstract Figure


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