Left Atrial Appendage Occlusion In Patients With Nonvalvular Atrial Fibrillation

Background and ObjectiveAccording to the 2018 Chinese report on cardiovascular diseases,stroke has become the leading cause of mortality and morbidity in China,and a large number of cardioembolic stroke occurred in patients with atrial fibrillation(AF).Oral anticoagulation(OAC)therapy is the standard treatment for stroke prevention in AF patients.Although effective in preventing stroke,the potential for increased hemorrhagic events and poor patient compliance renders OAC a problematic treatment for stroke prevention.Chinese epidemiological study shows that the rate of Chinese AF patients who received standard oral anticoagulation therapy is extremely low(1.7%).Moreover,the Asian patients with AF were at higher risk of warfarin-related intracranial hemorrhage,major bleeding events and non-warfarin-related bleeding events in comparison with the Caucasian AF patients.Percutaneous left atrial appendage closure(LAAC)is a minimal invasive therapy that seals the communication between the left atrium and its appendage in order to decrease the risk of embolic events in AF patients.Therefore,LAAC may become an alternative treatment option for stroke prevention.However,data on the percutaneous LAAC procedures in Chinese population remains very limited and the efficacy and safety of this procedure needs to be further investigated.With the accumulation of LAAC cases,device-related thrombus(DRT)after LAAC has become a clinical concern,as it defeating the purpose of LAAC procedure.Due to the great anatomic variability of the left atrial appendage(LAA),a single LAAC device may not always adequately seal the LAA especially in the single-lobulated LAA with giant ostia anatomy.In these cases,technical innovation with the current LAAC device is necessary.Therefore,we aimed to evaluate the efficacy and safety of LAAC,to investigate the incidence,risk factors,clinical course and management of DRT and to testify the initial feasibility of kissing-Watchman in complex LAA anatomy.Contents1.a single-center observational study to evaluate the efficacy and safety of LAAC in AF patients2.a single-center experience to investigate the risk factors of DRT after Watchman implantation3.to provide a meta-analysis on the incidence of DRT and odds ratio of ischemic events in patients with DRT after Watchman implantation in comparison with patients without DRT and to literaturely review the risk factors of DRT4.to determine the initial feasibility of kissing-Watchman LAAC in a single-lobulated LAA with a giant ostiumMethods1.Patients with nonvalvular atrial fibrillation who underwent LAAC in the first affiliated hospital of the Airforce Medical University from June 2015 to January 2019 were enrolled in this study.LAAC should be considered for stroke prevention in NVAF patients with a CHA2DS2-VASc score?2 and with one of the following criteria:(1)contraindications for long-term anticoagulant therapy;(2)recurrent stroke or embolism under standard antithrombotic therapy;(3)HAS-BLED scores?3.In NVAF patients with a CHA2DS2-VASc score<2,a LAAC procedure would be performed in patient who refuses lifelong anticoagulation therapy or who experience recurrent atrial fibrillation after cryoablation/radiofrequency.2.Under general anesthesia,a femoral vein access was built and a guidewire was introduced.Then advance the Watchman access sheath over the guidewire into the left upper pulmonary vein and a pigtail catheter(5 French)was introduced.The access sheath with the pigtail catheter was pull back from the LUPV and introduced into the bottom of the LAA.Under echocardiographic and fluoroscopic control,LAA anatomy and dimension were confirmed.Fluoroscopy and TEE was used to guide the deployment of the device.After the confirmation that the device release criteria had been met,the Watchman device was released afterwards.Patients with a maximal LAA ostium diameter >31 mm underwent kissing-Watchman procedure.3.After implantation,patients were treated with antithrombotic regime for the first 1.5 month according to the physician decision:(1)Warfarin maintaining a INR range from 2 to 3;(2)Novel oral anticoagulants(Rivaroxaban 20 mg qd or Dabigatran 110 mg bid);(3)Dual antiplatelet therapy(Clopidogrel 75 mg qd plus Asprin 100 mg qd).4.Patients underwent routine LAA imaging around 1.5-month post-operation to assess device dislocation,to confirm appropriate sealing of the LAA and to verify the absence of device-related thrombus(DRT)prior to discontinuing anticoagulation therapy.If the1.5-month TEE documented either residual peridevice>5mm or presence of DRT,the original antithrombotic regime should be resumed.DRT was defined as echo density on the left atrial side of the device and along with the following 4 imaging characteristic(1)not explained by imaging artifact;(2)inconsistency with normal healing/device incorporation;(3)visible in multiple TEE planes;and(4)in contact with the Watchman device.The management of DRT following diagnosis was intensification of pre-existing antithrombotic regimen or prolonging antithrombotic duration and careful imaging follow-up until complete DRT dissolution.5.If Warfarin or NOAC was discontinued at the 1.5-month follow-up visit,Clopidogrel 75 mg plus Aspirin 100 mg daily would then be prescribed until completion of the 6-month follow-up visit and lifelong Aspirin 100 mg would be prescribed for maintenance.6.Patients underwent routine perioperative follow-up for acute or subacute pericardial effusion/tamponade,access-related complication,device-related complication and any bleeding or embolic event.7.Typically the post-operation imaging follow-up was performed 1.5-month after the Watchman implantation.Clinical follow-up visits were typically annually and a telephone interview was conducted at 6-month post-operation.Endpoint events such as ischemic stroke,transient ischemic attack(TIA),other embolic events,hemorrhagic stroke or gastrointestinal bleeding were collected at all visits.8.The average risk rate for the study population was calculated on the basis of CHA2DS2-VASc score and HAS-BLED score in each patient,and then relative risk reduction was calculated using actual risk rate and calculated risk rate.9.Baseline characteristics,procedural characteristics and post-operation antithrombotic regime were compared in subjects with DRT versus without DRT using a Student‘s t-test or Chi-square test.Categorical variables are presented as percentages.Continuous variables are presented as mean±standard deviation.The SPSS statistical software version 24 was used for all statistical calculation.A 2-sided p value <0.05 was then considered statistically significant.10.The database includes Pub Med,EMbase,CNKI and Wan Fang from December 1999 to December 2018.All literature were screened,extracted and reviewed according to the inclusion and exclusion criteria.The meta-analysis was conducted to evaluate the DRT incidence and odds ratio of ischemic events in patients with DRT in comparison with those without DRT by using Stata software.Results1.A total of 114 patients with nonvalvular atrial fibrillation,71 males and 43 females with an average age of(65.0±9.5)years received LAAC.The average CHA2DS2-VASc score was(3.1±1.5)and average HASBLED score was(2.5±1.3).The average maximal left atrial appendage(LAA)ostium diameter was 23.0±4.6.All patients reach both technical and device success.Immediate TEE imaging revealed a >3mm residual leakage in 4 cases(3.5%)overall.Perioperative major bleeding occurred in 2 cases(1.8%),which included 1 case experienced a pericardial tamponade who were treated by pericardial catheter drainage and 1 case experienced gastrointestinal bleeding who were treated with blood transfusion.Following LAAC,patients received Warfarin,NOACs,dual antiplatelet therapy and single antiplatelet therapy(36.3%,55.3%,7.1% and 0.9% respectively).The mean follow-up period was 18.7±12.0 months.During follow-up,ischemic stroke was occurred in 2 cases(1.8%),hemorrhage stroke was occurred in 3 cases(2.6%),death was occurred in 3 cases(2.6%),DRT was found in 6 cases(5.3%)by TEE and no severe peridevice leak(>5mm)occurred.Actual ischemic stroke rate was 1.8%,and the calculated ischemic stroke risk based on CHA2DS2-VASc score was 3.8%,and the relative risk reduction was 52.6%.Actual ischemic stroke/TIA/peripheral emboli rate was 1.8%,and the calculated ischemic stroke/TIA/peripheral emboli risk based on CHA2DS2-VASc score was 5.3%,and the relative risk reduction was 66.0%.Actual major bleeding rate except for hemorrhage stroke events was 1.8%,and the calculated major bleeding risk except for hemorrhage stroke events based on HAS-BLED score was 5.3%,and the relative risk reduction was 66.0%.Actual major bleeding rate except for perioperation bleeding events was 0.0%,and the calculated risk based on HAS-BLED score was 5.3%,and the relative risk reduction was 100.0%.2.Six cases was adjudicated as DRT positive according to independent review by 2 experienced echocardiographers.The mitral regurgitation was more common in DRT group than in the non-DRT group(53.7% vs.100%,p=0.034).Mean serum creatinine was higher in DRT group(117.83±28.92 ?mol/L vs.95.97±22.26 ?mol/L,p=0.023).Mean Baseline PT-INR was lower in the DRT group(1.04±0.12 vs.1.35±0.65,p=0.000).Patients receiving NOAC was more common in DRT group(100% vs.49.5%,p=0.028).3.Overall,11 studies involving 4664 patients were included.The results of meta-analysis showed that incidence of DRT after Watchman implantation was 3.0%(95%CI: 2%~4%).The odds ratio of ischemic events among patients with DRT was 3.57(95%CI 2.13~6.00)in comparison with non-DRT group.Predictors of DRT included patient characteristics(including high CHA2DS2-VASc score,spontaneous contrast in the LA cavity),device-related characteristics(connector pin of the Watchman deice)and procedure-related characteristics(including the presence of peridevice leakage and deep implantation).4.Successful LAAC with the kissing-Watchman device was achieved in all 4 patients,with the maximum LAA ostia diameter of 35,36,33,30 mm respectively.The lateast TEE follow-up revealed that there were no peridevice leakage >3 mm,device embolism or device-related thrombi.There were no major adverse events including device embolism,stroke/transient ischemic attack,other systemic embolism,major bleeding(gastrointestinal or intracranial)or death during the 12-month clinical follow-up.Science and technology novelty search of ministry of education showed that our study was the first study in the world to apply the kissing-Watchman technique in the single-lobulated LAA with gaint ostium anatomy.Conclusion1.LAAC were successful in all 114 patients with the Watchman occluder.During follow-up,the relative risk reduction on ischemic stroke and ischemic stroke/TIA/peripheral emboli are 52.6% and 66.0% respectively and the relative risk reduction on major bleeding and major bleeding excluding perioperative bleeding are 66.0% and 100.0%.LAAC is feasible and safe for nonvalvular AF patients to prevent the incidence of stroke in Chinese population.2.The DRT incidence is 5.3% after LAAC with Watchman device.Presence of mitral regurgitation,higher serum creatinine,lower baseline PT-INR and NOAC regime during the first 1.5-month post-operation can be associated with DRT formation.3.According to the meta-nanlysis,the incidence of DRT after Watchman implantation is 3.0%(95%CI: 2%~4%).DRT is associated with 3.57-fold increase in ischemic events.Predictors of DRT includes patient characteristics,device-related characteristics and procedure-related characteristics.4.In patients with single-lobulated left atrial appendage and giant ostia anatomy,the implantation of kissing-Watchman is safe and feasible which leads to favorable results during 12-month clinical follow-up.Larger cohorts and long-term follow-up are needed to corroborate the safety and efficacy of this technical innovation.Science and technology novelty search of ministry of education shows that our study is the first study in the world to apply the kissing-Watchman technique in the single-lobulated LAA with gaint ostium anatomy.