The results of this prospective study show that IDE was notuncommon within 6 months post LAAC,especially in patients with persistent AF,larger LAA ostial diameter and LA size. IDE confers an increased risk for DRT, but may not be necessarily associated with thromboembolic events and poor clinical outcome on optimal antithrombotic therapy.
Incidence of IDE after LAAC
In canine models, the device surface is often completely endothelialized within3months after implantation[14, 15].By contrast, IDEpost LAAC occurs frequently even well beyond this timeperiodin humans[11, 13, 17, 18].In this study, almost two-thirds of patients had IDE detected by cardiac CT at 6 months post procedure, whichwas similar to most previous reports [22, 24, 25] but somewhat differed from others . In the study of Granier et al,IDE occurred in 14 out of 23 patients(61%) after 10 months of LAAC.Lindner et al reported anIDE rate of 56% at median follow-up of 6 months post LAAC procedure. Likewise, in another study including 46 patients undergoing successful LAAC, Sivasambu et alobserved that IDE occurred in 28 patients at 45 days during follow-up.Interestingly, cardiac CT demonstrated that contrast medium entered the left atrial appendage through the fabric rather than around the device in 10 patients .Conversely, Zhao and co-workers reported an IDE rate of 8.3% at 6 months in 84 patients who received successful LAAC and ablation of AF.The explanation for different occurrence rates of IDE after LAAC is multifactorial, and may be, at least partly, related toheterogenous definitions of IDE, various types of LAA occluder, and different cardiac imaging techniques[14, 30, 32].
Recently, cardiac CT has been shown to be more sensitive to detect device residual leak into the LAAcompared with transesophageal echocardiography, owing to its superior spatial resolution, three-dimensional assessment and largely operator independent nature[24, 33].By cardiac CT, the linear attenuation coefficient within theLAA can be measuredand, residual patent LAA has an attenuation either ≥100HU or ≥25% of that measured in LA could be defined as IDE, irrespective of peri-device leak. This may partly account for the higher prevalence of IDE in our study.Similar results have been demonstrated by Lindner[30, 32],who defined LAA as patent if attenuation of the left atrium exceeded that of the left atrial appendage by 50 HU.
Risk factors for IDE
The potential predisposing factorsofIDE post LAAC remainnot fully clear.Hypercoagulable state, comorbidities, and device size and type may play a role[13, 17].Sharma et al reported a 70-year-old woman with severe mitral regurgitationwho suffered poordevice endothelialization 1.5 years after Watchman procedure. It was considered that an eccentric mitral regurgitation jet may cause shearing force on the device and impede normal endothelialization. Massarenti et al observed IDE 10 months after LAAC in an elderly male with hereditary hemorrhagic teleangectasia, suggesting that IDEcould be due to abnormal vascular smooth muscle development and endothelial remodeling.Additionally, Granier et al found that patients with IDEwere more likely to have diabetes, permanent AF and larger devices implanted.In the present study, patients with IDE had larger LAA ostialdiameter and LA size.The factors together with persistent AF were independent determinants for IDE by multivariate analysis.Persistent AFmay involve in increased LA size and subsequentIDE, although the exact mechanisms remain unknown.
Animalstudies have demonstrated different processes of endothelialization amongdevices implanted[14, 15]. Watchmanoccluder does not impact left atrial appendage adjacent structures, favoring surface recovery. In comparison, Amplatzer Cardiac Plug (ACP)(St. Jude Medical, Minneapolis, Minnesota)is more likely to trigger IDE because the disk could potentially jeopardize left atrial appendage neighboring structures.In this study, IDE was detected in 7 out of 8 patients with implantation of LeftearTM, structurally similar to ACPTM.However,Lindner et al  found no statistically relevant difference in the use of WatchmanTM and AMPLATZER™ AMULET™ (St. Jude Medical, St Paul, MN, USA) between patients with IDE and those with CDE.These observations suggest that the effect of different devices on IDE require further investigations.
Identifying predictive factors of IDE may have clinical implications, especially for the follow-up and postoperative medications for patients after LAAC. Theoretically,IDE leads to residual filling of the LAA with very low velocity and blood turbulence and stagnation, which could trigger thrombus formation behind (and ultimately on) the LAA closure device.Several studies have shown that occurrence of IDE later or very late afterLAAC increased the risk ofDRT and subsequentthromboembolic events[7, 11-13]. Therefore, current practice on duration of anticoagulant therapy from animal studies(i.e., 45 days with warfarin or 3 months with direct oral anticoagulants immediately after LAAC) seems to be inadequate for thrombosis prevention. In the current study,4 patients were found with DRT at 6 months post LAAC,and 3 of them had IDEat the same area. Although no thromboembolic events occurred at 6-month clinical follow-up, prolonged antithrombotic treatment were given in these patients.This finding highlights that standard cardiac CT follow-up and prolonged anticoagulant therapy are encouraged especially for patients with IDE after LAAC procedure.
We recognizelimitations in our study. First, patients number included in the current study is limited, selection bias may exist and the conclusion derived from current study may be underpowered. Second, as a single center study, the treatment regimen of patients included may not reflect the general status of LAAC therapy. Third, 6-month’s clinical follow-up duration does not allow us to fully answer the long-term outcomes of patients with IDE, as well as the appropriate antithrombotic regimen in this population. Forth, individual features of baseline echocardiography, such as mitral regurgitation degree, was not analyzed in the current study, which may have adverse influence on IDE.