Anna Olasinska-Wisniewska
Marek Grygier*- Chair and 1st Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
Transcatheter interventions enable safe and efficient treatment of various structural heart diseases. However, therapy does not finished with the end of the procedure. Device thrombosis is a possible serious complication. Therefore, careful patient management should include optimal antiplatelet or antithrombotic medication to enhance safe and complete endothelial coverage of the implanted device. In case of thrombus formation careful diagnostic evaluation and prompt treatment is crucial. This paper provides an update to current knowledge and understanding of prevention and management of device related thrombosis.
Patent Foramen Ovale (PFO)/atrial Septal Defect (ASD)
The percutaneous intervention has become a feasible and safe method of interatrial shunts closure.
According to current guidelines (1) percutaneous closure of ASD II is recommended in patients with significant shunt with signs of right ventricle overload and pulmonary vascular resistance (PVR) lower than 5 WU and should be considered in patients with paradoxical embolism. PFO closure may be proposed (2) to patients with a diagnosis of cryptogenic stroke after careful exclusion of other potential sources of embolism.
The procedure of ASD/PFO closure is commonly performed and relatively safe. However, thrombus formation is a recognizable and potentially harmful complication. This phenomenon is observed in 1.0–2.0% of patients (2) in all available types of devices. The risk of septal occluder device thrombosis may be even higher since asymptomatic patients may not undergo proper planned echocardiographic surveillance (3). Although uncommon, it may result in serious complications, including systemic embolism, and recurrent neurologic episodes (3). Thrombus formation may occur during procedure on either the delivery sheath or the device (4) or after the intervention, and has been noted even up to 5 years after the procedure (5). The incidence of thrombus formation is highest within the first 4 weeks after device implantation and is extremely rare after 8–12 months (6).
The majority of ASD/PFO occluders are composed of metal (usually nitinol) and a polyester mesh (4). Coagulation within the wire mesh facilitates fibrous tissue growth into the device which promotes a complete endothelialization and final occlusion of the shunt (7). Endothelialization and scar tissue formation on the implanted device is necessary to obtain complete closure of the intra-atrial communication and to prevent large subsequent thrombus formation (8). Increase in the coagulations cascade noted (9) after the procedure is an integral part of the sealing process (10). According to study by Anzai et al. (8) these processes may be visualized in transesophageal echocardiography (TEE) as plain forms of thrombi on the device and represent a natural healing process. Such findings do not necessarily suggest higher risk of embolization, and may resolve with time, with or without anticoagulation therapy.
Inclusion of pharmacological anticoagulation may counteract this desired process of healing and is associated with a risk for hemorrhagic complications. However, excessive coagulation may lead to uncontrolled thrombus formation on the device surface and the risk of embolic complications (7).
Currently preprocedural and postprocedural pharmacological therapy in the prevention of the device related thrombosis is commonly accepted and based on clinical practice and randomized clinical trials.
In majority of the centers aspirin (ASA) and clopidogrel are started preprocedurally, with a loading doses of 300 and 600 mg, respectively. Patients after ASD closure usually should receive dual antiplatelet therapy (DAPT) for 3 months and continue ASA up to 6 months. The decision to continue ASA therapy longer than 6 months is left at physician discretion.
Post procedural management after PFO closure is based on results of randomized clinical trials [RCT—CLOSE (11), CLOSURE I (12), DEFENSE-PFO (13), RESPECT Trail (14)]. Patients without history of thromboembolism, atrial fibrillation or other indications to use anticoagulation should receive DAPT therapy with aspirin and clopidogrel in the first six months and continue with a single drug for at least 5 years [based on latest consensus (2)]. The extension of the therapy with single antiplatelet drug beyond 5 years should be based on estimation of the balance between patient's overall risk of stroke for other causes and hemorrhagic risk. However, in the daily clinical practice DAPT is usually used for 6–8 weeks followed by single antiplatelet therapy up to 1 year (Supplementary Figure 1).
Sherman et al. (3) pointed out higher risk of thrombosis in atrial fibrillation and suggested reconsideration of the safety of the procedure and lifelong use of oral anticoagulation in this particular group of patients.
Nevertheless, device thrombosis was noted either in patients with antiplatelet therapy or anticoagulants. Nkomo et al. (15) described thrombus formation on CardioSEAL device despite warfarin use with acceptable international normalized ratio (INR). They explained that warfarin might reveal a procoagulant effect during initiation of therapy if the patient did not receive concomitant heparin at the same time.
Transthoracic echocardiography (TTE) is usually unable to detect thrombus formation on the device (16). Krumsdorf et al. (16) suggested a routine TEE examination in adult patients, including those with good echocardiographic windows, after 4 weeks, 6 and 12 months, however nowadays such practice is rather rare in majority of centers. For children, follow-up only by TTE as an imaging tool might be sufficient. Sherman et al. (3) proposed early (3 months) echocardiographic surveillance and TEE in cases when transthoracic echocardiography suggests thrombosis or when transthoracic images are suboptimal.
Once the thrombosis was identified, based on the literature, over 80% of patients were successfully treated with only conservative medical therapy (3, 8, 16). The mobility and potential friability of thrombus is associated with a high risk of embolization early after procedure and therefore requires an aggressive management (4, 17). Moreover, the observation that 76% of thrombi occurred on the left atrial side of a device highlights the risk of systemic embolization (3).
According to the literature reports thrombi were treated with UFH alone (18) or UFH with subsequent anticoagulation (16, 19), or only oral anticoagulant (8, 16), and even with recombinant tissue plasminogen activator with a glycoprotein IIb/IIIa inhibitor (tirofiban) (20) or a glycoprotein IIb/IIIa inhibitor (abciximab) with heparin (17). Summary of studies reporting DRT is presented in Supplementary Table 1.
The majority of thrombi resolves within 4 weeks to 6 months after introduction of anticoagulation (16). In analysis by Krumsdorf et al. (16) the thrombus disappeared after 4 weeks in 11 out of 17 patients. A TEE should be performed following anticoagulation treatment to confirm resolution of the device-related thrombus. Thrombolysis or even surgical removal of the device should be considered in patients who do not respond to medical therapy. In cases treated with surgery thrombus should be removed together with the device especially if unsuccessful medical treatment was associated with cerebral embolization (8, 16, 21, 22).
Several authors tried to discriminate predictors of device related thrombus formation after transcatheter closure. Sherman et al. (3) in their review pointed out that all types of commercially available devices had thrombosis reports. The data from their review in no way demonstrate that one device is superior to another. Krumsdorf et al. (16) reported 1,000 patients, 593 of them with PFO and 407 with an ASD. Twenty of them had device associated thrombi during the 1 or 6-month follow up. The thrombi occurred more often in the CardioSEAL (7.1%), the PFO- Star device (6.6%) or the StarFLEX (5.7%) devices compared to the Amplatzer device (0.0%) (p < 0.05). Paroxysmal atrial fibrillation after the procedure (6.2 vs. 20%; p < 0.05) and persisting atrial septal aneurysm despite effective transcatheter closure (1.3 vs. 20%, p < 0.01) were significant predictors for thrombus formation (16). A correlation with atrial septal aneurysm was however not mentioned in other reports. Thus, the significance of this finding should be treated with caution.
Left Atrial Appendage Closure (LAAC)
Atrial fibrillation is the most common arthytmia and a second cause of stroke. The left atrial appendage (LAA) has a thrombogenic potential, particularly in the setting of atrial fibrillation (AF), and may be the main source (up to 90%) of the majority of AF-attributable emboli in patients with non-valvular atrial fibrillation. Percutaneous LAA closure was introduced either as an option to oral anticoagulants (USA) or to avoid long term oral anticoagulation in patients with contraindication to pharmacological therapy, including those with previous bleeding or at very high risk of bleeding complications (Europe) (23). Even 10–30% of patients may present relative, and 2–3% absolute contraindications to oral anticoagulants. The efficacy and safety of LAA occlusion in patients with AF has been demonstrated in several studies including two large randomized clinical trials the PROTECT-AF and PREVAIL and prospective registries (CAP, ASAP, EWOLUTION, ACP/Amulet European Registries) (24–30). Two major systems are currently used most frequently worldwide—Watchmann (Boston Scientific, USA) and Amplatzer Cardiac Plug/Amulet (Abbott, USA), and several other devices used occasionally or in clinical trials—Ultraseal (Cardia Inc, USA), WaveCrest (Coherex Medical, USA), Occlutech (Occlutech International AB, Sweden), LAmbre LAA Closure System (Lifetech, China).
Thrombus in the LAA confirmed by TEE usually precludes the LAAC, as it may be mobilized from the LAA during the procedure. If present, an attempt to resolve the thrombus should be first initiated—with 3–4 weeks of vitamin K antagonists (VKA) or novel oral anticoagulants (NOAC) until its complete resolution. There are only some exceptional reports of LAA closure despite presence of the thrombus (31).
It must be pointed out, that thrombus may occur within hours without anticoagulation in favorable circumstances (atrial fibrillation promotes prothrombotic activity in left atrium (LA) and LAA), thus periprocedural anticoagulation is necessary to prevent from intraprocedural thrombotic complications. Anticoagulants are usually stopped 1–3 days before the procedure and INR should be normalized if VKA is used, however some operators advocate to perform procedure on anticoagulants similarly to atrial fibrillation ablation. Patient receives aspirin (usually higher dose -300 mg) and clopidogrel 1 day before the procedure. Unfractionated heparin is given intraprocedurally (to achieve ACT 250–350 s) after atrial septum puncture. The use of brain protection devices during LAA procedures [like Sentinel, Boston Scientific (USA)] is under clinical evaluation (32).
The thrombus formation results from a local tissue response to an implantation and may occur on all available devices. The healing response to nitinol-based devices is initiated by thrombotic material formation and then its transformation into connective tissue within 4 weeks (33). Accumulation of plane thrombus may however turn into excessive, unwanted thrombus formation (33).
LAA closure enables discontinuation of long term anticoagulation. However, shortly after the procedure antiplatelet or antithrombotic prophylaxis is used to prevent DRT. Published data regarding DAPT or OAC choice after the procedure are conflicting. In the study of Chun et al. (34) DAPT administered for 6 weeks after LAAC was associated with less frequent device-related thrombus (1,7%) compared to OAC (15,8%) regardless of the type of device. Plicht et al. (35) reported a higher rate of devices related thrombus (DRT) (Amplazter Cardiac Plug) treated with DAPT. It is possible that nitinol cage (Watchman, Boston Scientific) and nitinol plug devices (Amplatzer, St Jude Medical) may have different thrombogenicity and endothelialization profiles and different needs for antithrombotic prevention. Despite several published analyses, the precise duration and type of optimal therapy is unclear. Current treatment strategies for oral anticoagulants and/or anti-platelet therapy have been derived largely from protocols of randomized clinical trials with Watchman device for LAAC (Supplementary Figure 1).
In fact, in patients eligible for oral anticoagulants, the scheme of post-implantation treatment is similar to PROTECT-AF one (27): warfarin with aspirin are administrated for 45 days, followed by DAPT—clopidogrel (75 mg daily) until the 6-month and aspirin (81–325 mg daily) for life. New studies suggest that use of NOAC instead of warfarin within the first 45 days after interventional LAA closure is safe and effective (36, 37).
Patients with contraindication for oral anticoagulants, who constitute majority of population qualified to LAA closure at least in Europe, receive DAPT as a reasonable alternative based on the large registries (38). The multicenter, prospective, nonrandomized ASAP study (28) was the first one conducted in patients who were considered ineligible for even short term treatment with warfarin. Use of antiplatelet agent (clopidogrel or ticlopidine) for 6 months and lifelong aspirin was proved to be safe alternative to OAC. Similarly, in the study by Urena et al. (39) antiplatelet therapy consisting of aspirin (80–325 mg/24 h) plus clopidogrel (75 mg/24 h), or aspirin or clopidogrel alone were administered according to the operators' discretion for 30–180 days after the AMPLATZER Cardiac Plug (ACP) implantation, and afterwards single- antiplatelet therapy was introduced. No cases of device thrombosis were observed in the 6-month follow-up. In EWOLUTION registry (40), following LAA closure with Watchman device, patients received DAPT, VKA, NOAC, single antiplatelet or no therapy (60.3, 15.4, 10.9, 7, and 6.5%, respectively). Device thrombus (2.6%) and stroke (0.4%) rates were low and did not vary among different post-implantation medication strategies (40).
The incidence of thrombus formation on devices varies widely in current registries, and ranges between 0 and 17.6% (33, 35, 41–46), with most of them reporting 2–4% (Supplementary Table 1). These differences may be explained by the different sample sizes, lack of consensus on the definition of device-associated thrombus, or reporting bias related to different imaging methods, the variations in imaging technique (TEE, computed tomography (CT), 4-dimensional CT) and frequency of imaging assessment during follow-up (41, 44). Moreover, in daily practice up to 72% of patients do not undergo LAA imaging during follow-up (except the first one after 6 weeks), which may be explained by the overall frailty of these high risk patients or a belief that the result of TEE would not change strategy in patients with high risk of bleeding.
Older age and history of ischemic stroke or transient ischemic attack (TIA), permanent atrial fibrillation, vascular disease, higher CHA2DS2-VASc, large LAA diameter and spontaneous echo contrast were risk factors for device-related thrombus, whereas DAPT and oral anticoagulants use at discharge were associated with a lower risk of thrombus formation (33, 35, 41, 44, 46, 47). Among procedural factors—larger device size and deep implantation—were related to the risk of thrombus formation (33, 47). Main et al. (24) found that the nidus for most DRT appeared to be the central portion of the device (“threaded insert”). Although the remainder of the LA facing portion of the device is covered by a permeable polyester fabric, the center portion contains exposed nickel titanium alloy (nitinol) (24). Newer generation device—Watchman FLX has minimal area of metal screw facing the left atrium to encourage endothelialization and reduce post-implant thrombus formation (48). Ketterer et al. (45) found a clopidogrel resistance documented by platelet function testing in 3 of 4 patients (75%) with DRT. They suggested platelet activity and response to clopidogrel testing and changing to an alternative P2Y12 receptor inhibitor as an option (45). Contrary, Plicht et al. (35) found no genetic risk for clopidogrel resistance or other coagulation disorders in patients with thrombi.
Device related thrombus may occur during the procedure (44, 49) and at every stage of follow up after the procedure (33). In the analysis of device arms of 4 prospective FDA trials (PROTECT-AF, PREVAIL, CAP and. CAP2) by Dukkipati et al. (44) device related thrombus was detected on 0.8% at 45 days and in 1.7% at 6 months and 1.8% at 12 months. According to Main et al. (24) incident DRT has higher prevalence at 6 and 12 months when compared with 1.5 months post-procedure. It may be partially explained with the hypothesis that DRT may initially be too thin to be detected by TEE or CCT and become apparent at later stages of follow-up (33).
Recently published papers showed that thrombus on the device is an independent factor strongly associated with strokes and TIA during follow-up (41, 42, 44). Considering all types of devices, a 4 to 7.3% rate of ischemic stroke or TIA has been reported in patients with device-related thrombus (41). It must be however emphasized that this population of patients has the propensity for other sources of emboli, including vascular disease.
In the largest prospective analysis of 1,739 patients in the PROTECT-AF and PREVAIL trials and two registries (CAP—Continued Access to PROTECT AF registry and CAP2—Continued Access to PREVAIL registry) (44) the incidence of device-related thrombus (DRT) was 3.7%. Twenty-five percent of patients with DRT experienced an ischemic stroke or systemic embolism in comparison with 6.8% patients without DRT which means that DRT 3-fold increased risk of stroke or systemic embolism. It should be however mentioned that the majority of patients with DRT (73.8%) did not experience any stroke/systemic embolism and the majority of strokes/systemic embolisms (86.6%) occurred in patients who never manifested a DRT (44).
There are conflicting data concerning risk of thrombus formation in patients with incomplete LAA occlusion. Hypothetically, incomplete sealing of the orifice may enhance thrombus formation and embolization of thrombi potentially leading to strokes. Lam et al. (50) described a case of thrombus formation in a patient with incomplete LAA closure with a Watchman device without clinical symptoms of embolization. Complete resolution of thrombus was achieved after 3 months of warfarin treatment and transcatheter LAA closure with a second-generation Amplatzer Cardiac Plug was performed. On the other side, Viles-Gonzalez et al. (51) performed a study to assess the risk of stroke related to incomplete occlusion and potential risk of thrombus formation. They did not observed any case of thrombus in patients with residual leak. According to their argumentation it could be postulated that even partial occlusion of the LAA could prevent large thrombus from migrating into the systemic circulation and that small clots may not have clinical significance.
Reddy et al. in PROTECT -AF trial (27) used follow-up TEE imaging performed at 45 days, 6 months, and 12 months to assess for device stability, peri-device leaks, and device-related thrombus. Dukkipati et al. (44) suggested a reevaluation of the TEE surveillance strategy and they proposed 1. routine additional TEE surveillance at 6 months 2. an escalated TEE monitoring strategy targeted to patients with thrombus risk factors such as permanent AF, lower left ventricle ejection fraction, history of stroke/TIA, vascular disease and larger LAA diameter, 3 delaying the first TEE to the 4 month time point instead of 6 weeks, because the thrombus occurs most likely after OAC discontinuation at 6 weeks and indeed after receiving DAPT. These are not a standard recommendation, however their adaptation seem to be reasonable in some particular groups of patients.
The manifestation of the DRT in fact impels the anticoagulation introduction—warfarin or “new” anticoagulants—rivaroxaban, dabigatran, apixaban (38, 44, 52). This treatment should be continued for weeks to months until thrombus resolution is confirmed by TEE. However, majority of patients qualified to LAA occlusion (at least in Europe) have by definition strict contraindication for treatment which enhances bleeding. Therefore, the long-term strategy remains uncertain and several factors, including patient characteristics (CHA2DS2-VASc score, HAS-BLED score, creatinine clearance), echocardiographic findings (low left ventricle ejection fraction, “smoke” in left atrium, decreased LAA velocity), and procedural factors (large device, deep implantation, incomplete closure) should be considered. After thrombus resolution a careful and individually driven surveillance is necessary, since thrombus may reappear and currently there is no established scheme for them.
Interatrial Shunt Devices
Interatrial shunt devices were developed to reduce the left atrial pressure in patients with chronic heart failure with preserved EF (HFpEF) and with reduced EF (HFrEF) while avoiding excessive left to right shunting. Three devices—V-Wave (V-Wave, Caesarea, Israel), interatrial septal device system-IASD (DC Devices Inc, Tewksbury, MA, USA) and atrial flow regulator (AFR) (Occlutech, Sweden)—are currently available to create a restrictive interatrial communication (53).The last one is used also in clinical studies in patients with pulmonary hypertension resistant to pharmacological treatment.
The observational data are still limited. First, Søndergaar et al. (54) presented the results of pivotal trial with interatrial septal device system (IASD), implanted in eleven patients with HFpEF. They did not observe any patient with device thrombosis and suggested that with the particular construction of the device, mainly the flat device legs and used pharmacological protocol the risk of stroke would be low. In the REDUCE LAP-HF I study (55) one of 22 patients of a treatment group had a small thrombus which was observed on the tip of the device delivery system in the right atrium. The delivery system was removed and exchanged. A new system was then reinserted, and the IASD device was successfully implanted. The one month follow up of a study group was uncomplicated. There are however no strict data on echocardiographic management in the follow up.
The V-Wave shunt device is another shunt prosthesis which first-in-man implantation was described in 2015 by Amat-Santos et al. (56). Del Trigo et al. (57) presented first results in 10 patients and then Rodes-Cabau et al. (53) expanded the study group to the overall 38 patients with HFrEF and HFpEF. The authors also did not observe thrombus formation during and after the V-Wave device implantation.
Further studies are needed to determine the optimum pharmacological treatment after shunt device implantation (57). Treatment with oral anticoagulation for 3 months followed by ASA monotherapy lifelong was used after V-Wave implantation (53, 58). In patients after IASD implantation aspirin with clopidogrel for 6 months followed by ASA monotherapy lifelong were implemented and in those with indications for oral anticoagulation and/or antiplatelet therapy for a co-existing condition the preprocedural regimen was continued (55, 58). However, this frail population should be also assessed in terms of increased risk of bleeding during antithrombotic and antiplatelet treatment (58).
Summary
Device related thrombosis after percutaneous procedures is rare but can be associated with serious complications. Therefore, optimal antiplatelet/antithrombotic treatment as well as careful echocardiographic assessment in follow up must be implemented in those patients. When detected, device related thrombosis warrants treatment with anticoagulation and aggressive follow-up with appropriate surveillance imaging.
Author Contributions
AO-W and MG contributed substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work. AO-W and MG drafted the work and revised it critically for important intellectual content, provided approval for publication of the content. AO-W and MG both agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Supplementary Material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcvm.2019.00075/full#supplementary-material
References
1. Baumgartner H, Bonhoeffer P, De Groot NM, de Haan F, Deanfield JE, Galie N, et al. ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J. (2010) 31:2915–57. doi: 10.1093/eurheartj/ehq249
2. Pristipino C, Sievert H, D'Ascenzo F, Mas JL, Meier B, Scacciatella P, et al. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. EuroIntervention. (2018) 25:EIJ-D-18-00622.
3. Sherman JM, Hagler DJ, Cetta F. Thrombosis after septal closure device placement: a review of the current literature. Catheter Cardiovasc Interv. (2004) 63:486–9. doi: 10.1002/ccd.20220
4. Yorgun H, Canpolat U, Kaya EB, Aytemir K, Oto A. Thrombus formation during percutaneous closure of an atrial septal defect with an Amplatzer septal occluder. Tex Heart Inst J. (2011) 38:427–30.
5. Raghu A, Kawalsky D, Feldman M. Embolic stroke due to a left atrial thrombus two years after placement of an atrial septal defect closure device. Am J Cardiol. (2017) 98:1294–6. doi: 10.1016/j.amjcard.2006.05.067
6. Kovacevic P, Srdanovic I, Ivanovic V, Rajic J, Petrovic N, Velicki L. Late complications of transcatheter atrial septal defect closure requiring urgent surgery. Postepy Kardiol Interwencyjnej. (2017) 13:335–8. doi: 10.5114/aic.2017.71617
7. Brandt RR, Neumann T, Neuzner J, Rau M, Faude I, Hamm CW. Transcatheter closure of atrial septal defect and patent foramen ovale in adult patients using the Amplatzer occlusion device: no evidence for thrombus deposition with antiplatelet agents. J Am Soc Echocardiogr. (2002) 15(10 Pt 1):1094–8. doi: 10.1067/mje.2002.121666
8. Anzai H, Child J, Natterson B, Krivokapich J, Fishbein MC, Chan VK, et al. Incidence of thrombus formation on the CardioSEAL and the Amplatzer interatrial closure devices. Am J Cardiol. (2004) 93:426–31. doi: 10.1016/j.amjcard.2003.10.036
9. Rodes-Cabau J, Palacios A, Palacio C, Girona J, Galve E, Evangelista A, et al. Assessment of the markers of platelet and coagulation activation following transcatheter closure of atrial septal defects. Int J Cardiol. (2005) 98:107–12. doi: 10.1016/j.ijcard.2004.03.022
10. Bedard E, Rodes-Cabau J, Houde C, Mackey A, Rivest D, Cloutier S, et al. Enhanced thrombogenesis but not platelet activation is associated with transcatheter closure of patent foramen ovale in patients with cryptogenic stroke. Stroke. (2007) 38:100–4. doi: 10.1161/01.STR.0000251712.55322.69
11. Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. (2017) 377:1011–21. doi: 10.1056/NEJMoa1705915
12. Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, et al. CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. (2012) 366:991–9. doi: 10.1056/NEJMoa1009639
13. Lee PH, Song JK, Kim JS, Heo R, Lee S, Kim DH, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO. Trial. J Am Coll Cardiol. (2018) 71:2335–42. doi: 10.1016/j.jacc.2018.02.046
14. Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, et al. RESPECT investigators. long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. (2017) 377:1022–32. doi: 10.1056/NEJMoa1610057
15. Nkomo VT, Theuma P, Maniu CV, Chandrasekaran K, Miller FA, Schaff HV, et al. Patent foramen ovale transcatheter closure device thrombosis. Mayo Clin Proc. (2001) 76:1057–61. doi: 10.4065/76.10.1057
16. Krumsdorf U, Ostermayer S, Billinger K, Trepels T, Zadan E, Horvath K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients. J Am Coll Cardiol. (2004) 43:302–9. doi: 10.1016/j.jacc.2003.10.030
17. Willcoxson FE, Thomson JD, Gibbs JL. Successful treatment of left atrial disk thrombus on an Amplatzer atrial septal defect occluder with abciximab and heparin. Heart. (2004) 90:e30. doi: 10.1136/hrt.2003.027946
18. Acar P, Aggoun Y, Abdel-Massih T. Images in cardiology: thrombus after transcatheter closure of ASD with an Amplatzer septal occluder assessed by three dimensional echocardiographic reconstruction. Heart. (2002) 88:52. doi: 10.1136/heart.88.1.52-a
19. Chessa M, Carminati M, Butera G, Bini RM, Drago M, Rosti L, et al. Early and late complications associated with transcatheter occlusion of secundum atrial septal defect. J Am Coll Cardiol. (2002) 39:1061–5. doi: 10.1016/S0735-1097(02)01711-4
20. Vanderheyden M, Willaert W, Claessens P, Branders I, Ex P, Vermeersch P. Thrombosis of a patent foramen ovale closure device: thrombolytic management. Catheter Cardiovasc Interv. (2002) 56:522–6. doi: 10.1002/ccd.10253
21. Uysal F, Bostan ÖM, Senkaya Signak I, Güneş M, Çil E. Huge thrombus formation 1 year after percutaneous closure of an atrial septal defect with an Amplatzer septal occluder. Anatol J Cardiol. (2016) 16:63–4. doi: 10.14744/AnatolJCardiol.2015.6538
22. Divchev D, Schaefer A, Fuchs M, Breymann T, Drexler H, Meyer GP. Thrombus formation on an atrial septal defect closure device: a case report and review of the literature. Eur J Echocardiogr. (2007) 8:53–6. doi: 10.1016/j.euje.2005.10.011
23. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. ESC scientific document group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. (2016) 37:2893–962. doi: 10.15829/1560-4071-2017-7-7-86
24. Main ML, Fan D, Reddy VY, Holmes DR, Gordon NT, Coggins TR, et al. Assessment of device-related thrombus and associated clinical outcomes with the WATCHMAN left atrial appendage closure device for embolic protection in patients with atrial fibrillation (from the PROTECT-AF Trial). Am J Cardiol. (2016) 117:1127–34. doi: 10.1016/j.amjcard.2016.01.039
25. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF Trial. Circulation. (2013) 127:720–9. doi: 10.1161/CIRCULATIONAHA.112.114389
26. Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective randomized eval- uation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. (2014) 64:1–12. doi: 10.1016/j.jacc.2014.04.029
27. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation. (2011) 123:417–24. doi: 10.1161/CIRCULATIONAHA.110.976449
28. Reddy VY, Möbius -Winkler S, Miller MA, Neuzil P, Schuler G, Wiebe J, et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study. J Am Coll Cardiol. (2013) 61:2551–6. doi: 10.1016/j.jacc.2013.03.035
29. Boersma LVA, Schmidt B, Betts T, Sievert H, Tamburino C, Teiger E, et al. Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION registry. Eur Heart J. (2016) 37:2465–74. doi: 10.1093/eurheartj/ehv730
30. Tzikas A. Left atrial appendage occlusion with amplatzer cardiac plug and amplatzer amulet: a clinical trials update. J Atr Fibrillation. (2017) 10:1651. doi: 10.4022/jafib.1651
31. Tarantini G, D'Amico G, Latib A, Montorfano M, Mazzone P, Fassini G, et al. Percutaneous left atrial appendage occlusion in patients with atrial fibrillation and left appendage thrombus: feasibility, safety and clinical efficacy. EuroIntervention. (2018) 13:1595–602. doi: 10.4244/EIJ-D-17-00777
32. Meincke F, Spangenberg T, Kreidel F, Frerker C, Virmani R, Ladich E, et al. Rationale of cerebral protection devices in left atrial appendage occlusion. Catheter Cardiovasc Interv. (2017) 89:154–8. doi: 10.1002/ccd.26677
33. Pracon R, Bangalore S, Dzielinska Z, Konka M, Kepka C, Kruk M, et al. Device thrombosis after percutaneous left atrial appendage occlusion is related to patient and procedural characteristics but not to duration of postimplantation dual antiplatelet therapy. Circ Cardiovasc Interv. (2018) 11:e005997. doi: 10.1161/CIRCINTERVENTIONS.117.005997
34. Chun KRJ, Bordignon S, Urban V, Perrotta L, Dugo D, Fürnkranz A, et al. Left atrial appendage closure followed by 6 weeks of antithrombotic therapy: a prospective single-center experience. Heart Rhythm. (2013) 10:1792–9. doi: 10.1016/j.hrthm.2013.08.025
35. Plicht B, Konorza TF, Kahlert P, Al-Rashid F, Kaelsch H, Jánosi RA, et al. Risk factors for thrombus formation on the Amplatzer Cardiac Plug after left atrial appendage occlusion. JACC Cardiovasc Interv. (2013) 6:606–13. doi: 10.1016/j.jcin.2013.02.014
36. Bösche LI, Afshari F, Schöne D, Ewers A, Mügge A, Gotzmann M. Initial experience with novel oral anticoagulants during the first 45 days after left atrial appendage closure with the watchman device. Clin Cardiol. (2015) 38:720–4. doi: 10.1002/clc.22478
37. Enomoto Y, Gadiyaram VK, Gianni C, Horton RP, Trivedi C, Mohanty S. Use of non-warfarin oral anticoagulants instead of warfarin during left atrial appendage closure with the Watchman device. Heart Rhythm. (2017) 14:19–24. doi: 10.1016/j.hrthm.2016.10.020
38. Grygier M, Wojakowski W, Smolka G, Demkow M, Wasek W, Sorysz D, et al. Left atrial appendage occlusion: consensus document of Association of Cardiovascular Interventions and Heart Rhythm Section of Polish Cardiac Society. Kardiol Pol. (2018) 76:677–97. doi: 10.5603/KP.a2018.0057
39. Urena M, Rodés-Cabau J, Freixa X, Saw J, Webb JG, Freeman M, et al. Percutaneous left atrial appendage closure with the AMPLATZER cardiac plug device in patients with nonvalvular atrial fibrillation and contraindications to anticoagulation therapy. J Am Coll Cardiol. (2013) 62:96–102. doi: 10.1016/j.jacc.2013.02.089
40. Bergmann MW, Betts TR, Sievert H, Schmidt B, Pokushalov E, Kische S, et al. Safety and efficacy of early anticoagulation drug regimens after WATCHMAN left atrial appendage closure: three-month data from the EWOLUTION prospective, multicentre, monitored international WATCHMAN LAA closure registry. EuroIntervention. (2017) 13:877–84. doi: 10.4244/EIJ-D-17-00042
41. Fauchier L, Cinaud A, Brigadeau F, Lepillier A, Pierre B, Abbey S, et al. Device- related thrombosis after percutaneous left atrial appendage occlu- sion for atrial fibrillation. J Am Coll Cardiol. (2018) 71:1528–36. doi: 10.1016/j.jacc.2018.01.076
42. Lempereur M, Aminian A, Freixa X, Gafoor S, Kefer J, Tzikas A, et al. Device-associated thrombus formation after left atrial appendage occlusion: a systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet. Catheter Cardiovasc Interv. (2017) 90:E111–21. doi: 10.1002/ccd.26903
43. Maksym J, Mazurek T, Kochman J, Grygier M, Kapłon-Cieślicka A, Marchel M, et al. Dual antiplatelet therapy is safe and efficient after left atrial appendage closure. Kardiol Pol. (2018)76:459–63. doi: 10.5603/KP.a2017.0245
44. Dukkipati SR, Kar S, Holmes DR, Doshi SK, Swarup V, Gibson DN, et al. Device-related thrombus after left atrial appendage closure. Circulation. (2018) 138:874–85. doi: 10.1161/CIRCULATIONAHA.118.035090
45. Ketterer U, D'Ancona G, Siegel I, Ortak J, Ince H, Kische S. Percutaneous left atrial appendage occlusion: device thrombosis in clopidogrel non-responders. Int J Cardiol. (2016) 204:196–7. doi: 10.1016/j.ijcard.2015.11.160
46. Sedaghat A, Schrickel JW, Andrié R, Schueler R, Nickenig G, Hammerstingl C. Thrombus formation after left atrial appendage occlusion with the amplatzer amulet device. JACC Clin Electrophysiol. (2017) 3:71–5. doi: 10.1016/j.jacep.2016.05.006
47. Kaneko H, Neuss M, Weissenborn J, Butter C. Predictors of throm- bus formation after percutaneous left atrial appendage closure using the WATCHMAN device. Heart Vessels. (2017) 32:1137–43. doi: 10.1007/s00380-017-0971-x
48. Grygier M, Olasinska-Wiśniewska A, Araszkiewicz A, Trojnarska O, Babicz-Sadowska A, et al. The Watchman FLX - a new device for left atrial appendage occlusion - design, potential benefits and first clinical experience. Postepy Kardiol Interwencyjnej. (2017) 13:62–66. doi: 10.5114/aic.2017.66188
49. Bartuś K, Myć J, Bartuś M, Lee RJ, Litwinowicz R, Dziewierz A, et al. Rapid left atrial appendage thrombus formation before suture ligation with LARIAT. Postepy Kardiol Interwencyjnej. (2018) 14:435–7. doi: 10.5114/aic.2018.79876
50. Lam SC, Bertog S, Sievert H. Incomplete left atrial appendage occlusion and thrombus formation after Watchman implantation treated with anticoagulation followed by further transcatheter closure with a second-generation Amplatzer Cardiac Plug (Amulet device). Catheter Cardiovasc Interv. (2015) 85:321–7. doi: 10.1002/ccd.25456
51. Viles-Gonzalez JF, Kar S, Douglas P, Dukkipati S, Feldman T, Horton R, et al. The clinical impact of incomplete left atrial appendage closure with the Watchman Device in patients with atrial fibrillation: a PROTECT AF (Percutaneous Closure of the Left Atrial Appendage versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) substudy. J Am Coll Cardiol. (2012) 59:923–9. doi: 10.1016/j.jacc.2011.11.028
52. Qazi AH, Wimmer AP, Huber KC, Latus GG, Main ML. Resolution (and Late Recurrence) of WATCHMAN Device-Related Thrombus Following Treatment with Dabigatran. Echocardiography. (2016) 33:792–5. doi: 10.1111/echo.13174
53. Rodés-Cabau J, Bernier M, Amat-Santos IJ, Ben Gal T, Nombela-Franco L, García Del Blanco B, et al. Interatrial shunting for heart failure: early and late results from the first-in-human experience with the V-wave system. JACC Cardiovasc Interv. (2018) 11:2300–10. doi: 10.1016/j.jcin.2018.07.001
54. Søndergaard L, Reddy V, Kaye D, Malek F, Walton A, Mates M, Franzen O, et al. Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure. Eur J Heart Fail. (2014) 16:796–801. doi: 10.1002/ejhf.111
55. Feldman T, Mauri L, Kahwash R, Litwin S, Ricciardi MJ, van der Harst P, REDUCE LAP-HF I Investigators and study coordinators. transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): a Phase 2, Randomized, Sham-Controlled Trial. Circulation. (2018) 137:364–75. doi: 10.1161/CIRCULATIONAHA.117.032094
56. Amat-Santos IJ, Bergeron S, Bernier M, Allende R, Barbosa Ribeiro H, Urena M, et al. Left atrial decompression through unidirectional left-to-right interatrial shunt for the treatment of left heart failure: first-in-man experience with the V-Wave device. EuroIntervention. (2015) 10:1127–31. doi: 10.4244/EIJY14M05_07
57. Del Trigo M, Bergeron S, Bernier M, Amat-Santos IJ, Puri R, Campelo-Parada F, et al. Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proof-of-principle cohort study. Lancet. (2016) 387:1290–7. doi: 10.1016/S0140-6736(16)00585-7
Keywords: antithrombotic, antiplatelet, ASD, PFO (patent foramen ovale), LAA (left atrial appendage) closure, Interatrial shunt device
Citation: Olasinska-Wisniewska A and Grygier M (2019) Antithrombotic/Antiplatelet Treatment in Transcatheter Structural Cardiac Interventions—PFO/ASD/LAA Occluder and Interatrial Shunt Devices. Front. Cardiovasc. Med. 6:75. doi: 10.3389/fcvm.2019.00075
Received: 15 January 2019; Accepted: 20 May 2019;
Published: 07 June 2019.
Edited by:
Jolanta Siller-Matula, Medical University of Vienna, AustriaReviewed by:
Gidon Yehuda Perlman, Hadassah Medical Center, IsraelDavid Chistian Reineke, Inselspital, Switzerland
Copyright © 2019 Olasinska-Wisniewska and Grygier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Marek Grygier, marek.grygier@skpp.edu.pl