Peri-Device Leaks after Percutaneous Left Atrial Appendage Closure: Clinical Significance and Unmet Diagnostic Needs

Figures & data

Table 1. Summary of definitions, frequency, modality for detection, and impact on outcomes of PDL in percutaneous LAAO studies

Device	Year	Patients (n)	Definition and Timing of PDL	Presence of PDL or Leak (LARIAT)	Anticoagulation Regimen	Imaging	Impact of PDL on outcomes
WATCHMAN (Boston Scientific)	2009 2012 2015 2015 2017 2019 2019	463 445 18 219 16 46 46	>5 mm, 45 days >3 mm/1-3 mm/<1 mm, 12 months Presence of contrast, 1–6 months Any size, 12 months Presence of contrast, 6 months >5 mm/<5 mm, 45 days Presence of contrast, 45 days	14%^31 12%/21%/<1%^30 56%^20 21%^32 69%^33 None/59%^34 39%^34	See notes below	TEE TEE CT TEE CT TEE CT	N/A None N/A None N/A N/A N/A
AMPLATZER amulet (St Jude)	2014 2015	24 9	>3 mm, 1–3 months Presence of contrast, 1–6 months	None^Citation35 67%^20		TEE CT	N/A N/A
AMPLATZER cardiac plug (St Jude)	2015 2015 2015 2017 2017 2017	167 24 18 19 339 1,088	>3 mm/<3 mm, 0–2 years Presence of contrast, 1–6 months Presence of contrast, 3 months Presence of contrast, 6 months Any size, 134 days >3 mm, 67 days	None/8%^36 62%^21 71%^20 42%^33 13%^29 2%^37		TEE CT CT CT TEE TEE	N/A N/A N/A N/A None N/A
LARIAT (SentreHEART)	2015 2016 2016 2016	259 58 98 712	Any size, 12 months >3 mm, 1 month and 3 months >5 mm/<5 mm, 12 months >5 mm/2-5 mm, 3 months	14%^32 None^38 5%/15%^16 <1%/7%^39		TEE TEE TEE TEE	None N/A None N/A
LAmbre (Lifetech)	2017 2018	153 60	>3 mm, 12 months >5 mm, 6 months	<1%^40 6%^41		TEE TEE	N/A N/A
Occlutech (Occlutech)	2017	28	<3 mm, 3 months	7%^Citation42		TEE	N/A
Ultraseal (Cardia)	2018 2018	12 126	>5 mm, 45 days >5 mm/3-5 mm/1-3 mm/<1 mm, <6 months	None^43 None/6%/12%/3%^Citation44		TEE TEE	N/A N/A
Wavecrest (Coherex medical)	Ongoing	73	>3 mm, 6 weeks	4%45		N/A	N/A

Notes. Abbreviations: PDL, peri-device leak; TEE, transesophageal echocardiogram; CT, computed tomography; N/A, not applicable.

Anticoagulation regimen in patients receiving LAAO by study:

³¹45 days warfarin (until no PDL or PDL<5 mm), 75 mg clopidogrel + 81–325 mg aspirin (until 6 month follow-up), 81–325 mg aspirin (indefinitely)

³⁰45 days warfarin (until no PDL or PDL<5 mm), clopidogrel + aspirin (until 6 month follow-up), aspirin (indefinitely).

²⁰“typically” aspirin + clopidogrel for 1–3 months, followed by aspirin alone indefinitely.

³²Watchman: 45 days warfarin, oral antiplatelet agent for 6 months, continuation of either oral anticoagulants or antiplatelet agents “was left to the operator’s discretion”.

Lariat: “oral anticoagulants and antiplatelet agents were discontinued immediately after the procedure in the majority and at 4–6 weeks in some. Subsequent continuation of these agents was left to the operator’s discretion based on patient situation”.

³³Watchman: 45 days warfarin, dual-antiplatelet therapy for 6 months, single-antiplatelet therapy indefinitely.

ACP: dual-antiplatelet therapy for several weeks to months, and a single-antiplatelet drug or no medication thereafter.

³⁴Oral anticoagulation for 45 days unless PDL >5 mm, clopidogrel up to 6 months, aspirin indefinitely.

³⁵Dual anti-platelet therapy (aspirin 80 mg/day and clopidogrel 75 mg/day) for a minimum of three months followed by aspirin indefinitely.

³⁶Following implantation, a loading dose (600 mg) of clopidogrel was administered, and treatment was started with 300 mg aspirin (ASA) on the first day and 100 mg daily thereafter. Clopidogrel was maintained for 3–6 months, barring hemorrhagic complications, and ASA for 6–12 months. If thrombus occurred, subcutaneous enoxaparin in a therapeutic dose was added for 2 weeks, clopidogrel was prolonged and the TOE was repeated to check for disappearance. If the result was negative, the decision to prolong the treatment for another week or hospitalize the patient and begin treatment with intravenous heparin was evaluated.

²¹Anticoagulation therapy was discontinued at discharge in all patients (one patient had thrombus treated with 3 weeks of LMWH).

²⁹Antithrombotic therapy recommendation by the device manufacturer after LAA closure was aspirin 80 to 100 mg/day and clopidogrel 75 mg/day for 1 to 3 months, followed by aspirin 80 to 100 mg/day for at least another 3 months. However, the choice and duration of antithrombotic therapy were individualized on the basis of physician preference and recorded at admission and last follow-up visit

• Antithrombotic therapy use post–LAA closure was available in 255 patients; of these, 159 were on dual-antiplatelet therapy, 79 were on single-antiplatelet therapy, 16 were on OAC, and 1 was receiving no antithrombotic agent post–LAA closure.

³⁷Discharged on a single-antiplatelet agent (23.0%), dual antiplatelets (54.3%) or an oral anticoagulant (18.9%).

³⁸Patients with a contraindication to warfarin remained off warfarin. Patients with a CHADs-VASC score of 2 or higher who could tolerate warfarin (i.e., noncompliant or labile international normalized ratio level) were recommended to continue warfarin or a NOAC. Patients with a CHADS-VASC score of 1, anticoagulation was left to the discretion of the referring physician.

¹⁶Post-procedural medical therapy (including antithrombotic therapy) was prescribed according to the operator’s preference

• 85% of patients were discharged on antithrombotic therapy: 50% on antiplatelet therapy (aspirin in 18%, clopidogrel in 2%, and dual-antiplatelet therapy in 30%) and 35% on OAC (warfarin in 26%, rivaroxaban in 5%, and dabigatran in 4%).

• At 6-month follow-up, 21% of patients were on OAC and 44% on antiplatelet therapy.

• At 12-month follow-up, 19% were on OAC and 48% on antiplatelet therapy. Patients were kept on OAC either because leaks were observed or because they underwent AF ablation procedures at follow-up.

³⁹Anticoagulation was resumed after LAA exclusion in all patients except those with prohibitive bleeding (67.4%) and high fall risk (11.6%). The other 21% patients were on OAC at 6 weeks, and all of them were off OAC at 6, 12, and 24 months, unless they were found to have a thrombus on follow-up TEE (n ¼12) that required reinitiating of OAC.

⁴⁰Clopidogrel 75 mg daily for 3 months, then aspirin 100 mg daily indefinitely

⁴¹Dual-antiplatelet therapy with aspirin and clopidogrel for 3 months, followed by aspirin alone. At 1 month a relevant leak of ≥5 mm was observed in 3/60 (5%) patients, which persisted during 12- month follow-up. After its detection, antiplatelet therapy was switched to oral anticoagulation.

⁴²100 mg aspirin and 75 mg clopidogrel was recommended for 3 months

• 2 patients required warfarin for device thrombus and maintained INR > 2 until 3-month follow-up, then phenprocoumon.

• 2 patients required warfarin for device thrombus and maintained INR > 2 until 3-month follow-up, then phenprocoumon.

⁴³Aspirin 81 mg/day and clopidogrel 75 mg/day for 3 months and single-antiplatelet therapy (usually aspirin) indefinitely.

⁴⁴Most patients (∼90%) were discharged on single or dual-antiplatelet therapy, whereas only 4% of patients received oral anticoagulation.

• 5 patients with device-related thrombosis received oral anticoagulation.

• 5 patients with device-related thrombosis received oral anticoagulation.

Not reported.

Figure 2. Examples of current LAAO devices and possible device-specific mechanisms of PDL at the time of device implantation. (a) Single lobe, membrane-coated devices such as the Watchman (Boston Scientific) interact with LAA in one circumferential zone at the level of the LAA landing zone where PDL may occur with these devices. In lobe and disc devices such as the Amplatzer Amulet (Abbott) interact with the LAA at two circumferential territories including the landing zone and then more distally in the body of LAA. These contact sites and the area between the lobe and disc represent potential regions where PDL can occur. The uniformity of LAA-device contact can be influenced by the presence of an additional lobe that can result in off-axis implantation and resultant PDL of both device types. (b) Leak following epicardial LAAO with the LARIAT device is always centrally located and could be modulated by the morphology of the LAA body and ostium. Purple and blue arrows represent (turbulent in some cases) flow into and out of the LAA , respectively. Abbreviations: LA, left atrium; LAA, left atrial appendage; LAAO, LAA occlusion; LSPV, left superior pulmonary vein; LIPV, left inferior pulmonary vein; LLR, left lateral ridge; MV, mitral valve; LV, left ventricle; PDL, peri-device leak; Cx, circumflex artery

Figure 1. Examples of variability in LAA anatomy that may present challenges to imaging and device sizing and selection. (a) Various shapes of the LAA ostium have been described including round, oval, triangular, and teardrop however the association between LAA ostial shape and successful closure is not well established. (b) Morphologic variation in the body of the LAA are well-recognized including the so-called windsock, cactus, chicken wing, and cauliflower variants as well as the presence of more than one LAA lobe which may impact the success of endovascular device-based closure. Abbreviations: D1, D2 maximum diameters in 2 dimensions; MV, mitral valve; Cx, circumflex artery

Figure 3. PDL as a precursor to DRT: Putative mechanisms of impaired endothelialization following implantation. (a) Following endovascular LAAO, over time, the LAAO device should ideally be covered by healthy endothelium to prevent thrombogenicity and resultant PDL. (a1) The nature of LA flow (high-velocity laminar vs. low-velocity turbulent) may impact the efficacy of endothelialization. (b) In the context of (b1) low-velocity turbulent flow in the LA, impaired endothelialization may result thereby exposing the thrombogenic surface of the LAAO device to the coagulation system at a time when patients may be discontinuing anticoagulation therapy resulting in DRT and risk of cardioembolism. In the context of PDL (b2), persistent flow in and out of the LAA around the device may also lead to impaired endothelialization and PDT but also delay thrombosis of the LAA and allow for the embolization of LAA thrombi

Abbreviations: LA, left atrium; LAA, left atrial appendage; LAAO, LAA occlusion; PDL, peri-device leak; DRT, device-related thrombosis.

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