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

ABSTRACT

Oral anticoagulation reduces the ischemic stroke risk in patients with nonvalvular atrial fibrillation (NVAF) but inherently increases the bleeding risk. Percutaneous left atrial appendage occlusion (LAAO) offers an alternative to long-term anticoagulation in patients at risk for cardioembolic events due to underlying atrial fibrillation. Although long-term clinical data remain limited, percutaneous LAAO appears to be a safe and effective means of reducing hemorrhagic stroke and non-procedural-related bleeding events compared to warfarin. Incomplete closure of the LAA resulting in a peri-device leak (PDL) is common after interventions targeting the LAA and has been variably associated with an increased risk of embolic stroke in patients following LAAO. However, the clinical significance of PDL remains unclear, in part, due to variability in the definitions used for PDL, modalities used for the detection of PDL, and the confounding impact of continuing therapeutic anticoagulation in patients found to have PDL on surveillance imaging. In the current review, we examine the association of PDL with ischemic stroke and systemic embolization and explore mechanistic considerations in the development of PDL as they pertain to the unmet need for improving the diagnostic assessment of PDL from an anatomic and physiologic perspective.

KEYWORDS:

• left atrial appendage occlusion (LAAO)
• peri-device leak (PDL)
• imaging

Introduction

Arterial thromboembolism resulting in ischemic stroke is the most common and serious complication of nonvalvular atrial fibrillation (NVAF). The risk of ischemic stroke in non-anticoagulated patients with NVAF may be as high as 9% per year in those with a prior history of a stroke or transient ischemic attack and ranges from 1.5% to 3% per year in elderly patients and those with diabetes or hypertension.¹ Oral anticoagulation reduces ischemic stroke risk by approximately 60% but also imparts a 0.2–0.5% annual risk of serious, life-threatening bleeding complications.^2–6 Approximately 30% of patients with NVAF do not receive therapeutic anticoagulation due to relative or absolute contraindications related to bleeding risk and, even when appropriately administered, anticoagulant therapy is associated with increased bleeding and a residual risk of ischemic stroke.^7,8

The left atrial appendage (LAA) is the most common site of thrombus formation and cardioembolism in patients with NVAF.⁹ Percutaneous left atrial appendage occlusion (LAAO) has emerged as a viable approach for patients with NVAF who cannot tolerate long-term anticoagulation by providing a mechanical seal of the appendage, thereby preventing embolization of LAA thrombi.¹⁰ The Watchman device (Boston Scientific, St. Paul, Minnesota) is the most commonly implanted LAAO device in the U.S. and has the most robust clinical data having been studied in two randomized controlled trials and accompanying continued access registries.^11–14 Data from the Watchman trials, registries, and meta-analysis suggest that the Watchman device reduces post-procedural bleeding (particularly hemorrhagic stroke) and mortality, however with an increased risk of ischemic stroke compared to warfarin that may be related in part to peri-procedural factors around the time of implantation.¹² Of note, a larger proportion of the ischemic strokes after LAAO were nondisabling compared with warfarin, such that the outcomes relating to hemorrhagic and disabling/fatal strokes are more favorable after LAAO.¹⁴

Incomplete closure of the LAA resulting in peri-device leak (PDL) is one such factor that is often recognized at the time of device implantation but may also be identified later on follow-up surveillance imaging.¹⁵ The clinical significance of PDL is not well understood and has been postulated to be a mediator of increased stroke risk following LAAO however definitive clinical data linking PDL to stroke risk has remained elusive.^15,16 Here we briefly review the incidence and clinical implications of PDL, advantages, and limitations of existing modalities used to identify PDL, and discuss the absence of a clear gold standard technique capable of addressing the unmet need of definitive identification and quantitation of PDL.

Discussion

Peri-device leak after LAAO

Incidence of PDL: impact of diagnostic modality

A wide range of devices are available or in development, including Watchman (Boston Scientific, St. Paul, Minnesota), Amulet (Abbott Vascular, St. Paul, Minnesota), WaveCrest (Biosense Webster, Irvine, California), Occlutech LAA occluder (Occlutech International AB, Helsingborg, Sweden), LAmbre closure system (LifeTech), Ultraseal (Cardia), and LARIAT (SentreHEART, Redwood City, California). Comprehensive discussions of the efficacy, technical aspects, and regulatory status of the devices used for LAAO are available in several recent reviews.^17,18 Many, but not all, studies of these devices have systematically defined and reported rates and mechanisms of PDL (Table 1).¹⁷ The incidence of PDL likely depends on the interaction between the LAAO device, anatomical characteristics of the LAA including variability in the morphology of the LAA ostium and body, and possibly tissue characteristics of the underlying atrial tissue (e.g., fibrotic remodeling) (Figure 1). The occurrence of any degree of PDL occurs in approximately 30–40% of patients following LAAO at 12 months post-implantation as detected by transesophageal echocardiogram (TEE), and any PDL as detected by cardiac computed tomography (CT) has been reported to be as high as 50–60%.^19–21 The definition of “significant” PDL remains elusive as a definitive link to adverse clinical outcomes has not been established. An arbitrary definition of significant PDL that was utilized in the Watchman trials and has generally been accepted in other studies is a ≥5 mm diameter gap between the device edge and the LAA tissue with the residual flow by TEE using a Nyquist limit set around 25cm/s. Using this definition and modality, significant PDL occurs in 10−20% of patients after endovascular or epicardial LAA closure.^16,17

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.

Existing modalities for the detection of PDL provide different information about the nature and degree of the leak and, in the case of TEE, may be operator-dependent in the sensitivity for PDL detection. Three-dimensional (3D) TEE may be more sensitive than two-dimensional (2D) TEE for the detection of PDL.²² A recent study of leak following LARIAT found that in patients who had experienced an ischemic stroke, 3D TEE identified patients with small leaks (<3 mm) not seen on 2D TEE.¹⁶ Both 2D and 3D TEE provide information regarding the mechanism of PDL (Figure 2) including peri-device flow and the associated structural gap between device and LAA, and TEE may also identify low-velocity flow within the LAA suggestive of incomplete endothelialization of the LAAO device particularly when no leak is detected between the LAA and device (i.e., no PDL per se).²³ Cardiac CT is more sensitive for the detection of PDL as has been observed by multiple investigators and may provide greater insight into the mechanisms of PDL as discussed below.^15,20,21,24 However, the detection of contrast in the LAA following LAAO is not proof of PDL per se because residual device permeability after device implantation may also account for contrast opacification of the LAA. Furthermore, 3D reconstructions from cardiac CT may improve LAAO device sizing which may translate to improved procedural success and reductions in PDL.^22,25 However, neither TEE nor CT provides quantitative information regarding the degree of PDL or residual device permeability which may be a critical factor in the prognostic significance of PDL on thrombotic risk.

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

PDL and stroke: impact of study heterogeneity

In addition to the variability of the definitions and modalities used for the identification of PDL, small sample sizes, incomplete follow-up, physician discretion on the management of PDL (i.e., continue anticoagulation or not), and small numbers of clinical events have hampered the ability of investigators to characterize the clinical significance of incomplete percutaneous closure of the LAA. In contrast to a study of surgical LAA closure showing an increased risk of stroke in those with incomplete LAA closure (detected using cardiac CT), most studies of percutaneous LAAO have not demonstrated an association between PDL and stroke risk.^15,24,26,27 A retrospective study of 98 patients who underwent LAAO with the pericardial LARIAT device observed that in 3 of 5 patients who experienced a recurrent embolic stroke and who had a TEE at the time of the event were found to have a leak of <5 mm.¹⁶ The investigators also noted that 2 of 3 leaks were not detected by 2-dimensional TEE but as noted above were only observed on 3D TEE, and further noted that PDL increased over time in 5%, 15%, and 20% of patients with significant PDL detected by TEE at the time of implantation, at 6 and 12 months, respectively. In a large and comprehensive study of PDL, Tzikas et al. examined 1,001 patients who underwent successful implantation of the AMPLATZER™ Cardiac Plug (ACP).²⁸ The investigators observed that 98.1% of patients had complete closure and the presence of TEE-detected significant PDL (>3 mm in this case) was observed in 1.9% of patients but was not associated with adverse events at follow-up in their study. In addition, device-related thrombus (DRT) was also not associated with adverse events in their study however patients identified with DRT were treated with anticoagulation which may have obscured any relationship of DRT with ischemic events in this study. In another study of 344 patients treated with ACP, the presence of severe PDL (>5 mm) detected by TEE was observed in 0.6% of patients and, along with DRT, was not associated with adverse events at follow-up.²⁹ In a sub-study of the Watchman PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial, investigators observed “major” PDL defined as >3 mm in 32.4% of patients but did not observe any association with PDL and an increased risk of thromboembolism.³⁰

In a recent study of patients treated with different LAAO endovascular devices, cardiac CT-detected PDL (defined as any contrast in the LAA) was common and decreased from 3 to 12 months (68.5% to 56.7%, P = 0.02). The only identified predictor of PDL was a device compression ratio of less than 10%. At a median follow-up of 236 days, 9.1% of patients experienced a major adverse cardiac event (stroke, DRT, or cardiovascular death).²⁴ Although not statistically significant, patients with MACE had a greater frequency of PDL compared to patients without MACE (12% vs 4.3%, P = 0.3). The three mechanisms observed to contribute to PDL included the absence of device sealing presumed to be due to incomplete endothelialization, presence of a gap between the device and LAA, and an off-axis position of the device. These mechanisms were also previously described in another study of cardiac CT in the identification of PDL following LAAO with Watchman and ACP devices.²⁰

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

PDL and putative mechanisms of thrombotic risk

Despite the uncertainties surrounding the association between PDL and thrombotic risk, it is generally accepted that complete sealing of the LAA is preferred due to the possibility that a residual leak following LAAO could permit embolization (“escape”) of LAA thrombus and/or prevent endothelialization of the device and thereby contribute to DRT which in contrast to PDL has more directly been linked to the risk of stroke.⁴⁶ However, it is unclear if small size leaks would permit the escape of an LAA thrombus of sufficient size to result in a clinically meaningful embolic event.

Different mechanisms of PDL including off-axis device implantation, device under-sizing, and incomplete closure due to appendage morphologic variations (Figure 2) may each be associated with unique flow disturbances and thus portend differential risks of impaired endothelialization. Turbulent flow around the device could activate platelets and clotting factors resulting in thrombus formation and left atrial flow may be modulated by the coexistence of mitral regurgitation which is commonly seen in patients with atrial fibrillation.⁴⁷ Furthermore, the risk of PDL may be distinct for different devices, underscoring the need for further investigation into the prognostic significance of PDL in larger studies with systematic ascertainment of PDL and outcomes. In patients with PDL, persistent flow around the device may delay or inhibit device endothelialization and thus render the device susceptible to device-related thrombus (DRT) formation – an effect that may be modulated by the underlying tissue substrate and degree of fibrosis (Figure 3). The notion that perturbed and residual flow detected by TEE may be a risk factor for DRT is supported by the observation that residual LAA flow following surgical LAA closure is associated with thrombus formation and embolic events.²⁷ Although PDL may be associated with an increased risk of DRT, this association has not been uniformly established which may reflect the variability in the diagnostic modality, timing, and definition used for identifying PDL.^46,48

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.

Novel strategies to prevent and detect PDL

As noted above, a causal relationship between PDL following percutaneous LAAO and adverse clinical events has not been clearly demonstrated, possibly because PDL may not be a mediator of stroke risk or because of the arbitrariness of PDL definitions used to-date and variability in study design elements, including LAAO device, sample size, confounding from anticoagulation in patients with PDL, and the timing and modality of the diagnostic imaging tool used to detect PDL. Existing data suggest that PDL is common despite the use of TEE to facilitate procedural planning and device selection. Cardiac CT is a promising modality for procedural planning capable of acquiring high-resolution delineation of cardiac and LAA anatomy, and an emerging consensus exists that pre-procedural insights afforded by cardiac CT in terms of LAA size and shape may be useful in guiding LAAO device type and size.⁴⁹ Although device selection guided by cardiac CT has been shown to reduce LAAO procedure time, existing data have to-date not demonstrated that pre-procedural cardiac CT guidance reduces PDL following LAAO.⁵⁰ Lastly, cardiac CT cannot be used intra-procedurally and is thus only suitable as a planning or post-procedure monitoring modality. Furthermore, due to initial device permeability, smaller-sized leaks may not be detected easily or discerned due to the spatial resolution limitations of cardiac CT and contrast in the LAA thus inappropriately attributed to device permeability alone.

Intracardiac echo allows for real-time and high-resolution detection of PDL, typically does not obscure fluoroscopic guidance, and allows for the procedure to be performed under local anesthesia but does not provide full 3D imaging necessary to ensure complete sealing of the LAA, and often does not provide information regarding LAA depth and is associated with a steep learning curve.⁵¹ Perhaps the most promising intra-procedural modality for PDL detection is 3D TEE,⁵² but this approach faces several drawbacks, including the semi-quantitative nature of flow assessment, learning curve, and operator- and patient-related factors affecting the acquisition of high-quality LAA images which can be limited by acoustic shadowing and reverberation artifacts. Furthermore, the frequent use of general anesthesia during LAAO requires additional clinical staff including an anesthesiologist and at times an imaging cardiologist. The need for additional staff requirements significantly impedes the efficiency of the procedural workflow, increases cost, increases the risk of gastrointestinal injury, and may limit the primary operating physician’s ability to collect anatomical and physiological information according to his or her discretion.⁵³

In light of the limitations of existing modalities for PDL detection, novel diagnostic tools capable of providing real-time, high-resolution 3D reconstructions of the LAA obtained by the operating physician and minimally affected by operator- and patient-factors are needed. New tools with the ability to generate 3D anatomical reconstructions may improve the measurement of the LAA, optimize device sizing, and possibly reduce PDL. Any new methods or tools would also benefit from the ability to assess the physiologic significance of PDL. Quantification of PDL and residual device permeability may provide critical information to guide the LAAO procedure and provide additional insights into the clinical significance of incomplete closure.

Conclusions

PDL is an increasingly recognized and likely underreported event following LAA closure. Additional research is needed to characterize the incidence of PDL and the relationship between PDL size, location, and hemodynamics on clinical outcomes. In order to support these efforts – and, most importantly, minimize PDL altogether – standardized and comprehensive imaging approaches are needed to ensure full occlusion of the LAA and/or better quantify leak physiology. There is a need for real-time, high-definition 3D functional imaging not achievable with available imaging devices, and the areas outlined in this review may help to guide improved device design and development of novel imaging tools. Such tools may also be useful in other procedures where residual leaks occur, such as percutaneous atrial septal defect repairs or management of paravalvular leak in TAVR/TMVR patients.

Acknowledgments

We would like to acknowledge the support of Mr. Cassio Lynm of Amino Creative, LLC in the design of our figure graphics.

Disclosure statement

Mazen Albaghdadi MD MSc – Consultant and grant support from CSI, Inc. Grant support from Boston Scientific, Consultant for K2 Medical, Inc. Andrew O. Kadlec, MD, PhD – Consultant to K2 Medical. Andrew Adler – Consultant to K2 Medical. Alexander Romanov, MD PhD, FEHRA, FHRS, FESC – Nothing to disclose. Usman R Siddiqui MD FHRS – Consultant to K2 Medical. Karl-Heinz Kuck, MD – Consultant to K2 Medical. Horst Sievert, MD – Study honoraria to institution, travel expenses, consulting: 4tech Cardio, Abbott, Ablative Solutions, Ancora Heart, Append Medical, Axon, Bavaria Medizin Technologie GmbH, Bioventrix, Boston Scientific, Carag, Cardiac Dimensions, Cardiac Success, Cardimed, Celonova, Comed B.V., Contego, CVRx, Dinova, Edwards, Endologix, Endomatic, Hemoteq, Hangzhou Nuomao Medtech, Holistick Medical, K2, Lifetech, Maquet Getinge Group, Medtronic, Mokita, Occlutech, Recor, Renal Guard, Terumo, Trisol, Vascular Dynamics, Vectorious Medtech, Venus, Venock, Vivasure Medical. Martin B. Leon, MD – Nothing to disclose. Torsten Vahl, MD – Abbott Laboratories: Grant/Research Support, Consulting Fees. Boston Scientific: Grant/Research Support, Consulting Fees. Edwards Lifesciences: Grant/Research Support, JenaValve Technology: Grant/Research Support, Consulting Fees, Medtronic: Grant/Research Support, Siemens Healthineers: Grant/Research Support, Consulting Fees.

Additional information

Funding

K2 Medical provided funding in support of this paper.