An International Consensus Practical Guide on Left Atrial Appendage Closure for the Non-implanting Physician: Executive Summary

Keywords

anticoagulation - atrial fibrillation - bleeding - left atrial appendage closure - left atrial appendage occlusion - stroke - prevention

Introduction

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults and is associated with increased mortality and morbidity from stroke, heart failure, dementia, and hospitalizations.[1] Due to longer life expectancy and better treatment of conditions associated with high AF risk, such as heart failure, the prevalence and incidence of AF have been continuously rising.[2]

Stroke prevention is central to AF management, and multiple oral anticoagulant (OAC) drugs are recommended. These are categorized in two broad classes[3]: (i) vitamin K antagonists (VKAs), which reduce the synthesis of functional coagulation factors; and (ii) direct oral anticoagulants (DOACs), which inhibit the action of certain coagulation factors. In the trials comparing VKAs with placebo, OAC reduced the risk of stroke by 64% and all-cause mortality by 26%.[4] However, in Europe and North America, VKAs have been almost entirely replaced by DOACs in the management of AF patients without significant valvular heart disease. In a meta-analysis of trials comparing VKA with DOACs, involving more than 70,000 patients with AF, treatment with DOACs was associated with a significant reduction in all strokes by 19%, which was mainly driven by a significant reduction in hemorrhagic stroke (Hazard Ratio [HR] 0.49, 95% confidence interval [CI] 0.38–0.64).[5] In the trials, the risk of major bleeding in the gastrointestinal (GI) tract is not much reduced in comparison to VKAs, and may actually be increased as compared with VKAs with some DOACs. There remains a residual risk of stroke in 0.8 per 100 patient-years.[6]

Nonetheless, anticoagulants generally increase the risk of bleeding; thus, doctors, patients, and caregivers are sometimes reluctant to use them, especially in more clinically complex patients.[7]

Although the balance between stroke prevention and major bleeding is improved with DOACs, the bleeding problem is not eliminated.[8] The major bleeding rate remains between 1 and 3 per 100 patient-years, but over a 3-year period it was 11% in an LAAC/OAC meta-analysis and in the DOAC versus VKA pre-approval trials it was 5.9% with DOACs over 32 months.[9] In AF patients with a GI bleed on anticoagulant there is a very high risk of a recurrent bleed (27 per 100 patient-years).[10] In some situations of severe bleeds (e.g., intracranial hemorrhage [ICH]) there remains treatment uncertainty.[11] Indeed, any bleeding is a “red flag” for adverse outcomes in such high-risk patients, yet OAC is often discontinued leading to worse outcomes.[12]

In patients who have suffered serious bleeding and/or are at high risk of bleeding or in whom VKA/DOAC treatment has failed to prevent AF-related stroke, there is increasing use of interventional techniques. Closure or occlusion of the left atrial (LA) appendage,[13] the intra-cardiac site at which most thrombi form in patients with AF, can be achieved by a reasonably safe catheter-based procedure known as LA appendage closure (LAAC) or LA appendage occlusion (LAAO). However, knowledge of LAAC is often limited outside the interventional cardiology and electrophysiology communities.

Patients with AF who might benefit from this therapeutic approach are often under the care of a general cardiologist, general or primary care physician, gerontologist, nephrologist, gastroenterologist, neurologist or stroke physician, etc. An understanding and appreciation of the value and applicability of LAAC are needed by all of those who care for patients with AF at risk of stroke but with a medical history, comorbidity, or lifestyle that prevents adequate long-term anticoagulation.

This is an executive summary of a practical guide for the non-implanting physician, written by an international multidisciplinary expert group consisting of members of the European Society of Cardiology Council on Stroke and physicians from other interested specialties. This practical guide is not meant to be a manual for those who implant the device. The full document has been published in Europace,[14] and the current executive summary provides the salient points from the full document.

Evidence Base for LAAC

The efficacy and safety of LAAC were first shown in the randomized PROTECT-AF (data collection from 2005) and PREVAIL (data collection from 2010) clinical trials in which AF patients without obvious contraindications to warfarin were randomized to either LAAC with Watchman (with warfarin and aspirin for at least 45 days after the procedure) or warfarin aiming at an international normalized ratio (INR) of 2 to 3 (n = 1114). After a 5-year follow-up, LAAC provided stroke prevention comparable to VKA with a significant reduction in major bleeding, hemorrhagic stroke, disabling/fatal stroke, cardiovascular death, and all-cause death.[15]

The PRAGUE-17 randomized trial (data collection from 2015) compared LAAC (Amulet or Watchman) with DOAC, mainly apixaban, (n = 402) showing noninferiority for LAAC in the prevention of stroke/transient ischemic attack (TIA), cardiovascular death, and clinically relevant bleeding and superiority in preventing nonprocedural bleeding over 4 years.[16]

[Fig. 1] shows clinical outcomes from the three RCTs comparing LAAC versus VKA/DOAC.[17] It can be seen that the point estimate for the ischemic stroke rate is 5.6% with LAAC compared with 3.6% with OAC. This adverse trend is not significant but it is a concern that detracts from a more extensive acceptance of LAAC therapy as a legitimate alternative to OAC prophylaxis. One propensity-matched analysis has suggested that strokes in patients with LAAC are less disabling than those seen in patients receiving DOAC therapy.[18]

Fig. 1 Clinical outcomes from the PROTECT, PREVAIL, and PRAGUE-17 randomized clinical trials. LAAC, left atrial appendage closure; OAC, oral anticoagulation; SE, systemic embolism. (Adapted with permission from Turagam et al.[17])

There are multiple observational studies and registries of AF patients undergoing LAAC with various devices (ACP, Amulet, Watchman, Watchman FLX), mostly showing a 60 to 80% reduction in the rate of ischemic stroke and major bleeding compared with predicted rates based on the CHA₂DS₂-VASc and HAS-BLED score values (e.g., ACP registry,[19] Amulet Observational Study,[20] EWOLUTION,[21] NCDR-LAAO registry,[22] [23] PINNACLE FLX[24]).

A recent meta-analysis of studies comparing LAAC with DOAC (n = 4411) showed the risk of stroke/TIA to be similar between LAAC and DOAC, whereas LAAC was superior in reducing cardiovascular mortality, and major and non-major bleeding.[25] In the randomized LAAOS-III study (n = 4770), surgical LAAC in addition to DOAC (continued in approximately 70% of all study patients) was associated with a 33% reduction in the risk of stroke/TIA after 3 years.[26] A recent network meta-analysis based on seven RCTs, with overall 73,199 patients, found that both LAAC and DOACs reduced the risk of all-cause death compared with VKAs, with LAAC ranked as the best treatment for reducing major bleeding and death, while DOACs emerged as the best treatment for preventing stroke or systemic embolism.[27]

Factor XI inhibitors are currently being investigated for thromboprophylaxis in AF patients and ongoing trials include OCEANIC-AF and OCEANIC-AFINA with asundexian,[28] AZALEA-TIMI 71[29] and LILAC-TIMI 76 with abelacimab,[30] and LIBREXIA-AF with milvexian and comparing factor XI inhibitors against DOACs or placebo.[31] The OCEANIC-AF trial was stopped early due to an excess of stroke and thromboembolism compared with apixaban, although major bleeding was less.[32] Pending other ongoing trial data showing these new drugs can prevent thromboembolism without a substantial bleeding risk, a comparison with LAAC will be needed. Of note, the AZALEA trial was also terminated prematurely but because there was substantially less bleeding with abelacimab than with rivaroxaban.

Currently, there are no RCT-based data on LAAC in patients who are intolerant of or contraindicated for OAC, who are a subgroup of AF patients treated with LAAC in clinical practice today and the subgroup that would likely have the greatest benefit from LAAC ([Table 1]). Patient recruitment into these trials has been slow, e.g., ASAP-TOO,[33] CLOSURE-AF,[34] STROKECLOSE,[35] CLEARANCE,[36] COMPARE-LAAO,[37] [38] and LAA-KIDNEY[39] among others. The ASAP-TOO trial was terminated prematurely due to slow enrolment but patient follow-up is still active.

Table 1 Ongoing randomized trials comparing LAAC versus best medical care in AF patients with contraindications for long-term anticoagulation

	CLOSURE-AF[34]	STROKE-CLOSE[35]	CLEARANCE [36]	LAA-KIDNEY[39]	COMPARE LAAO [37] [38]
Patient population	AF and high bleeding risk (HAS-BLED ≥3; prior major bleeding)	AF and ICH within 12 months	AF and ICH or intracerebral amyloid vasculopathy	AF and end-stage kidney disease	NVAF patients with CHA2DS2-VASc ≥2 and absolute contraindication to (D)OAC
Number of patients	1000	600	530	430	609
Randomization	LAAC versus best medical care	Amulet versus best medical care (2:1)	Watchman FLX versus best medical care	Amulet versus best medical care	Amulet or Watchman FLX versus nothing +/− APT (2:1)
Primary endpoint	Stroke, SE, major bleeding, or CV death at 2 years	Stroke, SE, major bleeding, or all-cause mortality at 2 years	Stroke, SE, major bleeding, or CV death at 3 years	Time to first stroke, SE, CV death, or major bleeding	• Any stroke. • Composite of stroke, TIA, and SE

Abbreviations: AF, atrial fibrillation; APT, antiplatelet therapy; CRF; CV, cardiovascular; CHA₂DS₂-VASc, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65–74 years, Sex category (female); (D)OAC, (direct) oral anticoagulant; ICH, intracerebral bleeding; LAAC, left atrial appendage closure; NVAF, Non-valvular atrial fibrillation; SE, systemic embolism; TIA, transient ischemic attack.

Based on the currently available evidence and clinical experience, LAAC is now being investigated in broad populations of AF patients in large-scale trials. In the OPTION trial,[40] [41] AF patients undergoing catheter ablation for AF were randomized to LAAC or DOAC after ablation. In the CHAMPION-AF trial[42] and CATALYST trial,[43] AF patients with no contraindications to DOACs and CHA₂DS₂-VASc of ≥2 for men and CHA₂DS₂-VASc of ≥3 for women are randomized to LAAC or DOAC ([Table 2]). In the OCCLUSION-AF trial[44] AF patients with a recent ischemic stroke are randomized to either LAAC or DOAC.[45]

Table 2 Ongoing large-scale randomized trials comparing LAAC versus DOAC

	OPTION[41]	CHAMPION-AF[42]	CATALYST[43]
Patient population	CHA2DS2-VASc ≥ 2 (men) CHA2DS2-VASc ≥ 3 (women)	CHA2DS2-VASc ≥ 2 (men) CHA2DS2-VASc ≥ 3 (women)	CHA2DS2-VASc ≥ 3 initially, now updated to CHA2DS2-VASc ≥ 2 (men) CHA2DS2-VASc ≥ 3 (women)
Number of patients	1600	3000	2650
Randomization	WM FLX vs. OAC	WM FLX vs. DOAC	Amulet vs. DOAC
Primary endpoint	Stroke, SE, or death at 3 years (non-inferiority) Major or clinically relevant bleeding at 3 years (superiority)	Stroke, SE, or CV death at 3 years (non-inferiority) Major or clinically relevant bleeding at 3 years (superiority)	Stroke, SE, or CV death at 2 years (non-inferiority) Major or clinically relevant bleeding at 2 years (superiority)
Enrolment status	Completed	Completed	Enrolling

Abbreviations: CV, cardiovascular; CHA₂DS₂-VASc, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65–74 years, Sex category (female); DOAC, direct oral anticoagulant; LAAC, left atrial appendage closure; SE, systemic embolism; WM FLX, Watchman FLX.

There are also several observational studies on special AF patient subpopulations undergoing LAAC (i.e., patients with prior ICH, prior ischemic stroke, renal failure, stroke despite anticoagulation) suggesting a net benefit of LAAC in the prevention of stroke and bleeding. Some of those studies are propensity score matched comparing LAAC in AF patients with a prior ICH to standard therapy[46] or LAAC to DOAC.[47]

Indications for LAAC

Stroke reduction in patients with AF requires more than thromboprophylaxis, hence the move toward a holistic or integrated care approach to AF management. Such evidence-based holistic management is recommended in many guidelines including the Atrial fibrillation Better Care (ABC) pathway.[48] [49] Other guidelines have used (untested) variants of the pathway, such as SOS and AF-CARE.[50] [51] A practicing clinician's perspective on recent AF guidelines has recently been published.[52] Adherence to the ABC pathway strategy is associated with a 31% reduction in stroke, as well as lower mortality and bleeding, which is supported by various retrospective and prospective cohort studies from different parts of the world,[53] as well as post-hoc analysis from adjudicated outcomes from clinical trials.[54] [55]

Transcatheter LAAC has been increasingly used as an antithrombotic approach in patients with AF, especially in the United States of America.[22] [56] Although contemporary European AF registry–based studies reported a <1% use of LAAC in clinical practice,[57] [58] a trend toward increasing use of LAAC in Europe has been recently observed, including the changing profile of AF patients undergoing the procedure (i.e., less frail and generally less comorbid patients).[59]

Guideline recommendations and consensus statements on the use of transcatheter LAAC for the prevention of stroke and systemic thromboembolism in patients with AF are summarized in [Tables 3] and [4] and [Fig. 2].

Table 3 Recommendations for the use of LAA closure in the international guideline documents

Guideline recommendations for transcatheter LAAC for stroke prevention in patients with AF at increased (moderate to high) risk of stroke
Society	Wording of recommendation	AF patient group(s) for which LAA closure is recommended	Class/Strength	Level of evidence
ACCP 2018[60]	We suggest	With absolute contraindications for OAC In ICH survivors at high risk of recurrent ICH (e.g., those with probable cerebral amyloid angiopathy)	Weak Ungraded	Low
CSANZ 2018[61]	May be considered	With contraindications to OAC	Strong	Low
ESC 2020[63]	May be considered	With contraindications for long-term OAC (e.g., ICH without a reversible cause)	IIb	B
CCS 2020[64]	We suggest	With absolute contraindications to OAC	Weak	Low
APHRS 2021[48]	May be considered	With clear contraindications for long-term OAC (e.g., ICH without a reversible cause)	NA	NA
SCAI/HRS[65]	May be considered	With contraindications for long-term anticoagulant treatment (e.g., those with a previous life-threatening bleed without reversible cause)	IIb	B
ACC/HRS/ ACCP/HRS[140]	Is reasonable	With a moderate to high risk of stroke (CHA2DS2-VASc score ≥2), and a contraindication to long-term oral anticoagulation due to a non-reversible cause	IIa	B-NR
	May be reasonable	With AF and a moderate to high risk of stroke and a high risk of major bleeding on oral anticoagulation, LAAO may be a reasonable alternative to oral anticoagulation based on patient's preference, with careful consideration of procedural risk and with the understanding that the evidence for oral anticoagulation is more extensive	IIb	B-R
ESC 2024[51]	May be considered	Percutaneous LAA occlusion may be considered in patients with AF and contraindications for long-term anticoagulant treatment to prevent ischemic stroke and thromboembolism	IIb	C

Abbreviations: ACC/AHA/HRS, American College of Cardiology/American Heart Association/Heart Rhythm Society; ACCP, American College of Chest Physicians; AF, atrial fibrillation; APHRS, Asia Pacific Heart Rhythm Society; B-NR, level of evidence B according to non-randomized data; B-R, level of evidence B according to randomized data; CCS, Canadian Cardiovascular Society; CSANZ, Cardiac Society of Australia and New Zealand; ESC, European Society of Cardiology; ICH, intracerebral hemorrhage; INR, international normalized ratio; LAA, left atrial appendage; LAAC, left atrial appendage closure; LAAO, left atrial appendage occlusion; OAC, oral anticoagulant.

Table 4 Recommendations for the use of LAA closure in consensus statements

Consensus statements for percutaneous LAAC for stroke prevention in patients with AF at increased (or moderate to high) risk of stroke
Group	Wording of the statement	Consensus statement
EHRA/EAPCI 2020[66]	May receive/be considered for	Patients eligible for long-term OAC Patients who are eligible for long-term OAC may receive an LAAC instead of long-term OAC only if they refuse OAC despite explanation.
	May receive/be considered for	Patients at high risk of bleeding with long-term OAC In patients with an elevated bleeding risk during long-term OAC, LAAC may be considered.
	May receive/be considered for	Patients noncompliant to OAC In patients with documented noncompliance, LAAC can be discussed as a therapeutic alternative after attempts to resolve the reasons for noncompliance.
	Should	AF patients with CHA2DS2-VASc score ≥2 (3 in females) who have absolute contraindications for long-term OAC may be considered for LAAC if a single antiaggregant can be given for a minimum period (2–4 weeks). In patients with an elevated bleeding risk during long-term OAC (e.g., post-ICH) an individual risk–benefit assessment needs to be performed between OAC and LAAC. Any AF patients with an increased risk for stroke and embolism and no contraindication for OAC should receive personal and detailed advice that according to current evidence long-term OAC treatment is the preferred prophylactic strategy.
	Should not	In patients who are opposed to chronic drug intake, LAAC is currently not offered as an equally effective treatment alternative.
The Munich consensus document 2017[67]	Potential indications	Patient not eligible for long-term OAC therapy (absolute or relative contraindications to OAC), including: • High risk of bleeding (ICH or gastrointestinal bleeding), • History of major or minor bleeding with or without OAC (symptomatic bleeding in critical organ, i.e., ocular, pericardial, spinal cord, or recurrent epistaxis needing medical attention), • Increased risk of bleeding due to a physical condition and/or comorbidities (i.e., recurrent falls with head trauma and significant musculoskeletal injury, need for additional dual antiplatelet therapy for coronary artery disease/stenting, diffuse intracranial amyloid angiopathy, bowel angiodysplasia, severe renal insufficiency/hemodialysis, blood cell dyscrasia), or • Inability to take OAC for reasons other than high risk of bleeding (intolerance, documented poor adherence, documented variability in the INR on VKA, high-risk occupation with increased injury potential, patient's choice). Thromboembolic event or documented presence of thrombus in the LAA despite adequate OAC therapy.

Abbreviations: AF, atrial fibrillation; CHA₂DS₂-VASc, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65–74 years, Sex category (female); EAPCI, European Association of Percutaneous Coronary Intervention; EHRA, European Heart Rhythm Association; ICH, intracranial hemorrhage; INR, international normalized ratio; VKA, vitamin K antagonist; LAA, left atrial appendage; LAAC, left atrial appendage closure; OAC, oral anticoagulant.

Fig. 2 Possible candidates for left atrial appendage closure (LAAC). AF, atrial fibrillation; ASD, atrial septal defect; CHA₂DS₂-VASc, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65–74 years, Sex category (female); LAA, left atrial appendage; OAC, oral anticoagulation.

Formal guideline documents have consistently recommended percutaneous LAAC for AF patients with contraindications to long-term OAC, using a low class of recommendation and low level of evidence, although the 2023 ACC/AHA/ACCP/HRS guidelines have recently upgraded this to a level IIa recommendation and have added a IIb recommendation for LAAO as an alternative to oral anticoagulation ([Table 3]).[48] [50] [60] [61] [62] [63] [64] [65] The 2024 ESC guidelines on AF management maintain a class IIb recommendation for LAAC.[51] Consensus documents explain the recommendations in more detail and extend the implications ([Table 4]),[66] [67] thus also including AF patients who:

• Suffer from major bleeding events during anticoagulant therapy

• Have a high risk of nonmodifiable anticoagulant bleeding

• Had a thromboembolic event or LAA thrombosis while on optimal OAC[68]

• Refuse or are noncompliant to long-term OAC

• Undergo catheter ablation with electrical isolation of the LAA

• Have a procedure involving transseptal puncture and need long-term thromboembolic protection

Methodological differences (rigid interpretation of the evidence base, particularly clinical trials for guidelines, and a less formal process also utilizing observational data for consensus documents) result in official professional society recommendations in guidelines and broader non-official advice in consensus documents.[69]

The most recent consensus documents addressing the use of transcatheter LAAC for the prevention of stroke and systemic embolism in patients with AF emphasize that LAAC should not be routinely offered to patients unwilling to take OAC therapy or who are simply noncompliant with their anticoagulation medication, before providing them with detailed counseling. Careful individual risk–benefit assessment and shared decision-making should be undertaken in each patient[70] ([Practical Box 1]).

Practical Box 1

When to consider referral for LAAC
AF and significant risk of stroke CHA2DS2VASc ≥2 (men) CHA2DS2VASc ≥3 (women) and:
• History of recurrent or irremediable major bleeding
• Recurrent non-major bleeding
• Predicted high risk of bleeding (HAS-BLED ≥3)
• Bleeding disorder (coagulopathy or angiodysplasia)
• Indication for long-term antiplatelet therapy
• Cerebral microbleeds/amyloid cerebral vasculopathy
• Advanced renal failure including dialysis
• Hepatic failure
• Stroke despite appropriate OAC
• Nonadherence to OAC despite attempts to educate the patient
• Electrically isolated LAA after ablation

Referral Considerations

Responsibility of the Referring Physician

All patients with AF who are being considered for any cardiac intervention must be assessed by taking a cardiac history relating to the presence of AF, major structural or functional heart disease, potentially reversible causes of bleeding, or alternative causes of stroke besides AF. Routine investigations including 12-lead surface electrocardiogram (ECG) and basic laboratory tests will have been performed before a patient is considered for LAAC therapy.

The need for thromboembolic protection in patients with AF must be firmly established utilizing guideline-recommended risk scores, such as the CHA₂DS₂-VASc score, or given that female–male differences in contemporary data are less apparent,[71] [72] using the non-sex CHA₂DS₂-VASc (CHA₂DS₂-VA) score.[73] [74] Their bleeding risk should also be assessed using a validated structured bleeding risk assessment that addresses modifiable and non-modifiable bleeding risks, such as the HAS-BLED score.

Responsibility of the Implanting Physician

The first responsibility of the interventional specialist is to confirm the indication for LAAC. There is a practical value of holding a multidisciplinary team (MDT) meeting to assess patients who have been or are to be referred for LAAC. As the indication is often for non-cardiac problems (neurological, GI, hematological, renal, etc.) such an MDT can assess patient data at an early stage and achieve consensus on an agreed management plan.[75]

Pre-procedural diagnostic workup usually includes transesophageal echocardiography (TOE) or cardiac computed tomography (CT) to delineate LAA anatomy and suitability for closure, and to rule out LAA thrombosis. LAA thrombosis can also be excluded using TOE or intracardiac echocardiography (ICE) at the beginning of the procedure.[76] In general, the presence of LAA thrombus is considered as a contraindication to LAAC. Nonetheless, several case series of LAAC have been reported in patients with a thrombus present only in the distal part of the LAA[77] (see below).

The selection of a specific LAA closure device and its size will depend on the operator's experience and the LAA anatomy as assessed by preprocedural CT or TOE and by peri-procedural TOE or ICE and selective LAA angiography. Cardiac CT offers a better understanding of LAA anatomy and the most accurate measurements.[78] [79]

If the patient is on a DOAC, the treatment may be stopped 1 day before the procedure (i.e., last dose of rivaroxaban or edoxaban in the morning, or apixaban and dabigatran in the evening before the procedure) without bridging ([Practical Box 2]).

Practical Box 2

Before LAAC at the implanting center
Clinical examination and biochemistry: rule out infection; assess renal function
Transthoracic Echocardiogram (TTE): LV function, valves, pericardium
Cardiac CT or TOE: LAA anatomy; device selection and size; rule out LAA thrombus
Stop OAC; loading dose of antiplatelets
Intravenous prophylactic antibiotics

Current Methods of Percutaneous LAA Closure

Procedural Steps

LAAC is a standardized procedure that requires specific training of the implanter and interventional team. It is most often undertaken under general anesthesia and is guided by TOE, but ICE or micro/mini TOE is increasingly used making it possible to perform the procedure with local analgesia and light sedation.

Femoral Venous Puncture

Femoral venous access is usually obtained under ultrasound guidance to reduce the risks of vascular complications.[80] [81] [82] [83] [84]

Transseptal Access

Transseptal puncture is a crucial step to safely access the left atrium and successfully deploy a LAAC device. This technique requires specific training and has a learning curve.

Deployment of the Occluder Inside the LAA

Procedural imaging is of crucial importance for a successful LAAC. The procedure is guided by TOE or ICE, depending on the operator's experience. Device deployment is additionally controlled by fluoroscopy and fusion of preprocedural CT images with fluoroscopy is occasionally used ([Fig. 3]). TOE/ICE is also crucial to confirm the optimal placement of the device and complete sealing of the LAA.

Fig. 3 Fusion of fluoroscopy image with a three-dimensional reconstructed computed tomography (CT) scan image to guide left atrial appendage (LAA) occluder positioning and deployment. A, tracheal landmark used for the fusion between the CT scan image (blue and red colors) and the fluoroscopy system; B, transesophageal echocardiography probe used to guide the LAA occluder positioning; C, quadripolar catheter placed inside the coronary sinus to guide the transseptal puncture (optional); D, transseptal puncture area; E, LAA in right anterior projection; F, catheter positioned in front of the LAA entrance before occluder release.

Infective Endocarditis Prophylaxis

Periprocedural antibiotic prophylaxis and standard surgical aseptic measures in the catheter laboratory environment are recommended during the LAA implant procedure (ESC guidelines). Elimination of potential sources of sepsis (including of dental origin) should be considered 2 or more weeks before implantation.[85]

LAAC Devices

A range of devices has been developed to provide safe and efficient LAAC ([Table 5]).[86] [87] [88] [89] [90] [91] Of these the Watchman FLX, Amulet, and LAmbre devices have been extensively studied ([Fig. 4], Panels A, B, and C). Another form of LA occlusion may be achieved using a noose inserted epicardially around the os of the LAAC—the LARIAT device ([Table 3] and [Fig. 5]).

Table 5 Different types of occluders currently in use and their characteristics

	Company	Structure	Features	Limitations
Watchman FLX ([Fig. 4A]) [86] [87] [88]	Boston Scientific, Marlborough, Massachusetts, USA	Endocardial Single component	High degree of conformability, sealing, and safety	Shallow LAAs with proximal bifurcation
AMPLATZER Amulet-ACP ([Fig. 4B])[89]	Abbott, St Paul, Minnesota, USA	Endocardial Dual component	Possible to seal complex LAA anatomies	More complex to maneuver
LAmbre ([Fig. 4C])[90]	Lifetech Scientific, Shenzhen, China	Endocardial Dual component	Possible to seal complex LAA anatomies	More complex to maneuver
LARIAT ([Fig. 5])[91]	SentreHeart, Redwood City, California, USA	Epicardial suture	Adjustable size No need for postprocedural OAC	Both epicardial and endocardial access Postprocedural pericardial pain Not suitable in case of prior cardiac surgery or thoracic radiation

Abbreviations: LAA, left arial appendage; OAC, oral anticoagulant.

Fig. 4 Panel A: Watchman FLX (Boston Scientific). The Watchman FLX is deployed at the proximal part of the left atrial appendage (LAA), at the level of the circumflex artery and the ridge. There are two rows of anchors distributed across the distal half of the device. Small arrow, circumflex artery; large arrow, Watchman FLX; **, distal part of the LAA.. Panel B: Amulet (Abbott). The Amulet is deployed at the proximal part of the LAA, at the level of the circumflex artery and the ridge. Amulet is a dual-seal technology consisting of a lobe to anchor in the neck of the LAA and a disc to close off the opening into the LAA. Small arrow, circumflex artery; large arrow, the lobe of the Amulet; **, distal part of the LAA. Panel C: LAmbre (Lifetech) offers a design very similar to the Amulet, with a distal anchoring umbrella and a proximal disc. LA, left atrium; LV, left ventricle.

Fig. 5 LARIAT Suture Delivery Device (SentreHeart). After proper alignment, the LARIAT suture is tightened from the epicardium, providing a ligature of the left atrial appendage (LAA) at its neck.

Management of Acute and Early Post-implantation Complications

LAAC has become a relatively low-risk procedure ([Table 6]).[92] [93] [94] [95] Some complications may occur over the longer term, such as late pericardial effusions or device-related thrombosis (DRT), and all physicians following up patients post-procedure must be aware of these.

Table 6 Incidence of periprocedural LAAC complications

Complication	SURPASS registry	Amulet IDE
Pericardial tamponade/effusion	0.32%	2.4%
Device embolization	0.01%	0.7%
Stroke	0.09%	0%
Death	0.07%	0%
Device-related thrombosis at 45 days	0.23%	2.2%
Peri-device leaks at 45 days	12.9% (<3 mm) 3.7% (3–5 mm) 0.4% (>5 mm)	27% (<3 mm) 9% (3–5 mm) 1% (>5 mm)

Abbreviation: LAAC, left atrial appendage closure.

Source: Data were derived from the SURPASS registry of 66.894 Watchman FLX implants performed in the US from August 2020 to March 2022 and from 915 Amulet implants in the randomized Amulet IDE trial 2016–2020.[93] [94] [95]

Pericardial Tamponade

Pericardial effusion or tamponade incidence has decreased from the initially reported rate of 4.3% in the PROTECT AF trial[96] to 0.3% in the SURPASS study that included 16,048 Watchman FLX implants.[93] Most tamponades/effusions occur during the procedure or within 24 hours. To minimize their occurrence, imaging guidance with TOE/ICE is essential for all procedural phases, from transseptal puncture to device placement and release.

LAA perforation can sometimes be managed by just finalizing the LAA device implantation. For significant active pericardial bleeding, autotransfusion is possible to minimize blood loss and the need for transfusion. Reversal of anticoagulation should be considered only in cases with severe hemodynamic deterioration. Surgical intervention is rarely needed ([Table 7]).

Table 7 Mechanisms of pericardial effusion and tamponade and their prevention and treatment

Most frequent mechanisms of pericardial effusion/tamponade

Transseptal puncture

Manipulation of a stiff guidewire

Recurrent repositioning of the device

Deep positioning of the device

How to prevent effusion/tamponade

CT scan/TOE preprocedure

TOE/ICE intra-procedure

Angio intra-procedure

Pericardial effusion/tamponade—what to do?

Percutaneous drainage in the catheter laboratory

Blood transfusion

Intensive care unit

Surgical drainage as backup

Abbreviations: CT, computed tomography; ICE, intracardiac echocardiography; TOE, transesophageal echocardiogram.

Note: The table lists the most frequent mechanisms of pericardial effusion and actions to prevent and manage them.

Although most pericardial effusions occur within 24 hours of LAAC, late pericardial effusions can rarely occur. If a pericardial effusion is suspected, the patient should be immediately referred to the implanting center or the nearest cardiology site for echocardiography and possible pericardiocentesis.

Device Embolization

Device embolization is a rare complication with the most recent LAAC devices (0.01% with WATCHMAN FLX in SURPASS). The risk of embolization is increased with device under-sizing, very proximal implantation, misalignment of the device to the axis of the LAA, and sinus rhythm ([Table 8]). Device embolization can to a large extent be prevented by adequate preprocedural and intra-procedural imaging. Smaller LAAC devices that embolize will most often travel through the left heart and aortic valve to the descending aorta, whereas larger devices will remain in the left atrium or left ventricle. Device embolization is rarely associated with hemodynamic deterioration. Percutaneous retrieval is usually successful with a snare catheter or retrieval forceps ([Fig. 6]). If the device becomes entangled in the mitral valve apparatus, percutaneous snaring can potentially damage the valve and acute surgery might be required.

Table 8 Mechanisms of device embolization and its treatment

Most frequent mechanism of device embolization

Device under-sizing

Too proximal implantation of the device

Inadequate coaxial placement of the device within LAA

Sinus rhythm

Device embolization—what to do?

Catheter-based retrieval of devices

Surgical removal of the device (rarely needed)

Abbreviation: LAA, left atrial appendage.

Fig. 6 Embolization of an ACP device (Abbott) to the left atrium (LA) due to inappropriate sizing (A). Effective device retrieval with a goose neck snare (B).

Device-related Thrombosis

The incidence of DRT varies from 2 to 4%, although recent data with newer devices have reported a lower incidence of 1 to 2% per year ([Fig. 7]).[97] [98] [99] [100] [101] [102] [103] [104] [105] [106] DRT is most frequently detected by routine imaging at scheduled follow-up visits after the procedure. It can be diagnosed with TOE or cardiac CT and it is associated with a 4 to 5 times higher risk of stroke/TIA.[107] Besides patient-related risk factors, the risk of DRT can be increased by device implantation that is too deep resulting in incomplete LAA sealing.[108] Hypercoagulability disorders, iatrogenic pericardial effusion, renal failure, and permanent AF are other risk factors for DRT.[107] However, as new devices coated with thromboresistant fluorinated polymers are introduced DRT should become rare and post-implant antithrombotic therapy may be simplified or eliminated.[109]

Fig. 7 Incidence per 100 patient-years of device-related thrombosis (DRT) in left atrial appendage closure (LAAC) registries with more than 100 patients.[97] [98] [99] [100] [101] [102] [103] [104] [105] [106]

Management of DRT usually implies escalation of antithrombotic therapy (low molecular weight heparin [LMWH] or DOACs), but this may be challenging or even harmful in patients who are at high bleeding risk. The common practice is to minimize time on anticoagulants until thrombus resolution is verified by imaging ([Figs. 8] and [9]).

Fig. 8 Device-related thrombosis (DRT) after left atrial appendage (LAA) occlusion in a patient implanted with an Amulet device. The 3-month follow-up computed tomography (CT) scan shows the Amulet device in a good position (yellow arrow) with a large thrombus on the device disk (red arrow).

Fig. 9 Flowchart showing an algorithm for treatment of device-related thrombosis (DRT). ASA, acetylsalicylic acid; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; OAC, oral anticoagulant; FU, follow-up; LMWH, low molecular weight heparin; CT, computed tomography; TOE, transesophageal echocardiogram; VKA, vitamin K antagonist.

Procedure-related Stroke

During early experience, periprocedural stroke occurred occasionally and mainly due to air embolism, but is nowadays rare. In the SURPASS registry, the rate of all-cause stroke was 0.09% in hospital and 0.38% at 45 days.[93] Procedural stroke/TIA may be related to the presence of thrombus/smoke in the LAA or LA, air embolization during the procedure, or development of thrombi on the delivery system or implanted device.

Peri-device Leak (PDL)

The anatomy of the LAA is highly variable and can be very complex, including the landing zone for the LAA device, which is most often non-circular. Consequently, there is a risk of PDL after implantation or in some cases, a smaller lobe of the appendage may not have been occluded by the device.[110] PDL can be diagnosed by TOE or even better with CT. With current procedural techniques and devices, small PDLs are rather frequent, whereas moderate leaks (3–5 mm) are less common and severe leaks (>5 mm) very rare. Medical therapy is usually needed and is chosen according to bleeding risk. For PDL >5 mm, interventional leak closure with plugs, occluders, coils, or radiofrequency (RF) ablation may be considered but medical therapy may also be sufficient ([Figs. 10] and [11])[111] ([Practical Box 3]).

Practical Box 3

LAAC: Benefits, procedure, and periprocedural risk
Stroke prevention similar to OAC
No need for long-term OAC; reduced risk of bleeding
Procedure performed with local analgesia/light sedation guided by ICE or micro/mini-TEE
Procedure performed with sedation/general anesthesia guided by TEE
Duration of procedure: 30–60 minutes
Procedural risks:
• Pericardial tamponade/effusion: 0.32–2.4%
• Device embolization: 0.01–0.7%
• Stroke: 0.09%
• Death: 0.07%

Fig. 10 Follow-up computed tomography (CT) scan (6 months) of a Watchman FLX device that is not positioned correctly (yellow arrow) showing a severe leak (white arrow). A three-dimensional segmented model demonstrates that the device is rotated by 90 degrees causing the leak at the inferior site of the device.

Fig. 11 Flowchart showing a therapeutic approach when a peri-device leak is detected during follow-up. DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulants; TOE, transesophageal echocardiogram.

Special Populations

There is a large range of medical circumstances in which LAAC therapy may offer an advantage over OAC ([Fig. 12]). Many of these conditions may be associated with severe bleeding complications, ineffectiveness of anticoagulants against thromboembolism, or patient adherence difficulties. Even minor bleeding may have severe effects, for example, patients suffering from cerebral amyloid angiopathy.

Fig. 12 Clinical populations where left atrial appendage closure (LAAC) may be considered for patients with atrial fibrillation (AF) at risk of stroke but refractory to or contraindicated for anticoagulation and when no otherwise satisfactory management is available. LAA, left atrial appendage.

Detailed discussion of these “Special Population” scenarios are in [Supplementary Material] (available in the online version). If the use of OAC could be substituted by LAAC, the bleeding risk is mitigated while stroke prevention is retained. Nonetheless, robust long-term data on this population group are lacking.

Anticoagulant/Antiplatelet Therapy Regimens after Left Atrial Appendage Closure

Antithrombotic therapy is required after LAAC to prevent DRT especially in the initial phase, before device endothelization ([Fig. 13]).[70] [112] [113]

Fig. 13 Three-dimensional echocardiogram demonstrating endothelium growing over the device which was implanted 7 weeks previously.

Published data on antithrombotic regimens were derived from studies performed on patients who were eligible for anticoagulation (who received VKA or DOAC), as well as from studies performed on patients with intolerance or relative contraindications to anticoagulation, mainly related to prior major bleeding complications (who received antiplatelet therapy).[112]

Clinical RCT data on patients without LAAC have shown that dual antiplatelet therapy with aspirin-clopidogrel had similar major bleeding and ICH rates to warfarin (ACTIVE-W).[114] When aspirin was compared with apixaban in AF patients who refused or were deemed ineligible for warfarin, there was clear superiority of apixaban for the reduction of stroke/SE but the rates of major bleeding and ICH were similar (AVERROES).[115] In the BAFTA trial of elderly (age ≥75 years) AF patients managed in primary care, aspirin monotherapy had similar rates of major bleeding or ICH as warfarin.[116] In elderly AF patients with high-risk features for bleeding, low-dose edoxaban 15 mg was superior for stroke risk reduction, with a nonsignificant difference in major bleeding or ICH to placebo, although major GI bleeding was increased with edoxaban (ELDERCARE-AF).[117]

In practice, after LAAC there is a need to tailor the antithrombosis regimen according to the patient. The best antithrombotic therapy after LAAC needs to provide a balance between the prevention of DRT and the occurrence of major bleeding. The rationale for choosing between the available options ([Table 9] and [Fig. 14]) should be based on physician's assessment of individual patient characteristics, such as bleeding risk and stroke risk, an overall clinical evaluation of the patient's condition, comorbidities, and preference, as well as an evaluation of the reasons for LAAC.[69] [70] [118] As reported in [Table 9], discontinuations of OAC or antiplatelet therapy after LAAC is subject to the absence of other clinical indications for that medication and an assessment, including proper imaging (TOE or CT), demonstrating that there are no significant PDLs (>5 mm), thrombus on the device, or recent history of clinical events. Currently accepted antithrombotic regimens are illustrated in [Fig. 14].

Table 9 List of main antithrombotic schemes used after LAAC

Antithrombotic regimen	Supporting studies	Main scheme
VKA*	PROTECT-AF, PREVAIL, Amulet IDE	1. Aspirin + VKA (INR 2.0–3.0) for at least 45 days post-implant 2. Aspirin + clopidogrel from 45 days until 3 months post-implant 3. Then aspirin alone until 12 months post-implant
DOAC*	PINNACLE FLX, EWOLUTION;	1. Aspirin + DOAC for at least 45 days post-implant 2. Aspirin + clopidogrel from 45 days until 3 months post-implant 3. Then aspirin alone until 12 months post-implant
Dual antiplatelet	ASAP, EWOLUTION, AMULET Registry, Amulet IDE	1. Aspirin + clopidogrel until 3 months (WATCHMAN FLX) or 6 months (Amulet) post-implant 2. Then aspirin alone until 12 months post-implant

Abbreviations: DOAC, direct oral anticoagulation; INR, international normalized ratio; LAAC, left atrial appendage closure; VKA, vitamin K antagonist.

Note: *OAC schemes are not recommended with the Amulet device unless residual flow around the device is >5 mm.

Fig. 14 Upper panel: Manufacturer-recommended antithrombotic regimens after left atrial appendage closure (LAAC) (adapted and updated[120] [121]). LAAC, left atrial appendage closure; OAC, oral anticoagulant. Lower panel: Emerging strategies for antithrombotic regimens after LAAC (limited evidence and some ongoing studies): initial anticoagulant without concomitant aspirin[122] [123] [124] followed by a dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) period; single antiplatelet[125] [126] [127] [128]; low-dose DOAC.[129] [130] [131] [132] [133] (D)OAC, (direct) oral anticoagulant. Hatching indicates variable adoption depending on benefit–risk.

[Table 9] lists of the main antithrombotic schemes used after LAAC.

In a pooled analysis of data from patients in the PROTECT-AF, PREVAIL, CAP, CAP2, ASAP, and EWOLUTION studies, patients receiving either OACs or antiplatelets post-LAAC implant were matched and compared with regard to the occurrence of nonprocedural bleeding and stroke/systemic thromboembolism over 6 months following implantation. Although DRT was more frequently observed with antiplatelet therapy, the occurrence of major bleeding and stroke/systemic thromboembolism was similar between regimens based on antiplatelets or OAC.[119] [Fig. 14] shows various manufacturer recommendations and less “official” strategies for thrombotic therapy post implant.[120] [121] [122] [123] [124] [125] [126] [127] [128] [129] [130] [131] [132] [133]

Observational data from the years 2016 to 2018 in the United States highlighted how the antithrombotic regimen approved by the FDA for use of the Watchman device was rarely applied.[122] In particular, discharge after implantation on VKA or DOAC without concomitant aspirin was common and associated with lower risk of adverse outcomes. Updated data were presented at the HRS conference in 2023, confirming this finding.[123] In a recent meta-analysis comparing initial antithrombotic therapy following LAAO, monotherapy with DOAC had the highest likelihood of lower thromboembolic events and major bleeding.[124]

A simplified regimen with a short period (2–4 weeks) of a single antiplatelet (ASA or clopidogrel) has also been applied to very select patients with an extremely high bleeding risk on the basis of expert consensus,[70] and reported in observational studies.[125] [126] [127] Additional data on this approach may become available from the CLOSURE-AF[34] and the ARMYDA-Amulet[128] ongoing studies.

Limited but promising observational data are available on post-LAAC treatment with low-dose DOACs, showing reduction of DRT, thromboembolism, and major bleeding events compared with a standard, antiplatelet-based antithrombotic therapy.[129] [130] However, further controlled data are required to assess the value of this strategy. The small, randomized ADALA trial[131] aimed to compare long-term low-dose DOAC therapy (apixaban 2.5 mg twice daily) to a standard dual antiplatelet therapy scheme. The study was terminated after a planned interim analysis showed a significant reduction of bleedings and DRT at 3 months post-implant in the low-dose DOAC arm.[132] The larger ongoing randomized ANDES trial[133] may confirm these preliminary findings.

Post-Discharge LAAC Patient Follow-up

In clinical studies, assessment of the patient's clinical status as well as of the antithrombotic medication was performed 6 months after the implant. In clinical routine, this is less common.

After 1 year of LAAC, a large majority of patients reduce the antithrombotic regimen to a single agent or stop this therapy. In controlled clinical studies TOE imaging was mandatory at the 12-month follow-up visit, although this is rarely done in clinical practice. It was noted that, depending on the device type and the medication used, not uncommonly DRT may occur late after implantation.[134] This may be associated with an increased risk for stroke during long-term follow-up.[135]

Similarly, the presence of PDL at the 12-month imaging contributes to an increased rate of stroke.[136] [137] Both scenarios, DRT as well as PDL, have an impact on the future medical management of the patient. Therefore, it may be advisable to incorporate routine imaging at the 12-month follow-up visit, which is not a common practice in many centers.

In clinical studies with long-term follow-up, patient management beyond 1 year was usually limited to routine clinical assessment. Depending on comorbidities, it seems appropriate to tailor the individual follow-up schedule to the individual risk profile depending on co-existing medical conditions (e.g., every 6–12 months). Specific device-related imaging is not recommended.

In case of adverse clinical events such as stroke, unscheduled visits including imaging for DRT or PDL should be considered ([Practical Box 4]).

Practical Box 4

After LAAC: Postprocedural risk, medication, and follow-up
Same-day procedure or short hospitalization stay
TTE before discharge: Device position and screening for pericardial effusion
Cardiac CT or TEE: 45 days to 3 months; screening for DRT and PDL
Device-related thrombosis (DRT): 0.23–2.2%
Peri-device leak (PDL): <3 mm: 12.9–27%; 3–5 mm: 3.7–9%; >5 mm: 0.4–1%
Postprocedural medication to reduce risk of DRT: DAPT or OAC 1–3 months, SAPT 6–12 months, reduced-dose DOAC 3–12 months (depending on risk for DRT and bleeding)
Endocarditis prophylaxis 6 months

Other Cardiac Procedures after Left Atrial Appendage Closure

Direct Current Cardioversion

Direct current cardioversion (DCCV) is frequently used in AF patients as part of a rhythm control strategy. According to current guidelines, patients should be treated by anticoagulation at least 3 weeks before DCCV (AF duration >48 hours) and 4 weeks after to prevent thromboembolic complications. However, patients after LAAC are often at high bleeding risk and therefore unsuitable for anticoagulation before and after DCCV. In two prospectively enrolled patient cohorts involving a total of 242 LAAC patients, DCCV was used effectively without thromboembolic events despite the majority of patients being not on anticoagulant before and after DCCV.[138] [139] In those studies, the majority of patients underwent TOE before DCCV to rule out DRT, large PDLs, device malposition, and other cardiac thrombi.

Currently, the recommendations below can be used as a guide for DCCV in this patient group. There are no specific precautions for pharmacological cardioversion in LAAC patients.

• DCCV should be avoided the first 3 weeks after LAAC unless there is an acute indication, e.g., acute cardiac decompensation considered to be related to AF.

• TOE should always be performed before to rule out DRT, large PDL, device malposition, other cardiac thrombi. CT can be used as an alternative to TOE.

• DCCV can be performed without anticoagulation before and after.

• Anticoagulation can be considered before and after DCCV in patients with a predicted very high risk of thromboembolic events (severe left atrial dilatation, pronounced spontaneous contrast or sludge in the left atrium, left ventricular ejection fraction (LVEF) <25%, high CHA₂DS₂-VASc score etc.) depending on an individual assessment of bleeding risk. Recent ACC/AHA/ACCP/HRS guidelines recommend (CoR: IIb, LOE: N-BR) pre-cardioversion imaging for LAAO patients who are not anticoagulated, and anticoagulation peri-cardioversion if there is a DRT or PDL.[140]

Atrial Fibrillation Catheter Ablation

AF catheter ablation and all other types of transcatheter cardiac ablation using various energy delivery sources (RF, cryo, or pulsed-field) can be performed in patients after LAAC. TOE should be performed before AF ablation to rule out DRT, and elective ablation should not be performed before the first follow-up imaging after LAAC, which is typically done after 45 days or later. Anticoagulation post-ablation is recommended but adjusted according to the predicted bleeding risk for the individual patient.

Transcatheter Mitral Interventions, Transcatheter Aortic Valve Implantation and Percutaneous Coronary Intervention

Transcatheter mitral interventions, transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI), can all be performed in LAAC patients. Elective mitral intervention or TAVI should be planned not earlier than 45 days after LAAC or later, if possible. TOE should be performed before mitral intervention to rule out DRT or malposition of the device. For PCI, there are no specific LAAC-related precautions.

Conclusion

The advice provided is aligned with current guidelines and guidance documents provided by professional societies. A discussion aid for patients and non-implanting healthcare professionals is provided in [Supplementary Material S1] (available in the online version).

For patients with high AF-related stroke risk who cannot be treated with anticoagulants to prevent stroke and other systemic emboli, LAAC is the only option and is often considered in such circumstances. These patients include those with anticoagulant-related major or life-threatening bleeding, a substantial threat of such bleeding in the presence of anticoagulants, failure of anticoagulants to prevent an embolic ischemic stroke, or inability to comply sufficiently with anticoagulation treatment regimens, etc.

LAAC has been shown to be almost as effective and safer than VKA therapy but data comparing DOACs and LAAC are still insufficient to justify considering LAAC as a valid alternative to DOAC for treatment unless anticoagulation is contraindicated. For the time being LAAC is a second-line therapy. However, many patients may qualify for LAAC treatment, and this Practical Guide is to aid the referral of patients for consideration for LAAC therapy as necessary.

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