Cigna Nonpharmacological Treatments for Atrial Fibrillation - (0469) Form

The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Each coverage request should be reviewed on its own merits. Medical directors are expected to exercise clinical judgment where appropriate and have discretion in making individual coverage determinations. Where coverage for care or services does not depend on specific circumstances, reimbursement will only be provided if a requested service(s) is submitted in accordance with the relevant criteria outlined in the applicable Coverage Policy, including covered diagnosis and/or procedure code(s). Medical Coverage Policy: 0469 Reimbursement is not allowed for services when billed for conditions or diagnoses that are not covered under this Coverage Policy (see “Coding Information” below). When billing, providers must use the most appropriate codes as of the effective date of the submission. Claims submitted for services that are not accompanied by covered code(s) under the applicable Coverage Policy will be denied as not covered. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. This Coverage Policy addresses nonpharmacological treatments for atrial fibrillation including transcatheter ablation of the pulmonary veins (pulmonary vein isolation), surgical and percutaneous transcatheter closure of the left atrial appendage and surgical and minimally invasive maze procedures. Coverage Policy Transcatheter ablation of the pulmonary veins (pulmonary vein isolation) (Current Procedural Terminology [CPT®] codes 93656, 93657) is considered medically necessary for ANY of the following indications: • Recurrent symptomatic paroxysmal atrial fibrillation after a therapeutic trial of Class I or Class III antiarrhythmic drug therapy (e.g., amiodarone, dronedarone, flecainide, propafenone, sotalol). Initial rhythm control of recurrent symptomatic paroxysmal atrial fibrillation Symptomatic persistent atrial fibrillation AND refractory or intolerant to at least one Class I or Class III antiarrhythmic medication (e.g., amiodarone, dronedarone, flecainide, propafenone, sotalol). Symptomatic atrial fibrillation (e.g., palpitations, chest pain, dyspnea) associated with heart failure and reduced ejection fraction (HFrEF) of ≤ 40%. Transcatheter ablation of the pulmonary veins for ANY other indication is considered not medically necessary. Vein of Marshall alcohol ablation (VOM ethanol infusion) for the treatment of paroxysmal/persistent atrial fibrillation is considered not medically necessary. Percutaneous transcatheter closure of the left atrial appendage (CPT code 33340) for non-valvular atrial fibrillation using a U.S. Food and Drug Administration (FDA) approved device is considered medically necessary for the prevention of stroke when ALL of the following criteria are met: Individual has an increased risk of stroke and systemic embolism based on CHADS2* ≥ 2 or CHA2DS2-VASc** score ≥ 2 and systemic anticoagulation therapy is recommended. Attestation that for this individual the long-term risk of systemic anticoagulation outweighs the risk of the device implantation. CHADS2 score: Congestive heart failure, hypertension, age greater than 75, diabetes, stroke/transient ischemia attack/thromboembolism. Medical Coverage Policy: 0469 ** CHA2DS2-VASc score: Congestive heart failure, hypertension, age greater than or equal to 65, diabetes, stroke/transient ischemia attack/thromboembolism, vascular disease, sex category. Percutaneous transcatheter closure of the left atrial appendage for ANY other indication is considered not medically necessary. Surgical closure of the left atrial appendage (e.g., clip; CPT code 33268) in conjunction with other cardiac surgical procedures using a U.S. Food and Drug Administration (FDA) approved device is considered medically necessary for the prevention of stroke. Closure of the left atrial appendage NOT performed in conjunction with an open cardiac surgical procedure (CPT codes 33267, 33269) is considered not medically necessary. The closure of a peridevice leak (PDL) after a left atrial appendage occlusion is considered experimental, investigational or unproven. Cigna covers the surgical Maze or modified Maze procedure (CPT codes 33256, 33257, 33259), performed during cardiopulmonary bypass with or without concomitant cardiac surgery, as medically necessary for medically refractory, intermittent (i.e., paroxysmal or persistent) or continuous (i.e., permanent), symptomatic atrial fibrillation when rhythm control is considered essential. Cigna does not cover a minimally invasive off-pump Maze procedure including a hybrid or convergent ablation procedure (CPT codes 33254, 33255, 33258, 33265, 33266) for any indication including the treatment of atrial fibrillation because each is considered experimental, investigational or unproven. General Background Atrial fibrillation (AF) is a heart condition that causes an irregular and often abnormally fast heart rate (tachycardia). A normal heart rate should be regular and between 60 and 100 beats a minute when resting. In AF, the heart rate is irregular and can sometimes be very fast possibly higher than 100 beats a minute. This can cause symptoms such as dizziness, shortness of breath, and tiredness that affect quality of life. AF may increase the risk of suffering a stroke and/or peripheral thromboembolism owing to the formation of atrial thrombi, usually in the left atrial appendage (LAA). The mechanisms causing and sustaining AF are multifactorial, and AF can be complex and difficult to manage. AF symptoms range from non-existent to severe. The appearance of AF is often associated with exacerbation of underlying heart disease, either because AF is a cause or consequence of deterioration, or because it contributes directly to deterioration. Other atrial arrhythmias are often encountered in patients with AF. Atrial tachycardias are characterized by an atrial rate of ≥ 100 bpm with discrete P waves and atrial activation sequences. Many potentially reversible causes of AF have been reported, including binge drinking, cardiothoracic and noncardiac surgery, pericarditis, myocardial infarction (MI), myocarditis, hyperthyroidism, electrocution, pneumonia, and pulmonary embolism. AF is the most common arrhythmia treated in clinical practice and the most common arrhythmia for which patients are hospitalized. Approximately 33% of arrhythmia-related hospitalizations are for AF (Morady, et al, 2019; Nyong, et al., 2016; January, et al., 2014). Ugowe et al. (2018) conducted a systematic review that aimed to assess the racial and ethnic differences in the epidemiology, management, and outcomes of patients with AF. The authors reported that underrepresented racial and ethnic groups have a higher prevalence of established risk factors associated with the development of AF but an overall lower incidence and prevalence Medical Coverage Policy: 0469 of AF as compared with non-Hispanic whites. There are racial and ethnic differences in detection, awareness and AF-associated symptoms. Nonwhite populations also have decreased use of rhythm control modalities and anticoagulation for stroke prevention. Additionally, underrepresented racial and ethnic groups had increased morbidity and mortality relative to white groups. The study concluded that racial and ethnic differences in AF warrant further analysis to understand the factors contributing to the differences in prevalence and management to ensure the delivery of high-quality care that prevents stroke, reduces deaths, and decreases expenses associated with caring for underrepresented population. In many people, AF is recurrent and progresses from paroxysmal, to persistent with the need for cardioversion into normal heart rhythm, or it can progress into permanent forms. AF may be described in terms of the duration of episodes as follows (Passman, et al., 2023; Spragg and Kumar, 2022; Morady, et al., 2019; Nyong, et al., 2016; January, et al., 2014): Paroxysmal (i.e., self-terminating or intermittent) AF: Recurrent AF (≥ 2 episodes) that terminates spontaneously or with intervention within 7 days of onset, usually less than 24 hours. Episodes may recur with variable frequency. Persistent AF: Continuous AF that fails to self-terminate within 7 days. • Longstanding persistent AF: Continuous AF > 12 months duration. • Permanent AF: Used when there is a joint decision by the patient and the clinician to cease further attempts to restore and/or maintain sinus rhythm. Nonvalvular AF: AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. Lone AF: occurs in patients younger than 60 years who do not have hypertension or any evidence of structural heart disease. Treatment for AF focuses on the management of underlying causes, reducing the risk of stroke with antithrombotic agents (i.e., anticoagulant [e.g., warfarin] and antiplatelet drugs [e.g., aspirin), pharmacologically controlling the heart rate and or rhythm, and resetting the heart rhythm to sinus rhythm through the use of direct current cardioversion. If AF episodes continue despite these approaches, implantable pacemakers, or thermal energy ablation or surgical techniques, have been proposed. These treatment objectives are not mutually exclusive. Treatment strategies can be broadly subdivided into rate control (the ventricular rate is controlled and the atria are allowed to fibrillate) or rhythm control (there is an attempt to reestablish and maintain normal sinus rhythm). Several randomized trials have compared a rate-control strategy with a rhythm control strategy. In the largest such study (Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) AFFIRM Investigators, 2002), the prevalence of sinus rhythm was 35% in the rate control arm and 63% in the rhythm control arm at five years, but there was no significant difference in total mortality, stroke rate, or quality of life. Patients in the rate control arm required hospitalization at a significantly lower rate (73%) compared to patients in the rhythm-control arm (80%), and the incidence of adverse drug effects was also significantly lower in the rate-control arm than in the rhythm control arm. This study demonstrated that a rate control strategy is preferable in patients aged 65 or older who are asymptomatic or minimally symptomatic. This trial did not address AF in younger, symptomatic patients without significant underlying heart disease, however. Restoration of sinus rhythm still must be considered a useful therapeutic approach in these patients. The decision of which strategy to pursue is individualized, and is based on the nature, frequency and severity of symptoms, length of duration of AF, comorbidities, response to prior cardioversions, age, side effects and efficacy of antiarrhythmic drugs, and patient preference. Left atrial size is also a consideration. Left atrial enlargement is associated with AF and is a strong predictor of recurrence. AF can be more easily induced and maintained in an enlarged atrium, and conversion to sinus rhythm is less likely to be maintained in the presence of left atrial enlargement (January et al., 2014). Medical Coverage Policy: 0469 A major goal of therapy in patients with AF is to prevent thromboembolic complications such as stroke. Because of the risk of hemorrhage from anticoagulants, their use is limited to patients whose risk of thromboembolic complications is greater than the risk of hemorrhage. It is useful to risk stratify patients with AF to identify appropriate candidates for anticoagulation. The strongest predictors of ischemic stroke and systemic thromboembolism are a history of stroke or transient ischemic episode and mitral stenosis. A simple clinical scheme to risk stratify patients on the basis of the major risk factors is the CHADS2 (cardiac failure, hypertension, age, diabetes, stroke) score. Each of the first four risk factors counts as 1 point, and a prior stroke or transient ischemic event is 2 points. There is a direct relationship between the CHADS2 score and the annual risk of stroke in the absence of aspirin or warfarin therapy. The CHADS2 score has been superseded by the CHA2DS2-VASc score because it more accurately discriminates low-risk from intermediate-risk patients. In this risk- scoring system, cardiac failure, hypertension, diabetes, vascular disease, age 65-74 years, and female gender are 1 point each, and age 75 or older and prior stroke or transient ischemic event are 2 points. (Morady, et al., 2019). A consideration in patients treated with an oral anticoagulant is the risk of bleeding. Several risk- scoring systems have been developed to assess a patient’s susceptibility to hemorrhagic complications. The scoring system with a balance of simplicity and accuracy is the HAS-BLED score. The components of this score are hypertension, abnormal renal or liver function, stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly (> 75 years), and concomitant drug (antiplatelet agent or nonsteroidal anti-inflammatory drug) or alcohol use. Each of these components is 1 point. As the score increases from 0 to the maximum of nine, there is a stepwise increase in the risk of bleeding in patients treated with warfarin (Morady, et al., 2019). Catheter Ablation of Atrial Fibrillation (AF) Catheter ablation targeting the pulmonary veins has been considered an intermediate step prior to surgical intervention. Catheter ablation is used to destroy myocardial tissue by delivering energy over electrodes on a catheter placed next to an area of the endocardium determined to be integral to the onset and/or maintenance of the arrhythmia. A high percentage of patients with paroxysmal AF have excitatory foci in the superior aspect of the left atrium, in close proximity to the pulmonary veins. Specifically, the small area of cardiac muscle extending across the ostium of each pulmonary vein is notable for the frequent presence of excitatory foci. Transcatheter ablation of arrhythmogenic foci in the pulmonary veins is also referred to as pulmonary vein isolation (PVI), because the ablation is intended to interrupt conduction of the abnormal excitatory foci from the pulmonary veins to other areas of the atria. Several catheters with specialized tips are used to perform ablation. Many ablations performed use radiofrequency energy, cryothermy (cryoballoon ablation) or infrared laser. Access to the left atrium is typically obtained using a special trans-septal-sheath-dilator combination inserted into the femoral vein and advanced over a guidewire into the right atrium. Using this system, the intra-atrial septum is punctured (trans- septal puncture), allowing access by ablation catheters to the pulmonary veins. PVI has been proven effective in a subset of patients as an intermediate step prior to surgical intervention. Cardiac ablation is typically performed by an interventional cardiologist (Morady, et al., 2019). Yao et al. (2020) conducted a study that evaluated sex-specific differences in AF presentation, symptom severity and health-related quality of life, symptomatic and asymptomatic arrhythmia recurrence, AF burden, and health care utilization. The results reported that freedom from any atrial tachyarrhythmia and symptomatic atrial tachyarrhythmia were similar between male and female patients. Post-ablation, the median AF burden was 0.00% in male and female with no difference observed between the sexes. Periprocedural complications occurred twice as frequently Medical Coverage Policy: 0469 in female patients. In comparison to male patients, female patients also reported a significantly worse symptom score and quality of life at baseline and all follow-up intervals, but they derived similar magnitude of improvement post-ablation. There was no difference between male and female patients with respect to emergency department visits, hospitalization, cardioversion, or repeat ablation. The authors concluded that when compared with male patients, female patients have significantly worse symptom scores and quality of life at baseline. Despite this, they have similar benefit in freedom from recurrent arrhythmia and similar improvements in quality of life following AF ablation. Radiofrequency Ablation: A wide range of success rates for radiofrequency catheter ablation of atrial fibrillation (AF) has been reported in the literature (Wilber, et al., 2010; Calkins, et al., 2009; Oral, et al., 2006; Stabile, et al., 2006; Pappone, et al., 2006). A meta-analysis of 63 studies in which radiofrequency catheter ablation of paroxysmal or persistent AF was performed reported an overall single-procedure success rate of 57% at a mean follow-up of 14 months and a multiple-procedure success rate of 71% (Calkins, et al., 2009). Cryoballoon Ablation: Evidence in the peer-reviewed literature suggests that transcatheter cryoablation/CB ablation of the pulmonary veins is technically feasible and an effective alternative for the treatment of a subset of patients with paroxysmal or persistent AF. The evidence suggests that cryoablation reduces volume of contrast used, decreases the fluoroscopy and total procedure time, without compromising the success of PVI (Luik, et al., 2015; Aryana, et al., 2015; Jourda, et al., 2015; Skelly, et al., 2015; Straube, et al., 2014; DeVille, et al., 2014; Mugnai, et al., 2014; Andrade, et al., 2014; Xu, et al., 2014; Packer, et al., 2013; Malmborg, et al., 2013; Vogt, et al., 2013; Andrade, et al., 2011; Kojodjojo, et al., 2010; Kühne, et al., 2010; Tang, et al., 2010; Linhart, et al., 2009; Noheria, et al., 2008). Laser Balloon Ablation: The literature search identified nine clinical studies (n=60–353) that compared the efficacy and safety of laser balloon ablation (LBA) with cryoballoon ablation (CBA) or radiofrequency ablation (RFA) for the treatment of paroxysmal or persistent AF. Study designs included randomized controlled trials (Schmidt, et al., 2017; Dukkipati, et al., 2015; Schmidt, et al., 2013), nonrandomized controlled trials (Bordignon, et al., 2013), prospective cohort studies (Wissner, et al., 2014; Metzner, et al., 2011), a trial with historical controls (Bordignon, et al., 2016), and a retrospective cohort study (Tsyganov, et al., 2015). Follow-up ranged from immediately post-ablation to 12 months. The HeartLight Endoscopic Ablation System is the only FDA-approved LBA system for AF and has been approved for the treatment of drug-refractory recurrent symptomatic PAF. Ongoing studies assessing laser balloon ablation for AF can be found at ClinicalTrials.gov. Several additional types of ablation catheters have been developed including, a high-intensity focused ultrasound balloon catheter, microwave catheter, and a high-density mesh ablator catheter. These devices are being evaluated in clinical trials but have not yet received FDA approval. Additional well-designed trials with long-term follow-up are needed before a definitive assessment can be made of the safety and efficacy of these methods compared to the established ablation methods (Morady, et al., 2019; Buch, et al., 2018; Koch, et al., 2012). U.S. Food and Drug Administration (FDA): Numerous radiofrequency ablation catheters have received FDA approval through the premarket application (PMA) process for treatment of arrhythmias. Some examples of FDA approved devices are described below. According to the FDA, the product code dedicated to ablation catheters for the treatment of atrial fibrillation is OAE. The Arctic Front® CryoCatheter System (Medtronic CryoCath, Quebec Canada) received FDA approval through the PMA process on December 17, 2010. According to the approval letter, the device is indicated for the treatment of drug refractory recurrent symptomatic paroxysmal atrial Medical Coverage Policy: 0469 fibrillation. The system is comprised of the Arctic Front CryoAblation Catheters (models 2AT232 and 2AF282), Freezor® MAX CryoAblation Catheter, CryoConsole Gen V Model, Manual Retraction Kit and Accessories. The Freezor MAX catheter is used as an adjunctive device in the endocardial treatment of paroxysmal atrial fibrillation, in conjunction with Arctic Front CryoCatheter for the following uses: gap cryoablation to complete electrical isolation of the pulmonary veins • • cryoablation of focal trigger sites creation of ablation line between the inferior vena cava and the tricuspid valve In a PMA supplement approved on June 18, 2021 (P100010/S110), the FDA expanded the indication for the Arctic Front Advance and Arctic Front Advance Pro Cryoablation Catheter to include the treatment of recurrent symptomatic paroxysmal atrial fibrillation as an alternative to antiarrhythmic drug therapy as an initial rhythm control strategy. The HeartLight® Endoscopic Ablation System (CardioFocus, Inc., Marlborough, MA) received FDA approval through the PMA process on April 1, 2016 (P150026). According to the approval letter, the device is indicated for the treatment of drug refractory recurrent symptomatic paroxysmal atrial fibrillation. The HeartLight System consists of the HeartLight Catheter, Endoscope and Balloon Fill Media, and a console. The HeartLight Catheter is a sterile, single-use, disposable device that delivers infrared laser energy to create a rise in tissue temperature resulting in thermal ablation of the target tissue. The FDA Summary of Safety and Effectiveness Data (SSED) states that the CardioFocus HeartLight Endoscopic Ablation System has been marketed in Germany, The Czech Republic, The United Kingdom, The Netherlands, Belgium, Switzerland, Spain, Italy, Sweden and Australia. A clinical study named HeartLight (Dukkipati, et al., 2015) was performed to establish a reasonable assurance of safety and effectiveness of the HeartLight System to treat drug refractory recurrent symptomatic paroxysmal atrial fibrillation (AF) in the US under IDE G090080. Data from this clinical study were the basis for the PMA approval decision. Additional ablation catheters have since been approved, and various PMA supplements have been approved since the initial approval on most devices. Literature Review - Transcatheter ablation of the pulmonary veins: A number of studies in the peer-reviewed literature have demonstrated that transcatheter ablation of the pulmonary veins (pulmonary vein isolation) may be a secondary treatment option for patients with recurrent symptomatic paroxysmal or persistent AF when antiarrhythmic drug therapy (ADT) has failed to restore sinus rhythm. It has been increasingly used for prevention of paroxysmal AF episodes. Whether it should be considered first-line therapy has been a subject of debate and evaluated in several randomized studies. The randomized controlled trials have demonstrated that cryoballoon catheter ablation as an initial, first-line rhythm control strategy is an effective first-line treatment strategy in recurrent symptomatic paroxysmal atrial fibrillation (Andrade, et al., 2021; Kuniss, et al., 2021; Wazni, et al., 2021). On the basis of these findings, current professional society guidelines have classified pulmonary vein isolation as first-line therapy for recurrent symptomatic paroxysmal atrial fibrillation, as an initial rhythm control strategy prior to therapeutic trials of antiarrhythmic drug therapy paroxysmal AF as a Class IIa recommendation. Catheter-based pulmonary vein isolation is most commonly performed with radiofrequency. Alternative energy sources have also been developed, including cryoballoon and balloon-based laser ablation (Spragg and Kumar, 2022; Calkins, et al., 2017; January, et al., 2014). Atrial fibrillation frequently occurs in patients with heart failure (HF). The combination of AF and HF may increase the risk of stroke, dementia, HF hospitalization and all-cause mortality. Several randomized clinical trials have demonstrated that performing CA in patients with AF and HF Medical Coverage Policy: 0469 showed improvement in peak oxygen consumption, BNP (brain natriuretic peptide) levels, 6- minute walk distance, QOL, and functional capacity. Recently, CA had been shown to improve mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) and simultaneous AF compared to rate control or pharmacological rhythm control. The current professional society guidelines have classified catheter ablation for patients with heart failure and symptoms caused by atrial fibrillation as a Class IIa recommendation (Heidenreich, et al., 2022 Mulder, et al., 2022; Gopinathannair, et al., 2021; Packer, et al., 2021). Randomized Controlled Trials: Andrade et al. (2021) conducted the randomized Early Aggressive Invasive Intervention for Atrial Fibrillation (EARLY-AF) trial of initial rhythm control in patients with symptomatic, untreated atrial fibrillation. The study compared the catheter cryoballoon ablation to antiarrhythmic drugs to prevent the recurrence of atrial tachyarrhythmia, as assessed by an implantable continuous rhythm monitor. The study included patients (n=303) aged 18 years or older with symptomatic, paroxysmal atrial fibrillation (AF) and at least one episode of atrial fibrillation detected on electrocardiography within 24 months before randomization. Patients were randomized into two groups: catheter cryoballoon ablation group (n=154) or antiarrhythmic drug therapy group (n=149). Patients in the catheter ablation group underwent pulmonary-vein isolation using a 23-mm or 28-mm cryoballoon (Arctic Front Advance, Medtronic). The antiarrhythmic drug therapy group were prescribed daily therapy within one week after randomization. In the event of inefficacy or unacceptable side effects during the first 90 days, patients were switched to a prespecified second or third agent. Follow-up occurred telephonically at seven days and at visits at three, six, and 12 months. The implantable cardiac monitor automatically transmitted on a daily basis and manual transmissions were obtained at least weekly. The primary outcome measured the first recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) lasting 30 seconds or longer between 91 and 365 days after the initiation of an antiarrhythmic drug or the catheter ablation procedure. The secondary outcomes measured the first recurrence of symptomatic atrial tachyarrhythmia between 91 and 365 days after the initiation of treatment, the arrhythmia burden, the success of multiple ablation procedures, quality of life, health care utilization, and serious adverse events. At 1 year, a clinically significant recurrence of atrial tachyarrhythmia had occurred in 101 of the 149 patients assigned to receive antiarrhythmic drugs (67.8%) (p<0.001) compared to 66 of the 154 patients assigned to undergo cryoablation (42.9%). Symptomatic atrial tachyarrhythmia recurred in 11.0% of the patients in the ablation group and in 26.2% of those who received antiarrhythmic drugs. Serious adverse events were noted in five patients (3.2%) who underwent ablation and in six patients (4.0%) who received antiarrhythmic drugs. The authors concluded that catheter cryoballoon ablation resulted in a significantly lower rate of recurrence of atrial tachyarrhythmia, as assessed by continuous cardiac rhythm monitoring, than antiarrhythmic drug therapy. Packer et al. (2021) conducted a sub analysis of the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial. The CABANA trial assessed effect of catheter ablation compared to medical therapy on cardiovascular events and mortality. The sub analysis assessed treatment outcomes of AF in patients with heart failure. Of the 2204 patients that were randomized in the CABANA trial, 778 had heart failure with a NYHA class II or greater at baseline. There were 378 patients that underwent ablation and 400 received drug therapy. The primary outcome measured a composite of all-cause mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes measured death or cardiovascular hospitalization and AF recurrence. In the intention-to-treat analysis, ablation had a 36% relative reduction in the primary end point and a 43% relative reduction in all-cause mortality compared to drug therapy alone over a median follow-up of 48.5 months. AF recurrence decreased and quality of life and symptom scores improved in the ablation arm when compared to drug therapy. Treatment-related adverse events in the ablation arm included hematoma (3.2%), pseudoaneurysm (1.2%), esophageal ulcer (1.2%), and severe pericardial chest pain (0.6%). Treatment-related adverse events in the drug therapy arm included hyper- or hypothyroidism (2.5%), gastrointestinal abnormality Medical Coverage Policy: 0469 excluding moderate or severe diarrhea (1.3%), major proarrhythmic event (0.8%), and liver injury or failure (0.5%). Deaths attributed to HF occurred in six patients in the ablation arm and four patients in the drug therapy arm. Death or cardiovascular hospitalization occurred in 212 (56.1%) of 378 patients in the ablation arm and 245 (61.3%) of 400 patients in the drug therapy arm. HF hospitalization occurred in 34 (9.0%) of 378 patients in the ablation arm and 37 (9.3%) of 400 patients in the drug therapy arm. Limitations of the study included that HF was defined phenotypically by the enrolling clinicians (NYHA class II or III symptoms), and confirmatory testing was not required. Secondly, baseline echocardiography to define EF in all subjects was not required. Lastly, in patients who had a baseline EF measured, only 9% had value < 40%. The authors concluded that patients with clinically defined HF, ablation provided clinically important reductions in mortality and recurrent AF and improved QoL relative to drug therapy. No health disparities were identified by the investigators. Dukkipati et al. (2015) conducted a multicenter (n=19) randomized controlled trial (n=353, 334 analyzed) comparing the efficacy and safety of visually guided laser ablation (VGLB) ablation with standard irrigated radiofrequency ablation (RFA) during PV isolation (PVI) catheter ablation of drug refractory paroxysmal atrial fibrillation (PAF). Patients were randomized 1:1 to either LBA or RFA and assessed at 1-, 3-, 6-, and 12-months follow-up. Inclusion criteria: ≥ 2 symptomatic AF episodes (≥ 1 minutes) within the previous 6 months; refractory intolerance to an antiarrhythmic drug (class I, II, or III). Exclusion criteria: PV size > 35 mm; left atrial thrombus; left atrial diameter > 55 mm; LVEF <30%; previous left atrial ablation for AF or atrial flutter (AFL); New York Heart Association class III or IV symptoms; myocardial infarction within the previous 60 days; unstable angina; cardiac surgery within the previous 3 months; coronary artery bypass grafting within the previous 6 months; any history of cardiac valve surgery; a thromboembolic event within the previous 3 months; uncontrolled bleeding; active infection; atrial myxoma; severe pulmonary disease or gastrointestinal bleeding; previous valvular cardiac surgery procedure; presence of an implantable cardioverter-defibrillator; women of childbearing potential who were pregnant, lactating, or not using adequate birth control; inability to be removed from antiarrhythmic drug therapy. The HeartLight (CardioFocus) LBA system was used to perform VGLB ablation with the typical laser energy dose of 8.5 W × 20 seconds per lesion. The ThermoCool Navistar (Biosense Webster) irrigated RFA catheter was used to perform RFA. Primary efficacy endpoint: Freedom from protocol-defined treatment failure, defined as: (1) documented symptomatic AF (≥ 1 minutes); (2) ablation-induced left AFL or atrial tachycardia (AT) or AT of unknown origin; (3) failure to acutely isolate all PVs; (4) use of any antiarrhythmic drug (class I, II, or III); or (5) left heart ablation/surgery or implantable cardioverter-defibrillator placement for AF. Primary safety endpoint: Primary adverse events (AEs), defined as: transient ischemic attack (within 1 month of treatment) or stroke; cardiac perforation; tamponade; significant effusion; PV stenosis; diaphragmatic paralysis (persisting beyond blanking period); atrio-esophageal fistula; death; major bleeding requiring transfusion; myocardial infarction (Q-wave only [within 1 week of treatment]); and AF/AFL requiring cardioversion. Secondary endpoints: 12-month drug-free rate of freedom from symptomatic AF or atypical AFL/AT; AEs; procedural data. Primary endpoints outcomes (LBA; RFA): Freedom from treatment failure (% patients): 61.1%; 61.7%; non-inferiority (p=0.003), suggesting non-inferiority. Patients experiencing ≥ 1 AEs (number [%]): 20/170 (11.8%); 25/172 (14.5%); non-inferiority (p=0.002), suggesting non- inferiority. Clinical outcomes (LBA; CBA): 12-month drug-free rate of freedom from symptomatic AF or atypical AFL/AT (number [%] patients): 106/167 (63.5%); 106/166 (63.9%); (p=0.94). Total AEs: 24/170 (14.1%); 27/172 (15.7%); p value not statistically significant (NS). There was a 3.5% rate of phrenic nerve injury, but no pulmonary valve stenosis; both complications are frequently reported with other balloon technologies. Procedural data (LBA; RFA): Procedure time (mean minutes ± SD): 236.0 ± 52.8; 193.0 ± 63.6; (p<0.0001), favoring RFA. Fluoroscopy time (mean minutes ± SD): 35.6 ± 18.2; 29.7 ± 21.0; p=0.006, favoring RFA. Acute PVI success: 649/664 (97.7%); 658/664 (99.1%); (p=0.05). Study limitations include lack of blinded Medical Coverage Policy: 0469 assessment, allocation concealment and power analysis not reported, and use of ≥ 1-minutes definition for documenting symptomatic AF compared with the 30-second standard duration. Schmidt et al. (2013) conducted a single center randomized controlled trial (n=99) to compare the asymptomatic cerebral lesions (ACL) incidence between irrigated radiofrequency current (RFC), the single big cryoballoon (CB), and the endoscopic laser-balloon (LB). No follow-up was noted. Inclusion criteria: adults with drug refractory paroxysmal PAF. Exclusion criteria: Left atrial size > 50 mm; LVEF < 45%; any contraindications for MRI scanning; stage III renal failure; presence of intracardiac thrombus; CHADS (congestive heart failure [C], high blood pressure [H], age ≥ 75 years [A], diabetes [D], stroke or transient ischemic attack [S]) score > 3. Patients were randomized 1:1:1 to either LBA, CBA, or RFA. One- to 2-days post ablation, all patients underwent cerebral MRI scans. LBA group: A point-by-point method was used to apply laser energy. CBA group: A 28 mm balloon was used for all procedures. RFA group: A maximum power of 40 W, a cutoff temperature of 43° Celsius (C), and a flushing rate of 17 to 25 milliliters per minute (mL/min) was used for irrigated ablations. Outcome measures: ACL incidence; procedure time; PVI isolation rate. Outcome measure results: AEs (LBA; CBA; RFA): ACL incidence: 8/33 (24.2%); 6/33 (18.2%); 8/33 (24.2%); (p=0.8). No major procedural complications were reported. Procedural data (LBA; CBA; RFA): Procedure time (mean minutes ± SD): 149 ± 34; 129 ± 29; 103 ± 33; (p≤0.05), favoring CBA and RFA over LBA. PVI rate: 100%; 100%; 100%. Study limitations include small sample size, lack of power analysis, lack of blinding of outcome assessors, no follow-up, and only obtaining pre-procedural cerebral magnetic resonance imaging (MRI) scans in 20 patients; thus, the existence of pre-procedural ACLs in the remaining 79 patients was unknown. Nonrandomized Controlled Trials: In a matched historical controls study, Bordignon et al. 2016 compared LBA with RFA in 80 patients undergoing PVI for persistent AF at a single German center. Follow-up was 12 months. Results suggest that the use of LBA for PVI in patients with drug- refractory persistent AF of short duration produces similar clinical outcomes when compared with RFA. Study limitations include nonrandomized design, potential selection bias due to retrospective matching of LBA and RFA groups, and small sample size. Wissner et al. (2014) conducted a multicenter, prospective cohort study (n=86) comparing laser balloon ablation (LBA) (n=44), cryoballoon ablation (CBA) (n=20), and radiofrequency ablation (RFA) (n=22) in adults undergoing pulmonary vein isolation (PVI) for highly symptomatic, drug- refractory paroxysmal AF (PAF) or short-standing, persistent AF. The study excluded individuals with previous left atrial ablation procedure; long-standing, persistent AF; left atrial diameter > 60 mm; severe valvular heart disease; contraindications to post-interventional oral anticoagulation. All patients underwent pre- and post-procedural cerebral MRI to detect true incidence of new ACLs. Radiologists interpreting the MRI were blinded to ablation technique. Outcome measures included ACL incidence; adverse events; acute PVI success; procedural data. Adverse events (LBA; CBA; RFA): new asymptomatic embolic lesions (number [%] patients): 5/44 (11.4%); 1/20 (5.0%); 4/22 (18.2%); p=0.4148. New embolic lesions (number [%] patients): 6/44 (13.6%); 1/20 (5.0%); 4/22 (18.2%); p=0.4870. Phrenic nerve palsy (PNP): 1/44 (2.3%); 0/20 (0%); 0/22 (0%); p=NR. Procedural data (LBA; CBA; RFA): procedure time (mean minutes ± SD): 195 ± 47; 164 ± 29; 208 ± 69; P=0.0021, favoring CBA over LBA; p=NR for LBA versus RFA. Acute PVI success: 41/44 (93.2%); 20/20 (100%); 22/22 (100%); p=NR. Study limitations include nonrandomized design, small sample size, method of group allocation not reported, and statistically significant differences between groups at baseline. Bordignon et al. (2013) conducted a nonrandomized controlled study (n=140) to compare the safety and efficacy of the cryoballoon (CB) and the laser balloon (LB). Patients with drug- refractory paroxysmal atrial fibrillation (PAF) were prospectively allocated in a 1:1 fashion to undergo a PVI procedure with the 28 mm CB or the LB and were followed for 12 months using 3- Medical Coverage Policy: 0469 day Holter ECG recording. Inclusion criteria was PAF refractory to ≥ 1 membrane active antiarrhythmic drug; age 18 to 75 years; no prior PVI attempt; left atrial size < 50 millimeters (mm); left ventricular ejection fraction (LVEF) > 45%; ability to receive therapeutic oral anticoagulation. Exclusion criteria was not reported. The primary efficacy endpoint was a documented AF recurrence ≥ 30 seconds between 90 and 365 days after the index ablation. Secondary endpoints: Procedural data. In total, 269 of 270 PVs (99.6%) and 270 of 273 PVs (98.9%) were acutely isolated in the CB and LB group, respectively. Mean procedural time was 136 ± 30 minutes for the CB group and 144 ± 33 minutes for the LB group (p=0.13). Mean fluoroscopy time was longer in the CB group (21 ± 9 minutes vs 15 ± 6 minutes; p< 0.001). During 12 months follow-up, 37% of patients in the CB group and 27% in the LB group experienced an AF recurrence (p=0.18). Phrenic nerve palsies occurred in 5.7% (CB) and 4.2% (LB) of patients, respectively. Vein of Marshall alcohol ablation (VOM ethanol infusion): The vein of Marshall is a remnant of the left superior vena cava and has been associated with multiple arrhythmias (e.g., atrial arrhythmias, ventricular arrhythmias, and accessory pathways). VOM can control the electrical potential of the atrial tissue and contribute to atrial fibrillation (AF). Vein of Marshall (VOM) ethanol infusion during atrial fibrillation ablation is being evaluated as a treatment for persistent atrial fibrillation. It is proposed that ethanol infusion into the VOM increases the chances of remaining free of atrial fibrillation. There is currently a paucity of evidence in the published peer- reviewed medical literature evaluating the safety and effectiveness of VOM ethanol infusion during a catheter ablation for the treatment of persistent atrial fibrillation. The evidence evaluating VOM ethanol infusion during a catheter ablation for the treatment of persistent atrial fibrillation is primarily in the form of a randomized controlled trial, retrospective reviews, prospective case series, observational studies, and review articles (He, et al., 2022; Lai, et al., 2021; Valderrábano, et al., 2020; Liu, et al., 2019). Clinical trials evaluating VOM ethanol infusion for the treatment of atrial fibrillation are now underway. Literature Review: Valderrábano et al. (2020) conducted a randomized controlled trial that assessed if adding vein of Marshall ethanol infusion to the catheter ablation procedure reduced the recurrence of atrial fibrillation in patients with persistent atrial fibrillation (VENUS trial). Adults aged 18–85 years with symptomatic persistent AF (sustained AF lasting > 7days) refractory to at least one antiarrhythmic agent were included in the study. Patients (n=343) were randomly assigned in a 1:1.15 ratio to accommodate for 15% technical vein of Marshall ethanol infusion failures to catheter ablation alone (n=158) or catheter ablation combined with vein of Marshall ethanol infusion (n=185). The primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without antiarrhythmic drugs, at both six and 12 months. There were 12 secondary outcomes, included that measured AF burden, freedom from AF after multiple procedures, perimitral block, and others. Clinical assessments and 12-lead electrocardiograms were obtained at baseline and at one, three, six, nine and 12 months after the initial ablation. Additionally, patients underwent continuous one month monitoring (MediLynx) at six and 12 months after ablation. Of the 343 randomized patients, 316 (92.1%) completed the trial and adherence to the 30-day event monitor at six and 12 months was 85.1% and 83.3%, respectively. Catheter ablation with vein of Marshall ethanol infusion, compared with catheter ablation alone, resulted in freedom from atrial fibrillation or prolonged atrial tachycardia in 49% vs 38% at both six and 12 months, a difference that was statistically significant (p=0.04). Of the 12 secondary outcomes, nine were not significantly different, but AF burden (p=0.01), freedom from AF after multiple procedures (p=0.04), and success achieving perimitral block (p<0.001) were significantly improved in vein of Marshall–treated patients. Adverse events were similar between groups. The authors noted several limitations which include: potential investigator bias in the catheter ablation group, the vein of Marshall ethanol infusion procedure was not completed in all patients randomized to it, adherence to monitoring was incomplete and the primary outcome could not be ascertained in 27 patients because of lacking monitoring data and ten patients had Medical Coverage Policy: 0469 repeat procedures performed during the blanking period. Additional limitations include the small patient population, short term follow-up and included over 90% of white patients and the results may not be applicable to other races or ethnic groups. Authors concluded that among patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at six and 12 months, however further research is needed to assess longer-term efficacy. No health disparities were identified by the investigators. Okishige et al. (2020) conducted a prospective comparative study that evaluated if adding infusion of ethanol into the vein of Marshall (VOM-EI) during radiofrequency (RF) ablation or cryoablation (CB) improved rhythm control in paroxysmal AF. Adults (n=342) aged 44–82 who had experienced multiple episodes of AF within the previous six months were included in the study. Most of the study patients were male (73 %). Patient were divided into two groups with different treatment strategies. Group 1 included RF only (n=90) and CB only (n=120). Group 2 included RF combined with VOM-EI (n=80) and CB combined with VOM-EI (n=52). Patients in Group 1 (n=210) underwent ablation of the mitral isthmus and patients in Group 2 (n=132) underwent catheter ablation of paroxysmal AF with either RF or cryoballoon (CB) for PVI combined with VOM- EI. Patients were evaluated at one, two, three, six, nine, 12, and 15 months after the procedure. The long-term outcome measured the freedom from any atrial arrhythmias documented after a blanking period of 90 days after the procedure. EI-VOM was successful in 117 out of 132 patients (88.6%) and PVI was successful for 100% in both groups. Freedom from AF after approximately 450 days was non-significant between Group 1 and Group 2 (p=0.167). Arrhythmia-free survival after one year were 63.8% (RF + VOM) and 82.7 % (CB + VOM), respectively. Comparison between CB + VOM versus RF + VOM reached statistical significance (p=0.0292) in favor of CB + VOM. The periprocedural complication rate was comparable in both groups (p=0.14) with a significant difference in the incidence of phrenic nerve palsy with cryoablation (0 % RF, 2.0 % CB; p<0.05). Among the treatment arms, however, recurrent AF occurred in a significantly larger proportion of patients in Groups RF, CB and RF + VOM-EI, than in Group CB + VOM-EI, and those differences reached statistical significance (p=0.048). Author noted limitations included the nonrandomized study design and the lack of a control group along with small patient population and short-term follow-up and AF recurrent episodes could have been missed in some patients. Also noted was that the assignment of the study patients into the four groups might not be appropriate, because grouping of patients depended on whether the VOM was present or not. Lastly, the examinations to evaluate the efficacy of ablation procedure (12-lead ECG and Holter monitoring) might not be sufficient. An additional limitation of the study included that the study was performed in China, and the results may not be applicable to other races or ethnic groups. The authors concluded that the VOM-EI failed to demonstrate any significant improvement in the ablation long-term results of paroxysmal AF. However, CB ablation combined with a VOM-EI had a significantly improved outcome compared to a PVI with RF ablation combined with a VOM-EI. No health disparities were identified by the investigators. Further studies in large, diverse populations with long-term follow-up are needed to evaluate efficacy, optimize protocols and outcomes. Professional Societies/Organizations American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS): An updated guideline on the Management of Patients with Atrial Fibrillation (AF) was published by the AHA, ACC, and HRS in 2014 (January, et al, 2014). The authors noted that the decision whether to pursue catheter ablation depends on many variables, including the type of AF (paroxysmal versus persistent verses longstanding persistent), degree of symptoms, presence of structural heart disease, candidacy for alternative options such as rate control or antiarrhythmic drug therapy, likelihood of complications, and patient preference. Efficacy of radiofrequency catheter ablation for maintaining sinus rhythm is superior to current Medical Coverage Policy: 0469 antiarrhythmic drug therapy for maintenance of sinus rhythm in selected patient populations. Cryoballoon ablation is identified as an alternative to point-by-point radiofrequency ablation to achieve pulmonary vein isolation. The evidence supporting the efficacy of catheter ablation is strongest for paroxysmal AF in younger patients with little to no structural heart disease and in procedures performed in experienced centers. Evidence is insufficient to determine whether AF catheter ablation reduces all-cause mortality, stroke, and heart failure. Recurrences of AF after catheter ablation are common during the first three months and do not preclude long-term success, although they are associated with an increased risk of procedural failure and rehospitalization. A number of centers have reported late AF recurrences >1 year after catheter ablation. Complications of radiofrequency catheter ablation for AF noted in the AHA/ACC/ESC guideline include, but are not limited to, pulmonary vein stenosis, thromboembolism, atrioesophageal fistula and left atrial flutter, in addition to potential complications inherent in any cardiac catheterization procedure. Laser balloon ablation is not addressed in the guideline. The guidelines recommended the following for the treatment of symptomatic paroxysmal AF: • AF catheter ablation is recommended for symptomatic paroxysmal AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication when a rhythm control strategy is desired. AF catheter ablation is indicated for recurrent symptomatic paroxysmal AF as an initial rhythm control strategy prior to therapeutic trials of antiarrhythmic drug therapy, after weighing risks and outcomes of drug and ablation therapy. The guidelines recommended the following for the treatment of symptomatic persistent AF: AF catheter ablation is reasonable for selected patients with symptomatic persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication. AF catheter ablation may be considered before initiation of antiarrhythmic drug therapy with a class I or III antiarrhythmic medication for symptomatic persistent AF when a rhythm-control strategy is desired, however the usefulness/effectiveness is uncertain and not well established. In the 2019 focused update to the 2014 AHA/ACC/HRS guideline on the Management of Patients with AF there were not updated recommendations made to the existing recommendations for catheter ablation to maintain sinus rhythm as stated above. American Heart Association (AHA), American College of Cardiology (ACC), and Heart Failure Society of America: In 2022, the AHA/ACC/HFSA updated the Guideline for the Management of Heart Failure recommended that for patients with HF and symptoms caused by AF, AF ablation is reasonable to improve symptoms and QOL (Heidenreich, et al.). The supportive text for the recommendation stated that in a randomized controlled trial (CASTLE- AF [Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF]), selected patients with HFrEF with paroxysmal or persistent AF and an implanted cardioverter-defibrillator or cardiac resynchronization therapy defibrillator device who did not respond to or could not take antiarrhythmic drugs were randomized to receive AF catheter ablation versus medical therapy (rate or rhythm control) in addition to guideline-directed management and therapy for HFrEF (Marrouche, et al., 2018). Patients in the AF catheter ablation group had significantly reduced overall mortality rate, reduced rate of hospitalization for worsening HF, and improved LV ejection fraction as compared to the medical therapy group. An additional RCT in a population of patients with persistent AF, HFrEF, and an implanted cardioverter defibrillator or cardiac resynchronization therapy defibrillator device demonstrated that AF catheter ablation was superior to amiodarone for maintenance of sinus rhythm, with secondary endpoint analyses suggesting a lower rate of unplanned hospitalization and death (Di Biase, et al., 2016). Medical Coverage Policy: 0469 Left Atrial Appendage (LAA) Closure Three main approaches to stroke prevention in AF are: elimination of AF; prevention of clot formation with antiplatelet or anticoagulant agents; and physical elimination of the left atrial appendage (LAA) which excludes the site of clot formation. Among patients with non-valvular AF, most of the thrombus material is located within or involves the LAA. Approximately 90% of left atrial thrombi form in the LAA. Most patients with AF receive anticoagulant therapy to reduce the risk of systemic embolization. There are varying degrees of bleeding risk associated with anticoagulation and not all individuals are candidates for this therapy. The optimal approach to reducing the risk of embolization in patients for whom long-term anticoagulation is indicated, but who are unable to take it, is unclear. Percutaneous approaches, often referred to as LAA exclusion procedures, that mechanically prevent embolization of LAA thrombi have been developed. At present, there are two categories of percutaneous LAA occlusion devices: endocardially and epicardially delivered. In addition, LAA exclusion at the time of surgery has been proposed for some patients undergoing cardiac surgery for reasons such as valve replacement or repair or coronary artery bypass graft surgery (Hijazi and Saw, 2023; Morady, et al., 2019; Whitlock, et al., 2014). Several studies have reported that women had higher rates of in-hospital adverse events following LAAC than men did. It is recommended that further research is warranted to identify sex-specific, racial/ethnic, and socioeconomic pathways during the patient selection process to minimize complications in patients undergoing LAAC (Darden, et al., 2021; Sanjoy, et al., 2021). Percutaneous transcatheter closure of the LAA (CPT® Code 33340): The Watchman™ Left Atrial Appendage Closure Device (Boston Scientific, Maple Grove, MN) is a self-expanding nickel- titanium system. Implantation is performed percutaneously with a catheter delivery system, with venous access and trans-septal puncture to enter the left atrium. After implantation of device, patients receive anticoagulation with warfarin or other agents for approximately one to two months. During this acute period, anticoagulation may be necessary due to risk of thrombus formation related to altered blood flow around the implant. Patients are monitored with transesophageal echocardiography to assess blood flow and complete LAA closure (LAAC). After this period, patients will receive antiplatelet agents (e.g., aspirin and/or clopidogrel) indefinitely. The Amplatzer™ Cardiac Plug (St. Jude Medical, Minneapolis, MN) closes off the LAA in a manner like the Watchman. The technique for implanting this device is also like that of the Watchman system. The Amplatzer Cardiac Plug is shorter than the Watchman device and may be more advantageous in individuals with short appendages. The Amulet has more stabilizing wires, up to 10 pairs, for improved device stability and larger lobe size to occlude larger appendages. U.S. Food and Drug Administration (FDA): The Watchman LAA Closure Technology received FDA premarket approval on March 2015 (P130013). The approval noted that the device is indicated to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation who: are at increased risk for stroke and systemic embolism based on CHADS2 (cardiac failure, hypertension, age ≥ 75 years, diabetes, stroke) or CHA2DS2 -VASc1 (congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke/transient ischemic attack/thromboembolism, vascular disease, aged 65 to 74 years, sex category [female]) scores and are recommended for anticoagulation therapy • are deemed by their physicians to be suitable for warfarin • have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin Medical Coverage Policy: 0469 In July 2020, a premarket approval application (PMA) supplement (P130013/S035) was approved for a modified version of the Watchman LAA Closure Device with Delivery System, referred to as the Watchman FLX Left Atrial Appendage Closure Device with Delivery System, to expand the indications to include anticoagulation therapy. These devices are indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who: are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2 -VASc scores and are recommended for anticoagulation therapy; are deemed by their physicians to be suitable for anticoagulation therapy; and • have an appropriate rationale to seek a non-pharmacologic alternative to anticoagulation therapy, taking into account the safety and effectiveness of the device compared to anticoagulation therapy In September 2021, the FDA informed health care providers of the potential for differences in procedural outcomes between women and men undergoing implant of a left atrial appendage occlusion (LAAO) device. The letter explained that the FDA would be working with manufacturers to evaluate information from several sources and included recommendations for the providers. The letter was prompted by the data reported in the National Cardiovascular Data Registry LAAO Registry. In September 2023, a premarket approval application (PMA) supplement (P130013/S057) was approved for a modified version of the Watchman LAA Closure Device with Delivery System, referred to as the WATCHMAN FLX™ Pro Left Atrial Appendage Closure (LAAC) Device with Delivery System. This supplement was a design modification that included increasing the size of the device and the addition of radiopaque markers and a device coating (FDA 2023). The Amplatzer™ Amulet™ Left Atrial Appendage Occluder received FDA premarket approval on August 14, 2021 (P200049). The approval notes that the device is indicated to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation who: are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2 VASc scores; and are suitable for short term anticoagulation therapy; and • have appropriate rationale to seek a non-pharmacologic alternative to oral anticoagulation, ‐ taking into consideration the safety and effectiveness of the device Other devices that have not received FDA approval for the use of LAA closure include, but are not limited to, the following: The Lariat® Loop Applicator (Sentreheart, Palo Alto, CA) is a suture delivery device that is designed to close a variety of surgical wounds in addition to LAAC. The Lariat Loop Applicator device did receive 510(k) marketing clearance from FDA in 2006 as suture delivery device but does not have FDA approval as a LAA closure device. Its intended use is to facilitate suture placement and knot tying in surgical applications where soft tissues are being approximated or ligated with a pretied polyester suture. The technical approach differs from that of the Watchman system. The Lariat suture loop ligates the LAA from the epicardial space, with assistance of catheters and balloons in the left atrium. The WaveCrest® Device (Biosense Webster, Irvine, CA) device consists of a single-lobe, nitinol-based design for occluding the LAA. Unlike the Watchman device, the WaveCrest device is covered by a foam layer on the LAA side and polytetrafluoroethylene on the side facing the left atrium. It has several anchors along the LAA side and is designed to be separately deployed from the lobe. This device is meant to be deployed quite proximally in the LAA, rather than deep within the structure. This device is proposed as another alternative to the Watchman device if the LAA is too small to accommodate deeper devices. Medical Coverage Policy: 0469 The device has CE Mark approval and is available in Europe in 2013. A prospective, multicenter, RCT of the WaveCrest® Left Atrial Appendage Occlusion System compared to an existing FDA-approved LAA Closure Device for the reduction in risk of embolic stroke in subjects with non-valvular atrial fibrillation is ongoing. The trial will enroll 1,250 patients at approximately 90 hospitals and follow them for five years. PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) device (Appriva Medical, Inc., Sunnyvale, CA, USA) is no longer in production. LAmbre™ LAA Closure System (Lifetech Scientific, Shenzhen, China) is a self-expanding LAA occluder constructed from a nitinol mesh and polyester membranes and consists of an umbrella and a cover connected by a short central waist. The device is delivered by an 8- 10 French sheath and has full recapture and repositioning capabilities. LAmbre™ LAA Closure System received the CE mark in June 2016. Literature Review - Percutaneous transcatheter closure of the LAA: The Watchman device received FDA approval based upon the results of PROTECT AF and PREVAIL randomized controlled trials (RCT). The Amplatzer™ Amulet™ Left Atrial Appendage Occluder received FDA approval based upon the results of The Prospective Amulet Observational Study. Randomized Controlled Trials - SWISS-APERO: Galea et al. (2022) conducted a multicenter randomized, superiority-controlled trial that assessed if Amulet is superior to Watchman 2.5/FLX (Watchman) when used for percutaneous left atrial appendage closure. Patients (n=221) with nonvalvular atrial fibrillation and a clinical indication for LAAC were eligible if they were age ≥ 18 years, capable of providing written informed consent, with a CHA2DS2-VASc score ≥ 2 and either HAS-BLED score ≥3 or the presence of high-bleeding risk features. Patients were randomized to receive either the Amulet (n=111) or Watchman (n=110), of whom 25 (22.7%) patients included before October 2019 received Watchman 2.5, and 85 (77.3%) patients received Watchman FLX. The primary end point measured the crossover to a nonrandomized device during LAA closure procedure or residual LAA patency detected by cardiac computed tomography angiography (CCTA) at 45 days. The secondary outcomes included procedural complications, device related thrombus, peridevice leak at transesophageal echocardiography, and clinical outcomes at 45 days. The primary end point was measured in 205 patients and occurred in 71 (67.6%) patients in the Amulet and 70 (70.0%) patients in the Watchman group (p=0.713), not a significant difference between groups. A single justified crossover occurred in a patient with Amulet who fulfilled LAA patency criteria at 45-day CCTA. Major procedure-related complications and the periprocedural complication rate were significantly higher in the Amulet group (p=0.047; p=0.023, respectively). At 45 days, the peridevice leak rate at transesophageal echocardiography was significantly higher with Watchman than with Amulet (p=0.020), although none was major (i.e., >5 mm). Device- related thrombus and clinical outcomes at 45 days did not differ significantly between the groups (p=0.225; p=0.409, respectively). Limitations noted by the authors included the short-term follow-up, the implanted devices could not be blinded, the trial was not powered to show differences with regard to clinical end points and the new Watchman FLX became available in October 2019; therefore a minority yet sizable proportion of patients received Watchman 2.5. However, the results were consistent between the types of Watchman devices. Additionally, the authors noted that the observed rates of procedural complications in both arms in our study were higher than those reported by previous studies (0.5%–5%). This could possibly be due to the studies definition of procedure-related complications which included minor events and counted as procedural complications events that occurred > 7 days after LAAC if they were deemed procedure related. Lastly, the prognostic significance of residual patent left atrial appendage (PA) after percutaneous LAAC remains unclear. An additional imitation of the study included that the studied population resided in Switzerland, Medical Coverage Policy: 0469 Belgium, France and Italy and the results may not be applicable to other races or ethnic groups. The authors concluded that that the Amulet was not associated with a lower rate of crossover or residual LAA patency compared with Watchman at 45-day CCTA. Amulet, however, was associated with lower peridevice leak rates at transesophageal echocardiography, higher procedural complications, and similar clinical outcomes at 45 days compared with Watchman. No health disparities were identified by the investigators, however there were more males enrolled than females. Amulet IDE: Lakkireddy et al. (2021) conducted the randomized controlled Amulet IDE trial that evaluated the safety and effectiveness of the Amulet occluder compared to the Watchman device. Patients (n=1878) were included in the study if they were age ≥ 18 years with documented paroxysmal, persistent, or permanent non-valvular atrial fibrillation and were at increased risk of stroke or systemic embolism defined as CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3. Patients were randomized to receive the Amulet occluder (n=934) or Watchman device (n=944). The primary outcomes measured safety (composite of procedure-related complications, all-cause death, or major bleeding at 12 months), effectiveness (composite of ischemic stroke or systemic embolism at 18 months) and the rate of LAA occlusion at 45 days. Secondary outcome measurements included a composite of all strokes, systemic embolism, or cardiovascular/unexplained death at 18 months, major bleeding at 18 months and superiority test of the three primary endpoints. Patients implanted with the Amulet occluder were discharged on either aspirin plus clopidogrel or aspirin plus OAC at the discretion of the investigator, while patients assigned to and implanted with the Watchman device received aspirin plus warfarin per the device instructions. When LAA occlusion was confirmed by TEE at the 45-day visit, cessation of OAC was required for all patients. Patients were then instructed to take aspirin and clopidogrel until the six months visit when clopidogrel was discontinued and aspirin continued indefinitely. The Amulet occluder was non-inferior to the Watchman device for the primary safety endpoint, the primary effectiveness endpoint and the composite of stroke, systemic embolism, or cardiovascular/unexplained death (All: p<0.001 for non-inferiority). Major bleeding and all-cause death were similar between groups. Procedure-related complications were higher for the Amulet occluder (4.5% vs. 2.5%), largely related to more frequent pericardial effusion and device embolization. LAA occlusion was significantly higher for the Amulet occluder compared with the Watchman device (p<0.001 for non-inferiority; p=0.003 for superiority). Author noted limitations included: a high number of excluded patients which may limit the generalizability of the findings; echocardiographic core lab was not blinded; the Amulet device was compared to the first- generation Watchman device, not the newer generation; and it is unknown which antithrombotic regimen provides the best outcomes. The authors concluded that the Amulet occluder was non- inferior for safety and effectiveness of stroke prevention for NVAF compared with the Watchman device, and superior for LAA occlusion. However, additional studies are needed to better understand the higher occurrence of late pericardial effusion in Amulet patients receiving post- procedure OAC. No health disparities were identified by the investigators. Lakkireddy et al. (2023) reported the three-year results from the Amulet IDE randomized noninferiority controlled trial. The medication regimen and key clinical outcomes were reported through 3 years and included: 1) the composite of ischemic stroke or systemic embolism (SE); 2) the composite of all strokes, SE, or cardiovascular (CV) death; 3) major bleeding; and 4) all-cause death and CV death. From 18 months to three years, 92% of Amulet occluder patients and 86.7% of Watchman device patients completed the visits with comparable deaths and withdrawals (Watchman device group: 69 deaths and 30 withdrew; Amulet occluder group: 70 deaths and 19 withdrew). At three years, a significantly higher percentage of patients were free from oral anticoagulation usage with Amulet (96.2%) compared to Watchman (92.5%) (p<0.01). Clinical outcomes were comparable and not significant between groups for the composite of ischemic stroke or SE (p=0.69); the composite of all strokes, SE, or CV death (p=0.31); major bleeding (p=0.46); all-cause death (p=0.08); and CV death (p=0.14). Through 3 years, device factors Medical Coverage Policy: 0469 (device-related thrombus or peridevice leak) preceded ischemic stroke events and CV deaths occurred more frequently in Watchman compared to Amulet patients, however this did not reach statistical significance. The study concluded that the Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through three years in a high-risk population compared to the Watchman device. No health disparities were identified by the investigators. PRAGUE-17: Osmancik et al. (2020) conducted a multicenter, randomized, noninferiority trial (PRAGUE-17) comparing percutaneous left atrial appendage closure (LAAC) with direct oral anticoagulant (DOACs). Patients were eligible to be enrolled if they had non-valvular AF; were indicated for oral anticoagulation (OAC); had a history of bleeding requiring intervention or hospitalization, had a history of a cardioembolic event while taking an OAC, and/or a CHA2DS2- VASc of ≥ 3 and HAS-BLED of > 2. Patients (n=402) were randomized to receive LAAC or DOAC. Patients randomized to the DOAC group could receive rivaroxaban, apixaban, or dabigatran at the manufacturer-recommended dose. Medication compliance was monitored by querying patients about regular medication use during each visit. Patients randomized to LAAC underwent implantation with a commercially available Amulet (Abbott Inc., St. Paul, Minnesota) or Watchman/Watchman-FLX (Boston Scientific Inc., St. Paul, Minnesota) device. Following LAAC, the recommended antithrombotic regimen was aspirin 100 mg/day plus clopidogrel 75 mg/day for 3 months. If a TEE then showed no device-related thrombus or leak of ≥ 5mm, clopidogrel was withdrawn; aspirin was continued indefinitely. The primary outcome measured safety, efficacy, stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or non-major clinically relevant bleeding, or procedure/device related complications. For both groups, outpatient follow-up occurred at six weeks and three, six, nine, and 12 months and every six months thereafter. The minimum follow-up for the last enrolled patient was the six-month visit. During each visit, patients were asked about the endpoint occurrence, all other changes in clinical status, hospitalization or other health care utilization, and medication changes. LAAC was successful in 181 of 201 (90.0%) patients. The implanted devices were either Amulet, Watchman, or Watchman-FLX in 61.3%, 35.9%, or 2.8%, respectively. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42%with DOAC (p=0.44; p=0.004 for noninferiority). There were no significant differences between groups for the components of the composite endpoint: all-stroke/TIA, clinically significant bleeding, and cardiovascular death. Major LAAC-related complications occurred in nine (4.5%) patients. Limitations included that the study was underpowered to evaluate the relative differences in the individual components of the primary endpoint. The high event rate allowed sufficient power to assess the primary endpoint. Although the mean follow-up is substantial, additional follow-up is needed to determine the relative long- term differences between groups. In the DOAC group, no medication logs were kept; however, the observed ischemic stroke rate suggests reasonable DOAC compliance. The authors concluded that among patients at high risk for stroke and increased risk of bleeding, LAAC was non-inferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. Osmancik et al. (2022) reported the four-year results from the PRAGUE-17 randomized noninferiority controlled trial that compared percutaneous left atrial appendage closure (LAAC) to direct oral anticoagulant (DOACs). The primary outcome measured the composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure/device-related complications (LAAC group only). The patents that completed the per-protocol analysis included 181 and 199 in the LAAC and DOAC groups, respectively. After 3.5 years median follow-up, LAAC was remained non-inferior to DOACs for the primary endpoint (p=0.27; p=0.006 for noninferiority). There were not any significant differences between the groups in cardiovascular death (p=0.19), all-stroke/transient ischemic attack (p=0.72), clinically relevant bleeding (p=0.28) and nonprocedural clinically relevant bleeding (p=0.039). The authors concluded LAAC remains non-inferior to DOACs for preventing major Medical Coverage Policy: 0469 cardiovascular, neurological, or bleeding events after four years of follow-up. No health disparities were identified by the investigators. PROTECT AF: A non-inferiority RCT compared LAA closure with Watchman device to warfarin treatment in patients with non-valvular atrial fibrillation (NVAF), the PROTECT AF trial (Reddy, et al. 2014; Reddy, et al., 2013a; Holmes, et al., 2009). The trial included 707 patients, randomized 2:1, with the device group n=463 and warfarin group n=244 and a follow-up time was 3.8±1.7 years (Reddy et al., 2014). Inclusion criteria: age ≥18 years; paroxysmal, persistent, or permanent NVAF and eligible for warfarin treatment; and CHADS2 score ≥1. In the Watchman group the device implanted under transesophageal echocardiography (TEE) guidance with concomitant warfarin and Aspirin (ASA) (81-325 mg/day) for 45 days, on day 45, warfarin stopped, clopidogrel (75 mg/day) started until the six month visit and then only ASA continued. In the warfarin group warfarin treatment was provided with a target INR 2-3. The primary efficacy outcome was stroke, systemic embolization, or cardiovascular death. The primary safety outcome was a composite of major bleeding events and procedure-related complications. At mean follow-up of 3.8 years, there were 39 events in 463 pts (8.4%) in the device group for primary event per 100 patient/years (pt/yrs), compared with 34 events in 244 patients (13.9%) for primary event rate of 3.8 in 100 pt/yrs in warfarin group. In the primary efficacy outcome, there was a non- inferiority > 99%, and in the primary safety endpoint a non-inferiority > 98%. Complications included in the Watchman group: serious pericardial effusion (4.8%); major bleeding (4.8%); procedure related ischemic stroke (1.3%); device embolization (0.6%); and hemorrhagic stroke (0.6%). In the warfarin group: major bleeding (7.4%); and hemorrhagic stroke (3.7%). This study demonstrated the non-inferiority of LAA closure compared to warfarin treatment. The study was limited in that it included warfarin but did not include a comparison with the newer anticoagulants. The study included patients with warfarin but does not address the patients who are unable to take anticoagulants. PREVAIL: A non-inferiority RCT of that compared LAA closure with Watchman device and long- term warfarin treatment in patients with NVAF, the PREVAIL study (Holmes, et al., 2014). The study included 407 patients (randomized 2:1); with 68 patients enrolled through roll-in process with the Watchman group, n=269 and warfarin group, n=138. The follow-up time was a median of 12 months. The inclusion criteria included: NVAF; CHADS2 ≥ 2 or 1 CHADS2 plus 1 high-risk characteristic. In the Watchman group, the device was implanted guided by fluoroscopy and TEE; post-implant patients were treated with warfarin and ASA for 45 days; TEE performed at 45 days, 6 months, and 12 months. Warfarin was discontinued if the day 45 TEE documented closure of LAA or residual peri-device flow <5 mm and no definite visible large thrombus on device; then clopidogrel 75 mg/day and ASA 81-325 mg/day was prescribed until six months when clopidogrel discontinued. In the warfarin group warfarin treatment was given with target INR 2.0-3.0. At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group and did not achieve the prespecified criteria non-inferiority. The rate for the second coprimary efficacy endpoint (stroke or SE > 7 days’ post-randomization) was 0.0253 vs 0.0200 achieving non-inferiority. Early safety events occurred in 2.2% of the Watchman arm. Complications (reported for Watchman-group only) (% of patients): device embolization (0.7%); arteriovenous fistula (0.4%); cardiac perforation (0.4%); pericardial effusion with cardiac tamponade (0.4%); major bleed requiring transfusion (0.4%). Non-inferiority was not achieved for overall efficacy in this study. The patients in this study were required to be candidates for long-term anticoagulation to facilitate randomization against a control group treated with warfarin. The trial does not address the safety and efficacy of LAA occlusion when anticoagulation is contraindicated. In addition, the study does not include comparison with new oral anticoagulants. Reddy et al (2017) reported final five-year results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial. For the PREVAIL trial, the first composite Medical Coverage Policy: 0469 coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve non-inferiority (posterior probability for non-inferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve non-inferiority (posterior probability for non-inferiority=97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p=0.27), as were all-stroke/SE (HR: 0.961; p=0.87). The ischemic stroke/SE rate was numerically higher with LAA closure, but this difference did not reach statistical significance (HR: 1.71; p=0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAA closure (HR: 0.20; p=0.0022; HR: 0.45; p=0.03; HR: 0.59; p=0.027; HR: 0.73; p=0.035; HR: 0.48; p=0.0003, respectively). The author transitional outlook states that further studies are needed to compare the benefit of LAA occlusion against oral anticoagulants other than warfarin in patients with AF, and to assess advantages for those with contraindications to anticoagulation. Nonrandomized Controlled Trials: Kar et al. (2021) reported the results of the prospective, nonrandomized, multicenter US Food and Drug Administration PINNACLE FLX study (Protection Against Embolism for Non-valvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) that evaluated the safety and effectiveness of the next- generation WATCHMAN FLX LAA closure device in patients with non-valvular atrial fibrillation in whom oral anticoagulation is indicated and who have an appropriate rationale to seek a nonpharmacological alternative. Patients (n=400) were included in the study if they met the following criteria: non-valvular atrial fibrillation (NVAF) and a CHA2DS2-VASc score of ≥ 2 for men or ≥ 3 for women, were able to take the prescribed post-implant antithrombotic medication regimen, had a rationale for a nonpharmacological approach to stroke prevention, and had no other diagnoses that would require long-term anticoagulation. The primary safety outcome measured the occurrence of one of the following events within seven days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness outcome measured the incidence of effective LAA closure (peri-device flow ≤ 5 mm), which was assessed by the echocardiography core laboratory at 12-month follow-up. After device placement, treatment with a direct oral anticoagulant (DOAC) was required through at least the 45-day follow-up, with apixaban or rivaroxaban strongly recommended. Patients were also prescribed concomitant low-dose (81–100 mg) aspirin. On evidence of adequate LAA seal (leak ≤ 5 mm) at the 45-day TEE evaluation, patients were directed to discontinue DOAC therapy and begin a dual antiplatelet therapy regimen of clopidogrel (75 mg) plus low-dose aspirin until six months postimplant, followed by low-dose aspirin indefinitely. If a leak > 5 mm was measured at the 45- day follow-up, patients continued DOAC plus aspirin and were reevaluated at six months post- implant. If there were no leaks >5 mm at the subsequent follow-up visit, patients could forego dual antiplatelet therapy and proceed straight to lifelong low-dose aspirin. Post-implant follow-up visits were required at 45 days, six, 12, 18, and 24 months. The primary safety and efficacy outcomes were met (both: p<0.0001). Device-related thrombus was reported in seven patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolization’s. Author reported study limitations included the lack of a control group, the procedural safety and efficacy of closure of the next-generation LAA closure device was not directly compared with that of the predicate device and clinical event incidence with the first- generation device cannot be directly compared with a similar population treated with oral anticoagulation. Secondly, the incidence of anatomic and effective closure that are surrogates for the clinical outcomes of stroke and systemic embolism outcomes will be reported when the prespecified two-year follow-up is complete. Thirdly, the results should not be generalized to patients who have absolute contraindications to oral anticoagulant therapy. Lastly, the study sample size was not large enough to provide robust estimates of the incidence of rare events, such as device embolization. The authors concluded that LAA closure with the next-generation LAA Medical Coverage Policy: 0469 closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Hildick-Smith et al. (2020) conducted The Amulet Observational Study prospectively that evaluated the safety and efficacy of left atrial appendage occlusion (LAAO) with the Amplatzer™ Amulet™ occluder. Patients (n=1088) were age 18 years and older with history of paroxysmal, persistent or permanent non-valvular atrial fibrillation eligible for an Amulet LAA Occluder device. Left atrial appendage occlusion was performed by 93 implanters at 61 centers in 17 countries. Primary outcomes measured: the rate of ischemic stroke, systemic embolism and cardiovascular (CV) death at two years; the rate of major bleeding events at two years; the assessment of acute (0–7 days) serious adverse events; and the assessment of late (> 7 days–2 years) serious adverse events. Secondary outcomes measured the rates of technical and procedural success along with the rate of patients taking OAC and antiplatelet drugs through two years. Patient follow-up occurred at discharge, 1–3 months, six months, one year, and two years (±3months) post-procedure. A transesophageal echocardiography (TOE) was required per protocol at the 1–3- month visit. Patients not implanted were followed for seven days and then withdrawn per protocol. Antithrombotic medication and adverse events were assessed at each visit. The follow-up rate at two years was 94.2%, with 864 of the 917 expected two-year visits performed. The 40 patients who withdrew consent were followed for an average of 167± 210 days, while the 15 patients lost to follow-up were followed for an average of 743± 227 days. Major adverse events (≥ 7 days post-procedure) occurred in 4.0%, including death (0.3%), stroke (0.4%), major vascular (1.3%), and device embolization (0.2%). A total of 80.2% of patients were discharged on antiplatelet therapy alone. Peridevice flow was < 3mm in 98.4% at follow-up TOE. Device-related thrombus (DRT) was seen in 1.6% of cases. Cardiovascular death or ischemic stroke occurred in 8.7% of patients at two years. The ischemic stroke rate was 2.2% year, a 67% reduction compared to the CHA2DS2-VASc predicted rate. Major bleeding occurred at rates of 10.1% during the first year and 4.0% during the second year. Author noted limitations included that the study enrolled an all- comer population (not consecutive) and the lack of a control group. Additionally, although using CHA2DS2-VASc and HAS-BLED scores to compare observed to predicted event rates standard clinical practice, the methodology is imperfect. Finally, the current study only evaluated a single LAAO device, and results may not be applicable to other devices, in other patient populations, or with other post-implant antithrombotic medication regimens. Authors concluded that using the Amplatzer Amulet device during LAAO resulted in a reduction of the ischemic stroke rate by 67% compared to the predicted risk. Closure was complete in 98.4% of cases and DRT seen in only 1.6%. The Amulet occluder allows for prevention of AF-related thromboembolic events without the need for long-term OAC. No health disparities were identified by the investigators. Professional Societies/Organizations American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS): In 2019, the ACC/AHA/HRS published a focused update to the 2014 guideline for the management of patients with atrial fibrillation (AF). The 2019 focused update stated that a patient has an increased risk of stroke when the CHA2DS2-VASc score is 2 or greater in men or 3 or greater in women and included the following recommendation for percutaneous LAA occlusion (January, et al., 2019): Percutaneous LAA occlusion may be considered in patients with AF at increased risk of stroke who have contraindications to long-term anticoagulation. Oral anticoagulation remains the preferred therapy for most patients with AF and an increased risk of stroke. However, for patients who are poor candidates for long-term oral anticoagulation (because of the propensity for bleeding or poor drug tolerance or adherence), the Watchman device provides an alternative. Several unresolved issues remain, including the optimal patient selection and periprocedural antithrombotic regimen. Medical Coverage Policy: 0469 The guideline stated that percutaneous LAA occlusion with the Watchman device has been compared with warfarin in patients with AF (in the absence of moderate to severe mitral stenosis or a mechanical heart valve) at increased risk of stroke in two RCTs: the PROTECT AF (Reddy, et al., 2014) and the PREVAIL (Holmes, et al., 2014) trials. A meta-analysis combining data from these two trials and their registries demonstrated that patients receiving the device had significantly fewer hemorrhagic strokes than did those receiving warfarin, but there was an increase in ischemic strokes in the device group (Holmes, et al., 2015). However, when periprocedural events were excluded, the difference in ischemic strokes was not significant. The guideline stated that the current FDA labeling specifies that patients should be deemed suitable for anticoagulation and, in particular, a period of periprocedural anticoagulation. Patients unable to take oral anticoagulation were excluded from the Watchman RCTs. There is increasing experience outside the United States with LAA closure in oral anticoagulation–ineligible patients using an antiplatelet regimen only (ASAP study [ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology] Reddy, et al., 2013b; EWOLUTION study Boersma, et al., 2017); and this is the focus of an ongoing RCT The Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation (ASAP-TOO) (Holmes, et al., 2017). Society for Cardiovascular Angiography and Interventions (SCAI), Heart Rhythm Society (HRS) and American College of Cardiology (ACC): In 2023, the SCAI/HRS/ACC published an expert consensus statement on transcatheter left atrial appendage closure. The statement stated that transcatheter left atrial appendage closure (LAAC) is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk who are not suited for long-term oral anticoagulation and who have adequate life expectancy (minimum > 1 year) and quality of life to benefit from LAAC. Additionally, physicians performing LAAC should have a prior experience, including ≥ 50 prior left-sided ablations or structural procedures and ≥ 25 transseptal punctures (TSPs). The consensus statement recommended that interventional imaging physicians should have experience in guiding ≥ 25 TSPs before supporting any LAAC procedures independently. The consensus statement also stated that “combined procedures with LAAC (e.g., structural interventions, pulmonary vein isolation ablation) are not routinely recommended pending data from ongoing RCTs” (Saw, et al., 2023). Surgical closure of the LAA with other cardiac surgical procedures (CPT Code 33268): Surgical resection of the LAA was first proposed for patients with AF as a potential therapy to reduce mortality. For decades there was heterogeneity of surgical techniques for LAA closure with few well-conducted clinical studies. The two general approaches to surgical LAA closure are exclusion and excision. Exclusion can be performed with sutures from the endocardial or epicardial surface or with a stapler. Excision can be performed by stapled excision or removal and oversewing. Surgical ligation or amputation of the LAA is feasible without significant morbidity or mortality in patients with AF who are undergoing cardiac surgery with cardiopulmonary bypass for other indications. Surgical LAA occlusion is most performed in patients undergoing mitral valve or Maze surgery (Hijazi and Saw, 2023; Sarraf, et al., 2018; Price, et al., 2016; Masoudi, et al., 2015). U.S. Food and Drug Administration (FDA): The AtriClip LAA Exclusion System (AtriCure, Inc., West Chester, OH) received 510(k) approval in June 2010 (K093679). The indications for use state the AtriClip LAA Exclusion System is indicated for the occlusion of the left atrial appendage, under direct visualization, in conjunction with other open cardiac surgical procedures. The FDA 510(k) approval lists numerous predicate devices. The FDA 510(k) approval was based on the Exclusion of the Left Atrial Appendage with the AtriClip LAA Exclusion Device in Patients Medical Coverage Policy: 0469 Undergoing Concomitant Cardiac Surgery (EXCLUDE) clinical trial (ClinicalTrials.gov Identifier: NCT00779857). Additional modification approvals have been granted however the indicated use remains unchanged. Literature Review - Surgical closure of the LAA (CPT Code 33268): Epicardial LAA clipping has been approved by the U.S. Food and Drug Administration (FDA) and is increasingly being used to exclude the LAA in patients with AF undergoing cardiac surgery. The AtriClip™ device (AtriCure, Inc., West Chester, OH) is used during both open and thoracoscopic surgery, either as a stand- alone procedure or as part of a combined approach with other procedures, thoracoscopic ablation or staged catheter ablation. The AtriClip LAA Exclusion System consists of a single use, sterile, self-closing, implantable Clip preloaded on a Single Use Clip Applier, and a Selection Guide to aid in appropriate Clip size selection. The frame assembly of the implantable Clip consists of two springs connecting two opposing tubes which are covered with pressure pads. When closed, the Clip applies uniform pressure over the length of the Clip to ensure consistent, reproducible, and secure occlusion of the LAA (Toale, et al., 2019; FDA 2010). Randomized Controlled Trial: Gerdisch et al. (2022) conducted a randomized controlled trial (ATLAS) that evaluated the efficacy and safety of prophylactic left atrial appendage exclusion (LAAE) using an implantable clip device (AtriClip, AtriCure, Inc., Mason, OH, USA) during open cardiac surgery. Patients age ≥ 18 years, undergoing a structural heart procedure, with no preoperative AF, CHA2DS2-VASc ≥ 2 and HAS-BLED ≥2 were included in the study. Patients (n=562) were randomized 2:1 to LAAE (n=376) or no LAAE (n=186). LAAE was evaluated with intraoperative transesophageal echocardiography (TE). The primary efficacy endpoints measured (1) perioperative complications associated with the AtriClip placement, (2) intraoperative successful exclusion of the LAA, and (3) composite thromboembolic event rates between the group of patients diagnosed with POAF (through 365 days after the index procedure. LAAE success (no flow nor residual stump >10 mm) was 99%. One LAAE-related serious adverse event (0.27%) occurred and was resolved without sequelae. POAF developed during hospital stay in 47.3% of patients (178 of 376) in the LAAE arm compared to 38.2% of patients (71 of 186) in the no LAAE arm (p=0.047. Through one year, 3.4% of LAAE patients and 5.6% of no LAAE patients had TE. OAC was used by 32.5% of POAF patients. Bleeding was significantly higher with OAC than without (16.1% vs 5.4%, p=0.008). The study did enroll more men than women and the population studies was primarily White, and the results may not be applicable to other races or ethnic groups. The authors concluded that ATLAS demonstrated a high rate of successful LAAE with low LAAE-related serious adverse events in cardiac surgery patients. Whitlock et al. (2021) conducted the Left Atrial Appendage Occlusion Study (LAAOS III) which is a multicenter, randomized controlled trial that evaluated the efficacy and safety of concomitant left atrial appendage occlusion in participants with a history of atrial fibrillation undergoing cardiac surgery for another indication. The aim of the study was to determine whether concomitant occlusion would prevent ischemic stroke or systemic embolism in participants who continued to receive usual care, including anticoagulation. Included patients were aged 18 years or older who were scheduled to undergo cardiac surgery with cardiopulmonary bypass and had a history of atrial fibrillation and a score of at least 2 on the CHA2DS2-VASc scale. Patients were excluded if they were undergoing off-pump surgery, mechanical-valve implantation, heart transplantation, surgery for complex congenital heart disease, or isolated implantation of a left ventricular assist device. Additionally, patients with a previous surgery that involved opening the pericardium; and those who had previously undergone implantation of a left atrial appendage closure device were excluded. Patients were randomized to the occlusion group (n=2379) or the no-occlusion group (n=2391) left atrial appendage occlusion at the time of cardiac surgery for another indication. The primary outcome measured the first occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or noncerebral systemic embolism during follow-up. Strokes of undetermined cause were included as ischemic strokes in the primary analysis. Secondary Medical Coverage Policy: 0469 outcomes measured any stroke or noncerebral systemic embolism; ischemic stroke, noncerebral systemic embolism, or death from any cause; 30-day mortality; the volume of chest-tube drainage in the first 24 hours after surgery; re-exploration for bleeding within the first 48 hours after surgery; hospitalization for heart failure; myocardial infarction; and major bleeding. The mean duration of follow-up was 3.8 years, and follow-up was completed by 97.9% of the participants; 50 participants (1.1%) had withdrawn consent and 49 (1.0%) had been lost to follow-up. Ischemic stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group, which was clinically significant in favor of the occlusion group (p=0.001). There were no significant differences found between the groups in perioperative bleeding, heart failure or death. The cause of death was attributed to stroke in 1.3% of the trial participants. At hospital discharge, 83.4% of the participants in the occlusion group and 81.0% of those in the no-occlusion group were receiving oral anticoagulation, and the corresponding values were 79.6% and 78.9% at the 1-year visit and 75.3% and 78.2% at the 3- year visit, respectively. Death occurred in 538 participants in the occlusion group (22.6%) and in 537 (22.5%) in the no-occlusion group. Author noted limitations included the lack of information about the relative efficacy of left atrial appendage occlusion as compared with oral anticoagulation. Furthermore, the findings from LAAOS III apply primarily to surgical occlusion of the appendage performed as a concomitant procedure and not to stand-alone surgical or endovascular occlusion. Additionally, the study was unable to discern whether all surgical closure methods are comparable or examine whether occlusion was sustained over follow-up. The authors concluded that among patients with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. Nonrandomized Controlled Trials: Mahmood et al. (2020) reported the short-term outcomes of left atrial appendage (LAA) exclusion in patients with atrial fibrillation undergoing isolated coronary artery bypass graft surgery. The National Readmissions Database was queried for patients who underwent coronary artery bypass graft repair with and without LAA ligation. Only patients with a history of atrial fibrillation were included in the analysis. The primary outcome of the study was 30-day readmissions following discharge. Secondary outcomes were in-hospital mortality and stroke. Of a total of 253,287 patients undergoing coronary artery bypass graft surgery, 7.0% received LAA closure. LAA exclusion was associated with a greater risk of postoperative respiratory failure (8.2% versus 6.2%) and acute kidney injury (21.8% versus 18.5%), but it did not significantly change the rate of blood transfusions or occurrence of cardiac tamponade. LAA exclusion was associated with a nonsignificant reduction in stroke (7.9% versus 8.6%), no difference in in-hospital mortality (2.2% versus 2.2%), and a greater risk of 30-day readmission (16.0% versus 9.6%). A case series (n=291) by Caliskan et al. (2018) evaluated the safety, effectiveness, and durability of the Atriclip implanted in patients undergoing open heart surgery. Of these patients, 40 were included in the initial device trial and the remaining 251 were from a consecutive institutional registry. At a mean follow-up of 36 months (range 1-97 months), there were no device-related complications. Selected patients followed five years post-implant demonstrated complete LAA occlusion. Subgroup analysis of patients with discontinued anticoagulation revealed a relative risk reduction of 87.5% with an observed ischemic stroke-rate of 0.5/100 patient-years versus an expected rate of 4.0/100 patient-years in similar patients. Ailawadi et al. (2011) reported results of the multicenter Exclusion of Left Atrial Appendage with AtriClip Exclusion Device in Patients Undergoing Concomitant Cardiac Surgery (EXCLUDE) clinical trial (n=70). This nonrandomized, prospective multicenter trial was designed to assess the safety Medical Coverage Policy: 0469 and efficacy of the AtriClip. Patients undergoing elective cardiac surgery via median sternotomy with AF or a Congestive Heart Failure, Hypertension, Age > 75 Years, Diabetes Mellitus, Stroke score greater than 2 were eligible for concomitant AtriClip. Safety was assessed at 30 days, and efficacy of LAA exclusion was assessed at operation (by transesophageal echocardiography) and 3-month follow-up (by computed tomography angiography or transesophageal echocardiography). Patients (mean age, 73 years) undergoing open cardiac surgery were enrolled in the study. Intraprocedural successful LAA exclusion was confirmed in 67 of 70 patients (95.7%). Significant adverse events occurred in 34 of 70 patients (48.6%). There were no adverse events related to the device and no perioperative mortality. At 3-month follow-up, one patient died and 65 of 70 patients (92.9%) were available for assessment. Of the patients who underwent imaging, 60 of 61 patients (98.4%) had successful LAA exclusion by computed tomography angiography or transesophageal echocardiography imaging. Closure of the left atrial appendage as a standalone procedure: Standalone surgical LAA exclusion is being evaluated for patients with atrial fibrillation at increased risk of stroke who are not good candidates for oral anticoagulation. The evidence evaluating standalone surgical LAA exclusion is primarily in the form of retrospective reviews, prospective case series, observational studies, and review articles (Cartledge, et al., 2022; Wang, et al., 2021; Branzoli, et al., 2020; Franciulli, et al., 2020). In general, these studies have limitations such as small sample sizes and short-term follow-up that limit the generalizability of their results. Wang et al. (2021) conducted a prospective cohort study that assessed the safety and efficacy of minimally invasive thoracoscopic left atrial appendage occlusion compared to transcatheter left atrial appendage closure for stroke prevention in recurrent nonvalvular atrial fibrillation patients after radiofrequency ablation. Adults (n=209) age ≥ 18 years with recurrent atrial fibrillation after radiofrequency ablation and CHADS2 score ≥ 2 were included in the study. Patients were placed into two groups, the thoracoscopic LAA occlusion group (n=138) and the transcatheter LAA closure group (n=71). The thoracoscopic LAA group had the atrial appendages sutured with a modern stapler and the transcatheter LAA closure group received the WATCHMAN device. Patients were followed up by telephone or at the outpatient clinic at 1 week/45 days/3 months/6 months/12 months/twice annually after one year. Neurologic examinations were performed 12 months/once annually after one year. The efficacy outcomes measured the composite endpoint for stroke/SE and death and the composite endpoint for events from the 3rd month after surgery to the end of follow-up. Additionally, safety was measured using operation-related stroke and the differences in complications between the two groups. The study reported that the length of hospital stay in thoracoscopic LAA occlusion group was significantly longer than that in transcatheter LAA closure group (p<0.001). The two groups had similar nonsignificant results regarding the efficacy endpoints and the incidence of TIA/stroke (p=0.559; p=0.496, respectively). The incidence of bleeding in the thoracoscopic LAA occlusion group was significantly lower than that in the intervention group (p=0.022). The incidence of operative complications was 3/138 (2.17%) in thoracoscopic LAA occlusion group and 1/71 (1.41%) in transcatheter LAA closure group. Author noted limitations included the single-center study design and the type of local treatment to the LAA was chosen by the patient with a full explanation from the physician. Additional limitations included the small patient population, short term follow-up and the population only included patients in China and the results may not be applicable to other races or ethnic groups. The authors concluded that the groups had similar effects in preventing stroke. Thoracoscopic LAA occlusion has the advantage of low risk of bleeding, but it is accompanied by longer hospital stays. Randomized controlled studies with large patient populations and long-term follow-up are needed. No health disparities were identified by the investigators. Branzoli et al. (2020) conducted a prospective study that evaluated the safety and effectiveness of a standalone thoracoscopic exclusion of the LAA using an epicardial clip for stroke prevention in patients with permanent AF with an absolute contraindication to OAC. Patients (n=45) with non- Medical Coverage Policy: 0469 valvular atrial fibrillation (NVAF) and CHA2DS2 term OAC or at high risk of life BLED mean 4.9 ± 0.9 were included in the study. All patients were implanted with an LAA epicardial clip, guided by preoperative computed tomography (CT) and intraoperative transesophageal echocardiography (TEE). The thoracoscopic access was evaluated at 10 days and clinical evaluations were scheduled at two months, six months, and yearly thereafter, including electrocardiogram, laboratory workout, and physical examination. The Questionnaire for Verifying Stroke validated screening tool to identify the occurrence of neurological events occurrence. Clinical and ‐ CT/TEE follow up period: 16.4 ± 9.1months). There were not any procedure ‐ ‐ intraprocedural transesophageal echocardiography (TEE) showed complete LAA occlusion in all ‐ up of 16.4 ± 9.1 months (range, 2–34), with all patients off oral patients. At a mean follow anticoagulation (OAC), novel oral anticoagulation (NOAC) or antiplatelet therapy (APT), no ischemic stroke or hemorrhagic complications occurred. Computed tomography or TEE at follow demonstrated a correct LAA occlusion in all patients. Author noted limitations included the small ‐ patient population and limited follow-up. The authors concluded that thoracoscopic epicardial closure of the LAA with the AtriClip PRO2 device is a potentially safe and efficient treatment for stroke prevention in patients with NVAF contraindicated for anticoagulant therapy or APT. However, the effect of the therapy with regard to the reduction of ischemic stroke and hemorrhagic complications in the long populations with long-term follow-up are needed to evaluate efficacy, optimize protocols and outcomes. No health disparities were identified by the investigators. VASc of 6.5 ± 1.1 with contraindications to long threatening bleeding if on antiplatelet therapy (APT) with HAS ‐ ‐ Free Status (QVSFS) was used at each scheduled visit and the latest follow up as a ‐ up was complete for all 45 patients and ranged from 2–34 months (mean follow related complications and ‐ term should be evaluated. Further studies in large, diverse ‐ In a systematic review, Toale et al., (2019) assessed the safety and efficacy of the AtriClip device in patients with AF. Data including demographics, medical history intervention(s) performed, periprocedural outcomes and follow-up were assessed and analyzed. A total of 922 patients were identified in eleven studies. LAA occlusion was achieved in 902 out of 922 patients (97.8%). No device-related adverse events were reported across the studies. The reported incidence of stroke or transient ischemic attack post-clip placement ranged from 0.2 to 1.5/100 patient-years. Four hundred and seventy-seven of 798 patients (59.7%) had ceased anticoagulation on follow-up. Reported limitation of this study are that this review assesses data from several heterogeneous studies of differing design and methodology. Epicardial clipping was performed via several different approaches including open placement via sternotomy/minithoracotomy and thoracoscopic techniques. The approach to combined ablative procedures varied both within and across studies. Though some patients underwent epicardial clipping as part of a stand-alone procedure, others underwent ablation, epicardial maze or other operations for the management of AF. Postoperatively, the approach to anticoagulation was inconsistent across studies. Data regarding postprocedural stroke rates should be interpreted with caution, particularly as other potential embolic factors such as carotid stenosis were not recorded or adjusted for many included patients. Studies with long-term outcomes data comparing the safety and efficacy of epicardial clipping with established surgical and percutaneous methods of LAA closure are needed. Clear guidelines are needed regarding the need for postoperative anticoagulation in patient’s postepicardial clipping. The efficacy and safety of stand-alone thoracoscopic LAA appendectomy has not been established. Randomized controlled trials with larger patient populations and long-term follow-up are needed. Closure of a peridevice leak (PDL) after a left atrial appendage occlusion: The safety and efficacy of left atrial appendage occlusion using FDA approved devices has been established, however a complication that can occur at the time of implantation or during follow-up is a peridevice leak. The clinical consequences of PDL are unknown. Closure of the PDL using coils, plugs, and radiofrequency ablation techniques is being investigated, however there is insufficient evidence in the peer-reviewed literature that correcting the leak leads to better clinical outcomes Medical Coverage Policy: 0469 ‐ ‐ up opposed to OAC or observation (Alkhouli, et al., 2022; Dukkipati, et al., 2022; Della Rocca, et al., 2022; Piayda, et al., 2021; Sleiman, et al., 2021; Della Rocca, et al., 2020). Ledesma et al. (2021) analyzed the post-approval outcomes following left atrial appendage closure with the watchman device to determine the frequency and timing of adverse events. Within the 2,257 reports there were 3,652 adverse events reported. The study reported that the incidence of peridevice leaks was 0.2% (n=83). The size of the reported leaks ranged from 0.5 mm to 9.2 mm. Forty-three percent of the leaks were < 5 mm, 15% were 5 mm, 25% were > 5 mm with 17% not reporting leak size. Additionally, 22% patients with peridevice leak experienced stroke or TIA. Seventy-one (86%) peridevice leaks were managed conservatively. Six patients underwent cardiac surgery, four patients underwent percutaneous closure, one patient was managed with an embolization coil, and one underwent a second Watchman implant. No health disparities were identified by the investigators. U.S. Food and Drug Administration (FDA): The FDA label for post-procedure information issued on July 21, 2022 (P130013/S035) stated that “cessation of OAC therapy is at physician discretion provided that any leak demonstrated is ≤ 5 mm. If adequate seal is not demonstrated, subsequent OAC therapy cessation decisions are contingent on demonstrating leak is ≤ 5 mm.” Additionally, the FDA recommended that TEE imaging at 45 days and at 12 months be performed to assess the WATCHMAN FLX Device to confirm absence of intra-cardiac thrombus. To assess for leakage, a color Doppler assessment should be performed that includes the device/LAA border and to measure any residual leak around the device into the LAA. If there is evidence of leak > 5 mm, the FDA recommended to continue or restart anticoagulation therapy. Literature Review: Studies addressing the significance of PDL on clinical outcomes primarily include retrospective studies with inconsistent results. Alkhouli et al. (2022) used retrospective data from the LAAO registry and explored the association of a peridevice leak with adverse clinical events. A total of 51,333 patients were included in the study, of which 37,696 (73.4%) had no leak, 13,258 (25.8%) had small leaks, and 379 (0.7%) had large leaks. The authors reported that small (> 0–5 mm) leaks after LAAO were associated with a modestly higher incidence of thromboembolic and bleeding events; large leaks (> 5 mm) were not associated with adverse events, although higher proportions of these patients were maintained on anticoagulation. Additionally, there were no significant differences in adverse events between patients with large leaks and patients with small or no leaks. Dukkipati et al. (2022) used combined data two FDA randomized clinical trials (PROTECT-AF and PREVAIL) and 1 FDA nonrandomized prospective registry (CAP2). All patients in this study were implanted with the Watchman 2.5 percutaneous LAA closure device and underwent protocol mandated. TEE at 45 days and 1 year after device implantation. Outcomes of the patients with PDL ≤ 5 (n=404) was compared to patients without PDL (n=634). The presence of PDL ≤ 5 at one year, but not at 45 days, was associated with an increased five-year risk of ischemic stroke or systemic embolism (p=0.014), largely driven by an increase in non-disabling stroke (p=0.04), while disabling or fatal stroke rates were similar (p=0.56) between groups. The authors concluded that a PDL ≤ 5 was not associated with an increased risk of cardiovascular or unexplained death (p=0.45) or all-cause death (p=0.42) however, have twice the risk of ischemic stroke or systemic embolism at five years. Further studies are needed to determine the prevalence of peridevice leak and adverse events. Piayda et al. (2021) reported the results from a multi-center, retrospective registry that assessed the safety and feasibility of peridevice leakage closure after LAAO. Patients (n=95; n=104 leaks closed) treated with PDL closure irrespective of the initial percutaneous LAAO device were included in the analysis. Detachable coils were the most frequent approach (42.3%), followed by the use of Amplatzer™ Vascular Plug II (Abbott, Chicago, IL, 29.8%) and the Amplatzer™ Duct Occluder II (Abbott, Chicago, IL, 17.3%). PDL closure was 100% with 94.2% of devices placed successfully within the first attempt. There were no major complications requiring surgical or transcatheter Medical Coverage Policy: 0469 interventions. During follow-up (median f/u 96 days), persistent leaks were found in 18 patients (18.9%), yielding a functional success rate of 82.7%, although PDLs were significantly reduced in size. There were not any patients that had a leak > 5mm. Major adverse events during follow-up occurred in five patients (2 ischemic strokes, 2 intracranial hemorrhages, and 1 major gastrointestinal bleeding). The authors concluded that several interventional techniques have become available to achieve PDL closure. They are associated with high technical and functional success and low complication rates. Improved clinical outcomes were not reported. No health disparities were identified by the investigators. Della Rocca et al. (2020) conducted a prospective, non-randomized trial that reported on the feasibility and efficacy of transcatheter leak closure with detachable coils in patients with incomplete left atrial appendage (LAA) closure. Patients (n=30) with high thromboembolic risk and clinically relevant residual leaks underwent percutaneous closure of the LAA patency using embolization coils. Transesophageal echocardiography was performed at 60 ± 15 days post- procedure. The complication rate was 6.1%. After a median follow-up period of 54 days, transesophageal echocardiography revealed complete LAA sealing or small residual leaks in 28 patients and moderate residual leaks in two patients (6.7%). The authors concluded that transcatheter LAA leak occlusion using endovascular coils appears to be a safe, effective, and promising approach in patients at high risk with incomplete LAA closure. Improved clinical outcomes were not reported. No health disparities were identified by the investigators. The studies are limited by study design, small patient population and short-term follow-up. Clinical trials are currently underway. Future studies should address whether closure of persistent peridevice leaks reduces the risk of subsequent ischemic stroke and improves clinical outcomes when compared to OAC or observation. Professional Societies/Organizations American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS): The ACC/AHA/HRS published a joint guideline for the management of patients with atrial fibrillation (AF) (January, et al., 2014). In 2019 a focused update to the 2014 guideline included the following recommendation for cardiac surgery LAA occlusion/excision (January, et al., 2019): surgical occlusion of the LAA may be considered in patients with AF undergoing cardiac surgery, as a component of an overall heart team approach to the management of AF American Heart Association (AHA)/American Stroke Association (ASA): Joint guidelines from these organizations for the primary prevention of stroke included the following recommendations regarding LAA closure which are based on data derived from a single randomized trial or nonrandomized studies (Meschia, et al., 2014): closure of the LAA may be considered for high-risk patients with AF who are deemed unsuitable for anticoagulation performed at a center with low rates of periprocedural complications • the patient can tolerate the risk of at least 45 days of post-procedural anticoagulation Society for Cardiovascular Angiography and Interventions (SCAI), Heart Rhythm Society (HRS) and American College of Cardiology (ACC): In 2023, the SCAI/HRS/ACC published an expert consensus statement on transcatheter left atrial appendage closure. In 2023, the SCAI/HRS/ACC published an expert consensus statement on transcatheter left atrial appendage closure. The statement referenced peridevice leaks (PDLs) and stated that the clinical impact and management of PDLs are not fully understood and at the time of implantation all efforts should be made to minimize leaks (Saw, et al., 2023). Medical Coverage Policy: 0469 Society of Thoracic Surgeons (STS): The STS published clinical practice guidelines for the surgical treatment of atrial fibrillation (Badhwar, et al., 2017) that addressed left atrial appendage excision or exclusion in the section on additional considerations for surgical ablation therapy. The STS recommendation stated that it is reasonable to perform left atrial appendage excision or exclusion in conjunction with surgical ablation for AF for longitudinal thromboembolic morbidity prevention (limited evidence). Maze and Related Procedures Surgical techniques for the treatment of AF can be broadly categorized into open heart procedures such as the “cut-and-sew” and/or the Cox-Maze procedure performed on a non-beating heart and the minimally invasive procedures that use epicardial radiofrequency ablation, a thoracoscopic or mediastinal approach, and hybrid/convergent catheter ablations/open surgical procedures which are generally performed on the beating heart. In the open-heart approach, access to the chest is made via a large incision down the sternum. The Cox-Maze procedure is generally performed in conjunction with valvular or coronary artery bypass graft surgery. Minimally invasive surgical procedures are sometimes referred to as “mini-Maze” procedures, but the 2012 consensus statement from the Heart Rhythm Society recommends that the phrase “maze” procedure only be used to describe the biatrial lesion set of the Cox-Maze procedure. The statement recommends that less extensive lesion sets be referred to as a surgical AF ablation procedure. The minimally invasive approach involves several small keyhole incisions in the intercostal spaces on either side of the chest cavity to allow entry of several devices, including a surgical camera used to guide the procedure and an energy source for ablation (Je, et al., 2015; Stulak, et al., 2014; Calkins et al., 2012). Surgical Maze Procedure: The surgical maze procedure was introduced in 1987. The initial two iterations were associated with high rates of pacemaker implantation and are no longer performed. The third version (Cox maze III) became the standard surgical procedure to restore sinus rhythm in patients with AF but is not widely performed because of surgeons' reluctance to perform this complicated “cut and sew” atrial lines of ablation operation approach in association with valve or coronary artery bypass procedures or as a stand-alone procedure. The Cox maze IV operation is less invasive, using radiofrequency or cryoablation to replicate surgical lines of ablation (January, et al., 2014). U.S. Food and Drug Administration (FDA): The Maze procedures are not subject to regulation by the FDA. Any medical devices, drugs, biologics, or tests used as a part of this procedure may be subject to FDA regulation. Literature Review: The peer-reviewed medical literature includes both relatively large retrospective and prospective studies documenting the safety and efficacy of the surgical Maze procedure performed during cardiopulmonary bypass with or without concomitant cardiac surgery. Study results suggest that the Maze procedure adds little or no additional risk when performed simultaneously with other open-heart surgeries such as valvular repair or replacement. The Maze III procedure was used most often; however, several studies reported modifications to this procedure, such as use of cryoprobes or thermal probes for creation of ablation lines. Outcome measures in the studies vary. Some studies measure atrial function, primarily using echocardiography. Duration of follow-up in the studies is highly variable; some studies report outcomes after several months, while others follow patients for several years. Most studies do not describe ongoing medical therapies; thus, it is not possible to determine whether patients were still receiving antiarrhythmic medications or anticoagulants postoperatively (Phan, et al., 2014a; Phan et al., 2014b; Stulak, et al., 2014; Johansson, et al., 2014; Yanagawa, et al., 2013; Ad, et al., 2013; Albåge, et al., 2013; Saint, et al., 2013; Melby, et al., 2013; Okada, et al., 2013; Albrecht, et al., 2009; Doty, et al., 2007). Medical Coverage Policy: 0469 Minimally Invasive Off Pump Maze Procedures: Despite its high success rate, the surgical Maze procedure has not been widely adopted other than for patients undergoing cardiac surgery because of the need for cardiopulmonary bypass. Surgical techniques for treating AF have evolved over the past 20 years, with the introduction of minimally invasive approaches. Numerous minimally invasive off-pump Maze procedures including hybrid or convergent ablation procedures are being investigated to treat atrial fibrillation (AF). While minimally invasive surgical procedures have the advantage of minimal surgical dissection and accelerated recovery, limitations include the inability to map and isolate the source of AF and the necessity of transmural ablation lines, which can be difficult to achieve due to varying thickness of cardiac tissue. Any approach to surgical ablation carries risk of serious complications, including phrenic nerve palsy, coronary artery injury, and esophageal perforation. Literature Review Evidence in the peer-reviewed, published scientific literature is insufficient to allow strong conclusions in terms of safety and long-term efficacy of minimally invasive approaches for the treatment of AF including hybrid or convergent ablation procedures. Published evidence evaluating these minimally invasive procedures is primarily in the form of single center retrospective or prospective case series with few controlled clinical trials. Generally, the outcomes of the studies demonstrate improvement in AF following ablation. However, comparison between clinical studies is difficult and limited by heterogeneous study populations, use of different lesion sets and energy sources, differences in type of designs and lack of standardized outcome measures and definitions of success. Follow-up time varies across studies as well as definition of procedure success used to assess clinical outcomes. Furthermore, there is no clear consensus among authors regarding patient selection criteria. Further scientific research, involving well-designed controlled clinical trials with long-term net health outcome data, are still needed to clearly define and establish a role for minimally invasive off-pump Maze procedures for the treatment of AF. The data are insufficient to reach conclusions about the relative effectiveness of these procedures compared to the classic surgical Maze procedure for the treatment of AF or to catheter-based ablation (Maclean, et al., 2020; Khan, et al., 2020; Luo, et al., 2019; Pearman, et al., 2017; Pison, et al., 2014; Ismail, et al., 2014; Kurfirst, et al., 2014; Lawrance, et al., 2014b; La Meir, et al., 2013a; Gehi, et al., 2013; La Meir, et al., 2012; Boersma, et al., 2012; Kasirajan, et al., 2012; Edgerton, et al., 2009, 2010. van der Heijden et al. (2023) conducted a randomized controlled trial that evaluated the effectiveness and safety of hybrid ablation compared to repeat catheter ablation in patients with persistent atrial fibrillation (persAF). Patients, (n=41) > age 18 years with symptomatic (long- standing)-persAF refractory to one or more class I or III antiarrhythmic drugs and no prior (catheter) ablation were included in the study. Patients were randomized to hybrid ablation (n=19) or catheter ablation (n=22). The primary effectiveness outcome measured freedom from any recurrent supraventricular tachyarrhythmia off anti-arrhythmic drugs (AADs), lasting ≥ 5 minutes at 12 months. The secondary effectiveness outcome measured freedom from any recurrent supraventricular tachyarrhythmia off AADs lasting ≥ 30 seconds at 12-month follow-up. Additional outcomes measured the freedom from AAD use, the number of arrhythmia-related re- hospitalizations, and reinterventions such as cardioversions and redo catheter ablations. Changes in quality of life (QOL) were also measured. The primary safety outcome measured major adverse events and complications that occurred within 12 months of follow-up. Secondary safety outcomes measured the total number of serious adverse events. Patients in the HA group received closure of the LAA either using AtriClip (n=17) or the Lariat closure device (n=2). In the CA group, transvenous PVI and the box lesion were created in all patients. Freedom from any recurrent supraventricular tachyarrhythmia off anti-arrhythmic drugs lasting ≥ 30 seconds or ≥ 5 minutes was significantly higher in the HA group compared with the CA group (89% vs 41%, p=0.002; 95% vs 41%, p<0.001, respectively). It was more likely for the HA group compared to the CA Medical Coverage Policy: 0469 group to receive AADs until three months after the procedure but more patients in the HA group were off AADs after 1 year (95% vs 36%, p=0.005). No significant differences were reported between the groups in the number of major adverse events, minor complications, QOL and AF related symptoms. Lastly, median procedure time and length of hospital stay were significantly longer in the HA group, whereas the exposure to radiation dose and time were significantly higher in the CA group. An author noted limitation was that all procedures were conducted in a single, highly specialized center with experienced cardiac surgeons and electrophysiologists, which decreases the generalizability and external validity of the results. Additionally, the authors noted that the study was not double-blinded and the rate of patients in sinus rhythm at one year might be overrated. Limitations also included the small sample size; short-term follow-up and the study was done in the Netherlands and results may not be applicable to other races or ethnic groups. Further studies in large, diverse populations with long-term follow-up are needed to evaluate efficacy, optimize protocols and outcomes. Doll et al. (2023) conducted a prospective, multi-center, randomized controlled trial (CEASE-AF) that evaluated if hybrid epicardial-endocardial ablation (HA) would have superior effectiveness when compared to catheter ablation (CA), including repeat (rCA), in persistent and longstanding persistent atrial fibrillation (PersAF/LSPAF). Nine hospitals in Poland, Czech Republic, Germany, United Kingdom, and the Netherlands enrolled patients aged 18–75 with symptomatic, drug refractory PersAF and left atrial diameter (LAD) > 4.0 cm or symptomatic LSPAF; and had failed at least one class I or III anti-arrhythmic drugs (AAD). The primary effectiveness outcome measured the freedom from documented AF/atrial flutter (AFL)/atrial tachycardia (AT) episodes >30 s through the 12-months follow-up visits in the absence of Class I or III AADs except for AADs at doses not exceeding previously failed doses. The safety outcome measured the major complications that occurred during the study. Patients (n=154) were randomized (2:1) to either HA (n=102) or CA (n=52). The HA first stage (index procedure) included endoscopic epicardial ablation where pulmonary veins (PV) and left posterior atrial wall were isolated and the left atrial appendage was excluded. Endocardial touch-up ablation was performed 91–180 days post-index procedure. Endocardial CA was performed using current RF catheter technology, PVI was mandatory during the index procedure. Additional ablation strategies were in accordance with current guidelines. Follow-up visits occurred at 3- and 6-months after the first ablation (T0), then 6- and 12-months after T0; to allow for staged endocardial ablation in the HA arm or repeat endocardial ablation in the CA arm. The freedom from documented AF/atrial flutter (AFL)/atrial tachycardia (AT) episodes >30 s through the 12-months was statistically significant in HA when compared to CA (71.6% vs 39.2%, 95% CI 14.3%–48.0%, p<0.001). Major complications through 30-days after index procedures plus 30-days after second stage/rCA were similar between groups, and not statistically significant (HA: 7.8% vs CA: 5.8%, p=0.75). Procedure duration was significantly longer with HA compared to CA (p<0.001). Fluoroscopy time was significantly lower with HA compared to CA (p=0.001). The authors noted the following limitations: all patients in the HA arm had LAA management but the effectiveness LAA exclusion was not evaluated, the different overall number of procedures differs between HA and CA and symptom-driven ECG monitoring was performed at unscheduled visits, which could have underestimated actual failure rates in both arms. Additional limitations included that the study was conducted in specific countries limiting generalizability to other ethnicities, the small sample size and short-term follow-up. Further studies in large, diverse populations with long-term follow-up are needed to evaluate efficacy, optimize protocols and outcomes. DeLurgio et al. (2020) conducted a multicenter, randomized controlled trial (CONVERGE) that evaluated the effectiveness of the combined hybrid epicardial and endocardial ablation (Hybrid Convergent) for the treatment of persistent and long-standing persistent AF with endocardial catheter ablation. Adults 18–80 years, with symptomatic persistent AF that was refractory or intolerant to at least one class I/III antiarrhythmic drug (AAD) and had a left atrium size of ≤ 6.0 cm. There was no limitation on duration of AF. Patients (n=153) were randomized 2:1 to the Medical Coverage Policy: 0469 Hybrid Convergent group (n=101) or the catheter ablation group (n=51). In-person follow-up visits were performed at seven days, one, three, six, and 12 months and included an electrogram and review of medications and adverse events. The trial also included an in-person longer-term follow-up visit at 18 months and phone follow-up at two, three, four, and five years. A total of 96% patients in the Hybrid Convergent group and 98% in the catheter ablation group completed the 12-month visit. Six- and 12-month Holter data were available for 97.1% and 96.1% patients in the Hybrid Convergent group, and 100% and 98% patients in the catheter ablation group. Hybrid Convergent had significant improvement in persistent and long-standing atrial fibrillation (p=0.036) and success off antiarrhythmic drugs (p=0.0128) when compared to catheter ablation. At 18 months using 7-day Holter, 74.0% Hybrid Convergent and 55% CA patients experienced ≥ 90% AF burden reduction, which was clinically significant (p=0.0395) in favor of the Hybrid Convergent group. A total of 2.9% patients had primary safety events within seven days, and 4.9% between eight and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved. Author noted limitations included: the absence of empirical endocardial posterior wall ablation in the catheter ablation group; only using irrigated radiofrequency catheters for endocardial ablation in both groups; cryoablation was not included and electrical isolation or exclusion of LAA was not performed. Additional limitations included small patient population, unequal randomization and short-term follow-up. No health disparities were identified by the investigators. In 2022 DeLurgio et al. evaluated the safety and effectiveness of HC vs CA in the longstanding persistent atrial fibrillation (LSPAF) subgroup from the CONVERGE trial, which is described in detail above. The primary outcome measured freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety outcome measured major adverse events through 30 days with HC. Secondary effectiveness outcomes measured (1) percent of patients achieving ≥ 90% AF burden reduction vs baseline and (2) AF freedom. Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Freedom from AF, AFL, or AT without a new or increased dose of previously failed AAD was significantly higher at 12 and 18 months in the HC arm compared to catheter ablation arm (p=0.022, p=0.006, respectively). Freedom from AF, AFL, or AT off class I or III AADs was significantly higher in the HC arm compared to CA arm at 12 and 18 months 12 months (p=0.031; p=0.038, respectively). In LSPAF patients, the MAE rate in the HA arm was 7.9%, which included 1 cardiac tamponade, 1 stroke, and 1 phrenic nerve injury. No MAEs occurred in the catheter ablation arm. Author noted limitations include the post hoc nature of the analysis and small population size of the subgroups. The authors noted that the data should be interpreted with caution because CIs and P values were not adjusted for multiplicity. Lastly, patients were randomized 2:1 to hybrid convergent and catheter ablation arms, but randomization was not stratified by baseline AF subtype. Haldar et al. (2020) conducted a randomized controlled trial that evaluated if thoracoscopic surgical ablation (SA) is superior to catheter ablation (CA) as a first-line procedure in long- standing persistent atrial ablation (LSPAF), refractory or intolerant to at least one AAD (CASA-AF study). Adults (n=120) with symptomatic LSPAF, European Heart Rhythm Association EHRA symptom score > 2, left ventricular ejection fraction > 40%, referred for treatment and suitable for both procedures were included in the study. Patients were randomized to SA (n=60) or CA (n= 60), five patients withdrew consent post-randomization in the SA arm and were excluded from analyses. Study treatment was received by 115 patients of whom 110 completed all follow-up visits. In the SA group, six patients crossed over to CA due to lung or cardiac adhesions precluding access for SA and two patients had incomplete lesion sets due to adverse anatomical features: one patient did not have the left pulmonary vein (PV) isolated nor the LAA excluded, and the other did not have LAA exclusion. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary measured outcome was freedom from AF/atrial tachycardia (AT) > 30 s without anti-arrhythmic drugs at 12 months. Secondary measured outcomes included clinical Medical Coverage Policy: 0469 success (> 75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients’ symptoms and quality-of-life scores; and cost-effectiveness. The authors concluded that SA was significantly more expensive (p<0.01) and provided significantly fewer quality- adjusted life-years (QALYs) compared with CA (p=0.02). The reduction in AF/AT burden >75% was recorded in 67% (36/54) vs. 77% (46/60) (p=0.3) in SA and CA groups, respectively. Procedure-related adverse events rate over the 12-month follow-up period was greater in the SA than the CA arm: 40% (22/55) vs. 15% (9/60) p=0.003]. There were not any significant differences in freedom from AF/AT (p=0.83), procedure-related serious adverse events within 30 days of intervention (p=0.46), 12-month follow-up period procedure-related serious adverse events (p=0.65). One death was reported after SA. The authors noted that the main limitation of this study was that the interventions were performed in four highly specialized centers in the UK, which may have an impact on the generalizability of results. Additionally, the study was not double-blinded and thoracoscopic AF ablation which includes LAA exclusion may reduce stroke and bleeding risks. The study also had a small patient population with short term follow-up. The authors concluded that single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. No health disparities were identified by the investigators. Professional Societies/Organizations The American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Rhythm Society (HRS): In 2014, the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Rhythm Society (HRS) published an updated guideline which supersede the 2011 focused updates and the 2006 guidelines for the management of patients with atrial fibrillation (January, et al., 2014). In 2019, the ACC/AHA/HRS published a focused update of the 2014 guideline. These guidelines did not provide recommendations regarding the use of minimally invasive maze procedures for treatment of AF. The surgical or minimally invasive maze procedures were not included in the 2019 focused update (January, et al., 2019). The following recommendations for surgical maze procedures are included in the 2014 guideline: An AF surgical ablation procedure is reasonable for selected patients with AF undergoing cardiac surgery for other indications. A stand-alone AF surgical ablation procedure may be reasonable for selected patients with highly symptomatic AF not well managed with other approaches.