Table of Contents
EDITORIAL
Year : 2016  |  Volume : 1  |  Issue : 3  |  Page : 4-8

In-depth analysis of confusion and argument focusing on left atrial appendage closure


1 Department of Interventional Cardiology, Helmut-G.-Walther Klinikum, The Second Hospital, Lichtenfels, Germany
2 Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
3 Department of Cardiology, No. 2 Hospital, Jilin University, Changchun, China

Date of Web Publication26-Dec-2018

Correspondence Address:
Jiangtao Yu
Department of Interventional Cardiology, Helmut-G.-Walter Klinikum, The Second Hospital, Lichtenfels
Germany
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2470-7511.248351

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  Abstract 


Left atrial appendage closure (LAAC) technology has been developing over 10 years from its research and development to routine clinical application and has acquired solid evidence-based support through the Protection in Patients with Atrial Fibrillation, PREVAIL, and other registered studies. However, this technology still faces misinterpretation and confusion over its concept and acceptance as a universal clinical application. In this review, we try to provide an in-depth analysis of current perceptions and arguments focused on LAAC from its concept, operation, and other important issues.

Keywords: Atrial fibrillation, left atrial appendage closure, stroke, thrombus


How to cite this article:
Yu J, Jiang L, Xue X. In-depth analysis of confusion and argument focusing on left atrial appendage closure. Cardiol Plus 2016;1:4-8

How to cite this URL:
Yu J, Jiang L, Xue X. In-depth analysis of confusion and argument focusing on left atrial appendage closure. Cardiol Plus [serial online] 2016 [cited 2021 Mar 2];1:4-8. Available from: https://www.cardiologyplus.org/text.asp?2016/1/3/4/248351




  Introduction Top


Contemporary cardiology is one of the fastest growing clinical disciplines today. Interventional cardiology is the core and soul of cardiology. Apart from the well-developed percutaneous coronary interventions, the new emerging noncoronary interventions, including transcatheter aortic valve implantation (TAVI), MitraClip, and left atrial appendage closure (LAAC), have rapidly developed to maturity through repeated explorations and clinical practice. Especially, in Germany, the newly-advanced technologies referenced above have been widely used in the routine treatment of thousands of patients, which benefit patients greatly by improving and extending the quality of their lives.

LAAC technology has been developing over 10 years from research and development to routine clinical application. According to openly published multicenter international clinical trials and evidence-based practices, this technology, and its related devices received European CE certification in 2009. At present, at least 6 LAAC devices are available in Europe, which consist of the routinely-used Boston Scientific's Watchman system, St. Jude Medical's ACP/Amulet system, Coherex Medical's WaveCrest system with CE-mark, but no peer-reviewed reports of outcomes, and newly-added devices such as Lifetech's Lambre occluder from China and Occlutech's occlude in Germany, approved by Europe CE Mark in July, 2016. Today, emerging technology continues to develop and improve LAAC devices.

As of this writing, over 20,000 patients around the world have received LAAC using a variety of occluders; over 15,000 patients received Watchman device. Percutaneous LAAC and related devices have been approved in clinical use by national drug and device administration authorities in more than 50 countries worldwide. Evidence strongly suggests the time for the use of LAAC as a routine clinical practice has arrived.

Any novel technology in interventional cardiology, from its emergence as a concept to universal clinical application, is subject to misunderstanding and confusion. Only by clarifying the misunderstanding and confusion, can a new technology be universally implemented widely and safely. LAAC is no exception. In this paper, we analyze the confusion and arguments associated with LAAC from its concept, operation, and other related issues of critical importance.


  Conception Top


Recognition of the left atrial appendage closure

As a newly-emerging technology, a process is needed to transition LAAC from awareness to acceptance then standard practice. Safety and efficacy must be evaluated for any new clinical technology to be considered successful. There are accumulating evidence-based studies to establish the short-and medium-term effectiveness of LAAC,[1] which include international multicenter randomized controlled studies, and prospective and retrospective registration evidence. Strong evidence was demonstrated by the PROTECTion in Patients with Atrial Fibrillation (PROTECT-AF) randomized controlled clinical trial which reported 2-year follow-up results suggesting the efficacy of LAAC is not inferior to warfarin.[2] In 2014, the PROTECT-AF study published the 3.8-year follow-up results in the Journal of the American Medical Association,[3] which revealed revolutionary evidence that LAAC reduced all-cause mortality in patients by 34% when compared to warfarin. Device development and improvements combined with patient recovery and treatment success improved the LAAC procedure success rate from 90% in the initial exploration stage to 98% in recent standardized operations. Furthermore, perioperative safety has also improved significantly as evidenced in a marked decrease in the rate of severe adverse events during perioperation from 8.7% in the PROTECT-AF study to 2.7% in the recent EWOLUTION REgistry on WATCHMAN Outcomes in Real-Life Utilization study.[4] Overall, LAAC technology is widely recognized as safe and effective has become one of the most promising trends in interventional cardiology worldwide. Only through active open-minded study and an in-depth understanding of LAAC technology can we refresh our theoretical and practical understanding of current and emerging therapeutic strategies in atrial fibrillation.

Indications

In August 2012, LAAC was included for the first time as a general guideline for atrial fibrillation treatment by the European Society of Cardiology Atrial Fibrillation Working Group. This guideline was based primarily on the 2-year follow-up results of the PROTECT-AF clinical trial. At that time, however, the PREVAIL study[5] and the 3.8-year results of the PROTECT-AF study[3] had not been widely announced. According to the ESC guideline in 2012, the indication of LAAC was confined to patients for whom long-term oral anticoagulant was contraindicated.[6] Due to a lack of clear evidence-based proof, these patients had no treatment alternative except LAAC. Consequently, these patients were impossible to enroll into a randomized controlled trial. After the guideline on LAAC in 2012, and with other evidence-based proofs still accumulating, it is reasonable to suggest that international associations should elevate the recommendation level in future guidelines on LAAC. From a clinical viewpoint, patients with atrial fibrillation should be prevented from a thrombotic event, especially stroke. Regarding indications for LAAC, we, therefore, hold that the categories of absolute and relative be considered. Absolute indications include contraindications for long-term oral anticoagulant or with a history of bleeding or severe bleeding tendency with a HAS-BLED score ≥3. Relative indications include renal insufficiency, hepatic dysfunction, refusing anticoagulant medication, poor medication compliance, and lack of monitoring oral anticoagulant; however, the number of such patients in this category is considerable and might gradually become the majority receiving LAAC.

Each patient with atrial fibrillation should be educated to understand the primary concept of LAAC, a recognition of the danger of thrombotic events induced by atrial fibrillation, and all available strategies to prevent thrombosis. To achieve the aim of preventing thrombosis, physicians should introduce LAAC technology objectively to patients and their relatives to make them fully understand its efficacy and safety and to provide them with the optimal treatment options. Although many methods, including radiofrequency ablation, rhythm control and anticoagulation, are used to treat atrial fibrillation, nowadays, there is no single treatment to remedy all underlying problems. Under these circumstances, LAAC technology can be provided to patients individually, which is an important option for them. In the well-known PROTECT-AF and the PREVAIL studies, the inclusion criteria are relatively broad, which offers new options for the majority of patients with atrial fibrillation. With the continuing exploration and development of evidence-based medicine studies, it is reasonable to believe that LAAC's indications will be broadened as other interventional technologies are used.

Role of the left atrial appendage closure in the treatment of atrial fibrillation

In clinical practice, the treatment of atrial fibrillation is divided into three major categories: (1) prevention of thrombotic events, especially stroke, (2) rhythm or heart rate control, and (3) treatment of heart failure. In our opinion, when considering treatment options for atrial fibrillation, saving and prolonging life and preventing death are the highest priorities followed by addressing a patient's rhythm or heart rate, and treatment of heart failure, which are long-term processes requiring ongoing management. Since thrombotic events can lead to death in a very short time, the core treatment in atrial fibrillation should be the prevention of thrombotic events with emphasis on stroke. As a new emerging technology, LAAC is a late arrival compared to other methods. However, LAAC's superiority to warfarin in the prevention of thrombotic events combined with technological advances, its status in the treatment of atrial fibrillation has become elevated. According to the 3.8-year follow-up results in the PROTECT AF study, LAAC reduced the all-cause mortality by 34% in comparison with warfarin. In addition to a decreased incidence of stroke, from a clinical perspective LAAC can address the challenge of prolonged life versus death to some extent, so it becomes critical to elevate the status of LAAC in the treatment of atrial fibrillation.

Relationship between left atrial appendage closure technology and catheter ablation

Currently, LAAC attracts resistance from some individual catheter ablation doctors and debates from academia. Regarding the treatment of atrial fibrillation, the goals between LAAC and catheter ablation are inconsistent. The former aims at preventing thrombotic events, especially stroke, while the latter focuses on symptomatic relief. Optimal treatment of atrial fibrillation requires a complementary approach that incorporates both strategies instead of distinctly separate ones. Accordingly, some international heart centers have recently tried a one-stop strategy to treat atrial fibrillation using a combination of LAAC and catheter ablation,[7],[8] which appears to be the approach but is fraught by multiple constraints. In Europe, for example, a one-stop strategy as described above was implemented but had little success. To the best of our knowledge, LAAC has at least five constraints: (1) Costs. Regarding the expensive cost of LAAC or catheter ablation, a tremendous economic burden would be placed on the patient and insurance company if all patients with atrial fibrillation were to receive the one-stop strategy. Even in European countries with adequate health insurance programs, it is impossible to cover all patient costs. (2) Success rate of radiofrequency ablation. Unlike paroxysmal atrial fibrillation with a high success rate of radiofrequency ablation, the success rate in chronic atrial fibrillation is still not high, which remains a big concern. In other words, in this patient cohort, is catheter ablation worthwhile? (3) Anticoagulant therapy cannot be replaced with catheter ablation. It is well-known that catheter ablation may partially relieve the symptoms in patients, but not solve the thrombotic problems. Consequently, there are no recommendations to prevent thrombotic events with catheter ablation in current clinical guidelines. (4) Avoid excessive use of clinical technology. According to the health insurance policy in Germany, a one-stop strategy to treat atrial fibrillation using LAAC and catheter ablation is not approved unless the patient undergoes a special application process or has the procedure performed separately. (5) Mechanism of atrial fibrillation. Clarifying the mechanism of atrial fibrillation is no easy task. Although some superior therapeutic effects can be achieved via a variety of interventional techniques, including the freezing of balloon ablation, we are still in a stage of exploration.

There is an ongoing need for in-depth clinical investigations on the successful prevention and treatment of atrial fibrillation. As a result, we recommend only patients with paroxysmal atrial fibrillation who have commercial or private health insurance be considered for the one-stop strategy with catheter ablation plus LAAC. As for the majority of patients with atrial fibrillation, the optimal therapy should consist of prevention of thrombotic events with LAAC in combination with rhythm or heart rate control with affordable medicine, which we hold as the most economical and effective strategy for the integrated administration of atrial fibrillation.

Comparison of different types of left atrial appendage closure occluders

As of this writing, there are two major categories of LAAC occluders on the market: (1) “built-in” occluder, for example, WATCHMAN and Occlutech, and (2) “cover-out” occluder, for example, ACP and Lambre. Of the occluders available, the WATCHMAN device has overwhelming advantages compared to other occluders using evidence-based proof. Up to now, the WATCHMAN occluder has the most extensive clinical application with over 15,000 cases worldwide. It is quality and efficacy have received wide recognition based on international multicenter randomized controlled studies, and prospective or retrospective registration evidence. Consequently, WATCHMAN is the only LAAC device approved by the US Food and Drug Administration. A built-in occlude-like WATCHMAN has a many advantages, including: (1) fast endothelialization, (2) a smaller surface area than other cover-out occluders, (3) has no effect on adjacent structures, for example, pulmonary vein, and (4) easy placement without anatomical limitations including the ostial level and form of left atrial appendage. That said, it is difficult to place the built-in occluder when the diameter of the opening is much larger than its depth, even when the anatomy of the left atrial appendage is rare. Although the cover-out occluder is easy to place, and less dependent on the depth of the left atrial appendage, it raises concern for how to minimize the effect on the adjacent structures, and how to facilitate the endothelialization of occluder surface when placed in the obvious rugged LAA opening. These concerns require further in-depth exploration. Although no head-to-head comparisons among the LAA occluders are available, evidence-based studies are expected in the future.

Cost-effectiveness of the left atrial appendage closure

Recently, several studies compare the cost-effectiveness of LAAC with the traditional anticoagulant warfarin and new oral anticoagulants (NOACs).[9],[10] The results indicate the cost of LAAC operation is equal to 10 years of warfarin or <5 year of NOACs. However, this result was made under the assumption that patients had no occurrence of bleeding complications while taking anticoagulants. Taking into account current trends in the market economy, the cost of LAAC devices will gradually decrease as the cost-effectiveness of LAAC will continually increase. Summarily, LAAC in the treatment of atrial fibrillation will have socioeconomic significance in developed and especially developing countries.


  Operation Top


The physician and the team

LAAC is one of the most challenging and complicated technologies in interventional cardiology. During the LAAC procedure, the physician is required to keep a mind of “walking on a wire.”

Only with this philosophy can he/she perform the procedure safely and successfully. Due to the wall of the left atrial appendage is very weak, and its structure is diverse and complex, patient safety must be closely monitored while performing the LAAC procedure. To learn and master the LAAC technology, a trainee must receive hands-on instruction from a skilled physician. Instruction must include a comprehensive series of study, observation, and hands-on experience as a surgeon's assistant during the procedure. Training is also critical for the echocardiologist, cath laboratory nurses, and anesthesiologists. In addition to in-depth knowledge and experience, the physician must possess strong characteristics such as leadership, professionalism, conscientiousness, creativity, courage, and perseverance on behalf of his/her patients. He/she must be viewed as someone known to be highly knowledgeable in their field and in command when performing the LAAC procedure. In addition, all staff must engage in team building activities to maintain the overall synergy.

The interval between LAAC procedures should never exceed 2–3 weeks because a physician's acuity and manual dexterity will weaken if his/her skills are not maintained. Adhering to regular surgery schedule will ensure the skill level does not diminish and the team can remain responsive, integrated, highly functional and harmonious. Who can perform the LAAC surgical procedure? Although cardiac electrophysiologists have practical knowledge and skill in atrial septal puncture, percutaneous coronary intervention physicians and structural heart disease interventional physicians can also quickly learn and master the technology after rigorous training. The operation of LAAC is not always performed by cardiac electrophysiology physicians. In Germany, 30% of cardiac electrophysiologists and 70% of noncardiac electrophysiology physicians perform the LAAC procedure. Depending on the department or country, other well-trained cardiovascular interventional physicians can also perform the LAAC procedure. In fact, as a noncoronary intervention technology, the operation of LAAC can be performed by all well-trained cardiac physicians who embrace this technology. In summary, a highly skilled LAAC physician should have at least the following five attributes: (1) commitment to LAAC technology; (2) dedication to ongoing LAAC training; (3) ingenuity; (4) a positive and confident mindset; and (5) excellent team building skills.

During the LAAC procedure, patient safety is critical whether administering intravenous sedation or endotracheal intubation anesthesia. To the best of our knowledge, endotracheal intubation anesthesia can keep patients in absolute inactivity when releasing the LAA occlude. This method is considered much safer and recommended when a patient's health is vulnerable as a result of advanced age, respiratory insufficiency, heart failure, or when the physician lacks the experience to address the advanced complications that might occur. Under these circumstances, patients can rest under anesthesia during the operation, or under endotracheal intubation anesthesia, also known for its high level of safety when local conditions are available. However, some physician holds transesophageal echocardiography (TEE) is unnecessary during the LAAC procedure. It is our belief that TEE is beyond the scope of the standard operation. After years of practice with a large number of cases, we hold the escort of TEE is critical to the quality of the procedure and for patient safety.(Note: In one incident, a patient treated at our hospital required a full dose of Heparin. Although spontaneous intracardiac thrombosis still occurred, it was detected early with TEE which averted a severe adverse event.

Transseptal puncture

Correct transseptal puncture is key to the success of LAAC. Without the escort of TEE, the transseptal puncture needle will generally fall into the oval fossa. From the location of the oval fossa, however, it is difficult to make the delivery sheath into the left atrial appendage, and also difficult to manipulate the closure device due to lack of coaxiality with the work axis. In normal procedures, transseptal puncture is recommended using the escort of TEE. When selecting the puncture location, it is also recommended to avoid the oval fossa area and select the middle region and posterior partial as the puncture site. Doing so not only greatly reduces blindness and improves patient safety during the transseptal puncture but also ensures the delivery sheath into the left atrial appendage and its coaxiality.


  Transesophageal Echocardiography and Cardiac Computed Tomography Top


TEE has numerous real-time, dynamic, noninvasive, and high-resolution characteristics.[11] Accordingly, the escort of TEE plays a primary role in the whole LAAC process and cannot be substituted by other measures such as cardiac computed tomography (CT), magnetic resonance imaging (MRI), transthoracic ultrasound, etc. Unlike TEE, cardiac CT is used only as an alternative measure due to disadvantages such as the contrast needed, high radiation, and low ability to detect the left atrial appendage thrombi.[12],[13]


  Other Problems Top


The decompression and endocrine function of the left atrial appendage

This is one of the problems often queried in LAAC, and in our opinion, a supposition that cannot be supported currently by evidence-based medicine.[14] In the condition of sinus rhythm with a normal contraction of the atrium, the left atrial appendage can decompress the pressure of the left atrial. However, when atrial fibrillation occurs, the left atrial appendage can no longer release pressure. Conversely, thrombosis can easily occur similar to sand deposits developing in a reservoir. Fortunately, this adverse effect can be eliminated by LAAC. The atrial myocardial cell has endocrine function; however, the left atrial appendage is only a small part of the left atrium. Even when occluded by LAAC, the endocrine function of the left atrium is not obviously affected. Furthermore, LAAC only closes the cavity, which leaves the myocardial cells undamaged. Theoretically, LAAC has no effect on the endocrine function. Currently, there are no large-scale data to prove the serious effect of LAAC on the endocrine function. Even with limited negative influence on the function of decompression and endocrine in LAAC, it is less important than the prevention of thrombotic events. Can LAAC substitute for oral anticoagulation therapy? Can LAAC reduce the incidence of thrombosis and hemorrhagic complications? The answers to these questions are critical. From a macro perspective, LAAC has few long-term adverse effects due to a lack of proven clinic evidence.

Postinterventional medicine therapy

There is no expert consensus about the postinterventional medicine therapy of LAAC. However, in numerous multicenter, random control clinical trials, patients received strict post-interventional anticoagulation therapy. Postinterventional anticoagulation can be divided into two phases: (1) 45 days after LAAC during the process of rapid endothelialization when it is reasonable to add effective anticoagulants, such as warfarin and NOACs, to avoid the formation of thrombus on the surface of the device. If a patient experiences bleeding events while taking warfarin and NOACs, or is at high risk of bleeding, Heparin subcutaneous injection should be considered as an alternative therapy, and (2) after 45 days patients should receive a TEE examination to exclude thrombus on the surface of the device. If no thrombus is detected, anticoagulation therapy should be changed to dual antiplatelet therapy including aspirin (100 mg/days) and clopidogrel (75 mg/days). Six months after the operation, Clopidogrel resistance should be monitored by a second TEE examination to exclude the potential for late-occurring thrombus. When appropriate, a lifetime dosage of 100 mg/days aspirin is recommended to prevent cardiovascular complications.

In this review, we attempt to clarify some of the ongoing confusion and arguments from three aspects on LAAC (recognition, operation, and other questions). Ongoing discussions will likely stimulate further explorations. We recommend to physicians who are confident with and committed to LAAC to: (1) Understand this revolutionary and subversive technology, (2) help popularize LAAC technology, (3) ensure the ongoing normalization and safety of LAAC, and (4) continue benefitting patients suffering from atrial fibrillation.

Financial support and sponsorship

Nil.

Conflicts of interest

Dr. Yu has research donation or travel expense reimbursement of the following companies received in the last 12 months: Abbott, Avidal, BBraun, Biotronic, Boston Scientific, Daiichi-Sankyo, Lifetech, Symetis.



 
  References Top

1.
Yu J, Guan S, Huemmer H, Cheng F, Halmàgyi L, Muenzel M, et al. Percutaneous left atrial appendage closure in patients with non-valvular atrial fibrillation with Watchman® left atrial appendage device: Single center experience and results up to three years follow-up. J Am Coll Cardiol 2015;66:8297.  Back to cited text no. 1
    
2.
Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (Watchman left atrial appendage system for embolic protection in patients with atrial fibrillation) trial. Circulation 2013;127:720-9.  Back to cited text no. 2
    
3.
Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: A randomized clinical trial. JAMA 2014;312:1988-98.  Back to cited text no. 3
    
4.
Boersma LV, Schmidt B, Betts TR, Sievert H, Tamburino C, Teiger E, et al. Implant success and safety of left atrial appendage closure with the WATCHMAN device: Peri-procedural outcomes from the EWOLUTION registry. Eur Heart J 2016;37:2465-74.  Back to cited text no. 4
    
5.
Holmes DR Jr., Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. J Am Coll Cardiol 2014;64:1-12.  Back to cited text no. 5
    
6.
Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: An update of the 2010 ESC guidelines for the management of atrial fibrillation – Developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385-413.  Back to cited text no. 6
    
7.
Calvo N, Salterain N, Arguedas H, Macias A, Esteban A, García de Yébenes M, et al. Combined catheter ablation and left atrial appendage closure as a hybrid procedure for the treatment of atrial fibrillation. Europace 2015;17:1533-40.  Back to cited text no. 7
    
8.
Patel MR, Biviano AB. Atrial fibrillation ablation and left appendage closure in heart failure patients. Curr Opin Cardiol 2015;30:259-66.  Back to cited text no. 8
    
9.
Amorosi SL, Armstrong S, Da Deppo L, Garfield S, Stein K. The budget impact of left atrial appendage closure compared with adjusted-dose warfarin and dabigatran etexilate for stroke prevention in atrial fibrillation. Europace 2014;16:1131-6.  Back to cited text no. 9
    
10.
Reddy VY, Akehurst RL, Armstrong SO, Amorosi SL, Beard SM, Holmes DR Jr., et al. Time to cost-effectiveness following stroke reduction strategies in AF: Warfarin versus NOACs versus LAA closure. J Am Coll Cardiol 2015;66:2728-39.  Back to cited text no. 10
    
11.
Saw J, Fahmy P, Spencer R, Prakash R, McLaughlin P, Nicolaou S, et al. Comparing measurements of CT angiography, TEE, and fluoroscopy of the left atrial appendage for percutaneous closure. J Cardiovasc Electrophysiol 2016;27:414-22.  Back to cited text no. 11
    
12.
Wang Y, Di Biase L, Horton RP, Nguyen T, Morhanty P, Natale A, et al. Left atrial appendage studied by computed tomography to help planning for appendage closure device placement. J Cardiovasc Electrophysiol 2010;21:973-82.  Back to cited text no. 12
    
13.
Ismail TF, Panikker S, Markides V, Foran JP, Padley S, Rubens MB, et al. CT imaging for left atrial appendage closure: A review and pictorial essay. J Cardiovasc Comput Tomogr 2015;9:89-102.  Back to cited text no. 13
    
14.
Regazzoli D, Ancona F, Trevisi N, Guarracini F, Radinovic A, Oppizzi M, et al. Left atrial appendage: Physiology, pathology, and role as a therapeutic target. Biomed Res Int 2015;2015:205013.  Back to cited text no. 14
    



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