Author + information
- Received April 27, 2015
- Revision received August 6, 2015
- Accepted August 27, 2015
- Published online December 1, 2015.
- Horst Sievert, MD∗∗ (, )
- Abdi Rasekh, MD†,‡,
- Kryzstof Bartus, MD, PhD§,
- Remo L. Morelli, MD‖,
- Qizhi Fang, MD¶,
- Jonas Kuropka, MD∗,
- Duong Le, MD‖,
- Sameer Gafoor, MD∗,
- Luisa Heuer, MD∗,
- Payam Safavi-Naeini, MD†,‡,
- Trisha F. Hue, PhD#,
- Gregory M. Marcus, MD¶,
- Nitish Badhwar, MD¶,
- Ali Massumi, MD†,‡ and
- Randall J. Lee, MD, PhD¶∗∗ ()
- ∗CardioVascular Center Frankfurt CVC, Frankfurt, Germany
- †St. Luke’s Hospital, Houston, Texas
- ‡Texas Heart Institute, Baylor College of Medicine, Houston, Texas
- §Department of Cardiovascular Surgery and Transplantology, Jagiellonian University, John Paul II Hospital, Krakow, Poland
- ‖St. Mary’s Hospital, San Francisco, California
- ¶Department of Medicine and Cardiovascular Research Center, University of California, San Francisco, California
- #San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco, California
Objectives This study sought to assess long-term clinical outcomes in adults with nonvalvular atrial fibrillation (AF) who are ineligible for oral anticoagulation therapy and underwent left atrial appendage (LAA) ligation with the Lariat device.
Background LAA exclusion has been used to prevent thrombus formation within the LAA in AF patients and is believed to decrease the risk of cardioembolic events.
Methods LAA ligation with the Lariat device was performed in 139 patients with nonvalvular AF. LAA closure was verified during the procedure by LA angiography and transesophageal echocardiography. A follow-up transesophageal echocardiography was performed at 30 to 45 days post-procedure. After the procedure, patients received aspirin only, clopidogrel only, aspirin plus clopidogrel, or no antithrombotic drugs. Patients did not receive transition oral anticoagulation therapy post-LAA ligation. Patients were followed for LAA closure and adverse events, including stroke, systemic events, and death.
Results Acute closure was accomplished in 138 of 139 treated patients (99%). In 1 patient, a posterior lobe was partially closed. At the day-30 to day-45 transesophageal echocardiography (n = 127), 114 (90%) had complete LAA closure, and 13 (10%) had a 2- to 4-mm leak. There were no leaks ≥5 mm. The periprocedural adverse event rate was 11.5%, including 2 cardiac perforations and 1 death due to pulmonary embolus. Over a mean follow-up of 2.9 ± 1.1 years, the event rate for the composite endpoint of stroke and systemic embolism was 1.0% per year (n = 4). The combined stroke, embolism, and death of any cause event rate was 2.8% (n = 11) per year.
Conclusions The findings from this analysis of post-procedure event rates suggest that LAA ligation with the Lariat device effectively closes the LAA and may be a beneficial approach to reduce the risk of embolic events in AF patients ineligible to oral anticoagulation therapy. However, future randomized clinical trials are needed to verify these results and to determine device and procedural safety.
Atrial fibrillation (AF) is the most common arrhythmia in the world, with an estimated prevalence of 3 million in the United States (1,2). AF is associated with a significant, increased risk of morbidity and mortality associated with a 5-fold increase in the frequency of stroke (1). The risk of embolic stroke in the general population increases with age, and in people over the age of 75 years, AF is among the most important causes of embolic stroke (2).
Currently, chronic oral anticoagulation (OAC) treatment is the most frequently used prophylactic approach in patients with AF at high risk of thromboembolic events (3,4). However, as many as 20% of patients with AF cannot take OAC therapy (5–7), and the risk of bleeding events while on OAC therapy can lead to increased death and disability (8–10). Although the newer OAC medications have been shown to be either noninferior or superior to warfarin therapy with equivalent or decreased bleeding events (11–16), there remains a yearly 2% to 3% incidence of major bleeding (11–16). These OAC-contraindicated patients have limited or no options (17–19) and present a significant health care problem should a cardioembolic stroke occur (20,21).
The Watchman device results from PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF), the CAP (Continued Access PROTECT AF) registry, and long-term follow-up from Protect AF demonstrate that exclusion of the LAA is noninferior to warfarin therapy, can be implanted into the LAA with reasonable safety, and has mortality benefits when compared with warfarin therapy (22–24). However, in the United States, the Watchman device for LAA exclusion requires OAC therapy for at least 45 days to prevent thrombus formation on the device (22). Therefore, use of the implantable LAA exclusion devices would not mitigate the risk of bleeding in patients with contraindications to OAC therapy.
The Lariat suture delivery device (SentreHeart, Inc., Redwood City, California) is a percutaneous endocardial/epicardial approach for LAA exclusion (25,26). The LAA ligation approach with the Lariat suture delivery device provides a potential alternative to AF patients at high risk of thromboembolic events that have contraindications to OAC therapy. The present study assessed safety, long-term clinical efficacy of stroke prevention, and death.
This prospective multicenter observational study includes 5 clinical sites: CardioVascular Center Frankfurt CVC (Frankfurt, Germany), St. Luke’s Hospital (Houston, Texas), John Paul II Hospital (Krakow, Poland), St. Mary’s Hospital (San Francisco, California), and the University of California, San Francisco (San Francisco, California). All participants provided written informed consent, and the protocol was approved by the institutional review board of each institution. Study objectives were as follows: 1) to determine the effectiveness of LAA closure with the Lariat device; 2) to assess procedural and 30-day periprocedural safety; and 3) to obtain long-term clinical follow-up.
Pre-specified 30-day periprocedural adverse events included the following: 1) bleeding requiring transfusion; 2) cardiac perforation; 3) cardiac tamponade; 4) cerebrovascular accident; 4) chest pain/discomfort; 5) death; 6) device breakage; 7) inability to remove device; 8) infection; 9) myocardial infarction; 10) pericardial effusion; 11) pericarditis lasting >2 days; 12) pleural effusion; 13) pneumothorax/hemothorax; 14) pulmonary edema; 15) pulmonary embolism; 16) renal failure requiring renal replacement therapy; 17) stroke—ischemic; 18) stroke—hemorrhagic; 19) systemic embolism; 20) transesophageal echocardiography (TEE) complication; 21) thrombosis; 22) transient ischemic attack; 23) vascular damage; 24) vascular access complications; 25) ventricular fibrillation; and 26) ventricular tachycardia.
Defined composite clinical endpoints include the following: 1) stroke and systemic embolism; and 2) stroke, systemic embolism, and death of any cause. Adverse events and clinical endpoints were self-reported and adjudicated by the principal investigator of each institution, then reviewed with a principal investigator of another institution. Two sites were new institutions with no previous experience with the Lariat procedure. Another site had performed <10 Lariat cases before enrolling its first patient. The other 2 institutions had performed >20 Lariat cases before enrolling its first patient.
Men and women 45 to 90 years of age with nonvalvular AF and long-term ineligibility for OAC therapy were approached, screened, and enrolled between March 1, 2009 and November 30, 2012. Patients were enrolled in the study only if they consented to the Lariat procedure and fulfilled both the inclusion and exclusion criteria.
Study patients met all of the following inclusion criteria: 1) age 18 years or older; 2) nonvalvular AF; 3) at least 1 risk factor of embolic stroke (CHADS2 [Congestive Heart Failure History, Hypertension History, Age ≥75 Years, Diabetes Mellitus History, Stroke or Transient Ischemic Attack Symptoms Previously] ≥1); 4) ineligible for long-term OAC therapy; and 5) a life expectancy of at least 1 year. The pre-specified criteria for ineligibility for long-term OAC therapy included the following: 1) previous hemorrhagic stroke or intracranial bleeding in the absence of reversible cause and/or while on appropriate OAC therapy; 2) other bleeding events (e.g., diffuse bleeding gastrointestinal, genitourinary bleeding, epitasis, hemoptysis, bleeding into joints) without available treatment for the underlying cause; 3) history of syncope or falls resulting in cranial or facial fracture and with sufficiently high clinical suspicion of recurrence that the risks of OAC would outweigh the benefits; 4) blood dyscrasia (e.g., thrombocytopenia, anemia) without available treatment for the underlying cause; 5) previous OAC therapy has been demonstrated to be unsuitable and its use has been discontinued by the patient’s treating physician (e.g., for poor anticoagulant control, nonbleeding intolerance, allergy, need for other treatments that may interact with OAC); and 6) cerebral aneurysm at high risk for bleed that cannot be surgically corrected.
Patients were excluded from the study if they met any of the following exclusion criteria: 1) history of pericarditis; 2) history of cardiac surgery; 3) pectus excavatum; 4) myocardial infarction within 3 months; 5) previous embolic event within the past 30 days; 6) New York Heart Association class IV heart failure symptoms; 7) left ventricular function <30%; and 8) thoracic radiation. Patients meeting the criteria for the study enrollment underwent a screening contrast cardiac computed tomography (CT) scan. Additional exclusion criteria based on LAA anatomy included the following: 1) an LAA width >40 mm; 2) a superiorly oriented LAA with the LAA apex directed behind the pulmonary trunk; 3) bilobed LAA or multilobed LAA in which lobes were oriented in different planes exceeding 40 mm; or 4) a posteriorly rotated heart.
Percutaneous suture ligation of LAA
LAA ligation using the Lariat suture delivery device and accessories has been described previously (25,26). Briefly, patients were prepped and draped with sterile preparation of the subxyphoid and bilateral groin regions. Once the patient was anesthetized, a TEE was performed to rule out LAA thrombus. Pericardial access using a 17-gauge Pajunk needle (Norcross, Georgia) was performed as previously described (25,26). Once epicardial access was obtained, serial dilation of the pericardial access was performed to allow placement of the epicardial sheath. Transseptal catheterization was performed with TEE guidance. Five to 10 thousand units of heparin were administered intravenously once the transseptal catheterization was completed with an activated clotting time level maintained at >250 s. The EndoCath balloon catheter (SentreHeart) was back-loaded onto the endocardial magnet-tipped guidewire and inserted into the transseptal sheath. The endocardial magnet-tipped guidewire was positioned into the most anterior lobe of the LAA. The epicardial sheath was then used to advance the epicardial magnet-tipped guidewire and connect to the endocardial magnet-tipped guidewire. The Lariat snare device was advanced through the epicardial sheath over the epicardial guidewire to the base of the LAA. From the endocardial side, the EndoCath balloon was positioned to identify the LAA os. The snare was closed, and verification of complete capture of the LAA at the LAA os was made with TEE and LA angiography. After releasing the tightened suture, verification of LAA closure was made with color Doppler flow and LA angiography. Successful closure of the LAA was defined as complete capture of all LAA lobes, absence of a contrast leak on left LA angiogram, and ≤1-mm jet as visualized by color Doppler on TEE. A pericardial drain was left in the pericardial space overnight.
Follow-up TEE was performed between 30 and 45 days post-procedure and read by an independent echosonographer at each center. If a leak >3 mm was noted on the follow-up TEE, a repeat TEE was performed between 6 and 12 months post-LAA ligation. Patients were followed by phone at 1 month, at outpatient appointments between 3 and 6 months, and then annually by either clinic or phone visits. Additionally, patients were monitored by their referring physicians within 1 month of the procedure and then as needed. Patients were treated post-procedure with aspirin (ASA) only, clopidogrel only, the combination of ASA and clopidogrel, or no antithrombotic therapy. The decision to expand, extend, or stop therapy based on the follow-up TEE was left to the implanting physician. No patients received transition OAC therapy post-LAA ligation. Patients were specifically followed for adverse events, including incidence of ischemic/hemorrhagic stroke, stroke of undefined etiology, systemic embolism, cardiovascular related deaths, and deaths of any cause.
Incidence density rates were calculated using person-time, beginning at the date of the LAA ligation procedure attempt and ending at the date of first outcome event (e.g., stroke, systemic embolism, or death due to any cause), date of subsequent LAA occlusion device procedure (if applicable), or date of last contact.
A total of 143 patients were enrolled in the study. Baseline characteristics are shown in Table 1. The mean age was 67.4 ± 10.8 years, with men comprising 61% (n = 85) of the study participants. The mean CHADS2 score was 2.4 ± 1.2. The mean CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age ≥75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 75 Years, Sex Category) score was 3.6 ± 1.8. The mean HAS-BLED (Hypertension, Abnormal Renal and Live Function, Stroke, Bleeding Labile International Normalized Ratio, Elderly, Drugs or Alcohol) score was 2.8 ± 1.2. Post-procedure LAA ligation antithrombotic regiment included ASA (n = 83, 60%), clopidogrel (n = 3, 2%), ASA plus clopidogrel (n = 9, 6%), or no therapy (n = 44, 32%).
Of 143 patients, 139 (97%) completed the LAA ligation procedure (Figure 1). Capture of the LAA with the Lariat suture delivery device was not attempted in 4 patients due to pericardial adhesions precluding pericardial access. These 4 patients did not have any history of pericarditis or evidence of adhesions by transthoracic echocardiography or CT. Successful LAA closure was achieved in 138 of 139 patients attempted (99%). A single patient had incomplete closure related to a multilobed LAA in which a posterior lobe was only partially closed. One hundred and twenty-seven of 139 patients (91%) had a 30- to 45-day follow-up TEE, and the other 12 patients refused the follow-up TEE. At that follow-up TEE, 114 of 127 patients (90%) exhibited complete closure (≤1 mm leak), and 13 of 127 patients (10%) had a 2- to 4-mm leak. Four patients had leaks of 4 mm. There were no leaks ≥5 mm.
Adverse events occurring within the first 30 days of the LAA ligation procedure are reported in Table 2. There were no LAA perforations or lacerations attributed to the Lariat suture delivery device, endocardial balloon catheter, or the magnet-tipped guidewires. There were 16 periprocedural adverse events (11.5%). Five adverse events (3.6%) required additional corrective interventions. Two patients required surgery due to right ventricle (RV) perforation/laceration. In 1 of the 2 patients, the guidewire in the pericardial space was kinked, and continued attempted advancement of the dilator resulted in the RV perforation. In the other patient requiring surgery, a straight 8-F sheath was left in the pericardial space for drainage, resulting in perforation of the RV when the patient moved from a supine to a seated position. One patient had a post-procedure pericardial effusion requiring reinsertion of a pericardial drain but did not require surgical intervention. One patient developed a late pericardial effusion 1 week after LAA closure requiring pericardial drainage. Another patient developed a pleural effusion 1 week after LAA ligation; pleuracentesis removed 300 cc of serous fluid, and there was no clinical evidence of subsequent recurrence. One patient died 1 day post-procedure due to a pulmonary embolus confirmed by transthoracic echocardiography with acute dilation of the RV and increased pulmonary arterial pressures by color flow Doppler. Another patient with chronic obstructive pulmonary disease was difficult to wean from ventilation, resulting in a prolonged hospitalization. The mean length of hospital stay was 3.5 ± 2.8 days with 1 day being the shortest hospital stay and 16 days being the longest hospital stay. Procedural complications occurred after all the sites had performed at least 6 cases.
Chest pain, as expected, occurred in all patients as a result of the drain left in the pericardial space during recovery. However, chest pain was resolved within 2 days after drain removal, except in 8 patients (5.8%). These 8 patients were treated for pericarditis with colchicine and nonsteroidal anti-inflammatory drugs until resolution of their symptoms. During the follow-up TEE at 45 days, a thrombus was detected in 2 patients. The patients received OAC therapy to resolve the thrombus. Neither of these patients had leaks, nor did they have a stroke or evidence of a thromboembolism during follow-up. No procedure-related adverse events were observed >30 days post-procedure.
The total patient population was followed for a total of 405.5 person-years with a mean follow-up of 2.9 ± 1.1 years. The stroke, systemic embolism, and death rates are shown in Table 2. Of the 4 patients with incident stroke or systemic embolism, 2 exhibited evidence of a cardioembolic stroke based on head CT. One patient with a confirmed embolic stroke had partial closure of his LAA (the patient with a multilobed LAA). The other 2 patients sustaining a stroke had head CT consistent with either small vessel disease or a hemorrhagic stroke. Three of the 4 strokes occurred within the first year after the procedure, with the fourth stroke occurring at 16 months post-procedure (Figure 2). Two of the 4 patients that initially had a residual leak of 4 mm underwent closure of the leaks with an Amplatzer plug II (St. Jude Medical, St. Paul, Minnesota) (at 7 months and 15 months, respectively). Neither of these 2 patients had a stroke or systemic embolism event. The patients continue to be followed in the study, but follow-up times for endpoint analysis in these patients were censored at 7 and 15 months, respectively.
There were 7 total deaths during follow-up, including 1 periprocedure death due to pulmonary embolus; the remaining 6 deaths were unrelated to the procedure as determined by the clinical site investigator and reviewed by another investigator. Of those 6 deaths, 2 were cardiovascular-related deaths due to end-stage heart failure and complications associated with left ventricular assist device implantation (215 days post-procedure), and the other was a cardiac arrest during a hospitalization for existing comorbidities (812 days post-procedure). Other causes of death included sepsis associated with pulmonary disease, death 6 months after an embolic stroke, death associated with multiple existing comorbidities, and 1 is unknown. The proportion of surviving patients is shown in Figure 2.
A comparison of the mean CHADS2 score from the National Registry of AF (27,28) with the mean CHADS2 score of our patient population of 2.4 would predict an annualized stroke rate of 6.2% (Figure 3). A mean CHA2DS2-VASc score of 3.6 would predict an annualized stroke rate of approximately 4%. The stroke and systemic embolism rate of 1.0% per year in this Lariat population would represent an 84% reduction in risk.
The present study supports the notion that exclusion of the LAA in patients with AF who are at risk of stroke prevents thrombus formation within the LAA with subsequent reduction of expected cardioembolic events. The event rate for stroke and systemic embolism was 1% per year, whereas the composite event rate for stroke, systemic embolism, and death of any cause was 2.8% per year. This study is consistent with previous studies with LAA occlusion devices or OAC therapy, demonstrating estimated reduction in stroke in nonvalvular AF patients (13,15,22,29,30).
A unique feature of this study is that patients were not treated with OAC therapy following LAA ligation with the Lariat device. The clinical implication of this observation is that LAA ligation presents a potential therapy for patients with a contraindication to OAC. The low long-term composite event rates of stroke of any cause and systemic embolism are encouraging, supporting the study of the Lariat device for LAA exclusion in patients with true contraindications to OAC. Patients with contraindications to OAC are an undertreated group of patients who represent an unmet clinical need. Most of the recent studies (11–14) on novel OAC excluded patients with significant bleeding events. The majority of the Watchman LAA occlusion device trials required transition to OAC therapy post-device implantation with the exception of the ASAP (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology) study (31), which demonstrated a 77% reduction in the expected stroke rate in patients implanted with the Watchman device when treated with aspirin and clopidogrel or ticlopidine for 6 months. Patients were followed for a mean of 14.4 months. The European registry data of the Amplatzer Cardiac Plug device predominantly used antiplatelet agents following LAA occlusion and demonstrated a 58% reduction in the expected stroke rate with an average follow-up of 13 months (30). The combined results presented in this study and the results from ASAP study and the European registry data of the Amplatzer Cardiac Plug device suggest the benefit of LAA occlusion in contraindicated patients. However, none of the studies were prospective randomized studies. Additionally, long-term follow-up is needed to assess for late cardioembolic events that can occur >1 year post-implantation as described in the long-term follow-up data from the PREVAIL (Prospective Randomized Evaluation of the Watchman LAAC Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy) trial (32).
Successful complete closure of the LAA was performed in 99% of patients in which Lariat suture deployment was attempted. One patient had an unsuccessful closure with a partially closed posterior lobe; an embolic event occurred in this patient. The observation of an embolic event occurring in the patient with incomplete closure of the entire LAA is consistent with surgical literature of an increased risk of cardioembolic events noted with partial closures of the LAA (33–35); this highlights the need to ascertain complete capture of all LAA lobes before releasing the suture from the snare. Thrombus formation following LAA ligation was seen in 2 patients (1.4%) at the site of LAA closure, but thrombus formation did not lead to any cardioembolic events. Thrombus formation most likely is due to the ischemia-related inflammatory response associated with LAA ligation. In a recent anatomic analysis of the LAA after ligation, there was atrophy of the LAA and evidence of scarring at the site of ligation (36). The initial inflammatory response inherently causes endothelial cell injury at the site of closure, providing the environment for platelet aggregation and thrombus formation. The 1.4% rate of thrombus formation is consistent with other studies reporting thrombus formation between 1.2% and 2.0% with LAA ligation using the Lariat device (25,37,38). In a nationwide survey, the majority of thrombus formation (79%) following LAA ligation with the Lariat device occurs within the first 3 months (38). Although the incidence of thrombus formation and the incidence of stroke is low after 1 year (25,38), a 12-month follow-up TEE in addition to a TEE between 45 and 90 days should be considered. The incidence of thrombus formation seen with the Lariat device is consistent with LAA occlusion devices reporting thrombus formation in 4% to 7% of patients (22,29,30). Future studies are needed to determine the duration of OAC needed once such a thrombus is observed.
Leaks following LAA ligation were seen in 10% of patients. LAA leaks following LAA ligation with the Lariat device are centrally located in contrast to eccentric leaks associated with LAA implant devices and have been reported not to be associated with embolic events (39). The concentrically located leaks with LAA ligation may make leaks more conducive to closure with vascular plugs or with atrial septal defect closure devices (40,41). Because the published surgical reports suggest that partial closure of the LAA is associated with increased risk of cardioembolic events, 2 of the 4-mm leaks were closed with the Amplatzer Vascular Plug II at the discretion of the physician. LAA leaks were not associated with embolic events, but the sample size is too small to make definitive conclusions. Although a recent comparison study of leaks associated with the Lariat and Watchman devices did not demonstrate a relationship between leaks and cardioembolic events, future prospective studies are needed to determine the significance of leaks and cardioembolic events with the Lariat device. Leaks may occur due to incomplete closure of the snare and/or the suture being released on a large amount of tissue. A leak may result due to the loop of the suture remaining a fixed diameter while the tissue thins from tissue atrophy or remodeling, resulting in slippage of the suture loop.
The finding that stroke of any cause and death occurred mainly in the first year is consistent with other interventional trials in which there are early events and evidence of benefits only after long-term follow-up (22,31,42). The early event rates for both stroke and death also highlight the need to properly select patients without comorbidities that may contribute to early mortality. Our adverse events were limited to procedural complications and symptoms attributed to inflammation rather than device-related complications. The 2 patients requiring surgery were related to either pericardial sheath placement or the sheath itself, highlighting the need for careful management of guidewire and sheath placement. The inflammatory response associated with LAA ligation and subsequent necrosis of the LAA is potentially a contributing factor to persistent pericarditis and the late pericardial effusion seen in this study (36). The late pericardial effusion is thought to be similar to the Dressler syndrome of open-heart surgery or myocardial infarction (25,36). The use of colchicine and nonsteroidal anti-inflammatory drugs post-LAA ligation for at least 3 weeks has been advocated to decrease the inflammatory-induced adverse events (43).
LAA exclusion with the Lariat device and not leaving a foreign material within the left atrium is an appealing alternative for patients with contraindications to OAC therapy. However, the Lariat procedure is a complex procedure compared with LAA device implantations due to the need for both a “dry” pericardial access and transseptal catheterization; thus, any potential benefits needs to be balanced by potential consequences of the Lariat procedure (44). The device and procedural adverse events rate in this study was 11.5% with 5 adverse events (3.6%) requiring additional corrective interventions and 1 periprocedural death. Initial users of the Lariat device reported reasonable LAA closure rates with acceptable complications rate (25,26,45). However, the expanded use of the Lariat device has demonstrated continued acceptable LAA closure results with higher bleeding and complication rates (46,47). The concern of major bleeding requiring transfusion associated with the Lariat procedure highlights the need for proper patient selection and adequate training to mitigate potential associated complications of perforations and lacerations of the LA, LAA, or RV. The use of the micropuncture needle and colchicine seems to help mitigate complications and major bleeding episodes (48,49). Nevertheless, a multicenter, randomized, prospective trial in patients with contraindications to OAC therapy is required to demonstrate the safety and clinical efficacy of the Lariat procedure.
This is an observational study including only patients with attempted LAA ligation with the Lariat device and has limitations inherent to that study design. Although adverse events and outcome events were pre-specified, the events were self-reported and adjudicated by the PI of each institution, then reviewed by another PI from a different institution. Additionally, clinical follow-up after 1 year post-procedure commonly included telephone calls, which could affect the accuracy of the event rates. However, the outcome events of stroke, systemic embolism, and death are endpoints that are easily detected. All strokes were evaluated by a neurologist. Because our composite endpoint was defined as stroke of any cause, misreporting of either embolic or nonembolic stroke events were less critical for the final analysis. Likewise, death was pre-specified as any cause, therefore discrimination between cardiovascular death and noncardiovascular death is less critical for the final analysis.
We are unable to directly assess differences in risk of stroke and embolic events against AF patients using other therapies (e.g., patients taking ASA, apixaban, or warfarin) because we evaluated a unique cohort of OAC-ineligible patients, and patients were treated post-procedure with ASA only, clopidogrel only, the combination of ASA and clopidogrel, or no antithrombotic therapy. The present analysis includes a fairly small number of participants, but this is intended as a report of our initial results. Our current population includes a large number of patients (28%) with a CHADS2 score of 1, and these results may not be generalizable to all high-risk patients. However, the proportion of patients with CHADS2 score of 1 are similar to the populations in other AF treatment trials, such as the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) study (13) and AVERROES (A Phase III Study of Apixaban in Patients With Atrial Fibrillation) (15), and the mean CHADS2 score of 2.4 of this study is similar to the mean CHADS2 score of 2.1 of other trials (13,15). Although this was a multicenter study, the number of primary operators were small and very experienced in ligation with the Lariat, which may have resulted in the low complication rates observed. However, the primary operators did train new operators throughout the study, which demonstrates that proper training can help mitigate potential complications.
Percutaneous LAA ligation with the Lariat device effectively excludes the LAA in AF patients. The low incidence of stroke and systemic embolic events in this high-risk AF population following LAA ligation suggests that LAA ligation may be an option for the prevention of stroke and systemic embolism in patients who have contraindications to OAC therapy. However, the adverse events associated with the Lariat procedure support the need for prospective randomized studies to confirm the expected reduction of stroke and systemic embolic events and to determine device and procedural safety following percutaneous LAA ligation with the Lariat device.
COMPETENCY IN MEDICAL KNOWLEDGE: The initial experience and long-term results of LAA ligation with the Lariat device demonstrate an effective method for LAA closure that may be an option for patients with AF and high risk of cardioembolic stroke who are intolerant to long-term anticoagulation therapy. However, the procedure may be associated with adverse events requiring corrective interventions, thus highlighting the need to adequate expertise, training, and judicial selection of patients.
TRANSLATIONAL OUTLOOK: The low incidence of stroke and systemic embolic events in this high-risk AF population following LAA ligation are encouraging results that need validation in a prospective, multicenter, randomized trial to determine the clinical benefit in the prevention of stroke, systemic embolism, and death, as well as safety of LAA ligation with the Lariat device.
Dr. Sievert has received study honoraria, travel expenses, or consulting fees from Abbott, Aptus, Atrium, Biosense Webster, Boston Scientific, Carag, Cardiac Dimensions, CardioKinetix, CardioMEMS, Cardiox, Celonova, CGuard, Coherex, Comed B.V., Contego, Covidien, CSI, CVRx, ev3, FlowCardia, Gardia, Gore, GTIMD Medical, Guided Delivery Systems, Hemoteq, InSeal Medical, InspireMD, Kona Medical, Lumen Biomedical, Lifetech, Lutonix, Maya Medical, Medtronic, Occlutech, pfm Medical, Recor, ResMed, SentreHeart, Spectranetics, Svelte Medical Systems, Tendyne, Trireme, Trivascular, Valtech, Vascular Dynamics, Venus Medical, Veryan, Vessix; and has stock options with Cardiokinetix, Access Closure, Coherex, and SMT. Dr. Bartus is a consultant to SentreHeart, Inc. Dr. Hue has received research support from SentreHeart. Dr. Marcus has received research support from SentreHeart, Pfizer, and Medtronic; and is a consultant to and equity holder in InCarda. Dr. Lee is a consultant to and equity holder in SentreHeart. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- atrial fibrillation
- computed tomography
- left atrial appendage
- oral anticoagulation
- right ventricle
- transesophageal echocardiography
- Received April 27, 2015.
- Revision received August 6, 2015.
- Accepted August 27, 2015.
- American College of Cardiology Foundation
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