XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
Original Article
Experience of left atrial appendage closure performed under conscious sedation
Asian Cardiovascular & Thoracic Annals 0(0) 1–5 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492314548231 aan.sagepub.com
Ngai-Yin Chan, Chun-Leung Lau, Ping-Tim Tsui, Ying-Keung Lo and Ngai-Shing Mok
Abstract Background: Percutaneous left atrial appendage closure is typically performed with transesophageal echocardiography guidance under general anesthesia. This study was performed to investigate the safety, feasibility, procedural characteristics, and outcomes of performing this procedure under conscious sedation without an anesthetist’s support. Methods: Eleven patients (6 men; mean age 64.6 10.4 years) with atrial fibrillation (median CHA2DS2VASc score 3) underwent transesophageal echocardiography-guided left atrial appendage occlusion under conscious sedation. Results: All patients had successful procedures. Procedural duration and fluoroscopic times were 93.8 25.3 and 16.2 6.5 min, respectively. The doses of midazolam and fentanyl required were 5.4 1.8 mg and 54.5 27 mg, respectively. No complications arose from conscious sedation. Watchman (mean size 29 5 mm) and Amplatzer Cardiac Plug (mean size 24 4 mm) devices were implanted in 5 and 6 patients, respectively. One patient had device displacement due to over-compression on day one, and underwent successful percutaneous retrieval without any long-term sequelae. Warfarin was stopped in all patients after day 45, with transesophageal echocardiography showing optimal device position without a significant jet flow. In a mean follow-up of 12.1 10.1 months, no thromboembolic complications were observed. Conclusions: Percutaneous left atrial appendage occlusion can be performed safely and effectively under conscious sedation. This approach will significantly reduce the complexity and costs of this increasingly performed procedure.
Keywords Anticoagulants, Atrial fibrillation, conscious sedation, echocardiography, transesophageal, stroke
Introduction Percutaneous left atrial appendage closure (LAAC) is a recently available interventional therapy for stroke prevention in patients with atrial fibrillation.1–5 It has been shown to be non-inferior to warfarin in terms of the composite endpoint of stroke, cardiovascular death, and systemic embolism, but with an excess of the safety events of major bleeding, pericardial effusion, and device embolization.1 The reported increase in safety events was likely related to the experience of the operators,6 and with longer follow-up, the difference in safety events between the LAAC and warfarin groups became nonsignificant because of a gradual accumulation of bleeding complications in the latter.7 Currently, LAAC may be considered in patients with a high stroke
risk and contraindications to long-term oral anticoagulation.8 Transesophageal echocardiography (TEE) is an essential imaging technique to guide the implantation of LAAC devices, and as a result, general anesthesia (GA) is very commonly, if not always, required.1–5 GA entails an increase in the complexity and costs of LAAC procedures. On the other hand, it is also associated with its own set of complications including potential neurotoxicity and a low risk of mortality.9,10
Princess Margaret Hospital, Hong Kong Corresponding author: Ngai-yin Chan, Princess Margaret Hospital, 2-10 Princess Margaret Hospital Road, Lai Chi Kok, Kowloon, Hong Kong. Email: [email protected]
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
[1–5] [PREPRINTER stage]
(AAN)
2
Asian Cardiovascular & Thoracic Annals 0(0)
Whether conscious sedation (CS) with intravenous midazolam and fentanyl without the presence of an anesthetist can replace GA in LAAC procedures, and the procedural characteristics and outcome of this simpler approach, have not been reported before.
Patients and methods The study included 11 patients who had atrial fibrillation and in whom anticoagulation therapy was indicated for stroke prevention. The baseline characteristics are listed in Table 1. They underwent LAAC with either an Amplatzer Cardiac Plug (ACP; St. Jude Medical, St. Paul, MN, USA) or a Watchman device (Atritech, Plymouth, MN, USA) for the following reasons: preference of the patient, contraindication for long-term oral anticoagulation because of bleeding complications or international normalized ratio fluctuation, or left atrial appendage (LAA) thrombus despite warfarin, which subsided only with high-dose dabigatran (150 mg twice daily). All patients gave informed consent to undergo the procedure, and the study protocol was approved by the ethics committee of the investigational center. Either ACP or Watchman devices were implanted according to the preference of the operator and
Table 1. Baseline characteristics of 11 patients undergoing left atrial appendage closure under conscious sedation. Variable
n ¼ 11
Sex (M/F) Age (years) Median CHA2DS2VASc score Paroxysmal atrial fibrillation Persistent atrial fibrillation Comorbid conditions Hypertension Ischemic stroke or TIA Heart failure Coronary artery disease Hypertrophic cardiomyopathy Diabetes Dyslipidemia Reasons for LAAC Preference of patients Contraindication to anticoagulation LAA thrombus despite warfarin Left ventricular ejection fraction Left atrial size (cm)
6/5 64.6 10.4 3 8 (73%) 3 (27%) 7 6 2 1 1 1 2
(64%) (55%) (18%) (9%) (9%) (9%) (18%)
6 (55%) 3 (27%) 2 (18%) 65.5% 12.7% 3.6 0.9
LAAC: left atrial appendage closure; TIA: transient ischemic attack.
availability of devices. The details of the design of LAAC devices and implantation techniques have been described previously.1,11 Essentially, the procedure was guided by TEE and fluoroscopy. All patients fasted for at least 8 h before the procedure. Instead of GA, the procedure was performed under CS with incremental doses of intravenous midazolam and fentanyl. After an initial dose of midazolam 3 mg, supplementary midazolam and fentanyl were given in 1 mg and 50 mg steps, respectively. Arterial blood pressure and oxygen saturation were continuously monitored. No anesthetist was present during the procedure. TEE was performed one day before the procedure to rule out LAA thrombus and obtain a preliminary assessment of the LAA anatomy. In particular, the ostial size, the depth, and for an ACP, the landing zone of the LAA were measured in different TEE views. During the procedure, these measurements were repeated for determination of the size of device to be implanted. The ACP device is available in sizes 16–30 mm with 2 mm increments, and the Watchman device is available in sizes 21–33 mm with 3 mm increments. A posterior and low transseptal puncture was guided by TEE in bicaval and short-axis views. The LAAC device was implanted by the techniques reported previously.1,11 Before release and final deployment of the device, several criteria including optimal device position as assessed by TEE and fluoroscopy, had to be satisfied.1,11 Acute procedural success was defined as successful implantation of the LAAC device with no significant jet flow or residual leak on a TEE Doppler study. All patients were closely monitored in the coronary care unit for 2 days after the procedure. In particular, chest radiography and a complete blood count were performed to detect aspiration pneumonia. Oral anticoagulants (warfarin or dabigatran) had been taken by all patients for 4 weeks and stopped 3 to 5 days before the procedure. Aspirin (81–325 mg) was given within 24 h of the procedure. During the procedure, intravenous heparin 100 U kg1 was administered to maintain an activated clotting time >250 s. Aspirin and warfarin were continued for 45 days. An international normalized ratio of 2–3.0 was targeted. If TEE performed after 45 days revealed an optimal device position, warfarin could be replaced with clopidogrel 75 mg daily and continued for 6 months. Aspirin was recommended as lifelong therapy. TEE surveillance was performed on day 1 to detect early device displacement or dislodgement. TEE was carried out on day 45 to assess device position and residual jet flow. If the residual jet flow was 5 mm or less, warfarin could be stopped, otherwise, it had to be continued and reassessment by TEE would be arranged. The patient would have clinical follow-up every 3 months.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
Chan et al.
3
This was a descriptive study and continuous variables are presented as mean standard deviation. Statistics were performed with the Statistical Package for Social Science version 19 software (SPSS, Inc., Chicago, IL, USA).
Results All patients underwent LAAC device implantation under CS with an acute procedural success rate of 100%. The potential complication of aspiration pneumonia was not observed in any patient. Displacement of an ACP device was detected by TEE surveillance on day 1, and it was successfully retrieved by a percutaneous technique. The displacement of this device was judged to be due to over-compression and unrelated to the use of CS instead of GA for the procedure. The patient was free from any long-term sequelae. The procedural characteristics are summarized in Table 2. The 45-day TEE examination in the remaining 10 patients revealed a satisfactory position of the LAAC device, with no significant jet flow or residual leak, and oral anticoagulant could be stopped in all patients. In a mean follow-up of 12.1 10.1 months, no thromboembolic complications have been observed.
Table 2. Procedural characteristics of left atrial appendage closure in 11 patients. Variable LAAC device Amplatzer Cardiac Plug Watchman LAAC device size (mm) Amplatzer Cardiac Plug Watchman Acute procedural success Procedural time (min) Fluoroscopic time (min) Dose of sedative drugs Midazolam (mg) Fentanyl (mg) Complications Device displacement PE/hemopericardium Thromboembolism Air embolism Aspiration pneumonia Death
n ¼ 11
6 (55%) 5 (45%) 24 4.0 29 5.0 11 (100%) 93.8 25.3 16.2 6.5 5.4 1.8 54.5 27 1 (9%) 0 0 0 0 0
LAAC: left atrial appendage closure; PE: pericardial effusion.
Discussion Assessment of the size and anatomy of the LAA, and confirmation of optimal positioning of the LAAC device requires TEE guidance. This in turn necessitates the use of GA to reduce patient pain and discomfort during the procedure. However, this requirement increases the complexity and cost of LAAC procedures, and of equal importance, GA has its own set of complications. The inhaled anesthetic agent may be neurotoxic and cause cognitive dysfunction, especially in the elderly.9 Furthermore, it was shown in a meta-analysis that there was a significant relationship between the risk of perioperative and anesthetic-related mortality and human development index.10 Therefore, it is desirable to avoid GA. In our study, we have shown that administering light and moderate sedation with mean doses of 5.4 mg and 54.5 mg of intravenous midazolam and fentanyl, respectively, was both safe and effective to facilitate LAAC procedures guided by TEE. Interestingly, despite the recommended use of GA in various landmark studies, LAAC procedures were reported to be performed under sedation in 50% of centers in a recently published European survey.12 However, no details of the types of sedative drug, procedural characteristics and outcome, or the need for the presence of anesthetists was available. It was also recently reported in a study involving 80 patients that CS with intravenous propofol and midazolam was used during LAAC procedures.13 The focus of this study was the use of different antithrombotic regimens after device implantation, and similar to the previously mentioned study, details of the sedation procedure, especially the need for an anesthetist to administer propofol, were not available. In fact, propofol sedation is generally more preferably conducted by anesthetists.14 Our study is thus the first to report on the safety, feasibility, and procedural details of LAAC procedures under CS with intravenous midazolam and fentanyl without support from anesthetists. This has important implications in reduction of the complexity and costs of this increasingly performed procedure. We achieved a mean procedural time of 93.8 min and a mean fluoroscopic time of 16.2 min in our patients, which were comparable to a study involving 100 patients who underwent ACP device implantation under GA.11 In that study, the mean procedural and fluoroscopic time were 95.8 and 15.4 min, respectively. Whether the time taken for GA and its recovery was recorded was not reported. In contrast, a much shorter mean procedural time of 51.5 min was reported in another study involving 150 patients who underwent Watchman device implantation under GA.2 The differences in procedural time may be related to the learning curve effect and the types of LAAC device.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
4
Asian Cardiovascular & Thoracic Annals 0(0)
Other approaches to eliminate the need for GA in LAAC procedures have been explored previously. Ho and colleagues15 reported the use of intracardiac echocardiography to guide LAAC device implantation in 10 patients. They showed that optimal images comparable to TEE could be obtained with an intracardiac echocardiographic probe positioned inside the coronary sinus. In a case report by Ronco and colleagues,16 a micro-transesophageal echocardiographic probe was used to guide LAAC device implantation under conscious sedation. Aspiration pneumonia is a potential complication of CS. Likewise, it also occurs during GA or the TEE examination itself.17 In our study, special emphasis was put on surveillance for this complication by monitoring with chest radiography and a complete blood count. No aspiration pneumonia was found in our patients. Whether aspiration pneumonia occurs more commonly in LAAC procedures under CS compared to GA requires further investigation in a larger patient population. The widely held belief of an advantage of GA in LAAC device implantation is its ability to produce a short period of apnea during deployment of the device. However, in our experience in this small study, device deployment was not affected to any significant extent by respiratory motion. Displacement of an ACP device was detected in one patient by TEE surveillance on day 1. In this patient, all of the device release criteria, namely lobe position at the intended landing zone with at least two-thirds situated distal to the left circumflex artery, orientation of the device aligned with the LAA neck, good separation between the lobe and the disc, concavity of the disc, and LAA ostium covered by the disc with no leak, were satisfied except that the shape of the lobe appeared over-compressed. Overcompression by the ACP device may result in failure of the stabilizing wires on the lobe to hook onto the LAA wall, with a risk of immediate or late displacement and dislodgement. It was therefore judged to be unrelated to the use of CS instead of GA. The most appropriate antithrombotic regimen after LAAC device implantation remains an open question. In the randomized landmark trial of PROTECT-AF studying the Watchman device, aspirin and warfarin were given for 45 days after implantation, followed by 6 months of aspirin plus clopidogrel if the day-45 TEE revealed no significant residual jet flow around the device.1 Lifelong aspirin was required. In the ASAP study, 150 patients who underwent Watchman device implantation but were ineligible for warfarin, received 6 months of aspirin and clopidogrel after the procedure, followed by lifelong aspirin.2 For the ACP device, only dual antiplatelet treatment with aspirin and clopidogrel was recommended for a variable period of 1 to 6 months after implantation, followed by a lifelong
single antiplatelet agent.5 In our study, both ACP and Watchman devices were used. The more aggressive antithrombotic regimen involving use of warfarin in the early post-procedure period was followed. This was a small pilot study on the feasibility and safety of using CS instead of GA for LAAC procedures. It was not a comparative study using a conventional GA group for comparison. The results may need to be confirmed in a randomized controlled study with a larger patient population. Both ACP and Watchman devices were used in this study. Although both belong to the LAAC device family, this still results in heterogeneity in the study. Lastly, the levels of pain, discomfort, and satisfaction experienced by the patients were not assessed in this study. Nevertheless, we concluded that LAAC procedures can be performed safely and effectively under CS with intravenous midazolam and fentanyl instead of GA. Without the need of support from an anesthetist, the complexity and costs of this increasingly performed procedure can be substantially reduced. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest statement None declared.
References 1. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomized non-inferiority trial. Lancet 2009; 374: 534–542. 2. Reddy VY, Mo¨bius-Winkler S, Miller MA, et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix feasibility study Watchman left atrial appendage closure technology). J Am Coll Cardiol 2013; 61: 2551–2556. 3. Park JW, Bethencourt A, Sievert H, et al. Left atrial appendage closure with Amplatzer Cardiac Plug in atrial fibrillation: initial European experience. Catheter Cardiovasc Interv 2011; 77: 700–706. 4. Nietlispach F, Gloekler S, Krause R, et al. Amplatzer left atrial appendage occlusion: single-center 10-year experience. Catheter Cardiovasc Interv 2013; 82: 283–289. 5. Urena M, Rodes-Cabau J, Freixa X, et al. Percutaneous left atrial appendage closure with the Amplatzer Cardiac Plug device in patients with non-valvular atrial fibrillation and contraindication to anticoagulation therapy. J Am Coll Cardiol 2013; 62: 96–102. 6. Reddy VY, Holmes D, Doshi SK, Neuzil P and Kar S. Safety of percutaneous left atrial appendage closure.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
Chan et al.
7.
8.
9. 10.
11.
5
Results from the Watchman left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011; 123: 417–424. Reddy VY, Doshi SK, Sievert H, 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: 720–729. Camm AJ, Lip GY, De Caterina R, et al. 012 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. Eur Heart J 2012; 33: 2719–2747. Hudson AE and Hemmings HC Jr. Are anaesthetics toxic to the brain? Br J Anaesth 2011; 107: 30–37. Bainbridge D, Martin J, Arango M, Cheng D; Evidencebased Peri-operative Clinical Outcomes Research (EPiCOR) Group. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet 2012; 380: 1075–1081. Meerkin D, Butnaru A, Dratva D, Bertrand OF and Tzivoni D. Early safety of the Amplatzer Cardiac Plug
12.
13.
14.
15.
16.
17.
for left atrial appendage occlusion. Int J Cardiol 2013; 168: 3920–3925. Lip GY, Dagres N, Proclemer A, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation in Europe: results of the European Heart Rhythm Association survey. Europace 2013; 14: 141–143. Chun KR, Bordignon S, Urban V, et al. Left atrial appendage closure followed by 6 weeks of antithrombotic therapy: a prospective single-center experience. Heart Rhythm 2013; 10: 1792–1799. Metzner J and Domino KB. Risks of anesthesia or sedation outside the operating room: the role of the anesthesia care provider. Curr Opin Anaesthesiol 2010; 23: 523–531. Ho IC, Neuzil P, Mraz T, et al. Use of intracardiac echocardiography to guide implantation of a left atrial appendage occlusion device (PLAATO). Heart Rhythm 2007; 4: 567–571. Ronco F, Pascotto A, Barbierato M and Grassi G. Percutaneous left atrial appendage closure in awake non intubated patient: multimodality intraprocedural imaging. Cardiovasc Revasc Med 2012; 13: 360–361. Otto CM. Textbook of clinical echocardiography. 3rd ed. Elsevier Saunders, 2004.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
(AAN)
[1–5] [PREPRINTER stage]
Original Article
Experience of left atrial appendage closure performed under conscious sedation
Asian Cardiovascular & Thoracic Annals 0(0) 1–5 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492314548231 aan.sagepub.com
Ngai-Yin Chan, Chun-Leung Lau, Ping-Tim Tsui, Ying-Keung Lo and Ngai-Shing Mok
Abstract Background: Percutaneous left atrial appendage closure is typically performed with transesophageal echocardiography guidance under general anesthesia. This study was performed to investigate the safety, feasibility, procedural characteristics, and outcomes of performing this procedure under conscious sedation without an anesthetist’s support. Methods: Eleven patients (6 men; mean age 64.6 10.4 years) with atrial fibrillation (median CHA2DS2VASc score 3) underwent transesophageal echocardiography-guided left atrial appendage occlusion under conscious sedation. Results: All patients had successful procedures. Procedural duration and fluoroscopic times were 93.8 25.3 and 16.2 6.5 min, respectively. The doses of midazolam and fentanyl required were 5.4 1.8 mg and 54.5 27 mg, respectively. No complications arose from conscious sedation. Watchman (mean size 29 5 mm) and Amplatzer Cardiac Plug (mean size 24 4 mm) devices were implanted in 5 and 6 patients, respectively. One patient had device displacement due to over-compression on day one, and underwent successful percutaneous retrieval without any long-term sequelae. Warfarin was stopped in all patients after day 45, with transesophageal echocardiography showing optimal device position without a significant jet flow. In a mean follow-up of 12.1 10.1 months, no thromboembolic complications were observed. Conclusions: Percutaneous left atrial appendage occlusion can be performed safely and effectively under conscious sedation. This approach will significantly reduce the complexity and costs of this increasingly performed procedure.
Keywords Anticoagulants, Atrial fibrillation, conscious sedation, echocardiography, transesophageal, stroke
Introduction Percutaneous left atrial appendage closure (LAAC) is a recently available interventional therapy for stroke prevention in patients with atrial fibrillation.1–5 It has been shown to be non-inferior to warfarin in terms of the composite endpoint of stroke, cardiovascular death, and systemic embolism, but with an excess of the safety events of major bleeding, pericardial effusion, and device embolization.1 The reported increase in safety events was likely related to the experience of the operators,6 and with longer follow-up, the difference in safety events between the LAAC and warfarin groups became nonsignificant because of a gradual accumulation of bleeding complications in the latter.7 Currently, LAAC may be considered in patients with a high stroke
risk and contraindications to long-term oral anticoagulation.8 Transesophageal echocardiography (TEE) is an essential imaging technique to guide the implantation of LAAC devices, and as a result, general anesthesia (GA) is very commonly, if not always, required.1–5 GA entails an increase in the complexity and costs of LAAC procedures. On the other hand, it is also associated with its own set of complications including potential neurotoxicity and a low risk of mortality.9,10
Princess Margaret Hospital, Hong Kong Corresponding author: Ngai-yin Chan, Princess Margaret Hospital, 2-10 Princess Margaret Hospital Road, Lai Chi Kok, Kowloon, Hong Kong. Email: [email protected]
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
[1–5] [PREPRINTER stage]
(AAN)
2
Asian Cardiovascular & Thoracic Annals 0(0)
Whether conscious sedation (CS) with intravenous midazolam and fentanyl without the presence of an anesthetist can replace GA in LAAC procedures, and the procedural characteristics and outcome of this simpler approach, have not been reported before.
Patients and methods The study included 11 patients who had atrial fibrillation and in whom anticoagulation therapy was indicated for stroke prevention. The baseline characteristics are listed in Table 1. They underwent LAAC with either an Amplatzer Cardiac Plug (ACP; St. Jude Medical, St. Paul, MN, USA) or a Watchman device (Atritech, Plymouth, MN, USA) for the following reasons: preference of the patient, contraindication for long-term oral anticoagulation because of bleeding complications or international normalized ratio fluctuation, or left atrial appendage (LAA) thrombus despite warfarin, which subsided only with high-dose dabigatran (150 mg twice daily). All patients gave informed consent to undergo the procedure, and the study protocol was approved by the ethics committee of the investigational center. Either ACP or Watchman devices were implanted according to the preference of the operator and
Table 1. Baseline characteristics of 11 patients undergoing left atrial appendage closure under conscious sedation. Variable
n ¼ 11
Sex (M/F) Age (years) Median CHA2DS2VASc score Paroxysmal atrial fibrillation Persistent atrial fibrillation Comorbid conditions Hypertension Ischemic stroke or TIA Heart failure Coronary artery disease Hypertrophic cardiomyopathy Diabetes Dyslipidemia Reasons for LAAC Preference of patients Contraindication to anticoagulation LAA thrombus despite warfarin Left ventricular ejection fraction Left atrial size (cm)
6/5 64.6 10.4 3 8 (73%) 3 (27%) 7 6 2 1 1 1 2
(64%) (55%) (18%) (9%) (9%) (9%) (18%)
6 (55%) 3 (27%) 2 (18%) 65.5% 12.7% 3.6 0.9
LAAC: left atrial appendage closure; TIA: transient ischemic attack.
availability of devices. The details of the design of LAAC devices and implantation techniques have been described previously.1,11 Essentially, the procedure was guided by TEE and fluoroscopy. All patients fasted for at least 8 h before the procedure. Instead of GA, the procedure was performed under CS with incremental doses of intravenous midazolam and fentanyl. After an initial dose of midazolam 3 mg, supplementary midazolam and fentanyl were given in 1 mg and 50 mg steps, respectively. Arterial blood pressure and oxygen saturation were continuously monitored. No anesthetist was present during the procedure. TEE was performed one day before the procedure to rule out LAA thrombus and obtain a preliminary assessment of the LAA anatomy. In particular, the ostial size, the depth, and for an ACP, the landing zone of the LAA were measured in different TEE views. During the procedure, these measurements were repeated for determination of the size of device to be implanted. The ACP device is available in sizes 16–30 mm with 2 mm increments, and the Watchman device is available in sizes 21–33 mm with 3 mm increments. A posterior and low transseptal puncture was guided by TEE in bicaval and short-axis views. The LAAC device was implanted by the techniques reported previously.1,11 Before release and final deployment of the device, several criteria including optimal device position as assessed by TEE and fluoroscopy, had to be satisfied.1,11 Acute procedural success was defined as successful implantation of the LAAC device with no significant jet flow or residual leak on a TEE Doppler study. All patients were closely monitored in the coronary care unit for 2 days after the procedure. In particular, chest radiography and a complete blood count were performed to detect aspiration pneumonia. Oral anticoagulants (warfarin or dabigatran) had been taken by all patients for 4 weeks and stopped 3 to 5 days before the procedure. Aspirin (81–325 mg) was given within 24 h of the procedure. During the procedure, intravenous heparin 100 U kg1 was administered to maintain an activated clotting time >250 s. Aspirin and warfarin were continued for 45 days. An international normalized ratio of 2–3.0 was targeted. If TEE performed after 45 days revealed an optimal device position, warfarin could be replaced with clopidogrel 75 mg daily and continued for 6 months. Aspirin was recommended as lifelong therapy. TEE surveillance was performed on day 1 to detect early device displacement or dislodgement. TEE was carried out on day 45 to assess device position and residual jet flow. If the residual jet flow was 5 mm or less, warfarin could be stopped, otherwise, it had to be continued and reassessment by TEE would be arranged. The patient would have clinical follow-up every 3 months.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
Chan et al.
3
This was a descriptive study and continuous variables are presented as mean standard deviation. Statistics were performed with the Statistical Package for Social Science version 19 software (SPSS, Inc., Chicago, IL, USA).
Results All patients underwent LAAC device implantation under CS with an acute procedural success rate of 100%. The potential complication of aspiration pneumonia was not observed in any patient. Displacement of an ACP device was detected by TEE surveillance on day 1, and it was successfully retrieved by a percutaneous technique. The displacement of this device was judged to be due to over-compression and unrelated to the use of CS instead of GA for the procedure. The patient was free from any long-term sequelae. The procedural characteristics are summarized in Table 2. The 45-day TEE examination in the remaining 10 patients revealed a satisfactory position of the LAAC device, with no significant jet flow or residual leak, and oral anticoagulant could be stopped in all patients. In a mean follow-up of 12.1 10.1 months, no thromboembolic complications have been observed.
Table 2. Procedural characteristics of left atrial appendage closure in 11 patients. Variable LAAC device Amplatzer Cardiac Plug Watchman LAAC device size (mm) Amplatzer Cardiac Plug Watchman Acute procedural success Procedural time (min) Fluoroscopic time (min) Dose of sedative drugs Midazolam (mg) Fentanyl (mg) Complications Device displacement PE/hemopericardium Thromboembolism Air embolism Aspiration pneumonia Death
n ¼ 11
6 (55%) 5 (45%) 24 4.0 29 5.0 11 (100%) 93.8 25.3 16.2 6.5 5.4 1.8 54.5 27 1 (9%) 0 0 0 0 0
LAAC: left atrial appendage closure; PE: pericardial effusion.
Discussion Assessment of the size and anatomy of the LAA, and confirmation of optimal positioning of the LAAC device requires TEE guidance. This in turn necessitates the use of GA to reduce patient pain and discomfort during the procedure. However, this requirement increases the complexity and cost of LAAC procedures, and of equal importance, GA has its own set of complications. The inhaled anesthetic agent may be neurotoxic and cause cognitive dysfunction, especially in the elderly.9 Furthermore, it was shown in a meta-analysis that there was a significant relationship between the risk of perioperative and anesthetic-related mortality and human development index.10 Therefore, it is desirable to avoid GA. In our study, we have shown that administering light and moderate sedation with mean doses of 5.4 mg and 54.5 mg of intravenous midazolam and fentanyl, respectively, was both safe and effective to facilitate LAAC procedures guided by TEE. Interestingly, despite the recommended use of GA in various landmark studies, LAAC procedures were reported to be performed under sedation in 50% of centers in a recently published European survey.12 However, no details of the types of sedative drug, procedural characteristics and outcome, or the need for the presence of anesthetists was available. It was also recently reported in a study involving 80 patients that CS with intravenous propofol and midazolam was used during LAAC procedures.13 The focus of this study was the use of different antithrombotic regimens after device implantation, and similar to the previously mentioned study, details of the sedation procedure, especially the need for an anesthetist to administer propofol, were not available. In fact, propofol sedation is generally more preferably conducted by anesthetists.14 Our study is thus the first to report on the safety, feasibility, and procedural details of LAAC procedures under CS with intravenous midazolam and fentanyl without support from anesthetists. This has important implications in reduction of the complexity and costs of this increasingly performed procedure. We achieved a mean procedural time of 93.8 min and a mean fluoroscopic time of 16.2 min in our patients, which were comparable to a study involving 100 patients who underwent ACP device implantation under GA.11 In that study, the mean procedural and fluoroscopic time were 95.8 and 15.4 min, respectively. Whether the time taken for GA and its recovery was recorded was not reported. In contrast, a much shorter mean procedural time of 51.5 min was reported in another study involving 150 patients who underwent Watchman device implantation under GA.2 The differences in procedural time may be related to the learning curve effect and the types of LAAC device.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
4
Asian Cardiovascular & Thoracic Annals 0(0)
Other approaches to eliminate the need for GA in LAAC procedures have been explored previously. Ho and colleagues15 reported the use of intracardiac echocardiography to guide LAAC device implantation in 10 patients. They showed that optimal images comparable to TEE could be obtained with an intracardiac echocardiographic probe positioned inside the coronary sinus. In a case report by Ronco and colleagues,16 a micro-transesophageal echocardiographic probe was used to guide LAAC device implantation under conscious sedation. Aspiration pneumonia is a potential complication of CS. Likewise, it also occurs during GA or the TEE examination itself.17 In our study, special emphasis was put on surveillance for this complication by monitoring with chest radiography and a complete blood count. No aspiration pneumonia was found in our patients. Whether aspiration pneumonia occurs more commonly in LAAC procedures under CS compared to GA requires further investigation in a larger patient population. The widely held belief of an advantage of GA in LAAC device implantation is its ability to produce a short period of apnea during deployment of the device. However, in our experience in this small study, device deployment was not affected to any significant extent by respiratory motion. Displacement of an ACP device was detected in one patient by TEE surveillance on day 1. In this patient, all of the device release criteria, namely lobe position at the intended landing zone with at least two-thirds situated distal to the left circumflex artery, orientation of the device aligned with the LAA neck, good separation between the lobe and the disc, concavity of the disc, and LAA ostium covered by the disc with no leak, were satisfied except that the shape of the lobe appeared over-compressed. Overcompression by the ACP device may result in failure of the stabilizing wires on the lobe to hook onto the LAA wall, with a risk of immediate or late displacement and dislodgement. It was therefore judged to be unrelated to the use of CS instead of GA. The most appropriate antithrombotic regimen after LAAC device implantation remains an open question. In the randomized landmark trial of PROTECT-AF studying the Watchman device, aspirin and warfarin were given for 45 days after implantation, followed by 6 months of aspirin plus clopidogrel if the day-45 TEE revealed no significant residual jet flow around the device.1 Lifelong aspirin was required. In the ASAP study, 150 patients who underwent Watchman device implantation but were ineligible for warfarin, received 6 months of aspirin and clopidogrel after the procedure, followed by lifelong aspirin.2 For the ACP device, only dual antiplatelet treatment with aspirin and clopidogrel was recommended for a variable period of 1 to 6 months after implantation, followed by a lifelong
single antiplatelet agent.5 In our study, both ACP and Watchman devices were used. The more aggressive antithrombotic regimen involving use of warfarin in the early post-procedure period was followed. This was a small pilot study on the feasibility and safety of using CS instead of GA for LAAC procedures. It was not a comparative study using a conventional GA group for comparison. The results may need to be confirmed in a randomized controlled study with a larger patient population. Both ACP and Watchman devices were used in this study. Although both belong to the LAAC device family, this still results in heterogeneity in the study. Lastly, the levels of pain, discomfort, and satisfaction experienced by the patients were not assessed in this study. Nevertheless, we concluded that LAAC procedures can be performed safely and effectively under CS with intravenous midazolam and fentanyl instead of GA. Without the need of support from an anesthetist, the complexity and costs of this increasingly performed procedure can be substantially reduced. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest statement None declared.
References 1. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomized non-inferiority trial. Lancet 2009; 374: 534–542. 2. Reddy VY, Mo¨bius-Winkler S, Miller MA, et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix feasibility study Watchman left atrial appendage closure technology). J Am Coll Cardiol 2013; 61: 2551–2556. 3. Park JW, Bethencourt A, Sievert H, et al. Left atrial appendage closure with Amplatzer Cardiac Plug in atrial fibrillation: initial European experience. Catheter Cardiovasc Interv 2011; 77: 700–706. 4. Nietlispach F, Gloekler S, Krause R, et al. Amplatzer left atrial appendage occlusion: single-center 10-year experience. Catheter Cardiovasc Interv 2013; 82: 283–289. 5. Urena M, Rodes-Cabau J, Freixa X, et al. Percutaneous left atrial appendage closure with the Amplatzer Cardiac Plug device in patients with non-valvular atrial fibrillation and contraindication to anticoagulation therapy. J Am Coll Cardiol 2013; 62: 96–102. 6. Reddy VY, Holmes D, Doshi SK, Neuzil P and Kar S. Safety of percutaneous left atrial appendage closure.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
XML Template (2014) [12.8.2014–10:21am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/AANJ/Vol00000/140186/APPFile/SG-AANJ140186.3d
(AAN)
[1–5] [PREPRINTER stage]
Chan et al.
7.
8.
9. 10.
11.
5
Results from the Watchman left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011; 123: 417–424. Reddy VY, Doshi SK, Sievert H, 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: 720–729. Camm AJ, Lip GY, De Caterina R, et al. 012 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. Eur Heart J 2012; 33: 2719–2747. Hudson AE and Hemmings HC Jr. Are anaesthetics toxic to the brain? Br J Anaesth 2011; 107: 30–37. Bainbridge D, Martin J, Arango M, Cheng D; Evidencebased Peri-operative Clinical Outcomes Research (EPiCOR) Group. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet 2012; 380: 1075–1081. Meerkin D, Butnaru A, Dratva D, Bertrand OF and Tzivoni D. Early safety of the Amplatzer Cardiac Plug
12.
13.
14.
15.
16.
17.
for left atrial appendage occlusion. Int J Cardiol 2013; 168: 3920–3925. Lip GY, Dagres N, Proclemer A, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation in Europe: results of the European Heart Rhythm Association survey. Europace 2013; 14: 141–143. Chun KR, Bordignon S, Urban V, et al. Left atrial appendage closure followed by 6 weeks of antithrombotic therapy: a prospective single-center experience. Heart Rhythm 2013; 10: 1792–1799. Metzner J and Domino KB. Risks of anesthesia or sedation outside the operating room: the role of the anesthesia care provider. Curr Opin Anaesthesiol 2010; 23: 523–531. Ho IC, Neuzil P, Mraz T, et al. Use of intracardiac echocardiography to guide implantation of a left atrial appendage occlusion device (PLAATO). Heart Rhythm 2007; 4: 567–571. Ronco F, Pascotto A, Barbierato M and Grassi G. Percutaneous left atrial appendage closure in awake non intubated patient: multimodality intraprocedural imaging. Cardiovasc Revasc Med 2012; 13: 360–361. Otto CM. Textbook of clinical echocardiography. 3rd ed. Elsevier Saunders, 2004.
Downloaded from aan.sagepub.com at TUFTS UNIV on December 10, 2015
