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Hybrid pericardial suture ligation of the left atrial appendage: A call to study!
EDITORIAL COMMENTARY
Hybrid pericardial suture ligation of the left atrial appendage: A call to study! Suraj Kapa, MD, FHRS, Paul A. Friedman, MD, FHRS From the of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota. “The detachment of larger or smaller fragments from the end of the softening thrombus which are carried along by the current of blood and driven into remote vessels. This gives rise to the very frequent process on which I have bestowed the name of Embolia.” Rudolf Virchow Virchow’s triad consists of circulatory stasis, endothelial injury, and hypercoagulability. Among these, the most critical component for thromboembolism in atrial fibrillation may be stasis, particularly in the left atrial appendage (LAA). The role of anticoagulation for stroke prevention in atrial fibrillation is well established.1 However, the potential for systemic toxicity (bleeding) has led to interest in exclusion of the LAA from the central circulation as an alternate stroke prevention strategy. The Protect AF trial found that endocardial placement of a plug at the LAA ostium is noninferior to warfarin for AF-associated stroke prevention in the intermediate term and is superior to warfarin leading to a reduced risk of a composite primary end-point of cardiovascular death, all stroke, and systemic embolism after 4 years, highlighting the promise of this strategy.2 Despite these encouraging results, the potential for device dislodgment, erosion, migration, or infection persists, prompting the development of LAA ligation procedures that eliminate the need for an endovascular foreign body.3 The report in this issue of HeartRhythm by Miller et al4 discusses the safety and efficacy of percutaneous LAA exclusion using pericardial suture ligation via a combined endocardial transseptal and epicardial percutaneous approach. Although prior studies on a combined epicardial/ endocardial approach to achieve pericardial suture ligation of the LAA have been published, they focused on either proof of concept or on a relatively healthy population in whom the risk of thromboembolism or bleeding was otherwise low.5,6 The work by Miller et al offers further information by evaluating the safety and efficacy in a population that is more reflective of those in whom such a technology will be used— Dr. Friedman is co-inventor of the Aegis Sentinel epicardial appendage closure system. Address reprint requests and correspondence: Dr. Paul A. Friedman, Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905. E-mail address: [email protected].
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
individuals at high risk for thromboembolism who are also at high risk for bleeding. Miller et al found a high rate of complications, including pericardial effusions requiring pericardiocentesis (20%) and LAA perforation (9%), with need for open surgical correction in half of those (4.5%). These findings parallel those recently reported by Price et al7 highlighting an important question: is it safe, and can it be made safer?
Is safe, effective, and better possible? A number of potential mechanisms may account for the relatively high rate of complications found by Miller et al. An intervention using sophisticated multicomponent tools applied to a complex 3-dimensional anatomy that is invisible under the fluoroscopy used to guide the procedure and only partially imaged at any time via tomographic echocardiographic images will necessarily require a learning curve. Three of the 4 centers in the study had performed fewer than 10 procedures. A learning curve for LAA exclusion procedures has previously been reported.8 Development and systematic use of an operator training program may mitigate learning curve procedural challenges.9 Whether any such program was available to the centers in the current report is unclear. A frequent complication was pericardial effusion. Bleeding in the pericardial space may stem from cardiac perforation, irritation of pericardial fat, disruption of pericardial bridging vessels, or reactive inflammation. With the hybrid approach, intravenous heparin is administered to avoid transseptal puncture–associated thromboembolism; this may potentiate otherwise minor trauma associated with movement of the semirigid metal suture delivery loop within the pericardium. Blood is a potent mediator of inflammation in the pericardium; thus, heparin use may have facilitated complications. Moreover, some patients with complications underwent repeated attempts at loop closure, suggesting that a less aggressive strategy may be preferable. Interestingly, in a report by Bartus et al,6 only 2 of 89 patients developed pericardial effusion compared to 8 of 41 in the present study. This may reflect the high volume and center experience of Bartus et al or their routine practice of leaving a pericardial drain in place postoperatively, in contrast to the practice http://dx.doi.org/10.1016/j.hrthm.2014.08.028
Kapa and Friedman
Editorial Commentary
reported by Miller et al.4 In the report by Miller et al, the lack of systematic colchicine use may have contributed to inflammatory complications. Although no patients had an open LAA (45-mm leak) at 3 months, 24% had an LAA leak Z1 mm but o5 mm. A potential challenge of external ligation is determination of the amount of force to apply. Excessive force may lead to LAA tear, whereas inadequate force may result in LAA opening after repetitive cardiac motion against an inadequately tightened suture. In the present study, a tensor was used to apply a prespecified amount of force to the external LAA loop. We previously found that ostial ligation with sufficient force for closure results in loss of distal LAA electrograms within seconds, presumably due to tissue anoxia.10 This raises the possibility that electrogram loss may be a surrogate for sufficient closure, although this has not been validated clinically. Although the clinical significance of leaks is unknown, intuitively they are best avoided. In the end, the goal of LAA exclusion is to safely attenuate the risk of stroke in atrial fibrillation patients at least as effectively as oral anticoagulation, especially in patients who are at high risk for bleeding. Because of differences in patients studied, center experience, and study methodology, whether the hybrid system compares favorably or unfavorably to other stroke prevention strategies with regard to safety remains unknown. However, the study by Miller et al adds to the clarion call for well-developed operator and center training programs with the introduction of a new complex technology and the need for formal studies to assess the role of this technology in clinical practice.
1861
References 1. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257–e354. 2. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P; Protect AF Investigators. 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. 3. Friedman PA, Holmes DR. Non-surgical left atrial appendage closure for stroke prevention in atrial fibrillation. J Cardiovasc Electrophysiol 2011;22:1184–1191. 4. Miller MA, Gangireddy SR, Doshi SK, Aryana A, Koruth JS, Sennhauser S, d’Avila A, Dukkipati SR, Neuzil P, Reddy VY. Multicenter study on acute and long-term safety and efficacy of percutaneous left atrial appendage closure using an epicardial suture snaring device. Heart Rhythm 2014;11:1853–1859. 5. Stone D, Byrne T, Pershad A. Early results with the LARIAT device for left atrial appendage exclusion in patients with atrial fibrillation at high risk for stroke and anticoagulation. Catheter Cardiovasc Interv 2013; [Epub ahead of print]. 6. Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov SJ, Lee RJ. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol 2013;62:108–118. 7. Price MJ, Gibson DN, Yakubov SJ, et al. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the US transcatheter LAA ligation consortium. J Am Coll Cardiol 2014;64:565–572. 8. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation 2011;123:417–424. 9. Holmes DR, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy. J Am Coll Cardiol 2014;64:1–12. 10. Friedman PA, Asirvatham SJ, Dalegrave C, Kinoshita M, Danielsen AJ, Johnson SB, Hodge DO, Munger TM, Packer DL, Bruce CJ. Percutaneous epicardial left atrial appendage closure: preliminary results of an electrogram guided approach. J Cardiovasc Electrophysiol 2009;20:908–915.
Hybrid pericardial suture ligation of the left atrial appendage: A call to study! Suraj Kapa, MD, FHRS, Paul A. Friedman, MD, FHRS From the of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota. “The detachment of larger or smaller fragments from the end of the softening thrombus which are carried along by the current of blood and driven into remote vessels. This gives rise to the very frequent process on which I have bestowed the name of Embolia.” Rudolf Virchow Virchow’s triad consists of circulatory stasis, endothelial injury, and hypercoagulability. Among these, the most critical component for thromboembolism in atrial fibrillation may be stasis, particularly in the left atrial appendage (LAA). The role of anticoagulation for stroke prevention in atrial fibrillation is well established.1 However, the potential for systemic toxicity (bleeding) has led to interest in exclusion of the LAA from the central circulation as an alternate stroke prevention strategy. The Protect AF trial found that endocardial placement of a plug at the LAA ostium is noninferior to warfarin for AF-associated stroke prevention in the intermediate term and is superior to warfarin leading to a reduced risk of a composite primary end-point of cardiovascular death, all stroke, and systemic embolism after 4 years, highlighting the promise of this strategy.2 Despite these encouraging results, the potential for device dislodgment, erosion, migration, or infection persists, prompting the development of LAA ligation procedures that eliminate the need for an endovascular foreign body.3 The report in this issue of HeartRhythm by Miller et al4 discusses the safety and efficacy of percutaneous LAA exclusion using pericardial suture ligation via a combined endocardial transseptal and epicardial percutaneous approach. Although prior studies on a combined epicardial/ endocardial approach to achieve pericardial suture ligation of the LAA have been published, they focused on either proof of concept or on a relatively healthy population in whom the risk of thromboembolism or bleeding was otherwise low.5,6 The work by Miller et al offers further information by evaluating the safety and efficacy in a population that is more reflective of those in whom such a technology will be used— Dr. Friedman is co-inventor of the Aegis Sentinel epicardial appendage closure system. Address reprint requests and correspondence: Dr. Paul A. Friedman, Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905. E-mail address: [email protected].
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
individuals at high risk for thromboembolism who are also at high risk for bleeding. Miller et al found a high rate of complications, including pericardial effusions requiring pericardiocentesis (20%) and LAA perforation (9%), with need for open surgical correction in half of those (4.5%). These findings parallel those recently reported by Price et al7 highlighting an important question: is it safe, and can it be made safer?
Is safe, effective, and better possible? A number of potential mechanisms may account for the relatively high rate of complications found by Miller et al. An intervention using sophisticated multicomponent tools applied to a complex 3-dimensional anatomy that is invisible under the fluoroscopy used to guide the procedure and only partially imaged at any time via tomographic echocardiographic images will necessarily require a learning curve. Three of the 4 centers in the study had performed fewer than 10 procedures. A learning curve for LAA exclusion procedures has previously been reported.8 Development and systematic use of an operator training program may mitigate learning curve procedural challenges.9 Whether any such program was available to the centers in the current report is unclear. A frequent complication was pericardial effusion. Bleeding in the pericardial space may stem from cardiac perforation, irritation of pericardial fat, disruption of pericardial bridging vessels, or reactive inflammation. With the hybrid approach, intravenous heparin is administered to avoid transseptal puncture–associated thromboembolism; this may potentiate otherwise minor trauma associated with movement of the semirigid metal suture delivery loop within the pericardium. Blood is a potent mediator of inflammation in the pericardium; thus, heparin use may have facilitated complications. Moreover, some patients with complications underwent repeated attempts at loop closure, suggesting that a less aggressive strategy may be preferable. Interestingly, in a report by Bartus et al,6 only 2 of 89 patients developed pericardial effusion compared to 8 of 41 in the present study. This may reflect the high volume and center experience of Bartus et al or their routine practice of leaving a pericardial drain in place postoperatively, in contrast to the practice http://dx.doi.org/10.1016/j.hrthm.2014.08.028
Kapa and Friedman
Editorial Commentary
reported by Miller et al.4 In the report by Miller et al, the lack of systematic colchicine use may have contributed to inflammatory complications. Although no patients had an open LAA (45-mm leak) at 3 months, 24% had an LAA leak Z1 mm but o5 mm. A potential challenge of external ligation is determination of the amount of force to apply. Excessive force may lead to LAA tear, whereas inadequate force may result in LAA opening after repetitive cardiac motion against an inadequately tightened suture. In the present study, a tensor was used to apply a prespecified amount of force to the external LAA loop. We previously found that ostial ligation with sufficient force for closure results in loss of distal LAA electrograms within seconds, presumably due to tissue anoxia.10 This raises the possibility that electrogram loss may be a surrogate for sufficient closure, although this has not been validated clinically. Although the clinical significance of leaks is unknown, intuitively they are best avoided. In the end, the goal of LAA exclusion is to safely attenuate the risk of stroke in atrial fibrillation patients at least as effectively as oral anticoagulation, especially in patients who are at high risk for bleeding. Because of differences in patients studied, center experience, and study methodology, whether the hybrid system compares favorably or unfavorably to other stroke prevention strategies with regard to safety remains unknown. However, the study by Miller et al adds to the clarion call for well-developed operator and center training programs with the introduction of a new complex technology and the need for formal studies to assess the role of this technology in clinical practice.
1861
References 1. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257–e354. 2. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P; Protect AF Investigators. 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. 3. Friedman PA, Holmes DR. Non-surgical left atrial appendage closure for stroke prevention in atrial fibrillation. J Cardiovasc Electrophysiol 2011;22:1184–1191. 4. Miller MA, Gangireddy SR, Doshi SK, Aryana A, Koruth JS, Sennhauser S, d’Avila A, Dukkipati SR, Neuzil P, Reddy VY. Multicenter study on acute and long-term safety and efficacy of percutaneous left atrial appendage closure using an epicardial suture snaring device. Heart Rhythm 2014;11:1853–1859. 5. Stone D, Byrne T, Pershad A. Early results with the LARIAT device for left atrial appendage exclusion in patients with atrial fibrillation at high risk for stroke and anticoagulation. Catheter Cardiovasc Interv 2013; [Epub ahead of print]. 6. Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov SJ, Lee RJ. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol 2013;62:108–118. 7. Price MJ, Gibson DN, Yakubov SJ, et al. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the US transcatheter LAA ligation consortium. J Am Coll Cardiol 2014;64:565–572. 8. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation 2011;123:417–424. 9. Holmes DR, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy. J Am Coll Cardiol 2014;64:1–12. 10. Friedman PA, Asirvatham SJ, Dalegrave C, Kinoshita M, Danielsen AJ, Johnson SB, Hodge DO, Munger TM, Packer DL, Bruce CJ. Percutaneous epicardial left atrial appendage closure: preliminary results of an electrogram guided approach. J Cardiovasc Electrophysiol 2009;20:908–915.