- Email: [email protected]
Can we isolate the pulmonary veins?
EDITORIAL COMMENTARY
Can we isolate the pulmonary veins? Juna Misiri, MD,* Samuel J. Asirvatham, MD, FHRS*† From the *Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, and †Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota. Ablation for atrial fibrillation (AF) ranks as one of the greatest successes and a perplexing failure of contemporary cardiac electrophysiology. Despite tremendous continued enthusiasm, several experienced interventional electrophysiologists consider AF ablation as a palliative rather than a curative procedure.1 This likely reality has resulted from the increasingly documented high rates of recurrence of AF following ablation.2–5 The cornerstone for AF ablation is pulmonary vein (PV) isolation, which involves some form of circumferential atrial ablation. The lack of uniform long-term success has prompted 2 important questions: (1) Do we need to isolate the PVs or are other targets more appropriate? (2) Can we effectively and permanently isolate the PVs? It is essential to answer the latter question before we can address the former. In this issue of HeartRhythm, McClellan et al6 enlighten us on the potential relationship of specific PV anatomy and AF ablation outcomes. One hundred two patients underwent PV anatomy assessment with cardiac magnetic resonance or computed tomography. The authors report the correlation between anatomic variance, such as common left-sided PVs and the characteristic of the left atrial endocardial ridge, and recurrences following ablation. In most other cardiac arrhythmias, although topology (infarction, surgical scar, etc.) correlates with arrhythmogenesis in outcomes, the fact that anatomy impacts outcomes is not entirely intuitive. Possible questions that arise include whether varying pulmonary anatomy is a cause for AF or whether it simply represents a more difficult landscape for successful ablation. More generally, a fundamental question emerges: Is there anatomic and spatial fixity or altered atrial electrophysiology?
Anatomy and arrhythmogenesis McClellan et al6 report that a minority of patients have conventional 4-PV anatomy. This is in contrast to findings from autopsy studies in nonablation, presumably non-AF patients.7 The implication that variant anatomy may underlie the arrhythmogenesis for AF appears simplistic. More likely,
Address reprint requests and correspondence: Dr. Samuel J. Asirvatham, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905. E-mail address: asirvatham.samuel @mayo.edu.
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
the complex developmental anatomic forces that underlie normal and variant adult PV anatomy may have correlates with arrhythmogenesis.8,9 The position and presence of conduction tissue remnants, the left superior vena cava, and neuroectodermal pericardiac remnant tissue all may be affected by whether or not, for example, the carina between 2 PVs exist.
Anatomy and causes for difficulty in ablation McClellan et al6 found that abnormal anatomy, such as a common left PV, accessory vein, and the prominence of the left endocardial ridge between the PVs, PV ostia, and left atrial appendage, was the only independent predictor of the likelihood for AF recurrence after ablation. Regional anatomy clearly impacts the difficulty with transmural ablation at any given site in the heart. With regard to the PVs, however, we have a definite endpoint of electrical isolation of the PVs to know whether we were successful with PV isolation. Unfortunately, for reasons that are unclear, despite clear evidence at the time of procedure for entrance and/or exit block into the PV, along with meticulous demonstration that it was indeed PV potentials that were successfully eliminated,10,11 recurrent conduction is very common. In general, catheter contact and stability are more straightforward at the ostium of the PV, where there is a decreased likelihood for variant atrial anatomy (ridges, diverticula, etc.). Appropriately, ablationists are reluctant to ablate near the ostia for fear of PV stenosis. However, when a large common PV is present, it may be likely that we are more willing to ablate where we are comfortable with catheter contact relatively closer to the vein when a large vein is present. Transmural ablation of the endocardial ridge may be an important part of successful long-term ablation. As a result, prominent ridges, which presumably are more difficult to transmurally ablate, would be associated with recurrent postablation AF. Epicardial to the ridge is the consistent location of the vein and ligament of Marshall, along with a consistent fat pad containing ganglionated plexi.12 These remnants of the left superior vena cava and associated nodal and neural complexes may be an essential target for ablation that is rendered more difficult when the ridge is prominent. Regardless of PV isolation alone, the anterior left PV ablation circle necessarily involves this ridge if one is to http://dx.doi.org/10.1016/j.hrthm.2013.12.035
558 avoid intra-vein or intra-appendage ablation.7 At the present time, whether incomplete ablation and the resulting edema fool us into thinking we have indeed permanently isolated the vein or regrowth of cardiac or vascular tissue across the ablation circle simply prevents permanent isolation is unknown. However, data from studies with more careful attention to local atrial complete ablation, including pacing for capture and obliteration of local endocardial signals along with measurements of contact force, suggest that improved outcomes are possible if we completely ablate atrial tissue regardless of the difficulty posed by local anatomy.13,14
Anatomy and fixity of substrate Electrophysiologists have long understood the complex and multiple electrophysiologic abnormalities that constitute potential substrate for AF genesis. These include anchor points from multiple wavelet generation, rotors, and heterogeneous fibrosis that promote abnormal conduction and possibly repolarization. More recently, demonstration of anatomic fixity both temporally and spatially for such substrates, including rotors, has been demonstrated and thus potentially represents an attractive target for ablation.15 For such approaches to be successful, the same localized substrate needs to be operative for any induced or spontaneously occurring in a particular patient. If this is indeed true, then this suggests that anatomy, rather than ongoing pathologic changes (which presumably would be random), constitutes primary and fixed substrates for AF genesis. Whether such anatomic causes for localized abnormality result from variant PV anatomy, local atrial fiber geometry, or the closely related cardiac autonomic nervous system and whether related nonmyocardial structures represent the primary target need assessment.16,17
Anatomic non-isolation Peri-PV ablation impacted by venous anatomy may in turn affect success with ablation that has nothing to do with whether or not we are isolating the PV. The fat pads and ganglia, cardiac telocytes, and potential rotor sites all occur close to the PV ostia. Newer approaches forgo the need for PV isolation and focus directly on autonomic ganglia ablation and, in recent studies, direct ablation of the PV myocardium with novel approaches that hopefully prevent PV stenosis.18,19 In their carefully conducted study, McClellan et al point out a fact of PV anatomy correlation with AF ablation outcomes.
Heart Rhythm, Vol 11, No 4, April 2014 Further investigation is needed to determine the gross, histologic, and developmental anatomic correlates for ablation success beyond the impact on PV isolation alone.
References 1. den Uijl DW, Tops LF, Delgado V, et al. Effect of pulmonary vein anatomy and left atrial dimensions on outcome of circumferential radiofrequency catheter ablation for atrial fibrillation. Am J Cardiol 2011;107:243–249. 2. Hof I, Chilukuri K, Arbab-Zadeh A, et al. Does left atrial volume and pulmonary venous anatomy predict the outcome of catheter ablation of atrial fibrillation? J Cardiovasc Electrophysiol 2009;20:1005–1010. 3. Kato R, Lickfett L, Meininger G, et al. Pulmonary vein anatomy in patients undergoing catheter ablation of atrial fibrillation: lessons learned by use of magnetic resonance imaging. Circulation 2003;107:2004–2010. 4. Mansour M, Holmvang G, Sosnovik D, et al. Assessment of pulmonary vein anatomic variability by magnetic resonance imaging: implications for catheter ablation techniques for atrial fibrillation. J Cardiovasc Electrophysiol 2004;15: 387–393. 5. Sohns C, Sohns JM, Bergau L, et al. Pulmonary vein anatomy predicts freedom from atrial fibrillation using remote magnetic navigation for circumferential pulmonary vein ablation. Europace 2013;15:1136–1142. 6. McClellan AJA, Ling LH, Ruggiero D, et al. Pulmonary vein isolation: the impact of pulmonary venous anatomy on long-term outcome of catheter ablation for paroxysmal atrial fibrillation. Heart Rhythm 2014;11:549–556. 7. Gami AS, Noheria A, Lachman N, et al. Anatomical correlates relevant to ablation above the semilunar valves for the cardiac electrophysiologist: a study of 603 hearts. J Interv Card Electrophysiol 2011;30:5–15. 8. Christoffels VM, Moorman AF. Development of the cardiac conduction system: why are some regions of the heart more arrhythmogenic than others? Circ Arrhythm Electrophysiol 2009;2:195–207. 9. Sylva M, van den Hoff MJ, Moorman AF. Development of the human heart. Am J Med Genet A 2013; Apr 30:0. 10. Asirvatham SJ. Pulmonary vein-related maneuvers: part I. Heart Rhythm 2007;4: 538–544. 11. Asirvatham SJ. Pacing maneuvers for nonpulmonary vein sources: part II. Heart Rhythm 2007;4:681–685. 12. Kapa S, Venkatachalam KL, Asirvatham SJ. The autonomic nervous system in cardiac electrophysiology: an elegant interaction and emerging concepts. Cardiol Rev 2010;18:275–284. 13. Neuzil P, Reddy VY, Kautzner J, et al. Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial treatment: results from the EFFICAS I study. Circ Arrhythm Electrophysiol 2013;6:327–333. 14. Steven D, Sultan A, Reddy V, et al. Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial. J Am Coll Cardiol 2013;62:44–50. 15. Jones AR, Krummen DE, Narayan SM. Non-invasive identification of stable rotors and focal sources for human atrial fibrillation: mechanistic classification of atrial fibrillation from the electrocardiogram. Europace 2013;15:1249–1258. 16. Lo LW, Scherlag BJ, Chang HY, Lin YJ, Chen SA, Po SS. Paradoxical long-term proarrhythmic effects after ablating the “head station” ganglionated plexi of the vagal innervation to the heart. Heart Rhythm 2013;10:751–757. 17. Gherghiceanu M, Hinescu ME, Andrei F, et al. Interstitial Cajal-like cells (ICLC) in myocardial sleeves of human pulmonary veins. J Cell Mol Med 2008;12: 1777–1781. 18. DeSimone CV, Madhavan M, Venkatachalam KL, Knudson MB, Asirvatham SJ. Percutaneous autonomic neural modulation: a novel technique to treat cardiac arrhythmia. Cardiovasc Revasc Med 2013;14:144–148. 19. Asirvatham SJ. Methods to identify the pulmonary vein ostium. Heart Rhythm 2005;2:1090–1093.
Can we isolate the pulmonary veins? Juna Misiri, MD,* Samuel J. Asirvatham, MD, FHRS*† From the *Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, and †Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota. Ablation for atrial fibrillation (AF) ranks as one of the greatest successes and a perplexing failure of contemporary cardiac electrophysiology. Despite tremendous continued enthusiasm, several experienced interventional electrophysiologists consider AF ablation as a palliative rather than a curative procedure.1 This likely reality has resulted from the increasingly documented high rates of recurrence of AF following ablation.2–5 The cornerstone for AF ablation is pulmonary vein (PV) isolation, which involves some form of circumferential atrial ablation. The lack of uniform long-term success has prompted 2 important questions: (1) Do we need to isolate the PVs or are other targets more appropriate? (2) Can we effectively and permanently isolate the PVs? It is essential to answer the latter question before we can address the former. In this issue of HeartRhythm, McClellan et al6 enlighten us on the potential relationship of specific PV anatomy and AF ablation outcomes. One hundred two patients underwent PV anatomy assessment with cardiac magnetic resonance or computed tomography. The authors report the correlation between anatomic variance, such as common left-sided PVs and the characteristic of the left atrial endocardial ridge, and recurrences following ablation. In most other cardiac arrhythmias, although topology (infarction, surgical scar, etc.) correlates with arrhythmogenesis in outcomes, the fact that anatomy impacts outcomes is not entirely intuitive. Possible questions that arise include whether varying pulmonary anatomy is a cause for AF or whether it simply represents a more difficult landscape for successful ablation. More generally, a fundamental question emerges: Is there anatomic and spatial fixity or altered atrial electrophysiology?
Anatomy and arrhythmogenesis McClellan et al6 report that a minority of patients have conventional 4-PV anatomy. This is in contrast to findings from autopsy studies in nonablation, presumably non-AF patients.7 The implication that variant anatomy may underlie the arrhythmogenesis for AF appears simplistic. More likely,
Address reprint requests and correspondence: Dr. Samuel J. Asirvatham, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905. E-mail address: asirvatham.samuel @mayo.edu.
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
the complex developmental anatomic forces that underlie normal and variant adult PV anatomy may have correlates with arrhythmogenesis.8,9 The position and presence of conduction tissue remnants, the left superior vena cava, and neuroectodermal pericardiac remnant tissue all may be affected by whether or not, for example, the carina between 2 PVs exist.
Anatomy and causes for difficulty in ablation McClellan et al6 found that abnormal anatomy, such as a common left PV, accessory vein, and the prominence of the left endocardial ridge between the PVs, PV ostia, and left atrial appendage, was the only independent predictor of the likelihood for AF recurrence after ablation. Regional anatomy clearly impacts the difficulty with transmural ablation at any given site in the heart. With regard to the PVs, however, we have a definite endpoint of electrical isolation of the PVs to know whether we were successful with PV isolation. Unfortunately, for reasons that are unclear, despite clear evidence at the time of procedure for entrance and/or exit block into the PV, along with meticulous demonstration that it was indeed PV potentials that were successfully eliminated,10,11 recurrent conduction is very common. In general, catheter contact and stability are more straightforward at the ostium of the PV, where there is a decreased likelihood for variant atrial anatomy (ridges, diverticula, etc.). Appropriately, ablationists are reluctant to ablate near the ostia for fear of PV stenosis. However, when a large common PV is present, it may be likely that we are more willing to ablate where we are comfortable with catheter contact relatively closer to the vein when a large vein is present. Transmural ablation of the endocardial ridge may be an important part of successful long-term ablation. As a result, prominent ridges, which presumably are more difficult to transmurally ablate, would be associated with recurrent postablation AF. Epicardial to the ridge is the consistent location of the vein and ligament of Marshall, along with a consistent fat pad containing ganglionated plexi.12 These remnants of the left superior vena cava and associated nodal and neural complexes may be an essential target for ablation that is rendered more difficult when the ridge is prominent. Regardless of PV isolation alone, the anterior left PV ablation circle necessarily involves this ridge if one is to http://dx.doi.org/10.1016/j.hrthm.2013.12.035
558 avoid intra-vein or intra-appendage ablation.7 At the present time, whether incomplete ablation and the resulting edema fool us into thinking we have indeed permanently isolated the vein or regrowth of cardiac or vascular tissue across the ablation circle simply prevents permanent isolation is unknown. However, data from studies with more careful attention to local atrial complete ablation, including pacing for capture and obliteration of local endocardial signals along with measurements of contact force, suggest that improved outcomes are possible if we completely ablate atrial tissue regardless of the difficulty posed by local anatomy.13,14
Anatomy and fixity of substrate Electrophysiologists have long understood the complex and multiple electrophysiologic abnormalities that constitute potential substrate for AF genesis. These include anchor points from multiple wavelet generation, rotors, and heterogeneous fibrosis that promote abnormal conduction and possibly repolarization. More recently, demonstration of anatomic fixity both temporally and spatially for such substrates, including rotors, has been demonstrated and thus potentially represents an attractive target for ablation.15 For such approaches to be successful, the same localized substrate needs to be operative for any induced or spontaneously occurring in a particular patient. If this is indeed true, then this suggests that anatomy, rather than ongoing pathologic changes (which presumably would be random), constitutes primary and fixed substrates for AF genesis. Whether such anatomic causes for localized abnormality result from variant PV anatomy, local atrial fiber geometry, or the closely related cardiac autonomic nervous system and whether related nonmyocardial structures represent the primary target need assessment.16,17
Anatomic non-isolation Peri-PV ablation impacted by venous anatomy may in turn affect success with ablation that has nothing to do with whether or not we are isolating the PV. The fat pads and ganglia, cardiac telocytes, and potential rotor sites all occur close to the PV ostia. Newer approaches forgo the need for PV isolation and focus directly on autonomic ganglia ablation and, in recent studies, direct ablation of the PV myocardium with novel approaches that hopefully prevent PV stenosis.18,19 In their carefully conducted study, McClellan et al point out a fact of PV anatomy correlation with AF ablation outcomes.
Heart Rhythm, Vol 11, No 4, April 2014 Further investigation is needed to determine the gross, histologic, and developmental anatomic correlates for ablation success beyond the impact on PV isolation alone.
References 1. den Uijl DW, Tops LF, Delgado V, et al. Effect of pulmonary vein anatomy and left atrial dimensions on outcome of circumferential radiofrequency catheter ablation for atrial fibrillation. Am J Cardiol 2011;107:243–249. 2. Hof I, Chilukuri K, Arbab-Zadeh A, et al. Does left atrial volume and pulmonary venous anatomy predict the outcome of catheter ablation of atrial fibrillation? J Cardiovasc Electrophysiol 2009;20:1005–1010. 3. Kato R, Lickfett L, Meininger G, et al. Pulmonary vein anatomy in patients undergoing catheter ablation of atrial fibrillation: lessons learned by use of magnetic resonance imaging. Circulation 2003;107:2004–2010. 4. Mansour M, Holmvang G, Sosnovik D, et al. Assessment of pulmonary vein anatomic variability by magnetic resonance imaging: implications for catheter ablation techniques for atrial fibrillation. J Cardiovasc Electrophysiol 2004;15: 387–393. 5. Sohns C, Sohns JM, Bergau L, et al. Pulmonary vein anatomy predicts freedom from atrial fibrillation using remote magnetic navigation for circumferential pulmonary vein ablation. Europace 2013;15:1136–1142. 6. McClellan AJA, Ling LH, Ruggiero D, et al. Pulmonary vein isolation: the impact of pulmonary venous anatomy on long-term outcome of catheter ablation for paroxysmal atrial fibrillation. Heart Rhythm 2014;11:549–556. 7. Gami AS, Noheria A, Lachman N, et al. Anatomical correlates relevant to ablation above the semilunar valves for the cardiac electrophysiologist: a study of 603 hearts. J Interv Card Electrophysiol 2011;30:5–15. 8. Christoffels VM, Moorman AF. Development of the cardiac conduction system: why are some regions of the heart more arrhythmogenic than others? Circ Arrhythm Electrophysiol 2009;2:195–207. 9. Sylva M, van den Hoff MJ, Moorman AF. Development of the human heart. Am J Med Genet A 2013; Apr 30:0. 10. Asirvatham SJ. Pulmonary vein-related maneuvers: part I. Heart Rhythm 2007;4: 538–544. 11. Asirvatham SJ. Pacing maneuvers for nonpulmonary vein sources: part II. Heart Rhythm 2007;4:681–685. 12. Kapa S, Venkatachalam KL, Asirvatham SJ. The autonomic nervous system in cardiac electrophysiology: an elegant interaction and emerging concepts. Cardiol Rev 2010;18:275–284. 13. Neuzil P, Reddy VY, Kautzner J, et al. Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial treatment: results from the EFFICAS I study. Circ Arrhythm Electrophysiol 2013;6:327–333. 14. Steven D, Sultan A, Reddy V, et al. Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial. J Am Coll Cardiol 2013;62:44–50. 15. Jones AR, Krummen DE, Narayan SM. Non-invasive identification of stable rotors and focal sources for human atrial fibrillation: mechanistic classification of atrial fibrillation from the electrocardiogram. Europace 2013;15:1249–1258. 16. Lo LW, Scherlag BJ, Chang HY, Lin YJ, Chen SA, Po SS. Paradoxical long-term proarrhythmic effects after ablating the “head station” ganglionated plexi of the vagal innervation to the heart. Heart Rhythm 2013;10:751–757. 17. Gherghiceanu M, Hinescu ME, Andrei F, et al. Interstitial Cajal-like cells (ICLC) in myocardial sleeves of human pulmonary veins. J Cell Mol Med 2008;12: 1777–1781. 18. DeSimone CV, Madhavan M, Venkatachalam KL, Knudson MB, Asirvatham SJ. Percutaneous autonomic neural modulation: a novel technique to treat cardiac arrhythmia. Cardiovasc Revasc Med 2013;14:144–148. 19. Asirvatham SJ. Methods to identify the pulmonary vein ostium. Heart Rhythm 2005;2:1090–1093.