Abstract
While isolation of the pulmonary veins is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients, there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins. Various computational approaches have been used to identify targets for effective ablation of persistent AF. This paper aims to discuss the clinical aspects of computational approaches that aim to identify critical sites for treatment. Various analyses of electrogram characteristics have been performed with this aim. Leading techniques for electrogram analysis are Complex Fractionated Atrial Electrograms (CFAE) and Dominant Frequency (DF). These techniques have been the subject of clinical trials of which the results are discussed. Evaluation of the activation patterns of atria in AF has been another avenue of research. Focal Impulse and Rotor Modulation (FIRM) mapping and forms of Body Surface Mapping aim to characterize multiple atrial wavelets, macro-reentry and focal sources which have been proposed as basic mechanisms perpetuating AF. Both invasive and non-invasive activation mapping techniques are reviewed. The presence of atrial fibrosis causes non-uniform anisotropic impulse propagation. Therefore, identification of fibrosis by imaging techniques is an avenue of potential research. The leading contender for imaging-based techniques is Cardiac Magnetic Resonance (CMR). As this technology advances, improvements in resolution and scar identification have positioned CMR as the mode of choice for analysis of atrial structure. AF has been demonstrated to be associated with obesity, inactivity and diseases of modern life. An opportunity exists for detailed computational analysis of the impact of risk factor modification on atrial substrate. This ranges from microstructural investigation through to examination at a population level via registries and public health interventions. Computational analysis of atrial substrate has moved from basic science toward clinical application. Future directions and potential limitations of such analyses are examined in this review.
| Original language | English |
|---|---|
| Article number | 1158 |
| Journal | Frontiers in Physiology |
| Volume | 9 |
| Issue number | SEP |
| DOIs | |
| Publication status | Published or Issued - 18 Sep 2018 |
Keywords
- Ablation techniques
- Atrial fibrillation
- Fibrosis
- Imaging
- Imaging
- Lifestyle interventions
- Mapping & localization
- Three-dimensional
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
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Targeting the substrate in ablation of persistent atrial fibrillation : Recent lessons and future directions. / Stiles, Martin K.; Sanders, Prash; Lau, Dennis H.
In: Frontiers in Physiology, Vol. 9, No. SEP, 1158, 18.09.2018.Research output: Contribution to journal › Review article › peer-review
TY - JOUR
T1 - Targeting the substrate in ablation of persistent atrial fibrillation
T2 - Recent lessons and future directions
AU - Stiles, Martin K.
AU - Sanders, Prash
AU - Lau, Dennis H.
N1 - Funding Information: Sanders, P., Berenfeld, O., Hocini, M., Jaïs, P., Vaidyanathan, R., Hsu, L. F., et al. (2005). Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans. Circulation 112, 789–797. doi: 10.1161/CIRCULATIONAHA.104.517011 Sanders, P., Mishima, R. S., Linz, D., and Lau, D. H. (2018). In search of atrial fibrillation driver sites: is temporally stable frequency mapping a new armamentarium? J. Cardiovasc. Electrophysiol. 29, 523–525. doi: 10.1111/jce Sanders, P., Morton, J. B., Davidson, N. C., Spence, S. J., Vohra, J. K., Sparks, P. B., et al. (2003). Electrical remodeling of the atria in congestive heart failure: electrophysiological and electroanatomic mapping in humans. Circulation 108, 1461–1468. doi: 10.1161/01.CIR.0000090688.49283.67 Shiroshita-Takeshita, A., Brundel, B. J., Burstein, B., Leung, T. K., Mitamura, H., Ogawa, S., et al. (2007). Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure. Cardiovasc. Res. 74, 75–84. doi: 10.1016/j.cardiores.2007.01.002 Sohns, C., Lemes, C., Metzner, A., Fink, T., Chmelevsky, M., Maurer, T., et al. (2017). First-in-Man analysis of the relationship between electrical rotors from noninvasive panoramic mapping and atrial fibrosis from magnetic resonance imaging in patients with persistent atrial fibrillation. Circ. Arrhythm Electrophysiol. 10:e004419. doi: 10.1161/CIRCEP.116.004419 Spach, M. S., and Dolber, P. C. (1986). Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ. Res. 58, 356–371. doi: 10.1161/01.RES.58.3.356 Stiles, M. K., Brooks, A. G., Kuklik, P., John, B., Dimitri, H., Lau, D. H., et al. (2008). High-density mapping of atrial fibrillation in humans: relationship between high-frequency activation and electrogram fractionation. J. Cardiovasc. Electrophysiol. 19, 1245–1253. doi: 10.1111/j.1540-8167.2008.0 1253.x Stiles, M. K., John, B., Wong, C. X., Kuklik, P., Brooks, A. G., Lau, D. H., et al. (2009). Paroxysmal lone atrial fibrillation is associated with an abnormal atrial substrate: characterizing the “second factor”. J. Am. Coll. Cardiol. 53, 1182–1191. doi: 10.1016/j.jacc.2008.11.054 Teh, A. W., Kistler, P. M., Lee, G., Medi, C., Heck, P. M., Spence, S. J., et al. (2012). Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation. Heart Rhythm 9, 473–480. doi: 10.1016/j.hrthm.2011.11.013 Thanigaimani, S., Brooks, A. G., Kuklik, P., Twomey, D. J., Franklin, S., Noschka, E., et al. (2017a). Spatiotemporal characteristics of atrial fibrillation electrograms: a novel marker for arrhythmia stability and termination. J. Arrhythm 33, 40–48. doi: 10.1016/j.joa.2016.05.009 Thanigaimani, S., Lau, D. H., Agbaedeng, T., Elliott, A. D., Mahajan, R., and Sanders, P. (2017b). Molecular mechanisms of atrial fibrosis: implications for the clinic. Exp. Rev. Cardiovasc. Ther. 15, 247–256. doi: 10.1080/14779072.2017.1299005 Thomas, M. C., Dublin, S., Kaplan, R. C., Glazer, N. L., Lumley, T., Longstreth, Jr. W. T., et al. (2008). Blood pressure control and risk of incident atrial fibrillation. Am. J. Hypertens. 21, 1111–1116. doi: 10.1038/ajh.2008.248 Verheule, S., Tuyls, E., Gharaviri, A., Hulsmans, S., van Hunnik, A., Kuiper, M., et al. (2013). Loss of continuity in the thin epicardial layer because of endomysial fibrosis increases the complexity of atrial fibrillatory conduction. Circ. Arrhythm Electrophysiol. 6, 202–211. doi: 10.1161/CIRCEP.112.9 75144 Verma, A., Jiang, C. Y., Betts, T. R., Chen, J., Deisenhofer, I., Mantovan, R., et al. (2015). Approaches to catheter ablation for persistent atrial fibrillation. N. Engl. J. Med. 372, 1812–1822. doi: 10.1056/NEJMoa1408288 Vogler, J., Willems, S., Sultan, A., Schreiber, D., Lüker, J., Servatius, H., et al. (2015). Pulmonary vein isolation versus defragmentation: the chase-af clinical trial. J. Am. Coll. Cardiol. 66, 2743–2752. doi: 10.1016/j.jacc.2015. 09.088 Walters, T. E., Lee, G., Morris, G., Spence, S., Larobina, M., Atkinson, V., et al. (2015). Temporal stability of rotors and atrial activation patterns in persistent human atrial fibrillation. JACC Clin. Electrophysiol. 1, 14–24. doi: 10.1016/j.jacep.2015.02.012 Walters, T. E., Lee, G., Spence, S., and Kalman, J. M. (2016). The effect of electrode density on the interpretation of atrial activation patterns in epicardial mapping of human persistent atrial fibrillation. Heart Rhythm 13, 1215–1220. doi: 10.1016/j.hrthm.2016.01.030 Wong, C. X., Abed, H. S., Molaee, P., Nelson, A. J., Brooks, A. G., Sharma, G., et al. (2011). Pericardial fat is associated with atrial fibrillation severity and ablation outcome. J. Am. Coll. Cardiol. 57, 1745–1751. doi: 10.1016/j.jacc.2010. 11.045 Wong, C. X., Sullivan, T., Sun, M. T., Mahajan, R., Pathak, R. K., Middeldorp, M., et al. (2015). Obesity and the risk of incident, post-operative, and post-ablation atrial fibrillation. JACC: Clin. Electrophysiol. 1, 139–152. doi: 10.1016/j.jacep.2015.04.004 Wong, K. C., Paisey, J. R., Sopher, M., Balasubramaniam, R., Jones, M., Qureshi, N., et al. (2015). No benefit of complex fractionated atrial electrogram ablation in addition to circumferential pulmonary vein ablation and linear ablation: benefit of complex ablation study. Circ. Arrhythm. Electrophysiol. 8, 1316–1324. doi: 10.1161/CIRCEP.114.002504 Yamabe, H., Kanazawa, H., Ito, M., Kaneko, S., and Ogawa, H. (2016). Prevalence and mechanism of rotor activation identified during atrial fibrillation by noncontact mapping: lack of evidence for a role in the maintenance of atrial fibrillation. Heart Rhythm 13, 2323–2330. doi: 10.1016/j.hrthm.2016. 07.030 Zghaib, T., Keramati, A., Chrispin, J., Huang, D., Balouch, M. A., Ciuffo, L., et al. (2018). multimodal examination of atrial fibrillation substrate: correlation of left atrial bipolar voltage using multi-electrode fast automated mapping, point-by-point mapping, and magnetic resonance image intensity ratio. JACC Clin. Electrophysiol. 4, 59–68. doi: 10.1016/j.jacep.2017.10.010 Zhao, J., Hansen, B. J., Wang, Y., Csepe, T. A., Sul, L. V., Tang, A., et al. (2017). Three-dimensional integrated functional, structural, and computational mapping to define the structural “fingerprints” of heart-specific atrial fibrillation drivers in human heart ex vivo. J. Am. Heart Assoc. 6:e005922. doi: 10.1161/JAHA.117.005922 Conflict of Interest Statement: PS reports having served on the advisory board of Biosense-Webster, Medtronic, Abbott, Boston Scientific and CathRx. PS reports that the University of Adelaide receives on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic, Abbott, and Boston Scientific. PS reports that the University of Adelaide receives on his behalf research funding from Medtronic, Abbott, Boston Scientific, Biotronik and Liva Nova. DL reports that the University of Adelaide has received on his behalf lecture or consulting fees from St Jude Medical, Boehringer Ingelheim, Bayer, and Pfizer. Funding Information: DL is supported by the Robert J. Craig Lectureship from the University of Adelaide. PS is supported by Practitioner Fellowships from the NHMRC and NHF of Australia. Publisher Copyright: Copyright © 2018 Stiles, Sanders and Lau.
PY - 2018/9/18
Y1 - 2018/9/18
N2 - While isolation of the pulmonary veins is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients, there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins. Various computational approaches have been used to identify targets for effective ablation of persistent AF. This paper aims to discuss the clinical aspects of computational approaches that aim to identify critical sites for treatment. Various analyses of electrogram characteristics have been performed with this aim. Leading techniques for electrogram analysis are Complex Fractionated Atrial Electrograms (CFAE) and Dominant Frequency (DF). These techniques have been the subject of clinical trials of which the results are discussed. Evaluation of the activation patterns of atria in AF has been another avenue of research. Focal Impulse and Rotor Modulation (FIRM) mapping and forms of Body Surface Mapping aim to characterize multiple atrial wavelets, macro-reentry and focal sources which have been proposed as basic mechanisms perpetuating AF. Both invasive and non-invasive activation mapping techniques are reviewed. The presence of atrial fibrosis causes non-uniform anisotropic impulse propagation. Therefore, identification of fibrosis by imaging techniques is an avenue of potential research. The leading contender for imaging-based techniques is Cardiac Magnetic Resonance (CMR). As this technology advances, improvements in resolution and scar identification have positioned CMR as the mode of choice for analysis of atrial structure. AF has been demonstrated to be associated with obesity, inactivity and diseases of modern life. An opportunity exists for detailed computational analysis of the impact of risk factor modification on atrial substrate. This ranges from microstructural investigation through to examination at a population level via registries and public health interventions. Computational analysis of atrial substrate has moved from basic science toward clinical application. Future directions and potential limitations of such analyses are examined in this review.
AB - While isolation of the pulmonary veins is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients, there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins. Various computational approaches have been used to identify targets for effective ablation of persistent AF. This paper aims to discuss the clinical aspects of computational approaches that aim to identify critical sites for treatment. Various analyses of electrogram characteristics have been performed with this aim. Leading techniques for electrogram analysis are Complex Fractionated Atrial Electrograms (CFAE) and Dominant Frequency (DF). These techniques have been the subject of clinical trials of which the results are discussed. Evaluation of the activation patterns of atria in AF has been another avenue of research. Focal Impulse and Rotor Modulation (FIRM) mapping and forms of Body Surface Mapping aim to characterize multiple atrial wavelets, macro-reentry and focal sources which have been proposed as basic mechanisms perpetuating AF. Both invasive and non-invasive activation mapping techniques are reviewed. The presence of atrial fibrosis causes non-uniform anisotropic impulse propagation. Therefore, identification of fibrosis by imaging techniques is an avenue of potential research. The leading contender for imaging-based techniques is Cardiac Magnetic Resonance (CMR). As this technology advances, improvements in resolution and scar identification have positioned CMR as the mode of choice for analysis of atrial structure. AF has been demonstrated to be associated with obesity, inactivity and diseases of modern life. An opportunity exists for detailed computational analysis of the impact of risk factor modification on atrial substrate. This ranges from microstructural investigation through to examination at a population level via registries and public health interventions. Computational analysis of atrial substrate has moved from basic science toward clinical application. Future directions and potential limitations of such analyses are examined in this review.
KW - Ablation techniques
KW - Atrial fibrillation
KW - Fibrosis
KW - Imaging
KW - Imaging
KW - Lifestyle interventions
KW - Mapping & localization
KW - Three-dimensional
UR - http://www.scopus.com/inward/record.url?scp=85055112150&partnerID=8YFLogxK
U2 - 10.3389/fphys.2018.01158
DO - 10.3389/fphys.2018.01158
M3 - Review article
AN - SCOPUS:85055112150
VL - 9
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
IS - SEP
M1 - 1158
ER -