Multi-polar stimulation of the left ventricle during cardio-resynchronisation therapy in patients with congestive heart failure: Randomised pilot study outcomes from parallel groups
Published 2020-04-07
Keywords
- cardiac resynchronization therapy,
- chronic heart failure,
- multipolar lead,
- multipoint pacing,
- multisite pacing
How to Cite
Copyright (c) 2020 Ponomarenko A.V., Mikheenko I.L., Morzhanayev E.A., Filippenko A.G., Losik D.V., Shabanov V.V., Peregudov I.S., Zhizhov R.E., Artemenko S.N., Romanov A.B.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Abstract
Background. Cardiac resynchronisation therapy (CRT) has been used for the treatment of patients with congestive heart failure (CHF) and wide QRS complexes for more than ten years. Nevertheless, the percentage of patients unresponsive to this therapy is 30%. There is recent evidence for increased responder proportions to treatments with multipolar pacing of the left ventricle (LV) in CRT. Accordingly, the aim of this study is to evaluate the effectiveness of multi-polar pacing of LV in patients with CHF and indications for CRT.
Methods. Sixty-two patients [42 men, mean age 62.5 (58–68) years] with CHF and indications for CRT (for example patients with symptomatic heart failure and QRS duration ≥130 ms with left bundle branch block and left ventricular ejection fraction ≤ 35%) were included in this prospective, pilot, randomised study. Patients were implanted with cardiac resynchronisation devices with multi-polar electrodes. After implantation, patients were randomised into two groups according to the programming of the LV stimulation vector: true bipolar stimulation (group 1, stimulation vector LVring-LVtip, n = 31) and extended-bipolar LV stimulation (group 2, standard programming LV ring to RV, n = 31). The main objective of the study was to assess the effects of true bipolar stimulation on the increase of the number of CRT responders. Responders were defined as patients with a 15% decrease in the left ventricular end systolic volume compared with the initial characteristics as detected by echocardiography. Secondary points included changes in a) left ventricular ejection fraction (LVEF), b) 6-min walk test dynamics, and c) brain natriuretic peptide. The observation period was 12 months.
Results. The LV electrode was implanted in the anterior (6%), antero-lateral (8%), lateral (18%), posterior (2%), or postero-lateral (66%) branches of the coronary sinus, and the average LV stimulation threshold was 1.7 ± 1.1 V. No intra-operative complications were detected. Four patients (6.5%) underwent LV electrode re-positioning on the second day after surgery owing to diaphragmatic nerve stimulation. At the end of the observation period, the average threshold used for LV stimulation of patients in the true bi-polar stimulation group with the LVring-LVtip vector was 1.9 ± 1.5 V compared with 1.6 ± 1.3 V in the case of the extended-bipolar LV stimulation group (p = 0.88). The number of responders in the true bipolar stimulation group was 25 (80.6%) compared with 21 (67.7%) patients in the extended-bipolar LV stimulation group (p = 0.38). LVEF significantly increased in both groups compared with pre-operative values without significant differences between the groups (29.4 vs. 36.5, p < 0.001 in the extended bipolar LV stimulation group; 28.0 vs. 34.9, p < 0.001 in the true bi-polar stimulation group, p = 0.86 between groups). The distance covered during the 6-min walk test significantly increased in both groups compared with pre-operative values in the absence of a significant difference between the groups (p = 0.92). The decreased levels of the cerebral natriuretic peptide were 60.3 ± 42.3 pg/ml and 56.6 ± 38.5 pg/ml in the extended and true bipolar stimulation groups, respectively (p = 0.95).
Conclusion. Based on the results of this pilot study, the choice of a vector for true bipolar LV stimulation demonstrated its advantage and tendency to increase the number of responders in subjects with implanted CRT devices. Subsequent multi-centre randomised trials will help determine the role of true bipolar LV stimulation and extended-bipolar stimulation from different regions of the LV to increase the response to CRT.
Received 24 December 2019. Revised 18 January 2020. Accepted 20 January 2020.
Funding: The work is supported by a grant of the President of the Russian Federation No. МД-2893.2018.7.
Conflict of interest: Authors declare no conflict of interest.
Author contributions
Conception and study design: A.B. Romanov
Data collection and analysis: A.V. Ponomarenko, I.L. Mikheenko, E.A. Morzhanayev, A.G. Filippenko, R.E. Zhizhov, I.S. Peregudov
Statistical analysis: A.B. Romanov, I.L. Mikheenko
Drafting the article: A.V. Ponomarenko, I.L. Mikheenko, E.A. Morzhanayev
Critical revision of the article: A.B. Romanov, D.V. Losik, I.L. Mikheenko, A.V. Ponomarenko, V.V. Shabanov, S.N. Artemenko
Final approval of the version to be published: A.V. Ponomarenko, I.L. Mikheenko, E.A. Morzhanayev, A.G. Filippenko, D.V. Losik, V.V. Shabanov, I.S. Peregudov, R.E. Zhizhov, A.B. Romanov, S.N. Artemenko
References
- Birnie D.H., Tang A.S. The problem of non-response to cardiac resynchronization therapy. Curr Opin Cardiol. 2006;21(1):20-6. PMID: 16355025. https://doi.org/10.1097/01.hco.0000198983.93755.99
- Chung E.S, Leon A.R., Tavazzi L., Sun J.-P., Nihoyannopoulos P., Merlino J., Abraham W.T., Ghio S., Leclercq C., Bax J.J., Yu C.-M., Gorcsan J. 3rd, St John Sutton M., De Sutter J., Murillo J. Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation. 2008;117(20):2608-16. PMID: 18458170. https://dx.doi.org/10.1161/CIRCULATIONAHA.107.743120
- Auricchio A., Prinzen F.W. Non-Responders to cardiac resynchronization therapy. Circ J. 2011;75(3):521-7. PMID: 21325727. https://dx.doi.org/10.1253/circj.CJ-10-1268
- Young J.B., Abraham W.T., Smith A.L., Leon A.R., Lieberman R., Wilkoff B., Canby R.C., Schroeder J.S., Liem L.B., Hall S., Wheelan K., Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003;289(20):2685-94. https://dx.doi.org/10.1001/jama.289.20.2685
- Becker M., Franke A., Breithardt O.A., Ocklenburg C., Kaminski T., Kramann R., Knackstedt C., Stellbrink C., Hanrath P., Schauerte P., Hoffmann R. Impact of left ventricular lead position on the efficacy of cardiac resynchronisation therapy: a two-dimensional strain echocardiography study. Heart. 2007;93(10):1197-203. https://dx.doi.org/10.1136/hrt.2006.095612
- Romanov A., Goscinska-Bis K., Bis J., Chernyavskiy A., Prokhorova D., Syrtseva Y., Shabanov V., Alsov S., Karaskov A., Deja M., Krejca M., Pokushalov E. Cardiac resynchronization therapy combined with coronary artery bypass grafting in ischaemic heart failure patients: long-term results of the RESCUE study. Eur J Cardiothorac Surg. 2016;50(1):36-41. https://dx.doi.org/10.1093/ejcts/ezv448
- Sperzel J., Danschel W.-J. Gutleben K., Kranig W., Mortensen P., Connelly D.-J., Trappe H., Seidl K., Duray G., Pieske B., Stockinger J., Boriani G., Jung W., Schilling R., Saberi L., Hallier B., Simon M., Rinaldi C.A. First prospective, multi-centre clinical experience with a novel left ventricular quadripolar lead. Europace. 2012;14(3):365-72. PMID: 21993431. https://dx.doi.org/10.1093/europace/eur322
- Tomassoni G., Baker J., Corbisiero R., Love C., Martin D., Niazi I., Sheppard R., Worley S., Beau S., Greer G.S., Aryana A., Cao M., Harbert N., Zhang S.; Promote® Q CRT-D and Quartet® Left Ventricular Heart Lead Study Group. Postoperative performance of the Quartet® left ventricular heart lead. J Cardiovasc Electrophysiol. 2013;24(4):449-56. PMID: 23339555. https://doi.org/10.1111/jce.12065
- Forleo G.B., Di Biase L., Bharmi R., Dalal N., Panattoni G., Pollastrelli A., Tesauro M., Santini L., Natale A., Romeo F. Hospitalization rates and associated cost analysis of cardiac resynchronization therapy with an implantable defibrillator and quadripolar vs. bipolar left ventricular leads: a comparative effectiveness study. Europace. 2015;17(1):101-7. PMID: 25371428, PMCID: PMC4280828. https://doi.org/10.1093/europace/euu290
- Pappone C., Ćalović Ž., Vicedomini G., Cuko A., McSpadden L.C., Ryu K., Romano E., Saviano M., Baldi M., Pappone A., Ciaccio C., Giannelli L., Ionescu B., Petretta A., Vitale R., Fundaliotis A., Tavazzi L., Santinelli V. Multipoint left ventricular pacing improves acute hemodynamic response assessed with pressure-volume loops in cardiac resynchronization therapy patients. Heart Rhythm. 2014;11(3):394-401. http://dx.doi.org/10.1016/j.hrthm.2013.11.023
- Thibault B., Dubuc M., Khairy P., Guerra P.G., Macle L., Rivard L., Roy D., Talajic M., Karst E., Ryu K., Paiement P., Farazi T.G. Acute haemodynamic comparison of multisite and biventricular pacing with a quadripolar left ventricular lead. Europace. 2013;15(7):984-91. http://dx.doi.org/10.1093/europace/eus435
- Osca J., Alonso P., Cano O., Andrés A., Miro V., Tello M.J.S., Olagüe J., Martínez L., Salvador A. The use of multisite left ventricular pacing via quadripolar lead improves acute haemodynamics and mechanical dyssynchrony assessed by radial strain speckle tracking: initial results. Europace. 2016;18(4):560-7. http://dx.doi.org/10.1093/europace/euv211
- Rinaldi C.A., Leclercq C., Kranig W., Kacet S., Betts T., Bordachar P., Gutleben K.-J., Shetty A., Donal E., Keel A., Ryu K., Farazi T.G., Simon M., Naqvi T.Z. Improvement in acute contractility and hemodynamics with multipoint pacing via a left ventricular quadripolar pacing lead. J Interv Card Electrophysiol. 2014;40(1):75-80. http://dx.doi.org/10.1007/s10840-014-9891-1
- Zanon F, Baracca E., Pastore G., Marcantoni L., Fraccaro C., Lanza D., Picariello C., Aggio S., Roncon L., Dell’Avvocata F., Rigatelli G., Pacetta D., Noventa F., Prinzen F.W. Multipoint pacing by a left ventricular quadripolar lead improves the acute hemodynamic response to CRT compared with conventional biventricular pacing at any site. Heart Rhythm. 2015;12(5):975-81. http://dx.doi.org/10.1016/j.hrthm.2015.01.034
- Ponikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G.F., Coats A.J.S., Falk V., González-Juanatey J.R., Harjola V.-P., Jankowska E.A., Jessup M., Linde C., Nihoyannopoulos P., Parissis J.T., Pieske B., Riley J.P., Rosano G.M.C., Ruilope L.M., Ruschitzka F., Rutten F.H., van der Meer P., ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-200. http://dx.doi.org/10.1093/eurheartj/ehw128
- Lercher P., Lunati M., Rordorf R., Landolina M., Badie N., Qu F., Casset C., Ryu K., Ghio S., Singh J.P., Leclercq C. Long-term reverse remodeling by cardiac resynchronization therapy with MultiPoint Pacing: A feasibility study of noninvasive hemodynamics–guided device programming. Heart Rhythm. 2018;15(12):1766-74. PMID: 29940305. https://doi.org/10.1016/j.hrthm.2018.06.032
- Moss A.J., Brown M.W., Cannom D.S., Daubert J.P., Estes M., Foster E., Greenberg H.M., Hall W.J., Higgins S.L., Klein H., Pfeffer M., Wilber D., Zareba W. Multicenter automatic defibrillator implantation trial--cardiac resynchronization therapy (MADIT-CRT): design and clinical protocol. Ann Noninvasive Electrocardiol. 2005;10(4 Suppl):34-43. PMID: 16274414, PMCID: PMC6932697. https://doi.org/10.1111/j.1542-474X.2005.00073.x
- Eldridge S.M., Chan C.L., Campbell M.J., Bond C.M., Hopewell S., Thabane L., Lancaster G.A., PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. http://dx.doi.org/10.1136/bmj.i5239
- Ploux S., Strik M., van Hunnik A., van Middendorp L., Kuiper M., Prinzen F.W. Acute electrical and hemodynamic effects of multisite left ventricular pacing for cardiac resynchronization therapy in the dyssynchronous canine heart. Heart Rhythm. 2014;11(1):119-25. http://dx.doi.org/10.1016/j.hrthm.2013.10.018
- Lang R.M., Bierig M., Devereux R.B., Flachskampf F.A., Foster E., Pellikka P.A., Picard M.H., Roman M.J., Seward J., Shanewise J.S., Solomon S.D., Spencer K.T., St John Sutton M., Stewart W.J. Recommendations for Chamber Quantification: A Report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, Developed in Conjunction with the European Association of Echocardiography, a Branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440-63. PMID: 16376782. http://dx.doi.org/10.1016/j.echo.2005.10.005
- Klein N., Klein M., Weglage H., Przibille O., Fischer S., Trappe H.-J., Birkenhauer F., Pfeiffer D., Efface Phrenic Stim Study Group. Clinical efficacy of left ventricular pacing vector programmability in cardiac resynchronization therapy defibrillator patients for management of phrenic nerve stimulation and/or elevated left ventricular pacing thresholds: insights from the Efface Phrenic Stim study. Europace. 2012;14(6):826–32. http://dx.doi.org/10.1093/europace/eur412
- Pappone C., Ćalović Ž., Vicedomini G., Cuko A., McSpadden L.C., Ryu K., Romano E., Baldi M., Saviano M., Pappone A., Ciaccio C., Giannelli L., Ionescu B., Petretta A., Vitale R., Fundaliotis A., Tavazzi L., Santinelli V. Multipoint left ventricular pacing in a single coronary sinus branch improves mid-term echocardiographic and clinical response to cardiac resynchronization therapy. J Cardiovasc Electrophysiol. 2015;26(1):58-63. PMID: 25109276. https://doi.org/10.1111/jce.12513
- Butter C., Auricchio A., Stellbrink C., Fleck E., Ding J., Yu Y., Huvelle E., Spinelli J., Pacing Therapy for Chronic Heart Failure II Study Group. Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation. 2001;104(25):3026-9. http://dx.doi.org/10.1161/hc5001.102229
- van Campen C.M.C., Visser F.C., de Cock C.C., Vos H.S., Kamp O., Visser C.A. Comparison of the haemodynamics of different pacing sites in patients undergoing resynchronisation treatment: need for individualisation of lead localisation. Heart. 2006;92(12):1795-800. http://dx.doi.org/10.1136/hrt.2004.050435
- Bleeker G.B., Kaandorp T.A.M., Lamb H.J., Boersma E., Steendijk P., de Roos A., van der Wall E.E., Schalij M.J., Bax J.J. Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation. 2006;113(7):969-76. PMID: 16476852. http://dx.doi.org/10.1161/circulationaha.105.543678
- Spragg D.D., Dong J., Fetics B.J., Helm R., Marine J.E., Cheng A., Henrikson C.A., Kass D.A., Berger R.D. Optimal left ventricular endocardial pacing sites for cardiac resynchronization therapy in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2010;56(10):774-81. http://dx.doi.org/10.1016/j.jacc.2010.06.014
- Derval N., Steendijk P., Gula L.J., Deplagne A., Laborderie J., Sacher F., Knecht S., Wright M., Nault I., Ploux S., Ritter P., Bordachar P., Lafitte S., Réant P., Klein G.J., Narayan S.M., Garrigue S., Hocini M., Haissaguerre M., Clementy J., Jaïs P. Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. J Am Coll Cardiol. 2010;55(6):566-75. PMID: 19931364. https://doi.org/10.1016/j.jacc.2009.08.045
- Singh J.P., Klein H.U., Huang D.T., Reek S., Kuniss M., Quesada A., Barsheshet A., Cannom D., Goldenberg I., McNitt S., Daubert J.P., Zareba W., Moss A.J. Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial. Circulation. 2011;123(11):1159-66. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.000646
- Shetty A.K., Sohal M., Chen Z., Ginks M.R., Bostock J., Amraoui S., Ryu K., Rosenberg S.P., Niederer S.A., Gill J., Carr-White G., Razavi R., Rinaldi C.A. A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study. Europace. 2014;16(6):873–9. http://dx.doi.org/10.1093/europace/eut420
- Rogers D.P., Lambiase P.D., Lowe M.D., Chow A.W. A randomized double-blind crossover trial of triventricular versus biventricular pacing in heart failure. Eur J Heart Fail. 2012;14(5):495-505. PMID: 22312038. https://doi.org/10.1093/eurjhf/hfs004
- Lenarczyk R., Kowalski O., Sredniawa B., Pruszkowska-Skrzep P., Mazurek M., Jędrzejczyk-Patej E., Woźniak A., Pluta S., Głowacki J., Kalarus Z. Implantation feasibility, procedure-related adverse events and lead performance during 1-year follow-up in patients undergoing triple-site cardiac resynchronization therapy: A substudy of TRUST CRT randomized trial. J Cardiovasc Electrophysiol. 2012;23(11):1228-36. PMID: 22651239. https://doi.org/10.1111/j.1540-8167.2012.02375.x
- Bordachar P., Gras D., Clementy N., Defaye P., Mondoly P., Boveda S., Anselme F., Klug D., Piot O., Sadoul N., Babuty D., Leclercq C. Clinical impact of an additional left ventricular lead in cardiac resynchronization therapy nonresponders: The V3 trial. Heart Rhythm. 2018;15(6):870-6. http://dx.doi.org/10.1016/j.hrthm.2017.12.028
- Siciliano M., Migliore F., Badano L., Bertaglia E., Pedrizzetti G., Cavedon S., Zorzi A., Corrado D., Iliceto S., Muraru D. Cardiac resynchronization therapy by multipoint pacing improves response of left ventricular mechanics and fluid dynamics: a three-dimensional and particle image velocimetry echo study. Europace. 2017;19(11):1833-40. PMID: 28025231. https://doi.org/10.1093/europace/euw331
- Niazi I., Baker J. 2nd, Corbisiero R., Love C., Martin D., Sheppard R., Worley S.J., Varma N., Lee K., Tomassoni G., MPP Investigators. Safety and efficacy of multipoint pacing in cardiac resynchronization therapy: the multipoint pacing trial. JACC Clin Electrophysiol. 2017;3(13):1510-8. http://dx.doi.org/10.1016/j.jacep.2017.06.022
- Forleo G.B., Santini L., Giammaria M., Potenza D., Curnis A., Calabrese V., Ricciardi D., D’agostino C., Notarstefano P., Ribatti V., Morani G., Mantica M., Di Biase L., Bertaglia E., Calò L., Zanon F. Multipoint pacing via a quadripolar left-ventricular lead: preliminary results from the Italian registry on multipoint left-ventricular pacing in cardiac resynchronization therapy (IRON-MPP). Europace. 2016;19(7):1170-7. http://dx.doi.org/10.1093/europace/euw094
- Ciconte G., Ćalović Ž., Vicedomini G., Cuko A., McSpadden L.C., Jiang C., Ryu K., Caporaso I., Stutz R., Winter D., Saviano M., Vitale R., Conti M., Santinelli V., Pappone C. Multipoint pacing improves peripheral hemodynamic response: Noninvasive assessment using radial artery tonometry. Pacing Clin Electrophysiol. 2018;41(2):106-13. http://dx.doi.org/10.1111/pace.13254
- Lercher P., Lunati M., Rordorf R., Landolina M., Badie N., Qu F., Casset C., Ryu K., Ghio S., Singh J.P., Leclercq C. Long-term reverse remodeling by cardiac resynchronization therapy with MultiPoint Pacing: A feasibility study of noninvasive hemodynamics–guided device programming. Heart Rhythm. 2018;15(12):1766-74. PMID: 29940305. https://doi.org/10.1016/j.hrthm.2018.06.032
- Leclercq C., Burri H., Curnis A., Delnoy P.P., Rinaldi C.A., Sperzel J., Lee K., Calò L., Vicentini A., Concha J.F., Thibault B. Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I. Eur Heart J. 2019;40(35):2979-2987. PMID: 30859220. https://doi.org/10.1093/eurheartj/ehz109
- Sieniewicz B.J., Jackson T., Claridge S., Pereira H., Gould J., Sidhu B., Porter B., Niederer S., Yao C., Rinaldi C.A. Optimization of CRT programming using non‐invasive electrocardiographic imaging to assess the acute electrical effects of multipoint pacing. J Arrhythmia. 2019;35(2):267-75. PMID: 31007792, PMCID: PMC6457383. https://doi.org/10.1002/joa3.12153
- Sohal M., Shetty A., Niederer S., Lee A., Chen Z., Jackson T., Behar J.M., Claridge S., Bostock J., Hyde E., Razavi R., Prinzen F., Rinaldi C.A. Mechanistic insights into the benefits of multisite pacing in cardiac resynchronization therapy: The importance of electrical substrate and rate of left ventricular activation. Heart Rhythm. 2015;12(12):2449-57. http://dx.doi.org/10.1016/j.hrthm.2015.07.012
- Gasparini M., Galimberti P., Bragato R., Ghio S., Raineri C., Landolina M., Chieffo E., Lunati M., Mulargia E., Proclemer A., Facchin D., Rordorf R., Vicentini A., Marcantoni L., Zanon F., Klersy C. Multipoint pacing versus conventional ICD in patients with a narrow QRS complex (MPP Narrow QRS trial): study protocol for a pilot randomized controlled trial. Trials. 2016;17(1):572. http://dx.doi.org/10.1186/s13063-016-1698-1
- Akerström F., Narváez I., Puchol A., Pachón M., Martín-Sierra C., Rodríguez-Mañero M., Rodríguez-Padial L., Arias M.A. Estimation of the effects of multipoint pacing on battery longevity in routine clinical practice. Europace. 2018;20(7):1161-7. PMID: 29036370. http://dx.doi.org/10.1093/europace/eux209
- Wells G., Parkash R., Healey J.S., Talajic M., Arnold J.M., Sullivan S., Peterson J., Yetisir E., Theoret-Patrick P., Luce M., Tang A.S.L. Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials. CMAJ. 2011;183(4):421-9. PMID: 21282316, PMCID: PMC3050946. http://dx.doi.org/10.1503/cmaj.101685
- Gurevitz O., Nof E., Carasso S., Luria D., Bar-Lev D., Tanami N., Eldar M., Glikson M. Programmable multiple pacing configurations help to overcome high left ventricular pacing thresholds and avoid phrenic nerve stimulation. Pacing Clin Electrophysiol. 2005;28(12):1255-9. PMID: 16403156. http://dx.doi.org/10.1111/j.1540-8159.2005.00265.x
