Всегда ли недостаточная динамика параметров левого желудочка свидетельствует о плохом ответе на сердечную ресинхронизирующую терапию?
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Kuznetsov V.A., Soldatova A.M., Enina T.N., et al. Does the lack of left ventricular reverse remodeling always mean non-response to cardiac resynchronization therapy? Therapeutic Archive. 2019; 91 (12): 10–15. DOI: 10.26442/00403660.2019.12.000102
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Материалы и методы. В исследование включено 112 человек (83,5% мужчин, средний возраст 54,6±9,9 года) со сниженной фракцией выброса (ФВ) ЛЖ ≤35%, II–IV функциональным классом (ФК) ХСН по NYHA, шириной комплекса QRS >120 мс. При ширине QRS <120 мс учитывалось наличие как минимум трех критериев механической диссинхронии по результатам эхокардиографии. Средний срок наблюдения составил 34,8±16,7 мес. Исходно, через 1 мес, 3 мес и каждые последующие 6 мес проводились клиническое обследование, электрокардиография, эхокардиография. Три пациента с увеличением конечно-систолического объема (КСО) ЛЖ в динамике не вошли в проспективное исследование в связи с отсутствием возможности полноценного динамического наблюдения. По динамике КСО ЛЖ пациенты разделены на группы: непрогрессоры (снижение <15%; n=18), респондеры (снижение 15–29%; n=41), суперреспондеры (снижение ≥30%; n=50).
Результаты. Исходно группы сопоставимы по основным клиническим характеристикам. Все группы продемонстрировали значимое увеличение ФВ ЛЖ, повышение толерантности к физической нагрузке, уменьшение ФК ХСН по NYHA. Межгрупповой анализ не выявил достоверных различий между непрогрессорами и респондерами по уровням средних значений клинических и функциональных показателей как исходно, так и на пике ответа. Отдаленная выживаемость суперреспондеров составила 100%, респондеров – 78%, непрогрессоров – 88,9% (Log-Rank test p=0,001). При сравнении выживаемости между непрогрессорами и респондерами различия оказались недостоверными (Log-Rank test p=0,150).
Заключение. Пациенты со снижением КСО ЛЖ <15% демонстрируют сопоставимую динамику клинических и функциональных показателей на фоне СРТ в сравнении с пациентами со снижением КСО ЛЖ 15–29%, а также сопоставимые уровни отдаленной выживаемости. C учетом прогрессирующего течения ХСН, стабилизация состояния с развитием незначительного обратного ремоделирования ЛЖ не должна рассматриваться как вариант отсутствия ответа на СРТ.
Ключевые слова: сердечная ресинхронизирующая терапия, респондеры, непрогрессоры, хроническая сердечная недостаточность.
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Aim. To evaluate clinical, morphological, functional features and mortality level in patients with different value of left ventricular reverse remodeling after cardiac resynchronization therapy (CRT).
Materials and methods. The study enrolled 112 patients (mean age 54.6±9.9 years, 83.5% men) with left ventricular ejection fraction (LVEF) ≤35%, NYHA functional class II–IV. We enrolled patients with QRS width >120 ms or QRS <120 ms + 3 parameters of mechanical dyssynchrony by echocardiography. Clinical, electrocardiographic and echocardiographic parameters were evaluated at baseline, 1, 3 months and each 6 months after implantation. Three patients with increase of left ventricular end-systolic volume (LVESV) were excluded from prospective trial due to lack of full follow-up data. According to the best decrease of LVESV (mean follow-up period 34.8±16.7 months) patients were classified as non-progressors (n=18; decrease in LVESV <15%), responders (n=41; decrease in LVESV 15–29%) and super-responders (SR) (n=50; reduction in LVESV ≥30%).
Results. At baseline groups were matched for main clinical characteristics, the proportion of patients with atrial fibrillation, width of the QRS complex, and the presence of left bundle-branch block. Echocardiographic parameters didn’t differ between the groups. All groups demonstrated significant reverse remodeling of the left ventricle, increase in LVEF, increase in 6-minute walking distance. SR demonstrated the best improvement of clinical and functional parameters after CRT. However, improvement in LVEF, LVESV, NYHA functional class between responders and non-progressors were found similar. Dynamics of these parameters were comparable. The survival rates were 100% in SR, 80% in responders and 88.9% in non-progressors (Log-Rank test p=0.001). Survival rates in responders and non-progressors didn’t differ significantly (Log-Rank test p=0.150).
Conclusion. Patients with reduction in LVESV less than 15% demonstrate improvement in clinical status, LVEF and survival rates compared to subjects with reduction in LVESV 15–29%. Non-progressors demonstrate similar survival as responders in long-term period. Taking into account the natural course of CHF functional stabilisation and absence of CHF progression in patients with lack of left ventricular reverse remodelling is a variant of good response and these patients should not be identified as non-responders.
Keywords: cardiac resynchronization therapy, responders, non-progressors, chronic heart failure.
2. Daubert C, Behar N, Martins RP, Mabo P, Leclercq C. Avoiding non-responders to cardiac resynchronization therapy: a practical guide. Eur Heart J. 2016;38(19):1463-72. doi: 10.1093/eurheartj/ehw270
3. Dhesi S, Lockwood E, Sandhu RK. Troubleshooting Cardiac Resynchronization Therapy in Non-responders. Can J Cardiol. 2017. doi: 10.1016/j.cjca.2017.04.007
4. Van’t Sant J, Mast TP, Bos MM, ter Horst IA, van Everdingen WM, Meine M, Cramer MJ. Echo response and clinical outcome in CRT patients. Neth Heart J. 2016;24(1):47-55. doi: 10.1007/s12471-015-0767-5
5. Кузнецов В.А., Колунин Г.В., Харац В.Е., Криночкин Д.В., Рычков А.Ю., Горбунова Т.Ю. и др. Регистр проведенных операций сердечной ресинхронизирующей терапии. Свидетельство о государственной регистрации базы данных № 2010620077 от 1 февраля 2010 г. [Kuznetsov VA, Kolunin GV, Kharats VE, Krinochkin DV, Rychkov AYu, Gorbunova TYu, et al. Register of performed operations of cardiac resynchronization therapy. Electronic database, state registration №2010620077 from 01.02.2010 (In Russ.)].
6. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekvål TM, Spaulding C, van Veldhuisen DJ. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Europace. 2015;17(11):1601-87. doi: 10.1093/europace/euv319
7. Maréchaux S, Guiot A, Castel A, Guyomar Y, Semichon M, Delelis F, Heuls S, Ennezat PV, Graux P, Tribouilloy C. Relationship between Two-Dimensional Speckle-Tracking Septal Strain and Response to Cardiac Resynchronization Therapy in Patients with Left Ventricular Dysfunction and Left Bundle Branch Block: A Prospective Pilot Study. J Am Soc Echocardiogr. 2014;27(5):501-11. doi: 10.1016/j.echo.2014.01.004
8. Van’t Sant J, Ter Horst IAH, Wijers SC, Mast TP, Leenders GE, Doevendans PA, Meine M. Measurements of electrical and mechanical dyssynchrony are both essential to improve prediction of CRT response. J Electrocardiol. 2015;48(4):601-8. doi: 10.1016/j.jelectrocard.2015.01.015
9. El Missiri AM. Echocardiographic assessment of left ventricular mechanical dyssynchrony – A practical approach. Egypt Heart J. 2014;66(3):217-25.
10. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16(3):233-71. doi: 10.1093/ehjci/jev014
11. Rickard J, Baranowski B, Wilson Tang WH, Grimm RA, Niebauer M, Cantillion D, Varma N. Echocardiographic Predictors of Long-Term Survival in Patients Undergoing Cardiac Resynchronization Therapy: What Is the Optimal Metric? J Cardiovasc Electrophysiol. 2017;28(4):410-5. doi: 10.1111/jce.13175
12. Daubert JC, Saxon L, Adamson PB, Auricchio A, et al. 2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management. European Heart Rhythm Association (EHRA); European Society of Cardiology (ESC); Heart Rhythm Society; Heart Failure Society of America (HFSA); American Society of Echocardiography (ASE); American Heart Association (AHA); European Association of Echocardiography (EAE) of ESC; Heart Failure Association of ESC (HFA). Europace. 2012;14:1236-86. doi: 10.1093/europace/eus222
13. Zhang Q, Zhou Y, Yu CM. Incidence, definition, diagnosis, and management of the cardiac resynchronization therapy nonresponder. Curr Opin Cardiol. 2015;30(1):40-9.
14. Steffel J, Ruschitzka F. Superresponse to Cardiac Resynchronization Therapy. Circulation. 2014;130(1):87-90. doi: 10.1161/CIRCULATIONAHA.113.006124
15. Friedman DJ, Upadhyay GA, Rajabali A, Altman RK, Orencole M, Parks KA, Singh JP. Progressive ventricular dysfunction among nonresponders to cardiac resynchronization therapy: Baseline predictors and associated clinical outcomes. Heart Rhythm. 2014;11(11):1991-8. doi: 10.1016/j.hrthm.2014.08.005
16. Foley PWX, Leyva F, Frenneaux MP. What is treatment success in cardiac resynchronization therapy? Europace. 2009;11(suppl 5):v58-v65. doi: 10.1093/europace/eup308
17. Cleland JGF, Ghio S. The determinants of clinical outcome and clinical response to CRT are not the same. Heart Failure Rev. 2012;17(6):755-66. doi: 10.1007/s10741-011-9268-9
18. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van derWall EE, Chan YS, Kong SL, Bax JJ. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005;112:1580-6. doi: 10.1161/CIRCULATIONAHA.105.538272
19. Ypenburg C, van Bommel RJ, Borleffs CJ, Bleeker GB, Boersma E, Schalij MJ, Bax JJ. Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. J Am Coll Cardiol. 2009;53:483-90. doi: 10.1016/j.jacc.2008.10.032
20. Кузнецов В.А., Солдатова А.М., Криночкин Д.В., Енина Т.Н. Сердечная ресинхронизирующая терапия при хронической сердечной недостаточности: нужно ли ждать быстрого ответа? Сердечная недостаточность. 2017;18(3):172-7 [Kuznetsov VA, Soldatova AM, Krinochkin DV, Enina TN. Cardiac resynchronisation therapy in patients with congestive heart failure: whether we should expect for an "early" response? Serdechnaya Nedostatochnost' = Journal of Heart Failure. 2017;18(3):172-7 (In Russ.)]. doi: 10.18087/rhfj.2017.3.2341
21. Kirk JA, Kass DA. Cellular and molecular aspects of dyssynchrony and resynchronization. Heart Failure Clin. 2017;13(1):29-41. doi: 10.1016/j.hfc.2016.07.003
22. Jones S, Lumens J, Sohaib SA, Finegold JA, Kanagaratnam P, Tanner M, Mason M. Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function. EP Europace. 2016;euw136. doi: 10.1093/europace/euw136
23. Cleland JGF, Abraham WT, Linde C, et al. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013;34(46):3547-56. doi: 10.1093/eurheartj/eht290
24. Risum N, Tayal B, Hansen TF, et al. Identification of typical left bundle branch block contraction by strain echocardiography is additive to electrocardiography in prediction of long-term outcome after cardiac resynchronization therapy. J Am Coll Cardiol. 2015;66:631-41. doi: 10.1016/j.jacc.2015.06.020
25. Kuznetsov V, Vinogradova T, Enina T, et al. Influence of atrioventricular junction ablation on survival of patients with congestive heart failure and atrial fibrillation receiving cardiac resynchronisation therapy in real clinical practice. Global Heart. 2014; 9(1):e42-e43.
26. Gasparini M, Kloppe A, Lunati M, Anselme F, Landolina M, Martine-Ferrer JB, Proclemer A, Morani G, Biffi M, Ricci R, Rordorf R, Mangoni L, Manotta L, Grammatico A, Leyva F, Boriani G. Atrioventricular junction ablation in patients with atrial fibrillation treated with cardiac resynchronization therapy: positive impact on ventricular arrhythmias, implantable cardioverter-defibrillator therapies and hospitalizations. Eur J Heart Fail. 2018 Oct;20(10):1472-81. doi: 10.1002/ejhf.1117
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2. Daubert C, Behar N, Martins RP, Mabo P, Leclercq C. Avoiding non-responders to cardiac resynchronization therapy: a practical guide. Eur Heart J. 2016;38(19):1463-72. doi: 10.1093/eurheartj/ehw270
3. Dhesi S, Lockwood E, Sandhu RK. Troubleshooting Cardiac Resynchronization Therapy in Non-responders. Can J Cardiol. 2017. doi: 10.1016/j.cjca.2017.04.007
4. Van’t Sant J, Mast TP, Bos MM, ter Horst IA, van Everdingen WM, Meine M, Cramer MJ. Echo response and clinical outcome in CRT patients. Neth Heart J. 2016;24(1):47-55. doi: 10.1007/s12471-015-0767-5
5. [Kuznetsov VA, Kolunin GV, Kharats VE, Krinochkin DV, Rychkov AYu, Gorbunova TYu, et al. Register of performed operations of cardiac resynchronization therapy. Electronic database, state registration №2010620077 from 01.02.2010 (In Russ.)].
6. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekvål TM, Spaulding C, van Veldhuisen DJ. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Europace. 2015;17(11):1601-87. doi: 10.1093/europace/euv319
7. Maréchaux S, Guiot A, Castel A, Guyomar Y, Semichon M, Delelis F, Heuls S, Ennezat PV, Graux P, Tribouilloy C. Relationship between Two-Dimensional Speckle-Tracking Septal Strain and Response to Cardiac Resynchronization Therapy in Patients with Left Ventricular Dysfunction and Left Bundle Branch Block: A Prospective Pilot Study. J Am Soc Echocardiogr. 2014;27(5):501-11. doi: 10.1016/j.echo.2014.01.004
8. Van’t Sant J, Ter Horst IAH, Wijers SC, Mast TP, Leenders GE, Doevendans PA, Meine M. Measurements of electrical and mechanical dyssynchrony are both essential to improve prediction of CRT response. J Electrocardiol. 2015;48(4):601-8. doi: 10.1016/j.jelectrocard.2015.01.015
9. El Missiri AM. Echocardiographic assessment of left ventricular mechanical dyssynchrony – A practical approach. Egypt Heart J. 2014;66(3):217-25.
10. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16(3):233-71. doi: 10.1093/ehjci/jev014
11. Rickard J, Baranowski B, Wilson Tang WH, Grimm RA, Niebauer M, Cantillion D, Varma N. Echocardiographic Predictors of Long-Term Survival in Patients Undergoing Cardiac Resynchronization Therapy: What Is the Optimal Metric? J Cardiovasc Electrophysiol. 2017;28(4):410-5. doi: 10.1111/jce.13175
12. Daubert JC, Saxon L, Adamson PB, Auricchio A, et al. 2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management. European Heart Rhythm Association (EHRA); European Society of Cardiology (ESC); Heart Rhythm Society; Heart Failure Society of America (HFSA); American Society of Echocardiography (ASE); American Heart Association (AHA); European Association of Echocardiography (EAE) of ESC; Heart Failure Association of ESC (HFA). Europace. 2012;14:1236-86. doi: 10.1093/europace/eus222
13. Zhang Q, Zhou Y, Yu CM. Incidence, definition, diagnosis, and management of the cardiac resynchronization therapy nonresponder. Curr Opin Cardiol. 2015;30(1):40-9.
14. Steffel J, Ruschitzka F. Superresponse to Cardiac Resynchronization Therapy. Circulation. 2014;130(1):87-90. doi: 10.1161/CIRCULATIONAHA.113.006124
15. Friedman DJ, Upadhyay GA, Rajabali A, Altman RK, Orencole M, Parks KA, Singh JP. Progressive ventricular dysfunction among nonresponders to cardiac resynchronization therapy: Baseline predictors and associated clinical outcomes. Heart Rhythm. 2014;11(11):1991-8. doi: 10.1016/j.hrthm.2014.08.005
16. Foley PWX, Leyva F, Frenneaux MP. What is treatment success in cardiac resynchronization therapy? Europace. 2009;11(suppl 5):v58-v65. doi: 10.1093/europace/eup308
17. Cleland JGF, Ghio S. The determinants of clinical outcome and clinical response to CRT are not the same. Heart Failure Rev. 2012;17(6):755-66. doi: 10.1007/s10741-011-9268-9
18. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van derWall EE, Chan YS, Kong SL, Bax JJ. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005;112:1580-6. doi: 10.1161/CIRCULATIONAHA.105.538272
19. Ypenburg C, van Bommel RJ, Borleffs CJ, Bleeker GB, Boersma E, Schalij MJ, Bax JJ. Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. J Am Coll Cardiol. 2009;53:483-90. doi: 10.1016/j.jacc.2008.10.032
20. [Kuznetsov VA, Soldatova AM, Krinochkin DV, Enina TN. Cardiac resynchronisation therapy in patients with congestive heart failure: whether we should expect for an "early" response? Serdechnaya Nedostatochnost' = Journal of Heart Failure. 2017;18(3):172-7 (In Russ.)]. doi: 10.18087/rhfj.2017.3.2341
21. Kirk JA, Kass DA. Cellular and molecular aspects of dyssynchrony and resynchronization. Heart Failure Clin. 2017;13(1):29-41. doi: 10.1016/j.hfc.2016.07.003
22. Jones S, Lumens J, Sohaib SA, Finegold JA, Kanagaratnam P, Tanner M, Mason M. Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function. EP Europace. 2016;euw136. doi: 10.1093/europace/euw136
23. Cleland JGF, Abraham WT, Linde C, et al. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013;34(46):3547-56. doi: 10.1093/eurheartj/eht290
24. Risum N, Tayal B, Hansen TF, et al. Identification of typical left bundle branch block contraction by strain echocardiography is additive to electrocardiography in prediction of long-term outcome after cardiac resynchronization therapy. J Am Coll Cardiol. 2015;66:631-41. doi: 10.1016/j.jacc.2015.06.020
25. Kuznetsov V, Vinogradova T, Enina T, et al. Influence of atrioventricular junction ablation on survival of patients with congestive heart failure and atrial fibrillation receiving cardiac resynchronisation therapy in real clinical practice. Global Heart. 2014; 9(1):e42-e43.
26. Gasparini M, Kloppe A, Lunati M, Anselme F, Landolina M, Martine-Ferrer JB, Proclemer A, Morani G, Biffi M, Ricci R, Rordorf R, Mangoni L, Manotta L, Grammatico A, Leyva F, Boriani G. Atrioventricular junction ablation in patients with atrial fibrillation treated with cardiac resynchronization therapy: positive impact on ventricular arrhythmias, implantable cardioverter-defibrillator therapies and hospitalizations. Eur J Heart Fail. 2018 Oct;20(10):1472-81. doi: 10.1002/ejhf.1117
Тюменский кардиологический научный центр – филиал ФГБНУ «Томский национальный исследовательский медицинский центр» Российской академии наук, Тюмень, Россия
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V.A. Kuznetsov, A.M. Soldatova, T.N. Enina, D.V. Krinochkin, S.M. Dyachkov
Tyumen Cardiology Research Center – Branch of Tomsk National Research Medical Center, Russian Academy of Science, Tyumen, Russia