Heart rate turbulence and brain natriuretic peptide level as predictors for life-threatening arrhythmias in patients with coronary artery disease
Authors:
Company: A.N. Bakoulev Scientific Center for Cardiovascular Surgery of Russian Academy of Medical Sciences
For citation: Golukhova EZ, Gromova OI, Merzlyakov VYu, at al. Heart rate turbulence and brain natriuretic peptide level as predictors for life-threatening arrhythmias in patients with coronary artery disease. Kreativnaya kardiologiya. 2013; 2: 62-77 (in Russian).
Keywords: malignant arrhythmias sudden cardiac death primary prevention heart rate turbulence brain natriuretic peptide implantable cardioverter defibrillators
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Material and methods. We prospectively enrolled 97 patients with coronary artery disease (confirmed by coronary angiography) at the mean age of 61±10 years. Most of patients (68%) had a New York Heart Association (NYHA) functional class of 0–II. The mean left ventricular ejection fraction (LVEF) was 50±13%; 20% of patients had LVEF ≤ 35%. Sixty patients had revascularization procedures during follow-up. We calculated following noninvasive electrophysiological markers as part of 24-hour Holter monitoring: microvolt T-wave alternans, signal-averaged electrocardiography, QT-interval duration and dynamics, heart rate turbulence and variability. Laboratory tests included: serum creatine and creatine clearance, brain natriuretic peptide (BNP), NT-proBNP, C-reactive protein and troponin T levels.
Results. Life-threatening ventricular arrhythmias were observed in 11 (11%) patients during mean follow-up period of 25±11 months. Intraoperative malignant ventricular arrhythmias developed in 8 (13%) patients of 60 operated ones. On univariate analysis, past angioplasty (P<0.05), past malignant arrhythmias or syncope (P<0.05), LVEF ≤ 47% (P<0.01), left atrium size ≥ 4.7 cm (P<0.05), left atrium index (P=0.01), filtered QRS duration (P<0.05), abnormal heart rate turbulence (HRT) (χ2 test=6.2, P=0.01), abnormal turbulence slope (χ2 test=9.5, P<0.01), BNP ≥ 158 pg/ml (P<0.01), NT-proBNP ≥ 787 pg/ml (χ2 test=4.4, P<0.05) were significantly associated with malignant arrhythmias in long-term follow-up. Past malignant arrhythmias or syncope (OR [95% CI] 0.04: 0.05–0.28; P<0.01), abnormal HRT (ОR [95% CI] 19.9: 2.2–178.7; P<0.01), and plasma BNP ≥ 158 pg/ml (ОR [95% CI] 18.5: 2.9–116.8; P<0.01) were independent predictors for the first endpoint on multivariate Cox regression analysis. Predictors for VF/VT during revascularization or early postoperative period on univariate analysis were: multivessel coronary stenosis (P<0.01) and left main coronary artery lesion (P<0.01).
Conclusion. Heart rate turbulence and plasma brain natriuretic peptide level could be additional noninvasive markers of life-threatening arrhythmias improving primary prevention of sudden cardiac death approach.
проведению электрофизиологических исследований, катетерной аблации и применению имплантируемых антиаритмических
устройств. М.: МАКС Пресс; 2013.
2. Fishman G.I., Chugh S.S., DiMarco J.P., Albert C.M., Anderson M.E., Bonow R.O. et al. Sudden cardiac death prediction and prevention:
report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop. Circulation. 2010; 122: 2335–48.
3. Бокерия Л.А., Ревишвили А.Ш. Внезапная сердечная смерть. М.: ГЭОТАР-Медиа; 2011.
4. Go A.S., Mozaffarian D., Roger V.L., Benjamin E.J., Berry J.D., Borden W.B. et al. Executive summary: heart disease and stroke statistics–
2013 update: a report from the American Heart Association. Circulation. 2013; 127 (1): 143–52.
5. Nichol G., Thomas E., Callaway C.W., Hedges J., Powell J.L., Aufderheide T.P. et al. Regional variation in out-of-hospital cardiac
arrest incidence and outcome. JAMA. 2008; 300: 1423–31.
6. Бокерия Л.А., Ревишвили А.Ш., Неминущий Н.М., Ломидзе Н.Н., Хафизов Б.Б. Имплантируемые кардиовертеры-
дефибрилляторы: показания и отдаленные результаты клинического применения у больных жизнеугрожающими
аритмиями. Анналы аритмологии. 2005; 1: 51–7.
7. Громова О.И., Александрова С.А., Макаренко В.Н., Голухова Е.З. Современные предикторы жизнеугрожающих аритмий.
Креативная кардиология. 2012; 2: 30–46.
8. Epstein A.E., Di Marco J.P., Ellenbogen K.A., Estes N.A., Freedman R.A., Gettes L.S. et al. 2012 ACCF/AHA/HRS Focused Update incorporated
into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and Heart Rhythm
Society. J. Am. Coll. Cardiol. 2013; 61 (3): e6–e75.
9. Moss A.J., Hall W.J., Cannom D.S., Daubert J.P., Higgins S.L., Klein H. et al. Multicenter Automatic Defibrillator Implantation
Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular
arrhythmia. N. Engl. J. Med. 1996; 335: 1933–40.
10. Moss A.J., Zareba W., Hall W.J., Klein H., Wilber D.J., Cannom D.S. et al. Multicenter Automatic Defibrillator Implantation Trial II
Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N. Engl.
J. Med. 2002; 346: 877–83.
11. Bardy G.H., Lee K.L., Mark D.B., Poole J.E., Packer D.L., Boineau R. et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N. Engl. J. Med. 2005; 352: 225–37.
12. Бокерия Л.А., Голухова Е.З., Ревишвили А.Ш., Базаев В.А. Отчет о выполнении межведомственной программы РАМН
«Совершенствование методик профилактики, диагностики и лечения жизнеугрожающих нарушений ритма сердца
(внезапная сердечная смерть)» на 2005–2008 гг. Анналы аритмологии. 2008; 4: 5–33.
13. Ghuran A., Reid F., La Rovere M.T., Schmidt G., Bigger J.T. Jr, Camm A.J. et al. Heart rate turbulence-based predictors of fatal and
nonfatal cardiac arrest (The Autonomic Tone and Reflexes After Myocardial Infarction substudy). Am. J. Cardiol. 2002; 89: 184–90.
14. La Rovere M.T., Bigger J.T. Jr, Marcus F.I., Mortara A., Schwartz P.J. Baroreflex sensitivity and heart-rate variability in prediction of
total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction)
Investigators. Lancet. 1998; 351 (9101): 478–84.
15. Bauer A., Barthel P., Schneider R. Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved
left ventricular f unction (ISAR-Risk). Eur. Heart J. 2009; 30: 576–83.
16. Exner D.V., Kavanagh K.M., Slawnych M.P. Noninvasive Risk Assessment Early After a Myocardial Infarction: The REFINE Study.
J. Am. Coll. Cardiol. 2007; 50: 2275–84.
17. Huikuri H.V., Exner D.V. CARISMA and REFINE Investigators. Attenuated recovery of heart rate turbulence early after myocardial
infarction identifies patients at high risk for fatal or near-fatal arrhythmic events. Heart Rhythm. 2010; 7 (2): 229–35.
18. La Rovere M.T., Pinna G.D. Baroreflex sensitivity and heart rate variability in the identification of patient of risk for life-threatining
arrhythmias: implications for clinical trials. Circulation. 2001; 103: 2072–77.
19. Hoshida K., Miwa Y., Miyakoshi M., Tsukada T., Yusu S., Yoshino H. et al. Simultaneous assessment of T-wave alternans and heart
rate turbulence on holter electrocardiograms as predictors for serious cardiac events in patients after myocardial infarction. Circ. J.
2013; 77 (2): 432–8.
20. Maeda S., Nishizaki M., Yamawake N., Ashikaga T. Ambulatory ECG-Based T-wave alternans and heart rate turbulence predict high risk
of arrhythmic events in patients with old myocardial infarction. Circ J. 2009; 73: 2223–8.
21. Rubart M., Zipes D.P. Mechanisms of sudden cardiac death. J. Clin. Invest. 2005; 115: 2305–15.
22. Scott P.A., Barry J., Roberts P.R., Morgan J.M. Brain natriuretic peptide for the prediction of sudden cardiac death and ventricular
arrhythmias: a meta-analysis. Eur. J. Heart Fail. 2009; 11: 958–66.
23. Galante O., Zahger D., Wagshal A., Katz A., Amit G. Brain natriuretic peptide (BNP) level predicts long term ventricular arrhythmias in
patients with moderate to severe left ventricular dysfunction. Harefuah. 2012; 151 (1): 20–3.
24. Фарафонова Т.Н. Нарушения ритма сердца в ранние сроки после операции коронарного шунтирования на работающем
сердце: Автореф. дис. … канд. мед. наук. М.: 2006.
Abstract
Objective. Aim of our investigation was: to estimate prognostic value of clinical and instrumental parameters, results of noninvasive electrophysiological tests and biomarkers as predictors of malignant ventricular arrhythmias in patients with coronary artery disease in long-term follow-up.Material and methods. We prospectively enrolled 97 patients with coronary artery disease (confirmed by coronary angiography) at the mean age of 61±10 years. Most of patients (68%) had a New York Heart Association (NYHA) functional class of 0–II. The mean left ventricular ejection fraction (LVEF) was 50±13%; 20% of patients had LVEF ≤ 35%. Sixty patients had revascularization procedures during follow-up. We calculated following noninvasive electrophysiological markers as part of 24-hour Holter monitoring: microvolt T-wave alternans, signal-averaged electrocardiography, QT-interval duration and dynamics, heart rate turbulence and variability. Laboratory tests included: serum creatine and creatine clearance, brain natriuretic peptide (BNP), NT-proBNP, C-reactive protein and troponin T levels.
Results. Life-threatening ventricular arrhythmias were observed in 11 (11%) patients during mean follow-up period of 25±11 months. Intraoperative malignant ventricular arrhythmias developed in 8 (13%) patients of 60 operated ones. On univariate analysis, past angioplasty (P<0.05), past malignant arrhythmias or syncope (P<0.05), LVEF ≤ 47% (P<0.01), left atrium size ≥ 4.7 cm (P<0.05), left atrium index (P=0.01), filtered QRS duration (P<0.05), abnormal heart rate turbulence (HRT) (χ2 test=6.2, P=0.01), abnormal turbulence slope (χ2 test=9.5, P<0.01), BNP ≥ 158 pg/ml (P<0.01), NT-proBNP ≥ 787 pg/ml (χ2 test=4.4, P<0.05) were significantly associated with malignant arrhythmias in long-term follow-up. Past malignant arrhythmias or syncope (OR [95% CI] 0.04: 0.05–0.28; P<0.01), abnormal HRT (ОR [95% CI] 19.9: 2.2–178.7; P<0.01), and plasma BNP ≥ 158 pg/ml (ОR [95% CI] 18.5: 2.9–116.8; P<0.01) were independent predictors for the first endpoint on multivariate Cox regression analysis. Predictors for VF/VT during revascularization or early postoperative period on univariate analysis were: multivessel coronary stenosis (P<0.01) and left main coronary artery lesion (P<0.01).
Conclusion. Heart rate turbulence and plasma brain natriuretic peptide level could be additional noninvasive markers of life-threatening arrhythmias improving primary prevention of sudden cardiac death approach.
References
1. Ревишвили А.Ш., Ардашев А.В., Бойцов С.А., Бокерия О.Л., Голухова Е.З., Давтян К.В. и др. Клинические рекомендации попроведению электрофизиологических исследований, катетерной аблации и применению имплантируемых антиаритмических
устройств. М.: МАКС Пресс; 2013.
2. Fishman G.I., Chugh S.S., DiMarco J.P., Albert C.M., Anderson M.E., Bonow R.O. et al. Sudden cardiac death prediction and prevention:
report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop. Circulation. 2010; 122: 2335–48.
3. Бокерия Л.А., Ревишвили А.Ш. Внезапная сердечная смерть. М.: ГЭОТАР-Медиа; 2011.
4. Go A.S., Mozaffarian D., Roger V.L., Benjamin E.J., Berry J.D., Borden W.B. et al. Executive summary: heart disease and stroke statistics–
2013 update: a report from the American Heart Association. Circulation. 2013; 127 (1): 143–52.
5. Nichol G., Thomas E., Callaway C.W., Hedges J., Powell J.L., Aufderheide T.P. et al. Regional variation in out-of-hospital cardiac
arrest incidence and outcome. JAMA. 2008; 300: 1423–31.
6. Бокерия Л.А., Ревишвили А.Ш., Неминущий Н.М., Ломидзе Н.Н., Хафизов Б.Б. Имплантируемые кардиовертеры-
дефибрилляторы: показания и отдаленные результаты клинического применения у больных жизнеугрожающими
аритмиями. Анналы аритмологии. 2005; 1: 51–7.
7. Громова О.И., Александрова С.А., Макаренко В.Н., Голухова Е.З. Современные предикторы жизнеугрожающих аритмий.
Креативная кардиология. 2012; 2: 30–46.
8. Epstein A.E., Di Marco J.P., Ellenbogen K.A., Estes N.A., Freedman R.A., Gettes L.S. et al. 2012 ACCF/AHA/HRS Focused Update incorporated
into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and Heart Rhythm
Society. J. Am. Coll. Cardiol. 2013; 61 (3): e6–e75.
9. Moss A.J., Hall W.J., Cannom D.S., Daubert J.P., Higgins S.L., Klein H. et al. Multicenter Automatic Defibrillator Implantation
Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular
arrhythmia. N. Engl. J. Med. 1996; 335: 1933–40.
10. Moss A.J., Zareba W., Hall W.J., Klein H., Wilber D.J., Cannom D.S. et al. Multicenter Automatic Defibrillator Implantation Trial II
Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N. Engl.
J. Med. 2002; 346: 877–83.
11. Bardy G.H., Lee K.L., Mark D.B., Poole J.E., Packer D.L., Boineau R. et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N. Engl. J. Med. 2005; 352: 225–37.
12. Бокерия Л.А., Голухова Е.З., Ревишвили А.Ш., Базаев В.А. Отчет о выполнении межведомственной программы РАМН
«Совершенствование методик профилактики, диагностики и лечения жизнеугрожающих нарушений ритма сердца
(внезапная сердечная смерть)» на 2005–2008 гг. Анналы аритмологии. 2008; 4: 5–33.
13. Ghuran A., Reid F., La Rovere M.T., Schmidt G., Bigger J.T. Jr, Camm A.J. et al. Heart rate turbulence-based predictors of fatal and
nonfatal cardiac arrest (The Autonomic Tone and Reflexes After Myocardial Infarction substudy). Am. J. Cardiol. 2002; 89: 184–90.
14. La Rovere M.T., Bigger J.T. Jr, Marcus F.I., Mortara A., Schwartz P.J. Baroreflex sensitivity and heart-rate variability in prediction of
total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction)
Investigators. Lancet. 1998; 351 (9101): 478–84.
15. Bauer A., Barthel P., Schneider R. Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved
left ventricular f unction (ISAR-Risk). Eur. Heart J. 2009; 30: 576–83.
16. Exner D.V., Kavanagh K.M., Slawnych M.P. Noninvasive Risk Assessment Early After a Myocardial Infarction: The REFINE Study.
J. Am. Coll. Cardiol. 2007; 50: 2275–84.
17. Huikuri H.V., Exner D.V. CARISMA and REFINE Investigators. Attenuated recovery of heart rate turbulence early after myocardial
infarction identifies patients at high risk for fatal or near-fatal arrhythmic events. Heart Rhythm. 2010; 7 (2): 229–35.
18. La Rovere M.T., Pinna G.D. Baroreflex sensitivity and heart rate variability in the identification of patient of risk for life-threatining
arrhythmias: implications for clinical trials. Circulation. 2001; 103: 2072–77.
19. Hoshida K., Miwa Y., Miyakoshi M., Tsukada T., Yusu S., Yoshino H. et al. Simultaneous assessment of T-wave alternans and heart
rate turbulence on holter electrocardiograms as predictors for serious cardiac events in patients after myocardial infarction. Circ. J.
2013; 77 (2): 432–8.
20. Maeda S., Nishizaki M., Yamawake N., Ashikaga T. Ambulatory ECG-Based T-wave alternans and heart rate turbulence predict high risk
of arrhythmic events in patients with old myocardial infarction. Circ J. 2009; 73: 2223–8.
21. Rubart M., Zipes D.P. Mechanisms of sudden cardiac death. J. Clin. Invest. 2005; 115: 2305–15.
22. Scott P.A., Barry J., Roberts P.R., Morgan J.M. Brain natriuretic peptide for the prediction of sudden cardiac death and ventricular
arrhythmias: a meta-analysis. Eur. J. Heart Fail. 2009; 11: 958–66.
23. Galante O., Zahger D., Wagshal A., Katz A., Amit G. Brain natriuretic peptide (BNP) level predicts long term ventricular arrhythmias in
patients with moderate to severe left ventricular dysfunction. Harefuah. 2012; 151 (1): 20–3.
24. Фарафонова Т.Н. Нарушения ритма сердца в ранние сроки после операции коронарного шунтирования на работающем
сердце: Автореф. дис. … канд. мед. наук. М.: 2006.
