Vol 28, No 6 (2021)
Original Article
Published online: 2019-06-27

open access

Page views 6782
Article views/downloads 923
Get Citation

Connect on Social Media

Connect on Social Media

Could autonomic nervous system parameters be still helpful in identifying patients with left ventricular systolic dysfunction at the highest risk of all-cause mortality?

Damian Kaufmann1, Grzegorz Raczak1, Małgorzata Szwoch1, Dariusz Kozłowski1, Joanna Kwiatkowska2, Ewa Lewicka1, Ludmiła Daniłowicz-Szymanowicz1
Pubmed: 31257569
Cardiol J 2021;28(6):914-922.

Abstract

Background: Autonomic imbalance is associated with poor prognosis of patients with systolic dysfunction. Most of the previous data were written several years ago and constituted to cardiovascular or arrhythmic mortality. The current treatment of these patients has improved substantially over the last decades, and thus, the population at risk of death may have altered as well. Consequently, data on high-risk patients with systolic dysfunction in the modern era are sparse and those from previous trials may no longer be applicable. The aim herein, was to verify whether well-known autonomic indices — baroreflex sensitivity (BRS) and heart rate variability (HRV) — remain accurate predictors of mortality in patients with systolic dysfunction.
Methods: Non-invasively obtained BRS and HRV were analyzed in 205 clinically stable patients with left ventricular ejection fraction (LVEF) ≤ 40%. 28 patients died within 28 ± 9 month follow-up.
Results: Baroreflex sensitivity, low-frequency (LF) in normalized units, LF to high-frequency ratio and standard deviation of average R-R intervals were significantly associated with mortality; cut-off values of the highest discriminatory power for abovementioned parameters were ≤ 3.0 ms/mmHg, ≤ 41, ≤ 0.7 and ≤ 25 ms, respectively. In bivariate Cox analyses (adjusted for LVEF, New York Heart Association [NYHA] or absence of implantable cardioverter-defibrillator [ICD]) autonomic indices remain significant predictors of death.
Conclusions: Baroreflex sensitivity and HRV — may still be helpful in identifying patients with left ventricular systolic dysfunction at the highest risk of all-cause mortality, independently of LVEF, NYHA class, and ICD implantation.

Article available in PDF format

View PDF Download PDF file

References

  1. Ponikowski P, Anker SD, AlHabib KF, et al. Heart failure: preventing disease and death worldwide. ESC Heart Fail. 2014; 1(1): 4–25.
  2. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859): 2163–2196.
  3. Mozaffarian D, Benjamin E, Go A, et al. Heart Disease and Stroke Statistics—2016 Update. Circulation. 2016; 133(4).
  4. Ponikowski P, Voors A, Anker S, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Journal of Heart Failure. 2016; 18(8): 891–975.
  5. Tomaszuk-Kazberuk A, Bolińska S, Młodawska E, et al. Does admission anaemia still predict mortality six years after myocardial infarction? Kardiol Pol. 2014; 72(6): 488–493.
  6. Murad K, Goff DC, Morgan TM, et al. Burden of Comorbidities and Functional and Cognitive Impairments in Elderly Patients at the Initial Diagnosis of Heart Failure and Their Impact on Total Mortality: The Cardiovascular Health Study. JACC Heart Fail. 2015; 3(7): 542–550.
  7. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015; 131(4): e29–322.
  8. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J. 2011; 33(14): 1750–1757.
  9. Premchand RK, Sharma K, Mittal S, et al. Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Card Fail. 2014; 20(11): 808–816.
  10. Zannad F, De Ferrari GM, Tuinenburg AE, et al. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J. 2015; 36(7): 425–433.
  11. Abraham W, Zile M, Weaver F, et al. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC: Heart Failure. 2015; 3(6): 487–496.
  12. Gronda E, Seravalle G, Brambilla G, et al. Chronic baroreflex activation effects on sympathetic nerve traffic, baroreflex function, and cardiac haemodynamics in heart failure: a proof-of-concept study. Eur J Heart Fail. 2014; 16(9): 977–983.
  13. De Ferrari GM, Stolen C, Tuinenburg AE, et al. Long-term vagal stimulation for heart failure: Eighteen month results from the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) trial. Int J Cardiol. 2017; 244: 229–234.
  14. Gold M, Veldhuisen DV, Hauptman P, et al. Vagus Nerve Stimulation for the Treatment of Heart Failure. J Am Coll Cardiol. 2016; 68(2): 149–158.
  15. Pinna GD, Maestri R, Capomolla S, et al. Applicability and clinical relevance of the transfer function method in the assessment of baroreflex sensitivity in heart failure patients. J Am Coll Cardiol. 2005; 46(7): 1314–1321.
  16. Camm AJ, Bigger JT, Breithardt G, et al. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996; 93(5): 1043–1065.
  17. La Rovere MT, Bigger JT, Marcus FI, et al. 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): 478–484.
  18. La Rovere MT, Pinna GD, Maestri R, et al. Prognostic implications of baroreflex sensitivity in heart failure patients in the beta-blocking era. J Am Coll Cardiol. 2009; 53(2): 193–199.
  19. La Rovere MT, Maestri R, Robbi E, et al. Comparison of the prognostic values of invasive and noninvasive assessments of baroreflex sensitivity in heart failure. J Hypertens. 2011; 29(8): 1546–1552.
  20. Perkiömäki JS, Hämekoski S, Junttila MJ, et al. Predictors of long-term risk for heart failure hospitalization after acute myocardial infarction. Ann Noninvasive Electrocardiol. 2010; 15(3): 250–258.
  21. Raczak G, Pinna GD, Maestri R, et al. Different predictive values of electrophysiological testing and autonomic assessment in patients surviving a sustained arrhythmic episode. Circ J. 2004; 68(7): 634–638.
  22. La Rovere MT, Pinna GD, Maestri R, et al. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation. 2003; 107(4): 565–570.
  23. La Rovere MT, Pinna GD, Maestri R, et al. Autonomic markers and cardiovascular and arrhythmic events in heart failure patients: still a place in prognostication? Data from the GISSI-HF trial. Eur J Heart Fail. 2012; 14(12): 1410–1419.
  24. Nolan J, Batin P, Andrews R, et al. Prospective study of heart rate variability and mortality in chronic heart : results of the United Kingdom heart failure evaluation and assessment of risk trial (UK- heart). Circulation. 1998; 98(15): 1510–1516.
  25. Ponikowski P, Anker SD, Chua TP, et al. Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1997; 79(12): 1645–1650.
  26. Powell BD, Saxon LA, Boehmer JP, et al. Survival after shock therapy in implantable cardioverter-defibrillator and cardiac resynchronization therapy-defibrillator recipients according to rhythm shocked. The ALTITUDE survival by rhythm study. J Am Coll Cardiol. 2013; 62(18): 1674–1679.
  27. Daniłowicz-Szymanowicz L, Suchecka J, Niemirycz-Makurat A, et al. Autonomic Predictors of Hospitalization Due to Heart Failure Decompensation in Patients with Left Ventricular Systolic Dysfunction. PLoS One. 2016; 11(3): e0152372.
  28. Daniłowicz-Szymanowicz L, Kaufmann D, Rozwadowska K, et al. Microvolt T-wave alternans and autonomic nervous system parameters can be helpful in the identification of low-arrhythmic risk patients with ischemic left ventricular systolic dysfunction. PLoS One. 2018; 13(5): e0196812.
  29. Maestri R, Pinna G. POLYAN: A computer program for polyparametric analysis of cardio-respiratory variability signals. Comput Methods Programs Biomed. 1998; 56(1): 37–48.
  30. Pinna GD, Maestri R, Raczak G, et al. Measuring baroreflex sensitivity from the gain function between arterial pressure and heart period. Clin Sci (Lond). 2002; 103(1): 81–88.
  31. Ranucci M, Porta A, Bari V, et al. Baroreflex sensitivity and outcomes following coronary surgery. PLoS One. 2017; 12(4): e0175008.
  32. Gouveia S, Scotto MG, Pinna GD, et al. Spontaneous baroreceptor reflex sensitivity for risk stratification of heart failure patients: optimal cut-off and age effects. Clin Sci (Lond). 2015; 129(12): 1163–1172.
  33. Schwartz PJ, La Rovere MT, De Ferrari GM, et al. Autonomic modulation for the management of patients with chronic heart failure. Circ Heart Fail. 2015; 8(3): 619–628.
  34. Køber L, Thune JJ, Nielsen JC, et al. Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med. 2016; 375(13): 1221–1230.
  35. Haugaa KH, Tilz R, Boveda S, et al. Implantable cardioverter defibrillator use for primary prevention in ischaemic and non-ischaemic heart disease-indications in the post-DANISH trial era: results of the European Heart Rhythm Association survey. Europace. 2017; 19(4): 660–664.
  36. Rahman F, Pechnik S, Gross D, et al. Low frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation. Clin Auton Res. 2011; 21(3): 133–141.
  37. Harada D, Asanoi H, Takagawa J, et al. Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application. Am J Physiol Heart Circ Physiol. 2014; 307(8): H1159–H1168.