Complexity analysis of heart rate variability in chronic obstructive pulmonary disease: relationship with severity and symptoms



Chronic obstructive pulmonary disease (COPD) negatively impacts autonomic control of the heart rate, as assessed by time and frequency domains of heart rate variability (HRV) analysis. However, it is unknown whether symbolic dynamic analysis may identify cardiac autonomic impairment, and whether such nonlinear indices may be associated with disease severity, prognostic markers, perceived dyspnea and functional capacity in patients with COPD. The current study assessed cardiac autonomic modulation by symbolic analysis of HRV in patients with COPD compared with healthy controls.


We recruited 54 COPD patients and 20 healthy controls. The interval between two successive R-wave peaks was calculated in the resting supine position. HRV was analyzed using symbolic markers and Shannon entropy (SE). The six-minute walk test (6MWT) was applied in a 30-m corridor.


We found a lower 6MWT distance in patients with COPD compared with healthy controls (p < 0.05). We found increased SE and decreased percentage of no variation patterns (0V%) in COPD patients compared with the control group (p = 0.001). Significant correlations were found between the percentage of one variation pattern (1V%) and the Medical Research Council dyspnea scale (r = 0.38, p = 0.01), BODE index (r = 0.38, p = 0.01), forced expiratory volume in the first second (FEV1) [L] (r = −0.44, p = 0.003) and FEV1 [%] (r = −0.35, p = 0.02). It was found that SE was inversely associated with 0V% (r = −0.87, p < 0.0001).


COPD patients present with depressed sympathetic modulation of HR and higher SE compared with healthy controls. This increased irregularity was inversely associated with 0V%. These results suggested that COPD patients seem to have a cardiac control shifted towards a parasympathetic predominance compared with controls. Symbolic dynamic and complexity index of HRV are related to disease severity, symptoms and functional impairment in these patients.

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  1. 1.

    World Health Organization (2002) World Health Report.

  2. 2.

    Young RP, Hopkins R, Eaton TE (2007) Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes. Eur Respir J 30(4):616–622

  3. 3.

    Gold Executive Committee. Global Initiative For Chronic Obstructive Lung Disease, 2007–2010

  4. 4.

    Barnes PJ, Celli BR (2009) Systemic manifestations and comorbidities of COPD. Eur Respir J 33(5):1165–1185

  5. 5.

    Wouters EFM (2005) Local and systemic inflammation in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2:26–33

  6. 6.

    Engström G, Lind P, Hedblad B, Wollmer P, Stavenow L, Janzon L, Lindgärde F (2002) Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins. Circulation 106(20):2555–2560

  7. 7.

    Sajadieh A, Nielsen OW, Rasmussen V, Hein HO, Abedini S, Hansen JF (2004) Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J 25(5):363–370

  8. 8.

    Mendes FAR, Moreno IL, Durand MT, Pastre CM, Ramos EMC, Vanderlei LCM (2011) Análise das respostas do sistema cardiovascular ao teste de capacidade vital forçada na DPOC. Rev Bras Fisioter. 15(2):102–108

  9. 9.

    European Society of Cardiology. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards ofmeasurement, physiological interpretation, and clinical use. Circulation 93(5):1043– 1065

  10. 10.

    Chen W-L, Chen G-Y, Kuo C-D (2006) Hypoxemia and autonomic nervous system dysfunction in patients with chronic obstructive pulmonary disease. Respir Med 100(9):1547–1553

  11. 11.

    Morgan BJ et al (1995) Combined hypoxia and hypercapnia evokes long-lasting sympathetic activation in humans. J Appl Physiol 79:205–213

  12. 12.

    Stewart AG et al (1994) Autonomic nerve dysfunction in COPD as assessed by the acetylcholine sweat-spot test. Eur Respirat J 7:1090–1095

  13. 13.

    Huikuri HV et al (1999) Measurement of heart rate variability: a clinical tool or a research toy? J Am Coll Cardiol 34(7):1878–1883

  14. 14.

    Huikuri HV, Mäkikallio TH, Perkiömäki J (2003) Measurement of heart rate variability by methods based on nonlinear dynamics. J Electrocardiol 36:95–99

  15. 15.

    Jokinen V et al (2003) Temporal changes and prognostic significance of measures of heart rate dynamics after acute myocardial infarction in the beta-blocking era. Am J Cardiol 92:907–912

  16. 16.

    Mäkikallio TH et al (2002) Clinical applicability of heart rate variability analysis by methods based on nonlinear dynamics. Card Electrophysiol Rev. 6:250–255

  17. 17.

    Mäkikallio TH et al (2001) Fractal analysis and time and frequency domain measures of heart rate variability as predictors of mortality in patients with heart failure. Am J Cardiol 87:178–182

  18. 18.

    Porta A et al (2001) Entropy, entropy rate and pattern classification as tools to typify complexity in short heart period variability series. IEEE Trans Biomed Eng 48:1282–1291

  19. 19.

    Guzzetti S et al (2005) Symbolic dynamics of heart rate variability: a probe to investigate cardiac autonomic modulation. Circulation 112:465–470

  20. 20.

    Porta A et al (2007) Assessment of cardiac autonomic modulation during graded head-up tilt by symbolic analysis of heart rate variability. Am J Physiol Heart Circ Physiol 293:H702–H708

  21. 21.

    Porta A, Baumert M, Cysarz D, Wessel N (2015) Enhancing dynamical signatures of complex systems through symbolic computation. Phil Trans R Soc A. 373:20140099

  22. 22.

    Chen W-L, Chen G-Y, Kuo C-D (2006) Hypoxemia and autonomic nervous dysfunction in patients with chronic obstructive pulmonary disease. Respir Med 100:547–553

  23. 23.

    Zoccal DB, Paton JF, Machado BH (2009) Do changes in the coupling between respiratory and sympathetic activities contribute to neurogenic hypertension? Clin Exp Pharmacol Physiol 36:1188–1196

  24. 24.

    Gestel AJRV (2012) Sympathetic overactivity and cardiovascular disease in patients with chronic obstructive pulmonary disease (COPD). Discov Med 14(79):359–368

  25. 25.

    Zupanic E, Zivanovic I, Kalisnik JM, Avbelj V, Lainscak M (2014) The effect of 4-week rehabilitation on heart rate variability and QTc interval in patients with chronic obstructive pulmonary disease. COPD 11(6):659–669

  26. 26.

    Esler M (2009) The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J Appl Physiol 108:227–237

  27. 27.

    Mohammed J, Derom E, De Backer T, De Wandele I, Calders P (2018) Cardiac autonomic function and reactivity tests in physically active moderately severe subjects with chronic obstructive pulmonary disease. J Chron Obstruct Pulmon Dis 15(1):51–59

  28. 28.

    Gestel AJV, Steier J (2010) Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD). J Thoracic Dis 2:215–222

  29. 29.

    Goulart Cda L, Simon JC, Schneiders Pde B, San Martin EA, Cabiddu R, Borghi-Silva A et al (2016) Respiratory muscle strength effect on linear and nonlinear heart rate variability parameters in COPD patients. Int J Chron Obstruct Pulmon Dis 11(6):1671–1677

  30. 30.

    Mazzuco A, Medeiros WM, Sperling MP, de Souza AS, Alencar MC, Arbex FF et al (2015) Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients. Int J Chron Obstruct Pulmon Dis. 10:1651–1661

  31. 31.

    Haarmann H, Mohrlang C, Tschiesner U, Rubin DB, Bornemann T, Rüter K, Bonev S, Raupach T, Hasenfuß G, Andreas S (2015) Inhaled β-agonist does not modify sympathetic activity in patients with COPD. BMC Pulm Med. 15:46

  32. 32.

    Wu YK, Huang CY, Yang MC, Huang GL, Chen SY, Lan CC (2015) Effect of tiotropium on heart rate variability in stable chronic obstructive pulmonary disease patients. J Aerosol Med Pulm Drug Deliv. 28(2):100–105

  33. 33.

    Rossinen J, Partanen J, Stenius-Aarniala B, Nieminen MS (1998) Albutamol inhalation has no effect on myocardial ischaemia, arrhythmias and heart rate variability in patients with coronary artery disease plus asthma or chronic obstructive pulmonary disease. J Intern Med 243(5):361–366

  34. 34.

    (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166(1):111–117

  35. 35.

    Celli BR, Cote CG, Marin JM et al (2004) The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 350(10):1005–1012

  36. 36.

    Radespiel-Tröger M, Rauh R, Mahlke C, Gottschalk T, Mück-Weymann M (2003) Agreement of two different methods for measurement of heart rate variability. Clin Auton Res 13:99–102

  37. 37.

    Phillips SA, Andaku DK, Mendes RG, Caruso FR, Cabiddu R, Jaenisch RB, Arena R, Borghi-Silva A (2017) Exploring vascular function biomarkers: implications for rehabilitation. Braz J Cardiovasc Surg. 32(2):125–135

  38. 38.

    Takahashi ACM, Porta A, Melo RC, Quitério RJ, Silva E, Borghi-Silva A et al (2012) Aging reduces complexity of heart rate variability assessed by conditional entropy and symbolic analysis. Intern Emerg Med 7:229–235

  39. 39.

    Goulart CL, Cabiddu R, Schneiders PB, Martin EAS, Trimer R, Borghi-Silva A, Silva ALG (2017) Is cardiac autonomic modulation during upper limb isometric contraction and Valsalva maneuver impaired in COPD patients. Int J COPD 12:849–857

  40. 40.

    Carvalho TD, Pastre CM, Godoy MF, Fereira C, Pitta FO, Abreu LC, Ramos EMC, Valenti VE, Vanderlei LCM (2011) Fractal correlation property of heart rate variability in chronic obstructive pulmonary disease. Int J COPD 6:23–28

  41. 41.

    Mazzuco A, Medeiros WM, Souza AS, Alencar ACN, Neder JA, Borghi-Silva A (2017) Are heart rate dynamics in the transition from rest to submaximal exercise related to maximal cardiorespiratory responses in COPD? Braz J Phys Therapy 21(4):251–258

  42. 42.

    Pichon A, de Bisschop C, Diaz V, Denjean A (2005) Parasympathetic airway response and heart rate variability before and at the end of methacholine challenge. Chest 127(1):23–29

  43. 43.

    Corbo GM, Inchingolo R, Sgueglia GA, Lanza G, Valente S (2013) C-reactive protein, lung hyperinflation and heart rate variability in chronic obstructive pulmonary disease a pilot study. COPD. 10(2):200–207

  44. 44.

    Bianchim MS, Sperandio EF, Martinhão GS, Matheus AC, Lauria VT, da Silva RP, Spadari RC, Gagliardi AR, Arantes RL, Romiti M, Dourado VZ (2016) Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults. Braz J Med Biol Res 49(3):1–7

  45. 45.

    Borghi-Silva A, Beltrame T, Reis MS, Sampaio LMM, Catai AM, Arena R, Costa D (2012) Relationship between oxygen consumption kinetics and BODE Index in COPD patients. Int J COPD 7:711–718

  46. 46.

    Leite MR, Ramos EMC, Kalva-Filho CA, Rodrigues FMM, Freire APCF, Tacao GY, Toledo AC, Cecílio MJ, Vanderlei LCM, Ramos D (2015) Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD. Respirology 20:273–278

  47. 47.

    Gatica CCG, Flores AA, Farías TY, Rodríguez FR (2014) Composición corporal y variabilidad del ritmo cardiacoen pacientes conenfermedad pulmonar obstructiva crónica candidatos a rehabilitación respiratória. Nutr Hosp 30(1):179–182

  48. 48.

    Kabbach EZ, Mazzuco A, Borghi-Silva A, Cabiddu R, Agnoleto AG, Barbosa JF, Junior LCSC, Mendes RG (2017) Increased parasympathetic cardiac modulation in patients with acute exacerbation of COPD: how should we interpret it? Int J COPD 12:2221–2230

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Correspondence to Audrey Borghi-Silva.

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Serrão, N.F., Porta, A., Minatel, V. et al. Complexity analysis of heart rate variability in chronic obstructive pulmonary disease: relationship with severity and symptoms. Clin Auton Res (2020).

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  • Respiratory disease
  • Symbolic analysis
  • Conditional entropy
  • Functional capacity