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Evaluation of heart rate variability

Ary L Goldberger, MD
Phyllis K Stein, PhD
Section Editor
Leonard I Ganz, MD, FHRS, FACC
Deputy Editor
Brian C Downey, MD, FACC


Evaluation of beat-to-beat heart rate dynamics, as a noninvasive albeit indirect probe of autonomic nervous system function, is of interest from a number of basic perspectives with potential translational applications. For example, a large body of clinical and experimental evidence that indicates an important role for the autonomic nervous system in the triggering or sustaining of malignant ventricular arrhythmias [1]. Higher sympathetic activity unopposed by vagal activity promotes arrhythmia in a variety of ways:

Reducing ventricular refractory period and the ventricular fibrillation threshold

Promoting triggered activity afterpotentials

Enhancing automaticity (see "Enhanced cardiac automaticity")

Vagal stimulation opposes these changes and reduces the effects of sympathetic stimulation by prolonging refractoriness, elevating the ventricular fibrillation threshold, and reducing automaticity. (See "Pathogenesis of ventricular arrhythmias in heart failure and cardiomyopathy", section on 'Pathogenesis'.)

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Literature review current through: Nov 2017. | This topic last updated: Nov 03, 2017.
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  1. Lown B, Verrier RL. Neural activity and ventricular fibrillation. N Engl J Med 1976; 294:1165.
  2. Zhao M, Sun L, Liu JJ, et al. Vagal nerve modulation: a promising new therapeutic approach for cardiovascular diseases. Clin Exp Pharmacol Physiol 2012; 39:701.
  3. Haskó G. Receptor-mediated interaction between the sympathetic nervous system and immune system in inflammation. Neurochem Res 2001; 26:1039.
  4. Jose AD, Taylor RR. Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. J Clin Invest 1969; 48:2019.
  5. Malik M, Camm AJ. Components of heart rate variability--what they really mean and what we really measure. Am J Cardiol 1993; 72:821.
  6. Buijs RM, Scheer FA, Kreier F, et al. Organization of circadian functions: interaction with the body. Prog Brain Res 2006; 153:341.
  7. Cevese A, Gulli G, Polati E, et al. Baroreflex and oscillation of heart period at 0.1 Hz studied by alpha-blockade and cross-spectral analysis in healthy humans. J Physiol 2001; 531:235.
  8. Hirsch JA, Bishop B. Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate. Am J Physiol 1981; 241:H620.
  9. Eckberg DL. Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol Respir Environ Exerc Physiol 1983; 54:961.
  10. Vanoli E, Adamson PB, Ba-Lin, et al. Heart rate variability during specific sleep stages. A comparison of healthy subjects with patients after myocardial infarction. Circulation 1995; 91:1918.
  11. Guilleminault C, Connolly S, Winkle R, et al. Cyclical variation of the heart rate in sleep apnoea syndrome. Mechanisms, and usefulness of 24 h electrocardiography as a screening technique. Lancet 1984; 1:126.
  12. Mietus, JE, Peng, et al. Detection of obstructive sleep apnea from cardiac interbeat interval time series. Comput Cardiol 2000; 27:753.
  13. Stein PK, Pu Y. Heart rate variability, sleep and sleep disorders. Sleep Med Rev 2012; 16:47.
  14. Stein PK, Le Q, Domitrovich PP, CAST Investigators. Development of more erratic heart rate patterns is associated with mortality post-myocardial infarction. J Electrocardiol 2008; 41:110.
  15. Stein PK, Domitrovich PP, Hui N, et al. Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses. J Cardiovasc Electrophysiol 2005; 16:954.
  16. Metra M, Nodari S, D'Aloia A, et al. A rationale for the use of beta-blockers as standard treatment for heart failure. Am Heart J 2000; 139:511.
  17. Floras JS. Sympathetic activation in human heart failure: diverse mechanisms, therapeutic opportunities. Acta Physiol Scand 2003; 177:391.
  18. Seely AJ, Macklem PT. Complex systems and the technology of variability analysis. Crit Care 2004; 8:R367.
  19. Zipes DP, Barber MJ, Takahashi N, Gilmour RF Jr. Influence of the autonomic nervous system on the genesis of cardiac arrhythmias. Pacing Clin Electrophysiol 1983; 6:1210.
  20. Malliani, A, Recordati, et al. Nervous activity of afferent cardiac sympathetic fibers with atrial and ventricular endings. Am J Physiol 1973; 339:457.
  21. Schwartz PJ, Pagani M, Lombardi F, et al. A cardiocardiac sympathovagal reflex in the cat. Circ Res 1973; 32:215.
  22. Cascio WE, Johnson TA, Gettes LS. Electrophysiologic changes in ischemic ventricular myocardium: I. Influence of ionic, metabolic, and energetic changes. J Cardiovasc Electrophysiol 1995; 6:1039.
  23. Barber MJ, Mueller TM, Henry DP, et al. Transmural myocardial infarction in the dog produces sympathectomy in noninfarcted myocardium. Circulation 1983; 67:787.
  24. Barber MJ, Mueller TM, Davies BG, et al. Interruption of sympathetic and vagal-mediated afferent responses by transmural myocardial infarction. Circulation 1985; 72:623.
  25. Takahashi N, Barber MJ, Zipes DP. Efferent vagal innervation of canine ventricle. Am J Physiol 1985; 248:H89.
  26. De Ferrari, GM, Vanoli, et al. Vagal activity and ventricular fibrillation. In: Vagal Control of the Heart, Levy, MN, Schwartz, PJ (Eds), Futura Publishing, Armonk 1994. p.613.
  27. Bailey JC, Watanabe AM, Besch HR Jr, Lathrop DA. Acetylcholine antagonism of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Circ Res 1979; 44:378.
  28. Kolman BS, Verrier RL, Lown B. Effect of vagus nerve stimulation upon excitability of the canine ventricle. Role of sympathetic-parasympathetic interactions. Am J Cardiol 1976; 37:1041.
  29. Haensel A, Mills PJ, Nelesen RA, et al. The relationship between heart rate variability and inflammatory markers in cardiovascular diseases. Psychoneuroendocrinology 2008; 33:1305.
  30. Stein PK, Barzilay JI, Chaves PH, et al. Higher levels of inflammation factors and greater insulin resistance are independently associated with higher heart rate and lower heart rate variability in normoglycemic older individuals: the Cardiovascular Health Study. J Am Geriatr Soc 2008; 56:315.
  31. Porges SW. The polyvagal theory: new insights into adaptive reactions of the autonomic nervous system. Cleve Clin J Med 2009; 76 Suppl 2:S86.
  32. Rosso R, Sparks PB, Morton JB, et al. Vagal paroxysmal atrial fibrillation: prevalence and ablation outcome in patients without structural heart disease. J Cardiovasc Electrophysiol 2010; 21:489.
  33. 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. Circulation 1996; 93:1043.
  34. Dynamic Electrocardiography, Malik M, Camm AJ (Eds), Blackwell Futura, Elmsford 2004.
  35. Strauss, HM. Heart Rate Variability. Am J Physiol 2003; 285:R927.
  36. Heart Rate Variability, Malik, M, Camm, AJ (Eds), Futura Publishing Company, Armonk 1995.
  37. Voss A, Schulz S, Schroeder R, et al. Methods derived from nonlinear dynamics for analysing heart rate variability. Philos Trans A Math Phys Eng Sci 2009; 367:277.
  38. Sassi R, Cerutti S, Lombardi F, et al. Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society. Europace 2015; 17:1341.
  39. Costa MD, Peng CK, Goldberger AL. Multiscale analysis of heart rate dynamics: entropy and time irreversibility measures. Cardiovasc Eng 2008; 8:88.
  40. Sloan RP, Huang MH, McCreath H, et al. Cardiac autonomic control and the effects of age, race, and sex: the CARDIA study. Auton Neurosci 2008; 139:78.
  41. Costa MD, Davis RB, Goldberger AL. Heart Rate Fragmentation: A New Approach to the Analysis of Cardiac Interbeat Interval Dynamics. Front Physiol 2017; 8:255.
  42. Mietus JE, Peng CK, Henry I, et al. The pNNx files: re-examining a widely used heart rate variability measure. Heart 2002; 88:378.
  43. Schmidt G, Malik M, Barthel P, et al. Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 1999; 353:1390.
  44. Stein PK. Heart rate turbulence: explorations of an emerging risk factor. J Cardiovasc Electrophysiol 2003; 14:453.
  45. Stein PK, Barzilay JI. Relationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults. J Cardiovasc Electrophysiol 2011; 22:122.
  46. Bauer, A, Schmidt, G. Heart rate turbulence in ischemic heart disease. In: Dynamic Electrocardiography. Malik M, Camm AJ (Eds), Futura Publishing Company, Elmsford, NY. p.211.
  47. Stein PK, Barzilay JI, Chaves PH, et al. Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS). J Cardiovasc Electrophysiol 2008; 19:1169.
  48. Barthel P, Schneider R, Bauer A, et al. Risk stratification after acute myocardial infarction by heart rate turbulence. Circulation 2003; 108:1221.
  49. Cygankiewicz I. Heart rate turbulence. Prog Cardiovasc Dis 2013; 56:160.
  50. Au-Yeung WT, Reinhall PG, Poole JE, et al. SCD-HeFT: Use of R-R interval statistics for long-term risk stratification for arrhythmic sudden cardiac death. Heart Rhythm 2015; 12:2058.
  51. Takahashi N, Kuriyama A, Kanazawa H, et al. Validity of spectral analysis based on heart rate variability from 1-minute or less ECG recordings. Pacing Clin Electrophysiol 2017; 40:1004.
  52. Nolan J, Batin PD, Andrews R, et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation 1998; 98:1510.
  53. Frey B, Heinz G, Binder T, et al. Diurnal variation of ventricular response to atrial fibrillation in patients with advanced heart failure. Am Heart J 1995; 129:58.
  54. Taylor JA, Carr DL, Myers CW, Eckberg DL. Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation 1998; 98:547.
  55. Tripathi KK. Very low frequency oscillations in the power spectra of heart rate variability during dry supine immersion and exposure to non-hypoxic hypobaria. Physiol Meas 2011; 32:717.
  56. Akselrod S, Gordon D, Ubel FA, et al. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 1981; 213:220.
  57. Peng CK, Mietus JE, Liu Y, et al. Exaggerated heart rate oscillations during two meditation techniques. Int J Cardiol 1999; 70:101.
  58. Bernardi L, Sleight P, Bandinelli G, et al. Effect of rosary prayer and yoga mantras on autonomic cardiovascular rhythms: comparative study. BMJ 2001; 323:1446.
  59. Peng CK, Henry IC, Mietus JE, et al. Heart rate dynamics during three forms of meditation. Int J Cardiol 2004; 95:19.
  60. Badra LJ, Cooke WH, Hoag JB, et al. Respiratory modulation of human autonomic rhythms. Am J Physiol Heart Circ Physiol 2001; 280:H2674.
  61. Lombardi F, Stein PK. Origin of heart rate variability and turbulence: an appraisal of autonomic modulation of cardiovascular function. Front Physiol 2011; 2:95.
  62. Nunan D, Sandercock GR, Brodie DA. A quantitative systematic review of normal values for short-term heart rate variability in healthy adults. Pacing Clin Electrophysiol 2010; 33:1407.
  63. Bigger JT Jr, Fleiss JL, Steinman RC, et al. RR variability in healthy, middle-aged persons compared with patients with chronic coronary heart disease or recent acute myocardial infarction. Circulation 1995; 91:1936.
  64. Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol 1998; 31:593.
  65. Stein PK, Barzilay JI, Chaves PH, et al. Heart rate variability and its changes over 5 years in older adults. Age Ageing 2009; 38:212.
  66. Bigger, JT. RR variability to evaluate autonomic physiology and pharmacology and to predict cardiovascular outcomes in human. In: Cardiac Arrhythmias: From Cell to Bedside, Zipes DP (Ed), Saunders, Philadelphia 1995. p.1151.
  67. Liao D, Barnes RW, Chambless LE, et al. Age, race, and sex differences in autonomic cardiac function measured by spectral analysis of heart rate variability--the ARIC study. Atherosclerosis Risk in Communities. Am J Cardiol 1995; 76:906.
  68. Kleiger RE, Bigger JT, Bosner MS, et al. Stability over time of variables measuring heart rate variability in normal subjects. Am J Cardiol 1991; 68:626.
  69. Stein PK. Heart rate variability and longevity. Am J Cardiol 2010; 106:910.
  70. Bigger JT Jr, Fleiss JL, Rolnitzky LM, Steinman RC. Stability over time of heart period variability in patients with previous myocardial infarction and ventricular arrhythmias. The CAPS and ESVEM investigators. Am J Cardiol 1992; 69:718.
  71. Björkander I, Forslund L, Ericson M, et al. Long-term stability of heart rate variability in chronic stable angina pectoris, and the impact of an acute myocardial infarction. Clin Physiol Funct Imaging 2009; 29:201.
  72. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59:256.
  73. La Rovere MT, Bigger JT Jr, 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; 351:478.
  74. Buccelletti E, Gilardi E, Scaini E, et al. Heart rate variability and myocardial infarction: systematic literature review and metanalysis. Eur Rev Med Pharmacol Sci 2009; 13:299.
  75. Erdogan A, Coch M, Bilgin M, et al. Prognostic value of heart rate variability after acute myocardial infarction in the era of immediate reperfusion. Herzschrittmacherther Elektrophysiol 2008; 19:161.
  76. Flapan AD, Wright RA, Nolan J, et al. Differing patterns of cardiac parasympathetic activity and their evolution in selected patients with a first myocardial infarction. J Am Coll Cardiol 1993; 21:926.
  77. Bigger JT Jr, Fleiss JL, Rolnitzky LM, et al. Time course of recovery of heart period variability after myocardial infarction. J Am Coll Cardiol 1991; 18:1643.
  78. Bigger JT Jr, Fleiss JL, Rolnitzky LM, Steinman RC. Frequency domain measures of heart period variability to assess risk late after myocardial infarction. J Am Coll Cardiol 1993; 21:729.
  79. Stein PK, Domitrovich PP, Kleiger RE, CAST Investigators. Including patients with diabetes mellitus or coronary artery bypass grafting decreases the association between heart rate variability and mortality after myocardial infarction. Am Heart J 2004; 147:309.
  80. Whang W, Bigger JT Jr. Comparison of the prognostic value of RR-interval variability after acute myocardial infarction in patients with versus those without diabetes mellitus. Am J Cardiol 2003; 92:247.
  81. Janszky I, Ericson M, Mittleman MA, et al. Heart rate variability in long-term risk assessment in middle-aged women with coronary heart disease: The Stockholm Female Coronary Risk Study. J Intern Med 2004; 255:13.
  82. Kotecha D, New G, Flather MD, et al. Five-minute heart rate variability can predict obstructive angiographic coronary disease. Heart 2012; 98:395.
  83. Yi G, Goldman JH, Keeling PJ, et al. Heart rate variability in idiopathic dilated cardiomyopathy: relation to disease severity and prognosis. Heart 1997; 77:108.
  84. Szabó BM, van Veldhuisen DJ, van der Veer N, et al. Prognostic value of heart rate variability in chronic congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol 1997; 79:978.
  85. Fauchier L, Babuty D, Cosnay P, et al. Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value. J Am Coll Cardiol 1997; 30:1009.
  86. 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; 79:1645.
  87. Mäkikallio TH, Huikuri HV, Hintze U, et al. Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure. Am J Cardiol 2001; 87:178.
  88. Fauchier L, Babuty D, Cosnay P, Fauchier JP. Prognostic value of heart rate variability for sudden death and major arrhythmic events in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1999; 33:1203.
  89. 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; 107:565.
  90. Fantoni C, Raffa S, Regoli F, et al. Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure. J Am Coll Cardiol 2005; 46:1875.
  91. Landolina M, Gasparini M, Lunati M, et al. Heart rate variability monitored by the implanted device predicts response to CRT and long-term clinical outcome in patients with advanced heart failure. Eur J Heart Fail 2008; 10:1073.
  92. Stein PK, Pu Y. Heart rate variability in congestive heart failure. In: Heart rate variability signal processing: Clinical applications, Kamath M, Watanabe M (Eds), CRC Press (Taylor and Francis LLC), Boca Raton, FL 2012. p.303.
  93. Yamada A, Hayano J, Sakata S, et al. Reduced ventricular response irregularity is associated with increased mortality in patients with chronic atrial fibrillation. Circulation 2000; 102:300.
  94. Lombardi F, Colombo A, Basilico B, et al. Heart rate variability and early recurrence of atrial fibrillation after electrical cardioversion. J Am Coll Cardiol 2001; 37:157.
  95. Tsuji H, Larson MG, Venditti FJ Jr, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 1996; 94:2850.
  96. Dekker JM, Crow RS, Folsom AR, et al. Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities. Circulation 2000; 102:1239.
  97. Shah SA, Kambur T, Chan C, et al. Relation of short-term heart rate variability to incident heart failure (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol 2013; 112:533.
  98. Hillebrand S, Gast KB, de Mutsert R, et al. Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: meta-analysis and dose-response meta-regression. Europace 2013; 15:742.
  99. Malik M, Camm AJ, Janse MJ, et al. Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: a substudy of EMIAT (The European Myocardial Infarct Amiodarone Trial). J Am Coll Cardiol 2000; 35:1263.
  100. Sullivan BA, Grice SM, Lake DE, et al. Infection and other clinical correlates of abnormal heart rate characteristics in preterm infants. J Pediatr 2014; 164:775.
  101. Crawford MH, Bernstein SJ, Deedwania PC, et al. ACC/AHA guidelines for ambulatory electrocardiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the guidelines for ambulatory electrocardiography). Circulation 1999; 100:886.
  102. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004; 110:588.