The LF/HF ratio does not accurately measure cardiac sympatho-vagal balance

Power spectral analysis of the beat-to-beat variations of heart rate or the heart period (R–R interval) has become widely used to quantify cardiac autonomic regulation (Appel et al., 1989; Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996; Berntson et al., 1997; Denver et al., 2007; Thayler et al., 2010; Billman, 2011). This technique partitions the total variance (the “power”) of a continuous series of beats into its frequency components, typically identifying two or three main peaks: Very Low Frequency (VLF) <0.04 Hz, Low Frequency (LF), 0.04–0.15 Hz, and High Frequency (HF) 0.15–0.4 Hz. It should be noted that the HF peak is shifted to a higher range (typically 0.24–1.04 Hz) in infants and during exercise (Berntson et al., 1997). The HF peak is widely believed to reflect cardiac parasympathetic nerve activity while the LF, although more complex, is often assumed to have a dominant sympathetic component (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996; Berntson et al., 1997; Billman, 2011). Based upon these assumptions, Pagani and co-workers proposed that the ratio of LF to HF (LF/HF) could be used to quantify the changing relationship between sympathetic and parasympathetic nerve activities (i.e., the sympatho-vagal balance) (Pagani et al., 1984, 1986; Malliani et al., 1991) in both health and disease. However, this concept has been challenged (Kingwell et al., 1994; Koh et al., 1994; Hopf et al., 1995; Eckberg, 1997; Houle and Billman, 1999; Billman, 2011). Despite serious and largely under-appreciated limitations, the LF/HF ratio has gained wide acceptance as a tool to assess cardiovascular autonomic regulation where increases in LF/HF are assumed to reflect a shift to “sympathetic dominance” and decreases in this index correspond to a “parasympathetic dominance.” Therefore, it is vital to provide a critical assessment of the assumptions upon which this concept is based.

[1]  F A Bainbridge,et al.  The relation between respiration and the pulse‐rate , 1920, The Journal of physiology.

[2]  N. A. Coulter,et al.  Respiratory sinus arrhythmia: a frequency dependent phenomenon , 1964 .

[3]  C. Davies,et al.  Sinus arrhythmia in man at rest. , 1967, Journal of applied physiology.

[4]  P G Katona,et al.  Cardiac vagal efferent activity and heart period in the carotid sinus reflex. , 1970, The American journal of physiology.

[5]  M. N. Levy Brief Reviews: Sympathetic-Parasympathetic Interactions in the Heart , 1971, Circulation research.

[6]  R. Hainsworth Circulatory responses from lung inflation in anesthetized dogs. , 1974, The American journal of physiology.

[7]  F R Calaresu,et al.  Influence of cardiac neural inputs on rhythmic variations of heart period in the cat. , 1975, The American journal of physiology.

[8]  A. Melcher Respiratory sinus arrhythmia in man. A study in heart rate regulating mechanisms. , 1976, Acta physiologica Scandinavica. Supplementum.

[9]  D L Eckberg,et al.  Nonlinearities of the Human Carotid Baroreceptor‐Cardiac Reflex , 1980, Circulation research.

[10]  J. Hirsch,et al.  Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate. , 1981, The American journal of physiology.

[11]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[12]  D L Eckberg,et al.  Human sinus arrhythmia as an index of vagal cardiac outflow. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[13]  D. Eckberg,et al.  Trigeminal‐baroreceptor reflex interactions modulate human cardiac vagal efferent activity. , 1984, The Journal of physiology.

[14]  P. Korner,et al.  Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. , 1986, Circulation.

[15]  J. Fagius,et al.  The diving response in man: effects on sympathetic activity in muscle and skin nerve fascicles. , 1986, The Journal of physiology.

[16]  M. Turiel,et al.  Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities as a Marker of Sympatho‐Vagal Interaction in Man and Conscious Dog , 1986, Circulation research.

[17]  D L Eckberg,et al.  Carotid baroreceptor-muscle sympathetic relation in humans. , 1987, The American journal of physiology.

[18]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[19]  R J Cohen,et al.  Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. , 1988, The American journal of cardiology.

[20]  G. Billman,et al.  Time-series analysis of heart rate variability during submaximal exercise. Evidence for reduced cardiac vagal tone in animals susceptible to ventricular fibrillation. , 1989, Circulation.

[21]  R J Cohen,et al.  Beat to beat variability in cardiovascular variables: noise or music? , 1989, Journal of the American College of Cardiology.

[22]  P. Reddy,et al.  Respiratory sinus arrhythmia in the denervated human heart. , 1989, Journal of applied physiology.

[23]  M. Kollai,et al.  Respiratory sinus arrhythmia is a limited measure of cardiac parasympathetic control in man. , 1990, The Journal of physiology.

[24]  G. Billman,et al.  Dynamic changes in cardiac vagal tone as measured by time-series analysis. , 1990, The American journal of physiology.

[25]  A. Malliani,et al.  Cardiovascular Neural Regulation Explored in the Frequency Domain , 1991, Circulation.

[26]  P. Schwartz,et al.  Sympathetic-parasympathetic interaction and accentuated antagonism in conscious dogs. , 1991, The American journal of physiology.

[27]  D. Singer,et al.  Reproducibility and relation to mean heart rate of heart rate variability in normal subjects and in patients with congestive heart failure secondary to coronary artery disease. , 1991, The American journal of cardiology.

[28]  W. C. Randall,et al.  SA nodal parasympathectomy delineates autonomic control of heart rate power spectrum. , 1991, The American journal of physiology.

[29]  J. Fleiss,et al.  The correlation between heart period variability and mean period length. , 1992, Statistics in medicine.

[30]  D. Eckberg,et al.  Important influence of respiration on human R-R interval power spectra is largely ignored. , 1993, Journal of applied physiology.

[31]  G A McPherson,et al.  Heart Rate Spectral Analysis, Cardiac Norepinephrine Spillover, and Muscle Sympathetic Nerve Activity During Human Sympathetic Nervous Activation and Failure , 1994, Circulation.

[32]  A. Kadish,et al.  Effect of physiologic and pharmacologic adrenergic stimulation on heart rate variability. , 1994, Journal of the American College of Cardiology.

[33]  D. Eckberg,et al.  Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects. , 1994, The Journal of physiology.

[34]  A. Kadish,et al.  Dissociation of heart rate variability from parasympathetic tone. , 1994, The American journal of physiology.

[35]  A Skyschally,et al.  Low‐frequency Spectral Power of Heart Rate Variability Is Not a Specific Marker of Cardiac Sympathetic Modulation , 1995, Anesthesiology.

[36]  J. Hartikainen,et al.  The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic 'tone'. , 1995, Acta physiologica Scandinavica.

[37]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[38]  H. Nagaraja,et al.  Heart rate variability: origins, methods, and interpretive caveats. , 1997, Psychophysiology.

[39]  M. Malik,et al.  Sympathovagal balance: a critical appraisal. , 1998, Circulation.

[40]  G. Billman,et al.  Low-frequency component of the heart rate variability spectrum: a poor marker of sympathetic activity. , 1999, American journal of physiology. Heart and circulatory physiology.

[41]  J S Floras,et al.  Limitations of the use of spectral analysis of heart rate variability for the estimation of cardiac sympathetic activity in heart failure. , 2001, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[42]  D L Eckberg,et al.  Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans. , 2001, American journal of physiology. Heart and circulatory physiology.

[43]  A. Malliani,et al.  Importance of ventilation in modulating interaction between sympathetic drive and cardiovascular variability. , 2001, American journal of physiology. Heart and circulatory physiology.

[44]  C. May,et al.  Continual recordings of cardiac sympathetic nerve activity in conscious sheep. , 2002, American journal of physiology. Heart and circulatory physiology.

[45]  J. Taylor,et al.  Short‐term cardiovascular oscillations in man: measuring and modelling the physiologies , 2002, The Journal of physiology.

[46]  F. Yasuma,et al.  Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm? , 2004, Chest.

[47]  J. Sacha,et al.  Different methods of heart rate variability analysis reveal different correlations of heart rate variability spectrum with average heart rate. , 2005, Journal of electrocardiology.

[48]  Julian F. Thayer,et al.  Accentuated antagonism in the control of human heart rate , 2000, Clinical Autonomic Research.

[49]  G. Billman,et al.  Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction. , 2005, American journal of physiology. Heart and circulatory physiology.

[50]  Giuseppe Mancia,et al.  Point: Counterpoint: Cardiovascular variability is/is not an index of autonomic control of circulation , 2006 .

[51]  Stephen W. Porges,et al.  Methodological issues in the quantification of respiratory sinus arrhythmia , 2007, Biological Psychology.

[52]  C. May,et al.  Increased cardiac sympathetic nerve activity in heart failure is not due to desensitization of the arterial baroreflex. , 2007, American journal of physiology. Heart and circulatory physiology.

[53]  G. Billman,et al.  Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation. , 2007, Journal of applied physiology.

[54]  J. Sacha,et al.  Alterations of an average heart rate change heart rate variability due to mathematical reasons. , 2008, International journal of cardiology.

[55]  G. Billman,et al.  Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training. , 2009, American journal of physiology. Heart and circulatory physiology.

[56]  B. Joung,et al.  Power spectral analysis of heart rate variability and autonomic nervous system activity measured directly in healthy dogs and dogs with tachycardia-induced heart failure. , 2009, Heart rhythm.

[57]  D. Goldstein,et al.  Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation , 2009, Cleveland Clinic Journal of Medicine.

[58]  J. Thayer,et al.  The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. , 2010, International journal of cardiology.

[59]  G. Billman Heart Rate Variability – A Historical Perspective , 2011, Front. Physio..