Ischemic heart disease (IHD) is the leading cause of death in the United States and is rapidly becoming the leading cause of death in developing countries around the world.^1,2 Traditional biomedical risk factors do not fully account for the development of IHD or for the triggering of adverse cardiac events. Psychosocial factors are now recognized as playing a significant and independent role in the development of IHD and its complications.^3,4 Consequently, efforts to alter psychosocial risk factors, particularly in the setting of cardiac rehabilitation, have received increased attention. However, the value of modifying psychosocial risk factors to reduce adverse cardiac events remains controversial.^5,6 Several large-scale randomized trials failed to demonstrate an advantage for stress management interventions in reducing cardiac morbidity or mortality,^7,8 but these studies also failed to adequately reduce psychosocial risk factors. Because emotional distress was not successfully reduced, it was not unexpected that medical end points also were not affected.

Although analysis of heart rate variability is widely used for the assessment of autonomic function, its fundamental framework linking low-frequency and high-frequency components of heart rate variability with sympathetic and parasympathetic autonomic divisions has developed in the 1980s. This simplified framework is no longer able to deal with much evidence about heart rate variability accumulated over the past half-century. This review addresses the pitfalls caused by the old framework and discusses the points that need attention in autonomic assessment by heart rate variability.

We analyzed the spectral components of RR interval variability under controlled respiration (15 breaths/min) in 56 patients (age range, 35-73 years) referred for coronary angiography; 14 patients had multivessel disease (group M), 21 had one-vessel disease (group S), and 21 had nonsignificant disease or normal coronary artery (group N). There were 43 healthy controls (age range, 36-71 years) (group C). The patients had no clinical evidence of heart failure, hypertension, diabetes mellitus, or acute stage of infarction and had taken no medication for 3 days. The autoregressive power spectral density of RR interval variability contains two major components, respiratory sinus arrhythmia (RSA) (0.25 Hz) and Mayer wave-like sinus arrhythmia (MWSA) (0.04-0.15 Hz), which have magnitudes that are quantitative markers of cardiac vagal activity and sympathetic activity with vagal modulation, respectively. We represented the magnitudes by the coefficient of component variance (CCV), which provided the amplitude relative to the mean RR interval. The age- and sex-adjusted mean of CCVRSA significantly decreased with advancing angiographic severity (1.64 +/- 0.09%, 1.66 +/- 0.12%, 1.22 +/- 0.13%, and 0.81 +/- 0.16% for groups C, N, S, and M, respectively) (p = 0.0001). The CCVRSA was unrelated to left ventricular function, previous myocardial infarction, or stenosis of any specific artery including the sinoatrial and atrioventricular node arteries. The CCVMWSA decreased only in group M (p = 0.0462). These results indicate that coronary artery disease is associated with vagal dominant impairment in autonomic cardiac function and that reduction in the vagal cardiac function correlates with the angiographic severity.

Background The primary mechanisms of respiratory sinus arrhythmia (RSA) are understood to be the modulation of cardiac vagal efferent activity by the central respiratory drive and the lung inflation reflex, and the degree of RSA increases with cardiac vagal activity. However, it is unclear whether RSA serves an active physiological role or merely reflects a passive cardiovascular response to respiratory input. We hypothesized that RSA benefits pulmonary gas exchange by matching perfusion to ventilation within each respiratory cycle. Methods and Results In seven anesthetized dogs, a model simulating RSA was made. After elimination of endogenous autonomic activities, respiration-linked heartbeat fluctuations were generated by electrical stimulation of the right cervical vagus during negative pressure ventilation produced by phrenic nerve stimulation (diaphragm pacing). The vagal stimulation was performed in three conditions: phasic stimulation during expiration (artificial RSA) and during inspiration (inverse RSA) and constant stimulation (control) causing the same number of heartbeats per minute as the phasic stimulations. Although tidal volume, cardiac output, and arterial blood pressure were unchanged, artificial RSA decreased the ratio of physiological dead space to tidal volume (V d /V t ) and the fraction of intrapulmonary shunt (Q _sp /Q _t ) by 10% and 51%, respectively, and increased O ₂ consumption by 4% compared with control. Conversely, reverse RSA increased V d /V t and Q _sp /Q _t by 14% and 64%, respectively, and decreased O ₂ consumption by 14%. Conclusions These results support our hypothesis that RSA benefits the pulmonary gas exchange and may improve the energy efficiency of pulmonary circulation by “saving heartbeats.”