RR Interval Spectral Power Research Articles

Auto-Entrainment Risk Assessment in Heart Failure

Risk assessment studies use a suite of nominally independent noninvasive heart rate metrics, often brought together in a statistical model to compute a risk score. The ongoing need to noninvasively identify the higher risk patients requiring more invasive investigations/interventions drives the search for better noninvasive predictive metrics, with increased sensitivity. Many varieties of autoregulatory malfunction occur within the cardiovascular system; thus, it seems a daunting challenge to build predictive models that account for all potential modes of failure. Auto-entrainment (AE) methodology was developed to help address this challenge. AE methodology tests intrinsic capacity to maintain a stable and coherent oscillatory dynamic of autoregulatory control via respiratory entrainment of the blood pressure and heart period. Using cardiovascular death (n=18) at follow-up (1.5 years) as the end point, analysis of AE measurements from 148 patients with heart failure revealed 2 parameters significantly predictive of death. Using logistic regression, the magnitude of systolic pulsus alternans measured during AE had predictive sensitivity of 90% (confidence interval, 62%-100% and specificity of 62% (confidence interval, 49%-74%). The capacity to maintain a stable oscillatory dynamic was measured by the fraction of the total RR-interval spectral power contained within the AE-band. This capacity had predictive sensitivity of 73% (confidence interval, 47%-99%) and specificity of 55% (confidence interval, 43%-66%). AE methodology provides a noninvasive platform to assess the integrity of cardiovascular autoregulatory control systems for risk assessment in heart failure patients.

Cardiovascular regulation during long-duration spaceflights to the International Space Station

Early evidence from long-duration flights indicates general cardiovascular deconditioning, including reduced arterial baroreflex gain. The current study investigated the spontaneous baroreflex and markers of cardiovascular control in six male astronauts living for 2-6 mo on the International Space Station. Measurements were made from the finger arterial pressure waves during spontaneous breathing (SB) in the supine posture pre- and postflight and during SB and paced breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early and late in the missions. There were no changes in preflight measurements of heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in-flight measurements. There were, however, increases in the estimate of left ventricular ejection time index and a late in-flight increase in cardiac output (CO). The high-frequency component of RR interval spectral power, arterial pulse pressure, and stroke volume were reduced in-flight. Postflight there was a small increase compared with preflight in HR (60.0 ± 9.4 vs. 54.9 ± 9.6 beats/min in the seated posture, P < 0.05) and CO (5.6 ± 0.8 vs. 5.0 ± 1.0 l/min, P < 0.01). Arterial baroreflex response slope was not changed during spaceflight, while a 34% reduction from preflight in baroreflex slope during postflight PB was significant (7.1 ± 2.4 vs. 13.4 ± 6.8 ms/mmHg), but a smaller average reduction (25%) during SB (8.0 ± 2.1 vs. 13.6 ± 7.4 ms/mmHg) was not significant. Overall, these data show no change in markers of cardiovascular stability during long-duration spaceflight and only relatively small changes postflight at rest in the seated position. The current program routine of countermeasures on the International Space Station provided sufficient stimulus to maintain cardiovascular stability under resting conditions during long-duration spaceflight.

Effect of antihypertensive drug therapy on short‐term heart rate variability in newly diagnosed essential hypertension

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short-term (5 min) heart rate variability (HRV) provides a non-invasive probe of autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never-treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high-frequency (HF) RR interval spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short-term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol-treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.

Spectral oscillations of RR intervals in sleep apnoea/hypopnoea syndrome patients.

A recent study has shown that daytime heart rate variability is reduced in obstructive sleep apnoea/hypopnoea syndrome (OSAHS) patients. In the present study, the hypothesis was that sympathovagal balance around apnoeas/hypopnoeas and nocturnal autonomic activity are altered in OSAHS patients. Frequency- and time-domain analyses of RR intervals were performed to monitor sympathovagal activity noninvasively. Fourteen untreated OSAHS patients and seven healthy subjects underwent overnight polysomnography. Low (LF) and total (TF) frequency power increased 2 min around the end of apnoeas/hypopnoeas (LF 229+/-38 ms2 TF 345+/-45 ms2) compared with undisturbed sleep (LF 106+/-18 ms2, TF 203+/-23 ms2). The increase in high frequency (HF) power was not significant. LF increase was proportionally higher than the HF increase (normalised LF (LFn) 67+/-1 units, normalised HF (HFn) 33+/-1 units) compared with undisturbed sleep (LFn 52+/-2 units, HFn 48+/-2 units). RR duration did not change around apnoeas/hypopnoeas (RR 904+/-28 ms). The LF and TF power increase was greater around arousal-inducing (LF 260+/-45 ms2 TF 390+/-65 ms2) compared with self-terminating (LF 161+/-31 ms2, TF 249+/-40 ms2) apnoeas/hypopnoeas; the LF and LFn increases were significant in both groups compared with undisturbed sleep and HF power differences were nonsignificant. RR intervals were longer around self-terminating apnoeas/hypopnoeas (RR 914+/-29 ms); the differences were not significant compared with undisturbed sleep. RR interval spectral power was not influenced by the event type. RR duration decreased (912+/-28 ms) and LF, HF and TF power increased (LF 111+/-16 ms2 , HF 62+/-6 ms , TF 173+/-21 ms2) across patients, compared with healthy controls (RR 1138+/-91 ms, LF 57+/-3 ms2, HF 35+/-3 ms2, TF 91+/-6 ms2). LFn and HFn did not change significantly. Sympathetic activity increases around apnoeas/hypopnoeas. The recurrent nocturnal fluctuations of sympathovagal balance and the overall increase of nocturnal autonomic activity may be of importance in the development of cardiovascular disease in sleep apnoea patients.

Global impairment of cardiac autonomic nervous activity late after the Fontan operation.

Atrial tachyarrhythmia is a common cause of morbidity and mortality in patients with univentricular physiology undergoing the Fontan operation. We examined cardiac autonomic nervous activity, a predictor of arrhythmia and sudden death in other cardiovascular disease, in patients late after the Fontan operation, employing heart rate variability (HRV) and baroreflex sensitivity. We measured HRV and baroreflex sensitivity in 22 consecutive patients (8 male, age 26+/-9 years) who had undergone the Fontan operation 13+/-6 years previously, and 22 age- and sex-matched healthy controls. Fontan patients had significantly lower HRV (P<0.0001). Baroreflex sensitivity was measured by the alpha-index method (square root of ratio of RR interval spectral power to systolic blood pressure (SBP) spectral power, in the LF and the HF band) and was also significantly depressed in the Fontan group (P<0.0001 for both). Both low frequency (LF) and high frequency (HF) components of HRV were reduced in the Fontan patients (P<0.0001), but there was interindividual variation so that the LF/(LF+HF) ratio may be high, normal, or low, and decreased with increasing right atrial dimensions (r=-0.62, P=0.006). Patients with a history of sustained atrial arrhythmia had a stronger baroreflex than those without (P=0.005). Autonomic nervous control of the heart is markedly deranged in patients late after the Fontan operation, with reduced HRV and baroreflex sensitivity. A relative suppression of the sympathetic-compared with the parasympathetic-system was observed in patients with marked right atrial dilation within the Fontan group. Furthermore, stronger baroreflexes were seen in Fontan patients in association with a higher incidence of sustained atrial tachyarrhythmia, implying that sinus node dysfunction is unlikely to be the dominant mechanism. Additional studies are clearly required to examine the prognostic importance of impaired BRS and HRV in these patients.

Effects of noradrenaline on human vagal baroreflexes

BACKGROUND. Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function.AIM. To understand better the role of NA in cardiovascular homeostasis.METHODS. We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz.RESULTS. The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (± SD) baseline level of 17.3 ± 6.6 to 34.1 ± 20.8 msJmmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0 ± 12.9 to 10.1 ± 7.4 during the low NA infusion rate and to 6.2 ± 6.2% during the high rate (P < 0.05 and 0.01, respectively).CONCLUSIONS. Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.

Very-low-frequency oscillations in heart rate and blood pressure in periodic breathing: role of the cardiovascular limb of the hypoxic chemoreflex

In chronic heart failure, very-low-frequency (VLF) oscillations (0.01-0.04 Hz) in heart rate and blood pressure may be related to periodic breathing, although the mechanism has not been fully characterized. Groups of ten patients with chronic heart failure and ten healthy controls performed voluntary periodic breathing with computer guidance, while ventilation, oxygen saturation, non-invasive blood pressure and RR interval were measured. In air, voluntary periodic breathing induced periodic desaturation and prominent VLF oscillations when compared with free breathing in both patients [RR interval spectral power from 179 to 358 ms2 (P<0.05); systolic blood pressure (SBP) spectral power from 3.44 to 6.25 mmHg2 (P<0.05)] and controls [RR spectral power from 1040 to 2307 ms2 (P<0.05); SBP spectral power from 3.40 to 9.38 mmHg2 (P<0.05)]. The peak in RR interval occurred 16-26 s before that in SBP, an anti-baroreflex pattern. When the patients followed an identical breathing pattern in hyperoxic conditions to prevent desaturation, the VLF RR interval spectral power was 50% lower (179.0+/-51.7 ms2; P<0.01) and the VLF SBP spectral power was 44% lower (3.51+/-0.77 mmHg(2); P<0.01); similar effects were seen in controls (VLF RR power 20% lower, at 1847+/-899 ms2, P<0.05; VLF SBP power 61% lower, at 3.68+/-0.92 mmHg2, P=0.01). Low- and high-frequency spectral powers were not significantly affected. Thus periodic breathing causes oxygen-sensitive (and by implication chemoreflex-related) anti-baroreflex VLF oscillations in RR interval and blood pressure in both patients with chronic heart failure and normal controls.

Mathematical Treatment of Autonomic Oscillations

To the Editor: Montano et al1 measured RR interval and muscle sympathetic nerve activity (MSNA) autoregressive spectral power before and after small- and large-dose atropine and drew inferences regarding human central autonomic mechanisms. I have several questions for the authors, as well as comments. Your finding that low-dose atropine does not alter low-frequency RR-interval spectral power (Table 2) is at variance with results published by Ikuta …

Mechanisms underlying very-low-frequency RR-interval oscillations in humans.

Survival of post-myocardial infarction patients is related inversely to their levels of very-low-frequency (0.003 to 0.03 Hz) RR-interval variability. The physiological basis for such oscillations is unclear. In our study, we used blocking drugs to evaluate potential contributions of sympathetic and vagal mechanisms and the renin-angiotensin-aldosterone system to very-low-frequency RR-interval variability in 10 young healthy subjects. We recorded RR intervals and arterial pressures during three separate sessions, with the patient in supine and 40 degree upright tilt positions, during 20-minute frequency (0.25 Hz) and tidal volume-controlled breathing after intravenous injections: saline (control), atenolol (0.2 mg/kg, beta-adrenergic blockade), atropine sulfate (0.04 mg/kg, parasympathetic blockade), atenolol and atropine (complete autonomic blockade), and enalaprilat (0.02 mg/kg, ACE blockade). We integrated fast Fourier transform RR-interval spectral power at very low (0.003 to 0.03 Hz), low (0.05 to 0. 15 Hz), and respiratory (0.2 to 0.3 Hz) frequencies. Beta-adrenergic blockade had no significant effect on very-low- or low-frequency RR-interval power but increased respiratory frequency power 2-fold. ACE blockade had no significant effect on low or respiratory frequency RR-interval power but modestly (approximately 21%) increased very-low-frequency power in the supine (but not upright tilt) position (P<0.05). The most profound effects were exerted by parasympathetic blockade: Atropine, given alone or with atenolol, abolished nearly all RR-interval variability and decreased very-low-frequency variability by 92%. Although very-low-frequency heart period rhythms are influenced by the renin-angiotensin-aldosterone system, as low and respiratory frequency RR-interval rhythms, they depend primarily on the presence of parasympathetic outflow. Therefore the prognostic value of very-low-frequency heart period oscillations may derive from the fundamental importance of parasympathetic mechanisms in cardiovascular health.

Sympathovagal balance: a critical appraisal.

Given the importance of the autonomic nervous system to cardiovascular health, it is not surprising that there is and has been great interest in measurements of human sympathetic and vagus nerve traffic as tools that might inform physiological and pathophysiological mechanisms. Pagani and coworkers1 advanced the provocative notion that the instantaneous balance between sympathetic and vagal nerve activities can be captured by a single number, obtained by dividing RR-interval spectral power centered at ≈0.1 Hz by spectral power centered at higher, primarily respiratory frequencies. This ratio, or sympathovagal balance, has been embraced with great enthusiasm2 because it offers new possibilities for understanding dynamic, critically important autonomic interrelations in humans by the use of totally noninvasive, unobtrusive means.3 The broad bases for this mathematical treatment are as follows: (1) 0.1-Hz RR intervals are importantly mediated by fluctuations of sympathetic nerve activity; (2) higher-frequency RR-interval rhythms are mediated almost exclusively by fluctuations of vagal-cardiac nerve activity; and (3) physiological interventions tend to provoke reciprocal changes of sympathetic and vagal neural outflows. Sympathovagal balance, the ratio of these periodicities, is taken to reflect the balance between the opposing neural mechanisms. This review examines the physiological foundations of sympathovagal balance. The ECG is recorded with the subject in a steady state (when rhythms are stationary) for a period sufficiently long to define events occurring over frequencies of interest. RR-interval spectral power is calculated from this series of intervals with an autoregressive algorithm, which yields center frequencies and absolute power of component fluctuations, based on a model whose order (the number of parameters) is selected automatically to minimize Akaike’s information criterion statistic.4 (The statistical uncertainty and consequences of the automatic selection of the autoregressive model have not been defined fully; however, it is clear that the model order importantly determines both …

Influence of cigarette smoking on human autonomic function.

Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.