Search PubMedSearch

Biomedical subjects

A L Goldberger

Publications and source records attributed to A L Goldberger.

At least 19 recordsLinked to original sources

Scaling behaviour of heartbeat intervals obtained by wavelet-based time-series analysis.

Biological time-series analysis is used to identify hidden dynamical patterns which could yield important insights into underlying physiological mechanisms. Such analysis is complicated by the fact that biological signals are typically both highly irregular and non-stationary, that is, their statistical character changes slowly or intermittently as a result of variations in background influences. Previous statistical analyses of heartbeat dynamics have identified long-range correlations and power-law scaling in the normal heartbeat, but not the phase interactions between the different frequency components of the signal. Here we introduce a new approach, based on the wavelet transform and an analytic signal approach, which can characterize non-stationary behaviour and elucidate such phase interactions. We find that, when suitably rescaled, the distributions of the variations in the beat-to-beat intervals for all healthy subjects are described by a single function stable over a wide range of timescales. However, a similar scaling function does not exist for a group with cardiopulmonary instability caused by sleep apnoea. We attribute the functional form of the scaling observed in the healthy subjects to underlying nonlinear dynamics, which seem to be essential to normal heart function. The approach introduced here should be useful in the analysis of other nonstationary biological signals.

Adult

Age-related alterations in the fractal scaling of cardiac interbeat interval dynamics.

We postulated that aging is associated with disruption in the fractallike long-range correlations that characterize healthy sinus rhythm cardiac interval dynamics. Ten young (21-34 yr) and 10 elderly (68-81 yr) rigorously screened healthy subjects underwent 120 min of continuous supine resting electrocardiographic recording. We analyzed the interbeat interval time series using standard time and frequency domain statistics and using a fractal measure, detrended fluctuation analysis, to quantify long-range correlation properties. In healthy young subjects, interbeat intervals demonstrated fractal scaling, with scaling exponents (alpha) from the fluctuation analysis close to a value of 1.0. In the group of healthy elderly subjects, the interbeat interval time series had two scaling regions. Over the short range, interbeat interval fluctuations resembled a random walk process (Brownian noise, alpha = 1.5), whereas over the longer range they resembled white noise (alpha = 0.5). Short (alpha s)- and long-range (alpha 1) scaling exponents were significantly different in the elderly subjects compared with young (alpha s = 1.12 +/- 0.19 vs. 0.90 +/- 0.14, respectively, P = 0.009; alpha 1 = 0.75 +/- 0.17 vs. 0.99 +/- 0.10, respectively, P = 0.002). The crossover behavior from one scaling region to another could be modeled as a first-order autoregressive process, which closely fit the data from four elderly subjects. This implies that a single characteristic time scale may be dominating heartbeat control in these subjects. The age-related loss of fractal organization in heartbeat dynamics may reflect the degradation of integrated physiological regulatory systems and may impair an individual's ability to adapt to stress.

Adult

Fractal dynamics of human gait: stability of long-range correlations in stride interval fluctuations.

Fractal dynamics were recently detected in the apparently "noisy" variations in the stride interval of human walking. Dynamical analysis of these step-to-step fluctuations revealed a self-similar pattern: fluctuations at one time scale are statistically similar to those at multiple other time scales, at least over hundreds of steps, while healthy subjects walk at their normal rate. To study the stability of this fractal property, we analyzed data obtained from healthy subjects who walked for 1 h at their usual, slow, and fast paces. The stride interval fluctuations exhibited long-range correlations with power-law decay for up to 1,000 strides at all 3 walking rates. In contrast, during metronomically paced walking, these long-range correlations disappeared; variations in the stride interval were random (uncorrelated) and nonfractal. The long-range correlations observed during spontaneous walking were not affected by removal of drifts in the time series. Thus the fractal dynamics of spontaneous stride interval are normally quite robust and intrinsic to the locomotor system. Furthermore, this fractal property of neural output may be related to the higher nervous centers responsible for the control of walking rhythm.

Adult

Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease.

Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.

Adult

Heart rate and respiratory rhythm dynamics on ascent to high altitude.

OBJECTIVE: To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS: 11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES: 24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS: All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS: These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress.

Adult

Is walking a random walk? Evidence for long-range correlations in stride interval of human gait.

Complex fluctuations of unknown origin appear in the normal gait pattern. These fluctuations might be described as being 1) uncorrelated white noise, 2) short-range correlations, or 3) long-range correlations with power-law scaling. To test these possibilities, the stride interval of 10 healthy young men was measured as they walked for 9 min at their usual rate. From these time series, we calculated scaling indexes by using a modified random walk analysis and power spectral analysis. Both indexes indicated the presence of long-range self-similar correlations extending over hundreds of steps; the stride interval at any time depended on the stride interval at remote previous times, and this dependence decayed in a scale-free (fractallike) power-law fashion. These scaling indexes were significantly different from those obtained after random shuffling of the original time series, indicating the importance of the sequential ordering of the stride interval. We demonstrate that conventional models of gait generation fail to reproduce the observed scaling behavior and introduce a new type of central pattern generator model that successfully accounts for the experimentally observed long-range correlations.

Adult

Gender- and age-related differences in heart rate dynamics: are women more complex than men?

OBJECTIVES: This study aimed to quantify the complex dynamics of beat-to-beat sinus rhythm heart rate fluctuations and to determine their differences as a function of gender and age. BACKGROUND: Recently, measures of heart rate variability and the nonlinear "complexity" of heart rate dynamics have been used as indicators of cardiovascular health. Because women have lower cardiovascular risk and greater longevity than men, we postulated that there are important gender-related differences in beat-to-beat heart rate dynamics. METHODS: We analyzed heart rate dynamics during 8-min segments of continuous electrocardiographic recording in healthy young (20 to 39 years old), middle-aged (40 to 64 years old) and elderly (65 to 90 years old) men (n = 40) and women (n = 27) while they performed spontaneous and metronomic (15 breaths/min) breathing. Relatively high (0.15 to 0.40 Hz) and low (0.01 to 0.15 Hz) frequency components of heart rate variability were computed using spectral analysis. The overall "complexity" of each heart rate time series was quantified by its approximate entropy, a measure of regularity derived from nonlinear dynamics ("chaos" theory). RESULTS: Mean heart rate did not differ between the age groups or genders. High frequency heart rate power and the high/low frequency power ratio decreased with age in both men and women (p < 0.05). The high/low frequency power ratio during spontaneous and metronomic breathing was greater in women than men (p < 0.05). Heart rate approximate entropy decreased with age and was higher in women than men (p < 0.05). CONCLUSIONS: High frequency heart rate spectral power (associated with parasympathetic activity) and the overall complexity of heart rate dynamics are higher in women than men. These complementary findings indicate the need to account for gender-as well as age-related differences in heart rate dynamics. Whether these gender differences are related to lower cardiovascular disease risk and greater longevity in women requires further study.

Adult

Correlation approach to identify coding regions in DNA sequences.

Recently, it was observed that noncoding regions of DNA sequences possess long-range power-law correlations, whereas coding regions typically display only short-range correlations. We develop an algorithm based on this finding that enables investigators to perform a statistical analysis on long DNA sequences to locate possible coding regions. The algorithm is particularly successful in predicting the location of lengthy coding regions. For example, for the complete genome of yeast chromosome III (315,344 nucleotides), at least 82% of the predictions correspond to putative coding regions; the algorithm correctly identified all coding regions larger than 3000 nucleotides, 92% of coding regions between 2000 and 3000 nucleotides long, and 79% of coding regions between 1000 and 2000 nucleotides. The predictive ability of this new algorithm supports the claim that there is a fundamental difference in the correlation property between coding and noncoding sequences. This algorithm, which is not species-dependent, can be implemented with other techniques for rapidly and accurately locating relatively long coding regions in genomic sequences.

Algorithms

Increased walking variability in elderly persons with congestive heart failure.

OBJECTIVES: To determine the effects of congestive heart failure on a person's ability to walk at a steady pace while ambulating at a self-determined rate. SETTING: Beth Israel Hospital, Boston, a primary and tertiary teaching hospital, and a social activity center for elderly adults living in the community. PARTICIPANTS: Eleven elderly subjects (aged 70-93 years) with well compensated congestive heart failure (NY Heart Association class I or II), seven elderly subjects (aged 70-79 years) without congestive heart failure, and 10 healthy young adult subjects (aged 20-30 years). MEASUREMENTS: Subjects walked for 8 minutes on level ground at their own selected walking rate. Footswitches were used to measure the time between steps. Step rate (steps/minute) and step rate variability were calculated for the entire walking period, for 30 seconds during the first minute of the walk, for 30 seconds during the last minute of the walk, and for the 30-second period when each subject's step rate variability was minimal. Group means and 5% and 95% confidence intervals were computed. MAIN RESULTS: All measures of walking variability were significantly increased in the elderly subjects with congestive heart failure, intermediate in the elderly controls, and lowest in the young subjects. There was no overlap between the three groups using the minimal 30-second variability (elderly CHF vs elderly controls: P < 0.001, elderly controls vs young: P < 0.001), and no overlap between elderly subjects with and without congestive heart failure when using the overall variability. For all four measures, there was no overlap in any of the confidence intervals, and all group means were significantly different (P < 0.05).

Adult

Physiological time-series analysis: what does regularity quantify?

Approximate entropy (ApEn) is a recently developed statistic quantifying regularity and complexity that appears to have potential application to a wide variety of physiological and clinical time-series data. The focus here is to provide a better understanding of ApEn to facilitate its proper utilization, application, and interpretation. After giving the formal mathematical description of ApEn, we provide a multistep description of the algorithm as applied to two contrasting clinical heart rate data sets. We discuss algorithm implementation and interpretation and introduce a general mathematical hypothesis of the dynamics of a wide class of diseases, indicating the utility of ApEn to test this hypothesis. We indicate the relationship of ApEn to variability measures, the Fourier spectrum, and algorithms motivated by study of chaotic dynamics. We discuss further mathematical properties of ApEn, including the choice of input parameters, statistical issues, and modeling considerations, and we conclude with a section on caveats to ensure correct ApEn utilization.

Algorithms

Effects of head-down bed rest on complex heart rate variability: response to LBNP testing.

Head-down bed rest is used to model physiological changes during spaceflight. We postulated that bed rest would decrease the degree of complex physiological heart rate variability. We analyzed continuous heart rate data from digitized Holter recordings in eight healthy female volunteers (age 28-34 yr) who underwent a 13-day 6 degree head-down bed rest study with serial lower body negative pressure (LBNP) trials. Heart rate variability was measured on 4-min data sets using conventional time and frequency domain measures as well as with a new measure of signal "complexity" (approximate entropy). Data were obtained pre-bed rest (control), during bed rest (day 4 and day 9 or 11), and 2 days post-bed rest (recovery). Tolerance to LBNP was significantly (P < 0.02) reduced on both bed rest days vs. pre-bed rest. Heart rate variability was assessed at peak LBNP. Heart rate approximate entropy was significantly (P < 0.05) decreased at day 4 and day 9 or 11, returning toward normal during recovery. Heart rate standard deviation and the ratio of high- to low-power frequency did not change significantly. We conclude that short-term bed rest is associated with a decrease in the complex variability of heart rate during LBNP testing in healthy young adult women. Measurement of heart rate complexity, using a method derived from nonlinear dynamics ("chaos theory"), may provide a sensitive marker of this loss of physiological variability, complementing conventional time and frequency domain statistical measures.

Adult

Lidocaine prophylaxis in coronary revascularization patients: a randomized, prospective trial.

Life-threatening ventricular ectopy can occur after cardiac operations. The actual incidence of ventricular ectopy and the ability to prevent it by the routine prophylactic use of lidocaine hydrochloride have not been established. We performed a double-blind, randomized, prospective trial involving 109 patients undergoing elective coronary artery revascularization. Patients received either lidocaine (n = 54) or a placebo (n = 55) after separation from bypass. A Holter monitor was affixed to each patient for subsequent review, and bedside intensive-care monitors with alarms were used for "real-time" surveillance. The code was broken when potentially malignant ventricular ectopy or side effects attributable to the study drug were noted. Three lidocaine patients and 2 placebo patients were dropped from the study because of hemodynamic instability or bleeding. Of the remaining 104 patients, the code was broken in 12 (24%) of the 51 in the lidocaine group (9 for ectopy and 3 for mental status changes) and 10 (19%) of the 53 in the placebo group (all for ectopy) (p = not significant). Twenty-four-hour Holter monitor evaluation demonstrated occasional ventricular ectopy in all patients and nonsustained ventricular tachycardia in 28% in the lidocaine group and 48% in the placebo group (p = not significant). The mean number of runs of ventricular tachycardia per patient was 0.53 in the lidocaine group and 1.6 in the placebo group (p = 0.035). There were no significant differences in terms of other ventricular ectopy, morbidity, or mortality. No ventricular fibrillation occurred in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac