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(Stroke. 1996;27:2059-2063.)
© 1996 American Heart Association, Inc.

Articles

Abnormal Heart Rate Variability as a Manifestation of Autonomic Dysfunction in Hemispheric Brain Infarction

Juha T. Korpelainen, MD, PhD; Kyosti A. Sotaniemi, MD, PhD; Heikki V. Huikuri, MD, PhD Vilho V. Myllyla, MD, PhD

the Departments of Neurology (J.T.K., K.A.S., V.V.M.) and Medicine, Division of Cardiology (H.V.H.), University of Oulu, and Department of Neurological Rehabilitation, Deaconess Institute of Oulu (J.T.K.) (Finland).

Correspondence to Juha Korpelainen, MD, Department of Neurology, University of Oulu, Kajaanintie 50 A, FIN-90220 Oulu, Finland.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Abnormal heart rate variability is related to prognostically unfavorable ventricular arrhythmias and sudden arrhythmic death in coronary artery disease. Short-term electrocardiographic (ECG) recordings have shown similar abnormalities of heart rate variability in patients with acute stroke. However, there is no information regarding the clinical significance of these abnormalities and of heart rate variability in long-term ECG recordings in stroke.

Methods In this prospective study, we analyzed the time domain and frequency domain measures of heart rate variability from 24-hour ECG recordings in 31 consecutive patients with hemispheric brain infarction in the acute phase and at 1 and 6 months after the infarction and in 31 age- and sex-matched healthy control subjects.

Results All the measured components of heart rate variability, ie, standard deviation of RR intervals (P<.001), total power (P<.0001), very-low-frequency power (P<.0001), low-frequency power (P<.001), and high-frequency power (P<.05), were significantly lower than those of the control subjects in both the acute phase and 1 and 6 months later. Impaired heart rate variability correlated with the severity of neurological deficits and disability. In five patients with increased intracranial pressure due to large brain infarction, no relevant spectral components were found.

Conclusions Hemispheric brain infarction seems to cause significant long-lasting damage to the cardiovascular autonomic regulatory system manifested as abnormalities of heart rate variability. Distorted heart rate variability in the acute phase of stroke may be prognostically unfavorable.

Key Words: autonomic nervous system • cerebral infarction • heart rate • spectrum analysis

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Disturbances of cardiovascular^{1 2 3} and other autonomic^{4 5 6 7 8 9} functions are frequently encountered in cerebrovascular diseases, but their pathophysiological mechanisms are incompletely understood. The association between increased sympathetic tone and cardiac complications in acute stroke has been well known for decades,^{1 2 3} but recent studies suggest that cardiovascular autonomic failure may also result from impaired parasympathetic functions.¹⁰

Analysis of heart rate variability is the most commonly used measure of the cardiovascular autonomic regulatory system, reflecting both sympathetic and parasympathetic functions. Power spectrum analysis of heart rate variability from ambulatory ECG recordings provides a tool for assessing quantitatively the effects of the different divisions of the autonomic nervous system on the heart.^{11 12} The spectrum of heart rate variability is usually divided into four different frequency components: total power, HF power, LF power, and VLF power. The HF component is considered to be a marker of parasympathetic activity, and the LF component reflects both sympathetic and parasympathetic modulations; however, the role of the VLF component is unclear.¹³ The method has been used for both clinical and research purposes in cardiology,¹³ but only a few studies have investigated heart rate variability in central nervous system diseases.^{14 15 16 17 18} These studies suggest that heart rate variability is diminished in stroke,¹⁴ in brain injuries,¹⁵ and in some degenerative diseases.^{16 17 18} However, a short recording time in the previous stroke studies has limited the analysis to only the HF component of heart rate variability.¹⁴ Moreover, the clinical correlations and the prognostic value of heart rate variability have remained unclear.

In the present prospective 6-month follow-up study, we analyzed the power spectrum of heart rate variability from ambulatory 24-hour ECG recordings in 31 consecutive patients with hemispheric brain infarction and in 31 age- and sex-matched healthy control subjects. The purpose of the work was to assess quantitatively the effects of brain infarction on autonomic cardiac regulation and to evaluate the clinical significance and the prognostic value of heart rate variability in ischemic stroke.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The series consisted of 31 consecutive patients (21 men and 10 women; mean±SD age, 52.2±11.1 years; range, 19 to 67 years) with acute hemispheric brain infarction who were admitted to the Department of Neurology, Oulu University Hospital. Patients with manifestations of other central or peripheral nervous system lesions and patients with any other disease or taking medication known to affect the autonomic nervous system were excluded. Patients with acute congestive cardiac failure and patients with previous cardiac and pulmonary diseases were also excluded. The protocol of the study was approved by the Ethics Committee of the Medical Faculty, University of Oulu, and informed consent was obtained in each case.

The infarct was located in the right hemisphere in 19 patients and in the left hemisphere in 12 patients. All the patients had neurological deficits clearly attributable to an acute hemispheric brain infarction in the territory of the internal carotid artery. Thirty of the 31 patients had unilateral signs of pyramidal tract lesion; most also had sensory deficits, and 1 patient had only aphasia. Neurological deficits of the patients were scored according to the Scandinavian Stroke Scale, and the disability was evaluated with the Barthel Index (Table 1).

View this table: [in this window] [in a new window]   Table 1. Barthel Index and Scandinavian Stroke Scale Scores of Patients With Hemispheric Brain Infarction

Cerebral CT verified a large cortical infarction in 16 cases and a small deep infarction in 8 cases. Even a repeated CT with contrast remained normal in 7 cases in the group of patients clinically classified as having hemispheric small deep infarcts. The first CT was performed within 24 hours after the infarction and the second CT 2 weeks later.

The control group consisted of 31 healthy subjects (21 men and 10 women; mean±SD age, 52.0±11.7 years; range, 19 to 67 years) who had no clinical manifestations of any cardiac, pulmonary, or nervous system disease and who were taking no medication known to affect those systems.

A two-channel 24-hour ambulatory ECG recording (Delmar Avionics electroscanner) was performed on all the patients from 1 to 7 (median, 3) days after the onset of the clinical symptoms and repeated 1 and 6 months later. Two patients with large cortical infarction died as a result of increased intracranial pressure a few days after the first recording. One patient was excluded from the study after the first recording because of treatment with a ß-adrenergic blocking agent needed for hypertension. The recording was performed only once on the control subjects.

For detection of arrhythmias, a two-channel oscilloscopic display and an arrhythmia analyzer were used. In addition, all the tapes were manually scanned by an experienced observer, and all the areas of questionable accuracy were verified by a direct printout. All the recordings were made with two-channel tape recorders and two bipolar leads.

The ECG data were digitally sampled and transferred from the Delmar Avionics scanner to a microcomputer for analysis of heart rate variability. Details of this analysis and the filtering technique have been described previously.¹⁹ Briefly, linear trends were abolished from the RR interval data segments of 512 samples to make the data more stationary. This was done by first fitting a straight line to a segment by a standard least-squares method and then subtracting it from the sample values. The RR interval series was passed through a filter that eliminates unwanted premature beats and noise and fills the resulting gaps with an average value computed in the local neighborhood. An RR interval was interpreted as a premature beat if it deviated from the previous qualified interval value by more than a given tolerance (eg, 30%), which was programmed on the basis of the prematurity index of ectopic beats in each patient. With this filtering technique, abrupt temporary changes in RR interval sequence, representing noise or ectopic beats, were removed and more stationary data were achieved for analysis. In addition, the RR intervals were reviewed on the computer display by an experienced observer, and the questionable portions were compared with the printouts of the ECG recordings. Only those RR intervals related to normal sinus beats in a stationary state and only those segments with greater than 85% of qualified beats were included in the final analysis.

Heart rate variability was measured from the 24-hour ECG recording with both time domain and frequency domain analysis.^{13 19} The SD of successive RR intervals and the RMSSD were used as the time domain measurements, and the power spectrum of heart rate variability was used as the frequency domain measurement.¹³ An autoregressive algorithm was used to estimate the power spectrum densities of RR interval variability with the sampling frequency of 256 Hz. The size of 10 was used for the model order in the analysis of the RR data. The computer program automatically calculates autoregressive coefficients to define the power spectrum densities.

The power spectra of heart rate variability were quantified by measuring the area under the spectral curve (Fig 1) in four frequency bands. The area under the spectral curve from 0.005 to 0.4 Hz represents the total power, which is divided into HF power (the area from 0.15 to 0.4 Hz), LF power (the area from 0.04 to 0.15 Hz), and VLF power (the area from 0.005 to 0.04 Hz). The 24-hour average spectral components were calculated from the segments of 512 RR intervals.

View larger version (10K): [in this window] [in a new window]   Figure 1. Power spectral analysis of heart rate variability in a healthy 61-year-old male control subject. The area under the spectral curve from 0.005 to 0.4 Hz represents the total power of heart rate variability, the area from 0.15 to 0.4 Hz represents HF power, the area from 0.04 to 0.15 Hz represents LF power, and the area from 0.005 to 0.04 Hz represents VLF power.

Statistical analyses were performed with the use of the Mann-Whitney two-sample test to compare the values of the control subjects and the patients in the acute phase and at 1 and 6 months after the infarction. The Mann-Whitney two-sample test, the Kruskal-Wallis test, and linear regression were used in analyzing the relations between heart rate variability and the clinical signs of the patients.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
A measurable power spectrum of heart rate variability was elicited in all the control subjects and in 25 of the 31 patients (81%) with brain infarction in the acute phase of brain infarction. The results of these groups are presented in Table 2. In the acute phase after infarction, all the time domain (SD of the RR interval, P<.0001; RMSSD, P<.05) and the frequency domain (total power, P<.0001; VLF power, P<.0001; LF power, P<.001; HF power, P<.05) measures of heart rate variability of the patients were significantly lower than those of the control subjects. A statistically significant difference between the patients and control subjects was still evident at the 1-month (SD of the RR interval, P<.001; RMSSD, P<.05; total power, P<.0001; VLF power, P<.0001; LF power, P<.001; HF power, P<.05) and at the 6-month (SD of the RR interval, P<.0001; RMSSD, P<.05; total power, P<.0001; VLF power, P<.0001; LF power, P<.001; HF power, P<.05) follow-up visits. The ratio of LF to HF in the patients and that in the control subjects were similar. No significant differences could be found between the results of the patients in the acute phase and those at 1 and 6 months after the infarction. Fig 2 presents an example of the suppressed power spectrum of heart rate variability in a patient with brain infarction.

View this table: [in this window] [in a new window]   Table 2. Heart Rate and Heart Rate Variability in Control Subjects and Patients With Hemispheric Brain Infarction in the Acute Phase and at 1 and 6 Months After Infarction

View larger version (9K): [in this window] [in a new window]   Figure 2. Power spectral analysis of heart rate variability in a 61-year-old male patient 4 days after right hemisphere brain infarction. Note the suppression of all the spectral components of heart rate variability.

Despite infrequent ectopic beats, none of the patients had serious arrhythmias during the ECG recording in the acute phase, at 1 month, and at 6 months. All the patients also had favorable cardiac outcome during the 6-month follow-up period. Arrhythmic events, cardiac failure, or any other cardiac events were not found.

The power spectrum of heart rate variability was related to the severity of the clinical signs caused by brain infarction. There was a statistically significant linear correlation between the suppression of heart rate variability and the severity of neurological deficits measured by the Scandinavian Stroke Scale for the following variables: SD of the RR interval (P=.003, r=.336), total power (P=.006, r=.295), VLF power (P=.026, r=.344), and LF power (P=.013, r=.249). A significant linear correlation was also found between the suppression of heart rate variability and the Barthel Index: SD of the RR interval (P=.013, r=.251), total power (P=.014, r=.243), VLF power (P=.005, r=.310), and LF power (P=.033, r=.191).

Heart rate variability was abnormally low in both the patients with cortical infarction and the patients with small deep infarction, and no significant difference could be found between these patient groups. The suppression of heart rate variability was not dependent on the side of the infarction, and the results of the male and female patients were similar.

In five patients with a large cortical infarction resulting in severe neurological deficits and poor outcome, the spectrum of heart rate variability could not be elicited. In these patients heart rate variability was quite random and unpredictable, and no discrete spectral peaks could be observed (Fig 3). All of these patients had definite clinical symptoms reflecting increased intracranial pressure. Two of them died for this reason a few days after the recording, and all the others had a decreased state of consciousness. None of these patients were mechanically ventilated during the ECG recording, however.

View larger version (12K): [in this window] [in a new window]   Figure 3. Power spectral analysis of heart rate variability in a 43-year-old male patient 1 day after right hemisphere brain infarction. The patient died 2 days later as a result of increased intracranial pressure.

The seven patients with normal CT had significantly lower heart rate variability than the control subjects, but their results did not differ from those of the other patients.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The results of this first prospective study that aimed at measuring heart rate variability in ischemic stroke demonstrate a significant suppression of heart rate variability as a manifestation of cardiovascular autonomic failure in hemispheric brain infarction. The suppression of all the components of heart rate variability indicates that both the sympathetic and the parasympathetic autonomic cardiovascular regulatory systems are impaired in patients with acute cerebral infarction. Variability was markedly low in the acute phase and all through the 6-month follow-up period, and the low level correlated with the severity of the neurological deficits and disability. In patients with increased intracranial pressure due to a large brain infarction, no relevant spectral components were found.

Only a few previous studies focused on heart rate variability in cerebrovascular diseases.^{10 14 15 20} Barron et al¹⁴ showed that both right hemisphere and left hemisphere brain infarction may result in impaired heart rate variability. Heart rate variability has shown to be suppressed in brain-dead patients with cerebellar or pontine lesion¹⁵ and in patients with severe subarachnoid or intracerebral hemorrhage.²⁰ In these studies, however, the duration of the ECG recording was only a few minutes, which limits the applicability of the power spectral analysis to the LF and VLF components.¹⁴ In addition, the patient groups were heterogeneous, and many of the patients were mechanically ventilated and under cardiovascular medication known to affect the function of the autonomic nervous system.^{14 15 20} In the present study we used 24-hour ECG recording time, which also permitted the analysis of the LF and VLF components of heart rate variability.²¹ In contrast to the previous studies, our patients were taking no medication, they had no manifestations of cardiac, pulmonary, or other diseases known to affect the autonomic nervous system, and none of them were mechanically ventilated. Thus, our results can only reflect the effects of hemispheric brain infarction on the autonomic cardiovascular regulatory system.

The abnormal heart rate variability observed in the present patients may result from damage of the cortical or subcortical structures or of the neural pathways known to regulate the cardiovascular autonomic system. Experimen-tal^{22 23} and human²⁴ studies suggest that the insular cortex lying within the middle cerebral artery territory is the most important cortical area controlling both sympathetically and parasympathetically mediated cardiovascular regulation. The insular cortex has extensive connections with the other important autonomic regulatory areas located in the subcortical limbic and forebrain regions, but the pathways linking it with the cardioregulatory centers have not been established in detail.²⁵ There is also some evidence for cortical asymmetry in the regulation of heart rate and other cardiovascular functions.²² It has been shown that stimulation of the human right insula increases sympathetic cardiovascular tone, whereas parasympathetic activity increases more frequently during left insular stimulation.²⁴ Moreover, it seems that supraventricular tachycardias are more often observed after the right than the left middle cerebral artery infarction.²⁶ In the present study all the patients had an infarction in the territory of the middle cerebral artery, but none of the patients had a pure insular lesion on either side of the brain. There were no differences between the results of right hemisphere and left hemisphere infarctions, and this agrees with previous findings.¹⁴ It therefore seems that abnormal heart rate variability may be caused by an infarction located at the various cortical and subcortical levels on both sides of the brain.

Previously, impaired heart rate variability has been shown to be prognostically unfavorable in coronary artery disease^{27 28} and in a Framingham cohort of elderly subjects,²⁹ with the VLF component being the best prognostic factor.^{28 29} Low heart rate variability is particularly related to an increased risk of cardiac arrhythmias and to sudden death after myocardial infarction,³⁰ but it is also related to an impaired prognosis in patients with coronary artery disease before a myocardial infarction.^{27 28} In the present series, heart rate variability was shown to be most markedly depressed in the patients with severe neurological deficits and disability evaluated by the Scandinavian Stroke Scale and the Barthel Index. The VLF component was also the most sensitive marker of abnormal heart rate variability in our patients, as it has been previously in patients with acute myocardial infarction. Moreover, the normal spectral components of heart rate variability had disappeared in patients with increased intracranial pressure due to large brain infarction. Thus, it seems that distorted heart rate variability is related to a poor outcome in patients with acute hemispheric brain infarction, and this suggests that monitoring of the dynamics of heart rate behavior might become a useful indicator of the outcome of cerebral infarction. Further studies in which techniques other than linear spectral analysis alone are used may be needed to assess with more confidence the usefulness of the analysis of heart rate dynamics in the risk stratification of patients with hemispheric brain infarction. Furthermore, it will be important to determine whether reduced overall heart rate variability is a result of a brain infarction or whether the abnormalities in cardiovascular autonomic regulation precede and perhaps predispose subjects to the onset of infarction. The influence of alertness of patients, which may affect the amount of heart rate variability, particularly in the acute phase after stroke, should also be studied.

In conclusion, hemispheric brain infarction seems to result in a significant dysfunction of the autonomic cardioregulatory system, manifesting itself as suppressed or distorted heart rate variability. These long-lasting abnormalities of heart rate variability, which reflect both sympathetic and parasympathetic autonomic failure, may be caused by damage located in the insular cortex or in its neural connections controlling cardiovascular regulation. Distorted heart rate variability in the acute phase of stroke seems to be prognostically unfavorable.

	Selected Abbreviations and Acronyms

 

ECG = electrocardiogram, electrocardiographic HF = high frequency LF = low frequency RMSSD = root mean square of the difference between successive normal RR intervals VLF = very low frequency

	Acknowledgments

 
This study was supported by grants from the Maire Taponen Foundation (Dr Korpelainen), the Medical Council of the Academy of Finland (Dr Huikuri), and the Finnish Foundation for Cardiovascular Research (Dr Huikuri).

Received April 1, 1996; revision received July 9, 1996; accepted July 10, 1996.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Natelson BH. Neurocardiology: an interdisciplinary area for the 80s. Arch Neurol. 1985;42:178-184.[Abstract]
2. Talman WT. Cardiovascular regulation and the lesions of the central nervous system. Ann Neurol. 1985;18:1-12.[Medline] [Order article via Infotrieve]
3. Oppenheimer S, Cechetto D, Hachinski V. Cerebrogenic cardiac arrhythmias. Arch Neurol. 1990;47:513-519.[Abstract]
4. Korpelainen JT, Sotaniemi KA, Myllyla VV. Asymmetric sweating in stroke: a prospective quantitative study of patients with hemispheral brain infarction. Neurology. 1993;43:1211-1214.[Abstract/Free Full Text]
5. Korpelainen JT, Sotaniemi KA, Myllyla VV. Ipsilateral hypohidrosis in brain stem infarction. Stroke. 1993;24:100-104.[Abstract/Free Full Text]
6. Korpelainen JT, Tolonen U, Sotaniemi KA, Myllyla VV. Suppressed sympathetic skin response in brain infarction. Stroke. 1993;24:1389-1392.[Abstract/Free Full Text]
7. Mayer SA, Fink ME, Homma S, Sherman D, LiMandri G, Lennihan L, Solomon RA, Klebanoff LM, Beckford A, Raps EC. Cardiac injury associated with neurogenic pulmonary edema following subarachnoid hemorrhage. Neurology. 1994;44:815-820.[Abstract/Free Full Text]
8. Nachtmann A, Siebler M, Rose G, Sitzer M, Steinmetz H. Cheyne-Stokes respiration in ischemic stroke. Neurology. 1995;45:820-821.[Abstract/Free Full Text]
9. Korpelainen JT, Sotaniemi KA, Myllyla VV. Asymmetrical skin temperature in ischemic stroke. Stroke. 1995;26:1543-1547.[Abstract/Free Full Text]
10. Korpelainen JT, Sotaniemi KA, Suominen K, Tolonen U, Myllyla VV. Cardiovascular autonomic reflexes in brain infarction. Stroke. 1994;25:787-792.[Abstract]
11. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482-493.[Abstract/Free Full Text]
12. Ori Z, Monir G, Weiss J, Sayhouni X, Singer DH. Heart rate variability. frequency domain analysis. Cardiol Clin. 1992;10:499-537.[Medline] [Order article via Infotrieve]
13. Huikuri HV. Heart rate variability in coronary artery disease. J Intern Med. 1995;237:349-357.[Medline] [Order article via Infotrieve]
14. Barron SA, Rogovski Z, Hemli J. Autonomic consequences of cerebral hemisphere infarction. Stroke. 1994;25:113-116.[Abstract]
15. Novak V, Novak P, deMarchie M, Schondorf R. The effect of severe brainstem injury on heart rate and blood pressure oscillations. Clin Auton Res. 1995;5:24-30.[Medline] [Order article via Infotrieve]
16. Maayan C, Axelrod FB, Akselrod S, Carley DW, Shannon CD. Evaluation of autonomic dysfunction in familial dysautonomia by power spectral analysis. J Auton Nerv Syst. 1987;21:51-58.[Medline] [Order article via Infotrieve]
17. Aharon-Peretz J, Harel T, Revach M, Ben-Haim A. Increased sympathetic and decreased parasympathetic cardiac innervation in patients with Alzheimer's disease. Arch Neurol. 1992;49:919-922.[Abstract]
18. Pisano F, Miscio G, Mazzuero G, Lanfranchi P, Colombo R, Pinelli P. Decreased heart rate variability in amyotrophic lateral sclerosis. Muscle Nerve. 1995;18:1225-1231.[Medline] [Order article via Infotrieve]
19. Huikuri HV, Valkama JO, Airaksinen KEJ, Seppanen T, Kessler KM, Takkunen JT, Myerburg RJ. Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease. Circulation. 1993;87:1220-1228.[Abstract/Free Full Text]
20. Kita Y, Ishise J, Yoshita Y, Aizawa Y, Yoshio H, Minagawa F, Shimizu M, Takeda R. Power spectral analysis of heart rate and arterial blood pressure oscillations in brain-dead patients. J Auton Nerv Syst. 1993;44:101-107.[Medline] [Order article via Infotrieve]
21. Huikuri HV, Kessler KM, Terracelli E, Castellanos A, Linnaluoto MK, Myerburg RJ. Reproducibility and circadian rhythm of heart rate variability in healthy subjects. Am J Cardiol. 1990;65:391-394.[Medline] [Order article via Infotrieve]
22. Oppenheimer S. The anatomy and physiology of cortical mechanisms of cardiac control. Stroke. 1993;24(suppl I):I-3-I-5.
23. Oppenheimer SM, Cechetto DF. Cardiac chronotropic organisation of the rat insular cortex. Brain Res. 1990;533:66-72.[Medline] [Order article via Infotrieve]
24. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology. 1992;42:1727-1732.[Abstract/Free Full Text]
25. Cechetto DF, Saper CB. Role of the cerebral cortex in autonomic function. In: Loewy AD, Spyer KM, eds. Central Regulation of Autonomic Functions. New York, NY: Oxford University Press; 1990:208-223.
26. Lane RD, Wallace JD, Petrosky PP, Schwatz GE, Gradman AH. Supraventricular tachycardia in patients with right hemisphere strokes. Stroke. 1992;23:362-366.[Abstract/Free Full Text]
27. Kleiger RE, Miller JP, Bigger JT, Moss AJ, and the Multicenter Post-Infarction Research Group. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59:256-262.[Medline] [Order article via Infotrieve]
28. Bigger JT Jr, Kleiger RE, Fleiss JL, Rolnitzky LM, Steinman RC, Miller JP, and the Multicenter Post-Infarction Research Group. Components of heart rate variability measured during healing of acute myocardial infarction. Am J Cardiol. 1988;61:208-215.[Medline] [Order article via Infotrieve]
29. Tsuji H, Venditti FJ, Manders ES, Evans JC, Larson MG, Feldman CL, Levy D. Reduced heart rate variability and mortality risk in an elderly cohort: the Framingham Study. Circulation. 1994;90:878-883.[Abstract/Free Full Text]
30. Huikuri HV, Koistinen MJ, Yli-Mayry S, Airaksinen KEJ, Seppanen T, Ikaheimo MJ, Myerburg RJ. Impaired low-frequency oscillations of heart rate in patients with prior acute myocardial infarction and life-threatening arrhythmias. Am J Cardiol. 1995;76:56-60.[Medline] [Order article via Infotrieve]

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