Archives of Physical Medicine and Rehabilitation
Volume 90, Issue 9 , Pages 1635-1638, September 2009

Analysis of Heart Rate Variability With Electromyography in Heart Transplant Recipients

  • Arzu On, MD

      Affiliations

    • Department of Physical Medicine, University of Ege, Izmir, Turkey
    • ,
  • Hale Karapolat, MD

      Affiliations

    • Department of Physical Medicine, University of Ege, Izmir, Turkey
    • Corresponding Author InformationReprint requests to Hale Karapolat, MD, Ege University Medical Faculty Physical Medicine and Rehabilitation Dept, 35100 Bornova/Izmir/Turkey
    • ,
  • Mehdi Zoghi, MD

      Affiliations

    • Department of Cardiology, University of Ege, Izmir, Turkey
    • ,
  • Sanem Nalbantgil, MD

      Affiliations

    • Department of Cardiology, University of Ege, Izmir, Turkey
    • ,
  • Tahir Yagdi, MD

      Affiliations

    • Department of Cardiac Surgery, University of Ege, Izmir, Turkey
    • ,
  • Mustafa Ozbaran, MD

      Affiliations

    • Department of Cardiac Surgery, University of Ege, Izmir, Turkey

Article Outline

Abstract 

On A, Karapolat H, Zoghi M, Nalbantgil S, Yagdi T, Ozbaran M. Analysis of heart rate variability with electromyography in heart transplant recipients.

Objective

To investigate vagal parasympathetic functions by electromyographic R-R interval variation analyses in heart transplant recipients.

Design

Cross-sectional and longitudinal study.

Setting

Department of physical medicine and rehabilitation, university hospital.

Participants

Early (n=8; <3mo) and late (n=17; >1y) heart transplant recipients and healthy volunteers (n=20) were included.

Interventions

Not applicable.

Main Outcome Measures

The R-R interval variations at rest and in response to deep breathing, Valsalva, and tilt/standup maneuvers were analyzed in all patient and control groups. Further, 8 early heart transplant recipients were followed up at the sixth and twelfth months after transplantation.

Results

Compared with controls, both early and late transplant recipients had significantly lower R-R interval variation ratios (P<.05). There were no statistically significant differences between the early and late groups (P>.05). R-R interval variation ratios showed no significant changes from baseline (P>.025) in the early heart transplant recipients.

Conclusions

The findings of the study suggest that parasympathetic activities are suppressed in the early stage after heart transplantation and do not significantly recover with time. The electromyographic analysis of R-R interval variation is a simple test that may offer an attractive alternative for routine evaluation of autonomic dysfunction in heart transplant recipients.

Key Words: Heart transplantation, Rehabilitation

List of Abbreviations: ECG, electrocardiogram, EMG, electromyogram

 

DURING HEART TRANSPLANTATION, postganglionic neural axons innervating the heart are severed, resulting in autonomic denervation of the heart.1 Despite the presence of publications that suggest autonomic reinnervation usually occurs within 1 to 5 years after heart transplantation, there is no consensus on this issue.1, 2, 3, 4

Cardiovascular autonomic reflexes are essential for the maintenance of arterial blood pressure during orthostatic stress and for prevention of wide fluctuations in arterial blood pressure in response to stress and exercise. Cardiac autonomic denervation is responsible for sudden arrhythmic death5, 6 and nonarrhythmic cardiac events such as myocardial infarction and rapid progression of atherosclerosis.7 It is also considered to be related to allograft rejection of transplanted hearts, although reports of this are controversial.8, 9 For this reason, assessment of cardiac autonomic function is crucial in heart transplant recipients. Although various techniques are used for this purpose, heart rate variability analysis from ambulatory ECG recordings is the most frequently used tool.4, 8, 9, 10, 11 Apart from the conventional power spectrum and frequency domain measures based on linear fluctuations of heart rate,4, 8, 9 new methods based on nonlinear dynamics and fractal analysis have been developed.10, 11 However, most of these techniques are complex. Thus, the measurement of heart rate variability by various methods is not a routine clinical tool.12

In recent years, R-R interval variation analysis by EMG has been a frequently used technique to assess the parasympathetic innervation of the heart, both in healthy subjects and in patients with dysautonomic dysfunction.13 R-R interval variation is a simple, reliable, and nontime-consuming procedure, which makes it suitable for routine clinical practice. Although routinely used for autonomic assessment in EMG laboratories, we came across no study that used this technique in heart transplant recipients. Considering that this technique may offer an easily applicable alternative for the evaluation of autonomic functions in heart transplant recipients, we analyzed R-R interval variations in a group of early and late transplant recipients and compared the results with a control group with intact cardiac innervation. We also aimed to follow up the early heart transplant recipients in order to investigate the course of autonomic function within the 1-year period after transplantation.

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Methods 

Twenty-five heart transplant recipients who met the inclusion criteria were selected from among the patients who had received heart transplantation at Ege University Hospital, Department of Cardiovascular Surgery. Eight patients were in the acute stage after transplantation (early transplant group, <3mo after transplantation), and the remaining 17 comprised the late transplant group (>1y after transplantation). Exclusion criteria were the presence of acute rejection, significant transplant vasculopathy, or allograft dysfunction; any systemic disorder known to affect the autonomic nervous system such as diabetes mellitus, heart and renal failure, syncope/orthostatic hypotension, and rhythm disorders; any medication that might affect autonomic responses such as antidepressants, clonidine, reserpine, or beta-blockers; and unwillingness to participate in the study. All transplant recipients had been receiving immunosuppressant treatment. The control group consisted of 20 healthy volunteers without any systemic or neurologic disorder. They were selected from employees of our hospital, or were the caregivers of inpatients. The local ethics committee of Ege University approved all aspects of this study. Informed consent was obtained from all patients and controls.

R-R interval variation analyses were performed in the early transplant group at the third, sixth, and twelfth months, while the analyses were recorded once in the late transplant and control groups.

The tests were carried out while the subjects were lying supine in a semidarkened room, with the ambient temperature controlled at between 21°C and 26°C. The recordings were taken in the morning, 2 hours after breakfast. The subjects were asked to avoid activities that would affect blood pressure (eg, running or jumping) before the tests. Before starting the assessment, all subjects were instructed to lie down for about 15 minutes in the EMG room. During the assessment, all subjects were kept awake and relaxed.

R-R interval variation analyses were performed using an automated software program14, 15 in the EMG.a QRS complexes were observed on the monitor, and heartbeat peaks and intervals between the 2 consecutive R peaks were automatically detected. Therefore, no trigger was necessary.

Recordings of the R-R interval variations were made using disposable pregelled surface electrodes with a 15×20mm recording area (Medtronic, 9013S0211a). The grounded electrode was placed on the forearm, and 2 surface recording electrodes were positioned on the dorsum of the hands of the subjects.

R-R Interval Variation Ratios During Normal and Deep Breathing 

R-R interval variations during normal breathing were recorded while the subjects breathed synchronously for 1 minute. Then the subjects were asked to perform deep breathing (6 successive deep respiratory cycles of 5s inspiration and 5s expiration) for 1 minute. The R-R interval variation ratios were calculated by the computer according to the following formula: the longest and shortest R-R intervals were measured, and the ratio of the difference between the longest and shortest R-R intervals to the mean of all R-R intervals was multiplied by 100.

Valsalva Test 

The R-R interval variations were recorded while the subject performed the Valsalva maneuver for 25 seconds after 10 seconds of normal breathing, and then another 25 seconds of normal breathing. The subjects performed the Valsalva maneuver by pausing and freezing the quicksilver bar of the manometer connected to a puff tube at 40mmHg while exhaling. The Valsalva ratio was calculated by the computer by dividing the maximum R-R interval obtained after performance of the Valsalva maneuver by the minimum R-R interval obtained during the Valsalva maneuver.

Tilt/Stand-Up Test 

The test was performed by recording the R-R interval variations when the patient stood up after 10 heartbeats, until 1 minute had passed. The tilt/stand-up ratio (30/15 ratio) was calculated as the proportion of the longest interval at the thirtieth heartbeat to the shortest interval at the fifteenth heartbeat.

Statistical Analyses 

SPSS for Windows, version 11.0,b was used to analyze the results. A P value below .05 was considered statistically significant. The group analyses performed included the Mann-Whitney U test for numerical data and the chi-square test for nominal data. The data obtained at the third month for the early transplant group and those obtained for the late transplant and control groups were compared using the Mann-Whitney U test. In the early group, the within-group change for repeated measures was analyzed with the Friedman test. If the Friedman test determined that differences existed among the repeated measures of the within-group, then the Bonferroni-adjusted Wilcoxon signed-rank test was performed to determine the differences from baseline values; a level of .025 was accepted as significant.

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Results 

The age range of the subjects was 15 to 60 years. The mean ages of the patients in the early, late, and control groups were 44.2±6.1 years, 38.2±13.8 years, and 43.2±11.5 years, respectively. There were no significant differences between the groups with regard to age or sex (P>.05). The mean duration from the time of transplantation was 36.7±32.7 months (range, 12–120mo) in the late heart transplant recipients.

The mean R-R interval variation ratios obtained in transplant and control groups are demonstrated in figure 1. Compared with the controls, both early and late transplant recipients had significantly depressed R-R interval variations at rest (2.1±1.0 and 2.8±1.0 vs 14.8±7.7; P<.05), in response to deep breathing (2.8±1.8 and 3.2±2.5 vs 29.0±10.7; P<.05), in response to the Valsalva maneuver (1.01±0.0 and 1.04±0.1 vs 1.9±0.6; P<.05), and in response to standing (0.99±0.02 and 0.99±0.02 vs 1.9±0.8; P<.05). There were no statistically significant differences between the early and late groups (P>.05). Follow-up measures of R-R interval variations in the early group showed that there were no statistically significant changes from baseline in all parameters measured (rest, 2.1±0.9 and 2.3±0.8; deep breathing, 2.3±0.6 and 2.6±0.9; Valsalva, 1.0±0.0 and 1.0±0.0; tilt, 1.0±0.0 and 0.99±0.1 at the sixth and twelfth months, respectively; P>.025).

  • View full-size image.
  • Fig 1. 

    R-R interval variations ratios measured at 3, 6, and 12 months in early heart transplant recipients (n=8), in late postheart transplant recipients (n=17), and in controls (n=20). Abbreviation: CI, confidence interval. *Statistically significant difference from controls.

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Discussion 

To our knowledge, this study is the first to use R-R interval variation analyses with EMG to assess autonomic functions in heart transplant recipients. Decreased R-R interval variation ratios in the acute stage supported previous reports that demonstrate severely suppressed autonomic function, in particular parasympathetic system function, after heart transplantation.1, 2, 3 Moreover, the lack of change in the R-R interval variation ratios at the 1-year follow-up and decreased R-R interval variation ratios in the late stage suggest that these functions do not recover in either the early or late periods after heart transplantation, a finding consistent with some previous studies.1, 3

Mediation of R-R interval variation at rest or in response to deep breathing, to the Valsalva maneuver, and to standing is the result of the combined effects of the cardiac vagus and sympathetic nerves acting on the sinoatrial node.16 The R-R interval variation at rest and during deep breathing indicates the influence of breathing on the sympathetic flow and vagus impulses to the sinoatrial node. Although related to complex mechanisms, the efferent pathway is via cardiac vagus nerve fibers, and the sympathetic influence is of minimal importance, especially when breathing is performed in the supine position.17 Thus, respiratory variation in heart rate, particularly the expiration:inspiration ratio, is presumed to be a sensitive index of cardiac efferent parasympathetic function.18 The Valsalva ratio is based on the reflex changes in the R-R intervals during and after performance of the Valsalva maneuver, which elicits a complex series of hemodynamic events.16 It can also be used as an effective measure of parasympathetic integrity.19 The R-R interval variation in response to standing reflects an integrated reflex response of the cardiovascular system. The mechanisms underlying the immediate heart rate response that follows the beginning of the standing maneuver are complex.20, 21 Although this response is predominantly related to the vagus nerve, it also involves hemodynamic modifications and is influenced by sympathetic stimulation. Thus, the 30:15 ratio (ie, the longest interval at the thirtieth heartbeat divided by the shortest interval at the fifteenth heartbeat) has been proposed in order to standardize an autonomic test of the parasympathetic division.21

In our study, the lack of variability in heart rate in response to normal breathing, deep breathing, the Valsalva maneuver, and standing suggests a failure of the parasympathetic input to the heart after heart transplantation. Although some studies have argued that parasympathetic reinnervation in heart transplant recipients develops late after transplantation,4 our results are in agreement with other studies that reported no parasympathetic reinnervation development in either the early or late periods.1, 3 Though posttransplant coronary arteriosclerosis, allograft rejection, myocardial infectious disease, and type of surgery have been considered factors that theoretically could affect the reinnervation process,9, 22 there is no conclusive evidence. Because we excluded the patients with acute rejection, significant transplant vasculopathy, or allograft dysfunction, and heart failure, we cannot come to any conclusion on this matter. We believe that additional studies should be carried out in this respect, particularly to investigate whether R-R interval variation testing may contribute to the ruling out of acute graft rejection.

Electromyographic R-R interval variation analysis is a simple and nontime-consuming procedure. Given that depth of respiration and rate of deep breaths a minute should be standardized and controlled, the test on deep breathing required training and subject cooperation. Likewise, the Valsalva test was influenced by the degree of the subject's cooperation. The tilt/stand-up test was the most difficult and time-consuming, because the responses were influenced by the velocity and effort made in the act of standing. The analysis at rest was the most stable condition because it did not require the subject's cooperation. Because it allowed the detection of vagal dysfunction in our transplant recipients, R-R interval analysis at rest may provide a fast and practical tool to evaluate parasympathetic function in patients with little cooperation necessary.

The clinical implications of our findings mainly concern the postoperative management of heart transplant recipients. Parasympathetic activity is an important protective factor in patients after myocardial infarction and heart failure.23 Furthermore, sympathovagal imbalance causes an increase in the frequency of arrhythmia24 and impairment in the regulation of the coronary blood flow.25 Arrhythmias are associated with the acute rejection period.26 In addition to its role in the development of heart disease, parasympathetic activity plays a critical role in normative physiologic processes. Baroreflex-mediated control of blood pressure rests on rapid responses in heart rate, largely mediated by the vagus nerve.23 In the absence of parasympathetic activity, heart rate variability would decrease markedly, and the increase in blood pressure as a result of sympathetic activity would be unpreventable during physical exercise. In this respect, continuous monitoring of the ECG and close follow-up of blood pressure should be maintained in heart transplant recipients, especially during the first several exercise sessions.

Study Limitations 

The major limitations of this study include the limited number of follow-up patients and a lack of comparison with other available R-R interval variation analysis techniques. The lack of pretransplant measurements is another limitation. However, most of the patients had chronic debilitating cardiac illness and were on beta-blocker therapy preoperatively, which made this assessment difficult and unreliable. In addition, the results of this study, which excluded certain conditions (eg, diabetes mellitus) by exclusion criteria, should not be generalized across all transplant recipients.

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Conclusions 

Parasympathetic system function is severely affected after heart transplantation, and parasympathetic recovery does not develop in either the early or the late periods postoperatively. Assessment of parasympathetic system function is particularly important in the postoperative management of heart transplant recipients. In patients with suppressed parasympathetic function, exercises should be performed under supervision, and care should be taken to avoid complications related to the failure of parasympathetic activities. The electromyographic R-R interval variation analyses, which could be easily applied in routine clinical practice, seem to be an attractive alternative for the assessment of parasympathetic function in heart transplant recipients both in isolation and in association with other autonomics tests. Further studies are warranted to demonstrate the efficacy of these techniques.

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References 

  1. Arrowood JA, Minisi AJ, Goudreau E, Davis AB, King AL. Absence of parasympathetic control of heart rate after human orthotopic cardiac transplantation. Circulation. 1997;96:3492–3498
  2. Doering LV, Dracup K, Moser DK, Czer LS, Peter CT. Evidence of time-dependent autonomic reinnervation after heart transplantation. Nurs Res. 1999;48:308–316
  3. Keeley EC, Toth ZK, Goldberg AD. Long-term assessment of heart rate variability in cardiac transplant recipients. J Heart Lung Transplant. 2000;19:310–312
  4. Uberfuhr P, Frey AW, Fuchs A, et al. Signs of vagal reinnervation 4 years after heart transplantation in spectra of heart rate variability. Eur J Cardiothorac Surg. 1997;12:907–912
  5. Barron HV, Viskin S. Autonomic markers and prediction of cardiac death after myocardial infarction. Lancet. 1998;351:461–462
  6. Hohnloser SH, Klingenheben T, Zabel M, Li YG. Heart rate variability used as an arrhythmia risk stratifier after myocardial infarction. Pacing Clin Electrophysiol. 1997;20:2594–2601
  7. Tsuji H, Larson MG, Venditti FJ, et al. Impact of reduced heart rate variability on risk for cardiac events (The Framingham Heart Study). Circulation. 1996;94:2850–2855
  8. Sands KE, Appel ML, Lilly LS, Schoen FJ, Mudge GH, Cohen RJ. Power spectrum analysis of heart rate variability in human cardiac transplant recipients. Circulation. 1989;79:76–82
  9. Koskinen P, Virolainen J, Koskinen PK, Häyry P, Kupari M. Evolution of heart rate variability in cardiac transplant recipients: a clinical study. J Intern Med. 1996;239:443–449
  10. Meyer M, Marconi C, Ferretti G, Fiocchi R, Cerretelli P, Skinner JE. Heart rate variability in the human transplanted heart: nonlinear dynamics and QT vs RR-QT alterations during exercise suggest a return of neurocardiac regulation in long-term recovery. Integr Physiol Behav Sci. 1996;31:289–305
  11. Costa M, Pimentel IR, Santiago T, Sarreira P, Melo J, Ducla-Soares E. No evidence of chaos in the heart rate variability of normal and cardiac transplant human subjects. J Cardiovasc Electrophysiol. 1999;10:1350–1357
  12. Huikuri HV, Mäkikallio T, Airaksinen KE, Mitrani R, Castellanos A, Myerburg RJ. Measurement of heart rate variability: a clinical tool or a research toy?. J Am Coll Cardiol. 1999;34:1878–1883
  13. Hilz MJ, Dütsch M. Quantitative studies of autonomic function. Muscle Nerve. 2006;33:6–20
  14. Stalberg E, Nogues MA. Automatic analysis of heart rate variations I. Muscle Nerve. 1989;12:993–1000
  15. Stalberg E, Nogues MA. Automatic analysis of heart rate variations II. Muscle Nerve. 1989;12:1001–1008
  16. O'Brien IA, O'Hare P, Corrall RJ. Heart rate variability in healthy subjects: effect of age and the derivation of normal ranges for tests of autonomic function. Br Heart J. 1986;55:348–354
  17. Pfeifer MA, Cook D, Brodsky J, et al. Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man. Diabetes. 1982;31:339–345
  18. Agarwal A, Anand IS, Sakhuja V, Chugh KS. Effect of dialysis and renal transplantation on autonomic dysfunction in chronic renal failure. Kidney Int. 1991;40:489–495
  19. Leon DF, Shaver JA, Leonard JJ. Reflex heart rate control in man. Am Heart J. 1970;80:729–739
  20. Borst C, Wieling W, van Brederode JF, Hond A, de Rijk LG, Dunning AJ. Mechanisms of initial heart rate response to postural change. Am J Physiol. 1982;243:676–681
  21. Ewing DJ, Campbel IW, Murray A, Neilson JM, Clarke BF. Immediate heart rate response to standing: simple test for autonomic neuropathy in diabetes. BMJ. 1978;1:145–146
  22. Bernardi L, Valenti C, Wdowczyck-Szulc J, et al. Influence of type of surgery on the occurrence of parasympathetic reinnervation after cardiac transplantation. Circulation. 1998;97:1368–1374
  23. Floras JS. Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure. J Am Coll Cardiol. 1993;22:72–84
  24. Valkama JO, Huikuri HV, Koistinen MJ, Yli-Mäyry S, Airaksinen KE, Myerburg RJ. Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease. J Am Coll Cardiol. 1995;25:437-3
  25. Burke MN, McGinn AL, Homans DC, Christensen BV, Kubo SH, Wilson RF. Evidence for functional sympathetic reinnervation of left ventricle and coronary arteries after orthotopic cardiac transplantation in humans. Circulation. 1995;91:72–78
  26. de Jonge N, Jambroes G, Lahpor JR, Woolley SR. Ventricular fibrillation during acute rejection after heart transplantation. J Heart Lung Transplant. 1992;11:797–798
  • a Medtronic A/S, Tonsbakken 16-18, DK-2740, Slovlunde, Denmark.
  • b SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.

 No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

PII: S0003-9993(09)00350-5

doi:10.1016/j.apmr.2009.03.012

Archives of Physical Medicine and Rehabilitation
Volume 90, Issue 9 , Pages 1635-1638, September 2009

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