Ann Thorac Surg 1996;61:591-593
© 1996 The Society of Thoracic Surgeons
Original Article: Cardiovascular
Effect of HeartMate Left Ventricular Assist Device on Cardiac Autonomic Nervous Activity
Shin Y. Kim, PhD,
Alvaro Montoya, MD,
Joseph P. Zbilut, PhD,
Kwabena Mawulawde, MD,
Henry J. Sullivan, MD,
Vassyl A. Lonchyna, MD,
Mark R. Terrell, MD,
Roque Pifarré, MD
Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois
Accepted for publication September 19, 1995.
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Abstract
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Background. Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology.
Methods. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation.
Results. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 ± 7 ms from 8 ± 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 ± 3.0 ms2; high frequency power, 2.1 ± 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance.
Conclusions. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.
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Introduction
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The use of a left ventricular assist device (LVAD) (HeartMate IP-1000; Thermo Cardiosystems, Woburn, MA) has become an accepted therapy as a bridge to cardiac transplantation in cases of hemodynamic deterioration with intractable cardiac failure [1]. Clinical performance of the LVAD support is evaluated via hemodynamic parameters and end-organ function [1]. However, the understanding of the effect of LVAD on the autonomic nervous system remains unclear [2].
The autonomic nervous system conveys information that reaches the sinus node in the heart through efferent vagal and sympathetic pathways. The effects of these two autonomic influences is the beat-to-beat variability of the heart rate. Two clinically applicable methods for assessment of the cardiac autonomic control have been developed: time or frequency measures of heart rate variability (HRV) [3–6]. Time domain analysis, which is a statistical analysis of the fluctuations in heart rate, is defined in terms of standard deviation or variance of the mean sinus R-R intervals over time. Frequency domain (power spectrum) analysis decomposes the sinus R-R interval signal into its frequency components and quantifies them in terms of their intensity, termed power. Time domain HRV study on humans showed that fluctuations in sinus rate were mediated solely by efferent vagal activity [6]. Frequency domain studies have provided strong suggestive evidence that HRV reflects oscillations in sympatho-vagal balance [3–5]. This study employed these two methods to describe the time course change of cardiac autonomic nerve activity of 3 patients who were assisted by the LVAD before cardiac transplantation.
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Material and Methods
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Patients
The implantation of the HeartMate LVAD as a bridge to cardiac transplantation and study protocol were approved by the Institutional Review Board. Each patient gave written informed consent to the protocol.
PATIENT 1.
A 51-year-old man with a 2-year history of ischemic cardiomyopathy and coronary bypass grafting x 5 was admitted. Despite maximal inotropic (dobutamine and dopamine) and intraaortic balloon pumping support, severe left ventricular failure developed with the evidence of a new myocardial infarction (pulmonary arterial pressure, 58/31 mm Hg; pulmonary capillary wedge pressure, 29 mm Hg; arterial systolic blood pressure, 76 mm Hg; cardiac index, 1.6 L•min-1•m-2). He underwent HeartMate LVAD implantation. Eight days later, he underwent orthotopic cardiac transplantation and was discharged 30 days later after transplantation.
PATIENT 2.
A 26-year-old man was admitted with dilated cardiomyopathy secondary to viral myocarditis. His hemodynamic status became seriously deteriorated in spite of inotropic (dobutamine and dopamine) and intraaortic balloon pumping interventions (pulmonary pressures, 60/40 mm Hg; pulmonary capillary wedge pressure, 30 mm Hg; arterial systolic blood pressure, 75 mm Hg; cardiac index, 1.7 L•min-1•min-2). He underwent HeartMate LVAD implantation, and subsequently underwent orthotopic cardiac transplantation 26 days later. He was discharged 4 weeks after transplantation.
PATIENT 3.
A 43-year-old man with a 2-year history of ischemic cardiomyopathy was admitted with congestive heart failure. In spite of maximal inotropic (dobutamine and dopamine) and intraaortic balloon pumping support, he showed evidence of continuing heart failure (pulmonary pressures, 59/30 mm Hg; pulmonary capillary wedge pressure, 36 mm Hg; cardiac index, 1.6 L • min-1 • m-2; arterial systolic blood pressure, 78 mm Hg) and underwent HeartMate LVAD implantation. Twenty-seven days later, he underwent orthotopic cardiac transplantation, and was discharged 20 days later.
Real-Time Data Acquisition
The analog output of a standard intensive care unit monitor was fed into an interface (Dataq, Akron, OH) for analog-to-digital conversion, sampling the electrocardiogram at 250 Hz. These data were collected on a personal computer (Everex 486/33, Fremont, CA) for later off-line analysis. The real-time data acquisition was made on the day before LVAD implantation (7:00 PM in all patients). The real-time data acquisition was repeated on the last day of LVAD support (7:00 PM) in patient 1 and patient 2, and on 12 different days at the same time of the day (at 2:30 PM) before cardiac transplantation in patient 3. At the time of study during the LVAD support, all patients were in supine position and fully awake, and did not receive any cardiovascular pharmacologic agents or mechanical ventilatory support.
Data Processing and Analysis
The R waves of the electrocardiogram in sinus rhythm were detected using a threshold detector (Dataq) to produce the series of 512 consecutive and stationary RR intervals, and subsequently subjected to fast Fourier transform (Matlab, Natick, MA) for power spectral analysis of heart rate variability. The cardiac autonomic efferent activity was assessed in the time domain as the standard deviation of the average of the R-R intervals as an index of vagal activity [6] and in the frequency domain as the spectral power of HRV over the frequency regions of interest. The total power of HRV was divided into two frequency bands. The power of the low-frequency (LF) component (0.04 to 0.15 Hz), although amplified by vagal activity [4], appears to reflect predominantly sympathetic modulation and its change [3, 5]. The power of the high-frequency (HF) component (0.16 to 0.4 Hz) is known to reflect vagal modulation [3, 4]. An index of sympatho-vagal balance was obtained from the ratio of LF over HF [3].
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Results
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The cardiac autonomic nerve activity clearly improved during the course of LVAD support (Table 1
; Fig 1). After 8 days (patient 1), 26 days (patient 2), or 24 days (patient 3) of LVAD support, the mean of the R-R intervals of the electrocardiogram increased to 677 ± 21 ms from 587 ± 20 ms. The standard deviation of the average of the R-R intervals, an index of vagal activity, increased to 27.2 ± 6.5 ms from 8.1 ± 0.6 ms. Low-frequency power (sympathetic activity) and HF power (vagal activity) increased by a mean of 9 and 22 times the baseline level (LF, 5.2 ± 3.0 ms2; HF, 2.1 ± 0.7 ms2), respectively. Total power increased by a mean of 12 times the baseline level (7.3 ± 3.6 ms2). The value of the LF over HF ratio substantially diminished from 2.3 ± 0.6 to 1.07 ± 0.17, which indicates improved sympatho-vagal balance in these patients during LVAD intervention.
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Fig 1. . Time course change in cardiac autonomic efferent neural activity of patient 3 during support by a HeartMate left ventricular assist device. Ordinate is the magnitude (ms2) of sympathetic (black bar) and vagal (white bar) activity. Abscissa is the day after left ventricular assist device implantation, where B is the day before left ventricular assist device implantation.
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Comment
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A substantial percentage of cardiac transplant candidates die while waiting for a donor heart. Therefore, temporary HeartMate LVAD support for patients waiting for donor hearts is becoming an accepted treatment in cases of hemodynamic deterioration by intractable cardiac failure [1]. Measurements of hemodynamic parameters and end-organ function are used for evaluation of the clinical performance of the LVAD. Understanding of the effect of a circulatory assist device on neurophysiology may be an important parameter for establishing the optimal device control for artificial blood pumping [2]. The purpose of this report was to address the effect of prosthetic circulation on the autonomic nervous activity in patients with a circulatory assist device.
The observation in the present study that HRV of these 3 patients before LVAD implantation was significantly depressed is consistent with previous reports on HRV in patients with congestive heart failure [7–9]. Although not clearly defined, a potential mechanism of this depression is the likely result of derangements in the autonomic neural activity of cardiac origin [5] combined with the exhaustive baroreceptor and renin-angiotensin system activation [9] of decreased left ventricular performance. The present study demonstrates that after LVAD placement, overall cardiac autonomic activity in these 3 patients appears to increase along with improvement of sympatho-vagal balance, shown by the decrease in LF/HF power ratio. This improvement of cardiac autonomic activity is described by the increase in the values of the standard deviation of the mean of the R-R intervals and all frequency components of the power spectrum, with a more apparent increase in vagal activity (HF power).
Although the present study provides no insight into the exact mechanisms of the observed results, it is theoretically possible that the recovery of diseased myocardium through LVAD-induced complete rest of cardiac mechanical work may contribute to the improvement of cardiac autonomic regulation in these patients. It is also conceivable that this improvement results from the normalization of baroreceptor and angiotensin system activity via the correction of low cardiac output by the LVAD support. Burch and DePasquale [10] proposed that complete bed rest would allow the diseased heart to return to health by unloading ventricular work. Subsequent clinical investigation supported this hypothesis: ventricular recovery was seen in patients with ischemic cardiomyopathy who had undergone only prolonged, complete bed rest [11]. This hypothesis may be true in patients with the LVAD, which entirely substitutes for ventricular pumping work at rest. Recently, Frazier [12] has reported the first long-term (505-day) implantation of a vented electric HeartMate LVAD in a 33-year-old man, who suddenly died of a neurologic thromboembolic event. In his report, Frazier showed the time-course recovery of the patient's natural heart by a series of consecutive echocardiograms, pathologic examinations of the tissue specimens obtained at the time of the LVAD implantation, and autopsy. Frazier's report also showed that even after the stop of LVAD support (after the patient was declared brain dead), normal sinus rhythm on the electrocardiogram and normal arterial pulse were demonstrated by the patient's natural heart, indicating the recovery of once-diseased heart.
The pharmacotherapy (inotropes) and the mechanical support (intraaortic balloon pumping and mechanical ventilation) before LVAD implantation were confounding but unavoidable variables, which can potentially influence cardiac autonomic activity in patients. To minimize the variation among patients, we compared the HRV variables between before and after LVAD support in each patient by using each subject as his own control.
In summary, although the results of only 3 case studies should be interpreted with great caution, it appears that LVAD support enhanced the cardiac autonomic activity in these patients. Recovery of the autonomic neural activity of cardiac origin via complete rest of cardiac mechanical work and the normalization of peripheral autonomic regulatory system via the correction of low cardiac output by LVAD support could be potential mechanisms of the improved cardiac autonomic activity in these patients. Additional study is warranted to confirm the present study results.
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Footnotes
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Address reprint requests to Dr Pifarré, Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL 60153.
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References
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- Frazier OH, Rose EA, MacManus Q, et al. Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device. Ann Thorac Surg 1992;53:1080–90.[Abstract]
- Yambe T, Nitta S-I, Ktahira Y, et al. Postganglionic sympathetic nerve activity with correlation to heart rhythm during left ventricular assistance. Artif Organs 1991;15:212–7.[Medline]
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- Pomeranz B, Macaulay RJB, Caudill MA, et al. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 1985;248:H151–3.[Medline]
- Lombardi F, Sandrone G, Pernpruner S, et al. Heart rate variability as an index of sympatho-vagal interaction after acute myocardial infarction. Am J Cardiol 1987;60:1239–45.[Medline]
- Hayano J, Sakakibara Y, Yamada A, et al. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol 1991;67:199–204.[Medline]
- Fei L, Keeling PJ, Gill JS, et al. Heart rate variability and its regulation to ventricular arrhythmias in congestive heart failure. Br Heart J 1994;71:322–8.[Abstract/Free Full Text]
- Ajiki K, Murakawa Y, Yanagisawa A, et al. Autonomic nervous system activity in idiopathic dilated cardiomyopathy and in hypertrophic cardiomyopathy. Am J Cardiol 1993;71:1316–20.[Medline]
- Nolan J, Flapan AD, Capewell FS, et al. Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function. Br Heart J 1992;67:482–5.[Abstract/Free Full Text]
- Burch GE, DePasquale NP. On resting the human heart. Am Heart J 1966;71:422.[Medline]
- McDonald CD, Burch GE, Walsh JJ. Prolonged bed rest in the treatment of idiopathic cardiomyopathy. Am J Med 1972;52:41–50.[Medline]
- Frazier OH. First use of an untethered, vented electric left ventricular assist device for long-term support. Circulation 1994;89:2908–14.[Abstract/Free Full Text]
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Abstract
Introduction
