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Ann Thorac Surg 1996;62:1708-1713
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Comparative Study on Cardiomyoplasty Patients With the Cardiomyostimulator On Versus Off

Ouz Tademir, MD, Kerem M. Vural, MD, Süha D. Küçükaksu, MD, Onurcan K. Tarcan, MD, Murat Özdemir, MD, Emine Kütük, MD, Kemal Bayazit, MD

Departments of Cardiovascular Surgery and Cardiology, Türkiye Yüksek htisas Hospital, Ankara, Turkey

Accepted for publication June 25, 1996.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Background. A major concern in evaluating dynamic cardiomyoplasty has been whether the synchronous stimulation of latissimus dorsi muscle is essential for benefit or not. We studied 10 patients to determine the efficacy of the systolic augmentation generated by the synchronous electrical stimulation of the latissimus dorsi muscle.

Methods. Left ventricular ejection fraction, end-systolic and end-diastolic volume indexes, and stroke volume index obtained during resting, peak exercise, and recovery periods ("on" values) were compared with those obtained 1 week after cessation of electrical stimulus ("off" values). Double product and estimated total body oxygen consumption at peak exercise were also calculated and compared.

Results. Higher ejection fractions (0.36 ± 0.07 versus 0.33 ± 0.06 at rest, 0.40 ± 0.07 versus 0.33 ± 0.07 at peak exercise, and 0.37 ± 0.06 versus 0.31 ± 0.06 at recovery) and lower end-systolic volume indexes with relatively constant end-diastolic volume indexes were observed with the cardiomyostimulator on. Further, exercise response was better with the cardiomyostimulator on. Double product indirectly reflected better myocardial oxygen supply/demand ratio when on at peak exercise (17 ± 2.2 mm Hg x beats/min x 10^-3 for on versus 19 ± 2.6 mm Hg x beats/min x 10^-3 for off). Estimated total body oxygen consumption was improved at peak exercise when the cardiomyostimulator was functional (12 ± 2.7 mL•kg^-1•min^-1 versus 11 ± 2.6 mL•kg^-1•min^-1).

Conclusions. Current data suggest a true systolic assist during synchronous contractions of the latissimus dorsi muscle. It is thought, therefore, that synchronous electrical stimulation is essential for maximum benefit and all the beneficial effect of cardiomyoplasty certainly cannot be attributed to simple wrapping itself.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Latissimus dorsi dynamic cardiomyoplasty (CMP) is still under investigation as an alternative therapeutic approach in the treatment of progressive heart failure. Since the first clinical experience in 1985, a major concern in evaluating CMP has been whether the synchronous stimulation of latissimus dorsi muscle (LDM) is essential for maximum benefit or only the wrapping is enough to stop or minimize the progressive dilatation and remodeling of cardiac mass. In some recent studies, it has been speculated that a more passive external constraining effect of the muscle wrap, rather than the systolic augmentation, may be a source of benefit [1–3]. It can also be speculated that wrapping without electrical stimulation of LDM could result in muscle regression or atrophy, but beyond the muscle maintenance, the real role of the synchronous electrical LDM stimulation with a cardiomyostimulator (CMS) in systolic assistance must be evaluated.

The main goal of this study was to investigate whether true systolic assistance is achieved with CMP or the procedure provides only a simple passive reinforcement limiting the progressive dilatation and remodeling of cardiac chambers.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Our study group consisted of 10 CMP patients (5 with ischemic disease and 5 with idiopathic disease) in their 18th to 24th month postoperatively. Indications for operation, operative technique, and stimulation protocol were the same as described by Chachques, Grandjean, and Carpentier [4, 5]. Implanted CMSs were Medtronic model SP 1005A or model 4710 (Medtronic, Inc, Minneapolis, MN) devices in 1:2 stimulation mode (CMS stimulates LDM at every other heart beat) with a synchronization delay of 45 to 60 milliseconds based on the echocardiographic timing after closure of the mitral valve. Mean pulse amplitude was 3.08 ± 0.41 V (range, 2.50 to 3.75 V). All the participating patients provided informed consent and were hospitalized during the CMS off phase (see below) as a safety measure.

Digital stress echocardiography (Freeland Cineview device; Prism Imaging, Broomfield, CO) was employed for obtaining the left ventricular ejection fraction, left ventricular end-systolic volume index (ESVI), and end-diastolic volume index (EDVI). Eight frames per cardiac cycle, triggered from the R wave at 50-millisecond intervals, were recorded in a continuous loop format. Apical two- and four-chamber views were acquired at rest, then the patient performed symptom-limited treadmill exercise according to the modified Bruce protocol [6]. Achievement of the target heart rate (70% of age-predicted maximum), hypotension, or limiting symptoms such as angina, dyspnea, or fatigue constituted the reasons for terminating exercise prematurely. Within 15 to 35 seconds after cessation of exercise, the second set (peak exercise) of views were obtained. A final echocardiographic examination was repeated at 5 minutes after termination of exercise, and this represented the recovery period. To calculate diastolic and systolic left ventricular volumes, we traced endocardial borders digitally in diastole and systole. Commercially available software (Cine'view Version 5.05; Prism Imaging) was used for the calculations of the left ventricular volumes and thus the ejection fraction, according to a modified Simpson's rule [7].

These data were acquired in two phases. Data obtained while the CMS was functional formed the "on" values, and then the CMS was switched off. One week after electrical stimulation ceased, all the parameters were measured again and recorded as the "off" values. The logic for waiting 1 week after the cessation of the electrical stimulus to obtain the off values was to emphasize the off period. After the off data were obtained, cardiomyostimulators were switched on with the original settings, and patients were discharged.

Ergometric test was based on the modified Bruce protocol, and the estimated total body oxygen consumption was calculated from the metabolic equivalent value [6, 8] (1 metabolic equivalent refers to 3.5 mL of oxygen•min^-1•kg^-1 for an average 70-kg, resting, 40-year-old male patient). Watts on the bicycle ergometer were converted to corresponding metabolic equivalent values on the standard table of estimated oxygen cost for the selected treadmill protocols [6]. Our goal was not to define reference values, but to give an idea for the comparison between the on and off phases (see Comment). In other words, what is important here is the change in the estimated total body oxygen consumption, not the value itself.

Double product (or rate-pressure product) roughly reflects the myocardial oxygen demand. It increases progressively with exercise, and peak double product could be used to characterize cardiovascular performance [6]. Double product was calculated from the following equation at the beginning of the exercise (when the patient was walking on the treadmill band just before starting to run) and at the peak exercise point: double product = heart rate (beats/min) x systolic blood pressure (mm Hg) x 10^-3.

Wilcoxon matched-pairs signed ranks test was used to compare the data obtained during periods of exercise within the same phase (ie, on and off), as well as for the comparison of the on and off data at the same exercise period. A p value less than 0.05 was considered statistically significant.

On and off data for the three exercise periods are presented in Table 1, as the means and the standard deviations. All statistical comparisons in the bar graphs (Figs 1, 3, 5, 7, and 8) represent the differences between the on and off values in the same exercise period. All statistical comparisons in the line graphs (figs 2, 4, and 6), represent the differences between the exercise periods within the same phase (on or off).

View larger version (22K): [in this window] [in a new window]   Fig 1. . Mean left ventricular ejection fraction (LVEF) with the cardiomyostimulator (CMS) off and on.

View larger version (25K): [in this window] [in a new window]   Fig 3. . End-systolic volume index with the cardiomyostimulator (CMS) off and on.

View larger version (28K): [in this window] [in a new window]   Fig 5. . End-diastolic volume index with the cardiomyostimulator (CMS) off and on. (NS = not significant.)

View larger version (22K): [in this window] [in a new window]   Fig 7. . Double product changes during periods of exercise with the cardiomyostimulator (CMS) on and off. (NS = not significant.)

View larger version (21K): [in this window] [in a new window]   Fig 8. . Estimated total body oxygen consumption (estVO2) at peak exercise with the cardiomyostimulator (CMS) on and off.

View larger version (16K): [in this window] [in a new window]   Fig 2. . Mean left ventricular ejection fraction (LVEF) changes during exercise periods with the cardiomyostimulator off (black squares) and on (white squares). (ns = not significant.)

View larger version (15K): [in this window] [in a new window]   Fig 4. . End-systolic volume index changes during exercise periods within cardiomyostimulator on (white squares) and off (black squares) phases. (ns = not significant.)

View larger version (16K): [in this window] [in a new window]   Fig 6. . End-diastolic volume index changes during exercise periods within cardiomyostimulator on (white squares) and off (black squares) phases. (ns = not significant.)

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

Left Ventricular End-Systolic Volume Index
End-systolic volume indexes were 84 ± 30 mL/m² versus 79 ± 29 mL/m² at rest, 84 ± 32 mL/m² versus 67 ± 24 mL/m² at peak exercise, and 88 ± 31 mL/m² versus 76 ± 30 mL/m² at recovery for the off and on phases, respectively. Higher ESVIs were observed in all three periods of exercise when the CMS was turned off (p < 0.05) (Table 1; Fig 3). When the CMS was on, ESVI decreased from 79 ± 29 mL/m² to 67 ± 24 mL/m² (p < 0.05) as a response to exercise and returned to resting values (76 ± 30 mL/m²) after the cessation of exercise. On the other hand, no substantial change in average ESVI occurred at peak exercise with the CMS off. In contrast, ESVI was found to be significantly increased after exercise (from 84 ± 38 mL/m² to 88 ± 31 mL/m²; p < 0.05). Exercise trends for the on and off phases are presented in Figure 4.

Left Ventricular End-Diastolic Volume Index
End-diastolic volume index values for resting, peak exercise, and recovery periods were 125 ± 32 mL/m², 124 ± 31 mL/m², and 122 ± 27 mL/m² with the CMS off and 124 ± 34 mL/m², 119 ± 32 mL/m², and 121 ± 35 mL/m² with the CMS on, respectively. No difference was detected in EDVIs between the on and off phases during all three periods of exercise. Trends in the on and off phases also lacked any significant change during exercise (Table 1; Figs 5, 6).

Left Ventricular Stroke Volume Index
Stroke volume index values calculated from the ESVI and EDVI measurements are represented in Table 1. The values were 40 ± 9 mL/m² versus 45 ± 12 mL/m² at rest, 40 ± 5 mL/m² versus 49 ± 12 mL/m² at peak exercise, and 34 ± 5 mL/m² versus 45 ± 12 mL/m² at recovery for the off and on phases, respectively.

Double Product Increase With Exercise
Double product roughly reflects the oxygen demand of the heart in a relatively constant oxygen supply state for the two phases. At the beginning of the exercise, there were no statistical difference between the on and off phase values (8.7 ± 1.7 mm Hg x beats/min x 10^-3 for on versus 8.98 ± 1.7 mm Hg x beats/min x 10^-3 for "off"; p = not significant). At peak exercise, however, double product was significantly decreased in the on phase (17.1 ± 2.2 mm Hg x beats/min x 10^-3 for on versus 18.9 ± 2.6 mm Hg x beats/min x 10^-3 for off; p < 0.05), reflecting the better (greater) oxygen supply/demand ratio in the on phase (Fig 7).

Estimated Total Body Oxygen Consumption at Peak Exercise
Mean estimated total body oxygen consumption was greater in the on phase (12.12 ± 2.7 mL•kg^-1•min^-1 versus 11 ± 2.6 mL•kg^-1•min^-1; p < 0.05) (Fig 8) at peak exercise.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Cardiomyoplasty is a new approach in the treatment of the patients with dilated heart failure. Since the first clinical experience in 1985, it has been a subject of many studies and controversies.

Initially, the principal mechanism by which the CMP was assumed to assist the failing heart was an augmentation of systolic ejection by active squeezing of the ventricles. However, although human studies have reported improvement in the clinical symptoms of patients undergoing this therapy [9–12], evidence for active systolic assist has been inconsistent [1]. Nonetheless, the results have led some to speculate that more passive external constraining effects of the muscle wrap may be a source of benefit [1–3].

In the study by Kass and associates [3], it is speculated that the muscle wrap provides an elastic constraint to the epicardial surface, limiting cardiac dilatation much like a girdle. Unlike the pericardium, which has a limited compliance, especially when stretched, skeletal muscle is said to stiffen more gradually as it is lengthened [13]. Thus, the wrapped LDM is thought to better accommodate enhanced cardiac filling when this is needed, without importantly increasing diastolic pressures.

It has also been concluded that chronic repetitive stimulation results in decreased muscle fiber dimension [14]; the CMP may gradually shrink around the heart without inducing constrictive physiology. This argument is supported by an experimental study by Capouya and associates [15]. They wrapped a nonstimulated muscle around the canine heart and then induced dilated cardiomyopathy with rapid pacing. The previously wrapped hearts has less chamber enlargement and a smaller decline in ejection fraction. Whether skeletal muscle itself is required or whether an artificial elastic "sock" placed around the heart could achieve similar effects is said to remain an intriguing question [3]. Kass and associates [3] concluded that the muscle wrap could provide an elastic constraining effect to the heart, which in turn partially reverses chronic chamber remodeling of heart failure. Active systolic assist is said to have a possible role in improved cardiac function and ejection fraction in some patients, but this does not appear to be a requirement for achieving the benefit from CMP according to Kass and associates [3]. In another study on 10 patients, data were obtained from right heart catheterization, Doppler echocardiography, and maximal exercise testing with expired gas analysis when the LDM was stimulated every other systole and after stimulation was discontinued for 1 hour. Comparing these data, Jondeau and colleagues [16] concluded that alterations in left ventricular diastolic rather than systolic function may be responsible for the long-term clinical benefits of CMP. Hamilton and associates [17] have studied the effect of CMP on the heart muscle when the skeletal muscle was being stimulated to coincide with alternate natural beats. Left ventricular function was assessed using radionuclide angiography during the beat immediately after skeletal muscle stimulation and during the beat immediately before stimulation. When the supported beat was compared with the unsupported beat, the results demonstrated that cardiomyoplasty improved the global and regional ejection fraction. The regurgitation index remained unchanged. The systolic peak emptying rate improved but the diastolic peak filling rate worsened. They concluded that this latter finding provides additional information regarding the diastolic function of the heart after cardiomyoplasty, which is presently not well understood. In these two studies, the benefit of CMP on diastolic function rather than systolic assistance is emphasized, but the off period was too short in both studies (1 hour in the former and only one cardiac cycle in the latter) to assess cardiac function without some lasting effects of systolic assistance. For that reason, we waited for 1 week after cessation of the electrical stimulation to obtain more accurate off data.

In our study, for both rest and exercise conditions, we observed statistically greater ejection fractions and stroke volume indexes and lower ESVIs with relatively constant EDVIs when the CMS was on, suggesting active systolic assistance. Further, exercise response and the trend of these parameters during the three periods of exercise (resting, peak exercise, and recovery) were statistically better during the on phase. In the exercise trends, we observed a statistically important increase in ejection fraction with exercise during the on phase, whereas no remarkable increase occurred with exercise during the off phase (see Fig 2). Exercise trends also showed an important stroke volume index increase with exercise in the on phase, whereas no parallel increase, even an important decrease at recovery, occurred in the off phase (see Fig 8). All of these results suggest a need for active systolic assist during exercise conditions in CMP patients. In our opinion, therefore, the girdling effect by itself cannot match the requirements of the individual during daily stresses and exertions.

Double-product comparisons may be interpreted as indirectly reflecting a better myocardial oxygen supply/demand ratio when the CMS was on. Normally double product is expected to increase with exercise. This increase, however, was more obvious when the CMS was off in our study. The lesser degree of exercise-induced double product increase in the on phase may partly be due to the contribution of LDM assistance to the cardiac work. Estimated total body oxygen consumption was improved at peak exercise when the CMS was functional. This increase may reflect the augmentation in the cardiac output including the LDM oxygen consumption during its active assistance. Although the use of the metabolic equivalent value in estimating total body oxygen consumption can be accurate only for healthy individuals and may not necessarily correlate for patients with heart failure, we use it in patients with cardiomyopathy. Our goal was not to define reference values, but only to give an idea of the comparison between the on and off phases. In other words, what is important here is the change in the value, not the value itself. Otherwise, the extrapolation of estimated oxygen consumption from the exercise test data might be misleading. The metabolic equivalent value, however, has also been used in studies of clinical assessment and follow-up of functional capacity in patients with chronic congestive cardiomyopathy [8].

In summary, all the presented data suggest an active systolic assist effect of CMP. We conclude that CMP offers a true systolic assist beyond a simple constraint or so-called girdling effect. One may speculate that, with their CMSs on, CMP patients can better accommodate daily efforts or stress conditions. Even the evolution of a "sleep-function CMS" may be considered for production in the future, so patients would switch off their CMSs during sleeping in the night, when a maximum assist effect is not necessary. This would provide "economical" use and extended longevity of their expensive CMSs, so the patients could avoid repetitive CMS replacements. Assuming that the muscle channel of the current device (Medtronic Model 4710) would be programmed off at night (8 hours each day), device longevity at standard parameters (1:2 mode, a burst of 6 pulses, 5 V) would be increased by 25%, from 6 years to 7.5 years (calculation based on data contained in the Medtronic model 4710 technical manual). Such a function would also provide a resting period for the transformed LDM and might retard the fibrotic degeneration and regression that is said to occur in the long term. Animal investigations (in sheep) demonstrated that half-day (12-hour) rest provided better muscle power preservation than full-day stimulation while obtaining good muscle fatigue resistance. The authors of that study [18] concluded that this intermittent stimulation pattern could reduce the risks of muscle damage. In another study, intermittent stimulation (a 8-hour rest per day) transformed LDM with better preservation than 24-hour stimulation in a goat model [19]. The effects of such intermittent stimulation on cardiac function are difficult to predict. This needs to be documented on each specific case, as some patients may be more dependent on CMP support than the others. None of our patients showed cardiac decompensation during the day or night when the muscle stimulation was stopped. However, this point needs further clinical investigation.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Address reprint requests to Dr Tademir, Kardiyovasküler Cerrahi Klinii, Türkiye Yüksek htisas Hastanesi, 06100, Sihhiye, Ankara, Turkey.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 

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3. Kass DA, Baughman KL, Pak PH, et al. Reverse remodeling from cardiomyoplasty in human heart failure. External constraint versus active assist. Circulation 1995;91:2314–8.[Abstract/Free Full Text]
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14. Pette D, Muller W, Leisner E, et al. Time dependent effects on contractile properties, fiber population, myosin light chains and enzymes of energy metabolism in intermittently and continuously stimulated fast twitch muscle of the rabbit. Pflügers Arch 1976;364:103–12.[Medline]
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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kerem M. Vural Kemal Bayazit Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tasdemir, O. Articles by Bayazit, K. Search for Related Content PubMed PubMed Citation Articles by Tasdemir, O. Articles by Bayazit, K.