Ann Thorac Surg 2003;76:1167-1170
© 2003 The Society of Thoracic Surgeons
Original article: cardiovascular
Continuous axial-flow left ventricular assist device (Jarvik 2000) maintains kidney and liver perfusion for up to 6 months
George V. Letsou, MDb*,
Timothy J. Myers, BSa,
Igor D. Gregoric, MDa,
Reynolds Delgado, MDa,
Nyma Shah, BSa,
Kimberly Robertson, BSa,
Branislav Radovancevic, MDa,
O. H. Frazier, MDa
a Texas Heart Institute, St. Luke's Episcopal Hospital, Houston, Texas, USA
b The University of Texas Medical School, Houston, Texas, USA
Accepted for publication April 18, 2003.
* Address reprint requests to Dr Letsou, Department of Cardiothoracic and Vascular Surgery, The University of Texas-Houston Medical School, 6431 Fannin St, MSB 1.210, Houston, TX 77030, USA.
e-mail: george.v.letsou{at}uth.tmc.edu
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Abstract
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BACKGROUND: The Jarvik 2000 axial flow left ventricular assist device (LVAD), under development for the past decade, has the potential to support patients temporarily until cardiac transplantation or as a permanent circulatory support, without the size limitations of other implantable systems.
METHODS: To assess its ability to perfuse the kidneys and liver, we monitored renal and hepatic function in 10 patients who received the Jarvik 2000 LVAD as a bridge to transplantation. Left ventricular assistance was maintained for up to 214 days (> 6 months), and renal and hepatic function were monitored at least weekly.
RESULTS: Renal function before LVAD implantation in these patients was normal in 7 (creatinine, < 1.5) and moderately impaired in 3 (creatinine, 1.2 to 2.0). Hepatic function was normal in 7 patients before LVAD implantation (total bilirubin< 1.2; serum glutamic-oxaloacetic transaminase (SGOT), < 40; serum glutamic-pyruvic transaminase (SGPT), < 50) and normal at the time of transplantation in all 10 patients. Of the 3 patients with abnormal hepatic function before LVAD implantation, 1 patient had also had moderate renal dysfunction.
CONCLUSIONS: Despite reduced pulsatility, the Jarvik 2000 LVAD improves or maintains excellent renal and hepatic function during periods of circulatory assistance in patients awaiting transplantation.
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Introduction
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In the field of mechanical circulatory support, safe, efficacious, cost-effective, long-term support of the left ventricle and extracardiac organs has been the goal for the last several decades. Axial flow pumps are now being tested for this purpose in humans [1, 2]. One such pump, the Jarvik 2000 (Jarvik Inc, New York, NY), has several potential advantages over other mechanical circulatory support systems. The Jarvik 2000 is smaller, can be inserted through a left thoracotomy, and requires a less extensive implant operation. Experimental studies have shown that prolonged minimally pulsatile circulatory support with the Jarvik 2000 pump in otherwise normal animals is not detrimental to extracardiac organ function, and that liver and kidney perfusion is maintained [3, 4]. To extend these animal findings to humans, we examined our initial experience with the Jarvik 2000 LVAD in 10 patients awaiting cardiac transplantation and assessed the device's effect on liver and kidney perfusion and function.
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Material and methods
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Patients
The ongoing clinical investigation is designed to evaluate the safety and efficacy of the Jarvik 2000 while supporting patients with severe heart failure. The study was reviewed and approved by the U.S. Food and Drug Administration and the Institutional Review Board of St. Luke's Episcopal Hospital. After meeting the study criteria, all patients gave informed consent before implantation of the Jarvik 2000. The study inclusion criteria included a cardiac index of less than 2.0 L/min/m2, a pulmonary capillary wedge pressure greater than 18 mm Hg, New York Heart Association (NYHA) class IV heart failure, and a body surface area (BSA) greater than 1.2 m2. Once enrollment was completed, prospective data collection concerning kidney and liver perfusion began. Data were collected prospectively from 10 patients who underwent implantation of the Jarvik 2000 while awaiting cardiac transplantation, and were supported for at least 30 days. No concomitant procedures were performed at device implantation.
Device description
The Jarvik 2000 is an axial-flow left ventricular assist device weighing 90 g and displacing a volume of 25 mL (Fig 1).
The titanium housing contains a brushless, electromagnetic, direct current (DC) motor, which causes the electromagnetic force necessary to rotate an impeller located within the center of the pump. The magnetic impeller has two curved hydrodynamic blades on the outer surface. The impeller is held in position by two ceramic bearings. Outflow stator blades, located downstream from the impeller, direct blood flow through the outflow graft. External batteries provide continuous DC power; alternating current (AC) power is never applied to the system. Pump speed is manually adjusted from 8,000 rpm to 12,000 rpm in increments of 1,000 rpm.
Intraoperative management
In each case, the Jarvik 2000 was inserted through a left thoracotomy. The surgical procedure was normally performed with the aid of partial cardiopulmonary bypass. The detailed surgical procedure has been previously described [2–5]. There were only minor modifications to this procedure in the cases reported here. No significant surgical complications were encountered.
Postoperative management
All patients were managed so as to maintain a cardiac index greater than 2.0 L/min/m2. Inotropic and vasopressor support were used as necessary to maintain adequate right heart function, low pulmonary vascular resistance, and a mean arterial blood pressure between 65 and 75 mm Hg. Extubation was performed as expeditiously as possible, and chest tubes were removed when thoracic bleeding subsided. Pump speed was adjusted to achieve the highest cardiac output while maintaining native aortic valve opening, as assessed by arterial pressure line monitoring when such monitoring was available and then by transesophageal echocardiography.
Data analysis
Standard statistical methods were used for data analysis. All data were recorded prospectively and expressed as the mean ± standard deviation (SD). The paired t test was used to determine statistical significance. Renal and hepatic function was measured preoperatively and on days 7, 14, 30, 60, and 90 postoperatively. Renal function was monitored by measuring blood urea nitrogen (BUN) and creatinine. Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and total bilirubin were used to monitor hepatic function.
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Results
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The demographics of the patient group in this analysis are listed in Table 1.
There were 8 men and 2 women, with a mean age of 52.6 years (range, 30 to 65 years). The diagnoses for patients in this group were evenly divided between idiopathic and ischemic cardiomyopathy. The mean duration of support was 102.4 days (range, 52 to 214 days). The mean posttransplantation follow-up time is 15.5 months, the longest being 26.7 months.
Renal function before LVAD implantation (baseline) and over the course of support is illustrated in Figure 2.
The mean BUN and creatinine values for the entire group were within the normal range at baseline and at day 60. Three patients had abnormal renal function at baseline, and one of these patients had persistently abnormal function at day 60. The mean values for BUN and creatinine at bas line were 24.9 and 1.3 mg/dL, respectively. The mean BUN and creatinine values for all measurements during support were 27.0 and 1.3 mg/dL, respectively. These values were not statistically different from baseline values (p > 0.05). The mean BUN value at day 7 was significantly different from the value at baseline (p < 0.013), but the mean BUN value during the remaining period of support was not. All mean creatinine values during support differed significantly from baseline values.
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Fig 2. Renal function (blood urea nitrogen [BUN] and creatinine) during support with the Jarvik 2000. The area within the dotted lines is the normal value range.
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Hepatic function at baseline and over the course of support is illustrated in Figure 3.
It tended to deteriorate in the first postoperative week, but then returned to normal. Mean values for total bilirubin, SGOT, and SGPT were above normal in 3 of 10 patients before LVAD implantation. Mean total bilirubin increased significantly in the first postoperative week, but was normal by day 60 and remained normal at day 90. Mean SGOT increased after LVAD implantation; by day 90, mean SGOT was significantly different from normal values. Mean SGPT remained normal throughout the period of LVAD implantation and support.
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Fig 3. Liver function (bilirubin [top], serum glutamico-xaloacetic transaminase (SGOT) [middle], and serum glutamic-pyruvic transaminase (SGPT) [bottom]) during support with the Jarvik 2000. The area within the dotted lines is the normal value range.
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At the time of heart transplantation, all renal and hepatic function values were normal. Other laboratory values, such as hematologic values, coagulation, and electrolytes, normalized during support. Pulmonary and neurologic functions were also normal at the time of heart transplantation.
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Comment
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Research on implantable long-term LVADs began in the 1960s and has continued through to the present day. Originally designed to capture the entire cardiac output and to produce flows of up to 10 L/min against physiologic resistance [6], pulsatile LVADs have evolved to the point that they have dramatically improved outcomes in heart failure patients [7]. There have also been reports of LVADs maintaining and improving hepatic and renal function during periods of extensive hemodynamic support in patients awaiting cardiac transplantation [8]. However, as experience has increased, it has become clear that such aggressive support may not be necessary in all cases of heart failure.
The safety of pulsatile LVADs in humans is well documented. McCarthy and colleagues at the Cleveland Clinic have clearly documented the safety and efficacy of the HeartMate LVAD (Thoratec, Pleasanton, CA) in preserving hepatic and renal function [9]. In contrast, the safety of long-term support with continuous-flow cardiac assist devices has been well documented only in animals. Therefore, we became interested in documenting the safety of such pumps in humans and their effect on the function of extracardiac organs, especially the kidneys and liver.
Liver function is an important predictor of survival after the implantation of pulsatile LVADs. Elevated total bilirubin in particular is an important predictor of mortality [10]. In severe hepatocellular disease caused by congestive heart failure, serum bilirubin is elevated, transaminase levels rise slightly, and LDH levels rise, though nonspecifically. In cases of intrahepatic biliary obstruction, alkaline phosphatase and GGTP levels rise. Fortunately, both kidney and liver function are easily assessed using standard values. In the present study, we chose to follow total bilirubin, SGOT, and SGPT.
No patient had markedly abnormal hepatic function before device implantation, and perhaps this explains the absence of severe hepatic dysfunction in our series. Moreover, normal liver function values were maintained throughout the entire course of hemodynamic support with the Jarvik 2000 LVAD. Interestingly, severe hepatic dysfunction after implantation was uncommon, possibly because of the smaller magnitude of the implantation operation. Therefore, it appears that prolonged continuous-flow mechanical circulatory support does not damage the liver physiologically. It should be noted, however, that in all 10 cases in our series, pulsatility, although markedly dampened, was maintained during support with the Jarvik 2000 LVAD.
Renal function is likewise a predictor of outcome after LVAD implantation. It is especially problematic in the perioperative period of pulsatile LVAD implantation. It has also been shown to be a predictor of poor outcome [9]. Renal failure is often associated with the need for transfusion of multiple units of blood in the intraoperative or early postoperative period. However, in our experience, this risk has been minimized by the less extensive operation required for implantation of the Jarvik 2000. Moreover, our enrollment criteria excluded patients with renal failure. No increases in serum creatinine were noted during the periods of circulatory support, and urine output was maintained after implantation. In short, renal function was well maintained in our patient population.
In conclusion, our data suggest that the Jarvik 2000 LVAD, an implantable continuous axial-flow device, can provide excellent physiologic support to the kidneys and liver for at least 2 months and for as long as 6 months after implantation. Concerns about impaired extracardiac organ function due to the dampened pulsatility of a continuous axial-flow circulatory support device appear to be unwarranted.
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References
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- Frazier O.H., Myers T.J., Gregoric I.D., et al. Initial clinical experience with an implantable axial-flow left ventricular assist system: the Jarvik 2000 Heart. Circulation 2002;105:2855-2860.[Abstract/Free Full Text]
- Frazier O.H., Gregoric I.D., Delgado R.M., et al. Initial experience with the Jarvik 2000 left ventricular assist system as a bridge to transplantation: report of 4 cases. J Heart Lung Transplant 2001;20:201.
- Myers T.J., Gregoric I., Tamez D., et al. Development of the Jarvik 2000 Heart ventricular assist system. J Heart Failure Circ Support 2000;3:133-140.
- Frazier O.H., Myers T.J., Jarvik R.K., et al. Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart. Ann Thorac Surg 2001;71(Suppl 3):S125-136.[Abstract/Free Full Text]
- Westaby S., Frazier O.H., Pigott D.W., Saito S., Jarvik R.K. Implant technique for the Jarvik 2000 heart. Ann Thorac Surg 2002;73:1337-1340.[Abstract/Free Full Text]
- Frazier O.H. Evolution of battery-powered, vented left ventricular assist devices. Ann Thorac Surg 1996;61:393-395.[Abstract/Free Full Text]
- Portner P.M., Jansen P.G.M., Oyer P.E., Wheeldon D.R., Ramasamy N. Improved outcomes with an implantable left ventricular assist system: a multicenter study. Ann Thorac Surg 2001;71:205-209.[Abstract/Free Full Text]
- McCarthy P.M., Savage R.M., Fraser C.D., et al. Hemodynamic and physiologic changes during support with an implantable left ventricular assist device. J Thorac Cardiovasc Surg 1995;109:409-418.[Abstract/Free Full Text]
- McCarthy P.M., Smedira N.O., Vargo R.L., et al. One hundred patients with the HeartMate left ventricular assist device: evolving concepts and technology. J Thorac Cardiovasc Surg 1998;115:904-912.[Abstract/Free Full Text]
- Masai T., Sawa Y., Ohtake S., et al. Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation. Ann Thorac Surg 2002;73:549-555.[Abstract/Free Full Text]
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Abstract
Introduction
