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Ann Thorac Surg 2006;82:1774-1778
© 2006 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Does Continuous Flow Left Ventricular Assist Device Technology Have a Positive Impact on Outcome Pretransplant and Posttransplant?

Stefan Klotz, MDa,*, Joerg Stypmann, MDb, Henryk Welp, MDa, Christof Schmid, MDa, Gabriele Drees, MDa, Andreas Rukosujew, MDa,b, Hans H. Scheld, MDa

a Department of Thoracic and Cardiovascular Surgery, University Hospital Muenster, Muenster, Germany
b Department of Cardiology and Angiology, University Hospital Muenster, Muenster, Germany

Accepted for publication May 16, 2006.

* Address correspondence to Dr Klotz, Department of Thoracic and Cardiovascular Surgery, University Hospital Münster, Albert-Schweitzer-Str. 33, 48149 Münster, Germany (Email: stefan.klotz{at}ukmuenster.de).

Presented at the Poster Session of the Forty-Second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: Left ventricular assist devices (LVADs) with continuous flow properties are increasingly used to bridge heart failure patients to cardiac transplantation. Advantages in comparison with the pulsatile LVADs are smaller size, better endurance, and lower thromboembolic events. However, whether these new pumps have similar pre- and posttransplant outcomes is not clear.

METHODS: Fifty patients with a continuous flow device (Micromed DeBakey, Houston, TX or InCor BerlinHeart, Berlin, Germany) were compared with an age-, disease-, and LVAD duration-matched control group (n = 80) supported with a pulsatile device (Novacor, WorldHeart, Oakland, CA or HeartMate, Thoratec Corp, Pleasanton, CA).

RESULTS: Age (44.3 ± 13.4 vs 46.1 ± 11.1 years), disease (idiopathic dilated cardiomyopathy, 58% vs 65%), and LVAD duration (138 ± 131 vs 128 ± 106 days) were comparable in both groups. Successful bridging to transplantation was similar with continuous flow in comparison with pulsatile device support (52% vs 56%, p = not significant [NS]). Thirty-day mortality after cardiac transplantation in patients with continuous flow LVAD support was 21.7% vs 22.2% with pulsatile LVADs (p = NS). Reasons for death were similar among the different LVAD groups. Long-term survival was similar in both LVAD groups compared with patients without previous LVAD support. Interestingly, severe rejections were significantly more frequent in patients with a continuous flow LVAD (p < 0.001).

CONCLUSIONS: The new generation of cardiac assist devices with continuous flow pattern has a similar rate of pre- and posttransplant mortality in comparison with pulsatile LVADs. However, the rate and severity of posttransplant rejection was significantly higher in the group with continuous flow devices. Further studies are warranted to explain the higher rate of severe rejections.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Left ventricular assist device (LVAD) support is often the only therapeutic option in patients with endstage heart failure. The largest experience worldwide has been obtained with the intracorporal pulsatile device Novacor LVAD (World Heart Corp, Oakland, CA) and the HeartMate VE LVAD (Thoratec Corp, Pleasanton, CA). So far, more than 1,400 patients have been supported with the Novacor LVAD, while the HeartMate system has been implanted in around 4,100 patients. The patient's body size is an important factor in allowing device placement for both systems. The size of these devices and the weight of approximately 1 kg require patients to have a body surface area of more than 1.5 m2.

In recent years, continuous axial flow pumps have become clinically available [1]. Beside the Jarvik 2000 innovative ventricular assist system (IVAS) (Jarvik Heart Inc, New York, NY), the MicroMed DeBakey IVAS (MicroMed, Houston, TX) and the only one in Europe approved, InCor BerlinHeart (BerlinHeart, Berlin, Germany), are mainly used. Because of the continuous flow properties of axial flow pumps, no valves or compliance chambers are needed in these systems. These pumps are significantly smaller and therefore can be used in smaller patients (Fig 1). Relatively simple mechanics may lead to fewer device failures and lower energy requirements. The MicroMed DeBakey LVAD is an electromagnetically actuated, implantable titanium axial flow pump that connects to the left ventricular apex and ascending aorta [2]. The axial flow motor is small and contains rotary blades that spin at 7,500 to 12,500 rpm and can pump approximately 5 to 6 L/minute against 100 mm Hg pressure. The pump is 3.1 cm in diameter and 7.6 cm in length, and weighs approximately 93 g. So far, more than 150 patients have received this device, and the initial experience suggests that bridging to transplantation can be successfully approached [3, 4]. The InCor BerlinHeart is an axial flow pump, which undergoes clinical trials in Europe and China. The first implant was done at the German Heart Institute in Berlin in June 2002. Accumulated experience with the system now amounts to more than 12,220 days. On July 11, 2005 the 200th InCor BerlinHeart was implanted in a patient in Germany. The longest support with this device is now more than 1,000 days. In 2005 we published our experience with 15 InCor implants at the University Hospital in Muenster [5].


Figure 1
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  		Fig 1. The pulsatile working HeartMate (A) and the axial flow pump InCor BerlinHeart (B).

 
Improvement of cardiac function with pulsatile LVADs is well-described [6–9]. Pulsatile LVADs provide profound left ventricular (LV) volume and pressure unloading while simultaneously restoring adequate systemic blood flow in endstage congestive heart failure patients [10]. We could show in 2004 that the effect of unloading is superior with a pulsatile device [11]; however, data regarding the effect of continuous flow on outcome pre- and posttransplant remain unknown. To explore whether continuous flow LVADs have an impact on outcome pre- and posttransplant, we evaluated the Muenster LVAD experience with implantable pulsatile and continuous flow long-term LVADs.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
We included in the study 50 patients with a continuous flow device (Micromed DeBakey, n = 30 and InCor BerlinHeart, n = 20) and compared them with an age-, disease-, and LVAD duration-matched control group (n = 80) supported with a pulsatile device (Novacor, n = 61 and HeartMate, n = 19). The mortality data were compared with patients after cardiac transplantation without previous LVAD support. Patients with extracorporeal LVAD systems and patients under the age of 17 years were excluded from the analysis.

The Ethics Committee of the University Hospital Muenster approved this study. Individual consent for this study was waived.

Statistics
Results are presented as mean values ± standard deviation. A Student t test was used for comparison of continuous variables. The {chi}2 test was used for categoric variables. A log-rank test was used for Kaplan-Meier analyses. A p value less than 0.05 was considered statistically significant. All statistical analysis was done using SPSS 11.5 (SPSS Inc, Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
The clinical characteristics and demographics at the time of enrollment in the study are presented in Table 1. There was a similar distribution regarding age, disease, body mass index (BMI), body surface area (BSA), the patients' status at the time of implantation, and LVAD duration between the two LVAD groups.


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  		Table 1. Demographics and Clinical Characteristics at Study Entry
 
Pretransplantation
The overall mortality rate pretransplant was 48% (n = 24) in the continuous flow group and 44% (n = 35) in the pulsatile group (p = not significant [NS]). Reasons for death are shown in Figure 2. Overall, there was no significant difference between the continuous flow and pulsatile groups. The time interval from LVAD implantation to death in the continuous flow group was similar to that of the pulsatile group (68 ± 54 days vs 76 ± 95 days, p = NS). The BMI was significantly higher in the pulsatile LVAD group in patients who died before cardiac transplant compared with patients who were successfully bridged to transplantation (25.7 ± 4.5 vs 24.0 ± 3.2 kg/m2, p < 0.05), while there was no difference between the continuous flow LVAD and control groups. In both groups, age was significantly higher in patients who died during LVAD support (Fig 3). Because of the observation that the smaller continuous flow device might not be suitable in patients with acute cardiogenic shock (due to partial unloading of the left ventricle), we repeated the analyses in patients who received an LVAD under emergency conditions in acute cardiogenic shock. From the 20 patients in the continuous flow group, bridging to transplantation or weaning was possible in n = 10 (50%). In the pulsatile group this was possible in 14 out of 24 patients (58%) of the emergency implants.


Figure 2
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  		Fig 2. Reasons for death pretransplant showed no significant difference between the continuous flow and pulsatile LVAD group. ({blacksquare} = continuous flow; {square} = pulsatile flow; HTx = heart transplantation; MOF = multiorgan failure; RHF = right heart failure.)

 

Figure 3
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  		Fig 3. Patients who died during left ventricular assist device support ({blacksquare}) were significantly older compared with patients who could be transplanted ({square}). (*p < 0.05.)

 
Posttransplantation
In the continuous flow group, 23 patients (46%) could be transplanted and 3 patients (6%) could be weaned from the device. In the pulsatile group, 45 patients (56%) could be transplanted (p = NS). The time from LVAD implantation to cardiac transplant was 220 ± 147 days in the continuous flow group and 167 ± 96 days in the pulsatile group (p = 0.084). The pulsatile LVADs in this study were implanted from the year 1993 to the year 2000 while the continuous flow LVADs were implanted starting from the year 2000. In recent years increasing organ shortage significantly affected waiting time [12]. Posttransplant 30-day mortality was 21.7% in the continuous flow group and 22.2% in the pulsatile LVAD group. Reasons for early death posttransplant are shown in Figure 4. There was no difference in long-term survival after transplantation between both LVAD groups (Fig 5). The corresponding numbers for patients at risk are included in Figure 5.


Figure 4
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  		Fig 4. Reasons for death posttransplant showed no significant difference between the continuous flow ({blacksquare}) and pulsatile ({square}) left ventricular assist device groups. However, there is a trend toward lower incidence of rejection, sepsis, and MOF while the incidence of cerebral accident is elevated. (HTx = heart transplant; MOF = multiorgan failure; RHF = right heart failure.)

 

Figure 5
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  		Fig 5. Kaplan-Meier survival analysis for transplanted patient with previous continuous flow LVAD support (– – –), previous pulsatile LVAD support (- - -), and without LVAD support (—).

 
From the transplanted patients with prior continuous flow LVAD support who survived longer than 30 days, 89% had rejections equal to or higher than International Society of Heart and Lung Transplantation (ISHLT) grade III [13], while the rate of rejection ISHLT grade III or greater in the pulsatile group was 33% (p< 0.001). All rejections, except one in each group, could be treated successfully.


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
We could demonstrate that the new smaller continuous axial flow devices have a similar pretransplant mortality and posttransplant early and long-term outcome as intracorporal pulsatile devices. However, time on LVAD was almost significantly longer in the continuous flow device group, most likely due to the increasing organ shortage in Europe and changes in the allocation policy [14]. In addition, age was a significant predictor for mortality pretransplant during LVAD support. The degree of LV unloading is significantly different among patients supported by an axial flow pump and a pulsatile device [11]. However, the optimal degree of LV unloading during device support remains unknown. The LVAD was originally designed to entirely off-load the heart while restoring systemic blood pressure. Complete resting of the myocardium was presumed to be beneficial for myocardial recovery and to maximize myocardial perfusion [15].

Outcome after LVAD support is well-studied in pulsatile devices, with comparable outcome rates in patients with and without prior LVAD support [16–18]. However, there are no data available comparing pulsatile with continuous flow LVADs. Two studies [19, 20] exploring the impact of both device types on biochemical markers for brain-injury and activation of the inflammatory system, respectively, found no differences in the early phase after LVAD surgery. In the latest report by Thohan and colleagues [21] the effect of cellular markers for reverse remodeling was similar in both LVAD groups. In addition, the degree of reduction in medically unresponsive pulmonary hypertension was similar in both device types [22, 23]. Our group previously could show that continuous flow devices do not unload the left ventricle to the extent of pulsatile LVADs [11]. However, the outcome of patients with continuous flow devices implanted in acute cardiogenic shock was comparable with patients with a pulsatile device.

Interestingly, we found that the risk of severe rejection was increased threefold after continuous flow LVAD support, compared with pulsatile LVAD support. The data in the literature regarding human leukocyte antigen (HLA) sensitization after LVAD support are not contradictive. While some authors reported an increased risk of HLA sensitization after LVAD support in pulsatile LVADs [24–26]; John and colleagues [27] did not find an increased risk after pulsatile support and Grinda and colleagues [28] even showed a lower risk after continuous flow support. The reasons for our high rate of severe rejection in patients with previous continuous support are not known so far. Further studies to evaluate the numbers of transfusion of red blood cells and platelets and changes in immunosuppression are warranted.

The new generation of cardiac assist devices with continuous flow pattern has a comparable rate of pre- and posttransplant mortality in comparison with pulsatile LVADs. Age is a predictor for pretransplant mortality during LVAD support. The rate and severity of posttransplant rejection was significantly higher in the group with the new continuous flow devices. Further studies are warranted to explain this higher rate of severe rejections.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Hetzer R, Jurmann MJ, Potapov EV, et al. [Heart assist systems--current status] Herz 2002;27:407-417.[Medline]
  2. DeBakey ME. A miniature implantable axial flow ventricular assist device Ann Thorac Surg 1999;68:637-640.[Abstract/Free Full Text]
  3. Goldstein DJ. Worldwide experience with the MicroMed DeBakey ventricular assist device as a bridge to transplantation Circulation 2003;108(suppl 1):II272-II277.
  4. Potapov EV, Loebe M, Nasseri BA, et al. Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device Circulation 2000;102(suppl 3):III183-III187.
  5. Schmid C, Tjan TD, Etz C, et al. First clinical experience with the Incor left ventricular assist device J Heart Lung Transplant 2005;24:1188-1194.[Medline]
  6. Frazier OH, Benedict CR, Radovancevic B, et al. Improved left ventricular function after chronic left ventricular unloading Ann Thorac Surg 1996;62:675-681.[Abstract/Free Full Text]
  7. Hetzer R, Muller J, Weng Y, et al. Cardiac recovery in dilated cardiomyopathy by unloading with a left ventricular assist device Ann Thorac Surg 1999;68:742-749.[Abstract/Free Full Text]
  8. Levin HR, Oz MC, Chen JM, et al. Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading Circulation 1995;91:2717-2720.[Abstract/Free Full Text]
  9. Muller J, Wallukat G, Weng YG, et al. Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy Circulation 1997;96:542-549.[Abstract/Free Full Text]
  10. Mancini D, Goldsmith R, Levin H, et al. Comparison of exercise performance in patients with chronic severe heart failure versus left ventricular assist devices Circulation 1998;98:1178-1183.[Abstract/Free Full Text]
  11. Klotz S, Deng MC, Stypmann J, et al. Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support Ann Thorac Surg 2004;77:143-149.[Abstract/Free Full Text]
  12. Smits JM, Vanhaecke J, Haverich A, et al. Waiting for a thoracic transplant in Eurotransplant Transpl Int 2006;19:54-66.[Medline]
  13. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection J Heart Lung Transplant 2005;24:1710-1720.[Medline]
  14. Komoda T, Drews T, Lehmkuhl HB, et al. Role of ventricular assist devices in the German heart allocation system J Artif Organs 2006;9:29-33.[Medline]
  15. Mancini DM, Beniaminovitz A, Levin H, et al. Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure Circulation 1998;98:2383-2389.[Abstract/Free Full Text]
  16. Drakos SG, Kfoury AG, Long JW, et al. Effect of mechanical circulatory support on outcomes after heart transplantation J Heart Lung Transplant 2006;25:22-28.[Medline]
  17. Minami K, El-Banayosy A, Sezai A, et al. Morbidity and outcome after mechanical ventricular support using Thoratec, Novacor, and HeartMate for bridging to heart transplantation Artif Organs 2000;24:421-426.[Medline]
  18. Schmid C, Welp H, Klotz S, et al. Outcome of patients surviving to heart transplantation after being mechanically bridged for more than 100 days J Heart Lung Transplant 2003;22:1054-1058.[Medline]
  19. Loebe M, Koster A, Sanger S, et al. Inflammatory response after implantation of a left ventricular assist device: comparison between the axial flow MicroMed DeBakey VAD and the pulsatile Novacor device ASAIO J 2001;47:272-274.[Medline]
  20. Potapov EV, Loebe M, bdul-Khaliq H, et al. Postoperative course of S-100B protein and neuron-specific enolase in patients after implantation of continuous and pulsatile flow LVADs J Heart Lung Transplant 2001;20:1310-1316.[Medline]
  21. Thohan V, Stetson SJ, Nagueh SF, et al. Cellular and hemodynamics responses of failing myocardium to continuous flow mechanical circulatory support using the DeBakey-Noon left ventricular assist device: a comparative analysis with pulsatile-type devices J Heart Lung Transplant 2005;24:566-575.[Medline]
  22. Martin J, Siegenthaler MP, Friesewinkel O, et al. Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation-a preliminary study Eur J Cardiothorac Surg 2004;25:971-977.[Abstract/Free Full Text]
  23. Salzberg SP, Lachat ML, von Harbou K, et al. Normalization of high pulmonary vascular resistance with LVAD support in heart transplantation candidates Eur J Cardiothorac Surg 2005;27:222-225.[Abstract/Free Full Text]
  24. Joyce DL, Southard RE, Torre-Amione G, et al. Impact of left ventricular assist device (LVAD)-mediated humoral sensitization on posttransplant outcomes J Heart Lung Transplant 2005;24:2054-2059.[Medline]
  25. Massad MG, Cook DJ, Schmitt SK, et al. Factors influencing HLA sensitization in implantable LVAD recipients Ann Thorac Surg 1997;64:1120-1125.[Abstract/Free Full Text]
  26. Pamboukian SV, Costanzo MR, Dunlap S, et al. Relationship between bridging with ventricular assist device on rejection after heart transplantation J Heart Lung Transplant 2005;24:310-315.[Medline]
  27. John R, Rajasinghe H, Chen JM, et al. Impact of current management practices on early and late death in more than 500 consecutive cardiac transplant recipients Ann Surg 2000;232:302-311.[Medline]
  28. Grinda JM, Bricourt MO, Amrein C, et al. Human leukocyte antigen sensitization in ventricular assist device recipients: a lesser risk with the DeBakey axial pump Ann Thorac Surg 2005;80:945-948.[Abstract/Free Full Text]
  29. Schmid C, Deng M, Hammel D, et al. Emergency versus elective/urgent left ventricular assist device implantation J Heart Lung Transplant 1998;17:1024-1028.[Medline]



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 Eur. J. Cardiothorac. Surg.Home page
A. Garatti, G. Bruschi, T. Colombo, C. Russo, M. Lanfranconi, F. Milazzo, M. Frigerio, and E. Vitali
Clinical outcome and bridge to transplant rate of left ventricular assist device recipient patients: comparison between continuous-flow and pulsatile-flow devices.
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[Abstract] [Full Text] [PDF]

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