HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) 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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Banayosy, A. Articles by Vigano, M. Search for Related Content PubMed PubMed Citation Articles by El-Banayosy, A. Articles by Vigano, M.

Eur J Cardiothorac Surg 1999;15:835-841
© 1999 Elsevier Science NL

The European experience of Novacor left ventricular assist (LVAS) therapy as a bridge to transplant: a retrospective multi-centre study

^a Herzzentrum Nordrhein Westfalen, Bad Oeynhausen, Germany
^b Westfälische Wilhelms-Universität, Münster, Germany
^c Hopital Henri Mondor, Paris, France
^d Klinikum Großhadern, Munich, Germany
^e Ospedale Niguarda Ca Granda, Milan, Italy
^f Deutsches Herzzentrum, Berlin, Germany
^g IRCCS Policlinico San Matteo, Pavia, Italy

Received 10 November 1998; received in revised form 3 March 1999; accepted 11 March 1999.

Corresponding author. Herzzentrum NRW, Klinik Fur Thorax und Kardiovaskularchirurgie, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany. Tel.: +49-5731-1353; fax: +49-5731-1343

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

 
Objective: Artificial heart devices have suffered from a negative press based on the early Jarvik experience of the 1980s. This is in stark contrast to realities of current left ventricular assist (LVAS) therapy. The Novacor N100 PC wearable left ventricular assist system (LVAS) was introduced in Europe in late 1993. This system allows implanted recipients to be completely autonomous with the system controlled by a small computer and powered by rechargeable batteries. This report represents the initial European experience with the Novacor LVAS. Methods: Since the system was introduced with regulatory approval as a commercial product, clinicians were not bound by the constraints of a study protocol and only minimal data were collected. This report presents the results of a retrospective study of 118 consecutive patients who had the LVAS implanted as a bridge to transplant, in 19 centres over the three year period ending in November 1996. Results: Mortality and morbidity varied widely between centres. The median implant time was 115 days (0–585 days) and 33% of patients returned home, supported by the LVAS. The overall survival on LVAS was 64%. The major causes of death were infection (14%) and MOF (6%). There were no significant device or system failures despite a cumulative patient experience of 24.8 years outside of a hospital environment. Patient selection and management varied greatly between centres and this was reflected in disparate outcomes. Conclusions: Optimal selection and management of LVAS patients has still to be established. While the data available for this report lacked the detail necessary to demonstrate direct causal relationships between selection and management, it was clear from the inter-centre differences that these two factors have a major impact on outcomes. This early experience has directed attention towards improved management regimes. Given the results obtained from the best centres and the ability to discharge patients to lead near-normal lives in the community, the authors believe that the Novacor LVAS now offers a real therapeutic alternative for selected end-stage heart failure patients for whom a donor heart is unavailable or who are unsuitable for transplantation.

Key Words: Left ventricular assist therapy • Bridge to transplant

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

 
Whilst the epidemiology of heart failure in Europe is poorly characterized, estimates put the prevalence in the range of 0.4% to 2%, in the general population [1]. This means that within the European Community, there are between 2 to 10 million people whose lives are impaired by this condition.

Unlike other common cardiovascular diseases, the age-adjusted mortality attributed to heart failure, also appears to be increasing [2]. Despite the improvements brought about by the advent of ACE inhibitors, medical treatment alone will result in about 50% of patients with NYHA IV failure dying within 1 year of diagnosis [3].

Cardiac transplantation is the only effective therapy currently available to this group of patients. However, the donor supply is restricted and diminishing [4], which currently allows for less than 10% of potential candidates receiving a graft and, despite one-year survival rates of over 80% [5], the morbidity of chronic immunosuppression increasingly compromises health related quality of life in these patients [6].

The use of chronic mechanical support, as an alternative to transplantation, was introduced (somewhat prematurely) by De Vries with the implantation of a Jarvik total artificial heart in 1982 [7]. This trial, involving 4 patients, was terminated by the FDA in 1990 [8], due to the unacceptable level of complications. In addition, and possibly of more significance, the patients were anchored to large consoles and clearly were unable to enjoy a reasonable quality of life. This device went on to be developed by Cardiowest and has been associated with good results as a bridge device. However, it is unfortunately this negative image of artificial heart devices which has endured but which bears little resemblance to the LVAS patients of today, who spend more than 50% of their time at home supported by the device. Many of these patients also resume work [9].

The first successful bridge to transplant took place at Stanford University Hospital in 1984 with the use of the electrically actuated Novacor LVAS [10]. Unlike the former Jarvik heart this ventricle is placed heterotopically, just below the diaphragm, allowing the natural heart to remain in place [11]. The pump follows the output of the natural heart, providing automatic control, a degree of redundancy and the possibility of removal should native ventricular recovery occur [12]. Although early systems also required a large console, a wearable version, which is supported by a small electronic controller and batteries worn on a belt, was introduced in 1993 [13,14] (Fig. 1) . Since this model (N100 PC) was released in Europe as a commercial product, clinicians were not bound by the constraints of a study protocol, and prospective data collection was abandoned.

View larger version (32K): [in this window] [in a new window]   Fig. 1. Diagram of the Novacor N100 PC wearable LVAS. (1) Pump/drive unit. (2) Valved conduits. (3) Inflow conduit. (4) Outflow conduit. (5) Percutaneous lead. (6) Filter. (7) Compact controller. (8) Primary power pack. (9) Reserve power pack. Implanted components: pump/drive unit; inflow conduit cannulating the left ventricle; outflow conduit anastamosed to ascending thoracic aorta. External components: compact controller, coupled to the pump/drive unit via a percutaneous lead with filter; rechargeable primary and reserve power packs

This paper represents the initial European Multi-Centre experience with the Novacor left ventricular assist system (N100 PC LVAS).

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

 
2.1. Patients
143 patients were implanted with a Novacor N100 PC LVAS, in 19 European Centres, between the study inclusion dates of November 1993 to October 1996. The number of implants per centre varied from 1 to 21. Since intention to treat was mostly not prospectively determined, we retrospectively excluded nine patients who were weaned from the device and 14 who were implanted as an alternative to transplant. Data were unavailable for two patients. This left 118 patients from 19 centres, who form the basis for this study of LVAS use as a bridge to transplant. Emergency implants were included.

2.2. Definitions of complications
In the absence of any internationally agreed definitions of adverse events, in the field of mechanical assist, we adopted a set of definitions developed by an international advisory board, for the purposes of this study (Table 1).

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

 
3.1. Patient characteristics
Patient demographics and pre-implant data are given in Tables 2 and 3. The patients were predominantly large males (89%) with a median age of 49 years who showed a haemodynamic pattern of cardiac decompensation despite maximum medical therapy. The majority (61%) had a diagnosis of idiopathic dilated cardiomyopathy, whilst patients with ischaemic heart disease made up the majority of the remainder (32%), and there were a small number with an acute myocarditis (3%), infarction (3%) or other diagnosis. Ventilator support was required for 20% of patients, intra aortic balloon counter pulsation (IABP) for 16% and 11% had both ventilator and IABP support, prior to implantation. Detailed information on pre-implant anti-failure therapy was not available for this cohort.

View larger version (41K): [in this window] [in a new window]   Fig. 2. Cumulative frequency of LVAS duration. 52% of patients were implanted for more than 4 months and 7% for at least 1 year.

It is also evident that renal, hepatic and neurohormonal recovery can take up to 3 months [16,17], which means that most patients should not be placed on the heart transplant waiting list until about this time.

3.3. Complications
The major complications experienced by this group of patients are similar to those for all forms of mechanical assist. The temporal distribution, however, shows a preponderance of early complications, suggesting a strong influence from patient selection, pre-morbid condition (Fig. 3) and, as described above, there was a wide variation between centres. During the chronic phase of support there was a continued decrease in the incidence of complications. Infections of the driveline exit site, device pocket and septicaemia are summarized in Fig. 4. Staphylococcus species (aureus, epidermidis) were the predominant cultures found.

View larger version (19K): [in this window] [in a new window]   Fig. 3. Temporal relationship of complications. The linearized rates (events/patient month, with 95% confidence) of the 5 major complications is shown to decrease with implant time, in all cases.

View larger version (15K): [in this window] [in a new window]   Fig. 4. Infections by site and organism. Cultures of driveline exit site infection, pump pocket infection, and septicaemia/blood samples. The number of patients with infection per site and percentage of total patients are given in the sub-title of each pie chart.

There were no significant device or system failures despite a large cumulative patient experience (24.8 years) outside of the protected environment of the hospital. In one patient there was a high residual volume caused by a kinked outflow graft which required reoperation, with no further complications. Five patients experienced what we describe as system failures. Two of these were related to the compact controller which in one case was the result of an electronic component malfunction and the other was due to a cable connection problem. In both cases the system operated in one of its back-up modes, with no harm to the patient. In two further cases pump function was compromised by clogged filters on the external vented cable. In the fifth case the drive cable was damaged and had to be repaired. (Table 6).

As with the incidence of complications, increased implant times were associated with improved survival; transplant rates increased from 27% in those patients supported for less than 30 days to 71% in those supported for more than 2 months (Fig. 5) .

View larger version (24K): [in this window] [in a new window]   Fig. 5. Interval outcomes. Of all patients that reached their endpoint (TX or died) within the first month (<31 days), 73% died whereas 27% were transplanted. This reflects the pre-morbid condition of many recipients. Longer implant times are associated with much improved outcomes.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

A major outcome from this study was the finding that so many patients were able to return home and resume their place in the community, despite the fact that the majority of these patients were amongst the highest risk group to be treated for end stage heart failure. In addition, although these patients came from a cross-section of the community with a range of technical skills and competence, they all coped exceedingly well with the practical day to day aspects of managing the system and there were no significant device problems in a cumulative home experience of over 24 years. Several of these patients were so well adapted to the Novacor that they were able to resume occupations ranging from working in a family delicatessen, working in the family vineyard, managing a bakery chain, working as an architect and working as a building-site surveyor. Clearly these patients were able to enjoy a quality of life which most would find acceptable.

The data for this retrospective study represent patients who were implanted at centres where LVAS therapy was still in its infancy, such that most of these patients were moribund prior to implantation. This is inevitable when introducing a new and unproven technology. Nevertheless a survival of 64% was achieved in this population. The results therefore represent a worst case situation as it is now clear that a more timely intervention brings much improved outcomes. We would therefore submit that Novacor LVAS therapy provides an acceptable solution to the current organ donor shortage by offering a life saving therapy for a group of patients whose prognosis would otherwise be very poor. The transplant waiting list mortality in those areas covered by Eurotransplant is currently approximately 26% [4]. However, this group of bridged patients would have had a mortality much higher than this, if they had not received an LVAS implant. It is also apparent that the quality of life offered by this device is fully acceptable to the majority of recipients, as evidenced by the number of recipients who were discharged home and by the duration of trouble free time which they spent back in the community.

Comparisons with other mechanical support devices show that whilst the survival and complication rates are similar [18], recipients do not receive the same benefits of discharge into the community as these systems have proved to be less reliable and durable [19,20].

The most surprising aspect of this exercise was both the extent and the nature of differences between centres. It was obvious that positive outcomes were not necessarily related to large numbers of implants. Poor outcomes are therefore more related to patient selection and management. This finding has initiated a major effort to share best practices among centres. Careful explant analysis has now identified the inflow graft as the major source of potential thrombo-embolic complications and a study of alternative grafts is underway.

The authors are of the opinion that even though this retrospective data analysis was problematic, it has served to show that Novacor LVAS therapy has the potential of offering a very real alternative for those patients with end stage failure for whom donor organs are either unavailable or who are unsuitable for transplantation [21].

	Appendix A. Participating centres (in alphabetic order)

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

 
Akademiska Sjukhuset, Uppsala, Sweden (S. Thelin). AKH Universitätklinik, Wien, Austria (D.G. Laufer, E. Wolner). CHU de Brabois, Nancy, France (T. Hubert, J.-P. Villemot). Cliniques Universtaires Saint Luc, Brussels, Belgium (R. Dion, L. Jacquet). Deutsches Herzzentrum Berlin, Germany (R. Hetzer, M. Loebe). Herzzentrum Nordrhein Westfalen, Bad Oeynhausen, Germany (A. El-Banayosy, R. Korfer). Hopital Broussais, Paris, France (A. Carpentier). Hopital Henri Mondor, Paris, France (D.Y. Loisance, D. Tixier). Hopital La Pitié Salpétrière, Paris, France (I. Gandjbakhch, A. Pavie). Hopital Laennec, Nantes, France (D. Duveau). Humboldt Universitat Charité, Berlin, Germany (W. Konertz). IRCCS Policlinico San Matteo Pavia, Italy (M. Vigano, L. Martinelli). Klinikum Großhadern, Munich, Germany (B. Reichert, H. Vetter). LKH University, Graz, Austria (K.-H. Tscheliessnigg). Ospedale Niguarda Ca Granda, Milan, Italy (E. Gronda, A. Pellegrini). Ospedale V. Monaldi, Naples, Italy (F. De Vivo). Ospital 12 de Octubre, Madrid, Spain (X.X. Rufilanches). Universita di Padova, Padova, Italy (D. Casarotto). Westfälische Wilhelms-Universität, Münster, Germany (M. Deng, H. Scheld).

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Participating... References

 

1. Task Force on Heart Failure of the European Society of Cardiology: Guidelines for the diagnosis of heart failure. Eur Heart J 1995;1995:741-751.
2. Garg R., Yusuf S. Epidemiology of congestive heart failure. In: Barnett D.B., Poleur H., Francis G.S., eds. Congestive cardiac failure: pathophysiology and treatment. New York: Marcel Dekker, 1993:9.
3. Ho K.K., Pinsky J.L., Kannel W.B., Levy D. The epidemiology of heart failure: the Framingham study. J Am Coll Cardiol 1993;22(4 Suppl A):6A-13A.
4. Euro Transplant International Foundation, Leiden, Netherlands.
5. Hosenpud J.D., Novick R.J., Bennett L.E., Keck B.M., Fiol B., Daily P. The registry of the International Society of Heart and Lung Transplantation: thirteenth official report. J Heart Lung Transplant 1996;15:655-674.[Medline]
6. Lough M.E., Lindsey A.M., Shinn J.A., Stotts N.A. Impact of symptom frequency and symptom distress on self-reported quality of life in heart transplant recipients. J. Heart Lung 1987;16:193.
7. DeVries W.C., Anderson J.L., Joyce L.D., Anderson F.L., Hammond E.H., Jarvik R.K., Kolff W.J. Clinical use of the total artificial heart. New Engl J Med 1984;310:273-278.[Abstract]
8. Statement on Jarvik Artificial Heart. Rockville, MD: FDA Press Office, 11 January 1990.
9. Fey O., El-Banayosy A., Arosuglu L., Posival H., Korfer R. Out-of-hospital experience in patients with implantable mechanical circulatory support: present and future trends. Eur J Cardiothorac Surg. 1997(11 Suppl):S51-S53.
10. Portner P.M., Oyer P.E., McGregor C.G.A., Baldwin J.C., Ream A.K., Wyner J., Zusman D.R., Shumway N.E. First human use of an electrically powered implantable ventricular assist system. Artif Organs 1985;9:36.
11. Vigano M., Martinelli L. Modified method for Novacor left ventricular assist device implantation. Ann Thorac Surg 1996;61:247-249.[Abstract/Free Full Text]
12. Muller J., Wallukat G., Weng Y-G., Dandel M., Spiegelsberger S., Semrau S., Brandes K., Theodoris V., Loebe M., Meyer R., Hetzer R. Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy. Circulation 1997;96:542-549.[Abstract/Free Full Text]
13. Loisance D., Cooper G.J., Deleuze P.H. Bridge to transplantation with the wearable Novacor left ventricular assist system: operative technique. Eur J Cardiothorac Surg 1995;9:95-98.[Abstract]
14. Vetter H.O., Kaulbach H.G., Schmitz C., Forst H., Uberfuhr P., Kreuzer E., Pfeiffer M., Brenner P., Dewald O., Reichart B. Experience with the Novacor left ventricular assist system as a bridge to cardiac transplantation, including the new wearable system. J Thorac Cardiovasc Surg. 1995;109:74-80.[Abstract/Free Full Text]
15. Herman M., Weyand M., Greshake B., von Eiff C., Proctor R.A., Scheld H.H., Peters G. Left ventricular assist device infection is associated with increased mortality but is not a contraindication to transplant. Circulation 1997;95:814-817.[Abstract/Free Full Text]
16. Novacor FDA submission, 1998.
17. Delgado R., Radovancevic B., Massin E.K., Frazier O.H., Benedict C. Neurohormonal changes after implantation of a left ventricular assist system. ASAIO J 1998;44:299-302.[Medline]
18. Mehta S.M., Pae W. Erosion of inlet cannula of left ventricular assist device manifested as innocuos bleeding in a stable patient: lessons learned in the prevention of catastrophic consequences. J Thorac Cardiovasc Surg 1996;112:544-545.[Free Full Text]
19. Mehta S.M., Aufiero T.X., Pae W.E., Miller C.A., Pierce W.S. Combined registry for the use of mechanical ventricular assist pumps and the total artificial heart in conjunction with heart transplantation: sixth official report. J Heart Lung Transplant 1995;14:585-593.[Medline]
20. Scheld H.H., Soeparwata R., Schmid C., Loick M., Weyand M., Hammel D. Rupture of inflow conduits in the TCI Heartmate system. J Thorac Cardiovasc Surg 1997;114:287-289.[Free Full Text]
21. Loisance D., Tixier D., Mazzucotelli J.P., Deleuze P.H., Baufreton C., Le Besnerais P. Mechanical circulatory support towards the permanent implantation. Eur J Cardiothorac Surg 1997(11 Suppl):S25-S28.

This article has been cited by other articles:

				E. B Friedrich and M. Bohm MANAGEMENT OF END STAGE HEART FAILURE Heart, May 1, 2007; 93(5): 626 - 631. [Full Text] [PDF]

				L. Santambrogio, T. Bianchi, M. Fuardo, F. Gazzoli, R. Veronesi, A. Braschi, and M. Maurelli Right ventricular failure after left ventricular assist device insertion: preoperative risk factors Interactive CardioVascular and Thoracic Surgery, August 1, 2006; 5(4): 379 - 382. [Abstract] [Full Text] [PDF]

				M. P. Siegenthaler, J.u. Martin, A. van de Loo, T. Doenst, W. Bothe, and F. Beyersdorf Implantation of the permanent jarvik-2000 left ventricular assist device: A single-center experience J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1764 - 1772. [Abstract] [Full Text] [PDF]

				T. A. Snyder, M. J. Watach, K. N. Litwak, and W. R. Wagner Platelet activation, aggregation, and life span in calves implanted with axial flow ventricular assist devices Ann. Thorac. Surg., June 1, 2002; 73(6): 1933 - 1938. [Abstract] [Full Text] [PDF]

				S. L. Tittle, D. Mandapati, G. S. Kopf, and J. A. Elefteriades Alternate technique for implantation of left ventricular assist system: left thoracotomy for reoperative cases Ann. Thorac. Surg., March 1, 2002; 73(3): 994 - 996. [Abstract] [Full Text] [PDF]

				P. M. Portner, P. G. M. Jansen, P. E. Oyer, D. R. Wheeldon, and N. Ramasamy Improved outcomes with an implantable left ventricular assist system: a multicenter study Ann. Thorac. Surg., January 1, 2001; 71(1): 205 - 209. [Abstract] [Full Text] [PDF]

				M. Loebe, T. Drews, E. Potapov, D.-V. Ngo, R. zu Dohna, and R. Hetzer Device selection in mechanical circulatory support Perfusion, July 1, 2000; 15(4): 313 - 318. [PDF]

				D R Wheeldon, P G. Jansen, and P M Portner The Novacor electrical implantable left ventricular assist system Perfusion, July 1, 2000; 15(4): 355 - 361. [PDF]

				S G Williams, D J Wright, and L B Tan Management of cardiogenic shock complicating acute myocardial infarction: towards evidence based medical practice Heart, June 1, 2000; 83(6): 621 - 626. [Full Text]

				C. Knosalla, Y.-g. Weng, S. Buz, M. Loebe, and R. Hetzer Pseudoaneurysm of the outflow graft in a patient with novacor N100 LVAD system Ann. Thorac. Surg., May 1, 2000; 69(5): 1594 - 1596. [Abstract] [Full Text] [PDF]

				A. El-Banayosy, L. Arusoglu, L. Kizner, G. Tenderich, K. Minami, K. Inoue, and R. Korfer NOVACOR LEFT VENTRICULAR ASSIST SYSTEM VERSUS HEARTMATE VENTED ELECTRIC LEFT VENTRICULAR ASSIST SYSTEM AS A LONG-TERM MECHANICAL CIRCULATORY SUPPORT DEVICE IN BRIDGING PATIENTS: A PROSPECTIVE STUDY J. Thorac. Cardiovasc. Surg., March 1, 2000; 119(3): 581 - 587. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) 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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Banayosy, A. Articles by Vigano, M. Search for Related Content PubMed PubMed Citation Articles by El-Banayosy, A. Articles by Vigano, M.