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Eur J Cardiothorac Surg 2000;18:112-116
© 2000 Elsevier Science NL

Results with the Novacor assist system and evaluation of long-term assistance

^a Department of Cardiac Surgery, Policlinico San Matteo, IRCCS, Piazzale Golgi 2, 27100 Pavia, Italy
^b Department of Biometry (Scientific Direction), Policlinico San Matteo, IRCCS, Piazzale Golgi 2, 27100 Pavia, Italy

Received 7 September 1999; received in revised form 28 February 2000; accepted 7 March 2000.

Corresponding author. Tel.: +39-382-503515; fax: +39-382-503059

	Abstract

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

 
Objective: The great number of patients awaiting heart transplant and the shortage of donors has led to the increasing use of left ventricular assist devices (LVAD) for those patients that cannot wait only on medical therapy. In this study we analyze our experience in order to evaluate the possibility of long-term assistance. Methods: We have implanted LVAD Novacor in 36 patients with a mean age of 50.4 years. They were all critical candidates for transplant on high doses of inotrops. We evaluated the clinical and hemodynamic results and studied statistically the relative risk of complications at different time intervals of support. Results: In all cases we had a statistically significant improvement of: cardiac output, wedge pressure, pulmonary vascular resistance and mean pulmonary pressure. Eleven patients died on the device, 23 underwent heart transplant and two are still on the device. Causes of death were mostly related to cerebrovascular events or multiorgan failure. Seven of the 23 patients who underwent heart transplant died with a survival rate after transplant of 69.5% and an overall survival rate of 50%. Complications occurred in 33 patients with: 24 strokes, eight TIAs, four cerebral hemorrhages, three peripheral embolisms, seven cable infections, two pocket infections, two sepsis, two major lung infections, one mediastinitis, one right ventricular failure and three multiorgan failure. Time-related analysis showed that these complications occurred mostly during the first 3 months of assistance and this is particularly true for cerebrovascular events. The incidence of infections remained constant during the follow-up period. With a mean time of assistance of 203.1 days we had only two cases of device malfunction at 662 and 1297 days. Conclusions: LVAD Novacor has provided reliable mechanical performance and good hemodynamic improvement. Most complications seem to occur in the first 90 days, therefore long-term assistance could be considered. A reduction of the high rate of thromboembolic complications remains mandatory to improve the clinical results.

Key Words: Heart failure • Heart assist device • Mechanical support • Heart transplant

	1. Introduction

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

 
The number of heart transplants performed remains far below that of potential candidates, and for this reason many patients with a severely compromised hemodynamic status still die awaiting a donor. Different left ventricular assist devices (LVAD) have been designed to support those patients for use as a bridge for transplant [1,2]. Their clinical use has provided a great amount of information that is extremely useful for further development of a permanent implant [3,4]. In our department we have used LVAD Novacor (Baxter Healthcare Corp., Novacor Division, Oakland, CA) in 36 patients with a long mean period of assistance. In this study we review the results obtained, focusing our interest on the incidence of mechanical and clinical complications that occurred during the follow-up period. We believe that this could be a guideline to evaluate the possibility of a permanent implant for those patients not suitable for heart transplant.

	2. Materials and methods

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

 
Since 8 November, 1992 in our department we have implanted the LVAS Novacor in 36 patients as a bridge for transplant. The mean age was 50.4 years (range 29–68 years); four were female and 32 male.

One patient had myocarditis, three had severe left ventricular failure after coronary surgery, eight had ischemic cardiomyopathy and 24 dilated cardiomyopathy. Preoperatively, 30 patients were on high-dose inotrops, associated in 17 cases with vasodilators. Six patients also had intra-aortic balloon pump and two were on a centrifugal pump.

Two patients had light renal failure (creatinine level>2.5 mg/dl) and six patients had liver dysfunction (two of them with associated coagulopathy). Preimplant mean hemodynamic indexes showed cardiac output 2.6±0.8 l/min, wedge pressure 28.3±7.6 mmHg, mean pulmonary pressure 39±8.2 mmHg, pulmonary vascular resistance 357±173 dyne/s cm^-5, and right ventricular ejection fraction 13.6±10.5%. From patient no. 3 we implanted the wearable system and from the fifth we used the valved conduit device. For the last nine cases we have begun implantation of the newer model with Vascutek (Sulzer Vascutek Ltd., Inchinnan, Renfrewshire, UK) inflow and outflow conduits.

The procedures were carried out creating a pocket anteriorly to the posterior rectus sheath between the left iliac crest and the costal margin. Cardiopulmonary bypass was instituted and cold crystalloid cardioplegia was used in 31 cases. The device was implanted using an orthodromic technique as previously described by our group [5]. The inflow anastomosis at the apex of the left ventricle was performed and, after de-airing the device, we connected the outflow conduit to the ascending aorta. All patients were weaned from bypass but in 31 cases inotropic support was necessary to improve the right ventricular performance. Postoperative anticoagulation protocol in the first 22 patients included heparin, started as soon as the bleeding was controlled, followed by warfarin, after drains were removed, in order to maintain an international normalized ratio between 2.5 and 3.5. Aspirin, ticlopidin or dipyridamol were also used. The subsequent eight patients were treated according to the La Pitié protocol [6], while from patient no. 33 onward, we returned to the original scheme.

Statistical analysis was carried out using the Student t-test to compare the hemodynamic parameters (P significant if less than 0.001). Follow-up time scale was subdivided into 3- and 6-month intervals. For each interval, we recorded, for every patient, the time under observation and the observed events. For each interval incidence rates were computed together with their 95% confidence intervals. The incidence rate is expressed as the number of events per 100 person-months of observation.

	3. Results

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

 
There was a postoperative statistically significant improvement regarding: cardiac output, wedge pressure, mean pulmonary pressure and pulmonary vascular resistance. The improvement of the right ventricular ejection fraction was not statistically significant (Table 1).

Two patients who died from multiorgan failure were in critical condition before implant. The first was on high-dose inotrops and intra-aortic balloon pump, and the second was on a centrifugal pump. Probably in both cases the LVAD was implanted too late when clinical conditions were deteriorating. The third patient developed multiorgan failure as a terminal complication of mediastinitis. The patient who had right ventricular failure underwent right ventricular assistance but he could not be weaned and died before transplant. Of the 23 transplanted patients, seven died after the procedure with a survival rate after transplant of 69.5% and an overall survival rate of 50%. Causes of death were: severe surgical bleeding in one case, multiorgan failure in two cases, graft failure in two case, acute rejection in one case and anaphylactic shock in the last case. All the other transplanted patients were discharged home after a period of rehabilitation.

Mean time on device was 203.1 days (range 12–1297 days). During this period 20 patients remained in hospital, seven went to a rehabilitation center and nine were discharged home.

Complications occurred in 33 patients (Table 2): there were 11 cases of bleeding requiring re-exploration, 36 cerebral events in 21 patients (24 strokes, eight transient ischemic attacks and four hemorrhages) including those with negative CT scan and those without permanent clinical lesions, three peripheral embolisms, seven cable infections, two pocket infections that required re-exploration, two sepses (Candida albicans, Staphylococcus aureus), two major lung infections, one mediastinitis, one right ventricular failure that required right ventricular assistance, and three multiorgan failure.

Cerebrovascular complications were the cause of death in five patients and left permanent lesions in six cases. Among this last group we had three cases of hemiplegia. The first was a patient who underwent heart transplant and is now in a nursing home. The second was discharged home and subsequently transplanted, while the third is waiting for a donor in a rehabilitation center. We had one patient with residual dysarthria and one case of behavior disorders who were transplanted and discharged home. The last patient with residual cerebral events had severe cerebellar syndrome. He remained in hospital until he underwent heart transplant but died due to multiorgan failure. Thromboembolic events were associated with various degree of infections in five cases, atrial fibrillation in two and atherosclerosis in two. The risk of cerebrovascular complications and infections at different intervals of assistance is shown in Figs. 1 and 2

View larger version (13K): [in this window] [in a new window]   Fig. 1. Time-related analysis of cerebrovascular events.

View larger version (13K): [in this window] [in a new window]   Fig. 2. Time-related analysis of infectious events.

We did not have any other mechanical problem and all patients discharged to rehabilitation center or at home were able to manage with the machine without problems.

	4. Discussion

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

 
The shortage of donors and the great number of patients awaiting for heart transplant has led to the increasing use of LVAD. This is particularly true for those cases in urgent need of transplantation that cannot wait for long time. Often these patients cannot be managed only with medical therapy and need a mechanical support such as intra-aortic balloon pump or centrifugal pump. These kinds of devices present several problems and contraindications [7,8] that limit their long-term use and neither allow any mobilization of the patient.

In our experience the LVAD Novacor was used for those critical cases that could not wait for a donor on medical treatment, and all cases showed a marked improvement of their clinical conditions and hemodynamic parameters [9,10]. The right ventricular ejection fraction did not show a statistically significant increase as reported by other authors [11]. The postimplant quality of life was reasonable and 16 patients (41.3%) were discharged from hospital [10]. The remaining 20 cases stayed in hospital because of complications experienced or to undergo heart transplant (mean period 58.3 days).

Mortality rate on the device was severely influenced by cerebrovascular events (45.4%), which are the main problem with LVAD [12]. Two other patients who died on the device were in very poor clinical condition and probably the device was implanted too late. We now believe that when a patient waiting for transplant requires intra-aortic balloon pump or even a centrifugal pump, it is better to consider a LVAD before clinical conditions deteriorate and compromise the results.

The mortality rate in the transplanted group was high at the beginning of our experience with LVADs; in fact in the last 11 patients of this series our survival rate after transplant was 90.9%. Total complications occurred mostly during the first 3 months of assistance and after this period, most of the events were infections or a limited number of thromboembolic complications.

The incidence of bleeding was relatively low (30.5%) and we were able to manage all patients without problems [13]. Only one case developed multiorgan failure after severe hemorrhagic shock and died on day 15.

Thromboembolic and hemorrhagic cerebral complications in our series remain the main problems correlated to the LVAD. Our incidence is higher compared with other authors but is similar to other series [12–15]. These differing reports can be explained also because we consider the cases with negative CT scan and those without permanent clinical lesions.

We could not find any correlation between cerebrovascular events and the following: coagulation parameters, different protocols used, different antiplatelet drugs given and different model of device implanted. The correlation with risk factors for thromboembolism (47.3%) such as infections, atrial fibrillation and atherosclerosis [16] remains important.

Contrary to other authors, our statistical analysis shows that incidence of cerebrovascular events is significantly higher in the first 90 days and decreases progressively with time [17]. This situation could be related to an incomplete assessment of anticoagulation or short periods of low cardiac output in the initial time of support [18].

The incidence of sepsis and infections was similar to other series [17,18] and we have managed all cases without problems. As reported by other authors, mediastinitis did not develop in our patients with driveline or abdominal wound infections [17]. The incidence rate in our statistical analysis remains constant during the time of assistance.

The device showed reliable long-term performance with a maximum support time of 1290 days, similar to the 4.4 years obtained on bench. The reduced performance in the second patient was not machine-related but probably due to the severe intractable hypertension that led to an early wear of the device. In both cases the transplant was not performed as emergency.

In conclusion, we believe that LVAD Novacor has provided quite reliable mechanical performance and good hemodynamic improvement. Time-related analysis shows that most complications seem to occur in the first 90 days, therefore long-term assistance could be considered. A reduction of the high rate of thromboembolic complications remains mandatory in order to improve the clinical results.

	Footnotes

 
Presented at the 13th Annual Meeting of the European Association for Cardio-thoracic Surgery, Glasgow, Scotland, UK, September 5–8, 1999.

	Appendix A. Conference discussion

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

 
Dr C. Yankah (Berlin, Germany): I note you had a very high rate of thromboembolic events. My first question is, how is your anticoagulation regime? Secondly, how often do you control your valve cage? How do you monitor it regularly to detect early thrombosis around the cage, and whether you have also observed formation of neointima in your lines?

Dr Di Bella: Well, we have changed our anticoagulation protocol, because at the beginning used the Chicago one that was recommended by Novacor. Then in the other eight cases we started to use the same protocol that was employed at La Pitié by Dr Szefner. I can tell you now that our protocol is to use warfarin, trying to maintain the INR between 2.5 and 3.5, and we use antiplatelet drugs, generally aspirin. About the second question, we try to keep the cage under control, but not really very often I must say. As to the third question about the neointima, in our department we are starting now to examine the explant inflow and outflow conduits to see which kind of neointima is growing inside the conduit. So I cannot answer now although I hope to answer very soon.

Dr R. Koerfer (Bad Oeynhausen, Germany): What is the reason for having the patient on the Novacor device for 4 years?

Dr Di Bella: Well, that case was a particular case, because we had a problem in finding donors at the beginning. And this patient was really reluctant, after a while, to have her transplant. So it was a problem related to the patient and not related to our policy.

	References

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

 

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15. Houel R., Moczar M., Clerin V., Loisance D.Y. Pseudointima in inflow conduits of left ventricular assist devices. Ann Thorac Surg 1999;68:717-723.
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