Orthotopic transplantation after implantation of a Jarvik 7 total artificial heart

J THoRAc CARDIOVASC SURG 1989;97:342-50

Orthotopic transplantation after implantation of a Jarvik 7 total artificial heart A total artificial heart was used to support the circulation in 33 heart transplantation candidates who were expected to die before procurement of a donor heart. Twelve of these patients (mean age 35 ± 10 years) underwent cardiac transplantation. Another patient is still being supported with the total artificial heart 90 days after implantation. The other 20 patients died during mechanical support because their condition could not be stabilized for transplantation, despite blood flow restoration. Fifty-six percent of the patients younger than 40 years underwent successful transplantation and six of nine patients are long-term survivors. By comparison, in the older group, 17.6 % of patients underwent transplantation and one of three survived long term. Forty-four percent of patients in the acute decompensation group bad successful transplantation and four of seven patients are long-term survivors. In the chronic decompensation group these figures were 29.4 % and three of five patients. All patients who were heavily immunosuppressed (n = 4) died of sepsis. Transplantation was considered and performed only when the patient's condition was correct and stable. In six patients an infection developed in the immediate posttransplant period. Three of the infections were resolved with antibiotic therapy. One originated in the mediastinum and is still unresolved, although the patient's condition is improving. Another patient died of !lIl anoxic coma caused by ventilatory problems. There were two late deaths at 14 and 19 months, one resulting from a combination of toxoplasmosis and rejection and the other from a Kaposi sarcoma caused by azathioprine treatment In conclusion, selection of the patient before implantation of the total artificial heart is critical to the outcome of the procedure. A strict policy of attempting heart transplantation only in the absence of any usual contraindications should be applied for patients subjected to bridge to transplant procedures. Survival after transplantation performed under such conditions seems to be equal to that of conventional orthotopic transplantation.

C. Cabrol, MD (by invitation), E. Solis, MD (by invitation), C. Muneretto, MD (by invitation), A. Pavie, MD (by invitation), I. Gandjbakhch, MD (by invitation), V. Bors, MD (by invitation), J. Szefner, MD (by invitation), P. Leger, MD (by invitation), and A. Cabrol, MD (by invitation), Paris, France Sponsored by Norman E. Shumway, MD, Stanford, Calif.

In recent years, heart transplantation has become a therapeutic option for patients with end-stage heart disease. This evolution has led to actuarial l-year and 5-year survival rates of 79% and 76%, respectively, and also to an improvement in the quality of life after transplantation in these patients.' Because of these results, indications for transplantation have been widFrom Groupe Hospitalier, Pitie-Salpetriere, Paris, France. Read at the Sixty-eighth Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, Calif., April 18-20, 1988. Address for reprints: C. Cabrol, MD, Groupe Hospitalier, PitieSalpetriere, 47 et 83, boulevard de l'Hopital, 75651 Paris Cedex 13, France.

342

ened, and the procedure has been offered to younger and older patients and to those desperately ill who require mechanical support before transplantation." With mechanical assistance as a bridge to transplantation, two main approaches have been used: (1) complete circulatory support during the waiting period with an orthotopic artificial heart- 5-7 and (2) the use of a heterotopic partial or total artificial heart (ventricular assist device).3.8-10 Other groups have reported the use of extracorporeal membrane oxygenation and intraaortic balloon counterpulsation as a bridge to transplantation.' This article will review our experience with patients who required implantation of a total artificial heart (T AH) and their progress after heart transplantation.

Volume 97 Number 3 March 1989

Jarvik 7 TAH

Table I. Causes of heart disease that indicate implantation of the TAH Coronary artery disease Acute Chronic Cardiomyopathy Acute Chronic Late acute rejection Post partum cardiomyopathy Valvular disease

100

:.:.:.

90

15 (45.4%)

80

11 (33.3%)

60

7

343

~ 40 years n:16

> 40 years

n:17

70

8 7 4

"" s sc Q>

C>

4 (12.1%) 2 1

(j;

Cl.

50

40 30 20 10

Patients and methods Thirty-three heart transplantation candidates who were expected to die before a donor heart could be found received a Jarvik 7 TAH (Symbion Inc., Salt Lake City, Utah) for hemodynamic support. Before implantation, all patients were desperately ill, with low cardiac output (mean 1.6 Ljmin). All were receiving maximal doses of inotropic drugs and had hepatic or renal problems, or both. Three patients were brought into the operating room in cardiac arrest with cardiac massage. The device implanted in 18 patients was the Jarvik 7 TAH. Their mean body surface area (BSA) was 1.84 ± 0.1 m'. Fifteen patients received the Jarvik 7-70 ml. Their mean BSA was 1.74 ± 0.1 m-. The device was implanted in the medial position in all of the patients and the drivelines were brought out in the left upper quadrant of the abdomen. The TAH were driven by a pneumatic drive console (Utah Drive, Symbion Inc., Salt Lake City, Utah) that provided alternating pulses of pressure and, if desired, vacuum to empty and fill the artificial ventricles. Immunosuppressive therapy after transplantation consisted initially of a combination of prednisone, azathioprine, and antithymocyte globulin. Cyclosporine was initiated when adequate renal function was achieved, generally on the second or third postoperative day." Results were assessed according to age, acute or chronic myocardial decompensation, and type of heart disease. Age was analyzed by dividing the patients into two groups: ::s40 years and >40 years. Myocardial decompensation was considered acute when heart failure was present for only 1 month before implantation of the TAH and chronic when it was of longer duration. Types of disease included cardiomyopathy, coronary artery disease, late acute rejection after transplantation, and postcardiotomy syndrome. The unpaired t test was used for the statistical comparisons, with p < 0.05 being considered significant.

Results Since 1968, we have performed 460 transplants in the heart transplant program at our hospital. Since April 1986, 33 patients have required preoperative mechanical support with a TAB as a bridge to transplantation. The series included 29 men and four women with a mean age of 39 ± 12 years (range 15 to 56 years). Indications for circulatory support are summarized in

...

-

Transplanted

Transplanted alive

Fig. 1. The influence of age (::S40 years and >40 years) on the outcome of patients with TAH support. The parts of the columns in white represent the percentage of patients who died during TAH support (transplanted columns) and those who died after transplantation (transplanted alive columns).

Table I. Twelve of these patients, mean age 35 ± 10 years (range 22 to 56 years), underwent cardiac transplantation. Another patient was receiving TAB support 90 days after implantation. Lyrnphotoxicity developed as a result of blood transfusions in this patient, and it has been very difficult to find a suitable heart. Afterward, a wound infection developed with subsequent contamination of the drivelines, which has been resolved. She is still awaiting transplantation in good condition. The influence of age on the outcome of these patients is depicted in Fig. 1. Fifty-six percent of the patients younger than 40 years had successful transplantation and six of nine patients are long-term survivors. By comparison, 17.6% of patients underwent transplantation in the older group and only one of the three survived long term. The influence of the status of these patients on their outcome is summarized in Fig. 2. Transplantation was successful in 44% of patients with acute decompensation, and four of the seven patients are long-term survivors. By comparison, there was a 29.4% success rate in the chronic group, with three of the five patients being long-term survivors. Table II is an overall analysis of patients with cardiomyopathy and ischemic heart disease. The results in the late acute rejection and the postcardiotomy groups are also summarized. Transplantation was more successful in patients in the cardiomyopathy group than in those in the ischemic heart disease group (46.2% versus 33%). Although the long-term survival rate after transplantation is greater in the cardiomyopathy group

The Journal of Thoracic and Cardiovascular Surgery

3 4 4 Cabrol et al.

100

Acute

90

n:16

Chronic n:17

80

70 60 ?f2. 50 Ql

g'40

~c

30

~

20 10 Transplanted

Transplanted alive

under TAH support

Fig. 2. The influence of the type of cardiac decompensation before TAH implantation on the outcome of these patients. The parts of the columns in white represent the percentage of patients who died during TAH support (transplanted columns) and those who died after transplantation (transplanted alive columns).

(five of six patients) than in the ischemic disease group (two of five patients), three patients with ischemic heart disease died in the early posttransplant period of mediastinitis (one patient), fulminant hepatitis (one patient), and an anoxic coma (one patient). These causes are not related to the ischemic disease. Table III summarizes the results obtained when the devices implanted were analyzed. The Jarvik 7-100 ml TAR was more successful (44.6% versus 26.6%) than the Jarvik 7-70 ml TAR. The long-term survival rate was also greater in the Jarvik 7-100 ml group (five of eight patients) than in the Jarvik 7-70 ml group (two of four patients). Figs. 3 and 4 present our preliminary hemodynamic data in the first 24 hours after implantation of the TAR. Left cardiac output and stroke volume are slightly higher in the Jarvik 7-100 ml device than in the Jarvik 7-70 ml TAR. Left atrial pressure was significantly higher (p < 0.05) in the Jarvik 7-100 ml group. When the group of patients undergoing transplantation (n = 12) was compared with the group of patients that died during mechanical support (n = 20), no significant differences were found in relation to age, BSA, and days under mechanical support. The only significant finding was extubation time after TAR implantation: 8 ± 6 days for the patients who died and 2 ± 1 days for those who underwent transplantation (p < 0.05). Results after transplantation Twelve patients received a heart transplant within 1 to 31 days of device implantation. They were 10 men

and two women with a follow-up period of 1 month to 2 years (mean 288 days). Seven patients are alive and well; one of them is still in the hospital, and six are at home or working full time. Six of the patients undergoing transplantation had an infection in the immediate posttransplant period. The site of infection was the mediastinum in two patients. One of them died of mediastinitis in association with rejection during the third week after transplantation; in the other, the infection is still unresolved but the patient's condition is improving. Another patient died of a fulminant hepatitis. Three infections had a nonspecific origin and all of them were resolved with antibiotic therapy. One patient died in the early posttransplant period of an anoxic coma resulting from ventilatory problems. There were two late deaths at 14 and 19 months, one from a combination of toxoplasmosis and rejection and the other from a Kaposi sarcoma caused by azathioprine treatment. Fig. 5 presents the l-year survival curve in our institution for patients with conventional orthotopic transplantation and for patients after bridge to transplant. We did not find a difference in survival curves between these two groups. Discussion Edward Youmans was a prominent nineteenth century chemist and popularizer of science who had a dream in 1859 in which he anticipated the development of an artificial heart." Since then, history has passed through Demikhov's first attempts" to use an artificial heart, Cooley's first clinical attempt" to use a TAR as a bridge to transplantation, and Copeland's first successful bridge to transplant operation." At present more than 100 implantations have been performed throughout the world, which shows that the use of a TAH has become a clinical reality. In our early experience, we2, 15 concluded that the best indications for the use of a TAR as a bridge to transplantation was in young patients with acute or chronic disease and in older patients with acute myocardial failure. We also determined that use of the deviceis contraindicated in immunosuppressed patients because of the high risk of infection. Those conclusions have not been altered by the analysis presented in this manuscript. We would like to discuss initially some practical points in the clinical setting and in the complex postoperative management of these patients. Clinical setting. Before implantation of the TAR, all our patients were assessed to assure that they had no contraindications to cardiac transplantation. After

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Jarvik 7 TAH

March 1989

345

Table II. Analysis according to type of disease Overall

Age (yr) TAH support (days) Jarvik 7~70 ml Jarvik 7-100 rnI Intubation time (days) Transplant Died during mechanical support Transplant, alive

Subgroups

Ischemic disease In = 15)

Cardiomyopathy In = 13)

Late acute rejection In = 4)

Postcardiotomy syndrome In = 4)

45.5 ± 7.3 14 ± 10.4 4 11 6.9 ± 6.3 5 (33.3%) 10 (66.7%) 2

35.4 ± 13 17.6 ± 9.8* 6 7 5.1 ± 5.2 6 (46.2%)* 6 (46.2%) 5

32 ± 13 16 ± 18.3 4 0 16 ± 18.3 0(0%) 4 (100%) 0

45.2 ± 9.6 6.7 ± 6.2 2 2 6.7 ± 6.2 1 (25%) 3 (75%) 1

This table analyzes our patients according to ischemic heart disease and cardiomyopathy. Two subgroups were also formed: late acute rejection and postcardiotomy syndrome. 'One patient still under TAH support.

implantation, they were removed from the transplantation list until their general condition and the function of their main organs appeared correct and stable; they were not returned to the waiting list to receive a donor heart until they were in the optimal condition to ensure survival. We have maintained this policy for two reasons: (1) because implantation of a donor heart has never reversed the status of an already severely compromised patient with major organ dysfunction or infection and (2) because the shortage of donor hearts makes it preferable to use them in the most suitable candidates. In 13 of our patients, implantation of the TAH brought a dramatic improvement in their condition. Two groups of patients were identified accordingly to their clinical course. The first compromised a few patients who received a TAH because of a sudden irreversible cardiac decompensation; they probably could have undergone conventional transplantation if a suitable heart had been available without delay. Because a donor heart was not available, they received a TAH, their condition improved rapidly, and they underwent transplantation a few days later when a suitable donor was referred to us. More commonly, the improvement after implantation was more progressive. Patients in this second group, although they did not have any permanent contraindication to transplantation, were not suitable for immediate transplantation. In such cases, implantation of the TAH stabilized their condition over several days or weeks so that they were then able to receive a donor heart. None of the patients who was in good condition died while awaiting transplantation. Thus donor availability did not play an important role in the outcome of patients receiving a TAH before transplantation. Unfortunately, a third group of patients was also

present. Despite all efforts and the satisfactory hemodynamics obtained with the TAH, no improvement in their previous organ dysfunction occurred (pulmonary, renal, hepatic) and further deterioration was seen. They were never placed on the waiting list for transplantation but were maintained on circulatory support, under the most appropriate therapy available, until they died of multiple organ failure, sepsis, or diffuse coagulopathy. It is not known whether another type of circulatory support (heterotopic artificial heart, biventricular assistance), necessitating a less traumatic operation, could allow more of these patients to become candidates for transplantation. In the future we will continue using the TAH, and we are also considering other types of support such as ventricular assist devices to further elucidate this point. Postoperative management. Four areas are the most important in the management of these patients: 1. 2. 3. 4.

Coagulation control Hemodynamic status Renal management Respiratory care

Coagulation protocol. Our coagulation protocol has been published previously." In our experience, thromboembolic complications have not been a problem because of the rigorous control to which these patients are subjected. In the same way, the amount of perioperative bleeding has been moderate despite severe coagulopathies and prolonged cardiopulmonary bypass pump runs in some patients. In these cases we believe that the systematic use of gelatin-resorcine-formol glue to seal the anastomotic sites has been of great help, as has our increasing experience in the management of these complex abnormal states. There was no evidence of clinical thromboembolic events or of major bleeding complications in any of the

The Journal of Thoracic and Cardiovascular Surgery

3 4 6 Cabrol et al.

100

0: Jarvik

9

7

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6

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0

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30 20

2

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6

12

18

24

Mean

Hours

Fig. 3. Blood flow of the TAH (mean ± 1 standard deviation) measured in the first 24 hours after implantation. BSAs between the two groups did not differ (BSA Jarvik 7-70 ml = 1.74 ± 1 m'; BSA Jarvik 7-100 ml = 1.84 ± 1 m'), There was no difference in blood flow characteristics during this period. LCD, Left cardiac output.

implantations in which this protocol was used. At explanation of the TAH, only small fibrin deposits in the inflow portion of the artificial ventricle and along the suture lines of the atrial cuff connectors were found. Hemodynamic status. During the early postoperative period, a correct hemodynamic balance should be obtained: Systemic, pulmonary, right atrial, and left atrial pressures should be kept within therapeutic ranges by controller regulation or intravenous infusion. Left atrial pressures greater than 15 mm Hg must be precluded to avoid pulmonary edema. Right atrial pressures should be maintained as low as possible to avoid renal venous hypertension, which causes a low glomerular filtration rate. The ideal cardiac output of a patient receiving a TAH is related to the preoperative status. We believe a cardiac output of 5 to 6 Ljmin is effective in the great majority of patients. Fig. 3 shows the mean cardiac output in all our implantations during the first 24 hours. Increased resistance with systemic or pulmonary hypertension, or both, is treated with vasodilators. We prefer sodium nitroprusside in the early postoperative period also, to increase glomerular filtration and urine output. Renal management. Renal failure may occur after implantation of a TAH, especially in patients with preexisting renal dysfunction. Almost all of our patients

6

12

18

24

30

Hours

Fig. 4. Comparison of the filling volume = stroke volume of the Jarvik 7-70 ml and Jarvik 7-100 ml in the first 24 hours after implantation. No differences were found in stroke volume during this period of time.

had decreased renal function before implantation. Therefore, maintaining or improving kidney performance is critical in the survival of these patients. We currently begin protecting the kidneys in the operating room by avoiding low perfusion pressures during extracorporeal circulation and using a membrane oxygenator to reduce cardiopulmonary bypass hemolysis. It is also important to maintain a good urinary output during the surgical procedure. After implantation of the TAH, the driving parameters should be controlled to improve glomerular filtration rate and to optimize blood urea nitrogen, creatinine levels, and urine output. All efforts should be made to maintain the urine output greater than 2 mljkgjhr during the first 36 hours with albumin, furosemide, and filling volume control. Carbon dioxide tension should be maintained at normal values to avoid renal damage; also, a moderate urine alkalinization protects the kidneys in the presence of oliguria. In patients with compromised renal function, nephrotoxic drugs are avoided. Those drugs excreted by the kidney are adjusted to appropriate dosages. Metabolic encephalopathy, acidosis, hyperkalemia, hypercalcemia, hypermagnesemia, hypernatremia, and hyperphosphatemia are indications for dialysis. Respiratory care. The patient is intubated on arrival in the intensive care unit. In routine cases, extubation is planned in the first 24 hours with sedation and ventilator settings gradually changed to meet this goal. This time allows for adequate rewarming, assurance of hemody-

Volume 97 Number 3

Jarvik 7 TAH

March 1989

Table m. Results obtained with the two TAH models that were implanted Jarvik 7-70 ml (n

Age (yr) TAH support (days) Intubation time (days) Transplant Died during mechanical support Transplant, alive

= 15)

35.2 ± 13.4 11.2 ± 10.9* 7 ± 5.7

100

90

80 '

Jarvik 7-100 ml (n

= 18)

41.5 ± 10 16 ± 8.9 5 ± 5.7

70

60 ?f2,

8 (44.6%) 10 (55.4%)

2

5

'One patient still under TAH support.

namic stability, and the initiation of spontaneous diuresis, before full awakening and extubation. The inspired oxygen concentration is gradually reduced, so that an oxygen tension of at least 80 mm Hg can be maintained. Ventilator rate is gradually decreased as the patient awakens. Extubation is usually performed when the patient is awake and nonacidotic, and an oxygen tension of at least 80 mm Hg on an inspired oxygen concentration of 40% and a carbon dioxide tension of 35 to 40 mm Hg on continuous positive airway pressure. In six of our patients a pulmonary infection developed leading to sepsis and death. Also, patients who received a heart transplant had a significantly shorter intubation time than patients who died during TAH support. Although intubation time is more related to the patient's preoperative status, we believe that prolonged intubation predisposes to infection and sepsis. Therefore, intensive physiotherapy is needed in the postoperative period to prevent atelectasis and to keep the airways clear of secretions. Postural drainage aided by vibration, tracheobronchial lavage, manual hyperinflation by an Ambu bag, and suction of secretions should be conducted every 3 hours. Specimens from the tracheobronchial aspirate should be sent for culture to detect early infection. Chest physiotherapy with percussion vibration and postural drainage is continued after extubation, especially in patients with heavy secretions or persistent atelectasis. Transplantation rate and survival rate were found to be higher for the patients who received the Jarvik 7-100 ml TAH than for those receiving the Jarvik 7-70 ml TAH (Table III). Preliminary hemodynamic data and comparisons between patients with good results (trans-

...... : conventional orthotopic transplantation _ : after bridge to transplant

'------------..... - _ ---- _._-----_ - - - .. -- - - .. ----

.

50

~ ;; 40 :;

(/l

4 (26.6%)* 10 (66.6%)

347

30

20 10 2

3

4

5

6

7

8

9

10

11 12Months

Fig. 5. One-year survival curve of the patients who had a bridge to transplant procedure (n = 12) and patients with conventional orthotopic transplantation (n = 210).

plantation) and bad results (death during TAH support) showed no difference in the first 24 hours (Figs. 3 and 4). Therefore we believe the difference is more related to the general status of the patient than to the hemodynamic performance of either artificial heart. Further analysis in this area should be done to reach a definitive conclusion. Infection after transplantation was common in our series and is a major risk in the use of prosthetic hearts. We believe this risk is related to the implantation of the device, to the prolonged instrumentation that attends the use of these mechanical devices, to a second operation in a short period of time, and finally to the immunosuppressive treatment of these patients. The l-year survival curve of the patients who had a bridge to transplant procedure was plotted against the survival curve of the heart transplant patients who did not have such support in our institution (Fig. 5). We found no difference between these two groups, but the small number of patients in the bridge to transplant group makes conclusions impossible. Conclusions Our experience indicates that the Jarvik 7 TAH is easy to run, safe and reliable, and allows in selected heart transplantation candidates an immediate and complete circulatory support so that the patient will remain in adequate condition until a transplantation can be done. Selection of the patient before implantation is critical to the outcome of the procedure. We currently prefer young patients with acute or chronic heart disease and older patients with acute decompensation of short

348

The Journal of Thoracic and Cardiovascular Surgery

Cabral et al.

duration. We try to avoid patients who are chronically ill or heavily immunosuppressed. Perioperative management needs to be improved in these extremely ill patients, who are subjected to a completely new type of hemodynamic support. A strict policy for heart transplantation should be applied for patients subjected to bridge to transplant procedures, with the definitive operation deferred until the patient's condition appears adequate and stable. Contraindications remain the same as for candidates subjected to conventional orthotopic transplantation. In such conditions, survival after transplantation seems to be equal to that after conventional orthotopic transplantation, which shows that this procedure does not compromise the patient's chance for successful transplantation. REFERENCES 1. Solis E, Kaye MP. The registry of the International Society for Heart Transplantation: third official reportJune 1986. J Heart Transplant 1986;5:2-5. 2. Solis E, Leger P, Muneretto C, et al. Clinical applications and patient selection in the use of a total artifical heart as a bridge for transplantation. Eur J Cardiothorac Surg 1988;2:65-71. 3. Farrar DJ, Hill J, Gray LA Jr, et al. Heterotopic prosthetic ventricles as a bridge to cardiac transplantation. N Engl J Med 1988;318:333-40. 4. Bolmann RM III, Spray TL, Cox JL, et al. Heart transplantation in patients requiring preoperative mechanical support. J Heart Transplant 1987;6:273-80. 5. Joyce LD, Johnson KE, Pierce WS, et al. Summary of the world experience with clinical use of total artificial hearts as heart support devices. J Heart Transplant 1986;5:22935. 6. Jarvik RK. Clinical application of the total artificial heart. Heart surgery. Rome: Casa Editrice Scientifica Internazionale, 1987:249-59. 7. Griffith BP, Kormos RL, Wei LM, Borovetz HS, Trento A, Hardesty RL. Use of the total artificial heart as an interim device: initial experience in Pittsburgh with four patients. J Heart Transplant 1986;5:210-4. 8. Hill JD, Farrar DJ, Hershon JJ, et al. Usc of a prosthetic ventricle as a bridge to cardiac transplantation for postinfarction cardiogenic shock. N Engl J Med 1986;314: 626-8. 9. Bolman RM III, Spray TL, Cox JL, et al. Heart transplantation in patients requmng preoperative mechanical support. J Heart Transplant 1987;6:273-80. 10. Pennock JL, Pierce WS, Campbell DB, et al. Mechanical support of the circulation followed by cardiac transplantation. J THORAC CARDIOVASC SURG 1986;92:994-1004. II. Cabrol C. La transplantation cardiaque a la PitieSalpetriere, Lab Sandoz 1986;61-78.

12. Fye WB. An artificial heart operation in 1859. J Heart Transplant 1986;5:178. 13. Demikhov YP. Experimental transplantation of vital organs. Hogh B, trans. New York: Consultants Bureau, 1962:212-3. 14. Cooley DA, Liotta D, Hallman GL, et al. Orthotopic cardiac prostheses for two staged cardiac replacement. Am J Cardiol 1969;24:723-30. 15. Cabrol C, Gandjbakhch I, Pavie A, et al. Total artificial heart as a bridge for transplantation: La Pitie 1986 to 1987. J Heart Transplant 1988;7:12-7.

Discussion Dr. Charles J. Hahn (Arzier, Switzerland). We are bridging patients in other ways because we have a special situation in our country. We provide complete circulatory support to European centers performing heart transplantation. This means that we have a selection of patients at the end stage of their cardiac failure. They all need complete support, and we supply it with the Pierce-Donachy device put into a heterotopic position. I have no time to discuss the advantages and disadvantages of the Jarvik TAH in the orthotopic position and the Pierce-Donachy device in the heterotopic position. There are two main advantages to our procedure: Extracorporeal circulation is not needed to put in place the cannulas of the heterotopic heart, and when the surgical team performs the transplantation, there is less bleeding because of fewer adhesions. Of course, the methods must be compared, as we have done with Dr. Cabrol for a long time. We have now performed 23 bridges to cardiac transplantation, with 20 patients undergoing transplantation. This means that we were able to correct multiorgan failure in 20 cases out of 23. Thirteen patients were discharged from the hospital; one died a few days later and 12 patients are living between 2 months and 2 years after the operation. The indications are the same as in the statistics reported by Dr. Cabrol. The bridging time ranges from I to 43 days. Forty-three days is not a long time, which explains why our patients did not have any infections. We also had no thromboembolic complications. Like Dr. Cabrol, I conclude that, with good patient selection and a well-trained team, the bridge to transplantation may be the only solution for some patients to survive, so long as we don't have enough donor hearts or a good prosthetic heart. Dr. Daniel Loisance (Creteil, France). I am rising to focus attention on the difficulties in the patient selection for the bridge to transplantation procedure. As most of us know, it is sometimes extremely difficult, in an emergency situation, to make the correct decision. Contraindications for transplantation are not always obvious. Evaluation of the actual potential of recovery of the native heart is equally difficult. Furthermore, the cost and ethical issues cannot be forgotten in a period of rising cost of health care and scarcity of donor grafts. For these various reasons, our group in Henri Mondor's Hospital, which is equipped with the Symbion system, has evaluated an alternative strategy to temporary implantation of a mechanical heart based on intravenous enoximone therapy.

Volume 97 Number 3 March 1989

This pharmacologic approach should permit better patient selection for cardiac transplantation. The strategy has been evaluated in the last 31 patients who were unresponsive to sympathomimetic therapy and referred for an immediate transplantation or a mechanical bridge to transplantation. In 29, the pharmacologic management avoided an immediate operation. Only 12 patients were selectedas good candidates and transplantation was performed within 6 days. In 17 responsive patients, some type of contraindication to transplantation was discovered. Nevertheless, in eight of those patients, a recovery of native heart function was observed, which permitted the patient to be discharged from the hospital. The most striking observation in this study has been the drastic reduction in the indications for mechanical heart implantation. Only three patients who were unresponsive to intravenous enoximone therapy required a mechanical heart. This experience suggests that new pharmacologic treatments may dramatically reduce the need for mechanical support in desperately ill patients who are unresponsive to sympathomimetic agents. Dr. William S. Pierce (Hershey. Pa.). Our group is somewhat unique in that we have had experience with both the artificial heart and the ventricular bypass system in these so-called bridge applications. In our experience with 50 cardiac transplants, three patients have had successful use of left ventricular bypass with a paracorporeal, pneumatically operated device. The longest period of bridging was 30 days in a patient who required the ventricular assist device. We believe this technique has important advantages over the artificial heart in terms of ease of application and reduced thromboembolic complications. Furthermore, when required, two pumps can be used to provide biventricular support. Since 1985, we have had the privilege of maintaining an international registry for the American Society for Artificial Internal Organs and the International Heart Transplant Society for the clinical use of circulatory support and the artificial heart. One hundred twenty-four patients have now been entered into this registry in the bridge category. The following is a sample of the information that is available through the registry. Left ventricular assist pump implantation: 29 patients, 22 undergoing transplantation, and 17 of those patients alive Right ventricular assist: only one patient, treated successfully Biventricular assistance: 44 patients, with 21 patients alive Total artificial heart: 50 patients recorded in the registry, with 22 of those patients alive All told, 124 patients have been "bridged," with 61 survivors. Further information regarding the registry and entry forms can be obtained from Dr. Walter Pae or from me. I would like to close by asking Dr. Cabrol to comment on two items: (1) the anticoagulation protocol that he is using in the patients with the Jarvik heart and (2) his feeling about the use of the TAH in the patient who has had a heart transplant but experiences acute rejection. Dr. Phillip E. Oyer (Stanford. Calif). Dr. Cabrol you indicated that you have used a left ventricular assist device in a

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number of patients. With this extensive experience with the Jarvik TAH, which to my knowledge is the largest of any single institution in the world, how do you now choose between a left ventricular assist device and a TAH? How do you make the distinction regarding which type of device is the best to use in a given patient? In addition, as you said, about half of the patients in whom the Jarvik TAH was implanted subsequently failed to qualify for a heart transplant. The question then becomes whether the failure to qualify for heart transplantation was related either to the device or, more important, to patient-related variables. That is, among those patients who did not come to transplantation, where there device-related problems or principally patient-related problems preventing transplantation? Dr. Cabrol (Closing). I would like to thank all of the discussants. The discussion with such pioneers in the field as Charles Hahn, William Pierce, and Phillip Oyer is a great honor for the team that presents this work. Dr. Loisance, we are waiting for better pharmacologic support in the future. So far we have used the maximal drug support presently available and the intraaortic balloon pump when possible before considering the placement of a TAH. The fact that three of our patients were brought into the operating room in irreversible cardiac arrest reflects the critical condition of those patients before implantation. Dr. Hahn, your series is an excellent one and our main hope is to obtain as good results as yours. Dr. Pierce, our coagulation control protocol was based on the modifications of the coagulation we observed with the appropriate tests in these patients; that is, exacerbated platelet activity, increased thrombin formation, and increased fibrinolysis. To normalize the platelet activity we used dipyridamole 150 to 350 mg intravenously every 6 hours and then aspirin 50 mg/day (the third or the fourth day). To counteract the excess thrombin formation we used low doses of heparin, 10 to 15 rug/day, in a continuous infusion, and to stop the fibrinolysis process we used aprotinin with an initial intravenous bolus of 1 million PI units followed by 4000 PI units/min in a continuous perfusion until the laboratory data were normalized. You also asked about our current policy for patients with irreversible rejection episodes. Because of the 100% mortality from infection in our four such cases, we have to decide in the future what to do in such situations. Either we must increase greatly the immunosuppressive therapy but not plan any further implantation of a TAH, or if the rejection episode appears too severe to respond to the increased immunosuppressive therapy, we must implant a TAH without any attempt at heavy immunosuppression which would compromise the success of the TAH implantation. Dr. Oyer, to answer your two questions: First, we used a ventricular assist device when we hoped the heart would recovery, for example, in patients unweanable from cardiac bypass after a conventionalcardiac operation. It happened that three of the patients that we could not wean from the ventricular assist device were suitable candidates for subsequent transplantation. When it was obvious from the very beginning that the heart would not recover, as in patients already in our waiting list for transplantation, we preferably used a TAH. Unfortunately, although we could reestablish a correct hemodynamic situation with the TAH, some of these patients had no improvement and even further aggravation of

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their previous hepatic or pulmonary dysfunction. That was why they died before we could plan a heart transplantation. They died during mechanical support from multiple organ failure often aggravated by a sepsis or coagulopathy. To conclude, it is impressive to see the extraordinary possibilitieswith such mechanical hearts. The patients not only

The Journal of Thoracic and Cardiovascular Surgery

survive in the hospital but also are able to go outside the hospital with the portable compressor and, for a few hours, have an almost normal family and social life. Such results must strongly encourage all research workers in the field to miniaturize the whole system to obtain the totally implantable artificial heart we are waiting for.

Notice of correction In the September 1988 issue of the JOURNAL, in the article by Naruke and associates entitled, "Prognosis and Survival in Resected Lung Carcinoma Based on the New International Staging System" (pages 440-7), errors were made in Table III and in the legends to Fig. 3 and Fig. 7. In Table III, in the section labeled "Squamous cell carcinoma," the number of patients should be as follows: Stage I, 179; Stage II, 109; Stage IlIA, 213; Stage IIIB, 51; Stage IV, 44. Fig. 3. Survival rates for 1479 patients in MO group after resection of lung cancer, according to postoperative N classification. Differences between groups: NO versus N1, p < 0.01; N1 versus N2, p < 0.01; N2 versus N3, p < 0.01. Fig. 7. Survival rates for 854 patients after resection of adenocarcinoma excluding 30 cases of alveolar cell type, according to postoperative stage. Differences between groups: stage I versus stage II, p < 0.01; stage II versus stage lIlA, p < 0.01; stage lIlA versus stage IIIB, P < 0.01; stage IIIB versus stage IV, NS.