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HETEROTOPIC ARTIFICIAL HEART AS BRIDGE TO CARDIAC TRANSPLANTATION
97
Letters
to
the Editor
HETEROTOPIC ARTIFICIAL HEART AS BRIDGE TO CARDIAC TRANSPLANTATION
S!R,—The clinical use of artificial hearts has been attempted for or as a bridge to cardiac transplantationThe bridging procedure has received increasing attention in the past 2 years and several attempts have been reported in the lay press but little has been published in scientific journals. In most cases, two artificial ventricles were placed in an orthotopic position after the patient’s heart had been removed, and the pneumatic energy source was outside the body. An alternative would be to have the prosthetic ventricles outside the body, provided total circulatory permanent heart replacementl
support can be achieved in this mode. The use of the prosthetic ventricles would be facilitated in this way, as would subsequent heart transplantation. The following case illustrates this approach. On Feb 10,1986, a 42-year-old man (weight 76 kg, body surface 1 ’79 m2) with severe cardiomyopathy who was a candidate for heart transplantation had an acute myocardial infarction with cardiogenic shock during cardiac catheterisation. His condition improved with medical treatment and intra-aortic balloon counterpulsation, allowing the patient to be transferred to our hospital. During the ensuing 3 days, his haemodynamic status was maintained at the price of increasing doses of dobutamine up to 35 g/kg/min and isoproterenol up to 0-16 g/kg/min. On day 4 of ventricular assistance, the patient became anuric and comatose; his mean arterial pressure fell from 60 to 40 mm Hg and the heart rate increased to 145/min. No donor heart being available, the use of an artificial heart was decided upon after the family’s consent had been obtained. The patient’s haemodynamic condition deteriorated further precluding his transfer to the cardiac operating theatre, so we had to operate in a room not equipped for extracorporeal circulation immediately next to the intensive care unit. area
The patient’s heart was exposed through a median sternotomy. The left ventricle was dilated and immobile and the right ventricle displayed weak contractions at a rate of 150/min. The interatrial groove was dissected up to a point close to the patent foramen ovale which was easily closed from outside the atrium by a large figure of88 suture under control of intra-atrial digital palpation (fig 1). After lateral clamping of the ascending aorta a 14 mm woven ’Dacron’ graft connected to a polyurethane cannula was anastomosed end-to-side to the aorta. 100 units of heparin was injected into the atrium and a polyurethane cannula with multiple holes was inserted through the roof of the left atrium to lie within the atrium and the left ventricle. The ends of these cannulas were brought out through the epigastric region and were connected to a Pierce-Donachy prosthetic ventricle driven by a modified Thoratec pneumatic console. The prosthetic left ventricle was immediately activated at a flow of4’21/min. The mean left atrial pressure fell from 21 to 8 mm Hg while the right atrial pressure increased to 25 mm Hg. The pulmonary artery was then clamped laterally and a 14 mm dacron graft connected to a cannula was anastomosed end-to-side. A cannula was inserted through the right atrial appendage into the atrium and the right ventricle. Both cannulas were brought out next to the left-ventricular cannulas and connected to another prosthetic ventricle. Flow was adjusted according to left and right atrial pressures and varied during the following 4 days between 4-5 and 5-11/min for the left prosthetic ventricle and between 4-1 and 4-6 1/min for the right prosthetic ventricle (fig 2).
Under total circulatory support, the patient became conscious after 4 hours, was extubated after 8 hours, and was drinking water within 10 hours. After 4 days and 4 hours of total circulatory support, a suitable donor heart was found. The patient was transferred to the cardiac surgery operating room with the artificial heart still functioning.
Extracorporeal
circulation
was
established between the
right
femoral artery and the superior and inferior vena cavae. The flow of the artificial heart was progressively reduced as the heart-lung
Fig I-Prosthetic ventricles connected from left and right ventricles to aorta and pulmonary artery without extracorporeal circulation. A: dissection of interatrial groove and external closure of patent foramen ovale. B: left cannula placed through roof of left atrium and mitral valve.
machine took over the systemic blood flow. The cannulas connected to the prosthetic ventricles were removed. The aorta and the pulmonary artery were divided above the anastomosis of the grafts after ascertaining that sufficient length of aorta and puhnonary artery was available from the donor heart. The transplantation was done without difficulty. The postoperative course was uneventful. Immunosuppression consisted ofmethylprednisolone, cyclosporin, antithymocyte globulin, and azathioprine in decreasing doses. The patient was discharged from the hospital 36 days after transplantation and resumed work 4 months after transplantation. Various types of ventricular artificial device have been developed which can be categorised into two groups according to flow characteristics. Ventricular assist devices are intended to assist failing but still functioning ventricles-ie, to provide a flow of 2-4 1/min. Artificial hearts are intended to take over the total function of the ventricles-ie, to provide a flow of 4-6 1/min. In contrast to ventricular assist devices, which are being used more and more for univentricular or biventricular assistance,3’ the clinical use of artificial hearts raises many technical and ethical questions.5,6 While use of a permanent artificial heart raises serious questions, the use of a temporary artificial heart as a bridge to transplantation is arousing growing interest in transplant surgeons.6 The development of this procedure depends upon both its efficiency and its practicability. Implantation of the prosthetic ventricles in an orthotopic position is . a major operation under extracorporeal circulation with a significant risk of bleeding, followed up by a more complex heart transplantation. This case demonstrates that total support of both ventricles can be achieved with heterotopic (extracorporeal) prosthetic ventricles in patients with severe cardiogenic shock or circulatory arrest while awaiting cardiac transplantation. The technique of implantation without extracorporeal circulation, which was developed in our laboratory with the aim of reducing the cost of experiments in sheep, turned out to be of critical importance for this patient, who could not have been transferred in time to the cardiac operating room. The absence of clotting factors and platelet disturbances, which would have resulted from extracorporeal
98 the immunisation schedules recommended for HDCV. We have immunised 376 people with PVRV in two French rabies control centres (163 vaccinees received a booster, 123 were given preexposure vaccination, and 90 were given post-exposure treatments for a total of 1013 injections).1 The vaccine was administered intramuscularly or subcutaneously. RFFIT was used for antibody titration; the lower limit of the test is 05 IU/ml. One month after the PVRV booster (n = 163) there was a highly significant increase in geometric mean antibody titre, which rose from 1.53 IU/ml to 10 IU/ml. For pre-exposure vaccination, the two immunisation schedules used were those most widely adopted since the recommendation of HDCV:2 either two injections on days 0 and 28 with a booster one year later (n 52) or three injections on days 0, 7, and 28 (n 71). All vaccinees were seronegative on day 0. Table i shows that there was a greater and more rapid increase in antibody levels with the three-injection schedule (mean 30-5 IU/n-il) than with the twoinjection schedule (8-40 IU/ml) (p < 0-002). =
Fig 2 Haemodynamics during total circulatory support of both left and right ventricles.
TABLE
=
I-SEROLOGICAL RESULTS OF TWO PRE-EXPOSURE IMMUNISATJON SCHEDULES
PAP = pulmonary artery pressure, PCWP= pulmonary capillary wedge pressure, RAP right atrial pressure. AoP=aortic pressure,
=
circulation, avoided bleeding problems. Cannulation of the left atrium through the flat and non-deformable atrial roof avoided the problems of suction often seen when the inflow cannula is placed through the left atrial appendage or through the apex of the heart. There has been one successful case of temporary left ventricle total support with an extracorporeal ventricular prosthesis reported and two cases of biventricular (total or partial?) support have been mentioned in the press.7 This is, to our knowledge the first reported case of bridge to transplant operation with total circulatory support by heterotopic extracorporeal artificial ventricles inserted without extracorporeal circulation. This alternative to the orthotopic artificial heart may open the way for new indications for bridging to transplant operations in patients who go into severe and irreversible cardiogenic shock while in units not equipped for cardiac surgery. A. CARPENTIER J. P. BRUGGERB. BERTHIER G. DREYFUS B. ABRY P. PERIER Department of Cardiovascular Surgery’ M. MELI R. ODERMATT and Laboratory for the Study CH. HAHN L. SCHAHMANECHE of Cardiac Prostheses, D. BENSASSON D. TOURNAY University of Paris VI, P. GUIBOURT R. GUILLEMAIN Hôpital Broussais, 75014 Paris, France; B. MOLLIN J. N. FABIANI and Cardiovascular Research Centre, C. DUBOST GAY J. Arzier, Switzerland
1. De Vries WC, Anderson JL, Joyce LD, et al. Clinical use of the total artificial heart. N
1984; 310: 273-78. Engl Med J 2. Cooley DA, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milaw JD. Orthotopic cardiac prosthesis for two staged cardiac replacement. Am J Cardiol 1969; 24: 723-30. 3. Zumbro GL, Shearer G, Kitchens WR, Galloway RF. Mechanical assistance for biventricular failure following coronary bypass operation and heart transplantation. Heart Transplant 1985; 4: 348-52. 4. Pierce WS, Parr GVS, Myers JL, Pae WE Jr, Bull AP, Waldhausen JA. Ventricular assist pumping in patients with cardiogenic shock after cardiac operations. N Engl J
Med 1981; 305: 1606-10. 5. Annas GJ. No cheers for temporary artificial hearts. Hastings Cent Rep 1985; 15: 27-28. 6. Relman AS. Artificial hearts: Permanent and temporary. N Engl J Med 1986; 314: 644-45. 7. Hill JD, Farrar DJ, Hershon JJ, et al. Use ofa prosthetic ventricle as a bridge to cardiac transplantation for postinfarction cardiogenic shock. N Engl J Med 1986; 314: 626-28.
RABIES VACCINE FOR HUMAN USE, CULTIVATED ON VERO CELLS
SIR,-Having had experience with human diploid cell strain rabies vaccine (HDCV), we have studied the new Pasteur inactivated rabies vaccine cultivated on Vero cells (1’VRV)1 using
*After one dose. t After two doses. TABLE 11-SEROCONVERSION RATE AND ANTIBODY LEVELS IN
POST-EXPOSURE TREATMENTS
For post-exposure treatment the HDCV protocol was used (six injections, on days 0, 3, 7, 14, 30, and 90). The immunogenicity of PVRV in post-exposure treatment was demonstrated by the increased antibody titres and the high percentage of seroconversion observed as early as day 14 (table 11) and by its protective effect over a follow-up over at least two years in patients bitten by laboratoryproven rabid animals (30% of cases). Most of the biting animals were dogs (45), followed by cats (27) and bovines (15 cases); rabies was confirmed by the laboratory in 20%,15 %, and 87% of animals,
respectively. The safety of PVRV was highly satisfactory. Some mild local reactions such as pain (13%), erythema (13%), or induration (4%) occurred at the inoculation site. Fever exceeding 37-5°C was observed in only 0-4% of cases, and no allergic-type reactions were reported. Comparative studies of the HDCV and PVRV are now being analysed and will be published. ’
Reims Rabies Control Centre
B. DUREUX PH. CANTON A. GERARD A. STRADY J. DEVILLE M. LIENARD
Institut Mérieux, Pans
N. AJJAN
Nancy Rabies Control Centre, CHU Brabois, 54500 Vandoeuvre-lès-Nancy, France
1. Fournier P, Montagnon B, Vincent-Falquet JC, Ajjan N, Drücker J, Roumiantzeff M A new vaccine produced from rabies virus cultivated on Vero cells. In: Vodopija I, Nicholson KG, Smerdel S, Bijok U, eds. Improvements in rabies post-exposure treatment. Zagreb: Zagreb Institute of Public Health, 1985: 115-21. 2. WHO Expert Committee on Rabies, 7th report. Tech Rep Ser, WHO 1984, no 709.
Letters
to
the Editor
HETEROTOPIC ARTIFICIAL HEART AS BRIDGE TO CARDIAC TRANSPLANTATION
S!R,—The clinical use of artificial hearts has been attempted for or as a bridge to cardiac transplantationThe bridging procedure has received increasing attention in the past 2 years and several attempts have been reported in the lay press but little has been published in scientific journals. In most cases, two artificial ventricles were placed in an orthotopic position after the patient’s heart had been removed, and the pneumatic energy source was outside the body. An alternative would be to have the prosthetic ventricles outside the body, provided total circulatory permanent heart replacementl
support can be achieved in this mode. The use of the prosthetic ventricles would be facilitated in this way, as would subsequent heart transplantation. The following case illustrates this approach. On Feb 10,1986, a 42-year-old man (weight 76 kg, body surface 1 ’79 m2) with severe cardiomyopathy who was a candidate for heart transplantation had an acute myocardial infarction with cardiogenic shock during cardiac catheterisation. His condition improved with medical treatment and intra-aortic balloon counterpulsation, allowing the patient to be transferred to our hospital. During the ensuing 3 days, his haemodynamic status was maintained at the price of increasing doses of dobutamine up to 35 g/kg/min and isoproterenol up to 0-16 g/kg/min. On day 4 of ventricular assistance, the patient became anuric and comatose; his mean arterial pressure fell from 60 to 40 mm Hg and the heart rate increased to 145/min. No donor heart being available, the use of an artificial heart was decided upon after the family’s consent had been obtained. The patient’s haemodynamic condition deteriorated further precluding his transfer to the cardiac operating theatre, so we had to operate in a room not equipped for extracorporeal circulation immediately next to the intensive care unit. area
The patient’s heart was exposed through a median sternotomy. The left ventricle was dilated and immobile and the right ventricle displayed weak contractions at a rate of 150/min. The interatrial groove was dissected up to a point close to the patent foramen ovale which was easily closed from outside the atrium by a large figure of88 suture under control of intra-atrial digital palpation (fig 1). After lateral clamping of the ascending aorta a 14 mm woven ’Dacron’ graft connected to a polyurethane cannula was anastomosed end-to-side to the aorta. 100 units of heparin was injected into the atrium and a polyurethane cannula with multiple holes was inserted through the roof of the left atrium to lie within the atrium and the left ventricle. The ends of these cannulas were brought out through the epigastric region and were connected to a Pierce-Donachy prosthetic ventricle driven by a modified Thoratec pneumatic console. The prosthetic left ventricle was immediately activated at a flow of4’21/min. The mean left atrial pressure fell from 21 to 8 mm Hg while the right atrial pressure increased to 25 mm Hg. The pulmonary artery was then clamped laterally and a 14 mm dacron graft connected to a cannula was anastomosed end-to-side. A cannula was inserted through the right atrial appendage into the atrium and the right ventricle. Both cannulas were brought out next to the left-ventricular cannulas and connected to another prosthetic ventricle. Flow was adjusted according to left and right atrial pressures and varied during the following 4 days between 4-5 and 5-11/min for the left prosthetic ventricle and between 4-1 and 4-6 1/min for the right prosthetic ventricle (fig 2).
Under total circulatory support, the patient became conscious after 4 hours, was extubated after 8 hours, and was drinking water within 10 hours. After 4 days and 4 hours of total circulatory support, a suitable donor heart was found. The patient was transferred to the cardiac surgery operating room with the artificial heart still functioning.
Extracorporeal
circulation
was
established between the
right
femoral artery and the superior and inferior vena cavae. The flow of the artificial heart was progressively reduced as the heart-lung
Fig I-Prosthetic ventricles connected from left and right ventricles to aorta and pulmonary artery without extracorporeal circulation. A: dissection of interatrial groove and external closure of patent foramen ovale. B: left cannula placed through roof of left atrium and mitral valve.
machine took over the systemic blood flow. The cannulas connected to the prosthetic ventricles were removed. The aorta and the pulmonary artery were divided above the anastomosis of the grafts after ascertaining that sufficient length of aorta and puhnonary artery was available from the donor heart. The transplantation was done without difficulty. The postoperative course was uneventful. Immunosuppression consisted ofmethylprednisolone, cyclosporin, antithymocyte globulin, and azathioprine in decreasing doses. The patient was discharged from the hospital 36 days after transplantation and resumed work 4 months after transplantation. Various types of ventricular artificial device have been developed which can be categorised into two groups according to flow characteristics. Ventricular assist devices are intended to assist failing but still functioning ventricles-ie, to provide a flow of 2-4 1/min. Artificial hearts are intended to take over the total function of the ventricles-ie, to provide a flow of 4-6 1/min. In contrast to ventricular assist devices, which are being used more and more for univentricular or biventricular assistance,3’ the clinical use of artificial hearts raises many technical and ethical questions.5,6 While use of a permanent artificial heart raises serious questions, the use of a temporary artificial heart as a bridge to transplantation is arousing growing interest in transplant surgeons.6 The development of this procedure depends upon both its efficiency and its practicability. Implantation of the prosthetic ventricles in an orthotopic position is . a major operation under extracorporeal circulation with a significant risk of bleeding, followed up by a more complex heart transplantation. This case demonstrates that total support of both ventricles can be achieved with heterotopic (extracorporeal) prosthetic ventricles in patients with severe cardiogenic shock or circulatory arrest while awaiting cardiac transplantation. The technique of implantation without extracorporeal circulation, which was developed in our laboratory with the aim of reducing the cost of experiments in sheep, turned out to be of critical importance for this patient, who could not have been transferred in time to the cardiac operating room. The absence of clotting factors and platelet disturbances, which would have resulted from extracorporeal
98 the immunisation schedules recommended for HDCV. We have immunised 376 people with PVRV in two French rabies control centres (163 vaccinees received a booster, 123 were given preexposure vaccination, and 90 were given post-exposure treatments for a total of 1013 injections).1 The vaccine was administered intramuscularly or subcutaneously. RFFIT was used for antibody titration; the lower limit of the test is 05 IU/ml. One month after the PVRV booster (n = 163) there was a highly significant increase in geometric mean antibody titre, which rose from 1.53 IU/ml to 10 IU/ml. For pre-exposure vaccination, the two immunisation schedules used were those most widely adopted since the recommendation of HDCV:2 either two injections on days 0 and 28 with a booster one year later (n 52) or three injections on days 0, 7, and 28 (n 71). All vaccinees were seronegative on day 0. Table i shows that there was a greater and more rapid increase in antibody levels with the three-injection schedule (mean 30-5 IU/n-il) than with the twoinjection schedule (8-40 IU/ml) (p < 0-002). =
Fig 2 Haemodynamics during total circulatory support of both left and right ventricles.
TABLE
=
I-SEROLOGICAL RESULTS OF TWO PRE-EXPOSURE IMMUNISATJON SCHEDULES
PAP = pulmonary artery pressure, PCWP= pulmonary capillary wedge pressure, RAP right atrial pressure. AoP=aortic pressure,
=
circulation, avoided bleeding problems. Cannulation of the left atrium through the flat and non-deformable atrial roof avoided the problems of suction often seen when the inflow cannula is placed through the left atrial appendage or through the apex of the heart. There has been one successful case of temporary left ventricle total support with an extracorporeal ventricular prosthesis reported and two cases of biventricular (total or partial?) support have been mentioned in the press.7 This is, to our knowledge the first reported case of bridge to transplant operation with total circulatory support by heterotopic extracorporeal artificial ventricles inserted without extracorporeal circulation. This alternative to the orthotopic artificial heart may open the way for new indications for bridging to transplant operations in patients who go into severe and irreversible cardiogenic shock while in units not equipped for cardiac surgery. A. CARPENTIER J. P. BRUGGERB. BERTHIER G. DREYFUS B. ABRY P. PERIER Department of Cardiovascular Surgery’ M. MELI R. ODERMATT and Laboratory for the Study CH. HAHN L. SCHAHMANECHE of Cardiac Prostheses, D. BENSASSON D. TOURNAY University of Paris VI, P. GUIBOURT R. GUILLEMAIN Hôpital Broussais, 75014 Paris, France; B. MOLLIN J. N. FABIANI and Cardiovascular Research Centre, C. DUBOST GAY J. Arzier, Switzerland
1. De Vries WC, Anderson JL, Joyce LD, et al. Clinical use of the total artificial heart. N
1984; 310: 273-78. Engl Med J 2. Cooley DA, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milaw JD. Orthotopic cardiac prosthesis for two staged cardiac replacement. Am J Cardiol 1969; 24: 723-30. 3. Zumbro GL, Shearer G, Kitchens WR, Galloway RF. Mechanical assistance for biventricular failure following coronary bypass operation and heart transplantation. Heart Transplant 1985; 4: 348-52. 4. Pierce WS, Parr GVS, Myers JL, Pae WE Jr, Bull AP, Waldhausen JA. Ventricular assist pumping in patients with cardiogenic shock after cardiac operations. N Engl J
Med 1981; 305: 1606-10. 5. Annas GJ. No cheers for temporary artificial hearts. Hastings Cent Rep 1985; 15: 27-28. 6. Relman AS. Artificial hearts: Permanent and temporary. N Engl J Med 1986; 314: 644-45. 7. Hill JD, Farrar DJ, Hershon JJ, et al. Use ofa prosthetic ventricle as a bridge to cardiac transplantation for postinfarction cardiogenic shock. N Engl J Med 1986; 314: 626-28.
RABIES VACCINE FOR HUMAN USE, CULTIVATED ON VERO CELLS
SIR,-Having had experience with human diploid cell strain rabies vaccine (HDCV), we have studied the new Pasteur inactivated rabies vaccine cultivated on Vero cells (1’VRV)1 using
*After one dose. t After two doses. TABLE 11-SEROCONVERSION RATE AND ANTIBODY LEVELS IN
POST-EXPOSURE TREATMENTS
For post-exposure treatment the HDCV protocol was used (six injections, on days 0, 3, 7, 14, 30, and 90). The immunogenicity of PVRV in post-exposure treatment was demonstrated by the increased antibody titres and the high percentage of seroconversion observed as early as day 14 (table 11) and by its protective effect over a follow-up over at least two years in patients bitten by laboratoryproven rabid animals (30% of cases). Most of the biting animals were dogs (45), followed by cats (27) and bovines (15 cases); rabies was confirmed by the laboratory in 20%,15 %, and 87% of animals,
respectively. The safety of PVRV was highly satisfactory. Some mild local reactions such as pain (13%), erythema (13%), or induration (4%) occurred at the inoculation site. Fever exceeding 37-5°C was observed in only 0-4% of cases, and no allergic-type reactions were reported. Comparative studies of the HDCV and PVRV are now being analysed and will be published. ’
Reims Rabies Control Centre
B. DUREUX PH. CANTON A. GERARD A. STRADY J. DEVILLE M. LIENARD
Institut Mérieux, Pans
N. AJJAN
Nancy Rabies Control Centre, CHU Brabois, 54500 Vandoeuvre-lès-Nancy, France
1. Fournier P, Montagnon B, Vincent-Falquet JC, Ajjan N, Drücker J, Roumiantzeff M A new vaccine produced from rabies virus cultivated on Vero cells. In: Vodopija I, Nicholson KG, Smerdel S, Bijok U, eds. Improvements in rabies post-exposure treatment. Zagreb: Zagreb Institute of Public Health, 1985: 115-21. 2. WHO Expert Committee on Rabies, 7th report. Tech Rep Ser, WHO 1984, no 709.