EDITORIALS
The Isotopic Cardiac Pacemaker Andrew A. Gage, M.D.
In this issue of The Annals (p 14), Dr. Smyth and his associates report their experience with 59 patients with isotopic pacemakers and compare the results with those obtained in 77 control patients with conventional pacemakers. As they pointed out, the two groups were not comparable but some conclusions and recommendations were thought to be justified. N o pulse generator failures occurred in the group with isotopic pacemakers whereas malfunctions were observed in the control group. The authors suggest that an isotopic pulse generator be considered for every patient with a life expectancy of 10 years or more in spite of the still existing restrictive and cumbersome protocols required for licensing by the United States Nuclear Regulatory Commission. This recommendation deserves careful consideration but, in practice, the licensing requirements and the amendments now under consideration could well curtail the physician’s and patient’s access to what may be the treatment of choice in a given patient. The first implantation of a plutonium 238powered pacemaker (Medtronic, Alcatel 9000) was performed i n France in 1970 by Laurens and Piwnica [Z]. The design life of the device was 10 years, a modest goal but far better than the average pulse generator life of twenty months obtainable from the mercury cell pacemakers available at the time. The capsule containing the fuel (150 mg of a plutonium alloy) as well as the entire hermetically sealed pulse generator housing had been submitted to extensive tests simulating credible accidents such as vehicle collision, airplane crash, collapse of a building, gunshot wound, drowning, burial, and cremation. The containment of the fuel under these stresses met the specifications of the regulatory agencies. The level of radiation on the surface of the device was safe; for inFrom State University of New York at Buffalo School of Medicine, and the Surgical Service, the Veterans Administration Hospital, 3495 Bailey Ave, Buffalo, NY 14215.
1
0003-4975/79/070001-02$01.25 @ 1979 by Andrew A. Gage
stance, with a pulse generator placed in the pectoral position, the annual dose to the torso equaled that of the natural radiation background in the United States and was far less than the exposure resulting from diagnostic radiological examinations. In 1972, our group was licensed by the Nuclear Regulatory Commission, and in July of that year we implanted an isotopic pulse generator (Medtronic) in a patient in whom we had originally used a conventional pacemaker (July, 1960) [l]. The protocol required a life expectancy of 10 years, provisions for follow-up at three-month intervals, an identification bracelet for the patient, consent for removal of the pacemaker in case of death, and accountability for all devices used. Subsequently, isotopic pulse generators became available from other manufacturers (Arco, Cordis, and Coratomic). Today, two models (Cordis and Coratomic) can be considered to be secondgeneration devices comparable in size and weight to conventional pacemakers. Our clinical experience with isotopic pacemakers has been comparable to that of Smyth and his colleagues, except that we have noted a higher incidence of electrode problems. In 1975, the Nuclear Regulatory Commission prepared an environmental impact statement (released in 1976) in which it was concluded that the benefits of the isotopic pulse generator outweigh the risks to the patient and the environment. However, the restrictions of licensure were not lifted and remained a deterrent to clinical use. In 1977, the commission proposed a rule change (announced in the Federal Register) to authorize routine clinical use of isotopic pacemakers. Evaluation of this change is still under consideration, especially in regard to the advances that have been made in battery technology, the lithium-iodine battery in particular, which led to construction of the hermetically sealed, longer-lived pulse generators. Since 1972, approximately two hundred hospitals have been licensed to implant isotopic
2
The Annals of Thoracic Surgery Vol 28 No 1 July 1979
pulse generators for limited investigational use. We were fortunate to obtain the data on two pacemakers reported to the Nuclear Regulatory Commission by Medtronic and Coratomic: 618 pacemakers, Model 9000 (Medtronic), and 377 of the 100 Series (Coratomic). Eight failures have occurred in the Medtronic devices and five in the Coratomic. These numbers expressed in statistical terms amount to a failure rate of 0.05% of units per month at a 90% confidence level (Coratomic) and 0.07% per month at a 95% confidence level (Medtronic). This random electronic failure rate (no failure was related to the power source per se) is far below the failure rate observed in the control series and is well below the 0.15% rate per month considered to be acceptable by the Nuclear Regulatory Commission. It is quite clear that the reliability of the isotopic pulse generator has been excellent. It is also clear that the paperwork for protocols and reports has been burdensome. With respect to safety, follow-up, and retrieval of isotopic pulse generators, the record has been flawless. It is difficult to envision any potential risk to the general public. The greatest probable risk is that of burying a patient without removing the pulse generator-a trivial risk compared with those of the disposal of radioactive waste materials and the threat of nuclear arms. At present, virtually all implanted pulse generators are powered by lithium-iodine batteries, some of which have reached a proven 8-year life. We have used programmable lithium-powered pulse generators, which at a low-output setting have a potential life expectancy of about 12 years. However, there are many other models in use (aiming at being the smallest, thinnest, and lightest device) with a calculated average life of about 7 years. Reduction of size is obviously desirable but the present devices are already so small that this criterion has become almost meaningless. It is certainly possible to design a lithium pacemaker of acceptable dimensions and a potential life of 20 years. However, that is a far cry from the 77-year calculated life of the isotopic device (Coratomic 100). Furthermore, the decay of the radioactive fuel is accurately predictable; the future behavior of any chemical system is not.
The mortality of a pacemaker population is estimated to be 50°/o at the 5-year point; therefore, a 10-year device would meet the requirements of the majority of patients. This argument, although fallacious in certain respects, is certain to weigh heavily in the deliberations of the Nuclear Regulatory Commission. It is certain that a lifetime isotopic pulse generator would be the first choice for some percentage of the patients, although this percentage remains to be determined. If an isotopic pacemaker were to be considered for every patient less than 60 years old, the demand could not be met. It is important, however, to preserve the option of the availability of such a device without overregulation and to place the decision as to which patients might best benefit into the hands of the physicians and surgeons, where it properly belongs. Assessments of the costlbenefit ratio are becoming increasingly important in the practice of medicine. An isotopic device costs $6,000 compared with an average price of $2,800 for a programmable lithium-powered unit. Up to now, retrieval of isotopic units was important for the purpose of checking the function of the device and to control disposal. Now that function has been demonstrated, in the future it would seem that after nondestructive testing and refurbishing, reuse of devices may well become important. These considerations as well as the avoidance of costly repeat operations lead to the conclusion that economic considerations favor the greater initial investment represented by the isotopic pacemaker. In conclusion, I wish to emphasize that it is important that the option to use an isotopic pacemaker be kept open, that its use not be foreclosed or severely restricted by unnecessary cumbersome regulatory protocols, and that the decision as to who might benefit from this pacemaker be entrusted to the medical profession. References 1. Gage A, Chardack W, Federico A: Isotopic cardiac pacemaker. Arch Surg 109:671, 1974 2. Laurens P, Piwnica A: Stimulateur cardiaque isotopique, recherche sur la securite et la fiabilite a long terme. Arch Ma1 Coeur 63:906, 1970
The Isotopic Cardiac Pacemaker Andrew A. Gage, M.D.
In this issue of The Annals (p 14), Dr. Smyth and his associates report their experience with 59 patients with isotopic pacemakers and compare the results with those obtained in 77 control patients with conventional pacemakers. As they pointed out, the two groups were not comparable but some conclusions and recommendations were thought to be justified. N o pulse generator failures occurred in the group with isotopic pacemakers whereas malfunctions were observed in the control group. The authors suggest that an isotopic pulse generator be considered for every patient with a life expectancy of 10 years or more in spite of the still existing restrictive and cumbersome protocols required for licensing by the United States Nuclear Regulatory Commission. This recommendation deserves careful consideration but, in practice, the licensing requirements and the amendments now under consideration could well curtail the physician’s and patient’s access to what may be the treatment of choice in a given patient. The first implantation of a plutonium 238powered pacemaker (Medtronic, Alcatel 9000) was performed i n France in 1970 by Laurens and Piwnica [Z]. The design life of the device was 10 years, a modest goal but far better than the average pulse generator life of twenty months obtainable from the mercury cell pacemakers available at the time. The capsule containing the fuel (150 mg of a plutonium alloy) as well as the entire hermetically sealed pulse generator housing had been submitted to extensive tests simulating credible accidents such as vehicle collision, airplane crash, collapse of a building, gunshot wound, drowning, burial, and cremation. The containment of the fuel under these stresses met the specifications of the regulatory agencies. The level of radiation on the surface of the device was safe; for inFrom State University of New York at Buffalo School of Medicine, and the Surgical Service, the Veterans Administration Hospital, 3495 Bailey Ave, Buffalo, NY 14215.
1
0003-4975/79/070001-02$01.25 @ 1979 by Andrew A. Gage
stance, with a pulse generator placed in the pectoral position, the annual dose to the torso equaled that of the natural radiation background in the United States and was far less than the exposure resulting from diagnostic radiological examinations. In 1972, our group was licensed by the Nuclear Regulatory Commission, and in July of that year we implanted an isotopic pulse generator (Medtronic) in a patient in whom we had originally used a conventional pacemaker (July, 1960) [l]. The protocol required a life expectancy of 10 years, provisions for follow-up at three-month intervals, an identification bracelet for the patient, consent for removal of the pacemaker in case of death, and accountability for all devices used. Subsequently, isotopic pulse generators became available from other manufacturers (Arco, Cordis, and Coratomic). Today, two models (Cordis and Coratomic) can be considered to be secondgeneration devices comparable in size and weight to conventional pacemakers. Our clinical experience with isotopic pacemakers has been comparable to that of Smyth and his colleagues, except that we have noted a higher incidence of electrode problems. In 1975, the Nuclear Regulatory Commission prepared an environmental impact statement (released in 1976) in which it was concluded that the benefits of the isotopic pulse generator outweigh the risks to the patient and the environment. However, the restrictions of licensure were not lifted and remained a deterrent to clinical use. In 1977, the commission proposed a rule change (announced in the Federal Register) to authorize routine clinical use of isotopic pacemakers. Evaluation of this change is still under consideration, especially in regard to the advances that have been made in battery technology, the lithium-iodine battery in particular, which led to construction of the hermetically sealed, longer-lived pulse generators. Since 1972, approximately two hundred hospitals have been licensed to implant isotopic
2
The Annals of Thoracic Surgery Vol 28 No 1 July 1979
pulse generators for limited investigational use. We were fortunate to obtain the data on two pacemakers reported to the Nuclear Regulatory Commission by Medtronic and Coratomic: 618 pacemakers, Model 9000 (Medtronic), and 377 of the 100 Series (Coratomic). Eight failures have occurred in the Medtronic devices and five in the Coratomic. These numbers expressed in statistical terms amount to a failure rate of 0.05% of units per month at a 90% confidence level (Coratomic) and 0.07% per month at a 95% confidence level (Medtronic). This random electronic failure rate (no failure was related to the power source per se) is far below the failure rate observed in the control series and is well below the 0.15% rate per month considered to be acceptable by the Nuclear Regulatory Commission. It is quite clear that the reliability of the isotopic pulse generator has been excellent. It is also clear that the paperwork for protocols and reports has been burdensome. With respect to safety, follow-up, and retrieval of isotopic pulse generators, the record has been flawless. It is difficult to envision any potential risk to the general public. The greatest probable risk is that of burying a patient without removing the pulse generator-a trivial risk compared with those of the disposal of radioactive waste materials and the threat of nuclear arms. At present, virtually all implanted pulse generators are powered by lithium-iodine batteries, some of which have reached a proven 8-year life. We have used programmable lithium-powered pulse generators, which at a low-output setting have a potential life expectancy of about 12 years. However, there are many other models in use (aiming at being the smallest, thinnest, and lightest device) with a calculated average life of about 7 years. Reduction of size is obviously desirable but the present devices are already so small that this criterion has become almost meaningless. It is certainly possible to design a lithium pacemaker of acceptable dimensions and a potential life of 20 years. However, that is a far cry from the 77-year calculated life of the isotopic device (Coratomic 100). Furthermore, the decay of the radioactive fuel is accurately predictable; the future behavior of any chemical system is not.
The mortality of a pacemaker population is estimated to be 50°/o at the 5-year point; therefore, a 10-year device would meet the requirements of the majority of patients. This argument, although fallacious in certain respects, is certain to weigh heavily in the deliberations of the Nuclear Regulatory Commission. It is certain that a lifetime isotopic pulse generator would be the first choice for some percentage of the patients, although this percentage remains to be determined. If an isotopic pacemaker were to be considered for every patient less than 60 years old, the demand could not be met. It is important, however, to preserve the option of the availability of such a device without overregulation and to place the decision as to which patients might best benefit into the hands of the physicians and surgeons, where it properly belongs. Assessments of the costlbenefit ratio are becoming increasingly important in the practice of medicine. An isotopic device costs $6,000 compared with an average price of $2,800 for a programmable lithium-powered unit. Up to now, retrieval of isotopic units was important for the purpose of checking the function of the device and to control disposal. Now that function has been demonstrated, in the future it would seem that after nondestructive testing and refurbishing, reuse of devices may well become important. These considerations as well as the avoidance of costly repeat operations lead to the conclusion that economic considerations favor the greater initial investment represented by the isotopic pacemaker. In conclusion, I wish to emphasize that it is important that the option to use an isotopic pacemaker be kept open, that its use not be foreclosed or severely restricted by unnecessary cumbersome regulatory protocols, and that the decision as to who might benefit from this pacemaker be entrusted to the medical profession. References 1. Gage A, Chardack W, Federico A: Isotopic cardiac pacemaker. Arch Surg 109:671, 1974 2. Laurens P, Piwnica A: Stimulateur cardiaque isotopique, recherche sur la securite et la fiabilite a long terme. Arch Ma1 Coeur 63:906, 1970
