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Preliminary clinical experience with a new radioisotope-powered cardiac pacemaker
Preliminary clinical experience with a new radioisotope-powered cardiac pacemaker A small light-weight nuclear-powered pacer has been developed. The pulse generator weighs 61 Gm. and occupies a volume of 33 sq. cm. It is a standard R-wave inhibited (VVI) demand pulse generator. The unit has met all United States and foreign atomic energy commission safety specifications including mechanical shock, industrialfire,accidental crush, cremation, impact, and corrosion. Its calculated life is in excess of 20 years. The unit has been shown to be insensitive to electromagnetic interference (EMI) over a wide range of commonly encountered sources of interference. An extensive dog testing program has been carried out and is continuing. The United States Atomic Energy Commission (AEC) has issued a license to conduct clinical trials. These began in October, 1974, and a total of 30 units have been implanted so far. An equal number of chemical battery-powered pulse generators has been implanted in a control series of 30 patients. Preliminary results have been gratifying. Nicholas P. D. Smyth, M.D.,* George J. Magovern, M.D.,** William J. Cushing, M.D.,** John M. Keshishian, M.D.,* Leo C. Kelly, C.V.T.,* and Martin Dixon, B.S.,** Washington, D.C., Cheverly, Md., and Pittsburgh, Pa.
J. he development of a new isotope-powered pacemaker (Coratomic C-100t) has been described, and details of basic design and in vitro bench testing were given in a previous publication.1 Subsequent in vivo studies of the system in dogs were later described.2 In addition, details of in vitro and in vivo testing of the pacer response to a variety of electromagnetic interference (EMI) sources were described separately.3 The new pacemaker passed all tests satisfactorily. The 20 dogs prepared for long-term study are housed in a kennel approved by the Atomic Energy Commission (AEC). To date, 264 unit months have been accumulated without a pacer failure. Clinical trials under license from the AEC began in October, 1974, at The Washington Hospital Center in Washington, D. C., The Allegheny General Hospital in Pittsburgh, Pennsylvania, and later at Prince Georges General Hospital, Cheverly, Maryland. From the Departments of Surgery, The Washington Hospital Center, Washington, D. C, Prince Georges General Hospital, Cheverly, Md., and The Allegheny General Hospital, Pittsburgh, Pa. Received for publication May 28, 1975. The Washington Hospital Center and Prince Georges General Hospital. **The Allegheny General Hospital. tCoratomic, Incorporated, Indiana, Pa. 262
Materials and methods The pulse generator is a unipolar R-wave inhibited demand (VVI)4 unit. The electronic circuit is comprised of discrete components mounted on epoxy fiberglass boards, with the following nominal characteristics: 1. The pulse width is 1.0 msec. This pulse width is optimal in terms of energy required to capture the heart. There is no advantage in using a narrower pulse width since conservation of battery power is unimportant in a radioisotope-powered unit. 2. The pulse amplitude is 8 Ma. Since the nuclear battery has excess power available, there is no need to reduce pulse amplitude to conserve battery power. 3. The basic rate is 72 beats per minute. 4. The noise rate is 90 beats per minute. A rate higher than the basic rate was selected in order to minimize the possibility of competition and also to allow recognition of the fact that the pacer is operating in the interference mode. 5. The noise rate turn-on is approximately 20 Hz. This rate is selected to prevent interference from all conceivable noise modes with the exception of an unimportant sporadic impulse. It is sufficiently low to rule out 60 Hz rates, which are the most probable. 6. The magnetic switch rate is 90 beats per minute. This is a fixed rate which allows checking of
Volume 71 Number 2 February, 1976
Radioisotope-powered cardiac pacemaker
263
Table I Lead No.
Length (cm.)
Resistance (il)
Type
Electrode area (sq. cm.)
L-IO L-20 L-30
62 62 51
= 155 = 155 = 135
Endocardial Endocardial Myocardial
0.15 0.30 0.13
pacemaker performance in the R-wave inhibited mode. Again, a higher than basic rate was selected in order to minimize the possibility of competition. 7. The R-wave sensitivity is ±1.5 mv. (A.A.M.I.* standard square wave), selected to sense the R wave but reject P and T waves and EMI. 8. The refractory period is 275 msec. This electronic refractory period begins with either a normal R wave or the pacemaker stimulus. The nuclear battery utilizes 0.25 Gm. of plutonium238 in oxide form contained within a tantalum alloy capsule. The capsule is surrounded by vacuum insulation, and decay heat of the plutonium isotope provides a thermal gradient through a semiconducting thermopile to produce electrical power. A toroidal transformer in a DC/DC converter provides for increasing the battery output voltage to that required by the transistorized electronic circuit. A hermetically sealed and welded titanium case surrounds the electronics and nuclear battery and protects them from corrosive body fluids, water vapor, or gaseous contaminants. It shields the pacer electronics from EMI and also acts as the anode in the unipolar pacing system. Within the confines of the hermetically sealed titanium enclosure, the electronics and nuclear battery are cushioned to provide for shock and vibration isolation of these two critical sub-assemblies. The expected life of the pulse generator is in excess of 20 years.1 The three leads which have been designed for use with the Coratomic C-100 pacer have the characteristics given in Table I. The electrode in the L-10 and L-20 leads is platinum iridium. In the L-30 it is made of MP35N,5 an alloy. In all leads an MP35N helical wire covered with silicone rubber insulation leads to a titanium pin at the base of the lead which is secured in the pulse generator by a titanium set screw. The set screw bears on the titanium connector pin to make electrical contact, interconnecting the lead to a platinum rhodium connector welded to one end of the feedthrough terminal. The MP35N * Association for the Advancement of Medical Instrumentation, Arlington. Va.
Electrode diameter (mm.) 2.25 2.25 1.52
CORATOWC INC.
centim«t«rs Fig. 1. Photograph of pulse generator. (From Smyth, N. P. D.: J. THORAC. CARDIOVASC. SURG. 70: 2, 1975, published
by The C. V. Mosby Company.
alloy, 35 per cent nickel, 35 per cent cobalt, 20 per cent chromium, and 10 per cent molybdenum, has a tensile yield strength of 262,000 p.s.i. It is used because of its extremely good fatigue and corrosion resistance in body fluids. The electrical connection between the pulse generator feedthrough and the lead are electrically insulated and protected from body fluids by Hysol R8-2038 epoxy material as used in the AEC pacer.6 The epoxy top of the pulse generator is locked to the titanium case by a locking bracket which assures that no separation occurs between the titanium case and epoxy cap. The design is such that the surgeon, after inserting the lead and tightening the set screw, places one or two synthetic nonabsorbable sutures around the rubber boot and ties them firmly. This assures a tight seal at the lead-to-pacer interface. A silicone rubber plug with three O ring protuberances is then glued in place to prevent body fluids from entering the set screw cavity. Opposite the lead side of the pacer, a suture hole is
2 64
The Journal of Thoracic and Cardiovascular Surgery
Symth et al.
SET SCREW Pr-Rh CONNECTOR FEED THROUGH SUTURE HOLE NUCLEAR BATTERY ELECTRONICS
*^\
Fig. 2. Coratomic C-100 pacer. provided to attach the pulse generator to the adjacent muscle tissue in the pocket made for the pacer. A photograph of the pulse generator is shown in Fig. 1. It is 6 cm. long, 4.7 cm. high, and 1.92 cm. wide. It weighs 61 Gm. and occupies a space of 33 c.c. A cutaway drawing of the unit is shown in Fig. 2. The clinical protocol, 7 approved by the AEC, defines patient selection as follows: The patients to be selected for this clinical study will be those who have heart block or other form of symptomatic bradycardia requiring an implanted pacer. The physician will select patients who have a life expectancy of at least ten and preferably twenty years, in order to obtain a maximum amount of data concerning the longevity and reliability of the unit. An influential factor, however, other than longevity is that the small size and weight of the Coratomic unit may enhance the longevity of the patient compared to other pacemakers, and data on all age groups will, therefore, be of value since additional variables other than life expectancy are important in the C-100 test. For example, the smaller size and weight of the unit may be statistically significant in reducing pressure necrosis, lead failure or other volume and shape induced failures unknown at this time. For this reason, life expectancy alone, although still significant, is not as dominant a factor as in the use of other nuclear pacemakers heretofore licensed for clinical applications, and patients with a life expectancy less than 20 years should form part of the statistical sample. In certain cases, also, the physician may judge the use of the C-100 to be paramount in prolonging life in an older patient who has had many previous operations, or is resistant to frequent operations, or is not mentally capable of handling a rechargeable unit. In these cases, expected to be
a small percentage, the physician may use his discretion in implanting the C-100 unit.* The protocol also requires a control group of patients defined as follows: A reference control group, identified as closely as possible in age, sex, stability and diagnosis will be used. An attempt should be made to include in this group pacer systems using lithium or rechargeable nickel cadmium batteries to provide comparative data on other potentially long lived systems. The number of patients in this group should be equal to the C-100 group. All data and information collected from this group will be identical to that obtained with the C-100 pacer. All patients in the control group will have unipolar electrodes and have R-wave inhibited electronics powered by conventional sources currently available.* Since October, 1974, thirty Coratomic C-100 pacers have been inserted either as initial implants or replacements in patients at The Washington Hospital Center, Washington, D. C , The Allegheny General Hospital in Pittsburgh, Pennsylvania, and Prince Georges General Hospital, Cheverly, Maryland. A similar number of chemical battery-powered units have been inserted as controls. The indications for insertion of the C-100 pacemaker included varying degrees of heart block—spontaneous and postsurgical, intermittent heart block, and sick *From Human Clinical Protocol for the Coratomic C-100 Radioisotope Powered Cardiac Pacer, August, 1974, Coratomic, Incorporated, Indiana, Pa.
Volume 71 Number 2 February, 1976
Radioisotope-powered cardiac pacemaker
265
Table II. Test group (30 patients) Patient
■ (yr.)
Sex
Diagnosis
Lead
L. W.
63 61 60 68 57 64 59 22 35 69 61 64 69 64 68 63 65 55 52 62 62 53 52 63 63 54 60 50 45 61
F M M F M F F F F M F F M F F F M M M F M F M M F M F F M M
Sinus bradycardia and A-V block Third-degree heart block Sinus bradycardia and LBBB Sick sinus node syndrome Sick sinus node syndrome Third-degree heart block Third-degree heart block Sinus bradycardia and intermittent third-degree heart block Third-degree heart block after AVR Third-degree heart block 2:1 A-V block Second and intermittent third-degree heart block Second and intermittent third-degree heart block BBBB with bradycardia Third-degree heart block Sinus bradycardia Third-degree heart block Intermittent third-degree heart block after AVR LBBB and intermittent RBBB after AVR Sinus bradycardia Intermittent third-degree heart block Third-degree heart block Third-degree heart block Third-degree heart block Sick sinus syndrome A-V block after AVR Third-degree heart block Heart block Complete heart block Complete heart block after AVR
Cordis 4 mm. Cordis 4 mm. Coratomic L-20 Coratomic L-10 Cordis 4 mm. Cordis 4 mm. Medtronic 6914 Medtronic 6914 Medtronic 6917 Cordis 4 mm. Coratomic L-20 Coratomic L-10 Coratomic L-10 Cordis 4 mm. Cordis 4 mm. Cordis 4 mm. Cordis 2 mm. Coratomic L-10 Medtronic 6917 Coratomic L-10 Coratomic L-10 Coratomic L-10 Coratomic L-10 Coratomic L-10 Coratomic L-10 Cordis 2 mm. Medtronic 6914 Medtronic 6907 Coratomic L-20 Coratomic L-10
A. T. E. B. L. D. T. A. M . J. T. C. L. H. B. M. N. L.
M. Z. S. S. D. N. M. K.
M. C. M. B. P. F. E. H. B. H. A. K. G. C. A. P.
W. S. F. J. H. F. J. B. H. D. H. T. J. W .
C. D.
Legend: I. Initial implant. R. Replacement. A-V. Atrioventricular. LBBB, Left bundle branch block. AVR, Aortic valve replacement. BBBB. Bilateral bundle branch block.
sinus node syndrome (see Table II). In 17 cases the units were inserted as initial implants. In 11 cases the Coratomic L-10 transvenous lead was used. In 3 cases the L-20 lead was used. In all other cases including the thirteen replacements, other leads, endocardial or myocardial, were used with a Coratomic adaptor so that only a titanium pin was inserted into the Coratomic pulse generator to minimize the possibility of corrosion in the pin socket. The indications for pacemaker insertion in the control group were similar, but there were no constraints regarding patient age. The details are listed in Table III. Results In the 60 patients in the test and control groups there were no infections. All patients were studied 1 week postoperatively, 1 month postoperatively, and then at 3 month intervals. Complete study of the pacer param-
eters was carried out on each occasion. Studies for muscle inhibition were also carried out. One patient was omitted from the test series because of severe muscle twitching noted at operation. He had exhibited this with a conventional "canned" unipolar unit before, and a conventional bipolar pulse generator was therefore used. Muscle inhibition was not detected in any of the 30 patients that comprise the test series. All patients demonstrated normal demand (VVI) 4 pacing function initially. There was one late complication. In one patient sensing was lost after 2 months, during which his complete heart block (after aortic valve insertion) reverted to sinus rhythm. (Patient E. H., see Table II). At reoperation he was found to have a low-voltage R wave of 3.8 to 4.2 mv. Another pulse generator made by a different manufacturer was tried, but it showed only partial sensing. Since the patient's rate was satisfactory (70 beats per minute), the lead was simply
The Journal of Thoracic and Cardiovascular Surgery
2 6 6 Symth et al.
Table III. Control group (30 patients) Age Patient
(yr.)
Sex
Diagnosis
H. K. J. L. A. R. H. W. P. B.
66 36 57 70 51
M M M M M
R. H. J. C. A. S. D. C. D. H. F. M. B. K. A. K. T. T. T. M.
56 65 79 74 44 76 65 58 84 74
M M F M F F F M F M
M. H. I. N. W. T.
56 52 69
F F M
J. D. C. G. D. M.
43 72 58
M M M
C. C.
64
M
W. M. S. A. P. B.
60 76 35
M M M
R. S. A. T.
58 58
M F
W. R.
61
M
F. D. M. B.
83 81
F F
Sick sinus syndrome A-V block Complete heart block after AVR Third-degree heart block Artrial fibrillation with a slow ventricular response Third-degree heart block after MI Sick sinus syndrome Third-degree heart block Third-degree heart block Sick sinus syndrome Third-degree heart block Third-degree heart block Third-degree heart block Third-degree heart block Atrial fibrillation with a slow ventricular response Sinus bradycardia Sinus bradycardia Sinus bradycardia with intermittent A-V block Sinus bradycardia Third-degree A-V block Intermittent heart block with bradycardia Atrial tachyarrhythmias with A-V block and frequent PVC's Symptomatic bradycardia Sinus bradycardia and LBBB Sinus bradycardia with intermittent sinus arrest Heart block Brady-tachycardia with frequent PVC's Extensive coronary disease with Stokes-Adams syndrome Nodal bradycardia—CHF Sick sinus node syndrome
Lead
Pulse
generator
* * * * *
Cordis 2 mm. Metronic 6914 Medtronic 6917 Cordis 2 mm. Cordis 2 mm.
CPI 301UD (lithium) Medtronic 5945 (Hg Zn) Medtronic 5945 (Hg Zn) CPI 301UD (lithium) CPI 301UD (lithium)
* * * *
Medtronic 6901 Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 4 mm. Cordis 2 mm. Cordis 2 mm.
Medtronic 5944 (Hg Zn) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301 UD (lithium) CPI 301 UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium)
Medtronic 6907 Cordis 4 mm. Cordis 4 mm.
Medtronic 5945 (Hg Zn) Arco LI2-D (lithium) Medtronic 5951 (Hg Zn)
Medtronic 6901 Cordis 2 mm. Medtronic 6907
Medtronic 5944 (Hg Zn) CPI 301UD (lithium) Medtronic 5945 (Hg Zn)
*
Medtronic 6907
Medtronic 5945 (Hg Zn)
* * *
Medtronic 6901 Medtronic 6907 Medtronic 6914
Medtronic 5944 (Hg Zn) Medtronic 5945 (Hg Zn) Medtronic 5945 (Hg Zn)
* *
Medtronic 6907 Cordis 4 mm.
*
Medtronic 6907
Medtronic 5945 (Hg Zn) Cordis Omni-Stanicor (Hg Zn) Medtronic 5951 (Hg Zn)
Biotronik IE-60K Biotronik IE-60K
Biotronik IDP-44 (Hg Zn) Biotronik IDP-44 (Hg Zn)
* * * *
* *
* * * *
* *
* *
Legend: MI. Myocardial infarction. PVC. Premature ventricular contraction. CHF. Congestive heart failure. CPI. Cardiac Pacemakers. Inc. For other abbreviations see Table II.
capped and no pulse generator of any kind was reimplanted. In the control group there was one early complication (Patient H. K., Table III). The lead became displaced on the second postoperative day. It was repositioned, and there have been no further problems. There were two late complications. In 1 patient (R. H., Table III), erosion of the pulse generator through the skin occurred 6 months postoperatively. The pulse generator was repositioned and there have been no further problems. In the second patient (I. N., Table III) the Arco lithium pulse generator was replaced 9
months postoperatively because of malfunction demonstrated by a sensing failure Muscle inhibition was detected in Patient W. T. (Table III). However, the patient is completely asymptomatic. Discussion 1. The smooth contour of the radioisotopic unit should reduce the incidence of skin erosion in thin patients and in patients with skin devitalized by multiple incisions. 2. The small size and weight of the pulse generator
Volume 71 Number 2 February, 1976
have been very gratifying to both patient and surgeon alike. These factors should be important considerations in the use of the unit in small children. 3. No patient has expressed any apprehension because his pulse generator is run by nuclear power. 4. There is a delicate balance in the trade-off between the pulse generator's R-wave sensitivity and its insensitivity to extrinisic EMI and intrinsic EMI (skeletal muscle potentials). Some sacrifice in EMI resistance seems inevitable if the pulse generator is to sense all R waves, which is one of its essential functions and is more important than EMI rejection. 8 , 9 A more sensitive model of the C-100 unit with these characteristics has been prepared.* The existing model will be retained for patients with satisfactory R waves, especially if total EMI resistance is deemed important. Conclusion Preliminary clinical experience has been described with 30 cases in which a new radioisotopic cardiac pacemaker has been used and an equal number of control cases in which chemical battery-powered pacers have been used. The over-all experience in this very brief period of follow-up is gratifying, and extensive clinical trials of the radioisotopic pacemakers have been started in a number of collaborating institutions. * The Coratomic C-101.
Radioisotope-powered
cardiac pacemaker
267
REFERENCES
1 Purdy, D. L., Magovern, G. J., and Smyth, N. P. D.: A New Radioisotope-Powered Cardiac Pacer, J. THORAC. CARDIOVASC. SURG. 69: 82,
1975.
2 Smyth, N. P. D., Magovern, G. J., Ramirez, R. G., Diaz, M. H., Dixon, C. M., Fecht, D. C , and Johnson, A.: In Vivo Study of a New Radioisotope-Powered Cardiac Pacer, J. THORAC. CARDIOVASC. SURG. 70: 2,
1975.
3 Toler, J. C : Electromagnetic Performance—Final Technical Report, Project A-1628, June, 1974, Georgia Institute of Technology. 4 Parsonnet, V., Furman, S., and Smyth, N. P. D.: Implantable Cardiac Pacemakers. Status Report and Resource Guideline—Report of the Inter-Society Commission for Heart Disease Resources, Circulation 50: A-21, 1974. 5 Younkin, C. N.: Multiphase MP35N Alloy for Medical Implants, J. Biomed. Mater. Res. Symposium, No. 5 (Part 1), pp. 219-226, 1974. 6 Purdy, D. L., and Shapiro, Z.: Design of Isotopic Generators, Paper Number C/E-6, Transactions of Eighth Japan Conference on Radioisotopes, November, 1967. 7 Human Clinical Protocol for the Coratomic C-100 Radioisotope Powered Cardiac Pacer, Coratomic, Incorporated, Indiana, Pa., Aug. 1, 1974. 8 Smyth, N. P. D., Parsonnet, V., Escher, D. J. W., and Furman, S.: The Pacemaker Patient and the Electromagnetic Environment, J. A. M. A. 227: 1412, 1974. 9 Smyth, N. P. D., Alferness, C , Shearon, L., Rockland, R. H., Keshishian, J. M., and Johnson, A.: Clinical Evaluation of New Pulse Generator with Narrow Pulse Width for Conservation of Battery Energy, J. THORAC. CARDIOVASC. SURG. 68: 471,
1974.
J. he development of a new isotope-powered pacemaker (Coratomic C-100t) has been described, and details of basic design and in vitro bench testing were given in a previous publication.1 Subsequent in vivo studies of the system in dogs were later described.2 In addition, details of in vitro and in vivo testing of the pacer response to a variety of electromagnetic interference (EMI) sources were described separately.3 The new pacemaker passed all tests satisfactorily. The 20 dogs prepared for long-term study are housed in a kennel approved by the Atomic Energy Commission (AEC). To date, 264 unit months have been accumulated without a pacer failure. Clinical trials under license from the AEC began in October, 1974, at The Washington Hospital Center in Washington, D. C., The Allegheny General Hospital in Pittsburgh, Pennsylvania, and later at Prince Georges General Hospital, Cheverly, Maryland. From the Departments of Surgery, The Washington Hospital Center, Washington, D. C, Prince Georges General Hospital, Cheverly, Md., and The Allegheny General Hospital, Pittsburgh, Pa. Received for publication May 28, 1975. The Washington Hospital Center and Prince Georges General Hospital. **The Allegheny General Hospital. tCoratomic, Incorporated, Indiana, Pa. 262
Materials and methods The pulse generator is a unipolar R-wave inhibited demand (VVI)4 unit. The electronic circuit is comprised of discrete components mounted on epoxy fiberglass boards, with the following nominal characteristics: 1. The pulse width is 1.0 msec. This pulse width is optimal in terms of energy required to capture the heart. There is no advantage in using a narrower pulse width since conservation of battery power is unimportant in a radioisotope-powered unit. 2. The pulse amplitude is 8 Ma. Since the nuclear battery has excess power available, there is no need to reduce pulse amplitude to conserve battery power. 3. The basic rate is 72 beats per minute. 4. The noise rate is 90 beats per minute. A rate higher than the basic rate was selected in order to minimize the possibility of competition and also to allow recognition of the fact that the pacer is operating in the interference mode. 5. The noise rate turn-on is approximately 20 Hz. This rate is selected to prevent interference from all conceivable noise modes with the exception of an unimportant sporadic impulse. It is sufficiently low to rule out 60 Hz rates, which are the most probable. 6. The magnetic switch rate is 90 beats per minute. This is a fixed rate which allows checking of
Volume 71 Number 2 February, 1976
Radioisotope-powered cardiac pacemaker
263
Table I Lead No.
Length (cm.)
Resistance (il)
Type
Electrode area (sq. cm.)
L-IO L-20 L-30
62 62 51
= 155 = 155 = 135
Endocardial Endocardial Myocardial
0.15 0.30 0.13
pacemaker performance in the R-wave inhibited mode. Again, a higher than basic rate was selected in order to minimize the possibility of competition. 7. The R-wave sensitivity is ±1.5 mv. (A.A.M.I.* standard square wave), selected to sense the R wave but reject P and T waves and EMI. 8. The refractory period is 275 msec. This electronic refractory period begins with either a normal R wave or the pacemaker stimulus. The nuclear battery utilizes 0.25 Gm. of plutonium238 in oxide form contained within a tantalum alloy capsule. The capsule is surrounded by vacuum insulation, and decay heat of the plutonium isotope provides a thermal gradient through a semiconducting thermopile to produce electrical power. A toroidal transformer in a DC/DC converter provides for increasing the battery output voltage to that required by the transistorized electronic circuit. A hermetically sealed and welded titanium case surrounds the electronics and nuclear battery and protects them from corrosive body fluids, water vapor, or gaseous contaminants. It shields the pacer electronics from EMI and also acts as the anode in the unipolar pacing system. Within the confines of the hermetically sealed titanium enclosure, the electronics and nuclear battery are cushioned to provide for shock and vibration isolation of these two critical sub-assemblies. The expected life of the pulse generator is in excess of 20 years.1 The three leads which have been designed for use with the Coratomic C-100 pacer have the characteristics given in Table I. The electrode in the L-10 and L-20 leads is platinum iridium. In the L-30 it is made of MP35N,5 an alloy. In all leads an MP35N helical wire covered with silicone rubber insulation leads to a titanium pin at the base of the lead which is secured in the pulse generator by a titanium set screw. The set screw bears on the titanium connector pin to make electrical contact, interconnecting the lead to a platinum rhodium connector welded to one end of the feedthrough terminal. The MP35N * Association for the Advancement of Medical Instrumentation, Arlington. Va.
Electrode diameter (mm.) 2.25 2.25 1.52
CORATOWC INC.
centim«t«rs Fig. 1. Photograph of pulse generator. (From Smyth, N. P. D.: J. THORAC. CARDIOVASC. SURG. 70: 2, 1975, published
by The C. V. Mosby Company.
alloy, 35 per cent nickel, 35 per cent cobalt, 20 per cent chromium, and 10 per cent molybdenum, has a tensile yield strength of 262,000 p.s.i. It is used because of its extremely good fatigue and corrosion resistance in body fluids. The electrical connection between the pulse generator feedthrough and the lead are electrically insulated and protected from body fluids by Hysol R8-2038 epoxy material as used in the AEC pacer.6 The epoxy top of the pulse generator is locked to the titanium case by a locking bracket which assures that no separation occurs between the titanium case and epoxy cap. The design is such that the surgeon, after inserting the lead and tightening the set screw, places one or two synthetic nonabsorbable sutures around the rubber boot and ties them firmly. This assures a tight seal at the lead-to-pacer interface. A silicone rubber plug with three O ring protuberances is then glued in place to prevent body fluids from entering the set screw cavity. Opposite the lead side of the pacer, a suture hole is
2 64
The Journal of Thoracic and Cardiovascular Surgery
Symth et al.
SET SCREW Pr-Rh CONNECTOR FEED THROUGH SUTURE HOLE NUCLEAR BATTERY ELECTRONICS
*^\
Fig. 2. Coratomic C-100 pacer. provided to attach the pulse generator to the adjacent muscle tissue in the pocket made for the pacer. A photograph of the pulse generator is shown in Fig. 1. It is 6 cm. long, 4.7 cm. high, and 1.92 cm. wide. It weighs 61 Gm. and occupies a space of 33 c.c. A cutaway drawing of the unit is shown in Fig. 2. The clinical protocol, 7 approved by the AEC, defines patient selection as follows: The patients to be selected for this clinical study will be those who have heart block or other form of symptomatic bradycardia requiring an implanted pacer. The physician will select patients who have a life expectancy of at least ten and preferably twenty years, in order to obtain a maximum amount of data concerning the longevity and reliability of the unit. An influential factor, however, other than longevity is that the small size and weight of the Coratomic unit may enhance the longevity of the patient compared to other pacemakers, and data on all age groups will, therefore, be of value since additional variables other than life expectancy are important in the C-100 test. For example, the smaller size and weight of the unit may be statistically significant in reducing pressure necrosis, lead failure or other volume and shape induced failures unknown at this time. For this reason, life expectancy alone, although still significant, is not as dominant a factor as in the use of other nuclear pacemakers heretofore licensed for clinical applications, and patients with a life expectancy less than 20 years should form part of the statistical sample. In certain cases, also, the physician may judge the use of the C-100 to be paramount in prolonging life in an older patient who has had many previous operations, or is resistant to frequent operations, or is not mentally capable of handling a rechargeable unit. In these cases, expected to be
a small percentage, the physician may use his discretion in implanting the C-100 unit.* The protocol also requires a control group of patients defined as follows: A reference control group, identified as closely as possible in age, sex, stability and diagnosis will be used. An attempt should be made to include in this group pacer systems using lithium or rechargeable nickel cadmium batteries to provide comparative data on other potentially long lived systems. The number of patients in this group should be equal to the C-100 group. All data and information collected from this group will be identical to that obtained with the C-100 pacer. All patients in the control group will have unipolar electrodes and have R-wave inhibited electronics powered by conventional sources currently available.* Since October, 1974, thirty Coratomic C-100 pacers have been inserted either as initial implants or replacements in patients at The Washington Hospital Center, Washington, D. C , The Allegheny General Hospital in Pittsburgh, Pennsylvania, and Prince Georges General Hospital, Cheverly, Maryland. A similar number of chemical battery-powered units have been inserted as controls. The indications for insertion of the C-100 pacemaker included varying degrees of heart block—spontaneous and postsurgical, intermittent heart block, and sick *From Human Clinical Protocol for the Coratomic C-100 Radioisotope Powered Cardiac Pacer, August, 1974, Coratomic, Incorporated, Indiana, Pa.
Volume 71 Number 2 February, 1976
Radioisotope-powered cardiac pacemaker
265
Table II. Test group (30 patients) Patient
■ (yr.)
Sex
Diagnosis
Lead
L. W.
63 61 60 68 57 64 59 22 35 69 61 64 69 64 68 63 65 55 52 62 62 53 52 63 63 54 60 50 45 61
F M M F M F F F F M F F M F F F M M M F M F M M F M F F M M
Sinus bradycardia and A-V block Third-degree heart block Sinus bradycardia and LBBB Sick sinus node syndrome Sick sinus node syndrome Third-degree heart block Third-degree heart block Sinus bradycardia and intermittent third-degree heart block Third-degree heart block after AVR Third-degree heart block 2:1 A-V block Second and intermittent third-degree heart block Second and intermittent third-degree heart block BBBB with bradycardia Third-degree heart block Sinus bradycardia Third-degree heart block Intermittent third-degree heart block after AVR LBBB and intermittent RBBB after AVR Sinus bradycardia Intermittent third-degree heart block Third-degree heart block Third-degree heart block Third-degree heart block Sick sinus syndrome A-V block after AVR Third-degree heart block Heart block Complete heart block Complete heart block after AVR
Cordis 4 mm. Cordis 4 mm. Coratomic L-20 Coratomic L-10 Cordis 4 mm. Cordis 4 mm. Medtronic 6914 Medtronic 6914 Medtronic 6917 Cordis 4 mm. Coratomic L-20 Coratomic L-10 Coratomic L-10 Cordis 4 mm. Cordis 4 mm. Cordis 4 mm. Cordis 2 mm. Coratomic L-10 Medtronic 6917 Coratomic L-10 Coratomic L-10 Coratomic L-10 Coratomic L-10 Coratomic L-10 Coratomic L-10 Cordis 2 mm. Medtronic 6914 Medtronic 6907 Coratomic L-20 Coratomic L-10
A. T. E. B. L. D. T. A. M . J. T. C. L. H. B. M. N. L.
M. Z. S. S. D. N. M. K.
M. C. M. B. P. F. E. H. B. H. A. K. G. C. A. P.
W. S. F. J. H. F. J. B. H. D. H. T. J. W .
C. D.
Legend: I. Initial implant. R. Replacement. A-V. Atrioventricular. LBBB, Left bundle branch block. AVR, Aortic valve replacement. BBBB. Bilateral bundle branch block.
sinus node syndrome (see Table II). In 17 cases the units were inserted as initial implants. In 11 cases the Coratomic L-10 transvenous lead was used. In 3 cases the L-20 lead was used. In all other cases including the thirteen replacements, other leads, endocardial or myocardial, were used with a Coratomic adaptor so that only a titanium pin was inserted into the Coratomic pulse generator to minimize the possibility of corrosion in the pin socket. The indications for pacemaker insertion in the control group were similar, but there were no constraints regarding patient age. The details are listed in Table III. Results In the 60 patients in the test and control groups there were no infections. All patients were studied 1 week postoperatively, 1 month postoperatively, and then at 3 month intervals. Complete study of the pacer param-
eters was carried out on each occasion. Studies for muscle inhibition were also carried out. One patient was omitted from the test series because of severe muscle twitching noted at operation. He had exhibited this with a conventional "canned" unipolar unit before, and a conventional bipolar pulse generator was therefore used. Muscle inhibition was not detected in any of the 30 patients that comprise the test series. All patients demonstrated normal demand (VVI) 4 pacing function initially. There was one late complication. In one patient sensing was lost after 2 months, during which his complete heart block (after aortic valve insertion) reverted to sinus rhythm. (Patient E. H., see Table II). At reoperation he was found to have a low-voltage R wave of 3.8 to 4.2 mv. Another pulse generator made by a different manufacturer was tried, but it showed only partial sensing. Since the patient's rate was satisfactory (70 beats per minute), the lead was simply
The Journal of Thoracic and Cardiovascular Surgery
2 6 6 Symth et al.
Table III. Control group (30 patients) Age Patient
(yr.)
Sex
Diagnosis
H. K. J. L. A. R. H. W. P. B.
66 36 57 70 51
M M M M M
R. H. J. C. A. S. D. C. D. H. F. M. B. K. A. K. T. T. T. M.
56 65 79 74 44 76 65 58 84 74
M M F M F F F M F M
M. H. I. N. W. T.
56 52 69
F F M
J. D. C. G. D. M.
43 72 58
M M M
C. C.
64
M
W. M. S. A. P. B.
60 76 35
M M M
R. S. A. T.
58 58
M F
W. R.
61
M
F. D. M. B.
83 81
F F
Sick sinus syndrome A-V block Complete heart block after AVR Third-degree heart block Artrial fibrillation with a slow ventricular response Third-degree heart block after MI Sick sinus syndrome Third-degree heart block Third-degree heart block Sick sinus syndrome Third-degree heart block Third-degree heart block Third-degree heart block Third-degree heart block Atrial fibrillation with a slow ventricular response Sinus bradycardia Sinus bradycardia Sinus bradycardia with intermittent A-V block Sinus bradycardia Third-degree A-V block Intermittent heart block with bradycardia Atrial tachyarrhythmias with A-V block and frequent PVC's Symptomatic bradycardia Sinus bradycardia and LBBB Sinus bradycardia with intermittent sinus arrest Heart block Brady-tachycardia with frequent PVC's Extensive coronary disease with Stokes-Adams syndrome Nodal bradycardia—CHF Sick sinus node syndrome
Lead
Pulse
generator
* * * * *
Cordis 2 mm. Metronic 6914 Medtronic 6917 Cordis 2 mm. Cordis 2 mm.
CPI 301UD (lithium) Medtronic 5945 (Hg Zn) Medtronic 5945 (Hg Zn) CPI 301UD (lithium) CPI 301UD (lithium)
* * * *
Medtronic 6901 Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 2 mm. Cordis 4 mm. Cordis 2 mm. Cordis 2 mm.
Medtronic 5944 (Hg Zn) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301 UD (lithium) CPI 301 UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium) CPI 301UD (lithium)
Medtronic 6907 Cordis 4 mm. Cordis 4 mm.
Medtronic 5945 (Hg Zn) Arco LI2-D (lithium) Medtronic 5951 (Hg Zn)
Medtronic 6901 Cordis 2 mm. Medtronic 6907
Medtronic 5944 (Hg Zn) CPI 301UD (lithium) Medtronic 5945 (Hg Zn)
*
Medtronic 6907
Medtronic 5945 (Hg Zn)
* * *
Medtronic 6901 Medtronic 6907 Medtronic 6914
Medtronic 5944 (Hg Zn) Medtronic 5945 (Hg Zn) Medtronic 5945 (Hg Zn)
* *
Medtronic 6907 Cordis 4 mm.
*
Medtronic 6907
Medtronic 5945 (Hg Zn) Cordis Omni-Stanicor (Hg Zn) Medtronic 5951 (Hg Zn)
Biotronik IE-60K Biotronik IE-60K
Biotronik IDP-44 (Hg Zn) Biotronik IDP-44 (Hg Zn)
* * * *
* *
* * * *
* *
* *
Legend: MI. Myocardial infarction. PVC. Premature ventricular contraction. CHF. Congestive heart failure. CPI. Cardiac Pacemakers. Inc. For other abbreviations see Table II.
capped and no pulse generator of any kind was reimplanted. In the control group there was one early complication (Patient H. K., Table III). The lead became displaced on the second postoperative day. It was repositioned, and there have been no further problems. There were two late complications. In 1 patient (R. H., Table III), erosion of the pulse generator through the skin occurred 6 months postoperatively. The pulse generator was repositioned and there have been no further problems. In the second patient (I. N., Table III) the Arco lithium pulse generator was replaced 9
months postoperatively because of malfunction demonstrated by a sensing failure Muscle inhibition was detected in Patient W. T. (Table III). However, the patient is completely asymptomatic. Discussion 1. The smooth contour of the radioisotopic unit should reduce the incidence of skin erosion in thin patients and in patients with skin devitalized by multiple incisions. 2. The small size and weight of the pulse generator
Volume 71 Number 2 February, 1976
have been very gratifying to both patient and surgeon alike. These factors should be important considerations in the use of the unit in small children. 3. No patient has expressed any apprehension because his pulse generator is run by nuclear power. 4. There is a delicate balance in the trade-off between the pulse generator's R-wave sensitivity and its insensitivity to extrinisic EMI and intrinsic EMI (skeletal muscle potentials). Some sacrifice in EMI resistance seems inevitable if the pulse generator is to sense all R waves, which is one of its essential functions and is more important than EMI rejection. 8 , 9 A more sensitive model of the C-100 unit with these characteristics has been prepared.* The existing model will be retained for patients with satisfactory R waves, especially if total EMI resistance is deemed important. Conclusion Preliminary clinical experience has been described with 30 cases in which a new radioisotopic cardiac pacemaker has been used and an equal number of control cases in which chemical battery-powered pacers have been used. The over-all experience in this very brief period of follow-up is gratifying, and extensive clinical trials of the radioisotopic pacemakers have been started in a number of collaborating institutions. * The Coratomic C-101.
Radioisotope-powered
cardiac pacemaker
267
REFERENCES
1 Purdy, D. L., Magovern, G. J., and Smyth, N. P. D.: A New Radioisotope-Powered Cardiac Pacer, J. THORAC. CARDIOVASC. SURG. 69: 82,
1975.
2 Smyth, N. P. D., Magovern, G. J., Ramirez, R. G., Diaz, M. H., Dixon, C. M., Fecht, D. C , and Johnson, A.: In Vivo Study of a New Radioisotope-Powered Cardiac Pacer, J. THORAC. CARDIOVASC. SURG. 70: 2,
1975.
3 Toler, J. C : Electromagnetic Performance—Final Technical Report, Project A-1628, June, 1974, Georgia Institute of Technology. 4 Parsonnet, V., Furman, S., and Smyth, N. P. D.: Implantable Cardiac Pacemakers. Status Report and Resource Guideline—Report of the Inter-Society Commission for Heart Disease Resources, Circulation 50: A-21, 1974. 5 Younkin, C. N.: Multiphase MP35N Alloy for Medical Implants, J. Biomed. Mater. Res. Symposium, No. 5 (Part 1), pp. 219-226, 1974. 6 Purdy, D. L., and Shapiro, Z.: Design of Isotopic Generators, Paper Number C/E-6, Transactions of Eighth Japan Conference on Radioisotopes, November, 1967. 7 Human Clinical Protocol for the Coratomic C-100 Radioisotope Powered Cardiac Pacer, Coratomic, Incorporated, Indiana, Pa., Aug. 1, 1974. 8 Smyth, N. P. D., Parsonnet, V., Escher, D. J. W., and Furman, S.: The Pacemaker Patient and the Electromagnetic Environment, J. A. M. A. 227: 1412, 1974. 9 Smyth, N. P. D., Alferness, C , Shearon, L., Rockland, R. H., Keshishian, J. M., and Johnson, A.: Clinical Evaluation of New Pulse Generator with Narrow Pulse Width for Conservation of Battery Energy, J. THORAC. CARDIOVASC. SURG. 68: 471,
1974.