Ll. Ze ANNUAL INVENTION STATEMENT Title. An Implantable Auxiliary Ventricle Full name of inventor. Adrian Kantrowitz, M.D., 546 East 17th Street, Brooklyn, New York 11219. My official title is Director of Surgical Services, Maimonides Hospital of Brooklyn, 4802 Tenth Avenue, Brooklyn, New York 11219, and Professor of Surgery, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203. The auxiliary ventricle was developed with the assistance of several research associates including Tetsuzo Akutsu, M.D., and in collaboration with the Avco-Everett Research Laboratory. Dr. Akutsu resides at 180 East 17th Street, Brooklyn, New York 11226, and is Director of the Division of Experimental Surgery at Maimonides Hospital, and Assistant Professor, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, The Avco-Everett Research Laboratory is located at 2385 Revere Beach Parkway, Everett, Massachusetts. Name and address of facility. The surgical research laboratory where the auxiliary ventricle was first ceveloped is located in the Edward Neimeth Institute for Medical Research, 4802 Tenth Avenue, Brooklyn, New York. Contribution of the facility to the discovery. I ama full-time employee of Maimonides Hospital. My salary is drawn entirely from hospital funds although a substantial portion of my time is devoted to research. Dr.-Akutsu has been associated with this research since he joined: the Maimonides Hospital Surgical Research Laboratory in June, 1964. His salary was derived entirely from Public Health Service Grant HB-06510 until Sept. 1, 1965, and since that time, partially from Grant HE-09934 as well. The Edward Neimeth Institute's contribution includes use o< laboratory animal quarters, operating rooms, offices, machine snop and an electronics laboratory. Qa 5. Patent policies of facility. Article 7 of the By-laws of Maimonides Hospital states the following patent policies: NAL] inventions, discoveries, and improvements made by any person in the employ of the Corporation or while receiving any compensation for his services ox while using any of the facilities of the Hospital, shall be the property of the corporation to be used by it for the purposes of furthering the medical sciences." "The Board of Trustees may, however, permit the dis- coverer or the inventor to participate in the income, if any, from the discovery of the invention. The provisions of this Article may be waived by the Board of Trustees." 6. Name and address of any other organization(s) contributing to discovery. The Avco-Everett Research Laboratory, 2385 Revere Beach Parkway, Everett, Massachusetts, is the only other organization involved in this discovery. 7. Contribution of the organization(s) in men, money, facilities. The Avco-Everett Research Laboratory's collaboration with this project began in 1962. Their con- ‘tribution to the device was to the design of the power supply and timing circuit. This work, while undertaken in collaboration with us, was done at their facility in Everett, Massachusetts. Questions regarding the number of men and financing can be referred to Avco-Everett. 8. Patent policies of these organizations. Patent policies of the Avco-Everett Research Laboratory may be obtained directly from the Avco Company. 9. Detailed description of the invention. The electronically controlled prosthesis, or auxiliary ventricle, consists of a flexible silicone rubber bulb in a firm case of the same contour. It is connected by cuffs of Dacron arterial graft to the ascending and descending aorta, paralleling the aortic arch. Two electrodes pick up the R wave of the ECG from the left ventricle triggering a solenoid valve that controls the application of compressed air from an ‘electronic timer to drive the unit. The time delay--before air is sent into the unit--is determined while left ventricular and central aortic pressure are observed on an oscilloscope. The LO. il. ~3- device hugs the mediastinum and is close to the aortic root. It contracts in series with the physiologic left ventricle, decreasing systolic pressure and thus reducing this chamber's work. Aortic pressure is increased during diastole, providing normal peripheral perfusion and in- creasing coronary flow. Other sites in the thoracic and ‘abdominal aorta have been explored. The U-shape occupies less space in the left chest and minimizes the risk of cuff kinking. Blood flows in a smooth curve from the aortic root through the proximal cuff to the auxiliary ventricle lending effective hemodynamic support. When the power source is turned off, blood flows through the device which is now merely acting as a valveless shunt from the ascend- ing to the descending aorta. An end-to-side anastomosis permits perfusion of the cranial and caudal areas. (See three attached figures) Detailed description of the timing circuit and driving mechanism can be obtained from the Avco-Everett Research Laboratory. Objectives, advantages, and uses of discovery. This intra- corporeal, avalvular controllable auxiliary ‘ventricle, or booster heart, offers assistance to the failing left heart. We feel that a device based on this principle will shortly be developed for clinical use, offering patients with myocardial insufficiency either prolonged or intermittent assistance. - Your opinion of the importance and usefulness of the discovery: In United States and elsewhere. Pathometric studies of the incidence of heart disease in man have been published widely both in the United States and else- where, i.e., "a National Program to Conquer Heart Disease, Cancer and Strokel', U.S. Government Printing Office, 1965, and "World Health Organization Statistics Annual, Volume I: Vital Statistics and Causes of Death," W.H.0O., May 1965. Because this incidence is high throughout the world (in the United States it is estimated that of the nearly one million cardiovascular-renal deaths, 54.8%, suffer from arterio- sclerotic heart disease including coronary disease), this discovery can’ be important and useful to any patient who is an appropriate candidate for such assistance. For a further explanation of its usefulness, see Item 10. 12. Your personal desires in applying for _a patent on the discovery. Development in the public interest. 13. Reasons, if any, why publication would not be adequate to 14. insure the availability of the discovery to the public. There are numerous publications which should insure priority and availability to N.I.H. Brief statement of how the invention was conceived, its reduction to actual practice, and the dates of these events. For many years I have been engaged in studies under - taken to develop a workable system that would diminish significantly the left ventricle's work of perfusing blood throughout the body of patients with myocardial insufficiency. As a Public Health Service Cardiovascular Research (a) Fellow at Western Reserve University working with Dr. Carl J. Wiggers, I began the essential studies on the physiology of the heart which led me to consider the construction of an auxiliary ventricle. This pump device is based on a fundamentally ditterent hemodynamic mechanism in which blood is withdrawn from the arterial system during cardiac systole. The same blood mass is returned intra-arterially during diastole. (a) Supported by a National Heart Institute Traineeship At Western Reserve University, later at Montefiore (b) (c) Hospital and subsequently at Maimonides Hospital, in collaboration with others, I became engaged in investi- gations of more effective methods of augmenting arterial * and coronary blood flow considering its extreme sensi- 1,2,3 tivity to increase in diastolic pressure. First attempts to create a functioning device to share the workload of the damaged myocardium were begun using the motor power of the hemidiaphragm. In these pre- liminary experiments in dogs, a portion of the diaphragm was wrapped around the aorta and stimulated by electronic circuitry during each diastole. This work in which I was associated with Dr. William M. P. Mekinnon was reported to the American College of Surgeons in 1958. We found that while we could utilize these muscle contractions to propel arterial blood peripherally, it only decreased left ventricular work 10-15%, and posed the formidable (b) With the support of a grant from the Playtex Park Research Institute. (c) With the support of USPHS Grant H-3023, Augmentation of Coronary Blood FlLow. (d) With the support of USPHS Grant H-3023 and continued with the support of USPHS Grant HE-05977 (formerly H-4462) Experimental Construction of an Auxiliary Ventricle. (e) Supported by USPHS Fellowship HF-9063 and Research Fellow-- ship Supply Grant, An Auxiliary Myocardium. 6 problem of chronic peripheral nerve stimulation. I felt thatmore effective results could be obtained with the use of a reservoir.” This led to the idea of a prosthetic device which would function in the arterial tree. Resolution of three problems was sought: the quality and type of appropriate material, the most effective site for location of the prosthesis, and its potential volume. Consequently, devices in-a variety of sizes were implanted in various ways at various sites in the abdominal or thoracic aorta in an attempt to perfect both the prosthesis and the implantation tecuuigue, At that time the bulb was made of Silastic 382 with cuffs of woven Teflon. Compressed aix served as the source of energy and we found that the best effects were obtained when the device was placed in the aortic arch bypass position. This intracorporeal unit, the forerunner of the present device, produced aortic counterpulsation. It was reported to the American Society for Artificial Internal Organs in 1963. Seeking yet more effective devices for long-term assistance, we, subsequently altered the design of the (£) Work continued with the support of HE-06510 (formerly H-6510) Integrated Electronic Control of Physiologic Systems. auxiliary ventricle to an ellipsoidal collapsible bulb in a rigid case of like cantour, connected by Dacron arterial graft to the aorta. It was inserted in bypass position parallel to the aortic arch. With this implanted ventricle, continuous aortic perfusion was achieved for 41 hours. in conscious, moving degs, and intermittently for 10 hours a day for 31 7,8,9,10,11,12 2 jowever, clotting and space problems persisted unti the development of the present device. Te minimize clotting within the unit, it was constructed of smoothed Silastic 372 ina U Shape, suggested by Dr. Akutsu, % makes the inner bulb sounder hemodynamically while offering the least physical and chemical interference. It eccuples as little space as possible in the left chest and is topographically situated to allow normal functioning of all adjacent organs. Close enough for maximum assistanc ay to the left ventricle, it augments arterial and coronary * flow, yet interferes minimally with normal phys: jt Oo ple Roy when turned off, acting then as a conduit. Offering the possibility of either consistent or intermittent 2 operation, its materials and design minimize thrombus a formation. Patency studies up to 14 months indicate oh the material's durability and inertness to blocd over prolonged ~8~ periods. Acute and chronic hemodynamic studies show a consistent reduction of left ventricular work and an in- crease in coronary flow and natural perfusion. The device was first described to the American Society for Artificial Internal Organs in 1965, and before other professional 13,14,15,16,17,18,19 societies. On February 4, 1966, the auxiliary ventricle was used in a patient suffering from severe intractable chronic congestive failure. The patient succumbed after 24 hours, although hemodynamic studies indicated good functioning of the unit for 18 hours. The full report of the case is being prepared. The unit used was fabricated by the Avco-Everett Research Laboratory from our specifications. wi fd at C REFERENCES Kantrowitz, A. and Arthur Kantrowitz: The Experimental Augmentation of Coronary Blood Flow. Surg. Forum, Amer. Coll. ef Surg. 1952. Kantrowitz, A. and Arthur Kantrowitz: Experimental Augmentation of Coronary Flow by Retardation of the Arterial Pressure Pulse. Surgery, 34:678, 1953. Kantrowitz, A. and A. Lerrick: Augmentation of Peripheral Arterial Flow by the Use of a Valve. Surg. Forum 151, 1954. Kantrowitz, A. and W.M.P. McKinnon: The Experimental Use of the Diaphragm as an Auxiliary Myocardiom. Surg. Forum 9:266, 1959, ntrowitz, A.t: Functioning Autogenous Muscle Used Experi- tally as an Auxiliary Ventricle. Trans. Amer. Soc. af. Intern. Organs, 6:395, 1960. # Nose, ¥Y., M, Schamaun and A. Kantrowitz: Experimental of an Electronically Controlled Prosthesis as an Awxil Left Ventricle. Trans. Amer. Soc. Artif, Intern. Organ 9:269, 1963. 1 Ss x U iar = r x, a 3 Nose, ¥., F. Russell, F. Gradel, and A. Kantrowitz: Long- Term Operation of an Blectronically Controlled, Plastic, Auxiliary Ventricle Im Conscious Dogs. Trans. Amer. Soc. Artif. Intern. Organs, 10:140, 1964. Nose, ¥., F. Russell, F. Gradel, and A. Kantrowitz: Permanently Implanted, Plastic, Auxiliary Ventricle. p 3 3 5 surg. Forum, Amer. Coll. of Surg., 15:269, 1964. Kantrowitz, A., ¥. Nose, F. Russell, and F. Gradel: A Plastic Auxiliary Ventricle Permanently implanted in the Chest. Bull. N.Y. Acad. Med., 40:952, 19464. Kantrowitz, A., F. Gradel, and Y. Nose: Prolonged Use of Aa Plastic, Implantable Auxiliary Ventricle in Conscious Dogs. Proc, 1l?th Ann. Conf. Engineering in Med. and Biol., 1, Nov rember, 1964. ped pnd ‘ fea Ww is. ~ lO. Kantrowitz, A.: Mechanical Auxiliary Ventricle, National Research Council, Proc. Conf. on Mechanical Devices to. Assist Pailing Heart. 1964. Kantrowitz, A., F. Gradel, and T. Akutsu: An Artificial, Implanted Auxiliary Left ventricle. Proc, Sympesium on Heart Substitutes, Heart Assn. Southeastern Pennsylvania. Charles C Thomas, Springfield, Illinois. (In press.) owite, A., F. Gradel, and T. Akutsu: The Auxiliary ger ants ‘ Ventricile,. IEEE. International Convention Record. 12,20-25, Gradel, F., Akutsu, T., Chaptal, P.A., and Kantrowitz, A.: Successful Hemodynamic Results with a New U-~Shaped Auxiliary Ventricle. Trans. Amer. Soc. Artif. Intern. Organs 11:277, 19665 Gradel, F., T. Akutsu, P.-A. Chaptal, H.R. Cottle, and A. Kantrowitz: Prolonged Arterio-Arterial Pumping in Dogs with a Mechanical Auxiliary Ventricle. . Amn. Surg., 163:347, 1966. . . Kantrowitz, A. and A.R. Kantrowitz: Design Criteria for Heart Punetion Support Devices, Tutorial Paper, Proceedin Gs of the 18th Annual Conference, Engineering in Med.. and Biol. 7:26 ‘Kantrowltz, A. and A.R,. Kantrowitze: Design Criteria for Heart Assistance Devices. Hahnemann Medical College Symposium: Engineering in the Practice of Medicine, 1965. {Submitted for publication.) Akutsu, Hemodynar RRIIIT tnt *, Gradel, and A. Kantrowite: Successful ‘esults with a New U-Shaped Auxiliary Ventricle. Cong. Physiol. Sciences, 288:139, 1965. ve Sor pede O« Ad ox 0 gy Chaptal, P.-A., T. Akutsu, and A. Kantrowite: Hemodynamic Effects of a Mechanical Auxiliary Ventriele Following Induced Heart Failure in Dogs. Amer. J. Cardiol. {Submitted £0 ox publication. } -~ii- 15. Brief statement concerning supporting evidence which you may have at hand which may be used as proof of item 14. All supporting evidence such as notes, drafts, pressure an flow graphs, ete. are on file in the Division of Experimental 3 $ Surgery of Maimonides Hospital and are available for review. 16. Brief statement on disclosure of the discovery to others. Vv a S ou have made a disclosure and the dates of such a ers velating to this device and its forerunners were sented before the Following groups: s p oa 1952, 1954, 1958 Surgical Forum, American College of Surgeons 1960 American Society for Artificial Internal Organs Research Society of America L961 Third IBM Medical Symposium Northeast Electronics Research and Engineering Meeting 1962 American Society for Artificial Internal Organs New York Academy of Sciences rookhaven National Laboratory New York Society for Cardiovascnlar Surgery 22nd International Congress of Physiological Sciences (Leiden) Fourth World Congress on Cardiology (Mexico City) e American Society for Artificial Internal Organs New York Surgical Society . New York Chapter of the American College of Cardiology and professional affiliations of persons or group eS Surgical Forum, American College of Surgeons American Society for Artificial Internal Organs Rockefeller University Symposium on Electronic Aids in Medicine Asian Pacific Congress on : Cardiology (Kyoto, Japan) National Academy of Sciences, National Research Council, conference on Mechanical Devices to Assist the Failing Heart orange County Heart Association, Symposium on Heart Disease fAnaheim, California) \ omy, cs ped New York Heart Association, Scientific Session on Research Minnesota Heart Association and Mayo Clinic Symposium on Clinical Application of Electronics in Cardiovascular Disease TREE L7th Annual Congerence, Engineering in Medicine and Bie Logy = American Society for Artificial Internal Organs Veterans! Administration Regional Office (New York City) Smerican Association of Operating Room Nurses New York Society for Thoracic Surgery TEEE LSth Annual Conference, Engineering in Medicine and Biology American College of Chest Physicians Phlebology Society of America Heart Association of Southeastern Pennsylvania, Fourth National Symposium: Heart Substitutes (Mechanical and Transplant )} Morgagni Society Wahnemann Medical College and IEEE Symposium, Engineering in the Practice of Medicine American Institute of Physics XXIII International Congress of Physiological Sciences Tokyo, Japan) American College of Cardiology ~13- In addition to these presentations at professional »societies, the device was discussed at the following hospitals: Leominster Hospital, Massachusetts, The Jewish General Hospital in Montreal, Jewish Chronic Disease Hospital, Newark City Hospital, Englewood Hospital, Coney Island Hospital 7th Annual Memorial Lecture in honor of Dr. Philip Ingram Nalteh, Brooklyn Hospital, Memorial Hospital, American College of Chest Physicians Workshop, Mt. Sinai Hospital Postgraduate Seminar 14th Annual Meeting (Miami), and before the Research Society of Maimonides Hospital of Brooklyn. Dates, current location, and names of persons present, if any, when you were developing vour experimental data. Dr. Tetsuzo Akutsu and I. may be addressed at 4802 Tenth Avenue, Brooklyn, New York. Dr. P.-A. Chaptal may be reached at Centre Hopitalier et Universitaire, Montpellier, France. Dr. Franz Gradel may be reached at Chir. Abt., Anna Seiler Haus, Inselsspital, Berne, Switzerland. Dr. ¥. Nose is in Cleveland, Ohio, Department of Artificial Organs, Cleveland Clinic, 2020 East 93rd Street, Dr. W.H.P. McKinnon is at New York Medical College, Fifth Avenue at LO6th Street, New York City. Dr. M. Schamaun is in the Department of Surgery, Kantonsspital, Zuxich, Switzerland. Dr. A. Lerrick ~ deceased Dr. Arthur Kantrowitg may be reached at the Avco-Everett Research Laboratories at 2385 Revere Beach Parkway, Everett, Massachusetts. The dates of their individual contributions to this research effort appear on the attached list of references. ~l4— 18. All information, which you have as to the state of the art and such specific information in the art as to which you may be aware, including any publication already made, ox public use being made of the artat the time of the discovery. (Give dates, names, and atidresses of pub- lishers and/or users.) The final aim of the intensive research now taking place in many laboratories throughout the world is the development of a permanently implantable cardiac assistance device with a portable power supply. Steps toward achievement of that goal are being taken by many investigators principally utilizing one of two methods of auxiliary heart function: the ventricular bypass procedure or that of diastolic augmentation {arterial counterpulsation). Since 1957, many research efforts have been directed toward attempts to supplant and/or augment cardiac function with a variety of assistance devices. In addition to the research al-~ ready reported by this investigator and his colleagues {reported in detail in Answer 14) significant achieve- ments were published from the following laborator ie Dr. Bert K. Kusserow, at the University of Vermont College of Medicine in 1958, reported a small solencid-driven diaphragm pump placed in the abdomen 1 ef dogs. In recent years, he has modified his techniques and design. C. Dennis, D.P. Hall, J. Moreno, and A. Senning at the State University of New York Downstate Medical Center reduced oxygen utilization of the heart using a left ventricular bypass in 1961 and their co-workers, in- cluding R.R. Capelletti, and S.A. Weslowski, reported their work in this area in 1962. | Domingo Liotta, C.W. Hall, W.S. Henly, A.C. Beall, Jz., D.A. Cooley, and MLE. DeBakey of Baylor University, Houston, reported their results in carrying out left ventricular bypass perfusion utilizing a pulsatile valved tubular shunt between the left atrium and the descending aorta. This has subsequently been refined considerably and a report on its use ina patient 6,7,8 appeared in 1963, These efforts referred to have been directed toward. the construction and development of methods which could be used for total cardiac replacement or mechanical ventricles operating in parallel with the intact heart. As we noted in Question 14, the auxiliary ventricle Functions in series with the natural heart and is based on the concept of providing elevated levels of diastolic ~16- perfusion pressure together with corresponding lawering of systolic pressure. It was reported first by us in 1958 and 1960. An alternate method of bringing about what are essentially the same hemodynamic changes was later developed at Harvard University by R.H. Clauss, C. Birtwell, et al. in 1961, and in the same year in St. Louis by V.L. William, T. Cooper and associates, in a study of its application in dogs with complete heart 9,10 block. Alse in 1962, D.H. Watkins and associates discussed the development of myocardial augmentation and its LL elinical application. A later paper by M. Soroff, Birtwell and others from the Tufts-New England Medical School in Boston, reported to the American Association for Artixicial Internal Organs, an “improved method of 12 counterpulsation™ along these same lines. A system, consisting of a valveless pulsatile plastic shunt of wide bore which bridges the ascending and descending aortic segments, was discussed by us in 1963, 1964, and ee OO on un ony [h ee references on pages /9 and 10) NM 10. -~17— Kusserow, B.K.: A Permanent Indwelling Intracorporeal . Blood Pump. Trans. Amer. Soc. Artif. Intern. Ofgans 4:227, 1958, Kusserow, B.K.:.. Further Experience with a Permanently Indwelling Intracorporeal Blood Pump. -Trans. Amer. .Soc. Artif. Intern. Organs, 4:227, 1958. , Kusserow, B.K. and J.F. Clapp: Partial Substitution of Ventricular Function over Extended Periods by a Mechanical Pump. Trans. Amer. Soc. Artif. Intern. Organs 7:332, 1961. Kusserow, B.K, and J.F. Clapp: A Small Ventricle-type Pump for Prolonged Perfusions: Construction and Initial Studies, Including Attempts to Power a Pump Biclogically with Skeletal Muscle. Trans. Amer. Soc. Artif. Intern. Organs 10:74, 1964, . Cappelletti, R.R., C. Dennis and S.A. Wesolowski: Protection from Ventricular Fibrillation by Parial Cardio- pulmonary or Total Left Ventricular Bypass... Trans. Amer. Soc. Artif. Intern. Organs, 8:100, 1962. ‘Liotta, D., C.W. Hall, W.S. Henly, D.A. Cooley, E.S. Crawford and M.E. DeBakey: Prolonged Assisted Circulation During and After Cardiac or Aortic Surgery. Amer. J. Cardiol., 12:309,. 1963. . Liotta, D., E.S. Crawford, D.A. Cooley, M.E. DeBakey, M, deUrquia and L. Feldman: Prolonged Partial Left Ventricular Bypass by Means of an Intrathoracic Pump Implanted in the Left Chest. Trans. Amer. Soc. Artif. Intern. Organs, 8:90, 1962. Liotta, D., C.W. Hall, W.S. Henly, A.C. Beall, Jr., D.A. Cooley, and M.E. DeBakey: Prolonged Assisted Circulation During and After Heart or Aortic Surgery. Trans. Amer. Soc. Artif. Intern. Organs, 9:182, 1963. Clauss, R.H., C. Birtwell, G.: Albertal, F. Lunzer, W.J. Taylor, A.M. Fosberg and D. BE. Harken: Assisted Circulation. J. Thorac. Cardiov. Surg., 41:447, 1961. Willman, V.L., T. Cooper, A. Riberi and C.R. Hanlon: Cardiac Assistance by Diastolic Augmentation: Hemodynamic Evalvation in Dogs with Complete Heart Block. Trans. Amer. Soc. Artif. Intern. Organs, 7:198, 1961. il. iz. ~18- Watkins, D.H., E.R. Duchesne and B.E. Pollock: Coordinated Post-systolic Myocardial Augmentation Combined With Systolic Neutralization: Development and Clinical Application to the Failing Heart. J. Thorac. Cardiov. Surg., 43:1, 1962. Deterling, R., Jr.: Assisted Circulation: An Improved Method for Counterpulsation. Trans. Amer. Soc. Artif. Intern. Organs, 8:35, 1962. ° ROOM A ANGMAR ARRON em: je RELATION OF AUXILIARY VENTRICLE — TO HEART AND AORTA Schematic Diagram of Auxiliary Ventricle System HE-06510 Integrated Electronic. Control of Physiologic Systems Principal Investigator: Adrian Kantrowitz, M.D. April, 1966