1 Historical Aspects of Mechanical Circulatory Support

J. Timothy Baldwin, John T. Watson

KEY POINTS Early Mechanical Circulatory Support Devices Ongoing Technology Developments and Devices and Technology Development Current State of MCS

EARLY MECHANICAL CIRCULATORY SUPPORT “­biocompatible” (a vague physiological term then and now). These DEVICES AND TECHNOLOGY DEVELOPMENT and other physiological ­parameters represented the ­defined ­design goals of the first generation of MCS systems.2 Despite this limited set Establishing the Concept of design inputs, engineers, biologists, and clinicians created teams In the 1930s, Carrel and Lindbergh1 developed an in vitro artificial and collaborations and used them, when appropriate, as quantifiable -like apparatus for keeping organs alive outside the body. They engineering design inputs to achieve the physiological goals in the removed the , kidneys, ovaries, adrenal glands, thyroid glands, early MCS systems. and spleens of small animals to watch them develop and function over Important progress on these early MCS systems resulted from the the course of several days.2 Acute animal studies in Russia and the cooperation and collaboration fostered by the National Heart, , United States followed in the 1940s. However, the meaningful ori- and Blood Institute (NHLBI). In 1977, following a recommendation gin of the modern era of mechanical circulation support (MCS) can from the Cardiology Advisory Committee, the NHLBI Devices and be traced to the development of the heart-lung machine by Gibbon Technology Branch (DTB) started the annual Contractors Meeting.4,8 (Table 1.1) and its first successful clinical use in 1953.3,4 The device The primary purpose of the meeting was to provide a public forum for was developed for so that surgical cardiac showcasing the progress of the contract research projects. The DTB procedures that require hours of circulatory support could be per- viewed the meeting as an opportunity for gathering the branch grant- formed. The success of the device and the need for prolonged cir- ees and contractors together to share ideas and network with other culatory support for patients who could not be weaned from the teams. After a decade of successful annual meetings sponsored by heart-lung machine or whose hearts could recover with longer dura- the NHLBI, the meeting was moved to Louisville, Kentucky, as the tions of support provided the initial impetus for developing devices “Cardiovascular Science and Technology: Basic and Applied” meeting that could provide long-term circulatory support. The optimism in under the leadership of Jack Norman,5 then to Washington, DC, with the 1950s and 1960s that circulation could be successfully supported the guidance of Hank Edmunds,5 and was finally integrated into the for extended periods by an artificial heart spurred its development Annual Meeting of the American Society of Artificial Internal Organs by pioneers such as Kolff, Akutsu, DeBakey, Liotta, and Kantrowitz.5 by then President Bob Eberhart (1993).7 This progression has pre- In 1963, DeBakey and Lederberg testified before the US Congress on served the spirit of collaboration of the original Contractors Meeting, the need for an artificial heart in very different domains: for patients which also includes the highly regarded Hastings Lecture dedicated otherwise healthy except for their failed heart and for isolated travel- to the memory of Dr. Frank Hastings, the first chief of the NHLBI ers on long space journeys.6 These hearings coincided with the debate Artificial Heart Program. about the implications of the Russian Sputnik Program and unbridled The annual meetings emphasized the importance of developing national enthusiasm for taking on large technologic challenges such as collaborative venues for the field to share results, both positive and the program to put the first man on the moon, which had begun just negative, and develop a common language across disciplines with pro- a few years earlier. cedural guidelines, which improve the comparability of data between In 1964, with special congressional approval, the National Heart research teams. Advisory Council established the mission-oriented Artificial Heart During the early period of the program, spanning from 1963 to Program (AHP) to design and develop devices to assist a failing 1980, progress on implantable, long-term ventricular assist systems heart and to rehabilitate (HF) patients.7 In the initial outpaced similar work on the more widely publicized total artificial planning stages of the program, cardiology and surgery experts heart (TAH) systems.9 In fact, short-term ventricular assist systems recommended that clinical systems be capable of a cardiac output were being fabricated for use in initial clinical trials in the late 1970s.10 of 10 L/min, be able to maintain normal blood pressure, and be The Institute of Medicine Committee report to “Evaluate the NHLBI

1 TABLE 1.1 Mechanical Circulatory Support Milestones Year Event 1953 First successful use of heart-lung machine for cardiopulmonary bypass (Gibbon) 1958 First successful use TAH in a dog (Kolff and Akutso) 1963 First successful use of LVAD in human (DeBakey) 1964 Artificial Heart Program established at NIH Six contracts awarded to analyze issues and need for program 1968 First clinical use of intraaortic balloon pump (Kantrowitz) 1969 First artificial heart in humans (Cooley) 1977 NHLBI RFPs for blood pumps, energy converters, and energy transmission NHLBI RFA on blood-material interactions 1980 NHLBI RFP for integration of blood pumps designed for 2-year use 1982 Barney Clark received first TAH implant for destination therapy (DeVries) 1984 NHLBI RFP for 2-year reliability studies First use of Pierce-Donachy VAD ( PVAD) as BTT (Hill) First implant of Novacor VAD First use of electromechanical VAD (Oyer) 1985 First use of CardioWest TAH as BTT (Copeland) 1988 First use of hemopump in humans (Rich Wampler)—first rotary blood pump used (Frazier) NHLBI awards four contracts to develop portable, durable TAHs 1989 Manual of operations for Novacor VAD NHLBI clinical trial completed 1991 First HeartMate VE implant (Frazier) 1994 FDA approval for pneumatic HeartMate VE as BTT 1996 NHLBI IVAS contracts awarded for Jarvik 2000, HeartMate II, CorAide VADS Pilot trial (PREMATCH) for destination therapy begins NHLBI awards two contracts for TAH Clinical Readiness Program (Abiomed, Penn State) 1998 FDA approval for HeartMate XVE as BTT FDA approval for Novacor as BTT REMATCH trial begins First DeBakey VAD implant (Wieselthaler) 1999 First human implant Arrow LionHeart VAD (first use of TETS) (Korfer) 2000 First HeartMate II implant (Lavee) First Jarvik 2000 implant (Frazier) 2001 REMATCH trial completed First implant of the AbioCor TAH (Dowling) 2002 FDA approval of HeartMate XVE as destination therapy 2003 CMS coverage decision for destination therapy 2004 NHLBI pediatric mechanical circulatory support program launched First implant of DuraHeart VAD (Korfer) 2006 First implant of HeartWare HVAD (Wieselthaler) First implant of Levacor VAD (Long) FDA approval of AbioCor TAH (Humanitarian Device Exemption) INTERMACS registry launched (PI: Kirklin ) 2007 First implant of Circulite Synergy device (Meyns); advent of miniature VADs Peter Houghton dies after a record 2714 days of VAD support 2008 HeartMate II BTT clinical trial completed 2009 FDA approval of HeartMate II for BTT HeartMate II destination therapy clinical trial completed 850th implant of the CardioWest TAH 2010 FDA approval of HeartMate II for destination therapy 2012 FDA approval of HVAD centrifugal flow pump for bridge-to-transplant therapy 2014 First implant of HM3 (Schmitto) 2017 FDA approval of HVAD for destination therapy FDA approval of HM3 centrifugal flow pump for bridge-to-transplant and bridge-to-recovery therapy

BTT, Bridge-to-transplant; CMS, Centers for Medicare and Medicaid Services; FDA, Food and Drug Administration; HM3, HeartMate; INTERMACS, Interagency Registry of Mechanically Assisted Circulatory Support for End-Stage Heart Failure; IVAS, Innovative Ventricular Assist System; LVAD, left ventricular assist device; NHLBI, National Heart, Lung, and Blood Institute; NIH, National Institutes of Health; PI, principle investigator; PVAD, paracorporeal ventricular assist device; REMATCH, Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure; RFA, request for application; RFP, request for proposal; TAH, total artificial heart; TETS, transcutaneous energy transfer system; VAD, ventricular assist device; VE, vented electric. CHAPTER 1 Historical Aspects of Mechanical Circulatory Support 3

Artificial Heart Program” contains a useful chronology of research and ­biologists working together and collaborating with other teams to- related important events from 1963 to 1991.11,12 ward the same defined physiological goals. As a result, the systems The first generation (1980) of implantable MCS systems was de- with the most promise exceeded the expectations of the program. signed to meet a 2-year operational goal during benchtop reliability These included the HeartMate II (HMII) (see Fig. 1.1) and the testing.13 Next followed the NHLBI Readiness Program.14 This pro- Jarvik 2000 VAS.17,18 The HMII, an axial-continuous flow system, gram aimed to ensure the functional reliability of the MCS systems that became the most clinically successful MCS system. In bench tests, demonstrated the greatest promise. Each awarded contractor placed 12 HMII systems met physiological requirements, and some operated MCS systems on “Mock Circulations” to assess their function during a indefinitely. simulated cycle of daily life for 2 years without interruption or mainte- The pivotal clinical trial with the HMII showed significantly im- nance. Success was completing the test with no more than one system proved survival and reduced adverse events for study patients. The un- failure at 2 years. expected result was underscored in the companion editorial to the release of the multicenter randomized trial. The author compared Clinical Application and Evolution of MCS the REMATCH trial with the HM XVE to the HMII trial using Kaplan- These early MSC programs created the engineering design basis for the Meier survival graphs.19 The survival results with HM XVE were ex- HeartMate XVE (HM XVE) (Fig. 1.1) that was used in the Randomized actly the same in 2009 as in 2001, very strongly suggesting that the Evaluation of Mechanical Assistance for the Treatment of Congestive improved HMII survival was largely due to the engineering design of Heart Failure (REMATCH) trial.15 In clinical use, the HM XVE and the systems. This again pointed to the value of the National Institutes other systems demonstrated that first-generation implantable systems of Health/NHLBI initiating the IVAS program. could achieve meaningful physiological objectives for 2 years and im- After the HMII trial, thrombus-related device malfunctions in- prove quality of life. However, many patients suffered serious adverse creased without explanation.20 There was speculation that the di- events such as bleeding, infection, and device malfunction. mensionally tight axial-flow channel of the HMII was a contributing Recognizing the initial success of MCS devices by multidisci- factor in thrombus formation. At the same time, magnetically levitated plinary teams created by the NHLBI programs, in 1994, the NHLBI ­centrifugal-flow systems were on the drawing board. These systems released the “Innovative Ventricular Assist System” (IVAS) request became technically feasible because of advances in permanent mag- for proposals to encourage innovation of totally implantable MCS nets. The potential advantage of the centrifugal-flow pump is the di- systems that were designed to achieve at least a 5-year functional mensionally wider blood flow channels that may reduce the potential lifetime with 90% reliability.16 This program was designed to incor- for thrombus formation. The importance of design is also seen in the porate the latest advances gained from first-generation MCS systems, widened internal flow patterns of the HeartMate 3 (HM3), which are the TAH, and in related engineering, clinical, and biology fields. likely responsible for the improved rate of “survival free of disabling The IVAS program was crucial to advancing the field of MCS stroke or reoperation to replace or remove a malfunctioning device” for longer survival and patient quality of life. The program again at 2 years compared to the HMII, despite the rates of disabling stroke brought together skilled teams of clinicians, engineers, and being similar.21 The HVAD (Fig. 1.2), also a centrifugal blood pump,

A B

Fig. 1.1 The HeartMate II (A and lower left in B) compared with the Heartmate XVE (B). The HeartMate II was the first rotary ventricular assist device to receive U.S. Food and Drug Administration approval for bridge to transplant and destination therapy. (Courtesy of Abbott.) 4 CHAPTER 1 Historical Aspects of Mechanical Circulatory Support

­triagency administrative factors and allowed the three agencies to join together on the steering committee and address questions rele- vant to their “agency mission” data collection. INTERMACS exceeded ­expectations for organizing, collecting, and analyzing clinical data and ­provided Medical Device Reports for adverse events to the FDA and data for CMS payment decisions. INTERMACS made an early decision to only curate data generated by patients implanted with FDA-approved durable MCS devices (i.e., devices with the potential for patient discharge).24 This requirement added additional rigor to the INTERMACS database as the im- plants were under design controls and thus not subject to random design modifications that may directly influence clinical outcomes. Fourteen device systems met this standard. In recent years, of the 14 systems, 3 adult ventricular assist systems, 1 pediatric device, and 1 TAH system became the primary MCS devices in clinical use, thus providing essentially all the Bridge and Destination therapy data for INTERMACS. Fig. 1.2 The HeartWare HVAD. (Reproduced with permission of Medtronic, Inc.) ONGOING TECHNOLOGY DEVELOPMENTS AND DEVICES The development of new MCS devices has been spurred by innova- tion, as well as building on the success of earlier concepts. Substantial activity has focused on the development of novel TAHs. To date, the SynCardia TAH (Fig. 1.4), based on the Jarvik-7 TAH developed in the early 1980s, is the only one that has received substantial use, ac- counting for over 95% of the more than 1700 worldwide TAH im- plants since the first TAH in 1969.25 Recent efforts to develop a newer generation of TAH include the CARMAT bioprosthetic TAH,26 the Cleveland Clinic continuous-flow total artificial heart (CFTAH),27 and the BiVACOR TAH.28 The CARMAT TAH, like the SynCardia TAH, is a positive displacement device. However, it utilizes bioprosthetic blood-contacting surfaces, electro-hydraulic pumps to activate the membrane between the two ventricles to product pulsatile flow, and an advanced control system involving implanted sensors to provide flows to meet patient demands. Four patients were implanted with the device in a pilot study, which is anticipated to lead to a pivotal study. Fig. 1.3 The HeartMate 3, like the HeartWare left ventricular assist The Cleveland Clinic TAH and BiVACOR TAH both involve a sin- device, is a centrifugal pump but, rather than using bearings, has a gle moving part, a rotor with impeller blades on each side, with each fully magnetically levitated (Full MagLev) rotor. (Courtesy of Abbot side driving the flow in the left and right centrifugal continuous-flow Laboratories, Lake Bluff, IL.) pumps that make up the device. These are considerably smaller than positive displacement TAHs, so small that a pediatric version of the Cleveland Clinical CFTAH is being developed for infants down to has different internal flow patterns from the HM3 (Fig. 1.3). In 2017, 0.3 m2 body surface area (BSA). The continuous-flow TAHs are both at the Heartware system received Food and Drug Administration (FDA) the stage of animal studies. approval for “Destination” therapy, following prior approval in 2012 as Novel, advanced ventricular assist devices (VADs) are being de- a bridge for cardiac transplantation.22 signed and developed to address the outstanding issues with adverse With the growth of MCS in the 1990s and early and its events and special populations. These include a minimally invasive profound impact on patient outcomes, it was recommended that the ­intraaortic balloon pump for long-term support (NuPulseCV, Raleigh, NHLBI create a mechanism to assess various MCS technologies as NC) and a valveless VAD that uses magnetically driven pistons to create they entered clinical use.11 To fulfill this vision, the NHLBI elected to pulsatile flow, known as the TorVAD (Windmill Technologies, Austin, develop a registry to collect data to improve patient MCS selection, TX).29,30 They also include newer generations of continuous-flow measure quality of life, meet the FDA regulatory requirements, and in- VADs such as a miniature implantable pump platform, the Revolution, form the Centers for Medicare and Medicaid Services (CMS) regarding in which minor modifications of components can be implemented to reimbursement decisions. This led to a solicitation that resulted in the adjust the pump performance to support the right or left side of the Interagency Registry of Mechanically Assisted Circulatory Support for heart (Vadovations, Inc., Oklahoma City, OK).31,32 End-Stage Heart Failure (INTERMACS).23 Some of the greatest attention has focused on the development of The NHLBI provided the necessary financial support for the MSC devices for children, specifically small ones. This was spurred contract to develop and run the registry, which was awarded to the on by the NHLBI Pediatric Circulatory Support Program spanning University of Alabama at Birmingham. This substantially reduced from 2004 to 2009 and the Pumps for Kids, Infants, and Neonates CHAPTER 1 Historical Aspects of Mechanical Circulatory Support 5

A B

Fig. 1.4 The SynCardia Temporary Total Artificial Heart (A), shown with the wearable driver system (B). (Courtesy of Syncardia Systems, Inc., Tucson, AZ.)

Program, which started in 2010.31,32 These programs led to the devel- thousands of patients with late-stage HF. MCS served as a cata- opment of various devices for children less than 20 kg with advanced lyst for a grassroots coalescing of key disciplines, ­organizations, HF because, when the programs began, the only device available for and talents dedicated to patient quality of life and the well-being these patients was the Berlin Heart EXCOR, but only through emer- of caretakers. It has attracted clinicians, engineers, and scientists, gency or compassionate use. Since then, the Berlin Heart received both senior and recent graduates, who voluntarily committed FDA approval and currently is the only FDA-approved MCS device their careers to MCS research, practice, and patients. Additionally, for these small children. However, 29% of patients supported by the program coordinators work well beyond their position descrip- device experienced strokes in the pivotal trial.33 Developers hope tions to provide 24/7 availability in the management and well-­ to lower rates of serious adverse events by incorporating the latest being of MCS patients and caregivers. As a benefit, patients have technologies realized in VADs for adults into the new generation of exceeded expectations in the scope of successful daily and recre- pediatric VADs. ational activities. The Jarvik 2015 Ventricular Assist System, which resulted from It is difficult to estimate the worldwide utilization of MCS. Based on the NHLBI programs, is poised to begin clinical evaluation.33 Progress increasing accrual rate in the INTERMACS Registry, the annual utili- continues on other devices that were developed independently of the zation in the United States may be around 3500 implants. Assuming NHLBI programs or resulted from them. These include a pediatric ro- that MCS use outside of the United States is similar,41–43 annual world- tary flow VAD (Vadovations, Inc., Oklahoma City, OK), the Pediatric wide implants may total 6000–7000 units. Of note is that TAH use has TorVAD (Windmill Technologies, Inc., Austin, TX), and the Penn State grown worldwide, now totaling well over a thousand patients since its Pediatric Total Artificial Heart (Penn State University, Hershey and first use.43 With the development of MCS therapy, many patients are University Park, PA).34–36 living well beyond 5 years, with the longest known patients alive after The development of novel MCS devices like these has been 15 years. These patients are informing the MCS research community led by a community of multidisciplinary teams. And, like the and fellow patients by sharing best practices with their MCS systems MCS devices they work on, the MCS community has evolved. through online organizations such as MyLVAD.44 Since the days of the DTB Contractors Meetings, the MCS com- An added research benefit of MCS is that while it extends pa- munity has continued to grow, collaborate, communicate, and tient survival, it is, in essence, extending the natural history of now use other various meetings and organizations to do so such their physiological condition. With a growing number of patients as the Gordon Research Conference on Assisted Circulation,37 living 5 years and longer with a device, there is a growing reser- the ITERMACS Registry,38 the International Society of Heart voir of opportunities to gain better understanding of the condition and forum for MCS39 and the Society of of HF itself. For ­example, the studies of myocardial recovery with Thoracic Surgeons STS National Database.40 device explant may reveal therapeutic strategies that deserve clin- ical research and trials involving patients without MCS.45 To this CURRENT STATE OF MCS end, the NHLBI held a working group on “Advancing the Science of Myocardial Recovery with Mechanical Circulatory Support” in June Over the past five decades, MCS has grown substantially from a 2016.46 Recommendations from this meeting were made to provide small community of researchers working to develop early success- some clear directions to advance the science of cardiac recovery in ful devices to meet modest goals and demonstrate the value of the the setting of mechanical circulatory support, and the hope is that therapy to one that includes significant numbers of research teams research to address important outstanding questions about myocar- and mature industry leaders in medical devices and has helped dial recovery will soon follow. 6 CHAPTER 1 Historical Aspects of Mechanical Circulatory Support

The interdisciplinary teams of clinicians, engineers, and scientists 20. RC1 Starling, Moazami N, Silvestry SC, et al. Unexpected abrupt that began in the early days of the Artificial Heart Program and formed increase in left ventricular assist device thrombosis. N Engl J Med. the underpinning of the dynamic MCS field have endured and evolved 2014;370(1):33–40. over the decades. These teams continue working on MCS therapy be- 21. Mehra MR, Goldstein DJ, Uriel N, et al. MOMENTUM 3 Investigators. Two-year outcomes with a magnetically levitated cardiac pump in cause patients with MCS devices are still beset by serious adverse events heart failure. N Engl J Med. Mar 11, 2018. https://doi.org/10.1056/ associated with the devices. Progress to address them has been modest NEJMoa1800866. [Epub ahead of print]. because, in part, terms for bleeding, stroke, infection, arrhythmias, and 22. Rogers JG, Pagani FD, Tatooles AJ, et al. Intrapericardial left right HF have been incompletely quantified. To take MCS devices to ventricular assist device for advanced heart failure. N Engl J Med Feb 2. the next level and overcome these issues, comprehensive biology, phys- 2017;375(5):451–460. ics, and engineering parameters that define the device design inputs 23. Kirklin JK, Naftel DC, Stevenson LW, et al. INTERMACS database for and goals are needed. durable devices for circulatory support: first annual report. J Heart Lung Transplant. 2008;27(10):1065–1072. 24. INTERMACS Device List (Approved and Unapproved): Website http:// DISCLOSURE www.uab.edu/medicine/INTERMACS/INTERMACS-documents. 25. http://www.syncardia.com/2016-press-releases/new-york-times-posts- Dr. Baldwin is an employee of the NHLBI, NIH. The comments ex- retro-report-documentary-the-total-artificial-heart-from-1st-implant-to- pressed here are those of the authors and do not reflect official posi- worlds-most-used-artificial-heart.html (Accessed 2/23/2018). tions of the NHLBI or NIH. 26. Latrémouille C, Carpentier A, Leprince P, et al. A bioprosthetic total artificial heart for end-stage heart failure: results from a pilot study. J Heart Lung Transplant. 2018;37(1):33–37. FUNDING 27. Fukamachi K, Karimov JH, Sunagawa G, et al. Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in No funding sources were used for this review. awake calves. J Artif Organs. 2017;20(4):381–385. 28. Timms D, Fraser J, Hayne M, Dunning J, McNeil K, Pearcy M. The BiVACOR rotary biventricular assist device: concept and in vitro REFERENCES investigation. Artif Organs. 2008;32(10):816–819. 29. Costantini H, Juricek C, Kagan V, et al. Management of a counterpulsation 1. Carrel A, Lindbergh CA. The culture of whole organs. Science. device outside of the intensive care unit. J Heart Lung Transplant. 1935;81(2112):621–623. 2017;36(4):S356–S357. 2. Report HEW-NHI. Cardiac Replacement: Medical, Ethical, Psychological, 30. Letsou GV, Pate TD, Gohean JR, et al. Improved left ventricular and Economic Considerations; 1969. unloading and circulatory support with synchronized pulsatile left 3. Stoney WS. Evolution of cardiopulmonary bypass. Circulation. ventricular assistance compared with continuous-flow left ventricular 2009;119(21):2844–2853. assistance in an acute porcine left ventricular failure model. J Thorac 4. Device and Technology Contractors Meeting Proceedings. Washington, Cardiovasc Surg. 2010;140(5):1181–1188. DC, Dec 1997. 31. Wampler R. Heart assist device. United States Patent US 9. August 22, 5. Annual Meeting Cardiovascular Science and Technology. Basic and 2017;737(651). United States Patent and Trademark Office. Applied I. Louisville, KY: Ed. Norman JC; 1989. 32. Wampler R. Heart assist device. United States Patent US 9. December 15, 6. Annual Meeting Cardiovascular Science and Technology. Basic and 2015;211(368). United States Patent and Trademark Office. Applied. Washington, DC: Ed. Edmunds LH; 1991. 33. Baldwin JT, Borovetz HS, Duncan BW, et al. The National Heart, Lung, 7. American Society of Artificial Internal Organs. https://asaio.com/. and Blood Institute Pediatric Circulatory Support Program. Circulation. 8. Frazier OH, Kirklin JK. Mechanical Circulatory Support (ISHLT 2006;113:147–155. Monograph Series). Elsevier; 2006. 34. Fraser, C. D., Jr., et al. (2012). Prospective trial of a pediatric ventricular 9. DeBakey ME. Development of mechanical heart devices. Ann Thorac assist device. N Engl J Med. 367(6): 532-541. Surg. 2005;79(6):S2228–S2231. 35. Snyder TA, Coghill P, Azartash-Namin K, Wu J, Stanfield J, Long JW. 10. Norman JC, Dasco CC, Reul GJ, et al. Partial artificial heart (ALVAD) Design of an implantable blood pump for mechanical circulatory support use with subsequent cardiac and renal allografting in a patient with stone in pediatric patients. In: ASME. Frontiers in Biomedical Devices; 2017. heart syndrome. Artif Organs. 1978;2(4):413–420. Design of Medical Devices Conference. 11. IOM Committee Report. The Artificial Heart: Prototypes, Policies and 36. Gohean JR, Larson ER, Hsi BH, Kurusz M, Smalling RW, Longoria RG. Patients; 1991. Scaling the low-shear pulsatile TORVAD for pediatric heart failure. 12. Hogness JR. Committee to Evaluate the Artificial Heart Program of the ASAIO J. 2017;63(2):198–206. National Heart, Lung, and Blood Institute, Division of Health Care Service, 37. Penn State Pediatric TAH (grant reference, but no publications in Institute of Medicine. The Artificial Heart: prototypes, policies, and patients. Pubmedn) n.d. Washington, DC: National Academy Press; 1991. 38. Conferences Gordon Research. https://www.grc.org/find-a-conference/ 13. Request for Proposal RFP NHLBI 80-3, Development of an Implantable ?keywords=assisted+circulation; 2003. Integrated Electrically Powered Left Heart Assist System. January 1980. 39. Interagency Registry for Mechanical Assisted Circulation Support 14. Request for Proposal RFP NHLBI 84-1, Device Readiness Testing of (INTERMACS). https://www.uab.edu/medicine/INTERMACS/. Implantable Ventricular Assist Systems. October 1983. 40. International Society for Heart and Lung Transplantation (ISHLT). http:// 15. Rose E, Gelijns A, Moskowitz A, et al. Long-term mechanical left ventricular www.ishlt.org/. assistance for end-stage heart failure. NEJM. 2001;345(20):1435–1443. 41. Society of Thoracic Surgery (STS). https://www.sts.org/. 16. Request for Proposal RFP NHLBI-HV-94-25, Innovative Ventricular Assist 42. Japanese registry for Mechanically Assisted Circulatory Support. System. August 1994. First report, The Journal of Heart and Lung Transplantation. October 17. HeartMate II website: http://heartmateii.com/. 2017;36(10):1087–1096. 18. Jarvik 2000 website: https://www.jarvikheart.com/products/. 43. INTERMACS. Quarterly Statistical Report Q3. https://www.uab.edu/ 19. Fang JC. Rise of the machines—left ventricular assist devices as permanent medicine/INTERMACS/images/Federal_Quarterly_Report/Federal_ therapy for advanced heart failure. NEJM. 2009;361:2241–2251. Partners_Report_2017_Q3.pdf; 2017. CHAPTER 1 Historical Aspects of Mechanical Circulatory Support 7

44. Copeland JG. SynCardia total artificial heart: update and future. Tex working group of the National, Heart, Lung, and Blood Institute. JACC Heart Inst J. 2013;40(5):587–588. Basic Transl Sci. 2017; 2(3):335–340, ASAIO J. 2017 Jul/Aug;63(4): 45. MyLVAD: Living with an LVAD. www.mylvad.com/content/living-lvad. 445–449, J Card Fail. 2017 May;23(5):416–421, and J Thorac Cardiovasc 46. Birks EJ. The promise of recovery. JACC:HF. 2016;4(7):577–579. Surg. 2017 Jul;154(1):165–170. 47. Drakos SG, Pagani FD, Lundberg MS, Baldwin JT. (2017) Advancing the science of myocardial recovery with mechanical circulatory support: a