PERSPECTIVES ON VOLUME 1 To commemorate the 50th anniversary of The Annals of Thoracic Surgery, a special STS presidential task force has selected articles that were published in Volume 1 (1965) describing important topics in cardiothoracic surgery. Each 2015 issue of The Annals will highlight one of these contributions through the eyes of a current thought leader. The expert commentaries will provide personal insight regarding the evolution of these challenges and implications for the future.
Chronic Implantable Mechanical Circulatory Support 50 Years Later: Still Shooting for the Stars! Mark S. Slaughter, MD Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, Kentucky
The past, like the future, is indefinite and exists only as a spectrum of possibilities.
–Stephen Hawking
F
ifty years ago, Zuhdi and colleagues [1] published the article “Assisted Circulation—The Concept of The Implanted Bypass Heart” in The Annals of Thoracic Surgery. In hindsight, it is quite remarkable how prescient, accurate, and applicable their experimental data, recommendations, and predictions are today. In their discussion section, they note that at a 1957 meeting of the American Society of Artificial Internal Organs, the idea of an intracorporeal implantable artificial organ was received with mixed feelings, and they remark that the challenges in developing these potentially lifesaving technologies were comparable to a “trip to the moon.” Little could they fathom that in 1965, only 4 years after the publication of their early preclinical work, Neil Armstrong not only would land on the surface of the moon but also walk on it and that Dr Cooley would implant a total artificial heart (TAH) in a human. Zuhdi and colleagues described what were some basic requirements to develop a permanently implanted heart that would “assist circulation and maintain life for indefinite periods of time.” This required developing conceptual formulas and applying engineering equations to predict power requirements of the heart, energy conversion, sources of energy, the implanted pumping section, external driving power, and controlling mechanisms. Although several of their calculations might be slightly different today because of additional knowledge gained over the years, they were remarkably accurate. In addition, they identified the major criteria for a “total bypass implantable heart” device: (1) it is inert, (2) it deters clot formation, (3) it does not destroy blood elements, (4) it can provide reproducible performance over long periods (approximately 20 years), (5) it is of sufficient size to be placed in a pleural cavity, and (6) it has a source of energy that is small, portable, preferably implantable, reliable, and long lasting. These device design criteria remain Address correspondence to Dr Slaughter, Department of Cardiovascular and Thoracic Surgery, University of Louisville, 201 Abraham Flexner Way, Ste 1200, Louisville, KY 40202; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
important characteristics for today’s left ventricular assist devices (LVADs) and TAHs as well. Based on their performance calculations and design criteria for a successful device, they were able to develop experimental prototypes of an implanted heart. Essentially, their novel device was composed of 2 independent but mirror-image hydraulically driven pulsatile pumps with silicone elastomer diaphragms housed in a poly(methyl methacrylate) chamber, which could provide up to 3.6 L/min flow against a peak pressure of 200 mm Hg. In vitro studies revealed that the connecting grafts needed to be nonporous to prevent leaking and rigid enough to not collapse during the negative-pressure phase and, most importantly, that no 2 pumps would pump exactly the same amount over long periods, thus requiring some mechanism for “equalization.” In vivo studies were also successful, with the longest voluntary survival of 6 hours and 30 minutes. They were also able to develop an algorithm of “skipped beats” on the right side that allowed equalization, as evidenced by the fact that no study participant experienced significant pulmonary hypertension. There was a large group of early pioneers that contributed to the field of mechanical circulatory support, including Drs Kolff, Kusserow, Kantrowitz, Nose, Liotta, Hastings, and DeBakey [1]. John Watson, PhD, deserves credit as well, because it was his vision while at the National Heart, Blood, and Lung Institute to fund a series of requests for proposals to develop reliable, durable, and safe implantable heart assist devices [2–4]. As a direct result of National Institutes of Health funding, new knowledge expanded into the areas of biomaterials, shear stress, blood elements and microparticles, bearings, and the possibility of continuous-flow pumps, which was then successfully translated into the development of mechanical assist devices in clinical use today. To compete with heart transplantation, initial efforts were focused on the development of a TAH. Although the first TAH was implanted in 1969, it was not until 1982 that the first TAH intended for permanent use was implanted by Dr DeVries in Utah. This TAH was the culmination of decades of work by Willem Kolff and was later named the Jarvik-7 TAH. With some modifications and additional clinical experience, predominantly by Dr Copeland, it Ann Thorac Surg 2015;99:749–51 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.01.016
750
PERSPECTIVES ON VOLUME 1 SLAUGHTER HISTORY OF MECHANICAL CIRCULATORY SUPPORT
is still in use today and is known as the SynCardia TAH (SynCardia Systems, Tuscon, AZ) [5]. Since then, additional attempts have been made to mimic the thengrowing success of heart transplantation with the development of the AbioCor TAH (Abiomed, Danvers, MA) [6], and the LionHeart TAH (Abiomed, Danvers, MA) [7]. Although the development of these devices resulted in a significant increase in our knowledge of mechanical circulatory support, the overall clinical results were not nearly as impressive. As suggested by Zuhdi and colleagues, a TAH would require balancing the flow between the right and left ventricles, which adds complexity, larger size, and increased power requirements; subsequently, a larger power source and a greater blood contacting surface area are also required, all of which may potentially contribute to clinically significant adverse events. Despite these daunting hurdles, there are several newer-generation TAHs in development today that are promising [8, 9]. Perhaps the greatest pearl of wisdom included in the article by Zuhdi and colleagues was the prediction that a “bypass implanted heart,” or LVAD, “presents many theoretical and practical advantages.” As noted by the INTERMACS registry (Fig 1), isolated LVADs have much better early- and long-term survival compared with either biventricular support or a TAH [10]. A major milestone in the development of LVADs was the surprising success of the Hemopump (Nimbus Medical, Inc, Rancho Cordova, CA), which was a catheter-based mechanical circulatory support device [11]. Drs Wampler and Frazier were able to demonstrate that a continuous-flow high-speed rotary pump was capable of providing hemodynamic support without destroying blood elements. Their innovation rapidly changed the field with a transformation from pulsatile-flow pumps
Fig 1. INTERMACS—Kaplan-Meier survival by flow type and device primary prospective implants: June 23, 2006 to June 30, 2014. (BiVAD ¼ biventricular assist device; LVAD ¼ left ventricular assist device; TAH ¼ total artificial heart.)
Ann Thorac Surg 2015;99:749–51
to continuous-flow devices. Continuous-flow technology has resulted in significant miniaturization, reduced power requirements, and increased reliability and durability and has enabled access to smaller patients, particularly women. Current outcomes with either axial- or centrifugal-flow LVADs for bridge-totransplantation procedures approach 90% survival at 1 year [12, 13], and for destination therapy the outcomes are similar to heart transplantation outcomes at 2 years for select patients [14]. The article by Zuhdi and colleagues was what we all hope our publications would be like. It was well written, scientifically accurate, and with a discussion that clearly and without bias described their results and made bold predictions for future progress. Thus their article not only contributed to the current knowledge of the time but was also a blueprint and challenge to those who would follow. Significant advancements have been made since this publication 50 years ago. Clinicians now have access to a new generation of clinically approved small continuous-flow pumps that assist the left ventricle, do not require a sternotomy for insertion, are being evaluated for efficacy in patients with less severe heart failure, and are used as a platform for myocardial recovery to avoid the need for heart transplantation. Although many significant technological advances with mechanical circulatory support have been made over the past 50 years, our field still faces many hurdles to overcome—namely, reducing adverse events related to the patient-device interface. As a technology to treat advanced heart failure, we have not “walked on the moon” yet, but we continue to “shoot for the stars” as a potential treatment and cure for millions of patients with advanced heart failure that will ultimately require something beyond medical therapy [15].
Ann Thorac Surg 2015;99:749–51
References 1. Zuhdi N, Ritchie C, Carey J, Greer A. Assisted circulation— the concept of the implanted bypass heart: an experimental study. Ann Thorac Surg 1965;1:229–43. 2. National Institutes of Health: National Heart, Lung, and Blood Institute. Request for proposals. Left heart assist blood pumps, RFP NHLBI 77–8; and Development of electrical energy converters to power and control left heart assist devices. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1976. 3. Watson JT, Carlsen RR. Request for proposal: Development of an implantable integrated electrically powered left heart assist system. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1980. 4. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. Innovative ventricular assist systems (request for proposal). Bethesda, MD: Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; 1994. 5. Torregrossa G, Morshuis M, Varghese R, et al. Results with SynCardia total artificial heart beyond 1 year. ASAIO J 2014;60:626–34. 6. Dowling RD, Gray LA Jr, Etoch SW, et al. The AbioCor implantable replacement heart. Ann Thorac Surg 2003; 75(6 Suppl):S93–9. 7. Mehta SM, Pae WE Jr, Rosenberg G, et al. The LionHeart LVD-2000: a completely implanted left ventricular assist device for chronic circulatory support. Ann Thorac Surg 2001;71(3 Suppl):S156–61.
PERSPECTIVES ON VOLUME 1 SLAUGHTER HISTORY OF MECHANICAL CIRCULATORY SUPPORT
751
8. Mohacsi P, Leprince P. The CARMAT total artificial heart. Eur J Cardiothorac Surg 2014;46:933–4. 9. Koerfer R, Spiliopoulos S, Finocchiaro T, Guersoy D, Tenderich G, Steinseifer U. Paving the way for destination therapy of end-stage biventricular heart failure: the ReinHeart total artificial heart concept. Eur J Cardiothorac Surg 2014;46:935–6. 10. INTERMACS: Quarterly Statistical Review 2014 2nd Quarter Available at: https://www.uab.edu/medicine/intermacs/ images/Federal_Quarterly_Report/Federal_Partners_Report_ 2014_Q2.pdf . Accessed: January 6, 2015. 11. Frazier OH, Wampler RK, Duncan JM, et al. First human use of the Hemopump, a catheter-mounted ventricular assist device. Ann Thorac Surg 1990;49:299–304. 12. Slaughter MS, Pagani FD, McGee EC, et al, HeartWare Bridge to Transplant ADVANCE Trial Investigators. HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2013;32:675–83. 13. Starling RC, Naka Y, Boyle AJ, et al. Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 2011;57:1890–8. 14. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation? J Thorac Cardiovasc Surg 2012;144:584–603. 15. Kirklin JK. Terminal heart failure: who should be transplanted and who should have mechanical circulatory support? Curr Opin Organ Transplant 2014;19:486–93.
Chronic Implantable Mechanical Circulatory Support 50 Years Later: Still Shooting for the Stars! Mark S. Slaughter, MD Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, Kentucky
The past, like the future, is indefinite and exists only as a spectrum of possibilities.
–Stephen Hawking
F
ifty years ago, Zuhdi and colleagues [1] published the article “Assisted Circulation—The Concept of The Implanted Bypass Heart” in The Annals of Thoracic Surgery. In hindsight, it is quite remarkable how prescient, accurate, and applicable their experimental data, recommendations, and predictions are today. In their discussion section, they note that at a 1957 meeting of the American Society of Artificial Internal Organs, the idea of an intracorporeal implantable artificial organ was received with mixed feelings, and they remark that the challenges in developing these potentially lifesaving technologies were comparable to a “trip to the moon.” Little could they fathom that in 1965, only 4 years after the publication of their early preclinical work, Neil Armstrong not only would land on the surface of the moon but also walk on it and that Dr Cooley would implant a total artificial heart (TAH) in a human. Zuhdi and colleagues described what were some basic requirements to develop a permanently implanted heart that would “assist circulation and maintain life for indefinite periods of time.” This required developing conceptual formulas and applying engineering equations to predict power requirements of the heart, energy conversion, sources of energy, the implanted pumping section, external driving power, and controlling mechanisms. Although several of their calculations might be slightly different today because of additional knowledge gained over the years, they were remarkably accurate. In addition, they identified the major criteria for a “total bypass implantable heart” device: (1) it is inert, (2) it deters clot formation, (3) it does not destroy blood elements, (4) it can provide reproducible performance over long periods (approximately 20 years), (5) it is of sufficient size to be placed in a pleural cavity, and (6) it has a source of energy that is small, portable, preferably implantable, reliable, and long lasting. These device design criteria remain Address correspondence to Dr Slaughter, Department of Cardiovascular and Thoracic Surgery, University of Louisville, 201 Abraham Flexner Way, Ste 1200, Louisville, KY 40202; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
important characteristics for today’s left ventricular assist devices (LVADs) and TAHs as well. Based on their performance calculations and design criteria for a successful device, they were able to develop experimental prototypes of an implanted heart. Essentially, their novel device was composed of 2 independent but mirror-image hydraulically driven pulsatile pumps with silicone elastomer diaphragms housed in a poly(methyl methacrylate) chamber, which could provide up to 3.6 L/min flow against a peak pressure of 200 mm Hg. In vitro studies revealed that the connecting grafts needed to be nonporous to prevent leaking and rigid enough to not collapse during the negative-pressure phase and, most importantly, that no 2 pumps would pump exactly the same amount over long periods, thus requiring some mechanism for “equalization.” In vivo studies were also successful, with the longest voluntary survival of 6 hours and 30 minutes. They were also able to develop an algorithm of “skipped beats” on the right side that allowed equalization, as evidenced by the fact that no study participant experienced significant pulmonary hypertension. There was a large group of early pioneers that contributed to the field of mechanical circulatory support, including Drs Kolff, Kusserow, Kantrowitz, Nose, Liotta, Hastings, and DeBakey [1]. John Watson, PhD, deserves credit as well, because it was his vision while at the National Heart, Blood, and Lung Institute to fund a series of requests for proposals to develop reliable, durable, and safe implantable heart assist devices [2–4]. As a direct result of National Institutes of Health funding, new knowledge expanded into the areas of biomaterials, shear stress, blood elements and microparticles, bearings, and the possibility of continuous-flow pumps, which was then successfully translated into the development of mechanical assist devices in clinical use today. To compete with heart transplantation, initial efforts were focused on the development of a TAH. Although the first TAH was implanted in 1969, it was not until 1982 that the first TAH intended for permanent use was implanted by Dr DeVries in Utah. This TAH was the culmination of decades of work by Willem Kolff and was later named the Jarvik-7 TAH. With some modifications and additional clinical experience, predominantly by Dr Copeland, it Ann Thorac Surg 2015;99:749–51 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.01.016
750
PERSPECTIVES ON VOLUME 1 SLAUGHTER HISTORY OF MECHANICAL CIRCULATORY SUPPORT
is still in use today and is known as the SynCardia TAH (SynCardia Systems, Tuscon, AZ) [5]. Since then, additional attempts have been made to mimic the thengrowing success of heart transplantation with the development of the AbioCor TAH (Abiomed, Danvers, MA) [6], and the LionHeart TAH (Abiomed, Danvers, MA) [7]. Although the development of these devices resulted in a significant increase in our knowledge of mechanical circulatory support, the overall clinical results were not nearly as impressive. As suggested by Zuhdi and colleagues, a TAH would require balancing the flow between the right and left ventricles, which adds complexity, larger size, and increased power requirements; subsequently, a larger power source and a greater blood contacting surface area are also required, all of which may potentially contribute to clinically significant adverse events. Despite these daunting hurdles, there are several newer-generation TAHs in development today that are promising [8, 9]. Perhaps the greatest pearl of wisdom included in the article by Zuhdi and colleagues was the prediction that a “bypass implanted heart,” or LVAD, “presents many theoretical and practical advantages.” As noted by the INTERMACS registry (Fig 1), isolated LVADs have much better early- and long-term survival compared with either biventricular support or a TAH [10]. A major milestone in the development of LVADs was the surprising success of the Hemopump (Nimbus Medical, Inc, Rancho Cordova, CA), which was a catheter-based mechanical circulatory support device [11]. Drs Wampler and Frazier were able to demonstrate that a continuous-flow high-speed rotary pump was capable of providing hemodynamic support without destroying blood elements. Their innovation rapidly changed the field with a transformation from pulsatile-flow pumps
Fig 1. INTERMACS—Kaplan-Meier survival by flow type and device primary prospective implants: June 23, 2006 to June 30, 2014. (BiVAD ¼ biventricular assist device; LVAD ¼ left ventricular assist device; TAH ¼ total artificial heart.)
Ann Thorac Surg 2015;99:749–51
to continuous-flow devices. Continuous-flow technology has resulted in significant miniaturization, reduced power requirements, and increased reliability and durability and has enabled access to smaller patients, particularly women. Current outcomes with either axial- or centrifugal-flow LVADs for bridge-totransplantation procedures approach 90% survival at 1 year [12, 13], and for destination therapy the outcomes are similar to heart transplantation outcomes at 2 years for select patients [14]. The article by Zuhdi and colleagues was what we all hope our publications would be like. It was well written, scientifically accurate, and with a discussion that clearly and without bias described their results and made bold predictions for future progress. Thus their article not only contributed to the current knowledge of the time but was also a blueprint and challenge to those who would follow. Significant advancements have been made since this publication 50 years ago. Clinicians now have access to a new generation of clinically approved small continuous-flow pumps that assist the left ventricle, do not require a sternotomy for insertion, are being evaluated for efficacy in patients with less severe heart failure, and are used as a platform for myocardial recovery to avoid the need for heart transplantation. Although many significant technological advances with mechanical circulatory support have been made over the past 50 years, our field still faces many hurdles to overcome—namely, reducing adverse events related to the patient-device interface. As a technology to treat advanced heart failure, we have not “walked on the moon” yet, but we continue to “shoot for the stars” as a potential treatment and cure for millions of patients with advanced heart failure that will ultimately require something beyond medical therapy [15].
Ann Thorac Surg 2015;99:749–51
References 1. Zuhdi N, Ritchie C, Carey J, Greer A. Assisted circulation— the concept of the implanted bypass heart: an experimental study. Ann Thorac Surg 1965;1:229–43. 2. National Institutes of Health: National Heart, Lung, and Blood Institute. Request for proposals. Left heart assist blood pumps, RFP NHLBI 77–8; and Development of electrical energy converters to power and control left heart assist devices. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1976. 3. Watson JT, Carlsen RR. Request for proposal: Development of an implantable integrated electrically powered left heart assist system. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1980. 4. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. Innovative ventricular assist systems (request for proposal). Bethesda, MD: Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; 1994. 5. Torregrossa G, Morshuis M, Varghese R, et al. Results with SynCardia total artificial heart beyond 1 year. ASAIO J 2014;60:626–34. 6. Dowling RD, Gray LA Jr, Etoch SW, et al. The AbioCor implantable replacement heart. Ann Thorac Surg 2003; 75(6 Suppl):S93–9. 7. Mehta SM, Pae WE Jr, Rosenberg G, et al. The LionHeart LVD-2000: a completely implanted left ventricular assist device for chronic circulatory support. Ann Thorac Surg 2001;71(3 Suppl):S156–61.
PERSPECTIVES ON VOLUME 1 SLAUGHTER HISTORY OF MECHANICAL CIRCULATORY SUPPORT
751
8. Mohacsi P, Leprince P. The CARMAT total artificial heart. Eur J Cardiothorac Surg 2014;46:933–4. 9. Koerfer R, Spiliopoulos S, Finocchiaro T, Guersoy D, Tenderich G, Steinseifer U. Paving the way for destination therapy of end-stage biventricular heart failure: the ReinHeart total artificial heart concept. Eur J Cardiothorac Surg 2014;46:935–6. 10. INTERMACS: Quarterly Statistical Review 2014 2nd Quarter Available at: https://www.uab.edu/medicine/intermacs/ images/Federal_Quarterly_Report/Federal_Partners_Report_ 2014_Q2.pdf . Accessed: January 6, 2015. 11. Frazier OH, Wampler RK, Duncan JM, et al. First human use of the Hemopump, a catheter-mounted ventricular assist device. Ann Thorac Surg 1990;49:299–304. 12. Slaughter MS, Pagani FD, McGee EC, et al, HeartWare Bridge to Transplant ADVANCE Trial Investigators. HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2013;32:675–83. 13. Starling RC, Naka Y, Boyle AJ, et al. Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 2011;57:1890–8. 14. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation? J Thorac Cardiovasc Surg 2012;144:584–603. 15. Kirklin JK. Terminal heart failure: who should be transplanted and who should have mechanical circulatory support? Curr Opin Organ Transplant 2014;19:486–93.
