PRO AND CON Michelle Capdeville, MD Section Editor
Pro: The Total Artificial Heart: Is It an Appropriate Replacement for Existing Biventricular Assist Devices? Zakir Rangwala, MD,* Dalia A. Banks, MD, FASE,* and Jack G. Copeland, MD†
C
ONGESTIVE HEART FAILURE (CHF) defines the endpoint of cardiac dysfunction in most cardiac diseases, and while advancements in medical therapy have been promising, the incidence of CHF is approximately 500,000 per year, and it is estimated that nearly 5 million patients in the U.S. suffer from some degree of heart failure. In fact, annual healthcare costs are up to $38.1 billion; and in the United States, $500 million per year, is spent on medical drug treatment for heart failure.1 Despite the best efforts of medical and surgical care, nearly 300,000 patients die of heart failure as a primary or contributory cause each year.1 Patients continue to decline in health, have a decline in quality of life, require increased hospitalizations, and ultimately succumb prematurely to their illness. While heart transplantation remains a viable solution for these patients, shortages in donor supply have limited transplants to fewer than 2,500 per year. Since 2005, the number of active new adult candidates on the heart transplant waiting list increased by 19.2%. Currently, it is estimated that up to 50,000 people per year die while waiting for a transplant. Of patients on the heart transplant list in 2008, 11.6% died after 36 months while still waiting for an available transplantation.2 Although medical algorithms have proved useful for the treatment of class I to class III CHF, patients with class III and, especially, class IV require more aggressive management for survival.3 For appropriate patients with isolated left ventricular failure, left ventricular assist devices (LVAD) have been shown to increase survival to transplantation, increase survival after transplantation, and improve quality of life.4 Patients with more severe disease prove to be much more difficult to manage. As left heart failure progresses to biventricular failure, replacement of total heart pump function is needed. Heart transplantation is currently the best treatment for patients with end-stage biventricular heart failure. The International Society of Heart and Lung transplant registry shows that more than half the patients
From the Departments of *Anesthesiology and †Cardiac Surgery, University of California San Diego, San Diego, CA. Address reprint requests to Dalia A. Banks, MD, FASE, University of California San Diego, VA Medical Center (125A), 3350 La Jolla Village Drive, San Diego, CA 92161-5085. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2602-0034$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.02.015 Key words: heart failure, total artificial heart, ventricular assist devices 836
who undergo transplantation have a survival rate of 11 years, with a much more dramatic improvement in quality of life than they would have had if they remained in medical therapy.5 Yet, heart transplantation has its limitations. Contraindications to heart transplantation include existence of recipient antibodies, high pulmonary vascular resistance, and adverse events related to immunosuppression, and these are just some of the relative contraindications to heart transplantation. The scarcity of donor hearts coupled with the progressive nature of heart failure lead patients to deteriorate while on the transplant waiting list, and some patients will die before a suitable donor becomes available. The use of mechanical circulatory support (MCS) has been the mainstay of non-surgical approaches to the failing heart. There exists a spectrum of MCS devices that address the varying degrees of cardiac dysfunction encountered in heart failure patients. These devices have a wide range of capabilities ranging from partial support to ventricular assist to full replacement. The total artificial heart (TAH) system has several unique features that are advantageous relative to ventricular assist devices (VAD). In the United States, 2 artificial heart systems have been used since the 1960s. ABIOCOR TAH
The AbioCor TAH by Abiomed, Inc. is a single-body, pulsatile device that uses an electrohydraulic actuator system rather than pneumatic drives. An implanted internal coil is coupled with an external coil that receives power from an external source. An oscillator in the external coil generates a magnetic field, which then gets converted into electrical energy by the internal coil. The external power source is a portable battery pack that can last for 2 hours. There is also a built-in internal battery that provides 20 to 30 minutes of power for limited disconnections from external sources. The AbioCor is capable of producing cardiac outputs of 8 L/min with a stroke volume of 60 mL. Its size and mass (900 gm) limit its usefulness; it will only fit in approximately 50% of men, 20% of women, and 0% of children. Initial testing of the AbioCor TAH began in 2001 at the University of Louisville. The preliminary trial, which included 14 patients, revealed that thromboembolism was a recurring complication.6 The most common causes of death were stroke (4 patients) and multiple system organ failure (3 patients). Intraoperative death occurred twice. Six patients survived between 53 and 151 days, 1 patient survived 293 days, and the longest surviving patient survived 512 days. The 30-day
Journal of Cardiothoracic and Vascular Anesthesia, Vol 28, No 3 (June), 2014: pp 836–839
PRO: TOTAL ARTIFICIAL HEART
survival rate was 71% compared to the predicted survival rate of 13% with only medical intervention. At 60 days, 43% were still alive. There were no reports of device-related malfunctions or infections. Several patients were able to become ambulatory, and 1 patient was discharged from the hospital for 9 months.7 In September 2006, the FDA approved the AbioCor for use under a Humanitarian Device Exemption (HDE), which limited the use of the AbioCor to patients with severe biventricular heart failure who were not candidates for transplantation and who had an expected 30-day survival less than 30%. To date, the AbioCor only has been used as destination therapy in patients with end-stage CHF, and the number of transplants is limited compared to the CardioWest TAH. Only 1 patient had received an AbioCor TAH since the HDE was granted. Although the AbioCor is no longer in production, a second generation AbioCor II is in development that will circumvent size limitations and potentially reduce the complications of thromboembolism and atrial suck-down events that have occurred with the AbioCor.8 SYNCARDIA TAH
In 2004, The SynCardia Total Artificial Heart (TAH-t) (CardioWest) became the first and only TAH to receive FDA approval, and in 2008 the Centers for Medicare and Medicaid Services also approved the TAH-t. It remains the only fully approved TAH system in use today. More than 11,000 TAH-t units have been implanted. While only approved for bridge-totransplant therapy in the United States, centers in Europe and Australia currently are performing destination implants. The current design is a pulsatile, pneumatically driven pump with 3 components: A prosthetic pair of ventricles made of polyurethane, drivelines, and an external pneumatic driver. Each prosthetic ventricle contains an air chamber and a blood chamber and is separated by a diaphragm. Ventricular systole occurs when air is driven into the chambers displacing the diaphragms causing ejection of blood from the blood chamber. During diastole, the diaphragm relaxes, allowing passive filling of blood into the prosthetic ventricles. Compressed air is delivered by an external driver console attached to the ventricles by PVC and polyurethane tubing. Parameters that can be adjusted include driving pressures for the left and right ventricles, beat rate, systolic duration, and vacuum pressure, all done through the external console. The ability to adjust systolic duration indirectly can adjust diastolic filling time, allowing cardiac output to increase with increased venous return. The TAH-t is able to deliver stroke volumes of up to 70 mL and can deliver cardiac outputs of up to 9.5 L/min. The first-generation external consoles were large 180-kg devices that restricted patient mobility and prevented hospital discharge. Advances in driver technology have led to the production of the Freedom driver, a 6-kg console that allows for patient discharge and mobility.9 Current guidelines from SynCardia recommend that implantation be limited to patients with a body surface area ≥ 1.7 m2 or an anteroposterior distance of ≥ 10 cm as measured by CT. In the near future, with the release of the next generation of TAH-t, a 50 mL heart will be available in addition to the present 70 mL version, extending the therapeutic window of TAH support to smaller adults and children.10
837
The capabilities of the TAH-t allow for rapid and full hemodynamic restoration in both ventricles for patients in severe biventricular heart failure. Organ perfusion is enhanced and backward failure is reduced to a degree superior to that of an LVAD or biventricular assist device (BiVAD).10 The TAH-t allows for much higher flows than possible with univentricular devices. TAH-t also has shown to have limited hemolysis and coagulation activation relative to the rotary VAD systems that exist today.11-14 While studies have shown that LVADs lead to recovery and return of function, there is a frequent unmasking of right heart failure. If right heart function is not augmented with an additional VAD, the increases in morbidity and mortality are significant. Placement of a right ventricular assist device and the unmasking of right heart failure following LVAD placement are associated with up to 50% mortality. If the patient requires a conversion to a dual-system BiVAD, they face a reduction in bridge-to-transplantation survival.12 The TAH-t’s pulsatile flow also may confer some advantages over traditional non-pulsatile, continous-flow VAD support. The pros and cons of pulsatile flow have been debated for years, but it offers practical and theoretical advantages. From a practical standpoint, the pulsatile TAH-t is not as pressure- and volume-sensitive as traditional VADs. When presented with hypertension and increased afterload, VAD flow and systemic perfusion may be compromised due to the impedance to forward flow. With reduced volume status, VADs will have a decrement in cardiac output. In contrast, the pulsatile nature in the TAH-t can sustain its ejection force even in the face of afterload increase as its blood chamber reservoir allows full filling of ventricles per beat. This system appears to be less volume- and pressure-sensitive, allowing the maintenance of full flows in a wide range of hemodynamic conditions.13 From a theoretical standpoint, pulsatility will decrease the likelihood of turbulent flow.11 This translates into less platelet activation and reduced risk for thrombosis. Pulsatile flow systems also have been shown to be associated with reduced inflammation, enhanced endothelial function, and maintenance of arterial integrity compared to continous-flow systems.13,14 Lastly, the characteristics of flow dynamics in MCS can affect the occurrence of post-implant bleeding and hemorrhagic stroke. Studies have shown that bleeding events after LVAD implantation are related to an acquired von Willebrand syndrome (AVWS), possibly stemming from the turbulent flow encountered in LVADs. The high shear can lead to denaturation of von Willebrand multimers, reducing the effect of platelet function and hemostasis.15 AVWS is not seen in TAH-t, as pulsatile flow coupled with flow through large orifices is free of protein denaturation. Spontaneous GI bleeding has been reported to be less than 4% with the TAH-t compared to continous-flow non-pulsatile devices that show GI bleeding rates between 20% and 50% in the first implant year.16 The embolic risk has been shown to be consistently higher in LVAD patients due to occult thrombi present in the native sluggish ventricles found in severe heart failure. Often, intraventricular thrombi are missed with conventional imaging modalities and only are found after direct visual inspection. In contrast, TAH-t implantation involves excision of the native
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ventricular tissue with almost complete elimination of thromboembolic risk from LV thrombi. Additionally, VAD function is complicated by ventricular arrhythmias that often accompany end-stage heart failure. TAHs obviate this problem. TAH-t has been shown to have a reduced thrombosis rate compared to other MCS devices. One trial demonstrated a 5% stroke rate17 whereas the VAD stroke rate has been recorded as high as 59% in some trials.18 The design features specific to the TAH-t including large cavity chambers, high flows, reduced flow turbulence, large cross-sectional areas of inflow and outflow valves and short prosthetic conduit lengths all contribute to a lower embolization risk. The largest and most comprehensive study looking at the TAH-t was conducted by Copeland et al.17 This study looked at 130 moribund patients with irreversible biventricular failure. The protocol group consisted of 81 patients who met the study’s inclusion criteria for TAH-t implantation and received the implant. The control group, which consisted of 31 patients, met the inclusion criteria defined by the authors but did not receive implantation. Fourteen patients did not meet the inclusion criteria. Overall survival to transplantation was 79% in patients receiving TAH-t versus 46% of the control group. Survival rate at one year was 70% compared to 31% in the control group. Survival at 1 and 5 years after heart transplantation was 86% and 64%, respectively, compared with 69% and 34% in the control group. The survival data of patients who were bridged to transplantation are comparable to the UNOS data, with 1- and 5-year survival rates at 84.7% and 69.8%, respectively. In addition to survival data, Copeland and colleagues also looked at secondary endpoints. They noted an immediate improvement in hemodynamic status with increased systemic pressures and reduced central venous pressures. Cardiac index rose from 1.9 L/ min/m2 to 3.2 L/min/m2. Most importantly, there was an improved quality of life in the TAH group. One week postimplementation, 75% of patients were out of bed, and 60% were able to walk 100 feet at 2 weeks post-implantation. From an anesthetic standpoint, patients scheduled for TAH transplantation may prove very difficult to manage. Similar to patients appropriate for VADs, TAH patients will be suffering
from end-stage heart failure and signs of end-organ dysfunction. Pulmonary hypertension and right-sided failure often are also present.19 If pulmonary hypertension is severe and fixed, cardiac transplantation is relatively contraindicated, and bridge to a TAH system may prove to be difficult. Patients should have arterial access monitoring and central venous access in addition to the standard American Society of Anesthesiologists monitors. Transesophageal echocardiography also has proved invaluable in the anesthetic management. A comprehensive prebypass TEE exam will reveal findings consistent with biventricular failure. An assessment of the hemodymanics and valvular integrity may be helpful in guiding the anesthetic and achieving the hemodynamic goals.20 End-stage biventricular failure also may lead to stasis of blood and will increase the risk of intracardiac clot,21 so inspection for intracardiac thrombus must be taken and findings communicated with the surgeon. In the post-implantation period, TEE is crucial in the de-airing process of the new device as well as the aorta and atria.19 The implantation of a TAH can distort the anatomy of the venous return to the native atria, so inspection of the vena cava and pulmonary veins for compression may be necessary with TEE as well.22 There are undisputed indications for TAH implantation: Failed cardiac transplantation, acute or chronic massive myocardial infarction, acquired ventricular septal defect, diffuse mural thrombosis, congenital conditions, severe hypertrophic cardiomyopathy, and catastrophic intraoperative cardiac damage. Additionally, the TAH-t has demonstrated the ability to circumvent the limitations that occur with LVAD implantation and has shown superior efficacy in the treatment of biventricular failure. Studies have shown a superior bridge to transplantation survival rate compared to BiVAD and LVAD systems with greater functional capacity and quality of life. With advances in MCS technology, patients are now afforded the ability to leave the hospital and return to normal activities, with remote monitoring capabilities allowing recognition of device malfunction. With continued support and research into TAH, there is hope for a definitive treatment for biventricular heart failure that parallels heart transplantation.
REFERENCES 1. Hunt SA, Abraham WT, Chin MH, et al: ACC/AHA 2005 Guideline update for the diagnosis and management of chrinic heart failure in the adult: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation 112:e154-e235, 2005 2. Colvin-Adams M, Smithy JM, Heubner BM, et al: Organ Procurement and Transplant Network Annual Report 2011: Heart. Am J Transplant 13(S1):119-148, 2013 3. Gray NA Jr, Selzman CH: Current status of the total artificial heart. Am Heart J 152:4-10, 2006 4. Shreenivas SS, Rame JE, Jessup M: Mechanical circulatory support as a bridge to transplant or for destination therapy. Curr Heart Failure 7:159-166, 2010 5. Stehlik J, Edwards LB, Kucheryavaya AY, et al: The Registry of the International Society for Heart and Lung Transplantation: Twentyeighth Adult Heart Transplant Report–2011. J Heart Lung Transplant 30:1078-1094, 2011 6. Frazier OH, Dowling RD, Gray LA Jr, et al: The total artificial heart: Where we stand. Cardiology 101:117-121, 2004
7. Dowling RD, Gray LA Jr, Etoch SW, et al: Initial Experience with the AbioCor implantable replacement heart system. J Thorac Cardiovasc Surg 127:131-141, 2004 8. Juretich JT, Corbett SC, Ritchie G, et al: Development Progress on a Second Generation Total Artificial Heart. ASAIO Journal. 52: 2 p48, Mar/Apr 2006 9. Arabia FA, Copeland JG, Smith RG, et al: CardioWest total artificial heart: A retrospective controlled study. Artif Organs 23: 204-207, 1999 10. Slepian MJ: The SynCardia Temporary Total Artificial Heart – Evolving Clinical Role and Future Status. US Cardiol 8: 39-46, 2011 11. Miller LW, Pagani FD, Russel SD, et al: Use of a continuousflow device in patients awaiting transplantation. New Engl J Medicine 357:885-896, 2007 12. Loebe M, Koster A, Sanger S, et al: Inflammatory response after implantation of a left ventricular assist device: comparison between axial flow MicroMed Debakey VAD and the pulsatile Novacor device. ASAIO J 47:272-274, 2001
PRO: TOTAL ARTIFICIAL HEART
13. Younis BA, Berger SA: A turbulence model for pulsatile arterial blood flows. J Biomech Eng 126:578-584, 2004 14. John R, Panch S, Hrabe J, et al: Activation of endothelial and coagulation systems in left ventricular assist device recipients. Ann Thoracic Surg 88:1171-1179, 2009 15. Uriel N, Pak SW, Jorde UP, et al: Acquired von Willebrand syndrome after continuous flow mechanical device support contributes to a high prevalence of bleeding during long term support and at the time of transplantation. J Am Coll Cardiol 56:12071213, 2010 16. Heilmann C, Geisen U, Beyersdorf F, et al: Acquired von Willebrand Syndrome in patients with ventricular assist device or total artificial heart. Thromb Hemost 103:962-967, 2010 17. Copeland JG, Smith RG, Arabia FA, et al: Cardiac replacement with a total artificial heart as a bridge to transplantation. New Engl J Medicine 351:859-867, 2004
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18. Frazier OH, Rose EA, Oz MC, et al: Multi-center clinical evaluation of the Heartmate vented electric left ventricular assist system in patients awaiting heart transplantation. J Thoracic Cardiovasc Surg 122:1186-1195, 2001 19. Thunberg CA, Gaitan BD, Arabia FA, et al: Ventricular assist devices today and tomorrow. J Cardiothorac Vasc Anesth 24:656-680, 2010 20. Gaitan BD, Thunberg CA, Stansbury LG, et al: Development, current status, and anesthetic management of implanted artificial heart. J Cardiothorac Vasc Anesth 25:1179-1192, 2011 21. Chumnavej S, Wood MJ, MacGillivray TE, et al: Perioperative echocardiographic examination for ventricular assist device implantation. Anesth Analg 105:583-601, 2007 22. Arabia FA, Copeland JG, Paive A, et al: Implantation technique for the CardioWest Total Artificial Heart. Ann Thora Surg 68: 698-704, 1999
Pro: The Total Artificial Heart: Is It an Appropriate Replacement for Existing Biventricular Assist Devices? Zakir Rangwala, MD,* Dalia A. Banks, MD, FASE,* and Jack G. Copeland, MD†
C
ONGESTIVE HEART FAILURE (CHF) defines the endpoint of cardiac dysfunction in most cardiac diseases, and while advancements in medical therapy have been promising, the incidence of CHF is approximately 500,000 per year, and it is estimated that nearly 5 million patients in the U.S. suffer from some degree of heart failure. In fact, annual healthcare costs are up to $38.1 billion; and in the United States, $500 million per year, is spent on medical drug treatment for heart failure.1 Despite the best efforts of medical and surgical care, nearly 300,000 patients die of heart failure as a primary or contributory cause each year.1 Patients continue to decline in health, have a decline in quality of life, require increased hospitalizations, and ultimately succumb prematurely to their illness. While heart transplantation remains a viable solution for these patients, shortages in donor supply have limited transplants to fewer than 2,500 per year. Since 2005, the number of active new adult candidates on the heart transplant waiting list increased by 19.2%. Currently, it is estimated that up to 50,000 people per year die while waiting for a transplant. Of patients on the heart transplant list in 2008, 11.6% died after 36 months while still waiting for an available transplantation.2 Although medical algorithms have proved useful for the treatment of class I to class III CHF, patients with class III and, especially, class IV require more aggressive management for survival.3 For appropriate patients with isolated left ventricular failure, left ventricular assist devices (LVAD) have been shown to increase survival to transplantation, increase survival after transplantation, and improve quality of life.4 Patients with more severe disease prove to be much more difficult to manage. As left heart failure progresses to biventricular failure, replacement of total heart pump function is needed. Heart transplantation is currently the best treatment for patients with end-stage biventricular heart failure. The International Society of Heart and Lung transplant registry shows that more than half the patients
From the Departments of *Anesthesiology and †Cardiac Surgery, University of California San Diego, San Diego, CA. Address reprint requests to Dalia A. Banks, MD, FASE, University of California San Diego, VA Medical Center (125A), 3350 La Jolla Village Drive, San Diego, CA 92161-5085. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2602-0034$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.02.015 Key words: heart failure, total artificial heart, ventricular assist devices 836
who undergo transplantation have a survival rate of 11 years, with a much more dramatic improvement in quality of life than they would have had if they remained in medical therapy.5 Yet, heart transplantation has its limitations. Contraindications to heart transplantation include existence of recipient antibodies, high pulmonary vascular resistance, and adverse events related to immunosuppression, and these are just some of the relative contraindications to heart transplantation. The scarcity of donor hearts coupled with the progressive nature of heart failure lead patients to deteriorate while on the transplant waiting list, and some patients will die before a suitable donor becomes available. The use of mechanical circulatory support (MCS) has been the mainstay of non-surgical approaches to the failing heart. There exists a spectrum of MCS devices that address the varying degrees of cardiac dysfunction encountered in heart failure patients. These devices have a wide range of capabilities ranging from partial support to ventricular assist to full replacement. The total artificial heart (TAH) system has several unique features that are advantageous relative to ventricular assist devices (VAD). In the United States, 2 artificial heart systems have been used since the 1960s. ABIOCOR TAH
The AbioCor TAH by Abiomed, Inc. is a single-body, pulsatile device that uses an electrohydraulic actuator system rather than pneumatic drives. An implanted internal coil is coupled with an external coil that receives power from an external source. An oscillator in the external coil generates a magnetic field, which then gets converted into electrical energy by the internal coil. The external power source is a portable battery pack that can last for 2 hours. There is also a built-in internal battery that provides 20 to 30 minutes of power for limited disconnections from external sources. The AbioCor is capable of producing cardiac outputs of 8 L/min with a stroke volume of 60 mL. Its size and mass (900 gm) limit its usefulness; it will only fit in approximately 50% of men, 20% of women, and 0% of children. Initial testing of the AbioCor TAH began in 2001 at the University of Louisville. The preliminary trial, which included 14 patients, revealed that thromboembolism was a recurring complication.6 The most common causes of death were stroke (4 patients) and multiple system organ failure (3 patients). Intraoperative death occurred twice. Six patients survived between 53 and 151 days, 1 patient survived 293 days, and the longest surviving patient survived 512 days. The 30-day
Journal of Cardiothoracic and Vascular Anesthesia, Vol 28, No 3 (June), 2014: pp 836–839
PRO: TOTAL ARTIFICIAL HEART
survival rate was 71% compared to the predicted survival rate of 13% with only medical intervention. At 60 days, 43% were still alive. There were no reports of device-related malfunctions or infections. Several patients were able to become ambulatory, and 1 patient was discharged from the hospital for 9 months.7 In September 2006, the FDA approved the AbioCor for use under a Humanitarian Device Exemption (HDE), which limited the use of the AbioCor to patients with severe biventricular heart failure who were not candidates for transplantation and who had an expected 30-day survival less than 30%. To date, the AbioCor only has been used as destination therapy in patients with end-stage CHF, and the number of transplants is limited compared to the CardioWest TAH. Only 1 patient had received an AbioCor TAH since the HDE was granted. Although the AbioCor is no longer in production, a second generation AbioCor II is in development that will circumvent size limitations and potentially reduce the complications of thromboembolism and atrial suck-down events that have occurred with the AbioCor.8 SYNCARDIA TAH
In 2004, The SynCardia Total Artificial Heart (TAH-t) (CardioWest) became the first and only TAH to receive FDA approval, and in 2008 the Centers for Medicare and Medicaid Services also approved the TAH-t. It remains the only fully approved TAH system in use today. More than 11,000 TAH-t units have been implanted. While only approved for bridge-totransplant therapy in the United States, centers in Europe and Australia currently are performing destination implants. The current design is a pulsatile, pneumatically driven pump with 3 components: A prosthetic pair of ventricles made of polyurethane, drivelines, and an external pneumatic driver. Each prosthetic ventricle contains an air chamber and a blood chamber and is separated by a diaphragm. Ventricular systole occurs when air is driven into the chambers displacing the diaphragms causing ejection of blood from the blood chamber. During diastole, the diaphragm relaxes, allowing passive filling of blood into the prosthetic ventricles. Compressed air is delivered by an external driver console attached to the ventricles by PVC and polyurethane tubing. Parameters that can be adjusted include driving pressures for the left and right ventricles, beat rate, systolic duration, and vacuum pressure, all done through the external console. The ability to adjust systolic duration indirectly can adjust diastolic filling time, allowing cardiac output to increase with increased venous return. The TAH-t is able to deliver stroke volumes of up to 70 mL and can deliver cardiac outputs of up to 9.5 L/min. The first-generation external consoles were large 180-kg devices that restricted patient mobility and prevented hospital discharge. Advances in driver technology have led to the production of the Freedom driver, a 6-kg console that allows for patient discharge and mobility.9 Current guidelines from SynCardia recommend that implantation be limited to patients with a body surface area ≥ 1.7 m2 or an anteroposterior distance of ≥ 10 cm as measured by CT. In the near future, with the release of the next generation of TAH-t, a 50 mL heart will be available in addition to the present 70 mL version, extending the therapeutic window of TAH support to smaller adults and children.10
837
The capabilities of the TAH-t allow for rapid and full hemodynamic restoration in both ventricles for patients in severe biventricular heart failure. Organ perfusion is enhanced and backward failure is reduced to a degree superior to that of an LVAD or biventricular assist device (BiVAD).10 The TAH-t allows for much higher flows than possible with univentricular devices. TAH-t also has shown to have limited hemolysis and coagulation activation relative to the rotary VAD systems that exist today.11-14 While studies have shown that LVADs lead to recovery and return of function, there is a frequent unmasking of right heart failure. If right heart function is not augmented with an additional VAD, the increases in morbidity and mortality are significant. Placement of a right ventricular assist device and the unmasking of right heart failure following LVAD placement are associated with up to 50% mortality. If the patient requires a conversion to a dual-system BiVAD, they face a reduction in bridge-to-transplantation survival.12 The TAH-t’s pulsatile flow also may confer some advantages over traditional non-pulsatile, continous-flow VAD support. The pros and cons of pulsatile flow have been debated for years, but it offers practical and theoretical advantages. From a practical standpoint, the pulsatile TAH-t is not as pressure- and volume-sensitive as traditional VADs. When presented with hypertension and increased afterload, VAD flow and systemic perfusion may be compromised due to the impedance to forward flow. With reduced volume status, VADs will have a decrement in cardiac output. In contrast, the pulsatile nature in the TAH-t can sustain its ejection force even in the face of afterload increase as its blood chamber reservoir allows full filling of ventricles per beat. This system appears to be less volume- and pressure-sensitive, allowing the maintenance of full flows in a wide range of hemodynamic conditions.13 From a theoretical standpoint, pulsatility will decrease the likelihood of turbulent flow.11 This translates into less platelet activation and reduced risk for thrombosis. Pulsatile flow systems also have been shown to be associated with reduced inflammation, enhanced endothelial function, and maintenance of arterial integrity compared to continous-flow systems.13,14 Lastly, the characteristics of flow dynamics in MCS can affect the occurrence of post-implant bleeding and hemorrhagic stroke. Studies have shown that bleeding events after LVAD implantation are related to an acquired von Willebrand syndrome (AVWS), possibly stemming from the turbulent flow encountered in LVADs. The high shear can lead to denaturation of von Willebrand multimers, reducing the effect of platelet function and hemostasis.15 AVWS is not seen in TAH-t, as pulsatile flow coupled with flow through large orifices is free of protein denaturation. Spontaneous GI bleeding has been reported to be less than 4% with the TAH-t compared to continous-flow non-pulsatile devices that show GI bleeding rates between 20% and 50% in the first implant year.16 The embolic risk has been shown to be consistently higher in LVAD patients due to occult thrombi present in the native sluggish ventricles found in severe heart failure. Often, intraventricular thrombi are missed with conventional imaging modalities and only are found after direct visual inspection. In contrast, TAH-t implantation involves excision of the native
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ventricular tissue with almost complete elimination of thromboembolic risk from LV thrombi. Additionally, VAD function is complicated by ventricular arrhythmias that often accompany end-stage heart failure. TAHs obviate this problem. TAH-t has been shown to have a reduced thrombosis rate compared to other MCS devices. One trial demonstrated a 5% stroke rate17 whereas the VAD stroke rate has been recorded as high as 59% in some trials.18 The design features specific to the TAH-t including large cavity chambers, high flows, reduced flow turbulence, large cross-sectional areas of inflow and outflow valves and short prosthetic conduit lengths all contribute to a lower embolization risk. The largest and most comprehensive study looking at the TAH-t was conducted by Copeland et al.17 This study looked at 130 moribund patients with irreversible biventricular failure. The protocol group consisted of 81 patients who met the study’s inclusion criteria for TAH-t implantation and received the implant. The control group, which consisted of 31 patients, met the inclusion criteria defined by the authors but did not receive implantation. Fourteen patients did not meet the inclusion criteria. Overall survival to transplantation was 79% in patients receiving TAH-t versus 46% of the control group. Survival rate at one year was 70% compared to 31% in the control group. Survival at 1 and 5 years after heart transplantation was 86% and 64%, respectively, compared with 69% and 34% in the control group. The survival data of patients who were bridged to transplantation are comparable to the UNOS data, with 1- and 5-year survival rates at 84.7% and 69.8%, respectively. In addition to survival data, Copeland and colleagues also looked at secondary endpoints. They noted an immediate improvement in hemodynamic status with increased systemic pressures and reduced central venous pressures. Cardiac index rose from 1.9 L/ min/m2 to 3.2 L/min/m2. Most importantly, there was an improved quality of life in the TAH group. One week postimplementation, 75% of patients were out of bed, and 60% were able to walk 100 feet at 2 weeks post-implantation. From an anesthetic standpoint, patients scheduled for TAH transplantation may prove very difficult to manage. Similar to patients appropriate for VADs, TAH patients will be suffering
from end-stage heart failure and signs of end-organ dysfunction. Pulmonary hypertension and right-sided failure often are also present.19 If pulmonary hypertension is severe and fixed, cardiac transplantation is relatively contraindicated, and bridge to a TAH system may prove to be difficult. Patients should have arterial access monitoring and central venous access in addition to the standard American Society of Anesthesiologists monitors. Transesophageal echocardiography also has proved invaluable in the anesthetic management. A comprehensive prebypass TEE exam will reveal findings consistent with biventricular failure. An assessment of the hemodymanics and valvular integrity may be helpful in guiding the anesthetic and achieving the hemodynamic goals.20 End-stage biventricular failure also may lead to stasis of blood and will increase the risk of intracardiac clot,21 so inspection for intracardiac thrombus must be taken and findings communicated with the surgeon. In the post-implantation period, TEE is crucial in the de-airing process of the new device as well as the aorta and atria.19 The implantation of a TAH can distort the anatomy of the venous return to the native atria, so inspection of the vena cava and pulmonary veins for compression may be necessary with TEE as well.22 There are undisputed indications for TAH implantation: Failed cardiac transplantation, acute or chronic massive myocardial infarction, acquired ventricular septal defect, diffuse mural thrombosis, congenital conditions, severe hypertrophic cardiomyopathy, and catastrophic intraoperative cardiac damage. Additionally, the TAH-t has demonstrated the ability to circumvent the limitations that occur with LVAD implantation and has shown superior efficacy in the treatment of biventricular failure. Studies have shown a superior bridge to transplantation survival rate compared to BiVAD and LVAD systems with greater functional capacity and quality of life. With advances in MCS technology, patients are now afforded the ability to leave the hospital and return to normal activities, with remote monitoring capabilities allowing recognition of device malfunction. With continued support and research into TAH, there is hope for a definitive treatment for biventricular heart failure that parallels heart transplantation.
REFERENCES 1. Hunt SA, Abraham WT, Chin MH, et al: ACC/AHA 2005 Guideline update for the diagnosis and management of chrinic heart failure in the adult: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation 112:e154-e235, 2005 2. Colvin-Adams M, Smithy JM, Heubner BM, et al: Organ Procurement and Transplant Network Annual Report 2011: Heart. Am J Transplant 13(S1):119-148, 2013 3. Gray NA Jr, Selzman CH: Current status of the total artificial heart. Am Heart J 152:4-10, 2006 4. Shreenivas SS, Rame JE, Jessup M: Mechanical circulatory support as a bridge to transplant or for destination therapy. Curr Heart Failure 7:159-166, 2010 5. Stehlik J, Edwards LB, Kucheryavaya AY, et al: The Registry of the International Society for Heart and Lung Transplantation: Twentyeighth Adult Heart Transplant Report–2011. J Heart Lung Transplant 30:1078-1094, 2011 6. Frazier OH, Dowling RD, Gray LA Jr, et al: The total artificial heart: Where we stand. Cardiology 101:117-121, 2004
7. Dowling RD, Gray LA Jr, Etoch SW, et al: Initial Experience with the AbioCor implantable replacement heart system. J Thorac Cardiovasc Surg 127:131-141, 2004 8. Juretich JT, Corbett SC, Ritchie G, et al: Development Progress on a Second Generation Total Artificial Heart. ASAIO Journal. 52: 2 p48, Mar/Apr 2006 9. Arabia FA, Copeland JG, Smith RG, et al: CardioWest total artificial heart: A retrospective controlled study. Artif Organs 23: 204-207, 1999 10. Slepian MJ: The SynCardia Temporary Total Artificial Heart – Evolving Clinical Role and Future Status. US Cardiol 8: 39-46, 2011 11. Miller LW, Pagani FD, Russel SD, et al: Use of a continuousflow device in patients awaiting transplantation. New Engl J Medicine 357:885-896, 2007 12. Loebe M, Koster A, Sanger S, et al: Inflammatory response after implantation of a left ventricular assist device: comparison between axial flow MicroMed Debakey VAD and the pulsatile Novacor device. ASAIO J 47:272-274, 2001
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13. Younis BA, Berger SA: A turbulence model for pulsatile arterial blood flows. J Biomech Eng 126:578-584, 2004 14. John R, Panch S, Hrabe J, et al: Activation of endothelial and coagulation systems in left ventricular assist device recipients. Ann Thoracic Surg 88:1171-1179, 2009 15. Uriel N, Pak SW, Jorde UP, et al: Acquired von Willebrand syndrome after continuous flow mechanical device support contributes to a high prevalence of bleeding during long term support and at the time of transplantation. J Am Coll Cardiol 56:12071213, 2010 16. Heilmann C, Geisen U, Beyersdorf F, et al: Acquired von Willebrand Syndrome in patients with ventricular assist device or total artificial heart. Thromb Hemost 103:962-967, 2010 17. Copeland JG, Smith RG, Arabia FA, et al: Cardiac replacement with a total artificial heart as a bridge to transplantation. New Engl J Medicine 351:859-867, 2004
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18. Frazier OH, Rose EA, Oz MC, et al: Multi-center clinical evaluation of the Heartmate vented electric left ventricular assist system in patients awaiting heart transplantation. J Thoracic Cardiovasc Surg 122:1186-1195, 2001 19. Thunberg CA, Gaitan BD, Arabia FA, et al: Ventricular assist devices today and tomorrow. J Cardiothorac Vasc Anesth 24:656-680, 2010 20. Gaitan BD, Thunberg CA, Stansbury LG, et al: Development, current status, and anesthetic management of implanted artificial heart. J Cardiothorac Vasc Anesth 25:1179-1192, 2011 21. Chumnavej S, Wood MJ, MacGillivray TE, et al: Perioperative echocardiographic examination for ventricular assist device implantation. Anesth Analg 105:583-601, 2007 22. Arabia FA, Copeland JG, Paive A, et al: Implantation technique for the CardioWest Total Artificial Heart. Ann Thora Surg 68: 698-704, 1999
