ASAIO Journal 2015
Review Article
The Evolving Role of the Total Artificial Heart in the Management of End-Stage Congenital Heart Disease and Adolescents Thomas D. Ryan, John L. Jefferies, Farhan Zafar, Angela Lorts, and David L.S. Morales
Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease. ASAIO Journal 2015; 61:8–14.
morbidity and reduced mortality for several childhood diseases. Because of these successes, there is now a generation of aging patients encountering previously unseen complications. One dramatic example is patients with congenital heart disease, both surgically palliated and uncorrected, who develop end-stage heart failure. According to the Congenital Heart Public Health Consortium (www.chphc.org), in the United States there are an estimated 2 million people living with congenital heart disease, including approximately 959,000–1.5 million adults. This encompasses “a substantial number of young adults with single ventricle physiology, systemic right ventricles or complex intracardiac baffles.”1 Familial and acquired cardiomyopathies constitute another group of patients at risk for heart failure, and whose numbers are increasing because of improved recognition, diagnosis and early therapy. When medical treatment is inadequate in the adult congenital heart disease (ACHD) patient with heart failure, surgical options are considered. These may include surgical revision or cardiac transplantation.2 Only 3000–5000 heart transplants are performed worldwide each year, with approximately 3% in ACHD.3 Not all patients are appropriate candidates for transplantation as some may have end-organ dysfunction requiring concurrent therapies not compatible with transplant, inability to tolerate the necessary immunosuppression or high panel reactive antibodies (PRA). Viable alternatives are needed for the patient with end-stage heart failure due to congenital heart disease that is ineligible for a further palliative surgical procedure or those unable to wait for a donor to become available. One intriguing option is placement of a total artificial heart (TAH) as a bridge to transplantation. The concept of mechanical circulatory support (MCS) as a bridge to transplant is familiar territory, with approximately 20% of all candidates temporized with some form of MCS.3 There are several options available,4 and overall the number of MCS devices implanted is now approaching, if not surpassing, the number of transplantations performed.5 The time gained with MCS may allow reversal of end-organ dysfunction by providing adequate cardiac output, or time for treatment of elevated PRA in the highly sensitized patient.
Key Words: mechanical circulatory support, total artificial heart, heart transplantation, adult congenital heart disease, pediatrics
O
ver the past several decades, advances in medical and surgical therapies have yielded dramatic improvements in From The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio. Submitted for consideration May 2014; accepted for publication in revised form August 2014. Disclosure: David L.S. Morales is a proctor for SynCardia, a member of the Berlin Heart CEC Committee, and has received travel reimbursement from SynCardia, Berlin Heart and Thoratec. Thomas D. Ryan, John L. Jefferies, Farhan Zafar and Angela Lorts have no conflicts of interest to declare. Correspondence: Thomas D. Ryan, MD, PhD, The Heart Institute, Cincinnati Children’s Hospital, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH 45229. E-mail: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs
History of the Total Artificial Heart and Current Use The story of the artificial heart is a fascinating narrative stretching back over 60 years and including some of the pioneers of modern medicine (Table 1). Although the exact origin of MCS is open to interpretation, the animal experiments by Glenn and Sewell6 published in 1950 showed proof of concept by supplying blood to the pulmonary artery with a mechanical pump and bypassing the right ventricle. Several attempts were made to use this technology in patients, but the first successful use of MCS was undertaken by Dodrill7 using the “Michigan
DOI: 10.1097/MAT.0000000000000156
8
TAH IN ADOLESCENTS AND ACHD
9
Table 1. Timeline of Important Dates in the Development and Use of the TAH6–22 Year 1950 1952 1953 1957 1967 1969 1975 1982 1985 1985–1991 1993 1993 1999 2001 2004 2006 2010 2012 2014
Notable Event Mechanical pump to bypass the right ventricle in a dog by Sewell and Glenn First successful use of MCS during cardiac surgery with the “Michigan Heart” by Dodrill First successful use of heart lung machine by Gibbon First TAH implanted in dog by Akutsu and Kolff First successful human heart transplant by Barnard First TAH in human as short-term bridge to transplant by Cooley and Liotta Calf supported with TAH for 18 days with Jarvik-type TAH Jarvik-7 implanted in patient Barney Clark for 112 days by DeVries and Kolff Jarvik-7 for bridge to heart transplant for 9 days by Copeland and colleagues Symbion (Jarvik-7) IDE for bridge to transplantation Development of fully implantable device by Abiomed (later named AbioCor) CardioWest (Jarvik-7) IDE as bridge to transplantation and destination therapy CE Mark (Europe) approval for CardioWest TAH SynCardia (Jarvik-7) formed; FDA approval (United States) of IDE for AbioCor TAH; first implantation of AbioCor in patient FDA approval (United States) for SynCardia TAH as use for bridge to transplant FDA approval (United States) of HUD designation for AbioCor TAH as destination therapy FDA approval (United States) of IDE for SynCardia Freedom Driver FDA approval (United States) of HUD designation for SynCardia TAH as destination therapy Anticipated release of SynCardia 50/50 TAH for use down to BSA 1.2 m2
BSA, body surface area; FDA, Federal Drug Administration; HUD, humanitarian use device; IDE, investigational device exemption; MCS, mechanical circulatory support.
Heart” in 1952, followed shortly thereafter by the groundbreaking work of Gibbon8 in 1953 with the first heart–lung machine used during the repair of an atrial septal defect. Finally, the first true TAH was implanted in a dog by Akutsu and Kolff9 in 1957. Once the TAH had proven application, its use in patients was the next goal. In 1969, Cooley and Liotta10 used a TAH to support a man suffering end-stage heart failure for 64 hours until a donor heart was implanted. The modern era of the TAH was ushered in by the work of Kolff et al11 when, in 1975, a calf was supported for 18 days with a Jarvik-type TAH, the precursor to current designs. This was followed in 1982 by Barney Clark’s 112 days of support with the Jarvik-712 and successful use of the device to bridge a patient to heart transplant in 1985.13 The Jarvik-7, in 100/100 (ml per artificial ventricle) and 70/70 capacities under the name Symbion, was granted an investigational device exemption (IDE) and was implanted in 198 patients from 1985 to 1991.14 With loss of the IDE in 1991, there was a halt of implantations in the United States until the 70/70 version was granted a new IDE in 1993 under the name CardioWest. Starting in 2001, the device was marketed as SynCardia and was given Federal Drug Administration (FDA) approval in 2004 after a 10-year clinical trial.23 Since 1986 greater than 1000 TAH of the Jarvik-7 type have been implanted at more than 90 institutions worldwide. There has been a steady increase in annual use over that time, with 433 TAH implantations from 2010 to 2013, including 161 in 2013 alone, as compared with 835 in the 25 years from 1985 to 2009 (direct communication, SynCardia Systems Inc.). The indications for implantation include severe biventricular failure, intractable arrhythmias, postinfarction ventricular defects unable to be repaired, ventricular failure with prior mechanical valve replacement, extensive ventricular thrombus, cardiac allograft failure, ascending aortic aneurysm or dissection with concurrent heart failure, and failure of other types of mechanical support.15,24,25 The ability to rescue the patient and prevent multisystem organ failure is dependent on the restoration of blood flow. The standard ventricular assist device (VAD) generally has a maximum cardiac output of 6–7 L/min and placement
may unmask right ventricular dysfunction. The 70/70 TAH not only supports both pulmonary and systemic circulation but also can achieve cardiac output of greater than 9 L/min at a significantly lower central venous pressure (CVP).23 When resuscitating end-organs, it is the low CVP provided that is the key difference from left VAD (LVAD) therapy or even early postoperative heart transplantation. Risk factors for poor outcome in LVAD, including right heart failure, elevated CVP and various markers of multisystem organ failure, have not been found to be significant risk factors in the TAH.26 In contrast to the Jarvik devices that require externalized drivelines, the AbioCor by Abiomed, originally described in a series of papers in 1993,16–18 is a completely implantable, electrohydraulic device capable of providing 8–10 L/min of cardiac output. After early work in a bovine model,19 an IDE was granted in 2001 and the first human implantation was performed by Gray and Dowling that same year.20 Potential Use of the Total Artificial Heart in the Management of End-Stage Congenital Heart Disease and Adolescent Patients Limited citations can be found regarding use of TAH in pediatric and ACHD patients. These include pediatric and adolescent patients with biventricular heart failure27,28; a 15-year-old with left ventricular thrombus in the setting of heart failure29; and 3 patients with “valvular and congenital re-operations.”30 Two applications in failing single ventricle palliation are in the literature, a 17-yearold with congenitally corrected transposition of the great arteries (CCTGA) and a failing systemic ventricle,31 and a 13-year-old with pulmonary atresia and intact ventricular septum who developed plastic bronchitis and severe circulatory failure.32 Both patients were successfully bridged to heart transplantation. TAH Experience to Date in the Adolescent Patient Population Of the 1091 TAH implanted worldwide from 1985 to 2012, 51 (4.7%) were in patients under the age of 21, regardless of diagnosis (Table 2; direct communication, SynCardia Systems
10
RYAN et al.
Table 2. Patient Characteristics for Adolescent (
Review Article
The Evolving Role of the Total Artificial Heart in the Management of End-Stage Congenital Heart Disease and Adolescents Thomas D. Ryan, John L. Jefferies, Farhan Zafar, Angela Lorts, and David L.S. Morales
Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease. ASAIO Journal 2015; 61:8–14.
morbidity and reduced mortality for several childhood diseases. Because of these successes, there is now a generation of aging patients encountering previously unseen complications. One dramatic example is patients with congenital heart disease, both surgically palliated and uncorrected, who develop end-stage heart failure. According to the Congenital Heart Public Health Consortium (www.chphc.org), in the United States there are an estimated 2 million people living with congenital heart disease, including approximately 959,000–1.5 million adults. This encompasses “a substantial number of young adults with single ventricle physiology, systemic right ventricles or complex intracardiac baffles.”1 Familial and acquired cardiomyopathies constitute another group of patients at risk for heart failure, and whose numbers are increasing because of improved recognition, diagnosis and early therapy. When medical treatment is inadequate in the adult congenital heart disease (ACHD) patient with heart failure, surgical options are considered. These may include surgical revision or cardiac transplantation.2 Only 3000–5000 heart transplants are performed worldwide each year, with approximately 3% in ACHD.3 Not all patients are appropriate candidates for transplantation as some may have end-organ dysfunction requiring concurrent therapies not compatible with transplant, inability to tolerate the necessary immunosuppression or high panel reactive antibodies (PRA). Viable alternatives are needed for the patient with end-stage heart failure due to congenital heart disease that is ineligible for a further palliative surgical procedure or those unable to wait for a donor to become available. One intriguing option is placement of a total artificial heart (TAH) as a bridge to transplantation. The concept of mechanical circulatory support (MCS) as a bridge to transplant is familiar territory, with approximately 20% of all candidates temporized with some form of MCS.3 There are several options available,4 and overall the number of MCS devices implanted is now approaching, if not surpassing, the number of transplantations performed.5 The time gained with MCS may allow reversal of end-organ dysfunction by providing adequate cardiac output, or time for treatment of elevated PRA in the highly sensitized patient.
Key Words: mechanical circulatory support, total artificial heart, heart transplantation, adult congenital heart disease, pediatrics
O
ver the past several decades, advances in medical and surgical therapies have yielded dramatic improvements in From The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio. Submitted for consideration May 2014; accepted for publication in revised form August 2014. Disclosure: David L.S. Morales is a proctor for SynCardia, a member of the Berlin Heart CEC Committee, and has received travel reimbursement from SynCardia, Berlin Heart and Thoratec. Thomas D. Ryan, John L. Jefferies, Farhan Zafar and Angela Lorts have no conflicts of interest to declare. Correspondence: Thomas D. Ryan, MD, PhD, The Heart Institute, Cincinnati Children’s Hospital, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH 45229. E-mail: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs
History of the Total Artificial Heart and Current Use The story of the artificial heart is a fascinating narrative stretching back over 60 years and including some of the pioneers of modern medicine (Table 1). Although the exact origin of MCS is open to interpretation, the animal experiments by Glenn and Sewell6 published in 1950 showed proof of concept by supplying blood to the pulmonary artery with a mechanical pump and bypassing the right ventricle. Several attempts were made to use this technology in patients, but the first successful use of MCS was undertaken by Dodrill7 using the “Michigan
DOI: 10.1097/MAT.0000000000000156
8
TAH IN ADOLESCENTS AND ACHD
9
Table 1. Timeline of Important Dates in the Development and Use of the TAH6–22 Year 1950 1952 1953 1957 1967 1969 1975 1982 1985 1985–1991 1993 1993 1999 2001 2004 2006 2010 2012 2014
Notable Event Mechanical pump to bypass the right ventricle in a dog by Sewell and Glenn First successful use of MCS during cardiac surgery with the “Michigan Heart” by Dodrill First successful use of heart lung machine by Gibbon First TAH implanted in dog by Akutsu and Kolff First successful human heart transplant by Barnard First TAH in human as short-term bridge to transplant by Cooley and Liotta Calf supported with TAH for 18 days with Jarvik-type TAH Jarvik-7 implanted in patient Barney Clark for 112 days by DeVries and Kolff Jarvik-7 for bridge to heart transplant for 9 days by Copeland and colleagues Symbion (Jarvik-7) IDE for bridge to transplantation Development of fully implantable device by Abiomed (later named AbioCor) CardioWest (Jarvik-7) IDE as bridge to transplantation and destination therapy CE Mark (Europe) approval for CardioWest TAH SynCardia (Jarvik-7) formed; FDA approval (United States) of IDE for AbioCor TAH; first implantation of AbioCor in patient FDA approval (United States) for SynCardia TAH as use for bridge to transplant FDA approval (United States) of HUD designation for AbioCor TAH as destination therapy FDA approval (United States) of IDE for SynCardia Freedom Driver FDA approval (United States) of HUD designation for SynCardia TAH as destination therapy Anticipated release of SynCardia 50/50 TAH for use down to BSA 1.2 m2
BSA, body surface area; FDA, Federal Drug Administration; HUD, humanitarian use device; IDE, investigational device exemption; MCS, mechanical circulatory support.
Heart” in 1952, followed shortly thereafter by the groundbreaking work of Gibbon8 in 1953 with the first heart–lung machine used during the repair of an atrial septal defect. Finally, the first true TAH was implanted in a dog by Akutsu and Kolff9 in 1957. Once the TAH had proven application, its use in patients was the next goal. In 1969, Cooley and Liotta10 used a TAH to support a man suffering end-stage heart failure for 64 hours until a donor heart was implanted. The modern era of the TAH was ushered in by the work of Kolff et al11 when, in 1975, a calf was supported for 18 days with a Jarvik-type TAH, the precursor to current designs. This was followed in 1982 by Barney Clark’s 112 days of support with the Jarvik-712 and successful use of the device to bridge a patient to heart transplant in 1985.13 The Jarvik-7, in 100/100 (ml per artificial ventricle) and 70/70 capacities under the name Symbion, was granted an investigational device exemption (IDE) and was implanted in 198 patients from 1985 to 1991.14 With loss of the IDE in 1991, there was a halt of implantations in the United States until the 70/70 version was granted a new IDE in 1993 under the name CardioWest. Starting in 2001, the device was marketed as SynCardia and was given Federal Drug Administration (FDA) approval in 2004 after a 10-year clinical trial.23 Since 1986 greater than 1000 TAH of the Jarvik-7 type have been implanted at more than 90 institutions worldwide. There has been a steady increase in annual use over that time, with 433 TAH implantations from 2010 to 2013, including 161 in 2013 alone, as compared with 835 in the 25 years from 1985 to 2009 (direct communication, SynCardia Systems Inc.). The indications for implantation include severe biventricular failure, intractable arrhythmias, postinfarction ventricular defects unable to be repaired, ventricular failure with prior mechanical valve replacement, extensive ventricular thrombus, cardiac allograft failure, ascending aortic aneurysm or dissection with concurrent heart failure, and failure of other types of mechanical support.15,24,25 The ability to rescue the patient and prevent multisystem organ failure is dependent on the restoration of blood flow. The standard ventricular assist device (VAD) generally has a maximum cardiac output of 6–7 L/min and placement
may unmask right ventricular dysfunction. The 70/70 TAH not only supports both pulmonary and systemic circulation but also can achieve cardiac output of greater than 9 L/min at a significantly lower central venous pressure (CVP).23 When resuscitating end-organs, it is the low CVP provided that is the key difference from left VAD (LVAD) therapy or even early postoperative heart transplantation. Risk factors for poor outcome in LVAD, including right heart failure, elevated CVP and various markers of multisystem organ failure, have not been found to be significant risk factors in the TAH.26 In contrast to the Jarvik devices that require externalized drivelines, the AbioCor by Abiomed, originally described in a series of papers in 1993,16–18 is a completely implantable, electrohydraulic device capable of providing 8–10 L/min of cardiac output. After early work in a bovine model,19 an IDE was granted in 2001 and the first human implantation was performed by Gray and Dowling that same year.20 Potential Use of the Total Artificial Heart in the Management of End-Stage Congenital Heart Disease and Adolescent Patients Limited citations can be found regarding use of TAH in pediatric and ACHD patients. These include pediatric and adolescent patients with biventricular heart failure27,28; a 15-year-old with left ventricular thrombus in the setting of heart failure29; and 3 patients with “valvular and congenital re-operations.”30 Two applications in failing single ventricle palliation are in the literature, a 17-yearold with congenitally corrected transposition of the great arteries (CCTGA) and a failing systemic ventricle,31 and a 13-year-old with pulmonary atresia and intact ventricular septum who developed plastic bronchitis and severe circulatory failure.32 Both patients were successfully bridged to heart transplantation. TAH Experience to Date in the Adolescent Patient Population Of the 1091 TAH implanted worldwide from 1985 to 2012, 51 (4.7%) were in patients under the age of 21, regardless of diagnosis (Table 2; direct communication, SynCardia Systems
10
RYAN et al.
Table 2. Patient Characteristics for Adolescent (
