TAH name
Timeline
No. of implants
Duration
Liotta
1969
1
64 h
Akutsu
1981
1
55 h
Jarvik-7100
1982–1992
44
6 years
Phoenix
1985
1
11 h
Penn State
1985–1989
4
1 year
Jarvik-7 70
1985–1992
159
11 years
Berlin
1986–1990
7
60 days
Unger
1986–1990
4
50 days
Vienna
1989
2
18 days
Brno
1988–1990
6
50 days
Poisk-IOM
1987–1990
16
100 days
CardioWest
1993–2002
218
31 years
Phoenix 7
1998
2
15 days
Abiocor
2001–2006
15
5 years
SynCardia
2002–2015
1100
464 years
Carmat
2013–2015
3
20 months
TOTAL
1969–2015
1584
520 years
“SynCardia type” Hearts
1982–2015
1522 (96%)
512 years (98%)
As of 2015, more than 1584 implants and 520 patient years with the Jarvik-7, CardioWest, and SynCardia TAHs (all essentially the same device) account for >98% of the world experience with human total artificial heart implantation (reported in ◘ Table 32.1).
The first two TAH cases, the Liotta heart (1969) and the Akutsu heart (1981), were associated with device support for less than 3 days and patient survival after transplant of hours to 8 days with deaths from sepsis. Dr. William DeVries implanted the Jarvik-7 with 100 ml ventricular volumes in Dr. Barney Clark in 1982 followed by a celebrated 112 days of survival. Several other implants done by DeVries in Louisville were associated with adverse events causing public concern [1]. In 1984, the FDA limited the use of all mechanical circulatory support devices to bridge to transplantation.
By 1983 cardiac transplantation, survival results were improved, and length of hospital stay was shortened thus setting the stage for successful bridge to transplantation.
At the University of Arizona in March 1985, the lifesaving potential of total artificial heart technology appeared clear when we implanted emergently a “Phoenix TAH.” Jack Copeland (JC) re-transplanted him after several hours of stable TAH support only to have the donor heart fail from sepsis. In the end JC and his staff were surprised with the excellent hemodynamic support provided by the Phoenix heart even in this septic patient.
On August 29, 1985, JC implanted a critically ill 25-year-old man with the Jarvik-7, 100 ml TAH. The device functioned very well and the patient survived to transplantation 9.5 days later and was discharged home. He lived 5.5 years with his transplanted heart enjoying excellent quality of life and return to work as a produce clerk in a grocery store. This case received worldwide public approval as the first successful bridge to transplantation with a total artificial heart [2]. JC’s team and others began occasional implants in very sick patients realizing that there was much to be learned about this new technology because so little was known about issues of patient selection, fitting the device into the patient, anticoagulation, prevention of infections, biocompatibility, quality of life, explantation and subsequent transplantation, durability, and many other issues. Much has been learned in the past 30 years. From mid-1985 until late 2014, the size of the TAH has been 70 cc. The smaller 50 cc ventricle model for smaller patients has just been introduced in late 2014.
In the mid-1980s work with pulsatile left ventricular assist devices (LVADs) had been done in other centers and by 1988 LVADs, and biventricular support were implemented as options in the Arizona’s center institutional surgical armamentarium, leading to formulation a selection protocol to select among the three types of devices [3].
The sicker patients that were considered for BiVAD or TAH implantation were not expected to live for more than hours to a few days. On maximal medical therapy, they had central venous pressures of 16–20 mmHg or greater, and some renal and hepatic dysfunction, but not enough that they would be eliminated as possible transplant candidates. They were on multiple inotropes and sometimes post-cardiac arrest, intubated, or on temporary device support such as cardiopulmonary bypass or ECMO.
Results with the TAH were good, also in a population of very sick patients. But when the FDA prohibited TAH use in the USA from 1991 through 1992, LVADs and BiVADs were used alternatively in the same patient population, and higher mortality rates were experienced, leading to the conclusion that patients experiencing rapid decompensation had better survival with TAH therapy than LVADs or BiVADs. In 1992, while a new IDE for study of the TAH was started (called CardioWest at the time) in five institutions, the implanted population received approximately 20% TAH, 20% BiVAD, and 60% LVAD.
In 2004 the FDA approved the SynCardia TAH-t as a bridge-to-transplant device for: “…temporary biventricular replacement for transplant eligible patients suffering from bi-ventricular failure and at imminent risk for death.” Documentation of experience in the FDA study [4], in an institutional study of 101 consecutive patients headed by JC [5], in the area of anticoagulation [6], and in multivariate analysis of risk factors [7] has established evidence for the worldwide use of the TAH. Survival to transplantation in the FDA trial was 79% and in the 101 consecutive patient single institution trial of 69%. Strokes occurred in 8 of 99 consecutive patients. Four implant-related strokes were in the first 48 h following operation, and two were in the two chronic survivors that developed device endocarditis. There were two strokes in the remaining 93 patients (2%) for an event rate of 0.08 strokes/patient year in endocarditis-free patients after the first 48 h postimplantation. GI bleeding was found in two patients (2%) that is much lower than the risk with continuous-flow devices (15–40%). There were no valve failures, or pump thrombosis, and low rates of hemolysis (10 mg/dl plasma-free hemoglobin), only two device exchanges in >1500 patients (again in contrast to the exchange rates for the continuous-flow devices of about 5–15% per year), a small number of driveline perforations (estimate of <6), and eight diaphragm perforations in >1500 patients (>3000 ventricles or 0.003 events per ventricle [0.3%]). The mean time to perforation was 1.2 years (range 124–971d). Two of the eight patients were successfully transplanted and six died, with mortality from lack of durability of 0.4%.
In summary, the results of multiple studies have shown that the stroke rate is favorable when compared to LVAD stroke rates. The reasons for such a remarkably low stroke rate are most likely related to two independent factors. The first is that the flow rates of the TAH are high (7–9 l/ min) and do not allow stasis to occur. The second is that the shear stress created by this device, even with 4 mechanical valves, has been found to be low, >100 times less than with rotary pumps. This results in less platelet activation and in turn less activation of the final pathway of the coagulation cascade perhaps partially accounting for the absence of pump thrombosis. Likewise, pump exchange with the TAH is rare (2 in >1500 patients). GI bleeding is rare (2%). There are no arrhythmias. In patients with acute, not chronic, renal failure and/or hepatic failure, return to normal function commonly occurs within weeks.
Because of several historical restrictions, only a few centers were able to use the TAH while LVADs were much more widely available. In ◘ Fig. 32.1 the blue bar below the graph represents the time period when the only drivers for the TAH were too large for discharge and limited in number to 36 worldwide. This prevented widespread use. In 2009 the Freedom Driver trial started in the USA and has now led to >200 patient years of outpatient support. The SynCardia TAH-t has been approved by the FDA since 2004 and approved for funding by CMS (Centers for Medicare and Medicaid Services) in 2008.
Fig. 32.1
Numbers of SynCardia TAH implants by year (Courtesy of SynCardia Systems, LLC)
Current use of the SynCardia TAH-t is at about 15 implants per month worldwide. As better selection criteria are used and smaller (6 pound/2.7 kg) quieter drivers improve quality of life, the true place of the TAH among MCS devices may become apparent (◘ Fig. 32.1). Right ventricular failure (RVF) with LVAD therapy and the management of INTERMACS I patients are among the challenges that have not been solved with LVAD therapy.
In 2015 a trial was started with a 50 cc ventricle pump that is 30% smaller and easier to fit into smaller patients perhaps down to 1.2 m2 BSA. Over 20 have been implanted in the first few months primarily in females with good survival results. A destination therapy trial is also starting.
De facto long-term implants have resulted in >127 1-year, 63 1.5-year, and 27 2-year survivors. There are now two patients on TAH for over 4 years. Around 72% of 1-year survivors in a recent multi-institutional study were transplanted with 100% surviving to discharge and 73% of those on renal replacement therapy experiencing return of renal function.
The SynCardia TAH-t continues to demonstrate success in areas not covered by other options. The adverse event profile is favorable. Selection of appropriate patients in programs that are new to the technology remains a problem that is slowly resolving. The overriding consideration in the mind of the author since he first used this device is that “it works.” Major benefits include replacement of diseased native ventricles, high flow, low CVP, automatic left-right balancing, a Starling mechanism, pulsatility, and low shear pump characteristics. The 50 cc model may increase usage. The new DT trial may provide long-term support for sicker patients.
32.1.2 Engineering View of TAH and Technical Management of Drivers and System
Ventricular assist devices (“VADs”) assist the native ventricle(s), while a total artificial heart (“TAH”) replaces both native ventricles. In this respect a TAH eliminates global cardiac dysfunction (such as large myocardial infarction, rejection, stone heart, amyloid, cardiac tumor, Chagas, muscular dystrophy, etc.) and solves issues with arrhythmias, ventricular septal defects, ventricular thrombus, or others related to native ventricles. It can further be used as bailout for DT LVAD patients with failing right ventricle.
The SynCardia TAH is a pulsatile displacement pump system pneumatically driven and has three integral parts: the implanted two artificial ventricles, the external pneumatic driver, and the air tubes or drivelines (◘ Fig. 32.2).
Fig. 32.2
SynCardia TAH components (Courtesy of SynCardia Systems, LLC)
The internal ventricle is made of segmented polyurethane solution (SPUS) and has two mechanical heart valves (SynHall™), identical to the original Medtronic Hall recently gone out of production. A flexible membrane of four layers separates air from blood (◘ Fig. 32.3). The ventricle has no sensors.
Fig. 32.3
SynCardia TAH ventricle (Courtesy of SynCardia Systems, LLC)
Drivelines for each ventricle are connected to the external driver. Currently two different external drive systems are in use: the “Companion 2” (C2) Driver System for initial implantation and in-hospital use which provides curves for the monitoring of the pumps (◘ Fig. 32.4). It weighs about 30 kg and fits on a hospital console with 360° rotatable screen or on a caddie resembling a carry-on suitcase. As of May 2015 the Companion 2 had been used in 367 patients for 72 years of support. The wearable Freedom Driver System for clinically stable patients at home weighs 6 kg and had supported 222 patients for 145 years. The noise of the driver still represents an issue that will be addressed in the near future by a new Freedom 2 Driver that is more portable weighing 3 kg and is very quiet.
Fig. 32.4
Screenshot from “Companion 2” Driver – SynCardia TAH (Courtesy of SynCardia Systems, LLC)
The cardiac output in most adult patients runs at 7±1 l/min at a preload of 5–10 mmHg. Ejection pressures are preset to be about 30 mmHg > anticipated PA pressure and 60 mmHg above the anticipated systolic pressure. The C2 driver can be set to overcome any physiologic systemic vascular resistance (i.e., up to 200 mmHg). The Freedom Driver in the current iteration works best at systolic pressures under 150 mmHg, so careful systolic pressure control is desirable in outpatient recipients. Normal settings for the device include pump pressures of 80 mmHg, vacuum of −10 mmHg, percent systole of 50% on the right. On the left they are 180 mmHg pump pressure, −10 mmHg vacuum, and percent systole of 50%. The ventricles fill and empty simultaneously from 2 separate pumps and are generally run at a beat rate between 120 and 130/min.
As seen in ◘ Fig. 32.3, the ventricle is partially filled and fully ejected with each beat. Under this condition the pneumatic ventricles exhibit:
Automatic balance between the left and right ventricles, preventing overflow to the lungs
An increased pump output response to increase in preload (Starling response)
The limit of the device is about 140 beats/minute giving 9.8 l/min flow at a fill volume of 70 ml. Once this is exceeded by further increasing preload, increase in back pressure will occur. In this situation, volume reduction maneuvers such as dialysis, reverse Trendelenburg position, and therapeutic phlebotomy would be urgently indicated. To anticipate and thus avoid overload of the device, the operator may use the fill volume (stroke volume) reading from the driver (◘ Fig. 32.5). In general, the fill volume serves as an index of the preload and is very helpful in dialysis patients to determine desired volume status. In all 70 cc ventricles, fill volumes of 50–60 cc are considered optimal and safe. Theoretically, this provides the possibility of increasing the stroke volume by 20 cc/beat for fill volume of 50 or 10 cc/beat for fill volume of 60. Thus the cardiac output reserve at a beat rate of 130 would be 2.6 l/min for the former and 1.3 l/min for the later. The fill volume is also directly related to the CVP. The fill volumes of the ventricles are adjusted by changing heart rate. If a lower fill volume is desired, the heart rate is increased and vice versa. In patients with intact renal function, changing any of the settings is rarely needed.
Fig. 32.5
Normal (left) and abnormal (right) wave forms for SynCardia TAH operation
As one might expect with four mechanical valves, there is a low-grade hemolysis with a mean free hemoglobin of 10–12 mg/dl. Hematocrits are usually 25. Oxygen delivery is adequate at rest and with exercise. Also, there is some fragmentation of the von Willebrand protein, but platelet-collagen binding is not decreased [8].
32.1.3 Clinical and Surgical Issues
Indications
The TAH represents an alternative way to assist the patient suffering from an end-stage chronic or an acute biventricular heart failure, when LVAD support is predicted to be unsuccessful in providing adequate systemic flow to meet metabolic demands.
While a timely mechanical circulatory support aims at a desirable ventricular remodeling with a reversal of the severity of heart failure, the concept behind TAH is to completely replace the heart with a mechanical device. Of course, in patients who are potential cardiac graft recipients, the object is to remove the native heart. Thus for those hearts that appear to have no chance of reverse remodeling, cardiectomy with replacement is the therapy of choice when LVAD and medical therapies will not suffice.
This difference encompasses all the resistances and the fears of the clinicians related to eventual technical failures of such a machine. The principal concerns regarding the replacement with a TAH are related to the absence of a backup circulation in case of abrupt technical complications.
Long clinical experience with SynCardia TAH has shown excellent technical data with a remarkably low incidence of technical failures. However, the miniaturization of continuous-flow assist devices and the possible reversibility or even the healing of right ventricular dysfunction over the long term still represent an obstacle to the diffusion of the TAH technology to biventricular ES-CHF, and, as a consequence, during the last years, an increasing off-label use of devices designed to assist the left ventricle in a setting of a biventricular failure has been experienced.
On the other end, up to now the SynCardia TAH is the only device with a large experience over 1 year of support in biventricular failure whose data are validated both for bridge to transplant as for destination therapy. Unfortunately, there are no randomized clinical trials comparing TAH with other devices in the treatment of biventricular heart failure, and the principal obstacle to such a trial is the absence of a unique and safe “competitor” to the TAH.
However, in such a complex scenario, TAH has its principal benefits when the replacement of one or both ventricles is mandatory:
Untreatable myocardial infarctions with or without complications
Neoplasms of the heart without secondary lesions
Irreversible post-transplant graft dysfunction
Irreversible right ventricular failure after LVAD and PGF after transplants
Untreatable severe arrhythmic cardiomyopathy
Previous mechanical aortic valve in patients who are not candidates for LVAD
Irreparable ventricular anatomical defects (e.g., ventricular rupture, significant ventricular septal defect following acute myocardial infarction, and so on)
Ventricular failure with prior mechanical prosthetic valve replacement
Severe biventricular failure
Severe hypertrophic and restrictive disease
Selected conventional operation misadventures
In these settings the risks of the replacement of the entire heart is justified in consideration of the actual lack of an alternative strategy. Biventricular failures that are not amenable to an intended implant of temporary RVAD+LVAD are a possible clinical indication for patients in INTERMACS class I/II. In this setting the implantation of a BiVAD with HVAD is preferred from many authors in light of an expected better quality of life and with the aim of a midterm reversal of right ventricular failure. Looking at the last INTERMACS report, it has to be noted how the risk of severe complications after BiVAD implantation remains significant, although reduced in the last era. However, clinical experience with the TAH as destination therapy has thus far been limited also if in this setting the implantation of a TAH appears at the moment the safest and easy solution. The principal advantages in favor of the TAH remain the extreme ease to manage TAH with respect to BiVAD and the low rate of technical failures during the long term.
Indication and Patient (and Model) Selection
Proper patient selection and timing of intervention are two of the most important factors in determining a successful outcome with the TAH. The main indication for the use of TAH is in patients who are heart transplant candidates with severe biventricular failure in imminent risk of death in whom a suitable donor heart is not available. LVADs have proven very effective in either bridging patient to heart transplantation or as destination therapy in those patients who are not candidates [9, 10] with near transplant survival outcomes but with a lower quality of life [11], higher incidence of adverse events, and with an incidence of RVF up to 40% [12]. However, the need for a right ventricular assist device (RVAD) identifies a patient population that has worse outcomes [13] and potentially manageable with a TAH.
The TAH continues to be used as a bridge-to-heart transplantation (BTT) in patients with severe biventricular failure, i.e., INTERMACS profile 1 and primarily profile 2 [14, 15]. However, the last few years has seen an increase in its use and better understanding of the indications for its implementation. Many potential indications for the use of a TAH have been conceptualized for many years; however, it has been in recent times that the TAH has been utilized for these very ill patients. For this reason, few of these cases have reached the medical literature and others are too early to report.
The need for re-transplantation is essential to provide long-term survival for a heart transplant recipient who is experiencing graft failure that is not responding to conventional therapy. If a donor has not become available and the patient is experiencing hemodynamic instability despite inotropic support, temporizing measures that will provide more time include the use of ECMO or biventricular support. The role of the TAH in this particular patient provides several advantages as long as the TAH is implanted prior to total cardiovascular collapse and end-organ damage. The TAH allows for immunosuppression to be discontinued and potentially lowers the increased risk of infection and kidney damage. Furthermore, it allows the patient to be ambulatory and potentially the benefit of being discharged home [16]. The use of the TAH for this indication is associated with a survival rate of 47%. However, the use of the TAH for hemodynamic collapse in the onset of acute rejection has not been described and is probably associated with a high rate of complications and poor outcomes. The role of the TAH in the chronic graft failure scenario will probably continue to increase as the transplant population has a mean survival of approximately 10 years and the donor shortage continues [17, 18].
The use of the TAH in the pediatric population with advanced heart failure as the result of an idiopathic, viral, or congenital structural abnormality provides significant advantages. In addition to correction of hemodynamic deterioration, it provides a surgical scenario that allows for the correction of some of the congenital abnormalities at the time of TAH implantation and prior to the time of transplantation. Although the 70 cc size of the SynCardia TAH dictates that the patient thoracic cavity has to be able to fit the device to allow sternal closure, the TAH has been until now utilized in children with BSA as small as 1.5 m2. The requirement in this scenario is that there is significant cardiomegaly with an enlarged mediastinal space to allow for the device to fit in [19–22]. Although smaller LVAD’s and biventricular assist devices have successfully been utilized in the small children, the 50 cc TAH is now available and may further expand the use of this technology in children and small adults with a BSA as low as 1.0–1.2 m2 and the 50 cc appearing as a game changer in this field. Approximately 30 patients with congenital heart disease had been implanted with the SynCardia TAH by the end of 2013. The majority of these patients were implanted in the last few years and in multiple centers. Some of the congenital abnormalities in these patients include corrected transposition of the great vessels and single ventricle. Although reports are just starting to appear, some of these patients are experiencing from altered hemodynamics and physiology secondary to a failed Fontan procedure. It is the expectation that the next few years will provide more evidence-based medical literature regarding the management in this complex population with the TAH. The implantation of the SynCardia TAH or any newer TAH in patients with congenital heart disease will challenge the surgeons to develop surgical modifications to the conventional implantation of the device as the cardiac abnormalities dictate modification and design.
The outcome of the patient with a primary cardiac malignancy is usually dismal with poor survival. Although the majority of cardiac tumors are benign, however a malignant tumor carries a fatal prognosis if unresectable. Diagnosis of these malignant tumors usually includes a biopsy at the time of presentation or occurs at the time of an optimistic but failed surgical resection. Imaging studies (echocardiography, computerized tomography, and MRI) are usually helpful but in some if not most instances failed to accurately delineate the extent of the disease [23]. Chemotherapy and radiation therapy have been utilized in unresectable cases. Heart transplantation has been utilized to treat selected patients with cardiac malignancies; however series show poor outcomes. The use of ventricular assist devices has been reported, and more recently the use of the HeartMate II LVAD used in the TAH configuration was described in a patient. A very small number of patients with cardiac tumors have received the SynCardia TAH. Mostly literature is based on case reports, without enough scientific information to make any prediction on outcomes. The use of the TAH in this population will generate controversy in the medical field. However, long-term use of the TAH followed by transplantation may 1 day play a role.
Acquired or ischemic ventricular septal defect (VSD) as a complication of myocardial infarction remains a condition with significant morbidity. Surgical correction is the most common therapy that carries a significant morbidity and mortality [24]. The use of MCS has been reported in the management of ischemic VSDs [25]. The successful use of the SynCardia TAH has also been reported [26]. A very small number of patients have been done for this indication to have a series of patients. The procedure probably will continue to have a significant morbidity and mortality as these patient population is in significant hemodynamic and physiologic impairment.
The patient populations experiencing from infiltrative (i.e., amyloid) or hypertrophic cardiomyopathy are ideal candidates for the use of a TAH as this therapy eliminates the effect of the disease process in both affected ventricles. Although the use of left ventricular assist devices (LVADs) have been reported [27], the utilization of the TAH continues to increase in this population. Another population that benefit from the TAH technology are those patients who experience from ventricular tachycardia (VT) storm or malignant arrhythmias despite multiple ablations. Although LVADs have been used as a group, the TAH continues to find a role in this group. However, medical reporting in these two populations will increase in the next few years.
LVADs have been extremely successful in the management of congestive heart failure both in the BTT and destination therapy who are failing medical therapy. However, despite the best managements, a number of BTT patients who have received LVADs continue to or relapse with right ventricular failure (RVF). The TAH has been successful in re-bridging these patients and eliminating the effects of RVF despite an LVAD [28]. However, this has not been tested in the destination (DT) population.
32.1.4 50 cc TAH System
The SynCardia TAH-t 50 cc is an identical smaller version of the CE marked 70 cc TAH-t, originally designed for patients with smaller chest dimensions and or less need of consistent doses of cardiac output.
The TAH-t cannulas have colored bands on them to permit to the clinicians to distinguish the model 50 and 70 cc TAH-t also after implantation. The 50 cc TAH-t cannulas have two colored bands on each cannula, whereas the 70 cc TAH-t cannulas have one colored band on each cannula, as shown in the picture in ◘ Fig. 32.6.
Fig. 32.6
SynCardia 70 and 50 cc systems (Courtesy of SynCardia Systems, LLC)
Until the introduction of the 50 cc model, TAH technology was restricted to patients with higher BSA, cardiothoracic ratio, and anteroposterior diameter at T10 level. A common problem, in oversizing, was the compression of the IVC by the RA quick connector and the compression of the left pulmonary veins by the LA quick connector. This problem may be often resolved by a delayed sternal closure waiting for the volume reduction of the lung after 24–48 h of effective perfusion and drying of the lung. Delayed sternal closure after the total artificial heart implantation might be beneficial for the outcomes preventing complications, as bleeding complications, tamponade, and sometimes several second-look operations. For that reason, delayed sternal closure after TAH-t implantation could be one option although it still has to be prospectively examined [29].
The new device has been designed as a pulsatile device similar to the 70 cc with the smaller dimensions, less stroke volume, and less cardiac output, as it shows in ◘ Table 32.2.
Table 32.2
Comparison between 50 and 70 cc TAH-t
# | Characteristic | 50 cc TAH-t | 70 cc TAH-t | Comparison |
|---|---|---|---|---|
1. | Type | Pulsatile | Pulsatile | Same |
2. | Mechanism of action | Pneumatic | Pneumatic | Same |
3. | Stroke volume (max) | 50 ml | 70 ml | 20 ml reduction |
4. | Cardiac output (max) | 7.5 L/min | 10.5 L/min | 3.0 L/min |
5. | Displacement volume (not including cannulas) | 250 ± 25 ml | 400 ± 20 ml | 150 ml reduction |
6. | Electrical power | External | External | Same |
7. | Valves | 25 M (mitral) and 23A (aortic) (titanium housing and pyrolytic carbon tilting disk) | 27 M (mitral) and 25A (aortic) (titanium housing and pyrolytic carbon tilting disk) | Next available smaller valve sizes selected |
8. | Diaphragms | Four diaphragms: one blood diaphragm and three redundant diaphragms (air and intermediate diaphragm assembly) Graphite between the diaphragms provides lubrification | Four diaphragms: one blood diaphragm and three redundant diaphragms (air and intermediate diaphragm assembly) Graphite between the diaphragms provides lubrification | Same number of diaphragm and same diaphragm thickness. Amount of graphite used for lubrification is scaled down
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