The Total Artificial Heart: From Initial Application to Therapeutic Option

Interest in development of mechanical cardiac support has grown out of the realization of the enormous impact of heart failure-related mortality, the limited potential to provide cardiac transplantation (approximately 2000 patients/year in the USA), and the long waiting period required, even in appropriately selected patients. Both left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed to assist in addressing these needs. This review focuses on TAH development. The first bridging TAH was implanted in 1969, and the first permanent device in 1982 with a patient survival of 112 days. Since that time, evolution of device design and manufacture, patient selection, and ancillary therapies have occurred. Worldwide clinical application now spans 27 years and includes experience with TAH implantation in 311 patients, with eight different pneumatically driven devices implanted either as permanent devices (N = 5) or as temporary, bridging therapy to transplantation (N = 306), with all but four implanted after 1984. Utah-developed TAHs represent the largest source of this experience (N = 287). In the earlier (Symbion manufactured) TAH series (N = 204, 1985–1992), 42% of implanted patients and 59% of transplanted patients were discharged alive from the hospital, and average support time was 24 days. In the current (Cardio West manufactured) series (N = 78, 1993–1996), 67% of implanted patients and 94% of transplanted patients were discharged alive, and average support time is 30 days. Of transplanted and discharged patients, 98% remain alive. With improvements in device design and manufacture, as well as anticoagulant regimens, the incidence of stroke with long-term deficits has decreased from 3 out of 7 in 1984-1985 to 1 out of 61 in 1988, with no permanent deficits since then. Infection rates have also decreased. Only one implanted patient died of TAH mechanical failure (an early experience). Based on this evolving experience, use of the TAH as a bridge to transplantation in selected patients who are not appropriate for an LVAD has become a viable current therapeutic option. Further TAH development and application is anticipated.     

The total artificial heart

The total artificial heart (TAH) is a form of mechanical circulatory support in which the patient’s native ventricles and valves are explanted and replaced by a pneumatically powered artificial heart. Currently, the TAH is approved for use in end-stage biventricular heart failure as a bridge to heart transplantation. However, with an increasing global burden of cardiovascular disease and congestive heart failure, the number of patients with end-stage heart failure awaiting heart transplantation now far exceeds the number of available hearts. As a result, the use of mechanical circulatory support, including the TAH and left ventricular assist device (LVAD), is growing exponentially. The LVAD is already widely used as destination therapy, and destination therapy for the TAH is under investigation. While most patients requiring mechanical circulatory support are effectively treated with LVADs, there is a subset of patients with concurrent right ventricular failure or major structural barriers to LVAD placement in whom TAH may be more appropriate. The history, indications, surgical implantation, post device management, outcomes, complications, and future direction of the TAH are discussed in this review.     

Successful heart transplantation in patients with total artificial heart infections

Background

Data are limited on clinical outcomes in patients awaiting heart transplant (HT) with total artificial heart (TAH) infections.

Methods

We retrospectively reviewed all TAH recipients at our center. TAH infection was classified as definite if a microorganism was isolated in cultures from the exit site or deep tissues around the TAH; as probable in patients without surgical or microbiologic evidence of infection but no other explanation for persistent or recurrent bloodstream infection (BSI); or possible in patients with clinical suspicion and radiographic findings suggestive of TAH infection, but without surgical intervention or microbiologic evidence.

Results

From 2012 to 2015, a total of 13 patients received a TAH, with a median age at implantation of 52 years (range: 28‐60). TAH infection occurred in nine patients (seven definite, one probable, one possible) a median of 41 days after implant (range: 17‐475). The majority of TAH infections were caused by Staphylococcus species. Seven of nine patients underwent HT (four had pre‐HT mediastinal washout, and five had positive HT operative cultures). Three patients had an active BSI caused by the same pathogen causing TAH infection at the time of HT, with one developing a post‐HT BSI with the same bacteria. No patient developed post‐HT surgical site infection caused by the TAH infection pathogen. No deaths among HT recipients were attributed to infection.

Conclusion

TAH infection is frequently associated with BSI and mediastinitis and Staphylococcus was the most common pathogen. A multimodal approach of appropriate pre‐ and post‐HT antimicrobial therapy, surgical drainage, and heart transplantation with radical mediastinal debridement was successful in curing infection.     

Human heart transplantation Experience with twelve cases

Transplantation of the human heart is rapidly becoming an accepted method for rehabilitation of patients with end-stage heart disease and incurable congenital defects. This report is concerned with 12 cases of human cardiac transplantation. All 11 patients receiving allografts survived operation with normal circulation provided by the transplanted heart. In 1 of these patients the lungs still attached to the heart were also transplanted. One xenograft (sheep's heart) was placed in a terminal patient in a desperate attempt to prolong life and resulted in failure from hyperacute rejection. Immunosuppressive therapy in all allograft recipients consisted of azathioprine, corticosteroids and antilymphocyte globulin (ALG). One patient died 54 hours later from pneumonia. In 1 moribund patient the transplanted heart functioned well for eight days, and death was secondary to preexisting disease. A 5 year old child had an uneventful early recovery and died suddenly eight days after operation with evidence of organ rejection. The 2 month old infant died 14 hours after transplantation of the heart and lungs. The remaining 7 patients have excellent hemodynamic function of their transplanted hearts up to four and a half months after operation.

This experience confirms the feasibility of human heart transplantation.     

Trends in utilization,mortality, major complications,and cost after total artificial heart implantation in the United States (2009-2015)

ObjectiveTotal artificial heart (TAH) is a viable bridge to transplant (BTT) strategy for patients with severe biventricular failure or complex congenital heart disease. These patients have higher mortality and morbidity than patients undergoing left ventricular assist device (LVAD) implantation. To assess national trends in in-hospital mortality, major complications, cost, length of stay, and disposition of patients undergoing TAH implantation.MethodsData from the National Inpatient Sample, the largest all-payer inpatient data set in the United States, and the US Census Bureau, for the years 2009 to 2015 were analyzed. Participants included all adult patients who received TAH from 2009 to 2015. Endpoints included in-hospital mortality, in-hospital complications, heart transplantation (HT) in the same admission, length of stay, cost, and disposition at the time of discharge.ResultsWe identified a total of 143 (weighted = 703) TAH implantations. The number of TAH implants increased during the study period (average annual change +5.8%, p = 0.03). Rates of in-hospital mortality and major complications including ischemic stroke, major bleeding, postoperative infections, acute kidney injury requiring dialysis, and HT did not change significantly over the study period. Although the length of stay and disposition patterns did not change over time, we found a significant increase in cost of hospitalization (average annual change +44,362, p = 0.01). The number of HT during the same hospital stay decreased significantly (average annual change −8.1%, p = 0.02).ConclusionIn-hospital mortality and complication rates associated with TAH implantation remain increased and did not change in the era of continuous flow LVADs.     

Stroke and the total artificial heart: neurologic considerations

Neurologic complications, particularly brain infarction (ischemic stroke), are frequent and serious sequelae of total artificial heart (TAH) implantation. Most strokes that occur in TAH patients are due to embolism of thrombotic fragments originating on prosthetic surfaces. The emboli tend to lodge in the middle cerebral artery or its cortical branches and cause cortical syndromes. Cardioembolic strokes are characteristically heralded by the abrupt onset of a maximal neurologic deficit in an awake, often active patient. Cardioembolic strokes have a tendency to undergo hemorrhagic transformation. Anticoagulation is a major issue in stroke management: In anticoagulated patients, hemorrhagic transformation often results in major neurologic worsening; therefore, this risk must be weighed against the danger of recurrent embolism in the absence of anticoagulation. We recommend avoiding anticoagulation during the initial 24 to 48 hours after a stroke, especially in patients with large cardioembolic infarcts. Because of the many invasive procedures producing bacteremia in TAH patients, combined with the large area of prosthetic surfaces, infective endocarditis is a potential concern. Weighing the risks and benefits of anticoagulation in patients with infective endocarditis is likely to produce a controversial choice. Anticoagulation should probably be continued in such patients if they have total artificial hearts. The following article discusses the foregoing issues and presents recommendations for managing acute stroke in TAH patients.     

Status,Indications, and Use of Cardiac Replacement Therapy in the Era of Multimodal Mechanical Approaches to Circulatory Support: A Scoping Review

The aim of this review is to describe the current use, indications, and outcomes of the Syncardia temporary total artificial heart (TAH) (Syncardia Systems, Tucson, AZ, USA), the only TAH currently approved as a bridge-to-transplant strategy in Canada, the United States, and Europe. With more than 1700 implantations worldwide, the Syncardia temporary TAH is the most commonly used pump. Globally, it represents 2% of the long-term mechanical circulatory support devices implanted, with a recent decrease in its use. The main candidates for TAH are heart transplant candidates suffering from acute or decompensated chronic irreversible biventricular failure at high risk of imminent death and for whom a suitable donor is not available. Most patients receiving a TAH are acutely ill, characterized by an INTERMACS profile of 1 or 2, and 20% are under extracorporeal membrane oxygenation. The TAH provides efficient circulatory support and allows the end-organ to recover from the initial hypoperfusion injury. More than 60% of patients implanted with a Syncardia TAH will later undergo transplantation, with a 1-year survival rate of 70% after transplantation, compared with a 1-year survival rate of ∼ 42% in nontransplant patients. Bleeding, infection, stroke, and acute kidney injury are the most common complications in this critically ill population. The new miniaturization of the console (Freedom Portable Driver) facilitates the recovery of TAH recipients by allowing ambulation, aggressive physiotherapy, and, eventually, hospital discharge. This last aspect is one of the main benefits of TAH compared with other biventricular assist devices. In conclusion, the Syncardia temporary TAH is a reasonable bridge-to-transplant option for selected patients with either biventricular failure or special anatomic conditions.     

The initial surgical intensive care unit nursing experience with the permanent total artificial heart

The Utah experience with implantation of the Jarvik-7 demonstrated that this TAH can be implanted successfully within the confines of the adult human mediastinum. The device has proven its capacity to sustain the patient's life without causing the patient pain. There is no immunologic rejection of the heart, and in fact most other organ systems appear to accommodate well to the artificial pump. As is the nature of any experiment, problems were encountered and questions raised. Laboratory investigation is underway to test the durability of various prosthetic valves in the Jarvik-7. Subsequent recipients of the Jarvik-7 implant have experienced embolic episodes. The quick connects are being scrutinized closely for a predilection for thrombi accumulation. The significance of reperfusing persons who have adapted to chronic states of low cardiac output is still not completely understood. The ramifications of rapidly reperfusing cellular and organ systems is currently being studied. Ethical considerations as described by Woolley are being discussed at length. Protocols are being established with flexible guidelines for management of the TAH patient. Some of these protocols include infection control, anticoagulation, and hematological guidelines; nutritional support, physical therapy, and rehabilitation programs. More extensive preoperative evaluation and testing protocols are being developed. Further clarifications of the nurses' responsibility in maintaining the TAH equipment are being made. Certification methods are being developed to ensure the nurse's competency. Data collection methods are being refined by adapting information flow charts and computer hard copies specifically to the TAH patient. The Utah experience with TAH implantation in humans is still in its infancy. Twenty years of animal research provided a strong base from which to approach the first human subject. However, "there are limitations in extrapolating information from the best animal models and relating it to the critically ill human being." Animals used in the research were young and healthy; human candidates who meet the criteria for implant are generally extremely debilitated. This, coupled with the absence of human historical perspective or precedent, left many unknowns for the first TAH recipient. Our patient expired on March 23, 1982 of pseudomembranous colitis. Despite his death after 112 days of life sustained on the mechanical heart, he participated in a successful pioneering scientific experiment.     

Long-term management after heart transplantation--an assessment of current status

Due to an improvement of results after heart transplantation, there is a continuously growing number of long-term surviving patients. Aimed at a characterization of established diagnostic and therapeutic protocols, the Working Group of Thoracic Organ Transplantation within the German Society of Cardiology performed a survey among all German heart transplantation centers. Based on the experience of 1,500 patients, the clinical relevance as well as approaches for prevention and treatment of rejection, infection, cardiac allograft vasculopathy, malignancy, hypertension, renal insufficiency, and quality of life were assessed by a questionnaire. As a result, a time dependency of expected complications could clearly be shown. While early after HTX acute rejection and infection episodes were judged as clinically important, later on cardiac allograft vasculopathy, malignancy, and renal insufficiency predominate as relevant complications. This spectrum was reflected by a differentiated diagnostic protocol (early after HTX more frequent diagnostic procedures for rejection and infection, later intensified examinations to identify cardiac allograft vascular disease and malignancy) as well as by different intensities of immunosuppression and concomittant medication. Regarding further improvement of survival rates and quality of life, future clinical and scientific activities should be focused on the prevention of late complications after heart transplantation.     

Some aspects of experimental heart transplantation

In 144 experiments carried out on dogs, the possibility was proved to use for the recipient's protection during transplantation either deep immersion hypothermia or total artificial circulation without it being filled with the donor's blood. In order to maintain cardiac activity after clinical death of a non-heparinized organism for the purpose of later heart transplantation the authors propose to use the direct mechanical cardiac massage (DMCM) which makes possible not only to restore adequate pulsating blood flow in the dead body but also to assess after restoration of the heart's pump function the suitability of using it for transplantation. Functional adaptation of a transplanted heart proceeds in 3 stages: pronounced heart failure (5-15 min), functional heart failure (4-6 hours), stabilization of cardiac activity (2-3 days). Implantation of a second heart in experimental left ventricular failure of the recipient helped to achieve an effective and prolonged reduction of excessive functional overload of the affected heart.     

Status of permanent cardiac replacement for end-stage congestive heart failure

Permanent replacement of the heart in patients with end-stage congestive heart failure has long been sought after as the most definitive solution to an ever-growing problem. While cardiac transplantation is an effective therapy for many patients with end-stage congestive heart failure, this potential has been limited by the donor organ shortage and other limitations of long-term survival inherent in cardiac transplantation. While research anddevelopment of the total artificial heart continues to be of considerable interest, present-day mechanical circulatory support most commonly involves the use of left ventricular assist devices as a bridge to transplantation. Pneumatic and electromechanical pumps are now commonly employed in modern transplant practices with excellent hemodynamic function. The TCI HeartMate left ventricular assist device is now approved by the Food and Drug Administration for clinical implantation, with excellent preliminary results. Advances in the area of temporary and extended mechanical circulatory support are crucial to the ultimate development of a totally implantable artificial heart.     

Interim cardiac replacement with a mechanical heart: staged cardiac transplantation

Lack of donor heart availability complicates the management of terminally ill patients who are candidates for cardiac replacement. The total artificial heart has been used as a bridge to transplantation in three patients with terminal cardiomyopathy. Acute allograft rejection and the lack of another donor heart prompted us to use the mechanical heart as a bridge to re-transplantation in a 33-year-old man. The cardiac prosthesis functioned well for 11 hours, when a second transplantation was performed, but the patient died of right heart failure 48 hours after the second transplantation. Critical factors in such cases include (1) a prompt decision to proceed with cardiac replacement; (2) avoidance of long periods of cardiopulmonary bypass; (3) prosthetic device availability; and (4) surgical team preparedness, with technical expertise in transplantation, allograft explantation, and total artificial heart implantation/explantation, with re-transplantation.     

Permanent and temporary pacemaker implantation after orthotopic heart transplantation

PURPOSE:To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR) between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for pemanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%)heart transplant recipients required temporary pacing and 4 of 114 (3.5%) patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5%) and atrioventricular (AV) block in 3 patients (21.4%). The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75%) and atrioventricular (AV) block in 1 patient (25%). We observed rejection in 3 patients (21.4%) who required temporary pacing and in 2 patients (50%) who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4%) with temporary pacing. Seven of the 14 patients (50%) died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.     

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Cardiomyocytes are a stable cell population with only limited potential for renewal after injury. Tissue regeneration may be due to infiltration of stem cells, which differentiate into cardiomyocytes. We have analysed the influx of stem cells in the heart of patients who received either a gender-mismatched BMT (male donor to female recipient) or a gender-mismatched cardiac transplant (HTX; female donor to male recipient). The proportion of infiltrating cells was determined by Y-chromosome in situ hybridization combined with immunohistochemical cell characterization. In BM transplanted patients and in cardiac allotransplant recipients, cardiomyocytes of apparent BM origin were detected. The proportions were similar in both groups and amounted up to 1% of all cardiomyocytes. The number of stem cell-derived cardiomyocytes did not alter significantly in time, but were relatively high in cases where large numbers of BM-derived Y-chromosome-positive infiltrating inflammatory cells were present. The number of Y-chromosome-positive endothelial cells was small and present only in small blood vessels. The number of BM-derived cardiomyocytes in both BMT and HTX is not significantly different between the two types of transplantation and is at most 1%.     

The total artificial heart: where we stand

The AbioCor total artificial heart (TAH) is undergoing clinical feasibility testing as destination therapy in patients with end-stage congestive heart failure. So far, the device has been implanted in 11 of a projected 15 patients. The TAH has performed reliably, providing adequate circulatory support while extending survival and improving quality of life in most recipients. Thromboembolism remains a problem but is being addressed by optimizing device and patient management and refining the anticoagulation protocol. Because the device is totally implantable and requires no penetration of the skin, infection has been minimized. All recipients so far have been men. The device is large and this limits its use in smaller patients (i.e. women, small men and children). A smaller version is being developed. Although it has yet to receive Food and Drug Administration approval, the early clinical results suggest that the AbioCor TAH may become an accepted alternative to heart transplantation for selected patients with end-stage congestive heart failure. Further investigation with regard to its primary clinical applicability, i.e. as a rescue device for sudden catastrophic heart failure, is warranted.     

Implantation of CardioWest total artificial heart in irreversible acute myocardial infarction shock-new hope for patients with infaust prognosis

Patients in whom cardiogenic shock develops after acute myocardial infarction have a very high death rate despite early reperfusion therapy. Often hemodynamic stabilization can be achieved only by implantation of a mechanical circulatory support system. When pharmacological therapy and onset of percutaneous assist devices fails in cases representing expansive myocardial impairment without any chance of recovery, the indication for implanting a total artificial heart is given. We report on our first experiences with this extensive and innovative management of irreversible cardiogenic shock patients. In five patients (male, mean age 50 years) the CardioWest total artificial heart was implanted. All patients were in irreversible cardiogenic shock despite maximal dosages of catecholamines, intraaortic balloon pump and/or femorofemoral bypass. In all patients early reperfusion therapy was performed. After implantation of the CardioWest system, rapid recovery of all dysfunctional organ systems occurred in all patients. Four of five patients underwent successful heart transplantation after a mean support time of 156 days. One patient died because of enterocolic necroses caused by embolic event after termination of dicumarol therapy. In summary, first experiences justify this extensive management in these young patients who otherwise would have died within a few hours.     

Assisted circulation by external heterotopic prosthesis as a bridge to heart transplantation

Eleven patients aged 7 to 58 years were placed on assisted circulation with Pierce (2 cases) or Abiomed (9 cases) external prosthetic ventricles as a bridge to cardiac transplantation. The indications were terminal cardiac failure following cardiomyopathy (7 cases), decompensated ischemic heart disease (3 cases) and subacute post-transplantation rejection (1 case). The duration of the assisted circulation ranged from 24 hours to 11 days. All patients were transplanted but 3 died after transplantation (27%). The circulatory assistance was satisfactory in all patients as shown by the regression of clinical signs of low cardiac output and the normalisation of diuresis. The complications observed during assisted circulation and after cardiac transplantation were: haemorrhage (36%), infection (27%) and thromboembolism (9%). These preliminary results with a 72% post-transplantation survival rate, show that both systems are effective "bridges to cardiac transplantation". The Abiomen device is excellent value for money and relatively simple to install and represents a good compromise between the sophisticated techniques of circulatory assistance and the problems of the cost of health care.     

Phase III rehabilitation after heart transplantation

INTRODUCTION: Longterm treatment after heart transplantation (HTX) improves survival, although the quality of life and exercise tolerance decreased continuously between one and ten years after transplantation. The role of physical exercise and psychological support in longterm treatment after HTX has not been determined. We analyzed the effects of a one year outpatient rehabilitation program in combination with a home based, computer assisted training program on exercise capacity, coronary risk factors and quality of life. METHODS: 20 heart transplant recipients in an intervention group and 12 patients after HTX in a control group participated in the study (IG (CG); 5.1+/-2.2 (4.5+/-2.3) years after HTX; age: 55+/-7 (54+/-8) years; body mass index: 28.3+/-1.0 (28.7+/-0.9) kg.m(-2)). Before and after the intervention, maximum and constant load exercise capacity, and self-reported quality of life were evaluated. The 12 month intervention period included 10 days of exercise testing as well as medical and psychological support. Furthermore, the IG group performed a computer-assisted and controlled home ergometer training every second day. RESULTS: After one year with 114+/-18 exercise training sessions, maximum oxygen consumption increased in the IG from 18.8+/-4.2 to 20.1+/-4.2 ml.min(-1).kg(-1) (p<0.05; CG 19.3+/- 4.5 to 18.5+/-2.8 ml.min(- 1).kg(-1); p<0.01 IG vs CG). In the IG, lower back pain, body fat, and blood pressure were all reduced, while the self-reported quality of life, endurance exercise capacity and HDL cholesterol were increased. No significant changes occurred in the control group. CONCLUSIONS: When initiated years after heart transplantation, longterm rehabilitation reduced coronary risk factors and significantly improved both the subjects' quality of life, as well as a near to normal capacity for physical work.     

The total artificial heart. An ethics perspective on current clinical research and deployment

The development of the total artificial heart (TAH) as a support before cardiac transplantation and as a possible permanent prosthesis has generated intense debate. The social commitment to TAH research entails immense health care costs because of the cost of the implant itself and also because of the large number of patients whose interests impel the research. The deployment of the pre-transplant TAH during the current shortage of donor hearts means that the TAH creates its own incentive as a way to compete in an expanded pool of donor heart candidates. Policies to address the orderly deployment and costs of the pretransplant TAH are needed. Research design and current pre-transplant clinical applications require careful consideration of planning for the termination of TAH support for severely injured but not brain dead patients.     

Results following implantation of mechanical circulatory support systems: The Montreal Heart Institute experience

BACKGROUND:

Mechanical circulatory support systems (MCSS) have been available in Canada since 1986. Accepted indications include bridging to transplantation or recovery. The present study reviewed the results following MCSS implantation at the Montreal Heart Institute (Montreal, Quebec).

METHODS:

From September 1987 to September 2006, 43 MCSS were implanted (32 Thoratec [Thoratec Corporation, USA], nine Cardio West TAH [SynCardia Systems Inc, USA], two Novacor [World Heart Corporation, Canada]) in 43 patients (mean [± SD] age 44±13 years; range 19 to 64 years). Indications for implantation included cardiogenic shock due to ischemic (n=19), viral (n=10) or other types of cardiomyopathies (n=14).

RESULTS:

The mean ejection fraction before implantation was 17.6±6.5% (range 10% to 45%). Before MCSS implantation, most patients showed signs of end-organ failure, including mechanical ventilation (77%), central venous pressure higher than 16 mmHg (44%), oliguria (35%) and hepatic dysfunction (19%). The mean duration of MCSS support was 22.8±32.8 days (range one to 158 days). Survival to transplantation or recovery was 74%. Only one patient was successfully bridged to recovery. Complications were common during MCSS support. They included re-exploration for bleeding (47%), respiratory failure (44%), renal failure requiring temporary dialysis (40%), infection (33%) and neurological events (16%). Only one patient had device failure. In patients successfully bridged to transplantation, early actuarial survival (one month) following transplantation averaged 71±8% and was 57±9% at one year.

CONCLUSION:

MCSS support with a left ventricular assist device or a total artificial heart provides an effective means of bridging terminally ill patients to transplantation or recovery. Early survival after transplantation shows satisfactory results. However, these results come at the expense of frequent device-related complications, and device failure remains a constant threat.