Current Cardiology Reports (2019) 21: 142 https://doi.org/10.1007/s11886-019-1242-5 HEART FAILURE (HJ EISEN, SECTION EDITOR) Current Role of the Total Artificial Heart in the Management of Advanced Heart Failure Nathaniel Melton1 & Behzad Soleimani2 & Robert Dowling2 Published online: 22 November 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The total artificial heart (TAH) is a form of mechanical circulatory support that involves resection of the native ventricles followed by placement of a device that can restore total pulmonary and systemic flow. Given the increasing burden of congestive heart failure and cardiovascular disease, the number of people in need of cardiac replacement therapy will continue to grow. Despite aggressive efforts to expand the donor pool, the number of heart transplants in the United States (US) has plateaued at less than 3000 per year. In addition, there is increasing recognition of the long-term complications of current generation left ventricular assist devices such as progressive aortic insufficiency, complications related to blood trauma, and both early and delayed right ventricular failure. These factors may serve to expand the role of the TAH in the treatment of patients with end-stage heart failure particularly if new generation devices are developed that are durable, have an improved safety profile, and are totally implantable. Purpose of Review To review the role and current evidence of the use of the TAH in the management of advanced heart failure and discuss development of recent TAHs that may have an impact on the field in the near future. Recent Findings Many patients that receive a heart transplant are bridged with a mechanical support device, most commonly a left ventricular assist device (LVAD). However, there is a small subset of patients with profound biventricular (BV) failure or structural abnormalities that preclude LVAD placement, who will require support with a biventricular assist device (BiVAD) or TAH. There are numerous studies showing the efficacy of the TAH in bridging to transplantation. Also, recent studies have shown equal rates of bridging to transplantation between patients receiving a TAH compared to a BiVAD. However, BiVAD support has a higher incidence of stroke in addition to complications related to the native heart such as arrhythmias and valve dysfunction. Currently, there are multiple new generation artificial hearts in both preclinical development and in clinical trials for both bridge to transplant and destination therapy. Summary TAH have been shown to be effective for circulatory support in select patients with end-stage heart failure. Current LVADs are associated with significant long-term complications related to retention of the native heart and pump design. Many of these complications may be addressed by the increased use of cardiac replacement therapy, i.e., total artificial hearts. Multiple generations of both pulsatile and advanced design continuous flow TAH are under development which have the potential to expand the role of TAHs. This article is part of the Topical Collection on Heart Failure * Nathaniel Melton 1 Department of General Surgery, UPMC Pinnacle, Brady Hall, Ninth [email protected] Floor, 205 South Front Street, Harrisburg, PA 17104, USA 2 Penn State Heart and Vascular Institute, Penn State Health Milton S. Behzad Soleimani Hershey Medical Center, Hershey, PA, USA [email protected] Robert Dowling [email protected] 142 Page 2 of 7 Curr Cardiol Rep (2019) 21: 142 Keywords Advanced heart failure . Total artificial heart . Mechanical circulatory support . Biventricular circulatory support . Bridge to heart transplantation Introduction with LVADs as a long-term therapy for end-stage heart failure patients [9], these devices have become more sophisticated and Adults with advanced heart failure experience symptoms that easier to implant [7, 8•]. With the introduction of second- interfere with daily life and have a limited prognosis [1–3]. generation continuous flow devices and refinements in surgical Cardiac transplantation remains the treatment of choice for select techniques, there was considerable optimism that the incidence patients who remain symptomatic despite optimal medical man- of both early and late right ventricular failure would no longer be agement [2, 3]. However, given the increasing burden of conges- an issue. However, this has not been realized and RV failure tive heart failure and cardiovascular disease, the number of peo- remains a major concern after the implantation of an LVAD ple in need of transplants continues to exceed the number of and is a major cause of early morbidity and mortality [10–13]. hearts available. The number of transplants performed in the Even with the newer, continuous flow, devices, the incidence USA has only increased from 2193 in 2006 to 3244 in 2017 ranges from 9 to 44% [10, 11, 13]. In addition, according to [4]. Despite this increase, the number of patients awaiting a heart the latest INTERMACS data, one of the major factors associated transplant has increased from 2424 in 2006 to 3623 in 2017 [5]. with an increased early hazard of mortality after LVAD implan- Additionally, there are many patients who are not deemed suit- tation was RV dysfunction [6]. able for transplant who will benefit from mechanical circulatory There have been multiple attempts to identify which patients support. This discrepancy has led to the significant increase in the are likely to suffer from RV failure early after LAVD placement. use of mechanical circulatory support devices (destination thera- Fitzpatrick et al. analyzed retrospective outcomes for patients py). According to the latest Interagency Registry for who underwent LVAD placement to determine a risk score for Mechanically Assisted Circulatory Support (INTERMACS) re- developing post-LVAD right ventricular failure [12]. They found port, the number of LVADs placed as destination therapy exceeds the most significant predictors of right heat failure after LVAD the number placed as a bridge to transplant [6]. In 2017, approx- placement to be cardiac index, RV stroke work index, severe pre- imately 50% of recipients had some form of a support device operative RV dysfunction, creatinine, previous cardiac surgery, prior to transplantation [5]. and systolic blood pressure. Similarly, Drakos et al. found that As a result of the continued discrepancy between the num- preoperative need for intra-aortic balloon counter pulsation, in- ber of patients on the waiting list and available hearts, me- crease pulmonary vascular resistance, and destination therapy chanical circulatory support has emerged as a standard long- were predictive of RV failure post-LVAD [11]. The sheer number term therapy for adult patients with intractable heart failure. of models to predict early RV dysfunction demonstrates both their This has led to the design of numerous implantable devices to limited predictive ability and the significance of this problem. treat advanced heart failure [1, 7, 8•]. From 2006 to 2017, a As previously mentioned, RV failure remains a major cause total of 25,145 of these devices were implanted in the USA of early post-LVAD morbidity [10–13]. However, late post- [6]. Many of these patients can be supported by left ventricular LVAD RV failure, defined as needing right ventricular me- assist devices (LVAD). However, a subset of these patients chanical support, inotropic support, or pulmonary vasodilators have severe biventricular failure (BV) and/or other conditions more than 14 days after LVAD implantation, is being increas- that would preclude LVAD implantation. In this subset of ingly recognized as a significant problem. According to the patients, the TAH may be the better treatment option. This latest INTERMACS data, 2% of patients required RV me- review paper will explore the role of the TAH in the manage- chanical support early after LVAD implantation, while 1% ment of advanced heart failure with an emphasis on which required late mechanical support [6]. Two recent studies found patients may benefit either acutely or in the long term from the incidence of late RV failure to be 7.3% and 11% [14, 15]. total heart replacement. We will also discuss new devices on Rame et al. found that late RV failure was associated with the horizon and their potential impact on patient management. significantly more gastrointestinal bleeding, sepsis, and acute renal dysfunction, but there was no difference in 1-year sur- vival [14]. Takeda et al., however, found that late RV failure Patient Selection was associated with a decreased 2-year survival, not during LVAD support, but after transplantation [15]. Left ventricular assist devices are the primary long-term mechan- For patients with biventricular (BV) failure, para-corporeal ical circulatory support device for patients with advanced con- biventricular assist devices (BiVADs), implantable BiVADs, gestive heart failure as a bridge to transplantation, destination and TAHs all are options to provide biventricular support. therapy, or as a bridge to myocardial recovery [3, 5, 6]. Since While these devices are associated with different adverse the milestone REMATCH trial demonstrated clinical success events, there is evidence of improved survival with placement Curr Cardiol Rep (2019) 21: 142 Page 3 of 6 142 of a TAH compared to a BiVAD [16]. In addition, the fourth Table 2 Current clinical Irreversible, severe biventricular failure INTERMACS report showed improved