**3. Indications for LVAD bridge-to-transplant**

#### **3.1. Current outcomes**

with end-stage heart failure who were not candidates for heart transplantation underwent either LVAD implantation using the HeartMate VE or received maximal medical therapy; these two groups were compared for long-term complication and mortality outcomes. In this landmark study, survival among the VAD placement group was found to be 52% compared to 25% in the medical management group at 1 year, with a further 48% relative risk reduction in mortality over the 2-year study period. Additionally, the LVAD cohort was also highlighted

However, we highlight the REMATCH study here primarily because it also identified a number of serious complications and limitations related to the use of LVAD support as durable therapy. The pulsatile flow HeartMate VE first-generation LVAD used in this study was found to have a rate of serious complications 2.35 times greater than in medical therapy group. Indeed, this group carried a relative risk of stroke 4.35 times that of the medical group. Intraperitoneal placement of the large LVAD device was associated with early satiety, and the extensive surgical dissection required for implantation was associated with a significant bleeding and infection risk. Over 21% of patients ultimately required device replacement. As a result, and primarily due to the long-term risk of infection and mechanical failure, the-year

Continuous-flow devices making use of either an axial flow model (second-generation LVADs) or a centrifugal flow model (third-generation) were the next innovation in LVAD performance. The second generation has key mechanical advantages compared prior, including elimination of valves and chambers and the introduction of an internal rotor suspended by contact bearings. These alterations were theorized to lead to a decreased rate of complications, due in part to their fewer moving parts. However, analysis of outcomes has also shown that the direct contact between the bearings and blood in second generation LVADs serves as

The second generation of LVADs were implemented into clinical practice in the late 1990's and demonstrated an acceptable safety profile for bridge to transplant when compared to existing pulsatile-flow devices despite the aforementioned higher-than-expected incidence of pump thrombosis. Approval of these later-generation LVAD's was primarily derived from three landmark clinical trials either directly comparing the pulsatile HeartMate XVE with the continuous flow HeartMate II [5], or with the use of historical controls to compare their outcomes [6, 7]. The earliest of these studies was a prospective multicenter trial of 133 patients with end-stage heart failure who underwent VAD therapy as a bridge to transplant [6]. Among these participants, a total of 100 (75%) survived to the principal aggregate outcome of either heart transplant, cardiac recovery, or survival to the end of the study; of note, of those patients on persistent mechanical support through the study, there was a 1-year survival of 67%. There was no control group in this study, but survival was compared favorably with a historical control of 53% 1-year survival among patients using the pulsatile-flow HeartMate XVE as a bridge to transplant. A followup study identified further improvements in survival among those using these devices, with that improvement being attributed to increased device experience [7]. Another major study evaluating the morbidity benefit of continuous over pulsatile-flow VADS identified an 1-year

as having improved quality of life.

48 Heart Transplantation

**2.2. The modern era of LVAD**

an area of thrombosis formation.

survival in the LVAD group was limited to 23% [4].

While left ventricular assist devices are increasingly used in the role of bridge to transplant, conflicting data exists regarding outcomes compared to the patients who proceed directly to transplant. Outcomes are improving both as a result of greater use of the continuous flow device, and as a result of more sophisticated algorithms for dealing with LVAD complications. Currently, current survival to transplant and post-transplant outcomes appear to be essentially equal between groups, especially in the absence of LVAD-related complications. Graft rejection also appears to be similar in patients who are bridged with LVADs compared to those without LVADs.

A number of additional risk stratification and preoperative predictive factors have been developed to help select LVAD candidates and predict in-hospital mortality. For example, a multivariable risk score has been generated from preoperative factors of destination-therapy patients, and this highlights risk factors such as low albumin, low platelet count, abnormal liver function test or evidence of right ventricular dysfunction [14]. More recently, a risk score for LVAD patients was developed which showed that age and center experience were determinants of long-term survival [15]. While conventionally, LVAD placement is increasingly likely with increasing severity of INTERMACS profile, the ROADMAP clinical trial has shown that early implantation in lower INTERMACS profiles (4–7) outcomes are as favorable as earlier trials with improvements in quality of life [16]. Survival patterns from the UNOS database suggest that with the current LVAD technology, patients supported with LVAD support as a bridge to therapy demonstrate an improved survival while listed for heart transplantation, and the use of LVADs as a bridging strategy could potentially improve patient survival while waiting for transplantation, in turn allowing for better allocation of donor hearts [17]. Similarly, a 2016 study utilizing the United Network of Organ Sharing (UNOS) database showed those patients who underwent LVAD implantation prior to being listed for heart transplantation had improved survival compared to those who were medically managed; this survival benefit extended to those who were implanted with a LVAD while awaiting heart transplantation [18]. In general, the implementation of the VAD has led to a number of significant effects upon heart transplantation and the donor population. (1) There are now a significant number of patients with end stage heart failure who would otherwise have died while awaiting emergency transplantation, who are now surviving to have heart transplants performed under non-emergent circumstances. This has a profound effect on the pool of available donors as well as the acuity of transplant. (2) Cardiogenic shock with multi-organ dysfunction, previously an indication for emergency transplantation, is increasingly becoming a contraindication to transplantation due to the relatively poor likelihood of successful transplantation. With the option for temporization and recover without risking the high perioperative mortality and loss of scarce allografts associated with transplantation, the procedure is now being supplanted by mechanical support and then transplantation when the patients are recovered and shock is reversed. (3) The overpopulation of waitlists by patients with LVADs with acuity Status 1A who receive priority over ambulatory patients will make heart transplantation increasingly unlikely as a therapy for the treatment of ambulatory heart failure. (4) The LVAD as a bridge to transplant has allowed end stage heart failure to be treated in certain patients as an ambulatory disease in an outpatient fashion, rather than a disease requiring continued ICU management [6].

Heart Transplantation in the Era of the Left Ventricular Assist Devices

http://dx.doi.org/10.5772/intechopen.76935

51

In addition to the patient indications listed above, there are a number of unique subpopulations with a need for heart transplantation that would potentially benefit from LVAD as a bridging therapy. For one, mechanical circulatory support is an acceptable bridge to transplantation in pediatric patients suffering from heart failure due to structural defects. The feasibility of mechanical support as a bridge to transplantation in this subgroup has been demonstrated in single- and multi-institutional [19] case reports. For example, a small retrospective case series in 2017 of five patients who underwent VAD placement for congenital

**4. Selected subpopulations**
