**6. ECMO as a bridge to transplant**

Worldwide, changes to heart allocation guidelines prioritize patients on mechanical circulatory support, including ECMO. This new allocation system became effective in the United States in 2018, in the United Kingdom in 2016, and in France in 2004. Since then, there has been an increasing use of VA-ECMO as a bridge to heart transplant worldwide. Across the United States, the use of VA-ECMO as a direct bridge to heart transplant increased from 1.1% in 2012 to 5.2 in 2022 [21, 22]. Advanced heart failure has remained the most common indication in patients who receive VA-ECMO as a bridge to transplant. Unfortunately, the term "advanced heart failure" is not clearly defined. Patients with advanced heart failure can be identified by signs of circulatory failure with attendant renal and hepatic dysfunction, frequent malignant arrhythmias, and the need for continuous intravenous inotropes. Options for mechanical circulatory support include the Intra-Aortic Balloon Pump (IABP), various ventricular assist devices (VAD), VA ECMO and Impella ® (Abiomed). The choice of device for support is based on patient factors as well as available technology and expertise, residual left ventricular function, right ventricular function, pulmonary artery pressures, status of the aortic valve and need to unload the left ventricle. Bridging to transplant with ECMO has been considered controversial and not preferred because, compared to VAD, it requires immobilization, anticoagulation, and ICU care. Also, there is a high rate of waitlist mortality in patients bridged to transplant with ECMO. This practice is associated with a survival to hospital discharge rate of less than 50% [23].

The versatility and efficacy in delivering biventricular as well as pulmonary support has continued to earn its place as an option for MCS delivery. In addition, the speed of deployment makes it suitable for emergency situations, such as critical sudden circulatory collapse. In an analysis of the post 2018 allocation change in the United States, 3.6% of transplants were on ECMO (bridge to decision) at the time of listing and 5.2% of transplants in the same period were on ECMO at transplantation (bridge to transplant) [21]. The success of ECMO bridging to heart transplant or VAD is estimated to be between 44 and 79% with the most prevalent complications estimated to include bleeding (46%), arrhythmia (26%), device thrombus (24%), and device malfunction (23%) [24–26].

Several centers have reported bridging to transplant with ECMO as a risk factor for worse post-transplant survival. An analysis of the UNOS database by Moonsamy et al. showed that bridging with ECMO was a significant predictor of post-transplant mortality with lower 1 year survival rate of transplants bridged on ECMO (68 vs. 90%) [27]. In a similar analysis by Fukuhara et al. ECMO as direct bridge to transplant demonstrated lower posttransplant survival compared with continuous flow LVAD with survival rates of 73.1 versus 93.1% at 90 days, and 67.4 versus 82.4% at 3 years respectively [16]. These results reflect the acuity of patients on ECMO and the attendant issues with coagulation, end-organ perfusion, deconditioning, debility and inflammatory response associated with VA ECMO support.

Aimed at reducing the afterload, ECMO support may be combined with Impella support in a combined mechanical circulatory support known as ECMO-Impella

## *Extracorporeal Membrane Oxygenation (ECMO) Use in Heart Transplantation DOI: http://dx.doi.org/10.5772/intechopen.114126*

combination therapy or ECPELLA, this has been used in cases of cardiogenic shock and was reported to be associated with activation of cardioprotective signaling [28]. The addition of Impella to ECMO support is based on the finding that, in contrast to ECMO, Impella reduces infarct size [29]. Hence the opinion that left ventricular unloading may mitigate myocardial injury in patients on ECMO. Delivery of hemodynamic support is done by titrating flow rates of the devices while avoiding complications. Weaning protocols for ECPELLA are individualized according to patients' clinical context. Generally, in patients who are bridged to heart transplant and in whom ECMO component of combined therapy was used to provide respiratory support, weaning the ECMO first may be favored as the lung recovers. While in patients who bridged for heart and lung transplant due to pulmonary failure and failure of both ventricles, weaning the Impella first would be the goal.

In a retrospective review of ECPELLA use in cardiogenic shock, Patel et al. reported that 30-day mortality was significantly lower in the ECPELLA cohort compared with the VA-ECMO cohort, this difference remained significant after adjusting for STEMI and PCI [30]. Also, one-year all-cause mortality was significantly lower in the ECPELLA group. The use of ECPELLA was associated with higher rates of hemolysis and need for hemofiltration [31].

Reviews of the practice of VA ECMO bridge to heart transplant in the United States since the 2018 change in UNOS allocation policy shows that there has been an increase in the use of temporary MCS, including ECMO, following the policy change [21, 32]. This increase in the use of temporary MCS was noted to have occurred in transplant centers but not in other critical care units, despite similar patient characteristics during two time periods. The allocation system may have driven a change in practitioners' behavior, not the patients [33]. Considering outcomes, Cogswell et al., Trivedi et al., as well as Kilic et al. reported a decrease in unadjusted post-transplant survival following the policy change [34–36]. Goff et al. reported no difference in unadjusted post-transplant survival following the policy change [37]. In contrast, patients supported on ECMO following the most recent allocation policy change were more likely to receive heart transplants, and less likely to die on the waitlist or be removed from the waitlist; they also had a lower average waitlist time [38].

These varying results may be attributable to informative censoring. More transplant candidates are waitlisted on ECMO since the most recent allocation policy change, however the demographics of patients waitlisted on ECMO did not change with the new policy. Comparatively, a greater percentage of ECMO bridges are undergoing transplant in the new era compared to the old allocation policy (78.6 vs. 37.6%). Following transplantation, 90-day survival in ECMO bridged patients were comparable in the two eras with a nonsignificant decrease in 1 year survival in the new era [14].

Kim et al. noted that there was improved waitlist and post-transplant outcomes in patients bridged with ECMO following the most recent change in heart allocation policy [39]. In their report, bridging with ECMO was strongly associated with worse 1-year mortality prior to the policy change, while ECMO patients transplanted after the policy change have similar post-transplant outcomes as non-ECMO patients. They concluded that their findings suggest that ECMO may be most effective as a bridging modality when patients are transplanted promptly following initial listing. There is also a possibility that nonrestrictive patient selection for ECMO bridging may be a possible alternative explanation. Despite these issues, when deaths within first 30 days of transplant were excluded, the use of ECMO was not associated with increased mortality [40, 41].

Predictors of failure of the ECMO bridge to transplant have been reported to include left ventricular EF, older age, ischemic heart disease, pre-ECMO cardiopulmonary resuscitation, and high Sequential Organ Failure Assessment (SOFA) scores [42, 43]. Other factors associated with failure include the presence of female sex, dilated cardiomyopathy, decompensated heart failure, the occurrence of complications such as stroke, and the need for dialysis [24]. There is little hope that a complete consensus will soon be reached on the age limit for successful bridging. Smedira et al. recommend 60 years with decompensated heart failure, while Chung et al. [43, 44] recommend 50 years with a SOFA score of 10. Analyses of the organ procurement and transplant network data on ECMO bridges in the pediatric population in the US showed that 45% of the cohort bridged on ECMO survived to transplantation, 10% of the cohort recovered enough to be removed from the waitlist, 11% were removed from waitlist due to clinical deterioration and 28% died while on the waiting list [24].

In an analysis of use of ECMO bridge to transplant by Dong et al., median bridging time in the BTT group was 13 days (interquartile range [IQR], 7–19 days) [45]. Generally, ECMO support longer than 14 days is a risk factor for posttransplant mortality [24, 46]. It is important to note that while ECMO is reliable for temporary bridge to transplantation, it is not an option for long-term mechanical circulatory support to bridge transplant candidates. When full flow on ECMO for more than a few days is required to achieve adequate organ perfusion, escalation of ECMO to LVAD provides a safe and durable support that provides cardiac unloading, high flow, and physiological circulatory patterns [47].

Outside the United States, experience with the use of ECMO as bridge for heart transplantation showed that, comparatively, temporary left ventricular assist devices were associated with a lower risk of death in the first year of the bridge when compared with VA-ECMO [25]. The higher mortality noted in patients who were bridged with VA-ECMO could be attributable to the higher prevalence of critically ill patients and more adverse events in the ECMO group [35].

In the United Kingdom, VA-ECMO bridge-to-transplant is uncommon, while temporary LVAD such as Impella ® (Abiomed), make up the vast majority of bridged patients. In a review following the change in allocation system, only a handful of patients were bridged using VA-ECMO [48].

Analysis of the French national registry shows ECMO bridged patients to have higher priority and shows that patients bridged with ECMO have higher incidence of being dependent on intravenous inotropes, mechanical ventilation, and dialysis. Despite these features suggesting higher acuity among heart transplant patients bridged on ECMO, French patients bridged on VA-ECMO had a comparably good outcome with equivalent mortality in single center analyses [49] and even lower risk of mortality in national database analysis [50]. Notably, the duration of extracorporeal life support was short with a mean duration of 6.3 ± 4.6 days [15].
