**6.1 Timing of unloading**

Various studies have demonstrated the advantages of LV unloading in ECLS patients. However, the timing and patient selection still represent a point of high debate among advanced heart failure specialists [4, 10]. The propensity score matched the multicenter study from Schrage et al., which demonstrated that LV unloading (with Impella) initiated before or shortly after the v-a ECMO implantation significantly improves survival compared to v-a ECLS alone [4]. However, a subgroup analysis of those patients who underwent delayed unloading (>2 h since ECLS), revealed no significant survival benefits [4]. Still, there is a point of discussion if the LV unloading has to be performed simultaneously in ECLS or if a delayed approach is more optimal in a clinical setting. The propensity score matched the study from Grandin et al., which demonstrated that patients who undergo an upright LV unloading have no differences in regard to on-support or in-hospital mortality but a lower incidence of renal injury compared to the delayed unloading cohort [11]. Moreover, initiation of a LV unloading after a period of v-a ECLS exposure might be associated with increased procedural risk and technical difficulties with the placement of an additional device [4, 11].

### **6.2 System choice**

Another important point of the LV unloading strategy is the choice of the system. Several important aspects should be taken into consideration during the decisionmaking process:


The current evidence-based data have demonstrated that the LV unloading in v-a ECLS patients improve the patients' outcomes [1, 4, 11, 12, 18]. However, no general recommendation or guideline on the technique of LV unloading exists [3]. The decision-making is often based on the expertise of the performing surgeon or interventional cardiologist and the internal standardized operational protocols of each clinic [3].

Although the LV unloading via an additional inflow cannula placed through the apex of the right superior pulmonary vein represents the most cost-effective and simplified approach, it is predominantly reserved for patients with central ECLS [3]. Since it requires a sternotomy or thoracotomy, it might be associated with an increased risk for collateral surgical damage [3]. Another major disadvantage is the necessity for surgical removal of the cannula for weaning. In this constellation, the utilization of specialized percutaneous venting cannulas represents a preferable and flexible solution and has been increasingly applied in recent years [7].

Currently, the vast majority of patients receive LV unloading with either IABP or Impella devices [11]. Both approaches provide similar survival benefits, however, have different complications and hemodynamic profiles [11]. The implantation site bleeding and vascular injury remain the major disadvantage for LV unloading since the addition of extra arterial access increases the risk for complications [4, 11]. However, in the case of an IABP it is significantly lower due to the size of the used catheter (7.5 Fr compared to 14 Fr in Impella CP in devices) [3]. Finally, yet importantly, the ECMELLA therapy is associated with significantly higher costs compared to LV unloading with a venting cannula or an IABP [3].

Despite its invasiveness, the ECMELLA approach has some unique advantages which have to be taken into consideration during the decision-making process [13]. The ECMELLA provides the highest level of temporary cardiopulmonary support currently available in surgical armaments [15, 19]. In patients suffering from systemic inflammation response syndrome and consecutive vasoplegia as a sequel of, or coincidently with, severe cardiogenic shock or after CPR, optimal flow rates of up to 11 L/min or even more might be necessary [15, 20, 21]. ECMELLA allows a controlled stepwise support reduction and de-escalation strategy: v-a ECLS explantation with further Impella support, which achieves a reduction of ECLS-related complications in patients requiring prolonged support [1]. The recently developed single arterial access ECMELLA 2.1 includes advantages of high flow support, patients' mobilization, and bedside explantation, with no need for a renewed exploration of the implantation site [13, 15, 17].

#### **6.3 Perspectives**

Currently, two randomized controlled trials investigating the impact of LV unloading in v-a ECLS patients have been launched: the REVERSE (NCT03431467) trial from the University of Pennsylvania and ANCHOR (NCT04184635) trial guided by the Hôpital Pitié Salpétrière from Paris. The REVERSE trial aims to investigate the impact of Impella CP as a vent in v-a ECLS patients, while the unloading has to be initiated within 10 h after implantation of the v-a ECLS. Planning to recruit 96 patients, the first results are expected in 2025. The ANCHOR trial compares 200 patients with acute myocardial infarction-related CS (AMICS) treated with v-a ECLS + IABP vs. a control group without tMCS. The finishing is scheduled for the end of 2024. However, no prospective study investigating different LV unloading strategies is currently available.

The self-expandable catheter-based microaxial pumps represent a promising improvement in MCS [22]. This technology allows percutaneous insertion of narrowprofiled devices, which expand during support aiming to reduce the risk for vascular complications and hemolysis by minimizing the shear stress on blood cells [22]. The HeartMate Percutaneous Heart Pump (PHP, Abbott Vascular, Santa Clara, CA, and US) was the first pump that was deployed via a 14 Fr femoral arterial sheath and delivered a self-expanding 24 Fr nitinol cannula and impeller across the aortic valve [22]. However, due to a high incidence of device malfunctions, the HartMate PHP was not implemented in clinical practice [22]. The recently presented Impella ECP (Abiomed Inc., Danvers, MA, and US) device has a 9 Fr catheter and an up to 18 Fr size expandable body. Currently, the ECP trial (NCT05334784) investigating the effect of the device on patients with high-risk coronary interventions is scheduled. Both devices were originally designed for periprocedural support during high-risk interventions (max. 6–12 h); however, self-expandable Impeller pumps can be potentially used for prolonged support in cardiogenic shock patients in future (**Table 2**) [22].


**Table 2.**

*Important studies on LV unloading in v-a ECLS patients.*
