Background: Recent international guidelines recommend the use of extracorporeal cardiopulmonary resuscitation (ECPR) with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in selected patients with refractory cardiac arrest. Recent data from smaller cohort studies suggest that additional unloading with left-ventricular (LV) Impella® pump (“ECMELLA”) during ECPR might be associated with survival benefits compared to VA-ECMO therapy alone. The “International Registry on Unloading during Cardiac Arrest” (IRUCA) working group hypothesized that ECMELLA treatment during refractory cardiac arrest was associated with lower in-hospital mortality than VA-ECMO treatment in this first systematic review and meta-analysis (PROSPERO ID: CRD42022339499).

Methods: Four blinded investigators of the IRUCA group performed the systematic literature review according to the PRISMA checklist by including clinical studies published between January 2017 and June 2022 on Medline, CENTRAL, Embase and abstract websites of large cardiology societies in the United States and Europe. If mortality data were not reported, aggregated data was retrieved from corresponding authors. The meta-analysis was performed by using a random-effects model.  Heterogeneity was tested with Cochrane Q test and publication bias with funnel plots.

Results: 129 records were screened in total, of which 13 studies were included in the meta-analysis. 1,038 adult patients with ECPR due to refractory cardiac arrest were included, out of which 255 (24.6%) received ECMELLA therapy and 783 (75.4%) received VA-ECMO therapy (see patient characteristics in Table). Compared to patients with VA-ECMO, patients with ECMELLA had more frequently shockable ECG rhythms, acute myocardial infarctions and percutaneous coronary interventions. ECMELLA treatment was associated with a 48% reduction in mortality [95% CI 0.30-0.89] compared to VA-ECMO treatment alone (P= 0.017). Study heterogeneity was not remarkable (I²=38.02%). The results remained robust in sensitivity analyses after excluding smaller studies or gray literature.

Conclusion: LV unloading with Impella® in patients with VA-ECMO was associated with improved survival across institutions and might be considered in selected patients with refractory cardiac arrest. ECMELLA use and mortality rates differed between institutions. Further scientific evidence is urgently required to formulate standardized guidelines on LV unloading during ECPR.