Extracorporeal Membrane Oxygenation for Early Graft Dysfunction Following Heart Transplantation: A Systematic Review and Meta-Analysis
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Background: Early graft dysfunction (EGD) is a major cause of early morbidity and mortality following heart transplantation (HT). The management of severe EGD often includes the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Studies evaluating the effectiveness of VA-ECMO are primarily retrospective single centre studies with variable results.
Objectives: The objectives of this systematic review and individual patient data (IPD) meta-analysis are to appraise the available evidence to: 1) evaluate overall prognosis (30-day mortality, in-hospital mortality, 1-year mortality), 2) characterize rates of other major VA-ECMO complications, 3) identify factors associated with prognosis (in-hospital mortality, 1-year mortality) and 4) compare the effect of different ways of delivering VA-ECMO (e.g., peripheral vs. central cannulation, early intraoperative vs. delayed postoperative cannulation) on outcomes in adult HT recipients who developed severe EGD and received VA-ECMO
Search methods: We searched Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Clinical Trials from January 1, 2009 to May 15, 2020. We included randomized and non-randomized studies published in any language, as abstracts or full texts that included adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint.
Data collection and analysis: We assessed risk of bias using QUIPS for objectives 1-3 and ROBINS-I for objective 4. One reviewer completed data extraction and a second reviewer verified. Authors of each identified study from the systematic review received invitations to participate in the IPD meta-analysis. We pooled study level data for 30-day mortality, in-hospital mortality, 1-year mortality and VA-ECMO complications using random-effects models with the metaprop command on STATA (StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC.). To identify prognostic factors, we analysed IPD using a mixed effects logistic regression with a random effects term for each IPD study. We calculated summary risk ratios using random effect models for the effect of the following interventions on survival to hospital discharge: central vs. peripheral cannulation, intraoperative (early) vs. postoperative (delayed) cannulation, LV unloading vs. no LV unloading, nitric oxide vs. no nitric oxide while on VA-ECMO support. We assessed the certainty in the evidence using the GRADE framework.
Results: We included 49 observational studies of 1,477 patients of which 15 studies of 448 patients provided IPD. In addressing prognosis using QUIPS, most studies (79%) proved at low or acceptable overall risk of bias. There were no important differences in short-term or 1-year mortality estimates between IPD and non-IPD studies. We are moderately certain in the short-term mortality estimate of 33% (95%CI: 27%, 39%) and 1-year mortality estimate of 50% (95%CI: 43%, 57%). With moderate certainty, estimates of bleeding and sepsis/infection while on VA-ECMO support were 38% (95%CI: 28%, 48%) and 21% (95%CI: 14%, 28%) respectively. Three factors were associated with increased short-term mortality with high certainty: recipient age (OR 1.02, 95% CI: 1.01-1.04), donor age (OR 1.01, 95% CI 1.00-1.03) and prior sternotomy (OR 1.57, 95%CI 0.99-2.49). Lastly, there is very low certainty evidence that VA-ECMO strategies of early intraoperative cannulation and peripheral cannulation reduce the risk of in-hospital mortality.
Conclusions: One third of patients who receive VA-ECMO for EGD do not survive to hospital discharge, and nearly half do not survive to 1 year after HT. Improving outcomes in this patient population will require careful consideration of recipient factors such as age and prior sternotomy and further research on optimal VA-ECMO strategies.
