Comparison of MIRACLE2 and downtime as predictors of outcome following out-of-hospital cardiac arrest and evidence for the potential of MIRACLE2 as a selection tool for mechanical circulatory support

Abstract Background Out-of-hospital cardiac arrest (OOHCA) is associated with high morbidity and mortality, driven primarily by poor neurological outcome. Appropriate application of invasive therapies, such as mechanical circulatory support (MCS), currently poses significant challenges. To guide patient selection, effective estimation of patients at high risk of neurological injury, particularly early on arrival to a heart attack centre, is essential. Purpose We compared the discrimination performance of MIRACLE2 score with downtime, and its components, low-flow and zero flow, as predictors of poor neurological outcome following OOHCA. Furthermore, we modelled the use of MIRACLE2 score as a selection criterion for MCS. Methods The European Cardiac Arrest Registry (EUCAR), a retrospective cohort of patients with OOHCA with likely cardiac aetiology, from 6 European centres (May 2012-September 2022), was utilised. The primary end point was poor neurological outcome on hospital discharge (Cerebral Performance Category 3-5). Results 1259 patient were included at the point of analysis. The median downtime was 25 minutes (IQR 15-36), with an average age of 62.9 ± 14.5 years. Baseline demographics (age, gender, co-morbidities) were similar across groups. In patients with a total downtime of <10 minutes and MIRACLE2 score >4, poor outcome occurred in 76.5%, whilst those with a downtime >30 minutes and MIRACLE2 score 0-2 had poor outcome in 24.0%. In a multivariable logistic regression analysis, MIRACLE2 had a stronger association with poor neurological outcome (OR 2.06 [CI 1.83–2.33], p<0.0001) than zero-flow (OR 1.08 [CI 1.03–1.14], p=0.005), low-flow (OR 1.04 [CI 1.00–1.00], p=0.004) and total downtime (OR 0.99 [CI 0.95–1.03]. MIRACLE2 had superior discrimination for poor neurological outcome with AUC of 0.870 (95% CI 0.846 to 0.891) than zero-flow [AUC of 0.616 (95% CI 0.583-0.648)], low-flow [AUC of 0.716 (95% CI 0.685-0.745)] and downtime [AUC of 0.726 (95% CI 0.695-0.754)]. When modelled for inclusion into landmark cardiogenic shock RCTs, based on study criteria (which all incorporate downtime, zero-flow or low-flow times), those modelled for exclusion from study recruitment, the positive predictive value of MIRACLE2 ≥5 for poor outcome was significantly higher (0.91) than CULPRIT-SHOCK (0.62), EUROSHOCK (0.53) and ECLS-SHOCK criteria (0.80) (p<0.001). Discussion: MIRACLE2 demonstrates superiority over downtime in predicting neurological outcome following out-of-hospital cardiac arrest in this large, multicentre, retrospective cohort study and has potential to improve patient selection for mechanical circulatory support in future cardiogenic shock trials.MIRACLE2 vs Downtime