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Introduction: Impella devices are primarily used for patients with cardiogenic shock or for patients undergoing high-risk percutaneous coronary intervention. They require purge solutions to maintain appropriate function, including to prevent motor failure and prevent blood clots. The manufacturer recommended purge solution is heparin in dextrose 5% water (D5W), however sodium bicarbonate in D5W is becoming a common alternative. There is very limited evidence comparing heparin-based to bicarbonate-based Impella purge solutions. The objective of this study is to compare heparin and bicarbonate purge solutions to assess the risk of Impella-related thrombosis. Methods: This retrospective observational study screened patients between September 14, 2016 and May 21, 2024. The primary outcome was a composite of Impella-related thrombosis by Impella removal, defined by consecutive elevated purge pressures greater than 800 mmHg, use of local thrombolytics, device removed or replaced due to complications, or ischemic stroke within one week after device removal. Secondary outcomes assessed bleeding (drop in hemoglobin > 2 g/dL) and mortality. Results: Among the 88 patients included in the study, there were 30 patients in the bicarbonate group and 58 patients in the heparin group. The primary outcome occurred in 20% vs. 17% of the bicarbonate and heparin group, respectively (p=0.75). The secondary outcomes assessing bleeding (0% vs. 3%, p=0.55) and in-hospital mortality (42% vs. 30%, p=0.30) were also similar between the two groups. Conclusions: Based on data collected, there was no significant increased risk of Impella-related thrombosis when comparing heparin to bicarbonate-based purge solutions. There were no statistically significant differences in rates of bleeding between the two groups, suggesting comparable safety. This trial suggests that bicarbonate-based purge solution may be an acceptable alternative to heparin, but additional studies may be warranted to further confirm these results.