Increasing Utilization of Extended Criteria Donor After Brain Death (DBD) Hearts Seldomly Used for Transplantation in the U.S. Due to Limitation of Ischemic Cold Storage - 2-Year Results of the OCS Heart EXPAND Prospective Multi-Center Trial (OCS Heart EXPAND)

Abstract

<h3>Purpose</h3> To evaluate the effectiveness of the OCS Heart perfusion technology to preserve and assess extended criteria DBD hearts that are seldomly transplanted due to limitations of ischemic cold storage. <h3>Methods</h3> OCS Heart EXPAND targeted DBD hearts with one or more of the following risk factors: expected cross clamp time of ≥4 hours; OR expected cross-clamp time of ≥ 2 hours with one or more of the following risk factors: Older donors age 45-55 years with no coronary cath. Or ≥ 55 years old; history of cardiac downtime ≥20 min with stable hemodynamics at time of offer; history of LVH with septal or posterior wall thickness between 13-16 mm; LVEF 40-50%; or history of diabetes, or carbon monoxide poisoning or non-specific angiogram irregularities with no significant CAD. Given the extended criteria nature of the donor hearts that were used in the EXPAND trial, it was not feasible to randomize these donor hearts to cold storage preservation given the associated clinical risks. For benchmarking, clinical outcomes from the OCS Heart EXPAND trial were compared to clinical outcomes of standard criteria heart transplants obtained from UNOS/SRTR database performed at the same EXPAND centers over the same period of trial enrollment. <h3>Endpoints</h3> Patients were followed up-to 2 years post-transplant and compared to the survival data obtained from UNOS for all standard criteria heart transplants from the same transplant centers (Concurrent Controls). <h3>Results</h3> OCS Heart EXPAND and its continued access protocol enrolled a total of 138 extended criteria donor hearts that were perfused and assessed on the OCS Heart System between 2015 and 2020; of those 116/138 were successfully transplant and analyzed for a utilization rate of 84%. Over the same period, there were 1,813 Concurrent Control standard criteria DBD heart transplants. Given that EXPAND trial enrolled extended criteria hearts, there were statistically significant differences in donor risk factors between EXPAND vs Concurrent Controls obtained from UNOS/SRTR (see table below). EXPAND Trial transplanted donor hearts that refused on average 60 times in UNOS match run before being accepted by an EXPAND trial center. The Kaplan-Meier 2-year patient and graft survival results were comparable between the two comparator arms: patient survival – EXPAND OCS 85.3% vs Control standard criteria hearts 87.8% SOC (p=0.8893), graft survival – EXPAND OCS 94.2% vs Control standard criteria hearts 95%.Donor CharacteristicsEXPAND Trial (N=116)Concurrent Controls* (N=1813)p-valueAge (years) – mean ± SD37.1 ± 11.833.5 ± 11.40.0010Age ≥ 55 years12 (10.3%)84 (4.6%)0.0128LV Ejection Fraction58.2 ± 8.461.5 ± 6.5<0.0001LVH >12 ≤ 16 mm22 (19.0%)Not collectedCross-clamp time ≥ 4 hours (Expected)53 (45.7%)268 (14.8%)< 0.0001Cross-clamp time ≥ 4 hours (Actual)113 (97.4%)268 (14.8%)< 0.0001LVEF between 40% - 50%27 (23.3%)93 (5.1%)< 0.0001Downtime ≥ 20 minutes33 (28.4%)69 (3.8%)< 0.0001⁎data from 2015-2022 SRTR heart transplant registry <h3>Conclusion</h3> The use of OCS Heart system resulted in significantly high utilization of extended criteria DBD hearts that are seldomly used for transplants in the U.S. due to limitations of cold storage. The 2-year patient and graft survival outcomes are comparable to standard criteria heart transplant outcomes in the U.S. These results provide prospective clinical evidence that extended criteria DBD donor hearts should be considered to increase transplantation rates.