BACKGROUND:Multiple advanced preservation technologies are now available and have demonstrated utility in organ assessment and preservation. The Paragonix SherpaPak Cardiac Transport System (SCTS) has become the most common method of static preservation, demonstrating superior outcomes to historic ice storage. To date, no preservation method has reported improved post-transplant survival. METHODS:Data from the GUARDIAN-Heart Registry, the largest real-world registry focused on organ preservation, were analyzed to quantify post-transplant clinical outcomes and survival in transplant cases utilizing ice cooler storage or moderate hypothermic preservation using SCTS. The independent contributions of the organ preservation method on outcomes, including severe primary graft dysfunction (PGD), right ventricular dysfunction (RVD), and mortality, were analyzed using propensity matching and logistic regression. RESULTS:Among 1,261 US adult heart transplants performed between October 2015 and January 2024, SCTS utilization was associated with significant reductions in incidence of severe PGD (Ice 10.8% vs SCTS 6.8%, p = 0.015) and severe RVD (Ice 9.9% vs SCTS 6.1%, p = 0.022). SCTS use was identified as an independent predictor of severe PGD (Odds Ratio = 0.60, p = 0.012) and severe RVD (OR = 0.75, p = 0.047). In the propensity-matched cohort, SCTS utilization was associated with a significant reduction in mortality after 2 years (Ice 10.5% vs. SCTS 5.7%, p = 0.042), and the Kaplan-Meier survival probability over 2 years was significantly higher in the SCTS cohort (p = 0.022). CONCLUSIONS:Moderate, controlled hypothermic preservation using SCTS significantly improves post-transplant outcomes and 2-year survival. This is the first study of any advanced heart preservation modality to demonstrate a significant impact on transplant survival.

BACKGROUND: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized. METHODS: Data from US adult heart -transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation -Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. RESULTS: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan -Meier terminal probability of 1 -year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD ( p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. CONCLUSIONS: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8 -fold increase in probability of 1 -year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating posttransplant morbidity.

Introduction: Severe mitral regurgitation (MR) secondary to papillary muscle rupture is a life-threatening complication. Surgical intervention is the primary treatment modality. However, percutaneous transcatheter procedures have emerged as an important alternative in high-risk individuals not deemed candidates for surgical interventions. We report a case of cardiogenic shock (CS) following a flail mitral leaflet managed using a double bridge approach.

This study evaluated differences in efficacy and safety outcomes with bivalirudin compared with unfractionated heparin (UFH) in patients with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA ECMO). We performed a retrospective study at an academic medical center that included patients greater than 18 years of age supported with VA ECMO due to cardiogenic shock from January 2009 to February 2021. The primary endpoint was ECMO-associated thrombotic events normalized to duration of ECMO support. Secondary safety endpoints included major bleeding (per ELSO criteria) and blood product administration. Overall, 143 patients were included in our analysis with 54 having received bivalirudin and 89 having received UFH. Median duration of ECMO support was 92 (interquartile range, 56–172) hours. ECMO-associated thrombotic events per ECMO day were significantly less among those that received bivalirudin ( P < 0.001). In adjusted regression, bivalirudin was independently associated with an increased time to thrombosis when compared with UFH (Exp[B] –3.8; 95% confidence interval, 1.7–8.8; P = 0.002). Patients receiving bivalirudin experienced less major bleeding events ( P = 0.02) with less total red blood cell and fresh frozen plasma administration ( P = 0.04 and P = 0.03, respectively). Bivalirudin is a safe and efficacious alternative to UFH in patients requiring VA ECMO for cardiogenic shock.

Traditional ice storage has been the historic standard for preserving donor's hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) (p = 0.03). When propensity matched, SCTS had improving 1-year survival (p = 0.10), significantly lower rates of severe PGD (p = 0.011), and lower overall post-transplant MCS utilization (p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization (p = 0.01), reduced incidence of severe PGD (p = 0.005), and improved 30-day survival (p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD (p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.

OBJECTIVESPoor pain control after cardiac surgery can be associated with postoperative complications, longer recovery, and development of chronic pain. The authors hypothesized that adding liposomal bupivacaine (LB) to plain bupivacaine (PB) will provide better and long-lasting analgesia when used for wound infiltration in median sternotomy.STUDY DESIGNProspective, randomized, and double-blinded clinical trial.SETTINGSingle institution, tertiary care university hospital.PARTICIPANTSAdult patients who underwent elective cardiac surgery through median sternotomy.INTERVENTIONSA single surgeon performed wound infiltration of LB plus PB or PB into the sternotomy wound, chest, and mediastinal tube sites.MEASUREMENTS AND MAIN RESULTSPatients were followed up for 72 hours for pain scores, opioid consumption, and adverse events. Sixty patients completed the study for analysis (LB group [n = 29], PB group [n = 31]). Patient characteristics, procedural variables, and pain scores measured at specific intervals from 4 hours until 72 hours postoperatively did not reveal any significant differences between the groups. Mixed-model regression showed that the trend of mean pain scores at movement in the LB group was significantly (p = 0.01) lower compared with the PB group. Opioid consumption over 72 hours was not significantly different between the 2 groups (oral morphine equivalents; median [interquartile range], 139 [73, 212] mg in LB v 105 [54, 188] mg in PB, p = 0.29). Recovery characteristics and adverse events were comparable.CONCLUSIONSLB added to PB for sternotomy wound infiltration during elective cardiac surgery did not significantly improve the quality of postoperative analgesia.

Purpose The Paragonix SherpaPak Cardiac Transport System (CTS) is a controlled hypothermic organ preservation technology which maintains donor heart temperatures between 4°C - 8°C. Available for clinical use since 2018, CTS has been implemented into centers' procurement regimen to achieve various goals. A subgroup analysis of real-world data collected in the GUARDIAN Heart registry was performed to evaluate outcomes at centers whose primary goal was to reduce post-transplant rates of severe primary graft dysfunction (PGD), or those centers who wished to safely grow a program without sacrificing existing post-transplant outcomes. Methods Between October 2015-August 2022, 761 adults from 9 US centers receiving donor hearts utilizing either CTS (N=419) or conventional ice storage (ICE, N=342) were analyzed from the GUARDIAN Heart registry. Centers were further delineated by those with baseline PGD rates >15% (Group A, 6 centers), and those with an already low PGD rate (∼ <10%) but seeking to grow their program by expanding donor access (Group B, 3 centers). Summary statistics were used for comparisons. Results In Group A (n=265 CTS, n=199 ICE), although there were few baseline differences including longer total ischemic time in the CTS cohort, post-transplant rate of PGD compared to ICE was reduced by 26% (p=0.065) and severe PGD was significantly reduced by 40% (p=0.046). In Group B (n=154 CTS, n=143 ICE), recipient age was significantly older in the CTS cohort, total ischemic time increased by 23% (43 minutes, p<0.001) compared to ICE, and total distance traveled to organ retrieval doubled (p<0.001). The rate of post-transplant use of MCS, however, decreased (17.5% v 9.7%, p=0.05) while severe PGD incidence remained stable (5.6% v 4.5%, p=0.68) for ICE and CTS. Conclusion This subgroup analysis of the GUARDIAN Heart Registry demonstrates that the SherpaPak CTS can be used to improve post-transplant outcomes as well as to safely extend acquisition of donor organs to greater distances without sacrificing recipient outcomes.

Purpose The decades long gold standard for preservation of donor hearts in ice appears to be rapidly shifting to advanced hypothermic preservation. At the time of this abstract, over 25% of donor hearts in the US in 2022 have been transported in a Paragonix SherpaPak Cardiac Transport System (CTS). This controlled hypothermic technology in clinical use since 2018 preserving organ temperatures between 4 - 8°C. Real-world evidence on the clinical benefits of using CTS compared to conventional ice storage (ICE) is evaluated in the GUARDIAN Heart Registry to assess whether improved outcomes are achieved with this technology. Methods Data from 877 adults at 16 US centers receiving donor hearts preserved and transported in either CTS (n=487) or ICE (n=390) between October 2015-August 2022 were analyzed in the GUARDIAN-Heart registry. Propensity matching was performed to balance baseline differences to further evaluate outcomes between cohorts (see Table). Summary statistics were used for comparisons. Results The CTS cohort demonstrated reduced severe primary graft dysfunction (PGD) compared to ICE in the unmatched cohort (p=0.08) (Table). When propensity matched, CTS had significantly lowered severe PGD by 60% (10.0% vs 4.0%, p=0.01). Survival was similar (Figure). Further analysis with ongoing enrollment through December 2022 will be available for presentation. Conclusion Utilization of the Paragonix CTS for organ preservation is associated with lower rates of severe PGD. This finding continues to fundamentally challenge the decades-long status quo of using ice for transporting donor hearts.

Before the 33rd Annual International Society for Heart and Lung Transplantation conference, there was significant intercenter variability in definitions of primary graft dysfunction (PGD). The incidence, risk factors, and outcomes of consensus-defined PGD warrant further investigation. We retrospectively examined 448 adult cardiac transplant recipients at our institution from 2005 to 2017. Patient and procedural characteristics were compared between PGD cases and controls. Multivariable logistic regression was used to model PGD and immediate postoperative high-inotrope requirement for hypothesized risk factors. Patients were followed for a mean 5.3 years to determine longitudinal mortality. The incidence of PGD was 16.5%. No significant differences were found with respect to age, sex, race, body mass index, predicted heart mass mismatch, pretransplant amiodarone therapy, or pretransplant mechanical circulatory support (MCS) between recipients with PGD versus no PGD. Each 10 minute increase in ischemic time was associated with 5% greater odds of PGD (OR = 1.05 [95% CI, 1.00–1.10]; p = 0.049). Pretransplant MCS, predicted heart mass mismatch ≥30%, and pretransplant amiodarone therapy were associated with high-immediate postoperative inotropic requirement. The 30 day, 1 year, and 5 year mortality for patients with PGD were 28.4%, 38.0%, and 45.8%, respectively, compared with 1.9%, 7.1%, and 21.5% for those without PGD (log-rank, p < 0.0001). PGD heralded high 30 day, 1 year, and 5 year mortality. Pretransplant MCS, predicted heart mass mismatch, and amiodarone exposure were associated with high-inotrope requirement, while prolonged ischemic time and multiple perioperative transfusions were associated with consensus-defined PGD, which may have important clinical implications under the revised United Network for Organ Sharing allocation system.

Background: Heart transplantation is the gold-standard treatment for end-stage heart failure; however, the waitlist exceeds the number of donor organs available. Currently, it remains difficult to obtain an assessment of organ viability for transplant in many donor circumstances. We have developed a system that can allow for assessment of organ viability and potentially expand the donor pool. Our device features normothermic perfusion in both Langendorff and “working heart” mode. The device will allow for ex vivo assessment of the heart in Langendorff, left heart, right heart, and physiologic perfusion. A prototype has been constructed and perfusion experiments initiated. The current focus is experimental methods to allow for extended perfusion. Methods: A brief series of Langendorff perfusion experiments were performed. Hearts were procured from research animals shortly after euthanasia. The hearts were given 500 mL of del Nido cardioplegia at an aortic root pressure of 200 mmHg. The hearts were transported from the OR to the laboratory and connected to the circuit which consisted of an integrated perfusion chamber/reservoir, a PediMag (Abbott) pump, and a Eurosets (Abbott) oxygenator. Whole blood from the donor animal was used as the perfusate with physiological correction guided by blood chemistries. The hearts were perfused at a predetermined aortic root pressure for 4 hours or until the heart lost viability. Results: Initial attempts resulted in significant myocardial edema resulting in loss of cardiac function. Recent attempts have successfully supported the heart for up to 2 hours. From the experiments, it is clear that additional iterations are necessary focusing on mitigating ischemia/reperfusion injury in prolonged warm perfusion models to allow for better assessment of cardiac function and viability prior to the initiation of “working heart” perfusion. Conclusion: The University of Pittsburgh Ex Vivo Perfusion Device is in development and having early successes. The device can successfully support a heart in Langendorff perfusion mode and is being developed to further advance in “full working heart” mode. Acknowledgements: The authors would like to acknowledge funding provided by the University of Pittsburgh Center for Medical Innovation, award F_275-2019, “Ex-Vivo Heart Perfusion System for Human Heart Support, Resuscitation, and Physiologic Testing.”

OBJECTIVES:. We aimed to investigate whether there are differences in outcome for pediatric patients when extracorporeal life support (ECLS) is initiated on-hours compared with off-hours. DESIGN:. Retrospective cohort study. SETTING:. Ten-year period (2009–2018) in United States centers, from the Extracorporeal Life Support Organization registry. PATIENTS:. Pediatric (>30 d and <18 yr old) patients undergoing venovenous and venoarterial ECLS. INTERVENTIONS:. The primary predictor was on versus off-hours cannulation. On-hours were defined as 0700–1859 from Monday to Friday. Off-hours were defined as 1900–0659 from Monday to Thursday or 1900 Friday to 0659 Monday or any time during a United States national holiday. The primary outcome was inhospital mortality. The secondary outcomes were complications related to ECLS and length of hospital stay. MEASUREMENTS AND MAIN RESULTS:. In a cohort of 9,400 patients, 4,331 (46.1%) were cannulated on-hours and 5,069 (53.9%) off-hours. In the off-hours group, 2,220/5,069 patients died (44.0%) versus 1,894/4,331 (44.1%) in the on-hours group (p = 0.93). Hemorrhagic complications were lower in the off-hours group versus the on-hours group (hemorrhagic 18.4% vs 21.0%; p = 0.002). After adjusting for patient complexity and other confounders, there were no differences between the groups in mortality (odds ratio [OR], 0.95; 95% CI, 0.85–1.07; p = 0.41) or any complications (OR, 1.02; 95% CI, 0.89–1.17; p = 0.75). CONCLUSIONS:. Survival and complication rates are similar for pediatric patients when ECLS is initiated on-hours compared with off-hours. This finding suggests that, in aggregate, the current pediatric ECLS infrastructure in the United States provides adequate capabilities for the initiation of ECLS across all hours of the day.

OBJECTIVES: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective cohort study. SETTING: Single-center, cardiothoracic ICU. PATIENTS: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. INTERNVENTIONS: IV bivalirudin or IV unfractionated heparin. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. CONCLUSIONS: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.

Purpose There has been an emphasis on treating cardiogenic shock (CS) with early mechanical circulatory support (MCS). Yet, algorithmic approaches for the use of specific MCS devices is institutionally dependent. We evaluated the impact of early, upfront Impella 5.0 vs. an alternative MCS device prior to Impella 5.0. Methods Retrospective analysis was performed on 28 consecutive patients at a single center between Jan. '19 - Aug. '20 implanted with Impella 5.0. Patients were separated into those receiving upfront Impella 5.0 and those that had a different MCS device prior to Impella 5.0. Clinical outcomes and hemodynamic data were collected at various time points. Results 16 patients (57%) with a mean age of 60 ± 10.2 years received upfront Impella 5.0, while 12 (43%) with a mean age of 58 ± 12.6 years received an alternative MCS device first (6 IABP, 6 Impella CP). Etiologies of CS in the upfront Impella 5.0 group were decompensated heart failure (HF) in 15 patients (94%) and MI in 1 patient (6%), and in the prior MCS group were decompensated HF in 5 patients (42%) and MI in 7 patients (58%). The mean duration of either IABP or Impella CP use before Impella 5.0 was 0.83 days. The upfront Impella 5.0 cohort had a trend towards higher initial filling pressures shown by elevated RAP, mPAP, PCWP, and reduced CI and CPO prior to implantation. Greater improvements were also seen in each of these variables at 72 hours compared to the alternative MCS group (Figure 1). Complications rates were higher in the alternative MCS group with significant hemolysis in the Impella CP arm with an average plasma free hemoglobin of 324 ± 268 mg/dL, and 1 major vascular complication requiring surgical intervention; and 1 ischemic stroke. Survival in the upfront Impella 5.0 group was 87% and only 56% in the alternative MCS group. Conclusion Early use of Impella 5.0 provides more hemodynamic support and may reduce complications and improve outcomes. It should be considered as initial strategy, when feasible, in patients with CS that require use of MCS.

We report a case of acute right ventricular failure in a patient with cardiogenic shock on left-sided mechanical circulatory support with Impella 5.0. The patient was successfully bridged to heart transplantation using additional right-sided support with Protek Duo. Key learning points of the case include prompt recognition of acute right ventricular failure in patients on left-sided support, early consideration of right-ventricular mechanical support platforms, and timely deployment of right-sided mechanical support.

BACKGROUND:Psychosocial evaluations are required for long-term mechanical circulatory support (MCS) candidates, no matter whether MCS will be destination therapy (DT) or a bridge to heart transplantation. Although guidelines specify psychosocial contraindications to MCS, there is no comprehensive examination of which psychosocial evaluation domains are most prognostic for clinical outcomes. We evaluated whether overall psychosocial risk, determined across all psychosocial domains, predicted outcomes, and which specific domains appeared responsible for any effects.METHODS:A single-site retrospective analysis was performed for adults receiving MCS between April 2004 and December 2017. Using an established rating system, we coded psychosocial evaluations to identify patients at low, moderate, or high overall risk. We similarly determined risk within each of 10 individual psychosocial domains. Multivariable analyses evaluated whether psychosocial risk predicted clinical decisions about MCS use (DT versus bridge), and postimplantation mortality, transplantation, rehospitalization, MCS pump exchange, and standardly defined adverse medical events (AEs).RESULTS:In 241 MCS recipients, greater overall psychosocial risk increased the likelihood of a DT decision (odds ratio, 1.76; P = 0.017); and postimplantation pump exchange and occurrence of AEs (hazard ratios [HRs] ≥ 1.25; P ≤ 0.042). The individual AEs most strongly predicted were cardiac arrhythmias and device malfunctions (HRs ≥ 1.39; P ≤ 0.032). The specific psychosocial domains predicting at least 1 study outcome were mental health problem severity, poorer medical adherence, and substance use (odds ratios and HRs ≥ 1.32; P ≤ 0.010).CONCLUSIONS:The psychosocial evaluation predicts not only clinical decisions about MCS use (DT versus bridge) but important postimplantation outcomes. Strategies to address psychosocial risk factors before or soon after implantation may help to reduce postimplantation clinical risks.

BackgroundStudies examining one‐year mortality respecting component blood transfusion are sparse. We hypothesize that component blood product transfusions are negatively associated with 90‐day and 1‐year survival for all patients requiring veno‐arterial (VA) or veno‐venous (VV) ECMO.Study Design and MethodsThis was an IRB‐approved retrospective cohort analysis of 676 consecutive patients requiring ECMO at the University of Pittsburgh between 2005 and 2016. Patients were analysed both as an entire cohort and as two subsets with respect to ECMO modality (VA vs. VV). Additional data collected and analysed included patient characteristics, laboratory values and blood product transfusion.ResultsMultivariable analysis revealed that platelet transfusion was associated with 90‐day mortality (OR: 1·05, P = 0·037) and one‐year mortality for the entire cohort (OR = 1·05, P = 0·046,). Platelet transfusion volume was also associated with mortality in the VA‐ECMO subset of patients at both 90 days (OR = 1·08, P = 0·03) and one year (OR: 1·11, P = 0·014). Age, peak International Normalized Raton ECMO, nadir haemoglobin (on ECMO) and final haemoglobin (after ECMO) were significantly associated with mortality for patients requiring VA‐ECMO. For VV‐ECMO patients, age, INR and peak creatinine on ECMO were associated with mortality. No individual component blood product was associated with one‐year mortality for patients requiring VV‐ECMO.ConclusionPlatelet transfusion was associated with increased 90‐day and 1‐year mortality for patients requiring VA‐ECMO.