Impact of controlled hypothermic preservation on outcomes following heart transplantation.

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 post-transplant morbidity.

A Paradigm Shift in Heart Preservation: Improved Post-transplant Outcomes in Recipients of Donor Hearts Preserved With the SherpaPak System.

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.

Sternotomy Wound Infiltration With Liposomal Versus Plain Bupivacaine for Postoperative Analgesia After Elective Cardiac Surgery.

OBJECTIVES: Poor 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 DESIGN: Prospective, randomized, and double-blinded clinical trial. SETTING: Single institution, tertiary care university hospital. PARTICIPANTS: Adult patients who underwent elective cardiac surgery through median sternotomy. INTERVENTIONS: A single surgeon performed wound infiltration of LB plus PB or PB into the sternotomy wound, chest, and mediastinal tube sites. MEASUREMENTS AND MAIN RESULTS: Patients 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. CONCLUSIONS: LB added to PB for sternotomy wound infiltration during elective cardiac surgery did not significantly improve the quality of postoperative analgesia.

On-Hours Compared to Off-Hours Pediatric Extracorporeal Life Support Initiation in the United States Between 2009 and 2018-An Analysis of the Extracorporeal Life Support Organization Registry.

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.

Charlson Comorbidity Index is Associated With Longer-Term Mortality and Re-Admissions Following Coronary Artery Bypass Grafting.

INTRODUCTION: The Charlson Comorbidity Index (CCI) is widely utilized for risk stratification by providers, payors, and administrative database researchers for non-cardiac surgical patients. CCI scores have not been validated in cardiac surgical patients. We hypothesize that the CCI will predict mid-term mortality and re-admissions, but performance may be different than purpose-built cardiac surgery risk calculators. METHODS: Patients undergoing isolated CABG between 2011 and 2017 were reviewed. Age-adjusted CCI scores were calculated based on clinical status at a time of index operation using prospectively captured data from institutional databases. Primary endpoint was 5-year mortality and 1-year re-admissions. The CCI, STS predicted mortality, and ASCERT 5-year mortality scores were compared in a sub-cohort of 500 patients. Patients underwent analysis using Cox Proportional Hazard ratios, Kaplan-Meier analysis, and ROC comparisons. RESULTS: Average CCI score for the overall population (n = 6064) was 3.40 ± 1.75. Kaplan-Meier analysis revealed significant difference in mortality stratified by CCI. Hazard ratio for 5-year mortality increased with each interval increase in CCI score value (HR 1.38 [1.33-1.43], P < 0.001), as did the risk of 1-year re-admission (HR 1.19 [1.15-1.22], P < 0.001). ROC curves for CCI, STS mortality, and ASCERT 5-year mortality risk demonstrate that all three scores are predictive at 5 y, but the ASCERT score performs best (ROC 0.76 versus 0.69, P = 0.004). CONCLUSIONS: The CCI can serve as a useful mid-term risk stratification tool in patients undergoing CABG when variables for the purpose-built STS and ASCERT scores are unavailable. However, the ASCERT score performs better at 5-year mortality calculation.

Primary Graft Dysfunction in Heart Transplant Recipients-Risk Factors and Longitudinal Outcomes.

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.

Acute right ventricular failure in a patient with nonischemic cardiogenic shock on left-sided mechanical circulatory support.

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.

Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates.

BACKGROUND: Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis. METHODS: One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2 g/kg after carfilzomib on day 16. Patients underwent repeat cycles as indicated. We compare calculated panel-reactive antibody (cPRA) for neat combined Class I and II IgG and C1q pre- and post-treatment using a cutoff for cPRA entry of ≥ 4000 and 500 MFI, respectively. RESULTS: From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving. CONCLUSIONS: A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding, facilitates successful transplantation, and is associated with excellent outcomes at 3 years.

Impact of Pre-Existing Mitral Regurgitation Following Left Ventricular Assist Device Implant.

OBJECTIVES: Optimal management of significant mitral regurgitation (SMR) during left ventricular assist device (LVAD) placement remains uncertain. This study evaluates the effect of untreated preop SMR on outcomes following LVAD implant. METHODS: Adults undergoing primary LVAD placement from April 2004 to May 2017 were included. Most recent preop transthoracic echocardiogram (TTE) was used to divide patients into an SMR group with moderate or greater regurgitation, and a group without SMR. Patients underwent LVAD implant without correction of SMR. Primary endpoint was 3-year postoperative survival, with secondary endpoints of length of stay (LOS), resolution of SMR following LVAD on postdischarge (30 day) TTE, and 1-year TTE. RESULTS: LVAD placement was performed in 270 patients, 172 (63.7%) without SMR and 98 (36.3%) with SMR. There were no differences in comorbidities including diabetes, hypertension, and renal disease. Preop ejection fraction was similar, but a higher pulmonary vascular resistance was recorded in the SMR group (3.6 vs 3.0 Wood Units, P = 0.048). There was no difference in 3-year mortality between the 2 cohorts (log-rank P = 0.0.803). The SMR group had decreased LOS (median 19.5 vs 22 days, P = 0.009). Of the 98 SMR patients, 91 (92.9%) had resolution of SMR to less than moderate at 30 days. At 1 year, 15% of those with preoperative SMR had recurrent SMR. CONCLUSIONS: Patients undergoing LVAD placement with preop SMR experience no differences in mortality, and a majority experience resolution of MR after implant. Longer-term SMR recurrence and need for mitral intervention with LVAD implant warrant further investigation.

The Preimplantation Psychosocial Evaluation and Prediction of Clinical Outcomes During Mechanical Circulatory Support: What Information Is Most Prognostic?

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.

Evaluation of a Health Care Performance Improvement Initiative to Facilitate Optimal Clinical Outcomes in Patients Receiving Ventricular Assist Device Support.

BACKGROUND: Ventricular assist device (VAD) patients are at high risk for morbidities and mortality. One potentially beneficial component of the Joint Commission VAD Certification process is the requirement that individual VAD programs select 4 performance measures to improve and optimize patients' clinical outcomes. PROBLEM STATEMENT: Review of patient data after our program's first certification visit in 2008 showed that, compared to national recommendations and published reports, our patients had suboptimal outcomes in 4 areas after device implantation: length of hospital stay, receipt of early (<48 hours) postsurgical physical therapy, driveline infection incidence, and adequacy of nutritional status (prealbumin ≥18 mg/dL). METHODS: Plan-Do-Study-Act processes were implemented to shorten length of stay, increase patient receipt of early physical therapy, decrease driveline infection incidence, and improve nutritional status. With 2008 as our baseline, we deployed interventions for each outcome area across 2009 to 2017. Performance improvement activities included staff, patient, and family didactic, one-on-one, and hands-on education; procedural changes; and outcomes monitoring with feedback to staff on progress. Descriptive and inferential statistics were examined to document change in the outcomes. OUTCOMES: Across the performance improvement period, length of stay decreased from 40 to 23 days; physical therapy consults increased from 87% to 100% of patients; 1-year driveline infection incidence went from 38% to 23.5%; and the percentage of patients with prealbumin within the normal range increased from 84% to 90%. IMPLICATIONS: Performance improvement interventions may enhance ventricular assist device patient outcomes. Interventions' sustainability should be evaluated to ensure that gains are not lost over time.

Outcomes of left ventricular assist device implantation in hypercoagulable patients.

BACKGROUND: The aim of this study was to evaluate outcomes of left ventricular assist devices (LVADs) in patients who tested positive for hypercoagulable hematologic disorders. METHODS: Adults undergoing continuous-flow LVAD implantation with preoperative hypercoagulability testing between 2004 and 2018 at a single center were reviewed. Hypercoagulability was defined as testing positive for antiphospholipid antibody, anticardiolipin antibody, lupus anticoagulant, protein C, protein S, factor V Leiden, and/or heparin-induced thrombocytopenia. The primary outcome was survival on the original LVAD. Secondary outcomes included rates of thromboembolic complications and readmission for intravenous heparin treatment. RESULTS: A total of 270 LVAD patients with pre-implant hypercoagulability testing were included, and 157 (58%) tested positive for a hypercoagulable disorder. Of those testing positive, 10 (6.4%) had a clinical pre-LVAD history of thromboembolic events. Survival was comparable between hypercoagulable and non-hypercoagulable patients (1 year: 73.3% vs 78.9%, P = .2195, 2-year: 60.7% vs 62.8%, P = .3627). Rates of pump thrombosis (14.0% vs 13.3%, P = .8618), hemolysis (4.5% vs 3.5%, P = .3536), stroke (18.5% vs 14.2%, P = .3483) and readmission for IV heparin therapy (87.3% (n = 137) vs 77.9% (n = 88), P = .7560) were similar. Outcomes were comparable in patients with positive hypercoagulable tests when stratified by pre-implant clinical history of hypercoagulability as well as stratified by recent preoperative exposure to heparin or warfarin. CONCLUSIONS: In this series, positive laboratory tests for hypercoagulability were common amongst patients undergoing LVAD implantation although few had positive clinical histories. Survival and freedom from thromboembolic complications were comparable to non-hypercoagulable patients. Hypercoagulability alone should therefore not serve as a contraindication to LVAD implantation.

Comparison of Hydromorphone versus Fentanyl-based Sedation in Extracorporeal Membrane Oxygenation: A Propensity-Matched Analysis.

INTRODUCTION: Data comparing sedatives in patients receiving extracorporeal membrane oxygenation (ECMO) are sparse. However, it is known that the ECMO circuit alters the pharmacokinetic properties of medications via drug sequestration of lipophilic agents and increased volume of distribution. OBJECTIVES: This study evaluated the difference in days alive without delirium or coma and the sedative requirements in patients receiving fentanyl versus hydromorphone in ECMO patients. METHODS: This single-center retrospective observational study evaluated adults receiving ECMO for more than 48 hours and continuous infusion of either fentanyl or hydromorphone for at least 6 hours. Of 148 patients evaluated, 88 received fentanyl and 60 received hydromorphone continuous infusion sedation. Outcomes included delirium-free and coma-free (DFCF) days, narcotic use, and sedative use. MAIN RESULTS: There was an increase in the number of DFCF days in the hydromorphone group at day 7 (p=0.07) and day 14 (p=0.08) and a significant reduction in daily fentanyl equivalent exposure. Propensity score matching yielded 54 matched pairs. An 11.1% increase was observed in the proportion of ECMO days alive without delirium or coma in the hydromorphone group at 7 days (53.2% vs 42.1%, p=0.006). Patients in the hydromorphone group received significantly fewer narcotics with a median of 555 µg (interquartile range [IQR] 287-905 µg) of fentanyl equivalents per day compared with 2291 µg (IQR 1053-4023 µg) in the fentanyl group (p<0.005). CONCLUSION: The use of hydromorphone-based sedation in ECMO patients resulted in more days alive without delirium or coma while significantly reducing narcotic requirements.

Belatacept for maintenance immunosuppression in cardiothoracic transplantation: The potential frontier.

Current immunosuppressive regimens with calcineurin inhibitors have improved the management of patients after transplantation. However, their adverse effects are linked to increased morbidity and limit the long-term survival of heart and lung transplant recipients. Belatacept, a costimulation inhibitor interfering with the interaction between CD28 on T cells and the B7 ligands on antigen presenting cells, has shown success and is currently approved for use in renal transplant recipients. Furthermore, it lacks many of the cardiovascular, metabolic, neurologic, and renal adverse of effects of calcineurin inhibitors that have the largest impact on long-term survival in cardiothoracic transplant. Additionally, it requires no therapeutic drug monitoring and is only administered once a month. Limitations to belatacept use have been observed that must be considered when comparing immunosuppression options. Despite this, maintenance immunosuppression with belatacept has the potential to improve outcomes in cardiothoracic transplant recipients, as it has with kidney transplant recipients. However, no large clinical trials investigating belatacept for maintenance immunosuppression in heart and lung transplant recipients exist. There is a large need for focused research of belatacept in cardiothoracic transplantation. Belatacept is a viable treatment option for maintenance immunosuppression, and it is reasonable to pursue more evidence in cardiothoracic transplant recipients.

Predictors of intra-aortic balloon pump hemodynamic failure in non-acute myocardial infarction cardiogenic shock.

OBJECTIVES: To characterize patient profile and hemodynamic profile of those undergoing intra-aortic balloon pump (IABP) for cardiogenic shock and define predictors of hemodynamic failure of IABP support. BACKGROUND: Clinical characteristics of IABP support in cardiogenic shock not related to acute myocardial infarction (AMI) remain poorly characterized. METHODS: We retrospectively studied a cohort of 74 patients from 2010 to 2015 who underwent IABP insertion for cardiogenic shock complicating acute decompensated heart failure not due to AMI. RESULTS: In the overall cohort, which consisted primarily of patients with chronic systolic heart failure (89%), IABP significantly augmented cardiac index and lowered systemic vascular resistance (P<.05). Despite this improvement, 28% of these patients died (24%) or require urgent escalation in mechanical circulatory support (MCS) (4%). Multivariable regression revealed that baseline left ventricular cardiac power index (LVCPI), a measure of LV power output derived from cardiac index and mean arterial pressure (P=.01), and history of ischemic cardiomyopathy (P=.003) were significantly associated with the composite adverse-event endpoint of death or urgent MCS escalation. An IABP Failure risk score using baseline LVCPI <0.28 W/m2 and ischemic history predicted 28-day adverse events with excellent discrimination. CONCLUSION: Despite hemodynamic improvements with IABP support, patients with non-AMI cardiogenic shock still suffer poor outcomes. Patients with ischemic cardiomyopathy and low LVPCI fared significantly worse. These patients may warrant closer observation or earlier consideration of more advanced hemodynamic support.

A Comprehensive Risk Score to Predict Prolonged Hospital Length of Stay After Heart Transplantation.

BACKGROUND: Prolonged hospital length of stay (PLOS) after heart transplantation increases cost and morbidity. To better inform care, we developed a risk score to identify patients at risk for PLOS after heart transplantation. METHODS: We queried the United Network for Organ Sharing Scientific Registry of Transplant Recipients database for adult patients who underwent isolated heart transplantation from 2003 to 2012. The population was randomly divided into a derivation cohort (80%) and a validation cohort (20%). The outcome of interest was PLOS, defined as a posttransplant hospital length of stay of more than 30 days. Associated univariables (p < 0.20) in the derivation cohort were included in a multivariable model, and a risk index was derived from the adjusted odds ratios of significant covariates. RESULTS: During the study period, 16,723 patients underwent heart transplantation with an average PLOS of 19 ± 21 days, and 2,020 orthotopic heart transplant recipients (12%) had PLOS. Baseline characteristics were similar between the derivation and validation cohorts. Twenty-four recipient and nine donor variables, cold ischemic time, and center volume were tested as univariables. Seventeen covariates significantly affected PLOS and comprised the prolonged hospitalization after heart transplant risk score, which was stratified into three risk groups. The risk model was subsequently validated, and predicted rates of PLOS correlated well with observed rates (R = 0.79). Rates of PLOS in the validation cohort were 8.3%, 11%, and 22% for low, moderate, and high risk groups, respectively. CONCLUSIONS: The risk of PLOS after heart transplantation can be determined at the time of transplant. The prolonged hospitalization after heart transplant score may lead to individualized postoperative management strategies to reduce duration of hospitalization for patients at high risk.

The Paradoxical Relationship Between Donor Distance and Survival After Heart Transplantation.

BACKGROUND: Concerns over prolonged allograft ischemia have limited the widespread adoption of long-distance organ procurement in heart transplantation (HT). We sought to assess whether donor distance from the center of transplantation independently affects mortality. METHODS: We queried the United Network for Organ Sharing (UNOS) database for adults undergoing isolated HT from 2005 to 2012. Risk-adjusted Cox proportional hazards models were constructed for the primary outcomes of 30-day and 1-year mortality, and the independent impact of donor distance from transplantation center at the time of procurement was assessed. RESULTS: We included 14,588 heart transplant recipients. The mean distance from location of the donor heart to transplantation center was 184.4 ± 214.6 miles; 1,214 HTs (8.3%) occurred at the same location as the donor heart. Ischemic times were inversely related to the distance from the site of donor procurement to recipient transplantation. After risk adjustment, longer donor distances (in miles) were associated with a significantly lower risk of mortality at both 30 days (hazard ratio [HR] 0.9993, 95% confidence interval [CI]: 0.9988 to 0.9998, p < 0.01) and 1 year (HR 0.9994, 95% CI: 0.9989 to 0.9999, p = 0.015). Risk-adjusted hazards for mortality were significantly reduced in recipients receiving hearts from more than 25 miles away. The hazard reduction was greatest in recipients receiving donor hearts from more than 500 miles away (1-year HR 0.64, p < 0.01; 30-day HR 0.47, p < 0.01). CONCLUSIONS: Longer distances between donor location and center of heart transplantation are associated with a reduced hazard for survival at 30 days and 1 year, despite greater ischemic times. Future studies are necessary to elucidate the protective factors surrounding long-distance heart donation.

Selective Localization of a Novel Dendrimer Nanoparticle in Myocardial Ischemia-Reperfusion Injury.

BACKGROUND: Dendrimer nanoparticle therapies represent promising new approaches to drug delivery, particularly in diseases associated with inflammatory injury. However, their application has not been fully explored in models of acute myocardial ischemia (MI) and reperfusion injury. METHODS: White male New Zealand rabbits underwent left thoracotomy with 30-minute temporary left anterior descending artery occlusion and MI confirmed by electrocardiography and histology (MI rabbits, n = 9), or left thoracotomy and pericardial opening for 30 minutes but no left anterior descending artery occlusion (control [C] rabbits, n = 9) rabbits. Following the 30-minute period, a dendrimer (generation 6 dendrimer conjugated to cyanine-5 fluorescent dye [G6-Cy5], 6.7 nm diameter) was administered intravenously and the chest closed in layers. Animals were sacrificed at 3 hours (3 MI, 3 C), 24 hours (3 MI, 3 C), or 48 hours (3 MI, 3 C) postsurgery. RESULTS: As compared to controls, MI rabbits had twofold G6-Cy5 uptake in the myocardial anterior wall as compared to the same region in nonischemic control rabbits at 24 hours postsurgery (6.01 ± 0.57 µg/g versus 2.85 ± 0.85 µg/g; p = 0.04). This trend was also present at 48 hours (6.38 ± 1.53 µg/g versus 3.95 ± 0.60 µg/g, p = 0.21) and was qualitatively evident on confocal microscopy. G6-Cy5 half-life in serum was approximately 12 hours, with 22% of the injected G6-Cy5 dose remaining at 48 hours. CONCLUSIONS: This study demonstrates for the first time that dendrimer nanodevices selectively localize in ischemic as compared to healthy myocardium. This indicates that dendrimer nanodevices are promising agents to deliver drugs specifically to the ischemic myocardium to attenuate the injury. Subsequent studies will assess the efficacy of a dendrimer-drug conjugate in ameliorating reperfusion injury following MI.

Renal Failure After Cardiac Operations: Not All Acute Kidney Injury Is the Same.

BACKGROUND: The Society of Thoracic Surgeons (STS) database does not distinguish between a decline in creatinine clearance vs new hemodialysis (HD) when qualifying acute renal failure (ARF) after a cardiac operation. We hypothesized that patients requiring HD experience significantly greater postoperative morbidity and death. METHODS: We included all patients who underwent STS index cardiac operations at our institution from 2008 to March 2015 and did not have preexisting renal failure (creatinine >4.0 mg/dL or preoperative HD). We identified patients meeting STS criteria for ARF: threefold rise in serum creatinine, creatinine exceeding 4.0 mg/dL (non-HD ARF) with minimum rise of 0.5 mg/dL, or HD (ARF-HD). After propensity matching non-HD ARF and ARF-HD groups across 14 variables (including baseline glomerular filtration rate), we compared incidences of our primary outcome, death, and secondary outcomes, intensive care unit (ICU) and hospital length of stay (LOS), and discharge to a location other than home. RESULTS: Among 4,154 study patients, we identified 113 (2.7%) that experienced new-onset non-HD ARF (n = 57) or ARF-HD (n = 56) postoperatively. Propensity matching resulted in 51 well-matched pairs who experienced non-HD ARF or ARF-HD (all p > 0.10). Patients requiring HD suffered significantly greater operative mortality (67% vs 22%, p < 0.01), longer ICU LOS (326 vs 176 hours, p < 0.01), and greater postoperative hospital LOS (34 vs 17 days, p < 0.01). ARF-HD patients also demonstrated a trend toward higher rates of discharge to a location other than home (71% vs 45%, p = 0.08). CONCLUSIONS: After cardiac operations, patients who experienced ARF-HD experienced triple the mortality and double the ICU and postoperative hospital LOS compared with patients who experienced non-HD ARF.