Impella 5.5 as a bridge to heart transplantation: Waitlist outcomes in the United States.

OBJECTIVES: The 2018 United Network for Organ Sharing allocation policy change has led to a significant increase in the use of mechanical circulatory support devices in patients listed for orthotopic heart transplantation. However, there has been a paucity of data regarding the newest generation Impella 5.5, which received FDA approval in 2019. METHODS: The United Network for Organ Sharing registry was queried for all adults awaiting orthotopic heart transplantation who received Impella 5.5 support during their listing period. Waitlist, device, and early post-transplant outcomes were assessed. RESULTS: A total of 464 patients received Impella 5.5 support during their listing period with a median waitlist time of 19 days. Among them, 402 (87%) patients were ultimately transplanted, with 378 (81%) being directly bridged to transplant with the device. Waitlist death (7%) and clinical deterioration (5%) were the most common reasons for waitlist removal. Device complications and failure were uncommon (<5%). The most common post-transplant complication was acute kidney injury requiring dialysis (16%). Survival at 1-year post-transplant survival was 89.5%. CONCLUSION: Since its approval, the Impella 5.5 has been increasingly used as a bridge to transplant. This analysis demonstrates robust waitlist and post-transplant outcomes with minimal device-related and postoperative complications.

Middle Ear Condition at the Time of Pediatric Myringotomy Tube Placement: Pain Associations Following Intraoperative Fentanyl/Ketorolac and Seasonal Variation.

BACKGROUND: Ketorolac-refractory pain behavior following bilateral myringotomy and pressure equalization tube placement (BMT) is associated with the absence of middle ear fluid. Intraoperative fentanyl/ketorolac affords more reliable pain control than ketorolac alone. We hypothesized that middle ear condition would correlate with postoperative pain despite such combination therapy. We further sought to demonstrate seasonal variation in ear condition and its influence on pain. METHODS: We conducted a single-institution retrospective cohort study of healthy children (9 months-7 years), who underwent BMT by a single surgeon from 2015 to 2020. Anesthetic care included sevoflurane/nitrous oxide/oxygen/air by mask and intramuscular fentanyl/ketorolac. Left/right middle ear fluid status was recorded at the time of BMT, and ear condition (primary exposure) was dichotomized as bilateral infected (mucoid or purulent) or normal/unilateral infected. The primary outcome was maximum postanesthesia care unit Face, Legs, Activity, Cry, and Consolability (FLACC) score: 4-10 (moderate-to-severe pain) versus 0-3 (no-to-low pain). Rescue oxycodone, acetaminophen administration, and emergence agitation were secondary outcomes. Statistical analysis incorporated generalized linear mixed-effect models (GLMMs) with random intercepts to account for clustering by anesthesia provider. A year-over-year monthly time-series analysis was conducted using an autoregressive integrated moving average (ARIMA) regression model. RESULTS: Excluding recurrent cases, 1149 unique evaluable subjects remained. Bilateral infection prevalence was 39.8% (457/1149; 95% confidence interval [CI], 37.0-42.6). Probability of moderate-to-severe pain behavior was 23.5% (270/1149; 95% CI, 21.1-26.0) overall. Compared to patients with bilateral infected middle ears, those with normal/unilateral infected ears were more likely to have a FLACC score ≥4 (26.7% [185/692] versus 18.6% [85/457]; odds ratio [95% CI], 1.7 [1.2-2.3]; P = .002). Variability in pain outcome explained by the multivariable GLMM was 4.7%. Fentanyl dose response was evidenced by oxycodone administration differences ( P ≤ 0.002). Moderate-to-severe pain and emergence agitation were more likely with reduced fentanyl dosing. Bilateral infection prevalence exhibited seasonality, peaking in March and nadiring in July. However, pain outcomes did not vary by season. CONCLUSIONS: Normal/unilateral infected ears at time of pediatric BMT are associated with higher incidence of moderate-to-severe postoperative pain following intraoperative fentanyl/ketorolac administration, but the predictive value of ear condition on pain is limited. Infections were less common in the summer.

Lack of volume-outcome association in ECMO bridge to heart transplantation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a bridge to cardiac transplantation. As the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change elevated waitlist status for patients receiving mechanical circulatory support (MCS), we aimed to determine if a center's annual heart transplant volume was associated with ECMO-support duration and posttransplant outcomes. METHODS: Adults heart transplant candidates between January 1, 2011, and December 31, 2021, were isolated in the UNOS database. VA-ECMO use was identified at the time of listing for transplant. Average annual transplant volume was calculated by the center, with stratification as high (≥20 cardiac transplants, high volume center [HVC]) or low (<20 cardiac transplants, low volume center [LVC]) volume centers. Results are reported as mean (interquartile range) or n (%). RESULTS: In total, 543 patients at HVCs and 275 at LVCs were listed for transplant supported with VA-ECMO. Those listed at HVCs were more likely to be supported by intra-aortic balloon pump (103 [19%] vs. 32 [11.6%], p = .008) and inotropes (267 [49.2%] vs. 106 [38.5%], p = .004) at time of listing. Patients at HVCs received ECMO support for 6 [4-9] days, compared to 8 [4-15] days at low-volume centers (p = .030), and but were cannulated a similar time before listing (2 [1-5] vs. 3 [1-7] days, p = .517). There were no differences in rates of transplant (p = .2126), waitlist mortality (p = .8645), delisting due to clinical deterioration (p = .8419), or recovery (p = .1773) between groups. Among transplanted patients, there were no differences in support duration (6 [4-8] vs. 6 [4-10], p = .187), or time from registration to transplant (5 [2-20] vs. 7 [3-22] days, p = .560). Posttransplant survival did not vary (p = .293). CONCLUSIONS: LVCs can successfully bridge patients to transplant with VA-ECMO and achieve comparable outcomes to HVCs.

Aortic root aneurysm repair in a neonate with Loeys-Dietz syndrome.

Loeys-Dietz syndrome is a connective tissue disorder known to cause aggressive aortopathy in paediatric patients, but it is extremely rare for cardiovascular events to present during infancy. We report the first successful aortic repair in a neonate with LDS presenting in extremis with an early onset, massive aortic aneurysm.

Pulmonary hypertension and mitral regurgitation in an infant with an anatomically normal mitral valve.

A full-term, female presented on her date of birth with severe pulmonary hypertension (PH) and mitral regurgitation (MR), requiring veno-arterial extracorporeal membrane oxygenation. After the treatment, her PH and MR were resolved with no anatomic abnormality present. We propose a positive feedback loop of PH causing right ventricular dilation and interventricular septal shifts, worsening MR, and elevated left atrial, and potentially pulmonary, pressures.

Natural Inhibitors of the RhoA-p115 Complex from the Bark of Meiogyne baillonii.

In an effort to find potent natural inhibitors of RhoA and p115 signaling G-proteins, a systematic in vitro evaluation using enzymatic and plasmonic resonance assays was undertaken on 11 317 plant extracts. The screening procedure led to the selection of the New Caledonian endemic species Meiogyne baillonii for a chemical investigation. Using a bioguided isolation procedure, three enediyne-γ-butyrolactones (1-3) and two enediyne-γ-butenolides (4 and 5), named sapranthins H-L, respectively, two enediyne carboxylic acid (6 and 7), two depsidones, stictic acid (8) and baillonic acid (9), aristolactams AIa and AIIa (10 and 11), and two aporphines, dehydroroemerine (12) and noraristolodione (13), were isolated from the ethyl acetate extract of the bark. The structures of the new compounds (1-6, 9, and 11) and their relative configurations were established by NMR spectroscopic analysis and by X-ray diffraction analysis for compound 9. Only stictic acid (8) exhibited a significant inhibiting activity of the RhoA-p115 complex, with an EC50 value of 0.19 ± 0.05 mM. This is the first time that a natural inhibitor of the complex RhoA-p115's activity was discovered from an HTS performed over a collection of higher plant extracts. Thus, stictic acid (8) could be used as the first reference compound inhibiting the interaction between RhoA and p115.

Teaching Medical Educators How to Teach Communication Skills: More than a Decade of Experience.

OBJECTIVES: Although opportunities exist for medical educators to gain additional training in teaching, literature that describes how to teach educators to teach communication skills to trainees is limited. The authors developed and evaluated a faculty development course that uses didactics, demonstration, drills, and role-play in a small-group format. METHODS: The course has been offered through the Institute for Clinical Research Education at the University of Pittsburgh for almost 15 years. Course effectiveness was evaluated with a survey of 62 clinicians who completed the course between 2003 and 2012. RESULTS: The response rate was 85%. A total of 98% would recommend the course to a colleague and 98% indicated the course was effective at developing teaching techniques. Their use of standardized patients, teaching in small groups, and role-play increased as a result of participation in the course. A total of 70% went on to formally teach communication skills at various medical education levels. CONCLUSIONS: This structured course effectively taught participants how to teach patient-doctor communication in both classroom and clinical settings. The majority put these techniques to use in formal settings. This course also provided educators with the skills necessary to meet the growing needs of training programs charged with teaching the next generation of providers to effectively communicate with patients. The description presented can serve as a framework for faculty development in teaching communication.

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential.

Thrombin, the major enzyme of the hemostatic system, is involved in biological processes associated with several human diseases. The capacity of a given individual to generate thrombin, called the thrombin generation potential (TGP), can be robustly measured in plasma and was shown to associate with thrombotic disorders. To investigate the genetic architecture underlying the interindividual TGP variability, we conducted a genome-wide association study in 2 discovery samples (N = 1967) phenotyped for 3 TGP biomarkers, the endogenous thrombin potential, the peak height, and the lag time, and replicated the main findings in 2 independent studies (N = 1254). We identified the ORM1 gene, coding for orosomucoid, as a novel locus associated with lag time variability, reflecting the initiation process of thrombin generation with a combined P value of P = 7.1 × 10(-15) for the lead single nucleotide polymorphism (SNP) (rs150611042). This SNP was also observed to associate with ORM1 expression in monocytes (P = 8.7 × 10(-10)) and macrophages (P = 3.2 × 10(-3)). In vitro functional experiments further demonstrated that supplementing normal plasma with increasing orosomucoid concentrations was associated with impaired thrombin generation. These results pave the way for novel mechanistic pathways and therapeutic perspectives in the etiology of thrombin-related disorders.

Contribution of anti-ß2glycoprotein I IgA antibodies to the diagnosis of anti-phospholipid syndrome: potential interest of target domains to discriminate thrombotic and non-thrombotic patients.

OBJECTIVES: Although the last international guidelines for aPL recommended determination of IgA aCL and anti-ß2glycoprotein I (aß2GPI) antibodies for the evaluation of APS in the absence of conventional IgG or IgM aCL and aß2GPI antibodies, the clinical value of these antibodies remains controversial. We evaluated the clinical utility of IgA aPL and of the determination of target domains of aß2GPI IgA antibodies. METHODS: A retrospective analysis was performed on sera from 439 patients referred for routine detection of aPL IgA by in-house ELISA. Sera positive for aß2GPI IgA were subsequently tested for aß2GPI domain 1 (D1) and domain 4/5 (D4/5) antibodies using ELISAs. RESULTS: The prevalence of aß2GPI IgA antibodies was 16% in patients, significantly different from controls (1%, P < 0.0001). These antibodies were associated with clinical contexts related to APS as thrombosis (28.6% vs. 15%, P = 0.009) and SLE (42% vs. 15%, P < 0.0001). Interestingly, determination of their target domains revealed a significant association between aß2GPI IgA directed against D4/5 and SLE without thrombosis (66.7 vs. 16.7%, P = 0.002). In contrast, aCL IgA were not more prevalent in patients than in controls. CONCLUSION: Our study confirmed the interest of aß2GP1 IgA in the exploration of APS and suggests that identification of target domains of aß2GP1 IgA may be useful in the evaluation of thrombotic risk in SLE patients.

Flap-based Closure of Acquired Tracheoesophageal Fistulas.

Iatrogenic tracheoesophageal fistulae management and repair are difficult to manage with few resourced describing management and repair. Two cases are presented describing the approach to and repair of a tracheoesophagea fistula; one with a free flap and one with local flap reconstruction. Both cases utilized allograft material to maintain separation between the alimentary and repiratory tracts. Laryngoscope, 134:3761-3764, 2024.

Anatomic Considerations of esophageal button battery ingestion for outcomes and imaging.

INTRODUCTION: Button batteries (BB) are a source of significant morbidity and mortality in young children. Little data is available regarding associations between esophageal impaction location and outcomes or need for surveillance imaging. METHODS: All patients treated at a single institution following BB ingestion between 2018 and 2022 were included for retrospective chart review. RESULTS: Twenty patients were treated at our institution BBs were located, or most significant damage observed, in the cervical esophagus (n = 10, 50 %), followed by thoracic esophagus (n = 6, 30 %), and abdominal esophagus (n = 4, 20 %). Patients with cervical esophageal impaction were younger (482 [370-866] days), than those with thoracic (1395 [871-2369] days) or abdominal esophageal impaction (2021.5 [1230.5-3419.5] days) (p = 0.003). Zargar Mucosal Injury Grade was significantly more severe in patients with cervical button battery impaction; 8/10 (80 %) had a ≥Grade IIIB injury, compared to 2/6 (33.3 %) thoracic impactions and 0/4 (0 %) abdominal impactions (p = 0.002). All patients who developed persistent esophageal stenosis (n = 6) had cervical battery impactions (6, 60 %, p = 0.015). Both TEFs (2/2) had anterior facing anode, while both (2/2) esophageal perforations had posterior. Only 1/20 (5 %) patients, and 1/7 (14.3 %) with serious complications, had a serious complication detected on routine, rather than clinically indicated follow-up surveillance. CONCLUSIONS: In our population, cervical BB impaction occurred more frequently in younger children, was associated with more severe mucosal injury, and had higher risk of stenosis. Nearly all complications were detected on clinically indicated rather than postoperative surveillance imaging.

Effect of Covalence and Degree of Cation Order on the Luminous Efficacy of Mn4+ Luminescence in the Double Perovskites, Ba2BTaO6 (B = Y, Lu, Sc).

The spectroscopic properties of the Mn4+ ion are investigated in the series of isostructural double perovskite compounds, Ba2BTaO6 (B = Y, Lu, Sc). A comparison of these properties highlights the influence of covalent bonding within the perovskite framework and the degree of order between the B3+-Ta cations on the energy and intensity of the Mn4+2E → 4A2 emission transition (R-line). These two parameters of the emission spectrum are of importance for practical application since they determine the phosphor luminous efficacy. The influence of covalent bonding within the corner shared BO6/2 and TaO6/2 perovskite framework on the energy of the R-line energy is investigated. From the spectroscopic data, we have derived information on the influence of the degree of order between the B3+ and Ta5+ cations on the intensity of the R-line. The lowest energy and the highest intensity of the R-line are found in the double perovskite, Ba2ScTaO6. The purpose of this work is to propose for first time an explanation of these effects in the considered double perovskites. The obtained results are useful guidelines for practical improvement and tuning of key parameters of phosphors to the desired values.

Taste and smell function in Wilson's disease.

OBJECTIVE: Wilson's disease (WD) is a metabolic disorder associated with abnormal copper metabolism that results in hepatic, psychiatric, and neurologic symptoms. No investigation of taste function has been made in patients with WD, although olfactory dysfunction has been evaluated. METHODS: Quantitative taste and smell test scores of 29 WD patients were compared to those of 790 healthy controls. Taste was measured using the 53-item Waterless Empirical Taste Test (WETT®) and smell using the 40-item revised University of Pennsylvania Smell Identification Test (R-UPSIT®). Multiple linear regression analysis controlled for age and sex. RESULTS: Average WETT® scores did not differ meaningfully between WD and control subjects (respective medians & IQRs = 32 [28-42] & 34 [27-41]); linear regression coefficient = 1.19, 95% CI [-0.81, 3.19], p = 0.242). In contrast, WD was associated with significantly reduced olfactory function [respective median (IQR) R-UPSIT® scores = 35 (33-37) vs. 37 (35-38); adjusted linear regression coefficient = -1.59, 95% CI [-2.34, -0.833]; p < 0.001)]. Neither olfaction nor taste were influenced by WD symptom subtype [23 (79.3%) were hepatic-predominant; 6 (20.7%) neurologic predominant]; R-UPSIT®, p = 0.774; WETT®, p = 0.912). No effects of primary medication or years since diagnosis (R-UPSIT®, p = 0.147; WETT®, p = 0.935) were found. Weak correlations were present between R-UPSIT® and WETT® scores for both control (r=0.187, p < 0.0001) and WD (r=0.237) subjects, although the latter correlation did not reach the 0.05 α level (p = 0.084). CONCLUSION: Although WD negatively impacts smell function, taste is spared. Research is needed to understand the pathophysiologic mechanisms responsible for this divergence.

A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.

BACKGROUND: Venous Thrombosis (VT) is a common multifactorial disease with an estimated heritability between 35% and 60%. Known genetic polymorphisms identified so far only explain ~5% of the genetic variance of the disease. This study was aimed to investigate whether pair-wise interactions between common single nucleotide polymorphisms (SNPs) could exist and modulate the risk of VT. METHODS: A genome-wide SNP x SNP interaction analysis on VT risk was conducted in a French case-control study and the most significant findings were tested for replication in a second independent French case-control sample. The results obtained in the two studies totaling 1,953 cases and 2,338 healthy subjects were combined into a meta-analysis. RESULTS: The smallest observed p-value for interaction was p = 6.00 10(-11) but it did not pass the Bonferroni significance threshold of 1.69 10(-12) correcting for the number of investigated interactions that was 2.96 10(10). Among the 37 suggestive pair-wise interactions with p-value less than 10(-8), one was further shown to involve two SNPs, rs9804128 (IGFS21 locus) and rs4784379 (IRX3 locus) that demonstrated significant interactive effects (p = 4.83 10(-5)) on the variability of plasma Factor VIII levels, a quantitative biomarker of VT risk, in a sample of 1,091 VT patients. CONCLUSION: This study, the first genome-wide SNP interaction analysis conducted so far on VT risk, suggests that common SNPs are unlikely exerting strong interactive effects on the risk of disease.

KNG1 Ile581Thr and susceptibility to venous thrombosis.

Three single nucleotide polymorphisms (SNPs) were recently found to be associated with activated partial thromboplastin time (aPTT). Because shortened aPTT levels have been observed in patients experiencing venous thrombosis (VT), we investigated the effects of these 3 aPTT-associated SNPs, rs2731672, rs9898, and rs710446, on the risk of VT in a sample of 1110 healthy patients and 1542 patients with VT. Among the 3 tested SNPs, only rs710446 was associated with VT risk; the rs710446-C allele was associated with an increased risk of VT (odds ratio 1.196, 95% confidence interval 1.071-1.336, P = .0012). This association also was observed in an independent sample of 590 controls and 596 patients (odds ratio 1.171, 95% confidence interval 0.889-1.541, P = .059). We also confirmed that the rs710446-C allele was associated with decreased aPTT levels, making this nonsynonymous Ile581Thr variant a new genetic risk factor for VT.

ABO blood group and von Willebrand factor levels partially explained the incomplete penetrance of congenital thrombophilia.

OBJECTIVE: We aimed to study the association among ABO blood group, von Willebrand factor, factor VIII plasma levels, and the risk of venous thrombosis (VT) in a cohort of 1774 relatives from 500 families with inherited thrombophilia. METHODS AND RESULTS: One hundred sixty-one of the 1774 relatives had a VT. Different risk groups were formed: no, low-(factor V Leiden or F2G20210A heterozygous carriers), and high-risk thrombophilia (antithrombin, protein C, protein S, factor V Leiden, or F2G20210A homozygous carriers and combined defects). Compared with group O, AB blood group was associated with increased risk of VT: hazard ratio (HR)=3.8 (2.0-7.2). The effect of blood group A and B was milder (HR=1.6 [1.1-2.5] and 1.8 [1.0-3.3], respectively). An increased risk of VT was observed with increasing levels of von Willebrand factor and factor VIII plasma levels (HR=2.96 [1.92-4.56] and HR=2.60 [1.92-4.56] for third versus first tertile of von Willebrand factor and factor VIII plasma levels, respectively). In multivariate analysis, AB group (HR=2.3 [1.1-4.8]), high-risk thrombophilia (HR=2.8 [1.6-4.6]), and high von Willebrand factor levels (HR=2.3 [1.3-4.0]) were significantly associated with increased risk of VT. The risk of VT in individuals with high-risk thrombophilia and AB group was 14.4× higher than in those without thrombophilia and O group (5.0-41.4). CONCLUSIONS: ABO blood group modifies the risk of VT in families with hereditary thrombophilia. Phenotyping of the ABO blood group should be performed to better assess the risk of VT in asymptomatic individuals from thrombophilic families.

Higher Rates of Dialysis and Subsequent Mortality in the New Allocation Era for Heart Transplants.

BACKGROUND: In 2018, a United Network for Organ Sharing (UNOS) policy change increased prioritization of patients bridged with temporary mechanical circulatory support devices, such as venoarterial ECMO, for cardiac transplantation. Considering increased waitlist acuity, we sought to characterize whether this was associated with an increased risk for development of postoperative acute renal failure requiring dialysis (AKI-D) and risk of death after transplantation. METHODS: Dialysis-naive adults receiving single-organ heart transplant between November 2009 and February 2020 were stratified by receipt of AKI-D. Era 1 and era 2 were defined by the periods of UNOS allocation before and after policy change, respectively. Multivariable logistic regression was performed to determine risk factors for AKI-D. Rates of AKI-D were compared by propensity score-matched cohorts. Survival was compared by Kaplan-Meier analysis. RESULTS: A total of 20 698 patients were included. Venoarterial ECMO use significantly increased in era 2 (5.6% vs 0.58%; P < .01). Overall prevalence of AKI-D was greater in era 2 (13.5% vs 10.2%; P < .01). Use of preoperative ECMO, intra-aortic balloon pump, and ventilators and longer ischemia times were identified as independent risk factors for development of AKI-D. Five- and 10-year survival rates were significantly decreased for patients with AKI-D. There was no short-term survival difference of patients with AKI-D between era 2 and the more contemporary era 1. CONCLUSIONS: Patients in whom AKI-D develops after transplantation have significantly worse short- and long-term outcomes. Preoperative use of ECMO, preoperative ventilator support, and longer ischemia times are risk factors for development of AKI-D, and their prevalence has increased since the allocation policy change.

Extended Support With the Impella 5.5: Transplant, ECMO, and Complications.

We report midterm results of Impella 5.5 use with focus placed on bridge-outcomes, venoarterial extracorporeal membrane oxygenation (VA-ECMO) transition, complications, and risk factors for mortality. A retrospective review of patients implanted with the Impella 5.5 at our medical center was conducted. Forty patients were included with varying bridge strategies. Sixteen (40%) patients were supported for <14 days, 13 (32.5%) for 14-30 days, and 11 (27.5%) for >30 days. Thirty day mortality was 22.5% (9/40). Twenty-five (62.5%) were successfully bridged to transplant or durable left ventricular assist device (LVAD), while four (10.0%) recovered without the need for any further cardiac support. Five of 11 (60%) patients initially supported with VA-ECMO were either transitioned to durable left ventricular assist device (dLVAD; n = 3, 27.3%), transplanted (n = 1, 9.1%), or recovered (n = 1, 9.1%). Of nine patients with >moderate right ventricle (RV) dysfunction, five (55.6%) were successfully bridged to transplant or LVAD. Five (12.5%) patients required interval cannulation to VA-ECMO, often in the setting of RV dysfunction, and all (100%) were successfully transplanted. Lower pulmonary artery (PA) systolic pressure ( P = 0.029), among other factors, was associated with mortality. In summary, the Impella 5.5 may be able to effectively stabilize patients in refractory left ventricular predominant cardiogenic shock for extended durations, allowing time for mechanical circulatory support (MCS) and transplant evaluations.

Use of extended criteria donor hearts in combined heart-kidney transplant confers greater risk of mortality.

BACKGROUND: Extended criteria donors (ECD) hearts have demonstrated acceptable outcomes in select populations. However, their use in patients undergoing simultaneous heart-kidney transplantation (SHKT) has not been explored. This study is assessed the effect of ECD hearts in patients undergoing SHKT vs isolated heart transplants (IHT). METHODS: The United Network for Organ Sharing (UNOS) database was queried for all adult patients undergoing IHT and SHKT. Patients were stratified by receipt of ECD heart, defined as donor hearts failing to meet established acceptable use criteria. Interaction effects between ECDs and simultaneous kidney transplants were generated. Postoperative outcomes, risk factors, and patient/graft survival were compared across cohorts using Fine-Gray, Kaplan Meier, and Cox Proportional Hazards analyses. RESULTS: Among 26,207 patients included, 1,766 (7%) underwent SHKT. ECD hearts were used in 25% of both IHT and SHKT cohorts. Five-year survival among SHKT/ECD patients (67.3%) was reduced (p < 0.01) compared to SHKT/SDC (80.3%), IHT/ECD (78.1%) and IHT/SCD (80.0%) groups. Among SHKT patients, use of ECD hearts was associated with increased risk (SHR: 1.48; p < 0.01) of renal graft failure compared to SCD hearts. Among SHKT patients, receipt of an ECD heart, and individual ECD criteria (coronary disease and size mismatch >20%), predicted mortality. The interaction effect of receiving both ECD and SHKT predicted mortality and graft failure (HR 1.43; p < 0.01). CONCLUSIONS: Patients undergoing SHKT with an ECD heart face greater risks of mortality and graft failure in comparison to those undergoing IHT with ECD hearts. Careful selection of donor organs should be applied to this high-risk cohort.