Longer Ischemia Time Research Articles

Impact of diabetes on epicardial reperfusion and mortality in a contemporary STEMI population undergoing mechanical reperfusion: insights from the ISACS STEMI COVID 19 Registry

Background and AimDiabetes has been shown in last decades to be associated with a significantly higher mortality among patients with ST‐segment elevation myocardial infarction (STEMI) treated with primary PCI (PPCI). Therefore, the aim of current study was to evaluate the impact of diabetes on times delays, reperfusion and mortality in a contemporary STEMI population undergoing PPCI, including treatment during the COVID pandemic. Methods and ResultsThe ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving PPCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 1st of March until June 30, 2019 and 2020. Primary study endpoint of this analysis was in-hospital mortality. Secondary endpoints were postprocedural TIMI 0-2 flow and 30-day mortality. Our population is represented by 16083 STEMI patients. A total of 3812 (23,7%) patients suffered from diabetes. They were older, more often males as compared to non-diabetes. Diabetic patients were less often active smokers and had less often a positive family history of CAD, but they were more often affected by hypertension and hypercholesterolemia, with higher prevalence of previous STEMI and previous CABG. Diabetic patients had longer ischemia time, had more often anterior MI, cardiogenic shock, rescue PCI and multivessel disease. They had less often out-of-hospital cardiac arrest and in-stent thrombosis, received more often a mechanical support, received less often a coronary stent and DES. Diabetes was associated with a significantly impaired postprocedural TIMI flow (TIMI 0-2: 9.8% vs 7.2%, adjusted OR [95% CI] = 1.17 [1.02-1.38], p = 0.024) and higher mortality (in-hospital: 9.1% vs 4.8%, Adjusted OR [95% CI] =1.70 [1.43-2.02], p < 0.001); 30-day mortality (10.8% vs 6%, Adjusted HR [95% CI] =1.46 [1.26-1.68], p < 0.001) as compared to non-diabetes, particularly during the pandemic. ConclusionsOur study showed that in a contemporary STEMI population undergoing PPCI, diabetes is significantly associated with impaired epicardial reperfusion that translates into higher in-hospital and 30-day mortality, particularly during the pandemic.

Tumor specimen cold ischemia time impacts molecular cancer drug target discovery

Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter. Therefore, ischemia time before final tissue preservation is the most important determinant of the quality of a tissue collection. Here we show the impact of ischemia time on tumor and matching adjacent normal tissue samples for mRNAs in 1664, proteins in 1818, and phosphosites in 1800 cases (tumor and matching normal samples) of four solid tumor types (CRC, HCC, LUAD, and LUSC NSCLC subtypes). In CRC, ischemia times exceeding 15 min impacted 12.5% (mRNA), 25% (protein), and 50% (phosphosites) of differentially expressed molecules in tumor versus normal tissues. This hypoxia- and decay-induced dysregulation increased with longer ischemia times and was observed across tumor types. Interestingly, the proteomics analysis revealed that specimen ischemia time above 15 min is mostly associated with a dysregulation of proteins in the immune-response pathway and less so with metabolic processes. We conclude that ischemia time is a crucial quality parameter for tissue collections used for target discovery and validation in cancer research.

Mechanical circulatory support early after pediatric heart transplantation—an analysis from the Pediatric Heart Transplant Society

BackgroundThe use of early Mechanical Circulatory Support (MCS) following pediatric heart transplantation is not well-published. This paper attempts to uncover the incidence, predisposing factors and outcomes of MCS in a large, international cohort. MethodsThe Pediatric Heart Transplant Society Database (an international, prospective, event-driven database) was retrospectively analyzed for all cases of primary heart transplant over an 11-year period (2010-2020), dividing the cohort based on need for MCS within 30 days of transplantation. ResultsOf 4321 primary transplants, 249 (5.8%) required MCS (230 ECMO, 19 VAD). In a Cox proportional hazard model, congenital heart disease (p = 0.0002), older donor age (p < 0.0001), and longer ischemic time (p = 0.018) were each related to an increased need for MCS; increasing recipient body surface area (p < 0.0001) and increasing donor left ventricular ejection fraction (p = 0.016) were both correlated with less MCS use. 1-year survival in those requiring MCS was 54.2%, compared with 94.8% in those who did not need MCS (p < 0.0001). Later survival in patients surviving to one year was similar between the groups. ConclusionsMCS is used infrequently following pediatric heart transplant, and is related to donor, recipient and transplant factors. Although mortality is high, those surviving the first year post-transplant have excellent outcomes. Judicious use in those patients who would otherwise perish is therefore justified.

23 Pre-surgical visceral adipose tissue may be a novel pre-surgical risk factor for acute kidney injury among clear cell renal cell cancer patients undergoing radical nephrectomy

Abstract Background Patients with renal cancer undergoing partial (PN) or radical nephrectomy (RN) are at risk for acute kidney injury (AKI). Established risk factor for AKI include baseline comorbidities (e.g., obesity, hypertension), normal renal parenchymal loss, and ischemia-reperfusion injury. Pre-surgical body composition may be an overlooked modifiable patient characteristic that influences risk of AKI. We hypothesized that patients with higher visceral adipose tissue quantity or lower skeletal muscle quantity would have a higher risk of AKI. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1239 patients with stage I-III clear cell renal cell carcinoma (ccRCC) undergoing PN or RN from 2000 to 2020. We excluded from analysis patients with solitary kidney, those without preoperative serum creatinine (sCr) measurements, and those without a sCr measurement within seven days following nephrectomy, yielding a study population of 1,200 ccRCC patients with longitudinal sCr assessment (n=754 PN; n=446 PN). AKI was defined as a binary variable using the Kidney Disease – Improving Global Outcomes (KDIGO) criteria, based on a threshold of either a 1.5x relative or 0.3 mg/dl absolute increase in sCr within seven days. The cross-sectional areas and radiodensities of visceral adipose and skeletal muscle tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. We used generalized linear models with a binomial family and identity link to estimate seven-day risk differences (RD) and 95% confidence intervals in subgroups defined by surgery type. Results AKI was more frequent among patients undergoing RN (66% vs 26% among PN). Male patients, those with higher eGFR prior to surgery, those with lower stage/smaller tumors, and those with a history of hyperlipidemia more frequently experienced AKI in the post-operative period. No associations were observed with other reported comorbidities (diabetes, hypertension). While no association was observed between BMI and risk of AKI, visceral adipose and skeletal muscle variables were significantly associated with risk of AKI in univariate models. After adjustment for age, sex, comorbidities, and other body composition variables, only higher visceral adipose tissue quantity remained significantly associated with increased risk of AKI [RD per 40 unit increase (95% CI): 5.2 (1.3, 9.2)]. Muscle characteristics were not associated with AKI in multivariable models. Among patients undergoing PN, we observed a higher frequency of AKI among male patients, those with higher stage/larger tumors, and those with longer ischemia times. No significant associations were observed with comorbidity histories. In univariate models, visceral adipose tissue quantity and quality as well as skeletal muscle quantity were associated with AKI risk; however, after adjustment for age, sex, comorbidities, and other body composition variables, we observed no significant associations between any body composition feature and AKI in patients undergoing PN. Conclusions Associations between pre-surgical body composition and risk of AKI vary by surgery type. Visceral adipose tissue quantity was associated with risk of AKI among patients undergoing RN, but not PN. This finding may be relevant for patient counseling, consideration for nephron-sparing surgery, and development of interventions to lower visceral adipose tissue quantity. Future studies should evaluate the impact of both pre-surgical and post-surgical change in body composition in relation on chronic kidney disease after nephrectomy.

Going the distance: Geographic effects of the lung transplant composite allocation score

BackgroundIn March 2023, the lung allocation policy underwent major changes from a tiered structure to a composite allocation score (CAS). The goal was to improve allocation equity for disadvantaged groups by deprioritizing transplant distance. This study examines the effects of CAS on geographic trends and transportation efficiency. MethodsA retrospective cohort study was conducted using the United Network for Organ Sharing (UNOS) database, queried for adult lung transplants from 9/1/2022 - 9/1/2023. Outcomes were nautical distance of transplant, ischemic time, and flight required for transport (estimated as distance >100 miles). Perioperative complications and early survival were analyzed, with propensity-matching to account for baseline differences. ResultsA total of 1394 pre-CAS and 1197 post-CAS patients were included in the study cohort. Post-CAS recipients were less likely to be ABO type O (39.2% vs 47.3%, p<0.001), and were less likely to be an identical ABO match (82.7% vs. 91.0%, p < 0.001). The CAS cohort travelled significantly further (354.0 mi. [IQR:139 – 657] vs. 195.0 mi. [IQR:78 – 388], p < 0.001). CAS patients had longer ischemic times (6.8 hrs. [IQR: 5.3 – 8.9] vs. 6.0 hrs. [IQR:4.8 – 7.5], p < 0.001), and CAS procurements were more likely to require a flight for transport (n = 934, 78.0% vs. n = 991, 71.1%, p<0.001). However, waitlist time was shorter (28 days [IQR = 9 – 83] vs. 33 days [IQR = 11 – 109]) as was length of stay (24.21 ± 17.84 days vs. 31.44 ± 30.19 days, p<0.001) for CAS recipients, which remained true after propensity-matching. ConclusionThe lung CAS policy change was intended to eliminate geographic boundaries for disadvantaged patients but has expanded transplant distances, with an expected increase in ischemic time and need for flights which affect transplant economics. Although efforts were made to improve transplant availability for the disadvantaged ABO type O group, early assessment of the recipient cohort showed that recipients with blood group type O were actually less likely to be transplanted under the new policy. Positive effects include an overall decrease in waitlist time, but further investigation is warranted to evaluate the effectiveness, equity, and economic sustainability of the new policy.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction

BackgroundPrimary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. MethodsWe included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. ResultsAmong 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. ConclusionCardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.

Exercise capacity and cardiac allograft ischemic time in recent heart transplant recipients

BackgroundProlonged ischemic times (IT) for transplant hearts transported under cold storage conditions are associated with an increased risk of mortality, however the impact of IT on functional outcomes, such as exercise capacity, is not fully understood. This prospective, observational cohort study aimed to determine the association between exercise capacity, a strong predictor for post-transplant survival, and relatively longer IT. MethodsThirty heart transplant recipients were grouped dichotomously according to relatively longer (>180 min) or shorter (≤180 min) IT. A cardiopulmonary exercise test (CPET) was performed post-transplant upon entry into cardiac rehabilitation, during which peak VO2 was measured using a metabolic cart. CPET variables, including exercise capacity and test duration, were compared between groups. ResultsThis cohort was predominantly male (n=22, 73%) with a median age of 57.5 years [Q1-Q3: 54.0 - 65.0]). Baseline demographics and characteristics were similar between groups aside from UNOS listing status, in which patients listed as Status 1 or 2 were more likely to have long IT. Twelve (40%) participants received a donor heart with long IT. Surprisingly, higher peak VO2 was observed in those with long (15.0±2.8) than short (13.1±3.7) IT (p=0.009). However, CPET duration was significantly shorter in recipients with a long IT (6.3 vs. 7.7 minutes, p=0.048) despite similar time since transplant, rate of perceived exertion, protocol performed, and exercise capacity. ConclusionsIn this modest-sized cohort, exercise capacity was higher in heart transplant recipients with donor IT >180 minutes compared to those with IT ≤180 minutes. However, exercise duration was significantly shorter in those with relatively longer IT.

Incidence of left ventricle thrombus formation in patients with STEMI in the current era of antithrombotic treatment

Abstract Funding Acknowledgements None. Introduction Left ventricular (LV) thrombus formation is a serious complication of acute ST-segment elevation myocardial infarction (STEMI) which may result in ischemic stroke and systemic thromboembolism. There is limited evidence on the incidence and impact of LV thrombus in STEMI patients in the current era of antithrombotic treatment. Purpose To evaluate the incidence of LV thrombus formation in STEMI patients and to assess clinical predictor factors of LV thrombus formation leading to in-hospital major cardiac events (MACCE). Methods We prospective collected data from 504 STEMI patients treated with primary percutaneous intervention (PCI) in our large volume university hospital from April 2019 to September 2019. All patients underwent echocardiography examination at presentation and at hospital discharge. Results Mean age of the patients was 66.2 years and 78.8% were male. The incidence of LV thrombus formation was 5% in overall cohort and 9.4% in anterior STEMI. Among patients with LV thrombus, the majority had anterior STEMI (96% vs 48.4%; p&amp;lt;0.001), lower LV ejection fraction (LVEF)(35% vs 43%; P&amp;lt;0.001), more increased LV dimension /volume (36%vs7.3%; p&amp;lt;0.001), more apical aneurism/dyskinesia presence (36% vs 9%; p&amp;lt;0.001), longer ischemia time (25 hours vs 14 hours; p&amp;lt;0.002), more increased TPI values (p-0.22) and underwent less coronary angiography (p&amp;lt;0.02) and primary PCI (P=0.021). Increased LV dimension/volume was associated with 3.35 times higher risk of having LV thrombus (p=0.023). Also anterior STEMI was associated with 14 times higher risk of having LV thrombus=0.012. Patients with LV thrombus had a numerically higher incidence of in-hospital MACCE events (20% vs 13.5%; p=0.36). Conclusion The incidence of LV thrombus formation in STEMI still remain high regardless of primary PCI treatment and current antithrombotic treatment, and is higher in patients with anterior STEMI, lower LVEF, adverse ventricular remodeling, apical aneurism/dyskinesia presence, late hospital presentation and longer ischemia time. The presence of LV thrombus was independently associated with in-hospital MACCE events.

Differential effects of obesity on perioperative outcomes in renal cell carcinoma patients based on race and ethnicity and neighborhood-level socioeconomic status.

Obesity is a well-established risk factor of renal cell carcinoma (RCC), however the impact of obesity on surgical outcomes for racial and ethnic minority patients with RCC is unclear. This study investigated whether a higher body mass index (BMI) or obesity (BMI ≥30 kg/m2) was associated with worse perioperative outcomes and if there were heterogeneous effects based on race, ethnicity, and neighborhood-level socioeconomic factor. In this single-center cross-sectional study, medical records of patients who underwent partial or radical nephrectomy between 2010 and 2022 were retrospectively reviewed. Logistic regression analysis was performed to assess associations of BMI and perioperative outcomes [ischemia time, estimated blood loss (EBL), and length of hospital stay]. A total of 432 patients, including 49.8% non-Hispanic White (NHW), 35.0% Hispanic, and 6.9% American Indian (AI) patients, were included. Median [interquartile range (IQR)] BMI was 30.2 (26.3-35.2) kg/m2, and Hispanic (31.5) and AI (32.5) patients had higher median BMI than NHW (29.1) patients (P=0.006). Median ischemia time, EBL, and length of hospital stay were 18.5 (IQR, 15.0-22.4) minutes, 150 (IQR, 75.0-300.0) mL, and 3 (IQR, 2-5) days. BMI ≥35 kg/m2 was associated with a longer ischemia time [>18.5 minutes; odds ratio (OR), 5.17; 95% confidence interval (CI): 1.81-14.76; P=0.002], and the association was stronger in NHW than Hispanic patients (BMI continuous OR, 1.13; 95% CI: 1.04-1.22; P=0.004 in NHW and OR, 1.07; 95% CI: 0.98-1.17; P=0.12 in Hispanics). Class I and II/III obese patients had over two-fold increased odds of a larger EBL (>150 mL) than patients with normal weight (OR, 2.17; 95% CI: 1.03-4.59; P=0.04 for class I and OR, 2.24; 95% CI: 1.04-4.84; P=0.04 for class II/III obese patients). This association was stronger in patients from neighborhoods with high social deprivation index (SDI) and in NHW patients (BMI ≥30 vs. <30 kg/m2, OR, 3.53; 95% CI: 1.57-7.97; P=0.002 in high SDI neighborhoods and OR, 2.38; 95% CI: 1.10-5.14; P=0.03 in NHW). BMI was not associated with a longer hospital stay. In this study, obesity increased likelihood of worse perioperative outcomes, and the associations varied based on race and ethnicity and neighborhood-level socioeconomic factors.

Strategy to Reduce Mortality Rates of ST-elevation Acute Myocardial Infarction Using Prehospital Thrombolysis: A Meta-analysis

Abstract Importance: Ischemic heart disease is the leading cause of death worldwide. In ST-elevation myocardial infarction (STEMI), delaying reperfusion from the onset of chest pain increases the incidence of mortality and morbidity. Prehospital thrombolysis (PHT) has been evaluated in the setting of STEMI. We performed a systematic analysis of studies of PHT in acute STEMI. Objective: The objective of this study was to evaluate the all-cause mortality benefit in STEMI with PHT during short-term and long-term follow-up. Data Sources: In December 2020, the Cochrane search strategy was used to analyze randomized control trials, nonrandomized control studies, and registry studies in PubMed, EMBASE, Cochrane Library, Google Scholar, ClinicalKey, and Clinical Trial Registries. The search was repeated, and the included studies were updated in June 2023 to include more recent literature. We restricted the analysis to full-text publications in English. Study Selection: Studies using any thrombolytic agent in treating acute myocardial infarction in prehospital and inhospital settings with or without percutaneous Coronary intervention (PCI) were included in the analysis. Selection criteria included patient history and symptoms, electrocardiogram findings, and cardiac markers. Data Extraction: We used the Cochrane Handbook for Systematic Reviews of Interventions for assessing bias, the PRISMA flow diagram to show the process of inclusion and exclusion of studies, and RevMan software to perform meta-analysis. Main Outcomes and Measures: Outcomes include all-cause hospital mortality rate of PHT versus inhospital thrombolysis (IHT), influence of ischemic median time on all-cause mortality with PHT, and effect of PHT before PCI. The measures must have been observed for a follow-up period of up to 35 days, 1-year, and 5-years. Results: Data from 63,814 patients from 32 studies were reviewed. Results indicate a reduction in all-cause mortality in patients assigned to PHT (odds ratio [OR] −0.68, P &lt; 0.00001) compared to IHT. There was a significant reduction in mortality when thrombolytics were administered before PCI (OR − 0.78, P = 0.0001). The overall survival was better with an ischemic time of &lt;2 h. Mortality was higher with longer ischemic time (3 h and 6 h). Among patients who presented within 2 h of the onset of chest pain, mortality was lower compared to primary PCI (pPCI). Conclusion: PHT offers faster reperfusion and reduces all-cause mortality compared to IHT. A strategy of PHT within the first 2-3 h of ischemic pain followed by PCI (if indicated) could offer better survival than pPCI.

Impact of controlled hypothermic preservation on outcomes following heart transplantation

BackgroundSevere 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 have not been well characterized. MethodsData from US adult heart-transplant recipients in the GUARDIAN-Heart registry (NCT04141605) were analyzed to quantify PGD severity (stratified by ISHLT definition), mortality, and associated risk factors. The independent contributions of organ-preservation method (traditional ice storage versus controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. ResultsAmong 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) versus 10.4% (47/452), p=0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% (17/281) versus 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. ConclusionsSevere 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.

(039) Clinical Outcomes of Corporal Burnett “Snake” Maneuver Modification for Ischemic Priapism

Abstract Introduction The conventional approach for managing ischemic priapism (IP) involves a stepwise process that includes corporal aspiration and irrigation, intracavernosal sympathetic agent injection, shunt surgeries with or without snaking, and penile prosthesis implantation. It is crucial to determine the most appropriate surgical shunt procedure for patients who do not achieve detumescence with medical treatment, as complication rates are known to increase with ischemia time. Objective This study compared the effectiveness and clinical outcomes of distal penile shunt procedures with or without corporal Burnett "Snake" maneuver in patients presenting with IP. Methods We conducted a retrospective study involving patients who presented to our emergency department with IP and underwent surgical treatment at our institution between 2005 and 2021. The patients were divided into two groups: Group 1 (n = 26) underwent distal shunt + Burnett snake maneuver, and Group 2 (n = 56) underwent distal shunt-only. Clinical history, clinical parameters of IP, medical and surgical treatment details, and follow-up information, including IP recurrence, erectile function (EF), and complications, were determined through physician-patient interviews during preoperative assessment and postoperative visits. Successful priapism resolution was defined as pain relief, detumescence, and no further intervention required until discharge. Priapism recurrence was defined as a new presentation to the hospital with IP. EF was assessed before distal shunt surgeries and during post-op visits. EF was graded on a 4-point patient-reported scale: 1 = fully rigid, always capable of penetration, 2 = diminished erection, capable of penetration with phosphodiesterase-5 inhibitors, 3 = diminished erection, capable of penetration with intracavernosal/intraurethral injection or vacuum pump, 4 = insufficient erection despite non-surgical treatment methods. Results The patient's demographic characteristics are shown in Table 1. IP resolution was observed in 24 out of 26 patients (92.3%) in Group 1 and in 30 out of 56 patients (53.6%) in Group 2 (p &amp;lt; 0.001) with a single surgical intervention. IP recurrence was observed in 1 out of 24 patients (4.2%) in Group 1 and in 18 out of 30 patients (60%) in Group 2 among those successfully treated with a single surgical intervention (p &amp;lt; 0.001). When comparing the EF status between groups, 6 out of 14 patients (42.8%) in Group 1 compared to 13 out of 26 patients (50%) in Group 2 had functional preservation of EF (level 1 + level 2) after priapism surgery, among those successfully treated with a single surgical intervention which had EF data in their charts (p = 0.66). Conclusions Our study demonstrates that Burnett snake maneuver is more effective than distal shunt-only procedures in resolving acute IP. Furthermore, this technique shows greater success in preventing IP recurrences. Regarding EF recovery, Burnett snake maneuver is at least as successful as distal shunt-only procedures, even in cases with longer ischemia times. Disclosure No.

Heart transplant outcomes in restrictive cardiomyopathy: UNOS registry analysis of the last three decades

PurposeRestrictive cardiomyopathy (RCM) comprises diverse etiologies with overall poor prognosis. Emerging therapies have significantly impacted some of these entities. However, these therapies may have limited impact in the end-stages and have only recently become available. We sought to assess outcomes before and after transplant in the RCM population stratified into 3 distinct time periods from the recent era. MethodsRetrospective analysis of the UNOS registry (n=62709) for all patients transplanted between 1987 - March 1, 2022 were stratified by RCM status with 1157 patients with RCM. Populations were grouped temporally into classic (1987-2000), contemporary (2000-2013), and current (2014-2022) eras. Multi-organ and repeat transplants were excluded from the analysis. Baseline demographics, listing status, hemodynamics, donor information, and life support methods were compared using Kruskal-Wallis and Pearson’s tests. Longitudinal survival was assessed via Kaplan-Meier survival analysis. Univariate and multivariate analysis using Cox modeling and competing outcomes analyses were performed. ResultsRCM patients were older, female, with older donors and longer ischemic times (p<0.001). There were no significant differences in overall survival compared to the non-RCM population, however, with increased transplant rates. Amyloidosis and chemotherapy/radiation portend the worst prognosis but have shorter waitlist times and up-trending survival in the current era. ConclusionRCM represents a small but significant population of those requiring heart transplant. RCM transplant outcomes appear to be improving across all subsets with shorter wait times and better survival. Early recognition is important to help mitigate adverse outcomes.

Early elevated donor-derived cell-free DNA levels in heart transplant recipients following precision-controlled cardiac transport system or ice-cooled organ transport.

Recent innovations in temperature-controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor-derived cell-free DNA (dd-cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. Single-organ heart transplant recipients between January 2020 and January 2022 were included if they had dd-cfDNA measures ≤6weeks post-transplant along with the baseline biopsy at 6weeks as part of the surveillance protocol and no biopsy-confirmed rejection ≤90 days. Elevated dd-cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34vs. 40 years, p=.04) with a longer total ischemic time (171vs. 212 min, p=.002). Recipients in the SCTS group had a greater risk of elevated dd-cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times>3.5h (Unadjusted odds ratio: 4.9, 95%-CI: 1.08-22.5, p=.039 and Adjusted odds ratio: 5.5, 95%-CI: 1.03-29.6, p=.046). Primary graft dysfunction rates and 1-year mortality were comparable between groups. Elevated dd-cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long-term outcomes including mortality despite a longer ischemic time in the SCTS group.

Surgical Complications After Lung Transplantation: The Reina Sofía Hospital Experience

To assess the incidence of surgical complications after lung transplantation and its influence on early mortality and long-term survival. Retrospective review of 792 lung transplants (LTs) performed from 1994 to 2022. Among them, 769 with complete data were selected. Patients with and without surgical complications were compared by univariable and multivariable analyses. There were 385 single LTs (50%), 371 double LTs (48%), 8 bilobar LTs (1%), and 5 combined liver LTs (1%). Two hundred forty-nine patients presented surgical complications (32%) as follows: bronchial (n=61), vascular (n=55), pneumothorax (n=33), and phrenic nerve palsy (n=22). Thirty-day mortality (noncomplicated vs complicated) was 57 (41%) vs 80 (59%), P < .001. Transplants for bronchiectasis (58%), pulmonary hypertension (50%), and re-transplants (78%) presented more surgical complications (P < .001). Double LT (40%), bilobar LT (88%), and combined liver LT (100%) presented more surgical complications (P < .001). Complicated recipients were younger (49 ± 15 vs 45 ± 17 years; P=.001), with longer ischemic times (429 ± 67 vs 450 ± 76 min [2nd graft]; P=.007), and required extracorporeal support (ECLS) more often (43% vs 57%; P < .001). Survival at 1, 5, 10, 15, and 20 years (noncomplicated vs complicated): 78%, 63%, 52%, 41%, 31% vs 52%, 42%, 35%, 26%, 22%; P < .001). Predictors of mortality were the need for ECLS (odds ratio [OR] 4.14; P < .001), postoperative ventilation (hours) (OR 1.01; P < .001), and vascular complications (OR 4.78; P < .001). Surgical complications remain an important source of morbidity and mortality after lung transplantation. Complex surgical procedures requiring ECLS develop frequent surgical complications needing long postoperative ventilation that are associated with early mortality and poorer long-term survival.

Positive donor blood cultures are not associated with worse heart transplant survival.

Recent evidence has demonstrated that transplantation of hearts with blood culture positive donors (BCPDs) to pediatric recipients is safe and effective. Few studies have analyzed the effect of BCPD on adult heart transplant recipients. The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from September, 1987 to March, 2021. Exclusion criteria included pediatric donors/recipients, donor ejection fraction <10% or >85%, inactive listed recipients, donors missing blood cultures, and recipients missing follow-up time. Outcomes were compared with fully adjusted logistic models. To account for discrepancies in BCPD and non-BCPD covariates, an inverse proportionally weighted model with regression adjustment (IPWRA) was used. A total of 60592 donors were non-BCPD, while 4009 were BCPD. 7% of hearts not transplanted were BCPD, while 6% of hearts transplanted were BCPD (p=.001). These rates have been nearly constant since 2005. There were no differences in short term survival between the two groups in the adjusted or IPWRA models (p=.103 and .277, respectively). Additionally, the BCPD group had longer ischemic time (3.24 vs. 3.06h, p<.001), older donor age (32.73 vs. 31.65years, p<.001), and older recipient age (52.76 vs. 52.09years, p=.001). The IPWRA revealed an average additional 3.4years of overall survival and 2.25years of graft function for BCPD versus non-BCPD recipients, although these results failed to reach statistical significance (p=.387 and .527, respectively). Given the need for more donor hearts, donors with positive blood cultures should be considered. Great care in evaluating such patients is advised to eliminate donors with untreated infections, while carefully selected donors can be considered and used.

Better Than Ice: Advancing the Technology of Donor Heart Storage With the Paragonix SherpaPak.

Better Than Ice: Advancing the Technology of Donor Heart Storage With the Paragonix SherpaPak.

Incidence of post-transplant cytomegalovirus viremia in patients receiving lungs after ex vivo lung perfusion

ObjectivesCytomegalovirus infection after lung transplant is associated with increased morbidity and mortality. Inflammation, infection, and longer ischemic times are important risk factors for cytomegalovirus infection. Ex vivo lung perfusion has helped to successfully increase the use of high-risk donors over the last decade. However, the impact of ex vivo lung perfusion on post-transplant cytomegalovirus infection is unknown. MethodsWe performed a retrospective analysis of all adult lung transplant recipients from 2010 to 2020. The primary end point was comparison of cytomegalovirus viremia between patients who received ex vivo lung perfusion donor lungs and patients who received non–ex vivo lung perfusion donor lungs. Cytomegalovirus viremia was defined as cytomegalovirus viral load greater than 1000 IU/mL within 2 years post-transplant. Secondary end points were the time from lung transplant to cytomegalovirus viremia, peak cytomegalovirus viral load, and survival. Outcomes were also compared between the different donor recipient cytomegalovirus serostatus matching groups. ResultsIncluded were 902 recipients of non–ex vivo lung perfusion lungs and 403 recipients of ex vivo lung perfusion lungs. There was no significant difference in the distribution of the cytomegalovirus serostatus matching groups. A total of 34.6% of patients in the non–ex vivo lung perfusion group developed cytomegalovirus viremia, as did 30.8% in the ex vivo lung perfusion group (P = .17). There was no difference in time to viremia, peak viral loads, or survival when comparing both groups. Likewise, all outcomes were comparable in the non–ex vivo lung perfusion and ex vivo lung perfusion groups within each serostatus matching group. ConclusionsThe practice of using more injured donor organs via ex vivo lung perfusion has not affected cytomegalovirus viremia rates and severity in lung transplant recipients in our center.

Abstract C085: Intersectionality of neighborhood socioeconomic deprivation, race/ethnicity, and obesity in renal cell carcinoma disparities in Hispanics and American Indians in Arizona

Abstract Background: Hispanic Americans (HAs) and American Indians (AIs) in Arizona experience marked disparities in renal cell carcinoma (RCC) with a younger age at diagnosis, higher stage, and higher mortality rates compared to non-Hispanic Whites (NHWs). The underlying factors causing the disparities are still under investigation. This study explored relationships between neighborhood characteristics, race/ethnicity, and obesity in RCC patients. Methods: Medical records of patients who underwent RCC surgical treatment between 2010 and 2021 at Banner University Medical Center Tucson/University of Arizona were reviewed. Social Deprivation Index (SDI) score was calculated using American Community Survey data and linked to the zip code of patient’s residence. Logistic regression analysis was performed to assess associations of SDI, race/ethnicity, and BMI with RCC characteristics and perioperative outcomes. Results: A total of 379 patients (49.9% NHWs, 34.6% HAs, and 7.4% AIs) with SDI data were included in this study. They lived in 116 zip code areas (86 in NHWs, 49 in HAs, and 13 in AIs). 18 patients (4.7%) lived in the most common zip code area. 51.7% of zip codes had only one patient living in the area. HAs and AIs were more likely to have an earlier age of diagnosis and higher BMI and live in high SDI neighborhoods compared to NHWs. SDI were positively associated with BMI in the total dataset and HAs, but not in NHWs. HA ethnicity and high BMI were significantly associated with earlier age of diagnosis. HAs had increased odds of having clear cell RCC, but the association was not significant after adjusting for SDI. HAs had an increased odds of clear cell RCC only in patients living in high SDI neighborhoods (OR 3.33, 95% CI 1.00-11.07). In patients living in low SDI neighborhoods, HAs had increased odds of advanced stage (OR 2.52, 95% CI 1.17-5.45), but not in patients living high SDI neighborhoods (P-interaction=0.02). BMI≥35 was associated with advanced stage in NHWs (OR 3.08, 95% CI 1.14-8.35), but not in HAs (P-interaction=0.07). SDI was not associated with advanced stage. SDI was associated with high grade in NHWs (OR 3.08, 95% CI 1.14-8.35), but not in HAs (P-interaction=0.06). Next, we investigated impacts of obesity on perioperative outcomes adjusting for SDI. BMI≥35 was associated with a longer ischemia time (OR 3.41, 95% CI 1.06-11.2), and this association was stronger in patients living in low SDI than high SDI neighborhoods and in HAs than NHWs. HAs with BMI 30-35 had increased odds (OR 7.83, 954% CI 1.18-51.81) of a greater estimated blood loss during the surgery. Patients with BMI 25-30 had significantly increased odds (OR 6.95 95% CI 1.18-41.00) of longer hospital stay after surgery. A stronger association was observed in NHWs, and the association was not significant in HAs. Conclusion: This study revealed that SDI is an underlying factor of obesity in RCC patients. The relationships between SDI, race/ethnicity, and obesity are complex, and obesity is impacting racial/ethnic groups differently. Citation Format: Ken Batai, Waheed Asif, Patrick Wightman, Alejandro Cruz, Celina I. Valencia, Francine C. Gachupin, Chiu-Hsieh Hsu, Juan Chipollini, Benjamin R. Lee. Intersectionality of neighborhood socioeconomic deprivation, race/ethnicity, and obesity in renal cell carcinoma disparities in Hispanics and American Indians in Arizona [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C085.

Modern outcomes of heart-lung transplantation: assessing the impact of the updated US allocation system.

In 2018, the United Network for Organ Sharing modified their heart allocation policy to reduce waitlist mortality and prioritize patients with the greatest acuity. Considering declining rates of combined heart-lung transplantation, this study sought to investigate the impact of the new allocation system on waitlist and post-transplant outcomes of patients listed for combined heart-lung transplantation. Adult patients listed for combined heart-lung transplant between 2012 and 2021 were included. Patients were stratified according to listing era. Competing risk regression was used to assess waitlist outcomes. Cox proportional hazards regression was used to establish risk factors for post-transplant mortality. A total of 511 patients were included, of whom 295 (57.8%) were listed in era 1 and 216 (42.2%) in era 2. Era 2 was associated with increased likelihood of transplant (adjusted standard hazard ratio (aSHR): 1.60 [1.23-2.07]; P < 0.01) and decreased waitlist mortality (aSHR: 0.43 [0.25-0.73]; P < 0.01). Despite longer ischaemic times and increased use of preoperative veno-arterial extracorporeal membrane oxygenation (ECMO) in era 2, early post-transplant survival was equivalent. Predicted heart mass ratio <0.8 (Hazard ratio (HR); 3.24; P = 0.01), ventilator support (HR: 3.83; P < 0.01) and greater ischaemic times (HR: 1.80; P < 0.01) independently predicted the mortality. Procedures at high centre volumes (HR: 0.36; P = 0.04) were associated with decreased mortality. Use of ECMO was not predictive of mortality in the modern era. The allocation policy change has led to improvements in waitlist outcomes in patients listed for heart-lung transplantation. Despite increased ischaemic times and use of ECMO, early post-transplant survival was equivalent.