Prolonged Ischemia Time Research Articles

Impact of Histidine-Tryptophan-Ketoglutarate Preservation Solution in Heart Transplantation with Extended Distance

<h3>Purpose</h3> In countries with such continental dimensions, and low organ donation rates and recovery, strategies to shorten the waiting time in heart transplantation (HT) list are still required. A prolonged ischemic time (pISQT, >240 min) has been reported to be a significant factor leading to primary graft dysfunction (PGD). Thus, optimal heart preservation is mandatory for transplant procedures with pISQT. Use of Histidine-Tryptophan-Ketoglutarate (HTK) solution has been suggested to improve extended organ preservations up to 180 min. This study investigated the impact of the donor distance (DD) from transplantation center and pISQT on PGD after HT using preservation with HTK solution. <h3>Methods</h3> Between January 2017 and December 2018, all 92 consecutive patients underwent HT at our institution after preservation with HTK solution were retrospectively evaluated divided into 2 groups according to the DD: (G1) 46 patients underwent HT with a DD <100km, and (G2) 46 patients after HT with a DD >100km. No significant differences were observed with regard to gender, age, diagnosis, donor inotropic support, and donor-recipient weight ratio among patients in G2 when compared with G1. The PGD was characterized using the ISHLT defined criteria. Descriptive analyses of the results are presented as mean values and standard deviations. The analytical studies were performed with the Fisher exact test. Kaplan-Meier and log-rank tests were performed to investigate survivals. All analyses were performed using R and p<0.05 was considered to be significant. <h3>Results</h3> The incidence of PGD was similar in both groups (p=0.81). After risk adjustment, longer DD were associated with a significantly lower risk of mortality at both 60 days (p=0.05, Figure 1). <h3>Conclusion</h3> This study illustrates that HTK solution may help to expand donor acceptance criteria to include more distant donor heart locations and accepting longer allograft ischemic times without increase in PGD and mortality after transplantation.

Incidence and impact of primary graft dysfunction in adult heart transplant recipients: A systematic review and meta-analysis

Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplant (HTx). To identify PGD incidence and impact on mortality, and to elucidate risk factors for PGD, we systematically reviewed studies using the ISHLT 2014 Consensus Report definition and reporting the incidence of PGD in adult HTx recipients.We conducted a systematic search in January 2020 including studies reporting the incidence of PGD in adult HTx recipients. We used a random effects model to pool the incidence of PGD among HTx recipients and, for each PGD severity, the mortality rate among those who developed PGD. For prognostic factors evaluated in ≥2 studies, we used random effects meta-analyses to pool the adjusted odds ratios for development of PGD. The GRADE framework informed our certainty in the evidence.Of 148 publications identified, 36 observational studies proved eligible. With moderate certainty, we observed pooled incidences of 3.5%, 6.6%, 7.7%, and 1.6% and 1-year mortality rates of 15%, 21%, 41%, and 35% for mild, moderate, severe and isolated right ventricular-PGD, respectively. Donor factors (female sex, and undersized), recipient factors (creatinine, and pre-HTx use of amiodarone, and temporary or durable mechanical support), and prolonged ischemic time proved associated with PGD post-HTx.Our review suggests that the incidence of PGD may be low but its risk of mortality high, increasing with PGD severity. Prognostic factors, including undersized donor, recipient use of amiodarone pre-HTx and recipient creatinine may guide future studies in exploring donor and/or recipient selection and risk mitigation strategies.

Use of Declined Donor Hearts: Is Quality Important?

<h3>Purpose</h3> Donor selection in heart transplant is not standardized. Many donor hearts (DH) are declined due to quality issues such as older age, low left ventricular ejection fraction, left ventricular hypertrophy, diastolic dysfunction, underlying coronary artery disease. Yet, DH declined at one center are subsequently accepted at another center. It is not well known whether DHs declined due to quality and accepted by another program have acceptable post-transplant outcomes. <h3>Methods</h3> Between 2017 and 2019, we assessed 532 DHs that were allocated to a single center at Cedars-Sinai (CS). We declined 218 offers due to poor quality. We had follow-up with organ procurement organizations and found that 45 of these DHs that we turned down for poor quality were accepted by another program and transplanted. 1-year post-transplant survival of these patients were compared to those patients whose donor was accepted and transplanted at CS (n=314). <h3>Results</h3> The 45 declined DHs had the following issues: abnormal cardiac studies (n=12), donor cardiac history (n=6), other medical history including cirrhosis or infectious processes (n=6), possible cardiac cause of death (n=3), older age (n=14), estimated prolonged ischemic time (n=1), and other reasons (n=3). Compared to those patients transplanted at CS, there was no difference in 1-year patient or graft survival. The declined donor patients compared to CS patients had similar age and gender but had a longer cold ischemic time and less patients listed as high urgency status (status 1-3) at transplant. (see table). <h3>Conclusion</h3> DHs declined for quality may be accepted at another program with good post-transplant survival. Contrary to belief, these DHs were mostly not transplanted into high urgency waitlist patients. Donor declines due to quality should be reviewed as they could lead to more lives saved.

Low‐dose steroids do make a difference: Independent risk factors for impaired linear growth after pediatric liver transplantation

Growth failure persists after pediatric liver transplantation and impairs pediatric development and quality of life. Steroid dose minimization attempts to prevent growth impairment, yet long-term assessment in pediatric liver recipients is lacking. We identified risk factors for impaired linear growth after pediatric liver transplantation, with a special focus on low-dose steroid therapy. This is a single-center retrospective analysis of height development in pediatric liver recipients up to 5years after transplantation. Risk factors for impaired linear growth (height Z-scores≤-2) at transplantation, after two (n=347) and five years (n=210) were identified by univariate and multivariate logistic regression. At transplantation, growth retardation was found in 52.2%, predominantly younger children. Height Z-scores improved from -2.23 to -1.40 (SE 0.11; 95%CI 0.74-1.16; p<.001) two years and -1.19 (SE 0.07;0.08-0.34; p=.017) five years post-transplant. Multivariate analysis showed previous growth impairment (OR=1.484; 95%-CI=1.107-1.988; p=.004), graft loss (49.006;2.232-1076; p=.006), and prolonged cold ischemic time (1.034;1.007-1.061; p=.011) as main long-term risk factors; steroid use was a significant predictor of 2-year but not 5-year growth impairment. In univariate analysis, impaired growth after 2 and 5years was associated with continuous low-dose (2.5mg/m2 BSA) steroid therapy (OR=3.323;1.578-6.996; p<.001/OR=8.352;1.089-64.07; p=.006)and graft loss (OR=2.513;1.395-4.525; p=.003/OR=3.378;1.815-7.576; p<.001). Furthermore, indication and era of transplantation affected growth. Our results show significant catch-up growth after pediatric liver transplantation, yet growth failure strongly affects particularly young liver recipients. The main influenceable long-term risk factor is pre-existing growth failure, emphasizing the importance of early aggressive nutritional therapy. Moreover, low-dose steroid therapy might impair growth and should therefore be critically questioned in long-term immunosuppression.

Research Highlights.

Research Highlights.

Impact of donor blood type on outcomes after prolonged allograft ischemic times

ObjectiveThe study objective was to determine the influence of allograft ischemic time on heart transplant outcomes among ABO donor organ types given limited prior reports of its survival impact. MethodsWe identified 32,454 heart transplants (2000-2016) from the United Network for Organ Sharing database. Continuous and categoric variables were analyzed by parametric and nonparametric testing. Survival was determined using log-rank or Cox regression tests. Propensity matching adjusted for preoperative variables. ResultsBy comparing allograft ischemic time less than 4 hours (n = 6579) with 4 hours or more (n = 25,875), the hazard ratios for death at 15 years after prolonged ischemic time (≥4 hours) for blood types O, A, B, and AB were 1.106 (P < .001), 1.062 (P < .001), 1.059 (P = .062), and 1.114 (P = .221), respectively. Unadjusted data demonstrated higher mortality for transplantation of O versus non-O donor hearts for ischemic time 4 hours or more (hazard ratio, 1.164; P < .001). After propensity matching, O donor hearts continued to have worse survival if preserved for 4 hours or more (hazard ratio, 1.137, P = .008), but not if ischemic time was less than 4 hours (hazard ratio, 1.042, P = .113). In a matched group with 4 hours or more of ischemic time, patients receiving O donor organs were more likely to experience death from primary graft dysfunction (2.5% vs 1.7%, P = .052) and chronic allograft rejection (1.9% vs 1.1%, P = .021). No difference in death from primary graft dysfunction or chronic allograft rejection was seen with less than 4 hours of ischemic time (P > .150). ConclusionsCompared with non-O donor hearts, transplantation with O donor hearts with ischemic time 4 hours or more leads to worse survival, with higher rates of primary graft dysfunction and chronic rejection. Caution should be practiced when considering donor hearts with the O blood type when anticipating extended cold ischemic times.

Effects of Donor Age and Ischemia Time on Outcome After Heart Transplant: A 10-Year Single-Center Experience.

In heart failure patients, heart transplant still remains the gold standard of care. Controversy prevails whether organs from older donors or with expected prolonged ischemia times may be accepted for transplant. Between 2010 and 2020, a total of 149 patients underwent heart transplant at our department. In a retrospective analysis, 4 different groups were defined according to donor age and total ischemia time. The younger group with short ischemia time consisted of 62 donors age < 50 years and total ischemia time < 240 minutes; the younger group with long ischemia time consisted of 32 donors age < 50 years and total ischemia time ≥ 240 minutes; the older group with short ischemia time consisted of 43 donors age ≥ 50 years and total ischemia time < 240 minutes; and the older group with long ischemia time consisted of 12 donors age ≥ 50 years and total ischemia time ≥ 240 minutes. Prolonged total ischemia time increased the risk of primary graft dysfunction (P = .02) and perioperative neurological events (P = .04). In contrast, there were no differences regarding durations of intensive care unit stay and hospital stay, perioperative bleeding, and renal failure. Although the younger donor age group showed excellent short-term survival (30-day survival rates of 97% for the younger group with short ischemia time and 91% for the younger group with long ischemia time), short-term and mid-term survival rates were impaired in patients with prolonged total ischemia time and older donor age (P = .02). Our results indicate that, in younger donors, prolonged ischemia times may be acceptable. However, in donors older than 50 years, the decision for acceptance as a donor should be made with great caution if the presumed ischemia time exceeds 4 hours.

Risk Factors of Ureteral Stenosis in Kidney Transplant Recipients: A Retrospective Study in National Referral Hospital in Indonesia.

Ureteral stenosis is one of the most common urological complications following kidney transplantations. It is occurred in 2–10% of patients and poses a significant problem to the patients as it may lead to permanent damage to renal damage. Identification of risk factors is important to prevent the incidence of ureteral stenosis. Thus, we aim to determine the risk factors of ureteral stenosis in the Indonesian population. This is a retrospective analysis of 487 kidney transplant patients performed in Cipto Mangunkusumo Hospital between 2014 and 2018. We collected and compared donor and recipient demography data in recipients who developed ureteral stenosis and recipients who did not develop ureteral stenosis. Ureteral stenosis was defined as the presence of hydronephrosis from ultrasound and increased number of serum creatinine. The overall incidence of ureteral stenosis post-kidney transplantation in our center is 6.6% (32 from 487 patients) from January 2014 until June 2018. We found that older donor and recipient age more frequent in developing ureteral stenosis post-kidney transplantation (p < 0.001). We also found that donors with number of arteries more than 2 (p < 0.001) and prolonged warm ischemic time (p < 0.05) are more frequently to develop ureteral stenosis post-kidney transplantation. There is no association between type II diabetes mellitus and hypertension with ureteral stenosis in this study. Donor age, recipient age, donor number of arteries more than 2, and prolonged warm ischemia time are associated with ureteral stenosis after kidney transplantation.

Implantation Strategies to Protect the Total Artificial Heart for Subsequent Heart Transplantation

Re-entry into the chest after one or more previous operative interventions can result in prolonged dissection, blood loss, structural damage, and catastrophic injuries, resulting in MOF and even death. Previous implantation of mechanical circulatory assist devices may lead to development of dense adhesions and solid scar tissue. This is certainly true for cases involving previous placement of the total artificial heart (TAH). Implantation of this device is on the rise, as is it is the only viable options for patients with biventricular failure, as the number of heart transplantations is stagnant worldwide. With the new heart transplantation allocation system in the United States, more and more patients with an implanted TAH are waiting for cardiac transplantation. Therefore, patients having an implanted TAH presenting for transplantation are at risk for complications during sternal re-entry or for complications as a result of prolonged ischemic time due to extended times of mediastinal dissection. Thoughtful and preemptive preparation of the surgical field at the time of initial implantation of the TAH has not only the potential, but a proven track record of decreasing operative time, duration of mediastinal dissection as well as risks for complications and adverse events in patients with subsequent heart transplantation. In conclusion, the measures for TAH protection taken at the time of implantation allow for expeditious and safe redo sternotomy, efficient mediastinal dissection, rapid identification and exposure of structures necessary for initiation of cardiopulmonary bypass and finally and importantly expeditious device removal in order to avoid delay in donor organ implantation and prolonged ischemic time.

Factors for Acute Kidney Injury Following Total Arch Replacement and Association with Temperature Management During Cardiopulmonary Bypass: A Single-center Retrospective Observational Study.

Many patients develop acute kidney injury (AKI) after vascular surgery. In this retrospective observational study, we investigated the risk factors for AKI defined using the Kidney Disease Improving Global Outcomes criteria after total arch replacement (TAR). Additionally, we investigated the influence of temperature manage-ment during cardiopulmonary bypass (CPB) on postoperative renal function by propensity score-matched anal-ysis. We retrospectively analyzed 161 consecutive patients who underwent TAR between 2016 and 2019. Postoperative AKI occurred in 48.7% of the patients. In the multivariate analysis, male sex (odds ratio [OR] 3.95, 95% confidence interval [95%CI] 1.56-8.27, p = 0.002), ACE inhibitors/ARB medication (OR 3.19, 95%CI 1.49-6.82, p = 0.003), preoperative chronic kidney disease (OR 2.47, 95%CI 1.17-5.23, p = 0.02), pro-longed CPB time (OR 2.36, 95%CI 1.05-5.34, p = 0.04), and lower body ischemic time during CPB (OR 2.20, 95%CI 1.05-4.46, p = 0.04) were identified as independent risk factors for AKI. Propensity score-matched anal-ysis showed no significant difference in the risk of AKI following TAR between mild hypothermia or normo-thermia and moderate hypothermia (37.2% vs. 41.9%, p = 0.83). In conclusion, modifiable risk factors for AKI included prolonged CPB time and lower body ischemic time. Temperature management during CPB had no clear effect on outcomes.

The preventive effect of sulforaphane on liver injury in a non-heart-beating donor model

Aim: In this preliminary study, we aimed to investigate the effect of sulforaphane (SFN) warm ischemia in a non-heart beat rat liver model (NHBD). Materials and Methods: Livers taken from NHBD 15,30,60 min after warm ischemia were stored up at University of Wisconsin solution for 5 h at 40C [cold storage (CS)] and were, then, exposed to 2 h of machine reperfusion (MRP) at 370C. In the study group, SFN 5 mg/kg was intraperitoneal given 30 min before the introduction of NHB. Firstly, we divided the rats into the control and SFN groups. Then, each group was divided into three groups (n=10 in each) including control I, II, III and SFN I, II, III groups (15-, 30-, and 60-min warm ischemia period, respectively).Control and study groups at the same time of ischemia were compared with each other in terms of lactate, AST, ALT, IL-6, TNF-α and morphologically.Results: In the group treated with SFN, AST, ALT, TNF-α, IL-6, and lactate levels were lower, compared to the control group. Histopathologically, Bcl-2 staining intensity and percentages of staining were statistically significant, compared to the control and study groups during 15-min warm ischemia. Although not statistically significant, the intensity and percentage of staining were higher at 30 min and identical at 60 min. Conclusion: Our study results suggest that, despite prolonged warm ischemia time, SFN can biochemically and morphologically protect the liver from the hazardous effects of ischemia reperfusion in an experimentally-controlled NHB in rats, indicating an increased utilization rate of NHBDs.

1198. Measurement of Pre-transplant Anti-cytomegalovirus (CMV) Immunoglobulin G Titer to Predict Risk of CMV Infection in CMV-seropositive Kidney Transplant Recipients

BackgroundAlthough cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a lower risk of CMV infection compared with CMV-seronegative recipients, some patients remain at risk of CMV infection after transplant. Low pre-transplant anti-CMV immunoglobulin G (IgG) titer has been reported as a predictor of CMV infection in CMV-seropositive liver and heart transplant recipients, but this association in CMV-seropositive kidney transplant (KT) recipients has not been explored. We investigated the pre-transplant anti-CMV IgG titer and other CMV infection risk factors in CMV-seropositive KT recipients.MethodsThis retrospective study was conducted on CMV-seropositive KT recipients aged >18 years old at Ramathibodi Hospital during 2017 and 2018. The cumulative incidence of CMV infection was estimated with Kaplan–Meier methodology. The pre-transplant anti-CMV IgG titer was measured with an enzyme-linked fluorescent immunoassay. Risk factors for CMV infection were analyzed with Cox proportional hazards models.ResultsOf the 340 included CMV-seropositive KT recipients (37% female; age [mean±SD]: 43±11 years), 69% and 64% received deceased-donor allograft and induction therapy, respectively. The anti-CMV IgG titer was < 20 and >20 AU/ml in 7.1% and 92.9% of patients, respectively. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%, including both asymptomatic CMV infection (69%) and tissue-invasive disease (31%). A pre-transplant anti-CMV IgG titer of < 20 AU/ml was significantly associated with CMV infection in both the univariate analysis (HR, 2.70; 95%CI, 1.21–6.05, [p=0.02]) and the multivariate analysis (HR, 2.98; 95% CI, 1.31–6.77, [p=0.009]). Other significant risk factors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06, [p=0.005]), anti-thymocyte induction therapy (HR, 2.90; 95% CI 1.09–7.74, [p=0.033]), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10, [p=0.002]).ConclusionA low pre-transplant CMV-specific humoral immunity is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. The universally available anti-CMV IgG titer test could potentially stratify those at risk and target preventive strategy appropriately.Disclosures All Authors: No reported disclosures

Early Graft Loss after Deceased-Donor Kidney Transplantation: What Are the Consequences?

Decreasing kidney discards continues to be of paramount importance for improving organ transplant access, but transplantation of nonideal deceased donor kidneys may have higher inherent risks of early graft loss (EGL). Patients with EGL (defined as graft failure within 90 days after transplant) are allowed reinstatement of waiting time according to United Network for Organ Sharing (UNOS) policy. The purpose of this study was to examine outcomes for patients experiencing EGL. We performed a single center retrospective review of adult deceased donor kidney transplant (DDKT)-alone recipients from 2001 to 2018, comparing those with EGL (including primary nonfunction [PNF]) to those without. EGL occurred in 103 (5.5%) of 1,868 patients, including 57 (55%) PNF, 25 (24%) deaths, 16 (16%) thrombosis, 3 (3%) rejection, and 2 (2%) disease recurrence. Kidney Donor Profile Index (KDPI) > 85% and donation after circulatory death (DCD) DDKTs did not increase risk of either EGL or PNF unless combined with prolonged cold ischemic time (CIT). For KDPI >85% with CIT >24 hours, the risk of EGL or PNF was tripled (EGL odds ratio [OR] 2.9, 95% CI 1.6-5.2; PNF OR3.6, 95% CI1.7-7.7). For DCD with CIT > 24 hours, increased risks were likewise seen for EGL (OR 2.4, 95% CI 1.3-4.3), and PNF (OR 3.2, 95% CI 1.5-7). One-year and 5-year patient survival rates were 60% and 50% after EGL, 80% and 73% after PNF, and 99% and 87% for controls, respectively. Only 24% of either EGL or PNF patients underwent retransplantation. EGL and PNF were associated with low retransplantation rates and inferior patient survival. Prolonged CIT compounds risks associated with KDPI > 85% and DCD donor kidneys. Therefore, policies promoting rapid allocation and increased local use of these kidneys should be considered.

Commentary: Right ventricular dysfunction after cardiac surgery: Machine learning to teach us what we already know?

Most pharmacologic and technologic advances over the past decades to address heart failure have focused on the left ventricle, while allowing the right ventricle (RV) to be a passive bystander. However, most surgeons who perform complex cardiovascular surgery with prolonged ischemic times have been humbled time and again by RV dysfunction postcardiotomy. Despite improvements in myocardial protection, RV failure, when it occurs, carries significant morbidity1,2 and is a feared complication after cardiac surgery.

Abstract 15874: An Ischaemia Time of Greater Than 6 Hours is Associated With Deleterious Outcomes in Pediatric Heart Transplantation

Introduction: The shortage of available donor organs means we must re-consider our current policies on donor selection. There is a broad variation in practice between centers as to the acceptable limit to ischaemia time (IT) in pediatric cardiac transplantation, with no recommendations in international guidelines. Hypothesis: We hypothesised that a prolonged ischaemia time was not associated with impaired post-transplant outcomes. Methods: Data from the Pediatric Heart Transplantation Society was analysed for all pediatric patients receiving heart transplants (Jan 1993 - June 2019). Transplants were separated into 5 categories depending on the IT (hours): &lt; 2.4, 2.5-3.4, 3.5-4.4, 4.5-6.0, &gt;6. Risk-adjusted outcomes were assessed by multivariable analysis, adjusting for donor, recipient, and peri-operative characteristics. Results: Data for 6,903 transplants were assessed (IT &lt; 2.4 in 980, 2.5-3.4 in 2032, 3.5-4.4 in 2310, 4.5-6.0 in 1162, &gt;6 in 281). In univariate analysis, increasing IT was associated with reduced 1-year survival (90.1%, 87.7% and 84.6%; p&lt;0.001) for the 3.5-4.4, 4.5-6.0 and &gt;6 groups, respectively. Similar findings, of a deleterious association with prolonged IT, were observed for freedom from infection (73.0%, 66.8% and 56.4%; p&lt;0.001), freedom from first rejection (67.4%, 62.6% and 61.0%; p = 0.01) and freedom from haemodynamically compromising rejection (89.1%, 85.4% and 85.3%; p=0.004) at 1-year. No significant differences in the risk of malignancy (p=0.2) and time to first CAV (p=0.08) between the IT groups were noted. We separately analysed the risk of graft failure by multiphase hazards modelling. In adjusted analysis, increasing IT was found to be a risk factor for graft failure (HR: 1.08, 95% CI: 1.00-1.16, p=0.04). Within this model, primary diagnosis was a predictor of the outcome (p&lt;0.001). Exploring this association, an IT of &gt; 6 hours was associated with graft failure in cardiomyopathy (HR: 2.87, 95% CI: 1.34 - 6.15, p=0.007), but not congenital heart disease patients. Conclusions: In this large multi-centre cohort study, we found a deleterious association between prolonged IT and post-transplant outcomes. We recommend that an IT greater than 6 hours should be avoided in pediatric cardiac transplantation.

Abstract 12932: The ABO Blood Group of Donor Hearts Determine the Impact of Cold Preservation Duration on Heart Transplant Outcomes

Background: Tolerance of donor hearts of different ABO blood types to allograft ischemic time has not been previously examined. Objectives: We determined the impact of allograft ischemic time on heart transplant outcomes with differing ABO donor organ types. Methods: We identified 32,454 heart transplants (2000-2016) from the United Network for Organ Sharing database. Continuous variables were analyzed with t-test and categorical variables were compared with Chi-squared test. Survival was determined using log-rank or Cox regression tests. Propensity matching adjusted for preoperative variables. Results: Comparing allograft ischemic times &lt;4 hours (hr, n=6579) versus ≥4hr (n=25,875), the odds ratio (OR) for death at 15 years following prolonged allograft ischemic time (≥4hrs) for blood type O, A, B, and AB were 1.106 (P&lt;0.001), 1.062 (P&lt;0.001), 1.059 (P=0.062), 1.114 (P=0.221), respectively. Unadjusted data demonstrated higher mortality for transplantation of O versus non-O donor hearts for allograft ischemic times ≥4 hours (OR=1.164, P&lt;0.001). Following propensity matching, O donor hearts continued to have worse survival if preserved for ≥4hrs (OR=1.137, P=0.008), but not if allograft ischemic time was &lt;4hrs (OR=1.042, P=0.113). In a matched group with ≥4hrs of allograft ischemic time, patients receiving O donor organs were more likely to experience death from primary allograft dysfunction (2.5% vs 1.7%, P=0.052) and chronic allograft rejection (1.9% versus 1.1%, P=0.021). No difference in death from primary allograft graft dysfunction or chronic allograft rejection was seen with &lt;4hr of allograft ischemic time (P&gt;0.150). Conclusions: Compared with non-O hearts, transplantation with O donor hearts stored for ≥4hrs leads to worse survival, with higher rates of primary graft dysfunction and chronic rejection. Caution should be practiced when considering donor hearts with the O blood type when extended cold preservation times are anticipated.

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

In Italy, 20minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n=1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n=9, 26.5%), or severe macroangiopathy at back-table evaluation (n=1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

Predictive factors of a prolonged total ischemic time in patients presenting with ST-segment elevation myocardial infarction

Abstract Introduction Total ischemic time (TIT), the time from symptom onset to therapeutic reperfusion of infarcted myocardium is a key factor in the treatment of patients with ST-segment elevation myocardial infarction (STEMI). The identification of the predictive factors of a prolonged TIT will allow design specific strategies to optimize this time and improve the quality of care of these patients. Our objective was to evaluate independent factors predicting prolonged TIT. Methods We performed a prospective observational study, with consecutive inclusion of all patients presenting within 24 hours of symptom onset of STEMI (n=546), transferred to our center for primary percutaneous coronary intervention (pPCI). Results The median TIT was 190 (137–281) minutes. No significant differences were found according to the year of study. In the univariate analysis, age showed a slight trend (p=0.05); for each year that is increased, the TTI increases 1.3 minutes. Women had higher TII than men [219 (145–332) vs. 187 (133–270) minutes; p=0.02]. No statistically significant differences were found in relation to the presence of cardiovascular risk factors. Patients treated during non-working hours had shorter TIT than those treated during working hours [179 (130–252) vs. 202 (142–307) minutes; p=0.03]. The distance to a 24h-PCI hospital was an independent predictive factor. Those patients whose first medical contact (FMC) was in a non-PCI-capable hospital or in a clinic showed the highest TIT [226 (147–336) and 205 (146–304) minutes, respectively; p&amp;lt;0.001]. Patients with initial non-diagnostic ECG presented a significantly longer TIT (p&amp;lt;0.001) than patients correctly diagnosed since the beginning, with a median difference of 188 minutes. A trend was observed for the Killip-Kimball classification variable (p=0.07). Patients with previous infarction had shorter TIT compared to those who have never had it (p=0.02). In the multivariate binary logistic regression analysis, the variables: initial non-diagnostic ECG, FMC (in a non-PCI-capable hospital or clinic) and the distance to 24h-PCI hospital (&amp;gt;90 km) were independent predictive factors of a TIT &amp;gt;180 minutes. An initial non-diagnostic or misinterpreted ECG sextuples the risk of a prolonged TIT. Conclusions In our area, the total ischemic time is determined by a non-diagnostic or misinterpreted EKG, the first medical contact and the distance to a 24h-PCI hospital. Funding Acknowledgement Type of funding source: None

Increased Succinate Accumulation Induces ROS Generation in In Vivo Ischemia/Reperfusion-Affected Rat Kidney Mitochondria.

Mitochondria are recognized as main reactive oxygen species (ROS) producers, involving ROS generation by mitochondrial complexes I and III. Lately, the focus has been shifting to the ROS generation by complex II. Contribution of complex II (SDH) to ROS generation still remains debatable, especially in in vivo settings. Moreover, it is not completely defined at what time of ischemia the first alterations in mitochondria and the cell begin, which is especially important with renal arterial clamping in vivo during kidney surgery, as it predicts the postischemic kidney function. The aim of this study on an in vivo rat kidney ischemia/reperfusion model was to determine if there is a connection among (a) duration of kidney ischemia and mitochondrial dysfunction and (b) succinate dehydrogenase activity, succinate accumulation, and ROS generation in mitochondria at low and saturating succinate concentrations. Our results point out that (1) mitochondrial disturbances can occur even after 30 min of kidney ischemia/reperfusion in vivo and increase progressively with the prolonged time of ischemia; (2) accumulation of succinate in cytosol after ischemia/reperfusion correlated with increased H2O2 generation mediated by complex II, which was most noticeable with physiological succinate concentrations; and (3) ischemia/reperfusion induced cell necrosis, indicated by the changes in LDH activity. In conclusion, our new findings on the accumulation of succinate in cytosol and changes in SDH activity during kidney ischemia/reperfusion may be important for energy production after reperfusion, when complex I activity is suppressed. On the other hand, an increased activity of succinate dehydrogenase is associated with the increased ROS generation, especially with physiological succinate concentrations. All these observations play an important role in understanding the mechanisms which occur in the early phase of ischemia/reperfusion injury in vivo and may provide new ideas for novel therapeutic approaches or injury prevention; therefore, more detailed studies are necessary in the future.

The Effect of Supplemental Cardioplegia Infusion before Anastomosis in Patients Undergoing Heart Transplantation with Long Ischemic Times.

BackgroundProlonged ischemic time is a risk factor for primary graft dysfunction in patients who undergo heart transplantation. We investigated the effect of a supplemental cardioplegia infusion before anastomosis in patients with long ischemic times.MethodsWe identified 236 consecutive patients who underwent orthotopic heart transplantation between February 2010 and December 2014. Among them, the patients with total ischemic times of longer than 3 hours (n=59) were categorized based on whether they were administered a complementary cardioplegia solution (CPS) immediately before implantation (CPS+, n=30; CPS−, n=29).ResultsThe mean total ischemic times in the CPS+ and CPS− groups were 238.1±30.1 minutes and 230.1±28.2 minutes, respectively (p=0.3). The incidence of left ventricular primary graft dysfunction (CPS+, n=6 [20.0%]; CPS−, n=5 [17.2%]; p=0.79) was comparable between the groups. In the Kaplan-Meier survival analysis, no significant difference in overall survival at 5 years was observed between the CPS+ and CPS− groups (83.1%±6.9% vs. 89.7%±5.7%, respectively; log-rank p=0.7). No inter-group differences in early mortality (CPS+, n=0; CPS−, n=1 [3.4%]; p=0.98) or complications were observed.ConclusionThe additional infusion of a cardioplegia solution immediately before implantation in patients with longer ischemic times is a simple, reproducible, and safe procedure. However, we did not observe benefits of this strategy in the present study.