Is Time Scheduling Important? An Analysis of Donor Heart Cross-clamp Times During Heart Transplantation.

Background: Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. Methods: A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results: Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P < 0.001). On unadjusted analysis, the survival difference among the 5 groups was insignificant (P = 0.07). Following adjustment, the periods of 11 am to 5 pm (HR: 1.09, 95% CI, 1.02-1.17; P = 0.012), 5 pm to 10 pm (HR: 1.11; 95% CI, 1.04-1.19; P = 0.002), and 10 pm to 4 am (HR: 1.07; 95% CI, 1.01-1.15; P = 0.034), were all independently associated with increased long-term mortality. Notably, the time of 8 am to 11 am was not associated with a change in survival (HR: 1.04; 95% CI, 0.96-1.14; P = 0.3). Conclusions: Given the independent association of donor timing and survival after adjustment in a large national cohort, further investigation into the role of donor circadian rhythm and donor procurement time is warranted in preclinical and clinical studies. Understanding the underlying mechanisms of this observation could potentially lead to the development of effective treatments and donor procurement processes that prepare the organs for transplantation in a better condition.

Does Size Matter? The Effect of Size of Distal Perfusion Catheter on Acute Limb Ischemia: A Meta-Analysis.

Prevention of limb ischemia in patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is primarily achieved through the use of distal perfusion catheters (DPC). Our objective was to assess the role of DPC, and specifically the size of the catheter, in reducing the incidence of acute limb ischemia (ALI) through a meta-analysis. Seventeen studies met criteria for analysis. Pooled analysis included a total of 2,040 patients, of which 904 patients received ECMO with DPC and 1,136 patients underwent ECMO without DPC. Compared with ECMO alone, ECMO with DPC, regardless of size, significantly decreased ALI (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.31-0.77; p = 0.002). When comparing reactive versus prophylactic placement of DPC, prophylactic DPC was associated with significantly decreased ALI (RR: 0.41, 95% CI: 0.24-0.71; p = 0.02). No differences in mortality (RR: 0.89, 95% CI: 0.76-1.03; p = 0.12) and bleeding events (RR: 1.43, 95% CI: 0.41-4.96; p = 0.58) were observed between the two groups. This analysis demonstrates that the placement of DPC, if done prophylactically and regardless of size, is associated with a reduced risk of ALI versus the absence of DPC placement, but is not associated with differences in mortality or bleeding events.

One Year Outcomes Following Transplantation with COVID-19-Positive Donor Hearts: A National Database Cohort Study.

The current understanding of the safety of heart transplantation from COVID-19+ donors is uncertain. Preliminary studies suggest that heart transplants from these donors may be feasible. We analyzed 1-year outcomes in COVID-19+ donor heart recipients using 1:3 propensity matching. The OPTN database was queried for adult heart transplant recipients between 1 January 2020 and 30 September 2022. COVID-19+ donors were defined as those who tested positive on NATs or antigen tests within 21 days prior to procurement. Multiorgan transplants, retransplants, donors without COVID-19 testing, and recipients allocated under the old heart allocation system were excluded. A total of 7211 heart transplant recipients met the inclusion criteria, including 316 COVID-19+ donor heart recipients. Further, 290 COVID-19+ donor heart recipients were matched to 870 COVID-19- donor heart recipients. Survival was similar between the groups at 30 days (p = 0.46), 6 months (p = 0.17), and 1 year (p = 0.07). Recipients from COVID-19+ donors in the matched cohort were less likely to experience postoperative acute rejection prior to discharge (p = 0.01). National COVID-19+ donor heart usage varied by region: region 11 transplanted the most COVID-19+ hearts (15.8%), and region 6 transplanted the fewest (3.2%). Our findings indicate that COVID-19+ heart transplantation can be performed with safe early outcomes. Further analyses are needed to determine if long-term outcomes are equivalent between groups.

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation.

INTRODUCTION: Primary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. METHODS: LT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. RESULTS: The PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. CONCLUSIONS: While PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Textbook outcome: A novel metric in heart transplantation outcomes.

OBJECTIVE: Assessing heart transplant program quality using short-term survival is insufficient. We define and validate the composite metric textbook outcome and examine its association with overall survival. METHODS: We identified all primary, isolated adult heart transplants in the United Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files from May 1, 2005, to December 31, 2017. Textbook outcome was defined as length of stay 30 days or less; ejection fraction greater than 50% during 1-year follow-up; functional status 80% to 100% at 1 year; freedom from acute rejection, dialysis, and stroke during the index hospitalization; and freedom from graft failure, dialysis, rejection, retransplantation, and mortality during the first year post-transplant. Univariate and multivariate analyses were performed. Factors independently associated with textbook outcome were used to create a predictive nomogram. Conditional survival at 1 year was measured. RESULTS: A total of 24,620 patients were identified with 11,169 (45.4%, 95% confidence interval, 44.7-46.0) experiencing textbook outcome. Patients with textbook outcome were more likely free from preoperative mechanical support (odds ratio, 3.504, 95% confidence interval, 2.766 to 4.439, P < .001), free from preoperative dialysis (odds ratio, 2.295, 95% confidence interval, 1.868-2.819, P < .001), to be not hospitalized (odds ratio, 1.264, 95% confidence interval, 1.183-1.349, P < .001), to be nondiabetic (odds ratio, 1.187, 95% confidence interval, 1.113-1.266, P < .001), and to be nonsmokers (odds ratio, 1.160, 95% confidence interval,1.097-1.228, P < .001). Patients with textbook outcome have improved long-term survival relative to patients without textbook outcome who survive at least 1 year (hazard ratio for death, 0.547, 95% confidence interval, 0.504-0.593, P < .001). CONCLUSIONS: Textbook outcome is an alternative means of examining heart transplant outcomes and is associated with long-term survival. The use of textbook outcome as an adjunctive metric provides a holistic view of patient and center outcomes.

Pulmonary Histoplasmosis Complicated by Nonvalvular Right Ventricular Wall Histoplasma capsulatum Endocarditis.

Histoplasmosis is commonly a self-limited fungal disease that primarily affects the lung and reticuloendothelial system. Cardiac involvement by histoplasmosis is uncommon. In this report, we provide a detailed description of severe pulmonary histoplasmosis complicated by the disease involvement of the free wall of the right ventricle. A 55-year-old female presented with cough, fevers, dyspnea, and 30-pound unintentional weight loss in 6 months. Her past medical history was significant for supraventricular tachycardia with permanent pacemaker implantation. Imaging studies revealed an intracardiac mass accompanied by mediastinal lymphadenopathy and bilateral lung nodules. Endobronchial ultrasound-guided transbronchial needle aspiration of station 4R lymph nodes revealed numerous yeast forms, morphologically consistent with Histoplasma capsulatum. The diagnosis was further corroborated by the elevated titers of serum antibodies against Histoplasma capsulatum. The right ventricular mass debulking with biopsy showed necrotizing granulomatous inflammation involving nonvalvular endocardium and myocardium of the free wall of the right ventricle. The report documents an unusual presentation of pulmonary histoplasmosis accompanied by nonvalvular endocarditis and suggests a possible association between the site of the cardiac infection and the presence of a permanent intravascular pacer device.

XPS™ Jensen lung as a low-cost, high-fidelity training adjunct to ex-vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) enables lung resuscitation before transplantation, and training is key, particularly in low-volume settings. To enable technique refinement and continuing education, we sought to demonstrate the value of a low-cost, high-fidelity EVLP simulator that would allow reproducible clinical scenarios. METHODS: In partnership with our EVLP manufacturer, we utilized the XPS™ Jensen Lung with our clinical system. The Jensen Lung has two simulated lung bladders and an in-line polymethylpentene fiber oxygenator. It allows titration of ventilator support which aids in accurate clinical simulation. For simulations, blood gases (BGs) were obtained and compared with integrated in-line perfusate gas monitors (PGMs). PaO2 , PCO2 , and pH were measured and compared. RESULTS: The PGM and BG values were not significantly different throughout the range of FiO2 and sweep gas flow rates evaluated. The "delta" PaO2 was measured between LA and PA and did not show any change between approaches. The pH measurement between BG and PGM was not significantly different. CONCLUSIONS: The XPS™ Jensen Lung simulator allows for a high-fidelity simulator of clinical EVLP. The correlation of the PGM and the BG measurement of the PaO2 and pH allow for a low-cost simulation, as the PGMs are in line in the circuit, and enable real-time tracking of perfusate gas parameters with the PGM. Implementation of a standardized clinical EVLP training program allows the maintenance of technique and enables clinical simulation training without the need for costly animal perfusions and the use of multiple BG measurements.

Is Transplantation With Coronavirus Disease 2019-Positive Donor Lungs Safe? A US Nationwide Analysis.

BACKGROUND: Since the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has caused debilitating lung failure in many patients. Practitioners have understandably been hesitant to use lungs from donors with COVID-19 for transplantation. This study aimed to analyze the characteristics and short-term outcomes of lung transplantation from donors with recent positive COVID-19 testing results. METHODS: Lung transplantations performed between January 2020 and June 2022 were queried from the United Network for Organ Sharing database. Pediatric, multiorgan, and repeat lung transplantations were excluded. Propensity scoring matched recipients of lungs from donors with recent positive COVID-19 testing results to recipients of lungs from donors with negative COVID-19 testing results, and comparisons of 30-day mortality, 3-month mortality, and perioperative outcomes were performed. RESULTS: A total of 5270 patients underwent lung transplantation during the study dates, including 51 patients who received lungs from donors with recent positive COVID-19 testing results. Forty-five recipients of lungs from donors with recent positive COVID-19 testing results were matched with 135 recipients of lungs from donors with negative COVID-19 testing results. After matching, there was no difference in 30-day (log-rank P = .42) and 3-month (log-rank P = .42) mortality. The incidence of other perioperative complications was similar between the groups. CONCLUSIONS: The 30-day and 3-month survival outcomes were similar between recipients of lungs from donors with recent positive COVID-19 testing results and recipients of lungs from donors with negative COVID-19 testing results. This finding suggests that highly selected COVID-19-positive donors without evidence of active infection may be safely considered for lung transplantation. Further studies should explore long-term outcomes to provide reassurance about the safety of this practice.

Prevalence of Violence against Providers in Heart and Lung Transplant Programs.

Workplace violence in healthcare institutions is becoming more frequent. The objective of this study was to better understand the nature of threat and physical acts of violence from heart and lung transplant patients and families toward healthcare providers and suggest programmatic mitigation strategies. We administered a brief survey to attendees at the 2022 International Society of Heart and Lung Transplantation Conference in Boston, Massachusetts. A total of 108 participants responded. Threats of physical violence were reported by forty-five participants (42%), were more frequently reported by nurses and advanced practice providers than physicians (67% and 75% vs. 34%; p < 0.001) and were more prevalent in the United States than abroad (49% vs. 21%; p = 0.026). Acts of physical violence were reported by one out of every eight providers. Violence against providers in transplant programs warrants closer review by health systems in order to ensure the safety of team members.

Donor and Recipient Hepatitis C Status Does Not Affect Rejection in Thoracic Transplantation.

BACKGROUND: Donors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients. METHODS: Adults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor-recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used. RESULTS: Meeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41). CONCLUSIONS: Use of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection.

Impact of Temporary Preoperative Mechanical Support on Heart Transplant Outcomes.

We sought to assess the impact of temporary preoperative mechanical circulatory support (TPMCS) on heart transplantation outcomes. A total of 4,060 adult heart transplants from June 1, 2006, to December 31, 2019, were identified in the Scientific Registry of Transplant Recipients database as having TPMCS. Recipients were divided into groups based on their type of TPMCS: intra-aortic balloon pump (IABP), temporary ventricular assist device (VAD), biventricular assist device (BIVAD), and extracorporeal membrane oxygenation (ECMO). Perioperative outcomes and survival were compared among groups. Recipients with IABP were associated with older age, a smoking history, and a significantly shorter wait list time ( p < 0.01). Recipients with ECMO had a significantly increased in-hospital mortality as well as an increased incidence of dialysis ( p < 0.01). Kaplan-Meier analysis revealed worse 1 and 5 year survival for recipients with ECMO. Cox model demonstrated a significantly increased risk of mortality with BIVAD (hazard ratio [HR], 1.33; 95% CI, 1.12-1.57; p < 0.01) and ECMO (HR, 1.64; 95% CI, 1.33-2.03; p < 0.01). While patients with IABP have a survival comparable to patients without TPMCS or durable left VAD, outcomes for BIVADs and ECMO are not as favorable. Transplantation centers must continue to make careful choices about the type of TPMCS utilized before heart transplant.

Allocation changes in heart transplantation: What has really changed?

OBJECTIVE: In 2018, the heart allocation system changed status classifications and broadened geographic distribution. We examined this change at a national level based on the immediate pre- and postchange periods. METHODS: Using the Scientific Registry of Transplant Recipients database, we identified all adult primary, isolated heart transplants from October 18, 2017, to October 17, 2019. Two time periods were compared: (1) October 18, 2017, to October 17, 2018 (pre); and (2) October 18, 2018, to October 17, 2019 (post). Comparisons were made between groups, and a multivariable logistic regression model was created to identify factors associated with pretransplant temporary mechanical circulatory support. Volume analysis at the regional, state, and center level was also conducted as the primary focus. RESULTS: A total of 5381 independent heart transplants were identified within the time frame. On unadjusted analysis, there was a significant increase in temporary mechanical circulatory support (pre, 11.1%; post, 36.2%, P < .01) and decrease in waitlist days (pre, 93 days; post, 41 days; P < .01). Distance traveled (nautical miles) (pre, 83; post, 225; P < .01) and ischemic time (hours) (pre, 3.0; post, 3.4; P < .01) were significantly increased. On multivariable analysis, the postallocation time period was independently associated with temporary MCS (odds ratio, 4.463; 95% confidence interval, 3.844-5.183; P < .001). Transplant volumes did not significantly change after the allocation change at a regional, state, and center level. CONCLUSIONS: Since the planned alteration to the allocation system, there have been changes in the use of temporary mechanical circulatory support as well as distance and ischemic time associated with transplant, but no significant volume changes were observed. Continued observation of outcomes and volume under the new allocation system will be necessary in the upcoming years.

Thoracic retransplantation: Does time to retransplantation matter?

OBJECTIVE: For some individuals, chronic allograft failure is best treated with retransplantation. We sought to determine if time to retransplantation impacts short- and long-term outcomes for heart or lung retransplant recipients with a time to retransplantation more than 1 year. METHODS: The United Network for Organ Sharing/Organ Procurement and Transplantation Network STAR file was queried for all adult, first-time heart (June 1, 2006, to September 30, 2020) and lung (May 1, 2005, to September 30, 2020) retransplantations with a time to retransplantation of at least 1 year. Patients were grouped according to the tertile of time to retransplantation (tertile 1: 1-7.7 years, tertile 2: 7.7-14.7 years, tertile 3: 14.7+ years; lung: tertile 1: 1-2.8 years, tertile 2: 2.8-5.6 years, tertile 3: 5.6+ years). The primary outcome was survival after retransplantation. Comparative statistics identified differences in groups, and Kaplan-Meier methods and a Cox proportional hazard model were used for survival analysis. RESULTS: After selection, 908 heart and 871 lung retransplants were identified. Among heart retransplant recipients, tertile 1 was associated with male sex, smoking history, higher listing status, and increased mechanical support pretransplant. Tertile 3 had the highest rate of concomitant kidney transplant; however, the incidence of morbidity and in-hospital mortality was similar among the groups. Unadjusted and adjusted analyses revealed no survival difference among all groups. Regarding lung retransplant recipients, tertile 1 was associated with increased lung allocation score, pretransplant hospitalization, and mechanical support. Unadjusted and adjusted survival analyses revealed decreased survival in tertile 1. CONCLUSIONS: Time to retransplant does not appear to affect heart recipients with a time to retransplantation of more than 1 year; however, shorter time to retransplantation for prior lung recipients is associated with decreased survival. Potential lung retransplant candidates with a time to retransplantation of less than 2.8 years should be carefully evaluated before retransplantation.

Disparities in heart transplantation.

PURPOSE OF REVIEW: Heart transplantation remains the gold standard therapy for end stage heart failure, but barriers remain, preventing equitable access to and affecting outcomes following transplantation. The objective of this review is to summarize current and historical literature on the disparities that persist, and to highlight the gaps in evidence for further investigation. RECENT FINDINGS: Although progress has been made to increase the rates of advanced heart failure therapies to racial/ethnic minority populations and those with lower socioeconomic status, differential access and outcomes remain. The disparities that persist are categorized by patient demographics, social influences, geopolitical factors, and provider bias. SUMMARY: Disparities in heart transplantation exist, which span a wide spectrum. Healthcare professionals need to be cognizant of these disparities that patients face in terms of access to and outcomes for heart transplantation. Further research and system changes are needed to make heart transplantation a fairer option for patients of varying backgrounds with end stage heart failure.