Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Cardiogenic Shock in Older Adults: A Focus on Age-Associated Risks and Approach to Management: A Scientific Statement From the American Heart Association.

Cardiogenic shock continues to portend poor outcomes, conferring short-term mortality rates of 30% to 50% despite recent scientific advances. Age is a nonmodifiable risk factor for mortality in patients with cardiogenic shock and is often considered in the decision-making process for eligibility for various therapies. Older adults have been largely excluded from analyses of therapeutic options in patients with cardiogenic shock. As a result, despite the association of advanced age with worse outcomes, focused strategies in the assessment and management of cardiogenic shock in this high-risk and growing population are lacking. Individual programs oftentimes develop upper age limits for various interventional strategies for their patients, including heart transplantation and durable left ventricular assist devices. However, age as a lone parameter should not be used to guide individual patient management decisions in cardiogenic shock. In the assessment of risk in older adults with cardiogenic shock, a comprehensive, interdisciplinary approach is central to developing best practices. In this American Heart Association scientific statement, we aim to summarize our contemporary understanding of the epidemiology, risk assessment, and in-hospital approach to management of cardiogenic shock, with a unique focus on older adults.

Prognostic Implications of Quantifying Vasoactive Medications in Cardiogenic Shock.

None.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Beyond Stage C: Considerations in the Management of Patients With Heart Failure Progression and Gaps in Evidence.

Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced "beyond stage C" HF.

Donation after circulatory determination of death in heart transplant: impact on current and future allocation policy.

PURPOSE OF REVIEW: Historically, the selection criteria for heart transplant candidates has prioritized posttransplant survival while contemporary allocation policy is focused on improving waitlist survival. Donor scarcity has continued to be the major influence on transplant allocation policy. This review will address the opportunity of donation after circulatory determination of death (DCDD) and potential impact on future policy revisions. RECENT FINDINGS: In 2018, changes to U.S. heart allocation policy led to several intended and unintended consequences. Beneficial changes include reduced waitlist mortality and broader geographic sharing. Additional impacts include scarcer pathways to transplant for patients with a durable left ventricular assist device, increased reliance on status exceptions, and expanded use of temporary mechanical support. DCDD is anticipated to increase national heart transplant volumes by ∼30% and will impact waitlist management. Centers that offer DCDD procurement will have reduced waitlist times, reduced waitlist mortality, and higher transplant volumes. SUMMARY: While DCDD will provide more transplant opportunities, donor organ scarcity will persist and influence allocation policies. Differential patient selection, waitlist strategy, and outcome expectations may indicate that allocation is adjusted based on the procurement options at individual centers. Future policy, which will consider posttransplant outcomes, may reflect that different procurement strategies may yield different outcomes.

Towards Allograft Longevity: Leveraging Omics Technologies to Improve Heart Transplant Outcomes.

PURPOSE OF REVIEW: Heart transplantation (HT) remains the optimal therapy for patients living with end-stage heart disease. Despite recent improvements in peri-transplant management, the median survival after HT has remained relatively static, and complications of HT, including infection, rejection, and allograft dysfunction, continue to impact quality of life and long-term survival. RECENT FINDINGS: Omics technologies are becoming increasingly accessible and can identify novel biomarkers for, and reveal the underlying biology of, several disease states. While some technologies, such as gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), are routinely used in the clinical care of HT recipients, a number of emerging platforms, including pharmacogenomics, proteomics, and metabolomics, hold great potential for identifying biomarkers to aid in the diagnosis and management of post-transplant complications. Omics-based assays can improve patient and allograft longevity by facilitating a personalized and precision approach to post-HT care. The following article is a contemporary review of the current and future opportunities to leverage omics technologies, including genomics, transcriptomics, proteomics, and metabolomics in the field of HT.

Proceedings from the metrics forum in heart transplantation for performance monitoring.

Regulatory oversight for heart transplant programs is currently under review by the United Network for Organ Sharing (UNOS). There is concern whether 1-year patient and graft survival truly represent heart transplant center performance. Thus, a forum was organized by the Thoracic and Critical Care Community of Practice (TCC COP) of the American Society of Transplantation (AST) for the heart transplant community to voice their opinions on matters involving program performance monitoring by UNOS. A TCC COP work group was formed to review outcome metrics for adult heart transplantation and culminated in a virtual community forum (72 participants representing 61 heart transplant programs) on November 12-13, 2020. One-year posttransplant survival is still considered an appropriate and important measure to assess program performance. Waitlist mortality and offer acceptance rate as pretransplant metrics could also be useful measures of program performance, recognizing that outside factors may influence these metrics. In depth discussion of these metrics and other issues including auditing thresholds, innovations to reduce risk-averse behavior and personally designed program scorecards are included in this meeting proceedings.

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Increased Opportunities for Transplantation for Women in the New Heart Allocation System.

BACKGROUND: Historically, women have had less access to advanced heart failure therapies, including temporary and permanent mechanical circulatory support and heart transplantation (HT), with worse waitlist and post-transplant survival compared with men. This study evaluated for improvement in sex differences across all phases of HT in the 2018 allocation system. METHODS AND RESULTS: The United Network for Organ Sharing registry was queried to identify adult patients (≥18 years) listed for HT from October 18, 2016, to October 17, 2018 (old allocation), and from October 18, 2018, to October 18, 2020 (new allocation). The outcomes of interest included waitlist survival, pretransplant use of temporary and durable mechanical circulatory support, rates of HT, and post-transplant survival. There were 15,629 patients who were listed for HT and included in this analysis; 7745 (2039 women, 26.3%) in the new and 7875 patients (2074 women, 26.3%) in the old allocation system. When compared with men in the new allocation system, women were more likely to have lower priority United Network for Organ Sharing status at time of transplant, and less likely to be supported by an intra-aortic balloon pump (27.1% vs 32.2%, P < .001), with no difference in the use of venoarterial extracorporeal membrane oxygenation (5.5% vs 6.3%, P = .28). Despite these findings, when transplantation was viewed in the context of risk for death or delisting, the cumulative incidence of transplant within 6 months of listing was higher in women than men in the new allocation system (62.4% vs 54.9%, P < .001) with no differences in post-transplant survival. When comparing women in the old with the new allocation system, the distance traveled for organ procurement was 187.5 ± 207.0 miles vs 272.8 ± 233.7 miles (P < .001). CONCLUSIONS: Although the use of temporary mechanical circulatory support in women remains lower than in men in the new allocation system, more women are being transplanted with comparable waitlist and post-transplant outcomes as men. Broader sharing may be making its greatest impact on improving transplant opportunities for women.

Impact of UNOS allocation policy changes on utilization and outcomes of patients bridged to heart transplant with intra-aortic balloon pump.

OBJECTIVE: Intra-aortic balloon pump (IABP) support may improve the hemodynamic profiles of patients in cardiogenic shock and bridge patients to heart transplant. In 2018, the United Network for Organ Sharing (UNOS) introduced new heart allocation criteria that increased the waitlist status of patients with IABPs to Status 2. This study assesses the impact of this change on IABP use and outcomes of patients with IABPs. METHODS: We queried the UNOS database for first adult heart transplant candidates with IABPs listed or transplanted before and after the UNOS policy changes (October 18, 2016-October 17, 2018, or October 18, 2018-September 4, 2020). We compared post-transplant survival and waitlist outcomes using Kaplan-Meier and Fine-Gray analyses. RESULTS: Two thousand three hundred fifty-eight patients met inclusion criteria. Utilization of IABPs for hemodynamic support increased by 338% in the two years after the policy change. Patients with IABPs listed after the policy change were more likely to receive a transplant and were transplanted more quickly (p < .001). Posttransplant survival was comparable before and after the policy change (p = .056), but non-transplanted patients were more likely to be delisted post-policy change (p < .001). CONCLUSION: The UNOS allocation criteria have benefited patients bridged with an IABP, given the higher transplant rate and shorter time to transplant.

Deep vein thrombosis and pulmonary embolism after heart transplantation.

INTRODUCTION: Venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in-hospital VTE after heart transplantation and its association with clinical outcomes. METHOD: Adult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post-transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies. RESULTS: There were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60-days of post heart transplant. Patients with VTE had longer hospital stay (P < .001), higher in-hospital mortality (P = .010), and worse 5-year survival (P = .009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE. CONCLUSION: The incidence of VTE in heart transplant recipients is high. Post-transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted.

Impact of socioeconomic deprivation on evaluation for heart transplantation at an urban academic medical center.

INTRODUCTION: For patients with advanced heart failure, socioeconomic deprivation may impede referral for heart transplantation (HT). We examined the association of socioeconomic deprivation with listing among patients evaluated at our institution and compared this against the backdrop of our local community. METHODS: We conducted a retrospective cohort study of patients evaluated for HT between January 2017 and December 2020. Patient demographics and clinical characteristics were recorded. Block group-level area deprivation index (ADI) decile was obtained at each patient's home address and Socioeconomic Status (SES) index was determined by patient zip code. RESULTS: In total, 400 evaluations were initiated; one international patient was excluded. Among this population, 111 (27.8%) were women, 219 (54.9%) were White, 94 (23.6%) Black, and 59 (14.8%) Hispanic. 248 (62.2%) patients were listed for transplant. Listed patients had significantly higher SES index and lower ADI compared to those who were not listed. However, after adjustment for clinical factors, ADI and SESi were not predictive of listing. Similarly, patient sex, race, and insurance did not influence the likelihood of listing for HT. Notably, the distribution of the referral cohort based on ADI deciles was not reflective of our center's catchment area, indicating opportunities for improving access to transplant for disadvantaged populations. CONCLUSIONS: Although socioeconomic deprivation did not predict listing in our analysis, we recognize the need for broader outreach to combat upstream bias that prevents patients from being referred for HT.

Chronic intermittent intravenous immunoglobulin in heart transplant recipients with elevated donor-specific antibody levels.

Donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor patient survival. In heart transplant, the efficacy of intermittent intravenous immunoglobulin (IVIg) in reducing de novo DSA levels and treating AMR has not been characterized. We retrospectively studied a cohort of 19 patients receiving intermittent IVIg for elevated DSA and examined changes in DSA levels and graft function. Intermittent IVIg infusions were generally safe and well tolerated. Overall, 23 of 62 total DSA (37%) were undetectable after treatment, 21 DSA (34%) had MFI decrease by more than 25%, and 18 (29%) had MFI decrease by less than 25% or increase. The average change in MFI was -51% ± 71% (P < .001). Despite reductions in DSA, among the six patients (32%) with biopsy-confirmed AMR, left ventricular ejection fraction (LVEF) decreased in five (83%) and cardiac index (CI) decreased in three (50%). Conversely, LVEF increased in 91% and CI increased in 70% of biopsy-negative patients. All six AMR patients were readmitted during treatment, four for confirmed or suspected rejection. IVIg infusions may stabilize the allograft in patients with elevated DSA and negative biopsies, but once AMR has developed does not appear to improve allograft function despite decreasing DSA levels.

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant.

BACKGROUND: Survival in pediatric heart transplantation has improved since the first successful transplant over 35 years ago leading to increasing numbers of patients entering adulthood. We sought to examine quality of life and various lifetime achievements in our institutional population of long-term adult survivors of pediatric heart transplant. METHODS: Participants ≥18 years of age who received a heart transplant as a pediatric patient (<18 years old), and who have survived ≥10 years post-transplant, completed two self-report surveys: (1) Ferrans and Powers QLI cardiac version which reports a measure of life satisfaction with a range of 0 (very dissatisfied) to 1 (very satisfied); and (2) CHONY Pediatric Heart Transplant Life Achievement Survey to examine lifetime achievement. RESULTS: Sixty-two and sixty-five participants completed the Ferrans and Powers QLI cardiac version and CHONY Pediatric Heart Transplant Life Achievement Survey. The mean overall QLI was 0.75 ± 0.14 with the most satisfaction in the family domain. QLI scores were analyzed by age at initial transplant, gender, indication for transplant, and whether patients currently followed by pediatric or adult providers, with no statistically significant differences noted. Seventy-two percent of participants demonstrated stable employment or schooling. Around thirty percent of participants showed the ability to reach academic milestones including college and post-graduate education and ten percent to start their own families. CONCLUSIONS: Our cohort of long-term adult survivors of pediatric heart transplant report a quality of life with scores thought to be reflective of a satisfactory quality of life, and many demonstrate achievement of major life milestones.

Biomarker-Based Assessment for Infectious Risk Before and After Heart Transplantation.

PURPOSE OF REVIEW: Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review, we discuss several biological markers, or biomarkers, that may be used to monitor immunologic status in this patient population. RECENT FINDINGS: While modest, data on the utility of immune biomarkers in heart transplant recipients suggest correlation between low level of immune response and increased infection risk. More novel assays, such as the detection of circulating levels of pathogen cell-free DNA in plasma and the use of Torque teno virus load as a surrogate for net state of immunosuppression, have potential to be additional important biomarkers. Biomarker approaches to individualize immunosuppression therapy among heart transplant recipients is a promising area of medicine. However, additional studies are needed to inform the optimal protocol in which to incorporate these biomarkers into clinical practice.

Critically appraising the 2018 United Network for Organ Sharing donor allocation policy: adding life boats or rearranging the deck chairs?

PURPOSE OF REVIEW: Due to the growing mismatch between donor supply and demand as well as unacceptably high transplant waitlist mortality, the heart organ allocation system was revised in October 2018. This review gives an overview of the changes in the new heart organ allocation system and its impact on heart transplant practice and outcomes in the United States. RECENT FINDINGS: The 2018 heart allocation system offers a 6-tiered policy and therefore prioritizes the sickest patients on the transplant waitlist. Patients supported with temporary mechanical circulatory support devices are prioritized as Status 1 or Status 2, resulting in increased utilization of this strategy. Patients supported with durable left ventricular assist devices have been prioritized as Status 3 or 4, which has resulted in decreased utilization of this strategy. Broader geographic sharing in the new heart allocation system has resulted in prolonged donor ischemic times. Overall, the new heart allocation system has resulted in significantly lower candidate waitlist mortality, shorter waitlist times, and higher incidence of transplantation. SUMMARY: The new United Network for Organ Sharing allocation policy confers significant advantages over the prior algorithm, allowing for decreased waitlist times and improved waitlist mortality without major impact on posttransplant survival.

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty-six (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.

Consensus conference on heart-kidney transplantation.

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

T cell repertoire analysis suggests a prominent bystander response in human cardiac allograft vasculopathy.

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor ß chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4+ and CD8+ memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFß) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.