Redefining the molecular rejection states in 3230 heart transplant biopsies: Relationships to parenchymal injury and graft survival.

The first-generation Molecular Microscope (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose not only T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov NCT02670408), plus 1589 service biopsies added to improve the power of the machine learning algorithms. The new system used 6 rejection classifiers instead of RATs and generated 7 rejection archetypes: No rejection, 48%; Minor, 24%; TCMR1, 2.3%; TCMR2, 2.7%; TCMR/mixed, 2.7%; early-stage ABMR, 3.9%; and fully developed ABMR, 16%. Using rejection classifiers eliminated cross-reactions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe-recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrophy-fibrosis, indicating long-term risk. Graft survival and left ventricular ejection fraction were reduced not only in hearts with TCMR but also in hearts with severe-recent injury and atrophy-fibrosis, even without rejection.

Optimizing cardiac status in the preliver transplant candidate.

PURPOSE OF REVIEW: Liver transplant is a widely accepted therapy for end-stage liver disease. With advances in our understanding of transplant, candidates are increasingly older with more cardiac comorbidities. Cardiovascular disease also represents a leading cause of morbidity and mortality posttransplant. RECENT FINDINGS: Preoperative cardiac risk stratification and treatment may improve short-term and long-term outcomes after liver transplant. Importantly, the appropriate frequency of surveillance has not been defined. Optimal timing of cardiac intervention in end-stage liver disease is likewise uncertain. SUMMARY: The approach to risk stratification of cardiovascular disease in end-stage liver disease is outlined, incorporating the AHA/ACC scientific statement on evaluation of cardiac disease in transplant candidates and more recent expert consensus documents. Further study is needed to clarify the ideal timing and approach for cardiovascular interventions.

UNOS policy change benefits high-priority patients without harming those at low priority.

The heart transplantation policy change (PC) has improved outcomes in high-acuity (Old 1A, New 1-3) patients, but the effect on low-priority (Old 1B/2, New 4-6) patients is unknown. We sought to determine if low-priority patient outcomes were compromised by benefits to high-priority patients by evaluating for interaction between PC and priority status (PS). We included adult first-time heart transplant candidates and recipients from the UNOS registry during a 19-month period before and after the PC. We compared clinical characteristics and performed competing risks and survival analyses stratified by PC and PS. There was a dependence of PC and PS on waitlist death/deterioration with an interaction sub-distribution hazard ratio (adjusted sdHR) of 0.59 (0.45-0.78), p-value < .001. There was a trend toward a benefit of PC on waitlist death/deterioration (adjusted sdHR: 0.86 [0.73-1.01]; p = .07) and an increase in heart transplantation (adjusted sdHR: 1.08 [1.02-1.14], p = .007) for low-priority patients. There was no difference in 1-year post-transplant survival (log-rank p = .22) when stratifying by PC and PS. PC did not negatively affect waitlisted or transplanted low-priority patients. High-priority, post-PC patients had a targeted reduction in waitlist death/deterioration and did not come at the expense of worse post-transplant survival.

Effect of UNOS policy change and exception status request on outcomes in patients bridged to heart transplant with an intra-aortic balloon pump.

BACKGROUND: Intra-aortic balloon pumps (IABP) are used to bridge select end-stage heart disease patients to heart transplant (HT). IABP use and exception requests both increased dramatically after the UNOS policy change (PC). The purpose of this study was to evaluate the effect of PC and exception status requests on waitlist and post-transplant outcomes in patients bridged to HT with IABP support. METHODS: We analyzed adult, first-time, single-organ HT recipients from the UNOS Registry either on IABP at the time of registration for HT or at the time of HT. We compared waitlist and post-HT outcomes between patients from the PRE (October 18, 2016 to May 30, 2018) and POST (October 18, 2018 to May 30, 2020) eras using Kaplan-Meier curves and time-to-event analyses. RESULTS: A total of 1267 patients underwent HT from IABP (261 pre-policy/1006 post-policy). On multivariate analysis, PC was associated with an increase in HT (sub-distribution hazard ratio (sdHR): 2.15, p < .001) and decrease in death/deterioration (sdHR: 0.55, p = .011) on the waitlist with no effect on 1-year post-HT survival (p = .8). The exception status of patients undergoing HT was predominantly seen in the POST era (29%, 293/1006); only four patients in the PRE era. Exception requests in the POST era did not alter patient outcomes. CONCLUSIONS: In patients bridged to heart transplant with an IABP, policy change is associated with decreased rates of death/deterioration and increased rates of heart transplantation on the waitlist without affecting 1-year post-transplant survival. While exception status use has markedly increased post-PC, it is not associated with patient outcomes.

Two is better than one: when to consider multiorgan transplant.

PURPOSE OF REVIEW: Patients with end-stage heart failure often present with concomitant end-stage renal or end-stage liver disease requiring transplantation. There are limited data regarding the risks, benefits and long-term outcomes of heart-kidney (HKT) and heart-liver transplantation (HLT), and guidelines are mainly limited to expert consensus statements. RECENT FINDINGS: The incidence of HKT and HLT has steadily increased in recent years with favourable outcomes. Both single-centre and large database studies have shown benefits of HKT/HLT through improved survival, freedom from dialysis and lower rates of rejection and coronary allograft vasculopathy. Current guidelines are institution dependent and controversial due to the ethical considerations surrounding multiorgan transplantation (MOT). SUMMARY: MOT is an effective and necessary option for patients with end-stage heart and kidney/liver failure. MOT is ethically permissible, and efforts should be made to consider eligible patients as early as possible to limit morbidity and mortality. Further research is needed regarding appropriate listing criteria and long-term outcomes.

Extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 infection.

Coronavirus disease 2019, the infectious disease caused by severe acute respiratory syndrome coronavirus-2, has resulted in a global pandemic with unprecedented health, societal, and economic impact. The disease often manifests with flu-like symptoms and is dominated by pulmonary complications, but widely diverse clinical manifestations involving multiple organ systems can result. We posit that viral tropism and the aberrant host immune response mediate the protean findings and severity in this disease. In general, extrapulmonary manifestations are a harbinger of or contemporaneously associate with disease progression, but in the case of some extrapulmonary findings (gastrointestinal and dermatologic), may track with milder disease. The precise underlying pathophysiological mechanisms remain incompletely elucidated, and additional immune phenotyping studies are warranted to reveal early correlates of disease outcomes and novel therapeutic targets.

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study.

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR). Plasma dd-cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd-cfDNA levels were correlated to paired events of biopsy-based diagnosis of rejection. The median dd-cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd-cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd-cfDNA levels were elevated 3-fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd-cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd-cfDNA assay.

Prognostic utility of MELD-XI in adult congenital heart disease patients undergoing cardiac transplantation.

BACKGROUND: Model of End-Stage Liver Disease eXcluding INR (MELD-XI) at cardiac transplant has demonstrated prognostic survival utility, but has not been specifically validated in adult congenital heart disease (ACHD) in a registry study. METHODS: Adults undergoing first-time orthotopic heart transplant from 2005 to 2015 in the United Network for Organ Sharing (UNOS) registry were examined in parallel: ACHD (n = 543), ischemic-dilated cardiomyopathy (IDCM, n = 6954) and valvular heart disease (VHD, n = 355). Our primary endpoint was a composite of death, graft failure, and retransplantation assessed at 3 months (early), and those with freedom from early endpoint were reassessed at 5 years (late). Interactions between hepatorenal indices and waitlist time were examined. Secondary outcomes relating to long-term morbidity were assessed at late endpoint. Freedom from endpoint analysis in ACHD at clinically relevant endpoints was also conducted. RESULTS: Model of End-Stage Liver Disease eXcluding INR score at transplant associated with an increased risk of early endpoint in all cohorts. At late endpoint, bilirubin level associated with increased risk uniquely in ACHD. CONCLUSIONS: Model of End-Stage Liver Disease eXcluding INR holds prognostic application to ACHD in early time points and demonstrates unique waitlist interactions. Transplant bilirubin level may hold significance in long-term risk stratification of the ACHD population. Time on waitlist is an important consideration to contextualize these values.

Heart and heart-liver transplantation in adults with failing Fontan physiology.

BACKGROUND: As the population of patients with a Fontan palliation grows so does, the number of patients with cardiac failure necessitating orthotopic heart transplant (OHT) and combined heart-liver transplant (CHLT). There is recent evidence that current era cardiac transplant in Fontan patients has improved outcomes, but most studies have a preponderance of pediatrics patients in their cohorts. We examine our institutional experience with adult OHT and CHLT transplantation for failed Fontan physiology. METHODS AND RESULTS: Retrospective analysis of patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center who underwent OHT or CHLT for failing Fontan physiology from January 1, 2002 to May 31, 2017. We identified 20 patients with single-ventricle physiology and Fontan palliation who underwent OHT or CHLT. The median age was 29.5 years (range 19-44). Five patients underwent CHLT because of biopsy proven hepatic cirrhosis. The median length of hospital stay was 23 days (range 8-76) post-OHT and 51 days (range 26-77) post-CHLT. During a median follow-up of 56 months (range 2-178), there was one mortality occurring at 34 months post-OHT due to coronary vasculopathy. Most frequent early postoperative complications included bleeding and infection (55% and 20%, respectively) and surgical reintervention for bleeding complications (n = 8, 40%). One CHLT patient experienced clinically significant hepatic rejection requiring admission and steroid treatment. CONCLUSIONS: Despite inherent risks and complexities of OHT or CHLT in patients with a failed Fontan, transplant is a reasonable therapy. Peri- and postoperative complications are common and may require surgical reintervention. Continued observation of practices and unifying themes may help improve patient selection, pre- and postoperative treatment and ultimately outcomes.

Temporary Venoarterial Extracorporeal Membrane Oxygenation: Ten-Year Experience at a Cardiac Transplant Center.

OBJECTIVE: Advances in extracorporeal membrane oxygenation (ECMO) have enabled rapid deployment in a wide range of clinical settings. We report our experience with venoarterial (VA) ECMO in adult patients over 10 years and aim to identify predictors of mortality. DESIGN: This is a retrospective analysis of all adult patients undergoing VA ECMO at a tertiary care center from January 1, 2004, to December 31, 2013. RESULTS: A total of 224 consecutive cases were reviewed. Eighty (35.7%) patients survived to discharge and 144 (64.3%) patients died. Patients requiring ECMO for heart transplant graft failure had lower mortality (51.6%) compared to all other etiologies (69.1%; P = .02). Forty-two percent (94 of the 224) of the patients required cardiopulmonary resuscitation (CPR) preceding ECMO and had higher rate of in-hospital mortality (74.5%) compared with patients without cardiac arrest (56.9%; P = .01). Patients with less than 30 minutes of CPR had a mortality rate of 40.0% compared to 91.4% for CPR > 30 minutes ( P = .001). In all, 24.1% of patients (54 of the 224) experienced ECMO-associated complications without significant increase in mortality, and 22.3% (50 of the 224) of the patients were transitioned to ventricular assist devices (VADs) or transplant. Patients bridged to a VAD including left ventricular assist devices and biventricular assist devices had a mortality rate of 56.1% versus 22.2% when bridged directly to transplant ( P = .01). Paradoxically, patients with an ejection fraction (EF) > 35% had a higher mortality compared to patients with an EF < 35% (75.3% vs 49.4%, respectively, P = .001). CONCLUSION: Extracorporeal membrane oxygenation in patients with heart transplant graft failure had the best outcome. In patients who had cardiac arrest, prolonged CPR > 30 minutes was associated with very high mortality. Paradoxically, patients with EF > 35% had a higher mortality than patients with EF < 35%, likely reflecting patients with diastolic heart failure or noncardiac causes necessitating ECMO. For transplant candidates, direct bridge from ECMO to transplant could achieve a very good outcome.

Primary graft dysfunction in heart transplantation.

PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is common early postheart transplantation; however, use of standardized definitions remains inconsistent. This review focuses on understanding the incidence, classification, risk factors, and management of PGD. RECENT FINDINGS: The incidence and mortality of PGD in heart transplant varies considerably in the published literature ranging from 1.0% to 31% and 3% to 75%, respectively. There is also considerable variation in management strategies with current data favoring early intervention. SUMMARY: PGD in heart transplantation remains a challenging problem associated with significant mortality and morbidity. There is need for a consistent and accessible definition to better define associated risk factors and optimize management strategies.

Survival After Heart Transplantation in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Outcomes of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients after heart transplantation have not been well studied. Diagnostic criteria were established in 1994 and subsequently revised in 2010. We sought to better characterize this population in a national cohort. METHODS: A total of 35,138 heart transplant-only recipients were identified from the United Network for Organ Sharing (UNOS) Thoracic Registry (1994-2011); 73 had ARVC. The non-ARVC group included ischemic cardiomyopathy, restrictive cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, and other. Survival was censored at 12 years. Multivariate Cox proportional hazard regression analysis was adjusted for age, sex, DM, race, ischemia time, dialysis, life support, wait time, and HLA mismatch. RESULTS: There were 73 ARVC and 35,065 non-ARVC patients. The ARVC cohort was associated with less ventricular assist device use (P = .001) and significantly decreased pulmonary arterial and capillary wedge pressures (P < .001). Survivals at 1, 5, and 10 years were, respectively, ARVC 87%, 81%, and 77%, and non-ARVC 87%, 72%, and 53% (log rank P = .07). The ARVC unadjusted hazard ratio for all-cause mortality was 0.59 (95% confidence interval [CI] 0.34-1.04; P = .073). Multivariate analysis yielded a hazard ratio of 0.68 (95% CI 0.35-1.30; P = .25). ARVC survival was similar to restrictive, hypertrophic, and dilated cardiomyopathies and significantly better than ischemic cardiomyopathy. CONCLUSIONS: This is the largest reported series of ARVC after heart transplantation, of which 11% were pediatric. Survival was similar to the non-ARVC cohort, with improved survival over ischemic and restrictive etiologies.

Emerging pharmacologic and structural therapies for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is the most common inherited heart disease. Although it was first described over 50 years ago, there has been little in the way of novel disease-specific therapeutic development for these patients. Current treatment practice largely aims at symptomatic control using old drugs made for other diseases and does little to modify the disease course. Septal reduction by surgical myectomy or percutaneous alcohol septal ablation are well-established treatments for pharmacologic-refractory left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients. In recent years, there has been a relative surge in the development of innovative therapeutics, which aim to target the complex molecular pathophysiology and resulting hemodynamics that underlie hypertrophic cardiomyopathy. Herein, we review the new and emerging therapeutics for hypertrophic cardiomyopathy, which include pharmacologic attenuation of sarcomeric calcium sensitivity, allosteric inhibition of cardiac myosin, myocardial metabolic modulation, and renin-angiotensin-aldosterone system inhibition, as well as structural intervention by percutaneous mitral valve plication and endocardial radiofrequency ablation of septal hypertrophy. In conclusion, while further development of these therapeutic strategies is ongoing, they each mark a significant and promising advancement in treatment for hypertrophic cardiomyopathy patients.

Cardiac Amyloidosis: Diagnosis and Treatment Strategies.

Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.

Heart Failure Therapies for End-Stage Chemotherapy-Induced Cardiomyopathy.

With ongoing advancements in cancer-related treatments, the number of cancer survivors continues to grow globally, with numbers in the United States predicted to reach 18 million by 2020. As a result, it is expected that a greater number of patients will present with chemotherapy-related side effects. One entity in particular, chemotherapy-related cardiomyopathy (CCMP), is a known cardiotoxic manifestation associated with agents such as anthracyclines, trastuzumab, and tyrosine kinase inhibitors. Although such effects have been described in the medical literature for decades, concrete strategies for screening, prevention, and management of CCMP continue to be elusive owing to limited studies. Late recognition of CCMP is associated with a poorer prognosis, including a lack of clinical response to pharmacologic therapy, and end-stage heart failure. A number of advanced cardiac therapies, including cardiac resynchronization therapy, ventricular assist devices, and orthotopic cardiac transplantation, are available to for end-stage heart failure; however, the role of these therapies in CCMP is unclear. In this review, management of end-stage CCMP with the use of advanced therapies and their respective effectiveness are discussed, as well as clinical characteristics of patients undergoing these treatments. The relative paucity of data in this field highlights the importance and need for larger-scale longitudinal studies and long-term registries tracking the outcomes of cancer survivors who have received cardiotoxic cancer therapy to determine the overall incidence of end-stage CCMP, as well as prognostic factors that will ultimately guide such patients toward receiving appropriate end-stage care.

Team-Based Care for Outpatients with Heart Failure.

Management of heart failure requires a multidisciplinary team-based approach that includes coordination of numerous team members to ensure guideline-directed optimization of medical therapy, frequent and regular assessment of volume status, frequent education, use of cardiac rehabilitation, continued assessment for the use of advanced therapies, and advance care planning. All of these are important aspects of the management of this complex condition.

Molecular states associated with dysfunction and graft loss in heart transplants.

BACKGROUND: We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies. METHODS: Genome-wide microarrays (19,462 genes) were used to define mRNA changes correlating with dysfunction (left ventricular ejection fraction [LVEF] ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival. RESULTS: Dysfunction is correlated with dedifferentiation-decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection. Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury. Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB). Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest. CONCLUSIONS: Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia.

Surveillance with dual noninvasive testing for acute cellular rejection after heart transplantation: Outcomes from the Surveillance HeartCare Outcomes Registry.

BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.

Impact of atrial fibrillation on outcomes in heart failure.

The prevalence of atrial fibrillation (AF) and heart failure increases with advancing age. It is estimated that the annual incidence of AF in the general heart failure population is approximately 5%, whereas as many as 40% of patients with advanced heart failure have AF. The goals of therapy in patients with heart failure and AF are symptom control and prevention of arterial thromboembolism. The adverse hemodynamic events of AF may lead to symptom deterioration and reduced exercise capacity. This review addresses the impact of AF on heart failure outcomes as they pertain to prognosis and management.

New UNOS allocation system associated with no added benefit in waitlist outcomes and worse post-transplant survival in heart-kidney patients.

BACKGROUND: The 2018 United Network for Organ Sharing (UNOS) heart transplant policy change (PC) sought to improve waitlist risk stratification to decrease waitlist mortality and promote geographically broader sharing for high-acuity patients awaiting heart transplantation. Our analysis sought to determine the effect of the UNOS PC on outcomes in patients waiting for, or who have received, a heart-kidney transplantation. METHODS: We analyzed adult (≥18 years old), first-time, heart-only and heart-kidney transplant candidates and recipients from the UNOS Registry. Patients were divided into pre-PC (PRE: October 18, 2016-May 30, 2018) and post-PC (POST: October 18, 2018-May 30, 2020) groups for comparison. Competing risks analysis (subdistribution and cause-specific hazards analyses) was performed to assess for differences in waitlist death/deterioration or heart transplantation. One-year post-transplant survival was assessed with Kaplan-Meier and Cox analyses. We included an interaction term (policy era × heart ± kidney) in our analyses to evaluate the effect of PC on outcomes in heart-kidney patients. RESULTS: One-year post-transplant survival was similar (p = 0.83) for PRE heart-kidney and heart-only recipients, but worse (p < 0.001) for POST heart-kidney vs heart-only recipients. There was a policy-era interaction between heart-kidney and heart-only recipients (HR 1.92[1.04,3.55], p = 0.038) indicating a detrimental effect of policy on 1-year survival in POST vs PRE heart-kidney recipients. No added beneficial effect of PC on waitlist outcomes in heart-kidney vs heart-only candidates was observed. CONCLUSIONS: There was no added policy-era benefit on waitlist outcomes for heart-kidney candidates when compared to heart-only candidates. POST heart-kidney recipients experienced worse 1-year survival compared to PRE heart-kidney recipients with no policy effect on heart-only recipients.