An Approach to Controlling Inflammation and Coagulation in Pig-to-Baboon Cardiac Xenotransplantation.

INTRODUCTION: Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. METHODS: Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). RESULTS: Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. CONCLUSION: Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.

Evolving Trends and Impact of Waitlist Transfusion on Recipient Outcomes Following Heart Transplantation.

BACKGROUND: This study evaluates the clinical trends, risk factors, and impact of waitlist blood transfusion on outcomes following isolated heart transplantation. METHODS: The UNOS registry was queried to identify adult recipients from January 1, 2014, to June 30, 2022. The recipients were stratified into two groups depending on whether they received a blood transfusion while on the waitlist. The incidence of waitlist transfusion was compared before and after the 2018 allocation policy change. The primary outcome was survival. Propensity score-matching was performed. Multivariable logistic regression was performed to identify predictors of waitlist transfusion. A sub-analysis was performed to evaluate the impact of waitlist time on waitlist transfusion. RESULTS: From the 21 926 recipients analyzed in this study, 4201 (19.2%) received waitlist transfusion. The incidence of waitlist transfusion was lower following the allocation policy change (14.3% vs. 23.7%, p < 0.001). The recipients with waitlist transfusion had significantly reduced 1-year posttransplant survival (88.8% vs. 91.9%, p < 0.001) compared to the recipients without waitlist transfusion in an unmatched comparison. However, in a propensity score-matched comparison, the two groups had similar 1-year survival (90.0% vs. 90.4%, p = 0.656). Multivariable analysis identified ECMO, Impella, and pretransplant dialysis as strong predictors of waitlist transfusion. In a sub-analysis, the odds of waitlist transfusion increased nonlinearly with longer waitlist time. CONCLUSION: There is a lower incidence of waitlist transfusion among transplant recipients under the 2018 allocation system. Waitlist transfusion is not an independent predictor of adverse posttransplant outcomes but rather a marker of the patient's clinical condition. ECMO, Impella, and pretransplant dialysis are strong predictors of waitlist transfusion.

Donation After Circulatory Death Heart Transplantation: A Narrative Review.

Heart transplantation is the definitive treatment for refractory, end-stage heart failure. The number of patients awaiting transplantation far exceeds available organs. In an effort to expand the donor pool, donation after circulatory death (DCD) heart transplantation has garnered renewed interest. Unlike donation after brain death, DCD donors do not meet the criteria for brain death and are dependent on life-sustaining therapies. Procurement can include a direct strategy or a normothermic regional perfusion, whereby there is restoration of perfusion to the organ before explantation. There are new developments in cold storage and ex vivo perfusion strategies. Since its inception, there has been a steady improvement in post-transplant outcomes, largely attributed to advancements in operative and procurement strategies. In this narrative review, the authors address the unique considerations of DCD heart transplantation, including withdrawal of care, the logistics of procuring and resuscitating organs, outcomes compared with standard donation after brain death, and ethical considerations.

Improved Graft Function following Desensitization of Anti-AT1R and Autoantibodies in a Heart Transplant Recipient Negative for Donor-Specific Antibodies with Antibody-Mediated Rejection: A Case Report.

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs.

The Role of Recipient Thyroid Hormone Supplementation in Primary Graft Dysfunction After Heart Transplantation: A Propensity-Adjusted Analysis.

OBJECTIVES: To investigate whether recipient administration of thyroid hormone (liothyronine [T3]) is associated with reduced rates of primary graft dysfunction (PGD) after orthotopic heart transplantation. DESIGN: Retrospective cohort study. SETTING: Single-center, university hospital. PARTICIPANTS: Adult patients undergoing orthotopic heart transplantation. INTERVENTIONS: A total of 609 adult heart transplant recipients were divided into 2 cohorts: patients who did not receive T3 (no T3 group, from 2009 to 2014), and patients who received T3 (T3 group, from 2015 to 2019). Propensity-adjusted logistic regression was performed to assess the association between T3 supplementation and PGD. MEASUREMENTS AND MAIN RESULTS: After applying exclusion criteria and propensity-score analysis, the final cohort included 461 patients. The incidence of PGD was not significantly different between the groups (33.9% no T3 group v 40.8% T3 group; p = 0.32). Mortality at 30 days (3% no T3 group v 2% T3 group; p = 0.53) and 1 year (10% no T3 group v 12% T3 group; p = 0.26) were also not significantly different. When assessing the severity of PGD, there were no differences in the groups' rates of moderate PGD (not requiring mechanical circulatory support other than an intra-aortic balloon pump) or severe PGD (requiring mechanical circulatory support other than an intra-aortic balloon pump). However, segmented time regression analysis revealed that patients in the T3 group were less likely to develop severe PGD. CONCLUSIONS: These findings indicated that recipient single-dose thyroid hormone administration may not protect against the development of PGD, but may attenuate the severity of PGD.

PCSK9 Inhibition in Patients After Heart Transplantation: a Retrospective Review and Literature Analysis.

PURPOSE OF REVIEW: Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. RECENT FINDINGS: Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.

Overcoming perioperative inflammation as a hurdle for successful preclinical orthotopic cardiac xenogeneic transplantations - particular in regard of the mandatory use of heart-lung machines.

INTRODUCTION: After orthotopic cardiac xenotransplantation, the combination of both the inflammatory responses to the exposure of a recipient to the xenogeneic organ and the use of cardiopulmonary bypass has been assumed to cause detrimental side effects. These have been described not only to affect the transplanted organ (heart) itself, but also the recipient's lungs. In this article, we summarize how these possible detrimental processes can be minimized or even avoided. METHODS: Data from eight pig-to-baboon orthotopic cardiac xenotransplantation experiments were analyzed with a special focus on early (within the first week) postoperative organ dysfunction and systemic inflammatory responses. Non-ischemic heart preservation and the careful management of the heart-lung machine were deemed essential to guarantee not only the immediate function of the transplanted xenogeneic organ but also the prompt recovery of the recipient. RESULTS: After weaning from cardiopulmonary bypass, very low catecholamine amounts were needed to ensure an adequate pump function and cardiac output. Central venous oxygen saturation and serum lactate levels remained within normal ranges. All animals were successfully weaned from ventilation within the first postoperative hours. Serum parameters of the transplants and native kidneys and livers were initially slightly elevated or always normal, as were hemoglobin, LDH, and platelet measurements. Markers of systemic inflammation, C-reactive protein, and IL-6 were slightly elevated, but the reactions caused no lasting damage. CONCLUSION: Consistent short-term and long-term results were achieved after orthotopic cardiac pig-to-baboon transplantation without detrimental inflammatory responses or signs of multiorgan failure. In comparison to allogeneic procedures, non-ischemic heart preservation was important for successful immediate organ function, as was the management of the heart-lung machine. Thus, we believe that genetically modified porcine hearts are ready for use in the clinical setting.

Association of tacrolimus time-to-therapeutic range on renal dysfunction and acute cellular rejection after orthotopic heart transplantation in a high use basiliximab population.

BACKGROUND: Currently, clinicians often delay initiation of tacrolimus after orthotopic heart transplantation (OHT) to help mitigate nephrotoxicity. This study aimed to determine if there is an association between the time-to-therapeutic range (TTT) of tacrolimus, early renal dysfunction, and acute cellular rejection (ACR) after OHT. METHODS: This was a retrospective, single center study with adult patients who underwent OHT from July 2013 to April 2020. Logistic regression analysis was utilized to examine the association of TTT with new renal dysfunction after tacrolimus initiation post-OHT. RESULTS: In a study of 317 patients, the unadjusted analysis showed patients who developed new renal dysfunction after tacrolimus initiation had a numerically shorter TTT (9.5 vs. 11.0 days, P = .065), and were more likely to have supratherapeutic tacrolimus levels (56% vs. 39.2%, P = .010). When adjusted for established risk factors for renal dysfunction, TTT was significantly associated with new renal dysfunction (OR .95; 95% CI [.90, .99], P = .03). There was no association between TTT and the incidence of ACR (11.1 vs. 10.8 days, P = .64). CONCLUSION: When adjusting for known risk factors, a shorter TTT was associated with new renal dysfunction. Supratherapeutic tacrolimus levels were also associated with new renal dysfunction. There was no association between TTT and ACR in the setting of high use basiliximab induction.

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.

Permanent pacing in a very long-term follow-up after orthotopic heart transplantation: A matter of when or why?

BACKGROUND: Orthotopic heart transplantation (OHT) is associated with a high incidence of conduction disturbances (CD) leading to permanent pacemaker (PPM) implantation. However, the improved posttransplant survival raises the question about the pacemaker dependence (PD) in a prolonged follow-up. HYPOTHESIS: The prevalence of PPM in OHT is high but not all patients are PD in a very long-term follow-up. Device implantation has no prognostic relevance. METHODS: We performed a retrospective analysis of patient medical records focusing on device interrogation data at the most recent follow-up. RESULTS: The study population consisted of 183 patients with a mean follow-up of 15.0 ± 6.8 years. One-fourth of the patients had undergone PPM implantation (n = 49, 26.8%). Among these, two-thirds were PD at last follow-up (n = 32, 65.3%). PPM was more often in biatrial OHT and cardiac allograft vasculopathy (OR 3.0, 95% CI 1.26-7.29, p = .013 and OR 2.0, 95% CI 1.03-3.87, p = .041, respectively). Early sinus node dysfunction (SND) was the most persistent CD. PPM was associated with a poorer outcome in OHT (HR 1.9, 95% CI 1.06-3.46, p = .031) and a higher rate of fatal septicemia (HR 5.1, 95% CI 1.41-18.14, p = .013). CONCLUSIONS: One-fourth of the OHT recipients develop CD requiring PPM implantation, although one-third among these are not PD in follow-up. Early SND is associated with a higher rate of PD. PPM is associated with an inferior prognosis.

Recipient-surgeon racial concordance in orthotopic heart transplantation outcomes.

BACKGROUND: Prior studies have demonstrated deleterious outcomes for physician-patient racial discordance. We explored recipient-surgeon racial concordance and short-term postoperative survival in adults undergoing orthotopic heart transplantation (OHT). METHODS: The United Network for Organ Sharing (UNOS) database was queried to identify White and Black adult (≥18 years) patients undergoing isolated OHT between 2000 and 2020. Surgeon race was obtained from publicly available images. All non-White and non-Black recipients and surgeons were excluded. Linear probability models were utilized to explore the relationship between recipient-surgeon racial concordance and 30-, 60-, and 90-day post-transplant mortality using a fixed effects approach. RESULTS: A total of 26,133 recipients were identified (mean age 52.79 years, 74.4% male) with 77.65% (n = 20,292) being White and 22.35% (n = 5841) being Black. A total of 662 White surgeons performed 25,946 (97.56%) OHTs during the study period while 17 Black surgeons performed 437 (1.67%) OHTs. Although some evidence of differences across groups was observed in cross-tabular specifications, these differences became insignificant after the inclusion of controls (i.e., comorbidities and fixed effects). This suggests that recipient race and physician race are not correlated with post-OHT survival at 30, 60, or 90 days. CONCLUSIONS: Recipient-surgeon racial concordance and discordance among adults undergoing OHT do not appear to impact post-transplant survival. Nor do we observe significant penalties accruing for Black patients overall once controls are accounted for. Given that worse outcomes have historically been demonstrated for Black patients undergoing OHT, further work will be necessary to improve understanding of racial disparities for patients with end-stage heart failure.

Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation.

Demand for organs is increasing while the number of donors remains constant. Nevertheless, not all organs are utilized due to the limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate whether an iron-chelator-supplemented Bretschneider solution could protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage. HTX was performed in foxhounds. The ischemic time was standardized to 4 h, 8 h, 12 h or 16 h, depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, the myocardial high energy phosphate and iron content and the in-vitro myocyte force were evaluated. Iron chelator supplementation proved superior at a routine preservation time of 4 h, as well as for prolonged times of 8 h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine triphosphate content in the supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content. This study shows that an iron-chelator-supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short- as well as long-term conservation.

Constrictive pericarditis following heart transplantation: Reality or fiction?

Constrictive pericarditis (CP) is a curable cause of diastolic heart failure with prior cardiac surgery being a recognizable etiology. We report a patient who developed CP one year following heart transplantation. Several clinical and imaging related factors may lead to diagnostic delays in similar patients, including the mistaken belief that transplanted hearts are devoid of pericardium and thus do not develop constriction. Post-transplantation pericardial effusion, mediastinitis, and cardiac rejection predispose to future CP. Caretakers should consider this entity in allograft recipients who develop heart failure symptoms of unclear etiology.

Impact of various sizing metrics on female donor to male recipient heart transplant outcomes.

BACKGROUND: This study evaluated the impact of various sizing metrics on outcomes of female donor to male recipient orthotopic heart transplantation (OHT). METHODS: We queried the United Network of Organ Sharing database to analyze all isolated, primary adult OHTs from January 1, 2010 to January 20, 020. Patients were stratified by donor-recipient sex pairing. Logistic regression was used to investigate risk-adjusted effects of current size matching criteria (weight ratio, body mass index [BMI] ratio, predicted heart mass [pHM] ratio) on 1-year posttransplant mortality. Kaplan-Meier analysis was used to compare posttransplant survival among cohorts. RESULTS: A total of 22,450 patients were analyzed, of which 3019 (13.4%) underwent female-to-male transplantation. Of sex-matched pairs, female-to-male donation had the lowest proportion of undersized hearts using weight and BMI ratio metrics (10.5% and 5.2%) but had the highest proportion of undersizing using pHM metrics (48.1%) (all p < 0.001). Female-to-male recipients had the lowest rate of unadjusted 1-year survival (90.0%, p = 0.0169), and increased hazards of mortality after risk adjustment (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.01-1.36, p = 0.034). Undersizing using pHM (donor-recipient ratio <0.85) was the only metric found to be associated in increased mortality after risk adjustment (OR: 1.32, 95% CI: 1.02-1.71, p = 0.035). CONCLUSION: Female-to-male heart transplantation has the worst survival of all sex-matching combinations. Although female donors in this cohort are appropriately sized using traditional metrics, half are under-sized using pHM. This, combined with its strong association with mortality, underscores the importance of routine pHM assessment when evaluating female donors for male recipients.

Impact of center donor acceptance patterns on utilization of extended-criteria donors and outcomes.

BACKGROUND: This study investigated the impact of transplanting center donor acceptance patterns on usage of extended-criteria donors (ECDs) and posttransplant outcomes following orthotopic heart transplantation (OHT). METHODS: The Scientific Registry of Transplant Recipients was queried to identify heart donor offers and adult, isolated OHT recipients in the United States from January 1, 2013 to October 17, 2018. Centers were stratified into three equal-size terciles based on donor heart acceptance rates (<13.7%, 13.7%-20.2%, >20.2%). Overall survival was compared between recipients of ECDs (≥40 years, left ventricular ejection fraction [LVEF] <60%, distance ≥500 miles, hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV], or ≥50 refusals) and recipients of traditional-criteria donors, and among transplanting terciles. RESULTS: A total of 85,505 donor heart offers were made to 133 centers with 15,264 (17.9%) accepted for OHT. High-acceptance programs (>20.2%) more frequently accepted donors with LVEF <60%, HIV, HCV, and/or HBV, ≥50 offers, or distance >500 miles from the transplanting center (each p < .001). Posttransplant survival was comparable across all three terciles (p = .11). One- and five-year survival were also similar across terciles when examining recipients of all five ECD factors. Acceptance tier and increasing acceptance rate were not found to have any impact on mortality in multivariable modeling. Of ECD factors, only age ≥40 years was found to have increased hazards for mortality (hazard ratio, 1.33; 95% confidence interval [CI], 1.22-1.46; p < .001). CONCLUSIONS: Of recipients of ECD hearts, outcomes are similar across center-acceptance terciles. Educating less aggressive programs to increase donor acceptance and ECD utilization may yield higher national rates of OHT without major impact on outcomes.

Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction.

BACKGROUND: Recent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD. METHODS: This was a single-center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6 months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3). RESULTS: 53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P < .001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26-10.88; P = .018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR = 0.416, 95% CI = 0.08-2.15; P = .296). CONCLUSION: We found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.

COVID-19 morbidity in patients after orthotopic heart transplantation - single center clinical observation.

INTRODUCTION: The study is a prospective clinical observation of patients after orthotopic heart transplantation in a large academic medical center in relation to COVID-19 morbidity. The study population was comprised of 552 patients. All patients were consulted and advised by telephone as regards the prophylaxis of SARS-CoV-2 infection. Hospital and outpatient follow-ups were limited to the minimum. Preventive modification of immunosuppression was not recommended in relation to the pandemic. Three patients with multiple comorbidities (a woman aged 60, a man aged 59, and another man aged 83; 2.25 years, 5.5 years, and 7.5 years after heart transplantation, respectively) and one patient with concomitant arterial hypertension (a woman aged 48, 5.5 years after heart transplantation) presented with a symptomatic COVID-19 infection. Three of the patients were on tacrolimus immunosuppression, and both female patients were additionally on therapy with mycophenolate mofetil, which was discontinued following the diagnosis of infection. One male patient received combined therapy of cyclosporine A and mycophenolate mofetil. The 60-year-old woman presented with gastrointestinal manifestations of the COVID-19 infection which were of moderate severity. The recovery was achieved. The 59-year-old man presented with myocardial infarction, exacerbated renal insufficiency that required hemodialysis and cardiorespiratory failure complicated by bacterial sepsis. As a result, the patient died. The 83-year-old male patient reporting fever, myalgia, fatigue, cough and dyspnea was admitted to hospital and deceased due to septic shock two days after admission. The 48-year old woman who presented with mild symptoms of the upper respiratory tract infection recovered after two weeks. Symptomatic treatment was used in all the patients. Another male patient (aged 45 years, 8 years after orthotopic heart transplant with no significant comorbidities) was an asymptomatic carrier of SARS-CoV-2 and remained under hospital care. CONCLUSIONS: Of 552 patients after orthotopic heart transplantation, two SARS-CoV-2-related deaths were reported.

Standardized Use of the Stanford Integrated Psychosocial Assessment for Transplantation in LVAD Patients.

BACKGROUND: Increased psychosocial risk portends poor outcomes following heart transplantation. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated, psychosocial risk assessment tool that helps stratify candidates for transplantation. We assessed the impact of psychosocial factors as measured by the SIPAT on clinical outcomes following left ventricular assist device (LVAD) implantation at our institution. METHODS AND RESULTS: A total of 115 individuals (mean age: 57 years, 75.6% men) who underwent LVAD implantation, for either bridge-to-transplant (63%) or destination therapy, from 2014 to 2016 were included for analysis. Correlations between SIPAT scores, baseline characteristics, and post-LVAD outcomes were assessed through a retrospective correlational design. At 1 year post-LVAD, the higher risk SIPAT group had more emergency department visits, urgent clinic visits, and readmissions in univariate analysis (rate ratio 1.7 [95% confidence interval (CI) 1.0-2.7, P = .035]). After multivariate analysis, this association retained near-statistical significance (rate ratio 1.6 [95% CI 1.0-2.8, P = .051]). There was also a trend toward more device-associated infections (rate ratio 2.1 [95% CI 0.96-4.4, P = .064]). There was no difference in incidence of other adverse events or 1-year mortality between the 2 groups. CONCLUSIONS: Higher psychosocial risk per SIPAT in patients undergoing LVAD implantation is associated with more emergency room visits, urgent visits and readmissions over 1 year, but not LVAD-related complications or mortality. Use of the SIPAT tool may help identify patients at higher risk for hospitalization and/or urgent care beyond traditional factors, but should not preclude LVAD implantation.

Abdominal Operations After Left Ventricular Assist Device Implantation and Heart Transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used to supplant the limited number of orthotopic heart transplantation (OHT). The present study aimed to perform a contemporary analysis of emergency abdominal operations after LVAD and OHT at a national level. METHODS: The 2005-2015 National Impatient Sample, the largest all-payer hospitalization database in the United States, was used to identify all adult patients who had received LVAD or OHT. The primary outcome of interest was the rate of emergency general surgery (EGS), which included laparotomy, small or large bowel resection, peptic ulcer operation, adhesiolysis, and cholecystectomy, during the same hospitalization as LVAD or OHT. Logistic regression was used to determine risk factors for EGS as well as the association between EGS and mortality in both the LVAD and OHT populations. RESULTS: Of the estimated 19,395 OHT and 23,441 LVAD performed, 445 (2.3%) OHT and 719 (3.1%) LVAD patients required EGS. The incidence of EGS in LVAD decreased from 5.4 to 3.3%, whereas it increased among OHT patients from 1.9 to 3.7%, P = 0.003. Occurrence of EGS after OHT and LVAD was associated with significantly higher inpatient risk-adjusted mortality (OHT adjusted odds ratio, 3.0; P = 0.004; LVAD adjusted odds ratio, 2.5; P < 0.001), incremental hospitalization costs (OHT, $106,778; P < 0.001; LVAD, $61,965; P < 0.001), and length of stay (OHT, 27.9 d; P < 0.001; LVAD, 20.8 d; P < 0.001). CONCLUSIONS: EGS remains an infrequent but high mortality and cost complication of OHT and LVAD. Further investigation of the impact of immunosuppression, anticoagulation, and perfusion strategies on incidence of abdominal complications is warranted.

Pulmonary arterial hypertension in adults with systemic right ventricles referred for cardiac transplantation.

BACKGROUND: Systemic right ventricular (RV) failure may progress necessitating referral for orthotropic heart transplantation (OHT). Pulmonary hypertension (PH) frequently coexists in adult congenital heart disease and can complicate the assessment for OHT. METHODS: Single-center case series of six patients (median age 34.9 years [IQR, 31.9-42.4]) with systemic RV physiology with PH referred for OHT evaluation from 2008 to 2017. RESULTS: One-third (n = 6) of 18 patients with systemic RV physiology referred for OHT evaluation had pulmonary arterial hypertension (PAH) defined as mean pulmonary artery pressure (mPAP) > 25 mm Hg and pulmonary vascular resistance (PVR) > 3 Wood Units. Two of the six patients were considered OHT-ineligible due to PH and comorbidities. Of the remaining four, two had pre-capillary PH and underwent heart-lung transplant (HLTx). The other two demonstrated reversibility of PVR with vasodilator testing and underwent OHT alone, one of whom died post-transplant from PH crisis. CONCLUSIONS: Pulmonary arterial hypertension is common in systemic RV patients referred for OHT. Systemic RV dysfunction places these patients at risk for post-capillary PH but pre-capillary PH can exist. Despite management with selective pulmonary vasodilators and afterload reduction, criteria for listing patients for HLTx vs OHT are not known and need further elucidation.