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Objectives: The aim of this study was to evaluate the impact of a shared-care model on outcomes in patients with left ventricular assist devices (LVADs) living in remote locations., Background: Health care delivery through shared-care models has been shown to improve outcomes in patients with chronic diseases. However, the impact of shared-care models on outcomes in patients with LVAD is unknown., Methods: LVAD recipients in the authors' program (2007 to 2018) were classified based on the levels of care provided and training and resources used: level 1, was defined as outpatient primary care without LVAD-specific care; level 2 was level 1 services and outpatient LVAD-specific care; level 3 was level 2 services and inpatient LVAD-specific care and implantation center (IC). The Kaplan-Meier method was used to compare rates of survival, bleeding, pump thrombosis, infection, neurologic events, and readmissions among levels of care., Results: A total of 336 patients were included, with 255 patients (75.9%) cared for in shared-care facilities. Median follow-up was 810 (interquartile range: 321 to 1,096) days. In comparison to patients cared for by IC, patients at levels 2 and 3 shared-care centers had similar rates of death, bleeding, neurologic events, pump thromboses, and infections. However, the rates of death, pump thromboses, and infections were higher for level 1 patients than in IC patients., Conclusions: Shared health care is an effective strategy to deliver care to patients with LVAD living in remote locations. However, patients in shared-care facilities unable to provide LVAD-specific care are at higher risk of unfavorable outcomes. Availability of LVAD-specific care should be strongly considered during patient selection and every effort made to ensure LVAD-specific training and resources are available at shared-care facilities., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS., Methods: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes., Results: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time., Conclusions: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging., Methods: We included consecutive patients who were considered for cardiac transplant from 2006 to 2015. Serum alloantibodies were detected with single-antigen beads on the Luminex platform (One Lambda Inc., Canoga Park, CA). Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. cPRA was determined at multiple times. LVAD-associated allosensitization was defined as development of cPRA > 10% in patients with cPRA ≤ 10% before LVAD implantation. Post-transplant outcomes of interest were acute cellular rejection (ACR), antibody-mediated rejection (AMR), and survival., Results: Allosensitization status was evaluated in 268 patients (20% female). Mean age was 52 ± 12 years, and 132 (49.3%) received CF LVADs. After LVAD implant, 30 patients (23%) became newly sensitized, and the level of sensitization appeared to diminish in many of these patients while awaiting transplant. During the study period, 225 of 268 patients underwent transplant, and 43 did not. A CF LVAD was used to bridge 50% of the transplant recipients. Compared with patients without new sensitization or those already sensitized at baseline, the patients with LVAD-associated sensitization had a higher risk of ACR (p = 0.049) and higher risk of AMR (p = 0.018) but a similar intermediate-term post-transplant survival. The patients who did not receive a transplant had higher level of allosensitization, with a baseline cPRA of 20% vs 6% in those who received an allograft and a high risk (40%) of death during follow-up., Conclusions: New allosensitization takes place in > 20% of patents supported with CF LVADs. Among patients who undergo transplant, this results in a higher risk of ACR and AMR, but survival remains favorable, likely due to the efficacy of current management after transplant. However, mortality in sensitized patients who do not reach transplant remains high, and new approaches are necessary to meet the needs of this group of patients., (Published by Elsevier Inc.)

Background: Little is known about mixed cellular and antibody-mediated rejection (MR) in heart transplantation. It remains unclear whether cardiac MR has distinctive pathologic and clinical features beyond those of simultaneous cellular rejection (CR) and antibody-mediated rejection (AMR). In this study we systematically explore the pathologic and clinical characteristics of MR in heart transplantation., Methods: The UTAH Cardiac Transplant Program database was queried for transplant recipients who survived long enough to have at least one endomyocardial biopsy (EMB) between 1985 and 2014. Only EMBs with both CR and AMR scores documented were included. In addition to detailed pathologic analyses, we also examined the incidence and prevalence of MR, the likelihood to transition from and to MR, and mortality associated with MR., Results: Patients (n = 1,207) with a total of 28,484 EMBs met the study inclusion criteria. The overall prevalence of MR was 7.8% and it was nearly twice as frequent within the first year post-transplant. Mild MR was by far the most common occurrence and was typically preceded by an immune active state. When CR increased in severity, AMR tended to follow, but the reverse was not true. On pathology, individual features of CR and AMR were more easily separated in cases of mild MR, whereas they substantially overlapped in more severe cases. MR was associated with a significant cardiovascular death risk that was incremental with severity., Conclusions: MR is not common, usually occurs early after transplant, and is associated with worse outcomes. MR reflects a complex interplay between cellular and humoral processes, which varies with rejection severity., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Growing evidence suggests worse cardiac allograft vasculopathy and mortality in patients with asymptomatic antibody-mediated rejection (AMR). Debate continues about whether therapeutic intervention is warranted to avoid adverse outcomes. In this study we examine the course of individual episodes of untreated asymptomatic AMR on follow-up endomyocardial biopsy (EMB)., Methods: The U.T.A.H. Cardiac Transplant Program database was queried for transplant recipients between 1985 and 2009 who survived beyond 1 year and had at least 1 episode of lone AMR with a follow-up EMB. All EMBs were screened for AMR by immunofluorescence and graded for severity. Data were analyzed based on time from transplant (early, ≤12 months; late, >12 months)., Results: Nine hundred fifty-eight patients with a total of 15,448 biopsies qualified for the study. Average age at transplant was 46.7 years; 13% of the patients were female. Within the first year post-transplant, asymptomatic AMR was diagnosed in 13.6% of biopsies compared with 5.2% beyond 1 year. AMR resolved in 65% (early) vs 75% (late) on follow-up EMB. More severe AMR was less likely to improve regardless of time from transplant. Furthermore, after an episode of AMR had resolved, the recurrence rate at 3, 6 and 12 months was 44%, 50.1% and 56.2%, respectively., Conclusions: The incidence of AMR is higher in the first year post-transplant and the likelihood of resolution is less on follow-up EMB, especially when more severe. A small but significant number of cases became worse or did not change. These new findings may be helpful in planning future studies that test whether therapeutic interventions on asymptomatic AMR favorably impact outcomes., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Both pulsatile-flow and continuous-flow left ventricular assist devices (LVADs) successfully provide patients a bridge to transplantation. Some data suggest that continuous-flow pumps increase the risk of allograft rejection, contributing to posttransplantation morbidity and mortality. We sought to analyze the relationship between LVAD flow characteristics and subsequent allograft rejection in bridge to transplant (BTT) patients., Methods: Patients with LVADs from the UTAH Transplant Affiliated Hospitals were retrospectively analyzed. Rejection was determined pathologically according to the International Society for Heart and Lung Transplantation revised cardiac allograft rejection scale. Multimodal statistical analyses were applied., Results: Of 1,076 patients who underwent transplantation over a 26-year period, 151 had LVADs. Of these, 111 (77 pulsatile flow, 34 continuous flow) patients had pathologic data available. There was no difference in overall rejection (grades 1R to 3R) between the pulsatile-flow LVAD and continuous-flow LVAD groups (2.00 ± 1.43 versus 1.50 ± 1.16 episodes/year; p = 0.076.) Patients with pulsatile-flow LVADs had more clinically relevant (grades 2R to 3R) rejection than did patients with continuous-flow LVADs (0.49 ± 0.72 versus 0.12 ± 0.33 episodes/year; p < 0.001). There was no survival difference at 1 year (p = 0.920) or 4 years (p = 0.721) after transplantation., Conclusions: Patients with continuous-flow LVADs have similar overall rejection rates and a reduced rate of clinically relevant rejection compared with patients with pulsatile-flow LVADs during the first year after transplantation. Although there is theoretical concern that nonphysiologic, nonpulsatile flow could alter the neurohormonal profile of patients in heart failure, we are encouraged that the type of LVAD circulation does not influence posttransplantation allograft survival., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recent efforts are being undertaken to update and refine current diagnostic criteria for antibody-mediated rejection (AMR) in heart transplantation. We believe that the appropriate reactants are those that best predict the adverse consequences of AMR and therefore tested various models using different reactants to find the best predictors of cardiovascular mortality in pathologically defined AMR., Methods: The study group included only patients in whom all immunofluorescence antibodies of interest had been tested on biopsy specimens obtained after 2002 when C4d was routinely added. We analyzed our data using 3 Cox proportional hazard models with time-varying covariates using an end point of cardiovascular mortality, as previously defined., Results: In 3,712 biopsy specimens from 422 patients, the 2-antibody model achieved a value of R(2) = 0.930 using C3d and C4d antibodies alone. A model that used 4 antibodies--C3d, C4d, human leukocyte antigen-D related (HLA-DR) and fibrin--was superior (R(2) = 0.988). The model that best predicted cardiovascular mortality included all 6 antibodies: HLA-DR, immunoglobulin (Ig) G, IgM, C3d, C4d, and fibrin (R(2) = 0.989). The models using 4 or 6 antibodies were significantly superior to the model using only C3d and C4d (for each interaction, p < 0.0001)., Conclusions: The combination of complement components, HLA-DR and fibrin, is valuable in defining AMR in patients at risk for allograft loss from cardiovascular causes. Fibrin is particularly important for detecting the presence of severe AMR, with a high likelihood of poor long-term patient outcome., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The United Network for Organ Sharing (UNOS) implemented a thoracic organ allocation policy change (APC) in July 2006 that aimed to reduce death on the waiting list by expanding regional organ sharing. As such, organs would be allocated to the sickest recipients with highest listing status across the region. Our aim was to determine the impact of the new policy on the procurement and transplant process within our program., Methods: We analyzed data supplied by UNOS as the contractor for the Organ Procurement and Transplantation Network and from the local organ procurement organization for 2 years before and 2 years after implementation of the APC., Results: The APC resulted in an increase in the proportion of Status 1A patients transplanted (24% to 43%, p = 0.015) and a decrease in the proportion of Status 2 patients transplanted (56% to 24%, p = 0.001). Significant increases were observed in mean graft ischemic time (196 minutes to 223 minutes, p = 0.022), number of patients transplanted with ventricular assist devices (17% to 31%, p = 0.036), and procurement costs. There was no significant difference in waiting-list mortality (6% to 5%, p = 0.75) and short-term post-transplant survival., Conclusions: The 2006 change in UNOS organ allocation policy resulted in an increase in Status 1A transplants, graft ischemic time and procurement costs, and a decrease in Status 2 transplants, but no effect on mortality on the waiting list within our center. To assess the full effect of the APC on outcomes, the long-term impact of the increased graft ischemic time on survival should be quantified.

Background: Organ transplant candidates with serum antibodies directed against human leukocyte antigens (HLA) face longer waiting times and higher mortality while awaiting transplantation. This study examined the accuracy of virtual crossmatch, in which recipient HLA-specific antibodies, identified by solid-phase assays, are compared to the prospective donor HLA-type in heart transplantation., Methods: We examined the accuracy of virtual crossmatch in predicting immune compatibility of donors and recipients in heart transplantation and clinical outcomes in immunologically sensitized heart transplant recipients in whom virtual crossmatch was used in allograft allocation., Results: Based on analysis of 257 T-cell antihuman immunoglobulin complement-dependent cytotoxic (AHG-CDC) crossmatch tests, the positive predictive value of virtual crossmatch (the likelihood of an incompatible virtual crossmatch resulting in an incompatible T-cell CDC-AHG crossmatch) was 79%, and the negative predictive value of virtual crossmatch (the likelihood of a compatible virtual crossmatch resulting in a compatible T-cell CDC-AHG crossmatch) was 92%. When used in a cohort of 28 sensitized patients awaiting heart transplantation, 14 received allografts based on a compatible virtual crossmatch alone from donors in geographically distant locations. Compared with the other 14 sensitized patients who underwent transplant after a compatible prospective serologic crossmatch, the rejection rates and survival were similar., Conclusion: Our findings are evidence of the accuracy of virtual crossmatch and its utility in augmenting the opportunities for transplantation of sensitized patients.

The clinical presentation and disease course of tuberculosis (TB) in a solid-organ transplant (SOT) recipient may be atypical and the risk of mortality is high. Herein we examine the role of the different tests used in diagnosis of TB and review the specifics of anti-mycobacterial therapy and the public health implications of TB in a SOT recipient.

Background: The current International Society for Heart and Lung Transplantation (ISHLT) diagnostic criteria for antibody-mediated rejection (AMR) designate AMR as either absent (AMR 0) or present (AMR 1), without grading its severity. Yet, the extent of histologic and immunofluorescence (IF) findings of AMR varies across endomyocardial biopsies (EMBs). In this study, we hypothesized that the severity of AMR, as assessed on EMBs, correlates with cardiovascular mortality in heart transplant recipients., Methods: All EMBs from 1985 to 2005 were evaluated. Biopsy specimens were uniformly studied by light microscopy and IF early post-transplant. A comprehensive vascular score (V1: no AMR, to V5: severe AMR) was prospectively assigned to each EMB, based on severity of both histologic and IF findings. Univariate Cox proportional hazards regressions were performed using indicators of vascular scores alone, combined, and cumulatively., Results: Nine hundred six patients were transplanted and included in the study. Mean age was 46.6 +/- 15.5 years and 82% were male. A total of 26,236 EMBs comprised the study data. As expected, histologic and immunopathologic findings of AMR varied in severity. An incremental risk of cardiovascular mortality was found with more severe AMR whether vascular scores were analyzed individually (p = 0.001), in combination (p = 0.01) or cumulatively (p = 0.006)., Conclusions: The severity of AMR on EMBs correlates with an incremental cardiovascular mortality risk after heart transplantation, suggesting that AMR should be viewed as a spectrum rather than just as present or absent. Supplementing the ISHLT AMR diagnostic guidelines with a consensus severity scale is warranted.

Background: The International Society for Heart and Lung Transplantation (ISHLT) recently established a diagnostic scheme for antibody-mediated rejection (AMR). Currently, however, confirmatory immunohistochemistry studies are recommended only if AMR is clinically or histologically suspected. In this study, we examine whether a pattern of repetitive AMR occurred early enough after transplantation to warrant prospective immunohistochemistry screening in all recently transplanted recipients., Methods: We queried our pathology database of adult and pediatric endomyocardial biopsies (EMBs) from 1985 to 2005. All EMB specimens were prospectively studied by immunofluorescence in the early post-operative period. AMR was defined as the presence of complement and immunoglobulin deposits on frozen section. Only patients classified as antibody-mediated rejectors (>or=3 episodes of AMR) were included. Cumulative incidence and time from transplant to first and third AMR episodes were obtained., Results: Three hundred seventy-five of 870 heart transplant recipients had >or=3 episodes of AMR. Mean age of recipients was 45.6 years and 78% were male. A total of 19,569 EMBs comprised the study data. By 100 days post-transplant, 85% of patients had their first and 54% their third AMR. In addition, patients showed a clear trend of early clustering of AMR-positive biopsies. Results were similar regardless of whether or not muromonab-CD3 (Orthoclone OKT3) induction was used., Conclusions: We advocate early immunohistochemical surveillance testing for AMR to supplement the diagnostic algorithm established by the ISHLT, because a pattern of AMR becomes manifest soon after transplantation. This change will allow earlier detection of asymptomatic AMR and may prompt changes in immunosuppression strategies to avoid adverse outcomes.

Background: Conflicting data exist regarding the impact of reversible pulmonary hypertension (PHTN) on post-transplant (Tx) outcomes. In this study we sought to determine the influence of reversible PHTN on outcomes after Tx., Methods: We retrospectively reviewed the records of adult patients who underwent heart Tx from 1993 to 2002. Patients were grouped depending on their measured pulmonary vascular resistance (PVR). Group 1 patients had a pre-Tx pulmonary vascular resistance (PVR) of < 3 Wood units (WU). Patients with reversible PHTN, defined as pre-Tx PVR > or = 3 WU and reversing to < 3 WU either with sub-lingual or intravenous vasodilatory agents, were divided into two groups based on their PVR before the reversibility test (PVR: Group 2, 3 to 4.5 WU; Group 3, > 4.5 WU)., Results: Records for 222 adult heart recipients were reviewed (Group 1, n = 171; Group 2, n = 35; Group 3, n = 16). Baseline clinical characteristics (age, gender, heart failure etiology, history of diabetes, ischemic time, donor age and gender) were similar in the three groups and the average follow-up was 58 months. One-month and 1-year mortality (Groups 1, 2 and 3: 2%, 0% and 13%; and 8%, 0% and 13%, respectively) did not differ significantly between groups. Actuarial mortality was assessed using Cox regression analysis, adjusted for age and gender, and no increased risk of death was demonstrated for patients with reversible PHTN (for Group 2: multivariate hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.17 to 1.32, p = 0.15; for Group 3: HR 0.98, CI 0.34 to 2.84, p = 0.97). No differences were observed between the three groups for various post-Tx events, such as hospital stay, ICU stay, extubation time, transfusions, acute allograft dysfunction, acute hepatic dysfunction, acute and chronic renal dysfunction, infections, neurologic complications, gastrointestinal complications and coronary allograft vasculopathy., Conclusions: Reversible pulmonary hypertension is associated with similarly good post-transplant survival outcomes and morbidity, regardless of severity.

Background: Determining which pretransplantation (TX) characteristics predict the development of chronic renal dysfunction (CRD) or death after heart TX would enable more accurate risk assessment at the time of candidate evaluation., Methods: A cohort of 278 patients underwent TX in three hospitals between 1993 and 2002. Predictive models for CRD (serum creatinine consistently above 2 mg/dL) and allograft loss (death or re-TX) were constructed using logistic and Cox regression, respectively., Results: Using logistic regression, CRD was more likely to develop in TX patients if they had a larger body surface area (odds ratio [OR] = 5.8 per m2, 95% confidence interval [CI] = 1.04 to 31.9, p = 0.04) or were inotrope dependent (OR = 1.8, 95% CI = 0.90 to 3.7, p = 0.09). Notably, the implementation of mechanical circulatory support as bridge to transplantation decreased the risk of CRD (OR = 0.30, 95% CI = 0.12 to 0.72, p = 0.007). Cox analysis demonstrated independent predictive ability of improved survival for males (hazard ratio [HR] = 0.42, 95% CI = 0.21 to 0.83, p = 0.01). Worse survival was observed with prior sternotomy (HR = 3.5, 95% CI = 2.0 to 6.0, p < 0.001), diabetes mellitus (HR = 1.9, 95% CI = 0.98 to 3.9, p = 0.06), and elevated serum creatinine (HR = 2.8 per mg/dL, 95% CI = 1.3 to 5.8, p = 0.007)., Conclusions: Certain pretransplant characteristics clearly predispose a patient to the development of CRD or increased mortality after heart transplantation. Interestingly, the risk of CRD after heart transplantation is greater for patients bridged to transplant with inotropes than with mechanical circulatory support. When hemodynamically indicated, timely implementation of pretransplant mechanical circulatory support should be considered.

Background: In our previously published work dealing with antibody-mediated (vascular) rejection (AMR), we defined patterns of rejection (AMR and cellular rejection [CR]) based on a review of biopsy diagnoses taken in the first 6 to 12 weeks post-transplant. We have shown the significance of these pattern designations in relation to patient and allograft outcome in five outcome analyses. The current retrospective analysis was done to determine whether our previous criteria for pattern designations provided the greatest degree of discrimination between AMR and CR., Methods: Six hundred sixty-five patients from the U.T.A.H. Cardiac Transplant Program were included in our study. Patients induced with OKT3 immunosuppression were excluded. We analyzed the relationship of a number of either AMR or CR episodes to cardiovascular mortality. We constructed Kaplan-Meier survival curves to assess the impact of incremental numbers of AMR or CR episodes on cardiovascular mortality., Results: Three or more episodes of AMR resulted in a statistically significant increase in cardiovascular mortality. By contrast, CR episodes did not increase the risk of cardiovascular mortality., Conclusions: Based on our findings, we believe that clinical trials should be designed to test treatments based on predominant rejection patterns and that end-points for trials should be defined by number of biopsies positive for either CR or AMR. This approach may lead to improved patient and allograft survival.

Background: The use of left ventricular assist devices is associated with human leukocyte antigen (HLA) allosensitization. We investigated whether prophylactic treatment with low-dose intravenous immunoglobulin (IVIG), analogous to the use of IgG anti-D (anti-Rh) in preventing Rh immunization, can abrogate HLA allosensitization after left ventricular assist device implantation., Methods: We retrospectively reviewed the data from 84 consecutive heart failure patients who underwent implantation of a left ventricular assist device as a bridge to transplantation. After implantation, panel reactive antibody (PRA) was measured biweekly to assess sensitization (defined by PRA > 10%). Patients who were sensitized before left ventricular assist device implantation were excluded from further analysis (n = 12). Patients who either did not require perioperatively transfusions of cellular blood products or received other immunomodifying regimens were also excluded from further analysis (n = 21). The rest of the patients were divided into two groups based on whether they received IVIG, 10 g daily for 3 days (IVIG group, n = 26; non-IVIG group, n = 25). The decision as to whether patients received IVIG was not randomized but was based on surgeon preference., Results: The sensitization rates (expressed as ratio of sensitized patients to total patients at risk) in the two groups were similar at consecutive time points (2, 4, 6, 8, 12, 20 weeks) after left ventricular assist device implantation. Also, mean PRA at the same time points did not differ between the two groups. Overall, 34.6% (9 of 26) of the IVIG group became sensitized during mechanical support, compared with 32% (8 of 25) of the non-IVIG group (p = 1.0). A PRA of 90% or greater (high-degree sensitization) occurred in 15.3% (4 of 26) of the IVIG group and 12.0% (3 of 25) of the non-IVIG group (p = 0.5)., Conclusions: The use of low-dose prophylactic IVIG after left ventricular assist device implantation affects neither the incidence nor the severity of HLA allosensitization.

Background: Allograft coronary vasculopathy is a major cause of death beyond the first year after cardiac transplantation. The aim of this study was to review our experience with percutaneous coronary intervention (PCI) with stents in cardiac transplant recipients., Methods: We identified patients who were treated with PCI using stents. Patient characteristics, procedure information and clinical outcomes were assessed for these patients by review of their medical records. We also compared results for those who had bare metal stents vs those who had drug-eluting stents., Results: Forty patients from our program's 865 cardiac transplant recipients received a total of 78 coronary stents. There were 35 males (87.5%) and 5 females (12.5%). The indication for PCI was progressive asymptomatic coronary vasculopathy in 18 patients (45%), angina in 5 (12.5%), acute myocardial infarction (MI) in 4 (10%) and congestive heart failure (CHF) in 6 (15%). Primary success (<50% residual stenosis) was obtained in 71 (91%) of 78 stents. During the mean follow-up of 40.8 +/- 34.5 months, 6 patients died (15%) and 2 (5%) were re-transplanted. There was a lower rate of re-stenosis with drug-eluting stents (2 of 13, 15%) compared with bare metal stents (20 of 65, 31%), although this difference was not statistically significant (p = 0.27)., Conclusions: In cardiac transplant recipients, PCI with stents can be performed with high rates of primary success. Restenosis rates are higher compared with PCI in native coronary arteries. A trend toward less restenosis with drug-eluting stents was observed, which needs to be confirmed in larger studies.

Background: Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS., Methods: We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups., Results: Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score >or=3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001)., Conclusion: Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required.

Background: Tricuspid valve insufficiency (TI) is common after orthotopic heart transplantation. However, tricuspid valve replacement or repair (TVR) is rare. The aim of this study is to evaluate our experience with TVR in cardiac transplant recipients., Methods: The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program database was queried for TVR in all adult and pediatric heart transplant recipients. Pre-operative parameters and cardiac hemodynamics were compared with post-operative findings., Results: Since 1985, we identified in our database 17 patients who had 16 TVR, and 2 tricuspid valve repair procedures. Thirty-four heart transplant recipients from the same period were used as controls. The indication for TVR was symptomatic right heart failure (RHF) in 89% of cases, and there was no significant difference between the control group and the surgery group in the average number of biopsies. A flail leaflet was found in 16 cases (89%). One patient died post-operatively due to cardiogenic shock, and 1 patient died 8 months after TVR due to progressive RHF. Improvement in heart failure symptoms was seen in 12 cases. The central venous pressure (CVP) decreased from 17.8 +/- 4.1 mm Hg to 11.0 +/- 7.3 mm Hg (p = 0.013). There was no significant change in cardiac output or renal function. However, the furosemide dose decreased significantly from 47.69 +/- 56.44 mg/day to 26.54 +/- 46.43 mg/day (p = 0.009)., Conclusions: After orthotopic heart transplantation, TVR is a safe and effective procedure to alleviate RHF symptoms. Flail leaflets are the most common operative finding, suggesting that biopsy-induced trauma is the likely cause of severe TI in these patients.

Background: Beta-blockers are frequently used after cardiac transplantation for blood pressure control. There is no well-known interaction between beta-blockers and cyclosporine A (CsA). However, recent reports have suggested that carvedilol, but not metoprolol, modulates P-glycoprotein (P-gp), a membrane protein that regulates CsA absorption. We evaluated the effects of carvedilol and metoprolol on CsA level when initiated in cardiac transplant recipients., Methods: Using our cardiac transplant database, we identified patients who were started on either carvedilol or metoprolol for blood pressure control. We then compared their CsA doses and levels before and within 2 weeks after the initiation of beta-blocker therapy., Results: We found 20 patients taking metoprolol and 12 patients taking carvedilol. With initiation of metoprolol, CsA level decreased in 12 patients and increased in 8 patients. The mean CsA level before and after metoprolol initiation was 236 ng/ml and 253 ng/ml, respectively (p = 0.50). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was not significantly adjusted (from a mean of 293 mg/day to a mean of 294 mg/day; p = 0.92). In the Carvedilol Group, CsA level increased in 10 of 12 patients. The mean CsA level before the initiation of carvedilol was 257 ng/ml. The mean CsA level after carvedilol initiation was 380 ng/ml (p = 0.009). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was reduced by 10%, from a mean of 319 mg/day to a mean of 288 mg/day (p = 0.004)., Conclusion: Carvedilol, but not metoprolol, was associated with a significant increase in CsA levels after initiation in cardiac transplant recipients. Although carvedilol and CsA do not interact at the level of cytochrome P450 system, it appears that carvedilol influences CsA levels through its effects on P-gp. An average reduction of 10% is necessary on the CsA dose upon initiation of carvedilol, and close follow-up of the level is essential.

Background: Diagnostic criteria for antibody-mediated rejection (AMR) of the cardiac allograft have recently been proposed as part of the International Society for Heart and Lung Transplantation (ISHLT) biopsy grading scheme. Histologic features of vascular adherence of macrophages (VASC) and endothelial activation or swelling in capillaries (ENDO) are proposed as criteria to prompt the immunohistochemical investigation of biopsies for AMR. The aim of this study was to determine whether VASC and ENDO are adequate to act as screening parameters to trigger further AMR investigation., Methods: We examined our database of biopsy findings where histologic vascular parameters as well as immunofluorescence (IF) to detect AMR were collected (n = 3,170). Histologic parameters were graded semi-quantitatively on a scale from 1 to 5, where 1 = absence and 5 = obvious and generalized presence of the finding., Results: Seven hundred sixty-eight of 3,170 biopsies had IF findings diagnostic of AMR in the absence of cellular rejection (ISHLT = 0). ENDO had a sensitivity of 63% and a specificity of 80%. VASC had a sensitivity of 30% and specificity of 99%. Combining the interpretation of the 2 tests did not result in a significant improvement of test sensitivity., Conclusions: Neither ENDO, VASC nor the combination of the tests indicated sufficiently high sensitivity to serve as a screening tool before further diagnostic investigation for AMR. Immunohistochemical testing remains necessary in the majority of cases to identify AMR.