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While there has been a global decrease in rates of heart failure (HF) prevalence between 1990 and 2019, the Eastern Mediterranean region (EMR) is experiencing an increase. In 2019, approximately 1,229,766 individuals lived with moderate to severe HF in the EMR. Despite the growth in the utilization of advanced heart failure (AHF) therapies in the EMR in the past two decades, current volumes are yet to meet the growing AHF burden in the region. Heart transplantation (HT) volumes in EMR have grown from 9 in the year 2000 to 179 HTs in 2019. However, only a few centers provide the full spectrum of AHF therapies, including durable mechanical circulatory support (MCS) and HT. Published data on the utilization of left ventricular assist devices (LVAD) in the EMR are scarce. Notably, patients undergoing LVAD implantation in the EMR are on average, 13 year younger, and more likely to present with critical cardiogenic shock, as compared to their counterparts in the Western world. Furthermore, AHF care in the region is hampered by the paucity of multidisciplinary HF programs, inherent costs of AHF therapies, limited access to short and long-term MCS, organ shortage, and lack of public awareness and acceptance of AHF therapeutics. All stakeholders in the EMR should work together to strategize tackling the challenging AHF burden in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

COVID-19 pandemic hampered operational efficiency of heart transplant (HT) programs worldwide. Little is known about the global and country-specific changes in HT volumes during the pandemic years 2020-2021. We aimed to describe the global and country-level impact of the COVID-19 pandemic on HT volumes in 2020-2021. This is a cross-sectional study of the Global Observatory on Donation and Transplantation, including the years 2019-2021. Among 60 countries that reported HT data in the years 2019-2020, we analyzed 52 countries with ≥1 transplant during each year. Overall, the number of HTs decreased during 2020 by 9.3% (1.82 to 1.65 PMP). While 75% (n = 39/52) of countries experienced a decrease in HT volumes in 2020, volumes were maintained/increased in the remaining countries. Countries with maintained HT volumes had a higher organ donation rate in 2020 compared to those with decreased volumes (P = 0.03), the only significant predictor of change in HT volumes (P = 0.005). In 2021, a 6.6% recovery from the previous year's drop in global HT rate was noticed, reaching 1.76 HT PMP. Only 1 in 5 countries with reduced volumes in 2020 recovered their baseline volumes in 2021. Only 30.8% of countries with maintained volumes in 2020 had continued growth in HT volumes in 2021. The latter group encompassed the United States of America, the Netherlands, Poland, and Portugal. Further work should define underlying causes of this heterogeneity in HT volume during the pandemic. Identifying policies and practices that helped certain countries mitigate the effect of the pandemic on HT activities may help other countries during similar health crises in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection., Methods: An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021., Results: There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID-19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID-19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID-19 infection, or who died of COVID-19 or its complications. The timing of candidate reactivation on the waiting list after COVID-19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty-one percent of the respondents felt COVID-19 vaccine should be mandatory before transplant, but this rate varied by geographic region., Conclusion: Our results reflect evolving experience of the heart transplant field at a time of lack of high-quality evidence. In the absence of longer-term outcome data for donors and transplant candidates with history of COVID-19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID-19., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiac allograft vasculopathy (CAV)-mediated by a heterogeneous myriad of immune and non-immune factors, which contribute to the progressive and diffuse thickening of the arterial allograft's tunica intima in one distinct form of CAV, and the build-up of plaque in another-is a major limiting factor of long-term survival post heart transplantation. Information on the optimal pharmacotherapeutic approaches for the prevention and management of CAV is conflicting, scattered, and inconsistent, with numerous recent studies adding to the literature. In this paper, we present a go-to clinical resource with the most updated and comprehensive information on the topic. Immunosuppressant therapy remains a staple, with mTOR inhibitors and mycophenolate mofetil (MMF) showing direct correlation with CAV prevention. More data is now available with calcineurin inhibitor (CNI) minimizing or sparing regimens. More novel approaches are being investigated for the roles of monoclonal antibodies, anti-thymocyte globulin, and bortezomib in preventing or delaying CAV. On the other hand, statins' established efficacy is attributed to lipid-lowering and lipid-independent immunomodulatory effects, with early initiation associated with improved outcomes. The choice of statin is dependent on drug-drug interactions. Other aiding approaches for the prevention of CAV include antioxidant vitamins, aspirin, vasodilators, folate therapy, and, most pertinently, cytomegalovirus prophylaxis. Larger clinical trials are needed before these options are institutionalised. For management of established CAV, early initiation of augmented immunosuppressive therapies may be effective, as well as CNI conversion to mTOR inhibitors with or without standard MMF and azathioprine therapy. Risk of acute rejection needs to be monitored during conversion. Finally, preclinical investigations highlight novel potential therapies for CAV prevention and attenuation, however robust clinical trials are needed to test their efficacy and safety., Competing Interests: Declaration of competing interest MRM is a consultant for Abbott (fees paid to Brigham and Women's Hospital), Portola, Bayer, Baim Institute for Clinical Research and Triple Gene; a trial steering committee member for Medtronic and Janssen; a scientific advisory board member for Leviticus, NupulseCV and FineHeart; and a DSMB member for Mesoblast. Other authors have no pertinent disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It is unclear whether pulmonary hemodynamics improvement with left ventricle unloading with left ventricular assist devices (LVADs) is sustained long term after heart transplant (HT). We sought to assess the effects on pulmonary vascular hemodynamics during continuous-flow (CF-LVAD) and pulsatile flow (PF-LVAD) support up to 5 years after HT. Invasive hemodynamics were evaluated before LVAD, before HT, and at 3 months, 1, and 3-5 years posttransplant. Thirty-eight patients were included in the study and divided into two groups according to the type of LVAD support. The two groups were well matched in age and gender. Mean pulmonary artery pressure (PAPm) and systolic PAP (PAPs) improved significantly in the PF-LVAD group (40 ± 10.6 to 19.8 ± 4.4 mm Hg and 62.7 ± 14.9 to 31.8 ± 5.9 mm Hg, respectively) and in the CF-LVAD group (37.4 ± 11.6 to 22.4 ± 7.7 mm Hg and 53.7 ± 18.0 to 34.6 ± 11.8 mm Hg, respectively). Reductions in PAPm and PAPs were more pronounced in PF-LVAD group than in CF-LVAD group (p = 0.005 and p = 0.03, respectively). After HT, the improvement in PAPm and PAPs was sustained after 3-5 years in patients who received PF-LVAD (22.6 ± 6.5 and 32.2 ± 9.2 mm Hg, respectively) and in patients who received CF-LVAD (22.2 ± 8.4 and 33.8 ± 9.6 mm Hg, respectively). In conclusion, long-term LVAD support resulted in significant improvement in PAPm and PAPs regardless of the pump generation. The improvement in hemodynamics observed during LVAD support was sustained 3-5 years posttransplant.

Background: Survival of patients on left ventricular assist devices (LVADs) has improved. We examined the differences in risk of adverse outcomes between LVAD-supported and medically managed candidates on the heart transplant waiting list., Methods and Results: We analyzed mortality and morbidity in 33,073 heart transplant candidates registered on the United Network for Organ Sharing (UNOS) waiting list between 1999 and 2011. Five groups were selected: patients without LVADs in urgency status 1A, 1B, and 2; patients with pulsatile-flow LVADs; and patients with continuous-flow LVADs. Outcomes in patients requiring biventricular assist devices, total artificial heart, and temporary VADs were also analyzed. Two eras were defined on the basis of the approval date of the first continuous-flow LVAD for bridge to transplantation in the United States (2008). Mortality was lower in the current compared with the first era (2.1%/mo versus 2.9%/mo; P<0.0001). In the first era, mortality of pulsatile-flow LVAD patients was higher than in status 2 (hazard ratio [HR], 2.15; P<0.0001) and similar to that in status 1B patients (HR, 1.04; P=0.61). In the current era, patients with continuous-flow LVADs had mortality similar to that of status 2 (HR, 0.80; P=0.12) and lower mortality compared with status 1A and 1B patients (HR, 0.24 and 0.47; P<0.0001 for both comparisons). However, status upgrade for LVAD-related complications occurred frequently (28%) and increased the mortality risk (HR, 1.75; P=0.001). Mortality was highest in patients with biventricular assist devices (HR, 5.00; P<0.0001) and temporary VADs (HR, 7.72; P<0.0001)., Conclusions: Mortality and morbidity on the heart transplant waiting list have decreased. Candidates supported with contemporary continuous-flow LVADs have favorable waiting list outcomes; however, they worsen significantly once a serious LVAD-related complication occurs. Transplant candidates requiring temporary and biventricular support have the highest risk of adverse outcomes. These results may help to guide optimal allocation of donor hearts.

Background: Cardiac donors routinely require vasoactive agents for circulatory stability after brain death. Nevertheless, inotropes have been associated with direct cardiac toxicity. Our study evaluated whether the use of high-dose inotropic support in potential donors was associated with increased early myocardial necrosis (MN) and worse clinical outcomes after cardiac transplantation., Methods: The UTAH Cardiac Transplant Program (UCTP) and Intermountain Donor Services databases were queried for records between 1996 and 2009. The high-dose donor inotropic support (HDIS) group was defined as patients on dopamine >10 μg/kg/min. The incidence of early MN, intensive care unit (ICU) length of stay, length of ventilator support, and mortality was evaluated., Results: Two hundred and forty-four recipients undergoing transplant met study criteria. The average donor age was 27 yr. The incidence of MN in the HDIS (n=29) and non-HDIS (n=204) groups was 14.8% and 6.7%, respectively, OR 2.67. Total ischemic time, ventilator support time, ICU stay, and actuarial survival were similar between both groups., Conclusion: The use of high-dose inotropic support to maintain donor stability appears to have a higher trend for early post-transplant MN without an impact on clinical outcomes. With the current growing shortage of organ donors, it appears reasonable to use donors on high-dose inotropic support., (© 2011 John Wiley & Sons A/S.)

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.)

Chronic kidney disease continues to be a major limiting factor for long-term survival of heart transplant recipients. Little is known about the early use of renin-angiotensin system (RAS) blocking agents and their impact on renal function and hemodynamics in heart transplant recipients. In this cohort study all eligible recipients of orthotopic heart transplants at the UTAH cardiac transplantation program from 2001 through 2007 were divided into 2 groups-patients who were started on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers within the first 4 weeks of transplantation and continued on these for ≥4 weeks during the first 3 months (RAS blockade group, n = 75) and those who were not (non-RAS blockade group, n = 52). All patients were followed for 1 year after transplantation. There were no significant differences at baseline between the 2 groups. Estimated glomerular filtration rate at 12 months was significantly higher in the RAS blockade group compared to the non-RAS blockade group (mean ± SD, 56.3 ± 22.4 vs 47.3 ± 18.1 ml/min/1.73 m(2), p = 0.036). At 12 months pulmonary artery systolic pressure was significantly lower in the RAS blockade group compared to the non-RAS blockade group (30.2 ± 7.4 vs 32.9 ± 9.3 mm Hg, p = 0.023). Left ventricular ejection fraction and pulmonary capillary wedge pressure were similar between the 2 groups. In conclusion, early RAS blockade after heart transplantation is safe, well tolerated, and associated with better renal function and hemodynamic profile at 1 year after transplantation., (Published by Elsevier Inc.)

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.)

Candidacy for heart transplantation is influenced by the severity of pulmonary hypertension. In this study, invasive hemodynamics from right-sided cardiac catheterization were compared with values obtained by validated equations from Doppler 2-dimensional transthoracic echocardiography. This prospective study was conducted in 40 patients with end-stage heart failure evaluated for heart transplantation or ventricular assist device implantation. Transthoracic echocardiography and right-sided cardiac catheterization were performed within 4 hours. From continuous-wave Doppler of the tricuspid regurgitation jet, pulmonary artery systolic pressure was calculated as the peak gradient across the tricuspid valve plus right atrial pressure estimated from inferior vena cava filling. Mean pulmonary artery pressure was calculated as (0.61 × pulmonary artery systolic pressure) + 2. Pulmonary vascular resistance (PVR) was calculated as (tricuspid regurgitation velocity/right ventricular outflow tract time-velocity integral × 10) + 0.16. Pulmonary capillary wedge pressure was calculated as 1.91 + (1.24 × E/E'). Pearson's correlation and Bland-Altman analysis of mean differences between echocardiographic and right-sided cardiac catheterization measurements were statistically significant for all hemodynamic parameters (pulmonary artery systolic pressure: r = 0.82, p < 0.05, mean difference 3.1 mm Hg, 95% confidence interval [CI] -0.2 to 6.3; mean pulmonary artery pressure: r = 0.80, p < 0.05, mean difference 2.5 mm Hg, 95% CI 0.3 to 4.6; PVR: r = 0.52, p < 0.05, mean difference 0.8 Wood units, 95% CI 0.3 to 1.4; pulmonary capillary wedge pressure: r = 0.65, p < 0.05, mean difference 2.2 mm Hg, 95% CI 0.1 to 4.3). Compared with right-sided cardiac catheterization, PVR by Doppler echocardiography identified all patients with PVR > 4 Wood units (n = 4), 73% of patients with PVR <2 Wood units (n = 8), and 52% of patients with PVR from 2 to 4 Wood units (n = 10). In conclusion, echocardiographic estimation of cardiopulmonary hemodynamics is reliable in patients with end-stage cardiomyopathy. The noninvasive assessment of hemodynamics by echocardiography may be able to decrease the number of serial right-sided cardiac catheterizations in selected patients awaiting heart transplantation. However, in patients with borderline PVR, right-sided cardiac catheterization is indicated to assess eligibility for transplantation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (<2 yr) heart transplant (HTx) recipients (56 ± 4 yr) and nine healthy controls (58 ± 5 yr). Measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and femoral artery blood flow were recorded during passive knee extension. Peripheral vascular function was assessed using brachial artery flow-mediated dilation (FMD). During passive limb movement, the HTx recipients lacked an HR response (0 ± 0 beats/min, Δ0%) but displayed a significant increase in CO (0.4 ± 0.1 l/min, Δ5%) although attenuated compared with controls (1.0 ± 0.2 l/min, Δ18%). Therefore, the rise in CO in the HTx recipients was solely dependent on increased SV (5 ± 1 ml, Δ5%) in contrast with the controls who displayed significant increases in both HR (6 ± 2 beats/min, Δ11%) and SV (5 ± 2 ml, Δ7%). The transient increase in femoral blood volume entering the leg during the first 40 s of passive movement was attenuated in the HTx recipients (24 ± 8 ml) compared with controls (93 ± 7 ml), whereas peripheral vascular function (FMD) appeared similar between HTx recipients (8 ± 2%) and controls (6 ± 1%). These data reveal that the absence of an HR increase in HTx recipients significantly impacts the peripheral vascular response to passive movement in this population and supports the concept that an increase in CO is a major contributor to exercise-induced hyperemia.

Objective: To determine the impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation., Methods: From January 1, 1993, to April 30, 2009, a total of 525 cardiac transplants were performed. Ventricular assist devices were placed as a bridge to transplant in 110 patients. We focused our analysis on the 2 most common causes of end-stage heart failure requiring transplantation: idiopathic dilated cardiomyopathy (n = 201) and coronary artery disease (n = 213). Data including gender, age, date of transplant, cause of heart failure, prior heart transplant, placement of a ventricular assist device, type of ventricular assist device, and panel-reactive antibody sensitization were analyzed to derive Kaplan-Meier survival probabilities and multivariable Cox regression models., Results: In patients with idiopathic dilated cardiomyopathy who received a ventricular assist device as a bridge to transplant, survival was decreased at 1 year (P = .008) and 5 years (P = .019), but not at 10 years, posttransplant. In patients with coronary artery disease, the use of a ventricular assist device as a bridge to transplant did not influence survival at 1, 5, and 10 tears posttransplant. In patients with idiopathic dilated cardiomyopathy who received a Heartmate I (Thoratec Corp, Pleasanton, Calif) ventricular assist device as a bridge to a cardiac transplant, elevation in the pretransplant panel-reactive antibody correlated with a decrease in long-term survival., Conclusion: In patients with idiopathic dilated cardiomyopathy, placement of a Heartmate I ventricular assist device as a bridge to a cardiac transplant is associated with an elevation in the pretransplant panel-reactive antibody and a decrease in 1- and 5-year survivals after cardiac transplantation., (2010 The American Association for Thoracic Surgery. Published by Mosby, 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.

Background: Little has been reported on the clinical significance of asymptomatic antibody-mediated rejection (AMR) alone or mixed rejection (MR), defined as concurrent cellular rejection (CR) and AMR in heart transplantation. In this study, we examined whether a differential impact on cardiovascular mortality (CVM) existed when comparing asymptomatic AMR, to stable MR or CR., Methods: The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program pathology database of all heart transplant recipients between 1985 and 2004 was queried. Patients were classified as cellular, antibody-mediated, or mixed rejectors based on their predominant pattern of rejection type in the first three months post-transplant. Kaplan-Meier survival curves were fit to each of the three groups and analyses were adjusted for age at the time of transplant, gender, and underlying primary cardiac disease., Results: Eight hundred and sixty nine heart transplant recipients qualified for analysis. Over the study period, patients with asymptomatic AMR or stable MR patterns had significantly worse CVM when compared to patients with stable CR pattern (AMR, 21.2%; MR, 18.0%; CR, 12.6%; AMR vs. CR, p = 0.009; MR vs. CR, p = 0.001). In contrast, CVM was comparable in patients with asymptomatic AMR or stable MR patterns (p = 0.9)., Conclusions: Asymptomatic or subclinical AMR and MR are clinically relevant, should be recognized, and deserve consideration for therapeutic intervention in hopes of avoiding adverse outcomes.

The life expectancy of patients with congenital heart disease is increasing. Thus, as the prevalence of adults with congenital heart disease increases, invasive cardiologists will have more exposure to these patients and will benefit from expertise in the anatomy of congenital heart defects. We present a case of performing right heart catheterization and myocardial biopsy in a cardiac transplant patient with a history of multiple congenital defects including a persistent left superior vena cava., ((c) 2008 Wiley-Liss, Inc.)

Endomyocardial biopsy is the gold standard to diagnose cardiac allograft rejection, although a noninvasive modality such as brain natriuretic peptide (BNP) is attractive. The authors examined the correlation of BNP levels with rejection patterns and allograft function in cardiac allograft recipients followed up to 8 years. One hundred forty-four consecutive patients underwent endomyocardial biopsy, right heart catheterization, and blood sampling. BNP levels decreased during the first 6 months after transplant but then reached a plateau. Time-dependent correlations were made between BNP levels and allograft rejection, left ventricular ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, and serum creatinine. BNP levels were not different between patients with any rejection pattern and no rejection prior to or after 6 months following transplant. BNP levels did not correlate with ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or creatinine in the first 6 months after transplant. Statistically significant correlations existed between BNP and these parameters after 6 months following transplant. In cardiac transplant recipients, BNP levels decrease in the first 6 months following transplant and then reach a plateau regardless of the presence, type, or severity of allograft rejection. BNP levels do predict allograft rejection but correlate with allograft function after 6 months following transplant.

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: 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: 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.

Heart failure is a common disease state that can be encountered at different stages in the course of a COVID-19 patient presentation. New or existing heart failure in the setting of COVID-19 can present a set of unique challenges that can complicate presentation, management, and prognosis. A careful understanding of the hemodynamic and diagnostic implications is essential for appropriate triage and management of these patients. Abnormal cardiac biomarkers are common in COVID-19 and can stem from a variety of mechanisms that involve the viral entry itself through the ACE2 receptors, direct cardiac injury, increased thrombotic activity, stress cardiomyopathy, and among others. The cytokine storm observed in this pandemic can be a culprit in many of the observed mechanisms and presentations. A correct understanding of the two-way interaction between heart failure medications and the infection as well as the proposed COVID-19 medications and heart failure can result in optimal management. Guideline-directed medical therapy for heart failure should not be interrupted for theoretical concerns but rather based on tolerance and clinical presentation. Initiating specific cardiac or heart failure medications to prevent the infection or mitigate the disease is also not an evidence-based practice at this time. Heart failure patients on advanced therapies including those with heart transplantation will particularly benefit from involving the advanced heart failure team members in the overall management if they contract the virus. [ABSTRACT FROM AUTHOR]

Heart transplantation (HT) has become a standard option for patients with end-stage heart failure (HF). However, the scarcity of donor availability remains a major hurdle for receiving this novel therapy, especially in the context of the rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic. We report the case of a patient in the United Arab Emirates (UAE) with advanced HF who was glucose-6-phosphate dehydrogenase deficient and had a history of type 2 diabetes mellitus with diabetic retinopathy and nephropathy, chronic kidney disease stage II, and hyperlipidemia. He was referred for HT abroad and was subsequently caught in the midst of the COVID-19 pandemic in New York, the US state most affected by the crisis at the time. Despite limited experience with favipiravir, we judged it to be the most appropriate agent with this patient's complex history given the lower risk for QT prolongation, no need for renal-dose adjustment, and no reported drug–drug interactions. Given the limited clinical experience with this agent, particularly for our patient, we decided to adopt strategies to mitigate and monitor the potential for QT prolongation. We outline the logistical, clinical, and pharmacological challenges that the poly-morbid patient and our HT program in the Middle-East faced under those novel circumstances. [ABSTRACT FROM AUTHOR]

• Within the past 2 decades, the number of brain-dead donors in Asia has increased significantly but remains lower than in Western countries. • More transplant centers have been registered in Asia since 2000, reaching 2160 centers in 2018. • The Asian continent witnessed a concomitant increase in deceased donor transplantation, primarily driven by kidney and liver transplants. • Public acceptance of brain death donation is an important area of focus in increasing organ availability in Asia. Organ shortage is the main limiting factor for further dissemination of organ transplantation therapies; implementation of brain-death (BD) criteria for organ donation purposes is essential for overcoming this limitation. Investigating and characterizing the effects of this intervention on organ availability and subsequent orthotopic organ transplantation in Asia, the world's most populous continent, should shed light on a global issue. The aim of this study was to describe temporal trends in brain-death donors (BDDs) and deceased-donor transplants (DDTs) in the Asian continent. We used data from the Global Observatory on Donation and Transplantation (GODT), the world's most comprehensive source of data relating to organ donation and transplantation activities. Available data on the number of BDDs and DDTs in 48 Asian countries was collated and analyzed for the years 2000–2019. The number of BDDs in Asia increased progressively, from 25 BBDs in 2000 to 5357 in 2019. The number of DDTs increased concomitantly, albeit with an initial decline between 2004 and 2008, with an exponential increase in the number of kidney and liver transplants, followed by heart and lung transplants. Data from the latest year with complete data (2019) demonstrated 25,557 deceased-donor organs were transplanted, representing a >3-fold increase in the number of transplanted organs compared with the nadir in 2008. Although the Asian continent has noticed a rapid increase in BD transplantation activities during the past 2 decades, it is self-evident that further dissemination and adoption of BD donation are fundamental to reducing organ shortage gap. [ABSTRACT FROM AUTHOR]