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Hypogammaglobulinemia (HGG) can occur following solid organ transplantation. However, there are limited data describing the prevalence, risk factors, and clinical outcomes associated with HGG following heart transplantation. We retrospectively reviewed data of 132 patients who had undergone heart transplantation at our institution between April 2014 and December 2018. We classified patients into three groups based on the lowest serum IgG level post-transplant: normal (≥700 mg/dL), mild HGG (≥450 and <700 mg/dL), and severe HGG (<450 mg/dL). We compared clinical outcomes from the date of the lowest IgG level. Mean age was 57 (47, 64) years, and 94 (71%) patients were male. Prevalence of severe HGG was the highest (27%) at 3-6 months following heart transplantation and then decreased to 5% after 1 year. Multivariate analysis showed that older age and Caucasian race were independent risk factors for HGG. Overall survival was comparable between the groups; however, survival free of infection was 73%, 60%, and 45% at 1 year in the normal, mild HGG, and severe HGG groups, respectively (P = .013). In conclusion, there is a high prevalence of HGG in the early post-heart transplant period that decreases over time. HGG is associated with an increased incidence of infection., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function., Methods and Results: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m 2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m 2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use., Conclusions: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The heart transplant (HT) guidelines recommendation to match recipient and donors within 30% of body weight lacks a strong evidence base and is not well established in patients bridged to transplant with left ventricular assist devices (LVAD). In light of the scarcity of donor hearts, we investigated the effect of size mismatch on hemodynamics, one-year survival and length of stay (LOS) following HT., Methods: Single-center retrospective analysis of consecutive HT patients from April 2007 to September 2017. Recipients were divided into 3 cohorts based on donor-to-recipient weight ratio (DRWR): (1) undersized (<0.7), (2) size-matched, (0.7-1.3); (3) oversized (>1.3)., Results: 288 consecutive patients were identified (mean age 53 ± 11 years; 76% male), 46 were undersized (0.61 ± 0.05), 210 size-matched (0.94 ± 0.16), and 32 oversized (1.65 ± 0.38). There was no significant difference in donor left ventricular end diastolic diameter (LVEDD) between the 3 groups (p = 0.11). The donor/recipient (D/R) predicted heart mass (PHM) was lowest in the undersized group (0.92 ± 0.13). There were no significant differences in 1-year survival in the overall and LVAD cohort (p = 0.65 and 0.59, respectively). Neither donor LVEDD nor D/R PHM differed among survivors or non-survivors. LOS was longer in the undersized group than the size-matched cohort (p = 0.004). The undersized group had hearts with the highest filling pressures and lowest cardiac index at 1 week among the remaining groups (p = 0.009, 0.017, and p = 0.05, respectively). There were no clinically significant differences in hemodynamics at 1 or 6 months., Conclusions: HT undersizing affects hemodynamics early but not later in the course and does not impact 1-year survival. The liberalization of size matching may increase the HT donor pool significantly., (Copyright © 2019. Published by Elsevier Inc.)

Heart transplantation (HTx) is the gold standard therapy to improve quality and quantity of life in end-stage heart failure patients. However, recipients are at risk of experiencing allograft rejection and post-transplant complications, in the acute as well as chronic phase. A 43-year-old man with a history of left ventricular non-compaction underwent orthotopic HTx. On Day 7, transthoracic echocardiography showed a sudden decrease in cardiac function with hypokinesis in a left ventricular anterior wall distribution. Coronary angiography revealed a large thrombus in the left main trunk. With intra-aortic balloon pump support, emergency percutaneous coronary intervention was performed. Endomyocardial biopsy showed no rejection. A left main trunk thrombus is rare in the early phase after HTx, but it can be a life-threatening complication. Transthoracic echocardiography is well known to be important in the management of heart transplant recipients, and coronary angiography as well as myocardial biopsy should be considered when left ventricular wall motion is impaired., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Although many risk factors are reported about graft rejection after heart transplantation (HTx), the effect of HLA mismatch (MM) still remains unknown, especially in the Japanese population. The aim of the present study was to investigate the influence of HLA MM on graft rejection among HTx recipients in Japan., Methods: We retrospectively investigated the association of the number of HLA MM including class I (A, B) and class II (DR) (for each locus MM: 0 to 2, total MM: 0 to 6) and the incidence of moderate to severe acute cellular rejection (ACR) confirmed by endomyocardial biopsy (International Society for Heart and Lung Transplantation grade ≥ 3A/2R) within 1 year after HTx., Results: Between 2007 and 2014, we had 49 HTx cases in our institute. After excluding those with insufficient data and positive donor-specific antigen, finally 35 patients were enrolled. Moderate to severe ACR was observed in 16 (45.7%) patients. The number of HLA-DR MM was significantly associated with the development of ACR (ACR+: 1.50 ± 0.63, ACR-: 1.11 ± 0.46, P = .029). From univariate analysis, DR MM = 2 was the only independent risk factor for ACR episodes (P = .017). The frequency of ACR within 1 year was significantly higher in those with DR MM = 2 (DR MM = 0 to 1: 0.3 ± 0.47, DR MM = 2: 1.17 ± 1.34 times, P = .007)., Conclusions: The number of HLA-DR MMs was associated with the development and recurrence of ACR episodes among HTx recipients within 1 year after transplantation in Japanese population., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

For 6 years after heart transplantation, a 23-year old female recipient had been treated with immunosuppressants including tacrolimus and mycophenolate mofetil (MMF), without any major rejection or graft dysfunction. She unexpectedly became pregnant for the first time, and we converted MMF to azathioprine (AZA), but she soon experienced a spontaneous abortion. After careful counseling under the continuation of AZA, she became pregnant again 3 months after the abortion. We closely monitored the concentration of immunosuppressive agents, cardiac function, fetal condition, and serological assay including human leukocyte antigen (HLA) sensitization, and she eventually delivered a normal male infant at 38 weeks gestation without any complications. AZA was converted to MMF soon after the delivery. There have been no complications in either the patient or infant after the delivery.Because pregnancy itself involves a risk of cardiac graft rejection in the recipient as well as fetal complications, it is important to educate HTx recipients about planned pregnancy and to conduct careful follow-up after pregnancy.

Background: Using hearts from marginal donors could be related to increased risk of primary graft dysfunction and poor long-term survival. However, factors associated with delayed myocardial recovery after heart transplantation (HTx) remain unknown. We sought to clarify risk factors that predict early low output after HTx, and investigated whether early low output affects mid-term graft dysfunction., Methods: We retrospectively analyzed patients who had undergone HTx at The University of Tokyo Hospital. We defined early low output patients as those whose cardiac index (CI) was <2.2 L/min/m(2) despite the use of intravenous inotrope at 1 week after HTx., Results: We included 45 consecutive HTx recipients, and classified 11 patients into early low output group, and the others into early preserved output group. We performed univariable logistic analysis and found that donor age was the only significant factor that predicted early low output (odds ratio 1.107, 95% confidence interval 1.034-1.210, p=0.002). CI of early low output patients gradually increased and it caught up with that of early preserved output patients at 2 weeks after HTx (2.4±0.6 L/min/m(2) in early low output group vs 2.5±0.5 L/min/m(2) in early preserved output group, p=0.684). Plasma B-type natriuretic peptide concentration of early low output patients was higher (1118.5±1250.2 pg/ml vs 526.4±399.5 pg/ml; p=0.033) at 1 week, 703.6±518.4 pg/ml vs 464.6±509.0 pg/ml (p=0.033) at 2 weeks, and 387.7±231.9 pg/ml vs 249.4±209.5 pg/ml (p=0.010) at 4 weeks after HTx, and it came down to that of early preserved output patients at 12 weeks after HTx., Conclusions: Donor age was a predictor of early low output after HTx. We should be careful after HTx from old donors. However, hemodynamic parameters of early low output patients gradually caught up with those of early preserved output patients., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Serial endomyocardial biopsies (EMBs) are scheduled even several years after heart transplantation (HTx) to monitor for late rejection (LR). However, repeated EMBs are associated with an increased risk for fatal complications and decrease the quality of life of the recipient. We retrospectively analyzed clinical data from 42 adult recipients who had received HTx and were followed > 1 year at the University of Tokyo Hospital. Five recipients experienced LR at 1130 ± 157 days after HTx, and all 5 had experienced acute cellular rejection (ACR) with ISHLT grade ≥ 2R within the first year, which was treated with methylprednisolone pulse therapy (sensitivity, 1.000; specificity, 0.7027). Logistic regression analyses demonstrated that positive panel reactive antibody (PRA) was the only significant predictor for LR among all parameters at 1 year after HTx (P = 0.020, odds ratio 24.00). Among the 5 recipients with LR, LR occurred earlier in the two PRA positive recipients than in those with a negative PRA (981 ± 12 versus 1230 ± 110 days, P = 0.042). Among the perioperative parameters, gender mismatch [n = 13 (31%)] was the only significant predictor for ACR within the first year in logistic regression analyses (P = 0.042, odds ratio 4.200). In conclusion, the current schedule of serial EMBs should perhaps be reconsidered for recipients without any history of ACR within the first year due to their lower risk of LR.

Although post-transplant lymphoproliferative disease (PTLD) is one of the major fatal complications encountered several years after heart transplant (HTx), little is known about early-PTLD emerging within the first year. We here describe the rare case of a 24-year-old female patient who suffered from early-PTLD (DLBCL: diffuse large B-cell lymphoma) associated with an Epstein-Barr virus (EBV) infection, that developed around the jejunum at 7 months after HTx. She suffered from acute abdominal peritonitis due to perforation of the jejunum soon after the first chemotherapy. She was treated successfully by emergent partial resection of the jejunum and colostomy after the discontinuation of everolimus (EVL) and successive low-dose chemotherapy under careful monitoring and adjustment of intravenous immunosuppressant including cyclosporine (CyA) and prednisolone to avoid a rejection reaction. Prophylactic strategies for early-PTLD in HTx recipients should be undertaken with caution.

Purpose Tricuspid regurgitation (TR) is a significant complication after heart transplantation (HTx). Tricuspid valve annuloplasty (TVA) may be performed empirically at the time of transplant to prevent the development of TR and right ventricular failure. This study aims to investigate the long-term impact of TVA on incidence of TR and survival. Methods All patients transplanted between 1/2010 - 8/2018 were enrolled. At our institution, we routinely perform DeVega TVA during HTx. All echocardiograms post-HTx were evaluated. TR was classified into 5 groups: none, trace, mild, moderate and severe. The incidence of significant TR (moderate or severe) over time and the effect of TR on survival were evaluated. Echocardiograms were evaluated starting 3 months post-HTx. Results 248 patients underwent HTx in this period, and 243 who underwent concomitant TVA were included in this analysis (mean age 54 years, 76% male). During 3.0 ± 2.1 years follow-up, 22 (9.1%) of patients developed significant TR. In the TVA group, survival free of significant TR was 96.9% at 6-months, 94.3% at 1 year, 91.6% at 2 years, 90.8% at 3 years, 90.8% at 4 years, and 88.8% at 5 years (Figure 1A). 5-year survival among those who experienced significant TR was numerically lower, but not significantly different (70.7% vs 81.5%, p=0.24) (Figure 1B). Only 8 (3.3%) patients required permanent pacemaker implantation over a median of 51 days (IQR 14-522) following HTx. Conclusion Significant TR after HTx is common and progressively worsens despite concomitant TVA. The association of significant TR with long-term survival and the benefit of TVA require further evaluation. [ABSTRACT FROM AUTHOR]

Purpose Cylex Immune Function Test (IFT)(ImmuKnow®) assesses T-cell activity by measuring ATP levels. It is a useful assay that measures global immune response in patients post heart transplantation (HTx). However, its role in guiding medical therapy is still limited. We aim to study the association of IFT with HTx rejection and infection. Methods We investigated all patients who received HTx from 4/2014 - 8/2018. All IFT levels measured were divided into 3 groups: rejection phase (within 1 month before rejection episode, ISHLT 1990 ≥ grade 1B), infection phase (within 1 month of infection requiring admission), other stable phase, and analyzed these IFT values. Rejection episodes within 1 month post-HTx were excluded. Results 156 HTx patients were included (mean age 54 years, 74% male). The mean follow-up period from HTx was 2.1 ± 1.4 years, over which 757 IFT values were collected. 25 IFT levels were assessed in rejection phase, 123 in infection phase and 611 were in stable phase. Mean IFT in infection phase was significantly lower compared to stable phase (166 ± 143 vs 264 ± 180 ng ATP/mL, p<0.001), while mean IFT in rejection phase was comparable to stable phase (273 ± 265 vs 264 ± 180 ng ATP/mL, p=0.9) (Figure 1). Conclusion Infection was associated with lower IFT levels compared to stable post-transplant levels. IFT may be a valuable tool in the detection of infection post-HTx and can guide reduction in immunosuppression. However, its role in predicting rejection needs further evaluation. [ABSTRACT FROM AUTHOR]

Hypogammaglobulinemia (HGG) can be identified in patients following solid organ transplantation and is thought to be predominantly due to immunosuppression. There is limited data describing the extent, degree and clinical outcomes associated with HGG following heart transplantation. The aim of this study is to investigate the prevalence and clinical significance of HGG in heart transplant recipients. We retrospectively reviewed data of patients who had underwent heart transplantation at our institution between 4/2014 and 12/2018. We excluded patients with multi-organ transplantation. We defined serum IgG <700 mg/dl as mild and <450 mg/dl as severe HGG. We classified patients into normal, mild HGG and severe HGG groups based on the lowest IgG level during follow-up. We compared clinical outcomes between the groups from the date of the lowest IgG level. We enrolled 132 patients who had at least one serum IgG value following heart transplantation during the study period. Mean age was 53±14 years old and 94 (71%) patients were male. During 761 (463, 1266) days of follow-up, patients had a median of 4 (3, 6) IgG measurements. Prevalence of severe HGG was highest (27%) 3-6 months post-heart transplant and then decreased to 5% at 1-2 years (Figure A). Survival freedom of infection was 51%, 35% and 17% at 2 years in the normal, mild HGG and severe HGG groups, respectively (P=0.03, Figure B). Overall survival and rejection-free survival were comparable between the groups. There is a high prevalence of HGG in the early post-heart transplant period that decreases over time. HGG is significantly associated with infectious complications. Further studies are needed to investigate the prophylactic treatment of HGG with IVIG in heart transplant recipients. [ABSTRACT FROM AUTHOR]