Objective: To analyze the basic thyroid hormone level on long term prognosis and peri-operative recovery in patients after heart transplantation (HT) at the terminal stage of heart failure (HF).
Methods: A total of 270 consecutive patients who received HT at the terminal stage of HF in our hospital from 2009-09 to 2014-07 were retrospectively studied. According to serum levels of thyroid stimulating hormone (TSH), the patients were divided into 3 groups: TSH < 0.55 mIU/L group, TSH (0.55-2.5) mIU/L group and TSH > 2.5 mIU/L group. The peri-operative recovery condition and long term prognosis were observed and compared among 3 groups.
Result: The average age of patients was at (44.58 ± 13.30) years including 228 (84.4%) male and 42 (15.6%) female. The average post-operative follow-up period was (31.88 ± 17.48) months with 100% follow-up rate. There were 41.8% of patients with hypothyroidism, and 46 (17.0%) patients with low T3 syndrome, 56 (20.7%) with subclinical hypothyroidism and 11 (4.1%) with clinical hypothyroidism. The ratio of low level thyroid hormone in HT patients was much higher than general population. For peri-operative recovery, the ICU stay time and mechanical ventilation time were similar among 3 groups,P>0.05, while TSH (0.55-2.50) mIU/L group had the shortest times and TSH > 2.50 mIU/L group had longest times. For long term prognosis, no matter uni-/multi- aviate regression analysis or Kaplan-Meier surviving curve all suggested that TSH > 2.50 mIU/L was the independent risk factor inlfuencing the prognosis of HT patients at the terminal stage of HF. Upon TSH increasing, the patients would have worse prognosis accordingly.
Conclusion: Serum level of TSH > 2.50 mIU/L was the independent risk factor in HT patients at the terminal stage of HF.

Objective To study the effect of de novo donor-specific antigen (DSA) on transplant heart function and recipient survival after heart transplantation.Methods 195 recipients went through heart transplantion from March 2013 to January 2016 in our center,13 patients with preoperative panel reactive antibody (PRA) and 10 patients suffered from in-hospital death were exclude from this study,and the actual number of patients enrolled in this study was 172.By detecting HLA typing and DSA,recipients were divided into DSA positive group,anti-HLA antigen positive but DSA negative group (DSA negative group) and anti-HLA negative group.Cardiac dysfunction,coronary heart disease and cardiovascular death were recorded as cardiac events during the follow-up period.By analyzing the cardiac events rate among 3 groups,the relationship between DSA and cardiac events was acknowledged.Results The mean follow-up period of all patients was (1.3 ± 0.8) years.Among 172 patients,6 were positive for DSA (3.4％).In the DSA positive group,66％ of DSA were directed at HLA Ⅱ,mainly against HLA-DQ,1 developed only anti-HLA I antibody,1 developed both anti-HLA Ⅰ and Ⅱ antibody.The median developing time of DSA was (256 ± 125) days,and the distribution was centralized in the first half year.84％ of patients in DSA positive group were witnessed cardiac events.One patient was diagnosed as coronary heart disease and received PCI at 145th days after DSA was developed.Four out of 6 patients experienced cardiac dysfunction with median developing time of (54 ± 13) days,and the cardiac function restored after treatment with immunosuppression modification,high-dose glucocorticoid and IVIG.In the DSA negative PRA positive group,the incidence of cardiac events was 13％.There was one cardiovascular death,and 2 cases of cardiac dysfunction.In the HLA antigen negative group,the incidence of cardiac events was 4％.Cox regression analysis revealed that DSA could be seen as an independent risk factor in leading to cardiac events and affecting mid-long term survival of recipients (P =0.02).Significant difference was observed in Kaplan-Meier analysis among 3 groups (P＜0.001).Conclusion DSA has strong impact on outcome after heart transplantation.Routine surveillance and appropriate treatment should be attached to DSA.

Objective To evaluate the effect of CYP3A5 genetic polymorphisms on tacrolimus (Tac) concentration/dosing and other clinical outcomes in a pilot cohort of 113 Chinese HTx recipients.Methods Association between CYP3A5 genetic variants and blood dose-adjusted trough concentrations (C0/D) of Tac at 1st month at the beginning of the immunosuppressive therapy was evaluated in cohorts of 113 patients,then at 1st,3rd,6th,and 12th months after transplantation in 41 patients who received Tac-based immunosuppressive therapy and never changed within one year after transplantation,respectively.In addition,we also evaluated the association between CYP3A5 genetic variants and other clinical outcomes,such as the classifications of endomyocardial biopsy and longterm prognosis.Results The CYP3A5 wild homozygote (* 1/* 1),mutant homozygote (* 3/* 3),and mutant heterozygote (* 1/* 3) occurred in 5,34 and 74 recipients respectively.The gene mutation rate of CYP3A5 in this cohort of Chinese HTx recipients was 80.5 ％ and the homozygous proportion was 65.5％.Compared with CYP3A5 expressors (* 1/* 1 or * 1/* 3),CYP3A5 nonexpressors (* 3/* 3) had a higher Tac C0/D at 1st month (47.34 ± 11.40 vs.116.11 ± 42.40 vs.293.70 ± 171.20,P =0.000),as well as other studied time points (3rd month:98.32 ± 39.43 vs.292.07 ± 141.08,P=0.003;6th month:90.00 ± 21.31 vs.341.68 ± 165.02,P =0.002;and 12th month:96.02 ± 29.33 vs.339.23 ± 162.30,P =0.018);and might have a lower classification of endomyocardial biopsy at 1st month (1.43 ± 0.73 vs.1.50 ± 0.58,P =0.867),3rd month (1.55 ±1.00 vs.2.00 ± 1.73,P =0.512),and 6th month (1.36 ± 0.84 vs.2.33 ± 1.53,P =0.132);as well as a higher mortality due to acute organ rejection (10％ vs.0,P =0.244) and all-cause mortality (20％ vs.9.7％,P =0.580).Conclusion In Chinese HTx recipients,the frequency of this * 3 allele is lower than that has been reported in the white population.The determinations of CYP3A5 genetypes in heart transplant recipients are helpful to guide the individualized Tac regimens.

Objective To assess the correlation between pre-operative N-terminal-pro-brain natriuretic levels and early survival rate among heart transplantion (HT) recipients in a single Chinese center.Methods According to the pre-operative NT-proBNP level of 284 HT recipients,the recipients were divided into two distinctive groups,≤5000 nmol/L group (237 cases) and ＞5000 nmol/L group (47 cases).The baseline characteristics and mortality for recipients with different primary cardiac diseases and on extracorporeal membrane oxygenation (ECMO) support were compared.Kaplan Meier method was used to calculate the 1-year survival rate of the two groups.Results The pre-operative NT-proBNP ＞5000 nmol/L group had an average pulmonary capillary wedge pressure of (25.1 ± 7.4)mmHg,noticeably higher than in ≤5000 nmol/L group [(21.4 ± 9.2) mmHg,P＜0.05].At the same time,the cardiac index (CI) in ＞5000 nmol/L group was (1.8 ± 0.5) L·min-1·m-2,significantly lower than in ≤5000 nmol/L group [(2.1 ± 0.6) L·min-1 ·m-2,P＜0.05].14.9％(7/47) of recipients in ＞5000 nmol/L group used ECMO support,and the corresponding ECMO-related morbidity was 71.4％ (5/7) and 1-year survival rate was 91.3％.6.8％ (16/237) of recipients in ≤ 5000 nmol/L group used ECMO support and the corresponding ECMO-related morbidity was 12.5％ (2/16) and 1-year overall survival rate was 96.9％.There was statistically significant difference in the ECMO usage,ECMO-related mortality rate and 1-year survival rate between the two groups (P＜0.05).Conclusion Recipients with pre-operative NT-proBNP ＞5000nmol/L have higher peri-operative ECMO-related morbidity and 1-year death rate.So determination of pre-operative NT-proBNP level may be beneficial to the timing of cardiac transplantation.

ObjectiveTo evaluate the clinical effect and reliability of basiliximab as immune inducer combined with classic triad resisting immune rejection scheme in preventing immune rejection after heart transplant.MethodsWe continuously collected the clinical information of 214 patients undergoing heart transplantation from June 2004 to January 2011.Basiliximab was used at 1st h before heart transplant and 4 days after the operation by 20 mg each time.Triad resisting immune rejection scheme included methylprednisone,cyclosporine A and mycophenolate mofetil.The endocardial biopsy was done to diagnose rejection postoperatively,and the severity of acute rejection was graded according to the standardized criteria of the International Society for Heart and Lung Transplantation (ISHLT).The recipients were followed up for 1year after the surgery,the data of the endocardial biopsy and rejection were collected,and the postoperative complications and deaths were observed.Results The first time of recipients to accept the endocardial biopsy was 20.1±7.3 days postoperatively,including 63 (29.4％) cases of Grade Ⅰ A,8 (3.7％) cases of grade Ⅰ B,and 12 (5.6％) cases of grade Ⅱ.One year after operation,143 recipients accepted the endocardial biopsy,including 29 (20.3％) cases of grade Ⅰ A,1(0.7％) case of grade Ⅰ B,12 (7.7％) cases of grade Ⅱ.During hospitalization,5 recipients died,including 3 cases due to transplant heart failure,1case due to multiple organ failure and 1due to sudden death.One year after discharge,there were 2 deaths,including one case of serious rejection and 1case of multiple organ failure One month after operation,infection occurred in 7 cases (3.3％),and acute renal insufficiency in 11cases (5.1％).ConclusionCombined use of Basiliximab with triad resisting immune rejection scheme was a kind of safe and effective therapy to prevent early acute rejection after heart transplantation.

Objective To determine the incidence and independent risk factors of new onset posttransplantation diabetes mellitus (PTDM) and its prognostic value in medium term survival rate in heart transplant recipients.Method We performed a retrospective study on all heart transplant recipients in a single center from June 2004 to May 2012,and selected 226 patients without DM in pretransplant period with median 41-month follow-up.According to the diagnostic criteria of the American Diabetes Association (ADA) 2006 revised edition of PTDM,the selected patients were divided into PTDM (group 1) and NPTDM (group 2).Univariate analysis and logistic regression analysis were used to determine preoperative and postoperative risk factors responsible for PTDM.Kaplan-Meier method and Log rank test were used for survival analysis.Result Of the 226 patients,53 case developed DM (23.5 ％).The multivariate analysis identified the following as predictive factors for the development of PTDM:age ([OR]:1.05,95％ CI:1.01 ～2.30,P =0.012),and first-degree relatives of family history of DM ([OR]:1.90,95％ CI:1.04～4.10,P =0.032).The 1-,3-and 5-year survival rate in PTDM patients post-transplantation was 100.0％,98.0％ and 89.8％,and that in NPTDM patients was 98.2％,94.2％ and 92.4％,respectively.Log Rank test displayed no significant difference between two survival curves (P＞0.05).Conclusion PTDM is a frequent comorbidity after HT.Age and first-degree relatives of family history of DM were significant and independent risk factors for the development of PTDM during the follow-up period.By appropriate treatment,the medium-term survival rate of patients with PTDM was unaffected.

Objective To investigate whether the preoperative nutritional risk index(NRI) can predict the clinical out-comes of the patients underwent homologous orthotopic heart transplantation after 4 weeks.Methods With the use of continu-ous sampling method, a total of 168 adult patients who underwent homologous orthotopic heart transplantation from March 2013 to March 2015 were enrolled in this study.According to the cut-off points of the NRI, the patients were divided into 4 groups (high, moderate, mild and no nutritional risk).4 weeks after transplantation, the data about the length of stay in ICU, infec-tive and non-infective complications were collected , and the predictive value of the preoperative NRI for the clinical outcomes of the patients underwent homologous orthotopic heart transplantation were evaluated after 4 weeks of operation.In addition, the enrolled patients were divided into 2 groups according to their nutritional risk(with or without), and the differences between the two groups were compared.Results Among the patients, the prevalence of high, moderate, and low nutritional risk was 7. 1％, 32.7％ and 9.5％, respectively.The prevalence of infective complications for the 4 groups(from high risk to no risk) was 16.7％、7.3％、6.3％ and 3.5％, and the corresponding prevalence of non-infective complications was 16.7％、9.1％、6.3％ and 2.4％, respectively.In addition, the length of ICU stay of the 4 group was(10.9 ±1.0)days,(7.8 ±0.5)days, (6.7 ±0.7)days and(5.9 ±0.6)days, respectively.There were significant differences of length of ICU stay, infective and non-infective complications among the 4 groups(P<0.05 for all).Totally, there were significant differences of clinical out-comes between patients with and without nutritional risk(P <0.05 for all).Conclusion Preoperative NRI can predict the clinical outcomes regarding infective and no-infective complications as well as length of ICU stay for the adult patients under-went homologous orthotopic heart transplantation .

Objective To summarize the incidence of cardiac allograft vasculopathy (CAV) after heart transplantation and the effect on the long-term survival of recipients. Methods Clinical data of 1 006 heart transplant recipients were retrospectively analyzed. Of 48 CAV patients, 4 cases were not included in this analysis due to lack of imaging evidence. A total of 1 002 recipients were divided into the CAV group (n=44) and non-CAV group (n=958) according to the incidence of CAV. The incidence of CAV was summarized. Clinical data of all patients were statistically compared between two groups. Imaging diagnosis, coronary artery disease, drug treatment and complications, postoperative survival and causes of death of CAV patients were analyzed. Results Among 1 006 heart transplant recipients, 48 cases (4.77%) developed CAV. Compared with the non-CAV group, the proportion of preoperative smoking history, preoperative hypertension history, coronary artery disease and perioperative infection was significantly higher in the CAV group (all P < 0.05). Among 44 patients diagnosed with CAV by imaging examination, 24 cases were diagnosed with CAV by coronary CT angiography (CTA), 4 cases by coronary angiography (CAG), and 16 cases by coronary CTA combined with CAG. Among 44 patients, the proportion of grade Ⅰ CAV was 45% (20/44), 30% (13/44) for grade Ⅱ CAV and 25% (11/44) for grade Ⅲ CAV, respectively. All patients received long-term use of statins after operation, and 20 patients were given with antiplatelet drugs. Among 44 CAV patients, 11 patients underwent percutaneous coronary intervention, 6 cases received repeated heart transplantation, and 8 patients died. Kaplan-Meier survival analysis demonstrated that there was no significant difference in the long-term survival rate between the CAV and non-CAV groups (P > 0.05), whereas the survival rate of patients tended to decline after the diagnosis of CAV (at postoperative 6-7 years). The long-term survival rates of patients with grade Ⅰ, grade Ⅱ and grade Ⅲ CAV showed no significant difference (P > 0.05). Even for patients with grade Ⅰ CAV, the long-term survival rate tended to decline. Conclusions CAV is a common and intractable complication following heart transplantation, and the long-term survival rate of patients after the diagnosis of CAV tended to decline. Deepening understanding of CAV, prompt prevention, diagnosis and treatment should be delivered to improve the long-term survival rate of patients after heart transplantation.

Objective To evaluate the effect of extracorporeal membrane oxygenation (ECMO) on early allograft dysfunction (EAD) after heart transplantation. Methods Clinical data of 614 heart transplant recipients were retrospectively analyzed. All recipients were divided into the ECMO group (n=43) and non-ECMO group (n=571) according to postoperative application of ECMO. In the ECMO group, the conditions of recipients undergoing ECMO after heart transplantation were summarized. Perioperative status and long-term prognosis of recipients were compared between two groups. Results Among 43 recipients undergoing ECMO, 17 cases underwent thoracotomy due to bleeding, 10 cases of infection, 4 cases of venous thrombosis of the lower limbs, and 1 case of stroke, respectively. Twenty-six recipients were recovered and discharged after successful weaning from ECMO, six died during ECMO support, six died after weaning from ECMO, five received retransplantation due to unsuccessful weaning from ECMO, and only one survived after retransplantation. Compared with the non-ECMO group, intraoperative cardiopulmonary bypass duration was significantly longer, the proportion of recipients requiring postoperative intra-aortic balloon pump (IABP), dialysis due to renal insufficiency, reoperation for hemostasis, infection, mechanical ventilation time≥96 h and tracheotomy was significantly higher, and the length of postoperative intensive care unit (ICU) stay was significantly longer in the ECMO group (all P < 0.05). The survival rate after discharge and 90-d survival rate in the ECMO group were 63% and 96%, significantly lower than 97% and 100% in the non-ECMO group (both P < 0.05). Survival analysis showed that the long-term survival rate in the ECMO group was significantly lower than that in the non-ECMO group (P < 0.05). After excluding the recipients who died within 90 d after heart transplantation, no significant difference was observed in the long-term survival rate (P > 0.05). Conclusions ECMO is an effective treatment of EAD after heart transplantation. The short-term survival rate of recipients using ECMO after heart transplantation is lower than that of those who do not use ECMO, and there is no significant difference in long-term survival of recipients surviving 90 d after heart transplantation.

Objective To evaluate the effect of renal insufficiency before heart transplantation on perioperative death, complications and long-term survival, and to compare the differences between preoperative serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) in preoperative risk assessment. Methods Clinical data of 1 095 heart transplant recipients were retrospectively analyzed. According to preoperative Scr level, all recipients were divided into the Scr < 133 μmol/L(n=980), Scr 133-176 μmol/L (n=83) and Scr≥177 μmol/L groups (n=32). According to preoperative eGFR, all recipients were divided into eGFR≥90 mL/(min·1.73m²) (n=436), eGFR 60-89 mL/(min·1.73m²) (n=418) and eGFR < 60 mL/(min·1.73m²) groups (n=241). Clinical prognosis of postoperative renal function, perioperative and long-term outcomes of recipients were compared among different groups. The effect of eGFR and Scr level on renal function injury and long-term survival after heart transplantation was assessed. Results With the increase of preoperative Scr level, the proportion of recipients undergoing postoperative continuous renal replacement therapy (CRRT) was increased, the proportion of recipients receiving postoperative mechanical circulatory support was elevated, the incidence of postoperative complications was increased, the duration of mechanical ventilation and intensive care unit(ICU) stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). With the decrease of preoperative eGFR, the proportion of recipients receiving postoperative CRRT was increased, the proportion of recipients using postoperative intra-aortic balloon pump (IABP) was elevated, the duration of mechanical ventilation and ICU stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). Scr≥177 μmol/L was an independent risk factor for postoperative death [adjusted hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.89-6.99, P < 0.01]. Among different groups classified by Scr and eGFR, the cumulative incidence rate of postoperative renal function injury and long-term survival rate were statistically significant among three groups (all P < 0.05). In patients with preoperative Scr < 133 μmol/L, the cumulative incidence rate of postoperative long-term renal function injury was significantly increased with the decrease of preoperative eGFR (P < 0.01). There was no significant difference in postoperative long-term survival rate among patients stratified by different eGFR (P > 0.05). Conclusions Renal insufficiency before heart transplantation is associated with poor perioperative and long-term prognosis. Preoperative Scr and eGFR are the independent risk factors for postoperative renal function injury. Scr yields low sensitivity in the assessment of preoperative renal function, whereas it has high accuracy in predicting perioperative death risk. And eGFR is a more sensitive parameter to evaluate preoperative renal function, which may identify early-stage renal functional abnormality and take effective measures during early stage to reduce adverse effect on prognosis.