廖中凯
中国医学科学院阜外医院 心血管内科
OBJECTIVES:The objectives of this study were to validate 3 existing heart transplant risk scores with a single-centre cohort in China and evaluate the efficacy of the 3 systems in predicting mortality.METHODS:We retrospectively studied 428 patients from a single centre who underwent heart transplants from January 2015 to December 2019. All patients were scored using the Index for Mortality Prediction After Cardiac Transplantation (IMPACT) and the United Network for Organ Sharing (UNOS) and risk stratification scores (RSSs). We assessed the efficacy of the risk scores by comparing the observed and the predicted 1-year mortality. Binary logistic regression was used to evaluate the predictive accuracy of the 3 risk scores. Model discrimination was assessed by measuring the area under the receiver operating curves. Kaplan-Meier survival analyses were performed after the patients were divided into different risk groups.RESULTS:Based on our cohort, the observed mortality was 6.54%, whereas the predicted mortality of the IMPACT and UNOS scores and the RSSs was 10.59%, 10.74% and 12.89%, respectively. Logistic regression analysis showed that the IMPACT [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.15-1.36; P < 0.001], UNOS (OR, 1.68; 95% CI, 1.37-2.07; P < 0.001) and risk stratification (OR, 1.61; 95% CI, 1.30-2.00; P < 0.001) scores were predictive of 1-year mortality. The discriminative power was numerically higher for the IMPACT score [area under the curve (AUC) of 0.691)] than for the UNOS score (AUC 0.685) and the RSS (AUC 0.648).CONCLUSIONS:We validated the IMPACT and UNOS scores and the RSSs as predictors of 1-year mortality after a heart transplant, but all 3 risk scores had unsatisfactory discriminative powers that overestimated the observed mortality for the Chinese cohort.
Interactive cardiovascular and thoracic surgery 2022
BACKGROUND AND OBJECTIVES:Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients.METHODS:We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality.RESULTS:In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314).CONCLUSIONS:CYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.
European journal of drug metabolism and pharmacokinetics 2019
INTRODUCTION:Radiation-induced heart disease (RIHD) is a serious side effect of cancer treatment, including coronary artery disease, valvular cardiac dysfunction, cardiomyopathy, aortopathy, and chronic constrictive pericarditis. Herein, this case we present was diagnosed as radiation-induced constrictive pericarditis and cardiomyopathy by means of cardiac magnetic resonance (CMR) and transthoracic echocardiogram, finally confirmed by pathology after performing heart transplant operation.CONCLUSIONS:This case supports a notion that RIHD often causes multiple heart impairment and CMR is helpful to diagnose cardiomyopathy after radiation.
Medicine 2017
The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ± 5.95 vs -1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).
Medicine 2016
OBJECTIVE:To assess the value of cardiopulmonary exercise test in the evaluation of cardiac function in patients with chronic left heart failure caused by dilated cardiomyopathy.METHODS:Fifty-three inpatients aged 18 year and over with chronic left heart failure caused by dilated cardiomyopathy at Fuwai Hospital from October 2010 to October 2011 were selected and divided into 2 groups according to the New York Heart Association (NYHA) heart function classification. One group had 20 cases for class II and another 33 cases for class III-IV. All of them received cardiopulmonary exercise tests. Synchronous measurement and record of gas exchange indices were taken during every breath, and so were heart rate, blood pressure, electrocardiogram and blood oxygen saturation. At the same time, other routine tests were also performed. After exercise test, anaerobic threshold and peak oxygen consumption indices were calculated and statistically analyzed. They also received subsequent follow-ups of 1 day, 1 week, 1 month, 6 months and 1 year, including activities, clinical manifestations and cardiac adverse events.RESULTS:At baseline, the differences in gender, age, body mass index, concurrent diseases, left ventricular end-diastolic diameter, left ventricular ejection fraction and serum creatinine had no statistical significance (P > 0.05). Compared with cardiac function class II group, the class III-IV group had higher left atrial diameter, level of amino terminal pro-B-type natriuretic peptide (NT-proBNP), incidence of atrial fibrillation ((51.4 ± 7.5) vs (43.6 ± 7.7) mm, (2 607 ± 1 782) vs (1 312 ± 901) µg/L, 42.4% (14/33) vs 5.0% (1/20)) and lower glomerular filtration rate, peak oxygen consumption, levels of anaerobic threshold ((72 ± 20) vs (97 ± 23) ml/min, (13.7 ± 2.6) vs (20.5 ± 3.6) ml·min(-1)·kg(-1), (10.7 ± 1.5) vs (13.3 ± 2.1) ml·min(-1)·kg(-1)) (all P < 0.01). And NT-proBNP and cardiac function classification showed a positive correlation (OR = 1.002, P = 0.003) while peak oxygen consumption, anaerobic threshold and cardiac function classification were negatively correlated (OR = 0.736, 0.608; P = 0.011, 0.001).CONCLUSIONS:Cardiopulmonary exercise test objectively reflects the cardiopulmonary reserve of heart failure patients with dilated cardiomyopathy. And the parameters of anaerobic threshold and peak oxygen consumption may reflect the patient's motor ability quantitatively and accurately.
Zhonghua yi xue za zhi 2014
OBJECTIVE:To access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients.METHODS:Data from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis.RESULTS:Hypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05).CONCLUSIONS:Hypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.
Zhonghua xin xue guan bing za zhi 2013
BACKGROUND:MicroRNAs (miRNAs) are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies. In this study, we monitored early myocardial injury and recovery after heart transplantation by detecting levels of circulating muscle-specific miR-133a, miR-133b and miR-208a.METHODS:7 consecutive patients underwent heart transplantation in Fuwai hospital and 14 healthy controls were included in our study. Peripheral vein blood was drawn from patients on the day just after transplantation (day 0), the 1st, 2nd, 3rd, 7th and 14th day after transplantation respectively. Serum from peripheral blood was obtained for cardiac troponin I (cTnI) measurement. Plasma was centrifuged from peripheral blood for measuring miR-133a, miR-133b and miR-208a by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The plasma concentration of miRNAs were calculated by absolute quantification method. The sensitivity and specificity of circulating miRNAs were revealed by receiver operating characteristic curve (ROC) analysis. Correlations between miRNAs and cTnI / perioperative parameters were analyzed.RESULTS:Similar to cTnI, miR-133a, miR-133b and miR-208a all showed dynamic changes from high to low levels early after operation. The Sensitivity and specificity of miRNAs were: miR-133a (85.7%,100%), miR-208a (100%,100%), and miR-133b (90%,100%). Correlations between miRNAs and cTnI were statistically significant (p < 0.05), especially for miR-133b (R2 = 0.813, p < 0.001). MiR-133b from Day 0-Day 2 (r > 0.98, p < 0.01), and cTnI from Day 1- Day 3 (r > 0.86, p < 0.05) had strong correlations with bypass time, particularly parallel bypass time. Obviously, miR-133b had a better correlation than cTnI. Circulating miR-133b correlated well with parameters of heart function such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and inotrope support, while cTnI only correlated with 3 of the 4 parameters mentioned above. MiR-133b also had strong correlations with ventilation time (r > 0.99, p < 0.001) and length of ICU stay (r > 0.92, p < 0.05), both of which reflected the recovery after operation. The correlation coefficients of miR-133b were also higher than that of cTnI.CONCLUSIONS:The dynamic change in circulating muscle-specific miRNAs, especially miR-133b can reflect early myocardial injury after heart transplantation. And miR-133b may have advantages over cTnI in forecasting graft dysfunction and recovery of patients after operation.
Journal of cardiothoracic surgery 2013
OBJECTIVE:Primary indications for endomyocardial biopsy (EMB) include heart transplant rejection surveillance and identifying cardiomyopathy or myocarditis. EMB procedures have not yet gained widespread acceptance because of concerns about possible complications associated with EMB procedures. In this single-center retrospective study, we analyzed the incidence of major and minor EMB procedure-related complications of 439 EMBs during the past 4.5 years.METHODS:From May 2004 to November 2008, 15 patients with cardiomyopathy and 1 patient with suspected cardiac tumor underwent 16 EMB procedures and 131 heart transplant recipients underwent 423 EMB procedures with the use of a modified Cordis bioptome. All EMB procedures were made via the right internal jugular vein approach and RV septum EMBs were performed under fluoroscopic guidance without additional echocardiographic monitoring. Operators were allowed to perform EMB procedure alone if a minimum of 50 EMB procedures had been previously supervised by a senior operator and all EMBs were performed by 4 operators. All patients underwent a 12-lead electrocardiogram (ECG), 12-hour continuous ambulatory ECG monitoring, chest X-ray and transthoracic echocardiography before and after EMB procedures to obtain a detailed evaluation of the incidence of conduction abnormalities, arrhythmias, pericardial effusions and worsening valve insufficiency.RESULTS:There was no major complications like cardiac tamponade, hemothorax and pneumothorax. Minor complications such as conduction abnormalities including temporary RBBB (lasting < 24 h after EMB procedures) were found in 2 cases (0.47%) and sustained RBBB (> 24 h) was evidenced in 1 case (0.23%). There were no A-V block, complex ventricular arrhythmias or episodes of atrial fibrillation during and post procedure. In addition, 4 cases (0.91%)of EMB induced mild-moderate tricuspid regurgitation during the procedure were diagnosed by echocardiography.CONCLUSION:The EMB procedure via the right internal jugular vein approach under fluoroscopic guidance is safe and associated with a very low complication rate when performed by experienced operators.
Zhonghua xin xue guan bing za zhi 2010
OBJECTIVE:To summarize and analyze clinical outcomes and experience about using extracorporeal membrane oxygenation (ECMO) in supporting heart transplant patients in the peri-operative period of in Fuwai Hospital retrospectively.METHODS:We performed 131 orthotopic heart transplantations from June 2004 to December 2008. Fourteen cases used veno-artery ECMO (Medtronic Ltd) for mechanical circulatory support in the peri-operative period of heart transplantation. Active clotting time(ACT) was maintained between 160 - 200 seconds, mean blood flow was 1.8 - 3.3 L/min during ECMO assistant period.RESULTS:Twelve survivals discharged with NYHAI, two patients died of multiple orgen failure with severe infection and complication of central nervous system. The ECMO time was 75 - 824 h and mean time 149 h. 12 survivals with ECMO assistance decreases the dose of vasoactive drugs, after bedside UCG evaluating heart function recovery with stable circulation, ECMO could be weaned off uneventfully after 100 h. Five patients with seven times bleeding complication and one patient with catheter-associated arterial thrombosis of distal limb, all ECMO patients with low-albuminemia and hyperbilirubinemia at some degree, eleven patients with increasing blood creatine and five patients were treated with continous renal replacement therapy, one patient with pertinacious hyperbilirubinemia was treated with plasma exchange and molecular absorbent recirculating system. Seven patients were extension incision healing and six patients were tracheotomy.CONCLUSIONS:ECMO can bridge patients with end-stage heart failure to heart transplant, and extend the use of marginal donors, grasp the ECMO indication and timing of application, avoiding irreversible dysfunction of the vital organs and preventing complication during ECMO, ECMO may decrease mortality of severe patients in the peri-operative period of heart transplantation.
Zhonghua xin xue guan bing za zhi 2009
Mononuclear cells (MNCs) isolated from peripheral blood by density gradient centrifugation were plated on human fibronectin-coated culture plates and cultured in EGM-2 medium. Attached spindle-shaped cells, reported as endothelial progenitor cells (EPCs) by some investigators, had elongated from adherent round cells, but had not proliferated from a small number of cells as supposed previously. The growth curve of the primary EPCs showed that the cells had little proliferative capacity. Flow cytometry analysis showed that the cells could express some of the endothelial lineage markers, while they could also express CD14, which is considered a marker of monocyte/macrophage lineages throughout culture. In endothelial function assays, the cells demonstrated a lower level of expression of eNOS than mature endothelial cells in the reverse transcription-polymerase chain reaction and did not show an ability to develop tube-like structures in angiogenesis assay in vitro. In this study, we identified the monocytoid function of EPCs by the combined Dil-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and Indian ink uptake tests. All the cells were double positive for Dil-Ac-LDL and Indian ink uptake at days 4, 14 and 28 of culture, which means the EPCs maintained monocytoid function throughout the culture. Therefore, although adult EPCs from peripheral MNCs have some endothelial lineage properties, they maintain typical monocytic function and have little proliferative capacity.
Cell research 2006
