Analysis for Risk Factors of Death in Atrial Fibrillation Patients With or Without Heart Failure / 中国循环杂志

Objective: To explore the risk factors of death in atrial fibrillation (AF) patients with or without heart failure (HF). Methods: A total of 2015 emergency AF patients from 20 hospitals in China from 2008-11 to 2011-10 were consecutively enrolled. Based on existing HF, the patients were divided into 2 groups: HF group, n=753 and Non-HF group, n=1263. The baseline condition and in-hospital treatment were recorded, patients were followed-up for 1 year to document all-cause death and the relevant risk factors were studied by multivariate Cox regression analysis. Results: Compared with Non-HF group, HF group had less male, lower heart rate (HR) and body mass index (BMI), less patients with previous histories of hypertension and hyperthyreosis, lower application rates of calcium antagonists and amiodarone, all P<0.05; HF group had the higher CHADS2score, more patients with previous histories of myocardial infarction, coronary artery disease, congenital heart disease (HD), valvular HD, rheumatic HD, left ventricular (LV) hypertrophy, smoking, LV dysfunction, cognitive disorder,pneumonectasis/chronic obstructive pulmonary disease (COPD), valvular surgery and major bleeding; higher application rates of diuretics, ACEI, digoxin, aspirin and warfarin, all P<0.05. 1991 patients finished follow-up study and during that period, compared with Non-HF group, HF group showed the lower usage rates of rhythm-control drugs and clopidogrel, while higher usage rates of ventricular-control drugs and warfarin, all P<0.05; higher incidences of death and major bleeding, all P<0.05. Cox regression analysis indicated that HF was the risk factor for 1 year mortality in AF patients (HR=1.50, 95% CI 1.17-1.92, P=0.001). In Non-HF group, age (HR=1.09, 95% CI 1.07-1.11, P<0.001), heart rate (HR=1.011, 95% CI 1.005-1.017, P<0.001), primary diagnosis (HR=1.63, 95% CI 1.13-2.35, P=0.01) and COPD (HR=2.18, 95% CI 1.47-3.22, P<0.001) were related to 1 year death. In HF group, age (HR=1.05, 95% CI 1.03-1.07, P<0.001), BMI (HR=0.92, 95% CI 0.88-0.96, P<0.001), systolic blood pressure (HR=0.991, 95% CI 0.984-0.998, P=0.012) and primary diagnosis (HR=2.50, 95% CI 1.48-4.21, P=0.001) were related to 1 year death. Conclusion: Baseline condition and in-hospital treatment were different in AF patients with or without HF. HF was the risk factor for 1 year mortality and the other risk factors were different in AF patients with or without HF.

Clopidogrel metabolism related gene polymorphisms in Chinese patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes (CYP2C19, ABCB1 and PON1) in Chinese patients with acute coronary syndrome (ACS) by genotype analysis.</p><p><b>METHODS</b>Genetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 *2-*8, *17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency (MAF) was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any "loss-of-function" (LOF) allele *2-*8 or "gain-of-function" (GOF) allele *17], intermediate (with only one LOF allele), Poor (with two or more LOF alleles), ultra (with one or two GOF alleles) or unknown (with one LOF allele and one GOF allele).</p><p><b>RESULTS</b>A total of 2800 ACS patients were enrolled [mean age (59.0 ± 12.3) years and 2236 males (79.9%)]. There were 74% patients with ST-segment elevation myocardial infarction (STEMI, n = 2072), 22.0% patients with non-ST-segment elevation myocardial infarction (NSTEMI, n = 617) and 4.0% patients with unstable angina (UA, n = 111). The minor allele frequency (MAF) for each genotype of CYP2C19 *2, *3, *4, *17 was 28.7%, 4.6%, 0.1% and 1.2%, respectively. There was no LOF allele *5-*8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37.8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10.3%, ultra in 1.9% and unknown in 0.6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56.4% and GOF carriers were 2.5%.</p><p><b>CONCLUSIONS</b>Our study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.</p>

Sirolimus use in heart transplantation recipients with chronic renal dysfunction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.</p><p><b>METHODS</b>From June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose.</p><p><b>RESULTS</b>The mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05).</p><p><b>CONCLUSION</b>Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.</p>

Association between serum NT-proBNP/hs-CRP and acute rejection after heart transplantation / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of the present work was to investigate the potential relationship between acute rejection and serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP)/high sensitivity C reactive protein (hs-CRP) in post-transplant patients.</p><p><b>METHODS</b>Sixty-one consecutive orthotopic heart transplantation recipients were prospectively recruited from the cardiac transplantation programme at Fuwai Hospital. Endomyocardial biopsies (EMB) were performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB were also performed when patients had new symptoms of heart failure or at 2 weeks after steroid pulse therapy. Serum NT-proBNP and hs-CRP were simultaneously measured before EMB procedure.</p><p><b>RESULTS</b>A total of 126 biopsy samples were obtained from the 61 patients. Serum NT-proBNP concentrations progressively decreased after transplantation (spearman correlation coefficient -0.520, P = 0.000). NT-proBNP levels within 6 months after transplantation were significantly higher than those beyond 6 months post transplantation [(11.86 +/- 11.16) x 10(-16) mol/L vs.(5.83 +/- 6.58) x 10(-16) mol/L, P = 0.002]. NT-proBNP concentrations in patients with rejection tended to be higher than patients without rejection (13.68 x 10(-16) mol/L vs. 9.26 x 10(-16) mol/L, P = 0.073). After time adjustment, the difference of NT-proBNP concentrations between patients with or without rejection becomes statistically significant (14.45 x 10(-16) mol/L vs. 9.1 x 10(-16) mol/L, P = 0.025). Receiver operating characteristics analysis for NT-proBNP versus rejection grade revealed an area under the curve of 0.566, indicating a low predictive value for NT-proBNP. A cutoff of 6.00 x 10(-16) mol/L yielded poor specificity (44.8%) and sensitivity (57.1%), the sensitivity and specificity were 38.1% and 61.0%, respectively with a cutoff of 8.00 x 10(-16) mol/L. hs-CRP levels within 6 months after transplantation tended to be higher than those beyond 6 months [(2.39 +/- 3.90) mg/L vs. (1.34 +/- 2.73) mg/L, P = 0.069]. hs-CRP concentrations in patients with rejection were similar as patients without rejection (2.995 mg/L vs. 1.833 mg/L, P = 0.138). The incidence of rejection was similar in patients with two higher biomarkers (5/20, 25%) compared to patients with two low biomarkers (3/26, 11.5%, P = 0.232).</p><p><b>CONCLUSIONS</b>NT-proBNP level decreased after transplantation. Although increased NT-proBNP concentrations were related to rejection, the diagnostic capacity was low. Elevated hs-CRP concentrations were not related to rejection after heart transplantation.</p>