Impact of corrected sinus node recovery time in predicting recurrence in patients with paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) and sinus node dysfunction (SND) have common underlying pathophysiological mechanisms. As an index of SND, corrected sinus node recovery time (CSNRT) may also reflect atrial function. The aim of the present study was to determine whether CSNRT predicts AF recurrence in patients undergoing AF ablation. METHODS: Consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent radiofrequency catheter ablation between January 2017 and December 2018 were enrolled. Clinical data, CSNRT, and other electrophysiology indices were collected and analysed between patients with or without AF recurrence. RESULTS: A total of 159 patients with PAF who underwent the same radiofrequency catheter ablation procedure were enrolled, including 25 patients with SND. During the one-year follow-up period, 22 patients experienced AF recurrence. Patients with recurrence had a significantly longer CSNRT and a larger left atrial volume index (LAVI) than patients without AF recurrence. SND (CSNRT > 550 ms) and a larger LAVI were independently associated with AF recurrence after ablation. A statistically significant CSNRT cut-off value of 550 ms predicted AF recurrence with 73% sensitivity and 85% specificity. CONCLUSION: CSNRT and LAVI are independent predictors of PAF recurrence following ablation.

A New ISL1 Loss-of-Function Mutation Predisposes to Congenital Double Outlet Right Ventricle.

Occurring in about 1% of all live births, congenital heart defects (CHDs) represent the most frequent type of developmental abnormality and account for remarkably increased infant morbidity and mortality. Aggregating studies demonstrate that genetic components have a key role in the occurrence of CHDs. Nevertheless, due to pronounced genetic heterogeneity, the genetic causes of CHDs remain unclear in most patients. In this research, 114 unrelated patients affected with CHDs and 218 unrelated individuals without CHDs served as controls were recruited. The coding regions and splicing donors/acceptors of the ISL1 gene, which codes for a transcription factor required for proper cardiovascular development, were screened for mutations by sequencing in all study participants. The functional characteristics of an identified ISL1 mutation were delineated with a dual-luciferase reporter assay system. As a result, a new heterozygous ISL1 mutation, NM_002202.2: c.225C>G; p. (Tyr75*), was discovered in an index patient with double outlet right ventricle and ventricular septal defect. Analysis of the proband's family unveiled that the mutation co-segregated with the CHD phenotype. The nonsense mutation was absent in the 436 control chromosomes. Biological analysis showed that the mutant ISL1 protein had no transcriptional activity. Furthermore, the mutation nullified the synergistic activation between ISL1 and TBX20, another CHD-associated transcription factor. This research for the first time links an ISL1 loss-of-function mutation to double outlet right ventricle in humans, which adds insight to the molecular pathogenesis underpinning CHDs, suggesting potential implications for timely personalized management of CHD patients.

Design, synthesis of novel azolyl flavonoids and their protein tyrosine Phosphatase-1B inhibitory activities.

A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS and HRMS spectra. All the newly prepared compounds were screened for their potential protein tyrosine phosphatase inhibitory activities. Bioactive assay manifested that most of the azolyl flavonoids exhibited good protein phosphatase 1B (PTP1B) inhibitory activities. Especially, triazolyl flavonoid 6a displayed the best inhibitory activity (IC50 = 1.6 µM) with 9.9-fold selectivity for PTP1B over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated 6a has lower cytotoxicity. Molecular modeling and dynamics studies revealed the reason of selectivity for PTP1B over TCPTP. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity.

TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of congestive heart failure, sudden cardiac death and cardiac transplantation. Aggregating evidence highlights the genetic origin of DCM. However, DCM is a genetically heterogeneous disorder, and the genetic components underlying DCM in most cases remain unknown. METHODS: The coding regions and splicing junction sites of the TBX20 gene were sequenced in 120 unrelated patients with idiopathic DCM. The available close relatives of the index patient carrying an identified mutation and 300 unrelated ethnically matched healthy individuals used as controls were genotyped for TBX20. The functional characteristics of the mutant TBX20 were assayed in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. RESULTS: A novel heterozygous TBX20 mutation, p.F256I, was identified in a family with DCM transmitted in an autosomal dominant fashion, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 600 control chromosomes and the altered amino acid was completely conserved evolutionarily among various species. Functional assays revealed that the mutant TBX20 had significantly diminished transcriptional activity. Furthermore, the mutation markedly reduced the synergistic activation of TBX20 with NKX2-5 or GATA4. CONCLUSIONS: This study links TBX20 loss-of-function mutation to idiopathic DCM in humans for the first time, providing novel insight into the molecular mechanism underpinning DCM.

Castleman disease of the neck: CT and MR imaging findings.

OBJECTIVE: To characterize the computed tomography (CT) and magnetic resonance imaging (MRI) findings of Castleman disease of the neck. METHODS: The imaging findings of 21 patients with Castleman disease of the neck were reviewed retrospectively. Of the 21 patients, 16 underwent unenhanced and contrast-enhanced CT scans; 5 underwent unenhanced and contrast-enhanced MRI scans. RESULTS: The unenhanced CT images showed isolated or multiple well-defined homogenous mild hypodensity lesions in fifteen cases, and a heterogeneous nodule with central areas of mild hypodensity in one case. Calcification was not observed in any of the patients. In five patients, MR T1-weighted images revealed well-defined, homogeneous isointense or mild hyperintense lesions to the muscle; T2-weighted images showed these as intermediate hyperintense. Sixteen cases showed intermediate to marked homogeneous enhancement on contrast-enhanced CT or MR T1-weighted images. Of the other five cases that underwent double-phase CT scans, four showed mild or intermediate heterogeneous enhancement at the arterial phase, and homogeneous intermediate or marked enhancement at the venous phase; the remaining case showed mild and intermediate ring-enhancement with a central non-enhanced area at the arterial and venous phases, respectively. CONCLUSION: Castleman disease of the neck can be characterized as solitary or multiple well-defined, mild hypodensity or homogeneous intense lesions on plain CT/MR scans, and demonstrates intermediate and marked enhancement on contrast-enhanced CT/MR scans. On double-phase CT scans, Castleman disease often demonstrates mild enhancement at the arterial phase, and gradually uniform enhancement at venous phase. Double-phase enhanced CT or MRI may help to differentiate Castleman disease from other diseases.

Microparticles: new light shed on the understanding of venous thromboembolism.

Microparticles are small membrane fragments shed primarily from blood and endothelial cells during either activation or apoptosis. There is mounting evidence suggesting that microparticles perform a large array of biological functions and contribute to various diseases. Of these disease processes, a significant link has been established between microparticles and venous thromboembolism. Advances in research on the role of microparticles in thrombosis have yielded crucial insights into possible mechanisms, diagnoses and therapeutic targets of venous thromboembolism. In this review, we discuss the definition and properties of microparticles and venous thromboembolism, provide a synopsis of the evidence detailing the contributions of microparticles to venous thromboembolism, and propose potential mechanisms, by which venous thromboembolism occurs. Moreover, we illustrate a possible role of microparticles in cancer-related venous thromboembolism.

Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation.

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia in humans and is responsible for substantial morbidity and mortality worldwide. Emerging evidence indicates that abnormal cardiovascular development is involved in the pathogenesis of AF. In this study, the coding exons and splice sites of the NKX2-5 gene, which encodes a homeodomain-containing transcription factor essential for cardiovascular genesis, were sequenced in 146 unrelated patients with lone AF as well as the available relatives of the mutation carriers. A total of 700 unrelated ethnically matched healthy individuals used as controls were genotyped. The disease-causing potential of the identified NKX2-5 variations was predicted by MutationTaster and PolyPhen-2. The functional characteristics of the mutant NKX2-5 proteins were analyzed using a dual-luciferase reporter assay system. As a result, two heterozygous NKX2-5 mutations, including a previously reported p.E21Q and a novel p.T180A mutation, were identified in two families with AF transmitted in an autosomal dominant pattern. The mutations co-segregated with AF in the families with complete penetrance. The detected substitutions, which altered the amino acids highly conserved evolutionarily across species, were absent in 700 control individuals and were both predicted to be causative. Functional analyses demonstrated that the NKX2-5 mutants were associated with significantly decreased transcriptional activity compared with their wild-type counterpart. The findings expand the spectrum of NKX2-5 mutations linked to AF and provide additional evidence that dysfunctional NKX2-5 may confer vulnerability to AF, suggesting the potential benefit for the early prophylaxis and personalized treatment of AF.

[The expression of T cell immune-related gene mRNAs in peripheral blood mononuclear cells from patients with venous thromboembolism].

OBJECTIVE: To explore the role of T cell-mediated immunity in the pathogenesis of venous thromboembolism (VTE) by analyzing the differential expression of T cell immune-related gene mRNAs peripheral blood mononuclear cells (PBMCs) between VTE patients and controls with GeneChip Human Genome. METHODS: Human cDNA microarray analysis was employed in PBMCs from 20 VTE patients and 20 hypertensive controls, and random variant model (RVM) corrected t-test was used for statistical analysis of differential gene expression. RESULTS: Six mRNA stripes including CD(247), CD(3D), CD(3G), Granzyme A (GzmA), Granzyme B (GzmB) and Zeta-chain-associated protein kinase 70 (ZAP70) were found to be associated with T cell-mediated immunity. Significant down-regulation of these six mRNAs was found in the VTE group compared with the controls (15.3050 ± 0.6346 vs 15.8053 ± 0.5567, 13.7878 ± 0.7731 vs 14.3820 ± 0.4857, 13.3299 ± 0.9104 vs 14.1246 ± 0.6011, 14.8893 ± 0.8675 vs 15.5305 ± 0.4624, 15.9113 ± 0.8123 vs 16.4553 ± 0.5055, 14.3652 ± 0.7717 vs 14.3652 ± 0.7717; all P values < 0.05). CONCLUSIONS: T cells' function including antigen recognition, signal transduction and cytotoxicity was impaired in VTE patients. T cell-mediated immunity dysfunction probably plays an important role in the pathogenesis of VTE.

Quantitative evaluation of cardiopulmonary functional reserve in treated patients with pulmonary embolism.

BACKGROUND: There is no research, either at home or abroad, focusing on assessing the cardiopulmonary functional reserve and exercise tolerance in patients with pulmonary embolism (PE), but the benefits of early exercise are well recognized. The goals of this study were to assess cardiopulmonary functional reserve in treated PE patients using the inert gas rebreathing method of the cardiopulmonary exercise test (CPET), and to compare it with traditional methods. METHODS: CPET on the bicycle ergometer were performed in 40 patients with age, gender, body mass index, systolic blood pressure, and pulmonary function matched. The first group was the PE group composed of 16 PE patients (5 male, 11 female) who were given the standard antithrombotic therapy for two weeks. The second group was composed of 24 normal individuals (10 male, 14 female). Both groups were evaluated by cardiac ultrasound examination, 6-minute walking test (6MWT), and CPET. RESULTS: (1) Right ventricular systolic pressure (RVSP) in the PE group increased significantly compared to the control group, (34.81 ± 8.15) mmHg to (19.75 ± 3.47) mmHg (P < 0.01). But neither right atrial end-systolic diameter (RASD) nor right ventricular end-diastolic diameter (RVDD) in the PE patients had changed when compared with the controls. The 6-minute walk distance was significantly reduced in the PE patients compared with normal subjects, (447.81 ± 79.20) m vs. (513.75 ± 31.45) m (P < 0.01). Both anaerobic threshold oxygen consumption (VO(2)AT) and peak oxygen consumption (VO(2)peak) were significantly lower in patients with PE, while CO(2) equivalent ventilation (VE/VCO(2) slope) was higher; VO(2)AT (9.44 ± 3.82) ml×kg(-1)×min(-1) vs. (14.62 ± 2.93) ml×kg(-1)×min(-1) (P < 0.01) and VO2peak (12.26 ± 4.06) ml×kg(-1)×min(-1) vs. (23.46 ± 6.15) ml×kg(-1)×min(-1) (P < 0.01) and VE/VCO(2) slope 35.47 ± 6.66 vs. 26.94 ± 3.16 (P < 0.01). There was no significant difference in resting cardiac output (CO) between the PE and normal groups, whereas peak cardiac output (peak CO) and the difference between exercise and resting cardiac output (ΔCO) were both significantly reduced in the PE group; peak CO (5.97 ± 2.25) L/min to (8.50 ± 3.13) L/min (P < 0.01), ΔCO (1.29 ± 1.59) L/min to (3.97 ± 2.02) L/min (P < 0.01). (2) The 6-minute walk distance did not correlated with CPET except for the VO2 peak in patients with PE, r = 0.675 (P < 0.01). CONCLUSIONS: The cardiopulmonary functional reserve was reduced in patients with PE. CPET is an accurate, quantitative evaluation of cardiopulmonary functional reserve for PE patients.

[The effects of aerobic exercise on cardiac output during exercise in patients with chronic heart failure].

OBJECTIVE: To observe the effects of aerobic exercise on cardiac output during exercise in patients with chronic heart failure (CHF). METHODS: A total of 50 CHF patients (echocardiography measured left ventricular ejection fraction < 0.49) were enrolled in the study and randomly divided into aerobic exercise group (n = 25) and control group (n = 25). Cardiopulmonary exercise testing (CPET) was performed. Patients of aerobic exercise group underwent aerobic exercise according to aerobic exercise prescription and exercise intensity is decided by anaerobic threshold before 10 J/s (1 minute before) of the oxygen consumption. After 6 supervised aerobic exercise training sessions in the hospital, patients were asked to perform the home-based aerobic exercise training. Patients in control group were required to maintain daily physical activities. CPET were reviewed 3 months later. RESULTS: Cardiac output (CO), peak CO, peak cardiac power output (peak CPO), resting heart rate (HR), heart rate at AT (HRAT), HR peak, resting mean arterial pressure (MAP), peak MAP at baseline were similar between aerobic exercise group and control [(4.2 ± 2.0) L/min vs. (3.3 ± 1.0) L/min, (6.2 ± 2.7) L/min vs. (5.2 ± 1.8) L/min, (1.8 ± 2.9) L/min vs. (2.0 ± 1.8) L/min, (1.3 ± 0.5) J/s vs. (1.2 ± 0.5) J/s, (76.8 ± 13.5) beats/min vs. (73.4 ± 11.9) beats/min, (91.5 ± 11.3) beats/min vs. (92.6 ± 12.4) beats/min, (106.0 ± 12.9) beats/min vs. (108.3 ± 17.4) beats/min, (80.8 ± 9.9) mm Hg (1 mm Hg = 0.133 kPa) vs. (87.6 ± 13.3) mm Hg, (98.8 ± 12.4) mm Hg vs. (102.7 ± 13.9) mm Hg, all P > 0.05]. Compared to baseline, CO, peak CO, peak CPO, HR, HRAT, HR peak, MAP, peak MAP after 3 months were similar between aerobic exercise group and control (all P > 0.05). The differences between baseline and 3 months later expressed as ΔCO, Δpeak CO, Δpeak CPO, ΔHR, ΔHRAT, ΔHR peak, ΔMAP, Δpeak MAP were also similar between aerobic exercise group and control group [(-0.7 ± 2.4) L/min vs. (0.7 ± 2.0) L/min, (1.1 ± 2.6) L/min vs. (1.4 ± 2.1) L/min, (0.1 ± 3.7) L/min vs. (-0.2 ± 2.5) L/min, (0.2 ± 1.0) J/s vs. (0.2 ± 0.5) J/s, (-0.4 ± 7.6) beats/min vs. (1.9 ± 9.9) beats/min, (3.4 ± 11.3) beats/min vs. (-2.8 ± 7.6) beats/min, (8.9 ± 14.5) beats/min vs. (3.7 ± 14.4) beats/min, (1.5 ± 12.8) mm Hg vs. (-1.3 ± 11.1) mm Hg, (6.4 ± 18.9) mm Hg vs. (1.3 ± 12.3) mm Hg, all P > 0.05]. CONCLUSION: Three months aerobic exercise training did not improve cardiac output and related parameters during exercise in this cohort patients with CHF.

Relationship of left heart size and left ventricular mass with exercise capacity in chronic heart failure.

BACKGROUND: Impaired exercise capacity is one of the most common clinical manifestations in patients with chronic heart failure (CHF). The severity of reduced exercise capacity is an indicator of disease prognosis. The aim of the current study was to investigate the association between left heart size and mass with exercise capacity. METHODS: A total of 74 patients were enrolled in the study, with 37 having congestive heart failure (left ventricular ejection fraction (LVEF) < 0.45) and the other 37 with coronary heart disease (by coronary angiography) serving as the control group (LVEF > 0.55). Echocardiography and cardiopulmonary exercise test were performed. The multiply linear regression model was used to evaluate the association between echocardiogrphic indices and exercise capacities. RESULTS: The study showed that left ventricular end diastolic/systolic diameter (LVEDD/LVESD), left atrial diameter (LAD) and left ventricular mass index (LVMI) were significantly enlarged in patients with chronic heart failure compared with controls (P < 0.01). The VO(2)AT, Peak VO(2), Load AT, and Load Peak in chronic heart failure patients were also significantly reduced compared with controls (P < 0.05), VE/VCO(2) slope was increased in patients with chronic heart failure (P < 0.01). Multivariate linear regression analysis indicated that the patients' exercise capacity was significantly associated with the left heart size and mass, however, the direction and/or strength of the associations sometimes varied in chronic heart failure patients and controls. Load AT correlated negatively with LVEDD in chronic heart failure patients (P = 0.012), while Load AT correlated positively with LVEDD in control patients (P = 0.006). VE/VCO(2) slope correlated positively with LAD (B = 0.477, P < 0.0001) in chronic heart failure patients, while the VE/VCO(2) slope correlated negatively with LAD in control patients (P = 0.009). CONCLUSION: The study indicates that the size of LVEDD and LAD are important determinants of exercise capacity in patients with CHF, which may be helpful to identify exercise tolerance for routine monitoring of systolic heart failure.

[Effects of aerobic exercise on exercise tolerance in patients with chronic heart failure].

OBJECTIVE: To explore the effects of aerobic exercise on exercise tolerance in patients with chronic heart failure (CHF). METHODS: A total of 50 CHF patients with left ventricular ejection fraction (LVEF) < 49% by echocardiography were enrolled. And they were randomly divided into exercise group (n = 25) and non-exercise group (n = 25). Cardiopulmonary exercise testing (CPET) was performed. The patients of exercise group underwent an aerobic exercise program in which exercise intensity was decided by anaerobic threshold (AT) before 10 J/s while those of non-exercise group performed daily activities. After 6 sessions of supervised aerobic exercise, the home-based aerobic exercise training began. CPET was re-examined 3 months later. RESULTS: The VO(2) AT, VO(2) peak, Load AT, Load peak, peak VO(2)/HR and VE/VCO(2) slope at baseline were similar between exercise group and non-exercise group (P > 0.05). The VO(2) AT, VO(2) peak, Load AT, Load peak and peak VO(2)/HR in patients of exercise group were increased compared with baseline, The differences between baseline and 3 months later expressed as ΔVO(2) AT, ΔVO(2) peak, ΔLoad AT, ΔLoad peak, Δpeak VO(2)/HR and ΔVE/VCO(2) slope, The differences of ΔVO(2) AT, ΔVO(2) peak, ΔLoad AT, ΔLoad peak and Δpeak VO(2)/HR between two groups were statistically significant [ΔVO(2) AT: 2.8 (1.2 - 3.5) ml×kg(-1)×min(-1) vs -0.3 (-2.8 - 0.1) ml×kg(-1)×min(-1), P < 0.01; ΔVO(2) peak: 3.4 (1.8 - 4.6) ml×kg(-1)×min(-1) vs -0.5 (-1.4 - 0.3) ml×kg(-1)×min(-1), P < 0.01; ΔLoad AT:15.0 (2.5 - 22.5) J/s vs 0.5(-4.2 - 3.8) J/s, P < 0.01; ΔLoad peak: 15.0 (1.3 - 25.0) J/s vs 0.0 (-8.8 - 15.0) J/s, P < 0.05; Δpeak VO(2)/HR: 2.3 (0.0 - 4.0) ml×kg(-1)×beat(-1) vs -0.1 (-0.7 - 1.2) ml×kg(-1)×beat(-1), P < 0.01]. The difference of ΔVE/VCO(2) slope was not statistically significant [-2.3 (-12.2 - 1.8) vs 1.0 (-0.4 - 2.6), P > 0.05]. CONCLUSION: After 3 months of aerobic exercise, exercise capacity may improve in the CHF patients.

[Reduced cardiopulmonary exercise capacity in patients with chronic heart failure: impact of left ventricular systolic dysfunction].

OBJECTIVE: To evaluate the cardiopulmonary exercise capacity in patients with chronic heart failure (CHF). METHODS: Cardiopulmonary exercise testing on bicycle ergometer was performed in 74 age, gender and BMI-matched patients. There were 37 patients with LVEF < 0.45 in CHF group and another 37 patients with LVEF > 0.50 in control group. VO(2)AT, VO(2)Peak, Load AT, Load peak and VE/VCO(2) slope were measured and compared. RESULTS: (1) VO(2)AT, VO(2)Peak, Load AT and Load peak were all significantly reduced in patients with CHF as compared with controls [VO(2)AT: (11.3 +/- 2.3) ml x kg(-1) x min(-1) vs (12.8 +/- 2.5) ml x kg(-1) x min(-1), P < 0.05; VO(2)peak: (15.2 +/- 4.3) ml x kg(-1) x min(-1) vs (17.3 +/- 3.9) ml x kg(-1) x min(-1), P < 0.05; Load AT: (25.2 +/- 18.8) J x s(-1) vs (45.6 +/- 18.7) J x s(-1), P < 0.01; Load peak: (54.9 +/- 22.5) J x s(-1) vs (80.3 +/- 21.6) J x s(-1), P < 0.01]; (2) VE/VCO(2) slope increased in patients with CHF as compared with controls [(36.7 +/- 6.7) vs (30.3 +/- 4.3), P < 0.01]; (3) None of VO(2)AT, VO(2), Peak Load AT, Load peak or VE/VCO(2) slope was correlated with LVEF [(r = 0.054, P > 0.05); (r = 0.03, P > 0.05); (r = 0.310, P > 0.05); (r = 0.174, P > 0.05); (r = -0.203, P > 0.05)]; VO(2)AT, VO(2)Peak, Load AT and Load peak were all correlated negatively with a higher NYHA grade [(r = -0.477, P < 0.01); (r = -0.591, P < 0.01); (r = -0.640, P < 0.01); (r = -0.672, P < 0.01)]; VE/VCO(2) slope correlated positively with a higher NYHA grade (r = 0.652, P < 0.01); None of VO(2)AT, VO(2)Peak, Load AT, Load peak or VE/VCO(2) slope was correlated with LVMI [r = 0.045, P > 0.05); (r = -0.017, P > 0.05); (r = -0.214, P > 0.05); (r = -0.123, P > 0.05); (r = 0.106, P > 0.05)]. CONCLUSION: (1) Cardiopulmonary exercise capacity is reduced in CHF patients. (2) None of VO(2)AT, VO(2)Peak, Load AT, Load peak and VE/VCO(2) slope is correlated with LVEF; VO(2)AT, VO(2)Peak, Load AT and Load peak all correlate negatively with the higher NYHA grade; VE/VCO(2) slope correlates positively with a higher NYHA grade; None of VO(2)AT, VO(2)Peak, Load AT, Load peak or VE/VCO(2) slope correlates with LVMI. An analysis of gas metabolism is a safe, accurate and scientific testing method of exercise tolerance.

[The expression and significance of immunity associated genes mRNA in patients with pulmonary embolism].

OBJECTIVE: To investigate the molecular alteration of immunity associated genes in patients with pulmonary embolism (PE) so as to preliminarily elucidate its pathogenetic mechanism. METHODS: Human cDNA microarray analysis was employed in this study, random variance model (RVM) corrected t-test was used for the statistical data analysis of differential gene expression. RESULTS: In comparison with control, mRNA expression of functional genes of neutrophils, monophagocytes, IFN regulating factors, TNF, adhesion molecules and T cells were significantly different in PE patients. However, gene expressions of B cell immune function and complement activation associated factors were not significantly different between two groups. CONCLUSION: Unbalance expression of immune function associated genes, especially down-regulated expression of T cell mediated function genes, in patients with PE indicates that the etiology of PE might be related to viral infection.

[Beta1-adrenergic receptor (Arg389Gly) polymorphism and response to bisoprolol in patients with chronic heart failure].

OBJECTIVE: The purpose of this study was to investigate the relation between the Arg389Gly polymorphism of the beta(1)-AR gene and chronic heart failure (CHF) and to evaluate the effect of this polymorphism on clinical response to beta-adrenoceptor blockade (bisoprolol) in patients with CHF. METHODS: One hundred and ten patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 3 months after the maximal tolerated dose of bisoprolol was reached, all indices (including BP, HR, LAD, LVEDD, LVESD, LVEF, BNP level, 6 min walk distance) were measured and compared with the Arg389Gly genotypes, which identified by PCR-restriction fragment length polymorphism analysis. We also determined the Arg389Gly genotypes in 100 healthy control subjects, and compared the distribution of Arg389Gly genotypes with that in CHF. RESULTS: No difference was observed between the two groups in any of the three genotypes (CC, CG and GG). The prevalences of the three genotypes in normal subjects and patients with CHF were Arg389Arg 0.53 vs. 0.51, Arg389Gly 0.40 vs. 0.40, Gly38Gly 0.07 vs. 0.09, respectively. After 3 months of bisoprolol usage, a significant improvement in LVEF was observed in CC group, which increased from (36.7 +/- 8.63)% to (44.1 +/- 9.53)%, CG group, from (35.76 +/- 8.39)% to (42.90 +/- 9.41)%, but not GG group, from (36.00 +/- 5.66)% to (37.33 +/- 5.64)%. The improvement in BNP was also observed in CC [from (502.93 +/- 160.80) ng/L to (325.26 +/- 135.63) ng/L], CG [from (525.76 +/- 157.66) ng/L to (331.79 +/- 133.97) ng/L], but not GG [from (505.33 +/- 125.07) ng/L to (429.67 +/- 182.39) ng/L]. Arg389-homozygous patients showed a substantially greater improvement in LVEF and BNP, compared with Gly389-homozygous patients (all P < 0.01). CONCLUSIONS: There was no difference in the prevalence of the three genotypes between healthy and CHF subjects. The Gly389 polymorphism of the beta(1)-AR gene was not associated with an increased risk of CHF. The Arg389 variant of the beta(1)-AR gene was associated with a greater response to bisoprolol than that of the Gly389 variant in patients with CHF.

[Effects of angiotensin converting enzyme inhibitor with different doses on plasma brain natriuretic peptide and norepinephrine in patients with chronic heart failure].

OBJECTIVE: To investigate the effects of angiotensin converting enzyme inhibitor (ACEI) with different doses on the plasma brain natriuretic peptide and norepinephrine (NE) of patients with chronic heart failure and the feasibility and safety of high dose ACEI treatment. METHODS: Sixty-six patients with chronic heart failure were randomly divided into 2 groups: low-dose group, treated by perindopril with the dosage of 2 mg/d initially and gradually increased up to 2-4 mg/d, and high-dose group, treated by perindopril with the dosage of 2 mg/d initially and gradually increased up to 8 approximately 10 mg/d. Treatment lasted for 12 weeks. Before and after the treatment peripheral blood was collected to test the plasma NE and brain natriuretic peptide levels, and the left ventricular ejection fraction (LVEF), left ventricular end diameter (LVED), blood pressure, and heart rate were examined. The differences of these indexes between the two groups and within the same group before and after the 12-week treatment were analyzed. Thirty healthy subjects were used as control group. RESULTS: The levels of plasma brain natriuretic peptide and NE of the chronic heart failure patients were significantly higher than those of the normal controls, and the higher the NYHA class of heart failure the higher the plasma levels of NE and brain natriuretic peptide. The plasma brain natriuretic peptide level was negatively correlated with LVEF (r = -0.327, P = 0.012) and positively correlated with plasma NE level (r = 0.402, P = 0.002) and LVED (r = 0.42, P = 0.015). The plasma brain natriuretic peptide and NE levels in the high-dose group were 6 microg/L +/- 4 microg/L and 250 ng/L +/- 63 ng/L respectively, both significantly lower than those of the low-dose group (8 microg/L +/- 4 microg/L and 387 ng/L +/- 211 ng/L respectively, both P < 0.05). Most of the patients in these 2 groups tolerated well. CONCLUSION: Plasma brain natriuretic peptide level is negatively correlated with the severity of heart failure and positively correlated with plasma NE. Treatment of CHF by perindopril with gradually increasing dose obviously decreases the plasma brain natriuretic peptide and NE levels and is tolerable for the patients.