Antioxidant therapy for chronic hepatitis C after failure of interferon： Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.
METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

免疫调节治疗对老年心力衰竭患者心功能及淋巴细胞亚群的影响

目的 研究免疫调节治疗对老年慢性心力衰竭(心衰)患者心脏功能、淋巴细胞亚群的影响.方法 入选96例60岁以上、纽约心功能分级(NYHA分级)为Ⅱ～Ⅳ级的老年慢性心衰患者,随机分为心衰试验组和心衰对照组各48例.心衰对照组采用常规治疗,心衰试验组在常规治疗的基础上加用胸腺五肽治疗3个疗程(共75 d).另以45例60岁以上健康老年人作为正常组.分别在用药前、用药第一个疗程后(第15天)、第三个疗程后(第75天)测定各组患者的左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、淋巴细胞亚群、血浆高敏C反应蛋白(hsCRP)、血浆B型利钠肽(BNP)和6 min步行距离(6MWT).结果 (1)治疗前,与正常组相比,心衰试验组和心衰对照组患者的血浆BNP、血浆hsCRP、抑制性T淋巴细胞(CD8)、LVEDD和LVESD增高,成熟T淋巴细胞(CD3)、辅助性T淋巴细胞(CD4)、B淋巴细胞(CD19)、自然杀伤细胞(NK细胞)、CD4/CD8、LVEF、6MWT降低(P＜0.05或P＜0.01),心衰试验组和心衰对照组两组间比较各项指标差异无统计学意义.(2)第一疗程后,与心衰对照组相比,心衰试验组的血浆CD3、CD4、CD19和NK数量显著增高(P＜0.05或P＜0.01);血浆BNP、hsCRP和CD8数量显著降低(P＜0.05或P＜0.01);CD4/CD8、LVEF值及6MWT有增高趋势,LVEDD、LVESD和生活质量评分有降低趋势,但差异无统计学意义.(3)第三疗程后,与心衰对照组相比,心衰试验组的血浆CD3、CD4、CD19数量、NK数量、CD4/CD8、LVEF值和6MWT显著增高(P＜0.05或P＜0.01);血浆BNP、hsCRP和CD8数量和生活质量评分显著降低(P＜0.05或P＜0.01).结论 免疫调节剂胸腺肽能够改善心衰患者淋巴细胞亚群比例失衡,进而改善心功能;免疫调节治疗为老年心衰患者提供了新的治疗途径.     

Pilates in heart failure patients: a randomized controlled pilot trial

Background: Conventional cardiac rehabilitation program consist of 15 min of warm-up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The Pilates method has been increasingly applied for its therapeutic benefits, however little scientific evidence supports or rebukes its use as a treatment in patients with heart failure (HF). Purpose: Investigate the effects of Pilates on exercise capacity variables in HF. Methods: Sixteen pts with HF, left ventricular ejection fraction 27 ± 14%, NYHA class I-II were randomly assigned to conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n = 8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific program. Results: At 16 weeks, pts in the mat Pilates group and conventional group showed significantly increase on exercise time 11.9 ± 2.5 to 17.8 ± 4 and 11.7 ± 3.9 to 14.2 ± 4 min, respectively. However, only the Pilates group increased significantly the ventilation (from 56 ± 20 to 69 ± 17 L/min, P= 0.02), peak VO(2) (from 20.9 ± 6 to 24.8 ± 6 mL/kg/min, P= 0.01), and O(2) pulse (from 11.9 ± 2 to 13.8 ± 3 mL/bpm, P= 0.003). The Pilates group showed significantly increase in peak VO(2) when compared with conventional group (24.8 ± 6 vs. 18.3 ± 4, P= 0.02). Conclusions: The result suggests that the Pilates method may be a beneficial adjunctive treatment that enhances functional capacity in patients with HF who are already receiving standard medical therapy.     

Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial

The encouraging results of recent multicenter clinical trials conducted in the US on the effect of carvedilol therapy in patients with chronic heart failure, prompted us to verify its tolerability in a group of elderly patients. For the open, randomized, placebo-controlled study, we selected 40 patients (28 men and 12 women, mean age 76.8+/-5.9 years) with mild, moderate or severe chronic heart failure. Exclusion criteria included dementia, chronic hepatitis, renal failure, severe vascular disease and respiratory failure. All patients were receiving treatment with digitalis, furosemide and ACE inhibitors. The study lasted 12 weeks. During the first week, all subjects received oral placebo or carvedilol, at a dose of 6.25 mg twice daily. The twice daily dose was then increased to 12.5 mg during weeks 2-4 and to 25 mg from weeks 5-12. At 0, after the 2 weeks of run-in, 4 and 12 weeks patients underwent assessment of systolic and diastolic blood pressure, heart rate, left ventricular ejection fraction, cognitive status and functional ability. Our findings indicate that elderly patients with congestive heart failure tolerate carvedilol therapy well. Carvedilol slightly improves heart function without altering functional or cognitive ability. A larger-scale trial in geriatric patients is now required to determine whether this treatment will reduce serious morbidity or mortality from heart failure.     

Effects of tai chi mind-body movement therapy on functional status and exercise capacity in patients with chronic heart failure: a randomized controlled trial

PURPOSE: To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure. METHODS: Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or =40% (mean [+/- SD] age, 64 +/- 13 years; mean baseline ejection fraction, 23% +/- 7%; median New York Heart Association class, 2 [range, 1 to 4]) were randomly assigned to receive usual care (n = 15), which included pharmacologic therapy and dietary and exercise counseling, or 12 weeks of tai chi training (n = 15) in addition to usual care. Tai chi training consisted of a 1-hour class held twice weekly. Primary outcomes included quality of life and exercise capacity. Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels. For 3 control patients with missing data items at 12 weeks, previous values were carried forward. RESULTS: At 12 weeks, patients in the tai chi group showed improved quality-of-life scores (mean between-group difference in change, -25 points, P = 0.001), increased distance walked in 6 minutes (135 meters, P = 0.001), and decreased serum B-type natriuretic peptide levels (-138 pg/mL, P = 0.03) compared with patients in the control group. A trend towards improvement was seen in peak oxygen uptake. No differences were detected in catecholamine levels. CONCLUSION: Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving standard medical therapy.     

免疫调节治疗对老年慢性心力衰竭患者细胞因子的影响

目的 研究免疫调节治疗对老年慢性充血性心力衰竭(CHF)患者心脏功能、细胞因子的影响.方法 入选96例年龄60～78岁CHF患者,美国纽约心功能分级(NYHA)Ⅱ～Ⅳ级,抽签随机分为治疗组(常规治疗的基础上加用胸腺五肽治疗,3个疗程,共75 d)和对照组(采用常规治疗),另以45例健康老年人为健康对照组,年龄60～80岁;分别在用药前、用药第1个疗程后(第15天)、第3个疗程后(第75天)测定各组患者的左心室射血分数(LVEF)、血清炎性细胞因子肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β),血清抗炎细胞因子白细胞介素-10(IL-10)、血浆高敏C反应蛋白(hsCRP)、血浆脑钠肽(BNP),并进行明尼苏达心力衰竭生活质量评分.结果 (1)治疗前,与健康对照组比较,治疗组和对照组患者血清TNF-α、IL-1β、TNF-α与IL-10比值、血浆BNP、hCRP、明尼苏达心力衰竭生活质量评分增高(P＜0.05或P＜0.01),LVEF、血清IL-10降低(P＜0.01),治疗组和对照组两组间比较各项指标差异无统计学意义;(2)第1个疗程后与对照组比较,治疗组的血清IL-10增高(P＜0.01);血清TNF-αIL-1β、血浆BNP、hsCRP降低(P＜0.05或P＜0.01);LVEF值有增高趋势,TNF-α与IL-10比值(治疗组与对照组分别为4.84±0.53与5.28±0.66)和生活质量评分有降低趋势,但差异无统计学意义.(3)第3个疗程后,与对照组比较,治疗组的血清IL-10、LVEF值显著增高(P＜0.05或P＜0.01);血清TNF-α、IL-1β、TNF-α与IL-10比值(治疗组与对照组分别为4.55±0.69与5.18±0.38)、血浆BNP、hsCRP和生活质量评分降低(P＜0.05或P＜0.01).结论 免疫调节剂胸腺肽能够改善细胞因子失衡,进而改善心功能;免疫调节治疗为老年CHF患者提供了新的治疗途径.

Abstract：

Objective To investigate the effect of immune modulation therapy on heart function and cytokines in elder patients with chronic heart failure (CHF). Methods The 96 patients aged 60-78 years with New York Heart Association(NYHA)functional. class Ⅱ-Ⅳ CHF were randomly divided into two groups: CHF treatment group received regular therapy and thymopetidum and CHF control group received regular therapy. Another 45 healthy individuals aged 60-80 years were involved as normal control. The ejection faction of left ventricle (LVEF), inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), anti-inflammatory cytokine interleukin-10 (IL-10), plasma high sensitive C-reactive protein (hsCRP), plasma brain natrium peptide (BNP)and Minnesota Living with Heart Failure Questionnaire (LHFQ) assessment were tested before therapy, 15 days and 75 days after treatment. Results (1) Before therapy, compared with normal control group, the levels of TNF-α, IL-1β, TNF-α/IL-10 ratio, BNP, hsCRP and LHFQ were significantly increased (P ＜ 0. 05 or P ＜ 0. 01 ), and the levels of IL-10, LVEF were markedly decreased (P＜0.01) in the patients of CHF treatment group and CHF control group. While no difference between the two CHF groups was observed. (2) After the first course of treatment,compared with CHF control group, the levels of IL-10 were increased (P＜0. 01), while the levels of TNF-α, IL-1β, BNP and hsCRP were decreased (P＜0.05 or P＜0.01) in CHF treatment group. The level of LVEF was increased, TNF-α/IL-10 ratio (4.84 ±0. 53 vs. 5.28±0. 66) and LHFQ were decreased even though there was no significant difference between the two groups. (3) After the second course of treatment, compared with CHF control group, the levels of IL-10 and LVEF were increased (P＜0. 05 or P＜0.01), while the level of TNF-α, IL-1β, TNF-α/IL-10 ratio (4.55±0. 69 vs. 5.18±0.38), BNP, hsCRP and LHFQ were decreased (P＜0.05 or P＜0.01) in CHF treatment group. Conclusions Thymopetidum, as an immunemodulating agent, might regulate the equilibrium of cytokines and improve the heart function of patients with CHF, indicating that immune modulation therapy might improve the treatment strategy for CHF patients.     

Exercise training improves heart rate variability in older patients with heart failure: a randomized, controlled, single-blinded trial

Reduced heart rate variability (HRV) in older patients with heart failure (HF) is common and indicates poor prognosis. Exercise training (ET) has been shown to improve HRV in younger patients with HF. However, the effect of ET on HRV in older patients with HF is not known. Sixty-six participants (36% men), aged 69±5 years, with HF and both preserved ejection fraction (HFPEF) and reduced ejection fraction (HFREF), were randomly assigned to 16 weeks of supervised ET (ET group) vs attention-control (AC group). Two HRV parameters (the standard deviation of all normal RR intervals [SDNN] and the root mean square of successive differences in normal RR intervals [RMSSD]) were measured at baseline and after completion of the study. When compared with the AC group, the ET group had a significantly greater increase in both SDNN (15.46±5.02 ms in ET vs 2.37±2.13 ms in AC, P=.016) and RMSSD (17.53±7.83 ms in ET vs 1.69±2.63 ms in AC, P=.003). This increase was seen in both sexes and HF categories. ET improved HRV in older patients with both HFREF and HFPEF.     

Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure

Background

Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the absolute refractory period intended to improve contraction. We previously tested the safety and efficacy of CCM in 428 NYHA functional class III/IV heart failure patients with EF ≤35% and narrow QRS randomized to optimal medical treatment (OMT) plus CCM (n = 215) versus OMT alone (n = 213) and found no significant effect on ventilatory anaerobic threshold (VAT), the study’s primary end point. In the present analysis, we sought to identify if there was a subgroup of patients who showed a response to CCM.

Methods and Results

The protocol specified that multiregression analysis would be used to determine if baseline EF, NYHA functional class, pVO₂, or etiology of heart failure influenced the impact of CCM on AT. Etiology and baseline pVO₂ did not affect efficacy. However, baseline NYHA functional class III and EF ≥25% were significant predictors of increased efficacy. In this subgroup (comprising 97 OMT and 109 CCM patients, ∼48% of the entire population) VAT increased by 0.10 ± 2.36 in CCM versus −0.54 ± 1.83 mL kg⁻¹ min⁻¹ in OMT (P = .03) and pVO₂ increased by 0.34 ± 3.11 in CCM versus −0.97 ± 2.31 (P = .001) at 24 weeks compared with baseline; 44% of CCM versus 23% of OMT subjects showed improvement of ≥1 class in NYHA functional class (P = .002), and 59% of CCM versus 42% of OMT subjects showed a ≥10-point reduction in Minnesota Living with Heart Failure Questionnaire (P = .01). All of these findings were similar to those seen at 50 weeks.

Conclusions

The results of this retrospective hypothesis-generating analysis indicate that CCM significantly improves objective parameters of exercise tolerance in a subgroup of patients characterized by normal QRS duration, NYHA functional class III symptoms, and EF >25%.