Prediction of the effectiveness of long term β blocker treatment for dilated cardiomyopathy by signal averaged electrocardiography

Objective—To determine whether the effectiveness of long term β blocker treatment for idiopathic dilated cardiomyopathy can be predicted by signal averaged electrocardiography (ECG).
Patients—31 patients with dilated cardiomyopathy and without bundle branch block were included in a retrospective study and 16 in a prospective study.
Methods—A signal averaged ECG was recorded before β blocker treatment, and three variables were measured from the vector magnitude: QRS duration, root mean square voltage for the last 40 ms (RMS40), and duration of the terminal low amplitude signals (< 40 µV) (LAS40). In the retrospective study, these variables were compared among good responders (showing  0.10 increase in ejection fraction 12 months after start of β blocker treatment) and poor responders without such improvement. The validity of the signal averaged ECG criteria for prediction of the response to β blocker treatment was examined in the prospective study.
Results—In the retrospective study, good responders (n = 16) had a shorter QRS duration (mean (SD): 122.9 (11) v 138 (14.4) ms, p < 0.005) and LAS40 (33.1 (8.9) v 42.5 (7.8) ms, p < 0.005), and a higher RMS40 (31.6 (16.3) v 19.0 (10.3) µV, p < 0.02) than poor responders (n = 15). Signal averaged ECG criteria for good response were defined as two or more of the following: QRS duration < 130 ms, RMS40 > 20 µV, LAS40 < 40 ms (sensitivity 81%, specificity 73%). In the prospective study, six of seven patients who met these criteria showed a good response to the β blocker treatment, while eight of nine who did not showed a poor response (χ² = 6.1, p < 0.02). The signal averaged ECG criteria gave a sensitivity of 86% and a specificity of 89% for predicting the effectiveness of β blocker treatment.
Conclusions—A signal averaged ECG might be useful in predicting the effectiveness of β blocker treatment for dilated cardiomyopathy.

Keywords: signal averaged ECG;  β blockers;  dilated cardiomyopathy     

beta blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study

OBJECTIVES: To examine clinical outcomes associated with optional beta blockade in a population of patients with evidence of heart failure after myocardial infarction. DESIGN AND PATIENTS: Data from the acute infarction ramipril efficacy (AIRE) study were analysed retrospectively. At baseline 22.3% of the patients were receiving a beta blocker. To minimise confounding, beta blocker and diuretic treatments, presence of clinical signs of heart failure, left ventricular ejection fraction, and 16 other baseline clinical variables were simultaneously entered in a multivariate Cox regression model. In addition, the same analysis was repeated separately within a high and a low risk group of patients, as defined according to the need for diuretic treatment. RESULTS: beta Blocker treatment was an independent predictor of reduced risk of total mortality (hazard ratio 0.66, 95% confidence interval (CI) 0. 48 to 0.90) and progression to severe heart failure (0.58, 95% CI 0.40 to 0.83) for the entire study population. There were similar findings in high risk patients requiring diuretics (0.59, 95% CI 0.40 to 0.86; and 0.58, 95% CI 0.38 to 0.89). CONCLUSIONS: beta Blocker treatment is associated with improved outcomes in patients with clinical evidence of mild to moderate heart failure after myocardial infarction. Most importantly, high risk patients with persistent heart failure appear to benefit at least as much as lower risk patients with transient heart failure.     

β Adrenergic blockers lower renin in patients treated with ACE inhibitors and diuretics

Objective—To examine the effect of concomitant intake of β blockers with angiotensin converting enzyme (ACE) inhibitors, diuretics, or both on plasma renin concentrations in a population based sample (MONICA survey, Augsburg, Germany).
Subject and methods—728 individuals were studied, of whom 171 were treated using monotherapy (ACE inhibitor (n = 21), diuretic (n = 10), or β blocker (n = 72)), or combination treatment (ACE inhibitor + diuretic (n = 32), ACE inhibitor + β blocker (n = 7), diuretic + β blocker (n = 22), ACE inhibitor + diuretic + β blocker (n = 7)). The remaining 557 individuals were untreated. Indications for treatment were hypertension (75%), coronary artery disease with (12%) or without (3%) hypertension, or unknown (10%).
Results—Mean (SEM) renin concentrations in individuals treated with an ACE inhibitor (41 (8) mU/l), a diuretic (41 (10) mU/l), or the combination of an ACE inhibitor and a diuretic (54 (10) mU/l) were raised compared with untreated individuals (17 (1) mU/l; p < 0.05 each). Monotherapy with a β blocker, however, decreased mean renin concentrations (12 (1) mU/l; p < 0.01 v untreated). Renin concentrations in individuals taking a β blocker with either an ACE inhibitor (21 (8) mU/l), or a diuretic (22 (4) mU/l), or with both an ACE inhibitor and a diuretic (21 (7) mU/L), were significantly lower compared with renin concentrations in groups not receiving β blocker treatment (p < 0.05 each).
Conclusion—These data suggest that the upregulation of renin by treatment with ACE inhibitors, diuretics, or both can be largely prevented by concomitant β blocker treatment.

Keywords: adrenergic β receptor blocker;  angiotensin converting enzyme inhibitor;  renin;  hypertension     

Reversal of severe pulmonary hypertension with beta blockade in a patient with end stage left ventricular failure

A 52 year old man with severe chronic left ventricular failure (New York Heart Association class IV) was considered unsuitable for cardiac transplantation because of high and irreversible pulmonary vascular resistance (PVR). In an attempt to produce symptomatic improvement, metoprolol was cautiously introduced, initially at 6.25 mg twice daily. This was slowly increased to 50 mg twice daily over a two month period and continued thereafter. After four months of treatment the patient's symptoms had improved dramatically. His exercise tolerance had increased and diuretic requirements reduced to frusemide 160 mg/day only. Assessment of right heart pressures was repeated and, other than a drop in resting heart rate, there was little change in his pulmonary artery pressure or PVR. His right heart pressures were reassessed showing a pronounced reduction in pulmonary artery pressure and a significant reduction in PVR, which fell further with inhaled oxygen and sublingual nitrates. He was then accepted onto the active waiting list for cardiac transplantation. A possible mechanism of action was investigated by assessing responses to beta agonists during treatment. Not only was there pronounced improvement in PVR but it was also demonstrated that beta receptor subtype cross-regulation may have contributed to the mechanism of benefit.     

Prevention of relapse in patients with congestive heart failure: the role of precipitating factors

Relapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only limited data on the role of precipitating factors that trigger relapse of CHF. Knowledge of potential precipitating factors may help to optimise treatment and provide guidance for patients with CHF. The literature was reviewed to identify factors that may influence haemodynamic homeostasis in CHF. Precipitating factors that may offer opportunities for preventing relapse of CHF were selected. Potential precipitating factors are discussed in relation to the pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment compliance, and inappropriate medical treatment. Poor treatment compliance in particular is frequently encountered in patients with CHF. Furthermore, studies of medical treatment under everyday circumstances indicate that some aspects of the management of CHF can be improved. In conclusion, the identification of precipitating factors for relapse of CHF may strongly contribute to optimal treatment. Improvement of treatment compliance and optimalisation of medical treatment may offer important possibilities to clinicians to reduce the number of relapses in patients with CHF.

Keywords: congestive heart failure; precipitating factors; prevention     

Exercise capacity in chronic heart failure is related to the aetiology of heart disease

Objective—To assess whether the underlying aetiology of chronic heart failure is a predictor of exercise performance.
Setting—Tertiary referral centre for cardiology.
Patients and outcome measures—Retrospective study of maximum exercise testing with metabolic gas exchange measurements in 212 patients with chronic heart failure who had undergone coronary angiography. Echocardiography and radionucleide ventriculography were used to determine indices of left ventricular function, and coronary arteriography was used to determine whether the cause of chronic heart failure was ischaemic heart disease (n = 122) or dilated cardiomyopathy (n = 90).
Results—The cardiomyopathy group was younger (mean (SD) age 58.45 (11.66) years v 61.49 (7.42); p = 0.02) but there was no difference between the groups in ejection fraction or fractional shortening. Peak oxygen consumption (O₂) was higher in the dilated group, while the slope relating carbon dioxide production and ventilation (E/CO₂ slope) was the same in both groups. Both groups achieved similar respiratory exchange ratios at peak exercise, suggesting that there was near maximum exertion. There was a relation between peak O₂ and age (peak O₂ = 33.9 − 0.267*age; r = 0.36; p < 0.001). After correcting for age, the peak achieved O₂ was still greater in the cardiomyopathy group than in the ischaemic group (p < 0.002).
Conclusions—Exercise performance for a given level of cardiac dysfunction appears to vary with the aetiology of heart failure. Thus the two diagnostic categories should be considered separately in relation to abnormalities of exercise physiology. The difference may in part account for the worse prognosis in ischaemic patients.

Keywords: exercise performance;  heart failure;  ischaemic heart disease;  dilated cardiomyopathy     

QT dispersion in patients with chronic heart failure: beta blockers are associated with a reduction in QT dispersion

OBJECTIVE: To compare QT dispersion in patients with impaired left ventricular systolic function and in matched control patients with normal left ventricular systolic function. DESIGN: A retrospective, case-control study with controls matched 4:1 for age, sex, previous myocardial infarction, and diuretic and beta blocker treatment. SETTING: A regional cardiology centre and a university teaching hospital. PATIENTS: 25 patients with impaired left ventricular systolic function and 100 patients with normal left ventricular systolic function. MAIN OUTCOME MEASURES: QT and QTc dispersion measured by three methods: the difference between maximum and minimum QT and QTc intervals, the standard deviation of QT and QTc intervals, and the "lead adjusted" QT and QTc dispersion. RESULTS: All measures of QT/QTc dispersion were closely interrelated (r values 0.86 to 0.99; all p < 0.001). All measures of QT and QTc dispersion were significantly increased in the patients with impaired left ventricular systolic function v controls (p < 0.001): 71.9 (6.5) (mean (SEM)) v 46.9 (1.7) ms for QT dispersion, and 83.6 (7.6) v 54.3 (2.1) ms(-1-2) for QTc dispersion. All six dispersion parameters were reduced in patients taking beta blockers (p < 0.05), regardless of whether left ventricular function was normal or impaired-by 9.4 (4.6) ms for QT dispersion (p < 0.05) and by 13.8 (6. 5) ms(-1-2) for QTc dispersion (p = 0.01). CONCLUSIONS: QT and QTc dispersion are increased in patients with systolic heart failure in comparison with matched controls, regardless of the method of measurement and independently of possible confounding factors. beta Blockers are associated with a reduction in both QT and QTc dispersion, raising the possibility that a reduction in dispersion of ventricular repolarisation may be an important antiarrhythmic mechanism of beta blockade.     

Atrial fibrillation is associated with a lower exercise capacity in male chronic heart failure patients

Objective—To study the influence of atrial fibrillation on peak oxygen uptake (peak O₂) in chronic heart failure. An unfavourable effect of atrial fibrillation has been shown in several patient populations, but the results have not been consistent in chronic heart failure.
Methods—Data were analysed from male heart transplant candidates who were able to perform graded bicycle ergometry until exhaustion with respiratory gas analysis and measurement of heart rate. Patients in atrial fibrillation (n = 18) were compared with patients in sinus rhythm (n = 93).
Results—Age, weight, height, and aetiology of chronic heart failure did not differ significantly between the two groups. Cardiac catheterisation at supine rest showed that heart rate was comparable, but that stroke volume and cardiac output were lower (p < 0.05) in atrial fibrillation. Systolic and diastolic left ventricular function, assessed by radionuclide angiography at rest, were not significantly different. Peak O₂ (mean (SD): 13.8 (3.6) v 17.1 (5.6) ml/kg/min; p < 0.01) and peak work load (78 (27) v 98 (36) W; p < 0.05) were lower in the patients with atrial fibrillation, though respiratory gas exchange ratio and Borg score were similar in the two groups. Patients with atrial fibrillation had a higher heart rate sitting at rest before exercise (93 (16) v 84 (16) beats/min) and at peak effort (156 (23) v 140 (25) beats/min) (p < 0.05).
Conclusions—Atrial fibrillation is associated with a 20% lower peak O₂ in patients with chronic heart failure, suggesting that preserved atrial contraction or a regular rhythm, or both, are critical to maintain cardiac output and exercise performance.

Keywords: peak oxygen uptake;  exercise capacity;  chronic heart failure;  atrial fibrillation     

Carcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure

A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide--a somatostatin analogue--followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, nonmetastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.     

Short-term haemodynamic effects of dopexamine in patients with chronic congestive heart failure

Dopexamine (FPL 60278) is a new dopamine analogue which possessesa combination of dopamine receptor and beta-2-adrenoreceptoragonist properties. The aim of our study was to evaluate theshort-term haemodynamic effects of dopexamine administered byintravenous infusion at different dosage rates. Eight patientswith chronic congestive heart failure were studied. A dose of1 µg kg^–1 min^–1 produced a 27% decrease insystemic vascular resistance index (32.6 to 23.9 res. unitsm², P<0.001 and a significant increase in cardiac index (2.7to 3.61min^–1 m^–2, P<0.001). Stroke volume indexand heart rate increased significantly by 22% and 7%, respectively.An increase in left ventricular stroke work index was also seenat the dose level inducing the maximum cardiac output. Leftventricular filling pressures and arterial blood pressures werenot affected. We conclude that administration of dopexamineto patients with congestive heart failure augments cardiac performanceat rest.     

Age dependent efficacy of implantable cardioverter-defibrillator treatment: observations in 450 patients over an 11 year period

Objective—To determine whether implantable cardioverter-defibrillator (ICD) treatment is beneficial in elderly patients with life threatening ventricular tachyarrhythmias.
Design—Since January 1984, ICDs were implanted in 450 patients to evaluate surgical risk, complications and mean survival in relation to patient age; 81 patients (18%) were  50 years at the time of ICD implant, 254 patients (56%) were between 51 and 64 years, and the remaining 115 (26%) were  65 years. Epicardial lead systems were implanted in 209 patients (46%), while transvenous lead systems were implanted in 241 (54%).
Results—13 patients (3%) died perioperatively, more often after epicardial (11 of 209 patients, 5%) than after transvenous ICD implantation (one of 241 patients, < 1%) (p < 0.05). During a mean (SD) follow up of 28 (24) months (range < 1 to 114 months), 90 patients (20%) died. Of these, nine (2%) died from sudden arrhythmic death; five (1%) died suddenly, probably as a result of non-arrhythmic causes; 55 (12%) died from other cardiac causes (congestive heart failure, myocardial infarction); and 21 (5%) died from non-cardiac causes. The three, five, and seven year survival for arrhythmic mortality was 95% in patients  50 years compared with a three year survival of 93% and a five and seven year survival of 91% in patients of 51 to 64 years, and a three, five, and seven year survival of 99% in patients  65 years. 362 patients (80%) received ICD discharges (21 (43) shocks per patient), with a similar incidence among all three patient groups ( 50 years, 80%; 51 to 64 years, 81%; 65 years, 79%). The time interval between ICD implant and the first ICD treatment was shorter in patients  65 years (8 (8) months) than in patients between 51 and 64 years (11 (14) months) or  50 years (11 (11) months) (p < 0.05). Survival time following first appropriate shock was 30 (24) months in patients  50 years, 30 (26) months in patients of 51 to 64 years, and 19 (20) months in patients  65 years.
Conclusions—Elderly patients benefit from ICD treatment, and survive for a considerable time after the first treatment. Therefore, elderly patients should be considered candidates for ICD implantation if life threatening ventricular tachyarrhythmias are present.

Keywords: cardioverter-defibrillator;  heart failure;  sudden death;  ICD discharges;  elderly patients     

Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p < 0.0001). As evaluated by stepwise regression analysis, incorporation of both PDGF β receptor tyrosine phosphorylation and immediate gain correlated strongly (adjusted r² = 0.579) with late loss, although PDGF β receptor tyramine phosphorylation alone correlated poorly with late loss. Multivariate regression analysis of coronary risk factors and clinical events revealed unstable angina as the most significant correlate of PDGF β receptor tyrosine phosphorylation (F value 20.009, p < 0.0001).
Conclusions—PDGF β receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with non-atherosclerotic arterial tissues. The association of PDGF β receptor tyrosine phosphorylation with immediate gain strongly correlates with vascular remodelling. PDGF β receptor tyrosine phosphorylation correlates with unstable angina pectoris.

Keywords: PDGF receptors;  atherosclerosis;  directional coronary atherectomy;  restenosis     

Hyaluronan production in human rheumatoid fibroblastic synovial lining cells is increased by interleukin 1β but inhibited by transforming growth factor β1

OBJECTIVES—To investigate the regulatory roles of interleukin 1β (IL1β), tumour necrosis factor α (TNFα), interferon γ (IFNγ) or transforming growth factor β1 (TGFβ1) on hyaluronan (HA) synthesis by human fibroblastic synovial lining cells.
METHODS—Concentrations of HA in culture supernatants of fibroblastic synovial lining cell line (RAMAK-1 cell line) with or without stimulation by IL1β, TNFα, IFNγ or TGFβ1 were measured by sandwich binding protein assay. Levels of HA synthase mRNA of the cells with or without stimulation were detected by reverse transcribed polymerase chain reaction. Molecular weights of HA in the culture supernatants of the cells with or without stimulation were measured using high performance gel permeation liquid chromatography.
RESULTS—HA synthesis by the cells was not significantly augmented by TNFα or by IFNγ. It was significantly stimulated by IL1β but inhibited by TGFβ1. Molecular weights of HA in the culture supernatants of the cells were unchanged by stimulation with TNFα. They were remarkably increased by stimulation with IL1β and IFNγ, but reduced with TGFβ1.
CONCLUSION—IL1β is an up regulator of HA synthesis, while TGFβ1 is a down regulator. HA production in the synovial lining cells of inflamed joints (for example, rheumatoid arthritis) might be regulated by the balance of these cytokines.

Keywords: synovial lining cells; hyaluronan, interleukin 1β; transforming growth factor β1     

慢性乙型肝炎肝衰竭患者血清甲胎蛋白和胸腺素β4水平变化

目的 探讨血清甲胎蛋白（AFP）和胸腺素β4水平在预测慢性乙型肝炎肝衰竭患者转归中的应用价值。方法 2015年1月~2016年7月我院收治的慢性乙型肝炎肝衰竭患者75例,采用ELISA法检测血清AFP和胸腺素β4水平。结果 治疗3个月,在75例慢性乙型肝炎肝衰竭患者中,43例患者（57.3%）死亡,32例患者（42.7%）生存;入院时,生存组血清AFP和胸腺素β4水平分别为（194.2±13.5） μg/L和（914.1±29.5） μg/L,均显著高于死亡组的【（98.4±9.5） μg/L和（504.2±15.4） μg/L,P﹤0.05】;以血清AFP大于或等于71.3 μg/L为截断点,其预测患者在3个月内生存的敏感度为81.5%,特异度为74.9%;以血清胸腺素β4大于472.7μg/L为截断点,其预测患者在3个月内生存的敏感度为76.2%,特异度为69.5%。结论 慢性乙型肝炎肝衰竭患者血清AFP和胸腺素β4水平对患者转归有一定的预测作用,两者水平越高,预后越好。     

Beta-blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long-term effects of atenolol vs. nebivolol

We compared the effects of 6 months administration of atenolol or nebivolol on resting and exercise hemodynamic parameters and maximal exercise capacity, in 26 patients with hypertension and left ventricular (LV) diastolic dysfunction (ejection fraction >50%, end-diastolic diameter <60 mm and increased pulmonary wedge pressure at rest and/or at peak exercise). Both atenolol and nebivolol administration was associated with a significant decrease in the resting and peak exercise heart rate and blood pressure and in LV mass, with an increase in the E/A ratio. This latter effect was greater with nebivolol. Nebivolol was associated with an increase in the peak VO(2), VO(2) at the anaerobic threshold and with a decrease in the VE/VCO(2) ratio. With regards to the hemodynamic parameters, compared to patients on atenolol, those on nebivolol showed a lower reduction in the cardiac index, a greater increase in the stroke volume index and a decline in the mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and peak exercise. Thus, although the two beta-blockers have a similar antihypertensive action, nebivolol administration was associated with a greater hemodynamic improvement, compared to atenolol.     

国产聚乙二醇化干扰素α治疗HBeAg阳性慢性乙型肝炎患者疗效研究

目的 观察国产聚乙二醇化干扰素α-2b（peg-IFN-α-2b）治疗血清HBeAg阳性的慢性乙型肝炎（CHB）患者的效果。方法 2015年1月~2017年12月纳入血清HBeAg阳性的CHB患者500例,被分为A组150例,给予国产peg-IFN-α-2b治疗,和B组350例,给予peg-IFN-α-2a治疗。两组均治疗24~48 w。在治疗结束后,随访24 w。结果 治疗前,A组血清HBV DNA定量为（6.1±0.7） lg cps/ml、谷丙转氨酶（ALT）为（81.1±29.8）u/l、体质指数为（22.1±2.9）、血清HBeAg定量为（3.1±0.6） lg s/co和HBsA定量为（4.4±0.6） IU/ml,与B组的（6.2±0.67） lg cps/ml、（80.7±27.9） U/L、（21.9±2.9）、（3.1±0.1） lg s/co和（4.4±0.5） IU/ml比,差异均无统计学意义（P>0.05）;在随访24 w结束时,A组血清ALT复常率为64.0%,血清HBV DNA阴转率为60.0%,与B组的66.9%和62.9%比,差异均无统计学意义（P>0.05）;两组不良反应发生率也无显著性相差（P>0.05）。结论 应用国产peg-IFN-α-2b治疗血清HBeAg阳性的CHB患者能获得与peg-IFN-α-2a治疗相似的疗效,但价格便宜,具有临床应用价值。     

Y型聚乙二醇干扰素α-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究*

目的 以标准剂量的聚乙二醇干扰素（PegIFN）α-2a联合利巴韦林作为阳性对照,评价新型试验药物Y型PegIFNα-2b注射液联合利巴韦林治疗2型/3型慢性丙型肝炎（CHC）患者的疗效和安全性。方法 采用多中心、随机开放、阳性药对照的Ⅲ期临床试验,筛选符合要求的2型/3型CHC患者,按照2:1的比例随机分配到Y型PegIFNα-2b组和PegIFNα-2a组,同时口服利巴韦林,疗程24 w,停药随访24 w。采用Abbott RealTime HCV Genotype II检测HCV基因型,采用Cobas TaqMan实时定量PCR法检测血清HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答（SVR）,并进行非劣效检验。结果 本试验实际入组2型/3型CHC患者255例,实际治疗241例。全分析集（FAS）数据显示,158例试验组和83例对照组患者SVR分别为85.4%（95% CI 79.94%~90.94%）和79.5%（95% CI 70.84%~88.20%,P=0.2402）;对符合方案分析集（PPS）人群分析显示,试验组和对照组患者SVR分别为87.9%（95% CI 82.45%~93.27%）和85.9%（95% CI 77.82%~94.01%,P=0.7060）,率差的95%可置信区间均符合非劣效标准;对PPS人群分析显示,85.8%受试者获得了早期病毒学应答（RVR）,RVR的阳性预测值为90.1%;试验组和对照组不良事件发生率相似,分别为95.6%和95.2%,严重不良事件发生率分别为3.8%和3.6%。结论 应用PegIFNα联合利巴韦林治疗2型/3型CHC患者,新型试验药物Y型PegIFNα-2b具有与对照药物PegIFNα-2a相似的疗效和安全性。     

聚乙二醇干扰素α-2a联合恩替卡韦治疗拉米夫定耐药的慢性乙型肝炎患者疗效分析*

目的 探讨聚乙二醇干扰素α-2a联合恩替卡韦治疗拉米夫定耐药的HBeAg阳性慢性乙型肝炎患者的疗效。方法 随机将85例拉米夫定耐药患者分为两组,给予45例CHB患者恩替卡韦治疗,40例患者接受恩替卡韦和聚乙二醇干扰素α-2a治疗。结果 在治疗24 w末,两组血清ALT和AST水平均较治疗前下降,在治疗48 w末,联合组血清ALT和AST水平较恩替卡韦治疗组显著降低,差异有统计学意义（P<0.05）;联合组血清HBeAg阴转和血清转换率均显著高于恩替卡韦治疗组（P<0.05）。结论 应用聚乙二醇干扰素α-2a联合恩替卡韦治疗拉米夫定耐药的HBeAg慢性乙型肝炎患者可提高HBeAg转阴率和血清转换率,治疗安全。     

Nocturnal desaturation in patients with stable heart failure

Objective—To determine the prevalence of sleep disordered breathing within a United Kingdom heart failure population.
Subjects—104 patients and 21 matched normal volunteers.
Methods—Overnight home pulse oximetry with simultaneous ECG recording in the patient group; daytime sleepiness was assessed using the Epworth sleepiness scale (ESS); 41 patients underwent polysomnography to assess the validity of oximetry as a screening test for Cheyne-Stokes respiration.
Results—Home oximetry was a good screening test for Cheyne-Stokes respiration (specificity 81%, sensitivity 87%). Patients with poorer New York Heart Association (NYHA) classes had higher sleepiness scores (p < 0.005). Twenty three patients had "abnormal" patterns of nocturnal desaturation suggestive of Cheyne-Stokes respiration. The mean (SEM) frequency of dips in SaO₂ exceeding 4% was 10.3 (0.9) per hour in the patients and 4.8 (0.6) in normal controls (p < 0.005). Ejection fraction correlated negatively with dip frequency (r = −0.5. p < 0.005). The patient subgroup with ⩾ 15 dips/hour had a higher mean (SEM) NYHA class (3.0 (0.2) v 2.3 (0.1), p < 0.05), and experienced more ventricular ectopy (220 (76) v 78 (21) beats/hour, p < 0.05). There was no excess of serious arrhythmia.
Conclusions—Nocturnal desaturation is common in patients with treated heart failure. Low ejection fraction was related to dip frequency. Lack of correlation between dips and ESS suggests that arousal from sleep is more important than hypoxia in the aetiology of daytime sleepiness in heart failure. Overnight oximetry is a useful screening test for Cheyne-Stokes respiration in patients with known heart failure.