Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population

Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II–IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) −2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5′-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56−2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36−10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69−3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20−3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08−55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.     

Applicability and clinical relevance of the transfer function method in the assessment of baroreflex sensitivity in heart failure patients.

OBJECTIVES: We sought to assess applicability, clinical correlates, and prognostic value of the transfer function method for measuring baroreflex sensitivity (TF-BRS). BACKGROUND: Abnormalities in autonomic reflexes play an important role in the development and progression of chronic heart failure (CHF). Simple and non-invasive techniques for clinical measurement of such reflexes are desirable. METHODS: In 317 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 years [48 to 59 years], New York Heart Association [NYHA] functional class II to III: 88%, left ventricular ejection fraction [LVEF]: 27% [22% to 33%]) we recorded electrocardiograms and non-invasive arterial pressure during paced breathing to measure TF-BRS. RESULTS: Owing to a high number of ectopic beats, TF-BRS could be computed in 72% of the patients; TF-BRS was lower in NYHA functional class III to IV and mitral regurgitation 2 to 3 (p < 0.0005 for both). Correlation with LVEF and standard deviation of all normal-to-normal intervals was 0.18 and 0.31 (p < 0.001 for both). During a mean follow-up of 26 months, 23% of the patients experienced a cardiac event. A depressed TF-BRS (< or =3.1 ms/mm Hg) was significantly associated with the outcome (hazard ratio 3.2, 95% confidence interval [CI] 1.7 to 6.0, p = 0.0003). Patients with a missing TF-BRS had a high event rate (36%). Combining this information with available TF-BRS measurements, a new prognostic index could be computed in 97% of the patients that significantly predicted the outcome after adjustment for clinical and functional variables (hazard ratio 2.5, 95% CI 1.3 to 4.6 p = 0.004). CONCLUSIONS: In CHF patients in sinus rhythm, TF-BRS conveys relevant clinical and prognostic information, but its measurability is markedly affected by ectopic activity. Nevertheless, a TF-BRS-based risk index carrying significant and independent prognostic information can be computed in almost all patients.     

Chronic kidney disease: an independent risk factor of all-cause mortality for elderly Chinese patients with chronic heart failure

Objective

To evaluate the prognostic value of chronic kidney disease (CKD) in elderly Chinese patients with chronic heart failure (CHF).

Methods

The study consisted of 327 elderly patients with CHF. All-cause mortality was chosen as an endpoint over the median follow-up period of 345 days. Cox regression analysis was used to identify the risk factors of mortality.

Results

The median age of the entire cohort was 85 years (60–100 years). The mortality for 168 elderly patients with CHF and CKD (51.4% of entire cohort) was 39.9% (67 deaths), which was higher than the mortality for CHF patients without CKD [25.2% (40/159 deaths)] and the mortality for entire cohort with CHF [32.7% (107/327 deaths)]. The Cox regression analysis showed that old age [hazard ratio (HR): 1.033; 95% confidence interval (95% CI): 1.004–1.064], CKD (HR: 1.705; 95% CI: 1.132–2.567), CHF New York Heart Association (NYHA) class IV (HR: 1.913; 95% CI: 1.284–2.851), acute myocardial infarction (AMI) (HR: 1.696; 95% CI: 1.036–2.777), elevated resting heart rate (HR: 1.021; 95% CI: 1.009–1.033), and decreased plasma albumin (HR: 0.883; 95% CI: 0.843–0.925) were independent risk factors of mortality for elderly patients with CHF.

Conclusions

CKD was an independent risk factor of mortality for elderly Chinese patients with CHF.     

Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group.

OBJECTIVES: To describe changes in haemoglobin over time and to determine the joint prognostic value of the current haemoglobin, CD4 lymphocyte count and viral load among patients from across Europe. PATIENTS: The analysis included 6725 patients from EuroSIDA, an observational, prospective cohort of patients with HIV from across Europe. METHODS: Normal haemoglobin was defined as haemoglobin greater than 14 g/dl for men and 12 g/dl for women; mild anaemia was 8-14 g/dl for men and 8-12 g/dl for women; severe anaemia was defined as less than 8 g/dl for both males and females. Linear regression techniques were used to estimate the annual change in haemoglobin; standard survival techniques were used to describe disease progression and risk of death. RESULTS: At recruitment to the study, 40.4% had normal levels of haemoglobin, 58.2% had mild anaemia and 1.4% had severe anaemia. At 12 months after recruitment, the proportion of patients estimated to have died was 3.1% [95% confidence interval (CI) 2.3-3.9] for patients without anaemia, 15.9% for patients with mild anaemia (95% CI 14.5-17.2) and 40.8% for patients with severe anaemia (95% CI 27.9-53.6; P < 0.0001). In a multivariate, time-updated Cox proportional hazards model, adjusted for demographic factors, AIDS status and each antiretroviral treatment as time-dependent covariates, a 1 g/dl decrease in the latest haemoglobin level increased the hazard of death by 57% [relative hazard (RH) 1.57; 95% CI 1.41-1.75; P < 0.0001], a 50% drop in the most recent CD4 lymphocyte count increased the hazard by 51% (RH 1.51; 95% CI 1.35-1.70; P < 0.0001) and a log increase in the latest viral load increased the hazard by 37% (RH 1.37; 95% CI 1.15-1.63; P = 0.0005). CONCLUSIONS: Severe anaemia occurred infrequently among these patients but was associated with a much faster rate of disease progression. Among patients with similar CD4 lymphocyte counts and viral load, the latest value of haemoglobin was a strong independent prognostic marker for death.     

Antihypertensive drugs as predictors of type 2 diabetes among subjects with impaired glucose tolerance

Aims: to examine the incidence rate of progression to Type 2 diabetes and baseline prognostic risk factors, focusing on hypertension and antihypertensive medication, in a cohort (n=207) with impaired glucose tolerance (IGT). Methods: after 2 and 4.6 (1.9–6.4) years new cases of diabetes were diagnosed by the oral glucose tolerance test (OGTT). Hypertension (BP 160/95 or antihypertensive medication) was included in multiple regression analyses to assess the effect of risk factors on the development of diabetes. Results: diabetes developed in 32 subjects (19%), an incidence of 41/1000 (95% CI 28–57/1000) person-years. In univariate analyses, progression to diabetes was associated with a high (>9.0 mmol/l) 2-h OGTT value (P=0.008), a high fasting insulin (>12.0 mU/l) level (P=0.000), a high triglyceride (≥1.3 mmol/l) level (P=0.028), a high BMI (≥28.0 kg/m²) (P=0.013) and hypertension (P=0.003). The risk for the development of diabetes was not increased in hypertensive subjects without antihypertensive medication compared with normotensive subjects (OR 0.8, 95% CI 0.3–2.6). However, it was increased in subjects with on medication, especially diuretics alone or in combination with other drugs. Hypertensive subjects on diuretics had higher levels of fasting insulin and triglycerides and higher BMIs at baseline than normotensive subjects. After adjustment for 2-h OGTT, fasting insulin, triglycerides and BMI, the OR for diabetes was 7.7 (95% CI 2.1–28.2) in hypertensive subjects using diuretics alone or in combination with other drugs and 2.6 (95% CI 1.0–6.7) in those using other drugs compared with normotensive subjects. The OR of diabetes corresponding to a one-unit increase in the 2-h OGTT concentration was 2.5 (95% CI 1.6–4.0) in the whole cohort. Conclusions: the rate of progression from IGT to Type 2 diabetes in this population was similar to that seen in other studies among Caucasian populations. The use of antihypertensive medication, especially diuretics, and a high 2-h OGTT level were significant predictors of subsequent deterioration to diabetes.     

COPD Predicts Mortality in HF: The Norwegian Heart Failure Registry

BackgroundChronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients.Methods and ResultsThe Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on β-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. β-blockers at baseline were associated with improved survival in patients with LVEF ≤40% independently of COPD.ConclusionCOPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients.     

Predictors of appropriate defibrillator therapy among patients with an implantable defibrillator that delivers cardiac resynchronization therapy

INTRODUCTION: The purpose of this study was to determine predictors of appropriate implantable defibrillator (ICD) therapy among patients with heart failure who are treated with a cardiac resynchronization therapy-defibrillator (CRT-D). METHODS AND RESULTS: Patients enrolled in the Ventak CHF/Contak CD study were treated with a CRT-D device and were required to have NYHA class II-IV CHF, QRS duration > or = 120 msec, and a class I or II indication for an ICD. The study database was retrospectively analyzed during the 6-month postimplant period to identify predictors of appropriate ICD therapy. Five hundred and one of the 581 patients enrolled in the trial had successful device implantation and were included in this analysis. Patients were mostly male (83%), 66 +/- 11 years old, and had coronary artery disease (69%), a mean left ventricular ejection fraction (EF) = 0.22 +/- 0.07, and NYHA class II (33%), III (58%), or IV (9%) CHF symptoms. During 6 months of follow-up, 73 of 501 (14%) patients received an appropriate ICD therapy. Two independent predictors of appropriate therapy were identified: a history of a spontaneous, sustained ventricular arrhythmia (HR = 2.05; 95% CI = 1.31-3.20; P = 0.002) and NYHA class IV CHF (HR = 1.81; 95% CI = 1.10-2.96; P = 0.019). When patients with NYHA class II were excluded from analysis, a history of a sustained ventricular arrhythmia and the presence of NYHA class IV CHF symptoms remained as independent predictors of appropriate ICD therapy. CONCLUSIONS: In a select population of advanced heart failure patients receiving a CRT-D, NYHA class IV CHF was a powerful independent predictor of appropriate ICD therapy. Approximately one-quarter of the patients with NYHA class IV CHF who received a CRT-D device received an appropriate ICD therapy within 3 months after implant. Additional studies are needed to confirm an association between class IV CHF symptoms and an increased frequency of ICD shocks.     

Fatigue and anaemia in patients with chronic heart failure

BACKGROUND: Fatigue is common in patients with chronic heart failure (CHF) and has great impact on functional ability and daily activity. Although anaemia is associated with fatigue, the relationship between fatigue and anaemia is unclear in CHF. The aim of this study was to describe the fatigue experience and its relationship to haemoglobin (Hb) concentration and to evaluate its effect on health-related quality of life in an unselected hospitalised CHF population. METHODS: Ninety three consecutive patients hospitalised with a diagnosis of CHF, enrolled in the EuroHeart Failure Survey, completed the Multidimensional Fatigue Inventory Scale (MFI-20). New York Heart Association (NYHA) functional class, quality of life and haemoglobin were also assessed. RESULTS: Anaemia (Hb < or = 125 g/L) was found in 31 (33%) patients. The perception of fatigue differed significantly between patients with CHF and healthy individuals. Anaemic patients reported significantly more fatigue compared to non-anaemic patients. Decreased haemoglobin and higher NYHA class explained 30% of the variance in General Fatigue. Perceived fatigue was also inversely related to global health and quality of life. CONCLUSION: Our findings suggest that the subjective experience of fatigue in patients with CHF is associated with low haemoglobin concentration and reduced functional status after controlling for age and sex.     

Plasma vascular endothelial growth factor in Japanese Type 2 diabetic patients with and without nephropathy

Aim: To determine whether plasma vascular endothelial growth factor (VEGF) level is elevated in Type 2 diabetic patients with an early stage of diabetic nephropathy. Methods: We studied 71 Japanese Type 2 diabetic patients with normal serum creatinine level (<100 μmol/l) (age 63.0 [60.3–65.6] years old, diabetes duration 15.6 [14.0–17.3] years, HbA1c 7.36% [7.06–7.66%], mean [95% confidence interval, CI]): normoalbuminuric patients (n=36); microalbuminuric patients (n=21); and proteinuric patients (n=14). Plasma VEGF concentration was measured by a quantitative sandwich enzyme immunoassay technique. Results: Plasma VEGF concentration was not related to the degree of albuminuria: normoalbuminuric patients (25 [13–95] ng/l, median [25th–75th percentile]); microalbuminuric patients (33 [15–120] ng/l); and proteinuric patients (54 [17–107] ng/l). Plasma VEGF level in patients with retinopathy (25 [15–95] ng/l, n=30) was not elevated as compared to those without retinopathy (53 [14–126] ng/l, n=34). Plasma VEGF tended to correlated negatively with diabetes duration (R's=−.217, P=.0690) and HbA1c (R's=−.221, P=.0647), whereas there was no correlation between plasma VEGF level and age, serum creatinine or urinary albumin to creatinine ratio (ACR) of the patients, respectively. Plasma VEGF level in the group of patients with HbA1c equal to or below the median (<7.2%) was significantly higher than that in the group of patients with HbA1c above the median (>7.2%) (P<.05). Conclusions: The results suggested that Type 2 diabetic patients with microalbuminuria and those with retinopathy are not necessarily associated with an elevation of circulating plasma VEGF concentration. Plausible association between plasma VEGF level and glycemic control remains to be seen.     

Effects of the angiotensin II antagonist losartan on endothelin-1 and norepinephrine plasma levels during cold pressor test in patients with chronic heart failure

We evaluate the acute hemodynamic and neurohormonal effects of losartan in 15 patients with symptomatic chronic heart failure (CHF), mean age 72 ± 8 years, which were classified in two subgroups: (A) Patients with left ventricular ejection fraction (LVEF) ≤0.35 (n = 7); (B) subjects with LVEF >0.35 (n = 8). Sympathetic reactivity (blood pressure, heart rate and plasma norepinephrine) and plasma endothelin-1 (ET-1) were evaluated by a cold pressor test (CPT). Single doses of losartan (50 mg p.o.) lowered delta DBP in both subgroups (A, 8 ± 9 to 0 ± 5 mmHg, P < 0.05; B, 10 ± 6 to 3 ± 4 mmHg, P < 0.05) and attenuated the rise of HR in patients with mild (4 ± 6 to −1 ± 2 bpm, P < 0.05) but not with severe (4 ± 5 to 2 ± 5 bpm, n.s.) impairment of left ventricular function. Losartan blunted the response (delta) of PNE during CPT (A, 142 ± 131 to 10 ± 74 pg/ml, P < 0.05; B, 129 ± 72 to 1 ± 144 pg/ml, P < 0.01). A significant rise in plasma ET-1 was observed during CPT in patients from subgroup B (0.64 ± 0.40 to 0.81 ± 0.40 fmol/ml, P < 0.05) but not in patients with LVEF ≤0.35 (1.79 ± 0.44 to 1.51 ± 0.66 fmol/ml, n.s.). Losartan attenuated the rise in ET-1 during CPT in patients with LVEF >0.35 (delta ET-1 0.17 ± 0.86 to 0.03 ± 0.11 fmol/ml, P < 0.05), with no significant changes in subgroup A. Acute effects of losartan were characterized by a more favorable hemodynamic and neurohumoral response in patients with chronic heart failure and preserved systolic ventricular function related to subjects with lower ejection fractions.     

Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy: results of the ALPHA Study.

OBJECTIVES: The aim of this study was to assess the prognostic value of T-wave alternans (TWA) in New York Heart Association (NYHA) functional class II/III patients with nonischemic cardiomyopathy and left ventricular ejection fraction (LVEF) < or =40%. BACKGROUND: There is a strong need to identify reliable risk stratifiers among heart failure candidates for implantable cardioverter-defibrillator (ICD) prophylaxis. T-wave alternans may identify low-risk subjects among post-myocardial infarction patients with depressed LVEF, but its predictive role in nonischemic cardiomyopathy is unclear. METHODS: Four hundred forty-six patients were enrolled and followed up for 18 to 24 months. The primary end point was the combination of cardiac death + life-threatening arrhythmias; secondary end points were total mortality and the combination of arrhythmic death + life-threatening arrhythmias. RESULTS: Patients with abnormal TWA (65%) compared with normal TWA (35%) tests were older (60 +/- 13 years vs. 57 +/- 12 years), were more frequently in NYHA functional class III (22% vs. 19%), and had a modestly lower LVEF (29 +/- 7% vs. 31 +/- 7%). Primary end point rates in patients with abnormal and normal TWA tests were 6.5% (95% confidence interval [CI] 4.5% to 9.4%) and 1.6% (95% CI 0.6% to 4.4%), respectively. Unadjusted and adjusted hazard ratios were 4.0 (95% CI 1.4% to 11.4%; p = 0.002) and 3.2 (95% CI 1.1% to 9.2%; p = 0.013), respectively. Hazard ratios for total mortality and for arrhythmic death + life-threatening arrhythmias were 4.6 (p = 0.002) and 5.5 (p = 0.004), respectively; 18-month negative predictive values for the 3 end points ranged between 97.3% and 98.6%. CONCLUSIONS: Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias. Patients with normal TWA tests have a very good prognosis and are likely to benefit little from ICD therapy.     

A propensity matched study of New York Heart Association class and natural history end points in heart failure

The association between higher New York Heart Association (NYHA) functional class and poor outcome in heart failure (HF) is well known. However, to what extent these associations are confounded by covariates such as age, the severity of disease, and co-morbidity burden is unknown. In the Digitalis Investigation Group (DIG) trial, 2,441 of the 7,788 patients with chronic HF had NYHA class III or IV symptoms. Propensity scores for NYHA classes III and IV were calculated for each patient and were then used to match 1,863 patients in NYHA classes III and IV with 1,863 patients in NYHA classes I and II. Kaplan-Meier and matched Cox regression analyses were used to estimate associations of NYHA class III or IV with mortality and hospitalizations during a median of 37 months of follow-up. Compared with 34% (641 of 1,863) patients in NYHA classes I and II (mortality rate 1,175 in 10,000 person-years of follow-up), 42% (777 of 1,863) patients in NYHA classes III and IV (mortality rate 1,505 in 10,000 person-years) died from all causes (hazard ratio 1.29, 95% confidence interval [CI] 1.14 to 1.45, p <0.0001). Hospitalizations due to all causes occurred in 66% (1,232 of 1,863) patients in NYHA classes I and II (hospitalization rate 3,898 in 10,000 person-years) and 71% (1,322 of 1,863) patients in NYHA classes III and IV (hospitalization rate 4,793 in 10,000 person-years) (hazard ratio 1.16, 95% CI 1.05 to 1.28, p = 0.003). The hazard ratios for patients in NYHA classes III and IV, compared with those for those in NYHA classes I and II, for other outcomes were 1.29 for cardiovascular mortality (95% CI 1.12 to 1.48, p <0.0001), 1.49 for HF mortality (95% CI 1.20 to 1.84, p <0.0001), 1.18 for cardiovascular hospitalization (95% CI 1.06 to 1.32, p = 0.002), and 1.17 for HF hospitalization (95% CI 1.03 to 1.34, p = 0.017). In conclusion, baseline NYHA class is a marker of hospitalization, disease progression, and mortality in a wide spectrum of ambulatory patients with chronic HF.     

Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia.

AIMS: Anaemia is common in chronic heart failure (CHF) and associated with worse outcome. This randomized, double-blind, placebo-controlled study evaluated the effect of two darbepoetin alfa dosing regimens on haemoglobin (Hb) rate of rise and clinical effects in patients with CHF and anaemia. METHODS AND RESULTS: Patients with CHF (>or=3 months), left ventricular ejection fraction (LVEF) 相似文献   

糖代谢异常对冠心病合并慢性心力衰竭的影响

目的探讨冠心病合并慢性心力衰竭（CHF）患者糖代谢异常的流行情况,以及糖代谢异常和CHF的严重程度的关系。方法研究对象分别来自北京、上海等7个城市,52家医院心内科,连续入选2005年6月至9月间所有符合CHF诊断标准的冠心病住院患者,共收集1009例,其中有效病例1004例。调查内容包括口服糖耐量试验、糖化血红蛋白、空腹血糖和血脂等;心功能分级使用美国纽约心脏病学会（NYHA）心功能分级。结果1004例患者中,过去确诊为糖尿病420（42％）例,新诊断为糖尿病175（17％）例,糖耐量异常208（21％）例,正常201（20％）例。心功能等级随着糖代谢异常程度的增加而增加[等级相关系数（L）=0．17,P=0．001]。多因素logistic回归分析发现,调整年龄等因素后,过去确诊为糖尿病、新诊断为糖尿病和IGT患严重CHF的OR值分别为1．7（95％CI：1．2～2．4）、1．4（95％CI：0．9～2．1）和1．2（95％CI：0．7～1．7）。结论CHF患者的糖代谢异常患病率较高。糖代谢异常和CHF的症状轻重相关,糖代谢异常者患严重CHF的危险性比血糖正常者高。     

Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. High Enalapril Dose Study Group

OBJECTIVES

We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril.

BACKGROUND

Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting.

METHODS

Two hundred and forty-eight patients with advanced CHF (age 56.3 ± 12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9 ± 4.3 mg/day, N = 122) and 60 mg/day in group 2 (mean dose achieved 42 ± 19.3 mg/day, N = 126).

RESULTS

At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6 ± 0.7 and had a mean systolic blood pressure (SBP) of 117 ± 18 mm Hg, a mean heart rate (HR) of 85 ± 16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0 ± 9.8%. In group 2, patients were in NYHA class 2.6 ± 0.7; their SBP was 118 ± 17 mm Hg, HR 83 ± 15 beats/min and LVEF 18.8 ± 8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9 ± 0.7) in both groups; SBP was 111 ± 16 and 111 ± 17 mm Hg, HR 77 ± 12 and 79 ± 13 beats/min and LVEF 31 ± 19% and 30 ± 12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF.

CONCLUSIONS

No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.     

Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: Prevalence and mortality in a population-based cohort

OBJECTIVES

The purpose of this study was to assess the relative proportions of normal versus impaired left ventricular (LV) systolic function among persons with congestive heart failure (CHF) in the community and to compare their long-term mortality during follow-up.

BACKGROUND

Several hospital-based investigations have reported that a high proportion of subjects with CHF have normal LV systolic function. The prevalence and prognosis of CHF with normal LV systolic function in the community are not known.

METHODS

We evaluated the echocardiograms of 73 Framingham Heart Study subjects with CHF (33 women, 40 men, mean age 73 years) and 146 age- and gender-matched control subjects (nested case–control study). Impaired LV systolic function was defined as an LV ejection fraction (LVEF) <0.50.

RESULTS

Thirty-seven CHF cases (51%) had a normal LVEF; 36 (49%) had a reduced LVEF. Women predominated in the former group (65%), whereas men constituted 75% of the latter group. During a median follow-up of 6.2 years, CHF cases with normal LVEF experienced an annual mortality of 8.7% versus 3.0% for matched control subjects (adjusted hazards ratio = 4.06, 95% confidence interval 1.61 to 10.26). Congestive heart failure cases with reduced LVEF had an annual mortality of 18.9% versus 4.1% for matched control subjects (adjusted hazards ratio = 4.31, 95% confidence interval 1.98 to 9.36).

CONCLUSIONS

Normal LV systolic function is often found in persons with CHF in the community and is more common in women than in men. Although CHF cases with normal LVEF have a lower mortality risk than cases with reduced LVEF, they have a fourfold mortality risk compared with control subjects who are free of CHF.     

Prospective validation of stress echocardiography as an identifier of cardiac resynchronization therapy responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) provides benefit for congestive heart failure (CHF), but predictors of the clinical response are debated. OBJECTIVE: The aim of this prospective study was to assess the predictive role of dobutamine stress echocardiography (DSE) in identifying a suitable candidate for CRT. METHODS: From March 2001 to December 2003, 71 CHF patients were prospectively enrolled on the basis of four criteria: New York Heart Association (NYHA) class III and IV; QRS > or =150 ms with a left bundle branch block pattern, and left ventricular ejection fraction (LVEF) < or =35% under optimal medical treatment. The combined endpoints were hospital readmission for class IV CHF, heart transplant (HT), and CHF-related death. RESULTS: The 67 patients completing the study presented with the following characteristics: age (70 +/- 10 years; 11 women); etiology (idiopathic in 44, ischemic in 23); NYHA class (40 in class III and 27 in class IV); LVEF 26% (+/-5%); QRS duration (190 +/- 28 ms); 6-minute walk test 330 m (+/-108); peak oxygen uptake 10.7 (+/-3.3 mL/kg/min); mitral insufficiency in 42 (> or =III grade); interventricular (IV) delay (62 +/- 21 ms); and intraventricular dyssynchrony in 30 patients. Over the follow-up period of 12.1 +/- 8.7 months, 20 (29.9%) of 67 patients presented with at least one hemodynamic event: hospitalization for CHF in 19 (28%) of 67, HT in 2 (3%) of 67, and CHF death in 7 (10%) 67. Univariate analysis identified NYHA class (P = .03), LVEF (P = .015), IV dyssynchrony before (P = .038) and after CRT (P = .0035), IV delay after CRT (P = .002), 6-minute walk distance (P = .01), and DSE Res+ (P = .008) as significant predictors of clinical events. A receiver operating curve established a cut-off value of 1.25 for the DSE responders (Res+: 34 patients at 10 microg/kg/min infusion rates), and the improvement at the 10 microg/kg/min level was 41% +/- 7% in Res+ and 29% +/- 8% in nonresponders (P<.0001). With a cut-off value of 1.25-fold the LVEF increase, the DSE test exhibits 70% sensitivity, 61.7% specificity, 43.8% positive predictive value, and 82.9% negative predictive value. Cox analysis identified IV dyssynchrony before CRT (P = .01) and DSE Res+ (P = .003) as independent predictive factors. CONCLUSIONS: Independent predictive factors of severe hemodynamic clinical outcome in patients with CRT are IV dyssynchrony and DSE.     

Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC₅₀ values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.     

多普勒超声心动图检测慢性心力衰竭患者心肌生物能量消耗水平的变化及临床意义

目的 分析慢性心力衰竭(心衰)患者的多普勒超声指标心肌生物能量消耗(MEE)与左心室结构指标及其收缩、舒张、整体功能指标及心衰严重程度(NYHA心功能分级)、C反应蛋白(CRP)、N末端B型利钠肽原(NT-proBNP)之间的关系,探讨MEE用于评估慢性心衰心功能状况的临床价值.方法 选择慢性心衰住院患者99例,据左室射血分数(LVEF)值分为LVEF正常的心衰(HFNEF)组37例,LVEF降低的心衰(HFREF)组62例(其中LVEF>35%、<50%及≤35%分别为30例及32例);据NYHA心功能分级分为Ⅱ级(26例)、Ⅲ级(42例)、Ⅳ级(31例);对照组30例.采用多普勒超声心动图检测并计算MEE及常规结构指标,左心室收缩(LVEF、LVFS)、舒张(E/A、EDT、IVRT)及整体功能指标(Tei指数),并测定各组血清CRP、血浆NT-proBNP水平,分析各组间各参数的差异,探讨MEE与上述指标间的相关性.结果 HFNEF组患者MEE水平与对照组差异无统计学意义(P>0.05),HFREF组患者MEE水平较对照组明显增加(P<0.01);慢性心衰组MEE随LVEF的降低及NYHA心功能分级级别的升高而显著增加(P<0.05);双变量相关分析显示,MEE与心室结构及收缩、舒张、整体功能指标、NYHA心功能分级及血清CRP、血浆NT-proBNP水平之间均具有相关性,其中关系最密切的是左心室收缩功能指标,即MEE与LVEF、LVFS均呈明显负相关[分别为r=-0.540、P<0.01,r=-0.454、P<0.01].结论 随左心室收缩功能障碍及心衰程度的加重,慢性心衰患者的MEE水平逐步升高,MEE与现有的心功能评价指标(如LVEF值、NYHA分级、NT-proBNP 等)均呈明显相关,特别与左心室收缩功能指标关系密切.MEE可从心肌生物能量学角度有效评定慢性心衰患者的心功能状况.     

艾滋病患者合并分枝杆菌血流感染的临床特征分析

目的: 了解艾滋病(AIDS)合并分枝杆菌血流感染的临床特征,提高对AIDS患者结核分枝杆菌(MTB)感染和非结核分枝杆菌(NTM)感染临床特征的鉴别诊断水平。方法: 采用回顾性研究方法,搜集2016年6月至2021年6月首都医科大学附属北京佑安医院确诊并收治的135例AIDS合并分枝杆菌血流感染的住院患者为研究对象,收集其临床资料,包括病史、症状、体征、实验室检查结果、病原学特点、影像学特征和诊治情况。分析比较合并MTB感染者和NTM感染者的相关资料。结果: (1)病原学检查:135例研究对象中MTB感染者64例(47.4%),NTM感染者71例(52.6%)。NTM分离株中以鸟分枝杆菌为主(40株,56.3%)。(2)临床表现:研究对象的临床表现主要为发热(83.7%,113/135)、咳嗽(44.4%,60/135)、乏力(30.4%,41/135)、腹泻(25.2%,34/135)等。MTB感染组发热(92.2%,59/64)、咳嗽(56.3%,36/64)、咳痰(32.8%,21/64)的发生率,以及体温峰值[(39.0±1.0)℃]均明显高于NTM感染组[分别为76.1%(54/71)、33.8%(24/71)、11.3%(8/71)、(38.6±1.2)℃],差异均有统计学意义(χ²=6.421,P=0.011;χ²=6.869,P=0.009;χ²=9.263,P=0.002;t=2.025,P=0.045)。(3)实验室检查:MTB感染组降钙素原[1.57(0.42,6.71)ng/ml]、白细胞计数[6.62(3.39,8.78)×10⁹/L]、血红蛋白[(95.5±21.5)g/L]、痰涂片抗酸染色阳性率(45.3%,29/64)均明显高于NTM感染组[分别为0.31(0.11,1.80)ng/ml、4.03(2.81,6.20)×10⁹/L、(78.7±14.6)g/L、11.2%(8/71)],差异均有统计学意义(Z=-3.433,P=0.001;Z=-2.798,P=0.005;t=5.344,P<0.001;χ²=19.609,P<0.001)。MTB感染组CD4⁺T淋巴细胞计数为14(8,55)×10⁶/L,明显高于NTM感染组的7(2,20)×10⁶/L,差异有统计学意义(Z=-3.434,P=0.001)。(4)影像学表现:MTB感染组粟粒影(17.2%,11/64)与胸腔淋巴结肿大(85.9%,55/64)的发生率高于NTM感染组[分别为1.4%(1/71)和71.8%(51/71)],差异均有统计学意义(χ²值分别为8.491和3.971,P值分别为0.004和0.046)。(5)治疗转归:MTB感染组住院时间为18(8,25)d,明显短于NTM感染组[26(15,38)d],差异有统计学意义(Z=-3.344,P=0.001)。MTB感染组死亡率为17.2%(11/64), 明显高于NTM感染组(2.8%,2/71),差异有统计学意义(χ²=5.328,P=0.021)。结论: CD4⁺T淋巴细胞明显降低的AIDS患者,如出现发热、咳嗽、咳痰等临床表现,同时伴有炎性指标明显升高、贫血、低蛋白血症和肺部典型的影像学改变时,应警惕合并分枝杆菌血流感染的可能。MTB与NTM感染虽然在临床表现和实验室检查方面存在一定差异,但缺乏特异性。