缺血性慢性心力衰竭与贫血的相关性研究

目的探讨缺血性慢性心力衰竭(CHF)与贫血的相关性。方法根据血红蛋白水平将196例患者分为贫血组54例和非贫血组1 42例,比较2组临床特征、预后、不同程度CHF患者贫血患病率及各项生化指标。结果 196例患者中,有54例出现贫血,占27.6%;轻度心力衰竭贫血患病率16.0%,明显低于重度心力衰竭(39.6%,P<0.01)。与非贫血组比较,贫血组年龄、男性比率及血肌酐明显升高,差异有统计学意义(P<0.05,P<0.01),LVEF明显降低(P<0.05);再次住院、再住院平均天数及随访期病死率明显升高(P<0.05)。与轻度心力衰竭患者比较,重度心力衰竭患者血红蛋白、红细胞平均血红蛋白浓度明显下降,差异有统计学意义(P<0.05)。结论贫血的发生与缺血性心脏病患者年龄、肾功能及心功能程度相关;贫血程度与心力衰竭程度相关;CHF合并贫血的患者预后差。     

Myocardial disease, anemia and heart failure

Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, very poor quality of life, end stage renal failure, or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these patients is the fact that they are often anemic. The anemia is due mainly to renal failure but also to the inhibitory effects of cytokines on the bone marrow. Anemia itself may further worsen the cardiac function and make the patients resistant to standard CHF therapies. Indeed anemia has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, higher doses of diuretics, worsening of renal function and reduced quality of life. In both controlled and uncontrolled studies the correction of the anemia with erythropoietin (EPO) and oral or IV iron is associated with improvement in all these parameters. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia. Anemia may also play a role in the worsening of coronary heart disease even without CHF.     

Decreased renal function as an independent predictor of re-hospitalization for congestive heart failure.

BACKGROUND: Patients with congestive heart failure (CHF) are often re-hospitalized, worsening both their quality of life and prognosis. Although renal dysfunction reportedly increases the risk of CHF, the association between renal dysfunction and re-hospitalization for CHF remains unclear. METHODS AND RESULTS: Patients with CHF and decreased renal function were reviewed. The estimated glomerular filtration rate (GFR) was calculated with the Modification of Diet in Renal Disease equation. Patients with decreased renal function (estimated GFR on admission <45 ml .min(-1) . 1.73 m(-2)) were re-hospitalized more frequently than were patients with preserved renal function (estimated GFR on admission >or=45). Patients with decreased renal function were older and had higher rates of anemia, worsening renal function during hospitalization, and previous hospitalization for CHF. Independent predictors of re-hospitalization for CHF identified with multivariate analysis were age, previous hospitalization for CHF, decreased renal function, and non-use of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. CONCLUSIONS: Renal dysfunction is an independent predictor of re-hospitalization for CHF, so careful follow-up is needed, even after discharge.     

The interaction between heart failure, renal failure and anemia - the cardio-renal anemia syndrome

BACKGROUND: Many patients with congestive heart failure (CHF) have chronic kidney insufficiency (CKI) and anemia. AIMS: The purpose of this review is to clarify the relationship between these three factors and to study the effect of correction of anemia in CHF and CKI. FINDINGS: Anemia, CHF and CKI are each capable of causing or worsening each other. Thus they form a vicious circle which can result in progressive CHF, CKI and anemia. Aggressive therapy of CHF, CKI and control of the associated anemia with erythropoietin and i.v. iron can prevent the progression of CHF and CKI, reduce hospitalization, and improve quality of life. CONCLUSION: CHF patients are a major source of end-stage renal failure patients and deserve special attention. If treated well and early, progressive heart failure and renal failure can be prevented. Cooperation between nephrologists, cardiologists, and other internists will improve the care of all three conditions and prevent their progression.     

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations

OBJECTIVES

This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization.

BACKGROUND

The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown.

METHODS

In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period.

RESULTS

The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 ± 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment.

CONCLUSIONS

Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.     

Therapy insight: congestive heart failure, chronic kidney disease and anemia, the cardio-renal-anemia syndrome

Congestive heart failure (CHF) and chronic kidney disease (CKD) often progress to end stage even with optimum medical therapy. One factor that is common to both conditions is anemia, which is present in about a third of CHF patients. CHF can cause or worsen both anemia and CKD, and CKD can cause or worsen both anemia and CHF. Thus, a vicious circle exists between these three conditions, with each causing or worsening the other. We have called this condition the cardio-renal-anemia syndrome. Anemia in CHF is associated with increased mortality and hospitalization, reduced cardiac function and evidence of more severe CHF and CKD than in nonanemic patients. Intervention studies in anemic CHF patients have shown that optimum medical treatment of CHF and the correction of the associated anemia with subcutaneous erythropoietin and oral iron or intravenous iron sucrose can improve cardiac function, patients' functional status, renal function and quality of life, and reduce the frequency of hospitalization and the dose of diuretics required.     

老年慢性心力衰竭患者贫血与心功能关系的探讨

目的研究老年慢性心力衰竭(CHF)患者中血红蛋白(Hb)水平变化与心功能的关系。方法对入选的286例年龄>60岁的CHF患者(CHF组)行临床、实验室和超声心动图检查,并进行心功能分级(NYHA);CHF组患者按Hb水平又分为贫血组(136例)和非贫血组(150例);根据NYHA分为轻、中度心力衰竭患者(203例),重度心力衰竭患者(83例);同时选择98例健康体检老年人为对照组,分别比较各组间不同性别血液学参数、血尿素、肌酐(Cr)、LVFF、左心室舒张末期内径(LVEDD)、贫血发生率、病死率,并采用改良简化的MDRD方程计算肾小球滤过率(GFR)。结果与对照组比较,CHF组男、女性患者的Hb、红细胞比容、LVEF和GFR均明显降低(P<0.01),尿素、Cr和LVEDD均明显升高(P<0.05,P<0.01);与轻、中度心力衰竭患者比较,重度心力衰竭患者Hb、红细胞比容、LVEF和GFR均明显降低,Cr、LVEDD、贫血发生率、病死率逐步升高(P<0.05,P<0.01)。CHF患者的Hb、LVEF均与Cr呈负相关,而与GFR呈正相关(P<0.01),Hb与LVEF呈正相关(P<0.01)。结论老年CHF男、女性患者常伴有贫血和肾功能损害,贫血和肾功能损害的程度均与CHF的严重程度呈正相关,贫血、肾功能损害均使CHF患者死亡危险性增高。     

慢性心力衰竭患者贫血与肾功能和神经内分泌细胞因子的关系

目的探讨慢性心力衰竭(CHF)患者贫血与肾功能和神经内分泌细胞因子之间的关系。方法对入选的121例CHF患者测定血红蛋白(Hb)、肾功能、TNF-α、可溶性细胞间黏附分子-1(sICAM-1)、白细胞介素-6(IL-6)、血管紧张素Ⅱ(AngⅡ)、NO、内皮素(ET)的变化;超声心动图测量LVEF,评价心功能;按Hb水平分为贫血组(47例)和非贫血组(74例)。结果随着心功能恶化,CHF患者LVEF和Hb水平逐渐降低,而尿素、肌酐(Cr)、血尿酸(BUA)水平明显增高(P<0.01);贫血发生率为38.8%,肾功能障碍发生率为24.0%,随着LVEF下降,贫血和肾功能障碍逐渐增加且程度加重(P<0.05)。贫血组患者血清TNF-α、sICAM-1、IL-6、AngⅡ、NO、ET水平明显高于非贫血组(P<0.01)。Hb和LVEF与尿素、Cr、BUA呈负相关;Hb与TNF-α、sICAM-1、IL-6、AngⅡ、NO、ET呈负相关,而与LVEF呈正相关(P<0.01)。结论CHF患者机体存在细胞因子的过度表达和肾素-血管紧张素系统的过度激活及伴随肾功能的降低,可能导致了CHF患者贫血的发生,且贫血也参与并加重了CHF发生发展的病理生理过程。     

Measurements of baseline and follow-up concentrations of cardiac troponin-T and brain natriuretic peptide in patients with heart failure from various etiologies

Since chronic heart failure (CHF) is a complex clinical syndrome, a single biomarker may not reflect all of its characteristics. In this study, the clinical significance of combination and serial measurement of biochemical markers of myocyte injury and myocardial load in patients with CHF from various etiologies was examined. Serum concentrations of cardiac troponin-T (cTnT) and plasma concentrations of brain natriuretic peptide (BNP) were measured simultaneously in 190 patients with CHF, including dilated cardiomyopathy (DCM) (n = 41), ischemic heart disease (n = 40), valvular or congenital disease (n = 53), hypertensive heart disease (n = 16), and hypertrophic cardiomyopathy (HCM) (n = 22). Serum cTnT concentrations ≥0.01 ng/ml were found in 46/190 patients (24%) at baseline (20% in DCM, 42% in ischemic heart disease, 21% in valvular or congenital disease, 43% in hypertensive heart disease, and 9% in HCM). Follow-up samples were obtained in 137 patients after a mean treatment period of 31.8 days. Although BNP decreased significantly in each disease category (P < 0.0001: DCM; P < 0.005: ischemic heart disease; P < 0.05: valvular or congenital disease; P < 0.005: hypertensive heart disease; P < 0.05: HCM), cTnT remained high in 36/137 patients (26%) (19% in DCM, 39% in ischemic heart disease, 25% in valvular or congenital disease, 38% in hypertensive heart disease, and 19% in HCM). The rate of adverse cardiac events was significantly higher in patients with high cTnT than in patients with low cTnT concentrations (P < 0.0001) (P < 0.05: DCM; P < 0.05: ischemic heart disease; P < 0.01: valvular or congenital disease). Multivariate analysis showed that both cTnT and BNP are independent prognostic factors, and patients with elevations of both cTnT and BNP had the poorest prognosis (P < 0.0001). In patients with CHF, the evolution and prognostic value of cTnT and BNP are different. The combined measurements of these markers should refine our understanding of the state and evolution of CHF.     

贫血对慢性心力衰竭患者住院期间死亡的影响

目的:了解慢性心力衰竭(CHF)患者贫血的发生率及其对住院期间死亡的影响。方法:收集2003-01-2008-06在我院住院的CHF患者的临床资料进行回顾性分析,根据患者血红蛋白(Hb)水平分为Hb正常组、轻度贫血组以及中重度贫血组3组。结果:贫血在CHF患者的发生率为32·5%;住院期间死亡患者的Hb、RBC均明显低于好转的患者(P0·01),贫血患者在住院期间的死亡率明显高于无贫血的患者(P0·01),以二分类Logistic回归住院期间死亡的危险因素进行分析得出:贫血的偏回归系数为1·296(P=0·039),优势比(OR)为3·655(95%CI:1·069~12·499);对于心功能NYHAⅢ~Ⅳ级的CHF患者,Hb的偏回归系数为-0·073(P=0·041),OR为0·93(95%CI:0·864~0·995)。结论:CHF患者贫血的发生率较高,贫血是CHF患者住院期间死亡的独立危险因素,Hb降低增加心功能Ⅲ~Ⅳ级的CHF患者住院期间的死亡。     

Are hematinic deficiencies the cause of anemia in chronic heart failure?

Background

Anemia in chronic heart failure (CHF) is common, varying in prevalence between 14.4% and 55%, and is more frequent in patients with more severe heart failure. Patients with CHF who have anemia have a poorer quality of life, higher hospital admission rates, and reduced exercise tolerance. We explored the relation between hematinic levels and hemoglobin (Hb) levels and exercise tolerance in a group of patients with CHF.

Methods

We analyzed data from 173 patients with left ventricular systolic dysfunction (LVSD), 123 patients with symptoms of heart failure, but preserved left ventricular (LV) systolic function (“diastolic dysfunction”), and 58 control subjects of similar age. Each underwent echocardiography, a 6-minute walk test, and blood tests for renal function and Hb and hematinic levels (vitamin B12, iron, and folate). We classified patients as having no anemia (Hb level >12.5 g/dL), mild anemia (Hb level from 11.5-12.5 g/dL), or moderate anemia (Hb level <11.5 g/dL).

Results

Of patients with LVSD, 16% had moderate anemia and 19% had mild anemia. Of patients with preserved LV function, 16% had moderate anemia and 17% had mild anemia. Four control subjects had a Hb level <12.5 g/dL. Of all patients, 6% were vitamin B12 deficient, 13% were iron deficient, and 8% were folate deficient. There was no difference between patients with LVSD and the diastolic dysfunction group. In patients with LVSDS, the average Hb level was lower in New York Heart Association class III than classes II and I. The distance walked in 6 minutes correlated with Hb level in both groups of patients with CHF (r = 0.29; P <.0001). Patients with anemia achieved a lower pVo₂ (15.0 [2.3] vs 19.5 [4.4], P < .05). Peak oxygen consumption correlated with Hb level (r = 0.21, P <.05) in the patients, but not in the control subjects. In patients with anemia, the mean creatinine level was higher than in patients with a Hb level >12.5 g/dL, but there was no clear relationship with simple regression. Hematocrit level and mean corpuscular volume were not different in the patients with diastolic dysfunction, patients with LV dysfunction, or the control subjects. Hematocrit levels were not influenced by diuretic dose. Patients with anemia were not more likely to be hematinic deficient than patients without anemia.

Conclusions

Patients with symptoms and signs of CHF have a high prevalence of anemia (34%) whether they have LV dysfunction or diastolic dysfunction, but few patients have hematinic deficiency. Hemoglobin levels correlate with subjective and objective measures of severity and renal function.     

Anemia and heart failure

Over the past few years, anemia has emerged as a powerful independent predictor of adverse outcomes in chronic heart failure (CHF). It affects up to 50% of patients with CHF, depending on the definition of anemia used and on the population studied. Even small reductions in hemoglobin are associated with worse outcome. However, the causes of anemia in CHF remain unclear, although impairment of renal function and inflammatory cytokines are proposed mechanisms. Both may act through impairment of the synthesis or action of erythropoietin. Preliminary studies have demonstrated improvement in symptoms, exercise tolerance, quality of life, and reductions in hospitalizations when patients with severe CHF were treated with erythropoietin. The benefits and the potential risks of such therapies will be further addressed in upcoming larger randomized trials. The recent interest in anemia reflects a new perspective in heart failure therapy, focusing on noncardiovascular comorbidities.     

Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET.

AIMS: Atrial fibrillation is common in patients with chronic heart failure (CHF). We analysed the risk associated with atrial fibrillation in a large cohort of patients with chronic heart failure all treated with a beta-blocker. METHODS AND RESULTS: In COMET, 3029 patients with CHF were randomized to carvedilol or metoprolol tartrate and followed for a mean of 58 months. We analysed the prognostic relevance on other outcomes of atrial fibrillation on the baseline electrocardiogram compared with no atrial fibrillation and the impact of new onset atrial fibrillation during follow-up. A multivariate analysis was performed using a Cox regression model where 10 baseline covariates were entered together with study treatment allocation. Six hundred patients (19.8%) had atrial fibrillation at baseline. These patients were older (65 vs. 61 years), included more men (88 vs.78%), had more severe symptoms [higher New York Heart Association (NYHA) class] and a longer duration of heart failure (all P<0.0001). Atrial fibrillation was associated with significantly increased mortality [relative risk (RR) 1.29: 95% CI 1.12-1.48; P<0.0001], higher all-cause death or hospitalization (RR 1.25: CI 1.13-1.38), and cardiovascular death or hospitalization for worsening heart failure (RR 1.34: CI 1.20-1.52), both P<0.0001. By multivariable analysis, atrial fibrillation no longer independently predicted mortality. Beneficial effects on mortality by carvedilol remained significant (RR 0.836: CI 0.74-0.94; P=0.0042). New onset atrial fibrillation during follow-up (n=580) was associated with significant increased risk for subsequent death in a time-dependent analysis (RR 1.90: CI 1.54-2.35; P<0.0001) regardless of treatment allocation and changes in NYHA class. CONCLUSION: In CHF, atrial fibrillation significantly increases the risk for death and heart failure hospitalization, but is not an independent risk factor for mortality after adjusting for other predictors of prognosis. Treatment with carvedilol compared with metoprolol offers additional benefits among patients with atrial fibrillation. Onset of new atrial fibrillation in patients on long-term beta-blocker therapy is associated with significant increased subsequent risk of mortality and morbidity.     

The frequency of systolic versus diastolic heart failure in an Egyptian cohort

BACKGROUND: All factors predisposing for congestive heart failure (CHF), such as coronary artery disease (CAD), hypertension and diabetes are increasing in prevalence in Egypt. Despite this, no data about CHF in our country are available. AIMS: To study the relative contribution of systolic vs. diastolic heart failure in Egyptians and the prevalence of risk factors in this population, as well as their prognosis. METHODS: This was a retrospective study of patients with a diagnosis of CHF over a 3.5-year period in a general cardiology clinic. Demographic, ECG and echocardiographic data for left ventricular systolic and diastolic function were collected. The differential effect of systolic versus diastolic CHF was analyzed regarding hospitalization and mortality. RESULTS: After exclusion of valvular diseases, we found 155 patients diagnosed with heart failure, 102 patients (66%) had systolic heart failure, and 53 (34%) had diastolic heart failure. Mean age was 60+/-10 and 63+/-11 years, respectively (P=0.13). Systolic CHF patients had significantly more CAD, while those with diastolic failure were mostly hypertensives (P<0.01) for both. There was no significant difference in the incidence of diabetes mellitus, cerebrovascular accidents or atrial fibrillation between the two groups. Patients with systolic failure required more hospitalization, P<0.05, and had a mortality rate of 17.6% vs. 11.3% for patients with diastolic heart failure (P=0.3). CONCLUSION: Diastolic heart failure is present in one-third of cases of CHF in Egyptians. Hypertension is very common in this group. These patients require less hospitalization but have a similar mortality rate.     

Clinical and prognostic value of advanced glycation end-products in chronic heart failure.

AIMS: Advanced glycation end-products (AGEs) have been proposed as a novel factor involved in the development and progression of chronic heart failure (CHF). We aimed to determine whether plasma levels of N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL), two well-known AGEs, are related to the severity and prognosis of CHF. METHODS AND RESULTS: A total of 102 CHF patients, aged 58 +/- 12 years, with an average left ventricular ejection fraction of 28 +/- 9% were followed for 1.7 (1.2-1.9) years. NYHA functional class and NT-pro-BNP were used as estimates of the severity of CHF. CML and CEL were determined by LC-MS/MS. CML levels were associated with NYHA functional class (P < 0.001) and NT-pro-BNP levels (P < 0.001). Survival analysis for the combined end-point of death, heart transplantation, ischaemic cardiovascular event, and hospitalization for heart failure revealed that CML levels predicted outcome, even after adjustment for age, gender, aetiology of CHF, identified risk modifiers, and several known predictors of outcome in CHF. The predictive value of CML subsided after correction for renal function. CEL was not associated with the severity or prognosis of CHF. CONCLUSION: Plasma AGEs, in particular CML levels, are related to the severity and prognosis of CHF. The fact that the relation between CML and prognosis subsided after correction for renal function may suggest that AGE accumulation in renal failure explains part of the prognostic value of renal function in CHF. However, further investigation is warranted to exclude the possibility that CML is just an innocent marker of renal function.     

Age-related hemodynamic, renal, and hormonal differences among patients with congestive heart failure

The purpose of this study was to determine if there were characteristics that distinguish elderly patients with heart failure (greater than 65 years of age) from younger patients with heart failure. We studied 128 consecutively admitted patients with chronic congestive heart failure (CHF) under uniform conditions, with measurement of systemic hemodynamics, vasoactive hormones and sodium status, and renal function. Additional characterization included the hemodynamic response to gravitational stress (head-up tilt; n = 65), and renal blood flow and function by steady-state clearance techniques (n = 46). Compared with younger patients with CHF, there was a greater frequency of ischemic heart disease in the elderly patients with CHF. Within the CHF population there was an increase of systemic vascular resistance and a trend of decreased heart rate with aging. Heart rate responsiveness was attenuated during tilt according to age. Circulating norepinephrine increased with aging, but a clear-cut age-related effect was not observed for renin system activity or sodium status. Both serum urea nitrogen and serum creatinine increased with age. More detailed renal studies confirmed an age-related decrease of glomerular filtration rate and a noncompensatory filtration fraction, despite increasing renal vascular resistance. We conclude that elderly patients with CHF have relatively greater vasoconstriction (or decreased compliance) and blunted heart rate responsiveness associated with increased circulating norepinephrine. Furthermore, renal function in the elderly patient with CHF is markedly compromised. These findings are consistent with superimposition of an aging effect on the CHF process, which must be considered in evaluating the response to drug therapy and the outcome of multicenter CHF trials.     

强离子隙在慢性心力衰竭患者中的水平改变及临床意义

目的探讨强离子隙(SIG)水平在慢性心力衰竭(CHF)患者中的改变及其与CHF患者心功能、N末端B型利钠肽前体(NT-proBNP)水平的相关性。方法选择CHF患者90例,根据心功能(NYHA)分级分为心功能Ⅱ级组30例、心功能Ⅲ级组30例和心功能Ⅳ级组30例;根据CHF病因分为冠心病组25例、高血压性心脏病组45例和扩张型心肌病组20例;选择健康体检者35例作为对照组,在测定血气、电解质等的基础上,应用Stewart-Figge方法学的方程式计算SIG,采用电化学免疫法测定NT-proBNP。结果与对照组比较,心功能Ⅱ、Ⅲ和Ⅳ级组患者SIG[(5.54±2.23)mmol/L、(7.65±3.12)mmol/L和(10.54±3.84)mmol/L vs(1.70±0.81)mmol/L]、NT-proBNP[(114.85±36.23)ng/L、(476.30±79.45)ng/L和(782.50±99.38)ng/L vs(42.74±11.29)ng/L]水平明显升高;且心功能Ⅱ、Ⅲ和Ⅳ级组间SIG水平比较,差异有统计学意义(P<0.05)。与治疗前比较,不同心功能组治疗后SIG和NT-proBNP水平明显下降,差异有统计学意义(P<0.01)。GHF患者SIG与NT-proBNP呈正相关(r=0.424,P<0.01)。结论 CHF患者血清SIG水平明显升高,且随着心功能不全程度的加重而升高,与NT-proBNP存在一定的相关性,对CHF的早期诊断、风险评估及治疗评价均具有指导意义。     

Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

BACKGROUND: Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. METHODS AND RESULTS: We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). CONCLUSION: These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.     

A Pilot Evaluation of the Long-term Effect of Combined Therapy With Intravenous Iron Sucrose and Erythropoietin in Elderly Patients With Advanced Chronic Heart Failure and Cardio-Renal Anemia Syndrome: Influence on Neurohormonal Activation and Clinical Outcomes

BackgroundThe prognosis in elderly patients with advanced chronic heart failure (CHF) and cardio-renal anemia syndrome (CRAS) is ominous, and treatment alternatives in this subset of patients are scarce.Methods and ResultsTo assess the long-term influence of combined therapy with intravenous (IV) iron and erythropoietin (rHuEPO) on hemoglobin (Hb), natriuretic peptides (NT-proBNP), and clinical outcomes in elderly patients with advanced CHF and mild-to-moderate renal dysfunction and anemia (CRAS) who are not candidates for other treatment alternatives, 487 consecutive patients were evaluated. Of them, 65 fulfilling criteria for entering the study were divided into 2 groups and treated in an open-label, nonrandomized fashion: intervention group (27, combined anemia therapy) and control group (38, no treatment for anemia). At baseline, mean age was 74 ± 8 years, left ventricular ejection fraction was 34.5 ± 14.1, Hb was 10.9 ± 0.9 g/dL, creatinine was 1.5 ± 0.5 mg/dL, NT-proBNP was 4256 ± 4952 pg/mL, and 100% were in persistent New York Heart Association (NYHA) Class III or IV. At follow-up (15.3 ± 8.6 months), patients in the intervention group had higher levels of hemoglobin (13.5 ± 1.5 vs. 11.3 ± 1.1; P < .0001), lower levels of natural log of NT-proBNP (7.3 ± 0.8 vs. 8.0 ± 1.3, P = .016), better NYHA functional class (2.0 ± 0.6 vs. 3.3 ± 0.5; P < .001), and lower readmission rate (25.9% vs. 76.3%; P < .001). In the multivariate Cox proportional hazards model, combined therapy was associated with a reduction of the combined end point all-cause mortality or cardiovascular hospitalization (HR 95%CI 0.2 [0.1-0.6]; P < .001).ConclusionLong-term combined therapy with IV iron and rHuEPO may increase Hb, reduce NT-proBNP, and improve functional capacity and cardiovascular hospitalization in elderly patients with advanced CHF and CRAS with mild to moderate renal dysfunction.     

The benefit of low-dose dopamine during vigorous diuresis for congestive heart failure associated with renal insufficiency: Does it protect renal function?

Background: Low-dose dopamine, a renal vasodilator, has been used empirically to improve renal function or outcome in critically ill patients with oliguria or acute renal failure. Hypothesis: This study was designed to investigate the efficacy of low-dose dopamine (2 μg/kg/min) as a renal-protective agent during vigorous diuresis for congestive heart failure (CHF) associated with mild or moderate renal insufficiency. Methods: Of 20 study patients (mean age 74.3 ± 15 years) with severe CHF, 10 (Group A) were randomized to a treatment strategy of intravenous bumetanide (1 mg b.i.d.) alone and another 10 (Group B) to low-dose dopamine and a similar diuretic regimen for a duration of 5 days or less if clinical edema remitted. Results: Group B patients showed a significant improvement in renal function and urinary output: serum blood urea nitrogen 48.9 ± 10.3 to 32.1 ± 14.4 mg/dl (p<0.05); serum creatinine 1.97 ± 0.24 to 1.49 ± 0.39 mg/dl (p“0.05); creatinine clearance 35.6 ± 11.6 to 48.8 ± 12.3 ml/min (p“0.05); and indexed urinary output 0.56±0.16 to 2.02±0.72 ml/kg/h (p“0.05). Group A patients showed a significant increase in urinary output but nonsignificant renal functional deterioration. Conclusion: The renal-protective effect of low-dose dopamine in the setting of CHF and vigorous diuresis is supported by this study.