Home-based intervention in congestive heart failure: long-term implications on readmission and survival

BACKGROUND: It is not known to what extent initially observed benefits of postdischarge programs of care for patients with chronic congestive heart failure (CHF) in respect to event-free survival, readmissions, and healthcare costs persist in the long term. Methods and Results- We prospectively studied the long-term effects of a multidisciplinary home-based intervention (HBI) in a cohort of CHF patients randomly allocated to either to HBI (n=149) or usual care (n=148). During a median of 4.2 years of follow-up, there were significantly fewer primary end points (unplanned readmission or death) in the HBI versus usual care group: a mean of 0.21 versus 0.37 primary events per patient per month (P<0.01). Median event-free survival was more prolonged in the HBI than usual care group (7 versus 3 months; P<0.01). Fewer HBI patients died (56% versus 65%; P=0.06) and had more prolonged survival (a median of 40 versus 22 months; P<0.05) compared with usual care. Assignment to HBI was both an independent predictor of event-free survival (RR 0.70; P<0.01) and survival alone (RR 0.72; P<0.05). Overall, HBI patients had 78 fewer unplanned readmissions compared with usual care (0.17 versus 0.29 readmissions per patient per month; P<0.05). The median cost of these readmissions was $A325 versus $A660/month per HBI and usual care patient (P<0.01). CONCLUSIONS: The beneficial effects of HBI in reducing frequency of unplanned readmissions in CHF patients persist in the long term and are associated with prolongation of survival.     

Matrix metalloproteinase-1 and its inhibitor, TIMP-1, in systolic heart failure: relation to functional data and prognosis

BACKGROUND: Structural remodelling of left ventricle is a common feature in the progression of congestive heart failure (CHF). Matrix metalloproteinases (MMPs) have been directly implicated as they degrade extracellular proteins. To test the hypothesis that MMP-and its inhibitor, tissue type inhibitor of matrix metalloproteinases (TIMP-1), could be related to functional status and prognosis in CHF, we examined the relationship of MMP-1 and TIMP-1 to peak oxygen consumption (VO2) and peak minute ventilation/carbon dioxide production relationship (VE/VCO2), and assessed their prognostic value. METHODS: We studied 50 patients with CHF, who were compared with 53 controls echocardiogram and ergoespirometry were performed, and serum levels of MMP-1 and TIMP-1 were assayed by ELISA. Patients were followed up for 17.5+/-8.9 months, and total mortality, readmissions for heart failure and cardiac transplantation were recorded. RESULTS: Patients with CHF had lower levels of MMP-1 (P=0.027), and higher levels of TIMP-1 and TIMP-1/MMP-1 ratio (both P<0.01) than controls. TIMP-1 levels and the TIMP-1/MMP-1 ratio correlated negatively with peak VO2 (Spearman, r:-0.51; P=0.001 and r: -0.42; P=0.030, respectively). During the follow-up period, 23 patients (47.9%) suffered endpoints--these patients had higher baseline peak VE/VCO2 (P=0.001), TIMP-1 (P=0.004), and TIMP-1/MMP-1 ratio values (P=0.002), whereas MMP-1 levels were lower (P=0.027). On multivariate analysis, VE/VCO2, MMP-1 levels and age were the only variables independently related to prognosis (all P<0.05). CONCLUSION: Poor functional capacity in CHF can be related to abnormal extracellular matrix turnover. Patients who suffered endpoints had more abnormal indices of matrix turnover, where MMP-1 levels showed independent prognostic value.     

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation

AIM: The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). METHODS AND RESULTS: Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. CONCLUSION: A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.     

Baseline and serial neurohormones in patients with congestive heart failure treated with and without bucindolol: results of the neurohumoral substudy of the Beta-Blocker Evaluation of Survival Study (BEST)

BackgroundSerial neurohormones may serve as markers of efficacy of congestive heart failure (CHF) therapy. We measured serial plasma big-endothelin (Big-ET), ET-1, N-terminal atrial natriuretic peptide, and brain natriuretic peptide (BNP) in 206 patients randomized to bucindolol or placebo in Beta-Blocker Evaluation of Survival Trial (BEST).Methods and ResultsNeurohormones were measured at baseline and 3 and 12 months. At baseline, BNP and Big-ET levels were greater in New York Heart Association (NYHA) Class IV than in Class III patients (median 122 pg/mL versus 447 pg/mL, P = .001; and 20.0 pg/mL versus 9.9 pg/mL, P = .003), and in patients with left ventricular ejection fraction (LVEF) ≤20% compared with LVEF >20% (median 211 pg/mL versus 99.1 pg/mL; and 12.9 pg/mL versus 8.0 pg/mL, both P = .003). Big-ET and BNP were the strongest predictors of the composite end point of CHF hospitalization or death. LVEF at 12 months correlated inversely with 12-month BNP levels (r = −0.41, P = .0001). Bucindolol had no effect on neurohormones except that bucindolol treated patients had lower Big-ET levels at 3 months than patients receiving placebo (median 9.1 pg/mL versus 10.9 pg/mL, P = .05). A decline in ET-1 was associated with increased risk of the composite endpoint.ConclusionsLack of effect of bucindolol on natriuretic peptide levels appears consistent with its overall lack of efficacy in BEST.     

Effects of a nurse-led, clinic and home-based intervention on recurrent hospital use in chronic heart failure

BACKGROUND: Few studies have examined the potential benefits of specialist nurse-led programs of care involving home and clinic-based follow-up to optimise the post-discharge management of chronic heart failure (CHF). OBJECTIVE: To determine the effectiveness of a hybrid program of clinic plus home-based intervention (C+HBI) in reducing recurrent hospitalisation in CHF patients. METHODS: CHF patients with evidence of left ventricular systolic dysfunction admitted to two hospitals in Northern England were assigned to a C+HBI lasting 6 months post-discharge (n=58) or to usual, post-discharge care (UC: n=48) via a cluster randomization protocol. The co-primary endpoints were death or unplanned readmission (event-free survival) and rate of recurrent, all-cause readmission within 6 months of hospital discharge. RESULTS: During study follow-up, more UC patients had an unplanned readmission for any cause (44% vs. 22%: P=0.019, OR 1.95 95% CI 1.10-3.48) whilst 7 (15%) versus 5 (9%) UC and C+HBI patients, respectively, died (P=NS). Overall, 15 (26%) C+HBI versus 21 (44%) UC patients experienced a primary endpoint. C+HBI was associated with a non-significant, 45% reduction in the risk of death or readmission when adjusting for potential confounders (RR 0.55, 95% CI 0.28-1.08: P=0.08). Overall, C+HBI patients accumulated significantly fewer unplanned readmissions (15 vs. 45: P<0.01) and days of recurrent hospital stay (108 vs. 459 days: P<0.01). C+HBI was also associated with greater uptake of beta-blocker therapy (56% vs. 18%: P<0.001) and adherence to Na restrictions (P<0.05) during 6-month follow-up. CONCLUSION: This is the first randomised study to specifically examine the impact of a hybrid, C+HBI program of care on hospital utilisation in patients with CHF. Its beneficial effects on recurrent readmission and event-free survival are consistent with those applying either a home or clinic-based approach.     

Relation of serum levels of mast cell tryptase of left ventricular systolic function, left ventricular volume or congestive heart failure

BACKGROUND: Activated mast cells (MC) present in the myocardium of patients with cardiomyopathy may contribute to left ventricular dilatation and systolic dysfunction. We sought to determine whether peripheral levels of tryptase, an MC-specific protease, are related to indices of left ventricular size and function, as well as congestive heart failure (CHF) or coronary artery disease (CAD). METHODS AND RESULTS: Serum tryptase was measured in 85 patients undergoing cardiac catheterization with left ventriculography and coronary angiography and examined in relation to left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), congestive heart failure (CHF), and angiographically evident CAD. Systemic tryptase levels were lower in patients with increased (>90 mL) LVEDV (6.2 [5.3-8.0] mcg/L versus 8.3 [6.6-10.3] mcg/L, P=.01) and in patients with CHF (6.2 [3.6-7.3] mcg/L versus 8 [6.2-10] mcg/L, P=.02) and tended to be lower in patients with depressed (<55%) LVEF (6.8 [5.2-9] mcg/L versus 8 [6.3-9.9] mcg/L, P=NS). Linear regression did not show a significant relationship between tryptase levels with either LVEF or LVEDV. Finally, tryptase levels were consistently elevated in relation to the presence of CAD. CONCLUSION: Despite increased numbers of MC in the myocardium of patients with cardiomyopathy, systemic levels of MC tryptase appear to be lower in relation to LV systolic dysfunction, LV dilatation, or clinical CHF. In contrast, the presence of angiographically significant CAD is associated with elevated systemic tryptase levels.     

Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction <or=30%

AIMS: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF 相似文献   

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes

AIMS: Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. METHODS AND RESULTS: Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). CONCLUSION: In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.     

Comparison of effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention in patients with ischemic cardiomyopathy

The REvascularization in Ischemic HEart Failure Trial (REHEAT) is a nonrandomized, case-controlled, prospective study assessing the hypothesis that surgical and percutaneous revascularizations in patients with ischemic cardiomyopathy are associated with comparable improvement in left ventricular ejection fraction (LVEF) and functional status 12 months after myocardial revascularization. The study population consisted of 141 patients with LVEFs of <40% and angiographically confirmed coronary artery disease. The primary end point was improvement in LVEF 12 months after intervention. Secondary end points were in-hospital major adverse events, length of hospitalization, exercise tolerance of treadmill stress testing after 12 months, 1-year survival, 1-year event-free survival, angina, and heart failure severity after 12 months. The case-controlled study included 55 patients who underwent percutaneous coronary intervention (PCI) and 54 who underwent coronary artery bypass grafting (CABG). The incidence of 30-day major adverse events was higher in the CABG group (40.7% vs 9%, p = 0.0003), whereas duration of hospital stay was shorter in the PCI group (6.8 +/- 3.6 vs 9.2 +/- 2.1 days, p = 0.00001). Increase in LVEF was comparable after PCI and CABG (6.0 +/- 7.2% vs 4.4 +/- 9.0% p = 0.12). Long-term functional status based on treadmill stress testing was better after PCI (Student's t test, p = 0.0003) but, according to Canadian Cardiovascular Society and New York Heart Association classifications, was similar in the 2 treatment arms (Wilcoxon test, p <0.01). Long-term survival was significantly better for patients after PCI (Wilcoxon test, p <0.01); however, major adverse event-free survival was better after CABG (Cox-Mantel test, p = 0.0013). In conclusion, PCI and CABG are associated with comparable improvements in LVEF in patients with ischemic cardiomyopathy. PCI offers a better 1-year survival rate than CABG, but the incidence of repeat revascularization is lower with CABG.     

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.     

Determinants of physical activity after hospitalization for coronary artery disease: the Tracking Exercise After Cardiac Hospitalization (TEACH) Study.

BACKGROUND: Little is known about physical activity levels in patients with coronary artery disease (CAD) who are not engaged in cardiac rehabilitation. We explored the trajectory of physical activity after hospitalization for CAD, and examined the effects of demographic, medical, and activity-related factors on the trajectory. DESIGN: A prospective cohort study. METHODS: A total of 782 patients were recruited during CAD-related hospitalization. Leisure-time activity energy expenditure (AEE) was measured 2, 6 and 12 months later. Sex, age, education, reason for hospitalization, congestive heart failure (CHF), diabetes, and physical activity before hospitalization were assessed at recruitment. Participation in cardiac rehabilitation was measured at follow-up. RESULTS: AEE was 1948+/-1450, 1676+/-1290, and 1637+/-1486 kcal/week at 2, 6 and 12 months, respectively. There was a negative effect of time from 2 months post-hospitalization on physical activity (P<0.001). Interactions were found between age and time (P=0.012) and education and time (P=0.001). Main effects were noted for sex (men more active than women; P<0.001), CHF (those without CHF more active; P<0.01), diabetes (those without diabetes more active; P<0.05), and previous level of physical activity (those active before hospitalization more active after; P<0.001). Coronary artery bypass graft patients were more active than percutaneous coronary intervention (PCI) patients (P=0.033). CONCLUSIONS: Physical activity levels declined from 2 months after hospitalization. Specific subgroups (e.g. less educated, younger) were at greater risk of decline and other subgroups (e.g. women, and PCI, CHF, and diabetic patients) demonstrated lower physical activity. These groups need tailored interventions.     

Intrathoracic impedance changes reflect reverse left ventricular remodeling in response to cardiac resynchronization therapy in chronic heart failure patients

Intrathoracic impedance monitoring has been reported to be useful for prediction of worsening chronic heart failure (CHF). However, it has not revealed the relation between changes in intrathoracic impedance and improvement of cardiac function in CHF patients with cardiac resynchronization therapy (CRT) implantation. Therefore, we investigated whether intrathoracic impedance change reflects reverse left ventricular (LV) remodeling in response to CRT in patients with CHF. The study subjects consisted of 29 CHF patients (23 males, mean age 64 ± 12 years) with CRT-defibrillator (CRT-D) implantation. The patients were divided into two groups based on whether the Opti-vol Fluid Index^? reached over 60 ohms (group A, n = 7) or not (group B, n = 22) within 6 months of observation after CRT-D implantation. Levels of plasma B-type natriuretic peptide (BNP) were measured, and LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were evaluated before and 6 months after CRT-D implantation. In group B, BNP (556 ± 88 pg/mL versus 330 ± 70 pg/mL, P < 0.05), LVEDV (177 ± 18 mL versus 149 ± 14 mL, P < 0.01), and LVESV (128 ± 14 mL versus 100 ± 12 mL, P < 0.01) were significantly decreased 6 months after CRT-D implantation. LVEF (28 ± 2% versus 35 ± 2%, P < 0.01) was significantly increased after CRT-D implantation. On the other hand, no significant changes were detected in any parameters in group A. These data showed intrathoracic impedance changes reflected reverse LV remodeling in response to CRT in patients with CHF. Therefore, the monitoring of changes in intrathoracic impedance is useful for predicting CRT responders in patients with 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.     

Health-Related Quality of Life Is a Mediator of the Relationship Between Medication Adherence and Cardiac Event-Free Survival in Patients with Heart Failure

BackgroundHealth-related quality of life (HRQOL) is an important patient-reported outcome that is related to medication adherence, hospitalization and death. The nature of the relationships among medication adherence, HRQOL, and hospitalization and death is unknown. We sought to determine the relationships among medication adherence, HRQOL, and cardiac event-free survival in patients with heart failure.Methods and ResultsWe enrolled 218 patients with heart failure. Patients’ medication adherence was measured objectively using the Medication Event Monitoring System. HRQOL was assessed using the Minnesota Living with Heart Failure Questionnaire. Patients were followed for up to 3.5 years to collect hospitalization and mortality data. Mediation analysis was used to determine the nature of the relationships among the variables. Patients with better medication adherence had better HRQOL (P = .014). Medication adherence and HRQOL were associated with cardiac event-free survival (both P < .05). Patients with medication nonadherence were 1.86 times more likely to experience a cardiac event than those with better medication adherence (P = .038). Medication adherence was not associated with cardiac event-free survival after entering HRQOL in the model (P = .118), indicating mediation by HRQOL of the relationship between medication adherence and cardiac event-free survival.ConclusionsHRQOL mediated the relationship between medication adherence and cardiac event-free survival. It is important to assess medication adherence and HRQOL regularly and develop interventions to improve medication adherence and HRQOL to decrease hospitalization and mortality in patients with heart failure.     

Plasma matrix metalloproteinase and inhibitor profiles in patients with heart failure

BACKGROUND: Changes in myocardial matrix metalloproteinases (MMPs) and the inhibitors of MMPs (TIMPs) have been demonstrated in congestive heart failure (CHF). The first objective of this study was to measure plasma profiles of MMPs and TIMPs in CHF patients (n = 24; 62 +/- 3 years; left ventricular ejection fraction [LVEF] = 24 +/- 2%) and age-matched nonfailing patients (n = 48; 63 +/- 2 years; LVEF >/= 55%). Cytokines such as tumor necrosis factor (TNF)-alpha can induce MMP expression in vitro. The second objective of this study was to determine the relationship between soluble TNF-alpha receptors (TNFR1; TNFR2) and MMP plasma profiles. METHODS AND RESULTS: Plasma levels of MMP-2, MMP-9, MMP-8, TIMP-1, TIMP-2, TNF-alpha, TNFR1, and TNFR2 were measured by enzyme-linked immunosorbent assay kits. Plasma MMP-9 levels were increased in CHF patients (25 +/- 6 versus 72 +/- 15 ng/mL, P <.05). Interestingly, plasma levels of MMP-8 were decreased in CHF patients (16 +/- 2 versus 9 +/- 2 ng/mL, P <.05). The MMP-9/TIMP-1 ratio was increased by 3-fold, whereas the MMP-9/TIMP-2 ratio was increased by 16-fold in CHF patients (both P <.05). With a 48-week follow-up in CHF patients, an absolute reduction in plasma TNFR1 from baseline was accompanied by reduced MMP-9 levels (-30 +/- 16 ng/mL; P =.058), whereas stable or increased plasma TNFR1 resulted in persistently elevated MMP-9 levels. CONCLUSIONS: The unique findings of this study were 2-fold. First, a discordant change in plasma MMP and TIMP levels occurred in CHF patients. Second, changes in cytokine activity were related to changes in plasma MMP levels. These changes in MMP/TIMP levels likely reflect the progression and/or acceleration of the LV remodeling process in CHF. Thus serial measurements of plasma MMP/TIMP levels may hold diagnostic/prognostic significance in CHF patients.     

内源性促红细胞生成素对慢性心力衰竭患者预后的影响

目的了解内源性促红细胞生成素(EPO)对慢性心力衰竭(CHF)患者预后的判定价值。方法选择住院的CHF患者115例,以患者是否存活分为死亡组55例,存活组60例。另选同期住院的年龄、性别相匹配的非CHF患者67例为对照组,以便建立logEPO和血红蛋白(Hb)的回归方程。对CHF患者进行全因死亡和因心力衰竭再次入院的随访观察,测定血EPO,并进行分析。结果与存活组比较,死亡组高龄患者多、心功能(NYHA)Ⅱ级比例低、Hb降低和B型钠尿肽(BNP)水平升高(P<0.01)。Kaplan-Meier生存曲线显示,贫血的CHF患者病死率增高(RR=2.50,95%CI:1.38～4.54,P=0.002)。ROC曲线评估EPO和BNP预测CHF患者死亡的最佳界值分别为44.4 U/L和752 ug/L(P=0.036,=0.000)。年龄、Hb、BNP和NYHA对CHF患者全因死亡有独立预测价值;而男性、BNP和Hb水平对因心力衰竭再次入院有独立预测价值。贫血的CHF患者EPO是独立于Hb的全因死亡的强预测指标(RR=2.86,95%CI:1.18～6.94,P=0.020)。结论贫血是CHF患者不良预后的独立预测因素。EPO是贫血CHF患者全因死亡的独立预测指标。     

Survival and hospitalization in heart failure patients with or without diabetes treated with beta-blockers

BACKGROUND: Physicians are still concerned about prescribing beta-blockers in diabetic patients with heart failure. METHODS: In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start beta-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on beta-blockers, 28% started treatment at the enrollment visit, and 47% were not started on beta-blockers. RESULTS: The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with beta-blockers, diabetic patients treated with beta-blockers, nondiabetic patients not treated with beta-blockers, nondiabetic patients treated with beta-blockers) showed that patients treated with beta-blockers had a higher event-free probability than patients not treated with beta-blockers regardless the presence of diabetes (P <.0001). CONCLUSIONS: On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from beta-blockers even if at a lower degree. Thus, there are no justifications to avoid beta-blockers in heart failure patients in the presence of diabetes.     

Levosimendan and prostaglandin E1 for uptitration of beta-blockade in patients with refractory, advanced chronic heart failure

BACKGROUND: In advanced chronic heart failure (CHF) 20% of patients do not tolerate beta-blockers and 50% do not reach target doses. AIM: To test whether levosimendan or prostaglandin E1 (PGE1) can facilitate uptitration of beta-blockers in advanced CHF. METHODS AND RESULTS: Seventy-five advanced CHF patients (LVEF<35%, NYHA class IIIb or IV) intolerant to beta-blocker uptitration to target doses (10 mg bisoprolol/day) were randomised to a monthly 24 h infusion with levosimendan (n=39) or a chronic infusion with PGE1 (n=36) for 3 months. Bisoprolol was uptitrated following predefined criteria. At 12 weeks, bisoprolol dose increased from 4 mg to 10 mg in both groups. Heart failure worsening occurred in 29 levosimendan patients (74%) versus 16 PGE1 patients (44%, p=0.008). Uptitration was impossible in 9 levosimendan patients (23%) versus 2 PGE1 patients (6%, p=0.03). The combined endpoint of death or urgent heart transplantation or implantation of a ventricular assist device was reached by 12 levosimendan patients (31%) versus 4 PGE1 patients (11%, p=0.04). After 1 year, LVEF increased from 23+/-7% to 28+/-11% (p=0.0004), and BNP decreased from 994+/-806 to 659+/-564 pg/ml (p=0.03). CONCLUSION: Levosimendan and PGE1 facilitate uptitration of beta-blockers in previously intolerant CHF patients. PGE1 treatment allowed uptitration in more patients and resulted in a better clinical outcome compared to levosimendan. This approach increased LVEF and decreased BNP after 1 year.     

Congestive heart failure is associated with the rate of bone loss

AIMS: To characterize relationships between mineral homeostasis, bone turnover, bone mass, and congestive heart failure (CHF), we evaluated 75 women with mild to moderate CHF. METHODS AND RESULTS: We examined the association in annual rate of change in spinal bone mineral density (BMD) with polymorphism of the vitamin D receptor (VDR) gene. Compared with the control group, the CHF group had reduced left ventricular ejection fraction (LVEF: 68.2 +/- 7.5% vs. 60.2 +/- 12.9%; P = 0.0249), human atrial natriuretic peptide (hANP) was elevated (hANP: 10.7 +/- 4.7 pmol L-1 vs. 25.8 +/- 24.2 pmol L-1; P = 0.001) and had lower peak VO2 (22.3 +/- 7.5 mL kg-1 min-1 vs. 15.8 +/- 7.4 mL kg-1 min-1; P = 0.0429). The CHF patients with the VDR FF genotype had a significantly high annual rate of decrease in BMD. In the CHF patients with the VDR FF genotype, urinary calcium excretion (FECa) was elevated (1.40 +/- 0.91% vs. 2.39 +/- 1.40%; P = 0.028), and serum bone-type alkaline phosphatase (B-ALP) was reduced (62.6 +/- 13.7 IU L-1 vs. 47.0 +/- 18.6 IU L-1; P = 0.0123). Also, FECa was correlated positively with furosemide dose (R = 0.881; P = 0.0087) and hANP concentrations (R = 0.635; P = 0.0147) and negatively with DeltaBMD (R = 0.72; P = 0.044) in the CHF patients with the VDR FF genotype. CONCLUSION: The CHF patients with the VDR FF genotype have higher rates of bone loss. These patients may need to increase their calcium intake and BMD may need to be followed more carefully over time.     

The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.

AIMS: Chronic heart failure (CHF) is a common and leading cause of death in industrialized countries. The potential benefits of micronutrient supplementation in CHF are extensive. Therefore, we examined the influence of long-term multiple micronutrient supplementation on left ventricular (LV) function, levels of pro-inflammatory cytokines, and quality-of-life (QoL) in elderly patients with CHF. METHODS AND RESULTS: Thirty CHF patients [age 75.4 (0.7), mean (SEM), LV ejection fraction (LVEF) < or =35%] were randomized to receive capsules containing a combination of high-dose micronutrients (calcium, magnesium, zinc, copper, selenium, vitamin A, thiamine, riboflavin, vitamin B(6), folate, vitamin B(12), vitamin C, vitamin E, vitamin D, and Coenzyme Q10) or placebo for 9 months in a double-blind fashion. All subjects were on stable optimal medical therapy for at least 3 months before enrolment. At randomization and at study end, tumour necrosis factor-alpha and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute walk test and QoL were assessed. Cardiac magnetic resonance scanning was performed to evaluate cardiac dimensions and LVEF. Two patients died during follow-up. The remaining patients (14 randomized to placebo and 14 to micronutrients) were well matched for LV function, symptoms, and exercise capacity. At the end of the follow-up period, LV volumes were reduced in the intervention group with no change in the placebo group [-13.1 (17.1)% vs. +3.8 (10.0)%; P<0.05]. LVEF increased by 5.3+/-1.4% in the intervention group and was unchanged in the placebo group (P<0.05). Patients taking micronutrients also had a significant improvement in QoL score between enrolment and study end [+9.5 (1.6)%; P<0.05], whereas those taking placebo had a slight deterioration [-1.1 (0.8)%; P=0.12]. Six-minute walk test and inflammatory cytokine levels remained unchanged in both groups. CONCLUSION: Long-term multiple micronutrient supplementation can improve LV volumes and LVEF and QoL scores in elderly patients with heart failure due to LV systolic dysfunction.