贫血增加慢性心力衰竭患者死亡率

目的调查贫血在慢性心力衰竭(CHF)住院患者中发生率,以及与CHF患者死亡率的关系。方法收集2007年1月1日至2009年12月31日在北京协和医院心内科住院,年龄≥21岁,临床诊断为心力衰竭,且左心室射血分数(LVEF)≤45%的缺血性(心肌梗死后至少40 d以上)或非缺血性心肌病患者进行回顾性研究,根据是否贫血[血红蛋白<120 g/L(男性)或110 g/L(女性)]分为两组,贫血组和对照组,并进行电话随访。结果共242例患者入选,对197例进行随访,14例(7.1%)失访,经过平均(20±9)个月(2～41个月)随访,共36例(20%)发生全因死亡,包括贫血组13例(34%)和对照组23例(16%)(χ2=6.415,P=0.011)。结论贫血在CHF住院患者中常见,贫血增加CHF死亡率,因此在积极抗心力衰竭治疗同时应高度重视贫血的纠正,以更好地改善CHF患者预后。     

Systolic dysfunction is a predictor of long term mortality in men but not in women with heart failure.

AIMS: To evaluate possible gender differences in clinical profile and outcome of patients hospitalised with heart failure. METHODS AND RESULTS: During 1996 a total of 1065 hospital in-patients had confirmed heart failure, with follow-up data through 2002. Women (58%) were significantly older, had higher prevalence of hypertension and diabetes, and lower prevalence of ischaemic heart disease, chronic pulmonary disease and alcoholism. The proportion of patients with normal left ventricular ejection fraction (LVEF) increased with age, but in all age groups women had normal LVEF more frequently than men. Echocardiography was performed less frequently in females: 62% vs. 71% in men, P<0.01, and this finding was consistent in all age groups. During follow-up (median 19 months) 507 patients died (216 men [48.8%] and 291 women [46.8%]). Gender was not a predictor of survival when LVEF was included in the model (RH Male Gender 0.8, 95% CI 0.6 to 1.1, P=0.2). There was a significant interaction gender-LVEF (P=0.048): survival was similar in both genders with LVEF >0.3 but women with LVEF 0.3 while men with severely depressed LVEF have a worse prognosis.     

Worsening renal function is not associated with response to treatment in acute heart failure

Background

About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality.

Methods

We performed retrospective chart review of patients admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN) values measured both on admission and discharge. Survival analysis was conducted using Cox proportional hazards model and correlation was measured using Spearman's rank correlation test.

Results

358 patients admitted for ADHF were evaluated. WRF was defined as > 20% reduction in eGFR from admission to discharge and response to treatment was assessed by ΔBNP. There was a statistically significant reduction in BNP and increase in BUN during the admission. ΔBNP did not correlate with either ΔGFR or ΔBUN. Patients who developed WRF and those who did not, had a similar reduction in BNP. On univariate survival analysis, ΔBUN, but not ΔeGFR, was associated with 1-year mortality. In multivariate Cox proportional hazards model, BUN at discharge was associated with 1-year mortality (HR: 1.02, p < 0.001), but ΔeGFR and ΔBUN were not associated with the primary endpoint.

Conclusion

During ADHF treatment, ΔBNP was not associated with changes in renal function. Development of WRF during ADHF treatment was not associated with mortality. Our study suggests that development of WRF should not preclude diuresis in ADHF patients in the absence of volume depletion.     

慢性肾脏疾病增加慢性心力衰竭患者死亡率

目的探讨慢性肾脏疾病(CKD)对慢性心力衰竭(CHF)患者死亡率的影响。方法对2007年1月1日至2009年12月31日在北京协和医院心内科住院,年龄≥21岁,临床诊断为心力衰竭,且左心室射血分数(LVEF)≤45%的缺血性(心肌梗死后至少40 d以上)或非缺血性心肌病患者进行回顾性研究,根据肾小球滤过率(eGFR)情况分为两组,一组为eGFR<60 ml.min-1.1.73 m-2(CKD组),另一组为eGFR≥60 ml.min-1.1.73 m-2(对照组),并进行电话随访。结果共筛选242例患者,除外41例不符合入选标准者,对201例进行随访,14例(7%)失访,经过2～41个月[平均(20±9)个月]的随访,共36例(19%)发生全因死亡,包括CKD组21例(30%)和对照组15例(13%)(P=0.003)。结论 CKD增加CHF患者死亡率。合并CKD的CHF患者,积极处理CHF的同时应高度重视CKD处理。     

Neurohormonal activation is associated with increased levels of plasma matrix metalloproteinase-2 in human heart failure.

AIMS: Development of heart failure depends on systemic and molecular abnormalities among which are the activation of neurohormonal systems and the increase of matrix metalloproteinases (MMPs). This study assessed the relationship between catecholamines and active MMPs in vivo in patients with severe congestive heart failure (CHF) and in vitro in human cardiac fibroblasts. METHODS AND RESULTS: Forty patients with CHF due to dilated cardiomyopathy, either idiopathic (n=20) or secondary to ischaemic heart disease (n=20), were compared with 20 healthy subjects. Plasma MMP-2 and MMP-9 activity, but not TIMP-2, were significantly higher in patients than in controls (median MMP-2, 270 vs. 214 ng/mL, P=0.006; MMP-9 16.3 vs. 8.7 ng/mL, P<0.0001). Similarly, noradrenaline, but not adrenaline, was significantly higher in patients (noradrenaline 645 vs. 157 pg/mL, P<0.0001; adrenaline 86.0 vs. 72.6 pg/mL, P=0.68). No difference in any parameter was observed between patient groups. The intra-group correlation between MMP-2 and noradrenaline was significant (r=0.33, P=0.01); indeed, noradrenaline appear to be a predictor of MMP-2. Moreover, this catecholamine increased MMP-2 in human cardiac fibroblasts. CONCLUSIONS: The positive correlation between noradrenaline and MMP-2 in severe CHF patients, together with the in vitro induction of MMP-2 by this catecholamine, suggests a potential biochemical link between noradrenaline and MMP-2.     

Increased interleukin-6 but not tumour necrosis factor-alpha predicts mortality in the population of elderly heart failure patients

BACKGROUND: Increased proinflammatory cytokines have mainly been studied in younger patients with heart failure and are regarded as prognostic markers. However, whether this holds true in elderly patients with heart failure remains uncertain. OBJECTIVES: To determine whether inflammation is equally important in the progression of heart failure in the elderly as has been previously reported in younger patients, and whether cytokine level can predict mortality in this population of elderly heart failure patients. METHODS: The cytokine profile in an elderly patient group with severe heart failure (n=54, mean [+/- SD] age of 80.1+/-5.0 years, New York Heart Association class III or IV) was compared with that of age-matched healthy individuals (n=70). Of the 54 study patients, 46% were hypertensive, 54% had coronary artery disease, 43% had atrial fibrillation and 24% had a previous stroke. One-year mortality was 24%. RESULTS: The results showed increased levels of interleukin-6 (IL-6), tumour necrosis factor-alpha and epidermal growth factor in the heart failure patients compared with those in the control group. Moreover, IL-6, tumour necrosis factor-alpha and vascular endothelial growth factor were significantly increased in patients who died within one year. Further logistic regression analyses showed that IL-6 was the only significant predictor of one-year mortality. In a subgroup of heart failure patients with atrial fibrillation, there were significant cytokine activations, whereas in a subgroup with ischemia or diabetes, cytokines were less activated. CONCLUSIONS: In the present octogenarian group with heart failure, there were significant increases of inflammatory cytokines that were associated with mortality, and IL-6 was the only cytokine to predict one-year mortality. Cytokine activation was more pronounced in the subgroup of patients with heart failure and concomitant atrial fibrillation.     

The use of more than one inotrope in acute heart failure is associated with increased mortality: A multi-centre observational study

Background: Although weakly supported by scientific evidence, according to guidelines the use of inotropes in acute heart failure is indicated in the presence of hypoperfusion refractory to fluid resuscitation. Aims: We examined the characteristics of the inotrope-treated patients, as well as, their in-hospital mortality. The frequency and dosing of inotropic infusions in patients admitted with acute heart failure was assessed in detail. Methods: We included 620 consecutive patients with acute heart failure who were admitted to hospital during three months during spring 2004 in an observational multi-centre study. Results: Of the patients 84 (14%) were treated with inotropes. Dopamine was used in 46 (7%), dobutamine 22 (4%), epinephrine 5 (1%), norepinephrine in 33 (5%), and levosimendan in 44 (7%) cases. The in-hospital mortality was 21% in the inotrope-treated group, and 5% in the control group. The mortality was 7% if only one inotrope was used. The mortality increased in proportion to the number of inotropes used. Lower blood pressure at admission, low ejection fraction, elevated C-reactive protein and cardiac markers correlated with the inotrope administration. Conclusion: Inotrope administration is a marker of increased mortality in patients with acute heart failure. Still, the use of a single inotrope during hospital stay seems rather safe.     

Prolonged exposure to high dietary lipids is not associated with lipotoxicity in heart failure

Previous studies have reported that elevated myocardial lipids in a model of mild-to-moderate heart failure increased mitochondrial function, but did not alter left ventricular function. Whether more prolonged exposure to high dietary lipids would promote a lipotoxic phenotype in mitochondrial and myocardial contractile function has not been determined. We tested the hypothesis that prolonged exposure to high dietary lipids, following coronary artery ligation, would preserve myocardial and mitochondrial function in heart failure. Rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM, HF) or high fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for sixteen weeks. Although high dietary fat was accompanied by myocardial tissue triglyceride accumulation (SHAM 1.47 ± 0.14; SHAM+FAT 2.32 ± 0.14; HF 1.34 ± 0.14; HF+FAT 2.21 ± 0.20 μmol/gww), fractional shortening was increased 16% in SHAM+FAT and 28% in HF+FAT compared to SHAM and HF, respectively. Despite increased medium-chain acyl-CoA dehydrogenase (MCAD) activity in interfibrillar mitochondria (IFM) of both SHAM+FAT and HF+FAT, dietary lipids also were associated with decreased state 3 respiration using palmitoylcarnitine (SHAM 369 ± 14; SHAM+FAT 307 ± 23; HF 354 ± 13; HF+FAT 366 ± 18 nAO min^− 1 mg^− 1) in SHAM+FAT compared to SHAM and HF+FAT. State 3 respiration in IFM also was decreased in SHAM+FAT relative to SHAM using succinate and DHQ. In conclusion, high dietary lipids promoted myocardial lipid accumulation, but were not accompanied by alterations in myocardial contractile function typically associated with lipotoxicity. In normal animals, high dietary fat decreased mitochondrial respiration, but also increased MCAD activity. These studies support the concept that high fat feeding can modify multiple cellular pathways that differentially affect mitochondrial function under normal and pathological conditions.     

Comparable long-term mortality risk associated with individual sulfonylureas in diabetes patients with heart failure

Aims

The aim was to investigate the outcomes of individual sulfonylureas in patients with heart failure (HF).

Methods

All patients hospitalized with HF for the first time in 1997-2006, alive 30 days after discharge, and who received anti-diabetic monotherapy with glimepiride (n = 1097), glibenclamide (glyburide) (n = 1031), glipizide (n = 557), gliclazide (n = 251), or tolbutamide (n = 541) were identified from nationwide registers. Risk of all-cause mortality was assessed by multivariable Cox regression models.

Results

Over the median observational time of 744 (Inter Quartile Range 268-1451) days, 2242 patients (64%) died. The analysis demonstrated similar hazard ratio (HR) for mortality for treatment with glimepiride (1.10 [95% confidence interval 0.92-1.33]), glibenclamide (1.12 [0.93-1.34]), glipizide (1.14 [0.93-1.38]), tolbutamide (1.04 [0.85-1.26]), and gliclazide (reference). Grouped according to pancreatic specificity, i.e., with tolbutamide, glipizide, and gliclazide as specific, and glibenclamide, and glimepiride as non-specific agents, no differential prognosis was found between the two groups (HR 1.04 [0.96-1.14], for non-specific, compared to pancreas specific agents). The prognosis was not dependent on prior acute myocardial infarction or ischemic heart disease (p for interactions >0.3).

Conclusions

In current clinical practice, it is unlikely that there are considerable differences in risk of mortality associated with individual sulfonylureas in patients with heart failure.     

AXL receptor tyrosine kinase is increased in patients with heart failure

Background

AXL is a membrane receptor tyrosine kinase highly expressed in the heart and has a conspicuous role in cardiovascular physiology. The role of AXL in heart failure (HF) has not been previously addressed.

Methods and results

AXL protein was enhanced 6-fold in myocardial biopsies of end-stage HF patients undergoing heart transplantation compared to controls from heart donors (P < 0.0001). Next, we performed a transversal study of patients with chronic HF (n = 192) and a group of controls with no HF (n = 67). sAXL and BNP circulating levels were quantified and clinical and demographic data were collected.sAXL levels in serum were higher in HF (86.3 ± 2.0 ng/mL) than in controls (67.8 ± 2.0 ng/mL; P < 0.0001). Also, sAXL correlated with several parameters associated with worse prognosis in HF. Linear regression analysis indicated that serum creatinine, systolic blood pressure and atrial fibrillation, but not BNP levels, were predictive of sAXL levels. Cox regression analysis indicated that high sAXL values at enrollment time were related to the major HF events (all-cause mortality, heart transplantation and HF hospitalizations) at one year follow-up (P < 0.001), adding predictive value to high BNP levels.

Conclusions

Myocardial expression and serum concentration of AXL is elevated in HF patients compared to controls. Furthermore, peripheral sAXL correlates with parameters associated with the progression of HF and with HF events at short term follow-up. All together these results suggest that sAXL could belong to a new molecular pathway involved in myocardial damage in HF, independent from BNP.     

An integrated multiple marker modality is superior to NT-proBNP alone in prognostic prediction in all-cause mortality in a prospective cohort of elderly heart failure patients

BackgroundIdentifying the individual mortality risk for elderly heart failure (HF) patients is challenging because of heterogeneity, comorbidity and higher age. To overcome this, an integrated multiple marker modality has been proposed for better prognostic prediction than a single variable, this has not been evaluated.AimThe aim of this study is to identify whether a multiple marker modality is better than N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone for all-cause mortality in elderly HF patients.MethodsA prospective cohort of 361 patients (65 ± 15 years) referred for echocardiography because of suspected HF was studied, among them, 179 had HF (71 ± 13). In this cohort blood sampling, electrocardiogram and clinical examinations were performed within approximately 24 hours after the echocardiography. To assess prognostic value of multiple marker modality for all-cause mortality, patients were followed up for 24 ± 7 months.ResultsIn the three multivariate analyses, NT-proBNP, cystatin C, red blood cell distribution width (RDW), midregional pro-atrial natriuretic peptide (MR-proANP), pulmonary artery pressure, estimated glomerular filtration rate (eGFR) less than 60 mL/min, anemia, diuretics and sinus rhythm are prognostic predictors of all-cause mortality in elderly HF patients. When analyzing all these variables in one multivariate analysis, only NT-proBNP, eGFR less than 60 mL/min, anemia and diuretics are prognostic predictors of all-cause mortality in elderly HF patients. Two different multiple marker models incorporating NT-proBNP, clinical and laboratory variables were created. The sensitivity and specificity of the two different multiple marker modalities are higher than for NT-proBNP alone. The risk score based on multivariate analysis Wald X² values is preferred considering its simplicity and feasibility in daily clinical practice.ConclusionA multiple marker modality was proven to improve prognostic prediction in elderly HF patients compared to NT-proBNP alone.     

Myocardial contractile dysfunction associated with increased 3-month and 1-year mortality in hospitalized patients with heart failure and preserved ejection fraction

Background

There is a clinical need for a contractility index that reflects myocardial contractile dysfunction even when ejection fraction (EF) is preserved. We used novel relative load-independent global and regional contractility indices to compare left ventricular (LV) contractile function in three groups: heart failure (HF) with preserved ejection fraction (HFPEF), HF with reduced ejection fraction (HFREF) and normal subjects. Also, we determined the associations of these parameters with 3-month and 1-year mortality in HFPEF patients.

Methods

199 HFPEF patients [median age (IQR): 75 (67–80) years] and 327 HFREF patients [69 (59–76) years] were recruited following hospitalization for HF; 22 normal control subjects [65 (54–71) years] were recruited for comparison. All patients underwent standard two-dimensional Doppler and tissue Doppler echocardiography to characterize LV dimension, structure, global and regional contractile function.

Results

The median (IQR) global LV contractility index, dσ*/dt_max was 4.30 s^− 1 (3.51–4.57 s^− 1) in normal subjects but reduced in HFPEF [2.57 (2.08–3.64)] and HFREF patients [1.77 (1.34–2.30)]. Similarly, median (IQR) regional LV contractility index was 99% (88–104%) in normal subjects and reduced in HFPEF [81% (66–96%)] and HFREF [56% (41–71%)] patients. Multi-variable logistic regression analysis on HFPEF identified sc-mFS < 76% as the most consistent predictor of both 3-month (OR = 7.15, p < 0.05) and 1-year (OR = 2.57, p < 0.05) mortality after adjusting for medical conditions and other echocardiographic measurements.

Conclusion

Patients with HFPEF exhibited decreased LV global and regional contractility. This population-based study demonstrated that depressed regional contractility index was associated with higher 3-month and 1-year mortality in HFPEF patients.