Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: Results from a pilot study in elderly chronic heart failure patients

Background

An accurate prognosis prediction represents a key element in chronic heart failure (CHF) management. Seattle Heart Failure Model (SHFM) prognostic power, a validated risk score for predicting mortality in CHF, is improved by adding B-type natriuretic peptide (BNP). We evaluated in a prospective study the incremental value of several biomarkers, linked to different biological domains, on death risk prediction of BNP-added SHFM.

Methods

Troponin I (cTnI), norepinephrine, plasma renin activity, aldosterone, high sensitivity-C reactive protein (hs-CRP), tumor necrosis factor-α ?(TNF-α), interleukin 6 (IL-6), interleukin 2 soluble receptor, leptin, prealbumin, free malondialdehyde, and 15-F_2t-isoprostane were measured in plasma from 142 consecutive ambulatory, non-diabetic stable CHF (mean NYHA-class 2.6) patients (mean age 75 ± 8 years). Calibration, discrimination, and risk reclassification of BNP-added SHFM were evaluated after individual biomarker addition.

Results

Individual addition of biomarkers to BNP-added SHFM did not improve death prediction, except for prealbumin (HR 0.49 CI: (0.31–0.76) p = 0.002) and cTnI (HR 2.03 CI: (1.20–3.45) p = 0.009). In fact, with respect to BNP-added SHFM (Harrell's C-statistic 0.702), prealbumin emerged as a stronger predictor of death showing the highest improvement in model discrimination (+ 0.021, p = 0.033) and only a trend was observed for cTn I (+ 0.023, p = 0.063). These biomarkers showed also the best reclassification statistic (Integrated Discrimination Improvement—IDI) at 1-year (IDI: cTnI, p = 0.002; prealbumin, p = 0.020), 2-years (IDI: cTnI, p = 0.018; prealbumin: p = 0.006) and 3-years of follow-up (IDI: cTnI p = 0.024; prealbumin: p = 0.012).

Conclusions

Individual addition of prealbumin allows a more accurate prediction of mortality of BNP enriched SHFM in ambulatory elderly CHF suggesting its potential use in identifying those at high-risk that need nutritional surveillance.     

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.     

Acute heart failure in the emergency department: short and long-term outcomes of elderly patients with heart failure

AIMS: Previous epidemiologic studies of acute heart failure (AHF) have involved patients admitted to hospital and fail to account for that unknown proportion discharged directly from the emergency department (ED). We examined discharge rates, and whether outcomes, including mortality, differed based on admission status in AHF. METHODS AND RESULTS: This population-based cohort included all patients > or =65 years presenting to an Alberta ED with HF (ICD9-CM 428.x; 1998 to 2001). Patients were either not admitted (Not-ADM) or directly admitted to hospital (ADM) and followed for one-year. Of 10,415 AHF patients evaluated in the ED, 35% were Not-ADM whereas 65% were ADM. Thirty days after ED presentation the rates of death, re-ED or initial/re-hospitalisation were 3.3%, 44% and 19% for Not-ADM, and 10.9%, 33% and 21% for the ADM patients, respectively (all p<0.0001). At one-year, the rates of death, re-ED or initial/re-hospitalisation were 20%, 82% and 58% for Not-ADM, and 34%, 72% and 60% for ADM, respectively (all p<0.0001). CONCLUSIONS: One third of AHF patients were not immediately admitted after an ED visit but most present again to the ED, two-thirds were hospitalised and 20% died within the first year. Our findings provide new impetus to undertake risk assessment and treatment strategies in the ED for AHF.     

Influence of left bundle branch block on long-term mortality in a population with heart failure.

BACKGROUND: The purpose of this study was to assess the independent contribution of left bundle branch block (LBBB) on long-term mortality in a large cohort with symptomatic heart failure (HF) requiring hospitalization. METHODS AND RESULTS: We studied a prospective cohort of 21 685 cases of symptomatic HF requiring hospitalization in the Register of Information and Knowledge about Swedish Heart Intensive care Admissions in 1995-2003. Long-term mortality was evaluated by Logistic regression analysis, adjusted for multiple covariates that could influence long-term prognosis. LBBB was present in 20% (4395 of 21 685) of HF admissions. Patients with LBBB had a higher prevalence of cardiac comorbid conditions than patients with no LBBB. 1-, 5-, and 10-year mortality was 31.5 vs. 28.4%, 69.3 vs. 61.3%, and 90.1 vs. 84.7% for HF patients with and without respectively LBBB. When adjusting for comorbidity, LBBB was associated with increased 5-year mortality (OR, 1.21; 95% CI, 1.10-1.35; P < 0.001). When left ventricular ejection fraction was included in the analysis LBBB had no longer any independent influence on 5-mortality (OR, 0.99; 95% CI, 0.62-1.56; P = 0.953). CONCLUSION: LBBB occurs in 1/5 in HF patients requiring hospitalization and is associated with a very high mortality. However, the high long-term mortality appears to be caused by cardiac comorbidities and myocardial dysfunction rather than the LBBB per se.     

重症心力衰竭患者的生存率及其影响因素

目的 :评价重症心力衰竭患者的死亡率及其影响因素。方法 :入选 1997年 1月至 2 0 0 0年12月我院心内科住院的NYHAⅢ～Ⅳ级心力衰竭患者 ,记录心力衰竭发生时间、年龄、性别等人口学因素、病因、超声心动图测定的左心室射血分数 (LVEF)、实验室检查结果 ,随访至 2 0 0 3年 9月 ,观察终点为全因死亡 ,用寿命表法统计 1年、3年和 5年死亡率 ,Kaplan- Meier法绘制心力衰竭的生存曲线 ,用单因素和多因素Cox回归模型分析以上临床指标对预后的影响。结果 :共 15 0例 ,其中男性 10 0例 ,女性 5 0例 ,平均年龄 (6 1. 88± 12 . 4 )岁 ,在平均 6 2个月的随访中共死亡 6 2例 ,自心力衰竭发生起 1年、3年和 5年累积死亡率分别为 2 0 . 37%、33. 6 0 %和 4 7. 83% ,生存时间的中位数为 4 7个月。多因素Cox回归显示 ,老年患者预后较差 [相对危险度RR 2. 0 5 8,95 %可信区间 (CI) 1 .0 96～ 3 96. 7,P =0 .0 2 5 ],入院时收缩压较高的患者 (RR 0 . 983,95 %CI 0 . 96 9～ 0 .997,P =0. 0 19)和LVEF≥ 4 0 %的患者预后较好 (RR 0 . 4 13,95 %CI0 . 2 2 1～ 0 . 772 ,P =0 . 0 0 6 )。结论 :重症心力衰竭患者的长期预后较差 ,年龄、入院收缩压和LVEF是影响预后的独立预测因素。     

Fragility is a key determinant of survival in heart failure patients

Background

Heart failure (HF) is a chronic condition with poor prognosis, and has a high prevalence among older adults. Due to older age, fragility is often present among HF patients. However, even young HF patients show a high degree of fragility. The effect of fragility on long-term prognosis in HF patients, irrespective of age, remains unexplored. The aim of this study was to assess the influence of fragility on long-term prognosis in outpatients with HF.

Methods and results

At least one abnormal evaluation among four standardized geriatric scales was used to identify fragility. Predefined criteria for such scales were: Barthel Index, < 90; OARS scale, < 10 in women and < 6 in men; Pfeiffer Test, > 3 (± 1, depending on educational grade); and ≥ 1 positive response for depression on the abbreviated Geriatric Depression Scale (GDS). We assessed 1314 consecutive HF outpatients (27.8% women, mean age years 66.7 ± 12.4 years with different etiologies. Fragility was detected in 581 (44.2%) patients. 626 deaths occurred during follow-up; the median follow-up was 3.6 years [P₂₅–P₇₅: 1.8–6.7] for the total cohort, and 4.9 years [P₂₅–P₇₅: 2.5–8.4] for living patients. Fragility and its components were significantly associated with decreased survival by univariate analysis. In a comprehensive multivariable Cox regression analysis, fragility remained independently associated with survival in the entire cohort, and in age and left ventricular ejection fraction subgroups.

Conclusion

Fragility is a key determinant of survival in ambulatory patients with HF across all age strata.     

Prognostic relevance of gradual weight changes on long-term mortality in chronic heart failure

Background and aimsWhile obesity has been linked to better ouctomes (the obesity paradox), cachexia is associated with higher mortality in patients with heart failure with reduced ejection fraction (HFrEF). As opposed to overt cachexia, little is known about the prognostic impact of gradual, long-term weight changes in stable HFrEF.Methods and resultsWe included ambulatory patients with clinically stable chronic HFrEF on individually optimized treatment. Next to other clinical and functional parameters, changes in body weight over the past one (n = 733, group 1) or two (n = 636, group 2) years were recorded. Four-year mortality was analysed with respect to baseline BMI and changes in body weight or BMI using fractional polynomials. In addition, outcome was stratified by BMI categories (18.5–25 kg/m²: normal weight, >25–30 kg/m²: overweight, >30 kg/m²: obesity).An obesity paradox was present in both groups, with overweight and obese patients having the best prognosis. In both groups, a gradual weight gain of 5% was associated with the lowest mortality, whereas mortality steadily increases with increasing weight loss. Excessive weight gain >10% was also related to higher mortality. Stratification by baseline BMI categories revealed that weight loss was most detrimental in normal weight patients, whereas the prognostic impact of weight change was weaker in obese patients.ConclusionIn patients with chronic HFrEF, gradual weight loss is associated with steadily increasing mortality, whereas a weight gain of 5% is related to the best prognosis. Prevention of any inappropriate weight loss might be a therapeutic goal in HFrEF patient care.     

Prognostic value of increased carbohydrate antigen in patients with heart failure

AIM:To study the prognostic value of carbohydrateantigen 125(CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide(NT-proBNP) in stable heart failure(HF) patients.METHODS:The predictive value of CA125 was retrospectively assessed in 156 patients with stable HF remitted to the outpatient HF unit for monitoring from 2009 to 2011.Patients were included in the study if they had a previous documented episode of HF and received HF treatment.CA125 and NT-proBNP concentrations were measured.The independent association between NT-proBNP or CA125 and mortality was assessed with Cox regression analysis,and their combined predictive ability was tested by the integrated discrimination improvement(IDI) index.RESULTS:The mean age of the 156 patients was 72 ± 12 years.During follow-up(17 ± 8 mo),27 patients died,1 received an urgent heart transplantation and 106 required hospitalization for HF.Higher CA125 values were correlated with outcomes:58 ± 85 KU/L if hospitalized vs 34 ± 61 KU/L if not(P 0.05),and 94 ± 121 KU/L in those who died or needed urgent heart transplantation vs 45 ± 78 KU/L in survivors(P 0.01).After adjusting for propensity scores,the highest risk was observed when both biomarkers were elevated vs not elevated(HR = 8.95,95%CI:3.11-25.73; P 0.001) and intermediate when only NT-proBNP was elevated vs not elevated(HR = 4.15,95%CI:1.41-12.24; P 0.01).Moreover,when CA125 was added to the clinical model with NT-proBNP,a 4%(P 0.05) improvement in the IDI was found.CONCLUSION:CA125 60 KU/L identified patients in stable HF with poor survival.Circulating CA125 level adds prognostic value to NT-proBNP level in predicting HF outcomes.     

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.     

Impact of diabetes mellitus on long-term survival in patients with congestive heart failure.

AIMS: To test the hypothesis that diabetic status may be used as a prognostic indicator in heart failure (HF) patients. METHODS AND RESULTS: We studied 1246 consecutive patients with left ventricular dysfunction. All patients had a cardiopulmonary exercise test and an echocardiogram. Cardiac catheterisation was systematically performed to define HF aetiology. Twenty-two percent of the patients were diabetic (hypoglycaemic drugs or fasting blood glucose >126 mg/dL); in diabetic patients, HF aetiology was ischaemic in 58% vs. 40% in non-diabetic patients ( p < 0.0001). Clinical follow-up (median 1200 days) was obtained for 1241 patients. There was a statistically significant effect of diabetes mellitus on cardiac survival that differed according to HF aetiology (interaction p > 0.01). Diabetes mellitus was an independent predictor of cardiovascular mortality in ischaemic patients (HR=1.54 [1.13; 2.09]; P = 0.006) but not in non-ischaemic patients (HR=0.65 [0.39; 1.07];p = 0.09). When diabetic patients were defined as patients receiving hypoglycaemic drugs at baseline, diabetes mellitus remained an independent predictor of cardiovascular mortality in ischaemic patients (HR=1.43 [1.03; 1.98]; p = 0.03) while diabetes mellitus was associated with a statistically significant decrease in cardiovascular mortality in non-ischaemic patients (HR=0.46 [0.23; 0.88]; p = 0.02). CONCLUSION: The prognostic impact of diabetes mellitus in HF patients is markedly influenced by the underlying aetiology and is particularly deleterious in those with ischaemic cardiomyopathy.     

Early heart rate recovery after exercise predicts mortality in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet. METHODS: Ninety-two stable CHF patients (83M/9F, mean age: 51+/-12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %)=(peak HR-resting HR/220-age-resting HR)x100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography. RESULTS: Fatal events occurred in 24 patients (26%) during 21+/-6 months of follow-up. HRR1 was lower in non-survivors (11.4+/-6.4 vs. 20.4+/-8.1; p<0.001). All cause-mortality rate was 65% in patients with HRR112 bpm (log-rank: 32.6; p<0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (chi2=19.2; odds ratio: 0.87; p<0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10-18, ml/kg/min), HRR1 was a strong predictor of mortality (chi2: 14.3; odds ratio: 0.8; p<0.001). CONCLUSIONS: Early heart rate recovery is an independent prognostic risk indicator in CHF patients and could be used in CHF risk stratification.