Identification of chronic heart failure patients with a high 12-month mortality risk using biomarkers including plasma C-terminal pro-endothelin-1

Objectives

We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Methods

We examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology). Plasma CT-proET-1 was detected using a chemiluminescence immunoassay.

Results

Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04–1.95, p = 0.03) after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF), age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40). Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01) than adding NT-proBNP (p<0.01). Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02).

Conclusions

Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes.     

Cardiac assessment of patients with late stage Duchenne muscular dystrophy

Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients. Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA. Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA. Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232–7.)     

Effects of growth hormone treatment on B-type natriuretic peptide as a marker of heart failure in adults with growth hormone deficiency.

OBJECTIVE: Patients with growth hormone deficiency (GHD) have abnormalities of cardiac structure and function. Growth hormone replacement (GHR) therapy can induce an increase in cardiac mass and improvement in left ventricular ejection fraction. B-type natriuretic peptide (BNP) levels have been successfully used to identify patients with heart failure and they correlate with both disease severity and prognosis. DESIGN: To investigate the effect of growth hormone replacement on BNP and inflammatory cardiovascular risk factors in adults with GHD we determined NT-proBNP and high sensitive C-reactive protein (CrP) before, 6 and 12 months after GHR. PATIENTS: Thirty adults (14 males, 16 females) with GHD mean age: 41.7+/-14.5 years (range: 17.2 to 75.4 years) were recruited from the German KIMS cohort (Pfizer's International Metabolic Database). RESULTS: During 12 months of GHR, a significant increase of IGF-1 (85.4+/-72.1 VS. 172.0+/-98 mug/dl; p=0.0001; IGF-1 SDS mean+/-SD: -3.85+/-3.09 VS. -0.92+/-1.82) was detectable. Mean baseline NT-proBNP was 112+/-130 pg/ml (range: 7 to 562). Twelve patients had normal BNP, whereas 18 revealed NT-proBNP values corresponding to those of patients with heart failure NYHA classification I (n=10), NYHA II (n=6) and NYHA III (n=2), respectively. Baseline BNP levels correlated significantly (p=0.044) with increased baseline CrP values. After 12 months of GHR, a significant decrease (p=0.001) in NT-proBNP levels mean: 68+/-81 pg/ml (range: 5 to 395) was detectable, associated with an improvement in NYHA performance status in 10 of the 18 with increased baseline NT-proBNP. CONCLUSIONS: Based on our study, approximately two-thirds of patients with GHD have increased NT-proBNP levels which may be useful as screening/diagnostic laboratory parameter for heart failure in such patients. GHR therapy decreases BNP levels in most patients with GHD.     

心脏彩超评估高血压左心室肥厚伴左心衰竭患者心功能的临床价值及与NYHA分级的关系研究

目的:探讨心脏彩超评估高血压左心室肥厚(LVH)伴左心衰竭患者心功能的临床价值,分析其超声指标与美国纽约心脏病协会(NYHA)分级的相关性。方法:选择2017年5月至2018年5月我院收治的127例高血压LVH伴左心衰竭患者为观察组,根据NYHA分级将其分为NYHAⅡ级组(41例)、Ⅲ级组(47例)、Ⅳ级组(39例),另选择100例体检的健康志愿者为对照组。所有受试者均接受心脏彩超获得相关参数[左心房内径(LAD)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室短轴缩短率(LVFS)、左心室后壁厚度(LVPWT)、室间隔厚度(IVST)、左心室射血分数(LVEF)、左心室舒张早期充盈峰最大充盈速度/舒张晚期充盈峰最大峰值速度(E/A)比值、Tei指数],分析心脏彩超相关参数与NYHA分级之间相关性。结果:观察组患者LAD、LVEDD、LVESD、LVPWT、IVST、Tei指数高于对照组(P0.05),LVFS、LVEF、E/A比值低于对照组(P0.05)。Tei指数随着NYHA分级增高而增高(P0.05),LVFS、LVEF、E/A比值随着NYHA分级增高而降低(P0.05)。Spearman秩相关分析结果显示,Tei指数与NYHA分级呈正相关(rs=0.398,P0.05),LVFS、LVEF、E/A比值与NYHA分级呈负相关(rs=-0.285,-0.442,-0.305,P0.05)。结论:高血压LVH伴左心衰竭患者发生明显左室肥厚和左心功能降低,心脏彩超可准确评估高血压LVH伴左心衰竭患者的心功能和病情严重程度,且部分心脏彩超相关参数与NYHA分级相关。     

Association of galectin-3 with changes in left ventricular function in recent-onset dilated cardiomyopathy

Abstract

Background: The course of newly diagnosed dilated cardiomyopathy (DCM) varies from persistent reduction of left ventricular ejection fraction (LVEF) to recovery or even worsening. The aim of the present study was to examine the prognostic value of selected biomarkers with regard to changes in LVEF.

Methods: Main inclusion criterion was LVEF ≤45% with exclusion of coronary artery or valvular heart disease. The primary endpoint was LVEF ≤35% in the follow-up echocardiogram. Galectin-3, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were related to the endpoint.

Results: Data from 80 DCM patients (55 male, mean age 53 years) were analyzed. Median LVEF was 25% (IQR 25–30). The endpoint was met for 24 patients (30%). These had higher baseline levels of galectin-3 (median 20.3?ng/mL [IQR 14.3–26.9] vs. 14.7?ng/mL [IQR 10.9–17.7], p?=?0.007) and NT-proBNP (3089?pg/mL [IQR 1731–6694] vs. 1498?pg/mL [IQR 775–3890]; p?=?0.004) in univariate Cox regression analysis. ROC analysis revealed that CRP (median 0.4?mg/dL [IQR 0.2–1.2]) was also related to the endpoint (p?=?0.043).

Conclusion: Higher levels of galectin-3, NT-proBNP, and CRP were associated with LVEF ≤35% in our cohort. An approach utilizing a combination of biomarkers for patient management should be assessed in further studies.     

血清NT-proBNP水平在小儿心源性与非心源性呼吸困难诊断鉴别的价值

目的：探究血清B 型利钠肽前体（NT-proBNP）水平在小儿心源性与非心源性呼吸困难诊断鉴别的价值。方法：本研究于 2013 年2月~2015年2 月期间,选择我院收治的急性呼吸困难患儿72 例为研究对象,根据临床诊断将其分为心源性呼吸困难组 （39例）和非心源呼吸困难组（33 例）。采用电化学发光免疫分析法（ECLIA）测量两组患儿血清NT-proBNP 水平,并采用受试者工 作特征曲线（ROC）曲线评估血清NT-proBNP 水平在小儿心源性与非心源性呼吸困难诊断鉴别中的价值。结果：心源性呼吸困难 组患儿血清NT-proBNP水平为(253.23± 39.38)ng/L,明显高于非心源性呼吸困难组患儿血清NT-proBNP水平（76.39± 17.39） ng/L（t=23.882,P<0.05）。小儿血清NT-proBNP 水平诊断心源性呼吸困难和非心源性呼吸困难的曲线下面积为0.914,曲线下面积 的95%的置信区间为（0.861,0.967）,当血清NT-proBNP水平为118.34ng/L 时,约登指数取最大值为0.923,敏感度为97.43% （37/39）、特异度为94.87%（32/33）。结论：NT-proBNP 作为一个特异性指标可用于小儿心源性呼吸困难与非心源性呼吸困难的鉴 别诊断。     

Seasonal changes in blood serum protein fractions and in activity of AspAT and AlAT in Arabian brood mares and their foals

In 34 pure breed Arabian horses divided into four groups (Gr. I--10 pregnant mares, Gr. II--7 barren mares, Gr. III--10 foals born in 1981, Gr. IV--7 foals born in 1982) seasonal changes in total blood serum protein, its electrophoretic fractions and the activity of AspAT and AlAT were studied. Seasonal cyclicity was found in all groups in the amount of total serum proteins, and alpha 2- and beta 1-globulin fractions. Cyclicity was found in the level of albumin and activity of AspAT in three groups, not Gr. II, and in gamma-globulin, not Gr. IV. beta 2-globulin and AlAT cyclicity was found in two groups and alpha 1-globulin cyclicity was found only in Gr. II. Out of nine indices studied, cyclicity was found in eight of them in pregnant mares, Gr. I; in seven in older foals, Gr. III; in six in the young foals, Gr. IV; and in five in barren mares, Gr. II.     

Application of determined NT-proBNP in physical standardized exercise

Natriuretic peptides can be used as markers of heart failure, its severity and also in the differential diagnosis of dyspnea. Moreover, the dynamics of natriuretic peptides in physical standardized exercise may be used in the assessment of latent heart failure. AIM OF THE STUDY: Can determination of NT-proBNP be used in the diagnosis of exercise-induced ischemia or latent heart failure? 18 probands (10 men, 8 women) under study were risk persons with unspecified ECG, without signs of manifest heart failure. They were subjected to ergometric bike exercises up to the subjective maximum, SPECT myocardium with estimated ejection fraction of the left ventricle at peak ergometric exercise. The following parameters were followed-up: a) before ergometric exercise: NT-proBNP, CRP, TNF-alpha, Hb, Htc, lactate b) at subjective maximum: NT-proBNP, Hb, Htc, lactate c) 30 min after stopping the exercise: NT-proBNP d) 60 min after stopping the exercise: NT-proBNP. The volume blood changes were taken into account (estimation from the dynamics of Htc, Hb with calculation of metabolic changes of NT-proBNP). To evaluate the dynamics of NT-proBNP, the group was divided into subgroups according to the results obtained in ergometric exercises. RESULTS: initial values of NT-proBNP within normal limits (< 59 pmol/l, 500 ng/l) in 94%, the submaximal pulse rate was reached in 94%, ischemic changes in ECG were observed in 59%, typical clinical signs of heart ischemia were recorded in 35%. Signs of heart dysfunction according to SPECT were found in 47% and ischemic symptoms were observed in 43%. In general, the plasmatic volume decreased by 24% at maximal exercise. Lactate concentration in the plasma increased in all cases. Conversion of NT-proBNP into volume blood changes revealed that increased NT-proBNP occurred only in 22%. Differences between NT-proBNP before exercises and at maximal exercise prior and after correction into volume blood changes were statistically insignificant. 30 and 60 min after the exercise, no significant differences were found in NT-proBNP concentrations. Dividing into subgroups according to the results of ergometric exercises, showed no significant differences in NT-proBNP concentrations. Dynamics of NT-proBNP changes during and after ergometric exercises cannot be used for the diagnosis of exercise-induced heart failure. The high stability of NT-proBNP related to physical activity was confirmed.     

Systemic inflammation and cell activation reflects morbidity in chronic heart failure

Chronic heart failure (CHF) leads to complex effects distant from the heart. As these changes may be reflected in the balance of systemic inflammatory and fibrotic immunomodulators we measured these potential biomarkers in ambulatory CHF patients. Using the New York Heart Association (NYHA; levels II-IV) functional classification, 30 CHF patients were compared with 21 age and gender matched controls. Peripheral blood levels of regulatory cytokines (TNF-α, TGF-β, KGF, IL-8, IL-10 and IL-12) and markers of cellular activation (CD11b, CD16, CD18, CD34, HLADR, CXCR1 and CCR5) were analysed by ELISA and flow cytometry, respectively. NYHA classification, which reflected increasing pulmonary microvascular pressure (E:E') but not ejection fraction, was positively associated with TGF-β and IL-10 (p≤0.03). Similarly, monocytes, as well as cell surface expression of the neutrophil adhesion molecule CD11b, and the macrophage complement receptor complex (CD11b/CD18), were increased in CHF patients (p≤0.03), while the chemokine receptor CXCR1 was decreased on cells of CHF patients. Twenty month follow-up of CHF subjects identified monocyte number as a powerful prognostic factor for cardio-pulmonary adverse events (p=0.001); however, no concurrent relationship with cellular activation marker expression was found. In subjects with CHF, monocytes, TGF-β, IL-10, CD11b/CD18 and CXCR1 expression in peripheral blood may act as novel biomarkers of immune activation and remodelling. Given the importance of dyspnea and the relationship of pulmonary microvascular pressure to the NYHA classification, we suggest these findings may reflect a contribution by the lung.     

不同类型心力衰竭患者心电图QRS波时限与血浆NT-proBNP水平的关系及其临床意义

目的：探讨不同类型心力衰竭患者心电图QRS 波时限与血浆N末端B型利钠肽原（NT-proBNP）水平之间的关系及其临床 意义。方法：选择我院2012 年7 月至2014 年6 月接收的慢性心力衰竭患者300 例,作为研究组,将患者分为收缩性心力衰竭组 （S组）和舒张性心力衰竭组（D组）;另外,选取我院非CHF 患者132 例,作为对照组。测定所有受试者的心电图QRS 波时限,及 血浆中NT-proBNP 水平,分析血浆NT-proBNP 水平与QRS 波时限及NYHA心功能分级关系。结果：与对照组相比,研究组QRS 波时限均延长,血浆NT-proBNP水平显著升高（P<0.05）,其中S 组比D 组明显延长,且S 组血浆NT-proBNP水平高于D 组 （P<0.05）。三组NYHA 分级对比发现,差异均具有统计学意义（P<0.05）;S 组患者血浆NT-proBNP水平与QRS 波时限及NYHA 心功能分级之间呈正相关;D 组患者血浆NT-proBNP水平与QRS 波时限及NYHA心功能分级之间无明显的相关性。结论：临床 上可以将NT-proBNP水平和QRS 波时限结合起来诊断慢性心力衰竭患者的类型,以便于之后的治疗。     

Biomarkers in outpatient heart failure management; Are they correlated to and do they influence clinical judgment?

Aims

Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation.

Methods and results

This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12–0.33; p < 0.01). NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group. NYHA class was significantly influenced by age, body mass index, anaemia, and the presence of two or more comorbidities.

Conclusion

In HF, biomarkers correlate only weakly with clinical signs and symptoms. NYHA classification is influenced by several comorbidities and patient characteristics. Clinical judgement seems to be influenced by a clinician’s awareness of NT-proBNP concentrations.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-013-0503-y) contains supplementary material, which is available to authorized users.     

慢性心力衰竭患者血清Galectin-3、hs-cTnT、Cys C和PTX-3水平变化及临床意义

目的:研究慢性心力衰竭(CHF)患者血清半乳糖凝聚素-3(Galectin-3)、高敏肌钙蛋白-T(hs-cTnT)、胱抑素C(Cys C)和正五聚体蛋白-3(PTX-3)水平变化及临床意义。方法:选择2017年2月～2018年6月我院收治的CHF患者100例,按照美国心脏病协会(NYHA)心功能分级标准将其分成NYHAⅡ级组39例、NYHAⅢ级组33例、NYHAⅣ级组28例,根据随访1年患者预后情况将主要心脏不良事件患者记作预后不良组(n=27),其余记为预后优良组(n=73),另取同期于我院进行体检的健康者30例作为对照组。分别比较CHF患者和对照组的心功能指标、血清Galectin-3、hs-cTnT、Cys C、PTX-3水平,分析CHF患者上述指标的相关性及其与CHF预后情况的关系。结果:对照组、NYHAⅡ级组、NYHAⅢ级组、NYHAⅣ级组左心室舒张末期内径(LVEDD)呈逐渐增大趋势,而左心室射血分数(LVEF)呈逐渐降低趋势(P0.05)。对照组、NYHAⅡ级组、NYHAⅢ级组、NYHAⅣ级组血清Galectin-3、hs-cTnT、Cys C和PTX-3水平呈逐渐升高趋势(P0.05)。经Pearson相关性分析可得:CHF患者LVEDD与血清Galectin-3、hs-cTnT、Cys C、PTX-3水平呈正相关关系,而LVEF与血清Galectin-3、hs-cTnT、Cys C、PTX-3水平呈负相关关系(P0.05)。CHF预后优良组血清Galectin-3、hs-cTnT、Cys C、PTX-3水平均低于预后不良组(P0.05)。结论:CHF血清Galectin-3、hs-cTnT、Cys C和PTX-3水平均呈明显高表达,且与患者的病情严重程度呈密切相关,临床上可通过检测上述指标水平,继而为CHF临床诊断、预后评估提供参考依据。     

左西孟旦和米力农治疗难治性心力衰竭的疗效比较及对血清NT-proBNP、ET-1水平的影响

目的:观察和比较左西孟旦(LEV)与米力农(MIL)治疗难治性心力衰竭(RHF)的临床效果及对患者血清N末端B型利钠肽原(NT-proBNP)、内皮素(ET)-1水平的影响。方法:选取我院2015年1月~2017年4月收治的102例RHF患者,采取随机数字表法均分为两组。MIL组给予MIL治疗,LEV组予以LEV治疗。比较两组的临床疗效,治疗前后超声心动图指标[左室射血分数(LVEF)、二尖瓣舒张早期/舒张晚期峰值流速(E/A)、左室舒张末期内径(LVIDd)]、血清NT-proBNP、ET-1水平的变化及不良反应的发生情况。结果:治疗7 d后,LEV组总有效率较MIL组明显升高(P0.05)。与治疗前对比,两组治疗7 d后LVEF、E/A值均显著上升(P0.01),LVIDd值均显著下降(P0.01),且LEV组LVEF、E/A值均显著高于MIL组,LVIDd值均显著低于MIL组(P0.01)。两组治疗7 d后血清NT-proBNP、ET-1水平较治疗前均显著降低(P0.01),且LEV组血清NT-proBNP、ET-1水平均明显低于MIL组(P0.01)。LEV组不良反应的发生率较MIL组明显降低(P0.05)。结论:与米力农相比,左西孟旦治疗难治性心力衰竭能更有效缓解或消除患者症状体征、抑制心室重构、改善心功能,且安全性更高,可能与其显著降低血清NT-proBNP、ET-1水平有关。     

In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment

Introduction

Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed.

Methods

Between 2011–2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N?terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C?reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used.

Results

Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III–IV. We obtained 886 repeated measures (median 3 [IQR 2–5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6–1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: β [95% CI]: 1.56 [1.17–2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: β [95% CI]: 1.58 [1.21–2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73–4.73]), CRP (1.69 [1.21–2.34]) and NYHA class (2.33 [1.51–3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82.

Conclusion

Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients.

     

Effects of endogenous serum neuregulin-1β on morbidity and mortality in patients with heart failure and left ventricular systolic dysfunction

Abstract

Context: Improved left ventricular ejection fraction (LVEF) following administration of recombinant human Neuregulin-1β (NRG), epidermal growth factor (EGF) involved in cardiomyocyte repair/survival, has been observed in patients with systolic heart failure (HF).

Methods: Serum NRG was measured by ELISA in 248 patients with NYHA class I–IV HF.

Results: NRG exhibited a marginally significant effect on LVEF trajectory over 11?months (p?=?0.07). There is no apparent level of NRG that predicts improved survival.

Conclusions: There is a potential relationship between serum NRG and improved LVEF, indicating the need to investigate the utility of NRG in predicting HF outcomes, including LVEF maintenance.     

Development of a Novel Heart Failure Risk Tool: The Barcelona Bio-Heart Failure Risk Calculator (BCN Bio-HF Calculator)

Background

A combination of clinical and routine laboratory data with biomarkers reflecting different pathophysiological pathways may help to refine risk stratification in heart failure (HF). A novel calculator (BCN Bio-HF calculator) incorporating N-terminal pro B-type natriuretic peptide (NT-proBNP, a marker of myocardial stretch), high-sensitivity cardiac troponin T (hs-cTnT, a marker of myocyte injury), and high-sensitivity soluble ST2 (ST2), (reflective of myocardial fibrosis and remodeling) was developed.

Methods

Model performance was evaluated using discrimination, calibration, and reclassification tools for 1-, 2-, and 3-year mortality. Ten-fold cross-validation with 1000 bootstrapping was used.

Results

The BCN Bio-HF calculator was derived from 864 consecutive outpatients (72% men) with mean age 68.2±12 years (73%/27% New York Heart Association (NYHA) class I-II/III-IV, LVEF 36%, ischemic etiology 52.2%) and followed for a median of 3.4 years (305 deaths). After an initial evaluation of 23 variables, eight independent models were developed. The variables included in these models were age, sex, NYHA functional class, left ventricular ejection fraction, serum sodium, estimated glomerular filtration rate, hemoglobin, loop diuretic dose, β-blocker, Angiotensin converting enzyme inhibitor/Angiotensin-2 receptor blocker and statin treatments, and hs-cTnT, ST2, and NT-proBNP levels. The calculator may run with the availability of none, one, two, or the three biomarkers. The calculated risk of death was significantly changed by additive biomarker data. The average C-statistic in cross-validation analysis was 0.79.

Conclusions

A new HF risk-calculator that incorporates available biomarkers reflecting different pathophysiological pathways better allowed individual prediction of death at 1, 2, and 3 years.     

上胸段硬膜外阻滞治疗慢性心力衰竭合并房颤的临床研究

目的:比较上胸段硬膜外阻滞对有无合并房颤的扩张型心肌病心衰患者的疗效差异。方法:入选40例扩张型心肌病心衰患者,根据入院心电图有无房颤分为房颤组和非房颤组。所有患者均在抗心力衰竭常规治疗基础上,给予胸段硬膜外阻滞治疗4周,比较治疗前、后NYHA心功能分级、血浆N末端脑钠肽前体(NT-pro BNP)水平、左室射血分数(LVEF)、左室舒张期内径(LVEDD)及左房前后径(LAD)的变化情况。结果:与治疗前比较,两组患者经治疗后的NYHA心功能分级、NT-pro BNP、LVEF、LVEDD及LAD均明显改善(均P0.05),差异有统计学意义,但两组间各指标治疗前后的差值无统计学意义(P0.05)。结论:对于慢性心力衰竭合并房颤的患者而言,给予抗心力衰竭常规治疗基础上联合上胸段硬膜外阻滞治疗有效,且房颤的存在与否不影响上胸段硬膜外阻滞的疗效。     

伊伐布雷定治疗高龄老年射血分数中间值心衰患者的疗效观察

目的 评价伊伐布雷定治疗高龄老年射血分数中间值心衰(HFmrEF)患者的临床疗效.方法 选择我院治疗的120例高龄老年HFmrEF患者,按随机数字表法分为观察组和对照组各60例,对照组给予规范化抗心衰治疗,观察组在此基础上加用伊伐布雷定治疗.随访6个月后,比较两组治疗前后静息心率(RHR)、氨基末端脑钠肽前体(NT-p...     

Prostacyclin I2 (PGI2) increases left ventricular ejection fraction (LVEF)

In order to evaluate the effect of PGI2 on left ventricular ejection fraction (LVEF) an intravenous infusion in 10 patients (3 males, 7 females; 36 to 63 years) with an impaired LVEF (34.7 +/- 14.8%) was performed. LVEF was determined by means of 99mTc-pertechnetate radionuclide ventriculography. An increase of LVEF to 36.2 +/- 13.5% during administration of PGI2 at a rate of 1 ng/kg/min for 15 min and to 43.8 +/- 15.8% during a rate of 5 ng/kg/min (p less than 0.01) for an additional 15 min was observed. Analyzing the data in more detail in 6 patients, an improvement in LVEF became obvious during the administration of 1 ng/kg/min (108, 109, 116, 118, 121, and 123% of pre-infusion value, respectively). In 5 out of these 6 patients a dose-increment to 5 ng/kg/min further increased LVEF (139, 179, 187, 148, and 128% of pre-infusion value, respectively). In contrast, in the other 4 patients no response of LVEF to PGI2 at a rate of 1 ng/kg/min could be observed. However, in 2 out of these 4 patients LVEF increased during the administration of 5 ng/kg/min (111 and 117% of pre-infusion value). Individual changes in hemodynamic parameters showed no correlation to the improvement seen in LVEF in response to PGI2. It is concluded that PGI2 may exert beneficial effects on LVEF, and might be used in certain clinical conditions, such as before heart transplantation, to achieve a temporary improvement in LVEF.     

Beneficial effect of long-term PGE1-treatment in left ventricular heart failure

Five male patients aged 34-47 years with congestive heart failure showed an improvement of left ventricular ejection fraction (LVEF) at rather low PGE1-doses (10-30 ng/kg/min) without affecting blood pressure or heart rate. LVEF was estimated by means of radionuclide ventriculography (RNV) prior to and during i.v.-infusion of PGE1 at increasing dose rates (10-100 ng/kg/min). Therefore, we administered to these responders PGE1 at a rate of 20 ng/kg/min i.v. continuously on a long-term basis by means of a portable infusion pump. Until up to 4 months the remarkable benefit in LVEF induced by PGE1 was still present to a comparable extent in all the patients. No rebound desensitization phenomenon occurred either on platelet activity or on LVEF. PGE1, via a more practical route of application or by a stable analogue, may be a promising therapy at this stage of cardiomyopathy (CMP).