The effect of diabetes on the diagnostic and prognostic performance of mid-region pro-atrial natriuretic peptide and mid-region pro-adrenomedullin in patients with acute dyspnea

Serum mid-regional pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM) are novel biomarkers for acute heart failure (AHF). Like other AFH biomarkers, the performance of these tests are affected by the presence of clinical variables such as renal failure and obesity. In a substudy of the Biomarkers from Acute Heart Failure Study, we show that diabetes did not influence the performance of these markers with regards to AHF diagnosis or 90-day all cause death. However, in patients without AHF, increased MR-proADM alone was associated with the presence of diabetes.     

心衰生物标记物研究新进展

心力衰竭(心衰)是临床最常见的危重疾病之一,其致死率不低于某些癌症。随着现代医学进展,年龄依赖性死亡率明显下降,冠脉事件显著减少,患者生存时间延长,心衰患病率较前增加。针对心衰的研究不断更新,心衰的病理生理机制日益趋向完善,不仅仅涉及先前众所周知的心肌损伤或者心脏前后负荷增加,更多因素先后被发现参与心衰的发生、发展,包括神经内分泌机制、炎症反应,内分泌信号系统和生化因素等。伴随心衰病理生理过程产生了一系列的生物标记物,某些生物标记物在协助临床医生诊疗心衰患者方面发挥重要作用。具体包括神经激素类生物(例如:脑钠肽、氨基末端-pro BNP、心房钠尿肽前体中段、肾上腺髓质素前体中段和嗜铬素A),炎症因子类生物标记物(例如:CRP、IL-6和ST2),内分泌生物标志物(例如:脂联素、抵抗素、瘦素和醛固酮),其他生物标记物(包括:肌钙蛋白I/T、乳糖凝集素-3、胱氨酸蛋白酶抑制剂C、生长分化因子-15和基质金属蛋白酶)。生物标记物凭借其高度敏感性及特异性,在心衰的诊断、危险分层及评估预后等方面发挥重要作用。本文就心衰生物标记物最新研究进展做一综述。     

The effect of diabetes on the diagnostic and prognostic performance of mid-region pro-atrial natriuretic peptide and mid-region pro-adrenomedullin in patients with acute dyspnea

Serum mid-regional pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM) are novel biomarkers for acute heart failure (AHF). Like other AFH biomarkers, the performance of these tests are affected by the presence of clinical variables such as renal failure and obesity. In a substudy of the Biomarkers from Acute Heart Failure Study, we show that diabetes did not influence the performance of these markers with regards to AHF diagnosis or 90-day all cause death. However, in patients without AHF, increased MR-proADM alone was associated with the presence of diabetes.     

Neurohormonal profile of patients with heart failure and diabetes

Background. Neurohormonal activation is generally recognised to play an important role in the pathophysiology, prognosis and treatment of chronic heart failure (HF). While the number of patients with diabetes increases, little if anything is known about neurohormonal activation in HF patients with diabetes. Methods. The study population consisted of 371 patients with advanced HF who were enrolled in a multicentre survival trial. Ten different plasma neurohormones were measured (noradrenaline, adrenaline, dopamine, aldosterone, renin, endothelin, atrial natriuretic peptide [ANP], N-terminal (pro)ANP, brain natriuretic peptide [BNP] and N-terminal (pro)BNP. Comparisons were made between patients with diabetes (n=81) and those without (n=290). Results. At baseline, the two groups were comparable regarding age (mean 68 years), left ventricular ejection fraction (23%), severity and aetiology of HF, while body weight was higher in those with diabetes (77.4 vs. 74.2 kg, p=0.04). Most plasma neurohormones were similar between groups, but patients with diabetes had higher values of BNP (94 vs. 47 pmol/l, p=0.03), while a similar trend was observed for N-terminal (pro)BNP (750 vs. 554 pmol/l, p=0.10). During almost five years of follow-up, 51/81 patients with diabetes died (63%), as compared with 144 of 290 non-diabetic patients (50%) who died (p=0.046). Natriuretic peptides and noradrenaline were the most powerful predictors of mortality in both diabetic and non-diabetic HF patients. Conclusion. HF patients with diabetes have higher (N-terminal (pro)) BNP levels than non-diabetic patients, while other neurohormones are generally similar. Natriuretic peptides are also good prognostic markers in diabetic HF patients. (Neth Heart J 2010;18:190-6.)     

Atrial natriuretic peptides in heart failure: pathophysiological significance, diagnostic and prognostic value

Neurohormonal activation in patients with heart failure is dominated by the deleterious long-term effects of activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. The natriuretic peptides, including brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), are also upregulated in heart failure, and partially counteract these deleterious effects by promoting vasodilation, natriuresis, and diuresis. Although BNP has been established as an important biomarker in the diagnosis and prognosis of heart failure, growing evidence suggests that measurement of plasma ANP, specifically its metabolite mid-regional pro-ANP, has similar diagnostic and prognostic value. Furthermore, its measurement may provide incremental diagnostic value when BNP levels fall into "grey zone" levels and may be a more potent prognostic marker of mortality.     

Biomarkers in heart failure with preserved ejection fraction

Biomarkers are widely used and studied in heart failure. Most studies have described the utility and performance of biomarkers in sub-studies of randomised clinical trials, where the vast majority of the patients suffered from heart failure with reduced ejection fraction (HFrEF), and not with preserved ejection fraction (HFpEF). As a result, there is a scarcity of data describing the levels, dynamics, clinical and biochemical correlates, and biology of biomarkers in patients suffering from HFpEF, whereas HFpEF is in fact a very frequent clinical entity. This article discusses the value of different biomarkers in HFpEF. We describe various aspects of natriuretic peptide measurements in HFpEF patients, with a focus on diagnosis, prognosis and the risk prediction of developing heart failure. Further, we will discuss several emerging biomarkers such as galectin-3 and suppression of tumorigenicity 2, and recently discovered ones such as growth differentiation factor-15 and syndecan-1.     

Regulation of expression of atrial and brain natriuretic peptide,biomarkers for heart development and disease

The mammalian heart expresses two closely related natriuretic peptide (NP) hormones, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The excretion of the NPs and the expression of their genes strongly respond to a variety of cardiovascular disorders. NPs act to increase natriuresis and decrease vascular resistance, thereby decreasing blood volume, systemic blood pressure and afterload. Plasma levels of BNP are used as diagnostic and prognostic markers for hypertrophy and heart failure (HF), and both ANF and BNP are widely used in biomedical research to assess the hypertrophic response in cell culture or the development of HF related diseases in animal models. Moreover, ANF and BNP are used as specific markers for the differentiating working myocardium in the developing heart, and the ANF promoter serves as platform to investigate gene regulatory networks during heart development and disease. However, despite decades of research, the mechanisms regulating the NP genes during development and disease are not well understood. Here we review current knowledge on the regulation of expression of the genes for ANF and BNP and their role as biomarkers, and give future directions to identify the in vivo regulatory mechanisms. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.     

实时三维超声心动图联合血清NT-proBNP、MR-proADM、sST2对心力衰竭患者诊断及预后的评估价值

摘要 目的：探讨实时三维超声心动图（RT-3DE）联合血清N末端脑钠肽前体（NT-proBNP）、肾上腺髓质素前体中段肽（MR-proADM）、可溶性人基质裂解素2（sST2）对心力衰竭（HF）患者诊断及预后的评估价值。方法：选择2020年3月至2022年10月阳光融和医院收治的112例HF患者（HF组）,另选择同期体检健康的50例志愿者（对照组）。所有受试者均接受RT-3DE检查,同时检测血清NT-proBNP、MR-proADM、sST2水平。对比两组RT-3DE参数和血清NT-proBNP、MR-proADM、sST2水平。HF患者出院后随访6个月,统计患者预后情况;根据预后将患者分为预后不良组（37例）和预后良好组（75例）。受试者工作特征（ROC）曲线分析RT-3DE参数联合血清NT-proBNP、MR-proADM、sST2诊断HF的临床价值及对预后不良的预测价值。结果：HF组左室收缩末期容积（LVESV）、左室舒张末期容积（LVEDV）、左室舒张末期容积指数（LVEDVI）、收缩末期容积指数（LVESVI）、血清NT-proBNP、MR-proADM、sST2水平高于对照组（P＜0.05）,左室射血分数（LVEF）低于对照组（P＜0.05）。RT-3DE参数联合血清NT-proBNP、MR-proADM、sST2诊断HF的曲线下面积（AUC）为0.902,高于各指标单独诊断。预后不良组LVESV、LVEDV、LVEDVI、LVESVI、血清NT-proBNP、MR-proADM、sST2水平高于预后良好组（P＜0.05）,LVEF低于预后良好组（P＜0.05）。RT-3DE参数联合NT-proBNP、MR-proADM、sST2预测HF预后不良的AUC为0.937,高于各指标单独预测。结论：HF患者LVESV、LVEDV、LVEDVI、LVESVI、血清NT-proBNP、MR-proADM、sST2水平增高,LVEF降低,联合RT-3DE参数和血清NT-proBNP、MR-proADM、sST2可提高对HF诊断和预后预测的效能。     

Galectin 3 complements BNP in risk stratification in acute heart failure

Background: Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure.

Methods: Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial.

Results: Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide.

Conclusion: In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.     

Comprehensive plasma metabolomic and lipidomic analyses reveal potential biomarkers for heart failure

Heart failure is a syndrome with symptoms or signs caused by cardiac dysfunction. In clinic, four stages (A, B, C, and D) were used to describe heart failure progression. This study was aimed to explore plasma metabolomic and lipidomic profiles in different HF stages to identify potential biomarkers. Metabolomics and lipidomics were performed using plasma of heart failure patients at stages A (n?=?49), B (n?=?61), and C+D (n?=?26). Analysis of Variance (ANOVA) was used for screening dysregulated molecules. Bioinformatics was used to retrieve perturbed metabolic pathways. Univariate and multivariate receiver operating characteristic curve (ROC) analyses were used for potential biomarker screening. Stage A showed significant difference to other stages, and 142 dysregulated lipids and 134 dysregulated metabolites were found belonging to several metabolic pathways. Several marker panels were proposed for the diagnosis of heart failure stage A versus stage B-D. Several molecules, including lysophosphatidylcholine 18:2, cholesteryl ester 18:1, alanine, choline, and Fructose, were found correlated with B-type natriuretic peptide or left ventricular ejection fractions. In summary, using untargeted metabolomic and lipidomic profiling, several dysregulated small molecules were successfully identified between HF stages A and B-D. These molecules would provide valuable information for further pathological researches and biomarker development.

     

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.     

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

Background

Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.

Methods

PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.

Results

In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.

Conclusions

BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.     

Prognostic and diagnostic significance of mid-regional pro-atrial natriuretic peptide in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 Study

Abstract

Purpose: To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea.

Methods: MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n?=?313), on day 2 (n?=?234), and before discharge (n?=?91) and compared for diagnosing acute heart failure (HF; n?=?143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n?=?84) separately.

Results: The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p?<?0.001) and the receiver-operating area under the curve (AUC) was 0.85 (95% CI 0.81–0.89) for MR-proANP and 0.86 (0.82–0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816?days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio (_lnMR-proANP) 1.98 (95% CI 1.17–3.34).

Conclusion: MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.     

Respiratory-related heart rate variability in progressive experimental heart failure

Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing. Spectral analysis of heart rate variability and respiration, echocardiography, hemodynamic measurements, plasma atrial natriuretic factor, and norepinephrine was obtained at baseline and every week, 30 min after pacing interruption. Progressive heart failure increased heart rate (from 91 +/- 4 to 136 +/- 5 beats/min; P < 0.001) and decreased absolute and normalized (percentage of total power) HF variability from week 1 and 2, respectively (P < 0.01). Absolute LF variability did not change during the study until it disappeared in two dogs at week 7 (P < 0.05). Normalized LF variability increased in moderate heart failure (P < 0.01), leading to an increased LF-to-HF ratio (P < 0.05), but decreased in severe heart failure (P < 0.044; week 7 vs. week 5). Stepwise regression analysis revealed that among heart rate variables, absolute HF variability was closely associated with wedge pressure, right atrial and pulmonary arterial pressure, left ventricular ejection fraction and volume, ratio of maximal velocity of early (E) and atrial (A) mitral flow waves, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide (0.45 < r < 0.65, all P < 0.001). In tachycardia-induced heart failure, absolute HF heart rate variability is a more reliable indicator of cardiac dysfunction and neurohumoral activation than LF heart rate variability.     

利钠肽系统与肾素-血管紧张素-醛固酮系统在心力衰竭中交互作用

慢性心力衰竭是以高发病率、高入院率及高死亡率为特征的临床综合征,也是各种心血管疾病发展的终末阶段。神经激素系统的激活在心力衰竭病理生理中起着关键作用,其以肾素-血管紧张素-醛固酮系统(RAAS)、交感神经系统(SNS)及利钠肽系统(NPs)为主要组成部分。在心衰的病理生理中,NPs与RAAS存在交互作用,其对于与心功能不全相关的血液动力学改变与组织重塑起重要的作用,并且最终可导致心衰的恶化。因此,能够同时作用于RAAS与NPs,并且能够纠正两者间调节紊乱的干预措施,对于慢性心衰的治疗将具有良好的疗效。本文将主要对RAAS、NPs及NPs与RAAS的交互作用在心衰中的病理生理作用进行综述,并展望针对NPs与RAAS的交互作用的临床应用前景。     

Relationship between Bone Mineral Density and Serum Osteoprotegerin in Patients with Chronic Heart Failure

Purpose

Heart failure (HF) had been reported with increased risk of hip fractures. However, the relationship between circulating biomarkers and bone mineral density (BMD) in chronic HF remained unclear.

Methods

This is a cross-sectional study which recruited stable chronic HF from registry of the Heart Failure Center of National Taiwan University Hospital. Patients underwent dual-energy x-ray absorptiometry (DEXA) measurements at hip and lumbar spines and biochemical assessments including B-type natriuretic peptide (BNP-32), myostatin, follistatin and osteoprotegerin (OPG).

Results

A total of 115 stable chronic HF individuals with left ventricular ejection fraction (EF) <45% (74% of male, mean age at 59) were recruited with 24 patients in NYHA class I, 73 patients in NYHA class II and 18 patients in NYHA class III. Results of BMD showed that Z scores of hip in NYHA III group (−0.12±1.15) was significantly lower than who were NYHA II (0.58±1.04). Serum OPG was significantly higher in subjects of NYHA III (9.3±4.6 pmol/l) than NYHA II (7.4±2.8 pmol/l) or NYHA I (6.8±3.6 pmol/l) groups. There’s a significant negative association between log transformed serum OPG and trochanteric BMD (R = −0.299, P = 0.001), which remained significant after multivariate analysis.

Conclusions

Our study demonstrated an inverse association between serum OPG and trochanteric BMD in patients with HF. OPG may be a predictor of BMD and an alternative to DEXA for identifying at risk HF patients for osteoporosis.     

Recent advances in natriuretic peptide research

The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular and renal homeostasis. They have recently emerged as potentially important clinical biomarkers in heart failure. Natriuretic peptides, particularly brain natriuretic peptide (BNP) and the inactive N-terminal fragment of BNP, NT-proBNP, that has an even greater half-life than BNP, are elevated in heart failure and therefore considered to be excellent predictors of disease outcome. Nesiritide, a recombinant human BNP, has been shown to provide symptomatic and haemodynamic improvement in acute decompensated heart failure, although recent reports have suggested an increased short-term risk of death with nesiritide use. This review article describes: the current use of BNP and its inactive precursor NT-proBNP in diagnosis, screening, prognosis and monitoring of therapy for congestive heart failure, the renoprotective actions of natriuretic peptides after renal failure and the controversy around the therapeutic use of the recombinant human BNP nesiritide.     

Midregional-proAtrial Natriuretic Peptide and High Sensitive Troponin T Strongly Predict Adverse Outcome in Patients Undergoing Percutaneous Repair of Mitral Valve Regurgitation

Background

It is not known whether biomarkers of hemodynamic stress, myocardial necrosis, and renal function might predict adverse outcome in patients undergoing percutaneous repair of severe mitral valve insufficiency. Thus, we aimed to assess the predictive value of various established and emerging biomarkers for major adverse cardiovascular events (MACE) in these patients.

Methods

Thirty-four patients with symptomatic severe mitral valve insufficiency with a mean STS-Score for mortality of 12.6% and a mean logistic EuroSCORE of 19.7% undergoing MitraClip therapy were prospectively included in this study. Plasma concentrations of mid regional-proatrial natriuretic peptide (MR-proANP), Cystatin C, high-sensitive C-reactive protein (hsCRP), high-sensitive troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), galectin-3, and soluble ST-2 (interleukin 1 receptor-like 1) were measured directly before procedure. MACE was defined as cardiovascular death and hospitalization for heart failure (HF).

Results

During a median follow-up of 211 days (interquartile range 133 to 333 days), 9 patients (26.5%) experienced MACE (death: 7 patients, rehospitalization for HF: 2 patients). Thirty day MACE-rate was 5.9% (death: 2 patients, no rehospitalization for HF). Baseline concentrations of hsTnT (Median 92.6 vs 25.2 ng/L), NT-proBNP (Median 11251 vs 1974 pg/mL) and MR-proANP (Median 755.6 vs 318.3 pmol/L, all p<0.001) were clearly higher in those experiencing an event vs event-free patients, while other clinical variables including STS-Score and logistic EuroSCORE did not differ significantly. In Kaplan-Meier analyses, NT-proBNP and in particular hsTnT and MR-proANP above the median discriminated between those experiencing an event vs event-free patients. This was further corroborated by C-statistics where areas under the ROC curve for prediction of MACE using the respective median values were 0.960 for MR-proANP, 0.907 for NT-proBNP, and 0.822 for hsTnT.

Conclusions

MR-proANP and hsTnT strongly predict cardiovascular death and rehospitalization for HF in patients undergoing percutaneous repair of mitral valve insufficiency. Both markers might be useful components in new scoring systems to better predict short- and potentially long-term mortality and morbidity after MitraClip procedure.     

Cardiac gene expression profiling – the quest for an atrium-specific biomarker

Biomarkers are gaining increasing interest to predict risk but also to aid in diagnostics. Tissue-specific biomarkers are of utmost importance to detect diseases of respective organs. As of yet there are no atriumspecific biomarkers for risk stratification of atrial disease, such as atrial fibrillation. Bioinformatics such as mRNA microarrays can help to detect tissue-enriched and possibly tissue-specific expressed genes that can be targets for biomarkers. We describe an approach to identify genes preferably expressed in atrial cardiomyocytes compared with ventricular cardiomyocytes by RNA microarray and confirmed by quantitative real-time polymerase chain reaction. By this approach we identified several atrium-enriched genes but also ventricle-enriched genes. As expected atrial natriuretic peptide (ANP) mRNA showed higher expression in atrial cardiomyocytes while with adrenergic stimulation expression was almost as high in ventricular as in atrial cells. Brain-type natriuretic peptide (BNP), however, was not different between atrial and ventricular cells giving a possible explanation for increased levels of NT-proBNP in atrial fibrillation patients. Interesting identified candidates are serpine1 and ltbp2 as atrium-enriched genes whereas alpha-adrenergic receptor subtype 1b and S100A1 expression was significantly higher in ventricular cells. The identified genes need to be confirmed in human tissue and might ultimately be tested as potential biomarkers for atrial stress. (Neth Heart J 2010;18:610–4.)     

川崎病患儿的心率变异性指标与血清NT-proBNP及cTnI水平的相关性

目的:研究川崎病患儿的心率变异性指标与血清氨基末端脑钠肽前体(NT-pro BNP)及肌钙蛋白I(cTnI)水平的相关性,为临床诊疗提供依据。方法:选取2013年7月到2015年7月我院收治的川崎病患儿120例为研究组,根据患者是否存在冠状动脉损害分为A组(有冠状动脉损害)60例和B组(无冠状动脉损害)60例,同时选取同期健康体检儿童60例为对照组,比较各组窦性N-N间期标准差(SDNN)、5min N-N间期平均值标准差(SDANN)、极低频功率(VLF)、低频功率(LF)、高频功率(HF)、NT-proBNP水平以及cTnI水平。结果:研究组SDNN、SDANN、VLF、LF以及HF显著低于对照组,且A组显著低于B组,差异具有统计学意义(P0.05);研究组NT-proBNP水平和cTnI水平显著高于对照组,且A组显著高于B组,差异具有统计学意义(P0.05);研究组NT-proBNP与SDNN和HF呈负相关关系(P0.05),cTnI与SDNN和HF呈负相关关系(P0.05)。结论:心率变异性指标与川崎病患儿冠状动脉损害有关,与NT-proBNP、cTnI呈负相关关系。