Association of B-type natriuretic peptide activation to left ventricular end-systolic remodeling in organic and functional mitral regurgitation

B-type natriuretic peptide (BNP) is activated with mitral regurgitation (MR), but it is unclear whether BNP activation is uniform in organic and functional MR and whether it merely reflects symptoms or is a biomarker of left ventricular (LV) geometric and functional alterations. Comprehensive Doppler echocardiography and hormonal measurements were performed prospectively in 99 patients, 50 with organic MR, 28 with functional MR (with similar LV enlargement 130 +/- 21 vs 141 +/- 40, p = 0.18, and age 64 +/- 13 vs 66 +/- 12 years, p = 0.56) and 21 controls subjects of similar age. Compared with the controls, the patients with MR displayed LV remodeling and BNP activation. In those with functional MR compared with those with organic MR, despite a lower regurgitant volume (25 +/- 25 vs 96 +/- 29 ml), higher BNP levels were noted (385 +/- 388 vs 70 +/- 97 pg/ml, p <0.0001), even after stratification by functional class (class I 120 +/- 122 vs 33 +/- 40, class II 318 +/- 470 vs 74 +/- 69, class III to IV 487 +/- 383 vs 268 +/- 165 pg/ml, p = 0.006). The major determinant of BNP activation was the LV end-systolic volume index (p <0.0001), independent of MR etiology, symptoms, other hormonal activation, and hemodynamic characteristics. The BNP level is a biomarker of LV alteration in patients with MR, independent of MR etiology. With BNP >90 pg/ml, the odds ratio of an end-systolic volume index value of >/=60 ml/m(2) was 16 (95% confidence interval 5.5 to 45). In conclusion, BNP activation with MR is more pronounced in those with functional than those with organic MR, even after stratification for functional class, and independently reflects the severity of the LV alteration. Pronounced BNP activation is linked to a higher end-systolic volume index, for which it is a biomarker, irrespective of MR etiology and symptoms.     

Comparison of B-type natriuretic peptide levels in patients with heart failure with versus without mitral regurgitation

Functional mitral regurgitation (MR) occurs most often in patients with heart failure (HF) and is associated with an adverse prognosis. Recently, B-type natriuretic peptide (BNP) has been validated as a marker of cardiac function and prognosis. We sought to assess the relation between functional MR and BNP levels in patients with HF, and hypothesized that MR is associated with higher BNP levels. In all, 201 patients admitted with the diagnosis of HF had a transthoracic echocardiogram and measurement of BNP levels within 48 hours. MR was graded as none/trace, mild, moderate, or severe using recently published guidelines of the American Society of Echocardiography. BNP was measured by a commercially available instrument (Biosite). The relation of MR to BNP was assessed using multivariable linear regression methods with a Tobin estimation to account for the truncation of BNP values at an upper limit of 1,300 pg/ml. Mean age of the patients was 67 +/- 11 years. The median BNP level was 826 pg/ml. The etiology of HF was predominantly diastolic in 64 patients (32%); 137 patients (68%) had significant left ventricular (LV) systolic dysfunction. Mean LV ejection fraction was 37 +/- 17%. MR was present in 112 patients (56%). After adjusting for clinical, hemodynamic, and echocardiographic variables, only LV ejection fraction (p = 0.016) and moderate or severe MR (p = 0.023) were significantly associated with BNP. When MR was grouped as any MR versus no MR, only LV ejection fraction (p = 0.017) and any degree of MR (p = 0.029) were significantly associated with BNP.     

Elevated B-type natriuretic peptide despite normal left ventricular function on rest and exercise stress echocardiography in mitral regurgitation.

AIMS: To determine whether elevated B-type natriuretic peptide (BNP) predicts left ventricular (LV) contractile dysfunction on exercise stress echocardiography in patients with severe mitral regurgitation (MR). METHODS AND RESULTS: Thirty three patients with moderate-to-severe or severe MR, a LV ejection fraction > or =60% and New York Heart Association Class I or II symptoms, and 12 controls underwent resting and exercise stress echocardiography. In 20 MR patients, BNP was within the normal range (mean +/- SD, 7.7 +/- 2.7 pmol/L), and in 13 MR patients, BNP was >12 pmol/L (19.6 +/- 7.6 pmol/L). LV end-systolic volume index after exercise was lower in controls than patients with MR (P < 0.0001), but similar in MR patients with normal and elevated BNP, respectively (controls 8.5 +/- 3.9, MR 20 +/- 7 vs. 20 +/- 9 cm(2)/m(2), P > 0.05). However, pulmonary artery systolic pressure (PAP) after exercise was higher in MR with high BNP (70 +/- 20 vs. 48 +/- 11 mmHg, <0.0001) and controls (38+/-11 mmHg). A two-fold increase in plasma BNP was associated with an average increase in resting PAP of 7.6 (95% CI 2.9, 12.2) mmHg, an increase in post-exercise PAP of 14.4 (95% CI 9.0, 19.9) mmHg and increase in left atrial area index of 2.1 (95% CI 0.5, 3.8) cm(2)/m(2). However, there was no significant association between the plasma level of BNP and any rest or post-exercise measure of LV systolic function (r < 0.25, P > 0.05 for all). CONCLUSION: The plasma level of BNP may be within the normal range in patients with moderate-to-severe or severe MR despite significant increases in LV end-systolic volume. Increase in BNP is associated with pulmonary artery hypertension on exercise and left atrial enlargement even when LV systolic function on exercise stress echocardiography is normal.     

B-type natriuretic peptide

INTRODUCTION: B-type natriuretic peptide is a neurohormone synthesized in the cardiac ventricles upon ventricular pressure overload and ventricular dilatation. This peptide with many favourable physiological properties has emerged as important candidate for development of diagnosis and prognostic tools and therapeutic agents in cardiovascular disease. EXEGESIS: Literature published until now shows the interest to measure B-type natriuretic peptide in the diagnosis of ventricular dysfunction or congestive heart failure. B-type natriuretic peptide is also a prognostic marker in patients with congestive heart failure and acute coronary syndrome. It could even help to guide patient treatment management. It is easily and rapidly measured at a reasonable cost. In general, a level less than 50 ng/l has a strong negative predictive value for congestive heart failure. CONCLUSION: B-type natriuretic peptide is available in daily clinical practice. Future interest has focused on development of drugs that modulate its effects in treatment of decompensated congestive heart failure. Studies are in progress and first results seem to be promising.     

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.

OBJECTIVES: This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample. BACKGROUND: Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample. METHODS: Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age > or =45 years) of Olmsted County, Minnesota. RESULTS: In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction < or =40% or < or =50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone. CONCLUSIONS: Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.     

经皮二尖瓣球囊扩张术后血浆B型钠尿肽水平的变化

目的:观察心房压力快速变化对血浆B型钠尿肽(BNP)水平的影响。方法:采用床边快速BNP试验法检测30例成功施行二尖瓣球囊扩张术(PBMV)的风湿性二尖瓣狭窄患者术前、术后20min及术后24h血浆BNP浓度,与正常对照组(8例)比较,并将患者血浆BNP浓度与平均左房压(mLAP)等血流动力学参数作相关分析。结果:术前,二尖瓣狭窄患者血浆BNP水平显著高于正常对照组[(123.55±69.49)ng/L∶(16·39±7·64)ng/L,P<0·01)];且与mLAP呈显著正相关(r=0·441,P<0·05);BNP浓度在心房颤动(房颤)患者与窦性心律患者间差异无统计学意义(P>0·05)。术后,房颤患者血浆BNP浓度无明显改变[术前(111.62±53.41)ng/L,术后20min(122.04±68.70)ng/L,术后24h(106.11±56.19)ng/L,两两比较P>0·05];而窦律患者有显著下降[术前(128.66±75.96)ng/L,术后20min(88.59±61.99)ng/L,术后24h(43.39±26.70)ng/L,两两比较P<0·05)]。窦律患者中,术后20min的BNP变化(ΔBNP)与mLAP变化(ΔmLAP)呈显著正相关(r=0·696,P<0·01);术后24h的BNP变化(ΔBNP')与二尖瓣口面积(MVA)的扩大值(ΔMVA)及左房内径(LAD)的变化(ΔLAD)无相关性(分别r=0·048,P>0·05;r=-0·070,P>0·05)。结论:二尖瓣狭窄患者血浆BNP水平的升高和左房压升高显著相关。BNP是反映窦律患者球囊扩张术后左房压变化的敏感指标。     

B-type natriuretic peptide in lymphedema

Lymphedema often responds to compression therapy which can also cause undesirable cardiac overload if heart failure coexists. We hypothesized that the biomarker B-type natriuretic peptide (BNP) can be used to screen lymphedema patients for undetected cardiac dysfunction. We studied unselected consecutive patients with lymphedema to determine their BNP status and compared these data with those obtained from healthy subjects without known cardiovascular diseases. Out of a total of 305 subjects with lymphedema screened, 102 (33%) consented to take part in this study. The majority (87%) were female with a mean age of 60.5 +/- 13.2 (SD) years, and 47% had just lower limb swelling. The groups were equally divided between cancer and non-cancer related causes. There were 45 females and 4 males under 60 years old, and 44 female and 9 male patients over 60 years old. Median (IQR) BNP (ng/L) were as follows: <60 years females = 17.9 (15.2) (median [RR: 3 - 64] and males = 12.4 (14.7) [RR: 0.2 - 44], >60 years females = 35.8 (57.9) [RR: 2 -247)] and males = 47.2 (44.1) [RR: 2 - 238]. For this population, the BNP concentration 100 ng/L was adopted as the value to exclude heart failure. Using this definition, 7 lymphedema subjects had BNP concentrations of 120 (19.8) ng/L, and all were found to have cardiac abnormalities on echocardiography. This study demonstrated that 93% of unselected subjects with lymphedema had BNP concentrations that exclude a diagnosis of heart failure. Those subjects with elevated BNP were found on subsequent echocardiography to have cardiac abnormalities. The use of a BNP assay is of potential value in screening patients who are more likely to have cardiac failure. Indicative factors include bilateral leg swelling, over the age of 50 years, breathlessness, where there is no known cause for the swelling. A BNP assay using a BNP concentration threshold of 100 ng/L (29 pmol/L) will identify those patients who require more detailed investigations.     

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation

BACKGROUND: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). METHODS: Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). RESULTS: ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). CONCLUSIONS: In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.     

Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation

OBJECTIVES: This paper will describe associations between plasma natriuretic peptide levels and the severity and symptoms of mitral regurgitation (MR). BACKGROUND: A biochemical test that assisted grading of the severity of MR and the interpretation of symptoms would be of clinical value. METHODS: Forty-nine patients with isolated MR and left ventricular (LV) ejection fractions (EFs) of >55% underwent transthoracic echocardiography, assessment of symptoms, and measurement of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and its amino-terminal portion, N-BNP. RESULTS: The level of each natriuretic peptide rose with increasing severity of MR and with increases in left atrial (LA) dimensions (p < 0.001 for all comparisons), but no significant correlation existed between any natriuretic peptide and the LV dimensions or EF. Natriuretic peptide levels were higher in symptomatic MR (n = 16, BNP geometric mean 16.9 [95% confidence interval (CI) 13.3 to 21.4] pmol/l) compared with asymptomatic MR (n = 33, BNP 7.1 [95% CI 6.0 to 8.4] pmol/l, p < 0.001), and higher in asymptomatic MR than in normal controls (n = 100, BNP 5.3 [95% CI 4.8 to 5.8] pmol/l, p < 0.0001). These differences were similar for N-BNP and ANP and remained statistically significant (p < 0.05) after adjustment for echocardiographic measures of LV function and severity of MR. Both the sensitivity and the specificity for symptoms for the natriuretic peptides (area under receiver-operator characteristic curve for BNP = 0.90, N-BNP = 0.89, ANP = 0.89) were similar to the MR score (0.88) and greater than for LA dimension (0.81), vena contracta width (0.82), and LV end-systolic dimension (0.63). CONCLUSIONS: Plasma natriuretic peptides levels increase with the severity of MR and are higher in symptomatic compared to asymptomatic patients, even when LV EF is normal.     

B-type natriuretic peptide in heart failure

PURPOSE OF REVIEW: This review focuses on recent literature pertaining to the role of B-type natriuretic peptide (BNP) in heart failure. RECENT FINDINGS: Heart failure is a common disorder that is associated with significant mortality and morbidity. The diagnosis of heart failure may at times be difficult when using conventional tools. The cardiac natriuretic peptides, particularly BNP, have evolved to be useful biomarkers in heart failure and other cardiovascular disorders. Recent studies have established a close association between plasma BNP and the amino-terminal fragment of the BNP prohormone (NT-proBNP) with the diagnosis of heart failure and independent prediction of mortality and heart failure events. Furthermore, preliminary data from randomized controlled trials suggest that knowledge of BNP and/or NT-proBNP level may optimize the management of patients with heart failure. Exogenous natriuretic peptide in the form of recombinant human BNP (nesiritide) has been shown to improve hemodynamics and dyspnea and is approved in the USA and several other countries for the management of patients with acute decompensated heart failure. The effect of nesiritide on clinical outcome, however, remains unclear. SUMMARY: When used in the appropriate clinical settings, BNP or NT-proBNP testing is extremely useful in establishing diagnosis and predicting prognosis in heart failure. Nesiritide holds promise in the management of patients with acute decompensated heart failure. Large-scale randomized controlled trials to evaluate BNP/NT-proBNP-guided therapy are currently in progress and studies of the impact of exogenous BNP on clinical outcomes in heart failure are likely to be forthcoming.     

B-type natriuretic peptide: beyond a diagnostic

The concept of the heart as an endocrine organ has been attractive since the discovery of atrial natriuretic peptide. This review focuses on the second discovered natriuretic peptide from the heart - B-type natriuretic peptide (BNP), widely used as a tool in the diagnosis of heart failure (HF). Controversy remains regarding its use as a therapeutic agent in HF. This article places into perspective some of the debate and provides insights into the therapeutics of BNP and the importance of its second messenger 3'5' cyclic guanosine monophosphate, which also is the second messenger for nitric oxide and is modulated by renal phosphodiesterases.     

脑钠素与原发性高血压

脑钠素(B-type natriuretic peptide,brain natri-uretic peptide,BNP)是一种由32个氨基酸组成的多肽物质,是继心钠素后利钠肽系统的又一个新成员。1988年首先由日本的Sudoh[1]从猪脑中分离出来,广泛分布于心、脑、肺、肾,主要由心室分泌,具有强大的排钠、利尿、扩血管作用。大量研究表明,血浆脑钠素水平是反映慢性心力衰竭(congestive heartfailure,CHF)的敏感指标,与心衰的严重程度成正比,并对心衰的预后有预测价值[2-5]。在急性心肌梗死(acute myocardial infarction,AMI)时监测脑钠素水平,对评价心梗严重程度、心功能及其预后有重…     

B-type natriuretic peptide in cardiovascular disease

Natriuretic peptide hormones, a family of vasoactive peptides with many favourable physiological properties, have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The rapid incorporation into clinical practice of bioassays to measure natriuretic peptide concentrations, and drugs that augment the biological actions of this system, show the potential for translational research to improve patient care. Here, we focus on the physiology of the natriuretic peptide system, measurement of circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-terminal BNP) to diagnose heart failure and left ventricular dysfunction, measurement of BNP and N-terminal BNP to assess prognosis in patients with cardiac abnormalities, and use of recombinant human BNP (nesiritide) and vasopeptidase inhibitors to treat heart failure.     

B型利钠肽与肝硬化性心肌病

肝硬化可并发心功能不全,目前认为是肝硬化特有的一种并发症,即肝硬化性心肌病.肝硬化性心肌病往往缺乏临床表现,容易为临床所忽视.B型利钠肽(BNP)是对早期心功能不全敏感性很高的神经内分泌激素,可早期预测心肌损伤和心功能不全.肝硬化时血浆BNP水平增高,与肝硬化的疾病严重程度相关,并预示了肝硬化性心肌病的存在.检测肝硬化患者的血浆BNP浓度,有利于早期发现肝硬化性心肌病的存在,以便早期进行预防和处理.