Plasma cardiac natriuretic peptides as biochemical markers of recurrence of atrial fibrillation in patients with mild congestive heart failure

To determine changes in plasma brain natriuretic peptide (BNP) after direct current cardioversion (DC) and to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and BNP and the recurrence of atrial fibrillation (AF) after DC in patients with mild congestive heart failure (CHF), plasma ANP and BNP were measured before and after DC in 71 patients with mild CHF and then followed. In 65 patients with successful DC, both ANP and BNP decreased 15 min after DC. Cox stepwise multivariate analysis among 14 variables such as age, history of AF, echocardiographic parameters, medication and ANP and BNP revealed that only low ANP (p=0.005) and high BNP before DC (p=0.0002) were independent predictors of recurrent AF. A ratio of ANP to BNP less than 0.44 was a significant risk factor for AF recurrence by Kaplan-Meier analysis (p=0.02). BNP began to decrease immediately after successful DC. High BNP and relatively low ANP compared with BNP were independent risk factors of AF recurrence in patients with mild CHF.     

Cardiac and plasma atrial natriuretic factor in experimental congestive heart failure

The cardiac and plasma levels of immunoreactive (IR-) atrial natriuretic factor (ANF) in cardiomyopathic hamsters with moderate and severe congestive heart failure were measured, compared with those of controls, and correlated by HPLC analysis of IR-ANF in atria, ventricles, and plasma and with the ultrastructure of atrial and ventricular cells. Congestive heart failure in the hamster produced a significant increase in plasma IR-ANF, a significant decrease in atrial IR-ANF, and a marked increase in ventricular IR-ANF. The HPLC pattern of IR-ANF was of the high mol wt type in atria and ventricles of control and cardiomyopathic animals. High mol wt forms of ANF appeared in the plasma of animals with severe congestive heart failure, but not in controls. Severe congestive heart failure produced a tremendous increase in the size of the Golgi complex, with a decrease in the number and size of secretory granules in atrial cardiocytes. Ventricular cardiocytes also showed a less marked increase in the size of the Golgi complex. Secretory-like granules indistinguishable from lysosomes were present in about 1% of ventricular cardiocytes of control hamsters; in hamsters with severe congestive heart failure, secretory granules, identical to those of atrial cardiocytes, were present in greater number in about 20% of ventricular cardiocytes. Immunocytochemistry (immunogold technique) revealed that secretory granules containing IR-ANF are not present in control ventricular cardiocytes but are localized in relatively large number in about 20% of ventricular cardiocytes in hamsters with severe congestive heart failure. These results suggest that the increased IR-ANF levels (including the high mol wt forms) in animals with congestive heart failure may come from hypersecretion of both atrial and ventricular cardiocytes.     

The natriuretic peptides in heart failure

Abstract. Synthesis and release of the natriuretic peptides rises incrementally with increasing degrees of cardiac dysfunction. The prime stimulus is intracardiac distending pressures with modulating inuences including age, gender, renal function and other aspects of neurohormonal status. Measurements of plasma natriuretic peptide concentrations and of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide, in particular, show promise in diagnosis of heart failure, risk stratication in those with known heart disease, and in adjustment of therapy. Recombinant B-type natriuretic peptide itself can be administered as a treatment. These diagnostic, prognostic and therapeutic applications of B-type natriuretic peptide require a considerable expansion beyond current evidence, but it appears likely that the true role of plasma peptide measurements and peptide administration will become rmly established within the coming 5 year period.     

Influence of atrial fibrillation on cardiac brain natriuretic peptide release during haemodynamic stress in heart failure

BACKGROUND: The determinants of release of brain natriuretic peptide (BNP) in heart failure (HF) are incompletely understood, particularly, the effect of heart rhythm and haemodynamic stress. AIMS: To investigate the effect of haemodynamic stress on cardiac BNP release in HF and differentiate this response for atrial fibrillation (AF) and sinus rhythm (SR). METHODS: In 18 HF patients (ejection fraction<40%, 9 in AF and 9 in SR) haemodynamics and BNP levels were measured from arterial and coronary sinus samples at baseline, after 10 min of 20 degrees passive head up tilt (HUT) and after 10 min of isometric handgrip (IHG) exercise. From these data, we calculated a transcardiac BNP gradient and compared results between the AF and SR cohort. RESULTS: During haemodynamic stress in both groups, there were no significance differences in left sided filling pressures. At baseline, there were no differences in BNP measurements between the SR and AF group. The transcardiac BNP gradient increased significantly in the SR (p=0.02) but not the AF cohort, after HUT. During IHG exercise, there was a significant decrease in cardiac BNP release in the AF cohort (p=0.03) but not the SR cohort. CONCLUSION: These data imply in HF, cardiac rhythm influences cardiac BNP release in response to haemodynamic stress.     

Significance of the system of atrial natriuretic peptides in heart failure and hypertension

This literature review presents current information on mechanisms of realization and action of natriuretic peptides in heart failure and hypertension. Significant role in degradation of natriuretic peptides belongs to neutral endopeptidase. Basing on theoretical and experimental data novel class of drugs - inhibitors of neutral endopeptidase - has been developed. The paper contains discussion of first results of the use of drugs from this class for the treatment of chronic heart failure.     

Subcutaneous administration of brain natriuretic peptide in experimental heart failure

OBJECTIVES: The objective of this investigation was to define for the first time the cardiorenal and humoral actions of repeated short-term administration of subcutaneous (SQ) brain natriuretic peptide (BNP) administration during the evolution of experimental heart failure. BACKGROUND: The rationale of this study was based on BNP as a vasodilating, natriuretic, renin-inhibiting and lusitropic peptide of cardiac origin. METHODS: First, we defined the cardiorenal and humoral responses to acute low and high dose (5 microg/kg or 25 microg/kg) of SQBNP in experimental heart failure to establish the acute efficacy of an SQ delivery. Second, we characterized the response to 10 days of repeated short-term administration of BNP during the evolution of experimental heart failure produced by rapid ventricular pacing. RESULTS: Plasma BNP and 3',5'-cyclic guanosine monophosphate rapidly increased and peaked at 30 min after acute SQBNP administration with increases in urinary sodium excretion, urine flow and renal blood flow in association with reductions in cardiac filling pressures. After 10 days of repeated short-term administration of SQBNP, cardiac output was increased and systemic vascular resistance and pulmonary capillary wedge pressure were decreased, as compared with untreated dogs with heart failure. CONCLUSIONS: This study demonstrated for the first time that repeated short-term administration of SQ BNP administration for 10 days during the evolution of left ventricular dysfunction in a canine model results in an improvement in cardiovascular hemodynamics. This investigation supports a potential novel strategy for the chronic administration of BNP in the therapeutics of heart failure.     

血浆脑钠肽与心房颤动

脑钠肽（brain natriuretic peptide,BNP）是一种心脏神经激素,其在心脏容量和压力超负荷引起心肌牵张时释放,参与体液平衡的调节.近些年来的研究表明BNP在心血管疾病的诊断、治疗及预后判定等方面均有重要的临床价值,尤其对于心力衰竭方面的应用更为广泛.近几年国外研究发现在心房颤动（atrial fibrillation,AF）患者中血浆BNP水平明显升高,表明其参与了AF发生的病理生理机制,至今国内的相关研究较少.本文就BNP与AF之间相关性研究的进展作一综述.     

血浆B型利钠肽与心房颤动研究进展

B型利钠肽（BNP）是一种心脏神经激素,其在心脏容量和压力超负荷引起心肌牵张时释放,参与体液平衡的调节。近年来的研究表明血浆BNP水平与心房颤动（AF）存在一定的相关性。该文就AF发作时血浆BNP的变化以及血浆BNP预测AF治疗的预后和预测AF相关的血栓事件进行综述。     

Bovine atrial natriuretic peptide in heart failure

The present study describes the concentration and molecular form of atrial natriuretic peptide (ANP) in Holstein dairy cattle with mild (bacterial endocarditis; BEC) or severe (dilated cardiomyopathy; DCM) heart failure. Significant increases in plasma concentration of ANP were observed in cattle with DCM (73.3 +/- 16.02 pmol/l, n = 4, P less than 0.01) and BEC (20.6 +/- 3.45 pmol/l, n = 7, P less than 0.05), when compared with those in control cattle (14.5 +/- 1.84 pmol/l, n = 12). The concentration of ANP in cattle with DCM was significantly (P less than 0.01) higher compared with that in cattle with BEC. Plasma concentration of ANP correlated significantly with right atrial pressure (r = 0.95, P less than 0.01) and left ventricular end-diastolic pressure (r = 0.84, P less than 0.01). Gel-permeation chromatography of ANP in plasma and the right atrium from control and cattle with BEC revealed a single peak corresponding to the elution position of authentic human ANP(99-126) in plasma, and two peaks corresponding to those of authentic human ANP(99-126) and pro-ANP in the atrial extract. In cattle with DCM, however, peaks corresponding to the elution positions of authentic human beta-ANP and/or pro-ANP were detected in addition to the peak corresponding to ANP(99-126). The content of ANP in the right atrium of cattle with DCM was significantly (P less than 0.05) increased compared with that in control cattle and those with BEC. The present study therefore suggests that the synthesis and secretion of ANP might be stimulated by atrial distention induced by increased atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性心力衰竭患者血浆肾上腺皮质激素及心钠素的含量及分析

目的:探讨慢性心力衰竭(CHF)患者血浆心钠素(ANP)、醛固酮(ALD)和皮质醇(COR)的含量变化及其意义。方法:检测54例CHF患者及16例同期住院无心衰患者的血浆ANP、ALD和COR含量,并评估血浆ANP 和ALD、COR的相关性。结果:CHF患者血浆ANP和ALD水平明显高于对照组(P<0.05),且与CHF程度有关, 而CHF患者血浆COR水平与对照组比较无显著性差异。CHF患者血浆ANP含量与ALD含量呈显著正相关(r= 0.474,P<0.001),而与COR含量无相关性(r=-0.071,P>0.05)。结论:血浆ANP和ALD含量有助于判断心衰的严重程度。     

Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration.

BACKGROUND. This study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure. METHODS AND RESULTS. The effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/min), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32 +/- 12 to 168 +/- 153 pg/ml (p less than 0.05) and from 32 +/- 9 to 137 +/- 113 pg/ml (p less than 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 +/- 295 pg/ml (p less than 0.05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332 +/- 121 to 407 +/- 113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2 +/- 2.5 versus 16.1 +/- 10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62 +/- 0.31 versus 0.24 +/- 0.16 pg/mg) was increased compared with that of controls (both p less than 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls. CONCLUSIONS. These data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF.     

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure

BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. AIMS: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. METHODS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. CONCLUSION: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function.     

Plasma atrial natriuretic peptide in carcinoid heart disease

Plasma atrial natriuretic peptide (ANP) concentration was determined and cardiac ultrasound studies were performed in 50 patients with malignant mid-gut carcinoid tumors. The extent of carcinoid-related heart disease varied among the patients. The patients with the most severe right-sided heart disease, who often had signs of right ventricular failure, had significantly (p less than 0.001) higher plasma ANP concentrations than either patients with less or no abnormal ultrasound findings or age- and sex-matched healthy control subjects. ANP levels were serially determined for 0.5 to 4 years (median 2.1) in 12 patients. The levels increased above the reference range in patients with clinical findings of right ventricular failure. In patients without cardiac decompensation the levels remained within the reference range. In 3 patients who had successful tricuspid and pulmonary valve replacements, signs and symptoms of right ventricular failure disappeared and plasma ANP levels declined and normalized. Five patients with progressive right ventricular failure and increasing plasma ANP levels during follow-up eventually died from cardiac decompensation. This study demonstrates the predictive value of serial determinations of plasma ANP in carcinoid heart disease. Such measurements can be an additional guide in the clinical management of these patients.     

慢性心力衰竭患者外周血中血浆肾素活性和利钠肽水平的变化及卡维地洛对其影响

目的　观察慢性心力衰竭 (心衰 )患者外周血中血浆肾素活性 (PRA)、心钠肽 (ANP)及脑钠肽 (N BNP)水平的变化及卡维地洛对其影响。方法　 6 0例慢性心衰患者随机分为常规治疗组 (血管紧张素转换酶抑制 +利尿剂 +地高辛 )和卡维地洛组 (常治疗药物 +卡维地洛 ) ,随访 12w ,采用放射免疫法测定二组治疗前后和 30例健康体检者 (正常对照组 )外周血中PRA、ANP、及N BNP水平。同时使用核素心室显像测定心衰患者左心室射血分数 (LVEF)。结果　心衰患者外周血中PRA、ANP及N BNP水平较正常对照组显著升高 ,其中ANP及N BNP水平在卡维地洛治疗前与LVEF负相关 ,在卡维地洛治疗后与LVEF密切相关 ,但PRA水平与LVEF无关。治疗后卡维地洛组外周血中PRA、ANP及N BNP水平较常规治疗组下降更明显。结论　外周血中ANP及N BNP水平在慢性心衰的病理生理机制中起着重要作用 ,甚至在 β受体阻滞剂治疗后仍可用于指导心衰患者的治疗。β受体阻滞剂能抑制心衰患者神经内分泌的过度激活。     

The role of natriuretic peptides in heart failure

Heart failure is a clinical syndrome associated with progressive cardiac, vascular, and renal dysfunction. Regardless of the initial injury, investigations have demonstrated that neurohormones play an important role in the complex multiorgan and cellular adaptations. Natriuretic peptides play a key role in this process, antagonizing the actions of the renin-angiotensin-aldosterone system, thus promoting vasodilatation and natriuresis. Other important physiologic properties of the natriuretic peptides are prolusitropic, sympathoinhibitory, antiproliferative, anti-ischemic, anti-inflammatory, and antioxidative. Administering exogenous natriuretic peptide is a US Food and Drug Administration-approved therapy for patients with advanced decompensated congestive heart failure. Also, measuring natriuretic peptide levels has diagnostic and prognostic value. More studies are needed to define the full potential of this unique family of endogenous peptides.     

The role of natriuretic peptides in heart failure

Heart failure is a clinical syndrome associated with progressive cardiac, vascular, and renal dysfunction. Regardless of the initial injury, investigations have demonstrated that neurohormones play an important role in the complex multiorgan and cellular adaptations. Natriuretic peptides play a key role in this process, antagonizing the actions of the renin-angiotensin-aldosterone system, thus promoting vasodilatation and natriuresis. Other important physiologic properties of the natriuretic peptides are prolusitropic, sympathoinhibitory, antiproliferative, anti-ischemic, anti-inflammatory, and antioxidative. Administering exogenous natriuretic peptide is a US Food and Drug Administration-approved therapy for patients with advanced decompensated congestive heart failure. Also, measuring natriuretic peptide levels has diagnostic and prognostic value. More studies are needed to define the full potential of this unique family of endogenous peptides.     

Plasma brain natriuretic peptide--an independent predictor of cardiovascular mortality in acute heart failure

PURPOSE: To examine the prognostic importance of both plasma atrial natriuretic and B-(brain natriuretic peptide) following an episode of acute heart failure. SUBJECTS AND METHODS: A prospective cohort of 91 patients admitted into hospital with acute heart failure were recruited. After initial in-hospital management plasma ANP and BNP levels were measured by radioimmunoassay, and echocardiography was performed on the same day. Patients were followed up for 12 months and the main outcome measure was cardiovascular death. RESULTS: Plasma ANP and BNP levels were significantly higher in patients who died of a cardiovascular cause within 12 months (P<0.001 and P<0.0001, respectively) or at 1-month (P<0.05 and P<0.001) after recruitment. By Kaplan-Meier estimated life-table curves, patients with above median plasma ANP or BNP levels had significantly higher 1-year mortality (42.5% vs. 11.6%, both P<0.005). By multivariate Cox proportional hazard regression analysis, the plasma BNP level was the most important prognostic factor predicting mortality (chi2 = 18.3, P<0.0001), followed by age (chi2 = 11.5, P<0.001). Other factors including ANP, left ventricular ejection fraction by M-mode echocardiography, pulmonary arterial pressure, sex, cause of heart failure as well as New York Heart Association class were not significant. CONCLUSION: A plasma BNP level has independent and at least short-term prognostic significance in patients admitted with acute heart failure. This non-invasive and readily available blood test should be considered for risk stratification in patients with acute heart failure.