Brain natriuretic peptide in diagnosis and treatment of heart failure

Currently we are in the midst of a chronic disease epidemic of congestive heart failure (CHF) worldwide. This epidemic is marked by a rapid rise in prevalent cases over the past decade that is due in part to the aging population and improved survival in patients with other cardiovascular conditions. At present there are 5 million Americans with congestive heart failure, with nearly 500000 new cases every year. To provide cost-effective treatment for patients with congestive heart failure, rapid and accurate differentiation of congestive heart failure from other causes of dyspnea must be accomplished. Although echocardiography is considered the gold standard for the detection of left ventricular dysfunction, it is expensive, is not always easily accessible, and may not always reflect an acute condition. B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted from the cardiac ventricles as a response to ventricular volume expansion, pressure overload, and resultant increased wall tension. BNP can be used in the diagnosis of CHF. However, the present American College of Cardiology/American Heart Association practice guidelines (2001) for the evaluation and management of CHF state that the role of blood BNP in the identification of patients with CHF remains to be fully clarified. We have discussed the role of BNP in the diagnosis and management of CHF.     

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction

Marked elevations of B-type natriuretic peptide （BNP） are not generally seen in patients with heart failure and preserved ejection fraction （HFpEF）. The objective of this study was to examine the clinical and laboratory characteristics of a large cohort of patients with HFpEF and markedly elevated BNP. A retrospective examination of 421 inpatients at a university hospital admitted with a diagnosis of HFpEF was performed. Clinical and echocardiographic data in 4 groups of patients with levels of BNP ≤ 100 pg/mL, 100-400 pg/mL, 400-1,000 pg/mL and 〉 1,000 pg/mL were compared. Patients with HFpEF and BNP 〉 1,000 pg/mL （28% of the population） were characterized by impaired renal function and greater use of anti-hypertensive medications. A subset of these patients with BNP 〉 1,000 pg/mL had normal renal function （21%） and were significantly older, more frequently female, and tended to have lower ejection fractions. Conversely, patients with HFpEF and BNP ≤100 pg/mL were younger and had preserved renal function. BNP was inversely related to the likelihood of subsequent admission for heart failure, but not to myocardial infarction or death. In conclusion： BNP 〉 1,000 pg/mL is seen in almost 1/3 of patients hospitalized with HFpEF. This elevation of BNP often reflects impaired renal function, but can also be seen in patients with preserved renal function but relatively impaired systolic function.     

Low levels of B-type natriuretic peptide predict poor clinical outcomes in patients with chronic and advanced heart failure

B-type natriuretic peptide (BNP) is a neurohormone produced mainly by ventricular myocytes in response to increased left ventricular end-diastolic pressure. Patients with acute decompensated heart failure often have elevated plasma BNP. However, recent clinical observations have demonstrated that in patients with advanced heart failure, the plasma level of BNP is lower than those with acute heart failure. We hypothesized that a lower circulating BNP level in patients with chronic and advanced heart failure is due to the exhaustion of the biosynthesis mechanisms and is associated with a poor outcome in these patients.     

B-type natriuretic peptide in reversible myocardial ischaemia

BACKGROUND: Coronary heart disease is associated with increased B-type natriuretic peptides (BNPs), and, although controversial, may cause exaggerated exercise-induced BNP secretion. We investigated BNP in relation to reversible myocardial ischaemia. Materials and methods: Serum N-terminal proBNP (NT-proBNP) was measured before and after an exercise electrocardiogram test (ETT) in 14 patients with and 45 patients without exercise-induced myocardial ischaemia. Statistical analysis was carried out on logarithmically transformed data. Results, however, are pre-transformed data. RESULTS: NT-proBNP increased with exercise both in ETT-positive patients (mean (SD) 71.4 (41.2) v 76.8 (44.0) ng/l; p<0.001) and ETT-negative patients (54.0 (61.2) v 60.1 (69.0) ng/l; p<0.001). Pre-exercise and post-exercise NT-proBNP were higher (p<0.05) in ETT-positive than in ETT-negative patients. Incremental NT-proBNP was similar in ETT-positive (4.7 (4.2) ng/l) and ETT-negative (6.2 (8.6) ng/l) patients. CONCLUSION: Serum NT-proBNP concentrations are higher in patients with exercise-induced myocardial ischaemia than in those without. Exercise-induced electrocardiographic myocardial ischaemia, however, is not associated with exaggerated BNP secretion.     

Plasma B-type natriuretic peptide for early diagnosis of allograft rejection after renal transplantation

B-type natriuretic peptides are predominantly synthesized in the ventricular myocytes. This is the response to volume overload or increased stress to the ventricular wall. Plasma B-type natriuretic peptide levels are elevated in patients with chronic renal failure due to reduced glomerular filtration and/or increased myocardial biosynthesis. Allograft renal transplantation significantly reduces plasma B-type natriuretic peptide. Our previous clinical observations have demonstrated that acute allograft renal rejection is associated with a sudden increase in plasma B-type natriuretic peptides. We hypothesized that plasma B-type natriuretic peptide may be used as a sensitive and specific biomarker for clinical diagnosis of acute allograft renal rejection.     

The diagnostic accuracy and utility of a B-type natriuretic peptide test in a community population of patients with suspected heart failure

BACKGROUND: National guidelines suggest the use of natriuretic peptides in suspected heart failure but there have been no studies comparing assays in primary care.Aim:To test and compare the diagnostic accuracy and utility of B-type natriuretic peptide (BNP) and N-terminal B-type natriuretic peptide (NT proBNP) in diagnosing heart failure due to left ventricular systolic dysfunction in patients with suspected heart failure referred by GPs to one-stop diagnostic clinics. DESIGN OF STUDY: Community cohort, prospective, diagnostic accuracy study. SETTING: One-stop diagnostic clinics in Darlington Memorial and Bishop Auckland General Hospitals and general practices in South Durham. SUBJECTS: Two hundred and ninety-seven consecutive patients with symptoms and signs suggestive of heart failure referred from general practice. METHOD: The study measured sensitivity, specificity, positive and negative predictive values (PPV, NPV), and area under receiver operating characteristic curve for BNP (near patient assay) and NT proBNP (laboratory assay) in diagnosis of heart failure due to left ventricular systolic dysfunction. The NPV of both assays was determined as a potential method of reducing the number of referrals for echocardiography. RESULTS: One hundred and fourteen of the 297 patients had left ventricular systolic dysfunction (38%). At the manufacturer's recommended cut-off of 100 pg/ml BNP gave a NPV of 82%. BNP performed better at a cut-off of 40 pg/ml with a NPV of 88%. At a cut-off of 150 pg/ml, NT proBNP gave a NPV of 92%. Using cut-offs of 40 pg/ml and 150 pg/ml for BNP and NT pro-BNP, respectively, could have prevented 24% and 25% of referrals to the clinic, respectively. CONCLUSIONS: In this setting, NT pro-BNP performed marginally better than BNP, and would be easier to use practically in primary care. A satisfactory cut-off has been identified, which needs validating in general practice. NT pro-BNP could be used to select referrals to a heart failure clinic or for echocardiography. This process needs testing in real-life general practice.     

Atrial natriuretic peptide during acute treatment of congestive heart failure

Atrial natriuretic peptide (ANP) induces potent diuretic/natriuretic, vasorelaxing and aldosterone inhibitory effects. Increased plasma levels in congestive heart failure (CHF) have been reported. The aim of this study was to investigate plasma immunoreactive ANP (ir-ANP) levels during acute treatment of CHF. Seven patients with CHF underwent cardiac catheterization. Ir-ANP plasma levels were followed up to two h after administration of an orally given phosphodiesterase inhibitor (Milrinone); a substance with positive inotropic and peripheral vasodilating properties. In all patients cardiac output increased and cardiac filling pressures decreased markedly. Initially high ir-ANP plasma levels decreased. Our patients did not have an increased blood volume. It is concluded that plasma ir-ANP levels in the pulmonary artery rapidly decrease when atrial pressure is reduced. These data suggest that atrial pressure is the major determinant for release of ir-ANP in man and that the ability to respond quickly to changes in cardiac filling pressures is maintained in patients with severe CHF. Plasma ir-ANP levels may also become useful as an index of the degree of heart failure and serve as a tool in monitoring response to drug therapy.     

B-type natriuretic Peptide predicts clinical presentations and ventricular overloading in patients with heart failure

Brain natriuretic peptide (BNP), a neurohormone secreted from the ventricular myocardium in response to hemodynamic load/wall stress, in congestive heart failure (CHF). This study was performed to evaluate the correlation between BNP level and clinical presentations and hemodynamic parameters obtained by echo-Doppler (echo-Doppler) analysis, and its relation with disease severity and ventricular load/wall stress. CHF patients (n=246) were subgrouped by clinical presentations and echo-Doppler findings into 4 groups: diastolic HF only, chronic HF, acute HF, and chronic HF with acute exacerbation. A BNP level of 81.2 pg/ml showed a sensitivity/ specificity of 53.3%/98.4% for detecting CHF (AUC, 0.882; p < 0.0001), and was found to be closely related with the NYHA classification (p < 0.0001). Log BNP was related with LVEF (r2=0.3015, p < 0.0001) and the Meridional wall stress index (r2=0.4052, p < 0.0001). The difference between the BNP levels of the subgroups and BNP control was significant (p < 0.0001), except between the HF group and the controls; control (n=114, 20.9 +/- 31.4 pg/ml), only diastolic HF (n=84, 89.8 +/- 117.6 pg/ml), chronic HF (n=60, 208.2 +/- 210.2 pg/ml), acute HF (n=28, 477.9 +/- 498.4 pg/ml), chronic HF with acute exacerbation (n= 74, 754.1 +/- 419.2 pg/ml). The BNP level was significantly higher in the only diastolic HF group than in the asymptomatic control group with diastolic dysfunction (89.8 +/- 12.8 vs. 22.8 +/- 5.1 pg/ml, p < 0.0001). BNP may be a good indicator for the differential diagnosis of a broad spectrum of heart failures. And, elevated BNP might help to diagnose diastolic HF in patients with diastolic dysfunction.     

Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure

To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.     

Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

OBJECTIVE:

We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure.

METHODS:

We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01857999","term_id":"NCT01857999"}}NCT01857999.

RESULTS:

We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm⁵.m², cardiac index 2.8 L/min.m², and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018). No significant difference was observed in the hemodynamic measurements.

CONCLUSION:

Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence.     

Relationship between B-type natriuretic peptide serum level,echocardiographic TEI index and the degree of diastolic dysfunction in patients with heart failure with preserved systolic function

Introduction

The growing number of heart failure (HF) patients is becoming an important issue in cardiology. B-type natriuretic peptide (BNP) is a recognized marker of HF, including in patients with preserved systolic function. The TEI index is an indicator of left ventricular function. The aim of the study was to evaluate the relationship between BNP serum level, TEI index and the degree of diastolic dysfunction in patients with HF symptoms and preserved systolic function.

Material and methods

Hundred patients with arterial hypertension and preserved systolic function were enrolled in the study. The study group consisted of 51 individuals with impaired diastolic function and HF symptoms. Fourty-nine hypertensive individuals without HF symptoms were assigned to the control group. B-type natriuretic peptide and echocardiographic examination were performed. Patients were divided into 4 subgroups – with normal diastolic function, impaired relaxation, pseudonormalization and restriction.

Results

Median value of BNP in patients with normal diastolic function was 28.36 pg/ml, 87.10 pg/ml in patients with impaired relaxation, 212.75 pg/ml and 461.56 pg/ml in the pseudonormalization and restriction group respectively (p < 0.0001). The median value of the TEI index was: 0.386 in patients with normal diastolic function, 0.507 in individuals with impaired relaxation, 0.639 and 0.725 in the pseudonormalization and restriction group respectively. All the differences were statistically significant (p < 0.0001). A significant positive correlation (r = 0.80, p < 0.001) between BNP and the TEI index was found.

Conclusions

In hypertensive patients with HF symptoms and preserved left ventricular systolic function a highly significant increase in BNP serum level and in the TEI index values related to the deterioration of diastolic dysfunction was found.     

B-type natriuretic peptide levels and continuous-flow left ventricular assist devices

We postulated that postoperative B-type natriuretic peptide (BNP) levels would be reflective of the degree of hemodynamic support rendered by various pump speeds settings (RPM) of continuous-flow left ventricular assist devices (LVADs). Twenty LVAD patients were evaluated prospectively (Jarvik 2000: n = 9, HeartMate II: n = 11). The mean age was 57.7 ± 14.9 years, and 14 were male. B-type natriuretic peptide levels were drawn while the patients were supported on LVADs at variable RPM settings. The RPM settings were correlated with the changes in BNP levels. Eleven patients underwent LVAD implantation for a lifelong support while the rest were as a bridge therapy to transplantation. Four patients required LVAD change out for various causes of pump failure. Postoperative BNP levels decreased dramatically with the initiation of LVAD support. The levels correlated inversely with the degree of hemodynamic support rendered at various RPM settings of the HeartMate II (p < 0.001). Overall, BNP levels decreased significantly in 2 days after RPM increase. We observed a significant inverse correlation between the postoperative BNP levels and the degree of LVAD support. The effective LVAD support seems to result in a marked reduction in BNP levels, and monitoring serial BNP levels may be helpful in managing patients supported on continuous LVAD.     

Changes of molecular forms of atrial natriuretic peptide after treatment for congestive heart failure

Summary In the present study, an attempt was made to clarify whether ANP molecular forms in the plasma of severe congestive heart failure patients differ from those in healthy persons and whether ANP molecular forms in the plasma of the patients were changed by successful treatment of cardiac disease.Twenty patients with congestive heart failure were treated at Kitasato University Hospital. They were classified as class III or IV by New York Heart Association criteria at the time of admission. Plasma ANP concentrations decreased after treatment from 356 ± 58.2 to 72.3 ± 14.8 pg/ml. The gel permeation chromatograms from the plasma of healthy persons showed low, or low and high molecular weight ANP peaks which correspond to the elution positions of authentic -ANP or ribonuclease A (mol.wt., 13.7 kdalton). In patients with severe congestive heart failure at a severe stage, middle molecular weight ANP consisted with the elution position of authentic-ANP was particularly noted in addition of low and high molecular weight ANP peaks. This middle molecular weight peak disappears in most of cases by successful treatment. Molecular forms in the plasma obtained from the coronary sinus and the inferior or superior vena cava were essentially the same.These results indicate that the middle molecular weight ANP supposed as-ANP may particularly be secreted in severe congestive heart failure patients.Abbreviations ANP atrial natriuretic peptide - NYHA criteria New York Heart Association criteria - SIADH Syndrome of inappropriate secretion of ADH