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.     

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。     

Plasma natriuretic peptides up to 2 years after acute myocardial infarction and relation to prognosis: an OPTIMAAL substudy

BACKGROUND: Few studies have compared the relative prognostic value of different natriuretic peptides after acute myocardial infarction (AMI). None has described peptide levels beyond the early post-AMI period. This study describes temporal profiles of 4 natriuretic peptides to 2 years after AMI and relationship with outcome. METHODS AND RESULTS: We assessed profiles of N-terminal proANP (N-ANP), B-type natriuretic peptide (BNP), N-terminal proBNP (N-BNP), and C-type natriuretic peptide (CNP) (study entry, 1 month, 1 year, and 2 years) in 236 patients with AMI complicated by clinical or radiologic evidence of heart failure. We assessed the prognostic value for baseline levels of each peptide for death or reinfarction. We observed distinct natriuretic peptide profiles. BNP and N-BNP levels were highest at baseline and fell thereafter. N-ANP levels increased from baseline to 30 days and fell thereafter. During follow-up (mean 938 days), 34 patients died and a further 25 suffered nonfatal AMI. Baseline natriuretic peptide levels did not have independent predictive power for outcome. N-BNP levels fell from baseline to 30 days in patients surviving to the end of follow-up (P = .005) but were similar at both times (P = .76) for those dying after 30 days. Age (P < .0005) and change in N-BNP from baseline to 30 days (P = .026) had independent predictive value for death after 30 days. CONCLUSION: N-ANP, BNP, N-BNP, and CNP show distinct plasma profiles after AMI. Failure of plasma N-BNP to fall in the 30 days after AMI indicates adverse prognosis.     

Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath

OBJECTIVES: This study sought to compare the utility of measurement of plasma brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (N-BNP) in the diagnosis of heart failure (HF) in patients with acute dyspnea. BACKGROUND: Plasma BNP is useful in differentiating HF from other causes of dyspnea in the emergency department. The N-terminal component of BNP has a longer half-life, and in HF increases in plasma N-BNP are proportionately greater. METHODS: We studied 205 patients (average age 70 +/- 14 years) presenting to the emergency department with acute dyspnea. Brain natriuretic peptide was analyzed using a point-of-care test and two locally developed radioimmunoassays. N-terminal BNP was measured using a locally developed radioimmunoassay and a commercially available assay. Final diagnosis of HF was adjudicated by two cardiologists. RESULTS: Patients with HF (n = 70) had higher mean levels of both hormones by all assays (p < 0.001 for all). Results with all assays correlated closely (r values between 0.902 and 0.969). Subjects with left ventricular (LV) dysfunction or left-sided valvular disease but no HF had intermediate levels of BNP and N-BNP (lower than subjects with HF, and higher than subjects without HF with no LV dysfunction or left-sided valvular disease) (p < 0.01 for all). Using optimum cut-offs, specificity for the diagnosis of HF ranged between 70% and 89% (highest for the N-BNP assays). Sensitivity ranged between 80% and 94% (highest for the point-of-care BNP assay). CONCLUSIONS: Measurement of BNP or N-BNP is useful in the diagnosis of HF in acute dyspnea. Commercially available assays compare favorably with well-validated laboratory assays. Differences in sensitivity and specificity may influence the assay choice in this setting.     

Reference ranges for natriuretic peptides for diagnostic use are dependent on age, gender and heart rate

BACKGROUND: Plasma natriuretic peptide levels may be useful in the diagnosis of heart failure. The available natriuretic peptide assays differ markedly in their performance characteristics. In addition, plasma levels are influenced by a number of factors including age and gender. AIMS: The aim of this study was to describe, in a healthy population, the influence of clinical and echocardiographic parameters on three natriuretic peptide moieties. METHODS: 1360 individuals were screened for the presence of left ventricular systolic dysfunction. We identified a cohort (n=720) of men aged 45-80 years (n=417) and women aged 55-80 years (n=303). None had history of cardiovascular disease or were taking any cardiovascular medication. All had normal echocardiographic and ECG findings. B-type (BNP), N-terminal pro-B-type (N-BNP) and N-terminal pro-Atrial (N-ANP) natriuretic peptides were assayed using in-house immunoluminometric assays. RESULTS: Of the considered clinical variables, only gender and heart rate (each P<0.005) were independently associated with levels of all three natriuretic peptides. Plasma levels of N-ANP (15%), BNP (25%) and N-BNP (75%) were higher in women compared to men. An increase in heart rate of 10 bpm corresponded to a reduction of 9% in N-ANP or BNP and a 15% reduction in N-BNP. Each 10 years of age was associated with 16% and 74% increase in ANP and N-BNP levels, respectively, but no increase in plasma BNP. Left ventricular ejection fraction could be assessed in 582 (81%) subjects and correlated positively with N-ANP (r(s)=6.48x10(-3), P<0.001) and BNP (r(s)=2.4x10(-2), P<0.001) but not N-BNP (P=0.405). No parameter of diastolic function was associated with any peptide level. CONCLUSIONS: In this healthy population, plasma levels of N-ANP, BNP and N-BNP were variably influenced by clinical covariates. While all three peptides were higher in women, only N-ANP and N-BNP were influenced by age. Levels of all peptides were inversely correlated with heart rate. Using this immunoluminometric assay, plasma BNP is not influenced by age, in contrast to N-ANP and N-BNP. In constructing normal ranges for diagnostic use, covariates such as age and gender must be considered, in addition to the format of assay being used.     

Comparison of plasma N-brain natriuretic peptide, peak oxygen consumption, and left ventricular ejection fraction for severity of chronic heart failure

We investigated whether a simple blood test of plasma N-brain natriuretic peptide (N-BNP), compared with echocardiographic left ventricular ejection fraction (LVEF), both measured at rest, correlated well with aerobic exercise capacity (peak oxygen consumption [VO₂]) in patients with chronic heart failure. Plasma N-BNP was found to significantly correlate with peak VO₂ (p <0.001) and exercise duration (p = 0.001), whereas LVEF showed very poor correlations with peak VO₂ and exercise duration (both p >0.3). The results suggest that N-BNP actually reflects functional cardiac impairment better than LVEF.     

Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations.

BACKGROUND: A range of neurohumoral substances have been suggested as diagnostic markers in heart failure. It is, however, undetermined which marker has the greatest diagnostic potential, and whether additional information is gained by a comprehensive neurohumoral evaluation. AIMS: The purpose of the study was to compare the value of epinephrine, norepinephrine, renin activity, aldosterone (ALDO), atrial (ANP) and brain (BNP) natriuretic peptides, arginine-vasopressin and endothelin (ENDO) as markers for left ventricular (LV) dimensions and ejection fraction (LVEF) in patients with systolic heart failure. METHODS: Forty-eight patients with symptomatic heart failure were examined with blood samples and magnetic resonance imaging along with 20 age and gender-matched normal controls. RESULTS: In multiple regression analyses, BNP was the strongest independent marker for LV end-diastolic (r=0.71, P<0.0001), and end-systolic (r=0.75, P<0.0001) volumes, myocardial mass (r=0.69, P<0.0001), and LVEF (r=-0.78, P<0.0001). ANP was a supplementary independent marker for LV end-diastolic (r=0.76, P<0.0001) and end-systolic (r=0.78, P<0.0001) (ANP and BNP combined) volumes, ENDO for myocardial mass [r=0.71, P<0.0001 (ENDO/BNP)], and ALDO for LVEF [r=-0.81, P<0.0001 (ALDO/BNP)]. CONCLUSION: BNP is the strongest marker for LV dimensions and LVEF in patients with systolic heart failure. However, a comprehensive neurohumoral evaluation may add some information to the diagnosis.     

Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure

Beta blockers are known to suppress renin release in hypertension and in patients taking angiotensin-converting enzyme (ACE) inhibitors. This study sought to explore the effect of additional beta blockade on neurohumoral modulation in patients with severe heart failure (HF) who received ACE inhibitors. Forty-nine patients with chronic HF who received ACE inhibitors were given metoprolol 50 mg or carvedilol 25 mg twice daily after a 4-week dose titration period in addition to standard therapy in a prospective trial. Samples of plasma renin activity (PRA), aldosterone, aminoterminal B-type natriuretic peptide (N-BNP), and atrial natriuretic peptide (ANP) were taken at baseline and at 4, 12, and 52 weeks after starting therapy. Treatment with either beta blocker significantly lowered PRA at 4 weeks compared with baseline (-2.0 +/- 0.6 nmol/L/hour, p = 0.006), but at 12 weeks, PRA had reduced to -1.1 +/- 0.6 nmol/L/hour (p = 0.08), but at 52 weeks, it was not significantly different from baseline (+1.05 +/- 0.6 nmol/L/hour, p = 0.13). Aldosterone levels did not change significantly from baseline at 4 or 12 weeks, although there was a nonsignificant trend for lower levels at 52 weeks (baseline 232 +/- 154 pmol/L, 52 weeks 192 +/- 100 pmol/L, p = 0.09). There was significant reduction in N-BNP and ANP together with an improvement in symptom and left ventricular systolic function at 1-year follow-up. These results indicate that the suppressive effect of beta blockers on PRA in patients with HF taking ACE inhibitors is temporary, and that there is no significant effect on serum aldosterone levels.     

Impact of oxidative stress on plasma adiponectin in patients with chronic heart failure

BACKGROUND: Adiponectin, which is an adipocyte-specific cytokine that has a beneficial effect in cardiovascular disease, may be downregulated by oxidative stress in patients with chronic heart failure (CHF). Plasma levels of both adiponectin and biomarkers of oxidative stress are increased and have a prognostic impact on CHF patients. METHODS AND RESULTS: The plasma adiponectin level was measured in 116 patients with CHF (left ventricular ejection fraction <45%) who underwent cardiac catheterization, and these findings were compared with the atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) levels, hemodynamic parameters and plasma oxidized low-density lipoprotein (oxLDL) level as a marker of oxidative stress. There was no correlation between the plasma adiponectin level and hemodynamic parameters, but there was a positive correlation with the cardiac natriuretic peptides [ANP (r(s)=0.464, p<0.0001) or BNP (r(s)=0.489, p<0.0001)]. There was a significant negative correlation between plasma adiponectin level and oxLDL (r=-0.245, p=0.0079). In the stepwise multivariate analysis, a high level of natriuretic peptide (log BNP) (p=0.0098), and a low level of oxLDL (p=0.0105) were independent predictors of a high adiponectin level in CHF patients. CONCLUSIONS: The plasma adiponectin level is regulated not only by cardiac natriuretic peptides but also by oxidative stress in patients with CHF.     

Gender-specific risk stratification with B-type natriuretic peptide levels in patients with acute dyspnea: insights from the B-type natriuretic peptide for acute shortness of breath evaluation study.

OBJECTIVES: We examined whether B-type natriuretic peptide (BNP) levels allow gender-specific risk stratification in patients with acute dyspnea. BACKGROUND: B-type natriuretic peptide levels determined in patients with heart failure correlate with the severity of disease and prognosis. Gender differences in risk prediction are poorly examined. METHODS: The BASEL (B-type natriuretic peptide for Acute Shortness of Breath Evaluation) Study enrolled 190 female and 262 male patients presenting with acute dyspnea. RESULTS: At 24 months, cumulative mortality was comparable in women and men (38% vs. 35%, p = 0.66). Cox regression analyses revealed that BNP levels >500 pg/ml indicated a 5.1-fold increase in mortality for women (95% confidence interval [CI] 3.0 to 8.5, p < 0.001) versus a 1.8-fold increase in men (95% CI 1.2 to 2.6; p = 0.007). The area under the receiver-operating characteristic curve (AUC) for BNP to predict death was significantly higher in female (AUC: 0.80, 95% CI 0.73 to 0.86) than in male patients (AUC: 0.64, 95% CI 0.57 to 0.71; p = 0.001 for the comparison of AUC(women) versus AUC(men)). Women with BNP >500 pg/ml displayed a higher mortality as compared with men with BNP >500 pg/ml (68% vs. 46%, p = 0.015). Interaction analysis showed that BNP is a stronger predictor of death in women than in men (p = 0.008). CONCLUSIONS: B-type natriuretic peptide plasma levels seem to be stronger predictors of death in women than in men.     

Cardiac hormones as diagnostic tools in heart failure

In patients with heart failure, plasma levels of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and the N-terminal fragments of their prohormones (N-ANP and N-BNP) are elevated, because the cardiac hormonal system is activated by increased wall stretch due to increased volume and pressure overload. Patients suspected of having heart failure can be selected for further investigations on the basis of having an elevated plasma concentration of N-ANP, BNP, and N-BNP. High levels of cardiac hormones identify those at greatest risk for future serious cardiovascular events. Moreover, adjusting heart failure treatment to reduce plasma levels of N-BNP may improve outcome. Cardiac hormones are most useful clinically as a rule-out test. In acutely symptomatic patients, a very high negative predictive value is coupled with a relatively high positive predictive value. Measurement of cardiac hormones in patients with heart failure may reduce the need for hospitalizations and for more expensive investigations such as echocardiography. However, there have also been conflicting reports on the diagnostic value of cardiac hormones, they are not specific for any disease, and the magnitude of the effects of age and gender on BNP in the normal subgroup suggests that these parameters need to be considered when interpreting cardiac hormone levels.     

Identification of previously undiagnosed left ventricular systolic dysfunction: community screening using natriuretic peptides and electrocardiography

AIMS: We examined strategies to improve the positive predictive value of natriuretic peptides in screening for undiagnosed left ventricular systolic dysfunction (LVSD) in the community. METHODS AND RESULTS: The value of B-type(BNP), N-terminal proB-type (N-BNP) and N-terminal proAtrial(N-ANP) natriuretic peptides was prospectively assessed in 1360 subjects (45-80 years) together with echocardiography and electrocardiography. Seventeen individuals had definite and 13 had borderline, LVSD. Receiver-operating-characteristic (ROC) curve analysis showed the superiority of BNP (ROC areas 0.942 for definite LVSD, P<0.03; 0.934 for borderline LVSD, P<0.003) compared to N-BNP or N-ANP. Peptide levels, major ECG abnormality and ischaemic heart disease (IHD) history were independent predictors of LVSD. Logistic regression modelling incorporating these factors improved ROC areas for all natriuretic peptides. The specificity of all natriuretic peptides is enhanced by consideration of these factors. CONCLUSIONS: In population screening for definite LVSD, consideration of plasma natriuretic peptide levels together with the presence of major ECG abnormalities and IHD history reduces by a factor of six (in comparison to consideration of plasma natriuretic peptide levels in isolation) the number of subjects requiring echocardiography to detect one case of LVSD (for BNP, 44 falling to seven). Similar improvements were evident for N-ANP and N-BNP. Inclusion of major ECG abnormalities and IHD history improves the performance of any natriuretic peptide used in screening programmes for ruling in undiagnosed LVSD.     

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.     

Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure: comparison with enalapril

BACKGROUND: In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. METHODS AND RESULTS: Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II the delayed heart/mediastinum count ratio was significantly increased (2.0+/-0.07 vs 2.15+/-0.07, p=0.013) and the washout rate was significantly decreased (33.0+/-1.4 vs 30.5+/-1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. CONCLUSION: These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP.     

Association of myocardial fibrosis, B-type natriuretic peptide, and cardiac magnetic resonance parameters of remodeling in chronic ischemic cardiomyopathy

The left ventricular (LV) scar size detected by cardiac magnetic resonance (CMR) imaging in ischemic cardiomyopathy (IC) has been correlated with mortality. However, the associations among myocardial fibrosis, ventricular geometry, and physiologic measures of myocardial performance remain to be defined. A retrospective analysis of patients with stable chronic IC (LV ejection fraction ≤50%) who underwent CMR imaging from 2004 to 2010 and had plasma B-type natriuretic peptide (BNP) measured within 14 days of the CMR study was undertaken. A total of 38 patients met the criteria (mean age 66 ± 10 years; 31 men [82%]). The duration of IC was 67 ± 69 months. The CMR characteristics included LV dilation (LV end-diastolic dimension 62 ± 8 mm) and severe systolic dysfunction (LV ejection fraction 28 ± 11%). The average quantitated myocardial fibrosis was 20 ± 12% of the LV mass. When stratified by fibrotic mass, increased myocardial scar size was associated with increased LV cavity size (p = 0.007), lower LV ejection fraction (p = 0.04), and higher BNP (p = 0.013). In comparison, when stratified by median BNP (475 pg/ml), an elevated BNP level was associated, not only with LV size, function, and degree of fibrosis, but also with increased meridional wall stress (p = 0.002) and worse New York Heart Association functional class (p = 0.006). In conclusion, in chronic IC, quantitated myocardial fibrosis is associated with CMR structural and functional LV abnormalities. Elevated BNP levels are related to high-risk structural and functional CMR abnormalities and wall stress and functional status. Myocardial fibrosis appears to be related to plasma BNP through the processes of ventricular remodeling.     

Plasma levels of brain natriuretic peptide in various forms of obstruction to the left ventricular outflow tract

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between plasma concentrations of brain natriuretic peptide (BNP) and the type or degree of stenosis in the left ventricular outflow tract (LVOT). METHODS: The relationship between BNP plasma level and pressure gradient (PG) in the LVOT and LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled ventricular septum. Three patients with AS showed LV systolic dysfunction (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak-systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic arterial pressure. RESULTS: In AS patients without LV systolic dysfunction and HOCM patients, there was a significant positive correlation between BNP and LVPSP (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p = 0.001), but no correlation was found between BNP and LVWth in patients with HOCM. In AS patients including systolic LV dysfunction, BNP was negatively correlated with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and LVEF in patients with HOCM. CONCLUSION: These results suggest that BNP level is closely associated with severity of stenosis in patients with HOCM, but mainly with severity of stenosis and also degree of LV systolic dysfunction in patients with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with uneven myocardial hypertrophy).     

Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure.

OBJECTIVES: The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis. BACKGROUND: Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling. METHODS: We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc., Cleveland, Ohio) in 140 patients with chronic systolic HF (LV ejection fraction <35%) and examined the plasma MPO levels' relationships with echocardiographic indexes of systolic and diastolic performance, as well as long-term clinical outcomes (death, cardiac transplantation, or HF hospitalization). RESULTS: Within the overall cohort, increasing plasma MPO levels were associated with increasing likelihood of more advanced HF (restrictive diastolic stage, right ventricular systolic dysfunction > or =3+, and tricuspid regurgitation area > or =1.8 cm2). Plasma MPO levels were predictive of long-term clinical outcomes (risk ratio [95% confidence interval] = 3.35 [1.52 to 8.86]), even after adjustment for age, LV ejection fraction, plasma B-type natriuretic peptide (BNP), creatinine clearance, or diastolic stage. In receiver-operator characteristic curve analyses, addition of MPO to BNP testing augmented the predictive accuracy of future adverse clinical events (area under the curve 0.66 for BNP only [chi-square test = 12.9, p = 0.0003], and 0.70 for BNP plus MPO [chi-square test = 15.87, p = 0.0004]). CONCLUSIONS: In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes.     

Amino-terminal pro-C-type natriuretic peptide in heart failure

The levels and pathophysiological role of amino terminal C-type natriuretic peptide in heart failure are unknown. The potential of plasma amino-terminal C-type natriuretic peptide (N-CNP) as a marker of cardiac function was investigated in symptomatic patients. In 305 patients with recent-onset dyspnea and/or peripheral edema, presenting to primary care, assay of plasma amino-terminal C-type natriuretic peptide and other plasma vasoactive hormones was conducted together with echocardiography. Heart failure was diagnosed in 77 (of the 305) patients by rigorous application of predefined criteria. Plasma amino-terminal C-type natriuretic peptide concentrations were elevated in patients with heart failure, and by univariate analysis were related to age, renal function, and other hormones. On multivariate analysis, tertile of plasma N-CNP interacted with tertile of plasma amino-terminal B-type natriuretic peptide to predict heart failure independent of age, gender, renal function, or echocardiographic left ventricular fractional shortening. N-CNP showed significant relations to concurrent plasma CNP, atrial natriuretic peptide (ANP), N-ANP, B-type (or brain) natriuretic peptide (BNP), N-BNP, endothelin-1, and adrenomedullin but not to echocardiographic indicators of left ventricular systolic function. Plasma amino-terminal C-type natriuretic peptide is elevated in heart failure and is related to other plasma hormones in heart failure. These findings suggest a possible compensatory response from the peripheral vasculature to heart failure by an endothelium-based vasodilator peptide and mandate further exploration of the role of C-type natriuretic peptide in this condition.     

The potential to improve primary prevention in the future by using BNP/N-BNP as an indicator of silent 'pancardiac' target organ damage: BNP/N-BNP could become for the heart what microalbuminuria is for the kidney.

Brain natriuretic peptide (BNP) or N-terminal pro-BNP (N-BNP) now appears to be the best independent predictor of cardiovascular mortality over and above the conventional ones like blood pressure. This may be because a high BNP/N-BNP is identifying any form of asymptomatic cardiac target organ damage (TOD) [especially silent ischaemia, left ventricular hypertrophy (LVH), left atrial dilatation/atrial fibrillation (LAD/AF) and LV systolic dysfunction (LVSD)]. There are strong hints that BNP/N-BNP will also identify those who are going to develop LVH, LAD/AF, and LVSD in a few years' time. Thus, the prospects are good that BNP/N-BNP could be used to identify 'pancardiac' TOD, even when it is silent and that this information could be 'harnessed' to improve primary prevention. BNP/N-BNP could become to the heart what microalbuminuria is to the kidneys, i.e. an indicator of early, silent TOD.     

Outpatient Management of Heart Failure

With the increasing prevalence of heart failure, the greater spectrum of proven therapies, the broader spectrum of cardiac dysfunction qualifying for treatment and the recognition that heart failure is difficult to diagnose, the need for an indicator of both the diagnosis and the efficacy of treatment in this condition is clear. Plasma concentrations of the B-type natriuretic peptides are related to cardiac function and cardiovascular prognosis. They parallel hemodynamic indicators of cardiac dysfunction and may therefore act as indicators of the adequacy of therapy. In the one published trial of outpatient treatment of heart failure guided by plasma BNP, 69 patients (LVEF <40%, NYHA II–IV) were randomised to treatment according to plasma peptide levels or a clinical score. The primary end point of total cardiovascular events was reduced in BNP-guided patients (19 versus 54 events) with p < 0.001 in a multivariate analysis. The natriuretic peptides and particularly plasma BNP and aminoterminal proBNP promised to provide an objective guide for optimising treatment in heart failure.