Serum BNP, hs-C-reactive protein, procollagen to assess the risk of ventricular tachycardia in ICD recipients after myocardial infarction.

AIMS: Ventricular arrhythmia is the main cause of sudden cardiac death. Intracardiac strain, myocardial and extracellular matrix remodelling, and subsequent myocardial fibrosis are involved in arrhythmia pathogenesis. The present study investigates the relationship between cardiac fibrosis [procollagen type I aminoterminal peptide (PINP), procollagen type III aminoterminal peptide (PIIINP), TIMP1, membrane metalloproteinase I], pressure overload [brain natriuretic peptide (BNP)] inflammation [high sensitivity (hs)-C-reactive protein] serum markers, and the incidence of ventricular tachycardia (VT) in implantable cardioverter-defibrillators (ICD) recipients. METHODS AND RESULTS: Serum markers were collected in 121 patients implanted for spontaneous sustained VT and a prior history of myocardial infarction. VT incidence was obtained during ICD interrogation. Over a 1 year period, 38 patients (31%) experienced at least 1 VT. In a multivariate analysis, a left ventricular ejection fraction <0.35 (OR = 2.19, 95%CI 1.00-4.79, P = 0.049), an increased serum BNP (OR = 3.75, 95%CI 1.46-9.67, P = 0.014), an increased hs-C-reactive protein (OR = 3.2, 95%CI 1.26-8.10, P = 0.006), an increased PINP (OR = 3.71, 95%CI 1.40-9.88, P = 0.009), and a decreased PIIINP (OR = 0.21, 95%CI 0.08-0.59, P = 0.003) were associated with a higher VT incidence. CONCLUSION: In coronary artery disease patients: (1) BNP is not only a marker of left ventricular dysfunction, but also a marker of VT; (2) combined 'high PINP and low PIIINP' is a strong VT marker; and 3) inflammatory process is involved in VT pathogenesis.     

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.     

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.     

Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma

Thirty adult patients with non-Hodgkin's lymphoma who were planned to receive up to 8-10 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) to a cumulative doxorubicin dose of 400-500 mg/m2 were studied to evaluate the value of serial plasma atrial natriuretic peptide (ANP), N-terminal pro-ANP (NT-proANP) and brain natriuretic peptide (BNP) measurements in the early detection of doxorubicin-induced left ventricular dysfunction. Plasma levels of natriuretic peptides were measured before every treatment course and 4 wk after the last one. Cardiac function was monitored with serial radionuclide ventriculography. Twenty-eight patients were evaluable for cardiotoxicity. Clinical heart failure developed in 2 patients (7%). Left ventricular ejection fraction (LVEF) decreased from 58.0+/-1.3% to 49.6+/-1.7% (p <0.001). Plasma levels of ANP increased from 16.4+/-1.3 pmol/l to 22.7+/-2.4 pmol/l (p= 0.002), NT-proANP from 288+/-22 to 380+/-42 pmol/l (p = 0.019) and BNP from 3.3+/-0.4 to 8.5+/-2.0 pmol/l (p = 0.020). There was a significant correlation between the increase in plasma ANP and the decrease in LVEF (r = -0.447, p = 0.029), and a trend towards significance between the increase in NT-proANP and the decrease in LVEF (r=-0.390, p=0.059). The decrease in LVEF started very early and could already be seen after the cumulative doxorubicin dose of 200 mg/m2, whereas the increase in plasma natriuretic peptides was not evident until the cumulative doxorubicin dose of 400 mg/m2. Our results show that neuroendocrine activation - increased concentrations of plasma natriuretic peptides - occurs when left ventricular function has reduced substantially and its compensatory capacity has been exceeded resulting in atrial and ventricular overload. Thus, serial natriuretic peptide measurements cannot be used in predicting the impairment of left ventricular function. On the other hand, our study suggests that natriuretic peptides are useful in the detection of subclinical left ventricular dysfunction in patients receiving doxorubicin therapy.     

Valsartan decreases type I collagen synthesis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Fibrosis, as well as myocyte hypertrophy, is the major determinant of prognosis in hypertrophic cardiomyopathy (HCM). Valsartan, an angiotensin II type 1 receptor blocker, may improve myocardial fibrosis in patients with HCM. METHODS AND RESULTS: Twenty-three patients with HCM were randomly divided into 2 groups: 11 patients had valsartan added to conventional treatment (V group) and 12 patients received the conventional therapy (C group). Plasma concentrations of brain natriuretic peptide (BNP), troponin T (TnT), aldosterone (ALDO), procollagen type I (PIP) and procollagen type III aminoterminal peptide (PIIINP) were measured before and 12 months after this study. Left ventricular wall thickness (LVWT) and ejection fraction (LVEF) were measured by echocardiography. PIP was decreased in the V group (123.2+/-63.1 ng/ml to 102.8+/-37.6, p<0.05), but unchanged in C group (110+/-40.5 ng/ml to 119.9+/-47.4, p=0.22). ALDO concentration was unchanged in the V group (88.5+/-26.2 pg/ml to 91.2+/-26.8, p=0.27), and increased in C group (92.6+/-36.6 ng/ml to 116.0+/-33.3, p<0.05). BNP, PIIINP, and TnT were unchanged by the treatment. There was no significant difference between the 2 groups in either LVWT or LVEF. CONCLUSION: Valsartan suppresses the synthesis of type I collagen in patients with HCM and this was associated with suppression of the increase in ALDO.     

Why is the concentration of plasma brain natriuretic peptide in elderly inpatients greater than normal?

BACKGROUND: Higher than normal levels of plasma brain natriuretic peptide (BNP) are often found in elderly patients without overt heart failure. OBJECTIVE: To investigate the relationships between echocardiographic findings and levels of BNP in inpatients undergoing rehabilitation. METHODS: Ejection fraction, early-to-atrial peak transmitral velocity ratio (EAR) and left ventricular mass index were calculated. The patients were 34 men and 83 women, aged 83.4 +/- 0.8 years (mean +/- SEM). RESULTS: The average BNP was 3.5 times higher than the normal range. Age of and BNP level in patients with mild renal dysfunction were significantly greater than age of and BNP level in those with normal renal function. BNP level in patients with left ventricular hypertrophy (LVH) was higher than that in patients without LVH, and there was a positive correlation between left ventricular mass index and BNP level. However, there was no difference between BNP levels of patients with ejection fraction < 50% and > or = 50% (n = 27 versus 90, ejection fractions 40 versus 64%, BNP levels 22.6 +/- 4.0 versus 17.5 +/- 1.6 pmol/l). Moreover, even elderly inpatients without LVH, without cardiovascular diseases, with sinus rhythm, with normal renal function, and with normal left ventricle systolic function had BNP levels that were greater than normal (n = 21, BNP level 11.0 +/- 1.5 pmol/l). We measured EAR of 76 of 90 patients with normal left ventricle systolic function, and 72 of the 76 patients had EAR < 1. CONCLUSION: These results indicate that renal dysfunction and systolic dysfunction as well as cardiac hypertrophy and lower than normal diastolic function contribute to the elevation of BNP levels in elderly inpatients who do not have overt heart failure.     

Factors that influence the serum of atrial natriuretic peptide and brain natriuretic peptide concentrations--is there a specific marker for senile patients?

To evaluate factors that influence of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in elderly people, we measured those levels in 54 men and 148 women (84.4 +/- 0.5 years old), and looked for associations of ANP and BNP with clinical factors and echocardiographic variables [left ventricular mass index and atrial to-early peak transmitral velocity ratio (A/E)]. ANP and BNP levels were 1.6 and 6.5 times higher than average. Sex was not a significant factor. We also looked for a link between cardiac rhythms and levels of ANP and BNP. Patients with atrial fibrillation had significantly higher levels of ANP and BNP than did patients with sinus rhythm. ANP and BNP levels were abnormally high in patients with left ventricular hypertrophy (LVH). We could measured A/E in 161 of 202 subjects; 154 of 157 subjects with normal LV systolic function had A/E > 1 which indicates abnormally low in LV diastolic function. Moreover, abnormally high LV diastolic stress might have been present, because 124 of 202 subjects had aortic regurgitation. We divided the patients into two groups: those 65 to 75 years old, and those over 75 years old. The older patients had significantly higher levels of ANP and BNP even without LVH and without a difference in renal function. Furthermore, the older patients had significantly higher levels of BNP even without LVH, with normal renal function, with sinus rhythm, with normal LV systolic function, and in NYHA Class I or II. These data indicate that ANP and BNP levels in people with senility may be associated with the cardiac rhythm and with abnormally low renal function, myocardial hypertrophy, abnormally high cardiac volume, and abnormally low diastolic function.     

Atrial and brain natriuretic peptide and endothelin-1 concentration in patients with idiopathic arterial hypertension: the dependence on the selected morphological parameters

INTRODUCTION: The aim of the work was to study the maintenance of atrial and brain natriuretic peptide (ANP, BNP) and endothelin-1 (ET-1) in patients with idiopathic arterial hypertension and the relationships between cardiac morphological parameters and concentrations of examined peptides in group of patients with left ventricular hypertrophy (LVH). METHODS: Seventy-six patients were enrolled in the study: 21 patients with confirmed idiopathic arterial hypertension (group 1), 18 with idiopathic hypertension and eccentric hypertrophy (group 1a), 14 with idiopathic hypertension and concentric hypertrophy (group 1b), and 23 patients without arterial hypertension, organic heart disease, or chronic respiratory tract diseases (group 2 - control group). All subjects were submitted for echocardiographic evaluation. Posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDd), left atrium diameter (LAD), left ventricular mass index (LVMI), ejection fraction (EF), fractional shortening (FS), midwall shortening fraction (MWS), and relative wall thickness index (RWT) were studied. Concentrations of ANP(1-28), BNP, and ET-1 were determined with the use of radioimmunological kits (RIA). The obtained results were subjected to statistical analysis. RESULTS: A considerable increase of ANP and BNP was observed in all patients with hypertension (group 1) in comparison to patients without hypertension (group 2). Significant increases of ANP were found in groups 1a and 1b in comparison to group 1 and 2, as well as considerably increase of BNP in group 1b compared to groups 1, 1a, and 2. In the group of patients with hypertension (group 1), a significant increase in the concentration of ET-1 compared to group 2 was found. However, the concentrations of ET-1 in groups 1 and 2 were not statistically different. Significant differences in concentrations of ET-1 between groups 1a, 1b, and 1 and 2 were seen. Significant correlations were found between concentrations of ANP, BNP, ET-1 and morphological parameters: PWT, IVST, LVMI and RWT. In group 1b, a correlation between concentrations of ANP, BNP, MWS, and LAD was found. The multiple regression analysis showed that RWT independently correlates with concentrations of ANP and BNP, and the concentration of BNP is in closer relation to RWT than ANP. In the case of ET-1, the multiple regression analysis did not show that LVMI or RWT had any independent influence on secretion of ET-1 in patients with idiopathic hypertension and LVH. CONCLUSIONS: Increased concentration of ANP in patients with idiopathic hypertension may point to the coexistence of complications with type of LVH. High concentration of BNP may specifically suggest concentric LVH. This is important - especially if there are difficulties in interpretations of results of other clinical examinations. However, increased concentrations of ET-1 in the plasma of patients with hypertension and LVH should not be treated as an indicator of LVH degree.     

Bedside tests of B-type natriuretic peptide in the diagnosis of left ventricular diastolic dysfunction in hypertensive patients

AIMS: To investigate the value of B-type natriuretic peptide (BNP) in diagnosing left ventricular diastolic dysfunction in patients with hypertension. METHODS: The left ventricular diastolic function and plasma BNP levels were assessed prospectively in 135 hypertensive patients. RESULTS: The plasma BNP in patients with (n=61) and without (n=74) diastolic dysfunction was 122+/-105 and 18+/-16 pg/ml, respectively (p<0.001). Increased BNP levels were associated with systolic blood pressure (p<0.05), left ventricular mass index (p<0.001), the E/A ratio of transmitral flow (p<0.01) and the isovolumic relaxation time (p<0.01). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis of diastolic dysfunction revealed an area under the curve (accuracy) of 0.904 (p<0.01). Using a cut-off value of >40 pg/ml, the sensitivity and specificity of plasma BNP in diagnosing left ventricular diastolic dysfunction were 79% and 92%, respectively. CONCLUSIONS: The plasma BNP levels in patients with hypertension are closely related to left ventricular hypertrophy and filling impairment. Plasma BNP may be used to facilitate the diagnosis of left ventricular diastolic dysfunction.     

Atrial and Brain Natriuretic Peptide and Endothelin-1 Concentration in Patients with Idiopathic Arterial Hypertension: The Dependence on the Selected Morphological Parameters

Introduction. The aim of the work was to study the maintenance of atrial and brain natriuretic peptide (ANP, BNP) and endothelin-1 (ET-1) in patients with idiopathic arterial hypertension and the relationships between cardiac morphological parameters and concentrations of examined peptides in group of patients with left ventricular hypertrophy (LVH). Methods. Seventy-six patients were enrolled in the study: 21 patients with confirmed idiopathic arterial hypertension (group 1), 18 with idiopathic hypertension and eccentric hypertrophy (group 1a), 14 with idiopathic hypertension and concentric hypertrophy (group 1b), and 23 patients without arterial hypertension, organic heart disease, or chronic respiratory tract diseases (group 2—control group). All subjects were submitted for echocardiographic evaluation. Posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDd), left atrium diameter (LAD), left ventricular mass index (LVMI), ejection fraction (EF), fractional shortening (FS), midwall shortening fraction (MWS), and relative wall thickness index (RWT) were studied. Concentrations of ANP(1-28), BNP, and ET-1 were determined with the use of radioimmunological kits (RIA). The obtained results were subjected to statistical analysis. Results. A considerable increase of ANP and BNP was observed in all patients with hypertension (group 1) in comparison to patients without hypertension (group 2). Significant increases of ANP were found in groups 1a and 1b in comparison to group 1 and 2, as well as considerably increase of BNP in group 1b compared to groups 1, 1a, and 2. In the group of patients with hypertension (group 1), a significant increase in the concentration of ET-1 compared to group 2 was found. However, the concentrations of ET-1 in groups 1 and 2 were not statistically different. Significant differences in concentrations of ET-1 between groups 1a, 1b, and 1 and 2 were seen. Significant correlations were found between concentrations of ANP, BNP, ET-1 and morphological parameters: PWT, IVST, LVMI and RWT. In group 1b, a correlation between concentrations of ANP, BNP, MWS, and LAD was found. The multiple regression analysis showed that RWT independently correlates with concentrations of ANP and BNP, and the concentration of BNP is in closer relation to RWT than ANP. In the case of ET-1, the multiple regression analysis did not show that LVMI or RWT had any independent influence on secretion of ET-1 in patients with idiopathic hypertension and LVH. Conclusions. Increased concentration of ANP in patients with idiopathic hypertension may point to the coexistence of complications with type of LVH. High concentration of BNP may specifically suggest concentric LVH. This is important—especially if there are difficulties in interpretations of results of other clinical examinations. However, increased concentrations of ET-1 in the plasma of patients with hypertension and LVH should not be treated as an indicator of LVH degree.     

Effect of spironolactone on left ventricular systolic and diastolic function in patients with early stage chronic kidney disease

Patients with early chronic kidney disease (CKD) have an increased risk for cardiovascular disease. Aldosterone levels are elevated and might impair ventricular function through adverse myocardial and vascular proinflammatory and fibrotic effects. In the Chronic Renal Impairment in Birmingham II (CRIB II) study, it was hypothesized that mineralocorticoid receptor blockade with spironolactone in addition to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers would improve left ventricular (LV) function and markers of inflammation, ventricular stretch, and collagen turnover in early CKD. A total of 112 patients with early CKD were randomized to spironolactone 25 mg/day or placebo for 40 weeks. Ventricular function was assessed by echocardiography and cardiac magnetic resonance imaging tagging. High-sensitivity C-reactive protein, N-terminal-pro-B-type natriuretic peptide, and aminoterminal propeptide of type III procollagen were measured. Spironolactone improved LV long-axis systolic function (Sm 8.2 ± 1.4 vs 7.7 ± 1.3 cm/s, p <0.05), torsion (7.77 ± 1.61° vs 6.77 ± 1.48°, p <0.05), and myocardial deformation (strain rate -1.14 ± 0.24 vs -1.09 ± 0.20 s(-1), p <0.05) compared to placebo, without a change in the ejection fraction. Markers of LV relaxation (E/e' ratio 7.2 ± 2.3 vs 8.5 ± 2.3, p <0.05) and suction (M-mode propagation velocity 56 ± 12 vs 50 ± 12 cm/s, p <0.05) were also improved. Spironolactone reduced N-terminal-pro-B-type natriuretic peptide (24.8 pmol/L [range 0.4 to 122.4] vs 39.4 pmol/L [range 10.8 to 102.4], p <0.01) and attenuated an increase in aminoterminal propeptide of type III procollagen observed with placebo. In conclusion, spironolactone improves markers of regional LV systolic and diastolic function in early CKD.     

A direct comparison of the natriuretic peptides and their relationship to survival in chronic heart failure of a presumed non-ischaemic origin

The natriuretic peptides have been validated as sensitive and specific markers of left ventricular dysfunction; brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NT-proANP) and N-terminal brain natriuretic peptide (NT-proBNP) elevations have been associated with New York Heart Association (NYHA) Class I-IV heart failure. We directly compared the association of each of these markers with 1-year survival in 173 patients with chronic heart failure of a presumed nonischaemic origin entering the PRAISE-2 Trial, a clinical study which assessed the therapeutic effect of Amlodipine in patients with NYHA Class III and IV heart failure and a left ventricular ejection fraction (LVEF) <30%. BNP, NT-proBNP, and NT-proANP levels were all correlated with 1-year mortality by univariate Cox proportional hazards analyses. With respect to multivariate Cox proportional hazards regression models containing variables deemed significant in univariate analyses, NT-proANP alone was identified as an independent predictor of 1-year mortality when log-transformed continuous covariates were utilized in the analysis. When the analysis was repeated using dichotomous covariates, NT-proANP remained the most significant predictor of 1-year mortality, followed by NT-proBNP, NYHA classification and BNP. We conclude that all three natriuretic peptides are significant predictors of short-term mortality in subjects with chronic congestive heart failure (CHF) of a presumed nonischaemic origin. Larger prospective studies are required to validate the clinical utility of NT-proANP as a discriminating marker of short-term survival, and to validate proposed cutoffs of approximately 2300 pmol/l for NT-proANP, 1500 pg/ml for NT-proBNP, and 50 pmol/l for BNP as prognostic indicators of adverse short-term outcome.     

Interleukin-4 and cardiac fibrosis in patients with heart failure

Interleukin-4 (IL-4) stimulates inflammatory responses, activates collagen synthesis, promotes fibrosis progression, and inhibits the production of inflammatory cytokines. We studied the relationship between the urinary IL-4 level and levels of markers of cardiac fibrosis and left ventricular volume in 98 patients with heart failure (HF). The left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI) were calculated, and IL-4, tumor necrosis factor-alpha (TNF-alpha), IL-6, and aminoterminal propeptide of procollagen type III (PIIINP) levels were recorded. Comparison of urinary IL-4 and PIIINP levels in patients and control subjects gave values of 12 (12) pg/mL and 4 (3) pg/mL (P<.0001), respectively, and 5 (2) ng/mL and 4 (1) ng/mL (P<.0001), respectively. The IL-4 level correlated with LVESVI and LVEDVI (r = -0.22, P<.05), and with PIIINP (r = 0.24, P<.05). In patients with hypertensive cardiomyopathy, there was a good correlation between IL-4 and PIIINP levels (r = 0.7, P<.01). Correlations were also observed between IL-4 and TNF-alpha (r = 0.3, P<.01) and IL-6 (r = 0.5, P<.0001). The urinary IL-4 level correlated with cardiac fibrosis and remodeling in patients with HF. The relationship was stronger in those with hypertensive cardiomyopathy.     

Relationship between left ventricular geometry and brain natriuretic peptide levels in elderly subjects

BACKGROUND: The plasma brain natriuretic peptide (BNP) level in elderly patients is elevated, but the mechanism of this increase is not clear. OBJECTIVE: To examine the relationship between left ventricular geometry and BNP levels in elderly subjects. METHODS: We investigated the effects of left ventricular (LV) geometry on plasma BNP levels by measuring these levels in elderly patients with or without LV hypertrophy. Patients were classified into 4 groups based on echocardiographic data: normal geometry; concentric remodeling; eccentric hypertrophy (EH), and concentric hypertrophy (CH). The samples were analyzed for BNP and endothelin-1 (ET-1). RESULTS: Among the 4 groups, there were no differences in plasma ET-1 levels, ejection fraction, percent fractional shortening, or indices of diastolic function. Plasma BNP levels in EH and CH were higher than those in the normal geometry and concentric remodeling groups. There was a good correlation between plasma BNP levels and the relative wall thickness in EH, and between plasma BNP levels and the posterior wall thickness in CH (r = -0.474, r = 0.396, respectively, both p < 0.05). There were also good correlations between plasma BNP levels and LV mass index (LVMI). A stepwise multiple regression analysis showed that age and LVMI were significant independent contributors to plasma BNP levels. CONCLUSIONS: These results suggest that aging, increased wall stress and the extent of cardiac hypertrophy contribute to elevated BNP levels in the elderly.     

Markers of type I and III collagen turnover as indicators of growth velocity in very low birth weight infants

Monitoring postnatal growth in very low birth weight (VLBW) infants is complicated by the difficulty of obtaining reliable measurements. A need thus exists for safe and reliable indicators of such infants' short-term growth velocity. We set out to study whether markers of type I collagen synthesis [amino-terminal propeptide of type I procollagen (PINP)] or degradation [via the matrix metalloproteinase pathway, carboxyl-terminal telopeptide of type I collagen (ICTP)] or of type III collagen synthesis [amino-terminal propeptide of type III procollagen (PIIINP)] could serve as such indicators. PINP, ICTP, and PIIINP were measured for 48 VLBW infants (mean birth weight, 923 g; range, 540-1485 g; mean gestational age, 27.6 wk; range, 23.7-32.7 wk) at the age of 1, 2, 4, and 8 wk. At each time point, these were compared with concurrent growth velocity rigorously assessed by frequent lower leg (knemometry) and weight measurements. PINP showed a significant positive correlation with lower leg growth velocity at 1, 2, and 4 wk and with weight growth velocity at 2, 4, and 8 wk. PIIINP showed a significant positive correlation with lower leg growth at 1, 2, and 8 wk and with weight growth at 2 and 8 wk. The ICTP/PINP ratio, reflecting type I collagen degradation in relation to its synthesis, showed close negative correlations with lower leg growth at 1 wk (r = -0.46; P = 0.003), 2 wk (r = -0.51; P = 0.002), and 4 wk (r = -0.56; P = 0.001) and with weight growth at 2 wk (r = -0.39; P = 0.018), 4 wk (r = -0.59; P = 0.0003), and 8 wk (r = -0.53; P = 0.005). A high ICTP/PINP ratio was an accurate predictor of impaired growth; a high ICTP/PINP ratio was a more rapid and at least as sensitive and specific indicator of slow growth as weight gain. We conclude that PINP, PIIINP, and the ICTP/PINP ratio all reflect postnatal growth velocity in VLBW infants. The most robust of these indicators is the ICTP/PINP ratio, which may thus serve as a clinical tool in assessing short-term growth of these infants.     

小儿先天性心脏病心房利钠肽、脑利钠肽、内皮素-1水平的研究

目的观察先天性心脏病（先心病）介入封堵术前后的心房利钠肽（ANP）、脑利钠肽（BNP）、内皮素-1（ET-1）的变化，探讨先心病ANP、BNP和ET-1的激活状况及其临床意义。方法检测70例先心病患者的ANP、BNP和ET-1水平，另选取年龄及性别与之相匹配的正常体检儿童30例作为对照组。结果先心病血循环中的ANP（25．6＋7．5）pmol／L、BNP（15．7＋7．4）pmol／L、ET-1（1．12＋0．31）pmol／L与对照组比较明显增高（均P=0．0001）。根据NYHA心功能分级，3个亚组随着疾病严重程度的加重，ANP、BNP、ET-1的激活就越明显。结论先心病患者存在着ANP、BNP和ET-1的明显激活并具有慢性心力衰竭的特征，并与疾病的严重性关系密切。     

Reduced levels of N-terminal-proatrial natriuretic peptide in hypertensive patients with metabolic syndrome and their relationship with left ventricular mass

OBJECTIVES: The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS. METHODS: One hundred and twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, echocardiographical and biochemical parameters, and levels of both N-terminal (NT)-proANP and alphaANP were assessed. RESULTS: Hypertensive patients affected by MS had higher LVM and increased frequency of LVH. NT-proANP levels were significantly lower in MS, independent of waist circumference (WC). Log(NT-proANP) levels were significantly inversely related to left ventricular mass index (LVMI) (beta = -0.360, P < 0.001) and LVM/height (beta = -0.370, P < 0.001) in the whole hypertensive population by multiple linear regression analysis. The relationship of log(NT-proANP) with LVM was more enhanced in patients with MS. CONCLUSIONS: The present study demonstrates that levels of NT-proANP are significantly reduced in hypertensive patients affected by MS, and they are significantly inversely related to the increased LVM observed in these patients. Our findings, while supporting previous experimental and clinical evidence of the antihypertrophic role of ANP in hypertension, may help to identify one of the possible mechanisms directly underlying LVH in MS.     

BNP in mitral valve restrictive annuloplasty for ischemic mitral regurgitation

Restrictive annuloplasty with undersized mitral rings is used to correct functional mitral regurgitation (MR) in patients with ischemic left ventricular dysfunction. Seventeen patients with severe coronary artery disease, previous myocardial infarction, moderate/severe functional MR and heart failure symptoms were prospectively evaluated. All patients received CABG associated with restrictive annuloplasty. Preoperatively and 6 months after the operation, clinical evaluation, echocardiography and blood sampling for BNP measurement were performed. Operative mortality occurred in 1 patient. MR degree decreased from 3.8+/-0.3 to 1.0+/-0.7 (p<0.01), LVEF increased from 36+/-11% to 43+/-8% (p<0.05), left ventricular end diastolic diameters changed from 54.7+/-5.2 mm to 51.5+/-5.8 mm (p=0.51). NYHA class improved from 2.94+/-1.02 to 1.21+/-0.42 (p<0.01). Mean plasma BNP levels decreased from 471+/-248 pmol/l to 55.6+/-52.8 pmol/l (p<0.05). Restrictive mitral annuloplasty is a safe procedure to be associated to CABG operation. We demonstrated mid-term reduction of BNP plasma values after MR correction thus suggesting the effectiveness of surgical treatment in modifying natural history of the disease.     

Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients

Abstract: Idarubicin has been shown to have similar or superior antileukemic activity to daunorubicin with less cumulative cardiotoxicity. However, data of acute cardiovascular effects of idarubicin are scanty but may have clinical significance in predicting late cardiovascular complications. In the present study we evaluated prospectively acute neurohumoral and cardiovascular effects of idarubicin containing induction chemotherapy in 10 patients with newly diagnosed AML or MDS. Idarubicin was administered intravenously 12 mg/m² on d 1, 3 and 5 as a part of the induction chemotherapy. Serial measurements of plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were performed at baseline and the day following each idarubicin infusion. Echocardiography was performed to assess cardiac systolic and diastolic function. Signal averaged electrocardiography (ECG) was recorded to observe myocardial late potentials associated with possible myocardial injury. In addition, ambulatory ECG recording was performed to assess arrhythmias. Plasma concentrations of ANP increased from 18.2 ± 1.5 pmol/l to 27.8 ± 3.5 pmol/l (p = 0.011), to 30.2 ± 3.0 pmol/l (p = 0.002) and to 40.8 ± 6.0 pmol/l (p = 0.006) after the first, second and third doses of idarubicin, respectively. Similarly, plasma concentration of BNP increased from 6.2 ± 1.9 to 9.0 ± 1.8 pmol/l (p = 0.049) and 17.5 ± 8.1 pmol/l (p = 0.203) after the first and third idarubicin infusion. Concomitantly, there was a trend towards an increase in left ventricular end diastolic diameter (LVEDD) (50.2 ± 1.8 to 54.4 ± 2.2 mm, p = 0.070). The increase in plasma BNP concentrations correlated significantly with the increase in LVEDD (r = 0.624; p = 0.002). No significant ECG changes or arrhythmias were associated with idarubicin infusions except in 1 patient who developed abnormal myocardial late potentials. Our results show that idarubicin causes acute neurohumoral activation associated with increased LVEDD indicating subclinical myocardial dysfunction. Whether these acute changes predict late clinical cardiomyopathy should be evaluated in prospective studies with larger number of patients and with higher cumulative anthracycline doses.     

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.