atrial-natriuretic-factor and Ventricular-Dysfunction

Heart failure is emerging as a major component of the public health problem of cardiovascular disease as we move into the twenty-first century. Current statistics indicate 4.9 million US citizens are afflicted with direct treatment costs estimated to be $18.8 billion per year. These figures are expected to worsen substantially as the prevalence of heart failure continues to increase. Epidemiologic studies also point to important increases in morbidity and have identified risk factors that aid in prognosis and that may contribute to our mechanistic understanding of heart failure pathophysiology. In addition, epidemiologic results indicate that many patients with mild-to-moderate clinical heart failure are still at substantial risk for morbidity and mortality during follow-up periods of only a few years. These data highlight the importance of enhancing physician and public awareness of heart failure. New methods of molecular epidemiology will point toward better and earlier detection of this common and frequently fatal condition.

Topics: Age Distribution; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Diastole; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Molecular Epidemiology; Natriuretic Peptide, Brain; Prevalence; Prognosis; Risk Factors; Severity of Illness Index; Sex Distribution; Survival Rate; Systole; United States; Ventricular Dysfunction

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction < 45%), diastolic dysfunction (time constant of left ventricular relaxation > 55 milliseconds, left ventricular end-diastolic pressure > 18 mm Hg), and left ventricular hypertrophy (left ventricular mass index > 120 g/m2) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean + 3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m2. The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prospective Studies; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction

Atrial stretch results in myocyte release of the prohormone atrial natriuretic factor (1-126). The N-terminal (1-98) fragment, proatrial natriuretic factor (proANF) is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply due to in vitro stability. This study was undertaken to evaluate the relation between proANF and routinely available measures of clinical status. ProANF was sampled from 202 patients (median age 68 years [range 15 to 85], 77% men) recruited from an active outpatient heart failure clinic. Patients were subgrouped according to New York Heart Association functional class, radionuclide ejection fraction (EF), echocardiographic left ventricular (LV) end-diastolic diameter, and Doppler-determined systolic pulmonary arterial pressure. The median proANF (pmol/L) values for patients in New York Heart Association classes I, II, III, IV were 725, 1,527, 1,750, and 5,172, respectively. The proANF value for the group with EF > 40% was 1,534 versus 1,993 for EF < or = 40% (p < 0.05). The value for the group with LV diameter < 60 mm ws 838 versus 1,751 for LV diameter > or = 60 mm (p < 0.01). The value for the group with systolic pulmonary artery pressure < 45 mm Hg was 1,241 versus 2,660 for systolic pulmonary artery pressure > or = 45 mm Hg (p < 0.01). ProANF correlated better than the other variables with New York Heart Association functional class and was more closely associated with noninvasive measurements than New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Middle Aged; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Dysfunction

Cytokines such as tumor necrosis factor-alpha (TNF) contribute to cardiac dysfunction in chronic heart failure (CHF). Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are thought to reflect cardiac functional and structural damage.. To study the relationship between BNP, ANP, and TNF, these parameters were measured in fasting venous blood samples of 25 CHF patients (age 66+/-2 years, pVO(2) 17.4+/-2.1 mL/kg/min, NYHA class 2.8+/-0.2, all mean+/-SEM) and 8 healthy controls (age 71+/-2 years). Patients with CHF had higher plasma levels of BNP (p<0.05), ANP (p<0.05), norepinephrine (p<0.01), and echocardiographic left ventricular end-diastolic diameter (LVEDD, p<0.05) compared to controls, whereas TNF and epinephrine were not significantly different. There were significant correlations between natriuretic peptides and markers of inflammation and myocardial dysfunction in CHF patients: BNP vs. TNF (r=0.64, p=0.0006), vs. LVEDD (r=0.59, p=0.0025); ANP vs. TNF (r=0.60, p=0.0016), vs. LVEDD (r=0.65, p=0.0006); TNF vs. LVEDD (r=0.57, p=0.004). After adjustment for NYHA, creatinine clearance, and age TNF correlated with BNP (all p=0.01) and ANP (all p<0.002). The cachectic CHF patients (n=7,>6% weight loss) had the highest BNP (p<0.001 vs. controls, p<0.05 vs. non-cachectic CHF) and ANP levels (p=0.01 vs. controls). Concentrations of uric acid, epinephrine, and norepinephrine also correlated with ANP and BNP.. In CHF, TNF is closely related to BNP and ANP (independently of CHF severity and ventricular dysfunction), particularly in patients with cardiac cachexia. TNF may causally contribute to intrinsic cardiac dysfunction thereby stimulating BNP and ANP secretion.

Topics: Age Factors; Aged; Atrial Natriuretic Factor; Biomarkers; Cachexia; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index; Tumor Necrosis Factor-alpha; Ventricular Dysfunction

Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting.. A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations.. After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034).. Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Coronary Artery Bypass; Data Collection; Europe; Female; Genes; Genetic Variation; Genotype; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Prospective Studies; Receptors, Atrial Natriuretic Factor; Risk Factors; Serine Endopeptidases; Troponin I; Ventricular Dysfunction; Young Adult

Natriuretic peptide levels B (BNP) and A (ANP) have been described in children with different diagnose of congenital heart defects (CHD). However, the impact of the type of cardiac load per se on natriuretic peptide levels, irrespective of diagnosis, has not been reported. The aim of the present study was to evaluate the levels of BNP and ANP in children with congenital and acquired heart disease according to different types of cardiac load. Plasma BNP and ANP were analysed in 137 children with CHD/heart disease, median age 2.9 (0.3-16.7) years. Haemodynamic load was classified as: no overload, pressure overload, volume overload of right and/or left ventricle and systolic ventricular dysfunction. Twenty-three children without heart disease served as controls for the natriuretic peptide measurements. The highest BNP and ANP values were observed in the systolic dysfunction, 613 ng l(-1) (81.8-3910) and 431 (43.8-1990), and volume groups, 29.8 (5.5-352) and 93.0 (15.9-346), respectively, whereas the values in the pressure, 17.9 (0.7-315) and 51.9 (8.7-210), and no overload groups, 10.3 (0.2-28.1) and 28.6 (8.6-105), respectively, were only slightly higher than those in the controls 4.7 (0.0-17.7) and 32.9 (11.7-212.2), respectively. The highest BNP and ANP values were seen in children with systolic dysfunction, while volume overload in the absence of heart failure resulted in higher levels than pressure overload.

Topics: Adolescent; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Case-Control Studies; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemodynamics; Humans; Infant; Male; Natriuretic Peptide, Brain; Systole; Ventricular Dysfunction

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction

Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes.. The present study evaluated 238 patients with advanced HF referred for cardiac transplantation evaluation who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from analysis. cTnI was detectable (cTnI > or =0.04 ng/mL) in serum of 117 patients (49.1%). Patients with detectable cTnI levels had significantly higher B-type natriuretic peptide (BNP) levels (P<0.001) and more impaired hemodynamic profiles, including higher pulmonary wedge pressures (P=0.002) and lower cardiac indexes (P<0.0001). A significant correlation was found between detectable cTnI and progressive decline in ejection fraction over time. Furthermore, detectable cTnI was associated with increased mortality risk (RR, 2.05; 95% CI, 1.22 to 3.43). After adjustment for other factors associated with adverse prognosis including age, sex, ejection fraction, and coronary artery disease, cTnI remained a significant predictor of death. cTnI used in conjunction with BNP further improved prognostic value.. cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.

Topics: Academic Medical Centers; Atrial Natriuretic Factor; California; Chronic Disease; Cohort Studies; Comorbidity; Disease Progression; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Survival Rate; Troponin I; Ventricular Dysfunction

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.

Topics: Adult; Aged; Atrial Natriuretic Factor; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction

Topics: Acute Disease; Atrial Natriuretic Factor; Electrocardiography; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Physical Examination; Protein Precursors; Ventricular Dysfunction

increased ANP levels after uncomplicated coronary artery surgery (CAS) indicate functional reduction.. prospective, randomized. Preoperative upto the 12 week postoperative.. Thoracic and Cardiovascular Surgery, University of Düsseldorf.. 15 patients (mean age: 58+/-6.1 years; 13 months, 2 weeks; no myocardial infarction, no congestive heart failure) with 3 vessel disease.. levels of atrial natriuretic peptide (ANP) (pg/ml; radioimmunoassay), Troponin T (TnT) (ng/ml; ELISA test), haemodynamic parameters, ECG monitoring, m-mode echocardiography (Echo).. increase of ANP, TnT levels during extracorporeal circulation (ECC), decrease after operation.. Maximal increase of ANP from preoperative 90+/-10 (M+/-SEM) pg/ml (p<0.05) up to intraoperative 380+/-38 pg/ml. Ten days postoperative ANP (26+/-33 pg/ml) still threefold increased compared to preoperative level. Increasement of TnT from preoperative 0.02+/-0.01 ng/ml upto intraoperative 3.44+/-0.47 ng/ml. Ten days postoperative TnT concentration normal (0.13+/-0.11 ng/ml). Correlation of ANP and TnT five min after bypass up to 6 hrs postoperative (p<0.05, r =3.4). Increase of left atrial diameter preoperative 42.2+/-1.1 mm up to 46.8+/-1.2 mm (p<0.05) 10 days postoperative. LVEDD, EF changed from preoperative 51.1+/-0.9 mm, 73+/-2% to 54.5+/-1.2 mm, 65+/-4% 10 days postoperative.. Threefold increase of ANP 10 days postoperative and return of TnT levels to normal under consideration of datas of echo show, that ANP is suitable to indicate the meanterm, functional, myocardial reduction. Increased ANP levels, atrial dilatation and dysfunction are important signs of cardial functional reduction after CAS.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Dilatation, Pathologic; Extracorporeal Circulation; Female; Heart Atria; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Troponin T; Ventricular Dysfunction

Initial signs of cardiac dysfunction caused by Duchenne muscular dystrophy are usually detected during adolescence. However, decreased physical activity can allow better tolerance of decreased cardiac function. Mild myocardial dysfunction secondary to ischemic or idiopathic cardiomyopathy is accompanied by elevation of plasma levels of norepinephrine and atrial natriuretic factor. This is considered an adaptation to maintain adequate perfusion. We evaluated neurohormone levels in 17 adolescents (median age 14 years) with Duchenne muscular dystrophy and different degrees of ventricular dysfunction determined by echocardiography. All patients were asymptomatic. Electrocardiographic abnormalities were present in 14 of 17 (82%). Shortening fraction was below normal in 9 of 17 (53%). Norepinephrine plasma levels were elevated in 3, and all had normal atrial natriuretic factor levels. There was no association between fractional shortening and norepinephrine plasma level (P = .66). The majority of younger adolescents with Duchenne muscular dystrophy and abnormal ventricular function do not show signs of inadequate perfusion, as evidenced by normal measurements of neurohormones.

Topics: Adolescent; Atrial Natriuretic Factor; Child; Echocardiography; Heart Rate; Humans; Male; Muscular Dystrophy, Duchenne; Norepinephrine; Systole; Ventricular Dysfunction

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Humans; Myocardium; Natriuretic Peptide, Brain; Protein Precursors; Ventricular Dysfunction

To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 months of age, and the animals were killed 6 hours, 3 days, and 7 days later. After the documentation of cardiac failure, the unaffected myocytes were enzymatically dissociated, and the expression of IGF-1 and IGF-1R was measured at these three time points after surgery. The level of expression of IGF-1R mRNA increased at 3 days and remained elevated at 7 days in both age groups. In addition, an increase in IGF-1R protein in these cells was found, with no apparent difference with age. This phenomenon was coupled with an upregulation of IGF-1 mRNA of comparable magnitude in the younger and older animals. In contrast, the increases in the dimensional properties of myocytes were delayed and of smaller magnitude in the older infarcted rats. Moreover, the expression of atrial natriuretic factor, used as a molecular marker of myocyte cellular hypertrophy, was greater at 3 days in 4-month-old rats and at 7 days in 16-month-old rats. Thus, aging may affect the hypertrophic response of myocytes after infarction but has no impact on the ability of the cells to enhance the expression of IGF-1 and IGF-1R, which may sustain only in part the growth reserve mechanisms of the pathological heart.

Topics: Aging; Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Hemodynamics; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Myocardial Infarction; Myocardium; Polymerase Chain Reaction; Rats; Rats, Inbred F344; Receptor, IGF Type 1; RNA, Messenger; Transcription, Genetic; Ventricular Dysfunction

This study examined the effect of low dose aspirin on cardiorenal and neurohumoral function and on the acute hemodynamic response to enalaprilat in a canine model of heart failure.. Low dose aspirin is frequently prescribed for patients with systolic dysfunction who also benefit from angiotensin-converting enzyme inhibition. Although high doses of potent cyclo-oxygenase inhibitors cause fluid retention and vaso-constriction and antagonize the effects of angiotensin-converting enzyme inhibitors, the effects of low dose aspirin in heart failure are unknown.. A model of heart failure was produced in 11 mongrel dogs by rapid ventricular pacing (250 beats/min for 12 to 14 days). Five dogs received 325 mg aspirin/day for the final 4 days of pacing before the acute experiment; six control dogs received no aspirin. Cardiorenal and neurohumoral function was measured during chloralose anesthesia. Hemodynamic and renal responses to enalaprilat were assessed.. Both groups demonstrated severe heart failure with decreased cardiac output; increased atrial pressures and systemic resistance; activation of plasma renin activity, aldosterone and atrial natriuretic factor; and sodium retention. Low dose aspirin had no detrimental effect on cardiorenal or neurohumoral function. Mean arterial pressure, pulmonary capillary wedge pressure and systemic vascular resistance decreased to a similar degree with enalaprilat in both groups. There was no difference between the groups with respect to renal response to enalaprilat.. The present study demonstrates that low dose aspirin has no adverse effect on hemodynamic, neurohumoral or renal function in heart failure. Furthermore, aspirin has no adverse effect on the acute response to enalaprilat. These findings suggest that there is no contraindication to concomitant treatment with low dose aspirin and angiotensin-converting enzyme inhibitors in humans with heart failure.

Topics: Aldosterone; Animals; Aspirin; Atrial Natriuretic Factor; Disease Models, Animal; Dogs; Drug Administration Schedule; Drug Interactions; Enalaprilat; Heart Failure; Hemodynamics; Kidney; Renin; Ventricular Dysfunction