NT-proBNP and BNP values in cardiac patients with different degree of left ventricular systolic dysfunction

We investigated the performance of brain natriuretic peptides (BNP and NT-proBNP) in detecting various degrees of left ventricular systolic dysfunction. The NT-proBNP assay (Roche) and the BNP assay (Bayer Shionoria) were performed in 46 patients (mean age 50 years; range 20-79 years) with various types of heart disease (chronic heart failure due to coronary artery disease, cardiomyopathy, acquired valve disease, congenital heart diseases) and different impairment of left ventricular systolic dysfunction was assessed by echocardiography. Patients were divided into four groups according to the left ventricular ejection fraction (LVEF) correlated with clinical severity. Significant differences in medians of NT-proBNP and BNP values between all groups were determined (P= 0.0161 for NT-proBNP and P=0.0180 for BNP). For identifying patients with severe systolic dysfunction (LVEF<40%), receiver operating characteristic (ROC) analysis for both BNP and NT-proBNP was performed. The diagnostic performances expressed as areas under the curve were of 0.69 for NT-proBNP (cut off value 367 pg/ml) and 0.60 for BNP (cut off value 172 pg/ml). However, the BNP showed higher sensitivity (85 % vs. 63 %) and a higher positive predictive value (69 % vs 55 %) than the NT-proBNP. The negative predictive values of BNP and NT-proBNP were similar (70 % and 71 % respectively). Brain natriuretic peptides are promising markers for the diagnosis of severe left ventricular systolic dysfunction.     

Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately.     

Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model

Bradykinin (BK) coronary outflow and left ventricular (LV) performance of kininogen-deficient Brown Norway Katholiek (BNK) rats and Brown Norway Hannover (BNH) controls were investigated. We analyzed whether the angiotensin-converting enzyme (ACE) inhibitor ramipril is able to attenuate LV dysfunction after induction of myocardial infarction (MI) in this animal model. Ex vivo, the basal BK content in the coronary outflow of buffer-perfused, isolated hearts was measured by specific radioimmunoassay. In vivo, left ventricular pressure (LVP), the maximal rate of LVP increase, LV end-diastolic pressure, the maximal rate of LVP decrease and heart rate were determined using a tip catheter 3 weeks after induction of MI. Compared to BNK rats, basal BK outflow was increased 30-fold in controls (p<0.01). In vivo, we found no significant differences between sham-ligated BNK and BNH rats in basal LV function. After MI, the impairment of LV function was significantly worse in BNK rats when compared to BNH rats. ACE inhibition significantly attenuated this LV dysfunction in both groups, when compared to untreated animals. Reduced basal BK level resulting from kininogen deficiency has no effect on basal LV function, but remains to be a risk factor for the ischemic heart. However, ACE inhibition is sufficient to improve LV function despite kininogen deficiency.     

Role of angiotensin II in sympathetic nervous system induced left ventricular dysfunction

Experiments were undertaken to determine whether angiotensin (Ang) II concentration increases during massive sympathetic nervous system (SNS) activation and whether such an increase plays a role in the pathogenesis of SNS-induced left ventricular (LV) dysfunction. We also sought to determine whether excessive Ca2+ uptake through L-type channels due to intense adrenoceptor activation is responsible for the LV dysfunction. AngII concentration was measured in the plasma and myocardium before and after massively activating the SNS with an intracisternal injection of veratrine. In separate experiments, rabbits were given losartan, enalaprilat, enalaprilat plus HOE-140, nifedipine, -Bay K 4866, or saline before massively activating the SNS. LV function was evaluated 2.5 h later. The intense SNS activity caused plasma and myocardial AngII to increase by 400 and 437%, respectively. AngII receptor blockade did not prevent LV dysfunction. In contrast, enalaprilat reduced the degree of dysfunction, but its cardioprotection was abolished by HOE-140. Although nifedipine prevented SNS-induced LV dysfunction, administration of the Ca2+ channel opener, -Bay K 4866, did not increase its severity. Our results indicate that AngII is not involved in the pathogenesis of SNS-induced LV dysfunction and that the cardioprotection provided by angiotensin converting enzyme (ACE) inhibition is due to activation of a bradykinin pathway. Furthermore, the finding that the magnitude of the LV dysfunction was reduced by enalaprilat, and not increased by -Bay K 4866, suggests that intense adrenoceptor activation of L-type Ca2+ channels is not the primary pathogenetic mechanism.     

Speckle-tracking echocardiography correctly identifies segmental left ventricular dysfunction induced by scarring in a rat model of myocardial infarction

Speckle-tracking echocardiography (STE) uses a two-dimensional echocardiographic image to estimate two orthogonal strain components. The aim of this study was to assess sensitivity of circumferential (S(circ)) and radial (S(rad)) strains to infarct-induced left ventricular (LV) remodeling and scarring of the LV in a rat. To assess the relationship among S(circ), S(rad), and scar size, two-dimensional echocardiographic LV short-axis images (12 MHz transducer, Vivid 7 echo machine) were collected in 34 Lewis rats 4 to 10 wk after ligation of the left anterior descending artery. Percent segmental fibrosis was assessed from histological LV cross sections stained by Masson trichrome. Ten normal rats served as echocardiographic controls. S(circ) and S(rad) were assessed by STE. Histological data showed consistent scarring of anterior and lateral segments with variable extension to posterior and inferior segments. Both S(circ) and S(rad) significantly decreased after myocardial infarction (P<0.0001 for both). As anticipated, S(circ) and S(rad) were lowest in the infarcted segments. Multiple linear regression showed that segmental S(circ) were similarly dependent on segmental fibrosis and end-systolic diameter (P<0.0001 for both), whereas segmental S(rad) measurements were more dependent on end-systolic diameter (P<0.0001) than on percent fibrosis (P<0.002). STE correctly identifies segmental LV dysfunction induced by scarring that follows myocardial infarction in rats.     

Beneficial effects of carvedilol as a concomitant therapy to angiotensin-converting enzyme inhibitor in patients with ischemic left ventricular systolic dysfunction

Studies are scant on the effects of short-term carvedilol treatment as an adjuvant to angiotensin-converting enzyme (ACE) inhibitor in patients with left ventricular (LV) systolic dysfunction. The objective of this study was to find the effects of short-term treatment of carvedilol on patients with ischemic LV systolic dysfunction (defined as LV ejection fraction (LVEF) 相似文献   

Neurohormones in an ovine model of compensated postinfarction left ventricular dysfunction

Clinical heart failure, often the result of myocardial infarction, may be preceded by a period of compensated left ventricular impairment. There is substantial need for an experimental model that reflects this human condition. In sheep, coronary artery ligation produced consistent left ventricular anteroapical myocardial infarctions resulting in chronic (5 wk), stable hemodynamic changes compared with sham controls, including reductions in ejection fraction (51 +/- 2 vs. 30 +/- 5%, P < 0.001), cardiac output (6.3 +/- 0.2 vs. 5.1 +/- 0.2 l/min, P < 0.01), and arterial pressure (93 +/- 2 vs. 79 +/- 3 mmHg, P < 0.001), and increases in cardiac preload (left atrial pressure, 3.3 +/- 0.1 vs. 8.3 +/- 1.3 mmHg, P < 0.001). These changes were associated with acute and sustained increases in plasma concentrations of atrial natriuretic peptide (ANP; 5 wk, 11 +/- 2 vs. 27 +/- 5 pmol/l, P < 0.001), brain natriuretic peptide (BNP; 3 +/- 0.2 vs. 11 +/- 2 pmol/l, P < 0.001), and amino-terminal pro-brain natriuretic peptide (NT-BNP; 17 +/- 3 vs. 42 +/- 12 pmol/l, P < 0.001). Significant correlations were observed between plasma levels of the natriuretic peptides (ANP, day 7 to week 5 samples; BNP and NT-BNP, day 1 to week 5 samples) and changes in left ventricular volumes and ejection fraction. In contrast, renin activity, aldosterone, catecholamines, and endothelin were not chronically elevated postinfarction and were not related to indexes of ventricular function. Coronary artery ligation in sheep produces the pathological, hemodynamic, and neurohormonal characteristics of compensated left ventricular impairment secondary to myocardial infarction. Plasma concentrations of the cardiac natriuretic peptides are sensitive markers of left ventricular dysfunction. This is a reproducible model that reflects the clinical condition and should prove suitable for investigating the pathophysiology of, and experimental therapies in, early left ventricular dysfunction.     

Myocardial material mechanics: characteristic variation of the circumferential and longitudinal systolic moduli in left ventricular dysfunction

Active systolic moduli for the circumferential (E theta) and longitudinal (E phi) axes of the left ventricle were determined along with circumferential and longitudinal contractile filament stress (sigma theta and sigma phi) and circumferential and longitudinal fiber strain (epsilon theta and epsilon phi). These material property parameters were determined at four points during cardiac systole. Thirty-nine patients comprising five clinical groups were evaluated using pressure and volume data acquired from single-plane cineangiography. The results indicate that the active moduli exponentially decrease during cardiac systole. Characteristic variations from normal differentiated the various pathological groups. With compensated volume overload, E theta was significantly reduced during the latter half of systole (p less than 0.25). With decompensated volume overload, both E theta and E phi were not significantly different from the normal group throughout cardiac systole. With compensated pressure overload, both E theta and E phi were significantly lower than the normal group at end-systole (p less than 0.005; p less than 0.005). With congestive cardiomyopathy, both E theta and E phi were significantly greater during the latter half of systole compared to the normal group (p less than 0.05 and p less than or equal to 0.025).     

Low-dose dexamethasone in the rat: a model to study insulin resistance

The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6 or 7 per group) received the following for 4 wk in experiment 1: 1) vehicle, 2) 2 microg/day subcutaneous dexamethasone, 3) metformin (400 mg x kg(-1) x day(-1) os), and 4) dexamethasone plus metformin. In experiment 2 the rats received the following: 1) vehicle, 2) dexamethasone, 3) dexamethasone plus arginine (2%; as substrate of the nitric oxide synthase for nitric oxide production) in tap water, and 4) dexamethasone plus isosorbide dinitrate (70 mg/kg; as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by dexamethasone already at week 1, before the increase in blood pressure (day 15) and without significant changes in body weight compared with vehicle. Dexamethasone-treated rats had significantly higher triglycerides, hematocrit, and insulin, whereas serum total nitrates/ nitrites were lower compared with vehicle. The concomitant treatment with metformin minimized all the described effects of dexamethasone. In experiment 2, only isosorbide dinitrate was able to prevent the observed dexamethasone-induced metabolic, hemodynamic, and insulin sensitivity changes. Chronic low-dose subcutaneous dexamethasone (2 microg/day) is a useful model to study the relationships between insulin resistance and blood pressure in the rat, and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.     

Profound cardioprotection with timolol in a female rat model of aging-related altered left ventricular function

Increasing evidence shows a marked beneficial effect with β-blockers in heart dysfunction via scavenging reactive oxygen species. Previously we showed that chronic treatment with either timolol or propranolol possessed similar beneficial effects for heart function in male rats as age increased, whereas only timolol exerted similar benefits in female rats. Therefore, in this study, we aimed first to examine the cellular bases for age-related alterations in excitation-contraction coupling in ventricular myocytes from female rats and, second, to investigate the hypothesis that age-related changes in [Ca(2+)](i) homeostasis and receptor-mediated system can be prevented with chronic timolol treatment. Chronic timolol treatment of 3-month-old female rats abolished age-related decrease in left ventricular developed pressure and the attenuated responses to β-adrenoreceptor stimulation. It also normalized the altered parameters of [Ca(2+)](i) transients, decreased Ca(2+) loading of sarcoplasmic reticulum and increased basal [Ca(2+)](i), and decreased L-type Ca(2+) currents in 12-month-old female rats compared with the 3-month-old group. Adenylyl cyclase activity, β-adrenoreceptor affinity to its agonist, and β-adrenoreceptor density of the 12-month-old group are normalized to those of the 3-month-old group. Moreover, timolol treatment prevented dysfunction of the antioxidant system, including increased lipid peroxidation, decreased ratio of reduced glutathione to oxidized glutathione, and decreased activities of thioredoxin reductase and glucose-6-phosphate dehydrogenase, in the left ventricle of hearts from the 12-month-old group. Our data confirmed that aging-related early myocardial impairment is primarily related to a dysfunctional antioxidant system and impairment of Ca(2+) homeostasis, which can be prevented with chronic timolol treatment.     

Regulation of MAP kinase-mediated endothelial dysfunction in hyperglycemia via arginase I and eNOS dysregulation

Emerging evidence suggests that arginase contributes to endothelial dysfunction in diabetes. Intracellular signaling pathways, which interplay between arginase and eNOS enzyme activity leading to the development of endothelial dysfunction in hyperglycemia are not fully understood. Here, we analyzed the possible involvement of hyperglycemia (HG) induced arginase expression in eNOS protein regulation and activity and also the impact of arginase inhibition on eNOS activity. Furthermore, the roles of p38 MAPK and Erk1/2 phosphorylation in upregulation of arginase expression and eNOS dysregulation in endothelial cells (ECs) under hyperglycemia were evaluated. Protein analysis showed a concurrent increase in arginase I expression and decrease in eNOS expression and phosphorylation at Ser¹¹⁷⁷ under HG conditions. There was no simultaneous change in phosphorylation of eNOS at Thr⁴⁹⁵ in HG. Arginase inhibition prevented increased arginase activity, restored impaired NO bioavailability and reduced superoxide anion generation. Inhibition of MAP-kinases demonstrated that, unlike Erk1/2, p38 MAPK is an upstream activator in a signaling cascade leading to increased arginase I in HG conditions. P38 MAPK protein expression and phosphorylation were increased in response to HG. In the presence of a p38 MAPK inhibitor, HG-induced arginase expression was blunted. Although Erk1/2 was activated in HG, increased arginase expression was not blocked by co-treatment with an Erk1/2 inhibitor. Activation of both, p38 MAPK and Erk1/2 in HG, induced a downregulation in eNOS activity. Hence, applying MAPK inhibitors increased eNOS phosphorylation in HG.In conclusion, these findings demonstrate contributions of arginase I in the development of endothelial cell dysfunction under HG conditions via impaired eNOS regulation, which maybe mediated by p38 MAPK.     

Losartan prevents contractile dysfunction in rat myocardium after left ventricular myocardial infarction

We studied the effects of chronic losartan (Los) treatment on contractile function of isolated right ventricular (RV) trabeculae from rat hearts 12 wk after left ventricular (LV) myocardial infarction (MI) had been induced by ligation of the left anterior descending artery at 4 wk of age. After recovery, one-half of the animals were started on Los treatment (MI+Los; 30 mg x kg(-1) x day(-1) per os); the remaining animals were not treated (MI group). Rats without infarction or Los treatment served as controls (Con group). MI resulted in increases in LV and RV weight and unstressed LV cavity diameter; these were partially prevented by Los treatment. The active peak twitch force-sarcomere length relation was depressed in MI compared with either Con or MI+Los. Likewise, maximum Ca2+ saturated twitch force was depressed in MI, whereas twitch relaxation and twitch duration were prolonged. Myofilament function, as measured in skinned trabeculae, was not significantly different among the Con, MI, and MI+Los groups. We conclude that Los prevents contractile dysfunction in rat RV trabeculae after LV MI. Our results suggest that the beneficiary effect of Los treatment results not from improved myofilament function but rather from improved myocyte Ca2+ homeostasis.     

Serum interleukin-6 and C-reactive protein are markedly elevated in acute decompensated heart failure patients with left ventricular systolic dysfunction

Cytokines play important roles in heart failure (HF). We examined whether cytokine levels are different in acute decompensated heart failure (ADHF) patients between with left ventricular systolic dysfunction (LVSDF) and with preserved LV ejection function (PLVEF). We studied 81 HF patients who were admitted to our hospital with acute decompensation. They were divided into two groups: LVSDF (LVEF) < 45% and PLVEF (LVEF ? 45%). Serum interleukin-6 (IL-6), highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), and IL-18 and plasma brain natriuretic peptide (BNP) were measured on admission and at discharge. On admission, IL-6 and hsCRP were higher in LVSDF than in PLVEF. IL-6 and hsCRP decreased after treatment in LVSDF, but not in PLVEF, while plasma BNP levels decreased in both HF with treatment. There was no difference in TNF-α or in IL-18 level between LVSDF and PLVEF, and they did not change after treatment in either group. In conclusion, cytokine profiles were different in ADHF between those with LVSDF and PLVEF. Activation of IL-6–hsCRP pathway may play a specific role in ADHF with LVSDF.     

Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity

The aim of this review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Disturbance of adipose tissue physiology is one of the primary events in the development of pathologies associated with the metabolic syndrome, such as obesity and type 2 diabetes. Several studies indicate that alterations in metabolism of glucocorticoids (GC) and androgens, as well as aldosterone in excess, are involved in the emergence of metabolic syndrome. Cross talk among adipose tissue, the hypothalamo-pituitary complex, and adrenal gland activity plays a major role in the control of food intake, glucose metabolism, lipid storage, and energy balance. Perturbation of this cross talk induces alterations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling, at the level of the zonae glomerulosa (aldosterone), fasciculata (GC and GC metabolites), and reticularis (androgens and androgen precursors DHEA and DHEAS). As a whole, these adrenocortical perturbations contribute to the development of metabolic syndrome at both the paracrine and systemic level by favoring the physiological dysregulation of organs responsive to aldosterone, GC, and/or androgens, including adipose tissue.     

Prevalence of left ventricular systolic dysfunction and heart failure in high risk patients: community based epidemiological study

ObjectivesTo determine the prevalence of left ventricular systolic dysfunction, and of heart failure due to different causes, in patients with risk factors for these conditions.DesignEpidemiological study, including detailed clinical assessment, electrocardiography, and echocardiography.Setting16 English general practices, representative for socioeconomic status and practice type.Participants1062 patients (66% response rate) with previous myocardial infarction, angina, hypertension, or diabetes.ResultsDefinite systolic dysfunction (ejection fraction <40%) was found in 54/244 (22.1%, 95% confidence interval 17.1% to 27.9%) patients with previous myocardial infarction, 26/321 (8.1%, 5.4% to 11.6%) with angina, 7/388 (1.8%, 0.7% to 3.7%) with hypertension, and 12/208 (5.8%, 3.0% to 9.9%) with diabetes. In each group, approximately half of these patients had symptoms of dyspnoea, and therefore had heart failure. Overall rates of heart failure, defined as symptoms of dyspnoea plus objective evidence of cardiac dysfunction (systolic dysfunction, atrial fibrillation, or clinically significant valve disease) were 16.0% (11.6% to 21.2%) in patients with previous myocardial infarction, 8.4% (5.6% to 12.0%) in those with angina, 2.8% (1.4% to 5.0%) in those with hypertension, and 7.7% (4.5% to 12.2%) in those with diabetes.ConclusionMany people with ischaemic heart disease or diabetes have systolic dysfunction or heart failure. The data support the need for trials of targeted echocardiographic screening, in view of the major benefits of modern treatment. In contrast, patients with uncomplicated hypertension have similar rates to the general population.

What is already known on this topic

The prognosis and symptoms of patients with left ventricular systolic dysfunction and heart failure can be greatly improved by modern treatmentsMany patients with heart failure do not have an assessment of left ventricular function, resulting in undertreatment of the condition

What this study adds

Patients with a history of ischaemic heart disease (especially those with previous myocardial infarction) or diabetes commonly have left ventricular systolic dysfunctionThese patients would be candidates for a targeted echocardiographic screening programmeIn contrast, the yield from screening patients with uncomplicated hypertension would be low