atrial-natriuretic-factor and Ventricular-Dysfunction--Left

Heart failure with reduced ejection fraction (HFrEF) is a progressive disorder whereby cardiac structure and function continue to deteriorate, often despite the absence of clinically apparent signs and symptoms of a worsening disease state. This silent yet progressive nature of HFrEF can contribute to the increased risk of death-even in patients who are 'clinically stable', or who are asymptomatic or only mildly symptomatic-because it often goes undetected and/or undertreated. Current therapies are aimed at improving clinical symptoms, and several agents more directly target the underlying causes of disease; however, new therapies are needed that can more fully address factors responsible for underlying progressive cardiac dysfunction. In this review, mechanisms that drive HFrEF, including ongoing cardiomyocyte loss, mitochondrial abnormalities, impaired calcium cycling, elevated LV wall stress, reactive interstitial fibrosis, and cardiomyocyte hypertrophy, are discussed. Additionally, limitations of current HF therapies are reviewed, with a focus on how these therapies are designed to counteract the deleterious effects of compensatory neurohumoral activation but do not fully prevent disease progression. Finally, new investigational therapies that may improve the underlying molecular, cellular, and structural abnormalities associated with HF progression are reviewed.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Apoptosis; Atrial Natriuretic Factor; Biphenyl Compounds; Calcium; Disease Progression; Diuretics; Drug Combinations; Fibrosis; Heart Failure; Humans; Mitochondria, Heart; Myocardium; Myocytes, Cardiac; Natriuretic Agents; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Stress, Mechanical; Stroke Volume; Tetrazoles; Valsartan; Ventricular Dysfunction, Left

The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure.

Topics: Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Heart Atria; Heart Failure; Humans; Sympathetic Nervous System; Vasoconstriction; Vasopressins; Ventricular Dysfunction, Left

Natriuretic peptide (NP) levels (B-type natriuretic peptide [BNP] and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research all over the world and have been incorporated into many cardiovascular guidelines for heart failure (HF). The roles of NP levels are evolving rapidly not only in diagnosis, therapy monitoring, and risk stratification of HF, but also in differential diagnosis of acute dyspnea, predicting death and rehospitalization in HF patients. NP assays have been applied in permanent cardiac pacing in recent years, whereas it is still not well known how NP levels change and whether NP levels can predict HF in permanent cardiac pacing. Therefore, this article reviews the role of NP levels in permanent cardiac pacing, mainly including NP changes in different cardiac pacing modes and cardiac resynchronization therapy.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Humans; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Ventricular Dysfunction, Left

As a result of population ageing and improved medical care that contribute to better life expectancy, heart failure occurs more and more commonly in the elderly. In the USA approximately 80% of patients discharged from hospital with newly diagnosed heart failure are over 65 years of age, whereas 50% are over 75. The average 5-year mortality rate is about 50% in subjects with systolic dysfunction and similar in those with preserved left ventricular systolic function. Disorders of the cardiovascular system occurring in the elderly (e.g. increased left ventricular mass, myocardial rigidity, atrial fibrillation, decreased maximum oxygen uptake in cardiopulmonary exercise tests) result from the physiological ageing; they may also be caused by a concomitant cardiac failure syndrome. In the elderly, heart failure is often accompanied by concomitant conditions that often make diagnosis and treatment of chronic heart disease difficult. Non-specific clinical symptoms in the elderly as well as those associated with age (e.g. easy fatigability, exertional dyspnea) make a correct diagnosis difficult. The recognized biochemical marker of heart failure--brain natriuretic peptide, N-terminal pro-brain natriuretic peptide--has a limited diagnostic value in the elderly. Echocardiography plays a key role in the diagnosis. Owing to altered metabolism, impairment of hepatic processes to various degrees and decreased renal excretion of drugs, treatment requires attention, individual choice of drugs and doses, as well as periodic modification of both the doses and the intervals between them. Correct treatment improves quality of life and prolongs it. The aim of the present work is to present the differences in the pathophysiology, diagnostic evaluation and management of chronic heart failure in the elderly, in light of the current views and standards.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Atrial Natriuretic Factor; Electrocardiography; Geriatric Assessment; Health Services for the Aged; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Poland; Prognosis; Quality of Life; Risk Factors; Ultrasonography; Ventricular Dysfunction, Left

Systolic heart failure (HF) is a progressive disorder that often begins with asymptomatic left ventricular (LV) systolic dysfunction and culminates in symptoms from fluid overload and poor end-organ perfusion. The progression to symptomatic HF is accompanied by marked activation of neurohormonal and cytokine systems, as well as a series of adaptive LV anatomical and functional changes, collectively referred to as LV remodelling. However, the mechanisms underlying symptom appearance have not been delineated and the weight of experimental and clinical evidence suggests that the development of symptomatic HF occurs independently of the haemodynamic status of the patient. The left atrium is a muscular chamber strategically located between the left ventricle and the pulmonary circulation with important mechanical function (modulation of LV filling), which is closely coupled with its endocrine (atrial natriuretic peptide synthesis and secretion) and regulatory (contribution to the control of sympathetic activity and vasopressin release) functions. In this narrative review we provide evidence supporting the concept that left atrial dilation and systolic dysfunction (left atrial remodelling) contributes to the progression of asymptomatic LV dysfunction to chronic symptomatic systolic HF as it is a prerequisite for the development of the pulmonary congestion and marked neuronhormoral activity that characterize the symptomatic state.

Topics: Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Disease Progression; Heart Failure, Systolic; Humans; Pressoreceptors; Ventricular Dysfunction, Left; Ventricular Remodeling

The natriuretic peptide system includes three known peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). They contribute to the regulation of cardiovascular homeostasis through diuretic, natriuretic, and vasodilatory properties. Among them, ANP has received particular attention because of its effects on blood pressure regulation and cardiac function. Although the potential for its therapeutic application in the treatment of hypertension and heart failure has been evaluated in several experimental and clinical investigations, no pharmacological approach directly targeted at modulation of ANP levels has ever reached the stage of being incorporated into clinical practice. Recently, ANP has also received attention as being a possible cardiovascular risk factor, particularly in the context of hypertension, stroke, obesity, and metabolic syndrome. Abnormalities in either peptide levels or peptide structure are thought to underlie its implied role in mediating cardiovascular diseases. Meanwhile, BNP has emerged as a relevant marker of left ventricular (LV) dysfunction and as a useful predictor of future outcome in patients with heart failure. This review deals with the major relevant findings related to the cardiovascular and metabolic effects of natriuretic peptides, to their potential therapeutic use, and to their role in mediating cardiovascular diseases.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Fibrosis; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Risk Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Ventricular Dysfunction, Left

The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular homeostasis. They have recently emerged as potentially important clinical markers in heart failure. Recent data have suggested an important role for these markers in establishing the diagnosis of heart failure in patients with unexplained dyspnea in both acute care and ambulatory settings. Other clinical uses of the natriuretic peptides, such as screening for asymptomatic ventricular dysfunction, establishing prognosis or guiding titration of drug therapy, are under investigation but have not yet sufficiently been validated for widespread clinical use.

Topics: Atrial Natriuretic Factor; Bayes Theorem; Biomarkers; Dyspnea; Heart Failure; Humans; Likelihood Functions; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reference Values; ROC Curve; Sensitivity and Specificity; Treatment Outcome; Ventricular Dysfunction, Left

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

The natriuretic peptide system (atrial natriuretic peptide, brain natriuretic peptide, BNP, and C natriuretic peptide) is an important marker of cardiac failure. These peptides are synthesized in atrial or ventricular myocytes in response to wall tension. In several studies the correlation between high BNP levels and mortality, in patients with acute coronary syndrome and heart failure, has been demonstrated. On the other hand, plasma levels of BNP could be considered as independent predictors of mortality in patients with heart failure. BNP could be used, for instance, as an early diagnostic marker for the differential diagnosis between cardiogenic and non cardiogenic dyspnea. In the Emergency Department its use will be important in the diagnosis of thoracic pain origin since it may help in the diagnostic and therapeutic course of this patient and to define the modality of hospitalization. Moreover, it can be used as a marker of heart failure severity and as an important negative prognostic factor. Some studies have confirmed that plasma BNP reflects the degree of left ventricular dysfunction and the prognostic significance after acute myocardial infarction and chronic heart failure.

Topics: Angina, Unstable; Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Protein Precursors; Syndrome; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Diagnosis, Differential; Electrocardiography; Female; Heart Failure; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Syndrome; Ventricular Dysfunction, Left

Natriuretic peptides are involved in the regulation of volume homeostasis. Their levels generally are increased in the setting of volume expansion and act on multiple effector systems to cause vasodilation and natriuresis in an effort to return volume status back to normal. In patients with end-stage renal disease, the natriuretic capabilities of these peptides are limited. However, there has been much interest in the potential applicability of measurement of these peptides as a surrogate marker of volume status and in the determination of dry weight. Furthermore, atrial natriuretic peptide and brain natriuretic peptide can serve as markers of left ventricular dysfunction and may have utility in determining cardiac prognosis in patients on long-term dialysis therapy.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Body Weight; Cohort Studies; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptides; Peritoneal Dialysis; Prognosis; Rats; Receptors, Neuropeptide; Ventricular Dysfunction, Left; Water-Electrolyte Balance

The natriuretic peptides are hormones released mainly from the cardiac ventricles in response to increased wall tension, and involved in volume homeostasis and cardiovascular remodeling. At today, Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP) have been identified. BNP is the more utilized, secondary to its major expression of left ventricle function. Recently, it has opened up the potential for the utilization of atrial natriuretic peptides in the everyday clinical practice. The levels of B-type natriuretic peptide are elevated in patients with left ventricular dysfunction and they correlate with both the severity of symptoms and the prognosis. Observational studies have suggested that, when used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department may be useful in establishing or ruling out the diagnosis of heart failure in patients with acute dyspnea. Furthermore, plasma peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors. BNP has been studied also in myocardial ischemia: in ST-segment elevation myocardial infarction, BNP rise substantially and rapidly. Elevated levels of BNP can also be detected in patients presenting with non-ST-segment elevation acute coronary syndromes, and even in those with transient myocardial ischemia exercise-induced.

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Ventricular Dysfunction, Left

The present review will cover the mechanisms of release and the potential pathophysiological role of different natriuretic peptides in critically ill patients. By focusing on the cardiovascular system, possible implications of natriuretic peptides for diagnosis and treatment will be presented. In critical illness such as sepsis, trauma or major surgery, systemic hypotension and an intrinsic myocardial dysfunction occur. Impairment of the cardiovascular system contributes to poor prognosis in severe human sepsis. Natriuretic peptides have emerged as valuable marker substances to detect left ventricular dysfunction in congestive heart failure of different origins. Increased plasma levels of circulating natriuretic peptides, atrial natriuretic peptide, N-terminal pro-atrial natriuretic peptide, brain natriuretic peptide and its N-terminal moiety N-terminal pro-brain natriuretic peptide have also been found in critically ill patients. All of these peptides have been reported to reflect left ventricular dysfunction in these patients. The increased wall stress of the cardiac atria and ventricles is followed by the release of these natriuretic peptides. Furthermore, the release of atrial natriuretic peptide and brain natriuretic peptide might be triggered by members of the IL-6-related family and endotoxin in the critically ill. Apart from the vasoactive actions of circulating natriuretic peptides and their broad effects on the renal system, anti-ischemic properties and immunological functions have been reported for atrial natriuretic peptide. The early onset and rapid reversibility of left ventricular impairment in patients with good prognosis associated with a remarkably augmented plasma concentration of circulating natriuretic peptides suggest a possible role of these hormones in the monitoring of therapy success and the estimation of prognosis in the critically ill.

Topics: Atrial Natriuretic Factor; Critical Illness; Humans; Intensive Care Units; Natriuretic Peptide, Brain; Prognosis; Systemic Inflammatory Response Syndrome; Ventricular Dysfunction, Left; Wounds and Injuries

The abnormal regulation of nitric oxide synthase activity represents an underlying feature of heart failure. Increased peripheral vascular resistance, and decreased renal function may be in part related to impaired endothelium-dependent nitric oxide (NO) synthesis. Paradoxically, the chronic production of NO by inducible nitric oxide synthase (iNOS) in heart failure exerts deleterious effects on ventricular contractility, and circulatory function. Consequently, pharmacologically improving endothelium-dependent NO synthesis and the concomitant inhibition of iNOS activity would be therapeutically advantageous. Interestingly, natriuretic peptides have been shown to differentially regulate endothelial NOS (eNOS) and iNOS activity. Moreover, in both patients and animal models of heart failure, pharmacologically increasing plasma natriuretic peptide levels ameliorated vascular tone, renal function, and ventricular contractility. Based on these observations, the following review will explore whether the therapeutic benefit of the natriuretic peptide system in heart failure may occur in part via the amelioration of endothelium-dependent NO synthesis, and the concomitant inhibition of cytokine-mediated iNOS expression.

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Renin-Angiotensin System; Treatment Outcome; Ventricular Dysfunction, Left

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles. It is released as N-terminal pro-BNP (NT-proBNP) and cleaved enzymatically to the NT fragment and the immunoreactive BNP. Measurement of BNP is now available as a rapid bedside assay that is easily available to physicians in an office, clinic, emergency department, or inpatient setting. It has proven utility in the emergency department diagnosis of congestive heart failure (CHF) in patients with unclear causes of dyspnea. The use of BNP level as a criterion for hospital admission has been studied as has its use as an aid in decision-making regarding the adequacy of treatment and readiness for hospital discharge. Treatment of chronic CHF in outpatients using BNP as a guide for the intensity of pharmacological therapy shows promise in further decreasing the rate of adverse events associated with this diagnosis. Other uses for BNP measurement include the prognostication of CHF exacerbation and myocardial infarction, and screening those at risk to identify patients that may benefit from early intervention and treatment of early CHF.

Topics: Atrial Natriuretic Factor; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Outpatients; Prognosis; Ventricular Dysfunction, Left

The evolving paradigm of heart failure has now been expanded to include the favorable neurohormonal, structural and hemodynamic profile of B-type natriuretic peptide [BNP]. As a marker of left ventricular dysfunction, BNP is a practical tool that facilitates diagnosis, contributes to prognostic evaluations and tracks disease severity. BNP elevations vary according to gender, disease states and perhaps obesity but in general elevated levels are consistent not only with left ventricular stress but likely represent the best surrogate for ongoing left ventricular remodeling. The full utility of BNP surveys has not yet been realized but emerging areas of use include clinical assessment by physician extenders, post-MI assessment, and a target of tailored therapy for heart failure. New biomarkers for heart failure similar to BNP are on the horizon but their clinical niche has yet to be determined.

Topics: Atrial Natriuretic Factor; Biological Assay; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

The prevalence of heart failure will increase in a number of industrialized countries as the proportion of elderly within the population increases. Despite recent advances in medical and surgical intervention, the prognosis for this disorder has not improved significantly. To make a major impact on the prognosis for heart failure, it would be important to be able to recognize various forms of heart disease before severe heart failure has developed. Chest X-radiography, ECG and echocardiography may not be adequate screening tools for heart failure in large populations. Natriuretic peptides are secreted from the heart in response to various cardiac abnormalities including ventricular dysfunction, volume overload, hypertrophy, and myocardial ischemia. Circulating levels of natriuretic peptides are elevated in various forms of structural cardiac disease regardless of etiology and the degree of ventricular systolic dysfunction. Natriuretic peptides, specifically B-type natriuretic peptide, are practically stable and can be measured without an extraction procedure. We have reviewed the recent status of plasma natriuretic peptide measurement for identification of patients with congestive heart failure, left ventricular dysfunction, and high risk of heart failure, especially in mass screening settings.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Congestive heart failure poses significant challenges to physicians with both diagnosis and management. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles. It correlates with ventricular function, NYHA classification, and prognosis. It is extremely useful in the emergency department in patients presenting with acute dyspnea. It has a particularly strong negative predictive value. In addition, it should be important in screening patients for heart diease, either for those who are at high risk (chemotherapy, diabetes) or as a possible screen before echocardiography. In the future, BNP may be used to modulate treatment of patients in the decompensated setting as well as in titrating outpatient therapy.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiotonic Agents; Dyspnea; Emergencies; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Cardiovascular Agents; Heart Failure; Humans; Models, Cardiovascular; Renin-Angiotensin System; Stroke Volume; Sympatholytics; Ventricular Dysfunction, Left; Ventricular Remodeling

Pathophysiology of congestive heart failure (CHF) has undergone a remarkable evolution during the last two decades. CHF is now regarded especially as a neurohormonal disease and not only as a cardiocirculatory impairment. Many studies have emphasized that an abnormal neuroendocrine activation precedes the development of clinically recognized heart failure and plays an important pathogenetic role in progression of this disease. In patients with CHF, moreover, circulating levels of some neurohormonal factors have an independent negative prognostic value. More recently immunological and molecular biology studies have also demonstrated the negative effects exerted by some cytokines and by apoptosis. Correction of neurohormonal disorder is the rationale of therapeutical approach to patients with CHF and appears the only way to significantly decrease mortality. In this review the role of neuroendocrine activation in the pathophysiology of CHF is analyzed.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Atrial Natriuretic Factor; Cytokines; Heart Failure; Humans; Natriuretic Peptide, Brain; Neurosecretory Systems; Neurotransmitter Agents; Prognosis; Rats; Renin-Angiotensin System; Risk Factors; Swine; Ventricular Dysfunction, Left

A blood test that would aid in the diagnosis and management of patients with congestive heart failure would have a favorable impact on the staggering costs of the disease. B-type naturetic peptide (BNP) is synthesized in the cardiac ventricles and its release is directly proportional to ventricular volume expansion and pressure overload. Levels of BNP correlate with left ventricular pressure, amount of dyspnea, and the state of neurohumoral modulation. BNP also correlates closely with New York Heart Association classification. A cut point of 100 pg/mL appears to discriminate patients with congestive heart failure from those without congestive heart failure. Measurement of BNP may also be an excellent screening tool for LV dysfunction. Key Words: Natriuretic peptides; neurohormonal; left-ventricular pressure;

Topics: Atrial Natriuretic Factor; Biomarkers; Endpoint Determination; Heart Failure; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF would clearly have a favorable impact on the staggering costs associated with the disease. B-type natriuretic peptide (BNP) may be the first potential "white count" for heart failure. The fact that a point-of-care, rapid assay for BNP has recently been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. Data suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography, and might also be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as assessment of the state of the patient's neurohormonal compensation.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; Sensitivity and Specificity; Ventricular Dysfunction, Left

As the population ages, the number of cases of congestive heart failure (CHF) is expected to climb. Primary care physicians will be increasingly called upon to treat patients with this serious cardiac derangement. In this article, Drs Ward and Anderson discuss the latest approaches to treatment, which are based on the current understanding that CHF results from left ventricular dysfunction, which causes a complex activation of multiple neurohormonal reflexes.

Topics: Adrenergic beta-Antagonists; Age Distribution; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arginine Vasopressin; Atrial Natriuretic Factor; Disease Progression; Family Practice; Heart Failure; Hemodynamics; Humans; Mineralocorticoid Receptor Antagonists; Primary Health Care; Renin-Angiotensin System; United States; Ventricular Dysfunction, Left

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF clearly would have a favorable impact on the staggering costs associated with the disease. BNP, which is synthesized in the cardiac ventricles and correlates with LV pressure, amount of dyspnea, and the state of neurohormonal modulation, makes this peptide the first potential "white count" for heart failure. The fact that a point-of-care rapid assay for BNP has been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. The author's data, and data from others, suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography. A low BNP level makes echocardiographic indices of LV dysfunction (systolic and diastolic) highly unlikely. BNP also might be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. In some instances, BNP levels may obviate the need for invasive hemodynamic monitoring and, in cases where such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies and in assessment of the state of neurohormonal compensation of the patient.

Topics: Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Humans; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

The natriuretic peptides (NPs), atrial natriuretic peptide, and brain natriuretic peptide (BNP) have been shown to have important roles in fluid volume homeostasis and blood pressure regulation. In addition, plasma NP levels are elevated in a number of cardiac pathologies and have been used as biochemical markers of left-ventricular dysfunction (LVD) in small- and large-scale clinical studies. In this review, the authors describe NP physiology and summarize the findings of selected studies that have examined the reliability and feasibility of NP measurement in LVD. In particular, BNP is proposed to be a biochemical marker that may provide a useful and inexpensive screening test of LVD. In addition, the authors discuss possible roles of the NPs in the etiology and progression of LVD. The findings of these studies suggest that the NPs may directly contribute to cardiac pathophysiology and LVD progression.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Disease Progression; Feasibility Studies; Homeostasis; Humans; Mass Screening; Metabolic Clearance Rate; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left; Water-Electrolyte Balance

The heart secrets two different natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which have potent vasorelaxant, diuretic, and natriuretic actions. They are main tools in the body's defense against volume overload and hypertension. The natriuretic peptides (NP) are synthetized as prohormones. The C-terminal endocrinological active peptides and their N-terminal prohormone fragments are found in plasma. The NP system is maximally activated in ventricular dysfunction. However, NP:s are also increased in patients with renal failure or pulmonary hypertension, and increases may be found in arterial hypertension or liver cirrhosis. Among all NP and prohormone fragments currently BNP is the most promising candidate analyte for routine diagnosis. BNP is also superior to other neurohormones for diagnosis of left-ventricular dysfunction (LVD) or estimating prognosis in LVD or during the subacute phase of myocardial infarction. For primary care physicians BNP measurement is useful to decide which patient with suspected heart failure warrants further investigation, particularly when assessment of left ventricular function is not readily available. BNP has an excellent negative predictive value particularly in high risk patients. For the cardiologists the NP:s are helpful for monitoring therapy and disease course in LVD patients and for estimating prognosis in LVD and myocardial infarction patients. There is now sufficient evidence to encourage physicians to gain experience with NP as a supplement in the diagnosis of patients suspected of having heart failure. An increase in BNP is serious enough to warrant follow-up examinations.

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

Congestive heart failure has become a major public health problem. A hallmark of this syndrome is neurohumoral activation, with elevation of natriuretic peptides, in particular atrial natriuretic peptide and brain natriuretic peptide of myocardial origin, which occurs with the onset of ventricular dysfunction. The natriuretic peptide system is important in cardiorenal regulation, specifically in the integrated control of intravascular volume and arterial pressure to maintain optimal circulatory integrity. Several therapeutic approaches have been established to mimic or potentiate the unique cardiovascular and renal beneficial actions of these peptides during heart failure. Recent investigations have also established a diagnostic utility for the natriuretic peptides to diagnose early asymptomatic left ventricular dysfunction. Thus, diagnostic and therapeutic use of the natriuretic peptides is emerging as a new strategy to delay the natural history of progressive heart failure from its earliest phase to chronic congestive heart failure.

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

Topics: Atrial Natriuretic Factor; Blood Pressure; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left; Water-Electrolyte Balance

Left ventricular hypertrophy in patients with hypertensive heart disease is associated with impaired relaxation and myocardial interstitial fibrosis leading to enhanced filling pressure, referred to as left ventricular diastolic dysfunction. Impairment of systolic function, characterized by reduced ejection fraction occurs at a later stage. Activation of the renin-angiotensin-aldosterone system contributes to progression to heart failure by at least two mechanisms: (1) increased left ventricular loading conditions due to vasoconstriction and retention of sodium; (2) direct effects on the myocardium resulting in myocyte hypertrophy and interstitial fibrosis.

Topics: Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Heart Failure; Humans; Hypertrophy, Left Ventricular; Neurotransmitter Agents; Norepinephrine; Renin; Stroke Volume; Systole; Ventricular Dysfunction, Left

Topics: Animals; Atrial Natriuretic Factor; Brain; Humans; Myocardial Infarction; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Blood Pressure; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Sodium, Dietary; Ventricular Dysfunction, Left; Ventricular Function, Left

It is sobering to recall that, despite much basic research and many small and large clinical trials, we still do not know how angiotensin-converting enzyme inhibitors work. This is true both in terms of their fundamental mode of action at a cellular level as well as in the patient in the clinical setting. New pharmaceutical compounds such as renin inhibitors, angiotensin II receptor antagonists and aldosterone antagonists are bringing new insights not only into the importance of different components of the renin-angiotensin-aldosterone system in heart failure but also into the mode of action of angiotensin-converting enzyme inhibitors. This manuscript also provides a brief update on the organization of the renin-angiotensin-aldosterone system and other angiotensin-II-forming pathways with special relevance to heart failure. Data on the potential relevance of genetic polymorphisms of the renin-angiotensin-aldosterone system are discussed. Possibly the single most important observation in clinical cardiovascular medicine in 1995 was the reporting of a highly significant interaction between angiotensin-converting enzyme inhibitors and aspirin on mortality in patients with ventricular dysfunction with or without heart failure. This has called into question the safety of aspirin use in heart failure.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Atrial Natriuretic Factor; Contraindications; Cough; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Polymorphism, Genetic; Receptors, Angiotensin; Renin; Renin-Angiotensin System; Ventricular Dysfunction, Left

In the early phase of asymptomatic left ventricular dysfunction, neurohumoral systems are activated and are closely associated with the deterioration of left ventricular function and the progression into symptomatic heart failure. Congestive cardiac failure is characterized by an increasing activation of the sympathetic nerve activity, the renin angiotensin aldosterone system, vasopressin and endothelin. Together with a reduced endothelial formation of NO, the activation of neurohumoral systems leads to vaso-construction and retention of sodium and water, and by this, to a deterioration of cardiac function. On the other side, systems are activated like prostaglandins, ANP, BNP, dopamine and bradykinin, which act as vasodilators and increase natriuresis and diuresis. In the early phase of cardiac failure, natriuretic and vasodilator mechanisms are able to counteract vasoconstrictor factors, preventing by this unfavorable effects on left ventricular function.

Topics: Animals; Atrial Natriuretic Factor; Endothelins; Heart Failure; Humans; Neurotransmitter Agents; Nitric Oxide; Renin-Angiotensin System; Sympathetic Nervous System; Vasomotor System; Vasopressins; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Catecholamines; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Neurosecretory Systems; Renin; Ventricular Dysfunction, Left

Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. A total of 109 hospitalized ADHF patients were randomly assigned to either a tolvaptan or a carperitide treatment group. Baseline clinical characteristics were not different between the two groups. We divided these patients based on the left ventricular ejection fraction (EF) by echocardiography, and blood pressure (BP) at the time of admission. Daily urine volume between the tolvaptan and carperitide groups in patients with preserved EF (≥ 50%) was not different, however, in those with reduced EF (< 50%), the urine volume was significantly higher in the tolvaptan group than in the carperitide group (day 2, 3, 4, P < 0.05 for all). Daily urine volume did not differ between these two groups in the high blood pressure group (BP ≥ 140 mmHg), but was significantly higher in the tolvaptan group than in the carperitide group (day 1, P = 0.021; day 3, P = 0.017) in the low blood pressure group (BP < 140 mmHg). The present study reveals that tolvaptan is more effective than carperitide, especially in ADHF patients with reduced left ventricular systolic function and without hypertension.

Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Atrial Natriuretic Factor; Benzazepines; Female; Heart Failure; Humans; Hypotension; Male; Middle Aged; Stroke Volume; Tolvaptan; Treatment Outcome; Ventricular Dysfunction, Left

To evaluate the role of atrial natriuretic peptide (ANP) in differentiating the aetiology of heart failure in children with left ventricular (LV) volume overload.. The study was conducted on 48 patients with LV volume overload (G one: rheumatic heart disease in failure; G2: compensated rheumatic heart disease; G3: congenital left to right shunt; and G4: dilated cardiomyopathy). Twelve healthy children served as a control group. New York Heart Association (NYHA) class, LV dimensions and functions using Vivid 7 dimensions were evaluated. Serum ANP was measured using the ELISA technique, before and 3 months after treatment with angiotensin converting enzyme inhibitor.. ANP was raised in all patients as compared to controls (G one: 28.33 ± 5.78, G2: 26.5 ± 4.11, G3: 28.5 ± 6.6, G4: 29.25 ± 4.5 pg/mL, control group: 5.54 ± 1.4 pg/mL, P < 0.001 for all) and varied significantly between different NYHA classes regardless of the underlying cardiac lesion. It was significantly higher in group 1 than 2 (P < 0.05). It decreased significantly after treatment (G1: 15.3 ± 5.3, G2: 10.7 ± 2.5, G3: 11.5 ± 3.8, G4: 15.7 ± 10.7 pg/mL, P < 0.001). The rate of change of ANP correlated with that of LV end diastolic diameter (r = 0.3, P < 0.05) irrespective of the underlying cause.. ANP increases in cases of LV volume overload irrespective of the aetiology of heart failure. It can differentiate between children in quiescent state from those in clinical failure even in the absence of echocardiographically detectable systolic dysfunction. Furthermore, it can monitor LV remodelling with treatment.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Child; Child, Preschool; Ductus Arteriosus, Patent; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Heart Failure; Heart Septal Defects; Heart Valve Diseases; Humans; Infant; Infant, Newborn; Male; Prospective Studies; Rheumatic Heart Disease; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

Continuous low-dose infusion of human atrial natriuretic peptide (hANP) in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) inhibits the renin-angiotensin-aldosterone system and compensates for the adverse effects of CPB.. We examined the influence of hANP infusion on cardiac and renal function in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG).. The subjects were 133 patients who underwent CABG and had a pre-operative ejection fraction < or =35%. They were randomized to receive 0.02 microg/kg/min of hANP from the initiation of CPB (hANP group) or placebo (saline) infusion.. Early post-operative mortality did not show a significant difference between the 2 groups, but perioperative complications were significantly less frequent in the hANP group (p = 0.015). Long-term all-cause mortality showed no difference, but the cardiac death-free rate at 5 or 8 years post-operatively was 98.5% in the hANP group and 85.5% in the placebo group (p = 0.0285). Post-operative ejection fraction was significantly larger and the post-operative brain natriuretic peptide level was significantly lower in the hANP group. Serum creatinine was significantly lower in the hANP group than the placebo group at 1 month, 6 months, and 1 year post-operatively, whereas the estimated glomerular filtration rate was significantly higher in the hANP group at these times.. In patients with left ventricular dysfunction undergoing CABG, hANP showed renal- and cardio-protective effects and reduced post-operative complications. It also improved the long-term prognosis. We suggest that hANP should be considered as part of perioperative management of patients with cardiac dysfunction undergoing cardiac surgery. (NU-HIT trial for LVD; UMIN000001652).

Topics: Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Creatinine; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Infusions, Intravenous; Male; Postoperative Complications; Stroke Volume; Ventricular Dysfunction, Left

In patients with acute decompensated heart failure (ADHF) and left ventricular systolic dysfunction (LVSD), the role of initial vasodilator therapy remains uncertain. The present study aimed to evaluate the acute efficacy of initial carperitide therapy and to predict its response in ADHF patients with LVSD.. Twenty-four consecutive patients with ADHF and LVSD were enrolled. Inclusion criteria were a left ventricular ejection fraction < 40%, systolic blood pressure (BP) > 90 mm Hg, and pulmonary capillary wedge pressure >or=18 mm Hg at baseline. Hemodynamic parameters were evaluated by right heart catheterization before and after carperitide infusion. Responders were defined as a >or=30% reduction of pulmonary capillary wedge pressure (PCWP) or a decrease to < 16 mm Hg within 6 h after carperitide infusion.. Seventeen (71%) of the 24 patients were responders for initial carperitide therapy. The responders had significantly higher systolic BP and cardiac index at baseline compared with nonresponders. The area under the curve (AUC) for systolic BP was 0.93 and a cut-off value of 120 mm Hg had a sensitivity of 94% and specificity of 86% for predicting the efficacy of carperitide. The AUC for the cardiac index was 0.88 and a cut-off value of 2.30 L/min/m(2) had a sensitivity of 65% and a specificity of 100% for predicting the response to carperitide.. The initial use of carperitide therapy safely reduces PCWP in ADHF patients with LVSD and baseline systolic BP may be useful for predicting the response to initial carperitide therapy for ADHF with LVSD.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Patient Admission; Sex Factors; Time Factors; Ventricular Dysfunction, Left

To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure.. This was a double-blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty-two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 microg/kg followed by a continuous infusion of 0.1-0.2 microg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7-9 days, and in CO was 12-13 days. Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855, maximal metabolite levels occurred at day 3.. Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1-3 days after starting the infusion, effects were sustained for up to at least a week.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Double-Blind Method; Echocardiography; Female; Heart Failure; Heart Rate; Humans; Hydrazones; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Placebos; Pulmonary Circulation; Pyridazines; Simendan; Systole; Time Factors; Ventricular Dysfunction, Left

Statins have pleiotropic effects, such as improvement in endothelial function and antiinflammatory, antiproliferative, and antioxidative effects, that should be beneficial for patients with chronic heart failure (CHF). The aim of this study was to investigate the long-term effect of statins on neurohumoral activation and cardiac function in patients with CHF.. We enrolled 38 outpatients with mild to moderate CHF and radionuclide left ventricular ejection fraction (LVEF) <40%. These patients were randomly assigned to receive atorvastatin (10 mg/d) or conventional treatment for heart failure and were prospectively followed up for at least 3 years. At entry, we measured plasma concentrations of brain natriuretic peptides (BNPs) and left ventricular end-diastolic dimension and LVEF by echocardiography; thereafter, these measurements were repeated at least every 6 months. The primary end point was defined as the improvement in cardiac function and BNP.. There were no significant differences in age, sex, New York Heart Association class, left ventricular end-diastolic dimension, LVEF, and serum cholesterol level at entry between patients with (n = 19) and without atorvastatin (control, n = 19). After a follow-up period of 31 +/- 14 months, BNP (median [25th, 75th percentile]) significantly decreased in the atorvastatin group (84 [36, 186] to 55 [37, 91] pg/mL, P = .02) but not in the control group. Left ventricular end-diastolic dimension significantly decreased (67.1 [59.9, 70.8] to 61.1 [58, 63.9] mm, P = .02), and LVEF also significantly increased in the atorvastatin group (33.3% +/- 7.4% to 39.1% +/- 12.1%, P = .01) but not in the control group.. Long-term atorvastatin therapy decreases neurohumoral activation and improves cardiac function in patients with mild to moderate CHF.

Topics: Aged; Atorvastatin; Atrial Natriuretic Factor; Disease-Free Survival; Echocardiography; Female; Follow-Up Studies; Heart Failure; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyrroles; Stroke Volume; Ventricular Dysfunction, Left

Cibenzoline is able to improve left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM), but the exact mechanism remains to be determined.. The present study was designed to elucidate the effect of intravenous administration of 1.4 mg/kg of cibenzoline on aortic and LV pressures, and transmitral Doppler flow pattern in 7 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 9 patients with hypertrophic nonobstructive cardiomyopathy (HNCM). Before and at the end of the administration, aortic and LV pressures, LV pressure gradient (LVPG) and transmitral Doppler velocity profiles were examined. After the administration of cibenzoline, LV minimal and end-diastolic pressures decreased from 9+/-4 mmHg to 1+/-5 mmHg (p=0.0049) and from 22+/-7 mmHg to 14+/-5 mmHg (p=0.0106) in patients with HOCM, and from 9+/-5 mmHg to 5+/-3 mmHg (p=0.0036) and from 20+/-6 mmHg to 14+/-3 mmHg (p=0.0033) in patients with HNCM. LVPG decreased in all patients with HOCM. E-wave velocity increased, A-wave velocity decreased, and thus the E/A ratio increased from 0.77+/-0.29 to 1.20+/-0.48 (p=0.0004).. Reduction of LV diastolic pressures by intravenous administration of cibenzoline may be related to an improvement in the E/A ratio in patients with HCM.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Hypertrophic; Catecholamines; Female; Humans; Imidazoles; Infusions, Intravenous; Laser-Doppler Flowmetry; Male; Middle Aged; Ventricular Dysfunction, Left

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery (n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls (n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 +/- 101 to 1,268 +/- 334 pg/ml (P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM (P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER (r = -0.57, P < 0.01) and tau (r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

Topics: Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Tachycardia; Ventricular Dysfunction, Left

Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modern pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malondialdehyde (MDA) and isoprostanes are often used as markers of lipid peroxidation and oxidative stress. We also studied whether long-term treatment with isosorbide-5-mononitrate (IS-5-MN) in combination with standard HF therapy affects P-MDA levels in patients with evidence of left ventricular (LV) dysfunction following acute myocardial infarction (AMI).. Ninety-two patients with clinical or echocardiographic evidence of LV-dysfunction following AMI were randomized to treatment with either IS-5-MN or placebo. In a subgroup of 83 patients with available plasma MDA, echocardiography, right-heart catherization, and plasma natriuretic peptides were evaluated. Control subjects were 80 healthy blood donors. A second study group consisted of 56 patients with CHF, evaluated with respect to LV function, brain natriuretic peptide and markers of oxidative stress (P-MDA and 8-isoprostane). The second control group comprised 50 healthy subjects.. Lipid peroxidation measured by P-MDA and 8-isoprostane was not increased in patients with LV dysfunction treated with standard HF therapy. No positive correlation was found to the severity of HF. Long-term IS-5-MN therapy did not influence P-MDA concentrations.. Although results from many experimental and clinical studies suggest that oxidative stress is increased in HF, this may not be true for patients treated with beta blockers and inhibitors of the renin-angiotensin system.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Captopril; Comorbidity; Delayed-Action Preparations; Dinoprost; Female; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Lipid Peroxidation; Losartan; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nitric Oxide Donors; Oxidative Stress; Ramipril; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

Several neurohumoral mechanisms involved in cardiovascular regulation are activated in the failing heart, but only limited information is available regarding the influence of long-term nitrate therapy.. This was a double-blind, randomized comparison of isosorbide-5-mononitrate (IS-5-MN), 60 mg given orally, once daily for 11 months to patients (n = 47) with left ventricular (LV) dysfunction following acute myocardial infarction (AMI). Forty-five patients received placebo. All patients received ramipril.Plasma natriuretic peptides (atrial [ANP] and brain [BNP] natriuretic peptide), epinephrine, norepinephrine (NEPI), antidiuretic hormone, aldosterone (Aldo), renin activity (PRA), substance P, neuropeptide Y-like immunoreactivity, calcitonin gene-related peptide, and vasoactive intestinal peptide were measured at baseline and at the end of the treatment period. Clinical, echocardiographic, and hemodynamic data were also obtained.. Chronic nitrate therapy does not significantly affect the neurohumoral status in patients with LV dysfunction after AMI, apart from a decrease in ANP. Some hormones are more closely associated with diastolic dysfunction/increased volume load (ANP and BNP) and others are more closely associated with systolic dysfunction (PRA, NEPI, Aldo). There is a temporal dissociation of these 2 groups of hormones 1 year post infarction: ANP and BNP decrease, whereas NEPI and Aldo show a slight increase. BNP levels do not reflect all important pathophysiologic mechanisms in heart failure. Consequently, the use of other neurohormonal factors than BNP for monitoring of heart failure therapy should be explored.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Double-Blind Method; Echocardiography; Female; Humans; Isosorbide Dinitrate; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Norepinephrine; Renin; Substance P; Ventricular Dysfunction, Left

The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, has vasodilatory and diuretic properties and can inhibit the RAAS. However, its effect on cardiac sympathetic nerve activity has not been determined.. We studied 58 patients with decompensated nonischemic acute heart failure who were treated with intravenous low-dose dopamine and diuretics. Twenty-nine patients (group A) were assigned to also receive intravenous ANP, whereas the remaining 29 patients (group B) continued their established drug regimen. The dopamine or ANP was continuously infused for >96 h. The left ventricular end-diastolic volume and ejection fraction were determined by echocardiography before and 4 wk after treatment. The delayed heart-to-mediastinum (H/M) count ratio, delayed total defect score, and washout rate were determined from (123)I-metaiodobenzylguanidine (MIBG) images 3 wk after treatment.. Fifty-six patients enrolled in the trial completed the entire protocol. After treatment of group A (n = 28), the left ventricular end-diastolic volume decreased from 186 +/- 42 to 174 +/- 48 mL (P < 0.05), and left ventricular ejection fraction increased from 32% +/- 9% to 36% +/- 7% (P < 0.05). In group B (n = 28), these parameters did not change significantly. In addition, 3 wk after treatment of group A, the total defect score was significantly lower (30 +/- 9 vs. 38 +/- 9, P < 0.01), the H/M count ratio was significantly higher (1.86 +/- 0.21 vs. 1.62 +/- 0.23, P = 0.0001), and washout rate was significantly lower (42% +/- 12% vs. 49% +/- 12%, P < 0.05) than in group B.. The present study demonstrates an improvement in echocardiographic parameters with ANP infusion. In addition, cardiac (123)I-MIBG scintigraphic parameters were better in patients who received ANP infusion along with dopamine and diuretics than in patients who received standard conventional therapy. These findings indicate that intravenous administration of ANP can benefit cardiac sympathetic nerve activity and improve left ventricular remodeling in patients with acute heart failure.

Topics: 3-Iodobenzylguanidine; Aged; Atrial Natriuretic Factor; Cardiotonic Agents; Dopamine; Drug Combinations; Female; Furosemide; Heart; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Sympathetic Nervous System; Treatment Outcome; Ventricular Dysfunction, Left

The prevalence of chronic heart failure (CHF) with systolic dysfunction is increasing. Plasma natriuretic peptides have been envisaged as diagnostic and predictive markers.. To investigate the relationship between the levels of B-type natriuretic peptide (BNP) and A-type natriuretic peptide (ANP) and the clinical and functional parameters of CHF in outpatients with CHF at baseline, compared with normal healthy controls; to find out the differences in a randomised controlled trial between patients treated with an angiotensin-converting enzyme (ACE) inhibitor, captopril, or an angiotensin receptor blocker (ARB), irbesartan. These differences were assessed throughout the six-month treatment period and at the sixth month.. Plasma BNP (pmol/L) and ANP (pmol/L) were determined in 68 hypertensive patients with dilated cardiomyopathy, NYHA class III-IV and ejection fraction (EF) < or = 40%, and in 26 normal controls. Statistical analysis for BNP and ANP was done by Students t-test. The patient group was randomly subdivided into two subgroups of 34 patients, each treated with either an ARB, irbesartan, or an ACE inhibitor (ACE-I), captopril. BNP and ANP were measured in both subsamples and correlated with clinical, functional and neurohormonal parameters throughout a follow-up period of six months and at the sixth month.. The mean EF in the patient sample was 33.43+/-6.52% and in the controls was 61.96 +/-3.53% (p=0.000). The mean BNP (pmol/L) in patients was 44.78+/-54.36 and in the controls was 7.12+/-8.28 (p=0.000) and the mean ANP (pmol/L) was 30.32+/-25.97 in patients and 11.18+/-7.92 in controls (p=0.000). A statistically significant difference was found between patients and healthy controls. Significant correlations were found between natriuretic peptides and EF. Between the baseline phase and the sixth month, BNP and ANP decreased significantly in the ARB group. At the sixth month, both BNP and ANP were lower in the ARB group. Evidence of clinical benefit was found with both ARB or ACE-I treatment throughout the six months, with patients moving from classes III and IV to class II NYHA. Improvement of EF was also found, with transition of patients with lower EF (even <30%) to higher values. EF was higher in the ARB group at the sixth month.. BNP and ANP can be useful diagnostic tools in hypertensive CHF patients with moderate-to-severe LV dysfunction. The decrease in BNP and ANP in the ARB group throughout six months, as well as the lower value at the sixth month, suggest a prognostic value of these parameters.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Biphenyl Compounds; Captopril; Cardiac Output, Low; Chronic Disease; Echocardiography; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Humans; Irbesartan; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Radiography, Thoracic; Radionuclide Ventriculography; Tetrazoles; Ventricular Dysfunction, Left

Nitrates are often administrated with a variety of other pharmacologic agents in the management of chronic heart failure (CHF). However, limited information is available concerning the long-term effects in patients with evidence of left ventricular (LV) dysfunction after acute myocardial infarction (AMI) already treated with standard heart failure therapy.. In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of a 60 mg dose of isosorbide-5-mononitrate (IS-5-MN) given daily for 11 months to 47 patients with clinical or echocardiographic evidence of left ventricular dysfunction after acute myocardial infarction. Forty-five patients received a placebo.. Invasive hemodynamic measurements did not show any difference between the treatment regimens. Overall changes in echocardiographic measurements were not significantly different between IS-5-MN therapy and the placebo groups. However, in a prespecified subgroup with left ventricular ejection fraction < or =40% at baseline, IS-5-MN therapy resulted in a lesser increase of end-diastolic volume index than the placebo (P =.047). IS-5-MN significantly reduced the serum concentration of atrial natriuretic peptide (mean 20.0 pmol/L, 95% CI 7.7-32.3, P =.002), whereas the placebo did not (P =.041 for the difference between the groups). The proportion of patients taking diuretics was significantly reduced in the IS-5-MN group, from 30 of 44 to 20 of 44 (P =.02), but not with placebo, which remained at 27 of 43 (P = 1.0, with P =.048 for the difference between the regimens).. Oral, long-term IS-5-MN therapy resulted in lower atrial natriuretic peptide levels and reduced the need for additional diuretics. Less LV dilatation was observed in patients with more severe LV dysfunction at baseline.

Topics: Aged; Atrial Natriuretic Factor; Delayed-Action Preparations; Diuretics; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Hemodynamics; Humans; Isosorbide Dinitrate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Ramipril; Ventricular Dysfunction, Left

C-type natriuretic peptide (CNP) is a vasodilator produced by the vascular endothelium. It shares structural and physiological properties with the cardiac hormones atrial natriuretic peptide and brain natriuretic peptide (BNP), but little is known about its pathophysiological role in chronic heart failure (CHF). We assessed the hypothesis that CNP is produced by the heart in patients with CHF.. Myocardial CNP production was determined (difference in plasma levels between the aortic root and coronary sinus [CS]) in 9 patients undergoing right and left heart catheterization as part of their CHF assessment (all male, age 59+/-9 years; New York Heart Association class 2.2+/-0.1; left ventricular ejection fraction 29+/-5%; creatinine 105+/-8 micro mol/L [all values mean+/-SEM]). BNP, established as originating from myocardium, was assessed from the same samples as a positive control. Analyses were performed by a blinded operator using a standard competitive radioimmunoassay kit (Peninsula Laboratories, Bachem Ltd UK). A step-up (29%) in plasma CNP concentration was found from the aorta to the CS (3.55+/-1.53 versus 4.59+/-1.54 pg/mL, respectively; P=0.035). The mean increase in CNP was 0.90+/-0.35 pg/mL (range 0.05 to 2.80 pg/mL). BNP levels increased by 57% from aorta to CS (86.0+/-20.5 versus 135.0+/-42.2 pg/mL; P=0.01). CS CNP levels correlated with mean pulmonary capillary wedge pressure (r=0.82, P=0.007).. We have shown that CNP is produced by the heart in patients with CHF. Although further evaluation is required to define its full pathophysiological role in this condition, CNP may represent an important new local mediator in the heart.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Chronic Disease; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Dysfunction, Left

To evaluate the effects of high thoracic epidural anesthesia (TEA) on global and regional myocardial function and on perioperative coronary risk in patients undergoing coronary artery bypass grafting.. Prospective and randomized clinical trial blinded for the primary outcome measure of 73 patients scheduled for coronary artery bypass grafting who had a left ventricular ejection fraction of 50% or more conducted from February 1, 2000, through August 31, 2000, at University Hospital, Münster, Germany.. Of 73 randomized patients, 37 were control subjects (who received general anesthesia only) and 36 were in the group who received general anesthesia and high TEA.. The primary outcome measure was regional left ventricular function after myocardial revascularization, assessed by transesophageal echocardiography. We further determined the plasma concentrations of cardiac troponin I and atrial and brain natriuretic peptides. Secondary outcome measures were postoperative complications recorded to 14 days and mortality recorded to 720 days.. High TEA was effective in all patients of this group, the somatosensory block extended from T1 through T7 vertebrae. Regional left ventricular function was significantly improved (mean [SD] global wall motion index, 0.74 [0.18] vs 0.38 [0.16]; P<.05), and cardiac troponin I concentrations were reduced by 72% (mean [SD], 5.7 [1.5] vs 1.6 [0.7] ng/mL, P<.05) in patients with high TEA. Natriuretic peptide concentrations peaked during reperfusion (atrial natriuretic peptide) and 24 hours after reperfusion (brain natriuretic peptide). High TEA reduced the mean (SD) peak concentrations of atrial natriuretic peptide by 54% (211 [63] vs 98 [33] ng/mL, P =.03) and brain natriuretic peptide by 43% (189 [39] vs 108 [21] ng/mL, P =.01). One of 36 patients who received high TEA and 3 of 37 controls died.. Reversible cardiac sympathectomy by high TEA improves regional left ventricular function and reduces postoperative ischemia after coronary artery bypass grafting. These effects of high TEA may improve the long-term outcome after myocardial revascularization.

Topics: Anesthesia, Epidural; Atrial Natriuretic Factor; Chi-Square Distribution; Coronary Artery Bypass; Echocardiography, Transesophageal; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sympathectomy; Treatment Outcome; Troponin I; Ventricular Dysfunction, Left

Plasma C-terminal atrial natriuretic peptide (C-ANP), N-terminal ANP (N-ANP), and brain natriuretic peptide (BNP) have diagnostic utility in detecting left ventricular dysfunction. Their relative value in monitoring symptom status during the chronic treatment of congestive heart failure (CHF) remains undefined.. Ninety-eight subjects with CHF were evaluated. Baseline natriuretic peptides were measured by radioimmunoassay, left ventricular ejection fraction (LVEF) was estimated with echocardiography, and New York Heart Association (NYHA) class was determined independently by attending heart failure specialists. Forty-one subjects were restudied during a 6- to 12-month follow-up period after optimizing therapy. At baseline, all natriuretic peptides and LVEF correlated positively with NYHA class (P <.005). Plasma BNP, however, correlated best with NYHA class. At follow-up, only changes of BNP correlated to changes of NYHA class (P =.04). BNP decreased (-45% +/- 12%, N = 14, P =.002) in subjects whose NYHA class improved whereas BNP remained unchanged (-1% +/- 10%, N = 25, P =.95) in those whose NYHA class was stable.. This investigation demonstrates the superiority of plasma BNP as compared to ANP and LVEF in objectively assessing NYHA class during the chronic treatment of CHF. Given that clinical assessment of CHF is subjective, plasma BNP is a useful objective biomarker in monitoring human CHF in the outpatient setting.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Radioimmunoassay; Single-Blind Method; Treatment Outcome; Ventricular Dysfunction, Left

Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers improve prognosis inpatients with chronic heart failure. Some patients, however, show little response to combined treatment with an ACE inhibitor and a beta-blocker. In addition, the ACE inhibitor cannot completely suppress angiotensin II production. Our objective was to examine whether replacing the ACE inhibitor with an angiotensin II antagonist can improve the condition of patients with chronic heart failure.. In 11 patients with chronic heart failure treated with an ACE inhibitor and a beta-blocker, who have had severe left ventricular dysfunction or high plasma level of natriuretic peptides, left ventricular dimension, and fractional shortening, plasma atrial and brain natriuretic peptide (ANP and BNP) levels were determined before and 3 months after the change of treatment.. After substituting the ACE inhibitor with an angiotensin II antagonist, patients showed New York Heart Association functional class improvement, and significant decrease in left ventricular dimension and BNP.. In patients with severe chronic heart failure treated with an ACE inhibitor and a beta-blocker, replacing the ACE inhibitor with an angiotensin II antagonist may be effective. However, this has to be confirmed by an adequately powered randomized controlled study.

Topics: Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome; Ventricular Dysfunction, Left

B-Type natriuretic peptide (BNP), a protein released from the left ventricle in response to volume expansion and pressure overload, has emerged as the first whole blood marker for the identification of individuals with congestive heart failure (CHF).. The purpose of this study was to assess the performance of a point-of-care assay to diagnose and evaluate the severity of CHF on the basis of the New York Heart Association (NYHA) classification system.. Through a prospective, multicenter trial, whole blood samples were collected from a total of 1050 inpatients, outpatients, and healthy control patients. Participants were divided into subgroups for BNP analysis: patients without cardiovascular CHF (n = 473), patients with hypertension and no cardiovascular disease (n = 168), NYHA class I CHF (n = 73), class II CHF (n = 135), class III CHF (n = 141), and class IV CHF (n = 60).. Circulating BNP concentrations determined from the bedside assay increased with CHF severity, as determined by the NYHA classification system, but were only statistically significant (P <.001) between individuals with and without CHF. Individuals without CHF had a median BNP concentration of 9.29 pg/mL. Median BNP values, with their corresponding interquartile ranges, for NYHA classification I through IV were 83.1 pg/mL (49.4-137 pg/mL), 235 pg/mL (137-391 pg/mL), 459 pg/mL (200-871 pg/mL), and 1119 pg/mL (728->1300 pg/mL), respectively. With the use of a decision threshold of 100 pg/mL, the assay demonstrated 82% sensitivity and 99% specificity for distinguishing control patients and patients with CHF.. BNP concentrations obtained from whole blood samples are useful in the diagnosis of CHF and staging the severity of the disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Point-of-Care Systems; Prospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left

Digitalis has a long history in the treatment of heart failure but its effects on cardiac hemodynamics and neurohormonal modulation are not well characterized.. The purpose of this study was to evaluate the relationship between atrial natriuretic peptide (ANP) and the hemodynamic responses to acute digitalis administration in patients with normal and impaired left ventricular function (LVD).. Thirty patients were enrolled in the study, 20 with LVD (LVEF=22+/-8%) and 10 control subjects (LVEF=77+/-10%). Hemodynamics and plasma ANP concentrations were measured supine and with leg elevation before and after digitalis. In patients with normal ventricular function, the hemodynamic stress of leg elevation in the pre-digitalis state resulted in significant (P<0.05) increases in PAWP and MPAP. Digitalis administration in the supine position produced reductions in heart rate, PAWP, MPAP and CI; SVR was increased. In LVD patients leg elevation further increased PAWP, RAP and MPAP. Digitalis in the supine position, however, reduced RAP, MPAP and PAWP and increased CI. These improved hemodynamics were preserved during the stress of leg elevation. Leg elevation following digitalis resulted in increased ANP concentrations despite decreased cardiac filling pressures.. Acute digitalis administration results in hemodynamic improvement in LVD patients which may in part result from digitalis stimulated release of myocardial ANP under conditions of hemodynamic stress.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Deslanoside; Drug Administration Schedule; Female; Heart Function Tests; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Probability; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left; Ventricular Function, Left

Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function.. We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286 +/- 31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33 +/- 3 pg/mL. Patients with restrictive like filling patterns on echocardiography had the highest BNP levels (408 +/- 66 pg/mL), and patients with symptoms had higher BNP levels in all diastolic filling patterns. The area under the receiver-operating characteristic curve for BNP to detect any diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95; P<0.001). A BNP value of 62 pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for detecting diastolic dysfunction.. A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography. In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction.

Topics: Aged; Area Under Curve; Atrial Function, Left; Atrial Natriuretic Factor; Chronic Disease; Diastole; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Ventricles; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Congestive heart failure (CHF) is characterized by neurohormonal activation, including increased plasma concentrations of atrial natriuretic peptide (ANP) and N-terminal ANP (N-ANP). Onset of atrial fibrillation (AF) further increases these peptides, but it may be hypothesized that concentrations decrease during longstanding AF due to inherent atrial degeneration.. We sought to investigate the relation between neurohormonal activation in patients with CHF and the duration of concomitant AF.. The study group comprised 60 patients (age 70 +/- 8 years) with advanced CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 0.35) and chronic AF (duration 21 (1-340) months). Plasma neurohormone concentrations were measured, and multiple regression analysis was performed to identify their clinical predictors.. Median plasma neurohormone concentrations were: ANP 113 pmol/l, N-ANP 1187 pmol/l, norepinephrine 496 pg/ml, renin 127 micro units/l, aldosterone 128 pg/ml and endothelin 8.1 pg/ml. Norepinephrine, renin, aldosterone and endothelin were not significantly related to the duration of AF. In contrast, ANP decreased along with the duration of AF (P = 0.03), while the same trend was observed for N-ANP (P = 0.10). However, for these peptides a first order interaction with LVEF was present, which was not observed in the other neurohormones. In patients with LVEF > 0.25 ANP and N-ANP increased along with the duration of AF, whereas in patients with LVEF < or = 0.25 an inverse relation between ANP (P = 0.02) and N-ANP (P = 0.04) and the duration of AF was present, longer-standing AF being associated with lower concentrations.. In patients with advanced CHF with low LVEF plasma ANP and N-ANP concentrations decrease during longstanding AF. This finding agrees with the concept that longstanding AF leads to impaired ability of the atria to produce these neurohormones due to inherent degenerative changes.

Topics: Aged; Aldosterone; Analysis of Variance; Atrial Fibrillation; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Male; Norepinephrine; Protein Precursors; Renin; Stroke Volume; Time Factors; Ventricular Dysfunction, Left

Angiotensin-converting enzyme inhibitors improve long-term survival in patients with left ventricular dysfunction after a myocardial infarction, but their mechanism of action is not entirely clear. The neurohormonal effects may be important in this respect, as well as an early hemodynamic unloading induced by these drugs. The primary objective was to assess the effect of trandolapril on plasma levels of atrial natriuretic peptide. A secondary objective was to assess the effects of trandolapril on selected neurohormones, vasoactive peptides and enzymes, which may be important in the development of left ventricular remodeling and heart failure following an acute myocardial infarction. A total of 119 patients with an acute myocardial infarction and a wall motion index < or =1.2 (16-segment echocardiographic model) were randomized to double blind treatment with trandolapril or placebo within 3-7 days after the onset of infarction. Blind treatment was discontinued 21 days after the index infarction. Venous blood samples were collected at rest, before randomization and on the day after treatment was discontinued. At the end of the study, there were no differences in plasma levels of atrial natriuretic peptide between the two treatment groups. Angiotensin-converting enzyme activity was suppressed and plasma renin activity was higher in the trandolapril group. No differences in plasma levels of N-terminal pro-atrial natriuretic peptide, brain natriuretic peptide, aldosterone, noradrenaline, adrenaline, vasopressin, big endothelin-1 and neuropeptide Y were found between the two treatment groups. There were positive correlations between several markers of neurohormonal activation at baseline and variables expressing left ventricular dysfunction and clinical heart failure. Neurohormonal activation is related to left ventricular dysfunction. The effects of 2-3 weeks of angiotensin-converting enzyme inhibition on neurohormonal activation does not predict the already established beneficial long-term effects after myocardial infarction. Thus, early modulation of circulatory neurohormone levels may not be a major mechanism for the efficacy of angiotensin-converting enzyme inhibitors in these patients. Selected plasma hormone markers may still be used to identify patients who might get the greatest benefit from treatment.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Double-Blind Method; Female; Humans; Indoles; Male; Myocardial Infarction; Neurotransmitter Agents; Renin; Ventricular Dysfunction, Left

This study assessed the prognostic value of Iodine-123-metaiodobenzylguanidine (MIBG) imaging and of the plasma level of cardiac natriuretic peptides in patients with left ventricular dysfunction resulting from cardiomyopathy. Predictors of cardiac death or hospitalization related to progressive heart failure were examined in 171 patients with chronic heart failure (96 patients with idiopathic cardiomyopathy and 75 patients with ischemic cardiomyopathy). All patients underwent MIBG imaging at rest and other hemodynamic studies. During a mean (+/-SD) follow-up period of 27+/-11 months, 11 patients died from heart failure and 16 required hospitalization. High MIBG washout was an independent predictor of cardiac death (relative risk [RR] = 1.158, p<0.0001) whereas the plasma level of brain natriuretic peptide (BNP: relative risk [RR] = 1.005, p<0.0001) and high MIBG washout (relative risk [RR] = 1.094, p<0.0001) were predictors of progressive heart failure (ie, combined cardiac death and hospitalization). Accelerated myocardial adrenergic nerve activity as assessed by MIBG imaging and the plasma levels of BNP are powerful predictors of the patient's prognosis.

Topics: 3-Iodobenzylguanidine; Aged; Atrial Natriuretic Factor; Cardiomyopathies; Death; Disease-Free Survival; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Regression Analysis; Treatment Outcome; Ventricular Dysfunction, Left

The study assessed the relative predictive potency of neurohumoral factors in patients with advanced left ventricular (LV) dysfunction during neurohumoral blocking therapy.. The course of heart failure is characterized by progressive LV deterioration associated with an increase in cardiac (natriuretic peptides) and predominantly extracardiac (norepinephrine, big endothelin [big ET]) hormone plasma levels.. Plasma hormones were measured at baseline and months 3, 6, 12 and 24 in 91 patients with heart failure (left ventricular ejection fraction [LVEF] <25%) receiving 40 mg enalapril/day and double-blind atenolol (50 to 100 mg/day) or placebo. After the double-blind study phase, patients were followed up to four years. Stepwise multivariate regression analyses were performed with 10 variables (age, etiology, LVEF, symptom class, atenolol/placebo, norepinephrine, big ET, log aminoterminal atrial natriuretic peptide, log aminoterminal B-type natriuretic peptide [N-BNP] and log B-type natriuretic peptide [BNP]). During the study, the last values prior to patient death were used, and in survivors the last hormone level, New York Heart Association class and LVEF at month 24 were used.. Thirty-one patients died from a cardiovascular cause during follow-up. At baseline, log BNP plasma level (x2 = 13.9, p = 0.0002), treatment allocation (x2 = 9.5, p = 0.002) and LVEF (x2 = 5.6, p = 0.017) were independently related to mortality. During the study, log BNP plasma level (x2 = 21.3, p = 0.0001) remained the strongest predictive marker, with LVEF (x2 = 11.2, p = 0.0008) log N-BNP plasma level (x2 = 8.9, p = 0.0027) and treatment allocation (x2 = 6.4, p = 0.0109) providing additional independent information.. In patients with advanced LV dysfunction receiving high-dose angiotensin-converting enzyme inhibitors and beta-blocker therapy BNP and N-BNP plasma levels are both independently related to mortality. This observation highlights the importance of these hormones and implies that they will likely emerge as a very useful blood test for detection of the progression of heart failure, even in the face of neurohumoral blocking therapy.

Topics: Adrenergic beta-Antagonists; Atenolol; Atrial Natriuretic Factor; Biomarkers; Double-Blind Method; Endothelin-1; Endothelins; Female; Heart Failure; Hormones; Humans; Male; Middle Aged; Norepinephrine; Placebos; Prognosis; Proportional Hazards Models; Protein Precursors; Random Allocation; Risk Factors; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

Congestive heart failure is a common and serious complication in patients undergoing chronic dialysis. However, there have been no studies on preferential medical therapies to improve left ventricular function in haemodialysis patients. Beta-blocker treatment is known to improve left ventricular function in patients with dilated cardiomyopathy; moreover, plasma levels of noradrenaline and natriuretic peptides are sensitive markers of left ventricular dysfunction. The present study investigated whether beta-blocker treatment could improve left ventricular function in haemodialysis patients with a dilated left ventricle. Our study group comprised 14 haemodialysis patients with a dilated left ventricle, who had undergone maintenance haemodialysis for a mean of 11 years. The following haemodynamic parameters were evaluated before and after 4 months of treatment with the beta-blocker metoprolol: left ventricular dimension at end-systole and end-diastole, and fractional shortening. Plasma levels of noradrenaline, atrial natriuretic peptide and brain natriuretic peptide were also determined. Dry body weight and haemoglobin concentration showed no significant change after compared with before treatment with metoprolol. Heart rate decreased significantly, from 79+/-9 beats/min to 69+/-9 beats/min, but systolic blood pressure remained unchanged. The left ventricular dimension both at end-systole and at end-diastole was decreased, and fractional shortening increased significantly. Plasma levels of noradrenaline did not change significantly, but those of atrial natriuretic peptide and brain natriuretic peptide decreased markedly [from 100+/-89 pg/ml to 46+/-29 pg/ml (P=0.0051) and from 549+/-516 pg/ml to 140+/-128 pg/ml (P=0.0035) respectively]. In conclusion, beta-blocker therapy with metoprolol can markedly attenuate left ventricular remodelling and decrease the plasma levels of natriuretic peptides in haemodialysis patients with a dilated left ventricle.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Renal Dialysis; Ultrasonography; Ventricular Dysfunction, Left

Doxorubicin-induced cardiotoxicity was used as a model to prospectively investigate neuroendocrine changes during the development of left ventricular dysfunction. Radionuclide ventriculography, frequency domain analysis of heart rate variability (HRV), and plasma noradrenaline and natriuretic peptide measurements were performed in 27 adult lymphoma patients at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m(2). The left ventricular ejection fraction (LVEF) decreased from 58.1+/-1.4% to 50.3+/-1.1% (P<0.001) and 49.3+/-1.7% (P<0.001) after cumulative doxorubicin doses of 400 and 500 mg/m(2) respectively. With a doxorubicin dose of up to 400 mg/m(2) there was an increase in sympathetic tone, characterized by a decrease in the normalized high-frequency (HF(nu)) power (P=0.011), and increases in the normalized low-frequency (LF(nu)) power (P=0.011), the LF/HF ratio (P=0.021) and the plasma noradrenaline concentration (P=0.034). The decrease in LVEF was correlated with the changes in LF(nu) and HF(nu) power (r=0.540, P=0.012) and LF/HF ratio (r=-0.452, P=0.04). However, after the cumulative doxorubicin dose of 500 mg/m(2) the changes in HRV components and plasma noradrenaline levels returned towards baseline. This was accompanied by increased concentrations of plasma atrial natriuretic peptide (P=0.004) and brain natriuretic peptide (P=0.021). Our findings suggest that doxorubicin-induced left ventricular dysfunction is associated with an early change in sympathovagal balance towards sympathetic predominance. Along with further progression of left ventricular dysfunction, there is an attenuation of sympathetic tone, which may be attributable to sympatho-adrenal inhibition by increased secretion of natriuretic peptides.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Autonomic Nervous System; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart Rate; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Prednisone; Prospective Studies; Radionuclide Ventriculography; Stroke Volume; Ventricular Dysfunction, Left; Vincristine

Myocardial blood flow (MBF) reserve is impaired in patients with symptomatic chronic heart failure. Whether this is already present in asymptomatic left ventricular (LV) dysfunction, and whether it is affected by angiotensin converting enzyme (ACE) inhibition, is unknown. We examined MBF in 20 patients with asymptomatic LV dysfunction and compared them to healthy volunteers. MBF (reserve) was assessed with positron emission tomography (PET) and N-13 ammonia at rest, during dipyridamole stress test (DST) and during cold pressor test (CPT). Further, in the LV-dysfunction group, we studied the effects of 3 months treatment with ACE inhibition with a second PET study. Patients were randomized double-blind to perindopril 4 mg daily or placebo. MBF at rest was similar in controls and patients. DST-induced MBF reserve, however, was decreased in patients vs. controls (1.71+/-0.2 vs. 2.62+/-0.5, respectively p < 0.05). Also CPT-induced MBF was lower in patients (1.14+/-0.06 vs. 1.23+/-0.03, p < 0.05). After 3 months double-blind treatment, CPT-induced MBF decreased in the placebo group (from 1.12+/-0.02 to 0.93+/-0.06), but was preserved in the perindopril group (from 1.16+/-0.08 to 1.14+/-0.08 shifts from baseline: -0.19+/-0.05 vs. -0.02+/-0.07 respectively p = 0.07). This was compatible with a trend to a smaller increase in coronary vascular resistance during CPT (1.23+/-0.08 vs. 1.03+/-0.06, placebo vs. perindopril, p = 0.06). In patients with asymptomatic LV dysfunction, MBF, both after vasodilation and after CPT, is already impaired. ACE inhibition with perindopril during this short-term treatment had no significant effects.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Flow Velocity; Exercise Test; Female; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Netherlands; Neurotransmitter Agents; Perindopril; Tomography, Emission-Computed; Treatment Outcome; Ventricular Dysfunction, Left

Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation.. The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001).. Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Cardiac Output; Cardiotonic Agents; Catecholamines; Chronic Disease; Deoxyepinephrine; Dopamine; Epinephrine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; New York; Norepinephrine; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Renin; Renin-Angiotensin System; Survival Analysis; Ventricular Dysfunction, Left; Ventricular Function, Left

To evaluate brain natriuretic peptide (BNP) as marker of left ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610 middle-aged subjects (50-67 years) who were further characterized with respect to hemodynamic and anthropometric parameters and by echocardiography.. Left ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and medication with beta adrenergic receptor blockers were significant and independently correlated with BNP (multivariate analysis, P < 0.05 each). As compared to subjects with normal LV function and mass-index (control), subjects with LV dysfunction (LV fractional shortening < 28%) or hypertrophy (LV mass-index > 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus control, P < 0.0001) was similar in magnitude to that associated with LV dysfunction (n = 39, +98% versus control, P < 0.03). These increases were markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive values of BNP varied considerably with the degree of LV dysfunction and the presence or absence of concomitant LV hypertrophy. With 0.81, the highest area under the receiver operator characteristic curve was obtained for the detection of severe LV dysfunction and concomitant hypertrophy and sensitivity, specificity, positive and negative predictive value for this condition were 71, 86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml.. The current study provides new insight into regulation and diagnostic value of BNP in middle-aged subjects and demonstrates important independent effects of LV function and mass upon BNP plasma concentrations. Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.

Topics: Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Ventricular Dysfunction, Left; Ventricular Function, Left

Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo.. Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; P<0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; P<0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4. 0%; P<0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by >90% (P<0.001).. Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of beta-blockade in heart failure.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carbazoles; Carvedilol; Double-Blind Method; Heart Failure; Humans; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Neuropeptides; Norepinephrine; Predictive Value of Tests; Prognosis; Propanolamines; Survival Analysis; Vasodilator Agents; Ventricular Dysfunction, Left

Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.

Topics: Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Disease; Double-Blind Method; Electrocardiography; Exercise Test; Humans; Indoles; Lactic Acid; Male; Middle Aged; Norepinephrine; Ventricular Dysfunction, Left; Ventricular Function, Left

Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure.. Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05).. Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Cross-Over Studies; Enalapril; Female; Fibrinolysis; Heart Failure; Heart Rate; Hemodynamics; Humans; Losartan; Male; Myocardial Ischemia; Plasminogen Activator Inhibitor 1; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Single-Blind Method; Tissue Plasminogen Activator; Ventricular Dysfunction, Left

Fifty patients with left ventricular diastolic heart failure (LVDHF), and 35 patients with left ventricular systolic heart failure (LVSHF) diagnosed by clinical manifestation and radionuclide ventriculography were studied and 20 normal persons served as controls. Plasma renin activity (PRA), angiotensin I (AT I), aldosterone (ALD), endothelin (ET) and atrial natriuretic peptide (ANP) concentrations were measured by radioimmunoassay. Fifty patients with LVDHF were divided into treatment group and control group in a randomized, double blind, control method. Enalpril, CoQ10 and VitE were given in treatment group while only CoQ10 and VitE were given in control group. The therapeutic efficacy was evaluated after 8 weeks of treatment. The results showed that plasma concentration of PRA, AT I, ALD, ET and ANP were increased in LVDHF, but lower than those in LVSHF. After treatment with enalapril plasma PRA was increased while AT I, ALD and ET level were decreased significantly but ANP level had no change in treatment group.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Double-Blind Method; Enalaprilat; Endothelins; Female; Humans; Male; Middle Aged; Renin; Ventricular Dysfunction, Left

Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established.. Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%.. These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Creatinine; Double-Blind Method; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Life Tables; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norway; Prognosis; Proportional Hazards Models; Protein Precursors; Severity of Illness Index; Survival Analysis; Ventricular Dysfunction, Left; Ventricular Function, Left

Acute myocardial infarction (AMI) leads to left ventricular dysfunction, the extent of which predicts mortality. We studied the effect of very early enalapril treatment in patients with left ventricular failure (Killip classification II-III) resulting from AMI. In a double-blind randomized trial, patients on conventional treatment were started on placebo (PL, n = 15) or 2.5 mg enalapril (EN, n = 15) twice daily as early as 24 to 30 h after AMI and were followed up over a period of 21 days. One patient died in each treatment group. There were three dropouts in the placebo group (progressive heart failure requiring antiotensin-converting enzyme inhibition) and one dropout in the enalapril group (malignant ventricular arrhythmias). Plasma atrial natriuretic peptide (ANP) and norepinephrine decreased similarly in both groups from elevated baseline concentrations. The patients with the highest baseline ANP levels died in both groups: EN: 579 fmol/ml (mean 65.3 +/- 34.4 fmol/ml), PL: 403 fmol/ml (mean 63.5 +/- 37.6 fmol/ml). Killip classification improved in 9 of 13 patients on enalapril but only in 5 of 11 patients on placebo. On echocardiography an increase in fractional shortening (FS) (3.2 +/- 7.5%, p < 0.05) was found with enalapril only. Patients on placebo required more diuretics, and plasma aldosterone increased threefold. Thus, very early enalapril treatment may help prevent left ventricular failure after AMI. Extremely high initial plasma ANP concentrations may predict an unfavorable outcome.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Double-Blind Method; Drug Administration Schedule; Echocardiography; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Survival Rate; Ventricular Dysfunction, Left

The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Cyclic GMP; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Ventricular Dysfunction, Left

In man, chronic antihypertensive calcium antagonist treatment improves cardiac function and reduces plasma ANF concentrations. Physical exercise increases cardiac workload and plasma ANF levels. In the present study, we investigated the effects of acute administration of the dihydropyridine calcium antagonist BAY t 7207 (BAY) during bicycle exercise on plasma ANF and plasma cyclic GMP levels, on mean arterial pressure (MAP), heart rate (HR), and on natriuresis and urinary urodilatin excretion. In a randomized, double-blind placebo controlled cross-over trial, 8 patients (age 56.8 +/- 2.5 y) with documented coronary artery disease and mildly impaired left ventricular function (EF 50.0 +/- 1.3%), received oral BAY (20 mg) or placebo. Forty-five minutes after medication, patients underwent a standardised exercise bicycle test in the supine position (6 min 25 W, 6 min 50 W). Before exercise, MAP was lower after BAY (88.8 +/- 4.1 mmHg) than after placebo (95.7 +/- 3.5 mmHg; p = 0.024), and HR was higher after BAY (76.8 +/- 3.5 bpm) than after placebo (69.5 +/- 3.6 bpm; p = 0.049). Plasma ANF tended to be higher after BAY (31.2 +/- 5.6 pg/ml) than after placebo (26.7 +/- 5.0 pg/ml), and plasma cGMP was not different (BAY 3.4 +/- 0.3, placebo 3.8 +/- 0.3 pmol/ml). During exercise, the relative increases in HR (+43%) and MAP (+17%) were identical after BAY and placebo. In contrast, ANF levels during exercise increased by 130 +/- 28% after placebo but only by 36 +/- 11% after BAY (p = 0.011). In parallel, plasma cyclic GMP increased by 61 +/- 13% after placebo and by 20 +/- 8% after BAY (p = 0.013). At the end of exercise, the BAY-induced reduction in plasma cyclic GMP reflected the reduction in diastolic arterial pressure (r = 0.717; p = 0.045). Compared to placebo, BAY treatment increased the fractional excretion rate of sodium from 0.46 +/- 0.11 to 0.90 +/- 0.22% (p = 0.016), without relation to urinary urodilatin excretion. Thus, the calcium antagonist BAY t 7207 attenuated the exercise-induced increase in plasma ANF and cyclic GMP probably due to its vasodilator effect. The relationship between blood pressure and the ANF system during exercise, which parallels findings during chronic antihypertensive treatment, may open a perspective for early evaluation of long-term therapy with calcium channel blockers.

Topics: Atrial Natriuretic Factor; Calcium Channel Blockers; Cross-Over Studies; Cyclic GMP; Diuretics; Double-Blind Method; Exercise Test; Humans; Male; Middle Aged; Peptide Fragments; Supine Position; Ventricular Dysfunction, Left

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norepinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n = 16) or placebo (n = 16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8/14 patients vs only 2/14 patients with placebo (P = 0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Coronary Circulation; Double-Blind Method; Echocardiography; Female; Heart; Humans; Male; Middle Aged; Myocardial Ischemia; Nisoldipine; Norepinephrine; Renin; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

Doses of sacubitril/valsartan (Sac/Val) achieved in clinical trials of heart failure with reduced ejection fraction (HFrEF) are often not reached in clinical practice.. The purpose of this study was to investigate associations among Sac/Val doses and changes in prognostic biomarkers, health status, and cardiac remodeling among individuals with HFrEF through 12 months of treatment with Sac/Val administered per usual care.. A total of 794 persons with HFrEF (ejection fraction [EF] ≤40%) were categorized according to average daily doses of Sac/Val divided into tertiles. Change from baseline to 12 months in biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, soluble ST2, atrial natriuretic peptide, urinary cyclic guanosine monophosphate), Kansas City Cardiomyopathy Questionnaire-23 scores, and parameters of cardiac reverse remodeling (left ventricular EF, indexed left atrial and ventricular volumes, and E/e') were assessed.. The average daily dose was 112 mg in Tertile 1 (low dose), 342 mg in Tertile 2 (moderate dose), and 379 mg in Tertile 3 (high dose). Similar changes in prognostic biomarkers were observed in all dose tertiles. Gains in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable regardless of dose category. Consistent reverse cardiac remodeling in all dose categories occurred; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2%, for low, moderate, and high doses, respectively; similar improvements in left atrial and ventricular volumes and E/e' were also observed across dose categories.. Among patients with HFrEF, similar improvement in prognostic biomarkers, health status, and cardiac remodeling were observed across various Sac/Val doses. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183.

Topics: Aminobutyrates; Atrial Natriuretic Factor; Biomarkers; Biphenyl Compounds; Dose-Response Relationship, Drug; Guanosine Monophosphate; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Stroke Volume; Troponin T; Valsartan; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Atrial Natriuretic Factor; Biomarkers; Female; Heart Atria; Humans; Natriuretic Peptide, Brain; Pre-Eclampsia; Pregnancy; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Healthy Volunteers; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Ventricular Dysfunction, Left

Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation as a prevention or treatment strategy in rodent heart failure models.. Two independent rodent heart failure models were used for the studies: transverse aortic constriction/myocardial infarction (MI) in mice and post-MI remodeling in rats. Seventy-five mice underwent a prevention treatment strategy with a KE comprised of hexanoyl-hexyl-3-hydroxybutyrate KE (KE-1) diet, and 77 rats were treated in either a prevention or treatment regimen using a commercially available β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG; KE-2) diet.. The KE-1 diet in mice elevated β-hydroxybutyrate levels during nocturnal feeding, whereas the KE-2 diet in rats induced ketonemia throughout a 24-hour period. The KE-1 diet preventive strategy attenuated development of left ventricular dysfunction and remodeling post-transverse aortic constriction/MI (left ventricular ejection fraction±SD, 36±8 in vehicle versus 45±11 in KE-1;. Chronic oral supplementation with KE was effective in both prevention and treatment of heart failure in 2 preclinical animal models. In addition, our results indicate that treatment with KE reprogrammed the expression of genes involved in ketone body utilization and normalized myocardial ATP production following MI, consistent with provision of an auxiliary fuel. These findings provide rationale for the assessment of KEs as a treatment for patients with heart failure.

Topics: Adenosine Triphosphate; Animals; Aorta; Atrial Natriuretic Factor; Constriction, Pathologic; Dietary Supplements; Fibrosis; Heart Failure; Heart Ventricles; Hydroxybutyrates; Mice; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Organ Size; Rats; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Aged, 80 and over; Angiography; Atrial Natriuretic Factor; Contrast Media; Echocardiography; Electrocardiography; Endomyocardial Fibrosis; Female; Gadolinium; Heart Failure; Humans; Hypereosinophilic Syndrome; Magnetic Resonance Spectroscopy; Prognosis; Protein Precursors; Respiration; Stroke Volume; Tachycardia, Supraventricular; Ventricular Dysfunction, Left

Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages.. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses.. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled.. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetic Cardiomyopathies; Disease Models, Animal; Echocardiography; Female; Heart; Heart Rate; Heart Ventricles; Male; Mice; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain; Severity of Illness Index; Ventricular Dysfunction, Left

In patients with reduced systolic function, the natriuretic peptide system affects heart failure (HF) progression, but the expression of key activating (corin) and degrading enzymes (neprilysin) is not well understood.. This pilot study (n=48) compared plasma levels of corin, neprilysin, ANP, BNP, and cGMP in control patients with normal ejection fractions (mean EF 63 ± 3%) versus patients with systolic dysfunction, with (EF 24 ± 8%) and without (EF 27 ± 7%) decompensated HF (dHF), as defined by Framingham and BNP criteria. Mean ages, use of beta blockers, and ACE-inhibitors-angiotensin receptor blockers were similar between the groups. Corin levels were depressed in systolic dysfunction patients (797 ± 346 pg/ml) versus controls (1188 ± 549, p<0.02), but levels were not affected by dHF (p=0.77). In contrast, levels of neprilysin (p<0.01), cGMP (p<0.001), and ANP (p<0.001) were higher in systolic dysfunction patients than controls and were the highest in patients with dHF.. Levels of neprilysin, ANP, BNP, and cGMP increased in patients with reduced systolic function and were the highest in dHF patients. Conversely, corin levels were low in patients with reduced EF with or without dHF. This pattern suggests possible enzymatic downregulation of natriuretic peptide activity in patients with reduced EF, which may have diagnostic and prognostic implications.

Topics: Aged; Atrial Natriuretic Factor; Down-Regulation; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Pilot Projects; Prospective Studies; Serine Endopeptidases; Ventricular Dysfunction, Left

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases that limits nitric oxide bioavailability. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) exerts a critical role for ADMA degradation and plays an important role in NO signaling. In the heart, DDAH1 is observed in endothelial cells and in the sarcolemma of cardiomyocytes. While NO signaling is important for cardiac adaptation to stress, DDAH1 impact on cardiomyocyte homeostasis is not clear. Here we used the MerCreMer-LoxP model to specifically disrupt cardiomyocyte DDAH1 expression in adult mice to determine the physiological impact of cardiomyocyte DDAH1 under basal conditions and during hypertrophic stress imposed by transverse aortic constriction (TAC). Under control conditions, cardiomyocyte-specific DDAH1 knockout (cDDAH KO) had no detectable effect on plasma ADMA and left ventricular (LV) hypertrophy or function in adult or aging mice. In response to TAC, DDAH1 levels were elevated 2.5-fold in WT mice, which exhibited no change in LV or plasma ADMA content and moderate LV hypertrophy and LV dysfunction. In contrast, cDDAH1 KO mice exposed to TAC showed no increase in LV DDAH1 expression, slightly increased LV tissue ADMA levels, no increase in plasma ADMA, but significantly exacerbated LV hypertrophy, fibrosis, nitrotyrosine production, and LV dysfunction. These findings indicate cardiomyocyte DDAH1 activity is dispensable for cardiac function under basal conditions, but plays an important role in attenuating cardiac hypertrophy and ventricular remodeling under stress conditions, possibly through locally confined regulation of subcellular ADMA and NO signaling.

Topics: Amidohydrolases; Animals; Arginine; Atrial Natriuretic Factor; Disease Models, Animal; Fibrosis; Genetic Predisposition to Disease; Hypertrophy, Left Ventricular; Male; Mice, Knockout; Myocytes, Cardiac; Nitric Oxide; Phenotype; Signal Transduction; Tyrosine; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

An innovative natriuretic peptide analog named C

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; Cardiotonic Agents; Echocardiography; Hemodynamics; Male; Myocardial Infarction; Natriuretic Peptide, C-Type; Natriuretic Peptides; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Vasodilation; Vasodilator Agents; Ventricular Dysfunction, Left

To evaluate left atrial (LA) volume and functions in obese subjects using real time three-dimensional echocardiography (RT3DE) and also the relationship between LA mechanical functions and N-terminal pro-atrial natriuretic peptide (NT-proANP).. This study included 40 obese (26 females and 14 males, mean age 51.9 years) and 40 normal weight subjects (23 females and 16 males, mean age 53.5 years) with normal coronary angiograms. All the study participants underwent RT3DE to assess LA volume and mechanical function. Plasma NT-proANP was determined by ELISA method.. There was no significant difference between groups in left ventricular (LV) diameters and ejection fraction, which reflect LV systolic function. However, transmitral deceleration time, isovolumetric relaxation time, and peak late diastolic tissue Doppler velocity values, which reflect LV diastolic function, were found to be significantly higher in obese subjects when compared with controls. LA maximum volume (LAVmax), LAVmax index (LAVI), LA minimal volume (LAVmin), before atrial contraction volume (LAVpreA), LA active emptying volume, LA total emptying volume, and LA active emptying fraction, which reflect LA reservoir and pump functions, were also higher in obese subjects when compared with controls. LA passive emptying fraction was significantly lower in obese subjects than in controls. NT-proANP levels were similar between groups. There were positive correlations between NT-proANP level and LAVI, LAVmax, LAVmin, LAVpreA, and LA total and active emptying volumes.. Left atrial mechanical functions and volumes are impaired in obese subjects. These findings may be regarded as early markers of subclinical cardiac failure in obese subjects who have not yet exhibited any clinical evidence of cardiovascular disease.

Topics: Atrial Natriuretic Factor; Echocardiography, Three-Dimensional; Enzyme-Linked Immunosorbent Assay; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Obesity; Protein Precursors; Ventricular Dysfunction, Left

Dilated cardiomyopathy is a major cause of heart failure (HF) that affects millions. Corin cleaves and biologically activates pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). High corin levels reduce the development of systolic dysfunction and HF in experimental dilated cardiomyopathy. Yet, patients with significant HF unexpectedly show low corin levels with high plasma ANP/BNP levels. Therefore, we examined the relationship between cardiac corin expression, ANP/BNP levels, and the stages of HF. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A-D HF. Cardiac systolic function (ejection fraction) continuously declined over time (P<0.001). Cardiac corin transcripts were decreased at early Stage B HF and remained low through Stages C and D (P<0.001). Cardiac corin levels were positively correlated with systolic function (r=0.96, P=0.003) and inversely with lung water (r=-0.92, P=0.001). In contrast, cardiac pro-ANP/BNP transcripts increased later (Stages C and D) and plasma levels rose only with terminal HF (Stage D, P<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate levels (r=0.82, P=0.01 and r=0.8, P=0.02, respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of HF, whereas significant increases in plasma ANP, BNP, and cyclic guanosine monophosphate levels were found only in later stage (C and D) HF. This dyssynchrony in expression of corin versus ANP/BNP may impair cleavage activation of pro-natriuretic peptides, and thereby promote the transition from earlier to later stage HF.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Disease Progression; Heart Failure; Male; Mice; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Serine Endopeptidases; Systole; Time Factors; Ventricular Dysfunction, Left

In Western countries heart disease is the leading cause of maternal death during pregnancy. The effect of pregnancy on the heart is difficult to study in patients with preexisting heart disease. Since experimental studies are scarce, we investigated the effect of pressure overload, produced by transverse aortic constriction (TAC) in mice, on the ability to conceive, pregnancy outcome, and maternal cardiac structure and function. Four weeks of TAC produced left ventricular (LV) hypertrophy and dysfunction with marked interstitial fibrosis, decreased capillary density, and induced pathological cardiac gene expression. Pregnancy increased relative LV and right ventricular weight without affecting the deterioration of LV function following TAC. Surprisingly, the TAC-induced increase in relative heart and lung weight was mitigated by pregnancy, which was accompanied by a trend towards normalization of capillary density and natriuretic peptide type A expression. Additionally, the combination of pregnancy and TAC increased the cardiac phosphorylation of c-Jun, and STAT1, but reduced phosphoinositide 3-kinase phosphorylation. Finally, TAC did not significantly affect conception rate, pregnancy duration, uterus size, litter size, and pup weight. In conclusion, we found that, rather than exacerbating the changes associated with cardiac pressure overload, pregnancy actually attenuated pathological LV remodeling and mitigated pulmonary congestion, and pathological gene expression produced by TAC, suggesting a positive effect of pregnancy on the pressure-overloaded heart.

Topics: Animals; Animals, Newborn; Aortic Valve Stenosis; Atrial Natriuretic Factor; Birth Weight; Capillaries; Disease Models, Animal; Echocardiography; Female; Fibrosis; Hypertrophy, Left Ventricular; Litter Size; Mice; Mice, Inbred C57BL; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Phosphatidylinositol 3-Kinases; Phosphorylation; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Rate; Proto-Oncogene Proteins c-jun; Real-Time Polymerase Chain Reaction; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; STAT1 Transcription Factor; Time Factors; Transcriptome; Ventricular Dysfunction, Left

The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/μl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1β, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Glucose; C-Reactive Protein; Connective Tissue Growth Factor; Diabetes Mellitus, Type 2; Down-Regulation; Echocardiography; Electrocardiography; Fibrosis; Glucose Tolerance Test; Glycosuria; Hypertrophy, Left Ventricular; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Interleukin-1beta; Male; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction; Troponin T; Tumor Necrosis Factor-alpha; Tyrosine; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Sympathetic over-activity is a hallmark of end stage renal disease (ESRD). Left ventricular (LV) disorders and volume overload are pervasive in ESRD and sympathetic over-activity may be a relevant mediator of the cardiovascular (CV) risk by these alterations in this population.. We investigated the relationship between a combined biomarker of LV disorders and volume excess, atrial natriuretic peptide (ANP), and the plasma concentration of nor-epinephrine (NE) in 227 ESRD patients without heart failure at baseline and modelled the risk for incident CV events by these biomarkers over a 3.5 years follow-up.. Plasma NE was strongly and independently related to ANP (β = 0.31, P < 0.001). In a multivariate Cox's regression analysis, ANP was an independent predictor of these events [HR (1-SD) 1.25, 95 % CI 1.01-1.54]. However, when NE was introduced into the multivariate model, HR by ANP reduced substantially (1.14, 95% CI 0.91-1.42) and was no longer significant (P = 0.25) while the CV risk signalled by NE was clinically relevant (HR 1.29, 95% CI 1.05-1.59) and statistically significant (P = 0.02).. In ESRD patients without heart failure, NE is strongly and independently related to ANP. The predictive power of ANP for CV events is largely captured by NE in a statistical model including both biomarkers. These data suggest that sympathetic over-activity may be a relevant mediator of the high risk of CV events triggered by LV disorders and volume excess in this population. However, further mechanistic and intervention studies are needed to prove the nature (causal/non causal) of these findings.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Predictive Value of Tests; Risk Factors; Sympathetic Nervous System; Ventricular Dysfunction, Left

Human atrial natriuretic peptide (hANP) and spontaneous nitric oxide (NO) donor share cyclic guanosine monophosphate (cGMP) as a second messenger, but their effect on myocardium may differ. We compared the effect of hANP and sodium nitroprusside (SNP) on left ventricular (LV) mechano-energetics in heart failure (HF).. Ten patients with HF due to previous myocardial infarction (LV ejection fraction: 45±3%) were instrumented with conductance and coronary sinus thermodilution catheters. LV contractility (Ees: slope of end-systolic pressure-volume relation) and the ratio of LV stroke work (SW) to myocardial oxygen consumption (SW/MVO2=mechanical efficiency) were measured in response to intravenous infusion of ANP (0.05 μg/kg/min) or SNP (0.3 μg/kg/min) to lower blood pressure by at least 10 mmHg, and changes in plasma cGMP.. SNP had no effect on Ees, SW, or MVO2, thus SW/MVO2 remained unchanged (40.54±5.84% to 36.59±5.72%, p=0.25). ANP increased Ees, and decreased MVO2 with preserved SW, resulting in improved SW/MVO2 (40.49±6.35% to 50.30±7.96%, p=0.0073). Infusion of ANP (10.42-34.95 pmol/ml, p=0.0003) increased cGMP levels, whereas infusion of SNP had no effect (10.42-12.23 pmol/ml, p=0.75).. Compared to SNP, the ANP-dependent increase in cGMP may ameliorate myocardial inotropy and energetics in HF.

Topics: Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Heart Failure; Humans; Infusions, Intravenous; Myocardial Contraction; Myocardial Infarction; Myocardium; Nitric Oxide Donors; Nitroprusside; Oxygen Consumption; Stroke Volume; Vasodilator Agents; Ventricular Dysfunction, Left

Myocardial infarction followed by adverse left ventricular (LV) remodeling is the most frequent proximate cause of heart failure. Hydrogen sulfide (H2S) is an important endogenous modulator of diverse physiological and pathophysiological processes. Its role in post-ischemic ventricular remodeling and the associated neurohormonal responses has not been defined. Here, we aimed at evaluating whether the slow-releasing water-soluble H2S donor GYY4137 (GYY) exerts cardioprotective effects and modulates the neurohormonal response to cardiac ischemic injury.. Treatment for 2 or 7 days with GYY (100 mg/Kg/48 h, IP) after acute myocardial infarction (MI) in rats preserved LV dimensions and function in vivo, compared to untreated infarcted (MI), placebo- and dl-propargylglycine- (PAG, an inhibitor of endogenous H2S synthesis) treated animals (n=9/group/time-point). LV dimensions and function in GYY-treated animals were comparable to healthy sham-operated rats. GYY-treated hearts had significantly less LV fibrosis than MI, placebo and PAG hearts. A higher density of blood vessels was found in the LV scar area of GYY-treated animals compared to all other infarcted groups. Despite preserved LV structure and function, treatment with GYY increased the levels of the natriuretic peptides ANP and BNP in association with enhanced cyclic GMP levels, paralleled by higher cGMP-dependent protein kinase type I (cGKI) protein levels.. Our data suggest that the slow-releasing H2S donor, GYY4137, preserves cardiac function, attenuates adverse remodeling and may exert post-ischemic cardioprotective (pro-angiogenic, anti-apoptotic, anti-hypertrophic and anti-fibrotic) effects in part through enhanced early post-ischemic endogenous natriuretic peptide activation.

Topics: Animals; Atrial Natriuretic Factor; Cardiotonic Agents; Humans; Hydrogen Sulfide; Ischemia; Morpholines; Myocardial Infarction; Natriuretic Peptide, Brain; Organothiophosphorus Compounds; Rats; Ventricular Dysfunction, Left; Ventricular Remodeling

A boy with Duchenne muscular dystrophy was admitted to our hospital due to a transient loss of consciousness. Transthoracic echocardiography revealed left ventricular (LV) dilatation and diffuse hypokinesis of the LV wall. The LV wall was thin, and both non-compaction of the LV wall and marked thinning of the posterior LV wall resulting from a lesion were observed. The plasma B-type natriuretic peptide (BNP) level ultimately increased to 7,795 pg/mL, and the patient died of cardiac arrest following ventricular tachycardia. Severe heart failure, a critical condition, and thinning of the LV wall may have contributed to the markedly high plasma BNP level in this case.

Topics: Adolescent; Atrial Natriuretic Factor; Biomarkers; Diuretics; Fatal Outcome; Heart Failure; Humans; Male; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Dysfunction, Left

Factors in the middle age that are associated with the risk for development of diastolic dysfunction in long term are not fully established. The Oulu Project Elucidating Risk of Atherosclerosis OPERA study randomly selected middle-aged subjects with hypertension and age- and gender-matched control subjects (n = 1,045, age 51 ± 6 years, men 49.8%). After >20 years of follow-up, majority of the subjects still alive were available for reexaminations (n = 600). After excluding the subjects with mitral regurgitation, left ventricular ejection fraction <50%, and those from whom echocardiographic septal E/E' could not be reliably measured, the present analysis included 460 subjects. E/E' was divided into 3 subgroups (subgroup 1: E/E' ≤8, subgroup 2: 8 < E/E' < 15, subgroup 3: E/E' ≥15), subgroup 3 suggesting a significant diastolic dysfunction. Several baseline variables were associated with diastolic dysfunction: greater age (p = 0.001), female gender (p = 0.001), shorter height (p <0.001), larger body mass index (p = 0.008), greater systolic blood pressure (p = 0.001), greater pulse pressure (p <0.001), lower baroreflex sensitivity (p = 0.007), lower estimated glomerular filtration rate (p = 0.02), greater atrial natriuretic peptide (p = 0.001), greater fasting plasma glucose (p = 0.001), more common occurrence of diabetes (p = 0.011), and more common usage of antihypertensive medication (p = 0.001). After adjustments in the multivariate model, only systolic blood pressure (p = 0.001), shorter height (p = 0.002), and estimated glomerular filtration rate (p = 0.006) retained a significant association with the risk of developing diastolic dysfunction. In conclusion, greater systolic blood pressure, short height, and lower estimated glomerular filtration rate of the middle-aged subjects were the main determinants of development of diastolic dysfunction during a 20-year follow-up.

Topics: Adult; Age Distribution; Atherosclerosis; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Blood Pressure; Body Height; Body Mass Index; Diabetes Complications; Diastole; Echocardiography; Female; Finland; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Predictive Value of Tests; Prevalence; Prospective Studies; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Sex Distribution; Ventricular Dysfunction, Left

Left ventricular (LV) assist device (LVAD) support reduces pathological loading. However, load-induced adaptive responses may be suppressed. Pathological loading dysregulates cardiac G protein-coupled receptor (GPCR) signaling. Signaling through G proteins is deleterious, whereas beta (β)-arrestin-mediated signaling is cardioprotective. We examined the effects of pathological LV loading/LV dysfunction and treatment via LVAD, on β-arrestin-mediated signaling, and genetic networks downstream of load.. An ovine myocardial infarction (MI) model was used. Sheep underwent sham thoracotomy (n = 3), mid-left anterior descending coronary artery ligation to produce MI (n = 3), or MI with placement of a small-platform catheter-based LVAD (n = 3). LVAD support was continued for 2 weeks. Animals were maintained for a total of 12 weeks. Myocardial specimens were harvested and analyzed.. MI induced β-arrestin activation. Increased interactions between epidermal growth factor receptor and β-arrestins were observed. LVAD support inhibited these responses to MI (P < .05). LVAD support inhibited the activation of cardioprotective signaling effectors Akt (P < .05), and, to a lesser extent, extracellular regulated kinase 1/2 (P not significant); however, MI resulted in regional activation of load-induced GPCR signaling via G proteins, as assessed by the induction of atrial natriuretic peptide mRNA expression in the MI-adjacent zone relative to the MI-remote zone (P < .05). MI-adjacent zone atrial natriuretic peptide expression was renormalized with LVAD support.. LVAD support inhibited cardioprotective β-arrestin-mediated signaling. However, net benefits of normalization of load-induced GPCR signaling were observed in the MI-adjacent zone. These findings may have implications for the optimal extent and duration of unloading, and for the development of adjunctive medical therapies.

Topics: Animals; Arrestins; Atrial Natriuretic Factor; beta-Arrestins; Cardiac Catheterization; Cardiac Catheters; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Heart-Assist Devices; Materials Testing; Myocardial Infarction; Myocardium; Phosphorylation; Prosthesis Design; Proto-Oncogene Proteins c-akt; Receptors, G-Protein-Coupled; Recovery of Function; RNA, Messenger; Sheep; Signal Transduction; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Doxorubicin is widely used against cancer; however, it can produce heart failure (HF). Among other hallmarks, oxidative stress is a major contributor to HF pathophysiology. The late INa inhibitor ranolazine has proven effective in treating experimental HF. Since elevated [Na+]i is present in failing myocytes, and has been recently linked with reactive oxygen species (ROS) production, our aim was to assess whether ranolazine prevents doxorubicin-induced cardiotoxicity, and whether blunted oxidative stress is a mechanism accounting for such protection.. In C57BL6 mice, doxorubicin treatment for 7 days produced LV dilation and decreased echo-measured fractional shortening (FS). Ranolazine (305 mg/kg/day) prevented LV dilation and dysfunction when co-administered with doxorubicin. Doxorubicin-induced cardiotoxicity was accompanied instead by elevations in atrial natriuretic peptide (ANP), BNP, connective tissue growth factor (CTGF), and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated on co-treatment with ranolazine. Alterations in extracellular matrix remodelling were confirmed by an increase in interstitial collagen, which did not rise in ranolazine-co-treated hearts. Levels of poly(ADP-ribose) polymerase (PARP) and pro-caspase-3 measured by western blotting were lowered with doxorubicin, with increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Furthermore, in HL-1 cardiomyocytes transfected with HyPer to monitor H2O2 emission, besides reducing the extent of cell death, ranolazine prevented the occurrence of oxidative stress caused by doxorubicin. Interestingly, similar protective results were obtained with the Na+/Ca2+ exchanger (NCX) inhibitor KB-R7943.. Ranolazine protects against experimental doxorubicin cardiotoxicity. Such protection is accompanied by a reduction in oxidative stress, suggesting that INa modulates cardiac redox balance, resulting in functional and morphological derangements.

Topics: Acetanilides; Animals; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Blotting, Western; Cardiotoxicity; Connective Tissue Growth Factor; Doxorubicin; Enzyme Inhibitors; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Piperazines; Poly(ADP-ribose) Polymerases; Ranolazine; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium; Ultrasonography; Ventricular Dysfunction, Left

To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs) and myocardial structure and function in the general community.. NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP) rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown.. DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography.. Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%). All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007) in the homozygotes G/G (43%) than the A/A+A/G (28%) group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03). There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected.. A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

Topics: Aged; Amino Acid Substitution; Atrial Natriuretic Factor; Diastole; Echocardiography, Doppler; Female; Gene Frequency; Genotype; Heart; Humans; Hypertension; Linear Models; Logistic Models; Male; Middle Aged; Minnesota; Multivariate Analysis; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Prevalence; Receptors, Atrial Natriuretic Factor; Ventricular Dysfunction, Left

The purpose of this study was to investigate the effectiveness of atrial natriuretic peptide on ischemic myocardium through the induction of heat-shock protein 72.. 30 isolated rabbit hearts perfused on isolated heart apparatus were randomly assigned to receive either warm Krebs-Henseleit solution with 1 µmol L(-1) atrial natriuretic peptide (n = 15) or warm Krebs-Henseleit solution without atrial natriuretic peptide (n = 15) in preischemic, ischemic, and postischemic conditions. In all rabbit hearts, global ischemia was produced by clamping the aortic and atrial inflow lines. Concentrations of atrial natriuretic peptide were measured in hearts with left ventricular dysfunction following ischemia, and correlated with the hypertrophic growth sustained by overexpression of heat-shock protein 72 microRNA-133.. The levels of atrial natriuretic peptide were markedly higher in the group that received atrial natriuretic peptide, and strongly correlated with both band lengths of heat-shock protein 72 and overexpression of microRNA-133 in the hypertrophic myocyte.. Perfusion levels of atrial natriuretic peptide induce increased expression of heat-shock protein 72 microRNA-133 in dysfunctional left ventricle.

Topics: Animals; Atrial Natriuretic Factor; Cardiotonic Agents; Disease Models, Animal; HSP72 Heat-Shock Proteins; Hypertrophy, Left Ventricular; MicroRNAs; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Perfusion; Rabbits; Stroke Volume; Time Factors; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left

The developmental origins of health and disease refer to the theory that adverse maternal environments influence fetal development and the risk of cardiovascular disease in adulthood. We used the chronically hypertensive atrial natriuretic peptide knockout (ANP-/-) mouse as a model of gestational hypertension, and attempted to determine the effect of gestational hypertension on left ventricular (LV) structure and function in adult offspring. We crossed normotensive ANP+/+ females with ANP-/- males (yielding ANP+/-(WT) offspring) and hypertensive ANP-/- females with ANP+/+ males (yielding ANP+/-(KO) offspring). Cardiac gene expression was measured using real-time quantitative PCR. Cardiac function was assessed using echocardiography. Daily injections of isoproterenol (ISO) were used to induce cardiac stress. Collagen deposition was assessed using picrosirius red staining. All mice were 10 weeks of age. Gestational hypertension resulted in significant LV hypertrophy in offspring, with no change in LV function. Treatment with ISO resulted in significant LV diastolic dysfunction with a restrictive filling pattern (increased E/A ratio and E/e') and interstitial myocardial fibrosis only in ANP+/-(KO) and not ANP+/-(WT) offspring. Gestational hypertension programs adverse LV structural and functional remodeling in offspring. These data suggest that adverse maternal environments may increase the risk of heart failure in offspring later in life.

Topics: Adrenergic beta-Agonists; Animals; Atrial Natriuretic Factor; Cardiomegaly; Female; Fibrosis; GATA Transcription Factors; Hypertension, Pregnancy-Induced; Isoproterenol; Male; Mice, Knockout; Models, Cardiovascular; Myocardium; Pregnancy; Ultrasonography; Ventricular Dysfunction, Left

Obesity and Type 2 diabetes mellitus (DM) induce left ventricular (LV) diastolic dysfunction, which contributes to an increasing prevalence of heart failure with a preserved LV ejection fraction. We investigated the effects of sitagliptin (SITA), an inhibitor of dipeptidylpeptidase-4 (DPP-4) and anti-diabetic drug, on LV structure and function of obese mice with Type 2 DM.. Obese Type 2 diabetic mice (Lepr(db/db), BKS.Cg-Dock7(m)+/+ Lepr(db)/J), displaying increased cardiomyocyte and LV stiffness at the age of 16 weeks, were treated with SITA (300 mg/kg/day) or vehicle for 8 weeks. SITA severely impaired serum DPP-4 activity, but had no effect on glycaemia. Invasive haemodynamic recordings showed that SITA reduced LV passive stiffness and increased LV stroke volume; LV end-systolic elastance remained unchanged. In addition, SITA reduced resting tension of isolated single cardiomyocytes and intensified phosphorylation of the sarcomeric protein titin. SITA also increased LV concentrations of cGMP and increased activity of protein kinase G (PKG). In vitro activation of PKG decreased resting tension of cardiomyocytes from vehicle-treated mice, but had no effect on resting tension of cardiomyocytes from SITA-treated mice.. In obese Type 2 diabetic mice, in the absence of hypoglycaemic effects, inhibition of DPP-4 decreases LV passive stiffness and improves global LV performance. These effects seem at least partially mediated by stimulatory effects on the myocardial cGMP-PKG pathway and, hence, on the phosphorylation status of titin and the hereto coupled cardiomyocyte stiffness modulus.

Topics: Animals; Atrial Natriuretic Factor; Compliance; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Diabetes Mellitus, Experimental; Diastole; Dipeptidyl-Peptidase IV Inhibitors; Drug Evaluation, Preclinical; Heart; Heart Ventricles; Male; Mice; Myocytes, Cardiac; Pyrazines; Random Allocation; Sitagliptin Phosphate; Triazoles; Ventricular Dysfunction, Left

Left ventricular dysfunction (LVD) occurs with myocardial ischemia and coronary artery disease (CAD). The natriuretic peptide system has compensatory vasodilatory, natriuretic and paracrine effects on LVD and subsequent heart failure. The aim of this study was to investigate the relationship between natriuretic peptide polymorphisms and risk of LVD in CAD patients.. We recruited 747 consecutive Southern Han Chinese patients with angiographically confirmed CAD, 201 had a reduced left ventricle ejection fraction (LVEF ≤45%, LVD group) and 546 had a preserved left ventricle ejection fraction (LVEF >45%). The reduced and preserved LVEF groups were matched by gender and age. Taqman assays were performed to identify five polymorphisms in the NPPA-NPPB locus (rs5065, rs5063, rs632793, rs198388 and rs198389).. Single-locus analyses found no significant difference in the allele and genotype frequencies of the reduced and preserved LVEF group, even after adjusting for confounding factors. Subgroup analyses performed by hyperlipidemia (HLP) demonstrated 3 polymorphisms, rs632793 (OR = 0.31, 95% CI 0.1-0.93, P = 0.04), rs198388 (OR = 0.26, 95% CI 0.09-0.79, P = 0.02) and rs198389 (OR = 0.26, 95% CI 0.09-0.80, P = 0.02) were associated with the reduced risk of LVD. No CAD-susceptible haplotypes were identified. Multifactor dimensionality reduction analysis did not detect any gene-to-gene interactions among the five loci. Three loci (rs5063, rs632793 and rs198388) formed the best model with the maximum testing accuracy (39.89%) and cross-validation consistency (10/10).. Three NPPA-NPPB polymorphisms (rs632793, rs198388 and rs198389) were associated with reduced risk of LVD in CAD patients with HLP.

Topics: Aged; Asian People; Atrial Natriuretic Factor; Case-Control Studies; Chi-Square Distribution; China; Coronary Angiography; Coronary Artery Disease; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Hyperlipidemias; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Phenotype; Polymorphism, Genetic; Protective Factors; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

The α2-isoform of the Na,K-ATPase (α2) is the minor isoform of the Na,K-ATPase expressed in the cardiovascular system and is thought to play a critical role in the regulation of cardiovascular hemodynamics. However, the organ system/cell type expressing α2 that is required for this regulation has not been fully defined. The present study uses a heart-specific knockout of α2 to further define the tissue-specific role of α2 in the regulation of cardiovascular hemodynamics. To accomplish this, we developed a mouse model using the Cre/loxP system to generate a tissue-specific knockout of α2 in the heart using β-myosin heavy chain Cre. We have achieved a 90% knockout of α2 expression in the heart of the knockout mice. Interestingly, the heart-specific knockout mice exhibit normal basal cardiac function and systolic blood pressure, and in addition, these mice develop ACTH-induced hypertension in response to ACTH treatment similar to control mice. Surprisingly, the heart-specific knockout mice display delayed onset of cardiac dysfunction compared with control mice in response to pressure overload induced by transverse aortic constriction; however, the heart-specific knockout mice deteriorated to control levels by 9 wk post-transverse aortic constriction. These results suggest that heart expression of α2 does not play a role in the regulation of basal cardiovascular function or blood pressure; however, heart expression of α2 plays a role in the hypertrophic response to pressure overload. This study further emphasizes that the tissue localization of α2 determines its unique roles in the regulation of cardiovascular function.

Topics: Adrenocorticotropic Hormone; Animals; Atrial Natriuretic Factor; Blood Pressure; Gene Knockout Techniques; Hypertension; Hypertrophy, Left Ventricular; Integrases; Mice; Mice, Knockout; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Ultrasonography; Vasoconstriction; Ventricular Dysfunction, Left

The NADPH oxidases (Noxes) are a family of ROS (reactive oxygen species)-generating enzymes which play a critical role in the development of cardiac remodeling associated with heart failure. The Noxes of their catalytic isoforms include multiple homologues in cardiovascular cells with wide range tissue distribution. It is still unclear which Noxes represent the major enzymatic source of ROS in the heart and play a predominant role in cardiac hypertrophy. In this study we investigated the differential expression changes of NAD(P)H oxidase P47phox isoform and Nox homologues in left ventricle and the effects of atorvastatin on cardiac remodeling in two-kidney two-clip(2K2C) hypertensive rats. The mRNA and protein expression of Nox2, Nox4 and P47phox showed a sustained increase at 4, 8, 12 weeks after surgery in 2K2C rats. Administration of atorvastatin attenuated cardiac dysfunction, hypertrophy and fibrosis of 2K2C rats. However, atorvastatin treatment had no effects on BP regulation. Further studies revealed that atorvastatin inhibited the increased expression of Nox2, Nox4, P47phox as well as 02"- production in 2K2C hypertensive rats. These findings indicate that Nox2, Nox4 and P47phox play a crucial role in the development of cardiac remodeling in the 2K2C hypertensive rats. Atorvastatin, independent of BP control, exerts anti-remodeling effects partially by inhibition of NAD(P)H oxidase-mediated cardiac oxidative stress.

Topics: Animals; Atorvastatin; Atrial Natriuretic Factor; Blotting, Western; Fibrosis; Hemodynamics; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Renovascular; Isoenzymes; Male; Membrane Glycoproteins; Myocardium; Myosin Heavy Chains; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases; Pyrroles; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

We investigated left ventricular diastolic dysfunction (LVDD) and its relationship with circulatory function and prognosis in cirrhosis with portal hypertension and normal creatinine. Conventional and tissue Doppler (TDI) echocardiography, systemic and hepatic hemodynamics, and the activity of endogenous vasoactive systems (AEVS) were measured prospectively in 80 patients. Plasma renin activity (PRA; >4 ng/mL/hour) was used as a surrogate of effective arterial blood volume. Patients were followed up for 12 months. Thirty-seven patients had LVDD (19 with grade 1 and 18 with grade 2). Left ventricular hypertrophy, left atrial volume, AEVS, and natriuretic peptide levels were significantly greater in patients with LVDD than without LVDD. Patients with grade 2 LVDD, compared to grade 1 LVDD and without LVDD, had significantly lower mean arterial pressure and higher Model for End-Stage Liver Disease (MELD) score, E-wave transmitral/early diastolic mitral annular velocity (E/e' ratio), cardiopulmonary pressures, PRA, and natriuretic peptide levels. Systolic and cardiac chronotropic function were significantly lower in patients with grade 2 LVDD than without LVDD. LVDD was more frequent in patients with ascites and increased PRA than patients without ascites or with ascites but normal PRA. Fourteen patients with LVDD developed hepatorenal syndrome (HRS) type 1 on follow-up. Survival was different according to degree of LVDD (without LVDD: 95%; grade 1 LVDD: 79%; grade 2 LVDD: 39%; P < 0.001). Independent predictive factors of mortality were MELD score and E/e' ratio.. LVDD occurs simultaneously with other changes in cardiac structure and function and is associated with an impairment of effective arterial blood volume. LVDD is a sensitive marker of advanced cirrhosis, type 1 HRS development, and mortality.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Diastole; Female; Heart Rate; Hepatorenal Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Prospective Studies; Renin; Severity of Illness Index; Ventricular Dysfunction, Left

Neuroendocrine and haemodynamic changes were compared between single-lead atrial (AAI) or dual-chamber (DDD) pacing modes in patients with sick sinus syndrome, in a crossover study.. Inpatients scheduled for their first pacemaker implantation were screened for the following inclusion criteria: sick sinus syndrome; intact atrioventricular conduction; normal QRS interval. All study patients were implanted with a dual-chamber pacemaker, programmed for AAI or DDD pacing mode. Patients were allocated randomly to AAI followed by DDD pacing or to DDD followed by AAI pacing, each mode being applied for 72 h. Echocardiographic, electrocardiographic and neuroendocrine parameters were tested at the end of each pacing mode.. From 152 inpatients screened for inclusion, 28 were selected for treatment. Plasma levels of atrial natriuretic peptide (ANP), endothelin, aldosterone and angiotension II were significantly lower, and aortic flow velocity-time integral was significantly higher, in AAI mode than in DDD mode. Aortic pre-ejection interval, interventricular mechanical delay and QRS duration were significantly higher in DDD than in AAI mode.. In patients with sick sinus syndrome, DDD pacing mode can induce neuroendocrine system activation, and left ventricular dysfunction and dyssynchrony. These findings discourage the routine use of DDD pacing in patients with sick sinus syndrome.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Blood Flow Velocity; Cross-Over Studies; Endothelins; Female; Heart Atria; Heart Rate; Humans; Male; Middle Aged; Pacemaker, Artificial; Sick Sinus Syndrome; Time Factors; Ventricular Dysfunction, Left

The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.

Topics: Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Calcineurin; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Chronic Disease; Disease Models, Animal; Echocardiography, Doppler, Color; Extracellular Signal-Regulated MAP Kinases; Hypertrophy, Left Ventricular; JNK Mitogen-Activated Protein Kinases; Male; Myocardium; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

GPR30 is a novel oestrogen receptor expressed in various tissues, including the heart. We determined the role of GPR30 in the maintenance of left ventricular (LV) structure and diastolic function after the surgical loss of ovarian hormones in the female mRen2.Lewis rat, a model emulating the cardiac phenotype of the post-menopausal woman.. Bilateral oophorectomy (OVX) or sham surgery was performed in study rats; the selective GPR30 agonist, G-1 (50 µg/kg/day), or vehicle was given subcutaneously to OVX rats from 13-15 weeks of age. Similar to the cardiac phenotype of sham rats, G-1 preserved diastolic function and structure relative to vehicle-treated OVX littermates independent of changes in blood pressure. G-1 limited the OVX-induced increase in LV filling pressure, LV mass, wall thickness, interstitial collagen deposition, atrial natriuretic factor and brain natriuretic peptide mRNA levels, and cardiac NAD(P)H oxidase 4 (NOX4) expression. In vitro studies showed that G-1 inhibited angiotensin II-induced hypertrophy in H9c2 cardiomyocytes, evidenced by reductions in cell size, protein content per cell, and atrial natriuretic factor mRNA levels. The GPR30 antagonist, G15, inhibited the protective effects of both oestradiol and G-1 on this hypertrophy.. These data show that the GPR30 agonist G-1 mitigates the adverse effects of oestrogen loss on LV remodelling and the development of diastolic dysfunction in the study rats. This expands our knowledge of the sex-specific mechanisms underlying diastolic dysfunction and provides a potential therapeutic target for reducing the progression of this cardiovascular disease process in post-menopausal women.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Calcium; Cardiotonic Agents; Cell Line; Collagen; Cyclopentanes; Echocardiography, Doppler; Estrogens; Female; Gene Expression Regulation; Genotype; Hypertrophy, Left Ventricular; Injections, Subcutaneous; Mice; Myocytes, Cardiac; NADPH Oxidase 4; NADPH Oxidases; Natriuretic Peptide, Brain; Ovariectomy; Phenotype; Quinolines; Rats; Rats, Inbred Lew; Rats, Transgenic; Receptors, G-Protein-Coupled; Renin; RNA, Messenger; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Concentration of natriuretic peptides (NPs) in arterial hypertension (AH) patients is higher than that in healthy people. One of the first symptoms of left ventricular hypertrophy (LVH) is left ventricular diastolic dysfunction (LVDD). The aim of this study was to examine whether determination of NPs in blood can be a useful indicator of LVDD detection in idiopathic AH patients. The study was conducted on three groups of patients: group Ia, 19 patients (average age 57 ± 3) with eccentric hypertrophy; group Ib, 13 patients (59 ± 4) with concentric hypertrophy; group II, 33 patients (58 ± 4) without AH or LVH. In all groups, mitral inflow profile was evaluated with Doppler test to detect LVDD, blood flow in upper right pulmonary vein, and concentration of atrial natriuretic peptide (ANP), N-terminal ANP (N-ANP), brain natriuretic peptide (BNP), and N-terminal BNP (N-BNP). In group Ia, significant correlations were observed between the following pairs: ratio of maximum early to late mitral inflow and ANP; deceleration time of early mitral inflow speed and ANP; atrial contraction (AR) and ANP; atrial contraction (AR) and N-ANP; similarly, in group Ib, significant correlations were observed between the following: relative wall thickness and BNP; isovolumic relaxation time and BNP; AR and BNP; relative wall thickness and N-BNP; isovolumic relaxation time and N-BNP; AR and N-BNP.

Topics: Atrial Natriuretic Factor; Echocardiography, Doppler; Female; Heart Atria; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptides; Ventricular Dysfunction, Left

A method for the estimation of severity of chronic cardiac failure (CCF) based on the quantitative evaluation of the regulatory and adaptive status (RAS) of the organism. Patients with FC I-III HCF concomitant with grade I-III hypertensive disease and/or coronary heart disease underwent cardiorespiratory synchronism test for the quantitative estimation of RAS (6 min walk), echocardiography, treadmill measuring maximum oxygen consumption (VO2max), measurement of plasma N-terminal precursor of brain natriuretic peptide. The lowering of RAS was especially pronounced when HCF FC changed from I to III, in agreement with results of traditional instrumental and laboratory tests. Specifically, left ventricle systolic and diastolic function was impaired, tolerance of physical exercise decreased while neurohumoral regulation was activated. There was positive correlation between RAS indices at HCF CF I and II for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for N-terminal precursor of brain natriuretic hormone. At HCF FC II and III, positive correlation was documented for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for the N-terminal precursor of brain natriuretic hormone. It means that the qualitative estimate of RAS obtained in the cardiorespiratory synchronism test can be used to assess severity of HCF in patients with hypertensive disease and/or coronary heart disease.

Topics: Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Dimensional Measurement Accuracy; Female; Heart Failure; Heart Function Tests; Humans; Hypertension; Male; Middle Aged; Oxygen Consumption; Predictive Value of Tests; Severity of Illness Index; Ventricular Dysfunction, Left

A 64-year-old woman was admitted to our hospital with acute decompensated heart failure (ADHF) and left ventricular systolic dysfunction. Initial treatment with carperitide (0.01 µg/kg/min) had little effect. Since she had a borderline systolic blood pressure (i.e., a systolic BP between 90 and 110 mm Hg) and atrial fibrillation with a rapid ventricular response, nicorandil (0.1 mg/kg/h) was added to carperitide. This combined therapy achieved rapid improvement of ADHF. To our knowledge, this is the first report of a patient with ADHF and borderline systolic blood pressure in whom the combination of carperitide and nicorandil was safe and effective.

Topics: Acute Disease; Atrial Natriuretic Factor; Drug Therapy, Combination; Female; Heart Failure; Humans; Middle Aged; Nicorandil; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Adipocytes; Adrenergic beta-Agonists; Aminobutyrates; Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Biphenyl Compounds; Cells, Cultured; Dose-Response Relationship, Drug; Drug Combinations; Female; Heart Failure; Humans; Isoproterenol; Lipolysis; Male; Middle Aged; Neprilysin; Receptors, Angiotensin; Tetrazoles; Valsartan; Ventricular Dysfunction, Left

Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. Ascending aortic banding (Ab) was performed to induce hypertrophy. Two months post-Ab, ischemia-reperfusion (I/R) injury was induced by ligating the left anterior descending (LAD) artery for 30 min. Permanent LAD ligation served as positive controls. A debanding (DeAb) procedure was performed after Ab or Ab + I/R to restore left ventricular (LV) loading properties. Cardiac function was assessed by echocardiography and in vivo hemodynamic analysis. Myocardial infarction (MI) size and myocardial fibrosis were assessed. LV hypertrophy was observed 4 mo post-Ab; however, systolic function was preserved. LV hypertrophy regressed within 1 mo after DeAb. I/R for 2 mo induced a small to moderate MI with mild impairment of LV function. Permanent LAD ligation for 2 mo induced large MI and significant cardiac dysfunction. Ab for 2 mo followed by I/R for 2 mo (Ab + I/R) resulted in moderate MI with significantly reduced ejection fraction (EF). DeAb post Ab + I/R to reduce afterload could not restore cardiac function. Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.

Topics: Analysis of Variance; Animals; Aorta; Atrial Natriuretic Factor; Coronary Vessels; Disease Models, Animal; Disease Progression; Fibrosis; Gene Expression Regulation; Heart Failure; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Ligation; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stroke Volume; Time Factors; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

C57BL/6-Kit(W-sh/W-sh) mice are generally regarded as a mast cell-deficient model, as they lack the necessary kit receptor for mast cell development. Further characterization of this strain, however, indicates that C57BL/6-Kit(W-sh/W-sh) mice also have a disruption in the Corin gene. Corin is a transmembrane serine protease critical for processing atrial natriuretic peptide (ANP) from pro-ANP through proteolytic cleavage. Pro-ANP is produced, stored and released by cardiac myocytes in response to atrial stretch and the stress generated by increased afterload such as increased ventricular pressure from aortic stenosis or myocardial infarction. ANP inhibits the effects of the renin-angiotensin system to preserve homeostasis under conditions of increased hemodynamic load, and changes in the level of its activating enzyme Corin have been observed during the progression to heart failure. Here, we investigate the effect of increased hemodynamic load on Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice. Ten-week old male mice were subjected to transverse aortic constriction for 8 weeks and were monitored for changes in cardiac structure and function by echocardiography. Hearts were collected 8 weeks after surgery for molecular and histological analyses. Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice developed rapidly progressive and substantial left ventricular dilation, hypertrophy, and markedly impaired cardiac function during the 8 weeks after surgery, compared to wildtype mice. Concomitant with this we observed increased levels of ANP transcript, but a lack of prepro-ANP or pro-ANP protein in heart tissue extracted from Corin-deficient mice. Surprisingly, fibrosis was not increased in Corin-deficient mice when compared to wildtype mice. These data indicate that Corin's involvement in ANP processing is a key element in the heart's response to increased hemodynamic load. Further, C57BL/6-Kit(W-sh/W-sh) strain is an effective model for investigating the involvement of Corin and, conversely, a less than optimal model for investigating mast cell, and immunological, functions in certain cardiovascular pathologies.

Topics: Animals; Aortic Diseases; Atrial Natriuretic Factor; Blotting, Western; Cardiomegaly; Echocardiography, Doppler; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Reverse Transcriptase Polymerase Chain Reaction; Serine Endopeptidases; Ventricular Dysfunction, Left

Topics: Acute Coronary Syndrome; Americas; Atrial Natriuretic Factor; Biomarkers; Dyspnea; Early Diagnosis; Emergency Service, Hospital; Europe; Heart Diseases; Heart Failure; Humans; Hypertension, Pulmonary; Intensive Care Units; Japan; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Survival Rate; Troponin; Ventricular Dysfunction, Left

Endothelin-1 levels in patients with chronic congestive heart failure were evaluated with respect to the severity of cardiac dysfunction. The relationships between three neurohormones, brain natriuretic peptide (BNP), human atrial natriuretic peptide (HANP), and endothelin-1,were evaluated.. Forty patients (17 men and 23 women, aged 64-98 years) with chronic congestive heart failure were evaluated. Echocardiography was performed for each patient, and the left ventricular ejection fraction (EF) was calculated. Titers of HANP, BNP and endothelin-1 in serum were measured. Exclusion criteria included acute myocardial infarction, unstable angina, and renal dysfunction (serum creatinine >1.6 mg/dl).. Endothelin-1 levels were correlated with HANP (r = 0.675, p < 0.0001) and BNP (r = 0.616, p < 0.0001) levels. Endothelin-1 levels were not correlated with the left ventricular ejection fraction or end-diastolic volume. BNP levels were correlated with the left ventricular ejection fraction (r = 0.315, p = 0.057).. These findings indicate that endothelin-1 interacts with HANP and BNP in patients with chronic congestive heart failure. Endothelin-1 is suggested to play an important role in chronic congestive heart failure with preserved ejection fraction.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Endothelin-1; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left

A 64-year-old man was admitted to our hospital with new-onset acute decompensated heart failure (ADHF). He had left ventricular systolic dysfunction and chronic atrial fibrillation with a rapid ventricular response. Initial treatment with low-dose recombinant human atrial natriuretic peptide (hANP) alone and no loop diuretics had an immediate effect on ADHF and left ventricular systolic dysfunction. This case demonstrates that low-dose hANP (0.01 microg/kg/min) monotherapy can be safe and effective for ADHF, with no loop diuretics being required during hospitalization. However, clinical trials will be needed to further evaluate the acute efficacy and safety of hANP monotherapy in patients with ADHF.

Topics: Acute Disease; Atrial Natriuretic Factor; Heart Failure, Systolic; Humans; Male; Middle Aged; Radiography; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Humans; Male; Middle Aged; Muscular Dystrophies; Natriuretic Peptide, Brain; Predictive Value of Tests; Ventricular Dysfunction, Left; Young Adult

atrial natriuretic peptide (ANP) is released from the heart in response to hypoxia and helps mitigate the development of pulmonary hypertension. However, the mechanism of hypoxia-induced ANP release is not clear. The cardiac atria are the primary source of ANP secretion under normal conditions, but right ventricular ANP expression is markedly up-regulated during adaptation to hypoxia. We sought to better understand mechanisms of cardiac ANP release during adaptation to hypoxia.. we measured hypoxia-induced ANP release from isolated perfused rat hearts obtained from normoxia and hypoxia-adapted rats before and after removal of the atria.. in both normoxia- and hypoxia-adapted hearts, ANP levels in the perfusate increased within 15 min of hypoxia. Hypoxia-induced ANP release was greater from hypoxia-adapted than normoxia-adapted hearts. Baseline and hypoxia-induced ANP release were considerably greater with the atria intact (213±29 to 454±62 and 281±26 to 618±87 pg/ml for normoxia- and hypoxia-adapted hearts respectively, P<0.001 for both) than with atria removed (94±17 to 131±32 and 103±26 to 201±55 pg/ml, respectively, P<0.002 for both). Hypoxia-induced ANP release was reduced over 80% by removing the atria in both normoxia- and in hypoxia-adapted hearts. Acute hypoxia caused a transient increase in lactate release and reductions in pH and left ventricular generated force, but no differences in pH or left ventricular generated force were seen between normoxia- and hypoxia-adapted rats.. we conclude that the right ventricle is not a major source of cardiac ANP release in normoxia- or hypoxia-adapted rats.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Calcium; Glucose; Heart Atria; Hydrogen-Ion Concentration; Hypertrophy, Right Ventricular; Hypoxia; Lactic Acid; Male; Myocardium; Perfusion; Potassium; Rats; Rats, Sprague-Dawley; Sodium; Ventricular Dysfunction, Left; Ventricular Pressure

Midregional pro-atrial natriuretic peptide (MR-proANP) was assessed for the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power compared with B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (HF).. MR-proANP is a biologically stable natriuretic peptide measured by a recently developed assay, with potential advantages over conventional natriuretic peptides such as BNP and NT-proBNP.. We measured MR-proANP, BNP, and NT-proBNP in 797 patients with chronic HF.. All 3 natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [95% confidence interval (CI): 0.753 to 0.844]), BNP (0.803 [95% CI: 0.757 to 0.849]), and NT-proBNP (0.730 [95% CI: 0.681 to 0.778]). During a median observation time of 68 months, 492 (62%) patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables. Proportion of explained variation showed that NT-proANP (4.36%) was a significantly stronger predictor of death than both NT-proBNP (2.47%, p < 0.0001) and BNP (2.42%, p < 0.0001).. Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.

Topics: Atrial Natriuretic Factor; Confidence Intervals; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Risk Factors; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Diastolic heart failure often coexists with atrial fibrillation (AF). Elevated plasma levels of natriuretic peptides are the left ventricular (LV) marker of diastolic dysfunction.. To evaluate the influence of sinus rhythm restoration on ANP and BNP levels in patients with normal and impaired LV diastolic function.. The study included 42 patients (19 men, 23 women), aged 58.6 +/- 8.2 years with non-valvular persistent AF with preserved LV systolic function who were successfully converted to sinus rhythm by DC cardioversion (CV) and maintained sinus rhythm for at least 30 days. On day 30 following CV in patients with sinus rhythm, Doppler echocardiography was performed to assess LV diastolic function. ECG, echocardiography, ANP and BNP plasma level measurements were made at baseline 24 h before CV and 24 h as well as 30 days after CV.. The average ANP level in the whole study group during AF was 254.9 +/- 79.9 pg/ml and the average BNP level was 113.6 +/- 49.1 pg/ml. There was an evident decrease in ANP/BNP serum concentration in all the patients after successful DC cardioversion. Measured on the 30th day after CV, ANP and BNP levels were 153.2 +/- 67.9 pg/ml and 61.9 +/- 25.1 pg/ml respectively (p < 0.001). Thirty days after CV normal LV diastolic function was diagnosed in 15 patients and in 27 patients impaired diastolic function: 20 with impaired LV relaxation and 7 with impaired LV compliance. The extent of natriuretic peptides drop was dependent on the LV diastolic function, being more substantial in the subgroup with impaired LV diastolic function. In the subgroup with LV diastolic dysfunction the average ANP serum concentration measured 30 days after conversion was reduced by 111.2 +/- 93.9 pg/ml (37%) (p < 0.001) and BNP level was reduced by 67.5 +/- 36.0 pg/ml (46%) (p < 0.001). In patients with normal diastolic function sinus rhythm restoration significantly influenced ANP level, while having no relevant effect on BNP plasma concentration. The average ANP reduction in this subgroup was 64.4 +/- 71.8 pg/ml (by 38%) and BNP reduction was 11.4 +/- 16.7 pg/ml (by 23%) (NS).. The drop in ANP and BNP plasma concentrations after conversion to sinus rhythm in patients with AF depends on the LV diastolic function. Restoration of sinus rhythm is associated with improvement of the heart's haemodynamics, especially in patients with impaired LV diastolic function, which may be inferred from the more pronounced decrease of BNP level after DC cardioversion in this subgroup, as compared to that with normal LV function.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Electric Countershock; Female; Heart Failure, Diastolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Dysfunction, Left

The diagnosis of the impaired left ventricle (LV) diastolic function during atrial fibrillation (AF) using traditional methods is very difficult. Natriuretic peptides seem to be useful for assessment of diastolic function in patients with AF.. To evaluate the influence of LV diastolic dysfunction on natriuretic peptides concentrations and to assess the diagnostic value of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with AF and impaired LV diastolic function.. The study included 42 patients (23 males, 19 females), aged 58.6 +/- 8.2 years with nonvalvular persistent AF with preserved LV systolic function who were converted into sinus rhythm by DC cardioversion (CV) and maintained sinus rhythm for at least 30 days. Echocardiography (ECG), ANP, and BNP level measurements were taken at baseline 24 hours before CV and 24 hours and 30 days after CV. On the 30th day following CV in patients with sinus rhythm, Doppler ECG was performed to assess LV diastolic function.. Thirty days after CV, normal LV diastolic function in 15 patients and impaired diastolic function in 27 patients was diagnosed: 20 with impaired LV relaxation and seven with impaired LV compliance. During AF and 24 hours, and 30 days after sinus rhythm restoration, significantly higher ANP and BNP levels were observed in patients with LV diastolic dysfunction as compared to the subgroup with normal LV diastolic function. The average values of ANP during AF in patients with normal and impaired diastolic function were 167.3 +/- 70.1 pg/mL and 298.7 +/- 83.6 pg/mL, respectively (P < 0.001), and the average values of BNP in the above mentioned subgroups were 49.5 +/- 14.7 pg/mL and 145.6 +/- 49.6 pg/mL respectively (P < 0.001). While comparing the diagnostic value of both natriuretic peptides it was noted that BNP was a more specific and sensitive marker of impaired LV diastolic function. ANP value >220.7 pg/mL measured during AF identified patients with impaired LV diastolic function with 85% sensitivity and 90% specificity. BNP value >74.7 pg/mL proved 95% sensitive and 100% specific in the diagnosing of such a group.. The increase of ANP/BNP concentration in patients with AF results not only from the presence of AF, but also reflects the impaired LV diastolic function. Natriuretic peptides, especially BNP, may be useful in diagnosing LV diastolic dysfunction in patients with AF.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left

The extent of adverse myocardial remodeling contributes essentially to the prognosis after myocardial infarction (MI). In this study we investigated whether inhibition of "mammalian target of rapamycin" (mTOR) attenuates left ventricular (LV) remodeling after MI.. Therapeutic strategies to inhibit remodeling are currently limited to inhibition of neurohumoral activation. The mTOR-dependent signaling mechanisms are centrally involved in remodeling processes and provide new therapeutic opportunities.. Everolimus (RAD) treatment was initiated on the day after or 3 days after induction of myocardial infarction (MI) in rats.. After 28 days, RAD-treated animals had reduced post-MI remodeling, with improved LV function and smaller LV end-diastolic diameters (8.9 + or - 0.3 mm vs. 11.4 + or - 0.2 mm, p < 0.05), end-diastolic volumes (304 + or - 30 microl vs. 414 + or - 16 microl, p < 0.05), and cardiac myocyte size (-40% vs. vehicle, p < 0.05). Infarct size was significantly reduced compared with vehicle-treated animals. The mTOR inhibition increased autophagy and concomitantly decreased proteasome activity in the border zone of the infarcted myocardium. Measurement of autophagic flux demonstrated that RAD did not decrease autophagosome clearance. When RAD treatment was initiated 3 days after MI, adverse remodeling was still attenuated and increased autophagy was still present. Sustained improvement of LV function was observed 3 months after MI, even when RAD treatment was discontinued after 1 month.. Inhibition of mTOR is a potential therapeutic strategy to limit infarct size and to attenuate adverse LV remodeling after MI.

Topics: Animals; Atrial Natriuretic Factor; Autophagy; Diastole; Echocardiography; Everolimus; Heart Ventricles; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Male; Microtubule-Associated Proteins; Myocardial Infarction; Myocytes, Cardiac; NF-kappa B; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Wistar; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus; TOR Serine-Threonine Kinases; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Remodeling

The purpose of this study was to evaluate late cardiac toxicity by comprehensive echocardiographic study, and to determine whether plasma atrial natriuretic peptide and brain natriuretic peptide levels might be indicators of neurohumoral activation. The study included 49 long-term survivors and 21 controls. A wide variety of echocardiographic parameters were measured or calculated. Plasma peptide levels were determined. Patients had significant changes in different echocardiographic parameters that are suggestive of LV systolic and diastolic dysfunction. Plasma peptide levels were not increased. The authors have found significant subclinic cardiotoxicity by echocardiography. Survivors seem to have normal plasma natriuretic peptide levels in long-term period.

Topics: Adolescent; Anthracyclines; Antineoplastic Agents; Atrial Natriuretic Factor; Cardiotoxins; Child; Cross-Sectional Studies; Cyclophosphamide; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

We compared the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) with a newly developed assay for the midregional part of pro-atrial natriuretic peptide (MR-proANP) concerning the detection of impaired left ventricular ejection function (LVEF) among patients with coronary artery disease (CAD).. Plasma levels of MR-proANP and NT-proBNP were determined in 102 consecutive patients with a history of ST-elevation myocardial infarction. Plasma levels of both markers were measured during a mean follow-up period of 687 days after acute myocardial infarction. Univariate analyses revealed inverse correlations between MR-proANP levels and LVEF (r=-0.39; p<0.001), NT-proBNP levels and LVEF (r=-0.39; p<0.001) and a positive correlation between MR-proANP and NT-proBNP (r=0.75; p<0.001). After adjustment for traditional risk factors, MR-proANP was the strongest predictor for LVEF (p=0.001) in multivariate analysis, being even superior to NT-proBNP. The area under the ROC curve (AUC) indicated moderate performance (AUC=0.73; p<0.01) of MR-proANP regarding the detection of a reduced LVEF<50%. The AUC of NT-proBNP for detection of impaired LVEF<50% was 0.68 (p=0.019). The negative predictive values of both markers were 86% for MR-proANP at a cut-off >135 pmol/L and NT-proBNP at a cut-off >560 pmol/L. At these cut-offs, the specificity of MR-proANP was 90%, and the specificity of NT-proBNP was 84%.. MR-proANP is a useful indicator for the exclusion of a preserved left ventricular function in patients with coronary artery disease. The study demonstrates that the diagnostic performance of MR-proANP is comparable to the "gold standard" NT-proBNP.

Topics: Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Echocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Ventricular Dysfunction, Left

Left atrial (LA) size is routinely assessed by M-mode on echocardiography. Recently, a superiority of apical measures of LA size has been suggested, but no biochemical calibration has been attempted yet. The aim of the current study was to compare echocardiographic parameters of LA size through biochemical calibration with the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP).. A total of 610 middle-aged (50-67 years) subjects from a population-based sample (MONICA Augsburg, Germany) were characterized with respect to LA area and volume from the apical two-chamber (2C) and four-chamber (4C) views in addition to M-mode echocardiography. ANP and BNP concentrations were determined by radioimmunoassay.. A significant correlation to ANP and BNP was present with all measures on LA size. The univariate correlation was lowest with M-mode diameter (r = 0.11 with ANP; r = 0.09 with BNP, both P < .03), whereas 2C volume displayed the closest correlation (r = 0.20 with ANP and r = 0.28 with BNP, both P < .001) and even slightly exceeded 2C area, 4C volume, and 4C area. 2C volume further displaced LV systolic function, mass index, and heart rate as statistically significant predictors of ANP (P < .001) and BNP (P < .001) on adjusted regression analysis, whereas M-mode diameter was displaced as a significant predictor of ANP and BNP (P = not significant).. The current population-based echocardiographic study allows new insight into the value of different measures of LA size. The closer association between natriuretic peptide concentrations and parameters derived from planimetry and volumetry suggests a superiority of these parameters LA diameter. LA volumetry should be included in routine echocardiography for optimized assessment of LA size.

Topics: Aged; Atrial Natriuretic Factor; Echocardiography, Three-Dimensional; Female; Heart Atria; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Ventricular Dysfunction, Left

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Fifty-six rats were exposed either to CIH (nadir O(2) 4-5%) or sham (handled normoxic controls, HC), 8 h/day for 6 wk. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Compared with HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH 141.3 +/- 33.1 vs. HC 184.4 +/- 21.2 ml x min(-1) x kg(-1), P < 0.01), maximal rate of LV pressure rise in systole (+dP/dt), and maximal rate of LV pressure fall in diastole (-dP/dt). CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3,564 +/- 354 vs. HC 2,628 +/- 242 microm(2), P < 0.05) and cell length (CIH 148 +/- 23 vs. HC 115 +/- 16 microm, P < 0.05), elevated terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-stained positive cell number (CIH 98 +/- 45 vs. HC 15 +/- 13, P < 0.01), elevated caspase-3 activity (906 +/- 249 vs. 2,275 +/- 1,169 pmol x min(-1) x mg(-1), P < 0.05), and elevated expression of several remodeling gene markers, including c-fos, atrial natriuretic peptide, beta-myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, or in LV collagen deposition on trichrome-stained slices. In conclusion, CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiac Myosins; Cardiac Output; Cardiomegaly; Caspase 3; Cell Size; Chronic Disease; Collagen; Disease Models, Animal; Hypertrophy; Hypoxia; Male; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Myosin Light Chains; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Research Design; RNA, Messenger; Ventricular Dysfunction, Left; Ventricular Pressure; Ventricular Remodeling

To assess factors of importance for long term prognosis in patients with acute myocardial infarction (AMI) and heart failure and normal or mildly reduced left ventricular systolic function.. Seventy-one consecutive AMI-survivors with clinical or radiological signs of heart failure and an echocardiographically determined wall motion score >1.2 (EF >35-40%) were followed during 11 years for mortality, heart failure readmissions and new ischemic events.. Seventeen patients died (24%) while the combined endpoint of death or a new ischemic event (MI or hospitalisation for angina pectoris) occurred in 40 (56%) and fatal or non-fatal heart failure in 20 (28%) patients, respectively. A pre-discharge echocardiographic assessment of diastolic function was obtained in 67 patients out of whom 56 (84%) had diastolic dysfunction, most frequently relaxation abnormalities (43%). Wall motion score did not differ between survivors and non-survivors (1.48+/-0.20 vs. 1.44+/-0.18; p=0.46). Adjusting for age, sex and wall motion score N-terminal pro-ANP, prolongation of the isovolumic relaxation time and exercise induced ST-depressions at discharge (global chi2=26.2; p<0.0001) remained as independent mortality predictors while re-admission for heart failure was predicted by wall motion score, N-terminal pro-ANP and previous heart failure (global chi2=23.7; p<0.001). Death or new ischemic events were associated with low Doppler A-wave flow velocity and male sex (global chi2=14.0; p<0.01).. Evaluation of diastolic function and a natriuretic peptide adds prognostically important information in AMI-patients with clinical heart failure and normal or mildly reduced left ventricular systolic function. Isovolumic relaxation time is an independent predictor of long term mortality and N-terminal pro-ANP of mortality and heart failure.

Topics: Aged; Atrial Natriuretic Factor; Diastole; Echocardiography, Doppler; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Prevalence; Prognosis; Protein Precursors; Severity of Illness Index; Systole; Ventricular Dysfunction, Left

Hemodynamic effects of surgical and percutaneous closure of atrial septal defect (ASD) were evaluated.. ASD causes volume overload of right ventricle (RV) and is associated with distortion and dysfunction of left ventricle (LV). The amount and timing of hemodynamic changes after ASD closure are not well known.. The study group consisted of 7 children treated surgically and 17 treated in the catheterization laboratory. In the control group, there were 51 healthy children. RV size and LV end-diastolic and systolic dimensions, volumes, and function were examined by two- and three- dimensional echocardiography and serum concentrations of natriuretic peptides measured prior to ASD closure, and 1, 6, and 12 months thereafter.. In all children with ASD, during the 1-year follow-up, the z score of RV end-diastolic diameter decreased from a median 5.00 SD to 2.25 SD (P < 0.001). Dilatation of RV did not resolve entirely during 1-year follow-up in either treatment group. End-diastolic LV diameter increased from -1.50 to -0.50 SD (P < 0.001). LV size increased slower in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides increased during the first month after ASD closure and normalized thereafter in patients treated percutaneously but remained higher than in controls in patients treated surgically.. During 1-year follow-up after ASD closure, RV size decreases but does not normalize in all patients. The size of the LV normalizes after ASD closure but the increase in LV size is slower in patients treated surgically. Serum levels of ANPN and proBNP are elevated prior to ASD closure but decrease thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically.

Topics: Adolescent; Atrial Natriuretic Factor; Biomarkers; Cardiac Catheterization; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Case-Control Studies; Child; Child, Preschool; Echocardiography; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right

Left ventricular end-diastolic pressure (LVEDP) during exercise workload is an important parameter to guide an exercise prescription for patients with cardiovascular disease. Plasma levels of neuro-hormonal factors can be used as a reflection of real-time LVEDP, but its utility is limited by its short half-life. By contrast, the N-terminal fragment of pro-ANP (NT-ANP) has a longer half-life of 1 h.. To determine whether plasma NT-ANP levels at 30 min after exercise can be used as a marker of LVEDP during peak exercise workload in patients with previous myocardial infarction.. Twenty patients with a previous history of myocardial infarction.. Cardiopulmonary exercise test was performed to determine peak VO(2) and anaerobic threshold. Plasma levels of ANP, BNP, NT-ANP, vasopressin and plasma catecholamine were measured at rest, maximum exercise, and 30 min after exercise (recovery).. With the exception of NT-ANP, the levels of each of neuro-hormonal factors peaked at maximum exercise and returned to baseline at recovery. By contrast, NT-ANP levels also increased at peak exercise but remained elevated at 30 min after exercise. Furthermore, NT-ANP levels at recovery correlated with ANP levels at maximum exercise (p<0.01, R=0.75), left ventricular ejection fraction (p<0.02, R=-0.54) and left ventricular systolic dimension (p<0.015, R=0.50).. Plasma NT-ANP levels at 30 min after exercise reflect ANP levels at maximum exercise and left ventricular overload during exercise. These data indicate that plasma NT-ANP after exercise may be a useful parameter to guide prescription of cardiac rehabilitation.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Exercise; Female; Half-Life; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Protein Precursors; Time Factors; Vasopressins; Ventricular Dysfunction, Left

The aim of this study was to evaluate the plasma levels of the adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in adult and pediatric patients with congestive heart failure (CHF) of various etiologies and to investigate their relations with haemodynamic variables e.g. echocardiographic left ventricular ejection fraction (LVEF) and fractional shortening (FS).. The study was made in 38 adult and 21 pediatric patients with CHF of various etiologies and compared with 15 adult and 10 pediatric normal healthy controls. Patients with CHF were classified according to the New York Heart Association (NYHA) functional classification into grades II to IV in adult patients and into grade IV in all pediatric patients. ADM and ANP plasma levels were determined prior to the treatment with enzyme immunoassay.. A statistically significant difference in the plasma levels of ADM and ANP were found between pediatrics and adult patients and corresponding healthy controls. Their levels were progressively increased with severity of NYHA class in adult patients. We found a significant positive correlation between plasma levels of each of ADM and ANP and pulse rate, systolic and diastolic blood pressure; and a significant negative correlation between their plasma levels and echocardiographic LVEF and FS. A significant positive correlation between plasma levels of ADM and ANP in both pediatrics and adult patients were also found.. Plasma levels of ADM and ANP increased in adult and pediatric patients with CHF irrespective of the cause. They were positively correlated with each other and negatively correlated with LVEF and FS. These findings might have important clinical implications in that a noninvasive blood test may be used to identify high-risk subjects for HF for more invasive procedures.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Child; Child, Preschool; Female; Heart Failure; Humans; Infant; Male; Middle Aged; Pulse; Ventricular Dysfunction, Left; Ventricular Function, Left

Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high-throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro-atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care.. 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45-89, interquartile range 51-67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton-Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at -70 degrees C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2-2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6-10.1%). Echocardiography was used as the diagnostic "gold standard", with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; ROC Curve; Stroke Volume; Systole; Ventricular Dysfunction, Left

Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients, and following an infarction, diabetes is associated with an increased risk for the development of left ventricular (LV) dysfunction and heart failure. The goal of this study was to determine if the progression of heart failure following myocardial infarction in type 2 diabetic (T2D) rats is accelerated compared with nondiabetic rats. Male nondiabetic Wistar-Kyoto (WKY) and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham surgery to induce heart failure. Postligation (8 and 20 wk), two-dimensional echocardiography and LV pressure measurements were made. Heart failure progression, as assessed by enhanced LV remodeling and contractile dysfunction, was accelerated 8 wk postligation in the T2D animals. LV remodeling was evident from increased end-diastolic and end-systolic diameters and areas in the GK compared with the WKY infarcted group. Furthermore, enhanced LV contractile dysfunction was evident from a greater deterioration in fractional shortening and enhanced myocardial performance index (an index of global LV dysfunction) in the GK infarcted group. This accelerated progression was accompanied by greater increases in atrial natriuretic factor and skeletal alpha-actin (gene markers of heart failure and hypertrophy) mRNA levels in GK infarcted hearts. Despite similar decreases in metabolic gene expression (i.e., peroxisome proliferator-activated receptor-alpha-regulated genes associated with fatty acid oxidation) between infarcted WKY and GK rat hearts, myocardial triglyceride levels were elevated in the GK hearts only. These results, demonstrating enhanced remodeling and LV dysfunction 8 wk postligation provide evidence of an accelerated progression of heart failure in T2D rats.

Topics: Actins; Animals; Atrial Natriuretic Factor; Blood Glucose; Cardiac Output, Low; Diabetes Mellitus, Type 2; Disease Models, Animal; Disease Progression; Fatty Acids, Nonesterified; Heart Rate; Male; Myocardial Infarction; Rats; Rats, Inbred Strains; Rats, Inbred WKY; RNA, Messenger; Ventricular Dysfunction, Left; Ventricular Remodeling

It has been reported that high intramyocardial peroxisome proliferator-activated receptor alpha (PPARalpha) stimulation or overexpression altered cardiac contractile function in mouse models of cardiac hypertrophy and heart failure. Nevertheless, it has never been demonstrated that clinically relevant doses of drugs stimulating PPARalpha activity such as fenofibrate increase the risk to develop heart failure in humans. To determine if fenofibrate accelerates the development of heart failure in large mammals, we have tested its effects on the progression of left ventricular dysfunction in pacing-induced heart failure in pigs. Fenofibrate treatment blunted reduction in left ventricular ejection fraction, reduced cardiac hypertrophy, and attenuated clinical signs of heart failure. Fenofibrate impeded the increase in atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 plasma levels. The expression of PPARalpha, fatty acyl-CoA-oxidase, and carnitine palmitoyltransferase-Ibeta was reduced at mRNA levels in the left ventricle from untreated heart failure pigs but maintained near normal values with fenofibrate. Fenofibrate prevented heart failure-induced overexpression of TNFalpha mRNA and enhanced catalase activity in left ventricle compared to placebo. These data suggest that a clinically relevant dose of fenofibrate does not accelerate but slows down heart failure development in the model of pacing-induced heart failure in large mammals.

Topics: Acyl-CoA Oxidase; Animals; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Cardiomyopathies; Carnitine O-Palmitoyltransferase; Endothelin-1; Female; Fenofibrate; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; PPAR alpha; RNA, Messenger; Swine; Tachycardia; Thiobarbituric Acid Reactive Substances; Ventricular Dysfunction, Left

Although studies have shown that endothelial nitric oxide synthase (eNOS) homozygous knockout mice (eNOS-/-) develop left ventricular (LV) hypertrophy, well compensated at least to 24 wks, uncertainty still exists as to the cardiac functional and molecular mechanistic consequences of eNOS deficiency at later time-points. To bridge the gap in existent data, we examined whole hearts from eNOS-/- and age-matched wild-type (WT) control mice ranging in age from 18 to 52 wks for macroscopic and microscopic histopathology, LV mRNA and protein expression using RNA Dot blots and Western blots, respectively, and LV function using isolated perfused work-performing heart preparations. Heart weight to body weight (HW/BW in mg/g) ratio increased significantly as eNOS-/- mice aged (82.2%, P < 0.001). Multi-focal replacement fibrosis and myocyte degeneration/death were first apparent in eNOS-/- mouse hearts at 40 wks. Progressive increases in LV atrial natriuretic factor (ANF) and alpha-skeletal actin mRNA levels both correlated significantly with increasing HW/BW ratio in aged eNOS-/- mice (r = 0.722 and r = 0.648, respectively; P < 0.001). At 52 wks eNOS-/- mouse hearts exhibited basal LV hypercontractility yet blunted beta adrenergic receptor (betaAR) responsiveness that coincided with a significant reduction in the LV ratio of phospholamban to sarcoplasmic reticulum Ca2+-ATPase-2a protein levels and was preceded by a significant upregulation in LV steady-state mRNA and protein levels of the 28 kDa membrane-bound form of tumor necrosis factor-alpha. We conclude that absence of eNOS in eNOS-/- mice results in a progressive concentric hypertrophic cardiac phenotype that is functionally compensated with decreased betaAR responsiveness, and is associated with a potential cytokine-mediated alteration of calcium handling protein expression.

Topics: Actins; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiomegaly; Gene Expression Regulation, Enzymologic; Gene Silencing; Heart Rate; Heart Ventricles; In Vitro Techniques; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Myocytes, Cardiac; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Organ Size; Perfusion; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Although long-term treatment with beta-blockers has been shown to improve morbidity and mortality in dilated cardiomyopathy (DCM), patient responses are heterogeneous.. To establish the appropriate indication for the initiation of beta-blocker therapy, we retrospectively analyzed 38 DCM patients treated with beta-blockers (metoprolol or carvedilol) and examined differences in baseline profiles between patients who could continue the therapy (responders) and those who could not (non-responders).. In 13 non-responders, the duration from onset of symptoms to beta-blocker initiation was longer (p < 0.05), systolic blood pressure was lower (p < 0.001), serum sodium concentration was lower (p < 0.05), left ventricular posterior wall thickness was thinner (p < 0.05), left ventricular end-diastolic pressure was higher (p < 0.05) and left ventricular wall stress was lower (p < 0.05) than in 25 responders. In 19 patients receiving carvedilol, 5 non-responders showed higher levels of human atrial natriuretic peptide (p < 0.05) and brain natriuretic peptide (p < 0.01) than 13 responders. Discriminant analysis with a linear discriminant function showed the following equation predicted response to beta-blocker therapy: h = 0.004 x systolic blood pressure - 0.002 x brain natriuretic peptide + 0.667 (R2 = 0.67, p < 0.001). The probability of predicting the response was 94.1% with h > or = 0.5.. We conclude that h > or = 0.5 is the appropriate indication for the initiation of beta-blocker therapy in DCM.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiomyopathy, Dilated; Discriminant Analysis; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Pressure

Plasma atrial (ANP) and brain (BNP) natriuretic peptide levels were compared to determine if transmitral flow velocity pattern is an instantaneous marker of body fluid balance in anuric patients on hemodialysis (HD). We measured plasma ANP and BNP levels and performed Doppler echocardiography in 38 anuric patients before and after HD. Patients with valvular disease, left ventricular systolic dysfunction having a fractional shortening < 0.3, arrhythmia, or left ventricular hypertrophy were excluded. The relationships between plasma ANP or BNP levels and the transmitral flow velocity pattern were evaluated. We also determined if the magnitude of the decrease in plasma ANP level was related to that in the early peak of transmitral flow velocity (peak E). The mean age of the subjects was 61.1 +/- 9.7 years. The ANP level of 213.6 +/- 146.1 pg/mL was related to peak E of 61 +/- 15 cm/s before HD (R = 0.504, P < 0.001), but not after HD. Plasma ANP level was not related to peak late transmitral flow velocity (peak A) or peak E/peak A before or after HD. BNP level was not related to the transmitral flow velocity pattern. The magnitude of decrease in hANP level during HD was significantly related to that in peak E (R = 0.342, P < 0.05). Before HD, peak E was related to the plasma ANP level, reflecting volume overload. Change in peak E showed a weak relationship with that of plasma ANP level in the same HD patient. The measurement of peak E during a HD session may potentially enable the assessment of hydration status during HD.

Topics: Aged; Atrial Natriuretic Factor; Blood Flow Velocity; Echocardiography, Doppler; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Systole; Ventricular Dysfunction, Left

Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT).. Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion.. Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline.. Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Biomarkers; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Gated Blood-Pool Imaging; Heart; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Postoperative Period; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Stroke Volume; Systole; Transplantation, Autologous; Ventricular Dysfunction, Left

Myocardial contractility is enhanced in transgenic (TG) mice with cardiac-restricted overexpression of the alpha1A-adrenergic receptors (alpha1A-AR). We tested the hypothesis that this enhanced inotropy protects against dysfunction and remodeling after myocardial infarction (MI).. We subjected alpha1A-TG and non-TG mice (NTG) to MI and determined changes in left ventricular (LV) function and diastolic dimension (LVDd) by echocardiography prior to and at 1, 3, 7, 12 and 15 weeks thereafter.. Although infarct size was similar in the NTG and alpha1A-TG groups (32+/-2 vs. 29+/-2% of LV, P=NS), mortality due to heart failure was lower after MI in the alpha1A-TG (37%, n=39) than that in the NTG animals (63%, n=56, P=0.026). NTG and alpha1A-TG mice showed similar reductions in LV fractional shortening (FS) and increases in LVDd at week-1 after MI. However, whereas NTG mice showed continuous deterioration over a 15-week period after MI in FS (fell by 40%, from 30+/-2 to 18+/-1%, P<0.01) and LVDd (increased by 24%, from 4.2+/-0.1 to 5.2+/-0.1 mm, P<0.01), the changes in both FS (fell by 14%, from 42+/-2 to 36+/-2%) and LVDd (increased by 8%, from 3.8+/-0.1 to 4.1+/-0.1 mm, both changes P<0.01 vs. NTG) were significantly less severe in the alpha1A-TG mice and did not progress after 3 weeks. At 15 weeks after MI, LV catheterization revealed better preservation of dP/dtmax in the alpha1A-TG vs. NTG mice (7270+/-324, vs. 5938+/-372 mmHg/s, P<0.05).. Enhanced inotropy resulting from transgenic overexpression of alpha1A-AR is well maintained chronically after MI and limits echocardiography-determined LV remodeling, preserves function, and reduces acute heart failure death.

Topics: Actins; Aging; Animals; Atrial Natriuretic Factor; Collagen; Echocardiography; Female; Fibronectins; Heart Failure; Hydroxyproline; Male; Mice; Mice, Transgenic; Myocardial Infarction; Myocardium; Myosin Heavy Chains; Nonmuscle Myosin Type IIB; Random Allocation; Receptors, Adrenergic, alpha-1; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts.. We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls.. There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples.. These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.

Topics: Adult; Aged; Angiotensin-Converting Enzyme 2; Atrial Natriuretic Factor; Biopsy; Cardiac Output, Low; Cell Count; Chymases; Disease Progression; Female; Gene Expression Regulation; Gene Expression Regulation, Enzymologic; Humans; Male; Mast Cells; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Renin-Angiotensin System; RNA, Messenger; Serine Endopeptidases; Ventricular Dysfunction, Left

Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.

Topics: Actin Cytoskeleton; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography, Doppler; Fibrosis; Gene Expression Regulation, Viral; Hepacivirus; Hepatitis C; Hypertrophy, Left Ventricular; Male; Mice; Mice, Transgenic; Mitochondria, Heart; Myocarditis; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; NF-kappa B; Organ Size; RNA, Messenger; RNA, Viral; Transcription Factor AP-1; Ventricular Dysfunction, Left; Viral Core Proteins

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Chagas Cardiomyopathy; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

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.

Topics: Aged; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; ROC Curve; Survival Analysis; Ventricular Dysfunction, Left

In most animal models of chronic hemodynamic overload of the left ventricle (LV) as well as in human end stage heart failure, the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) mRNA levels are decreased in parallel with increased atrial natriuretic peptide (ANP) mRNA levels. The situation in the remote myocardium following myocardial infarction (MI) is unclear.. (1) To examine SERCA2a mRNA levels in the non-infarcted LV myocardium of rats at the chronic stage of experimental MI and (2) To examine whether a negative linear correlation exists between SERCA2a and ANP mRNA levels in this model.. Anesthetized adult male Wistar rats underwent left coronary artery ligation or sham operation. Three months later, the rats were divided into three groups: sham-operated rats (sham, n=21), HF-free rats with MI (non-failing (NF)-MI, n=29) and rats with both MI and HF (congestive heart failure (CHF)-MI, n=14). LV remodelling and function were assessed by echocardiography and hemodynamic measurements. SERCA2a and ANP mRNA levels were determined by Northern and dot blot analysis with specific cDNA probes.. LV SERCA2a mRNA levels varied markedly in sham-operated rats (0.9-1.8). Mean ANP mRNA level increased markedly and mean SERCA2a mRNA level decreased moderately in the remote myocardium. In some NF-MI rats, SERCA2a mRNA levels were higher than those in some sham controls. Whereas ANP mRNA levels correlated well with MI severity (r2=0.79, p<0.001), this was not the case for SERCA2a mRNA levels (r2=0.42, p<0.01). We found no negative correlation between ANP and SERCA2a mRNA levels.. SERCA2a gene down-regulation in the non-infarcted myocardium of rats with MI does not correlate with ANP gene up-regulation, suggesting that the two genes are not antithetically regulated.

Topics: Animals; Atrial Natriuretic Factor; Calcium-Transporting ATPases; Disease Progression; Down-Regulation; Gene Expression Regulation; Male; Myocardial Infarction; Rats; Rats, Wistar; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Remodeling

Plasma adrenomedullin (AM) reflects cardiac dysfunction and predicts survival after myocardial infarction. The present study was designed to investigate whether the mature AM (mAM) reflects status of cardiac function, systemic blood volume, or inflammation in hemodialysis patients with cardiovascular disease, and whether mortality and additional cardiovascular morbidity can be predicted by mAM.. Plasma levels of mAM, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), norepinephrine (NE), and C-reactive protein (CRP) before hemodialysis were measured in 67 chronic hemodialysis patients with cardiovascular disease, along with 2-dimensional and Doppler echocardiographic variables.. By univariate regression analysis, mAM correlated negatively with pulmonary venous flow velocity ratio and left ventricular (LV) ejection fraction and positively with LV inflow velocity ratio, LV end-diastolic, end-systolic volume indexes, plasma CRP level, and removal fluid volume by ultrafiltration. Multivariate stepwise regression analysis revealed that mAM reflected all variables better than log [ANP], log [BNP], and log [NE]. During a 1-year follow-up period, 7 patients died and 8 had additional cardiovascular events. Event-free Kaplan-Meier curves based on the median mAM (4.55 pmol/L) showed that patients with high plasma mAM levels had higher mortality and morbidity than those with low plasma mAM levels (P = 0.0056). By Cox multivariate proportional hazard analysis, mAM was related to mortality and morbidity [hazard ratio (HR) 4.55, 95% CI 1.2-16.8, P= 0.023).. Plasma mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular morbidity in hemodialysis patients with cardiovascular disease.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Volume; C-Reactive Protein; Female; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptides; Predictive Value of Tests; Renal Dialysis; Ventricular Dysfunction, Left

Natriuretic peptide levels B (BNP) and A (ANP) have been described in children with congenital heart defects (CHD) with pressure and volume overload. However, the impact of ventricular morphology per se on natriuretic peptide levels has not been reported. The aim of the present study was to evaluate plasma BNP and ANP in children with CHD with left or right ventricular volume or pressure overload.. Plasma BNP and ANP were analysed in 61 children, median age 3.1 (0.3-16.2) years. Haemodynamic load was evaluated by echo-Doppler and/or catheterization measurements and classified as: pressure overload of the right (RV pressure) or left (LV pressure) ventricle, or volume overload of the right (RV volume) or left (LV volume) ventricle, of a sufficient degree to indicate surgery/catheter intervention. Twenty-three children, with a median age of 1.1 (0.1-8.3) years, without heart disease, served as controls for the natriuretic peptide measurements. Children in the LV volume group had significantly higher BNP and ANP values, 55.4 ng l-1 (10.7-352) and 164 (31.8-346), than children in the RV volume, 15.6 (0.0-105.1) and 57.2 (11.3-234.1), LV pressure, 6.8 (0.7-170) and 40.8 (12.6-210), and RV pressure, 18.0 (5.0-29.1) and 69.3 (8.7-182), groups respectively (P<0.0001). The values in the LV pressure group were close to the values in the Control group, 4.7 (0.0-17.7) and 32.9 (11.7-212.1), respectively (P=0.051 and P=0.378, respectively).. Plasma concentrations of BNP and ANP were higher in children with CHD with left ventricular volume overload compared with right ventricular volume overload or pressure overload.

Topics: Adolescent; Atrial Natriuretic Factor; Biomarkers; Child; Child, Preschool; Heart; Heart Defects, Congenital; Hemodynamics; Humans; Infant; Natriuretic Peptide, Brain; Reference Values; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right

1. As a result of its enormous surface area and necessary thinness for gas exchange, the alveolocapillary barrier is vulnerable to mechanical disruption from raised pulmonary microvascular pressure (Pmv). 2. Because surfactant protein-B (SP-B) leaks into the blood stream from the alveoli in response to alveolocapillary barrier damage and exercise leads to increased Pmv, we sought to determine whether exercise results in increased plasma SP-B. Moreover, in the setting of exercise-induced left ventricular dysfunction, the consequent increase in left heart filling pressure and, therefore, P(mv) would be expected to further increase plasma SP-B levels. 3. Twenty consecutive subjects referred for treadmill exercise stress echocardiography (ESE) had venous blood sampled immediately before and after ESE for batch atrial natriuretic peptide (ANP) and SP-B assay. Echocardiographic measures of pulmonary haemodynamics (pulmonary artery flow acceleration time (pafAT) and right ventricular outflow tract velocity time integral (rVTI)) were also taken pre- and post-exercise. 4. Although circulating ANP levels increased following exercise (P < 0.001), there was no change in circulating SP-B levels in the entire cohort. 5. Ten subjects had a positive ESE for ventricular dysfunction. Although circulating ANP was increased post-exercise in both the negative and positive ESE groups (P < 0.05 and P < 0.01, respectively), circulating SP-B only increased post-exercise in the positive ESE group (P < 0.05). Echocardiographic parameters supported an increment in P(mv) in the cohort with exercise-induced left ventricular dysfunction because this group had an increase in pafAT (P < 0.05; reflecting pulmonary artery pressure) and no change in rVTI. 6. Physical exertion associated with a Bruce protocol ESE is insufficient to increase circulating SP-B, despite evidence of increased left atrial and pulmonary vascular pressure. However, in the setting of exercise-induced myocardial dysfunction, there is a detectable increase in circulating SP-B. 7. The exaggerated increase in pulmonary vascular pressure in exercise-induced myocardial dysfunction may result in increased SP-B leakage from the alveoli into the circulation by altering the integrity of the alveolocapillary barrier to protein.

Topics: Atrial Natriuretic Factor; Exercise; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Pulmonary Surfactant-Associated Protein B; Ventricular Dysfunction, Left

The family of natriuretic peptides comprises several structurally related 22-53-amino acid peptides, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are vasoactive peptides with vasodilator and diuretic properties and play an important role in cardiovascular homeostasis. The salutary cardiovascular effects of natriuretic peptides suggest that ANP and BNP may have a pathophysiological significance in the cardiac dysfunction of septic patients. We determined plasma levels of the stable N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) as well as troponin I (TNI) as a marker of myocardial cell injury by ELISA methods in 19 septic patients and 19 healthy controls at day one of severe sepsis. Left ventricular ejection fraction (LVEF) was determined on day 1 of severe sepsis by echocardiography. Significantly higher concentrations of NT-proANP were measured in non-survivors (mean = 13415 pmol/l +/- SEM = 4295) and survivors (mean = 7386 pmol/l +/- SEM = 1807) as compared to controls (mean = 1404 pmol/l +/- SEM = 181; p<0.001). Levels of NT-proBNP were also significantly higher in non-survivors (mean = 3439 pmol/l +/- SEM = 1246; p<0.05) and survivors (mean = 1009 pmol/l +/- SEM = 263; p<0.001) as compared to controls (mean = 200 pmol/l +/- SEM = 24) and correlated well with an increase in TNI-levels (r = 0.71; p<0.001). NT-proANP and NT-proBNP may serve as useful laboratory markers to indicate myocardial dysfunction and may help to differentiate between survivors and non-survivors of severe sepsis.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Sepsis; Treatment Outcome; Troponin I; Ventricular Dysfunction, Left

Congestive heart failure (CHF) results in decreased cardiac sympathetic innervation.. The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates cardiac neuronal remodeling in CHF.. We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n = 8) or without (CHF group, n = 10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine cardiac structure and hemodynamic parameters. Myocardial nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls.. In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group (P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high nerve counts. OMA treatment prevented heterogeneous reduction of nerve density. The left ventricular TH-positive nerve densities were 128 +/- 170 microm(2)/mm(2), 261 +/- 185 microm(2)/mm(2), and 503 +/- 328 microm(2)/mm(2) (P < .05), and the atrial GAP43-positive nerve densities were 1,683 +/- 1,365 microm(2)/mm(2), 305 +/- 368 microm(2)/mm(2), and 1,278 +/- 1,479 microm(2)/mm(2) (P < .05) for the control, CHF, and CHF+OMA groups, respectively.. CHF results in heterogeneous cardiac denervation. Long-term OMA treatment prevented the reduction of nerve density and promoted beneficial cardiac structural remodeling.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Cardiovascular Agents; Disease Models, Animal; Dogs; Heart Atria; Heart Failure; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue; Pyridines; Renin; Stroke Volume; Thiazepines; Ventricular Dysfunction, Left; Ventricular Pressure; Ventricular Remodeling

Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.

Topics: Atrial Natriuretic Factor; Biomarkers; Cicatrix; Collagen; Collagen Type I; Echocardiography; Electrocardiography; Female; Heart; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Procollagen; Radiography, Thoracic; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

The mammalian heart contains specific growth hormone-releasing peptide (GHRP) binding sites whose physiological significance is unknown. We sought to compare the effects of GHRP and GH on progressive left ventricular (LV) dysfunction in the TO-2 hamster model of dilated cardiomyopathy.. TO-2 hamsters (8 weeks old) were injected with GHRP-6 (100 microg/kg day), GH (2 mg/kg day), or saline for 4 weeks; F1B hamsters served as controls. LV functional and structural changes were evaluated by echocardiography and pathology.. The increase in body weight of GH-treated TO-2 hamsters was greater than that of animals in the other two groups. Plasma GH and insulin-like growth factor-1 (IGF-1) concentrations were not increased by GHRP-6. LV fractional shortening (LVFS) decreased from 42.0+/-2.6% to 25.4+/-1.8% and the LV end-diastolic dimension (LVDd) increased from 4.0+/-0.1 to 5.0+/-0.1 mm in untreated TO-2 hamsters between 8 and 12 weeks. LVFS was substantially improved by treatment with GHRP-6 (33.4+/-2.0%) or GH (32.0+/-2.1%). The LVDd was significantly smaller in animals treated with GHRP-6 than in those treated with GH. The cross-sectional LV myocyte area and the amount of atrial natriuretic peptide mRNA in the LV were increased by GH but not by GHRP-6. Treatment woth GH at a lower dose (0.2 mg/(kg day)) exerted minimal cardiac and systematic growth effects without improving LV function.. GHRP can ameliorate the development of progressive LV dysfunction independently of the GH-IGF-1 axis, suggesting a potential new approach to the heart failure.

Topics: Animals; Atrial Natriuretic Factor; Calcium-Transporting ATPases; Cardiomyopathy, Dilated; Cricetinae; Cytoskeletal Proteins; Disease Progression; Growth Hormone; Insulin-Like Growth Factor I; Male; Membrane Glycoproteins; Mesocricetus; Models, Animal; Myocardium; Oligopeptides; Sarcoglycans; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Systole; Ventricular Dysfunction, Left

Clinical methods for the early detection of doxorubicine (adriamycin; ADR) -induced cardiotoxicity have not been established. This study prospectively investigated whether atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cardiac troponin T (TnT) are predictors for ADR-induced cardiotoxicity, and examined the correlations between the serum concentrations of these biomarkers and the functional alternations associated with ADR-induced myocardial damage.. Male Wistar rats were injected weekly with 2 mg/kg of ADR via the tail vein for 8 weeks to induce cardiotoxicity. Echocardiograms of each ether anesthetized rat were taken at 6, 8, 10 and 12 weeks after the first administration of ADR, and blood samples collected from the tail vein were used to quantify plasma ANP and BNP, and serum TnT after echocardiography. Plasma BNP and serum TnT significantly increased from 6 to 12 weeks (81.5 to 173.3 pg/ml (p<0.001), <0.01 to 1.09 ng/ml (p<0.05), respectively) with deterioration of left ventricular % fractional shortening (%FS) (58.6% to 36.8%). The %FS significantly correlated with TnT (r=-0.51, p<0.001) and BNP (r=-0.75, p<0.0001); however, the increase of TnT was antecedent to the increase of BNP and the deterioration of %FS.. Plasma BNP and serum TnT concentrations, especially TnT, measured by this highly sensitive method are useful predictors for ADR-induced cardiomyopathy.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Disease Progression; Doxorubicin; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Rats; Rats, Wistar; Troponin T; Ventricular Dysfunction, Left

Cardiac dysfunction has been reported in a substantial part of patients infected with the human immunodeficiency virus (HIV). However, most studies are from a time before the introduction of highly active antiretroviral treatment (HAART), which has significantly reduced HIV-associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide ventriculography.. Ninety-five consecutive patients with HIV infection were included. Mean HIV duration was 104 months, and 84% of the patients received HAART. All patients underwent radionuclide ventriculography, and plasma levels of atrial natriuetic peptide (ANP), brain natriuetic peptide (BNP), and endothelin-1 (ET-1) were measured. Thirty age- and sex-matched healthy volunteer subjects were included to establish reference values of radionuclide measurements of left and right ventricular ejection fraction and of left ventricular volume.. Of 95 patients with HIV, 1 (1%) had a reduced left ventricular ejection fraction and 6 (7%) had a reduced right ventricle ejection fraction (0.35-0.42) compared with reference values from the age- and sex-matched reference population. Patients with HIV and reduced cardiac function did not differ in the duration of HIV, CD4 count, CD4 nadir, or HIV RNA load. No correlations were found between reduced cardiac function and levels of the 3 peptides measured.. No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic function.

Topics: Adult; Antiretroviral Therapy, Highly Active; Atrial Natriuretic Factor; Denmark; Developed Countries; Endothelin-1; Female; HIV Infections; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Radionuclide Ventriculography; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Patients with hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) have increased concentrations of various neurohumoral factors. Thus, the aim of the present study was to evaluate the differences in the neurohumoral profiles of HCM and HHD.. Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II and endothelin-1 were measured in 40 patients with HCM, 35 with HHD, and 15 controls. Additionally, the concentrations of these neurohumoral factors in the coronary sinus and aortic root were measured in 12 HCM patients and 10 controls. Plasma concentrations of norepinephrine, ANP and BNP were significantly higher in HCM than HHD and controls. In HCM, there was no significant correlation between the left ventricular mass index and any neurohumoral factor. The plasma BNP concentration significantly correlated with left intraventricular pressure gradient in HCM. There were significant differences in the plasma concentrations of ANP and BNP between HCM with and without left ventricular diastolic dysfunction. Transcardiac production of BNP was significantly higher in patients with obstructive HCM than in those with non-obstructive HCM.. The significant neurohumoral differences between HCM and HHD were the plasma concentrations of norepinephrine, ANP and BNP. In HCM patients, the plasma BNP concentration may reflect the intraventricular pressure gradient and left ventricular diastolic dysfunction whereas the plasma ANP concentration reflects only the left ventricular diastolic dysfunction.

Topics: Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Coronary Vessels; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Pressure; Ventricular Dysfunction, Left; Ventricular Function

Greater change of postural blood pressure (BP) is often seen in elderly hypertensives and is recognized as a risk factor for cognitive decline and poorer cerebrovascular outcome, but its clinical significance still remains to be clarified. We performed a head-up tilting test, ambulatory BP monitoring, and brain MRI in 59 hypertensives and 27 normotensive subjects. We measured plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels at rest to assess cardiac burden. The 59 hypertensive patients were classified into 3 groups: an orthostatic hypertension (OHT) group with orthostatic increase in systolic BP (SBP) > or = 10 mmHg (n=16); an orthostatic hypotension (OHYPO) group with orthostatic SBP decrease < or = -10 mmHg (n=18); and an orthostatic normotension (ONT) group with neither of these two patterns (n=25). A group of 27 normotensive subjects (NT) was also included as a control. Plasma BNP (72 +/- 92 vs. 29 +/- 24 pg/ml, p < 0.05) and BNP/ANP ratio (4.6 +/- 3.3 vs. 2.4 +/- 1.5, p < 0.05) were significantly higher in the OHYPO than in the NT group. The BNP/ANP ratio was also higher in the OHT than in the NT group (5.1 +/- 3.9 vs. 2.4 +/- 1.5, p < 0.01). The number of silent cerebral infarct (SCI), prevalence of SCI and number of multiple SCIs was the highest in the OHT group, followed in order by the OHYPO, ONT and NT groups. Blood pressure and left ventricular mass index were not significantly different among the 3 hypertensive groups. In conclusion, hypertensive patients with greater change of postural BP (OHT and OHYPO) were shown to have increased risk of advanced silent brain lesions and greater cardiac burden.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Cerebral Infarction; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Hypotension, Orthostatic; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left

We compared the performance of different natriuretic peptides to diagnose mild forms of left ventricular dysfunction (LVD) and investigated the influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays on the diagnostic performance of these markers.. We measured BNP (Triage BNP), NT-proBNP (Biomedica), and N-terminal pro-A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients (age range, 28-83 years) with clinically suspected mild LVD. In patients with sufficient sample volume, we measured BNP and NT-proBNP with additional assays (Shionoria and Roche, respectively).. For identifying patients with mild systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence interval) areas under the curves (AUC) of 0.78 (0.63-0.89) and 0.75 (0.58-0.87), respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48-0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed equally well for the diagnosis of systolic LVD despite the poor agreement between NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic performance of the Triage BNP [AUC, 0.70 (0.56-0.81)] was significantly better (P = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34-0.65)]. Furthermore, the performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03) than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD.. The performance of BNP for the diagnosis of systolic or diastolic LVD is not affected by the assay used, whereas the performance of NT-proBNP for the diagnosis of isolated diastolic LVD is assay dependent.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Ventricular Dysfunction, Left

Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity.. We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography.. Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values.. In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Female; Heart Diseases; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Ventricular Dysfunction, Left; Ventricular Function, Left

Hypertension is associated with changes in concentrations of vasoactive peptides and procollagen propeptides, but their relationships with left ventricular hypertrophy and cardiac function are unclear.. We measured plasma levels of atrial natriuretic peptide (ANP), its amino terminal propeptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-1 (ET-1), and serum levels of the aminoterminal propeptide of type I procollagen (PINP) and the aminoterminal propeptide of type III procollagen (PIIINP) and echocardiographic parameters in 97 patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial.. Median values (reference values) of the peptides were: ANP 11.2 (6.9-14.9) pmol/l, NT-proANP 351 (143-311) pmol/l, BNP 1.1 (0.4-7.2) pmol/l, ET-1 8.7 (1.2-5.0) pmol/l, PIIINP 2.8 (1.7-4.2) microg/l and PINP 29 (19-84) microg/l. Plasma BNP levels in patients with left ventricular hypertrophy (1.2 pmol/l) and patients with echocardiographic signs of diastolic dysfunction (1.5 pmol/l) were greater than those in patients without hypertrophy (0.7 pmol/l) and normal diastolic parameters (0.9 pmol/l) (p<0.05). BNP was the only biochemical parameter that independently predicted interventricular septal diastolic diameter (p<0.05), left ventricular mass index (p<0.01) and ratio of the velocity-time integrals of the E and A waves of the mitral inflow in a stepwise logistic regression analysis (p<0.05).. The results show that BNP reflects the remodelling process in hypertension.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Diastole; Endothelin-1; Humans; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Protein Precursors; Ultrasonography; Ventricular Dysfunction, Left

To study the relationship between the TCM Syndrome Differentiation-types of congestive heart failure (CHF) and thyroid hormones, including triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), and atrial natriuretic peptide (ANP), as well as cardiac function parameters, including left ventricular ejection fraction (LVEF), mean velocity of circumferentid fiber shortening (mVcf) and A peak/E peak (A/E).. One hundred patients with CHF were divided into 4 Syndrome Differentiation-type groups, their cardiac function parameters, ANP and thyroid hormones were determined and compared with those in the 23 subjects in the control group.. In CHF patients with edema and blood stasis Syndrome type, the level of plasma ANP was significantly higher than that in the control group (P < 0.05); level of T3 was significantly lower than that in the control group and in CHF patients of other three (Xin-qi deficiency, Yin-deficiency and blood stasis) Syndrome groups (P < 0.01, P < 0.01, P < 0.05 and P < 0.01); levels of LVEF and mVcf were significantly lower than those in the other three Syndrome groups (all P < 0.01). Level of T4 in other three Syndrome groups significantly increased than that in the edema and blood stasis Syndrome type. A/E value showed a higher level in patients of all TCM type than that in the control (P < 0.01). Correlation analysis showed that T3 was positively correlated with LVEF and T4 (r = 0.200, P < 0.05, and r = 0.293, P < 0.01), and negatively correlated with ANP (r = -0.263, P < 0.01); T4 was negatively correlated with A/E (r = -0.226, P < 0.05).. The lowering of T3 and T4 and increasing of ANP may be one of the important reasons for lowering of LVEF in CHF patients with edema and blood stasis Syndrome-type. The decrease of T4 may be one of the important reasons for elevation of A/E and aggravation of left ventricular diastolic dysfunction in CHF patients of all the 4 TCM Syndrome-types.

Topics: Adult; Aged; Atrial Natriuretic Factor; Diagnosis, Differential; Female; Heart Failure; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Myocardial Contraction; Stroke Volume; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Ventricular Dysfunction, Left; Ventricular Function, Left

The presence of apoptotic cell death in cardiac myocytes is now well established and the contribution of apoptosis for the development of heart failure has been suggested. However, the mechanism responsible for the induction of apoptosis remains unclear. The present study was designed to investigate the involvement of Fas and caspase 3 in the transition from pressure overload-induced left ventricular hypertrophy (LVH) to left ventricular dysfunction (LVD).. Pressure overload induced LVH (10 days) and LVD (30 days) were induced by thoracic aortic banding. Changes in apoptosis-related genes were studied in rats with thoracic aortic banding. After 10 and 30 days, cardiac Fas mRNA expression was measured by RT-PCR. The mRNA expression of caspase 3 was detected by RNase protection assay. The activity of caspase 3 was measured by fluorometric assay. Protein levels of caspase 3 were measured by Western blot.. Rats with aortic banding had increased heart/body weight ratios after 10 and 30 days, compared to controls. Central venous pressure and lung weights were increased, left ventricular contractility was significantly impaired only in rats after 30 days of aortic banding, indicating LVD. Caspase 3 mRNA expression (7.1+/-0.1 vs. 2.8+/-0.4, P<0.05), caspase 3 activity (1418+/-181 vs. 849+/-154 AU, P<0.05) as well as caspase 3 protein levels were increased in rats with LVD but not with LVH. Similarly, Fas mRNA was increased in rats with LVD.. The activation of Fas and caspase 3 only after 30 days of aortic banding suggests that induction of these pathways may be involved in pressure overload-induced LVD.

Topics: Animals; Aorta, Thoracic; Apoptosis; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Blotting, Western; Caspase 3; Caspases; Disease Models, Animal; fas Receptor; Heart Failure; Hypertrophy, Left Ventricular; Male; Models, Cardiovascular; Myocardial Contraction; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stroke Volume; Up-Regulation; Ventricular Dysfunction, Left

The aim of the study was to investigate the diagnostic potential of natriuretic cardiac peptide measurement in the context of left ventricular dysfunction and comorbidities in a pacemaker population.. Ninety-five consecutive patients with pacemakers were included in the study. All patients underwent echocardiography and were asked to complete the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Brain natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (N-ANP) and atrial natriuretic peptide levels in plasma were measured.. Twenty-six percent of patients had reduced systolic left ventricular function; only 16 patients had a history of congestive heart failure. BNP was abnormally elevated in 64%, N-BNP in 72% and N-ANP in 96% of patients. Both BNP (r = 0.30; P < 0.01) and N-ANP (r = 0.39; P < 0.0005) correlated with MLHFQ. The strongest correlation was found between N-ANP and the ejection fraction (r = 0.6; P < 0.0001). Patients were stratified in a high-risk group and a low risk-group according to their N-ANP (N-ANP > 5000 fmol L(-1); n = 63 and N-ANP < 5000 fmol L(-1), n = 32) and BNP levels (BNP > 400 pg mL(-1); n = 17 and BNP < 400 pg mL(-1), n = 78). N-ANP was correlated with hypertension (P < 0.003) and atrial fibrillation (P < 0.03), and BNP with mitral insufficiency (P < 0.002).. Cardiac natriuretic peptides are markedly elevated in the majority of patients with pacemakers. The prognostic significance of BNP and N-ANP in left ventricular dysfunction warrants close follow-up schedules.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiac Pacing, Artificial; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Protein Precursors; Risk Assessment; Ultrasonography; Ventricular Dysfunction, Left

B-type natriuretic peptide (BNP) is a neurohormone that can be measured in blood and is useful in patients with congestive heart failure (CHF). We compared whole blood BNP concentrations to distance walked during a 6-min walk test in patients with CHF.. Forty-four patients with CHF underwent a 6-min walk test. The distance walked was compared to the BNP concentration on blood collected prior to the walk test. Patients were followed for 16 +/- 2.8 months after testing.. A significant correlation was observed between the BNP concentration and the distance walked (r = -0.47, p < 0.001). One patient without congestion died suddenly. Two patients died of progressive heart failure, and two other patients underwent cardiac transplantation. Each of the latter four patients had high BNP concentrations (median 1080 ng/l) and walked short distances (median 183 m). This study indicates that the BNP concentration in blood correlates inversely with the degree of physical capability of patients with heart failure.. The BNP concentration could be used as an alternative to the 6-min walk test to assess the severity of heart failure. The assay for BNP is non-invasive, inexpensive, and results are available at the bedside or in a heart failure clinic.

Topics: Adult; Aged; Atrial Natriuretic Factor; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Systole; Ventricular Dysfunction, Left; Walking

To study the effects of increased levels of myocardial angiotensin II type 1 (AT(1)) receptor on microvascular growth following myocardial infarction (MI).. MI was created in transgenic rats (TGR) with a cardioselective overexpression of the AT(1) receptor. We used Sprague-Dawley (SD) rats as controls. Some of the rats were treated with the selective AT(1) receptor blocker losartan (Los). Rats were sacrificed after 3 weeks.. MI caused left ventricular (LV) hypertrophy and LV dysfunction in both SD and TGR, which was prevented by AT(1) receptor blockade. Furthermore, MI decreased microvessel density in the non-infarcted myocardium (SD MI: 1653+/-37/mm(2), P<0.01 vs. sham-operated controls), however, microvessel density decreased significantly more in TGR with MI (1298+/-33/mm(2), P<0.01 vs. SD MI). AT(1) receptor blockade restored microvessel density (SD MI Los: 2046+/-195/mm(2); TGR MI Los: 1742+/-47/mm(2); P<0.01 vs. untreated). The differences in microvessel density were still present after correction for LV hypertrophy. The increase in microvessel density after AT(1) receptor blockade was not accompanied by increased myocardial vascular endothelial growth factor (VEGF) levels. Microvessel density correlated with parameters of myocardial stretch, such as LV end-diastolic pressure (-0.681, P<0.001) and N-ANP (-0.424, P=0.01).. Microvessel density after MI is decreased when the AT(1) receptor is overexpressed, and this is amenable to AT(1) receptor blockade. This suggests that efficacy of AT(1) receptor blockers post-MI may not only be due to attenuation of LV remodeling, but also to a stimulatory effect on angiogenesis.

Topics: Angiotensin Receptor Antagonists; Animals; Animals, Genetically Modified; Atrial Natriuretic Factor; Body Weight; Coronary Circulation; Endothelial Growth Factors; Heart Ventricles; Intercellular Signaling Peptides and Proteins; Lymphokines; Male; Microcirculation; Myocardial Infarction; Neovascularization, Pathologic; Organ Size; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Renin-Angiotensin System; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF ( n =12) and controls ( n =12) were investigated. Plasma ANP and BNP levels were determined every 2 min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76 pmol/l; controls, 0.75 pmol/l; P <0.01. BNP: CHF, 3.24 pmol/l; controls, 0.23 pmol/l; P <0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Specimen Collection; Body Weight; Female; Fourier Analysis; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Periodicity; Ventricular Dysfunction, Left

Clinical results of the Maze procedure for treatment of atrial fibrillation (AF) are excellent, suggesting improved ventricular function after restoring sinus rhythm. However, long-term corresponding effects on the release of cardiac natriuretic peptides and other vasoactive hormones are incompletely investigated after isolated Maze surgery.. Plasma levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), antidiuretic hormone, aldosterone, and angiotensin II were measured in 15 patients (mean age, 52 +/- 11 years) undergoing isolated surgical Maze (III) procedures for medically refractory AF, preoperatively and 6 months postoperatively. At the time of blood sampling, hemodynamic correlates were obtained at baseline and after 6 and 12 minutes of rapid ventricular pacing at 150 stimulations/minute.. All patients were free of AF at 6-month follow-up. The measured plasma levels of BNP, ANP, and angiotensin II were all significantly lower (p = 0.03) late after the isolated Maze procedure. Cardiac output was significantly higher postoperatively (p < 0.01). Other hemodynamic values and left atrial size were unchanged after surgery. Ventricular pacing caused almost identical hemodynamic changes in atrial pressures before and late after surgery, but the associated plasma ANP response was significantly attenuated postoperatively (p < 0.001).. Levels of cardiac natriuretic peptides and angiotensin II as markers of ventricular function are improved in the long term after clinically successful isolated Maze procedures. ANP response to hemodynamic challenge by ventricular pacing was attenuated postoperatively, possibly due to atrial scarring.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Cryosurgery; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Postoperative Complications; Vasopressins; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Atrial Natriuretic Factor; Biomarkers; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Ventricular Dysfunction, Left

In patients with chronic heart failure plasma levels of N-terminal proatrial natriuretic peptide (Nt-proANP) correlate to cardiac filling pressures. The aim of the present study was to examine the relation between Nt-proANP plasma levels and echocardiographic indices of cardiac dysfunction in patients recruited from primary care.. After clinical examination by the primary care physician, the patients were referred to one of two centres for echocardiography and blood sampling. In patients with mild to moderate symptoms of heart failure (n=52) and in asymptomatic patients with long-standing hypertension (n=46) or previous myocardial infarction (n=97), peptide levels were most closely related to parameters of left atrial wall stress. Patients who according to echocardiographic predefined criteria had diastolic or systolic dysfunction had two- and three-fold higher Nt-proANP than controls. According to receiver operating curve (ROC) analysis, Nt-proANP measurements were helpful in ruling out left ventricular systolic dysfunction, but not diastolic dysfunction.. In patients with mild to moderate cardiac disease, Nt-proANP plasma concentration was related to increased atrial wall stress. Peptide measurement could assist in ruling out the presence of LV systolic dysfunction, but was otherwise of limited value when used for diagnostic subgrouping into echocardiographically determined function categories.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Echocardiography; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Primary Health Care; Protein Precursors; Systole; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) is released into circulation in response to ventricular dilatation and pressure overload. Plasma BNP concentration correlates with left ventricular mass and dysfunction, which is prevalent in hemodialysis (HD) patients.. To evaluate the potential of BNP level for determination of hydration status, we measured inferior vena caval diameter (IVCD) and BNP levels and performed bioimpedance analysis in 49 HD patients.. Pre-HD BNP levels remained unchanged after HD. Agreement between IVCD and pre-HD BNP level in overhydration was significant (kappa = 0.304). The area under the receiver operating characteristic (ROC) curve for overhydration was 0.819 for pre-HD BNP level. When extracellular fluid/total-body water (ECF/TBW) ratios of HD patients were compared with those of 723 controls, pre- and post-HD BNP levels were significantly greater in overhydrated patients. The area under the ROC curve for overhydration by ECF/TBW ratio was 0.781 for pre-HD BNP level. However, there was no significance for pre- or post-HD BNP levels on assessment of normohydration or underhydration. Pre-HD BNP level correlated significantly with post-HD BNP level, post-HD diastolic blood pressure, pulse pressure, and ECF/TBW ratio. IVCD correlated significantly with post-HD BNP level.. BNP level seems to have a limited potential for assessment of overhydration in HD patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Body Water; Cyclic GMP; Diabetic Nephropathies; Electric Impedance; Extracellular Fluid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; ROC Curve; Sensitivity and Specificity; Ultrasonography; Vena Cava, Inferior; Ventricular Dysfunction, Left; Water Intoxication

Atrial arrhythmias often complicate congestive heart failure (CHF). We characterized inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing.. Endocardial pacing leads were implanted in the right ventricle, right atrium, and coronary sinus in 18 dogs. The right ventricular lead was connected to an implanted pacemaker capable of rapid ventricular pacing. The atrial leads were used to perform electrophysiologic studies in conscious animals at baseline in all dogs, during CHF induced by rapid ventricular pacing at 235 beats/min in 15 dogs, and during recovery from CHF in 6 dogs. After 20 +/- 7 days of rapid ventricular pacing, inducibility of sustained atrial tachycardia (cycle length 120 +/- 12 msec) was enhanced in dogs with CHF. Atrial tachycardia required a critical decrease in atrial burst pacing cycle length (< or = 130 msec) for induction and often could be terminated by overdrive pacing. Calcium antagonists (verapamil, flunarizine, ryanodine) terminated atrial tachycardia and suppressed inducibility. Effective refractory periods at 400- and 300-msec cycle lengths in the right atrium and coronary sinus were prolonged in dogs with CHF. Atrial cells from dogs with CHF had prolonged action potential durations and reduced resting potentials and delayed afterdepolarizations (DADs). Mitochondria from atrial tissue from dogs with CHF were enlarged and had internal cristae disorganization.. CHF promotes inducibility of sustained atrial tachycardia. Based on the mode of tachycardia induction, responses to pacing and calcium antagonists, and presence of DADs, atrial tachycardia in this CHF model has a mechanism most consistent with DAD-induced triggered activity resulting from intracellular calcium overload.

Topics: Action Potentials; Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Disease Models, Animal; Dogs; Echocardiography; Electrocardiography; Electrophysiologic Techniques, Cardiac; Heart Atria; Heart Failure; Heart Ventricles; Models, Cardiovascular; Recovery of Function; Stroke Volume; Survival Analysis; Tachycardia, Ectopic Atrial; Ventricular Dysfunction, Left

Based on currently available clinical evidence, we should use high-dose angiotensin converting enzyme inhibitor (ACE-I) for patients with acute myocardial infarction (MI), initiating it at incremental doses to avoid excessive hypotension. Recent animal studies with acute MI models failed to demonstrate the superiority of the combination therapy of ACE-I and angiotensin receptor blocker (ARB) to high-dose ACE-I treatment with comparable blood pressure reductions, which however might be attributed to the initiation of the targeted doses from the beginning. The aim of this study was to compare the effect of increasing the dose of ACE-I with that of adding ARB following a relatively low dose of ACE-I on the survival and left ventricular (LV) remodeling after MI.. Rats underwent left coronary artery ligation and were treated with either ACE-I temocapril (5 mg/kg/day) or vehicle for 2 weeks, which was initiated 3 days after the surgery. The rats treated with temocapril were further randomly assigned to receive either high-dose temocapril (10 mg/kg/day) or combination therapy (temocapril 5 mg/kg/day+olmesartan 2.5 mg/kg/day), which was continued for another 6 weeks.. Both treatments similarly reduced the blood pressure, improved survival and ameliorated LV enlargement. In contrast, several parameters of LV function were significantly ameliorated only by the high-dose ACE-I but not by the combination therapy.. After the initiation of a relatively low dose of ACE-I in acute MI, increasing the dose of ACE-I or adding ARB may equally improve survival and LV remodeling in the setting of an equal hypotensive effect. Further study with a longer treatment protocol is required to determine whether the several favorable effects on LV function elicited only by the high-dose ACE-I treatment provide further beneficial effects on survival and LV remodeling compared with the combination therapy.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Bradykinin; Collagen Type I; Collagen Type III; Drug Administration Schedule; Drug Therapy, Combination; Glyceraldehyde-3-Phosphate Dehydrogenases; Imidazoles; Male; Models, Animal; Myocardial Infarction; Myocardium; Norepinephrine; Olmesartan Medoxomil; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Tetrazoles; Thiazepines; Transforming Growth Factor beta; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Systole; Ventricular Dysfunction, Left

This study examines B-type natriuretic peptide (BNP) levels in patients with systolic versus non-systolic dysfunction presenting with shortness of breath.. Preserved systolic function is increasingly common in patients presenting with symptoms of congestive heart failure (CHF) but is still difficult to diagnose.. The Breathing Not Properly Multinational Study was a seven-center, prospective study of 1,586 patients who presented with acute dyspnea and had BNP measured upon arrival. A subset of 452 patients with a final adjudicated diagnosis of CHF who underwent echocardiography within 30 days of their visit to the emergency department (ED) were evaluated. An ejection fraction of greater than 45% was defined as non-systolic CHF.. Of the 452 patients with a final diagnosis of CHF, 165 (36.5%) had preserved left ventricular function on echocardiography, whereas 287 (63.5%) had systolic dysfunction. Patients with non-systolic heart failure (NS-CHF) had significantly lower BNP levels than those with systolic heart failure (S-CHF) (413 pg/ml vs. 821 pg/ml, p < 0.001). As the severity of heart failure worsened by New York Heart Association class, the percentage of S-CHF increased, whereas the percentage of NS-CHF decreased. When patients with NS-CHF were compared with patients without CHF (n = 770), a BNP value of 100 pg/ml had a sensitivity of 86%, a negative predictive value of 96%, and an accuracy of 75% for detecting abnormal diastolic dysfunction. Using Logistic regression to differentiate S-CHF from NS-CHF, BNP entered first as the strongest predictor followed by oxygen saturation, history of myocardial infarction, and heart rate.. We conclude that NS-CHF is common in the setting of the ED and that differentiating NS-CHF from S-CHF is difficult in this setting using traditional parameters. Whereas BNP add modest discriminatory value in differentiating NS-CHF from S-CHF, its major role is still the separation of patients with CHF from those without CHF.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Emergency Medical Services; Europe; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Respiration; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Systole; United States; Ventricular Dysfunction, Left

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

Natriuretic peptide hormones, a family of vasoactive peptides with many favourable physiological properties, have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The rapid incorporation into clinical practice of bioassays to measure natriuretic peptide concentrations, and drugs that augment the biological actions of this system, show the potential for translational research to improve patient care. Here, we focus on the physiology of the natriuretic peptide system, measurement of circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-terminal BNP) to diagnose heart failure and left ventricular dysfunction, measurement of BNP and N-terminal BNP to assess prognosis in patients with cardiac abnormalities, and use of recombinant human BNP (nesiritide) and vasopeptidase inhibitors to treat heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Recombinant Proteins; Ventricular Dysfunction, Left

Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock.. Retrospective, clinical study in the medical intensive care unit of a university hospital.. 17 patients with septic shock and 19 control subjects.. Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days.. In septic shock we found a significant increase in ANP (82.7+/-9.9 vs. 14.9+/-1.2 pg/ml) and BNP (12.4+/-3.6 vs. 5.5+/-0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=-0.56; p<0.05).. ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction.

Topics: Atrial Natriuretic Factor; Female; Follow-Up Studies; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Shock, Septic; Time Factors; Ventricular Dysfunction, Left

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Chronic Disease; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and patients with chronic heart failure (CHF) are reported to have high plasma ET-1 levels. The aim of this study was to investigate the relation between plasma ET-1 levels and clinical correlates in patients with CHF. The effects of maximal exercise on plasma ET-1 levels were also investigated.. Plasma concentrations of ET-1, norepinephrine, and atrial and brain natriuretic peptide (ANP and BNP) both at rest and after maximal cardiopulmonary exercise test were determined in 100 patients with CHF (60 +/- 12 years, New York Heart Association [NYHA] class I-III, left ventricular ejection fraction [LVEF]=36 +/- 8%, peak oxygen uptake [VO2] = 18.2 +/- 5.0 mL/min/kg) and 27 controls.. Patients with NYHA class II and III CHF had higher ET-1 levels (controls, NYHA class I, II, III: 2.1 +/- 0.6, 2.1 +/- 1.0, 2.6 +/- 0.9, 3.4 +/- 0.8 pg/mL, analysis of variance P <.0001). Maximal exercise did not alter ET-1 levels in controls or in each CHF subgroup. When all CHF patients were analyzed together, cardiothoracic ratio (P<.01), peak VO2 (P<.001), plasma norepinephrine (P<.01), plasma ANP (P<.01), and plasma BNP (P<.001) were significantly related with resting ET-1 levels on univariate analysis. Multivariate analysis revealed peak VO2 and plasma BNP levels showed an independent and significant relationship with the resting plasma ET-1 levels.. Resting ET-1 levels were increased in symptomatic patients with CHF, and maximal exercise did not increase ET-1 levels. Peak VO2 and plasma BNP levels were independently associated with resting plasma ET-1 levels in patients with CHF.

Topics: Aged; Anaerobic Threshold; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Endothelin-1; Exercise; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Norepinephrine; Severity of Illness Index; Statistics as Topic; Systole; Ventricular Dysfunction, Left

The selection of patients for cardiac transplantation (CTx) is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the left ventricular ejection fraction (LVEF), maximum oxygen uptake (peak VO2) and more recently, composite scoring systems e.g. the heart failure survival score (HFSS). Brain natriuretic peptide (BNP) is well established as an independent predictor of prognosis in mild to moderate chronic heart failure (CHF). However, the prognostic ability of NT-proBNP in advanced heart failure is unknown and no studies have compared NT-proBNP to standard clinical markers used in the selection of patients for transplantation. The purpose of this study was to examine the prognostic ability of NT-proBNP in advanced heart failure and compare it to that of the LVEF, peak VO2 and the HFSS.. We prospectively studied 142 consecutive patients with advanced CHF referred for consideration of CTx. Plasma for NT-proBNP analysis was sampled and patients followed up for a median of 374 days. The primary endpoint of all-cause mortality was reached in 20 (14.1%) patients and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 24 (16.9%) patients. An NT-proBNP concentration above the median was the only independent predictor of all cause mortality (chi2=6.03, P=0.01) and the combined endpoint of all cause mortality or urgent CTx (chi2 =12.68, P=0.0004). LVEF, VO2 and HFSS were not independently predictive of mortality or need for urgent cardiac transplantation in this study.. A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2 or HFSS.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Regression Analysis; ROC Curve; Sensitivity and Specificity; Survival Rate; Ventricular Dysfunction, Left

Primary prevention of cardiovascular disease has been aimed at risk factor identification and treatment without efforts to document early cardiovascular disease. The objective of the current study is to screen individuals with vascular and cardiac tests aimed at identifying early abnormalities likely to progress and to measure risk contributors susceptible to therapy.. A center was established for comprehensive screening of an asymptomatic population with 10 tests designed to detect early vascular and cardiac abnormalities and blood tests to identify potential targets for risk contributor intervention. The first 396 individuals screened in the center have been analyzed.. Using a scoring system from 0 (no disease) to 20 (advanced disease), 49% of the population exhibited scores of > or =5 and 39% exhibited scores of > or =6. These scores appear indicative of early disease mandating initiation of or change in medical therapy, which was recommended to the individuals screened and to their primary care physicians.. The screening tests utilized are effective in uncovering unsuspected early cardiovascular disease in which targeted treatment could be effective in reducing the incidence of cardiovascular events in susceptible individuals. Documentation of the sensitivity and specificity of this approach requires longitudinal study.

Topics: Adult; Aged; Arteries; Atrial Natriuretic Factor; Biomarkers; Blood Pressure Determination; Echocardiography; Elasticity; Electrocardiography; Female; Fundus Oculi; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Sex Factors; Systole; Vascular Diseases; Ventricular Dysfunction, Left

Peak oxygen consumption is a cornerstone for prognostic determination in patients with congestive heart failure. The purpose of this study was to assess whether plasma B-type natriuretic peptide (BNP) provided any additional prognostic information.. Plasma concentrations of atrial natriuretic peptide, N terminal pro-atrial natriuretic peptide, BNP, endothelin-1, norepinephrine, and peak VO2 were measured in 250 consecutive outpatients with mild to moderate heart failure (96% in New York Heart Association [NYHA] class II or III) and left ventricular ejection fraction (LVEF) <45%.. During a median follow-up of 584 days, 42 patients died (19 from sudden death) and 5 underwent urgent heart transplantation. Multivariate stepwise regression analysis showed that, among 13 variables including NYHA and LVEF, plasma BNP (chi2 = 11.9, P =.0001) was the strongest independent predictor of death or urgent transplantation, followed by serum sodium (chi2 = 8, P =.0046), resting heart rate (chi2 = 7.5, P =.0062), plasma endothelin-1 (chi2 = 7.2, P =.007), and peak VO2 (chi2 = 6.2, P =.012). Patients with plasma BNP above the upper quartile value (260 pg/mL) had a 1-year rate of death or urgent transplantation of 31%. The 1- and 2-year survival rates without urgent transplantation in patients with a peak VO2 < or =14 mL x kg(-1) x min(-1) were 71% and 59%, respectively, when plasma BNP was >137 pg/mL (median value), compared with 100% and 89%, respectively, when plasma BNP was < or =137 pg/mL (P =.008). Furthermore, plasma BNP was the only independent predictor of sudden death (chi2 = 19.9, P =.00001).. Plasma BNP provides additive independent prognostic information compared to peak VO2 alone in outpatients with mild to moderate heart failure.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Endothelin-1; Heart Failure; Heart Transplantation; Humans; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Prognosis; Protein Precursors; Regression Analysis; Risk; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

The reasons for the decrease or increase of urine output following the start of continuous venovenous hemodiafiltration (CVVHDF) have not yet been explained sufficiently. The renoprotective properties of natriuretic peptides were described.. The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 23 mechanically ventilated patients before and during the first 48 h of CVVHDF. Samples were drawn both from the ports proximal and distal to the filter. The results were compared between the group where daily diuresis (Vu) remained low or decreased and the group where diuresis increased to the level of 1.5 ml x kg(-1) x h(-1) or higher after 48 h of treatment. Left ventricular dysfunction (LVD) was defined as LV ejection fraction below 40%. A control group consisted of 10 patients exposed to abdominal surgery.. The average AVdiff (%) of ANP and BNP on filter were insignificant. Patients with increasing diuresis (n = 12) had significantly lower levels of both ANP (p < 0.001) and BNP (p < 0.005) than the patients with decreasing diuresis (n = 11). Significant correlations were revealed for ANP and Vu (p < 0.01) and for BNP and Vu (p < 0.05). The levels of both peptides were grossly elevated in comparison to controls and were predictive of survival. The differences between cardiac and non-cardiac patients were significant both for ANP and for BNP.. The elimination of ANP and BNP by the CVVHDF is negligible. The levels of natriuretic peptides are inversely related to Vu and predict survival. ANP and BNP levels correlate with left ventricular function even during acute renal failure and CVVHDF.

Topics: Acute Kidney Injury; Adult; Aged; Atrial Natriuretic Factor; Case-Control Studies; Diuresis; Female; Hemodiafiltration; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Predictive Value of Tests; Prognosis; Statistics, Nonparametric; Survival Rate; Ventricular Dysfunction, Left

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.. The aim of this study was to describe, in a healthy population, the influence of clinical and echocardiographic parameters on three natriuretic peptide moieties.. 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.. 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.. 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.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Echocardiography, Doppler; Female; Heart Failure; Heart Rate; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Protein Precursors; Random Allocation; Reference Values; Sex Factors; Ventricular Dysfunction, Left

We examined strategies to improve the positive predictive value of natriuretic peptides in screening for undiagnosed left ventricular systolic dysfunction (LVSD) in the community.. 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.. 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.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Electrocardiography; Female; Humans; Logistic Models; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; ROC Curve; Stroke Volume; Ventricular Dysfunction, Left

Several reports have documented the potential benefits of cell transplantation as an alternative to cardiac transplantation. This study was designed to investigate whether cardiomyocyte transplantation is effective in rats with chronic myocardial infarction.. Syngeneic Lewis rats were used in this study. Chronic myocardial infarction was induced in rats by ligating the left anterior descending artery. Four weeks later, after left ventricular (LV) dysfunction with akinetic regions was confirmed by echocardiography, the rats were randomized into two groups: a group that received fetal cardiomyocyte transplantation (TX group; n = 11); and a group that received an intramyocardial injection of culture medium only (control group; n = 12).. Four weeks after treatment, the TX group had smaller end-systolic dimension (LVDs) (7.5 +/- 0.9 vs 8.9 +/- 0.8 mm, p < 0.01) and better fractional shortening (FS) (26.2 +/- 5.9 vs 17.7% +/- 5.1%, p < 0.01) than the control group. However, there were no differences in LV end-diastolic dimension, LVDs, and FS between baseline and post-treatment values in the TX group. In addition, plasma levels of atrial natriuretic peptide were not significantly different between the two groups 4 weeks after treatment. In microscopic examination, small amounts of transplanted cardiomyocytes were found only in the periinfarct area, not in the center of scar area, and a thicker ventricular wall in the infarct area was detected in the TX group.. Fetal cardiomyocyte transplantation prevented, but did not reverse, cardiac remodeling that was accompanied with heart failure in myocardial infarction rats. Further investigation is warranted for optimal clinical application to the failing heart.

Topics: Animals; Atrial Natriuretic Factor; Cell Transplantation; Chronic Disease; Disease Models, Animal; Fetal Heart; Male; Myocardial Infarction; Myocardium; Random Allocation; Rats; Rats, Inbred Lew; Ventricular Dysfunction, Left

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

Several reports have suggested the usefulness of plasma brain natriuretic peptide (BNP) as a screening test for left ventricular hypertrophy (LVH) and systolic dysfunction (LVSD). Prior studies were limited by small sample sizes and selection bias and none compared the diagnostic performance of these peptides in men and women.. To examine the usefulness of natriuretic peptides for screening for elevated LV mass and LVSD in the community.. Community-based prospective cohort study of 3177 participants (1707 women) from the Framingham Study who attended a routine examination in 1995-1998.. Receiver operating characteristic (ROC) curves, test sensitivity, specificity, positive and negative predictive values, and likelihood ratios for identifying elevated LV mass (sex-specific 90th percentile or higher of LV mass/[height](2)), LVSD (ejection fraction < or = 50% and/or fractional shortening <29%), and moderate to severe LVSD (ejection fraction < or = 40% and/or fractional shortening <22%) at different discrimination limits of plasma BNP and N-terminal proatrial natriuretic peptide (NT-ANP), with echocardiography as the criterion standard.. The areas under the ROC curves for elevated LV mass or LVSD were at or below 0.75 for both peptides, were higher for men compared with women, and were similar for BNP and NT-ANP. The diagnostic performance of natriuretic peptides for LVSD improved in women but not in men when select high-risk subgroups were targeted. Discrimination limits based on high specificity (0.95) yielded better positive predictive values and likelihood ratios compared with age- and sex-specific reference limits yet only identified less than one third of participants who had elevated LV mass or LVSD.. In our large community-based sample, the performance of BNP and NT-ANP for detection of elevated LV mass and LVSD was suboptimal, suggesting limited usefulness of natriuretic peptides as mass screening tools.

Topics: Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Likelihood Functions; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Phenotype; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Systole; Ventricular Dysfunction, Left

Topics: Aged; Atrial Natriuretic Factor; Diastole; Echocardiography, Doppler; Humans; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Cardiovascular events are the major determinant of the prognosis in patients with chronic hemodialysis. The present study was designed to investigate whether increased plasma levels of atrial or brain natriuretic peptides (ANP or BNP) predict future cardiac events in such patients.. Fifty-three patients undergoing chronic hemodialysis without clinical symptoms suggestive of cardiac disorders were enrolled and their blood was sampled for ANP and BNP measurements. Electrocardiograms demonstrated left ventricular hypertrophy in 28 patients but no other abnormal findings. We followed them up for 11.3 +/- 0.2 months. The endpoint was cardiac events.. Cardiac events occurred in 13 patients (CE group). Both ANP and BNP levels were higher in CE group than in patients without cardiac events (ANP: 118 +/- 21 vs. 56 +/- 5 pg/ml, BNP: 769 +/- 204 vs. 193 +/- 25 pg/ml, respectively). Receiver operating characteristics curve revealed that the cut-off levels of ANP and BNP were 58 and 390 pg/ml, respectively. Using the Kaplan-Meier method, the incidence of cardiac events was significantly greater in patients with higher levels of ANP (50.0 vs. 0.0%) or BNP (72.7 vs. 11.9%) than in those with lower levels of the peptides.. Elevated levels of ANP or BNP indicate an increased risk of cardiac events and these peptides are clinically useful to predict cardiac events in patients with hemodialysis.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Dialysis; Risk Factors; Ventricular Dysfunction, Left

Salt-sensitive hypertension represents a major cause of left ventricular (LV) dysfunction. We therefore explored the potential effects of the selective endothelin-A (ETA) receptor antagonist darusentan on the development of hypertension, LV hypertrophy (LVH), and dysfunction in a genetic rat model of salt-sensitive hypertension.. Animals from the salt-sensitive Sabra rat strain (SBH/y) and the salt-resistant strain (SBN/y) were treated with either normal diet (SBH/y and SBN/y) or with deoxycorticosterone-acetate (DOCA) and salt (SBN/y-DOCA and SBH/y-DOCA). Additional groups were treated with 50 mg x kg(-1) x d(-1) of darusentan (SBH/y-DOCA-DA and SBN/y-DOCA-DA). Systolic blood pressure and LV weight increased in response to DOCA only in the SBH/y strain (+75 mm Hg and +30%; P<0.05). LV end-diastolic pressure increased and -dP/dtmax decreased in SBH/y-DOCA compared with SBH/y (P<0.05). This was paralleled by a 5-fold upregulation of LV mRNA expression of atrial natriuretic factor (ANF) and a significant reduction of sarcoplasmic reticulum (SR) Ca2+-reuptake and the SR Ca2+-ATPase to phospholamban protein ratio (-30%). Whereas treatment with darusentan in SBH/y-DOCA-DA reduced the SBP increase by 50%, LVH elevation of ANF mRNA and LV dysfunction were completely prevented (P<0.05); this was associated with a normalization of SR Ca2+-reuptake and SR Ca2+-ATPase to phospholamban ratio by darusentan (P<0.05). A moderate elevation of interstitial fibrosis in SBH/y-DOCA (P<0.05) remained unaffected by darusentan treatment.. In the Sabra model of salt-sensitive hypertension, ETA-receptor blockade demonstrated striking effects on the prevention of LVH and LV dysfunction beyond its considerable antihypertensive effect.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Calcium-Binding Proteins; Calcium-Transporting ATPases; Desoxycorticosterone; Disease Models, Animal; Endothelin Receptor Antagonists; Fibrosis; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Male; Organ Size; Phenylpropionates; Pyrimidines; Rats; Rats, Inbred Strains; Receptor, Endothelin A; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Sodium Chloride; Ventricular Dysfunction, Left

An early detection of patients with left-ventricular (LV) dysfunction is essential for effective treatment of congestive heart failure. The B-type natriuretic peptide (BNP) was described as a strong diagnostic parameter of LV-dysfunction. Aim of this study was to compare the diagnostic value of BNP and the aminoterminal part of pro-BNP (NT-pro-BNP) within an heterogenous patient population.. NT-pro-BNP and BNP were measured in 150 hospitalized cardiologic patients (age-median 64 years, 109 male versus 41 female). The values were correlated with clinical and haemodynamic parameters of the invasively determined LV-function.. Patients with pathologic haemodynamic values of the LV-function had significantly higher NT-pro-BNP and BNP levels than patients with normal haemodynamic parameters. In our study population a severe systolic LV-dysfunction (ejectionfraction EF<40 %) could be detected with a sensitivity and specifity of 100 % and 64 % by NT-pro-BNP and 100 % and 45 % by BNP. Sensitivity and specifity for the detection of any systolic dysfunction (EF<60 %) and of a systolic or diastolic dysfunction, respectively, were 94 %, 37 % and 88 %, 41 % for NT-pro-BNP (94 %, 40 % and 84 %, 44 % for BNP). The corresponding negative predictive values were 100 %, 96 % and 71 % for NT-pro-BNP and 100 %, 96 % and 68 % for BNP.. NT-pro-BNP and BNP were highly sensitive diagnostic parameters with a very good negative predictive value for LV-dysfunction. Because of the uncomplicated measurement, they could be used effectively to rule out LV-dysfunction in cardiovascular high risk patients by general practitioners.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Diagnosis, Differential; Dyspnea; Heart Failure; Humans; Likelihood Functions; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnosis, Differential; Emergency Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Odds Ratio; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Previous studies have not investigated the ef-ficacy of angiotensin II (AII) receptor antagonists against cardiac sympathetic overactivity in patients with chronic heart failure (CHF) using [(123)I]metaiodobenzylguanidine (MIBG) myocardial imaging. We studied 34 CHF patients with fractional shortening of the left ventricular (LV) diameter <==25% or LV ejection fraction <==45% in echocardiograms. An AII receptor antagonist (losartan or candesartan) was administered. Before and 6 months after the administration, MIBG myocardial imaging and echocardiography were performed, and neurohumoral factors were investigated. MIBG imaging revealed that the antagonist did not significantly change the heart-to-mediastinum ratio. However, the washout rate fell significantly (from 32.6% +/- 7.6% to 28.2% +/- 7.5%; P < 0.001). No significant changes occurred in LV diameter, fractional shortening, or LV ejection fraction. Circulating atrial (ANP) and brain natriuretic peptides (BNP), and aldosterone fell significantly. Changes in the MIBG washout rate correlated positively with changes in BNP ( r = 0.35, P < 0.05). In 19 patients also being treated with angiotensin-converting enzyme (ACE) inhibitors, the MIBG washout rate also fell significantly with AII antagonists, as did BNP and aldosterone. The decreased MIBG washout and BNP in patients with CHF induced by the AII receptor antagonists suggests the efficacy of these agents in modifying cardiac sympathetic function and neurohumoral factors, even with ACE inhibition. Combination therapy with AII receptor antagonists and ACE inhibitors appears effective for CHF.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Benzimidazoles; Biomarkers; Biphenyl Compounds; Blood Pressure; Creatinine; Echocardiography; Female; Heart; Heart Failure; Humans; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Potassium; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Angiotensin; Renin; Severity of Illness Index; Statistics as Topic; Stroke Volume; Tetrazoles; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

Conflict exists regarding the usefulness of measuring plasma B type natriuretic peptide (BNP) concentrations for identifying impaired left ventricular (LV) systolic function during mass screening. Various cardiac abnormalities, regardless of degree of LV dysfunction, are prone to carry a high risk of cardiovascular events.. To examine the validity of plasma BNP measurement for detection of various cardiac abnormalities in a population with a low prevalence of coronary heart disease and LV systolic dysfunction.. Participants in this cross sectional study attended a health screening programme in Iwate, northern Japan. Plasma BNP concentrations were determined in 1098 consecutive subjects (mean age 56 years) by direct radioimmunoassay. All subjects underwent multiphasic health checkups including physical examination, ECG, chest radiography, and transthoracic echocardiography.. Conventional diagnostic methods showed 39 subjects to have a wide range of cardiac abnormalities: lone atrial fibrillation or flutter in 11; previous myocardial infarction in seven; valvar heart disease in seven; hypertensive heart disease in six; cardiomyopathy in six; atrial septal defect in one; and cor pulmonale in one. No subjects had a low LV ejection fraction (< 40%). To assess the utility of plasma BNP measurement for identification of such patients, receiver operating characteristic analysis was performed. The optimal threshold for identification was a BNP concentration of 50 pg/ml with sensitivity of 89.7% and specificity of 95.7%. The area under the receiver operating characteristic curve was 0.970. The positive and negative predictive values at the cutoff level were 44.3% and 99.6%, respectively.. Measurement of plasma BNP concentration is a very efficient and cost effective mass screening technique for identifying patients with various cardiac abnormalities regardless of aetiology and degree of LV systolic dysfunction that can potentially develop into obvious heart failure and carry a high risk of a cardiovascular event.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Cross-Sectional Studies; Electrocardiography; Female; Humans; Japan; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Growth hormone (GH) application is a new strategy in the treatment of heart failure. However, clinical and experimental investigations have shown contradictory effects of GH on cardiac performance. We tested the hypothesis that GH could improve cardiac and renal function in volume overload-induced heart failure. The effect of 4 weeks of GH treatment (2 mg/kg daily) was investigated in Wistar rats with aortocaval shunt. GH application did not influence left ventricular contractility and end-diastolic pressure in rats with aortocaval shunt. In contrast, GH treatment normalized impaired diuresis (vehicle 10.8+/-0.6 mL/d, GH 15.8+/-0.7 mL/d; P<0.05) and sodium excretion (vehicle 1.5+/-0.1 mmol/d, GH 2.2+/-0.1 mmol/d; P<0.001) in shunt-operated rats, with a similar increase of fractional sodium excretion. The urinary excretion of cGMP, the second messenger of atrial natriuretic peptide and NO, was higher in animals with shunts than in sham-operated animals and was further increased by GH (vehicle 293+/-38 nmol/d, GH 463+/-57 nmol/d; P<0.01). Although the atrial natriuretic peptide plasma levels were unchanged after GH, the excretion of NO metabolites (nitrate/nitrite) was elevated (vehicle 2020+/-264 nmol/d, GH 2993+/-375 nmol/d; P<0.05) in parallel with increased renal mRNA levels of inducible NO synthase 2. The changes of renal function after GH and the increased excretion of NO metabolites and cGMP were abolished by simultaneous treatment with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester. GH treatment did not influence cardiac function in rats with aortocaval shunts. However, GH improved renal function by increasing diuresis and sodium excretion. The responsible mechanism might be the enhanced activity of the renal NO system.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Body Weight; Cyclic GMP; Enzyme Inhibitors; Growth Hormone; Heart; Heart Failure; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Kidney; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Organ Size; Rats; Rats, Wistar; Recombinant Proteins; RNA, Messenger; Ventricular Dysfunction, Left

Mast cells are believed to be involved in the pathophysiology of heart failure, but their precise role in the process is unknown. This study examined the role of mast cells in the progression of heart failure, using mast cell-deficient (WBB6F1-W/W(v)) mice and their congenic controls (wild-type [WT] mice). Systolic pressure overload was produced by banding of the abdominal aorta, and cardiac function was monitored over 15 wk. At 4 wk after aortic constriction, cardiac hypertrophy with preserved left ventricular performance (compensated hypertrophy) was observed in both W/W(v) and WT mice. Thereafter, left ventricular performance gradually decreased in WT mice, and pulmonary congestion became apparent at 15 wk (decompensated hypertrophy). In contrast, decompensation of cardiac function did not occur in W/W(v) mice; left ventricular performance was preserved throughout, and pulmonary congestion was not observed. Perivascular fibrosis and upregulation of mast cell chymase were all less apparent in W/W(v) mice. Treatment with tranilast, a mast cell-stabilizing agent, also prevented the evolution from compensated hypertrophy to heart failure. These observations suggest that mast cells play a critical role in the progression of heart failure. Stabilization of mast cells may represent a new approach in the management of heart failure.

Topics: Animals; Animals, Congenic; Atrial Natriuretic Factor; Chymases; Disease Models, Animal; Gene Expression; Heart Failure; Hypertrophy, Left Ventricular; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; ortho-Aminobenzoates; Serine Endopeptidases; Ventricular Dysfunction, Left; Ventricular Function, Left

Recent studies suggest that female gender is associated with a lower prevalence and a more benign prognosis of heart failure. In the current population-based study, it was our objective to evaluate the implications of gender on the association between impaired left ventricular (LV) function and mass as well as neurohumoral activation.. A total of 1883 subjects (992 female, 891 male) of two MONICA surveys in Augsburg, Germany, were analyzed. Participants of one of these surveys were additionally characterized with respect to neurohormonal activation. As compared to men, women were characterized by a slightly higher LV ejection fraction (EF, Teichholz-Method, 65.4 +/- 0.3% vs. 63.4 +/- 0.3, P<0.01) and a markedly lower LV mass index (LVMI 81 +/- 1 g/m(2) vs. 96 +/- 1, P<0.01). As compared to men with normal LV function, those with LV dysfunction (EF below mean minus two standard deviations, S.D.) were characterized by significantly increased LV mass (LVMI +48%, P<0.01), plasma BNP (+373%, P<0.01) and ANP (+57%, P<0.01), while no significant changes were observed in women (LVMI +3%, BNP +48%, ANP +27%, all P=n.s). Only a small subgroup of women with severe LVD (EF below mean - 3 S.D.) was characterized by significantly increased LV mass (LVMI +23%, P<0.05 vs. control and LVD), however, this increase was less pronounced as compared to men with severe LVD (LVMI +46%, P<0.01 vs. control). Gender-specific differences between LV function and structure were also confirmed by multivariate analysis. While LVMI was independently and significantly correlated with EF in male subjects in addition to systolic blood pressure, age, and body mass index (all P<0.01), these parameters displaced EF as a predictor of LVMI in female subjects.. Men with moderate or severe LV dysfunction are characterized by an increase in both LV mass and cardiac natriuretic peptide plasma concentrations. In contrast, LV mass and natriuretic peptide concentrations increase to a lesser extent and only with severe LV dysfunction in women. These observational data suggest gender-specific control of myocardial adaptations to hemodynamic overload and a more rapid induction of LV hypertrophy during myocardial dysfunction in male subjects.

Topics: Atrial Natriuretic Factor; Cardiomegaly; Cohort Studies; Cyclic GMP; Echocardiography; Female; Humans; Male; Regression Analysis; Renin; Sex; Ventricular Dysfunction, Left; Ventricular Remodeling

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).. Prospective study.. University hospital.. Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2).. 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).. 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.. 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.

Topics: Adult; Aged; Antineoplastic Agents; Atrial Natriuretic Factor; Diastole; Doxorubicin; Female; Humans; Lymphoma, Non-Hodgkin; Male; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; Systole; Ventricular Dysfunction, Left

The purpose of this study was to examine the effects of nipradilol on the cardiac function and mRNA expression in Wistar rats with a myocardial infarction (MI) that was created by ligation of the anterior descending coronary. Ten mg x kg(-1) x day(-1) of nipradilol were administrated to the rats in random order, and hemodynamic and Doppler-echocardiographic findings and myocardial mRNA expression were analyzed at 4 weeks after MI. Although left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) were increased in the MI rats, nipradilol significantly reduced the degree of the increase in both parameters. MI also significantly increased the weight of the left and right ventricles, and increased the left ventricular end-diastolic dimension (LVDd), effects that were attenuated by nipradilol. The MI rats showed decreased fractional shortening as systolic dysfunction and decreased E wave deceleration rate as diastolic dysfunction, and nipradilol significantly prevented these. Nipradilol significantly suppressed the increase in the non-infarcted myocardial mRNA expression of atrial natriuretic peptide, brain natriuretic peptide and collagen I and III. In conclusions, nipradilol prevents the cardiac remodeling that is accompanied by systolic and diastolic dysfunction, and inhibits abnormal myocardial gene expression after MI.

Topics: Adrenergic beta-Antagonists; Animals; Atrial Natriuretic Factor; Biomarkers; Collagen Type I; Collagen Type III; Disease Models, Animal; Echocardiography, Doppler; Myocardial Infarction; Natriuretic Peptide, Brain; Propanolamines; Rats; Rats, Wistar; RNA, Messenger; Ventricular Dysfunction, Left; Ventricular Remodeling

Natriuretic peptides ANP, BNP and CNP with their receptors A, B, and C play an important role in maintaining the homeostasis. They have vasodilating, diuretic and natriuretic actions and regulate the systemic resistance. These peptides have been proved to contribute in pathogenesis of many diseases, for example heart failure, hypertension, acute coronary events or hepatic and renal insufficiency. The aim of our study was the estimation whether ANP or BNP could be markers of postinfarct heart failure in patients after thrombolytic therapy. The survey was made in 96 patients with acute myocardial infarction (AMI), who were treated in Department of Cardiology of University School of Medicine in Wrocław. Patients were divided into 2 groups. The first group consisted of 56 patients with reperfusion after thrombolytic therapy and the second group created 40 patients without reperfusion. All patients were administered acethylsalicylic acid, 100 mg r-tPA (recombined tissue plasminogen activator) i.v. within 90 min and heparin in typical doses for the first 3-5 days. Venous blood samples for ANP and BNP estimation were taken before thrombolysis and then in 1st, 3rd, 5th and 30th day after treatment. We also measured the ejection fraction and activity of CPK and CK-MB in all the patients. Patients stayed under clinical observation for 12 months. Our study showed that the levels of ANP and BNP increase in 1st day after treatment in all patients with AMI. The normalization of ANP and BNP occurs in 3rd day after treatment in patients with reperfusion and in patients without reperfusion there are increased levels of these peptides even in 30th day. The increased level of BNP (> 160 pg/ml) is a significant risk factor of left ventricle systolic dysfunction, renewed AMI and sudden death in all patients with AMI after thrombolytic therapy whereas the increased level of ANP (> 100 pg/ml)--only in patients without reperfusion. Taking BNP as a marker of postinfarct heart failure it is possible to asses the risk of this complication in first day after thrombolytic therapy and choose the most proper treatment.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Guanylate Cyclase; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Receptors, Atrial Natriuretic Factor; Risk Factors; Thrombolytic Therapy; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Middle Aged; Myocardial Infarction; Prognosis; Prospective Studies; Protein Precursors; Systole; Ultrasonography; Ventricular Dysfunction, Left

The purpose of this prospective, observational study was to evaluate the relationship of left ventricular volumes, systolic function and plasma N-terminal proatrial natriuretic peptide (Nt-proANP) to cardiac morbidity and mortality in post-myocardial infarction patients with left ventricular ejection fraction > or =40%.. Two-dimensional echocardiographic recordings and Nt-proANP measurements were obtained in 834 patients who survived acute myocardial infarction. Patients were examined at 2-7 days and 3 months after the index infarction and followed up for 24 months. All measurements of left ventricular volumes, ejection fraction and Nt-proANP were performed in core laboratories. During follow-up 102 patients sustained one or more incidents of the combined primary end-point: cardiac death (n=11), recurrent infarction (n=55) or heart failure requiring hospitalization or treatment with an ACE inhibitor and a diuretic (n=52). Using Cox proportional hazards model, baseline Nt-proANP predicted these events (chi-square 25.3, P<0.0001), while baseline echo volumes and ejection fraction did not. During the subsequent 3-24 month period, 51 patients suffered a primary end-point: cardiac death (n=9), recurrent infarction (n=29), heart failure (n=21). An increase in left ventricular end-systolic volume was the strongest predictor for adverse events (chi-square 19.1, P<0.0001), especially for heart failure. Individual changes in Nt-proANP did not predict cardiac events, whereas both echocardiographic variables and Nt-proANP measured at 3 months had a prognostic impact on subsequent cardiac events (3-24 months).. In post-myocardial infarction patients with preserved left ventricular function (left ventricular ejection fraction > or =40%) baseline Nt-proANP, but not echocardiographic left ventricular volumes predicted adverse cardiac events. Early changes in left ventricular volumes and ejection fraction from baseline to 3 months had a further prognostic impact on subsequent events (3-24 months).

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Male; Middle Aged; Myocardial Infarction; Norway; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Remodeling

In the present study we examined plasma and pericardial fluid ANP and BNP concentrations in postinfarction ventricular dysfunction. The association of peptide levels to left ventricular (LV) dysfunction and to the localization of the myocardial infarction (MI) was studied.. Plasma and pericardial fluid samples were obtained from 37 patients undergoing coronary bypass surgery. According to the ECG and preceding coronary angiography, the patients were divided into three groups: previous anterior myocardial infarction (MI) (n=12), previous inferior/posterior MI (n=15) and no history of MI (n=10). When compared to the control group with no MI, the patients with anterior MI had elevated plasma ANP and BNP (134+/-13 vs. 81+/-15 pg/ml, P<0.01 and 95+/-10 pg/ml vs. 26+/-8 pg/ml, P<0.01, respectively) and pericardial fluid BNP (473+/-60 pg/ml vs. 57+/-8 pg/ml, P<0.001) levels. The plasma natriuretic peptide concentrations were not increased in the patients with inferior/posterior MI, but the pericardial fluid BNP concentrations were greater than in the patients with no history of MI (129+/-35 pg/ml vs. 57+/-8 pg/ml, P<0.05). Six of the 12 patients with previous anterior MI had LVEF> or =45%. Despite their normal LV systolic function, these patients had increased plasma and pericardial fluid BNP levels when compared to the group with no history of MI (68+/-18 pg/ml vs. 26+/-8 pg/ml, P<0.05 and 534+/-258 pg/ml vs. 57+/-8 pg/ml, P<0.01, respectively).. Previous anterior myocardial infarction was associated with increased cardiac BNP production even if the LV systolic function was normal (LVEF> or =45%). The high pericardial fluid BNP concentrations in postinfarction patients suggest that the BNP synthesis and release are augmented in the ventricular myocardium independent from the LVEF.

Topics: Adult; Aged; Analysis of Variance; Atrial Natriuretic Factor; Case-Control Studies; Coronary Artery Bypass; Female; Humans; Linear Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Paracrine Communication; Pericardial Effusion; Ventricular Dysfunction, Left

Although sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), individuals bearing a mutant cardiac myosin binding protein C (MyBP-C) gene usually have a better prognosis than individuals bearing beta-cardiac myosin heavy chain (MHC) gene mutations. Heterozygous mice bearing a cardiac MHC missense mutation (alphaMHC(403/+) or a cardiac MyBP-C mutation (MyBP-C(t/+)) were constructed as murine FHC models using homologous recombination in embryonic stem cells. We have compared cardiac structure and function of these mouse strains by several methods to further define mechanisms that determine the severity of FHC. Both strains demonstrated progressive left ventricular (LV) hypertrophy; however, by age 30 weeks, alphaMHC(403/+) mice demonstrated considerably more LV hypertrophy than MyBP-C(t/+) mice. In older heterozygous mice, hypertrophy continued to be more severe in the alphaMHC(403/+) mice than in the MyBP-C(t/+) mice. Consistent with this finding, hearts from 50-week-old alphaMHC(403/+) mice demonstrated increased expression of molecular markers of cardiac hypertrophy, but MyBP-C(t/+) hearts did not demonstrate expression of these molecular markers until the mice were >125 weeks old. Electrophysiological evaluation indicated that MyBP-C(t/+) mice are not as likely to have inducible ventricular tachycardia as alphaMHC(403/+) mice. In addition, cardiac function of alphaMHC(403/+) mice is significantly impaired before the development of LV hypertrophy, whereas cardiac function of MyBP-C(t/+) mice is not impaired even after the development of cardiac hypertrophy. Because these murine FHC models mimic their human counterparts, we propose that similar murine models will be useful for predicting the clinical consequences of other FHC-causing mutations. These data suggest that both electrophysiological and cardiac function studies may enable more definitive risk stratification in FHC patients.

Topics: Actins; Alleles; Animals; Atrial Natriuretic Factor; Blotting, Northern; Cardiomyopathy, Hypertrophic; Carrier Proteins; Disease Models, Animal; Echocardiography; Electrophysiology; Family Health; Male; Mice; Mutation; Mutation, Missense; Myocardium; RNA Splicing; RNA, Messenger; Sarcomeres; Time Factors; Transgenes; Ventricular Dysfunction, Left

Although echocardiography is an important tool for making the diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits its use as a routine screening tool for this purpose. Brain natriuretic peptide (BNP) accurately reflects ventricular pressure, and preliminary studies have found it to be highly sensitive and highly specific in diagnosing congestive heart failure in the emergency department. We hypothesized that BNP might therefore be useful as a screening tool before echocardiography in patients with suspected LV dysfunction.. Subjects included patients referred for echocardiography to evaluate the presence or absence of LV dysfunction. Patients with known LV dysfunction were excluded from analysis. BNP was measured by a point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of BNP levels were blinded from cardiologists making the assessment of LV function. Patients were divided into those with normal ventricular function, abnormal systolic ventricular function, abnormal diastolic function, and evidence of both systolic and diastolic dysfunction.. Two hundred patients in whom LV function was unknown were studied. In the 105 patients (53%) whose ventricular function was subsequently determined to be normal by echocardiography, BNP levels averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level of 75 pg/mL was 98% specific for detecting the presence or absence of LV dysfunction by echocardiography.. A simple, rapid test for BNP, which can be performed at the bedside or in the clinic, can reliably predict the presence or absence of LV dysfunction on echocardiogram. The data indicate that BNP may be an excellent screening tool for LV dysfunction and may, in fact, preclude the need for echocardiography in many patients.

Topics: Aged; Atrial Natriuretic Factor; Cardiotonic Agents; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Point-of-Care Systems; ROC Curve; Sensitivity and Specificity; Ultrasonography; Ventricular Dysfunction, Left

In the general population, the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are useful to predict left ventricular hypertrophy (LVH) and LV systolic dysfunction. Whether these cardiac hormones have a similar diagnostic potential in dialysis patients is unknown.. We studied the diagnostic value of ANP and BNP for alterations in LV mass and function in a cohort of 246 dialysis patients without clinical evidence of heart failure.. Both ANP and BNP were independently related to left ventricular mass (P < 0.0001) as well as to ejection fraction (P < 0.0001). In an analysis based on a prospectively defined threshold (95th percentile of the normal range), BNP had a significantly higher (P < 0.01) sensitivity (88%) than ANP (51%) for the diagnosis of LVH, but the positive predictive value of the two peptides was very similar (92 and 87%, respectively, P = NS). However, the negative predictive value of BNP for excluding LVH was 22% higher than that of ANP (53 vs. 31%, P = 0.05). Both natriuretic peptides had a high sensitivity for the detection of LV dysfunction (87 and 94%), but their positive predictive value was low (25 and 15%). Importantly, both ANP and BNP proved to be very useful for excluding this alteration (negative predictive value 97 and 96%, respectively). An analysis based on the "best cut-offs" of each peptide as identified on the basis of the ROC curves augmented the positive and negative prediction values of BNP for the diagnosis of LVH to 95 and 61%, respectively. This approach also raised the BNP-positive prediction value for the identification of LV dysfunction to 31% but did not modify the diagnostic potential of ANP (either for LVH or for LV dysfunction).. Measuring the plasma concentration of cardiac natriuretic hormones, particularly BNP, may be useful for the identification of dialysis patients with LVH or for excluding systolic dysfunction.

Topics: Aged; Atrial Natriuretic Factor; Cohort Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis, Continuous Ambulatory; Prognosis; Renal Dialysis; ROC Curve; Ventricular Dysfunction, Left

Proatrial natriuretic peptides are proposed to be sensitive and specific markers for various stages of heart deficiency. Here we present a rapid and specific sandwich immunoassay for the measurement of proANP 1-98 in biological fluids like plasma, serum urine. No sample preparation prior to the assay is necessary. Polyclonal antibodies specific for distinct epitopes of proANP 1-98, predicted to be highly immunogenic, were raised in sheep and purified by immunoaffinity chromatography prior to use in the assay. Antigen binding sites of the antibodies were determined by epitope mapping with a set of peptide fragments. The capture antibody, specific for proANP 16-23, is coated directly onto microtiter plates. Recombinant proANP 1-98 is used as a standard. The biotinylated detection antibody, specific for proANP 80-88, is incubated simultaneously with 20microl of sample for 150 min. Signal is generated with a streptavidin-HRPO-conjugate and TMB as substrate. The detection limit of the assay is 50 pmol/l; intraassay CVs are below 5%, interassay CVs are lower than 10%. Dilution curves show good linearity, recovery of synthetic peptide ranged between 85% and 91%. Reference values from healthy volunteers range from 0 to 2000 pmol/l in human plasma. We conclude this assay is a easy to handle, quick and reliable method for routine measurement of proANP 1-98 and the presented manuscript describes the procedure and performance of this ELISA in detail.

Topics: Animals; Atrial Natriuretic Factor; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Peptide Fragments; Protein Precursors; Sheep; Ventricular Dysfunction, Left

To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25-74 years from a geographical, urban population.. Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992-3. LVD was defined as a left ventricular ejection fraction (LVEF) 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8-27) and 7.8 pg/ml (3.4-13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32-3.36) in those with a fatal outcome and 1.27 ng/ml (0.9-2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF /= 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration >/= 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04).. LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cause of Death; Cohort Studies; Echocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Protein Precursors; Regression Analysis; Systole; Urban Population; Ventricular Dysfunction, Left

Anthracyclines are effective anticancer drugs for childhood cancer with dose-limiting cardiotoxicity. Children who have received anthracyclines thus need periodical cardiac evaluation. The plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been shown to increase in proportion to severity of cardiac dysfunction. We examined whether plasma levels of ANP and BNP, in addition to echocardiographic evaluation, can be used as specific markers for doxorubicin-induced cardiotoxic effects in children.. Consecutively, 34 patients (18 boys and 16 girls) who had previously received doxorubicin-containing chemotherapy were enrolled in this study. Plasma ANP and BNP were assayed simultaneously at the time of first cardiac function evaluation by echocardiography.. Of the 34 patients, 8 (23.5%) had left ventricular dysfunction as assessed by echocardiography. Both ANP and BNP plasma levels in these patients were significantly elevated in comparison with healthy controls (P < 0.01) or patients with normal cardiac function (P < 0.05). It should be also noted that ANP and BNP levels were correlated significantly with cardiac systolic function, but not with diastolic function.. These results suggest that plasma ANP and BNP levels could be markers for doxorubicin-induced cardiotoxicity in children. Measurement of natriuretic peptide levels during treatment may allow earlier-identification of individuals at risk for severe cardiac damage.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Blood Flow Velocity; Blood Pressure; Case-Control Studies; Child; Child, Preschool; Doxorubicin; Echocardiography, Doppler, Pulsed; Female; Humans; Incidence; Infant; Japan; Male; Natriuretic Peptide, Brain; Neoplasms; Stroke Volume; Time Factors; Ventricular Dysfunction, Left

Activation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) is considered a hallmark of myocardial remodeling. To determine magnitude and relative proportion of activation during the progression to heart failure, we assessed ANP and BNP gene expression in atrial and left ventricular (LV) tissue in a newly developed model of progressive rapid ventricular pacing-induced heart failure in rabbits.. Six animals underwent progressive pacing with incremental rates (330 beats per min (bpm) to 380 bpm over 30 days), resulting in congestive heart failure (CHF). Five animals underwent pacing at 330 bpm for 10 days only (early LV dysfunction, ELVD) and five additional animals served as control group (CTRL).. ELVD was characterized by decreased mean arterial pressure (P=0.05 vs. CTRL) as well as significantly impaired LV function (LV fractional shortening (FS) P<0.01 vs. CTRL) and dilatation (P<0.01 vs. CTRL). CHF was characterized by further decreased mean arterial pressure (P<0.01 vs. ELVD), further impaired LV function (FS P<0.03 vs. ELVD) and dilatation (P<0.01 vs. CTRL). In control animals, significant ANP expression was observed only in atrial tissue (P<0.02 vs. BNP) while BNP expression was ubiquitous but marginal (LV P<0.05 vs. ANP). In ELVD, activation of ANP (atria and LV P<0.05 vs. CTRL) and BNP (atria P<0.05 vs. CTRL, LV n.s.) was observed. In CHF, LV-BNP increased further markedly (P<0.01 vs. CTRL, P<0.05 vs. ELVD) while atrial ANP and BNP expression as well as LV ANP expression remained unchanged (all P=n.s. vs. ELVD).. The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditions and during the progression to heart failure and provide a molecular basis for the superiority of BNP as marker of LV dysfunction and CHF.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Disease Models, Animal; Disease Progression; Gene Expression; Heart Failure; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rabbits; RNA, Messenger; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP), NT-proBNP and NT-pro-atrial natriuretic peptide (NT-proANP) were measured in blood samples from 57 patients using immunoassays and immunoradiometric assays to evaluate the usefulness as diagnostic markers for the detection of heart failure. For the detection of impaired left ventricular ejection fraction (LVEF), receiver operating characteristic curves showed that BNP had the best diagnostic performance with an area under curve (AUC) of 0.75+/-0.06. However, NT-proBNP (AUC: 0.67+/-0.07) and NT-proANP (AUC: 0.69+/-0.08) showed no significant difference to BNP. In a further analysis for the detection of resting LVEF <40%, BNP again was the best marker with an AUC of 0.83+/-0.06. NT-proBNP showed only a slightly smaller AUC (0.79+/-0.07). The AUC for NT-proANP was significantly smaller (0.65+/-0.08) compared to BNP. Additionally, BNP and NT-proBNP correlated negatively with the resting LVEF (BNP: -0.472, p<0.001; NT-proBNP: -0.306, p=0.026), whereas NT-proANP showed no significant correlation. In summary, BNP was the best marker to detect patients with impaired LVEF compared to NT-proBNP and NT-proANP. However, NT-proBNP showed no significant differences to BNP and it is therefore a new promising alternative marker for the detection of left ventricular dysfunction.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Humans; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Ventricular Dysfunction, Left

The plasma levels of atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) are useful to evaluate left ventricular function in patients with old myocardial infarction(OMI). This echocardiographic study examined the clinical importance of the measurement of ANP and BNP in patients with OMI undergoing hemodialysis.. ANP and BNP levels were measured before and after hemodialysis in 36 patients with OMI and 42 patients without ischemic heart disease as controls(control group). Echocardiography was performed after hemodialysis. The patients with OMI were classified into two groups according to left ventricular percentage fractional shortening(% FS): Normal(OMI-N) group with %FS > or = 30%(n = 19) and low (OMI-L) group with %FS < 30%(n = 17).. The ANP, BNP levels and BNP/ANP ratio before and after hemodialysis were significantly higher in the OMI-L group than in the other groups. BNP level was significantly inversely correlated with %FS(r = -0.60, p < 0.05) and correlated with E wave and E/A, in mitral inflow only in the OMI-L group. The decrease in BNP level during hemodialysis was significantly greater in the OMI-L group than in the other groups, but not in ANP level.. These findings suggest that ANP and BNP levels are increased in patients with left ventricular dysfunction undergoing hemodialysis compared to those with normal left ventricular function. ANP level is convenient for decision of suitable dry weight. In contrast, BNP level that correlated inversely with impairment of left ventricular function is a more sensitive index of left ventricular function than ANP in patients with OMI undergoing hemodialysis.

Topics: Atrial Natriuretic Factor; Echocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Renal Dialysis; Ventricular Dysfunction, Left

Topics: Aged; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Female; Humans; Male; Myocardial Infarction; Vascular Patency; Ventricular Dysfunction, Left

Although echocardiography is important for making the diagnosis of left ventricular dysfunction, its cost and lack of availability limit its use as a routine screening test. B-Natriuretic peptide levels accurately reflect ventricular pressure, and preliminary studies with a rapid assay have found that levels are sensitive and specific for diagnosing heart failure in patients with dyspnea. We hypothesized that B-natriuretic peptide levels obtained through the use of a rapid assay should correlate with echocardiographic abnormalities of ventricular function.. We studied 400 patients who were referred for echocardiography at the San Diego Veteran's Healthcare System between June and August 2000 to evaluate ventricular function. B-natriuretic peptide levels were measured by a point-of-care immunoassay; cardiologists assessing left ventricular function were blinded to the assay results. Patients were grouped into those with normal ventricular function, systolic dysfunction only, diastolic dysfunction only, and both systolic and diastolic dysfunction.. Mean (+/- SD) B-natriuretic peptide concentration was 416 +/- 413 pg/mL in the 253 patients diagnosed with abnormal left ventricular function, compared with 30 +/- 36 pg/mL in the 147 patients with normal left ventricular function. Patients with both systolic and diastolic dysfunction had the highest levels (675 +/- 423 pg/mL). The area under the receiver operating characteristic (ROC) curve for B-natriuretic peptide levels to detect any abnormal echocardiographic finding was 0.95 (91% confidence interval: 0.93 to 0.97). B-Natriuretic peptide levels were unable to differentiate systolic vs. diastolic dysfunction. In patients with symptoms of heart failure and normal systolic function, B-natriuretic peptide levels >57 pg/mL had a positive predictive value of 100% for diastolic abnormalities.. A simple, rapid test for B-natriuretic peptide levels can reliably predict the presence or absence of left ventricular dysfunction on echocardiogram. For some patients, a normal level may preclude the need for echocardiography.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Echocardiography; Female; Humans; Male; Middle Aged; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

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.. 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.. 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.. 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)].. 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.

Topics: Aged; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Endothelin-1; Epinephrine; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Regression Analysis; Renin; Stroke Volume; Ventricular Dysfunction, Left

The objective of this study was to determine the primary event that occurs in Ca2+-regulatory sarcoplasmic-reticular (SR) proteins during subacute transition from concentric/mechanically-compensated left ventricular (LV) hypertrophy to eccentric/decompensated hypertrophy. Using Dahl salt-sensitive rats with hypertension, changes of myocardial contraction, intracellular Ca2+ transients, SR Ca2+ uptake, protein levels of SR Ca2+ ATPase (SERCA2), phospholamban, and calsequestrin (CSQ), and mRNA levels of SERCA2 and CSQ were serially determined and compared between the established stage of LV hypertrophy (LVH) and the subsequent stage of overt LV dysfunction (CHF). In LVH, isolated LV papillary muscle preparations showed an equal peak-tension level and a mild prolongation of the isometric tension decay compared to those of age-matched controls. The Ca2+ transients as measured by aequorin were unchanged. The Ca2+ uptake of isolated SR vesicles and the protein/mRNA levels of SR proteins were also equivalent to those of the controls. In contrast, in CHF, the failing myocardium showed a further prolongation of the contraction time course and a 39% reduction of the peak-tension development. The Ca2+ transients showed changes consisting of a decrease in the peak level and a prolongation of the time course. In addition, the SR Ca2+ uptake was decreased by 41%. Despite these functional changes, the protein and mRNA levels of the SR components remained equivalent to those of the age-matched controls. Thus, in this hypertensive animal, 1) at the LVH stage, myocardial contractility and intracellular capability to regulate Ca2+ remained normal; 2) at the CHF stage, impaired SR Ca2+ handling and the subsequent reduction of myocardial contraction were in progress; and 3) impairments of SR function occurred at the post-translational protein level rather than at the transcriptional/translational levels. Our findings support the role of SR proteins as the primary determinant of the contractile dysfunction that occurs during the heart-failure transition; however, post-translational modulators of these SR elements may also be critical.

Topics: Aequorin; Animals; Atrial Natriuretic Factor; Calcium; Calcium-Binding Proteins; Calcium-Transporting ATPases; Calsequestrin; Heart Failure; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Papillary Muscles; Rats; Rats, Inbred Dahl; RNA, Messenger; Ryanodine; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Ventricular Dysfunction, Left

To assess N-terminal pro-atrial peptide (N-ANP) as a predictor of total and cardiac death in patients with previous premature myocardial infarction (MI).. In this prospective cohort study, we measured plasma N-ANP by ELIZA assays and ejection fraction (EF) by radionuclide ventriculography in a cohort of 247 patients (193 men and 54 women) who had had MI at a relatively young age (males: first MI at age < or =55; females <60).. After 10 years 44 patients had died, 36 from cardiac causes. After using a stepwise procedure to adjust for other prognostic factors (i.e. plasma total homocysteine (tHcy), C-reactive protein and age), the relative risk (RR) was 2.00 (95% confidence interval (CI) 1.05-3.80) (p = 0.03) for death of all causes and 2.32 (95% CI 1.19-4.55) (p=0.01) for cardiac death when the top quartile was compared to the three lower quartiles of N-ANP. When radionuclide EF entered the Cox model, N-ANP became insignificant as a predictor of mortality.. N-ANP was a significant predictor of total death and cardiac death in young survivors of MI, but radionuclide EF was a more independent prognostic variable.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Protein Precursors; Radionuclide Ventriculography; Ventricular Dysfunction, Left

To examine the relationship between the persistence of ST segment depression in leads V5-V6 after Q-wave anterior wall myocardial infarction (MI) and the filling pattern of the left ventricle (LV).. Precordial ST segment depression predominantly in leads V5-V6 is associated with increased in-hospital morbidity and mortality after acute myocardial ischemia, perhaps due to reduced diastolic distensibility of the LV.. We prospectively studied 19 patients after Q-wave anterior wall MI (>6 months). All patients underwent 12-lead ECG recording, symptom-limited treadmill exercise testing with single photon emission computed tomography thallium-201 imaging, transthoracic Doppler echocardiography, cardiac catheterization and measurement of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels. Patients were classified based on the presence of ST segment depression in leads V5-V6: Group I = ST segment depression <0.1 mV (n = 10); Group II = ST segment depression > or =0.1 mV (n = 9).. Patients in Group II had greater LV end diastolic pressures (32.4 +/- 6.5 mm Hg vs. 14.8 +/- 6.1 mm Hg; p = 0.0001), higher plasma ANP (44.4 +/- 47.1 pg/ml vs. 10.7 +/- 14 pg/ml; p = 0.04) and BNP levels (89.4 +/- 62.7 pg/ml vs. 23.6 +/- 33.1 pg/ml; p = 0.01), greater left atrium area (20.6 +/- 3.1 cm2 vs. 17.8 +/- 2.4 cm2; p = 0.05), lower peak atrial (A), higher early (E) mitral inflow velocities, a higher E/A ratio and a lower deceleration time (167 +/- 44 ms vs. 220 +/- 40 ms; p = 0.05). Lung thallium uptake during exercise was more common in Group II (78% vs. 10%, p = 0.04).. Persistent ST segment depression in leads V5-V6 in survivors of Q-wave anterior wall MI is associated with increased LV filling pressure and a restrictive LV filling pattern.

Topics: Atrial Natriuretic Factor; Blood Flow Velocity; Cardiac Catheterization; Coronary Angiography; Echocardiography, Doppler; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Prospective Studies; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left; Ventricular Pressure

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.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Coronary Vessels; Disease Models, Animal; Endothelin-1; Epinephrine; Female; Hemodynamics; Ligation; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Neuropeptides; Norepinephrine; Peptide Fragments; Renin; Sheep; Ventricular Dysfunction, Left

The objective was to determine the independent association between atrial fibrillation (A-Fib) and activation of natriuretic peptides.. The association of A-Fib with activation of N-terminal atrial and brain natriuretic peptides (N-ANPs and BNPs, respectively) is uncertain but of great importance for the diagnostic utilization of natriuretic peptides. This uncertainty is related to the lack of appropriate controls, with left ventricular (LV) and atrial overload similar to A-Fib.. We prospectively measured N-terminal atrial and BNPs and endothelin-1 levels in 100 patients and 14 age- and gender-matched control subjects. The 32 patients with A-Fib were compared with 68 patients in sinus rhythm and similar LV and atrial overload (due to mitral regurgitation or LV dysfunction) measured simultaneously with hormonal levels with comprehensive Doppler echocardiography.. Patients with A-Fib compared with those in sinus rhythm had similar symptoms, comorbid conditions, cardioactive medications, pulmonary pressure, left atrial volume, and LV ejection fraction and filling characteristics but demonstrated higher N-ANP levels (2,613 +/- 1,681 vs. 1,654 +/- 1,323 pg/ml, p = 0.007) even after adjustment for the underlying cardiac disease (p < 0.0001). Conversely, BNP levels were similar in both groups (165 +/- 163 vs. 160 +/- 269 pg/ml, p = 0.9). In multivariate analysis, a higher N-ANP level was associated with A-Fib (p = 0.0003), symptom class (p < 0.0001) and endothelin-1 level (p = 0.032) independently of left atrial volume and LV ejection fraction. Conversely, BNP showed no independent association with and was most strongly associated with LV ejection fraction (p < 0.0001).. Atrial fibrillation is an independent determinant of higher N-ANP levels and blurs its association with LV dysfunction. Conversely, the BNP is not independently associated with A-Fib and is strongly determined by LV dysfunction, for which it is an independent marker.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Chronic Disease; Echocardiography, Doppler; Endothelin-1; Female; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; Reproducibility of Results; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

Topics: Algorithms; Atrial Natriuretic Factor; Heart Failure; Humans; Ventricular Dysfunction, Left; Ventricular Function, Left

There are few stable and reproducible large-animal models of chronic heart failure produced by ischaemic damage to the myocardium. Here we characterize a novel method of inducing myocardial damage in closed-chest sheep by catheter delivery of thrombogenic coils, and compare this with a newly described open-artery model of cardiac injury in sheep. Sham controls were compared with animals subjected to (a) 90 min of coronary artery occlusion/reperfusion by PTCA (percutaneous transluminal coronary angioplasty) balloon, and (b) permanent coronary artery occlusion induced by catheter delivery of thrombogenic coils (seven sheep/group). Both balloon occlusion/reperfusion and permanent coil occlusion resulted in well-defined anteroapical infarcts, as documented by ECG changes, significant rises in creatine kinase (both groups P<0.001) and troponin-T (both groups P<0.05), and post-mortem examination. Washout of enzymes was much more rapid in the reperfused group (P<0. 01). Infarction resulted in significant reductions in left ventricular (LV) ejection fraction (both groups P<0.01) and regional wall abnormalities. Ejection fraction 7 days post-coil (21.3+/-4.2%) was significantly lower (P<0.01) than that 7 days post-balloon (38. 8+/-4.5%). Coil-induced infarction was associated with acutely reduced arterial pressure (P<0.05), and increases in heart rate (P<0. 05), atrial pressures (P<0.05), plasma brain natriuretic peptide levels (P<0.05) and adrenaline levels (P<0.05). Rises seen in plasma endothelin levels in sham controls were blunted in the coil group (P<0.001). Haemodynamic changes were less marked in the balloon group. In conclusion, restriction of coronary artery occlusion to 90 min results in infarction, but less LV dysfunction with reduced early remodelling, compared with permanent occlusion. Acute changes in biochemical markers, haemodynamics, neurohormones and LV function confirm that these are excellent models of open- and closed-artery myocardial infarction leading to asymptomatic LV dysfunction.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Disease Models, Animal; Hemodynamics; Hormones; Myocardial Infarction; Myocardial Reperfusion Injury; Sheep; Ventricular Dysfunction, Left

To investigate the relationships between N-terminal atrial natriuretic peptide (N-ANP) and left ventricular geometry and function.. A cross-sectional study of a population-based cohort.. Follow-up of a health survey in Uppsala county, Sweden.. Two hundred and five men aged 70.. A Delfia sandwich immunoassay was used to measure the plasma levels of N-ANP. M-mode and Doppler echocardiographic examinations were used to measure left ventricular dimensions, mass, geometry and systolic function and to classify the subjects into four groups (normal geometry, concentric remodelling, concentric hypertrophy or eccentric hypertrophy). Left ventricular systolic dysfunction was defined as a left ventricular ejection fraction

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cross-Sectional Studies; Echocardiography; Follow-Up Studies; Humans; Hypertrophy, Left Ventricular; Immunoassay; Male; Protein Precursors; ROC Curve; Stroke Volume; Sweden; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Humans; Ventricular Dysfunction, Left

Although myocarditis has been implicated in the pathogenesis of heart failure, a definitive relationship between myocardial inflammation, cardiac dysfunction, and changes in myocyte gene expression has not been established. In this study, we examined the hypothesis that myocardial inflammation and replacement fibrosis following an autoimmune response can progress to cardiac dysfunction and may result in progression to the heart failure phenotype. SWXJ mice were immunized with cardiac myosin on day 0 and day 7, in order to induce an autoimmune response to the myosin protein. Cardiac catheterization via the right carotid artery was performed on days 14, 21, 28, 35, and 42, using a 1.4F Millar transducer-tipped catheter. Hearts were weighed, and cross-sections were cut and stained with either haematoxylin and eosin or Masson's trichrome, in order to identify areas of inflammation and/or fibrosis. Myocardial gene expression was determined by Northern blot analysis. In mice with histological evidence of myocarditis, the heart weight/body weight ratio increased beginning on day 14, and cardiac function decreased beginning on day 21. Myocardial inflammation was accompanied by significant fibrosis beginning on day 21. Quantitation of mRNA showed expression of ventricular atrial naturietic factor, as well as a decrease in myosin heavy chain alpha, beginning on day 21. These data demonstrate that autoimmune inflammation of the heart results in significant cardiac dysfunction, leading to phenotypic alterations similar to those demonstrated in human heart failure and animal models of heart failure.

Topics: Animals; Atrial Natriuretic Factor; Autoantigens; Autoimmune Diseases; Body Weight; Endomyocardial Fibrosis; Gene Expression Regulation; Heart; Heart Failure; Male; Mice; Mice, Inbred Strains; Models, Animal; Molecular Motor Proteins; Muscle Proteins; Myocarditis; Myocardium; Myosin Heavy Chains; Myosins; Organ Size; RNA, Messenger; T-Lymphocytes, Cytotoxic; Ventricular Dysfunction, Left

We have previously demonstrated that patients with symptomatic congestive heart failure (CHF), but not with asymptomatic left ventricular dysfunction (LVD), have augmented plasma atrial natriuretic peptide (ANP) response to exercise. Plasma brain natriuretic peptide (BNP) response to exercise is less extensively studied. The aim of this study was to determine whether responses of plasma BNP during exercise normalized for exercise workload are altered in patients with LVD and CHF.. Twenty-nine patients with LVD, 32 patients with CHF (NYHA classes II-III) and 27 age-matched control subjects were studied. Ventilatory, plasma ANP and BNP responses were assessed during symptom-limited cardiopulmonary exercise testing. Plasma natriuretic peptide levels were measured at rest and immediately after peak exercise. The increment in plasma BNP was divided by the increment in oxygen uptake (VO2) from rest to peak exercise, and this ratio [BNP exercise ratio: (peak BNP - rest BNP)/(peak VO2 - rest VO2)] was compared amongst the three groups.. Peak VO2 (Control, LVD and CHF: 28.2 +/- 1.7, 21.1 +/- 1.8, 16.2 +/- 0.6 ml, min(-1) kg(-1), respectively), anaerobic threshold and peak workload became smaller as heart failure worsened. Resting and peak plasma ANP levels were significantly higher only in CHF, whilst resting and peak plasma BNP levels displayed a significant and continuous increase from normal subjects to LVD and CHF. The ANP exercise ratio (1.25 +/- 0.36, 2.61 +/- 0.57, 7.72 +/- 1.65, ANOVA P = 0.0002) was significantly higher only in patients with CHF, whilst the BNP exercise ratio (0.35 +/- 0.10, 2.60 +/- 0.69, 4.98 +/- 0.97, ANOVA P = 0.0001) was significantly higher in patients with LVD and became progressively higher in patients with CHF.. These data showed that the BNP exercise ratio, an exercise plasma BNP response normalized with exercise workload, was augmented in patients with LVD, and became progressively higher in CHF, suggesting that an augmented exercise BNP ratio exists early in the course of developing CHF.

Topics: Anaerobic Threshold; Analysis of Variance; Atrial Natriuretic Factor; Blood Pressure; Case-Control Studies; Disease Progression; Energy Metabolism; Exercise; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Rest; Severity of Illness Index; Ventricular Dysfunction, Left

We have recently described a modified model of progressive rapid ventricular pacing-induced heart failure which evolves over a period of 38 days. To further characterize left ventricular remodeling during the progression of heart failure, we assessed left ventricular geometry, wall stress, and atrial natriuretic peptide (ANP) gene expression and protein content during control conditions, asymptomatic left ventricular dysfunction, and overt congestive heart failure (CHF). Although asymptomatic left ventricular dysfunction was characterized by a significant increase in systolic and diastolic left ventricular dimension (+30% and +6%, respectively, P<0.05 each) and a marked increase in left ventricular systolic wall stress (+68%, P<0.01), left ventricular ANP gene expression was unchanged as compared to control. In contrast, strong left ventricular ANP gene expression (+449%, P<0.05) was observed during overt CHF in the absence of further significant increases in left ventricular systolic wall stress. The onset of strong left ventricular ANP gene expression was associated with increased ANP content (+88%, P<0.05) and left ventricular mass index (+13%, P<0.05). In contrast, left atrial ANP gene expression and left ventricular diastolic wall stress increased progressively during asymptomatic left ventricular dysfunction (+39%, P=n.s. and +131%, P<0.01) and overt CHF (+76% and +336% vs. control, P<0.01 each). Progressive rapid ventricular pacing is associated with the induction of left ventricular ANP gene expression and protein synthesis exclusively during overt CHF. The current studies provide new insight into the temporal pattern of ANP-activation and the disparity between left ventricular systolic wall stress and ANP-activation in a large animal model of progressive CHF.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Dogs; Gene Expression; Heart Failure; Male; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction.. Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1-4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3-5 months after infarction. Clinical events were recorded over a mean period of 14 months.. Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = -0.60, n = 220, p < 0.001; and r = -0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3-5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death.. Plasma BNP measured within 1-4 days of acute myocardial infarction is a powerful independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

Topics: Atrial Natriuretic Factor; Biomarkers; Cyclic GMP; Epinephrine; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Norepinephrine; Predictive Value of Tests; Prospective Studies; Protein Precursors; Radionuclide Imaging; Ventricular Dysfunction, Left

Atrial natriuretic peptide secretion on exercise testing may be exaggerated by left ventricular dysfunction due to multivessel coronary disease rather than by scintigraphically detectable myocardial ischemia. The measurement of plasma atrial natriuretic peptide levels during exercise test may provide additional information regarding the severity of coronary heart disease.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Physical Exertion; Radiopharmaceuticals; Stroke Volume; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

An association between the DD allele of the angiotensin-converting enzyme gene and a poorer outcome in patients with heart failure has been found in whites. The DD allele frequency is lower in Chinese, but the M235T variant of the angiotensinogen gene is more common in Chinese than whites; it is not known to what extent polymorphisms of the renin-angiotensin system affect clinical status or prognosis in Chinese patients with heart failure.. We assessed the relations among polymorphism of the angiotensin-converting enzyme gene, angiotensinogen M235T (AGT) gene, and angiotensin type I receptor A1166C gene with left ventricular systolic function, left and right ventricular diastolic function, serum angiotensin-converting enzyme, plasma aldosterone and atrial natriuretic peptide levels at presentation, and clinical outcome at 1 year (survival, hospital admissions) in a cohort of Chinese patients with typical systolic heart failure (n = 82).. We confirmed the low prevalence of the angiotensin-converting DD and the angiotensin type I receptor CC genotypes, and high prevalence of the AGT TT genotype in Chinese subjects compared with whites. There was no relation between the various gene polymorphisms and survival at 1 year assessed by multiple regression or Cox regression survival analysis. The AC variant of the angiotensin type I receptor gene was associated with morbidity over a 1-year period (hospital admissions) and increased baseline aldosterone levels, but none of the other polymorphisms correlated with systolic or diastolic function, aldosterone or atrial natriuretic peptide levels. By multiple regression for effects on mortality rate, only atrial natriuretic peptide and age were significant.. In Chinese patients with heart failure, polymorphisms of the renin-angiotensin system do not appear to be related to survival or severity, probably because of the different prevalence of these genotypes in the Chinese. Thus this study illustrates that large interethnic differences in the frequencies of genotype polymorphisms of the renin-angiotensin system exist and results from one ethnic group cannot be extrapolated to another.

Topics: Aldosterone; Angiotensinogen; Asian People; Atrial Natriuretic Factor; Cohort Studies; Female; Gene Frequency; Genotype; Heart Failure; Hong Kong; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Prevalence; Receptors, Angiotensin; Renin-Angiotensin System; Survival Analysis; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

The purpose of this study was to determine whether circulating N-terminal pro-atrial natriuretic peptide (N-ANP) levels predict left ventricular hypertrophy in the general population after adjustment for relevant risk factors.. In a population-based sample of 3287 subjects aged 25-85 years, circulating N-ANP was measured in a subgroup of 389 subjects. Left ventricular mass and ejection fraction were determined by two-dimensional guided M-mode echocardiography. Left ventricular hypertrophy was defined as height adjusted mass above 145.5 g. m-1 and 125.4 g. m-1, in men and women, respectively. Fifty-one subjects with left ventricular hypertrophy had significantly higher N-ANP levels than controls (1075 vs 763 pmol. l-1;P<0.0001). A gradually increasing prevalence of left ventricular hypertrophy over increasing 500 pmol. l-1 intervals of N-ANP was observed (1.8 to 64. 3%; (Chi-squared P for trend <0.001). N-ANP was an independent predictor of left ventricular hypertrophy after adjustment for ejection fraction, body mass index, hypertension, valvular disease, a history of myocardial infarction, gender, and age. The adjusted odds ratio for left ventricular hypertrophy was 1.79 (95% CI 1.04-3. 07) for a 500 pmol. l-1 increase in N-ANP. A substantial proportion of subjects with elevated N-ANP levels had combined left ventricular hypertrophy and left ventricular dysfunction.. These results suggests that N-ANP is an independent predictor of left ventricular hypertrophy in the general population. N-ANP determination is, however, poorly suited to distinguish between subjects with isolated left ventricular hypertrophy and left ventricular dysfunction with or without left ventricular hypertrophy.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Prognosis; Risk Factors; ROC Curve; Ventricular Dysfunction, Left

We measured plasma concentrations of vasoactive peptides in 32 patients with acute myocardial infarction and evaluated their value as markers of left ventricular dysfunction. Plasma levels of atrial natriuretic peptide (ANP), the N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP) and endothelin-1 were measured serially by radioimmunoassays. The infarct size was estimated from the creatine kinase MB release curve. Coronary angiography and left ventricular cineangiography were performed in all patients during hospitalization and 6 months later in 15 patients. Myocardial infarction caused an increase in vasoactive peptides, the highest values for ANP (36.5+/-6.79 pmol/l), NT-proANP (1130+/-170 pmol/l) and endothelin-1 (9.72+/-0.68 pmol/l) being found on admission and those for BNP (56.0+/-7.13 pmol/l) on Day 2. Plasma levels of natriuretic peptides were dependent on infarct size, its location and degree of myocardial dysfunction and that of BNP also on infarct artery patency. Plasma endothelin-1 level was higher in patients with TIMI 3 than TIMI 0-2 flow. Plasma vasoactive peptides remained elevated during the 6-month follow-up period and they were dependent on the degree of myocardial dysfunction. BNP measured on any day of hospitalization showed the best correlation with ejection fraction measured during the acute phase of infarction or at 6 months. The results show that BNP is the best indicator of left ventricular dysfunction after myocardial infarction and its reliability is not dependent on the time point of measurement.

Topics: Analysis of Variance; Atrial Natriuretic Factor; Creatine Kinase; Endothelin-1; Female; Humans; Isoenzymes; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Regression Analysis; Time Factors; Ventricular Dysfunction, Left

A 47-year-old man with hypertensive heart disease and left heart failure due to left ventricular diastolic dysfunction was admitted to our hospital because of emergent hypertension. Chest radiography on admission showed slight cardiomegaly and mild pulmonary congestion with right pleural effusion Echocardiography showed concentric hypertrophy and normal contraction of the left ventricular wall Pulsed Doppler left ventricular inflow velocity wave and pulmonary venous flow velocity wave disclosed restrictive filling patterns. After Ca antagonist, nitrate, and diuretics were administered, blood pressure was normalized, and left ventricular inflow velocity wave showed the relaxation abnormality pattern and pulmonary venous flow velocity wave showed the normal pattern. Radioiodinated iodine-123 metaiodobenzyl guanidine (123I-MIBG) imaging in the state of normalized blood pressure showed decreased heart to mediastinum ratio and increased washout rate. Left heart catheterization and angiography revealed normal end-diastolic pressure and coronary arteries, but coronary flow reserve evaluated with Doppler flow wire and intracoronary adenosine triphosphate administration was impaired: Plasma level of atrial and brain natriuretic peptides, which were markedly elevated on admission, decreased with the improvement of heart failure. Doppler flow velocity patterns, plasma levels of atrial natriuretic peptide and brain natriuretic peptide, cardiac sympathetic nerve activity, and coronary flow reserve might be useful for evaluating the severity of left ventricular diastolic dysfunction in patients with hypertensive heart disease.

Topics: Atrial Natriuretic Factor; Calcium Channel Blockers; Coronary Circulation; Diastole; Diuretics; Echocardiography; Echocardiography, Doppler, Pulsed; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrates; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Ventricular Dysfunction, Left

Transgenesis has become a useful tool in effecting a complete or partial remodeling of the cardiac contractile apparatus. Although gene dosage effects were initially a concern, recent data showed that the heart is able to accommodate varying levels of transgenic over-expression without detectable ill effects. The present study was designed to test the limits of the transgenic paradigm in terms of the production of a cardiac phenotype due simply to the over-expression of a contractile protein. To this end, eight lines of mice which express an isoform of the essential myosin light chain 1 that is normally found in the adult ventricle (ELC1v) were generated. Overt phenotype was correlated both with the level of expression/protein replacement and copy number of the transgene. Two of the lines showed essentially complete replacement of the atrial isoform (ELC1a) with ELC1v. However, the phenotypes of the two lines differed dramatically. The line with the lower copy number (37 copies), and moderate over-expression (16 fold) showed no overt pathology while a line with very high copy number (94 copies) and extremely high levels of over-expression (27-50 fold) developed a significant atrial hypertrophy, dilation and cardiomyopathy. These data indicate that very high expression levels of a contractile protein can cause a cardiac pathology that is unrelated to its degree of replacement in the sarcomere and the unique role(s) it may assume in motor protein function.

Topics: Actins; Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Base Sequence; Biomarkers; Calcium-Transporting ATPases; Cardiomegaly; Connectin; Gene Dosage; Gene Expression; Heart Atria; Heart Defects, Congenital; Heart Ventricles; Mice; Mice, Transgenic; Molecular Sequence Data; Muscle Proteins; Myocardial Contraction; Myocardium; Myosin Light Chains; Protein Biosynthesis; Protein Isoforms; Protein Kinases; RNA, Messenger; Sequence Homology, Amino Acid; Transcription, Genetic; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Humans; Hypertrophy, Left Ventricular; Sensitivity and Specificity; Ultrasonography; Ventricular Dysfunction, Left

The present study was designed to study the progression of heart failure in rabbits with catecholamine-induced cardiomyopathy.. We investigated the effects of three repetitive applications (at 16-day intervals) of high-dose epinephrine (first infusion, 5 micrograms/kg/min for 60 minutes; second and third infusions, 4 micrograms/kg/min for 60 minutes) on hemodynamics, echocardiographic parameters, and plasma hormone levels in eight conscious rabbits chronically instrumented with a Doppler flow probe around the proximal abdominal aorta and a catheter in the right atrium. Mean arterial pressure and blood flow velocity, as well as the acceleration of blood flow velocity (df/dt) in the proximal abdominal aorta were progressively reduced, and right atrial pressure was significantly elevated. On echocardiography, progressive left ventricular (LV) dilatation with depressed LV systolic function and an increase in LV mass were observed. Plasma atrial natriuretic peptide level was enhanced approximately fourfold after each epinephrine infusion, with a tendency to return to baseline values. Plasma renin activity (PRA) was increased after the first epinephrine application (3.0 +/- 0.5 to 6.4 +/- 0.9 ng angiotensin I (AI)/mL/h; P < .05), followed by a return to control levels. After the second epinephrine infusion, a significant decrease to 1.0 +/- 0.3 ng AI/mL/h (P < .05) was observed. After the third catecholamine treatment, PRA levels insignificantly increased. Plasma vasopressin level significantly increased from 0.5 +/- 0.2 to 1.1 +/- 0.5 pg/mL (P < .05) after the second epinephrine infusion.. Repetitive infusions of high doses of epinephrine induce a cardiomyopathy with progressive hemodynamic deterioration, LV dilatation and hypertrophy, depressed systolic function, and different stages of neurohumoral compensation. This model appears to be suitable to study the progression of chronic heart failure by serial measurements in a small animal preparation.

Topics: Adrenergic alpha-Antagonists; Animals; Atrial Natriuretic Factor; Cardiomyopathies; Consciousness; Disease Models, Animal; Disease Progression; Echocardiography, Doppler; Epinephrine; Heart Failure; Hemodynamics; Male; Rabbits; Radioimmunoassay; Renin; Statistics, Nonparametric; Ventricular Dysfunction, Left

The degree of systolic dysfunction does not always correlate with functional impairment in patients with congestive heart failure. In contrast, diastolic dysfunction correlates well with functional impairment. In heart failure, both elevation of N-terminal proatrial natriuretic peptide and B-type natriuretic peptide are markers of a poor prognosis.. We investigated 32 patients (26 male, 6 female; mean age 55+/-2 years) with dilated cardiomyopathy and sinus rhythm. M-mode echocardiography and 2D-echocardiography were carried out in each patient. Pulsed-wave Doppler inflow signals were obtained and the following parameters were measured: maximal E wave and maximal A wave velocity, E/A ratio, E wave deceleration time, A wave deceleration time. Immediately after echocardiography blood samples were collected from patients in the supine position. N-terminal proANP and brain natriuretic peptide were measured using a radioimmuno assay.. The left ventricular ejection fraction was 34+/-1%, the left ventricular end-diastolic diameter on M-mode echocardiography was 68+/-1 mm, while left atrial diameter was 45+/-1 mm. Univariate analysis revealed a significant correlation between both left atrial diameter and ejection fraction and N-terminal proANP and brain natriuretic peptide. All transmitral Doppler parameters showed a significant correlation with N-terminal proANP and brain natriuretic peptide. On forward stepwise regression analysis, left atrial diameter and ejection fraction were able to predict both N-terminal proANP and brain natriuretic peptide. However, of the diastolic parameters only the E/A ratio remained significant. Mildly symptomatic patients differed significantly from severely symptomatic patients in all Doppler parameters. Mildly symptomatic patients had significantly lower levels of N-terminal proANP (0.571+/-0.079 vs 2.282+/-0.340 nmol. l(-1);P<0.001) and brain natriuretic peptide (51+/-14.8 vs 474.2+/- 86.8 pg. ml(-1);P<0. 001).. There is a close relationship between natriuretic peptides and diastolic Doppler parameters of left ventricular filling in patients with dilated cardiomyopathy. There is also a significant difference between patients with mild and severe functional impairment regarding both natriuretic peptides and transmitral Doppler parameters.

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Case-Control Studies; Diastole; Echocardiography; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Protein Precursors; Radioimmunoassay; Ventricular Dysfunction, Left

To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP).. 32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay.. Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p < 0. 001), left ventricular ejection fraction (r = -0.758; p < 0.001), and Doppler derived E/A ratio (r = 0.740; p < 0.001).. In patients with idiopathic dilated cardiomyopathy there is a relation between NT-pro-ANP and both systolic and diastolic variables. In a multivariate model NT-pro-ANP correlated with left atrial diameter, left ventricular ejection fraction, and Doppler derived E/A ratio on transmitral inflow.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Echocardiography, Doppler, Pulsed; Female; Humans; Male; Middle Aged; Protein Precursors; Regression Analysis; Stroke Volume; Systole; Ventricular Dysfunction, Left

Plasma renin activity is normal in left ventricular dysfunction in the absence of diuretic therapy. In health there is a reciprocal relationship between renin and atrial natriuretic peptide (ANP) but a positive correlation in advanced heart failure. The relationship between renin and ANP in mild left ventricular dysfunction is unknown.. Patients with left ventricular dysfunction (n = 35, 18 without diuretic therapy) were compared to 20 age-matched healthy subjects. Plasma concentrations of active renin (PARC), ANP and norepinephrine were measured after 20 min rest and 45 min after an infusion of normal saline (10 ml/kg body wt.). Basal plasma ANP was increased in patients with left ventricular dysfunction compared to healthy subjects, whether or not they were receiving diuretics. PARC was similar in healthy controls and patients untreated with diuretics but was increased in diuretic treated patients. After saline loading in healthy subjects PARC fell while ANP rose. Patients with left ventricular dysfunction had a smaller decline in PARC, that did not achieve statistical significance, but had a greater increase in plasma ANP compared to healthy subjects (P<0.05). The close reciprocal relationship between PARC and ANP observed in healthy subjects before and after saline loading (r = 0.8, P<0.001 and r = 0.6, P<0.01) was weakened in those not receiving diuretics (r = 0.4, P<0.05 and r = 0.24, ns) and lost in those receiving diuretics (r = 0.1 and r = 0.08).. Patients with left ventricular dysfunction have a disturbance of the normal reciprocal relationship between PARC and ANP which antedates diuretic treatment. This should be taken into account when interpreting plasma neuroendocrine measurements in patients with ventricular dysfunction.

Topics: Atrial Natriuretic Factor; Blood Volume; Diuretics; Female; Furosemide; Humans; Male; Middle Aged; Norepinephrine; Renin; Sodium Chloride; Stroke Volume; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Male; Natriuresis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Ventricular Dysfunction, Left

In previous studies on the use of natriuretic peptides to detect left-ventricular systolic dysfunction, a higher rate of cardiac disorders in the control groups than in the study groups could have led to bias. We investigated the effectiveness of plasma N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) concentrations to show left-ventricular systolic dysfunction in a random sample of the general population.. We randomly selected 2000 participants aged 25-74 years from family physicians' lists in Glasgow, UK. We sent all participants questionnaires. 1653 respondents underwent echocardiography and electrocardiography. We took a left-ventricular ejection fraction of 30% or less to show left-ventricular systolic dysfunction. NT-ANP and BNP were measured in plasma by RIAs.. 1252 participants had analysable electrocardiograms and echocardiograms, completed questionnaires, and available blood samples. Median concentrations of NT-ANP and BNP were significantly higher in participants with left-ventricular systolic dysfunction (2.8 ng/mL [IQR 1.8-4.6] and 24.0 pg/mL [18.0-33.0]) than in those without (1.3 ng/mL [0.9-1.8] and 7.7 pg/mL [3.4-13.0]; each p < 0.001). Among participants with left-ventricular systolic dysfunction, both symptomatic and asymptomatic subgroups had raised NT-ANP and BNP concentrations. A BNP concentration of 17.9 pg/mL or more gave a sensitivity of 77% and specificity of 87% in all participants, and 92% and 72% in participants aged 55 years or older.. Measurement of BNP could be a cost-effective method of screening for left-ventricular systolic dysfunction in the general population, especially if its use were targeted to individuals at high risk.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Male; Mass Screening; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Predictive Value of Tests; Random Allocation; ROC Curve; Scotland; Sensitivity and Specificity; Ventricular Dysfunction, Left

The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid.. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides.. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery.. The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074).. BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Topics: Aged; Atrial Natriuretic Factor; Autocrine Communication; Biomarkers; Cardiac Output, Low; Cardiac Volume; Coronary Artery Bypass; Coronary Disease; Diastole; Female; Hemodynamics; Humans; Hypertension; Male; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Paracrine Communication; Pericardial Effusion; Radioimmunoassay; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Echocardioscopy in M- and B-modes with measurement of routine parameters of central hemodynamics and thickness of carotid intimal-medial segment as well as radioimmunoassay of plasma concentrations of atrial natriuretic peptide (ANUP) were performed in 159 patients aged 42-63 years (17 healthy subjects and 142 patients with cardiac failure associated with ischemic heart disease and sinus rhythm, without history of myocardial infarction). The results were indicative of possible use of ANUP as a marker of initial cardiac insufficiency and a corrector of the disease prognosis.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiac Output; Carotid Arteries; Echocardiography; Heart Atria; Heart Failure; Humans; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Prognosis; Radioimmunoassay; Ventricular Dysfunction, Left

Plasma atrial natriuretic peptide (ANP), mainly from the atrium, brain natriuretic peptide (BNP), mainly from the ventricle, norepinephrine (NE), and endothelin-1 (ET-1) levels are increased with the severity of congestive heart failure (CHF). Although a close correlation between the left ventricular end-diastolic pressure (LVEDP) and plasma ANP in patients with left ventricular dysfunction has been reported, it is not yet known which cardiac natriuretic peptide is a better predictor of high LVEDP in patients with CHF.. To investigate the biochemical predictors of the high LVEDP in patients with left ventricular dysfunction, we measured plasma ANP, BNP, NE, and ET-1 levels and the hemodynamic parameters in 72 patients with symptomatic left ventricular dysfunction. Stepwise multivariate regression analyses were also used to determine whether the plasma levels of ANP, BNP, NE, and ET-1 could predict high LVEDP.. Although significant positive correlations were found among the plasma levels of ANP, BNP, ET-1, and NE and the LVEDP, only BNP (p = 0.0001) was an independent and significant predictor of high LVEDP in patients with CHF. In all eight patients with severe CHF measured for hemodynamics before and after the treatments, the plasma BNP levels decreased in association with the decrease of LVEDP, whereas other factors increased in some patients despite the decrease of LVEDP.. These findings suggest that plasma BNP is superior to ANP as a predictor of high LVEDP in patients with symptomatic left ventricular dysfunction.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Brain; Cardiac Catheterization; Diastole; Endothelin-1; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Prognosis; Regression Analysis; Ventricular Dysfunction, Left; Ventricular Function, Left

The aim of the study was to assess the relationship between changes in heart rate variability (HRV) and parameters of neuroendocrine activation in patients with various levels of left ventricular dysfunction. Measurements of HRV, plasma norepinephrine (PNE), and plasma atrial natriuretic peptide (ANP) were performed in 17 age- and gender-matched control subjects (group C) and in 39 patients with ischemic heart disease or cardiomyopathy who were subdivided into 3 equal groups according to their left ventricular ejection fraction: group N (normal); group M (mildly impaired); and group S (severely impaired). Spectral analysis of HRV (from 10-min electrocardiograms) was analyzed by the method of coarse-graining spectral analysis. PNE and ANP were significantly elevated in group S only (p<0.05). Log low-frequency power and log total power for group M were significantly lower than for group N (p<0.05). Log high-frequency power was significantly lower for group M than for group C (p<0.05). Thus, assessment of changes in HRV, which were observed earlier in the progress of left ventricular dysfunction than changes in neuroendocrine factors, may be a useful non-invasive method for the early detection of autonomic abnormality in patients with left ventricular dysfunction.

Topics: Aged; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Case-Control Studies; Female; Heart Rate; Humans; Male; Middle Aged; Neurosecretory Systems; Norepinephrine; Stroke Volume; Ventricular Dysfunction, Left

The purpose of this study was to examine cardiac geometry and function by Doppler echocardiography and to analyze mRNA expression of cardiac phenotype and extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels in the non-infarcted left ventricle (LV) and infarct site were measured by Northern blot analysis. LV internal diastolic dimension was greater in infarcted (MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm, p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/-3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7 m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control 35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP-2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1- (all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)-beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0-, 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated myocardium. Myocardial infarcted rat was characterized by cavity dilation and marked abnormalities of systolic and diastolic function, accompanied by a shift of myocytes to fetal phenotype and activation of collagen genes in the non-infarcted myocardium.

Topics: Actins; Animals; Atrial Natriuretic Factor; Collagen; Diastole; Echocardiography; Echocardiography, Doppler; Fetal Proteins; Gelatinases; Gene Expression Regulation; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Metalloendopeptidases; Muscle Proteins; Myocardial Infarction; Myocardium; Myosin Heavy Chains; Phenotype; Rats; Rats, Wistar; RNA, Messenger; Transforming Growth Factor beta; Ventricular Dysfunction, Left

The purpose of this study was to examine the effect of amlodipine, a long-acting calcium antagonist, on the left ventricular remodeling, including systolic and diastolic dysfunction, the change of cardiac gene expression in the myocardial infarcted rats (MI).. On the first day after myocardial infarction, the animals were randomly assigned to amlodipine treatment (n = 8) or untreated groups (MI; n = 9). We then performed Doppler-echocardiographic examinations and measured the hemodynamics at four weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed.. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 22 +/- 1 mmHg and 5 +/- 1 mmHg. Amlodipine reduced LVEDP and CVP to 15 +/- 1 mmHg (P < 0.01) and 3 +/- 0 mmHg (P < 0.01). The weight of right ventricle in MI was significantly larger than in the control rats (Control; 0.48 +/- 0.01 g/kg, MI; 0.79 +/- 0.04 g/kg, P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3 mm (P < 0.01) (Control; 6.2 +/- 0.3 mm). Amlodipine prevented an increase of the weight of right ventricle (0.62 +/- 0.03 g/kg, P < 0.01) and LVDd (7.9 +/- 0.2 mm, P < 0.01 to MI). The rats in MI showed systolic dysfunction shown by the decreased fractional shortening (Control; 31 +/- 2% versus MI; 15 +/- 1%, P < 0.01), and diastolic dysfunction shown by E wave deceleration rate (Control; 18.1 +/- 2.0 m/s2, MI; 32.6 +/- 2.1 m/s2, P < 0.01). Amlodipine significantly prevented systolic and diastolic dysfunction. The increases in beta-MHC, alpha-skeletal actin, and ANP mRNAs in the non-infarcted left ventricle and right ventricle at four weeks after the myocardial infarction were all significantly suppressed by the treatment with amlodipine. On the other hand, depressed alpha-MHC was restored to normal levels by amlodipine in both regions.. Amlodipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.

Topics: Actins; Amlodipine; Animals; Atrial Natriuretic Factor; Blotting, Northern; Calcium Channel Blockers; Collagen; Echocardiography; Gene Expression; Hemodynamics; Hypertrophy, Left Ventricular; Male; Myocardial Infarction; Myocardium; Myosin Heavy Chains; Rats; Rats, Wistar; RNA, Messenger; Ventricular Dysfunction, Left

In an attempt to identify and quantify the sites of atrial natriuretic peptide (ANP) degradation, particularly the lungs, a new tracer method to study ANP metabolism in vivo in humans was developed and applied to patients with left ventricular dysfunction. Thirteen male, normotensive, cardiac patients with different degrees of left ventricular myocardial involvement were enrolled in the study. The study protocol required constant infusion (3 patients) or bolus injection (10 patients) of 125I-labeled ANP just upstream of the right atrium and blood sampling from different sites (pulmonary artery, aorta, inferior vena cava, and femoral vein) during the hemodynamic study. Data analysis was based on a kinetic model consisting of three blocks in series (right heart, lungs and left heart, and periphery) supplied by the same plasma flow (plasma cardiac output). Plasma levels of native ANP were measured with a sensitive and specific immunoradiometric assay method. ANP values measured in the aorta (163.9 +/- 144.8 pg/mL, n = 80) were superimposable on those measured in the pulmonary artery (161.8 +/- 136.5 pg/mL, n = 80). Negligible extraction of 125I-labeled ANP was found in the lungs and left heart block (on average 0.08 +/- 3.92%), whereas the peripheral block extraction (46.2 +/- 7.8%) accounted for almost total hormone removal from the blood (whole body extraction was 46.4 +/- 6.6%). ANP metabolic clearance rate (3.11 +/- 1.48, range 1.4-6.8 L/min) declined with the progression of left ventricular dysfunction (plasma cardiac output 3.46 +/- 1.08, range 1.2-5.7 L/min), and a close correlation between metabolic clearance rate and cardiac output was evident. Our data suggest that lungs do not extract, or extract only very small amounts, of labeled ANP administered iv to patients with different degrees of left ventricular myocardial involvement, and whole body extraction of labeled ANP remains relatively stable with the progression of disease, and the large reductions in clearance values observed in our patients can be ascribed mainly to the reductions in cardiac output.

Topics: Adult; Aorta; Atrial Natriuretic Factor; Cardiac Output; Femoral Vein; Hemodynamics; Humans; Iodine Radioisotopes; Kinetics; Lung; Male; Middle Aged; Pulmonary Artery; Vena Cava, Inferior; Ventricular Dysfunction, Left

To determine whether blood natriuretic peptide concentrations are helpful in identifying or excluding left ventricular systolic dysfunction in stable survivors of acute myocardial infarction.. Comparison of blood natriuretic peptide concentrations with echocardiographic assessment of left ventricular systolic function in a general practice population.. Practices in Western District of Glasgow audit group.. 134 long term survivors of myocardial infarction recalled for echocardiography as part of a primary care secondary prevention audit.. Area under the receiver operating curve for brain natriuretic peptide and N-terminal atrial natriuretic peptide.. Brain natriuretic peptide was of some diagnostic utility in identifying the minority of subjects with severe left ventricular dysfunction (area under curve=0.73) but was unable to discriminate between patients with moderately severe dysfunction and those with preserved left ventricular function (area under curve for moderate or severe dysfunction=0.54). The corresponding values for N-terminal atrial natriuretic peptide for severe and moderate or severe dysfunction were 0.55 and 0.56 respectively.. Blood natriuretic peptide concentrations are not useful in identifying important left ventricular systolic dysfunction in stable survivors of myocardial infarction.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cohort Studies; Echocardiography; Family Practice; Female; Humans; Male; Middle Aged; Myocardial Infarction; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice.. We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40).. Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group.. Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Survival Analysis; Ventricular Dysfunction, Left

The purpose of this study was to analyze the effect of the angiotensin II type 1-receptor antagonist candesartan cilexitil on left ventricular systolic and diastolic function and mRNA expression of contractile proteins, collagen, and Ca2+ handling protein in myocardial-infarcted rats. After myocardial infarction, the animals were randomly assigned to candesartan cilexitil-treated or untreated groups (MI). We performed Doppler-echocardiographic examination and measured the hemodynamics at four and twelve weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. At four weeks in MI, left ventricular end-diastolic dimension increased (Control, 6.2+/-0.6 mm; MI, 8.7+/-0.6 mm; P < 0.01), fractional shortening decreased (Control, 41+/-5%; MI, 16+/-3%; P < 0.01) and E wave deceleration rate increased (Control, 14.3+/-2.0 m/sec2; MI, 23.3+/-2.3 m/sec2; P < 0.01). Candesartan cilexitil significantly prevented these changes. The mRNA expressions of beta-myosin heavy chain, alpha-skeletal actin, atrial natriuretic peptide, and collagens I and III in the non-infarcted left ventricle and right ventricle were increased at four weeks and were significantly suppressed by treatment with candesartan cilexitil. At four weeks, Na+-Ca2+ exchanger mRNA expression was increased, and candesartan cilexitil suppressed this increase. At twelve weeks, sarcoplasmic reticulum Ca2+-ATPase mRNA expression in the infarcted region including the adjacent non-infarcted left ventricle and right ventricle were decreased and candesartan cilexitil restored it to the control level. Candesartan cilexitil prevented the systolic and diastolic dysfunction and abnormal cardiac mRNA expression in myocardial-infarcted rats.

Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Benzimidazoles; Biphenyl Compounds; Calcium-Transporting ATPases; Collagen; Contractile Proteins; Echocardiography; Gene Expression; Heart Ventricles; Hemodynamics; Male; Myocardial Infarction; Organ Size; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; RNA, Messenger; Sodium-Calcium Exchanger; Tetrazoles; Ventricular Dysfunction, Left

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.

Topics: Aged; Aged, 80 and over; Aging; Atrial Natriuretic Factor; Biomarkers; Cardiac Volume; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

It is likely that abnormal baroreflex control mechanisms are at least partially responsible for autonomic dysfunction in chronic heart failure. We recently demonstrated that diastolic ventricular interaction is associated with impaired baroreflex control of vascular resistance in heart failure. We reasoned that by constraining left ventricular filling, such interaction would decrease baroreflex activity and, thereby, increase sympathetic and decrease parasympathetic outflow. We hypothesized, therefore, that diastolic ventricular interaction in chronic heart failure patients would be associated with autonomic dysfunction. We used radionuclide ventriculography to measure changes in left and right ventricular end-diastolic volumes during acute volume unloading achieved by -30 mm Hg lower-body negative pressure in 30 patients with chronic heart failure. An increase in left ventricular volume in association with a reduction in right ventricular volume indicates diastolic ventricular interaction (a larger increase indicating a greater degree of interaction). We also measured heart rate variability (n = 23) and resting venous plasma norepinephrine (n = 24), epinephrine (n = 24), and atrial natriuretic peptide (ANP) (n = 14). During lower-body negative pressure, while right ventricular volume decreased in all patients (P < 0.001), left ventricular end-diastolic volume increased (from 152 +/- 25 to 157 +/- 36 ml/m2, P = 0.01). The change in left ventricular volume was positively correlated with resting plasma norepinephrine (P < 0.01) and ANP (P < 0.005), and negatively correlated with the standard deviation of normal to normal R-R intervals (P < 0.005), the root-mean-square of differences between successive normal to normal R-R intervals (P < 0.05), total power (P < 0.01), low-frequency power (P < 0.01), and high-frequency power (P < 0.05). Diastolic ventricular interaction in patients with chronic heart failure is associated with sympathetic nervous system activation evidenced by increased plasma norepinephrine and reduced heart rate variability.

Topics: Atrial Natriuretic Factor; Baroreflex; Diastole; Epinephrine; Female; Heart Failure; Heart Rate; Heart Ventricles; Humans; Lower Body Negative Pressure; Male; Middle Aged; Norepinephrine; Radionuclide Ventriculography; Sympathetic Nervous System; Vascular Resistance; Ventricular Dysfunction, Left

We evaluated 30 consecutive patients and 48 age- and sex-matched controls to explore the possibility of a pathogenic contribution by plasma endothelin-1 in the cardiac expression of systemic sclerosis. Venous plasma endothelin-1 was measured by radio-immunoassay and left ventricular function by echocardiography. The patient group had elevated plasma endothelin-1 (2.6 +/- 0.2 vs. 1.8 +/- 0.1 pmol/1, P < 0.001), but endothelin-1 was not related to age, heart rate, blood pressure, total peripheral resistance, disease duration or systemic sclerosis score. Endothelin-1 was related to left ventricular hypertrophy in terms of septal thickness (r = 0.33, P < 0.01) and left ventricular mass index (r = 0.32, P < 0.01). Plasma endothelin-1 was further related to measures indicating reduced left ventricular filling; left atrial emptying index (r = -0.50, P < 0.0005), the first third filling fraction (r = -0.31, P < 0.05) and the time velocity integral of Doppler early/late filling velocity (r = -0.40, P < 0.001). Furthermore, circulating endothelin-1 was related to impaired left ventricular contractility as estimated by pre-ejection period/left ventricular ejection time (r = 0.32, P < 0.01) and end-systolic wall stress/volume index (r = -0.30, P < 0.05). We conclude that plasma endothelin-1 is elevated in relation to the degree of left ventricular hypertrophy, diastolic dysfunction and impaired contractility in systemic sclerosis. It may be of pathogenic importance to the cardiac involvement in systemic sclerosis which is not mediated via an increase in systemic blood pressure. It is not yet clear whether our findings are exclusive to systemic sclerosis patients or represent a generalized phenomenon in patients with impaired left ventricular function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathies; Case-Control Studies; Echocardiography; Endothelin-1; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Multivariate Analysis; Scleroderma, Systemic; Ventricular Dysfunction, Left

To study the acute effects of angiotensin-converting enzyme inhibition by intravenous enalaprilat infusion in patients with left ventricular dysfunction after cardiac surgery.. Prospective, consecutive sample, before-after trial.. Surgical intensive care unit in a tertiary care university hospital.. Eight patients with left ventricular dysfunction after cardiac surgery. Patients were defined as having left ventricular dysfunction if the pulmonary capillary wedge pressure persisted above 18 mmHg in spite of conventional vasoactive medication (inotropic or vasodilating and diuretic drugs) and intermittent mandatory ventilation during the first postoperative week.. Enalaprilat was infused initially at 1 mg/ hour. The rate was doubled every 30 minutes until pulmonary capillary wedge pressure decreased at least 20% or until a maximum total dose of 10 mg was achieved.. Central hemodynamics, systemic oxygenation, and hormonal regulation of circulation (plasma renin activity, plasma endothelin, atrial natriuretic peptide, norepinephrine, epinephrine, and vasopressin concentrations, serum angiotensin-converting enzyme activity, and serum levels of aldosterone) were assessed at baseline before enalaprilat infusion, and repeatedly over 2 hours after the infusion. Enalaprilat infusion (median dose, 2.0 mg; infusion time, 48 minutes) caused a significant decrease in pulmonary capillary wedge pressure (p = 0.004), lasting until the end of the 2 hours' follow-up. This coincided with inhibition of serum angiotensin-converting enzyme activity (p < 0.001), an increase in plasma renin activity (p = 0.022), and decreases in plasma endothelin (p = 0.035), atrial natriuretic peptide (p = 0.005), and serum aldosterone (p = 0.001) concentrations. Cardiac output, venous admixture, and oxygen delivery and consumption remained unchanged.. Adding enalaprilat to conventional therapy makes it possible to unload the left ventricle and to relieve overt neurohormonal activation temporarily while maintaining cardiac function and systemic oxygenation.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Enalaprilat; Endothelins; Female; Humans; Male; Middle Aged; Prospective Studies; Ventricular Dysfunction, Left

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Humans; Middle Aged; Reference Values; Ventricular Dysfunction, Left

In order to develop and validate an ovine model of myocardial infarction with subsequent impairement of left ventricular function, 15 instrumented sheep underwent selective microembolization of the left coronary arteries with 0.5 mL 90 microns polystyrene beads. Hemodynamics and plasma hormones were measured preembolization (baseline) and then at hours 2, 4, 6, and 12 and days 1, 2, 3, 5 and 7 postembolization. Of the 15 sheep studied, 2 (13%) died on the day of embolization from arrhythmias. In the remaining sheep, left ventricular systolic pressure and stroke work (both P < 0.001) were reduced promptly and remained below basal levels. Mean arterial pressure (P < 0.001) increased initially, then decreased to below basal levels by hour 6. Heart rate (P < 0.001) and left atrial pressure (P < 0.05) were increased while cardiac output was decreased (P < 0.05). Left ventricular ejection fraction at day 7 was reduced (38.8 +/- 3.5 vs 46.0 +/- 3.9% preembolization; P < 0.05). The cardiac enzymes creatine kinase (P < 0.001) and troponin-T (P < 0.001) were increased following microembolization and returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain natriuretic peptides (both P < 0.001) and plasma renin activity (P < 0.005) were all increased following embolization. This ovine model mimics the hemodynamic and neurohumoral features of acute myocardial infarction, resulting in left ventricular dysfunction, and should prove suitable for the study of interventions in a number of these conditions.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Chronic Disease; Creatine Kinase; Disease Models, Animal; Female; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin; Sheep; Stroke Volume; Ventricular Dysfunction, Left

To test the hypothesis that elevated plasma levels of natriuretic peptides may serve to identify patients with left ventricular (LV) dysfunction, we assessed the predictive diagnostic value of natriuretic peptide levels, in addition to clinical and electro-cardiographic risk factors, as noninvasive indicators of cardiac dysfunction. Plasma levels of atrial natriuretic peptide (cANP) (99-126), N-terminal fragment of proANP (nANP) (26-55), nANP(80-96), brain natriuretic peptide (BNP-32), proBNP(22-46), and C-type natriuretic peptide (CNP-22) were measured in 211 subjects before cardiac catheterization. The strongest correlations with parameters of LV function were found for nANP(80-96) (up to r = -0.55, p < 0.0001), whereas there was no significant correlation with proBNP(22-46) or CNP-22. In patients with LV ejection fractions (LVEF) < or = 45% (n = 38) nANP(26-55), nANP(80-96), cANP(99-126), and BNP-32 were significantly increased (p < 0.001). Partition values for elevated versus normal natriuretic peptide levels were obtained from normal controls and used to separate subjects with and without LV dysfunction. Receiver operating characteristic analysis for LVEF < or = 45% indicated a significantly better diagnostic accuracy for high levels of nANP(80-96), nANP(22-56), cANP(99-126), and BNP-32 than for proBNP and CNP-22. Multivariate analysis by logistic regression identified Q waves and bundle branch block in the electrocardiogram as well as elevated plasma levels of cANP, nANP(80-96), and nANP(26-55) as the strongest independent predictors of low ejection fractions. The relative risk of LV dysfunction was raised up to tenfold in subjects with high natriuretic peptide levels (p < 0.001). The addition of nANP(80-96) and nANP(26-55) to the combination of clinical and electrocardiographic risk factors did not further improve the diagnostic sensitivity for the detection of LVEF < or = 45%, but it markedly increased the overall accuracy (59% to 81%, p < 0.001) and specificity (55% to 81%, p < 0.001). Among natriuretic peptides, elevated nANP(80-96) and nANP(26-55) levels have the strongest impact on the detection of LV dysfunction. They add to the diagnostic information contained in clinical and electrocardiographic factors. Plasma levels alone or in combination with clinical factors seem to be of value for a refined identification of abnormal LV function in the individual patient.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Evaluation Studies as Topic; Female; Hemodynamics; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Risk Factors; ROC Curve; Ventricular Dysfunction, Left

Inhibition of the angiotensin-converting enzyme (ACE) in the setting of chronic left ventricular (LV) dysfunction has been demonstrated to have beneficial effects on survival and symptoms. However, whether ACE inhibition has direct effects on myocyte contractile processes and if these effects are mediated primarily through the AT1 angiotensin-II receptor subtype remains unclear. The present project examined the relationship between changes in LV and myocyte function and beta adrenergic receptor transduction in four groups of six dogs each: (1) Rapid Pace: LV failure induced by chronic rapid pacing (4 weeks; 216 +/- 2 bpm); (2) Rapid Pace/ACEI: concomitant ACE inhibition (ACEI: fosinopril 30 mg/kg b.i.d.) with chronic pacing; (3) Rapid Pace/AT1 Block: concomitant AT1 Ang-II receptor blockade [Irbesartan: SR 47436(BMS-186295) 30 mg/kg b.i.d.] with chronic pacing; and (4) CONTROL: sham controls. With Rapid Pace, the LV end-diastolic volume increased by 62% and the ejection fraction decreased by 53% from control. With Rapid Pace/ACEI, the LV end-diastolic volume was reduced by 24% and the ejection fraction increased by 26% from Rapid Pace only values. Rapid Pace/AT1 Block did not improve LV geometry or function from Rapid Pace values. Myocyte contractile function decreased by 40% with Rapid Pace and increased from this value by 32% with Rapid Pace/ACEI. Rapid Pace/AT1 Block had no effect on myocyte function when compared with Rapid Pace values. With Rapid Pace/ACEI, beta receptor density and cyclic AMP production were normalized and associated with an improvement in myocyte beta adrenergic response compared with Rapid Pace only. Although Rapid Pace/AT1 also normalized beta receptor density, cyclic AMP production was unchanged and myocyte beta adrenergic response was reduced by 15% compared with Rapid Pace only. ACE inhibition with chronic rapid pacing improved LV and myocyte geometry and function, and normalized beta receptor density and cyclic AMP production. However, AT1 Ang-II receptor blockade with chronic rapid pacing failed to provide similar protective effects on LV and myocyte geometry and function. These unique findings suggest that the effects of ACE inhibition on LV geometry and myocyte contractile processes in the setting of developing LV failure are not primarily caused by modulation of AT1 Ang-II receptor activation.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cyclic AMP; Dogs; Female; Male; Myocardial Contraction; Norepinephrine; Receptors, Adrenergic, beta; Ventricular Dysfunction, Left

The upregulation of left ventricular (LV) atrial natriuretic peptide (ANP) mRNA is a highly conserved marker of cardiac hypertrophy. The aim of this study was to further examine the pathway leading to ANP induction during pressure overload of the heart. Systolic wall stress was imposed acutely on isovolumetrically beating rat hearts in a Langendorff apparatus (sigma-=300 x 10[3] dyne/cm2). Northern and Western blots revealed that elevated wall stress induced LV c-fos and c-jun mRNAs (3.5- and 3-fold, P<.05 after 60 minutes), c-Fos and c-Jun proteins (3.9- and 4.3-fold, P<.05 after 120 minutes), as well as ANP mRNA (2.2-fold, P<.05 after 120 minutes). ANP upregulation was prevented by inhibition of protein synthesis (cycloheximide). Electrophoresis mobility shift assays were performed to link c-Fos and c-Jun (ie, components of the heterodimeric transcription factor AP-1) and ANP induction. A putative AP-1 binding site within the rat ANP promoter (nucleotides -512 to -473) bound specifically to nuclear proteins of wall stress-stimulated hearts. Antibodies directed against c-Fos protein resulted in a shift of this DNA/protein complex, suggesting physical interaction between AP-1 and the ANP promoter. Myocardial transfection of promoter constructs revealed that after acute imposition of wall stress, this AP-1 site enhanced a reporter gene (8- to 10-fold compared with a minimal promoter, P<.05). Interestingly, nuclear extracts of stimulated hearts as well as pure AP-1 protein bound to a putative CRE site (nucleotides -613 to -584) as well. Like the AP-1 site, this cAMP-responsible element (CRE) site was found to enhance the transfected ANP promoter/reporter gene significantly (17.5-fold, P<.05). Mutation of either AP-1 or CRE sites did not decrease reporter gene activity, whereas mutation of both resulted in loss of inducibility. These experiments suggest that LV ANP regulation after acute wall stress includes the activation of AP-1 and/or CRE cis acting elements. However, the transient nature of c-fos and c-jun upregulation also suggests that AP-1 is not the only mediator of ANP induction in LV hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Gene Expression Regulation; In Vitro Techniques; Male; Mutagenesis, Site-Directed; Myocardium; Promoter Regions, Genetic; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; Recombinant Fusion Proteins; RNA, Messenger; Stress, Mechanical; Systole; TATA Box; Transcription Factor AP-1; Transcription, Genetic; Ventricular Dysfunction, Left

To compare the stability of brain natriuretic peptide (BNP) to that of N-terminal atrial natriuretic peptide (NT-ANP) in whole blood and plasma stored under different conditions. To compare a rapid, simple, direct (unextracted) BNP assay to a conventional assay using plasma extraction.. Blinded, prospective, comparative study.. Tertiary referral cardiology department.. Forty two subjects (24 men, 18 women) comprising 28 patients with left ventricular systolic dysfunction (LVSD) ranging from mild to severe and 14 healthy volunteers.. Stability of NT-ANP and BNP when stored as whole blood or plasma at room temperature over three days. Reproducibility of measurements.. BNP was stable in whole blood stored at room temperature for three days; mean change in concentration -7.4% (95% CI 0.6 to -14.8), (direct), -6.3% (5.0 to -16.4), (extracted); whereas a significant decline in BNP concentration was noted in plasma stored at room temperature; -23.2% (-13.7 to -31.6), (direct); -14.4% (-3.2 to -24.3), (extracted). By contrast a small nonsignificant rise in NT-ANP concentration was noted both in whole blood and plasma stored at room temperature for three days; whole blood +8.6% (+22.3 to -3.5), plasma +6.3%, (23.2 to -8.4). The reproducibility of the BNP measurements, and particularly the rapid, direct, measurement, was superior to that for NT-ANP.. BNP is shown to be stable in whole blood for three days and can be measured using a rapid, simple assay. Routine assay of BNP is feasible in ordinary clinical practice and may be of value to general practitioners and hospital based physicians in the diagnosis and management of patients with LVSD. Samples can be sent to a central laboratory without special handling requirements.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Reproducibility of Results; Sensitivity and Specificity; Specimen Handling; Systole; Time Factors; Ventricular Dysfunction, Left

We have directly compared atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and N-terminal pro-ANP (N-ANP) as markers of patients with left ventricular ejection fraction (LVEF) < or = 35%, as measured by radionuclide ventriculography. Venous blood samples were obtained from an unselected group of 87 patients who had been referred for assessment of ventricular function. ANP, BNP, and N-ANP were measured by radioimmunoassay using commercial kits. Receiver-operating characteristic analysis was used for the objective assessment of the diagnostic performance of each assay. There was a weak negative correlation between LVEF and plasma levels of ANP-li (r = -0.50,), BNP-li (r = -0.57), and N-ANP-li (r = -0.49) (p <0.01 for each peptide). Areas under the receiver-operating characteristic curves for BNP (0.880) and N-ANP (0.832) were not significantly different from each other, but were both significantly greater than the value for ANP (0.761): BNP versus ANP, p <0.01; and N-ANP versus ANP, p <0.05. The optimal sensitivity and specificity of each assay for the detection of patients with LVEF < or = 35% were: BNP > 4 pmol/L-sensitivity 1.0, specificity 0.58; N-ANP >200 pmol/L-sensitivity 0.95, specificity 0.35; and ANP >10 pmol/L-sensitivity 0.90, specificity 0.30. Plasma concentrations of BNP and N-ANP provide sensitive indicators of moderate to severe LV dysfunction; both peptides, are objectively superior to ANP for identifying patients with LVEF < or = 35%. These simple tests could be used to screen patients with suspected ventricular dysfunction to reduce the demand for further cardiac investigations.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Gated Blood-Pool Imaging; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Protein Precursors; ROC Curve; Sensitivity and Specificity; Systole; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Female; Guanylate Cyclase; Heart Failure; Hemodynamics; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Physical Exertion; Prognosis; Receptors, Atrial Natriuretic Factor; Risk Assessment; Stroke Volume; Ventricular Dysfunction, Left

The neuroendocrine profile and echocardiographic features of 40 patients (81 +/- 1 years, means +/- standard error) with heart failure and impaired left ventricular systolic function were compared with those of an age-matched group of healthy subjects, 20 younger patients with heart failure (aged 58 +/- 1 years) and 15 younger healthy subjects. Normal elderly subjects had a neuroendocrine profile similar to that of healthy younger subjects apart from elevated plasma norepinephrine (958 +/- 84 vs 302 +/- 118 pg/ml; p< 0.001) and atrial natriuretic peptide ( 40 +/- 6 vs 28 +/- 5 pg/ml; p<0.05). Despite a similar severity of heart failure, elderly patients had smaller ventricular dimensions (left ventricular internal dimension in diastole 51 +/- 2 vs 69 +/- 3 mm;p<0.0001 and greater impairment of ventricular compliance using Doppler indexes. Plasma norepinephrine was higher (1,191 +/- 80 vs 620 +/- 67 ppg/ml; p<0.01), and plasma atrial natriuretic peptide, plasma active renin, and angiotensin II were lower in elderly patients than in the younger patients with heart failure. As functional capacity declines with age, elderly patients may have less severe cardiac dysfunction for any given level of functional impairment, and this may account for most of the differences in neuroendocrine activity with age. Age appears to be an important determinant of plasma norepinephrine and may be a confounding factor in interpreting the prognostic significance of this hormone.

Topics: Aged; Aged, 80 and over; Aging; Atrial Natriuretic Factor; Cardiac Output, Low; Echocardiography; Humans; Middle Aged; Neurosecretory Systems; Norepinephrine; Renin-Angiotensin System; Ventricular Dysfunction, Left

1. The effects of prolonged chlorothiazide treatment of left ventricular failure on cardiac hypertrophy, circulating vasoactive hormones and exchangeable body sodium were examined in rats with chronic myocardial infarction induced by left coronary artery ligation. Chlorothiazide therapy commenced either immediately or 2 weeks after infarction. For 4 weeks, the rats were given either chlorothiazide (50 mg day-1 kg-1) in their drinking water or drinking water alone. 2. Cardiac weight increased in untreated rats with infarction in comparison with sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium, plasma renin activity, plasma vasopressin and plasma osmolality remained unchanged. 3. Chlorothiazide raised haematocrit and plasma renin activity equally in rats with and without infarction, although exchangeable body sodium, plasma vasopressin and plasma osmolality were not changed by the treatment. Plasma atrial natriuretic peptide was 2-fold higher in rats with infarction and this response was not affected by chlorothiazide treatment. Chlorothiazide therapy did not prevent or reverse cardiac hypertrophy. 4. Chronic diuretic therapy in this experimental model of heart failure did not reduce extracellular sodium, plasma vasopressin or the extent of ventricular hypertrophy, possibly because the condition was associated with activation of the renin-angiotensin system.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Cardiomegaly; Chlorothiazide; Chronic Disease; Diuretics; Female; Myocardial Infarction; Myocardium; Organ Size; Rats; Rats, Wistar; Sulfonamides; Time Factors; Ventricular Dysfunction, Left

Screening for patients with asymptomatic left ventricular dysfunction is of considerable importance because they may benefit from early treatment with angiotensin converting enzyme inhibitors. It has been suggested that atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and cyclic guanosine 3',5'-monophosphate (cGMP) might be useful markers for screening.. To compare directly the power of the three immunoreactive forms of ANP (CT-ANP, beta-ANP, NT-ANP) and BNP and cGMP to detect asymptomatic left ventricular dysfunction.. Radionuclide ventriculography was used to study left ventricular ejection fraction in 37 patients with asymptomatic left ventricular dysfunction, 32 patients with mild to moderate congestive heart failure, and 38 controls. CT-ANP, NT-ANP, beta-ANP, BNP, and cGMP were measured at rest and 3 minutes after exercise. Plasma BNP was the most sensitive marker for patients with asymptomatic left ventricular dysfunction but it reached only a sensitivity of 58% and a specificity of 76% at rest and a sensitivity of 65% and a specificity of 84% after exercise. Combined measurements of all natriuretic peptides and cGMP did not improve the power to detect asymptomatic left ventricular function above that of a single BNP measurement.. Although natriuretic peptides and cGMP measured at rest and three minutes after ergometry may be useful for monitoring left ventricular dysfunction they are unlikely to be suitable for more general routine screening for completely asymptomatic left ventricular dysfunction.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cyclic GMP; Exercise Test; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

Topics: Adult; Analysis of Variance; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Vessels; Diastole; Female; Femoral Vein; Humans; Male; Middle Aged; Myocardial Ischemia; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

To determine if plasma levels of atrial natriuretic peptide are elevated in patients with hypertrophic cardiomyopathy and to determine the relationship of atrial natriuretic peptide to symptoms and echocardiographic indices of left ventricular structure and diastolic function in these patients.. A prospective study in which atrial natriuretic peptide was measured in peripheral venous plasma in 14 patients (age 44 +/- 14 years) with hypertrophic cardiomyopathy and 17 healthy controls. Echocardiography was performed in all cases and 30 controls to examine indices of left heart structure and function. All patients underwent clinical evaluation.. The concentration of atrial natriuretic peptide was significantly higher in patients with hypertrophic cardiomyopathy than controls, (17.86 +/- 8.72 vs. 6.22 +/- 3.26 pmol/l, P = 0.0001). Diastolic dysfunction was observed in 11 of 14 patients with hypertrophic cardiomyopathy. No correlation was demonstrated between atrial natriuretic peptide levels and the degree of diastolic dysfunction, septal or free wall thickness, left atrial size, degree of mitral regurgitation or New York Heart Association functional class.. Plasma levels of atrial natriuretic peptide are elevated in patients with hypertrophic cardiomyopathy but do not correlate with symptoms or echocardiographically-derived indices of left ventricular structure or diastolic function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Case-Control Studies; Echocardiography; Female; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) plasma levels increase in patients with myocardial infarction and may reflect the degree of left ventricular dysfunction. The changes in plasma level of BNP during exercise in the recovery phase and the clinical significance were investigated in 60 patients (55 men and 5 women; mean age 62.3 +/- 9.8 years) with initial acute infarction. Cardiopulmonary exercise testing was performed with a treadmill using the ramp protocol in 60 patients in the first month and 46 in the third month after the onset of the disease. Blood samples for measuring BNP and atrial natriuretic peptide (ANP) were obtained in the resting control state and immediately after peak exercise. Plasma BNP in the first month had a significant negative correlation with anaerobic threshold (AT) and peak oxygen uptake (peak VO2), and the serial change in plasma BNP from the first to third month had a significant negative correlation with the serial change of AT (peak: r = -0.35, p < 0.05) and peak VO2 (rest: r = -0.35, p < 0.05; peak: r = -0.45, p < 0.01). The serial change of plasma ANP had no relationships with the serial change of AT or peak VO2. Because the serial change ratio of plasma BNP reflects the serial change of exercise tolerance in the recovery phase of myocardial infarction, we conclude that the serial measurement of plasma BNP level is a useful non-invasive parameter for predicting latent heart failure in patients with myocardial infarction.

Topics: Aged; Atrial Natriuretic Factor; Exercise; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Oxygen Consumption; Ventricular Dysfunction, Left

To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment.. Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides.. Cardiac catheterisation unit, Norwegian central hospital.. A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction.. The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction.. Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor.. Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide as indicators of normal and impaired ventricular function in an unselected group of patients with coronary heart disease and a high frequency of previous myocardial infarction was relatively modest.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Cardiac Catheterization; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Diastole; Forecasting; Heart Diseases; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prognosis; Regression Analysis; Systole; Ventricular Dysfunction, Left

Left ventricular diastolic dysfunction is common in patients with systolic heart failure and the restrictive type of filling pattern appears to be associated with increased cardiac mortality. Both artrial and brain (or ventricular) natriuretic peptides are also proven markers of the severity of heart failure. The aim of this study was to determine in a large cohort of patients with systolic heart failure whether diastolic abnormalities, and in particular the restrictive filling pattern of transmitral flow velocity, correlate with plasma atrial and brain natriuretic peptide levels.. Sixty-eight consecutive patients with symptomatic systolic heart failure (ejection fraction < 0.5) underwent two-dimensional Doppler echocardiography of left ventricular systolic and diastolic function, together with measurement of atrial and brain natriuretic peptides.. The restrictive filling pattern was present in 62%, the abnormal relaxation pattern in 31% and only 7% were normal. Atrial and brain natriuretic peptide (ANP/BNP) levels were significantly higher in the restrictive compared to the abnormal relaxation group (ANP: 202.2 +/- 31.7 vs 102.5 +/- 22.1 pg.ml-1, P = 0.012; BNP: 277.8 +/- 27.7 vs 162.4 +/- 21.9 pg.ml-1, P = 0.002). In addition, a restrictive filling pattern was associated with lower ejection fractions (P = 0.026), higher pulmonary artery systolic pressure (P < 0.001), larger left atrial size (P = 0.044), and were more likely to be in New York Heart Association class III or IV than those with an abnormal relaxation pattern (P = 0.007). Both atrial and brain natriuretic peptides correlated inversely with ejection fraction (P < 0.001), fractional shortening (P < 0.001), and positively with pulmonary artery pressure (P = 0.004 and 0.001 respectively). There were no significant correlations between single diastolic parameters and atrial or brain natriuretic peptide levels for the total patient group except between mitral peak A wave velocity and brain natriuretic peptides (r = -0.3, P = 0.01). For those with abnormal relaxation pattern mitral, valve E-wave deceleration time correlated significantly with both atrial and brain natriuretic peptide levels (P < 0.01).. This study confirms that the restrictive filling pattern of transmitral flow velocity is a marker of more severe heart failure, as indicated by its association with higher atrial and brain natriuretic peptide levels, lower ejection fraction and higher pulmonary artery pressure. Thus, this easily obtained Doppler-derived marker of diastolic dysfunction is useful for identifying those patients with more severe heart failure.

Topics: Aged; Atrial Natriuretic Factor; Cardiac Output, Low; Diastole; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Mitral Valve; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prognosis; Stroke Volume; Ventricular Dysfunction, Left

This study was designed to determine whether plasma brain natriuretic peptide (BNP) increases in response to exercise in patients with congestive heart failure and to show what kind of hemodynamic abnormalities induce increased secretion of BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP and hemodynamic parameters were measured during upright bicycle exercise tests in seven patients with dilated cardiomyopathy and nine with mitral stenosis. At rest, there were no intergroup differences in cardiac output or pulmonary capillary wedge pressure; however, the group with dilated cardiomyopathy had higher left ventricular end-diastolic pressures and lower left ventricular ejection fractions than did the group with mitral stenosis. Plasma ANP levels were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml) and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80 pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma concentration of BNP but not of ANP significantly correlated with left ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and BNP in the two groups. The dilated cardiomyopathy group had a larger increment in BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p < 0.05), although the increase in pulmonary capillary wedge pressure was greater in the mitral stenosis group. Thus exercise increases plasma levels of BNP, and impaired left ventricular function may be a main factor in the greater increment in BNP during exercise in patients with congestive heart failure.

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Catheterization, Peripheral; Exercise; Exercise Test; Heart Failure; Hemodynamics; Humans; Middle Aged; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Statistics, Nonparametric; Ventricular Dysfunction, Left

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction--a randomized clinical trial in patients with left ventricular ejection fraction < or = 35%. The variability of these hormones has not been determined in a large cohort of patients. Immediate (short-term) variability was assessed by systematically comparing levels after 15 and 30 minutes of supine rest at the initial visit, and longer term variability was assessed by comparing 30-minute supine rest values at the initial visit with corresponding values taken at 30 minutes after 16 to 24 days of stable therapy. Initial values obtained at the first visit after 30-minute supine rest for all 209 patients were (mean +/- SEM) 512 +/- 21 pg/ml pg/ml for plasma norepinephrine, 1.9 +/- 0.2 ng/ml/hr for plasma renin activity, 3.0 +/- 0.1 pg/ml for plasma arginine vasopressin, and 129 +/- 5.3 pg/ml for plasma atrial natriuretic peptide. All variables were moderately increased relative to established normal values. There was a small but significant decrease from 15- to 30-minute supine posture in all neurohormones, except arginine vasopressin. In the presence of stable background therapy, no significant differences were found between measurements obtained after 30 minutes supine rest at the initial visit and 16 to 24 days later. Spearman correlation coefficients corresponding to immediate and longer term variability were high (range 0.55 to 0.79) (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Biomarkers; Disease Progression; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Norepinephrine; Randomized Controlled Trials as Topic; Renin; Supine Position; Ventricular Dysfunction, Left

Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50 +/- 11 vs. 158 +/- 37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4 +/- 2.4 vs. 0.6 +/- 0.4 ng/ml per h, P < 0.05) and aldosterone (36.4 +/- 12.5 vs. 2.5 +/- 0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion and regulation of the RAAS in experimental ELVD.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Cyclic GMP; Disease Models, Animal; Dogs; Heart Atria; Hemodynamics; Kidney; Male; Polysaccharides; Renin; Renin-Angiotensin System; Second Messenger Systems; Ventricular Dysfunction, Left

The present study was designed to compare the secretion patterns of two cardiac hormones--A-type (atrial) and B-type (brain) natriuretic peptides--from the ventricles in patients with old myocardial infarction.. Plasma levels of these two natriuretic peptides are increased, and their secretion from the ventricles is augmented, in patients with congestive heart failure.. We measured the plasma levels of these two types of natriuretic peptides at the aortic root and the anterior interventricular vein in 42 patients with old myocardial infarction (anterior in 22 and inferior in 20) and 18 control subjects.. The difference between the plasma levels of both A- and B-type natriuretic peptide in the anterior interventricular vein and aortic root was significantly greater in the groups with anterior and inferior infarction than in the control group (A-type [mean +/- SD] 380 +/- 290 and 247 +/- 205 pg/ml in the infarction groups vs. 11 +/- 14 pg/ml; B-type 497 +/- 445 and 75 +/- 73 pg/ml vs. 23 +/- 16 pg/ml, respectively). The difference between the plasma levels of each peptide at the anterior interventricular vein and aortic root had a significant negative linear correlation with left ventricular ejection fraction in both groups with infarction. The slope of the regression line of the arteriovenous difference of B-type natriuretic peptide at the anterior interventricular vein was significantly steeper in the anterior than in the inferior infarction group (left ventricular ejection fraction -12.801 vs. -1.891, p < 0.01).. These results indicate that 1) the secretion of A- and B-type natriuretic peptide from the left ventricular increases in proportion to the severity of left ventricular dysfunction, and 2) secretion of B-type natriuretic peptide is much greater from the infarct than from the noninfarct region, suggesting that the regional ventricular wall stretch caused by infarction strongly stimulates secretion of B-type natriuretic peptide.

Topics: Atrial Natriuretic Factor; Cardiac Catheterization; Female; Hemodynamics; Humans; Linear Models; Male; Middle Aged; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Ventricular Dysfunction, Left

Plasma levels of endothelin-1 are increased in patients with severe congestive heart failure related to various etiologies. However, conflicting data have been published in patients with moderate congestive heart failure. Moreover, the effect of exercise on plasma levels of endothelin-1 is not precisely known. We determined the plasma levels of endothelin-1 in a homogenous group of patients with idiopathic dilated cardiomyopathy in stage II of the New York Heart Association functional classification at rest and at peak exercise. In this group of patients, plasma levels of endothelin-1 were increased compared to a control group (2.9 +/- 0.27 vs. 1.96 +/- 0.24 pmol/l, P < 0.01, mean +/- S.E.M.), as were plasma levels of atrial natriuretic peptide (26.3 +/- 6.3 vs. 2.95 +/- 0.7 pmol/l, P < 0.001), plasma renin activity (12.6 +/- 2.98 vs. 1.75 +/- 0.23 ng/ml per h, P < 0.001) and plasma levels of aldosterone (217 +/- 29.3 vs. 154 +/- 18.8 pg/ml, P < 0.05). In contrast to the other hormones, exercise did not increase plasma levels of endothelin-1. There was no correlation between plasma levels of endothelin-1 and plasma levels of atrial natriuretic peptide, and no correlation between left ventricular ejection fraction, peak oxygen consumption and hormonal values. In conclusion, plasma levels of endothelin-1 are increased in a homogeneous group of patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure. Endothelin-1 could participate in the progression of heart failure. Exercise did not increase the plasma levels of endothelin-1 in contrast to the other hormones.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Disease Progression; Endothelins; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Physical Exertion; Renin; Rest; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Experimental myocardial infarction is a model of cardiac overload in which part of the cardiac muscle is removed. The resulting left ventricle insufficiency depends on the size of the infarct and time. The infarcted area remodels, due to proteolytic activity of inflammatory cells and collagenogenesis from fibroblast activity. The phenotype of the residual healthy cardiac muscle undergoes modification, and there are peripheral vascular changes which are partly dependent on the activation of pressor systems and/or inactivation of dilator systems. The changes are proportional to the infarct size at any given time after induction of the model. The degree of right ventricular hypertrophy and the drop in arterial pressure are upstream and downstream markers of the loss of left ventricular function and therefore indicate the extent of the remodelling. The increase of type V3isomyosin, the amount of subendocardial collagen, and the biosynthesis, storage and secretion of atrial natriuretic factor (ANF) are all proportional to the infarct size and the degree of cardiac overload. The level of urinary cGMP is also correlated with infarct size. These indices show ventricular remodelling, increased stress and energy restriction of the residual healthy cardiac muscle. The activation of peripheral pressor systems also depends on infarct size. They reflect the influence of defective cardiac pumping on the kidney, liver, brain and endothelium. Massive infarcts are accompanied by an increase in circulating renin and in renal renin content, by a decrease in angiotensinogen due to its consumption by renin, and to its insufficient hepatic synthesis, and by an increase in vasopressin secretion and biosynthesis in the hypothalamus. Converting enzyme inhibition has beneficial effect in this model by lowering cardiac load. It reduces arterial pressure, reverses bi-atrial and right ventricular hypertrophy, reduces the changes in the myosin isoenzyme patterns, and normalizes subendocardial fibrosis and the level of ANF. Although the effects of converting enzyme inhibition are beneficial in this model, they are restricted by their inability to normalize the load and stress when the initial loss of cardiac contractile material exceeds 40%.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Atrial Natriuretic Factor; Collagen; Cyclic GMP; Hypertrophy, Left Ventricular; Indoles; Isoenzymes; Kidney; Myocardial Infarction; Myocardium; Myosins; Perindopril; Rats; Rats, Wistar; Renin; Vasopressins; Ventricular Dysfunction, Left