natriuretic-peptide--brain and Renal-Insufficiency

The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P < 0.01). This network meta-analysis is the first to find that finerenone 7.5-10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%.

Topics: Eplerenone; Heart Failure; Hospitalization; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Peptide, Brain; Network Meta-Analysis; Peptide Fragments; Randomized Controlled Trials as Topic; Renal Insufficiency; Spironolactone; Treatment Outcome

Cardiac biomarkers play important roles in routine evaluation of cardiac patients. But while these biomarkers can be extremely valuable, none of them should ever be used by themselves-without adding the clinical context. This paper explores the non-cardiac pathologies that can be seen with the cardiac biomarkers most commonly used.. High-sensitivity troponin assay gained FDA approval for use in the USA, and studies demonstrated its diagnostic utility can be extended to patients with renal impairment. Gender-specific cut points may be utilized for high-sensitivity troponin assays. In the realm of the natriuretic peptides, studies demonstrated states of natriuretic peptide deficiency in obesity and in subjects of African-American race. Regardless, BNP and NT-proBNP both retained prognostic utilities across a variety of comorbid conditions. We are rapidly gaining clinical evidence with use of soluble ST2 and procalcitonin levels in management of cardiac disease states. In order to get the most utility from their measurement, one must be aware of non-cardiac pathologies that may affect the levels of biomarkers as although many of these are actually true values, they may not represent the disease we are trying to delineate. A few take-home points are as follows: 1. A biomarker value should never be used without clinical context 2. Serial sampling of biomarkers is often helpful 3. Panels of biomarkers may be valuable.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Renal Insufficiency; Risk Assessment; Risk Factors; Stroke; Troponin

Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Renal Insufficiency; Renal Replacement Therapy

The incidence of hemodynamically significant patent ductus arteriosus (hsPDA) increases with decreasing gestational age and is associated with many common morbidities of extreme prematurity. Controversies remain surrounding the definition of hsPDA, the population of infants requiring treatment, the appropriate timing and method of treatment, and the outcomes associated with PDA and its therapies.. This integrative literature review focuses on diagnostic and treatment recommendations derived from the highest levels of evidence.. PubMed and CINAHL were searched using key words "neonatal" and "patent ductus arteriosus" to discover the highest levels of evidence surrounding diagnosis, treatment methods, and outcomes.. The lack of consensus surrounding the diagnosis and clinical significance of PDA hinders meta-analysis across studies and confounds understanding of appropriate management strategies. Novel biomarkers, pharmaceutical choices, and transcatheter closure methods are expanding diagnostic and treatment options.. Infants weighing less than 1000 g are at highest risk. Prophylactic closure is no longer recommended, although early asymptomatic therapy is still preferred by some to avoid prolonged pulmonary overcirculation or decreased renal and gut perfusion. Conservative treatment measures such as fluid restriction and diuretic administration have not consistently proven effective and are in some instances detrimental. Cyclooxygenase inhibitors are effective but have adverse renal and mesenteric effects. Oral ibuprofen is associated with lower instance of necrotizing enterocolitis.. Well-defined staging criteria would aid in comparison and meta-analysis. Trials that include a control group that receives no therapy may help separate the outcomes associated with prematurity from those associated with PDA.

Topics: Biomarkers; Cardiac Catheterization; Conservative Treatment; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Echocardiography; Enterocolitis, Necrotizing; Fluid Therapy; Gastrointestinal Hemorrhage; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency; Septal Occluder Device

Several studies indicated that B-type natriuretic peptide (BNP) assay is able to detect patients even in the early phases of heart failure (HF), when the myocardial remodeling process may be still reversible. BNP assay may assist the physician to initiate appropriate and prompt pharmacological treatments. However, clinical relevance and result interpretation of BNP assay for the guide of therapy or in particular clinical conditions, such as renal failure or treatment with inhibitors of enzymes degrading BNP in HF patients, are still debated. The aim of this article is to discuss some still controversial issues concerning the clinical use of measurement of cardiac natriuretic peptides, and also to provide a general overview and some perspectives related to pathophysiological mechanisms of HF.

Topics: Atrial Natriuretic Factor; Biomarkers; Forecasting; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Renal Insufficiency

Conflicting renal effects of nesiritide have been reported in patients with acute decompensated heart failure. To answer this controversy, we performed a meta-analysis of randomized controlled trials to evaluate the influence of nesiritide on renal function in patients with acute decompensated heart failure.. Articles were obtained from PubMed, Medline, Cochrane Library and reference review. Randomized controlled studies that investigated the effects of continuous infusion of nesiritide on renal function in adult patients with acute decompensated heart failure were included and analyzed. Fixed-effect model was used to estimate relative risk (RR) and weight mean difference (WMD). The quality assessment of each study, subgroup, sensitivity, and publication bias analyses were performed.. Fifteen randomized controlled trials were eligible for inclusion. Most of included studies had relatively high quality and no publication bias was found. Overall, compared to control therapies, nesiritide might increase the risk of worsening renal function in patients with acute decompensated heart failure (RR 1.08, 95% CI 1.01-1.15, P = 0.023). In subgroup analysis, high-dose nesiritide strongly associated with renal dysfunction (RR 1.54, 95% CI 1.19-2.00, P = 0.001), but no statistical differences were observed in standard-dose (RR 1.04, 95% CI 0.98-1.12, P = 0.213), low-dose groups (RR 1.01, 95% CI 0.74-1.37, P = 0.968) and same results were identified in the subgroup analysis of placebo controlled trials. Peak mean change of serum creatinine from baseline was no significant difference (WMD -2.54, 95% CI -5.76-0.67, P = 0.121).. In our meta-analysis, nesiritide may have a dose-dependent effect on renal function in patients with acute decompensated heart failure. High-dose nesiritide is likely to increase the risk of worsening renal function, but standard-dose and low-dose nesiritide probably have no impact on renal function. These findings could be helpful to optimize the use of nesiritide in clinical practice.

Topics: Creatinine; Dose-Response Relationship, Drug; Heart Failure; Humans; Kidney; Kidney Function Tests; Models, Statistical; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Risk

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Pre-Eclampsia; Pregnancy; Renal Insufficiency; Shock, Septic; Tissue Distribution

Acutely decompensated congestive heart failure is a major public health problem, with constantly rising prevalence, morbidity, mortality and need for hospitalization in both America and Europe. In 2001, the FDA approved the use of the drug nesiritide, which is a recombinant form of human brain or B-type natriuretic peptide (BNP) for the treatment of acutely decompensated congestive heart failure. In 2005, suspicions arose that nesiritide may worsen renal function and increase the risk of short term mortality when given to patients with acutely decompensated heart failure.. The present study reviews the recent literature with respect to the risk of deterioration in renal function and survival after the use of nesiritide in these patients.. Administration of nesiritide may be considered for the treatment of heart failure and especially in patients with dyspnea at rest or with minimal activity.. Extreme caution is required when using nesiritide in patients with both heart failure and concurrent morbidities such as renal dysfunction.

Topics: Blood Urea Nitrogen; Creatinine; Dyspnea; Heart Failure; Humans; Infusions, Intravenous; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Survival Analysis

Concomitant cardiac and renal dysfunction has been termed the cardiorenal syndrome (CRS). This clinical condition usually manifests as heart failure with worsening renal function and occurs frequently in the acute care setting. A consistent definition of CRS has not been universally agreed upon, although a recent classification of CRS describes several subtypes depending on the primary organ injured and the chronicity of the injury. CRS may develop in adults and children and is a strong predictor of morbidity and mortality in hospitalized and ambulatory patients. The underlying physiology of CRS is not well understood, creating a significant challenge for clinicians when treating heart failure patients with renal insufficiency. This review summarizes recent data characterizing the incidence, physiology, and management of children who have heart failure and acute kidney injury.

Topics: Acute Kidney Injury; Child; Creatinine; Heart Failure; Humans; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Renal Insufficiency, Chronic; Syndrome

One of the most important comorbidities in heart failure is renal dysfunction. Diminished estimated glomerular filtration rate is a potent predictor of cardiovascular mortality and complications. On the other hand, worsening heart failure or acute decompensated heart failure can accelerate worsening of renal function--the so-called cardiorenal syndrome. Risk factors include hypertension, diabetes, elderly age, and prior history of heart or renal failure. The pathophysiology of the cardiorenal syndrome involves intrarenal hemodynamics, transrenal perfusion pressure and systemic neurohormonal factors. Clinical management of the patient with cardiorenal syndrome includes the challenge of diuretic resistance, which may involve correcting the underlying cause, combination diuretics or diuretic infusions. The key to improved outcome is the optimization of proven heart failure therapies. The use of vasodilator therapy is the current mainstay of treatment. Nesiritide, or recombinant B-type natriuretic peptide, has courted controversy regarding its role in cardiorenal syndrome. However, data are emerging that low doses appear to be renal-protective. Other more recent strategies include ultrafiltration, vasopressin antagonists and adenosine antagonists. All of these newer modalities promise more rapid volume removal, but their ultimate impact on survival or preservation of renal function is unknown at the present time. Because of the complex nature of these patients, and the compromised outcome, it is important that cardiologists, nephrologists and internists all work together toward the common goal of protecting the patient with cardiorenal syndrome, and use the best available evidence for management.

Topics: Canada; Cardiology; Cardiotonic Agents; Combined Modality Therapy; Comorbidity; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Humans; Kidney Function Tests; Male; Natriuretic Peptide, Brain; Prognosis; Renal Dialysis; Renal Insufficiency; Risk Assessment; Severity of Illness Index; Survival Analysis; Syndrome; Treatment Outcome

B-natriuretic peptide (BNP) and aminoterminal proBNP (NT-proBNP) are clinically useful for the diagnosis of decompensated heart failure and for prognosis in heart failure and acute coronary syndromes. Clinical use of these biomarkers in critically ill patients being treated in intensive care is not well established.. This is a narrative review of evidence identified searching MEDLINE with the strategy [(BNP OR NT-proBNP) AND (critical illness AND intensive care)]. Seven primary reports and two narrative reviews were retrieved. For completeness, literature from each of the following searches was reviewed: [(BNP OR NT-proBNP) AND (critical illness)] and [(BNP OR NT-proBNP) AND (intensive care)].. Primary literature used BNP and NT-proBNP for diagnosis, prognosis and monitoring. For diagnosis of acute lung injury in unselected intensive care patients and for diagnosis of heart failure in trauma patients, the biomarkers had low sensitivity and are of modest use. BNP and NT-proBNP were found to have a significant ability to prognosticate adverse outcomes in critically ill patients. A single paper examined the use of BNP as a non-invasive replacement for pulmonary capillary wedge pressure, finding little value. The impact of renal insufficiency on the markers was noted as a confounder in most studies. In the secondary searches, some preliminary data suggested a possible role for the natriuretic peptides in exclusion of a cardiac cause for certain conditions among intensive care unit (ICU) patients. However, the general findings were that the performance of BNP and NT-proBNP is unimpressive among ICU patients.. Currently, utilization of BNP and NT-proBNP does not appear to provide much useful information or have a substantial role in the care of critically ill patients in intensive care.

Topics: Acute Lung Injury; Adult; Critical Care; Critical Illness; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency; Wounds and Injuries

Heart failure is one of the leading causes of hospitalizations in the United States. Concomitant and significant renal dysfunction is common in patients with heart failure. Increasingly, the syndrome of heart failure is one of cardiorenal failure, in which concomitant cardiac and renal dysfunctions exist, with each accelerating the progression of the other. One fourth of patients hospitalized for the treatment of acute decompensated heart failure will experience significant worsening of renal function, which is associated with worse outcomes. It remains unclear whether worsening renal function specifically contributes to poor outcomes or whether it is merely a marker of advanced cardiac and renal dysfunction. Diuretic resistance, with or without worsening renal function, is also common in acute decompensated heart failure, although the definition of diuretic resistance, its prevalence, and prognostic implications are less well defined. The term cardiorenal syndrome has been variably associated with cardiorenal failure, worsening renal function, and diuretic resistance but is more comprehensively defined as a state of advanced cardiorenal dysregulation manifest by one or all of these specific features. The pathophysiology of the cardiorenal syndrome is poorly understood and likely involves interrelated hemodynamic and neurohormonal mechanisms. When conventional therapy for acute decompensated heart failure fails, mechanical fluid removal via ultrafiltration, hemofiltration, or hemodialysis may be needed for refractory volume overload. While ultrafiltration can address diuretic resistance, whether ultrafiltration prevents worsening renal function or improves outcomes in patients with cardiorenal syndrome remains unclear. Evidence regarding the potential renal-preserving effects of nesiritide is mixed, and further studies on the efficacy and safety of different doses of nesiritide in heart failure therapy are warranted. Newer therapeutic agents, including vasopressin antagonists and adenosine antagonists, hold promise for the future, and clinical trials of these agents are underway.

Topics: Acute Disease; Adenosine; Cardiotonic Agents; Dopamine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Ultrafiltration; Vasopressins

B-Type natriuretic peptide (BNP) is elevated in states of increased ventricular wall stress. BNP is most commonly used to rule out congestive heart failure (CHF) in dyspneic patients. BNP levels are influenced by age, gender and, to a surprisingly large extent, by body mass index (BMI). In addition, it can be elevated in a wide variety of clinical settings with or without CHF. BNP is elevated in other cardiac disease states such as the acute coronary syndromes, diastolic dysfunction, atrial fibrillation (AF), amyloidosis, restrictive cardiomyopathy (RCM), and valvular heart disease. BNP is elevated in non-cardiac diseases such as pulmonary hypertension, chronic obstructive pulmonary disease, pulmonary embolism, and renal failure. BNP is also elevated in the setting of critical illness such as in acute decompensated CHF (ADHF) and sepsis. This variation across clinical settings has significant implications given the increasing frequency with which BNP testing is being performed. It is important for clinicians to understand how to appropriately interpret BNP in light of the comorbidities of individual patients to maximize its clinical utility. We will review the molecular biology and physiology of natriuretic peptides as well as the relevant literature on the utilization of BNP in CHF as well as in other important clinical situations, conditions that are commonly associated with CHF and or dyspnea.

Topics: Animals; Biomarkers; Comorbidity; Critical Illness; Dyspnea; Heart Diseases; Heart Failure; Humans; Lung Diseases; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency; Sensitivity and Specificity

Acute decompensated heart failure poses a complex clinical challenge for the health care community. Evolving concepts of the pathophysiology and lack of consensus on appropriate outcome measures for drug approval underlie some of the current controversies about nesiritide. We outline the major controversies from the viewpoint that nesiritide should continue to be used judiciously by following its package insert recommendations and the Heart Failure Society of America's 2006 Comprehensive Heart Failure Practice Guidelines.

Topics: Acute Disease; Evidence-Based Medicine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Patient Selection; Practice Guidelines as Topic; Renal Insufficiency

The use of nesiritide for acute decompensated heart failure (ADHF) has been clouded with controversy since its approval in 2001. Extensive marketing and many review articles have established this drug as a safe and superior product to current standards. However, its safety has been called into question by the results of a meta-analysis, and its superiority of important outcomes (length of stay, mortality, decreased readmission rate) has never been proved by a randomized trial against agents with similar vasodilator properties (e.g., nitroglycerin). A review of the available literature on nesiritide in the areas of mortality, renal effects, retrospective studies, use in off-label indications, length of stay, and mortality is presented and illustrates why its use should be limited or even eliminated. After review of this article, the reader should be able to answer the question--if nesiritide had never been approved for use in patients with ADHF, would we have missed it?--with a negative reply.

Topics: Acute Disease; Drug Labeling; Heart Failure; Humans; Length of Stay; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Readmission; Practice Guidelines as Topic; Renal Insufficiency; Research Design

Nesiritide is US Food and Drug Administration-approved for the treatment of patients with acutely decompensated heart failure who suffer from symptoms at rest or with minimal exertion. Its approval was based on a clinical development program that focused on surrogates and short-term effects on symptoms rather than clinical outcomes. The association between its use and subsequent risk of death raises the question of whether the endpoints assessed in the clinical development program were adequate, and provides the opportunity to evaluate the process of weighing risks with benefits. We conclude that with nesiritide, the risks of therapy outweigh the benefits demonstrated to date.

Topics: Acute Disease; Animals; Biomarkers; Clinical Trials as Topic; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis. This may then result in cardiac remodelling. Serum biomarkers are available which can be used for diagnosis of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The problems with potential ischaemia markers are specificity and the reference diagnostic standard against which they can be judged. To date, only one, ischaemia-modified albumin(R), has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, have become recognised as the diagnostic reference standard for myocardial necrosis. The sensitive nature of these tests has also revealed that myocardial necrosis is also found in a range of other clinical situations, highlighting the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B-type natriuretic peptides can be shown to be diagnostic and prognostic in both ACS and detecting the sequelae of post-infarction myocardial insufficiency. The role of the B-type natriuretic peptides in detection of cardiac failure, both acute and chronic, is well defined but remains the subject of further studies, in ACS.

Topics: Biomarkers; Cardiovascular Diseases; Choline; Electrocardiography; Fatty Acids, Nonesterified; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Renal Insufficiency; Serum Albumin; Syndrome; Troponin I; Troponin T

Nesiritide is a recombinant form of human B-type natriuretic peptide, a naturally occurring endogenous hormone released by cardiac ventricles in response to an increase in ventricular wall stress. Its use in the treatment of acute decompensated heart failure (ADHF) has been evaluated in a series of randomised controlled clinical trials. It is currently approved in the US for the treatment of ADHF. Nesiritide induces a balanced vasodilation and an indirect increase in cardiac output, but has no actual inotropic effects and exerts a neutral effect on heart rate. In addition, it inhibits adverse neurohormonal activation and, in some individuals, promotes natriuresis and diuresis. In adults with ADHF, nesiritide reduces pulmonary capillary wedge pressure, right atrial pressure and systemic vascular resistance; decreases symptoms of heart failure; and enhances global clinical status. Important questions regarding the risks of nesiritide therapy have recently been raised, and resolution of the safety of nesiritide is a process that remains in evolution. The most frequently reported adverse effect is dose-related hypotension. In addition, nesiritide may cause an acute increase in serum creatinine concentration. This increase seems to be a haemodynamic response to a combination of volume depletion, vasodilation and neurohormonal inhibition. Nesiritide-induced changes in renal function have not been definitively shown to negatively affect mortality. The effect of nesiritide on all-cause mortality is currently unresolved. Recent meta-analyses of existing databases have raised concerns regarding adverse effects of the drug on 30-day mortality. However, reviews of large, observational, registry databases do not suggest an adverse inpatient mortality effect compared with other vasodilator therapies. Further resolution of the mortality question awaits completion of pending randomised controlled clinical trials. When used for approved indications and according to recommended dosage and administration regimens, nesiritide represents a reasonable treatment adjunct for ADHF.

Topics: Acute Disease; Arrhythmias, Cardiac; Heart Failure; Hemodynamics; Humans; Hypotension; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Assessment

Acute decompensated heart failure (ADHF) represents the most common discharge diagnosis in patients over age 65, and has an exceptionally high mortality and read-mission risk. ADHF is characterized by abnormal hemodynamics, including increase in pulmonary capillary wedge pressure and peripheral vasoconstriction, although cardiac index may be reduced, normal, or increased. Myocardial injury, which may be related to decreased coronary perfusion, activation of neurohormones, and/or renal dysfunction, may contribute to short-term and postdischarge cardiovascular events. Recent ADHF registries have provided valuable insights into the characteristics, treatment patterns, and clinical outcomes of these patients. Most patients with ADHF present with either normal systolic blood pressure or elevated blood pressures; hypotension is relatively uncommon. These patients have significant cardiovascular and noncardiovascular comorbidities that may contribute to the pathogenesis and/or adverse outcomes in ADHF. Therapies for ADHF have been targeted to improve symptoms and hemodynamics, as well as preserve or improve renal function, prevent myocardial damage, modulate neurohumoral and inflammatory activation, and manage other comorbidities that may cause and/or contribute to the progression of this syndrome. Concomitant therapies proven to provide long-term benefits in chronic heart failure are also essential. There remains an unmet need for therapeutic approaches for the early management of ADHF that may improve short- and long-term outcomes. Ongoing clinical trials are intended to provide data that will better define the benefits and risks of therapies for ADHF.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Coronary Disease; Heart Failure; Hospital Mortality; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Assessment

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126 amino acid atrial natriuretic peptide (ANP), 108 amino acid B-type natriuretic peptide (BNP) and 103 amino acid C-type natriuretic peptide (CNP) prohormones). The ANP prohormone contains four peptide hormones: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide and ANP. 2. Currently, the only natriuretic peptide available commercially to treat congestive heart failure (CHF) is BNP (Nesiritide/Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post-nesiritide treatment, a finding that needs further investigation. 3. The best of the natriuretic peptides for treating chronic CHF is the vessel dilator, which increases urinary flow up to 13-fold and sodium excretion up to fourfold, without the previously mentioned side-effects. The natriuretic and diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF. 4. Atrial natriuretic peptide does not cause significant improvement in acute renal failure (ARF) in humans. The only natriuretic peptide that significantly improves ARF is the vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model, vessel dilator decreases serum creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the vessel dilator. After 6 days of treatment with the vessel dilator, the proximal and distal tubules regenerate. 5. In cancer, vessel dilator, LANP, kaliuretic peptide and ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate adenocarcinoma cells, as well as small cell and squamous cell lung cancer cells within 24 h. In vivo, vessel dilator, LANP and kaliuretic peptide completely stop the growth of human pancreati

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neoplasms; Renal Insufficiency

Hypertension involves the entire cardiovascular system, and hypertensive vascular disease may promote and exacerbate cardiac and renal dysfunction. We discuss the coexistence of cardiorenal disease as a manifestation of vascular involvement in hypertension, and the relationship of biomarkers of renal vascular involvement in hypertension with cardiovascular endpoints.. Markers of renal dysfunction, especially microalbuminuria, have been considered recently as potent predictors of cardiovascular morbidity and mortality in all explored populations, including hypertensive individuals. Microalbuminuria, per se, is related to vascular injury and to the increased glomerular permeability of albumin as a direct manifestation of renal vascular involvement in hypertension, a systemic vascular disease. Left ventricular hypertrophy in hypertension develops even before proteinuria or impairment of renal function. Factors including anemia, inflammation and hyperuricemia are either induced or exacerbated by renal vascular disease, and each of these may exert additional influence in determining the increased incidence of cardiovascular events with progressive renal dysfunction.. The development and progression of vascular disease is the primary determinant in the progressive cardiac and renal dysfunction observed in hypertension and, therefore, is the underlying mechanism of the overall clinical manifestations of cardiorenal disease. Commonly used biomarkers of renal and vascular function are important tools for determination of the progression and, hence, management of hypertensive disease and its complications.

Topics: Albuminuria; Biomarkers; C-Reactive Protein; Disease Progression; Erythropoietin; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; Natriuretic Peptide, Brain; Renal Insufficiency; Uric Acid

Standard therapy for acute decompensated heart failure, a major health problem, consists of intravenous diuretics, vasodilators, and positive inotropic agents. Nesiritide, a recombinant form of human B-type natriuretic peptide, is the only drug specifically approved for this indication. Recent meta-analyses have reported an increased risk of worsening renal function and 30-day mortality with nesiritide administration. These data understandably require physicians to carefully reevaluate their current use of nesiritide in patients with acute decompensated heart failure. In performing this reevaluation, it is important to consider our understanding of the underlying disease state, the limitations and results of these meta-analyses, and new data that provide additional insight into the possible risks and benefits associated with nesiritide therapy. Until additional therapeutic trials are conducted, therapeutic choices must be based on symptomatic and hemodynamic improvement and limited, imperfect available data, which may continue to support the use of nesiritide for its established indication.

Topics: Acute Disease; Creatinine; Decision Making; Heart Failure; Humans; Meta-Analysis as Topic; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Research Design; Risk Assessment; Risk Factors

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

Renal insufficiency is becoming an increasingly common and devastating comorbidity in both acute and chronic heart failure settings. Part of the problem is due to the lack of insight into the underlying pathophysiology of salt and water balance leading to the congestive states. This review summarizes our current understanding regarding the cause and consequences of renal insufficiency in patients with heart failure, and addresses some of the limitations of current therapeutic strategies. Based on these limitations, this paper will explore the ongoing efforts to develop novel drug therapeutics to prevent or ameliorate renal impairment in patients with heart failure. These include natriuretic peptides and other vasodilators, adenosine receptor antagonists, and vasopressin receptor antagonists all currently undergoing late-stage clinical trials.

Topics: Adenosine; Angiotensin-Converting Enzyme Inhibitors; Antidiuretic Agents; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Neurotransmitter Agents; Prognosis; Renal Insufficiency; Treatment Outcome; Vasodilator Agents; Vasopressins

Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF.. Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine >0.5 mg/dL. Relative risk across all studies was determined by meta-analysis with Mantel-Haenszel fixed-effects models (RR(MH)). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration-approved doses of nesiritide (< or =0.03 microg x kg(-1) x min(-1)) significantly increased the risk of worsening renal function compared with non-inotrope-based control (RR(MH), 1.52; 95% CI, 1.16 to 2.00; P=0.003) or any control therapy, including non-inotrope- and inotrope-based therapies (RR(MH), 1.54; 95% CI, 1.19 to 1.98; P=0.001). Even low-dose nesiritide (< or =0.015 microg x kg(-1) x min(-1)) significantly increased risk (P=0.012 and P=0.006 compared with non-inotrope- and inotrope-based controls, respectively), as did nesiritide administered at any dose up to 0.06 microg x kg(-1) x min(-1) (P=0.002 and P=0.001, respectively). There was no difference in the need for dialysis between therapies.. Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.

Topics: Creatine; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Risk

Congestive heart failure remains a severe condition. Risk stratification is necessary to assess the prognosis and discuss the potential timing of heart transplant. Numerous criteria have been used, which may be combined to define prognostic scores which, however, are rarely used in routine. A few items, however, may be used to stratify the risk of mortality and sudden death.

Topics: Coronary Angiography; Echocardiography; Heart Failure; Humans; Hypertension; Liver Failure; Natriuretic Peptide, Brain; Oxygen Consumption; Renal Insufficiency; Risk Assessment; Stroke Volume

Biochemical markers are available to detect cardiac involvement in many pediatric disease states and should be considered.. Analyses of three markers are readily available in clinical laboratories for improved diagnosis.. Increased workload of the heart has been associated with the release of biochemical markers (natriuretic peptides and cardiac enzymes) that indicate that a new genetic program has been activated and maladaptation is occurring in the atria, ventricles, or both. This review summarizes those that have been identified in fetal and pediatric practice. The expression of such markers is traced from early embryonic development to fetal life, to the neonate, to childhood, and then to adult life.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Biomarkers; Child; Graft Rejection; Heart Diseases; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Renal Insufficiency; Sepsis; Troponin T

Topics: Atrial Natriuretic Factor; Biomarkers; Glomerular Filtration Rate; Humans; Natriuretic Peptide, Brain; Prognosis; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency

To assess prognostic meaning of worsening renal failure (WRF) occurring during management of chronic heart failure (HF) with reduced ejection fraction.. When WRF develops during titration of HF medical therapy, it commonly leads to less aggressive care.. A total of 151 patients enrolled in a prospective, randomized study of standard of care (SOC) HF therapy versus SOC plus a goal N-terminal pro-B type natriuretic peptide (NT-proBNP) < 1000 pg/mL were examined. Cardiovascular (CV) event (defined as worsening HF, hospitalization for HF, significant ventricular arrhythmia, acute coronary or cerebral ischemia, or CV death) at 1 year relative to WRF (defined as any reduction in estimated glomerular filtration rate) 90 days postenrollment were tabulated.. Those developing WRF by 3 months had an average 14% reduction in estimated glomerular filtration rate. There was no difference in incidence of WRF between study arms (43% in SOC, 57% in NT-proBNP, P = .29). During the first 3 months of therapy titration, incident WRF was associated with numerically fewer CV events at 1 year compared with those without WRF (mean 0.81 vs 1.16 events, P = .21). WRF was associated trend toward fewer CV events in the SOC arm (hazard ratio 0.45, 95% confidence interval 0.16-1.24, P = .12); the NT-proBNP-guided arm had numerically lower CV event rates regardless of WRF. Subjects with NT-proBNP <1000 pg/mL and WRF received higher doses of guideline directed medical therapies, lower doses of loop diuretics, and had significantly lower CV event rates (P < .001).. Modest degrees of WRF are common during aggressive HF with reduced ejection fraction management, but we found no significant association with CV outcomes. HF care guided by NT-proBNP was not associated with more WRF compared with SOC, and led to benefit regardless of final renal function.

Topics: Aged; Analysis of Variance; Biomarkers; Chronic Disease; Cohort Studies; Disease Progression; Diuretics; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prospective Studies; Renal Insufficiency; Risk Assessment; Severity of Illness Index; Stroke Volume; Survival Analysis; Time Factors; Treatment Outcome

This study aims to investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function and contrast-induced nephropathy (CIN) incidence in ST-segment elevation myocardial infarction and heart failure (STEMI-HF) patients with mild renal insufficiency undergoing primary percutaneous coronary intervention (PCI). A total of 116 participants were randomized into rhBNP (rhBNP, n = 57) and nitroglycerin group (NIT, n = 59), receiving intravenous rhBNP or nitroglycerin from admission to 72 h after PCI. Renal function was assessed by serum creatinine (SCr), estimated glomerular filtration rate (eGFR), Cystatin-C (Cys-C) and β2-microglobulin before and after primary PCI, and calculated the incidence of CIN within 72 h after PCI. There were no significant differences in SCr, eGFR and β2-microglobulin between the two groups (P > 0.05, respectively). Compared with the NIT group, the total urinary volume within 72 h was higher while the level of Cys-C at 24 and 72 h after PCI was lower in the rhBNP group. rhBNP was associated with a decline in the incidence of CIN (12.28 vs. 28.81 %, P < 0.05). No differences were detected in mortality and re-hospitalization in 3 months between the two groups. The incidence of renal injury was not different between rhBNP and nitroglycerin in STEMI-HF patients with mild renal insufficiency. However, infusion of rhBNP was associated with a decline in incidence of CIN.

Topics: Creatinine; Electrocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Recombinant Proteins; Renal Insufficiency; ST Elevation Myocardial Infarction

Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown.. 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01).. NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chronic Disease; Disease Management; Dizziness; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Quality of Life; Renal Insufficiency; Surveys and Questionnaires; Treatment Outcome

Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment.. The Answering question on tolvaptan's efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m(2) will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide.. This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109).

Topics: Acute Disease; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Diuretics; Drug Therapy, Combination; Furosemide; Glomerular Filtration Rate; Heart Failure; Humans; Japan; Natriuretic Peptide, Brain; Prospective Studies; Renal Insufficiency; Research Design; Tolvaptan

Mineralocorticoid receptor antagonist (MRA) use in acutely decompensated chronic heart failure (ADCHF) may improve congestion through diuretic effect and prevent neurohormonal activation. We aimed to evaluate the clinical effect and safety of spironolactone in ADCHF.. Prospective, experimental, single-center, and single-blinded trial. Patients were treated with: standard ADCHF therapy or oral spironolactone 50-100mg/d plus standard ADCHF therapy.. During a 1year period, 100 patients were enrolled, 50 included in the treatment group. Mean (SD) spironolactone dose (mg) at day 1 was 94.5±23.3 and at day 3 was 62.7±24.3. Worsening renal function (increase in pCr≥0.3mg/dL from day 1 to day 3) was more likely to occur in control group (20% vs. 4%; p=0.038), serum potassium did not differ between groups, and plasma NTproBNP had a significant decrease in spironolactone group at day 3 (median [IQR], 2488 [4579] vs. 1555 [1832]; p=0.05). Furthermore, a greater proportion of patients in the treatment group were free of congestion at day 3: less edema, rales, jugular venous pressure (JVP) and orthopnea (all, p<0.05). In addition, a significantly higher proportion of patients were on oral furosemide at day 3 (44% vs. 82%; p<0.001).. Our study supports the safety of high dose spironolactone in ADCHF and suggests a positive impact in the resolution of congestion. The important findings of our pilot study need to be confirmed in larger trials.

Topics: Acute Disease; Aged; Aged, 80 and over; Chronic Disease; Disease Progression; Diuretics; Edema; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Potassium; Pulmonary Edema; Renal Insufficiency; Single-Blind Method; Spironolactone; Treatment Outcome

Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers.. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers.. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders.. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function.

Topics: Aged; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency; Troponin I

The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study.. N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed.. Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median.. NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Female; Humans; Male; Membranes, Artificial; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Permeability; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Renal Insufficiency; Risk Factors; Survival Analysis; Treatment Outcome

The aim of this study was to evaluate the mode of death and hospitalizations in advanced heart failure (HF) patients with renal dysfunction and to examine the rate of concordance between events reported by the clinical events committee and site investigators (using case report forms) in the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Little is known about the cause of death and hospitalization in patients with advanced HF. FUSION II was a randomized, double-blind, placebo-controlled trial evaluating outpatient nesiritide infusions versus placebo, with 911 patients with advanced HF (New York Heart Association class III or IV) and renal dysfunction enrolled. There were 151 deaths and 1,041 hospitalizations at 24 weeks. The clinical events committee classified events as cardiac, renal, cardiorenal, other or noncardiovascular, or unknown. Kappa statistics and McNemar tests were used to assess agreement (overall and by individual modes of death and hospitalization indications). In conclusion, the most common cause of death or hospitalization was cardiac related, with 70% of deaths and 60% of hospitalizations due to cardiac causes. There was 74% agreement (26% disagreement) on cardiac cause of death (κ = 0.40, McNemar p = 0.001) and 75% agreement (25% disagreement) between the investigators and the clinical events committee on cardiac classification for hospitalization (κ = 0.49, McNemar p <0.0001).

Topics: Aged; Cause of Death; Clinical Trials Data Monitoring Committees; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Infusion Pumps; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Renal Insufficiency; Research Personnel

Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use.. Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One-year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique.. We identified key predictors of survival based on the patient's most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.

Topics: Adult; Aged; Blood Pressure; Carbon Monoxide; Disease-Free Survival; Female; Heart Rate; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Registries; Renal Insufficiency; Survival Rate; Vascular Resistance

Left ventricular (LV) hypertrophy is a powerful predictor of mortality in dialysis patients. Serial measurements of LV mass provide prognostic information. We evaluated the association between changes in biomarkers and changes in LV mass index (LVMI) in hemodialysis (HD) patients.. This was a prospective study of 21 stable HD patients with preserved LV ejection fraction (> or =50%). Echocardiography and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and cardiac troponin T were performed on the same day and repeated 6 and 12 months later.. At baseline, the NT-proBNP and BNP levels correlated with LVMI. Percent changes in LVMI were positively associated with those in log-transformed NT-proBNP levels during both the first (baseline vs. month 6, r = 0.78, p < 0.001) and the second 6 months (months 6 vs. 12, r = 0.73, p < 0.001). Among the 3 biomarkers, NT-proBNP was the only one that was related to changes in LVMI by multivariate correlation analysis, including age, sex, blood pressure, predialysis weight and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.. Our results show that changes in LVMI are closely correlated with variation in NT-proBNP levels in HD patients. These data have significant implications for the application of NT-proBNP as a biomarker for assessing changes in LVMI in HD patients.

Topics: Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Renal Dialysis; Renal Insufficiency; Ventricular Dysfunction, Left

We examined the mechanisms of renal resistance to atrial and brain natriuretic peptides (ANP and BNP) in pulmonary hypertension (PH). Compared to eight controls, nine PH patients showed a reduced ability to excrete an acute sodium load despite increased circulating ANP, BNP and cyclic guanosine monophosphate (cGMP), their second messenger. Patients' reduced urinary cGMP/BNP and natriuresis/urinary cGMP ratios demonstrated impaired generation of and reduced renal response to cGMP, respectively. Therefore, PH patients hyporesponsiveness to cardiac natriuretic peptides is likely located both upstream and downstream cGMP generation. Natriuretic peptide signalling pathway disruptions might be accessible to therapy.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Cyclic GMP; Down-Regulation; Female; Humans; Hypertension, Pulmonary; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Reference Values; Renal Insufficiency; Renin; Signal Transduction; Sodium Chloride

This retrospective substudy of the Follow-Up Serial Infusions of Nesiritide trial (FUSION I) assessed the feasibility of outpatient administration of nesiritide in 138 patients with co-morbid advanced heart failure and renal insufficiency (estimated creatinine clearance<60 ml/min). Patients received 1 of 3 treatments once weekly for 12 weeks: standard care (SC), SC plus nesiritide 0.005 microg/kg/min, or SC plus nesiritide 0.010 microg/kg/min. The addition of nesiritide to SC was well tolerated, with no evidence of worsening renal function, compared with SC only and was associated with a reduction in the rate of all-cause hospitalization or mortality through week 12, with hazard ratios of 2.027 (95% confidence interval 1.165 to 3.525) and 2.219 (95% confidence interval 1.233 to 3.992) for the SC-only group compared with the SC plus 0.005 microg/kg/min and SC plus 0.010 microg/kg/min nesiritide groups, respectively. These findings raise the hypothesis that adjunctive therapy with nesiritide on an outpatient basis may be beneficial for patients with advanced heart failure and renal insufficiency. Further study is warranted to test the validity of this finding.

Topics: Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Outpatients; Renal Insufficiency; Retrospective Studies; Severity of Illness Index; Survival Rate; Treatment Outcome

Nesiritide (B-type natriuretic peptide) reduces preload and afterload, and causes natriuresis, diuresis and suppression of norepinephrine, endothelin-1 and aldosterone. In this study, we sought to explore the safety and efficacy of nesiritide in patients with acute congestive heart failure (CHF) and renal insufficiency (RI).. We studied the effects of nesiritide in patients with RI in the VMAC trial database, a multi-centre, randomized controlled trial (n = 489) of patients with acute decompensated CHF.. The mean serum creatinine (SCr) in nesiritide-treated patients with RI (SCr > or = 2.0 mg/dl, n = 60, range 2.0-11.1 mg/dl) and without RI (SCr < 2.0 mg/dl, n = 209) was 3.0+/-1.51 and 1.2+/-0.34 mg/dl, respectively. Pulmonary capillary wedge pressure (PCWP) was reduced significantly and similarly in both RI and no RI groups starting at 15 min into nesiritide infusion from a baseline of 29.9+/-8.1 and 26.6+/-6.0 mmHg, respectively. Addition of placebo to standard therapies yielded no further improvement in PCWP in patients with RI; in contrast, nesiritide significantly reduced PCWP at every time point during 24 h. The effects of nitroglycerin were less robust than those of nesiritide, and PCWP was not significantly reduced by nitroglycerin at the 3 h primary end-point. At 24 h, 83% of the RI patients and 91% of patients without RI treated with nesiritide reported improvements in dyspnoea. Nesiritide was well tolerated in patients with RI and no RI, and renal function was preserved in both groups.. In patients with RI, nesiritide was safe and improved haemodynamics and dyspnoea.

Topics: Acute Disease; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heart Failure; Heart Function Tests; Humans; Infusions, Intravenous; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Probability; Reference Values; Renal Insufficiency; Risk Assessment; Severity of Illness Index; Survival Rate; Treatment Outcome

The association between N-terminal pro brain natriuretic peptide (NT-proBNP) level and long-term mortality in Japanese hemodialysis patients has not been fully assessed.. This prospective, multicenter study included 1428 hemodialysis outpatients. Baseline NT-proBNP levels were measured at the first hemodialysis session of the week and participants were followed for 5 years. The areas under the curve were calculated from receiver operating characteristic curves. Groups determined by quartiles of baseline NT-proBNP level were assessed by the Kaplan-Meier method and log-rank test. The association between NT-proBNP level and mortality was assessed using multivariate Cox proportional hazards models.. During the 5-year follow-up, we observed 370 deaths and 256 censored cases. The areas under the curve of pre-hemodialysis NT-proBNP for all-cause mortality and cardiovascular disease mortality after 1 year were 0.75 and 0.78, respectively, and significantly greater than the areas under the curve at the 3- and 5-year follow-up. Cut-off values for all-cause mortality and cardiovascular disease mortality after 1 year were 4550 and 5467 ng/L, respectively (sensitivity: 82% and 81%; specificity: 59% and 64%). Kaplan-Meier survival analysis showed that the group with pre-hemodialysis NT-proBNP ≥ 8805 ng/L had increased all-cause mortality (P < 0.001) and cardiovascular disease mortality (P < 0.001). Finally, multivariate Cox analysis showed that NT-proBNP level was associated with all-cause mortality (P < 0.001) and cardiovascular disease mortality (P = 0.004) independently from other clinical parameters.. NT-proBNP is a useful marker to predict both all-cause and cardiovascular disease mortality in hemodialysis patients.

Topics: Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Cardiovascular Diseases; Cause of Death; Female; Follow-Up Studies; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Renal Insufficiency; ROC Curve

Reduced nitric oxide (NO) and a decrease in cGMP signaling mediated by soluble guanylate cyclase (sGC) has been linked to the development of several cardiorenal diseases. Stimulation of sGC is a potential means for enhancing cGMP production in conditions of reduced NO bioavailability. The purpose of our studies was to determine the effects of praliciguat, a clinical-stage sGC stimulator, in a model of cardiorenal failure. Dahl salt-sensitive rats fed a high-salt diet to induce hypertension and organ damage were treated with the sGC stimulator praliciguat to determine its effects on hemodynamics, biomarkers of inflammation, fibrosis, tissue function, and organ damage. Praliciguat treatment reduced blood pressure, improved cardiorenal damage, and attenuated the increase in circulating markers of inflammation and fibrosis. Notably, praliciguat affected markers of renal damage at a dose that had minimal effect on blood pressure. In addition, liver fibrosis and circulating markers of tissue damage were attenuated in praliciguat-treated rats. Stimulation of the NO-sGC-cGMP pathway by praliciguat attenuated or normalized indicators of chronic inflammation, fibrosis, and tissue dysfunction in the Dahl salt-sensitive rat model. Stimulation of sGC by praliciguat may present an effective mechanism for treating diseases linked to NO deficiency, particularly those associated with cardiac and renal failure. Praliciguat is currently being evaluated in patients with diabetic nephropathy and heart failure with preserved ejection fraction.

Topics: Animals; Biomarkers; Blood Pressure; Chemokine CCL2; Cyclic GMP; Fibrosis; Guanylyl Cyclase C Agonists; Inflammation; Kidney; Male; Natriuretic Peptide, Brain; Nitric Oxide; Osteopontin; Peptide Fragments; Pyrazoles; Pyrimidines; Rats; Rats, Inbred Dahl; Renal Insufficiency; Signal Transduction; Soluble Guanylyl Cyclase; Tissue Inhibitor of Metalloproteinase-1

Coronary microvascular dysfunction (CMVD) is associated with adverse cardiovascular outcome. We aimed to determine the prevalence of CMVD and factors related to index of microcirculatory resistance (IMR) in consecutive patients with chronic coronary syndrome (CCS) undergoing elective coronary angiography.. Non-interventional physicians enrolled 274 patients with CCS before angiography, to minimize selection bias by PCI-operators. Fractional flow reserve (FFR) and IMR were measured in the LAD. Subjects with extensively diseased LAD, no measures due to technical reasons or violation of protocol were excluded from the analysis (n = 54). The proportion of patients with IMR corrected for collateral flow (IMR. We report that IMR

Topics: Coronary Angiography; Coronary Stenosis; Coronary Vessels; Fractional Flow Reserve, Myocardial; Hemoglobins; Humans; Microcirculation; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Renal Insufficiency; Vascular Resistance

Acute declines in kidney function occur in approximately 20%-30% of patients with acute decompensated heart failure, but its significance is unclear, and the importance of its context is not known. This study aimed to determine the prognostic value of a decline in kidney function in the context of decongestion among patients admitted with acute decompensated heart failure.. Using data from patients enrolled in the Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome Study (CARRESS) and Diuretic Optimization Strategies Evaluation (DOSE) trials, we used multivariable Cox regression models to evaluate the association between decline in estimated glomerular filtration rate (eGFR) and change in N-terminal pro-b-type natriuretic peptide (NT-proBNP) with a composite outcome of death and rehospitalization, as well as testing for an interaction between the two.. Among 435 patients, in-hospital decline in eGFR was not significantly associated with death and rehospitalization (hazard ratio [HR] = 0.89 per 30% decline, 95% confidence interval [CI] 0.74, 1.07), whereas decline in NT-proBNP was associated with lower risk (HR = 0.69 per halving, 95% CI 0.58, 0.83). There was a significant interaction (P = 0.002 unadjusted; P = 0.03 adjusted) between decline in eGFR and change in NT-proBNP where a decline in eGFR was associated with better outcomes when NT-proBNP declined (HR = 0.78 per 30% decline in eGFR, 95% CI 0.61, 0.99), but not when NT-proBNP increased (HR = 0.99, 95% CI 0.76, 1.30).. Decline in kidney function during therapy for acute decompensated heart failure is associated with improved outcomes as long as NT-proBNP levels are decreasing as well, suggesting that incorporation of congestion biomarkers may aid clinical interpretation of eGFR declines.

Topics: Acute Disease; Aged; Aged, 80 and over; Cardio-Renal Syndrome; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency

A prognostic equation and risk score calculator derived from the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) are being used to predict 1-year survival in patients with pulmonary arterial hypertension (PAH), but little is known about the performance of these REVEAL survival prediction tools in systemic sclerosis (SSc)-associated PAH (SSc-PAH).. Prospectively gathered data from the Johns Hopkins Pulmonary Hypertension Program and Pulmonary Hypertension Assessment and Recognition of Outcome in Scleroderma Registries were used to evaluate the predictive accuracy of the REVEAL models for predicting the probability of 1-year survival in patients with SSc-PAH. Model discrimination was assessed by comparison of the Harrell's C-index, model fit was assessed using multivariable regression techniques, and model calibration was assessed by comparing predicted to observed survival estimates.. The validation cohort consisted of 292 SSc-PAH patients with a 1-year survival rate of 87.4%. The C-index for predictive accuracy of the REVEAL prognostic equation (0.734, 95% confidence interval [95% CI] 0.652-0.816) and for the risk score (0.743, 95% CI 0.663-0.823) demonstrated good discrimination, comparable to that in the model development cohort. The calibration slope was 0.707 (95% CI 0.400-1.014), indicating that the overall model fit was marginal (P = 0.06). The magnitude of risk assigned to low distance on the 6-minute walk test (6MWD) and elevated serum levels of brain natriuretic peptide (BNP) was lower in the validation cohort than was originally seen in the REVEAL derivation cohort. Model calibration was poor, particularly for the highest risk groups.. In predicting 1-year survival in patients newly diagnosed as having SSc-PAH, the REVEAL prognostic equation and risk score provide very good discrimination but poor calibration. REVEAL prediction scores should be interpreted with caution in newly diagnosed SSc-PAH patients, particularly those with higher predicted risk of poor 1-year survival resulting from a low 6MWD or a high BNP serum level.

Topics: Aged; Atrial Pressure; Blood Pressure; Comorbidity; Female; Heart Rate; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Arterial Hypertension; Renal Insufficiency; Reproducibility of Results; Risk Assessment; Scleroderma, Systemic; Severity of Illness Index; Survival Rate; Vascular Resistance; Walk Test

Topics: Aged; Biomarkers; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Multiple Myeloma; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renal Dialysis; Renal Insufficiency

While persons with overt renal failure have a well-described rise in troponin and NT-proBNP, it is less well described what the relationship is between cardiac markers and persons with impaired renal function, not requiring dialysis.. We have collected ALL samples referred to our pathology practice over a 24h period and measured hs-cTnI, hs-cTnT, NT-proBNP, calculated the eGFR, and related our measurements to clinical outcomes.. For both men and women, for all of hs-cTnI, hs-cTnT and NT-proBNP, there was a graded response, as renal function worsened, the concentration of the cardiac marker increased.. There is a graded inverse relationship between eGFR and the concentrations of hs-cTnI, hs-cTnT and NT-proBNP. For women only there appeared to be an increase in mortality at lowest eGFR.

Topics: Biomarkers; Creatinine; Female; Humans; Male; Natriuretic Peptide, Brain; Outpatients; Renal Insufficiency; Troponin C

Worsening renal function (WRF) occurs in one-third of patients hospitalized for acute decompensated heart failure. Recently, WRF was categorized in two subtypes: persistent and transient WRF. Thus, we sought to investigate the different prognostic impact of persistent vs. transient WRF; we also evaluate the relation of two WRF phenotypes with congestion, B-type natriuretic peptide (BNP) changes, and diuretic response at discharge.. The prospective was a single centre study including patients screened for interventional Diur-heart failure Trial (NCT01441245). Patients were eligible if they were admitted with a primary diagnosis of acute heart failure with evidence of volume overload. Persistent WRF was defined as a sustained creatinine increase by at least 0.3 mg/dl throughout the hospitalisation; transient WRF was defined as creatinine increase by at least 0.3 mg/dl within 72 h and a return to baseline levels at discharge. Patients were followed for 6 months after discharge.. Our population included 192 acute decompensated heart failure patients. In total, 61 patients developed persistent WRF and 29 developed transient WRF. Patients with persistent WRF showed a lower mean urine output with respect to the transient WRF group and patients with preserved renal function (1618 ± 374 vs. 2132 ± 392 vs. 2075 ± 442 ml; P < 0.001). Similarly, patients with transient WRF demonstrated a higher rate of BNP decrease more than 30% than seen in patients with stable creatinine levels and in the persistent WRF group (95 vs. 76 vs. 54%; P = 0.001). Univariate Cox regression analysis demonstrated that BNP decrease less than 30% [HR 2.15 (1.40-3.40); P < 0.001] and persistent WRF [HR 1.70 (1.11-2.61); P = 0.01] were related to poor outcome; conversely, transient WRF should be considered as a protective factor [HR 0.42 (0.19-0.93); P = 0.03]. In the multivariable model, only persistent WRF appeared to be related to poor prognosis [HR 1.61 (1.02-2.57); P = 0.04].. WRF occurring during hospitalization has a different significance: transient deterioration appears to be associated with a favourable clinical course; conversely, persistent WRF is related to poor outcome.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Renal Insufficiency; Retrospective Studies; ROC Curve

Cardiopulmonary bypass usage provokes a systemic inflammatory response resulting in deterioration of renal function. However, risk factors for requiring renal replacement therapy (RRT) following off-pump coronary artery bypass graft surgery (CABG) have not yet been fully elucidated. We reviewed 718 consecutive patients undergoing elective off-pump CABG at our institution, excluding patients on chronic hemodialysis preoperatively. Sub-analysis of patients with preserved renal function, defined as a creatinine level below a cut-off value of 1.12 mg/dL (obtained by receiver operating characteristic curve), was also performed. Of the 718 patients, 41 (5.7 %) required RRT. There were 556 patients (77.4 %) with preserved renal function preoperatively, and 13 (2.4 %) of these required postoperative RRT. Multivariate analysis revealed that age (years) and preoperative serum creatinine (mg/dL) and brain natriuretic peptide (BNP) levels (pg/dL) were associated with RRT [odds ratios (OR) 1.052, 95 % confidence interval (CI) 9.064 and 1.001, respectively, all p < 0.05] in the total population, whereas low albumin concentration was the only independent predictor for RRT in patients with preserved renal function (OR 0.062, p < 0.0001). When creatinine levels were below 1.5 mg/dL, the predictive power of hypoalbuminemia for RRT requirement overwhelmed that of creatinine or BNP levels. Older age, preoperative elevated creatinine and BNP levels were associated with a requirement for RRT following off-pump CABG. In patients with preserved renal function, hypoalbuminemia was most significantly related to the RRT requirement.

Topics: Aged; Aged, 80 and over; Coronary Artery Bypass, Off-Pump; Creatinine; Female; Humans; Hypoalbuminemia; Japan; Kidney Function Tests; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Postoperative Complications; Renal Insufficiency; Renal Replacement Therapy; Risk Factors; ROC Curve

To characterize a novel "worst"-symptom visual analogue scale (WS-VAS) versus the traditional dyspnea visual analogue scale (DVAS) in an acute heart failure (AHF) trial.. AHF trials assess symptom relief as a pivotal endpoint with the use of dyspnea scores. However, many AHF patients' worst presenting symptom (WS) may not be dyspnea. We hypothesized that a WS-VAS may reflect clinical improvement better than DVAS in AHF.. AHF patients (n = 232) enrolled in the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) Trial indicated their WS at enrollment and completed DVAS and WS-VAS at enrollment and 24, 48, and 72 hours. Dyspnea was the WS in 61%, body swelling in 29%, and fatigue in 10% of patients. Clinical characteristics differed by WS. In all patients, DVAS scores were higher (less severe symptoms) than WS-VAS and the change in WS-VAS over 72 hours was greater than the change in DVAS (P < .001). Changes in DVAS were smaller in patients with body swelling and fatigue than in patients with dyspnea as their WS (P = .002), whereas changes in the WS-VAS were similar regardless of patients' WS. Neither score, nor its change, was associated with available decongestion markers (change in N-terminal pro-B-type natriuretic peptide, weight or cumulative 72-hour urine volume).. Many AHF patients have symptoms other than dyspnea as their most bothersome symptom. The WS-VAS better reflects symptom improvement across the spectrum of AHF phenotypes. Symptom relief and decongestion were not correlated in this AHF study.

Topics: Acute Disease; Aged; Biomarkers; Diuretics; Dyspnea; Edema; Fatigue; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pain Measurement; Prognosis; Renal Insufficiency; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes.. Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions.. A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo. Linear regression models for continuous endpoints and Cox models for time-to-event endpoints were used.. Of the 1,076 patients with available baseline hsTnT values, 107 (9.9%) had low hsTnT. No cardiovascular (CV) deaths through day 180 were observed in the low-hsTnT group compared with 79 CV deaths (7.3%) in patients with higher hsTnT. By univariate analyses, low hsTnT was associated with lower risk for all 5 primary outcomes: 1) days alive and out of the hospital by day 60; 2) CV death or rehospitalization for heart failure or renal failure by day 60; 3) length of stay; 4) worsening heart failure through day 5; and 5) CV death through day 180. After multivariate adjustment, only 180-day CV mortality remained significant (hazard ratio: 0.0; 95% confidence interval: 0.0 to 0.736; p = 0.0234; C-index = 0.838 [95% confidence interval: 0.798 to 0.878]).. No CV deaths through day 180 were observed in patients with hsTnT levels ≤0.014 μg/l despite high N-terminal pro-brain natriuretic peptide levels. Low baseline hsTnT may identify patients with acute heart failure at very low risk for CV mortality.

Topics: Acute Disease; Aged; Aged, 80 and over; Cardiovascular Diseases; Comorbidity; Emergency Service, Hospital; Female; Heart Failure; Humans; Kidney Failure, Chronic; Length of Stay; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Relaxin; Renal Insufficiency; Risk Assessment; Treatment Outcome; Troponin T

The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients.. OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CACS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations. Cardiovascular and overall mortality data were collected during a 7-years follow-up.. OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age.. Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Proportional Hazards Models; RANK Ligand; Renal Insufficiency; Solubility; TNF-Related Apoptosis-Inducing Ligand

CHD patients, especially those with associated hypoxaemia, usually have some level of renal function impairment, even though they are relatively young. The aim of the study was to evaluate those clinical and analytical factors that may contribute to microalbuminuria and determine the association of 24-hour proteinuria with thrombotic events and mortality.. A total of 251 CHD patients were studied and demographic characteristics, blood test, and 24-hour urinalysis were analysed.. Of the patients, 221 were non-hypoxaemic, and 30 were hypoxaemic (oxygen saturation of 84.3±5.9%). Of the non-hypoxaemic patients, 30 (13.6%), and of the hypoxaemic patients 9 (30%), showed proteinuria (>0.15 g/24 hours) (p=0.028). Hypoxaemic CHD patients also showed higher haematocrit (%) (50.7 (34.6; 72.1) versus 42.8 (34.6; 48.9), p<0.001), serum creatinine (mg/dl) (1.07±0.2 versus 0.96±1.9, p=0.004), microalbuminuria (mg/dl/24 hours) (1.2 (0.0; 261.5) versus 0.5 (0.0; 4.37), p<0.001), proteinuria (gr/24 hours) (1.0 (0.4; 3.1) versus 0.08 (0.04; 0.52), p=0.043), and N-terminal pro-B-type natriuretic peptide (pg/ml) (417.8 (35.7; 8534.0) versus 44.9 (0.0; 670.5), p<0.001) concentrations than non-hypoxaemic CHD patients. During a median follow-up of 26.0 (16.9; 57.7) months, five patients died - one patient had 24-hour proteinuria and four patients did not (p=0.581) - and three patients had some type of thrombosis - two patients had 24-hour proteinuria and one patient did not (p=0.014). Kaplan-Meier survival analysis showed no significant difference between CHD patients with and without 24-hour proteinuria (p=0.631).. CHD patients with proteinuria have significantly more thrombosis and more hypoxaemia than those patients without proteinuria.

Topics: Adolescent; Adult; Albuminuria; Creatinine; Female; Heart Defects, Congenital; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Outcome Assessment; Peptide Fragments; Proteinuria; Renal Insufficiency; Thrombosis; Young Adult

To compare noninvasive methods to assess pulse wave velocity (PWV) with the invasive gold standard in terms of absolute values, age-related changes, and relationship with subclinical organ damage.. Invasive aortic PWV (aoPWVinv) was measured in 915 patients undergoing cardiac catheterization (mean age 61 years, range 27-87 years). Carotid-femoral PWV (cfPWV) was measured with tonometry, using subtracted distance (cfPWVsub), body height-based estimated distance (cfPWVbh), direct distance × 0.8 (cfPWVdir0.8), and caliper-based distance (cfPWVcalip) for travel distance calculation. Aortic PWV was estimated (aoPWVestim) from single-point radial waveforms, age, and SBP.. Invasive and noninvasive transit times were strikingly similar (median values 60.8 versus 61.7 ms). In the entire group, median value of aoPWVinv was 8.3 m/s, of cfPWVsub and cfPWVbh 8.1 m/s, and of aoPWVest 8.5 m/s. CfPWVsub overestimated aoPWVinv in younger patients by 0.7 m/s and underestimated aoPWVinv in older patients by 1.7 m/s, with good agreement from 50 to 70 years of age. AoPWVestim differed from aoPWVinv by no more than 0.4 m/s across all age groups. CfPWVdir0.8, measured in 632 patients, overestimated aoPWVinv by 1.7 m/s in younger patients, with good agreement in middle-aged and older patients. CfPWVcalip, measured in 336 patients, underestimated aoPWVinv in all ages. In 536 patients with preserved systolic function, aoPWVinv and aoPWVestim were superior to cfPWVs in predicting coronary atherosclerosis, renal function impairment, left atrial enlargement, and diastolic dysfunction.. CfPWVsub, cfPWVdir0.8, and aoPWVestim are reasonable surrogates for aoPWVinv. AoPWVinv predicts subclinical organ damage better than cfPWVs, and as good as aoPWVestim.

Topics: Adult; Aged; Aged, 80 and over; Aging; Aorta; Body Height; Cardiac Catheterization; Cardiovascular Diseases; Carotid Arteries; Coronary Angiography; Coronary Artery Disease; Diastole; Echocardiography; Female; Femoral Artery; Humans; Male; Manometry; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulsatile Flow; Pulse Wave Analysis; Renal Insufficiency; Systole; Ventricular Dysfunction, Left

To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA.. We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA.. A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055).. Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Topics: Aged; Angioplasty; Diabetes Mellitus; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Kidney Function Tests; Male; Natriuretic Peptide, Brain; Renal Artery; Renal Artery Obstruction; Renal Insufficiency; Risk Factors

This study sought to assess the relationship between serum concentrations of the soluble ST2 (sST2) and B-type natriuretic peptide (BNP) and investigate the role of sST2 as a prognosticator in patients hospitalized with acute heart failure (HF) and renal insufficiency. sST2 was measured at admission and discharge in 66 patients hospitalized with acute decompensated HF and renal insufficiency (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m(2)) using a high sensitivity immunoassay. BNP was sampled at the same time and compared to sST2. Demographical, biochemical, and echocardiographic data were also obtained during hospitalization.There were positive correlations between sST2 and BNP levels at admission (r = 0.330, P = 0.007) and at discharge (r = 0.320, P = 0.009) in overall patients. However, there was no correlation between them at each timepoint in patients with severe renal insufficiency (eGFR < 30 mL/min/1.73 m(2), n = 17). sST2 level was not changed with the degree of renal function, even though BNP level was much higher in patients with severe renal insufficiency. During 3 month follow-up, 9 (13.6%) died and 16 (24.2%) were readmitted due to HF aggravation.On multivariate analysis, sST2 at discharge was independently associated with death or HF readmission during 3 months after discharge (hazard ratio, 1.038; 95% confidence interval, 1.011-1.066, P = 0.006). In conclusion, sST2 is not affected by renal function compared with BNP in acute HF patients. The measurement of predischarge sST2 can be helpful in predicting short-term outcomes in acute decompensated HF patients with renal insufficiency.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Demography; Echocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Immunoassay; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Receptors, Cell Surface; Renal Insufficiency; Young Adult

To investigate the long-term prognostic significance of baseline plasma IL-8 levels in a group of well-characterized male patients presenting with acute coronary syndrome.. IL-8 is a cytokine that has been implicated in the pathogenesis of atherosclerosis and acute coronary syndrome. Elevated plasma levels have been reported in patients with acute coronary syndrome.. Baseline plasma IL-8 levels were measured in 180 male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for the development of all-cause mortality for 5 years.. In a multivariate model that included a wide variety of baseline clinical, laboratory and angiographic parameters in the selection process, baseline plasma IL-8 levels (analyzed as a continuous variable) emerged as a significant predictor of all-cause mortality at 5 years (HR, 1.43; 95% CI, 1.08-1.88; p = 0.0123). Furthermore, in 3 additional multivariate models that also included in the selection process a number of contemporary biomarkers with established prognostic efficacy in ACS (i.e., NT-proBNP, hs-CRP, hemoglobin and RDW), IL-8 remained an independent predictor of all-cause mortality at 5 years.. Elevated baseline plasma levels of IL-8 are associated with an increased risk of long-term all-cause mortality in patients with acute coronary syndrome. Furthermore, this association is independent of a variety of clinical, laboratory and angiographic variables, including contemporary biomarkers with established prognostic efficacy in acute coronary syndrome.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Atherosclerosis; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Erythrocytes; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Humans; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renal Insufficiency

Few studies have attempted to evaluate the relationship between peritoneal permeability and fluid status in peritoneal dialysis (PD). The aim of the present study was to clarify the relationship between change in the dialysate-to-plasma ratio of creatinine (D/P Cr) and change in fluid status as evaluated by natriuretic peptides. We studied 49 PD patients (29 men, 62 ± 11 years, 36.7% with diabetes) who underwent a peritoneal equilibration test at least twice after PD initiation. We evaluated correlations between the rate of change in the D/P Cr (R C-D/P Cr), the rate of change in a human atrial natriuretic polypeptide (RC-αhANP), and the rate of change in brain natriuretic peptide (RC-BNP). The RC-αhANP was strongly correlated with RC-BNP (r = 0.637, p < 0.001). In contrast, the RC-D/P Cr was not correlated with RC-αhANP (r = 0.041, p = 0.781) or with RC-BNP (r = 0.114, p = 0.435). However, positive correlations between RC-D/P Cr and RC-αhANP (r = 0.530, p = 0.006) and between RC-D/P Cr and RC-BNP (r = 0.625, p = 0.001) were observed in patients with increased D/P Cr The present study showed a positive correlation between change in peritoneal transport characteristics and change influid status in patients whose D/P Cr increased.

Topics: Aged; Atrial Natriuretic Factor; Biological Transport; Creatinine; Dialysis Solutions; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis; Peritoneum; Permeability; Renal Insufficiency; Retrospective Studies

Kidney function and cardiovascular disease are closely connected and albuminuria is a proven marker of cardiovascular risk. The present study investigated the prevalence and characteristics of albuminuria in patients with hypertension. Outpatients with essential hypertension under medical treatment were enrolled in this study (n = 350, 70.0 ± 11.4 years old). Urine samples were collected for the measurement of albumin concentration, which are expressed as the ratio of urine albumin to creatinine concentration (mg/g Cr). Cross-sectional analyses were also performed of the relationships between urinary albumin and other variables. Urinary albumin was detected in 88.3% of patients, while only 35.4% showed abnormal albuminuria (≥30 mg/g Cr). The presence of abnormal albuminuria was independently correlated with systolic blood pressure, B-type natriuretic peptide, and C-reactive protein by multivariate analysis (P < 0.05). Furthermore, multivariate regression analysis identified systolic blood pressure, serum creatinine, B-type natriuretic peptide, and C-reactive protein as the only factors showing independent correlation with urinary albumin (P < 0.05). Thus, approximately 35% of hypertensive patients had abnormal albuminuria. Urinary albumin was closely associated with blood pressure, C-reactive protein, and B-type natriuretic peptide, indicating that the severity of albuminuria parallels that of systemic inflammation, cardiac load, and blood pressure.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Albuminuria; Biomarkers; Blood Pressure; C-Reactive Protein; Creatinine; Cross-Sectional Studies; Female; Humans; Hypertension; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors; Young Adult

Topics: Adult; Aged; Cohort Studies; Drug Administration Schedule; Female; Heart Failure; Heart, Artificial; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used prognostic parameter in patients with pre-capillary pulmonary hypertension (PH). As it accumulates in the presence of impaired renal function, the clinical utility of NT-proBNP in PH patients with concomitant renal insufficiency remains unclear. In a retrospective approach, patients with pre-capillary PH (group I or IV) and concomitant renal insufficiency at time of right heart catheterization (glomerular filtration rate (GFR) ≤60 ml/min/1.73 m2) were identified out of all prevalent pre-capillary PH patients treated at a single center. Forty patients with renal insufficiency (25.8%) were identified and matched regarding hemodynamic parameters with a control group of 56 PH patients with normal renal function (GFR >60 ml/min/1.73 m2). Correlations of NT-proBNP levels with hemodynamic and prognostic parameters (time to clinical worsening and overall survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had the strongest influence on NT-proBNP levels in a stepwise multiple linear regression model including hemodynamic parameters and age (r2 = 0.167). PH patients with renal insufficiency had significant higher levels of NT-proBNP (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated with invasive hemodynamic parameters in these patients. Using higher cut-off values than in patients with preserved renal function, NT-proBNP levels were significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001) and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency. Multivariate Cox's proportional hazards analysis including established prognostic parameters, age and GFR confirmed NT-proBNP as an independent risk factor for clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p = 0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels correlated with hemodynamic parameters and outcome regardless of renal function. By using higher cut-off values, NT-proBNP seems to represent a valid clinical marker even in PH patients with renal insufficiency.

Topics: Aged; Biomarkers; Capillaries; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency; Survival Analysis; Time Factors

Topics: Adenocarcinoma; Aged, 80 and over; Atrial Fibrillation; Cecal Neoplasms; Diagnosis, Differential; Diuretics; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Postoperative Period; Renal Insufficiency; Water-Electrolyte Balance

Preexisting renal failure diminishes the excretion of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), therefore limits the diagnostic value of this peptide for concomitant heart failure. The aim of this study was to evaluate the association between NT-proBNP and the stages of renal dysfunction in a typical population attended to emergency department with acute dyspnea.. In this cross-sectional study, all consecutive patients with acute dyspnea underwent clinical evaluation, laboratory assessment of NT-proBNP, and echocardiographic examinations. Among subjects, 54.5% were diagnosed as heart failure. Grouping variables according to renal function capacity and ejection fraction, independent variables were compared with Kruskal-Wallis or ANOVA with posthoc tests. Correlation and linear regression analysis were done to analyze the variables associated with NT-proBNP. The diagnostic performance of NT-proBNP was evaluated by receiver-operating characteristic (ROC) curve.. Serum median NT-proBNP level in patients with severe renal impairment was significantly higher than moderate and mildly decreased renal functions (p=0.001). In patients with moderate and severe left ventricular failure, NT-proBNP was significantly higher compared with normal subjects (LVEF>50%) (p=0.040, and 0.017, respectively). Renal dysfunction was associated in 56% of patients with heart failure. The area under the ROC curve of NT-proBNP for identifying left ventricular failure in patients with renal failure (eGFR<90 mL/min/1.73 m2) was 0.649 and reached significant difference (95% CI:0.548-0.749, p=0.005).. In addition to NT-proBNP measurement in clinical judgement of heart failure, renal functions have to be taken into consideration to avoid misdiagnosis.

Topics: Biomarkers; Cross-Sectional Studies; Dyspnea; Echocardiography; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Patient Admission; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency; ROC Curve

Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR).. We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro-B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: (a) annual percent change in eGFR, (b) rapid kidney function loss (> 3% per year for 5 years), and (c) incident eGFR < 60 mL/min per 1.73 m2. In multivariable models, we adjusted for demographics, comorbid conditions, echocardiographic parameters, medications, and baseline kidney function.. Among 535 participants, median NT-proBNP was 130.6 (interquartile range 61.8-280.9) pg/mL, and median B-type natriuretic peptide (BNP) was 32.5 (14.4-75.9) pg/mL. Individuals with NT-proBNP levels in the highest quartile (> 280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR < 60 mL/min per 1.73 m2 were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor.. N-terminal pro-B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD.

Topics: Aged; Asymptomatic Diseases; Biomarkers; Coronary Artery Disease; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renal Blood Flow, Effective; Renal Insufficiency; Risk Factors; United States; Ventricular Function

Few data are available to assess whether a low-moderate reduction in estimated glomerular filtration rates (eGFR) has a role per se on cardiovascular (CV) mortality or other biomarkers such as NT-proBNP allow to explain such association.. In a prospective study including 1,645 type 2 diabetic subjects of the population-based Casale Monferrato Study, who had no clinical evidence of heart failure and eGFR >45 ml/min/1.73 m2, we examined 6 years CV mortality. Multivariate Cox proportional hazards modeling were used to estimate the effect of NT-proBNP on the association between eGFR and mortality, independently of baseline CV risk factors, albumin excretion rate (AER) and C-reactive protein (CRP). During follow-up, 327 people died (149 of CV diseases) out of 8334.5 person-years. Compared to eGFR≥90 ml/min/1.73 m2, values of 60-89 and 45-59 ml/min/1.73 m2 conferred a fully adjusted hazard ratios (HRs) of CV mortality of 1.74 (1.08-2.82) and 1.95 (1.03-3.68), respectively. After further adjustment for NT-proBNP, however, HRs were no longer significant (HRs 1.42, 0.83-2.42 and 1.22, 0.59-2.51). In this model, HR for logNT-proBNP was 1.84 (1.52-2.22). Adding NT-proBNP to the model improved the C-statistic of CV mortality from 0.79 (0.76-0.83) to 0.84 (0.81-0.87), yielded an IDI of 0.03 (p = 0.02), and a NRI of 0.44 (p = 0.016).. In diabetic people a modest reduction in renal function increased 6-year CV mortality independently of albuminuria. This association, however, was mainly explained by the effect of NT-proBNP, that remained the strongest prognostic marker for a worse CV outcome, even after adjustment for other CV risk factors and pre-existing CVD.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency

Arterial stiffness is an established cardiovascular risk marker and an independent predictor of cardiovascular events and mortality in various groups of patients, including renal transplant recipients. Recent studies have noted that B-type natriuretic peptide (BNP) acts as a local paracrine molecule that modulates endothelial permeability and regeneration. The aim of this study was to evaluate the relationship between the serum N-terminal pro-BNP (NT-pro-BNP) level and arterial stiffness in renal transplant recipients.. Fasting blood samples were obtained from 66 renal transplant recipients. The cardio-ankle vascular index was calculated using the waveform device (CAVI-VaSera VS-1000). The serum NTpro-BNP levels were measured using an electrochemiluminescence immunoassay. A CAVI value of ≥9 was used to define a high level of arterial stiffness.. Thirty-two patients (48.5%) were classified into the high arterial stiffness group. Diabetes (p=0.030), smoking (p<0.001), duration of kidney transplantation (p=0.001), body weight (p=0.014), waist circumference (p=0.022), body mass index (p=0.001) and the fasting glucose (p=0.021) and serum NT-pro-BNP (p<0.001) levels were higher in the high arterial stiffness group than in the low arterial stiffness group. A multivariate forward stepwise linear regression analysis showed that the log-NT-pro-BNP level (β: 0.459, p<0.001) remained an independent predictor of the CAVI value in the renal transplant recipients.. The serum fasting NT-pro-BNP level is associated with arterial stiffness in renal transplant recipients.

Topics: Adult; Aged; Ankle Joint; Body Mass Index; Body Weight; Electrochemistry; Female; Humans; Immunoassay; Kidney Transplantation; Luminescence; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency; Risk Factors; Smoking; Vascular Stiffness

To analyse the relationship between objectively measured daily walking duration and cardiovascular biomarkers of inflammation, cardiac dysfunction and renal impairment.. Between March 2009 and April 2010, physical activity was assessed in 1253 community-dwelling individuals living in Germany aged ≥65 years (57% men) over 1 week using a thigh-worn accelerometer. C reactive protein (CRP), white blood cells (WBC), N-terminal pro-brain natriuretic peptide, high-sensitive troponin T (hsTnT), creatinine (Cr) and cystatin C (CysC) were also measured. Least-square means of daily walking duration were calculated for quartiles of each biomarker adjusted for sex, age, pre-existing cardiovascular disease and smoking status.. After adjustment for covariates, statistically significant linear associations with walking duration were observed for WBC, hsTnT, Cr and CysC. CRP quartiles 1 and 2 showed no significant difference followed by a significant inverse dose-response relationship. A similar pattern, but less pronounced, was seen for N-terminal pro-brain natriuretic peptide. Mean differences between the first two quartiles of CRP and its fourth quartile were 17 min. Between categories 1 (more beneficial) and 4 of WBC, hsTnT, Cr and CysC the differences were 15, 12, 23 and 20 min, respectively.. Increased walking duration is associated with a more favourable profile of cardiovascular biomarkers in elderly subjects.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Female; Germany; Humans; Inflammation; Male; Motor Activity; Natriuretic Peptide, Brain; Peptide Fragments; Population Surveillance; Renal Insufficiency; Risk Factors; Time Factors; Troponin I; Walking

Although tolvaptan is a recently approved drug for heart failure and causes aquaresis without affecting renal function, its clinical efficacy for patients with acute decompensated heart failure (ADHF) is yet to be elucidated.. We conducted a prospective observational study in patients with ADHF and high risk for worsening renal function (WRF). Risk stratification for WRF was done by scoring system. Of 174 patients, 114 patients were included as high-risk population for WRF. Incidence of WRF, urine output within 24h and 48 h, and changes in brain natriuretic peptide (BNP) were recorded in 44 patients treated with tolvaptan plus conventional therapy, and 70 patients with only conventional therapy. Urine output at 24h and 48 h after admission were both significantly higher in the tolvaptan group (p=0.001 and <0.001, respectively), and changes in BNP were not significantly different (p=0.351). However, the incidence of WRF was significantly lower in the tolvaptan group compared to the conventional group (22.7% vs 41.4%, p=0.045). Logistic regression analysis showed that treatment with tolvaptan was an independent factor for reducing WRF (hazard ratio 0.28, 95% confidence interval; 0.10-0.84; p=0.023).. In patients with ADHF with high risk of WRF, treatment with tolvaptan could prevent WRF compared to conventional therapy.

Topics: Acute Disease; Aged; Aged, 80 and over; Benzazepines; Comparative Effectiveness Research; Creatinine; Diuresis; Diuretics; Female; Furosemide; Heart Failure; Humans; Hypernatremia; Kidney Function Tests; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Renal Insufficiency; Time Factors; Tolvaptan; Urination

N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used for risk stratification in acute pulmonary embolism (PE). We aimed to clarify the impact of renal function on the validity of the NT-proBNP based prognosis, assuming that the biomarker is accumulated in renal insufficiency. The NT-proBNP based prediction of PE related in-hospital death was investigated according to renal function in 329 patients with acute PE. The normalized NT-proBNP ratios (NT-proBNP level divided by the age-adjusted normal upper range) were inversely correlated (r = -0.414, P < 0.001) to the estimated glomerular filtration rates (eGFR). A cut-off point of ≥ 2.5 for the normalized NT-proBNP ratio was found to be best for the prediction of mortality (AUC 0.716, 95% CI 0.626-0.805, P < 0.001) and was a significant predictor for death in univariate and multivariate analysis. A normalized NT-proBNP ratio ≥ 2.5 was a significant predictor for PE-mortality only in patients with an eGFR ≥ 60 ml/min/1.73 m². Renal insufficiency significantly predicted mortality in univariate but not in multivariate analysis. High-risk PE and cerebrovascular diseases were significantly more frequent in renal dysfunction and significantly predicted death in univariate and multivariate analysis. The validity of the NT-proBNP based short-term prognosis might be limited in renal dysfunction not only by accumulation, but also because renal insufficiency itself and concurrent conditions are contributing to PE related mortality.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Embolism; Renal Insufficiency; Retrospective Studies; Time Factors

Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes.. In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded.. The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 μmol/l (range 101.1-743.5 μmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model.. Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.

Topics: Albuminuria; Atherosclerosis; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency; Risk Factors; Uric Acid

The diagnostic value of N-terminal pro-brain natriuretic peptide (NT-pro BNP) for heart failure with preserved ejection fraction (EF; HF-PEF) was evaluated in hemodialysis (HD) patients.. In total, 83 patients were analyzed. Left-ventricular (LV) function was assessed using trans-thoracic Doppler echocardiography, and indices of hydration status were assessed using bioelectrical impedance analysis. Plasma NT-pro BNP levels were measured simultaneously.. A moderate negative correlation was found between NT-pro BNP and LVEF. Subsequently, 77 HD patients who maintained their LVEF (LVEF >50%) were analyzed. Patients with a clinical suspicion of LV diastolic dysfunction (LVDD; E/A ≤0.75) showed higher NT-pro BNP levels (p = 0.021), but no significant differences in hydration status were observed between the two groups.. The NT-pro BNP level may be a very helpful biomarker in screening for LVDD and HF-PEF and determining the need for echocardiography or a sophisticated cardiac study, even in HD patients.

Topics: Aged; Echocardiography, Doppler; Heart Failure; Heart Ventricles; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency; Ventricular Dysfunction, Left; Ventricular Function, Left; Water-Electrolyte Balance

Worsening renal function in patients admitted with heart failure is associated with increased morbidity. These changes are not usually apparent initially and often take up to 48 hours to be detected. Using the novel technique of metabolomic analysis, this study aims to determine if markers of renal injury are identifiable at presentation that are associated with the development of worsening renal function in high-risk patients with heart failure.. A prospective exploratory study enrolled a convenience sample of patients with suspected heart failure. Eligible patients had to be older than 18 years, have a B-type natriuretic peptide (BNP) level over 100 pg/mL, have a history of diabetes or hypertension, meet Boston criteria for heart failure (>8), and require hospital admission as judged by the treating physician. Patients receiving no more than one dose of diuretic prior to enrollment were excluded. Urine was collected during the emergency department (ED) stay. Initial creatinine and the peak value between 24 to 48 hours were used to determine worsening renal function as defined by a change of >0.3 mg/dL or absolute 25% increase. Urine samples underwent gas chromatography/mass spectrometry (GC/MS) profiling. Peak metabolite values were measured and data were log-transformed. Partial least squares-discriminant analysis (PLS-DA) was used to identify metabolites associated with worsening renal function. Specific urinary metabolites were ranked based on their regression coefficients.. The 24 enrolled subjects had a median age of 58 years (interquartile range [IQR] = 49.5 to 67.5 years) with 58% being male. Worsening renal function occurred in 10 subjects (41.7%). A total of 156 metabolites were identified. The optimal number of metabolites for class discrimination as determined by PLS-DA was three, with a classification accuracy of 78%. These metabolites were taurine, sulfuric acid, and talose.. Urinary metabolites found at the time of presentation may be markers of early renal injury. It is therefore possible that the process of renal injury is initiated prior to ED arrival in patients with suspected heart failure, and these may be used to identify a high-risk patient population.

Topics: Aged; Biomarkers; Creatinine; Discriminant Analysis; Female; Gas Chromatography-Mass Spectrometry; Glycine; Heart Failure; Humans; Inositol; Lactones; Male; Metabolomics; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Renal Insufficiency; Sulfuric Acids; Taurine

Topics: Ambulatory Care; Female; Heart Failure; Humans; Kidney; Male; Natriuretic Peptide, Brain; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Renal Insufficiency; Renal Insufficiency, Chronic

Guidelines recommend hospice care as a treatment option for end-stage heart failure (HF) patients. Little is known regarding utilization of hospice care in a contemporary cohort of patients hospitalized with HF and how this may vary by estimated mortality risk.. We analyzed HF patients ≥65 years (n = 58,330) from 214 hospitals participating in the Get With the Guidelines-HF program. Univariate analysis comparing patients discharged to hospice versus other patients was performed. Hospice utilization was evaluated for deciles of estimated 90-day mortality risk using a validated model. Multivariate analysis using admission patient and hospital characteristics was also performed to determine factors associated with hospice discharge.. There were 1,442 patients discharged to hospice, and rates of referral varied widely by hospital (interquartile range 0-3.7%) as shown in the univariate analysis. Patients discharged to hospice were significantly older and more often white, had lower left ventricular ejection fraction, higher B-type natriuretic peptide, and lower systolic blood pressure on admission. Utilization rates for each decile of 90-day estimated mortality risk ranged from 0.3% to 8.6%. Multivariable analysis found that factors associated with hospice utilization included increased age, low systolic blood pressure on admission, and increased blood urea nitrogen.. Hospice utilization remains low among HF patients, even those with the highest predicted risk of death.

Topics: Aged; Aged, 80 and over; Blood Pressure; Cohort Studies; Female; Heart Failure; Heart Rate; Hospice Care; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Patient Discharge; Prospective Studies; Renal Insufficiency; Risk Assessment; Stroke Volume; United States

Dual renin-angiotensin system (RAS) blockade has no more efficiency to decrease cardiovascular mortality than mono-blockade. Our goal was to explore differences between other cardiovascular markers in patients with RAS blockade.. We analyzed two groups of patients treated with a long-term ACE inhibitor (MONO-group, n = 20) and an ACE inhibitor and angiotensin II receptor blocker (DUAL-group, n = 15). Ambulatory blood pressure monitoring, echocardiography, arterial stiffness and levels of catecholamine, endogenous ouabain (EO), pro-brain natriuretic peptide and more types of urinary albumin measurements were performed.. In the DUAL-group, we found significantly better cardiac parameters, but the levels of EO and urinary albumins were similar in both groups. The level of EO correlates with nighttime mean arterial blood pressure (R = 0.556, p = 0.032) and arterial β-stiffness (R = 0.512, p = 0.042). Urinary immuno-unreactive albumin showed a relationship with diastolic dysfunction of the heart (R = -0.508, p = 0.045) diurnal index of diastolic blood pressure (R = -0.569, p = 0.021) in the MONO-group.. Cardiac parameters were more prosperous in the DUAL-group, but the levels of EO did not differ between groups. The level of EO correlated with blood pressure and arterial stiffness markers in the MONO-group only. The urinary immuno-unreactive albumin may be a new marker of cardiovascular conditions.

Topics: Aged; Albumins; Arteries; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Physiological Phenomena; Catecholamines; Cross-Sectional Studies; Diabetic Nephropathies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nephrosclerosis; Ouabain; Peptide Fragments; Renal Insufficiency; Renin-Angiotensin System; Retrospective Studies

To investigate the correlations between S100B and the severity of cardiac dysfunction, renal insufficiency (RI) and prognosis in chronic heart failure (CHF).. Serum levels of S100B, TNF-α, high sensitivity CRP and NT-proBNP were determined in CHF patients with (n=96) and without RI (n=146). Patients with RI only (n=62) and control subjects (n=64) served for comparison. Patients were followed up for one year.. S100B levels were higher in CHF patients with a further elevation in those with RI (P<0.01). Serum S100B levels correlated with left ventricular ejection fraction, left ventricular end-diastolic volume and NT-proBNP in CHF patients, and eGFR in patients with RI (all P<0.05). Increased S100B levels were associated with major cardiac events (MCE), and were independently associated with the presence of CHF (all P<0.05).. Increased serum S100B levels were associated with the severity of cardiac dysfunction, RI and an adverse prognosis in CHF patients. It represents an independent risk factor for CHF.

Topics: Aged; Body Mass Index; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Growth Factors; Peptide Fragments; Regression Analysis; Renal Insufficiency; ROC Curve; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Tumor Necrosis Factor-alpha

Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently indispensable for the treatment of heart failure. It is well known that hyperkalemia is likely to occur in renal failure; however, it has not yet been clarified how the serum potassium concentration changes as heart failure progresses. Currently, the cardio-renal decompensation syndrome holds that the serum potassium concentration is altered similarly by both heart failure and renal failure; however, there are no definitive reports on this. In order to use RAAS inhibitors more safely and effectively in heart failure, it is necessary to understand the factors affecting serum potassium concentration in the clinical setting.. We examined the clinical factors affecting serum potassium concentration in 1035 consecutive patients with cardiovascular disease who were hospitalized in our institution. Multiple regression analysis showed that the independent factors associated with an elevated serum potassium concentration were renal insufficiency evaluated by estimated glomerular filtration rate (eGFR) (P<0.0001), diabetes mellitus evaluated by HbA(1c) (P=0.0005) and the use of RAAS inhibitors (P=0.0010). The independent factors associated with a decreased serum potassium concentration were mean blood pressure (P<0.0001), heart failure evaluated by log BNP (P=0.0164) and the use of diuretics (P=0.0232).. The serum potassium concentration decreases with the severity of heart failure if renal function is preserved. From the perspective of potassium homeostasis, we could use the RAAS inhibitors more aggressively in patients with heart failure who do not have renal failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Child; Disease Progression; Diuretics; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hyperkalemia; Male; Middle Aged; Natriuretic Peptide, Brain; Potassium; Regression Analysis; Renal Insufficiency; Renin-Angiotensin System; Severity of Illness Index; Spironolactone; Young Adult

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Renal Insufficiency

NT-proBNP is a reliable index in case of cardiac diseases.. To evaluate the diagnostic usefulness of NT-proBNP as index of the closure of patent ductus arteriosus (PDA) in ELBW.. Considered 73 ELBW (mGA 26+3 weeks; mBW 789 g) with echocardiographical diagnosis of PDA. The closure of the duct was spontaneous in 22%, pharmacological in 49.3% and by surgical ligation in 28.7%. Plasma NT-proBNP levels were measured on day 3 in 35 preterm infants; in 20 of them concentrations of the peptide were assayed on day 3 and on closure of the duct.. On day 3 the median of NT-proBNP levels was 13718 pg/ml (range 1918-70000). Peptide concentrations did not differ between pharmacological treatment and surgical ligation (respectively 13718 and 12342 pg/ml; p = 0.33). Concentrations of NT-proBNP were significantly lower on the closure of the duct (p < 0.0001) compared to concentrations on day 3 (median 12666 at day 3 versus 2443.5 pg/ml at closure), with a decrease of 80.71%.. ELBW showed high variability of NT-proBNP concentrations both on day 3 and on closure of PDA. Although NT-proBNP high levels were indicative of the presence of hsPDA, due to the extreme heterogeneity of the values it was not possible to determine an absolute cut-off concentration of NT-proBNP below which closure of the duct occurred, while a decrease of NT-proBNP > or =80% was a reliable index of PDA closure.

Topics: Biomarkers; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Ibuprofen; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Ligation; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Remission, Spontaneous; Renal Insufficiency; Retrospective Studies

Assay of baseline B-type peptide (BNP and NT-proBNP) is useful for heart failure (HF) prognostication. In contrast, the prognostic value of NT-proBNP assay performed on admission of elderly subjects for acute dyspnea is uncertain. The aim of this study was to determine the vital prognostic value of NT-proBNP assay and other relevant variables available on admission in elderly patients hospitalized for acute dyspnea.. 254 patients over 70 years of age who were initially hospitalized with acute dyspnea were prospectively studied. The log-rank test and Cox proportional-hazards regression models were used to determine the prognostic value of NT-proBNP and creatinine clearance, measured within 24 h of initial admission, as well as age, gender, vascular risk factors and other clinical variables.. Mean age was 81+/-7 years, and 52% of the patients were women. During a median follow-up of 34 months, 134 patients (55%) died and 9 patients (4%) were lost to follow-up. The median survival time was 25 months, and almost half the deaths occurred during the first 6 months. In multivariate analysis the following three variables were independently associated with mortality (shown with their accompanying hazard ratios (HR)): NT-proBNP>2856 pg/mL (median), HR=1.6[95%CI:1.3-5.2]; creatinine clearance <30 mL/min, HR=1.7[95%CI:1.2-2.5]; and age>80 years, HR=1.7[95%CI:1.1-2.6]. The median survival time among patients with an admission NT-proBNP level of >2856 pg/mL (median) was 14 months, compared to >36 months in the rest of the population.. The admission NT-proBNP level, age, and creatinine clearance are predictive of vital outcome in elderly patients hospitalized for acute dyspnea.

Topics: Acute Disease; Age Distribution; Aged; Aged, 80 and over; Cause of Death; Creatinine; Dyspnea; Female; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Renal Insufficiency; Risk Factors

To evaluate the safety and patterns of use of targeted renal therapy (TRT) with the Benephit system. TRT, the delivery of therapeutic agents directly to the kidneys by renal arterial infusion, has the advantage of providing a higher local effective dose with potentially greater renal effects, while limiting systemic adverse effects due to renal first-pass elimination.. The Benephit System Renal Infusion Therapy (Be-RITe!) Multicenter Registry was a post-market registry following patients treated using the Benephit systems for TRT. The registry enrolled 501 patients (332 men; mean age 72.2+/-9.5 years) at high risk for contrast-induced nephropathy (CIN) during coronary or peripheral angiography/intervention or cardiovascular surgery. The Mehran score was used to compare the actual to predicted incidence of CIN within 48 hours post procedure.. Bilateral renal artery cannulation was successful in 94.2%, with a mean cannulation time of 2.0 minutes. Either fenoldopam mesylate, sodium bicarbonate, alprostadil, or B-type natriuretic peptide (BNP) was infused for 184+/-212 minutes. Mean creatinine levels did not change significantly (baseline, 24, and 48 hours post procedure: 1.95, 1.99, and 1.98 mg/dL, respectively; p = NS). In 285 patients who received TRT with fenoldopam and were followed for at least 48 hours, the incidence of CIN was 71% lower than predicted (8.1% actual CIN versus 28.0% predicted; p<0.0001). Only 4 (1.4%) patients required dialysis (versus the 2.6% predicted rate, p = NS).. The Benephit system and TRT during coronary and endovascular procedures in patients at high risk for renal failure is simple to use and safe. With the infusion of intrarenal fenoldopam, the incidence of CIN was significantly lower than predicted by risk score calculations.

Topics: Aged; Aged, 80 and over; Alprostadil; Catheterization; Contrast Media; Creatinine; Drug Delivery Systems; Equipment Design; Feasibility Studies; Female; Fenoldopam; Humans; Incidence; Infusions, Intra-Arterial; Male; Middle Aged; Natriuretic Peptide, Brain; Practice Patterns, Physicians'; Protective Agents; Radiography; Registries; Renal Artery; Renal Dialysis; Renal Insufficiency; Retrospective Studies; Sodium Bicarbonate; Time Factors; Treatment Outcome; United States

Topics: Alprostadil; Catheterization; Contrast Media; Drug Delivery Systems; Equipment Design; Fenoldopam; Humans; Infusions, Intra-Arterial; Natriuretic Peptide, Brain; Protective Agents; Radiography; Renal Artery; Renal Insufficiency; Research Design; Sodium Bicarbonate; Treatment Outcome

Topics: Heart Failure; Humans; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency

We assessed the effect of increases in serum creatinine on mortality in nesiritide-treated versus control subjects with acute decompensated heart failure (ADHF).. Mortality effect of nesiritide-related increases in serum creatinine differs from that of standard therapies.. Scios Inc., granted unrestricted access to data from all 5 randomized, controlled nesiritide infusion trials completed to date in patients hospitalized with ADHF. We used 2 different definitions of acute serum creatinine increase: >0.3 mg/dL and > 0.5mg/dL within 30 days of study enrollment and determined 30-day mortality risk for nesiritide-treated versus control subjects utilizing each definition.. A total of 1,270 subjects participated in the 5 trials. A >0.3 mg/dL increase in serum creatinine was associated with a significant increase in mortality risk in control subjects, (hazard ratio [HR]: 3.47, 95% confidence interval [CI]: 1.49-8.09) but not in nesiritide-treated subjects (HR: 1.65, 95% CI: 0.90-3.05). Results were similar for a >0.5 mg/dL increase (control HR: 5.12, 95% CI: 2.09-12.57 and nesiritide HR: 1.77, 95% CI: 0.90-3.51). In subjects with >0.3 mg/dL and >0.5 mg/dL increases in serum creatinine, respectively, the 30-day mortality odds ratios for nesiritide relative to control were 0.73 (95% CI: 0.29-1.93) and 0.52 (95% CI: 0.17-1.63) using a stratified Mantel-Haenszel analysis.. The impact of increased serum creatinine on mortality was attenuated in nesiritide-treated patients compared to control, suggesting that the mechanism and clinical significance of increases in serum creatinine associated with nesiritide treatment may differ from those associated with standard therapies. Further investigation is warranted.

Topics: Creatinine; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Renal Insufficiency; Survival Analysis

Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/E(a)).. NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis.. NT-proBNP (1) was higher (median and inter-quartile [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218; P=0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94).. NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.

Topics: Animals; Biomarkers; Case-Control Studies; Cat Diseases; Cats; Diagnosis, Differential; Dyspnea; Female; Heart Failure; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Renal Insufficiency; Respiration Disorders; ROC Curve

Urinary excretion is currently regarded as the main mechanism of elimination of N-terminal prohormone brain natriuretic peptide (NT-proBNP). The clinical implications and the value of measurement of urinary NT-proBNP in patients with heart failure are largely unknown.. We studied 94 patients (age, 58+/-11 years; 79% men) with chronic heart failure (CHF) and 20 age- and sex-matched healthy control subjects. Glomerular filtration rate and effective renal plasma flow were measured as clearance of (125)I-iothalamate and (131)I-hippuran, respectively. NT-proBNP levels were determined in both plasma and 24-hour urine collections. Mean left ventricular ejection fraction of CHF patients was 0.28+/-0.09. Plasma NT-proBNP levels were higher in CHF patients compared with control subjects (median, 547 versus 41 pg/mL; P<0.001). Urinary NT-proBNP excretion, however, was substantially lower in CHF patients (median, 0.13 versus 2.3 mL/min; P<0.001). Urinary NT-proBNP excretion was independent of estimated glomerular filtration rate. In both CHF patients and control subjects, there was a strong and inverse relation between plasma NT-proBNP concentrations and urinary NT-proBNP excretion (r=-0.72 and r=-0.65 respectively; both P<0.001). Decreased renal plasma flow in CHF was significantly associated with a lower excretion of NT-proBNP (P=0.026).. Urinary NT-proBNP excretion is lower in patients with CHF compared with control subjects and is inversely related to plasma NT-proBNP. Urinary NT-proBNP is associated with renal plasma flow but not with estimated glomerular filtration rate. Elevated levels of plasma NT-proBNP in patients with CHF might be explained not only by myocardial stress but also by a marked decrease in urinary excretion.

Topics: Aged; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Iodine Radioisotopes; Iothalamic Acid; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Radionuclide Imaging; Renal Circulation; Renal Insufficiency; Urine

Cardiovascular events (CVE) are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. These patients are often excluded from CV clinical trials, and the prognostic factors associated with CVE in patients with ESRD have not been fully explored. We investigated the role of BNP and NT-proBNP in predicting the outcome and prognostic value in hemodialysis with ESRD patients.. Baseline NT-proBNP and BNP, indices of dialysis adequacy, and biochemical characteristics were assessed in 217 dialysis patients with ESRD who were followed prospectively for 2 years or until death. CVE included cardiovascular death, myocardial infarction, heart failure and stroke.. Using multivariable Cox regression analysis, BNP and NT-proBNP remained predictive of cardiovascular mortality (BNP: hazard ratio 1.22, 95% confidence interval (CI) 1.21-11.04, p < 0.05; NT-proBNP hazard ratio 1.86, 95% CI 1.14-9.36, p < 0.05), fatal/nonfatal CHF (BNP: 1.35, 1.33-11.78, p < 0.05; NT-proBNP: 2.25, 1.54-12.68, p < 0.001) and fatal/nonfatal MI (BNP: 0.61, 2.38-19.53, p = 0.42; NT-proBNP: 1.90, 3.28-20.17, p < 0.001). NT-proBNP had better predictive value than BNP for mortality (area under the ROC curve (AUC) 0.83 vs. 0.61; p < 0.05).. These data showed that BNP and NT-proBNP are very sensitive and specific predictors of CVE in dialysis patients.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Causality; Comorbidity; Female; Humans; Incidence; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Dialysis; Renal Insufficiency; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis; Survival Rate

The heart secretes brain natriuretic peptide (BNP) in response to myocardial stretch. The aim of this study was to determine whether adverse effects after cardiac surgery were associated with higher serum BNP levels pre-operatively.. One hundred and thirty-five patients undergoing various cardiac procedures were included in the study, and N-terminal pro-BNP (NT-pro-BNP) was measured pre-operatively. Post-operative complications were defined as follows: (i) a post-operative length of stay in the intensive care unit (ICU) exceeding 48 h; (ii) mortality at 28 days; (iii) the need for inotropic agents and/or intra-aortic balloon pump (IABP); and (iv) renal failure. Serum NT-pro-BNP values were compared for patients with and without complications. The serum NT-pro-BNP level was also correlated with the euroSCORE and ejection fraction (EF).. Pre-operative serum NT-pro-BNP levels were significantly higher in patients with an ICU length of stay of more than 2 days or death prior to post-operative day 28 (3118 ng/l vs. 705 ng/l; P < 0.001). Pre-operative serum NT-pro-BNP levels were also significantly higher in patients needing inotropic agents (2628 ng/l vs. 548 ng/l; P < 0.001) or IABP insertion (3705 ng/l vs. 935 ng/l; P = 0.001) or developing renal failure (2857 ng/l vs. 945 ng/l; P < 0.001) post-operatively. The correlation between the serum NT-pro-BNP level and euroSCORE was good (r = 0.658; P < 0.001). The receiver operating characteristic (ROC) curves were used to assess the ability of serum NT-pro-BNP, euroSCORE and EF to predict outcome after cardiac surgery. This revealed an area under the ROC curve for the length of stay in the ICU or mortality at 28 days of 0.829 for serum NT-pro-BNP, 0.814 for euroSCORE and 0.328 for EF assessed by transesophageal echocardiography, indicating that the pre-operative serum NT-pro-BNP level is a good prognostic indicator for outcome after cardiac surgery.. Serum NT-pro-BNP is a good predictor for complications after cardiac surgery, and is as good as euroSCORE and better than EF.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiac Surgical Procedures; Echocardiography, Transesophageal; Female; Humans; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Renal Insufficiency; ROC Curve; Stroke Volume; Survival Rate; Treatment Outcome

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is related to stress-induced myocardial ischemia and/or volume overload, both common in patients with renal dysfunction. This might compromise the prognostic usefulness of NT-pro-BNP in patients with renal impairment before vascular surgery. We assessed the prognostic value of NT-pro-BNP in the entire strata of renal function. In 356 patients (median age 69 years, 77% men), cardiac history, glomerular filtration rate (GFR, ml/min/1.73 m(2)), and NT-pro-BNP level (pg/ml) were assessed preoperatively. Troponin T and electrocardiography were assessed postoperatively on days 1, 3, 7, and 30. The end point was the composite of cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariate analysis was used to evaluate the interaction between GFR, NT-pro-BNP and their association with postoperative outcome. Median GFR was 78 ml/min/1.73 m(2) and the median concentration of NT-pro-BNP was 197 pg/ml. The end point was reached in 64 patients (18%); cardiac death occurred in 7 (2.0%), Q-wave myocardial infarction in 34 (9.6%), and non-Q-wave myocardial infarction in 23 (6.5%). After adjustment for confounders, NT-pro-BNP levels and GFR remained significantly associated with the end point (p = 0.005). The prognostic value of NT-pro-BNP was most pronounced in patients with GFR > or =90 (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.80 to 1.76) compared with patients with GFR 60 to 89 (OR 1.04, 95% CI 1.002 to 1.07), and with GFR 30 to 59 (OR 1.12, 95% CI 1.03 to 1.21). In patients with GFR <30 ml/min/1.73 m(2), NT-pro-BNP levels have no prognostic value (OR 1.00, 95% CI 0.99 to 1.01). In conclusion, the discriminative value of NT-pro-BNP is most pronounced in patients with GFR > or =90 ml/min/1.73 m(2) and has no prognostic value in patients with GFR <30 ml/min/1.73 m(2).

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Renal Insufficiency; Sensitivity and Specificity; Vascular Surgical Procedures

To date, several different equations to predict the glomerular filtration rate (GFR) in patients with renal insufficiency have been developed for different patients groups. Our aim was to determine the prognostic factors of GFR in our homogenous patient group of obese, water-loaded patients with Type 2 diabetes and renal insufficiency, since we assumed that the endogenous creatinine clearance (ECC) alone may not be an accurate method to predict GFR.. We recruited 46 obese patients (37 men) with Type 2 diabetes and renal insufficiency in our nephrology center in Mettmann (Germany). However, two male patients were excluded from the analysis due to an outlying insulin level or low inulin clearance. The inulin clearance as a measure of renal function performed by the single shot method was compared with the GFR estimated by ECC, Cystatin C, and MDRD formula. Several multiple regression models were built to test the impact of the prognostic factors age, sex, body mass index (BMI), insulin resistance according to the homeostasis model assessment (HOMA), body water (TBW), brain natriuretic peptide (BNP), and proteinuria on the inulin clearance. In the main regression model to predict the inulin clearance by ECC, only the statistically significant prognostic factors of these models were selected, as well as the interaction between GFR predicted by ECC (GFR_ECC) and BMI.. The prognostic factors GFR_ECC, age, BMI, HOMA and proteinuria had a statistically significant impact on the inulin clearance (the gold standard of the GFR) in our patient population (p < 0.05). However, the interaction of GFR_ECC and BMI was not significant (p = 0.06) in our model. The model was validated and considered well-fitted with a coefficient of determination (R2) of 0.69.. The independent prognostic factors to determine GFR in obese, water-loaded diabetic patients are GFR_ECC, age, BMI, HOMA and proteinuria. However, our model should be revalidated and tested in a larger sample size to probably detect an interaction between GFR_ECC and BMI as an additional prognostic factor.

Topics: Age Factors; Aged; Blood Pressure; Body Mass Index; Creatinine; Diabetes Mellitus, Type 2; Disease Progression; Female; Glomerular Filtration Rate; Humans; Insulin; Insulin Resistance; Male; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Obesity; Prognosis; Proteinuria; Renal Insufficiency

While low brain natriuretic peptide (BNP) values have been shown to improve diagnostic accuracy by excluding congestive heart failure in acute dyspnea, the meaning of excessively elevated BNP is not clear. This is a retrospective analysis of clinical, echocardiographic, and laboratory data in patients with BNP values >2500 ng/L. Sixty-seven patients (36 men) with a median age of 79 years were included. The median BNP level was 3118 ng/L (2506-5000 ng/L). Forty-six percent of the patients had no dyspnea or New York Heart Association class II dyspnea. Most patients had impaired renal function. BNP value did not correlate with ejection fraction (r=0.2; P=.15) and weakly correlated with left ventricular end-diastolic diameter index (r=0.26; P=.02). Very high BNP values only poorly correlated with dyspnea and traditional echocardiographic markers of congestive heart failure. The clinical usefulness of very high BNP values is questionable and needs evaluation in a prospective trial.

Topics: Aged; Aged, 80 and over; Cardiac Output, Low; Echocardiography, Doppler; Female; Humans; Inpatients; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency; Retrospective Studies; Switzerland

The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly.. We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index).. During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit.. Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cystatin C; Cystatins; Humans; Inflammation; Longitudinal Studies; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency; Risk Assessment; Risk Factors; Troponin I; Ventricular Dysfunction, Left

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a byproduct of the brain natriuretic peptide (BNP) that was shown to be of prognostic value in pulmonary hypertension (PH). The role of NT-proBNP in PH has to be determined, especially under the influence of renal impairment that might lead to an accumulation of the peptide, and may be a sign of increased mortality per se.. We assessed NT-proBNP, BNP, renal function, and hemodynamic parameters (during right-heart catheterization) in 118 consecutive patients with isolated PH, excluding left-heart disease. Depending on the calculated creatinine clearance, patients were classified into different groups of renal function. Correlation analysis was performed on all key parameters. Results were then compared between the levels of renal function. The prognostic value of each parameter was assessed during a mean follow-up period of 10 months.. Twenty-two patients (approximately 19%) had significantly impaired renal function (creatinine clearance < 60 mL/min). Although the overall levels of NT-proBNP were correlated with hemodynamics, we observed no correlation in the group with significant renal dysfunction. Moreover, NT-proBNP was related to creatinine clearance. Finally, NT-proBNP and renal insufficiency were independent predictors of death during univariate and multivariate analysis, whereas BNP only predicted mortality in univariate analysis.. The diagnostic accuracy of NT-proBNP as a parameter of the hemodynamic status is diminished by renal function. However, NT-proBNP could be superior to BNP as a survival parameter in PH because it integrates hemodynamic impairment and renal insufficiency, which serves as a sign of increased mortality per se.

Topics: Biomarkers; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Renal Insufficiency; Risk Factors; Survival Rate

Anaemia is a negative prognostic factor for patients with heart failure and impaired renal function, but its role in stroke patients is unknown. Furthermore, anaemia has been shown to influence the level of N-terminal pro-brain natriuretic peptide (NT-proBNP), but this is only investigated in patients with heart failure, not in stroke patients. Two-hundred-and-fifty consecutive, well-defined ischemic stroke patients were investigated. Mortality was recorded at 6 months follow-up. Anaemia was diagnosed in 37 patients (15%) in whom stroke severity was worse than in the non-anaemic group, whilst the prevalence of renal affection, smoking and heart failure was lower. At 6 months follow-up, 23 patients were dead, and anaemia had an odds ratio of 4.7 when adjusted for age, Scandinavian Stroke Scale and a combined variable of heart and/or renal failure and/or elevation of troponin T using logistic regression. The median NT-proBNP level in the anaemic group was significantly higher than in the non-anaemic group, and in a multivariate linear regression model, anaemia remained an independent predictor of NT-proBNP. Conclusively, anaemia was found to be a negative prognostic factor for ischemic stroke patients. Furthermore, anaemia influenced the NT-proBNP level in ischemic stroke patients, an important aspect when interpreting NT-proBNP in these patients.

Topics: Aged; Aged, 80 and over; Anemia; Brain Ischemia; Causality; Comorbidity; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Regional Blood Flow; Renal Insufficiency; Stress, Physiological; Stroke

Cardiovascular dysfunction in patients with hemolytic-uremic syndrome (HUS) may be related to secondary issues such as volume overload, hypertension or electrolyte disturbances including hyperkalemia. Additionally, primary myocardial involvement has been increasingly recognized as a potential comorbid feature of HUS. We report a 9-month-old child with HUS who developed clinical signs of poor myocardial function with depressed myocardial function noted by echocardiography. Supportive care including mechanical ventilation and inotropic agents were necessary for approximately 10 days. Follow-up echocardiography revealed return of normal ventricular function. Previous reports of primary cardiac involvement with HUS have included thrombotic microangiopathy of the coronary vasculature resulting in myocardial ischemia, myocardial infarction or depressed myocardial function, myocarditis, congestive heart failure with dilated cardiomyopathy and pericardial effusion with tamponade. Given the potential for morbidity and mortality during the preoperative period in patients with HUS, anesthesiologists involved in the care of such patients should be aware of the potential for myocardial involvement in this disease process. Preoperatively, the routine evaluation of myocardial function may be indicated.

Topics: Anemia; Anti-Bacterial Agents; Cardiomyopathies; Cardiotonic Agents; Dopamine; Electrocardiography; Hemolytic-Uremic Syndrome; Humans; Infant; Intubation, Intratracheal; Male; Meropenem; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Oliguria; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency; Respiration, Artificial; Thienamycins; Vancomycin

Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable diagnostic and prognostic test in heart failure (HF). Limited information is available concerning its use in patients with renal failure, in whom dependence on renal clearance may negatively affect its performance.. We evaluated influence of renal function on NT-proBNP levels and on its prognostic value after hospital discharge in 283 acute HF patients. Admission and discharge NT-proBNP levels were higher in patients with decreased estimated glomerular filtration rate (eGFR). In these patients discharge NT-proBNP above median was associated to occurrence of death or readmission at 6 months (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.27-5.03); in patients with normal eGFR, a trend to this association was found (HR 1.64, CI 0.98-2.76). Decrease in NT-proBNP less than 30% of baseline was associated to outcome in patients with normal eGFR (HR 2.68, CI 1.54-4.68) and decreased eGFR (HR 2.54, CI 1.49-4.33).. Acute HF patients with renal failure have higher NT-proBNP levels than those with normal renal function. Discharge NT-proBNP has long-term prognostic value in HF patients with renal dysfunction. NT-proBNP variations during hospitalization provide additional prognostic information either in patients with normal or reduced eGFR.

Topics: Acute Disease; Aged; Biomarkers; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Portugal; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Renal Insufficiency; Survival Analysis

The present study aimed to evaluate the prognostic value of B-type natriuretic peptide (N-proBNP), renal dysfunction and anemia in chronic heart failure (CHF) patients.. We analyzed data from a prospective cohort of 153 patients (mean age 64 years) with CHF referred to our hospital center. Clinical, echocardiographic and laboratory data were drawn during hospital recovery in all patients. Kidney dysfunction was defined as a glomerular filtration rate (GFR) < 60 ml/min and anemia as a hematocrit < 35%. After discharge, patients attended the outpatient clinic of our institution.. Kidney dysfunction was diagnosed in 37% of cases, whereas anemia was present in 25% of patients. During follow-up (median time 456 days), 32 patients died. Multivariate Cox proportional hazard model revealed that N-proBNP [hazard ratio (HR) = 1.002; P < 0.001] and GFR (HR = 0.972; P < 0.005) were significant predictors for mortality after adjustment for confounding variables. Kaplan-Maier analysis demonstrated a progressive decrease in survival from lowest to highest tertiles of N-proBNP values (log rank = 28.7; P < 0.001) and from higher to lower GFR values (log rank = 5.63; P < 0.01). Moreover, parametric survival analysis by the Weibull model demonstrated that the estimated probability of survival adjusted for N-proBNP values was higher in patients with GFR > or = 60 ml/min than in those with GFR < 60 ml/min (P < 0.001).. Increased N-proBNP and decreased kidney function, but not anemia, are independent risk factors for mortality in patients with CHF.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Renal Insufficiency; Stroke Volume

Differentiating between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCMP) is difficult because of similar clinical and hemodynamic presentation. Brain natriuretic peptide (BNP) has been reported a useful noninvasive biomarker to differentiate CP from RCMP; however, its utility in patients with renal insufficiency has not been evaluated.. Consecutive patients with suspected CP or RCMP were enrolled. All but 7 patients underwent transseptal catheterization. BNP, renal function, and comorbid conditions were recorded at the time of the procedure. Renal function was estimated using the Cockcroft-Gault formula. Descriptive statistics, Student t-test, and Mann-Whitney U test were performed; P < .05 was significant. Twenty-two patients had hemodynamically or surgically proven CP or RC. In patients with CP, 9 had at least Stage II kidney disease (GFR <90 mL/min, mean 58) and 8 had normal or Stage I kidney disease (GFR >90 mL/min, mean 118). BNP was higher in patients with CP and renal insufficiency versus those with CP and normal renal function (433 versus 116 pg/mL; P = .016). BNP in patients with CP and normal renal function was lower than in patients with RC (116 versus 728 pg/mL; P = .005).. BNP has reduced clinical utility in renal insufficiency to differentiate CP from RCMP.

Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Cardiomyopathy, Restrictive; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pericarditis, Constrictive; Renal Insufficiency

Topics: Biomarkers; Heart Failure; Humans; Kidney Function Tests; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Renal Insufficiency; Syndrome

The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of renal insufficiency, NT-proBNP remained a valuable tool for the diagnosis of acute congestive heart failure and it provides important prognostic information.. We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels.. The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis.. A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration.. Glomerular filtration rates ranged from 15 ml/min/1.73 m2 to 252 ml/min/1.73 m2. Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of > 450 pg/ml for patients ages <50 years and >900 pg/ml for patients > or =50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR > or =60 ml/min/1.73 m2. Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73 m2, we found sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006).. The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function.

Topics: Aged; Biomarkers; Creatinine; Dyspnea; Echocardiography; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Renal Insufficiency; ROC Curve; Sensitivity and Specificity

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency; Reproducibility of Results

The plasma concentrations of natriuretic peptides, BNP and NTproBNP, have been shown to be markers for the diagnosis of congestive heart failure (CHF). In this study, plasma BNP and NTproBNP concentrations were evaluated and stratified according to renal function, body mass index (BMI), and New York Heart Association (NYHA) classification. Comparison studies between the 2 natriuretic peptide markers were performed. Assays for BNP were performed with a Triage reagent pack (Biosite, Inc) on an Access 2 immunoanalyzer (Beckman-Coulter); NTproBNP assays were performed with a Roche reagent pack on an Elecsys 20.10 immunoanalyzer (Roche Diagnostics). Plasma samples were collected from consecutive patients hospitalized for cardiac disorders at our institution. Nonparametric tests were used for statistical analyses. The results show that alterations of renal function had less impact on BNP (p = 0.9) than on NTproBNP concentrations (p <0.0001). BNP and NTproBNP levels were lower in obese patients with CHF (515 +/- 61 ng/L and 1652 +/- 124 ng/L, respectively) than in lean patients (900 +/- 85 ng/L and 6686 +/- 749 ng/L). Although NTproBNP levels averaged about 10 times higher than BNP levels, there was significant correlation between these 2 markers (Deming regression r2 = 0.40, IC: 0.95). In conclusion, plasma BNP and NTproBNP assays are both useful for the diagnosis of CHF and left ventricular dysfunction. However, renal function and obesity must be taken into account for clinical interpretation. These assays have good analytical performance and the choice between them depends on local preference.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Creatinine; Female; Heart Failure; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Renal Insufficiency; Statistics, Nonparametric

The rate of adoption of new therapies for cardiovascular diseases following the publication of favorable clinical trial results has been studied; however, less is known about the rates of de-adoption of a drug when negative studies are published.. To evaluate the use of nesiritide before and after March and April 2005 publications in 2 high-impact journals that suggested an increased risk of renal failure and mortality with intravenous nesiritide for acute decompensated heart failure.. Analysis of a large prospective hospital database, developed for quality and utilization benchmarking, of 491 acute care US hospitals at which 385,627 inpatient admissions occurred with a primary International Classification of Diseases, Ninth Revision (ICD-9) code for heart failure between January and August 2001 (prior to nesiritide release) and January 2004 to December 2005 (before and after publication periods). In addition, any patient admitted who received nesiritide in the absence of a primary or secondary heart failure code was evaluated for potential off-label use of the drug.. Use of nesiritide and other intravenous vasoactive therapy among patients admitted with heart failure.. Nesiritide use decreased from a peak of 16.6% (2351 of 14,167 admissions) in March 2005 to 5.6% (611 of 10,822 admissions) in December 2005 (P<.001). Among those patients treated with nesiritide, the mean duration of treatment changed minimally, from 2.3 to 2.1 days. Although the use of inotropes also decreased during the period under study, the changes were more modest; furthermore, of those patients who were prescribed intravenous vasoactive therapy, a higher percentage were prescribed inotropes after publication (3272 [21.5%] of 15 193 patients from January-April 2005 vs 5750 [29.6%] of 19 445 patients from May-December 2005, P<.001). The use of nesiritide, in the absence of an ICD-9 heart failure code, was small.. Rapid de-adoption of nesiritide occurred following 2 publications suggesting risk with the drug. Further analyses are required to evaluate the consequences of these changes on patient outcomes and to anticipate how publications of adverse findings can influence practice.

Topics: Aged; Aged, 80 and over; Drug Utilization; Female; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Publishing; Renal Insufficiency; Risk

Topics: Drug Approval; Drug Evaluation; Drug Labeling; Heart Failure; Humans; Information Dissemination; Natriuretic Peptide, Brain; Renal Insufficiency; Treatment Outcome

Nesiritide is a recombinant formulation of B-type natriuretic peptide used most commonly in the treatment of adults with decompensated congestive heart failure. The physiologic effects of BNP include natriuresis, diuresis, and smooth muscle relaxation. These physiologic effects result in its beneficial therapeutic effects, including a decrease in afterload, resulting in increased cardiac output with improved peripheral perfusion. The authors report on a 17-year-old with acute myelogenous leukemia who was admitted to the Pediatric ICU for treatment of septic shock, respiratory failure, myocardial dysfunction, and renal insufficiency. After the initial stabilization of his hemodynamic status, nesiritide was started and resulted in a stable balance of fluid intake versus output without the use of diuretics, improvement in myocardial function, and recovery of renal function manifested by a decrease of blood urea nitrogen and creatinine back to baseline values. The end-organ effects of nesiritide, previous reports regarding its use in the pediatric population, and its potential applications in the ICU setting are discussed.

Topics: Adolescent; Cardiomyopathies; Humans; Leukemia, Myeloid, Acute; Natriuretic Peptide, Brain; Renal Insufficiency; Respiratory Insufficiency; Shock, Septic; Treatment Outcome; Water-Electrolyte Balance

Plasma levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (N-BNP) are highly sensitive markers of ventricular dysfunction and/or hypertrophy and, in established disease, offer prognostic value and may be useful for guidance of therapy. Ng and co-workers report in this issue of Clinical Science that urinary levels of N-BNP may be as useful as plasma levels for the discrimination of patients with and without heart failure. This raises the potential for a relatively simple urine test that could be used for the diagnosis of heart failure. Roles in prognostication and the guidance of therapy may also be possible but, perhaps of most significance, measurement of urinary N-BNP may be applied to screening of patients at high risk of heart failure. The main limitations of the study were that the sample of heart failure patients comprised only 34 individuals with New York Heart Association functional Class IV and that the observed correlation between levels of urinary N-BNP and plasma creatinine seemed counter-intuitive. The latter issue needs clarification, as renal impairment is a frequent co-morbidity among patients with heart failure and will potentially confound any observed association between ventricular dysfunction and urinary N-BNP levels. Another caveat is that it is unclear if testing for urinary N-BNP can be cheaply and conveniently administered on a large scale. Nevertheless, this first demonstration of elevated N-BNP in the urine of patients with heart failure raises a number of exciting possibilities with regard to the management of patients with established or possible heart failure. Further investigation is required and eagerly awaited.

Topics: Biomarkers; Comorbidity; Creatinine; Heart Failure; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency

It is not known whether angiotensin II type 1 receptor antagonists can influence the function and morphology of small arteries in renal failure. We investigated the effect of 8-week losartan therapy (20 mg/kg per day) on isolated mesenteric resistance arteries by wire and pressure myographs in 5/6 nephrectomized rats. Plasma urea nitrogen was elevated 1.6-fold after nephrectomy, and ventricular synthesis of atrial and B-type natriuretic peptides was increased 2.2-fold and 1.7-fold, respectively, whereas blood pressure was not affected. Losartan did not influence these variables. The endothelium-mediated relaxation to acetylcholine was impaired in nephrectomized rats in the absence and presence of nitric oxide synthase and cyclooxygenase inhibition. Blockade of calcium-activated potassium channels by charybdotoxin and apamin reduced the remaining acetylcholine response, and this effect was less marked in nephrectomized than in sham-operated rats. Relaxation to levcromakalim, a vasodilator acting through adenosine triphosphate-sensitive potassium channels, was also impaired after nephrectomy. The arteries of nephrectomized rats showed eutrophic inward remodeling: Wall-to-lumen ratio was increased without change in wall cross-sectional area. All changes in arterial relaxation and morphology were normalized by losartan therapy. Aortic ACE content, measured by autoradiography, directly correlated to the plasma level of urea nitrogen, suggesting that renal failure has an enhancing influence on the vascular renin-angiotensin system. Losartan normalized relaxation and morphology of resistance arteries in experimental renal failure, independent of its influence on blood pressure, impaired kidney function, or volume overload. The mechanism of improved vasodilation by losartan may include enhanced relaxation through potassium channels.

Topics: Angiotensin Receptor Antagonists; Animals; Aorta; Atrial Natriuretic Factor; Blood Pressure; Endothelium, Vascular; Heart Ventricles; In Vitro Techniques; Losartan; Male; Mesenteric Arteries; Natriuretic Peptide, Brain; Nephrectomy; Peptidyl-Dipeptidase A; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Renal Insufficiency; RNA, Messenger; Vasoconstriction; Vasodilation

Topics: Aging; Confounding Factors, Epidemiologic; Female; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency; Reproducibility of Results; Sex Factors

Midwall fractional shortening (MFS) is a useful index to evaluate left ventricular myocardial function in patients with essential hypertension. The study investigated the prevalence and characterization of low MFS in hemodialysis patients.. MFS was calculated from M-mode echocardiograms in 67 patients (34 males, 33 females) receiving maintenance hemodialysis in whom fractional shortening was normal. Plasma levels of atrial and brain natriuretic peptides were also measured in these patients before and after hemodialysis. MFS was evaluated by stress-corrected MFS (ratio of observed to predicted MFS). The relationship of MFS to circumferential end-systolic stress in 122 healthy subjects was used to calculate the predicted MFS.. Stress-corrected MFS was depressed in 18 of the 67 patients (26.9%). In the low MFS group, duration of hypertension was significantly longer (p < 0.05), wall thickness was significantly greater (p < 0.001), left ventricular dimension was significantly smaller (p < 0.0001), and relative wall thickness was significantly greater (p < 0.0001) than in the normal MFS group. Reduction of brain natriuretic peptide level by hemodialysis in the low MFS group was significantly higher (p < 0.05) than in the normal MFS group.. Depression of stress-corrected MFS may be common in hemodialysis patients. Long duration of hypertension and concentric geometry of the left ventricle occur in patients with low MFS.

Topics: Aged; Atrial Natriuretic Factor; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Renal Dialysis; Renal Insufficiency; Ventricular Function, Left