natriuretic-peptide--brain and Myocardial-Ischemia

Galectin-3 is a lectin that binds beta-galactosides. It is involved in cardiac remodeling and fibrosis through the activation of macrophages and fibroblasts. ST2 is secreted by myocardial cells due to cardiac overload. These two biomarkers have been traditionally studied in the field of heart failure to guide medical therapy and detect the progression of the disease. Nevertheless, there are novel evidences that connect galectin-3 and ST2 with coronary heart disease and, specifically, with atrial fibrillation. The aim of this article is to concisely review the diagnostic and prognostic role of galectin-3 and ST2 in different cardiac diseases.

Topics: Atrial Fibrillation; Biomarkers; Blood Proteins; Coronary Disease; Disease Progression; Fibroblasts; Galectins; Heart; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Macrophages; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Survival Analysis; Troponin

Myocardial injury after noncardiac surgery (MINS) differs from myocardial infarction in being defined by troponin elevation apparently from cardiac ischemia with or without signs and symptoms. Such myocardial injury is common, silent, and strongly associated with mortality. MINS is usually asymptomatic and only detected by routine troponin monitoring. There is currently no known safe and effective prophylaxis for perioperative myocardial injury. However, appropriate preoperative screening may help guide proactive postoperative preventative actions. Intraoperative hypotension is associated with myocardial injury, acute kidney injury, and death. Hypotension is common and largely undetected in the postoperative general care floor setting, and independently associated with myocardial injury and mortality. Critical care patients are especially sensitive to hypotension, and the risk appears to be present at blood pressures previously regarded as normal. Tachycardia appears to be less important. Available information suggests that clinicians would be prudent to avoid perioperative hypotension.

Topics: Biomarkers; Humans; Intraoperative Complications; Myocardial Ischemia; Natriuretic Peptide, Brain; Postoperative Complications; Preoperative Care; Troponin

An increase in left ventricular volume after a myocardial infarction is a key component of the adverse remodelling process leading to chamber dysfunction, heart failure and an unfavourable outcome. Hence, the therapeutic strategies have been designed to reverse the remodelling process by medical therapy, devices or surgical strategies. Surgical ventricular reconstruction primarily combined with myocardial revascularization has been introduced as an optional intervention aimed to reduce the left ventricle through resection of the scar tissue and is recommended in selected patients with predominant heart failure symptoms, and with myocardial scarring and moderate left ventricular remodelling. This review outlines the rationale and the technique for reconstructing the left ventricle and the possible indications for using that technique, based on experiences from the centre with the largest international experience. The major contributions in the literature are briefly discussed.

Topics: Biomarkers; Cardiomyopathies; Contraindications, Procedure; Heart Ventricles; Humans; Mitral Valve; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Ventricular Remodeling

The possible use of biochemical markers in the postmortem diagnosis of myocardial ischemia is well known in the forensic setting, though several issues have limited its widespread adoption. The study presented herein focuses of N-terminal pro-B-type natriuretic peptide, troponin T, and troponin I, and the possible influence due to sampling site chosen, postmortem interval elapsed, and cardiopulmonary resuscitation attempts. Comparisons were performed between antemortem serum levels of these markers and postmortem levels measured in pericardial fluid and postmortem serum samples obtained from different sampling sites (n=16). Levels of these markers were also compared in cases characterized by various postmortem intervals (n=48, consisting of 24 ischemic heart disease cases and 24 controls) as well as in cases with and without cardiopulmonary resuscitation (n=22, consisting of 14 cases of hanging and 8 cases of drug intoxication). Our results indicate that N-terminal pro-B-type natriuretic peptide, troponin T, and troponin I values determined in postmortem serum from femoral blood (collected up to 24h after death) do not differ significantly from those measured in venous blood antemortem serum samples (collected at the upper limbs). In addition, our results reveal that the time elapsed after death should always be taken into consideration when cardiac troponins are measured in postmortem samples. Lastly, our findings reveal the absence of statistically significant differences between levels of the tested biomarkers (in postmortem serum from femoral blood) in cases without cardiopulmonary resuscitation compared to cases with cardiopulmonary resuscitation (at least for postmortem intervals up to 24h).

Topics: Adult; Biomarkers; Cardiopulmonary Resuscitation; Case-Control Studies; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Postmortem Changes; Troponin I; Troponin T

Since 1984, each year, more women than men die of ischemic heart disease (IHD) and heart failure (HF), yet more men are diagnosed. Because biomarker assessment is often the first diagnostic employed in such patients, understanding biomarker differences in men vs. women may improve female morbidity and mortality rates.Some key examples of cardiac biomarker utility based on sex include contemporary use of "unisex" troponin reference intervals under-diagnosing myocardial necrosis in women; greater use of hsCRP in the setting of acute coronary syndrome (ACS) could lead to better stratification in women; and greater use of BNP with sex-specific thresholds in ACS could also lead to more timely risk stratification in women.Accurate diagnosis, appropriate risk management, and monitoring are key in the prevention and treatment of cardiovascular diseases; however, the assessment tools used must also be useful or at least assessed for utility in both sexes. In other words, going forward, we need to evaluate sex-specific reference intervals or cutoffs for laboratory tests used to assess cardiovascular disease to help close the diagnostic gap between men and women.

Topics: Animals; Biomarkers; C-Reactive Protein; Creatine Kinase, MB Form; Female; Heart Failure; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Sex Characteristics; Troponin

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Cardiotonic Agents; Cardiotoxicity; Cardiotoxins; Coronary Thrombosis; Early Diagnosis; Echocardiography, Three-Dimensional; Humans; Hypertension; Magnetic Resonance Imaging, Cine; Myocardial Ischemia; Natriuretic Peptide, Brain; Neoplasms; Primary Prevention; Radiotherapy; Risk Factors; Troponin T; Ventricular Dysfunction, Left

Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood.. Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

Topics: Biomarkers; Electrocardiography; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Myocardial Ischemia; Natriuretic Peptide, Brain; Troponin I; Troponin T

Novel biomarkers of myocardial ischemia and inflammatory processes have the potential to improve diagnostic accuracy of acute coronary syndrome (ACS) within a shorter time interval after symptom onset.. The objective was to review the recent literature and evaluate the evidence for use of novel biomarkers in diagnosing ACS in patients presenting with chest pain or symptoms suggestive of cardiac ischemia to the emergency department or chest pain unit.. A literature search was performed in MEDLINE, EMBASE, Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED for studies from 2004 to 2010. We used the inclusion criteria: (1) human subjects, (2) peer-reviewed articles, (3) enrolled patients with ACS, acute myocardial infarction or undifferentiated signs and symptoms suggestive of ACS, and (4) English language or translated manuscripts. Two reviewers conducted a hierarchical selection and assessment using a scale developed by the International Liaison Committee on Resuscitation.. Out of a total 3194 citations, 58 articles evaluating 37 novel biomarkers were included for final review. Forty-one studies did not support the use of their respective biomarkers. Seventeen studies supported the use of 5 biomarkers, particularly when combined with cardiac-specific troponin: heart fatty acid-binding protein, ischemia-modified albumin, B-type natriuretic peptide, copeptin, and matrix metalloproteinase-9.. In patients presenting to the emergency department with chest pain or symptoms suggestive of cardiac ischemia, there is inadequate evidence to suggest the routine testing of novel biomarkers in isolation. However, several novel biomarkers have the potential to improve the sensitivity of diagnosing ACS when combined with cardiac-specific troponin.

Topics: Acute Coronary Syndrome; Biomarkers; Emergency Service, Hospital; Fatty Acid-Binding Proteins; Glycopeptides; Humans; Matrix Metalloproteinase 9; Myocardial Ischemia; Natriuretic Peptide, Brain; Serum Albumin; Serum Albumin, Human

Cardiac biomarkers in intensive care medicine are an excellent complement to existing clinical and diagnostic information in specific diseases. Due to their lack of specificity, the diagnostic properties of common cardiac biomarkers, such as natriuretic peptides and cardiac troponins, remain ambiguous, while their prognostic value has already been proven. In addition, there are several promising new biomarkers that might contribute to a "multimarker strategy" in the critically ill patient in the future, but further evaluation is still required.

Topics: Biomarkers; Creatine Kinase, MB Form; Critical Illness; Heart Failure; Humans; Intensive Care Units; Myocardial Ischemia; Natriuretic Peptide, Brain; Natriuretic Peptides; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Edema; Pulmonary Embolism; Sensitivity and Specificity; Shock, Cardiogenic; Troponin; Troponin C

Natriuretic peptides elicit vasodilation, increased sodium excretion and concomitant diuresis, and counteract the RAAS. In the heart itself, natriuretic peptides may also act anti-inflammatory and antifibrotic. This has led to the pursuit of natriuretic peptides and chemically modified peptides as adjunctive therapy in myocardial ischaemia. However, natriuretic peptide infusion may also influence the endogenous natriuretic peptide response and lipid accumulation. We hypothesised that a) natriuretic peptide infusion (BNP and CD-NP) is cardiomyocyte protective, b) affects the endogenous response, and c) facilitate cardiac lipid accumulation. We examined these effects in a minimally invasive porcine model of regional cardiac ischaemia and reperfusion. The studies were supplemented by a 48-hour porcine model of ischemia and reperfusion as well as an in vitro study of BNP administered in a HL-1 cell model of "ischaemia/reperfusion". Infarct size was determined by TTC staining, plasma troponin T release, and total RNA integrity in cardiac tissue samples. The endogenous response was assessed by a processing-independent proANP immunoassay and mRNA quantitation. Lipids in plasma and myocardial tissue were determined by TLC. The studies show that natriuretic peptides decrease cardiomyocyte damage, possibly partly through indirect mechanisms. Furthermore, BNP infusion completely inverts the endogenous response, whereas CD-NP infusion does not. Finally, both natriuretic peptides increase plasma free fatty acids, which is associated with an increased cardiac lipid accumulation in non-ischaemic myocardium. In conclusion, the studies suggest that natriuretic peptides are beneficial in terms of reduced cardiac injury. In addition, the endogenous natriuretic peptide response is inverted. The results advocate for pursuing natriuretic peptide treatment in ischaemia/reperfusion damage. However, the metabolic consequences in a cardiac tissue challenged by ischaemia should be pursued before testing the peptides in patients.

Topics: Animals; Blood Pressure; Caspase 1; Cholesterol; Cyclic GMP; Diuresis; Fatty Acids, Nonesterified; Female; Glycerol; Mice; Myocardial Infarction; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Reperfusion Injury; RNA, Messenger; Swine; Triglycerides; Troponin T; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Studies in victims of sudden cardiac death and those surviving a cardiac arrest have confirmed that extent of coronary artery disease is similar in those with and without angina, suggesting that it is the presence of myocardial ischemia rather than associated symptoms that determine the prognosis. Experimental models show that hypoxic myocardial tissue results in production of extra B-type natriuretic peptide (BNP), suggesting that BNP could potentially serve as a biomarker of myocardial ischemia. We performed a meta-analysis of the studies that link BNP to inducible myocardial ischemia as indicated by noninvasive stress tests. Values of true positive, false positive, true negative, and false negative were calculated from the reported sensitivity, specificity, disease prevalence, and total number of patients studied. Sixteen studies reporting data on 2,784 patients across 14 study populations were included in the final analysis. Mean age of participants was 55 to 69 years and 55% to 90% were men. Pooled sensitivity and specificity of BNP for detection of stress-induced myocardial ischemia were 71% (95% confidence interval [CI] 68 to 74) and 52% (95% CI 52 to 54), respectively. Pooled diagnostic odds ratio was 3.5 (95% CI 2.46 to 5.04) and summary receiver operating characteristic curve revealed an area under the curve of 0.71 ± 0.02 (mean ± SE). In conclusion, this meta-analysis suggests that an increased BNP level can identify inducible ischemia as detected by standard noninvasive stress tests. This raises the possibility of a whole new role for BNP in the diagnosis and management of myocardial ischemia.

Topics: Biomarkers; Diagnosis, Differential; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; ROC Curve; Stress, Psychological

Perioperative detection of cardiac biomarkers may help to identify patients at risk. Whether detection of these markers will be recommended in the preoperative setting for patients with cardiac diseases in the future has to be discussed as large prospective trials on this topic are missing. For preoperative evaluation of cardiac insufficiency quantification of brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are useful markers. Troponin is the marker of choice for detection of myocardial ischemia/infarction in the postoperative setting. In unstable patients coronary angiography and/or percutaneous coronary intervention (PCI) are indicated. However, in stable patients the decision for coronary angiography and/or PCI has to be made in each patient individually after interdisciplinary discussion between anesthesiologists, cardiologists and surgeons.

Topics: Biomarkers; C-Reactive Protein; Coronary Angiography; Heart; Heart Function Tests; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Perioperative Care; Risk Assessment; Surgical Procedures, Operative; Troponin

The initial evaluation of chest pain in the emergency department is based on the patient's clinical history, changes in the ECG and necrosis biomarkers. Although management of patients with ST-elevation myocardial infarction or non-ST-elevation myocardial infarction with positive markers of myocardial damage is well defined, exclusion of coronary artery disease or myocardial ischemia in the remaining patients is more challenging. This group represents the majority of patients admitted for chest pain syndromes and that have a substantial risk of an adverse outcome. Given that troponin, as a marker of myocardial damage, detects terminal events in the cascade of acute coronary syndrome, there is a need to search for biomarkers that are able to identify patients at high risk, allowing rapid, bedside stratification. Data suggest that clinical events are prone to occur more frequently in patients with coronary artery stenosis associated with myocardial ischemia. Accordingly, identification of systemic biomarkers of ischemia could facilitate identification of high-risk patients with a high burden of coronary atherosclerosis and plaque rupture. We describe six biomarkers that have been linked to myocardial ischemia. Until now, these biomarkers of ischemia are relevant in order to exclude ischemic heart disease (high negative predictive value) but still lack specificity. Future prospective studies should be performed in larger and more diverse sets of patients presenting with ischemia, and in a complementary fashion in order to provide valuable tools for clinical decision making.

Topics: Albumins; Biomarkers; Choline; Coronary Artery Disease; Cystatin C; Fatty Acids, Nonesterified; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Toll-Like Receptors; Troponin

B-type natriuretic peptide (BNP), initially identified in brain tissues, is now recognized as a key cardiac hormone. Numerous studies over the last decade have demonstrated that both exogenous and endogenous BNP prevent left ventricular (LV) hypertrophy in experimental settings, largely via activation of particulate guanylyl cyclase (pGC)-coupled receptors. BNP represents somewhat of a paradox, in that upregulation of BNP expression is widely used as a diagnostic marker for LV hypertrophy, diastolic dysfunction and heart failure in the clinic. We and others have postulated that BNP serves as an endogenous brake on the LV myocardium, seeking to curb the runaway train of signaling pathways that drive the progression from LV hypertrophy though remodeling, heart failure and death. This review summarizes the mechanisms of BNP's antihypertrophic actions, the role for cyclic GMP-mediated inhibition of pro-hypertrophic signaling, and BNP's impact on LV function. The improved understanding of the mechanisms of BNP regulation of LV hypertrophy and function that has emerged from both the experimental and clinical experience with this peptide provides new insight into the potential that BNP pharmacotherapy still offers for patients with LV hypertrophy.

Topics: Animals; Antioxidants; Biomarkers; Cardiotonic Agents; Cardiovascular Diseases; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Protein Biosynthesis; Protein Isoforms; Receptors, Atrial Natriuretic Factor; Signal Transduction; Transcription, Genetic; Ventricular Function, Left; Ventricular Remodeling

Sudden cardiac death(SCD) from early myocardial ischemia is often lack of typically morphological findings and clinical manifestation, thus cases of SCD may be suspected as criminal cases. It is necessary to clarify the cause of death, which is significance for medico-legal investigation. This article reviewed the latest advancement in the studies on the application of inorganic ions, CK-MB, cTn, ANP and BNP for certification of death from SCD in order to provide a practical way for diagnosis of SCD in forensic pathology.

Topics: Atrial Natriuretic Factor; Autopsy; Biomarkers; Calcium; Cause of Death; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Forensic Pathology; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Troponin

Cardiovascular disease is the leading cause of death among patients with Type 2 diabetes mellitus. The main forms of structural heart disease associated with diabetes are coronary heart disease and diabetic cardiomyopathy, which is characterized by left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction. Asymptomatic structural heart disease is common and associated with a poor prognosis in patients with diabetes. Contemporary practice guidelines do not recommend screening of asymptomatic individuals for structural heart disease. Potential screening modalities, such as echocardiography, are costly and inaccessible. A simple, inexpensive blood test for brain natriuretic peptide is a useful marker of structural heart disease and is a prime candidate for screening patients with Type 2 diabetes mellitus and prioritizing referral for echocardiography.

Topics: Biomarkers; Cardiomyopathies; Diabetes Mellitus, Type 2; Echocardiography; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Across the entire spectrum of ischemic heart disease, amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are a strong and independent prognostic indicator, representing a particularly strong predictor of heart failure or death. This risk is independent of all other variables, including renal function or troponin, and is proportional to the magnitude of NT-proBNP release, with higher risk observed among those with a more marked elevation of the marker. Although prospective studies on the effect of NT-proBNP measurement in guiding therapy in ischemic heart disease are lacking, among patients presenting with acute coronary syndromes, it is recommended to measure NT-proBNP on (or near) the time of admission. An elevated initial NT-proBNP concentration should prompt consideration of an early invasive management approach. Consideration should be given to repeating the NT-proBNP measurement after 24-72 hours and again at 3-6 months because these follow-up measurements provide more long-term prognostic information than single measures at presentation. In acute ischemic heart disease, an NT-proBNP value >250 ng/L is associated with an adverse prognosis. In patients with stable coronary artery disease, measurement may be performed for prognostication purposes at 6- to 18-month intervals. In the case of clinical suspicion of disease progression, a new sample may be warranted.

Topics: Biomarkers; Diagnosis, Differential; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index

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

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 and subsequent cardiac remodelling. Cardiac biomarkers can be used for diagnosis and assessment 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 challenges with potential ischaemia markers are specificity and the diagnostic reference standard for assessment. To date, only one, ischaemia modified albumin, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, has become the diagnostic standard as the biomarker of myocardial necrosis. The sensitive nature of troponin measurement has also revealed that myocardial necrosis is also found in a range of other clinical situations. This illustrates 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 for both acute ACS and detecting the sequelae of post infarction myocardial insufficiency. The role of the B type natriuretic peptides in detection of cardiac failure, acute and chronic, is well defined. Their role in ACS remains the subject of further studies.

Topics: Acute Coronary Syndrome; Acute Disease; Biomarkers; Cardiovascular Diseases; Chest Pain; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Troponin I; Troponin T

Brain natriuretic peptide (BNP) is one of the cardiac peptide hormones that are involved in water and electrolyte homeostasis in heart failure. There are two mechanisms for increased BNP gene expression: cardiomyocyte stretching and neurohormonal activation. Many recent studies reported an increase in BNP gene expression with elevated plasma concentrations of BNP/NT-proBNP and its precursor, proBNP, in overt heart failure as well as in myocardial ischemia or acute coronary syndrome. In addition, the elevated plasma concentrations of BNP and NT-proBNP are a prognostic marker of morbidity, mortality and later development of heart failure in patients with acute coronary syndrome. In the management of children with congenital heart disease the role of BNP as a diagnostic tool is less evident. This review summarizes recently known facts about the role of BNP in the diagnosis, management and prognosis of congestive heart failure, myocardial ischemia and congenital heart disease (Ref. 33). Full Text (Free, PDF) www.bmj.sk.

Topics: Biomarkers; Heart Defects, Congenital; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Cardioprotection is an all-encompassing term for physico-biochemical or therapeutic interventions which slow or ameliorate the progression of cardiomyocyte necrosis. There are a number of established and novel biomarkers to assess coronary artery disease at initiation, ischemia, necrosis and myocardial dysfunction. Established biomarkers such as creatine kinase-MB, cardiac troponins and natriuretic peptides have been utilized for the assessment of cardioprotection, especially during surgery. Novel markers are currently being investigated for detection and risk assessment in patients with acute coronary syndromes. Ischemia-modified albumin is used for the early detection of cardiac ischemia and could be a potential biomarker for assessing the early cardioprotective effects of damage-limiting interventional measures.

Topics: Animals; Biological Assay; Biomarkers; Creatine Kinase, MB Form; Disease Progression; Humans; Myocardial Infarction; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Necrosis; Predictive Value of Tests; Reproducibility of Results; Serum Albumin; Treatment Outcome; Troponin I; Troponin T; Ventricular Dysfunction

The recommendations from respected bodies concerning the treatment and follow up of patients undergoing coronary angioplasty for stable angina or acute coronary syndrome (ACS) are essential for reducing the risks related to the procedure, and for preventing the occurrence of long term complications. Measuring the levels of troponin and CK-MB is part of the diagnostic and prognostic strategy during the coronary angioplasty procedure. In this context, the frequent elevation of markers following uncomplicated angioplasty is a sign of minor irreversible myocardial damage, the prognostic significance of which remains under discussion. Recent data suggest that only a basal troponin elevation (more so than CK-MB) prior to angioplasty has a long term prognostic value in ACS ST- patients, and that troponin elevation occurring after the procedure in the presence of normal basal concentrations, is only associated with in-hospital complications. Determining the basal level of troponin would appear to be essential for interpreting any elevation in concentrations following angioplasty. The recommendations should integrate this fundamental point, if it is confirmed. On the other hand, the question has been raised whether other markers (CRP, BNP and/or NT-proBNP) should be systematically measured as a routine prior to angioplasty. An elevation of CRP before and/or after angioplasty is an unfavourable short and long term prognostic factor. Elevation of NT-proBNP before angioplasty is also an unfavourable long term prognostic factor. Recommending a multi-marker strategy might represent a future direction for identifying at risk patients prior to coronary angioplasty, thus enabling specific treatment to be proposed.

Topics: Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Creatine Kinase, MB Form; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stents; Troponin

The diagnostic approach to acute coronary syndromes (ACS) remains one of the most difficult and controversial challenges facing emergency physicians. In recent years, cardiac troponins have emerged as the biochemical "gold standard" for diagnosis of patients with acute chest pain, enhancing our ability to recognize ACS. Early diagnosis and treatment of myocardial ischemia improve patient outcomes, but conventional markers are often nondiagnostic at the time of arrival at the emergency department. Promising new biomarkers, which appear earlier after the onset of ischemia, are being studied and integrated into clinical practice. Some are markers of myocyte necrosis, but others, including ischemia-modified albumin and natriuretic peptides, detect myocardial ischemia and myocardial dysfunction. The aim of the present article is to review the diagnostic approach to ACS, focusing on recent literature describing novel biochemical markers. If ongoing and future studies confirm their role in probability-based models risk assessment, a new era in the diagnostic approach to ACS may be dawning.

Topics: Angina, Unstable; Biomarkers; Creatine Kinase; Humans; Myocardial Ischemia; Myoglobin; Natriuretic Peptide, Brain; Pregnancy-Associated Plasma Protein-A; Serum Albumin; Troponin

Topics: Biomarkers; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Survival Analysis

After brain natriuretic peptide (BNP) was isolated in 1988, rapid progress was made in cloning its cDNA and gene, facilitating studies of tissue-specific expression and molecular regulation of gene expression. This review focuses on the molecular determinants of regulation of the rat and human BNP genes, including signaling pathways that impact on changes in gene expression and cis regulatory elements responsive to these signaling pathways. For both rat and human genes, elements in the proximal promoter (-124 to -80), including GATA, MCAT, and AP-1-like, have been shown to contribute to basal and inducible regulation. More distal elements in the human BNP gene respond to calcium signals (an NF-AT site at -927), thyroid hormone (a thyroid-responsive element at -1000), and mechanical stretch (shear stress-responsive elements at -652 and -162). Understanding how BNP is regulated by signaling molecules that are activated in the hypertrophied and ischemic heart should be useful in understanding the underlying pathology. This may lead to therapeutic strategies that prevent hypertrophy while allowing for the beneficial effects of BNP production.

Topics: Animals; DNA, Complementary; Exons; Gene Expression Regulation; Humans; Inflammation; Models, Biological; Models, Genetic; Mutation; Myocardial Ischemia; Natriuretic Peptide, Brain; Promoter Regions, Genetic; Protein Processing, Post-Translational; Rats; Signal Transduction; Tissue Distribution

We reviewed the current medical literature that pertained to the question of whether myocardial ischemia triggers the release of B-type natriuretic peptides (BNPs) and, in particular, whether transient exercise-induced ischemia can be detected by the measurement of changes in these biomarkers. BNPs are well-established as markers of left ventricular dysfunction, particularly heart failure. There is accumulating evidence that various conditions with the common denominator of myocardial ischemia are also associated with increased circulating levels of these peptides.. Recently published methods and results, which includes our published and unpublished data, were reviewed.. The results show that exercise-induced ischemia or its associated regional wall-motion abnormalities trigger the release of BNPs and that the measurement of plasma levels of N-terminal pro brain natriuretic peptide and BNP before and immediately after symptom-limited exercise can distinguish patients with and without ischemia with a high degree of accuracy.

Topics: Animals; Biomarkers; Exercise; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Regression Analysis; Sensitivity and Specificity

Since the first biomarker of myocardial necrosis was described in 1954, cardiac-specific biomarkers have been increasingly identified. This, coupled with dramatic evolution in assay technology and resultant highly sensitive assays, has rendered a remarkable transformation in the medical use of biomarkers. Initially used to aid in diagnosis of myocardial infarction, newer biomarkers of inflammation, plaque instability, and ischemia may complement biomarkers of necrosis by providing tools to diagnose impending myocardial necrosis before irreversible damage occurs, and offering additional information for risk stratification. Importantly, biomarkers of different processes may be combined to enhance risk stratification above that of any single marker.

Topics: Angina, Unstable; Biomarkers; C-Reactive Protein; CD40 Ligand; Humans; Inflammation; Interleukins; Myocardial Infarction; Myocardial Ischemia; Myoglobin; Natriuretic Peptide, Brain; Necrosis; Peroxidase; Pregnancy-Associated Plasma Protein-A; Risk Assessment; Troponin

Chest pain is the most common clinical presentation of acute ischemic heart disease, but only one third of these patients are ultimately found to have an acute coronary syndrome. Initial assessment of the patient presenting with chest pain includes a careful history, physical examination, an initial electrocardiogram (ECG) and measurement of biochemical markers of myocardial injury. The natriuretic peptide system is activated in a broad spectrum of cardiovascular diseases, including acute coronary syndromes and stable coronary disease. A strong relation between plasma levels of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) obtained in the subacute phase, and long-term, all-cause mortality, as well as the rate of re-admissions for heart failure after myocardial infarction, has been documented. Persistently elevated NT-proBNP levels during the first 72 hours following admission for an acute coronary syndrome have recently been associated with the presence of refractory ischemia and high risk of short-term recurrent ischemic events. Patients with signs of exercise-induced ischemia by dobutamine stress echocardiography have been reported to have higher baseline BNP values. Moreover, BNP and NT-proBNP levels are increased acutely in proportion to the magnitude of the inducible perfusion defect observed during stress testing, suggesting that BNP and NT-proBNP are markers of acute ischemia. Recently, a relationship between circulating levels of BNP and NT-proBNP and long-term all cause mortality in patients with stable coronary artery disease has been documented.

Topics: Cardiovascular Diseases; Chest Pain; Coronary Disease; Electrocardiography; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain

The existing markers for myocardial necrosis, such as cardiac troponin, creatine kinase-MB, and myoglobin are thought to be released into blood following irreversible myocardial necrosis. Thus results of these tests are usually negative for patients with acute coronary syndromes (ACS) who present to the emergency department (ED) within the first 3 hours after the onset of chest pain. Given the need to make early therapeutic and triage decisions, biomarkers that can be used to diagnose and/or risk stratify ACS patients during their initial ED presentation will be important. Active research in this area has identified several classes of biomarkers that show promise for early detection of disease. These include tests for the presence of acute inflammation and infiltration (e.g., high sensitivity-C-reactive protein, myeloperoxidase), plaque instability (e.g., pregnancy-associated plasma protein-A, placental growth factor), platelet activation (e.g., whole blood choline, platelet density, CD40 ligand), and myocardial ischemia (e.g., ischemia modified albumin, free fatty acids, serum choline, and B-type natriuretic peptide). Each of these tests has demonstrated some utility for early diagnosis. However, as most lack specificity for myocardial disease, routine use may require a multi-marker approach.

Topics: Biomarkers; C-Reactive Protein; Coronary Disease; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peroxidase; Platelet Activation

Topics: Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Catheterization; Cardiac Volume; Controlled Clinical Trials as Topic; Diagnosis, Differential; Diastole; Diuretics; Echocardiography; Echocardiography, Doppler; Female; Heart Failure; Heart Rate; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Physicians, Family; Prognosis; Prospective Studies; Ventricular Dysfunction, Left

Fifty percent of patients who experience death or develop heart failure after acute coronary syndromes (ACS) have extremely elevated concentrations of plasma B-type natriuretic peptides. These elevations, however, seem not to reflect permanent ventricular dysfunction or heart failure and are assumed to exist already at the onset of ischemic symptoms. The underlying mechanisms of BNP/Nt-proBNP elevations in patients with ACS are still not known at present. Furthermore, the relationship of elevated BNP/Nt-proBNP with mortality but not with atherothrombotic complications of underlying disease makes it difficult to choose optimal therapeutic strategies based on plasma levels of these peptides. The remarkably high short- and long-term mortality rate associated with increases of BNP/Nt-proBNP elevations clearly show the need of further investigation to focus on this high-risk group of patients in order to clarify underlying pathomechanisms and to find optimal therapeutic approaches.

Topics: Acute Disease; Biomarkers; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Risk Factors

Topics: Coronary Angiography; Heart Diseases; Humans; Magnetic Resonance Angiography; Myocardial Ischemia; Natriuretic Peptide, Brain; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-proBNP) are released from the heart in response to increased wall stress. Assays for these peptides are now commercially available, and measurement of BNP and N-proBNP is becoming commonplace in patients with suspected heart failure. BNP and N-proBNP facilitate diagnosis and risk stratification in patients with heart failure, and may help guide response to therapy. This review focuses on the emerging role of BNP and N-proBNP measurement in patients with acute coronary syndromes (ACS). Although experimental studies demonstrate rapid BNP release in response to cardiac ischemia, it is unlikely that BNP will be used to diagnose cardiac ischemia, because many other conditions are also associated with modest BNP elevation. In contrast, BNP holds tremendous promise as a prognostic marker in patients with ACS. Studies to date have shown consistently that higher BNP levels are associated with worse clinical outcomes, and that BNP provides unique information to clinical variables, other biomarkers, and left ventricular ejection fraction. Future studies are needed to identify the therapeutic implications of BNP elevation in patients with ACS.

Topics: Acute Disease; Angina, Unstable; Atrial Natriuretic Factor; Cardiotonic Agents; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Protein Precursors; Syndrome

The role of the clinical laboratory in emergency cardiac medicine is rapidly evolving; with recent redefinitions of acute myocardial infarction (AMI) and unstable angina (UA) based on troponin levels, recommended acceleration of cardiac testing protocols, and increased clinical measurement of B-type natriuretic peptide (BNP). We briefly review the background pathophysiology of acute coronary syndromes (ACS) and congestive heart failure (CHF), along with an overview of the biochemistry and physiology of the natriuretic peptides.. The assay principles and performance characteristics of the rapid BNP assays are discussed. The performance characteristics of troponin assays are at the center of controversy regarding the redefinition of AMI and UA, and will be discussed.. We review the rapidly expanding evidence regarding the clinical utility of BNP for CHF patients. While BNP has gained wide acceptance as a rapid diagnostic tool, considerable controversy remains concerning its potential for prognosis, screening, and therapeutic monitoring. Although a thorough discussion of the use of cardiac markers is well beyond the scope of this review, overviews of the redefinitions of AMI and UA, and the trend toward accelerated testing protocols to obtain a quicker diagnosis or ruling-out of AMI are included. In addition to accelerating the retesting of existing markers, a recent test for ischemia modified albumin (IMA) promises another quantum leap in cardiac diagnoses.. The positive impact of these developments on the healthcare costs and overall improvement in the quality of healthcare delivery will be discussed. A brief analysis of the downstream costs of BNP testing is also offered.

Topics: Atrial Natriuretic Factor; Biomarkers; Emergencies; Heart Failure; Humans; Medical Laboratory Science; Myocardial Ischemia; Natriuretic Peptide, Brain

Cardiac Ischemia is an important trigger for the release of B-type natriuretic peptide (BNP). BNP and N-terminal pro-BNP (N-proBNP) are emerging as important biomarkers for risk stratification in patients with acute coronary syndromes. Higher levels of BNP and pro-BNP are associated with a greater risk for death and heart failure, independent of traditional clinical variables and levels of other biomarkers such as troponins and C-reactive protein. The therapeutic implications of these findings are not yet known.

Topics: Acute Disease; Biological Assay; Biomarkers; Coronary Disease; Heart Failure; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Risk Assessment

1. The major cardiovascular and renal actions of alpha-atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the fact that the heart is strategically located to sense changes in intravascular volume indicate the importance of these peptides in the overall control of the extracellular fluid volume under normal and pathophysiological conditions.2. This review examines the clinical and diagnostic significance of the measurement of plasma natriuretic peptides in diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure. 3. Raised plasma levels of ANP and BNP have repeatedly been found in patients with heart disease originating from diverse causes including tachycardias, valvular stenosis or ventricular dysfunction. The raised circulating levels of natriuretic peptide (ANP, N-terminal proANP and BNP in particular) are associated with (i) raised atrial and pulmonary wedge pressures; (ii) reduced ventricular systolic and diastolic function; (iii) presence (and possibly geometric form) of left ventricular hypertrophy; and (iv) severe myocardial infarction. Although both plasma ANP and BNP are raised in the presence of left ventricular hypertrophy, BNP appears to be a better index of left ventricular hypertrophy.4. Several situations where the measurement of natriuretic peptides may be of benefit in the overall assessment of heart disease are discussed. However, it is emphasized that the measurement of plasma natriuretic peptides alone appears to be of limited value as a specific diagnostic tool, given that raised levels are a consequence of haemodynamic and structural abnormalities arising from diverse pathological processes. Despite these limitations, the major value of plasma natriuretic peptides in the examination of patients with suspected heart disease rests on the premise that: (i) a normal value would not be consistent with cardiac disease; (ii) the presence of markedly raised levels may help to target those for subsequent detailed assessment of underlying cardiac dysfunction; and (iii) markedly raised levels of plasma natriuretic peptides after myocardial infarction can identify those at high risk of death.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Risk Factors

Growth hormone (GH) therapy in heart failure (HF) is controversial. We investigated the cardiovascular effects of GH in patients with chronic HF due to ischemic heart disease.. In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66 years; 95% male) with ischemic HF (ejection fraction [EF] < 40%) to a 9-month treatment with either recombinant human GH (1.4 mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP).. No changes in cardiac structure or systolic function were identified in either treatment group; nor did GH treatment affect QoL or functional class. In the GH group, circulating levels of IGF-1 doubled from baseline (+105%; p < 0.001) and NT-proBNP levels halved (-48%; p < 0.001) during the treatment period, with subsequently a partial return of both towards baseline levels. No changes in IGF-1 or NT-proBNP were observed in the placebo group at any time during the study.. In patients with chronic ischemic HF, nine months of GH treatment was associated with significant increases in levels of IGF-1 and reductions in levels of NT-proBNP, but did not affect cardiac structure, systolic function or functional capacity.

Topics: Aged; Biomarkers; Case-Control Studies; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Human Growth Hormone; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Single biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP).. Consecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints.. Among 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63-0.69), hs-cTnI 0.70 (95%CI 0.67-0.73, p=0.07 vs CJb), and BNP 0.66 (95%CI 0.62-0.69, p=0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72-0.77 vs AUC 0.74, 95%CI 0.71-0.77, p=0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3-1.9), and BNP for death (HR 1.6, 95%CI 1.3-2.1).. A dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone.. We included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment.. Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148.

Topics: Aged; Area Under Curve; Biomarkers; Coronary Artery Disease; Electrocardiography; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Tomography, Emission-Computed, Single-Photon; Troponin I

Heart failure (HF) is the end stage of many heart diseases, and ischemic heart disease (IHD) is the primary cause. Yiqi Fumai lyophilized injection, a contemporary Chinese medicine preparation, widely used in the treatment of IHF patients, shows clinical efficacy on improving symptoms and cardiac function, but the quality of the current literature does not address multiple important issues. This article describes a protocol for assessment of complementary treatment with Yiqi Fumai lyophilized injection in acute decompensated IHD.. The protocol is designed as a multicenter randomized controlled trial to assess the efficacy and safety of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated IHD. This trial will be carried out in 37 hospitals in China and expected to enroll 666 inpatients with acute decompensated IHF due to coronary heart disease. On the basis of standardized western medications, patients are randomized to either the treatment group (250 ml 5% glucose / sodium injection + 5.2 g Yiqi Fumai lyophilized injection) or the control group for 7 days and follow-up for 30 ± 3 and 60 ± 3 days. The primary outcome is change in brain natriuretic peptide (BNP) concentrations. The secondary outcomes are composite endpoint, left ventricular ejection fraction, blood troponin T/I, cardiothoracic ratio, life quality scale, scores of the four traditional Chinese medicine (TCM) diagnostic methods.. Standardized western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. The trial will provide clinical research evidence for application of complementary treatment with intravenous Yiqi Fumai lyophilized injection on decompensated IHF.. This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-15007396, http://www.chictr.org.cn/showproj.aspx?proj=12370 ) on November 6, 2015.

Topics: Adult; Aged; Biomarkers; Cardiovascular Agents; China; Drug Compounding; Drugs, Chinese Herbal; Female; Freeze Drying; Heart Failure; Humans; Injections, Intravenous; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Ischemia; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome; Troponin; Ventricular Function, Left

Inflammation and dysregulated immune responses play a crucial role in atherosclerosis, underlying ischaemic heart disease (IHD) and acute coronary syndromes (ACSs). Immune responses are also major determinants of the postischaemic injury in myocardial infarction. Regulatory T cells (CD4. Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes is a single-centre, first-in-class, dose-escalation, two-part clinical trial. Patients with stable IHD (part A) and ACS (part B) will be randomised to receive either IL-2 (aldesleukin; dose range 0.3-3×10. The study received a favourable opinion by the Greater Manchester Central Research Ethics Committee, UK (17/NW/0012). The results of this study will be reported through peer-reviewed journals, conference presentations and an internal organisational report.. NCT03113773; Pre-results.

Topics: Acute Coronary Syndrome; C-Reactive Protein; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Double-Blind Method; Humans; Immunologic Factors; Interleukin-2; Interleukin-6; Lymphocyte Count; Myocardial Ischemia; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Recombinant Proteins; T-Lymphocytes, Regulatory; Troponin

To investigate the effects of dexmedetomidine on perioperative cardiac adverse events in elderly patients with coronary heart disease.
 Methods: Sixty elderly patients, who were diagnosed as coronary heart disease and underwent gastric cancer operation, were randomly divided into 2 groups (n=30): the dexmedetomidine group (Dex group) and the control group. In the Dex group, dexmedetomidine was administered intravenously at 0.5 μg/(kg·h) after a bolus infusion at 0.5 μg/kg for 10 min before anesthesia induction. In the control group, equal volume of normal saline was infused instead of dexmedetomidine. The 2 groups received the same anesthesia treatment. The venous bloods were collected at the preoperative 0 h and postoperative 24 h. The concentrations of cardiac troponin (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP) and hypersensitive C-reactive protein (hs-CRP) were determined. The ECG was monitored at the above time and the postoperative incidence of cardiac adverse events was recorded.
 Results: The levels of cTnI, NT-proBNP and hs-CRP in serum were elevated in the 2 groups after the operation. Compared with the control group, the levels of cTnI, NT-proBNP and hs-CRP were significantly decreased in the Dex group (P<0.05). Compared with the control group, the incidence of bradycardia were significantly increased, while the myocardial ischemia and tachycardia were significantly decreased in the Dex group during the operation (P<0.05); the incidence of silent myocardial ischemia and arrhythmia was significantly reduced at 3 days after operation in the Dex group (P<0.05).
 Conclusion: Dexmedetomidine could decrease the incidence of cardiac adverse events in elderly patients with coronary heart disease.. 目的：观察右美托咪定对冠心病患者围手术期心脏不良事件的影响。方法：择期行开腹胃癌切除术的老年冠心病患者60例，采用随机数字表法将其分为右美托咪定组(Dex组)与对照组(Control组)，每组30例。两组患者麻醉管理一致，其中Dex组诱导麻醉前10 min静脉微量泵入右美托咪定0.5 μg/kg，10 min后继续泵注维持量0.5 μg/(kg·h)至手术结束；Control组在同一时点采用等量的生理盐水静脉输注。分别于术前、术毕、术后24 h采集静脉血标本，测定肌钙蛋白I(cTnI)、N-末端脑利钠肽原(N-terminal pro-brain natriuretic peptide，NT-proBNP)、超敏C反应蛋白(hypersensitive C-reactive protein，hs-CRP)的水平。记录术中、术后3 d心脏不良事件的发生情况。结果：两组患者术前血清cTnI，NT-proBNP，hs-CRP水平比较，差异无统计学意义(P>0.05)；术后24 h时血清cTnI，NT-proBNP，hs-CRP较术前都显著升高(P<0.05)，且Dex组在术后24 h时血清cTnI，NT-proBNP及hs-CRP水平明显低于Control组(P<0.05)。两组患者术中均未发生心肌梗死；与Control组比较，Dex组心动过缓发生率升高，心动过速和心肌缺血发生率降低(P<0.05)。Dex组术后无症状性心肌缺血和心律失常发生率与Control组相比明显降低(P<0.05)。结论：右美托咪定能够降低老年冠心病患者围手术期心脏不良事件的发生率。.

Topics: Adrenergic alpha-2 Receptor Agonists; Aged; Biomarkers; Bradycardia; C-Reactive Protein; Coronary Disease; Dexmedetomidine; Humans; Incidence; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Stomach Neoplasms; Tachycardia; Troponin I

The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function.. Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons.. We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.

Topics: Aged; Bone Marrow Transplantation; Cardiomyopathies; Coronary Vessels; Female; Granulocyte Colony-Stimulating Factor; Humans; Injections, Intra-Arterial; Injections, Intramuscular; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Stem Cell Transplantation; Stroke Volume; Tomography, X-Ray Computed; Transplantation, Autologous; United Kingdom

Tβ4 is an integral factor in repair of myocardium in animal models. To investigate whether Tβ4 is important in human cardiac disease and has a role in mediating the beneficial cardiac effects of bone-marrow-derived stem cell (BMSC) therapy, we measured serial plasma Tβ4 levels in patients enrolled on the REGENERATE-IHD cell therapy trial.. Plasma Tβ4 concentrations were measured in 13 patients who received BMSCs and 14 controls.. There was a significant increase in plasma Tβ4 in the BMSC group 24 h after intracardiac injection. Increases in Tβ4 levels were associated with improvement in New York Heart Association symptom class.. This exploratory study highlights the need for further study of Tβ4 in human cardiovascular disease.

Topics: Aged; Bone Marrow Cells; Cell Count; Chronic Disease; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Stem Cell Transplantation; Thymosin; Treatment Outcome

Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients.. This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery.

Topics: Adult; Aged; Biomarkers; Bone Marrow; Bone Marrow Transplantation; Cell- and Tissue-Based Therapy; Coronary Sinus; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Transplantation, Autologous; Ventricular Function, Left

Functional ischemic mitral regurgitation (FIMR) increases mortality independently of the baseline characteristics and ventricular function. The effect of treating FIMR with annuloplasty is unclear when mitral regurgitation is moderate. Myocardial revascularization alone has been shown to improve mitral valve function.. We randomized 31 patients with moderate (grade 2-4) FIMR to receive either coronary artery bypass grafting (CABG) alone or CABG plus downsizing mitral ring annuloplasty. The patients were followed up for clinical outcomes and echocardiographic assessment of mitral valve function and left ventricular dimensions at 3 and 12 months. Clinical improvement was assessed using the Minnesota quality-of-life questionnaire, 6-minute walk test, and brain natriuretic peptide levels.. The clinical course was similar in the 2 groups of patients during the study period. FIMR was perfectly corrected intraoperatively in the ring group. Echocardiographic follow-up at 3 months showed no difference in the FIMR grade between the 2 groups (66% less than grade 2 in the CABG alone and 86% in the CABG plus ring group; P = .316). The improvement in the CABG alone group was even more marked at 12 months (85% less than grade 2 in the CABG group and 85% in the CABG plus ring group). The left ventricular ejection fraction was significantly better at 3 months in the CABG alone group, although at 12 months, the left ventricular ejection fraction in the 2 groups had improved similarly.. Although initially effective at reducing moderate FIMR, the addition of a ring did not change the clinical course after CABG surgery. At 12 months, no echocardiographic difference was found in terms of residual mitral regurgitation, left ventricular dimensions and function, or clinical outcomes.

Topics: Aged; Biomarkers; Coronary Artery Bypass; Echocardiography, Doppler; Exercise Test; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Prosthesis Design; Quality of Life; Quebec; Recovery of Function; Severity of Illness Index; Stroke Volume; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ventricular Function, Left

The association between the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the severity of coronary artery disease (CAD) diagnosed by coronary angiography and other approaches has been investigated. The clinical application of NT-proBNP is restricted by the drawbacks of these techniques now available in screening out patients who need intensive or conservative treatment. Fractional flow reserve (FFR) is superior to coronary angiography and other functional indicators. Accordingly, we designed to investigate the association between NT-proBNP and myocardial ischemia from the perspective of anatomy and physiology in patients with unstable angina and preserved left ventricular function. Plasma samples were collected from 110 patients and NT-proBNP levels were measured by radioimmunoassay. The severity of coronary artery stenosis in patients was measured by coronary angiography and FFR. Stenosis ≥50% in the left main artery or stenosis of 70%, and fractional flow reserve (FFR) ≤0.80 in one or more coronary branches with diameter ≥2mm were defined as "positive", which require revascularization. NT-proBNP levels increased progressively between patients with negative and positive angiographic results (p<0.05), and between FFR-negative and FFR-positive patients (p<0.05). A significant correlation was observed between logNT-proBNP and logGS (GS=Gensini score, p<0.001). NT-proBNP level serves as a predictor of positive results of angiographic stenosis and FFR, with the area under the receiver operating characteristic curve being 0.697 and 0.787, respectively. NT-proBNP levels are correlated with the severity of anatomic coronary obstruction and inducible myocardial ischemia, but NT-proBNP per se is insufficient to identify clinically significant angiographic and physiological stenoses.

Topics: Aged; Angina, Unstable; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left

The impact of different forms of cardiac stress testing (exercise versus pharmacological stress testing) on cardiac wall stress and myocardial ischemia is incompletely understood.. In a prospective study, 331 consecutive patients with suspected myocardial ischemia referred for nuclear perfusion imaging were enrolled: 266 underwent exercise (bicycle) stress testing and 65 adenosine stress testing. Levels of B-type natriuretic peptide (BNP) measured before and 1 min after stress testing, ischemic ECG changes, and typical angina symptoms were used to compare the 2 testing modalities.. Cardiac wall stress as quantified by changes in BNP levels significantly increased in the exercise stress group, but not in the adenosine group (increase in BNP levels 22 pg/ml (IQR 6-46) versus -3 pg/ml (IQR -3 to 28); p<0.001). In the bicycle exercise stress group, patients with reversible defects on nuclear perfusion imaging more often had angina symptoms (25% vs. 9%, p=0.0001) and ischemic ECG changes (33% vs. 12%, p=0.0001) during the stress test, and a greater increase in BNP levels (28 (IQR 11-58) versus 16 (IQR 3-34) pg/ml, p=0.001) compared to those without reversible defects. Those differences between patients with and without reversible defects were not observed with the adenosine protocol (p-values all >0.05).. Exercise stress testing but not adenosine stress results in an increase of cardiac wall stress, angina symptoms and ECG changes. The absence of these surrogates of myocardial ischemia suggests that adenosine stress does not induce acute myocardial ischemia, but rather displays relative perfusion differences.

Topics: Aged; Angina Pectoris; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Radionuclide Imaging; Ultrasonography

Statins, beyond their lipid lowering role, exert beneficial effect on endothelial function in patients with atherosclerosis. Aim of the present study was to examine the short term pleiotropic effects of different doses of atorvastatin treatment, on endothelial function, arterial stiffness and indices of left ventricular remodeling in heart failure (HF) patients.. We studied the effect of 4 weeks administration of atorvastatin in 22 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery and arterial stiffness by augmentation index (AIx). Serum levels of matrix metalloproteinase-9 (MMP-9) and intracellular adhesion molecule-1 (sICAM-1) were measured as biomarkers of left ventricular remodeling and endothelial function, respectively, while, b-type natriuretic peptide (BNP) was measured as a marker of left ventricular function.. Compared to baseline, atorvastatin 40 mg/d significantly improved FMD values (3.18 ± 3.03% vs. 5.98 ± 2.49%, p = 0.001) and AIx values (25.98 ± 8.55% vs. 23.09 ± 8.87%, p = 0.046). In addition, compared to baseline measurements, treatment with atorvastatin 40 mg/d resulted in significantly decreased levels of serum logMMP-9 levels (2.47 ± 0.23 ng/ml vs. 2.39 ± 0.24 ng/ml, p = 0.04) and of logICAM-1 levels (2.46 ± 0.13 ng/ml vs. 2.37 ± 0.16 ng/ml, p < 0.001). No significant changes were found after treatment with atorvastatin 10 mg/d in the aforementioned parameters.. Short term treatment with 40 mg/d of atorvastatin exerts beneficial impact on arterial wall properties and on indices of left ventricle remodeling in heart failure patients.

Topics: Aged; Arteries; Atorvastatin; Cholesterol, LDL; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Male; Matrix Metalloproteinase 9; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Pyrroles; Regression Analysis; Ventricular Remodeling

To test the diagnostic accuracy for detecting an acute myocardial infarction (AMI) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation, myocardial ischaemia and necrosis; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10- to 12-hour troponin measurement.. Substudy of the point-of-care arm of the RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial.. The emergency departments of six hospitals.. Prospective admissions with chest pain and a non-diagnostic electrocardiogram randomised to point-of-care assessment or conventional management.. Blood samples taken on admission and 90 minutes from admission for measurement of cardiac markers [cardiac troponin I (cTnI), myoglobin and creatine kinase MB isoenzyme (CK-MB)] by point-of-care testing. An additional blood sample was taken at admission and 90 minutes from admission for analysis of high-sensitivity cTnI (two methods) and cardiac troponin T (cTnT), myoglobin, heart-type fatty acid-binding protein (H-FABP), copeptin and B-type natriuretic peptide (NTproBNP).. 1. Diagnostic accuracy compared with the universal definition of myocardial infarction utilising laboratory measurements of cardiac troponin performed at the participating sites together with measurements performed in a core laboratory. 2. Ability of biomarker measurements to predict major adverse cardiac events (death, non-fatal AMI, emergency revascularisation or hospitalisation for myocardial ischaemia) at 3 months' follow-up. 3. Comparison of incremental cost per quality-adjusted life-year (QALY) of different biomarker measurement strategies for the diagnosis of myocardial infarction.. Samples were available from 850 out of 1132 patients enrolled in the study. Measurement of admission myoglobin [area under the curve (AUC) 0.76] and CK-MB (AUC 0.84) was diagnostically inferior and did not add to the diagnostic efficiency of cTnI (AUC 0.90-0.94) or cTnT (AUC 0.92) measurement on admission. Simultaneous measurement of H-FABP and cTnT or cTnI did improve admission diagnostic sensitivity to 0.78-0.92, but only to the same level as that achieved with troponin measured on admission and at 90 minutes from admission (0.78-0.95). Copeptin (AUC 0.62) and NTproBNP (AUC 0.85) measured on admission were not useful as diagnostic markers. As a prognostic marker, troponin measured on admission using a high-sensitivity assay (AUC 0.73-0.83) was equivalent to NTproBNP measurement (AUC 0.77) on admission, but superior to copeptin measurement (AUC 0.58). From modelling, 10-hour troponin measurement is likely to be cost-effective compared with rapid rule-out strategies only if a £30,000 per QALY threshold is used and patients can be discharged as soon as a negative result is available.. The measurement of high-sensitivity cardiac troponin is the best single marker in patients presenting with chest pain. Additional measurements of myoglobin or CK-MB are not clinically effective or cost-effective. The optimal timing for measurement of cardiac troponin remains to be defined. Copeptin measurement is not recommended. H-FABP requires further investigation before it can be recommended for simultaneous measurement with high-sensitivity troponin in patients with acute chest pain.. ISRCTN37823923.. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 15. See the HTA programme website for further project information.

Topics: Acute Disease; Biomarkers; Cost-Benefit Analysis; Creatine Kinase, MB Form; Emergency Service, Hospital; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Glycopeptides; Humans; Myocardial Infarction; Myocardial Ischemia; Myoglobin; Natriuretic Peptide, Brain; Peptide Fragments; Point-of-Care Systems; Prognosis; Prospective Studies; Sensitivity and Specificity; Troponin I; Troponin T

Heart failure (HF) is associated with decreased quality of life, high re-admission rate and poor prognosis. In particular, ischemic heart failure (IHF) has a worse prognosis than nonischemic HF. The use of traditional Chinese medicine (TCM) alongside Western medicine to treat HF has developed into an integrative treatment model in China. There have been small clinical trials and experimental studies to demonstrate the efficacy of TCM for treating HF; however, there is still a lack of high-quality trials. Qishen Yiqi dripping pills (QSYQ), a TCM drug, have been commonly used alongside standardized Western medicine to treat IHF. This paper describes the protocol for the clinical assessment of QSYQ in IHF patients.. A randomized, double-blind, multicenter, placebo-controlled trial will assess the efficacy and safety of QSYQ in the treatment of IHF. The trial is to enroll 640 IHF patients from 32 hospitals in China. Besides their standardized Western medicine, patients will be randomized to receive treatment of either QSYQ or placebo for 6 months and follow-up monitoring for at least a further 6 months. The primary outcome is increased exercise capacity of patients, which will be measured using the 6-minute walking test (6MWT). The secondary outcomes include composite endpoints: all-cause mortality, frequency of hospitalization or emergency due to cardiovascular events, brain natriuretic peptide levels, left ventricular ejection fraction, and cardiothoracic ratio will be documented, as well as scores on the New York Heart Association classification and Minnesota quality of life index, and information obtained from the four TCM diagnostic methods. Blood lipid tests will also be administered.. The integrative treatment model of TCM alongside Western medicine has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of QSYQ in the treatment of IHF.

Topics: Biomarkers; Cardiovascular Agents; China; Double-Blind Method; Drug Therapy, Combination; Drugs, Chinese Herbal; Exercise Test; Exercise Tolerance; Heart Failure; Hospitalization; Humans; Lipids; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Quality of Life; Recovery of Function; Research Design; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Walking

Enhanced external counterpulsation (EECP) is a noninvasive treatment that is proven safe and effective in patients with coronary artery disease (CAD) and heart failure (HF). The aims of this study are to investigate the clinical effects of EECP therapy in patients with symptomatic CAD and chronic HF, and to find out an answer to the question: Does EECP therapy have any effect on the prognostic markers of HF?. This study was designed as a prospective cohort study. A total of 68 consecutive patients with symptomatic CAD and chronic HF referred to EECP therapy were enrolled in this study between November 2007 and December 2010; 47 patients (39 males and 8 females, 65 ± 7, years), have undergone EECP treatment, and 21 patients (20 males and 1 female, 62 ± 10 years), who did not want to participate in the EECP program comprised the control group. Statistical analysis was performed using t tests for dependent and independent samples, Mann-Whitney U test, Chi-square and Fischer exact tests.. EECP therapy resulted in significant Improvement in post-intervention New York Heart Association functional class (p<0.001), left ventricular ejection fraction (p<0.001), B-type natriuretic peptide levels (p<0.003), uric acid levels (p<0.05), free-T3/free-T4 ratio (p<0.034) and mitral annular E (p<0.05) velocity, compared with baseline, a finding not evident in the control group.. EECP treatment significantly improved clinical and some biochemical parameters, which are mostly prognostic markers in patients with symptomatic CAD and chronic HF.

Topics: Aged; Blood Pressure; Cohort Studies; Counterpulsation; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Oximetry; Plethysmography; Prognosis; Prospective Studies; Thyroxine; Triiodothyronine; Ultrasonography; Uric Acid

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. In this study we analyzed whether intracoronary autologous freshly isolated BMCs-Tx have beneficial effects on cardiac function in patients with ischemic heart disease (IHD).. In this prospective nonrandomized study we treated 12 patients with IHD by freshly isolated BMCs-Tx by use of point of care system and compared them with a representative 12 control group without cell therapy. Global ejection fraction (EF) and infarct size area were determined by left ventriculography.Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size (p < 0.001) and an increase of global EF (p = 0.003) as well as infarct wall movement velocity (p < 0.001) after 6 months follow-up compared to control group. In control group there were no significant differences of global EF, infarct size and infarct wall movement velocity between baseline and 6 months after coronary angiography. Furthermore, we found significant decrease in New York Heart Association (NYHA) as well as significant decrease of B-type natriuretic peptide (BNP) level 6 months after intracoronary cell therapy (p < 0.001), whereas there were no significant differences in control group 6 months after coronary angiography.. These results demonstrate that intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system is safe and may lead to improvement of cardiac function in patients with IHD.. ISRCTN54510226.

Topics: Aged; Biomarkers; Bone Marrow Transplantation; Cell Separation; Coronary Angiography; Female; Germany; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Point-of-Care Systems; Prospective Studies; Recovery of Function; Stroke Volume; Time Factors; Transplantation, Autologous; Treatment Outcome; Ventricular Function, Left

Immunological processes are implicated in the multifactorial pathophysiology of heart failure (HF). The multifunctional chemokine fractalkine (CX3CL1) promotes the extravasation of cytotoxic lymphocytes into tissues. We aimed to assess the prognostic value of fractalkine in HF. Fractalkine plasma levels were determined in 349 patients with advanced systolic HF (median 75 years, 66% male). During a median follow-up of 4.9 years (interquartile range: 4.6-5.2), 55.9% of patients died. Fractalkine was a significant predictor of all-cause mortality (p<0.001) with a hazard ratio of 2.78 (95% confidence interval: 1.95-3.95) for the third compared to the first tertile. This association remained significant after multivariable adjustment for demographics, clinical predictive variables and N-terminal pro-B-type natriuretic peptide (NT-proBNP, p=0.008). The predictive value of fractalkine did not significantly differ between patients with ischaemic and non-ischaemic HF aetiology (p=0.79). The predictive value of fractalkine tertiles was not significantly modified by tertiles of NT-proBNP (p=0.18) but was more pronounced in the first and third tertile of NT-proBNP. Fractalkine was also an independent predictor of cardiovascular mortality (p=0.015). Fractalkine levels were significantly lower in patients on angiotensin-converting enzyme inhibitor therapy (p<0.001). In conclusion, circulating fractalkine with its pro-inflammatory and immunomodulatory effects is an independent predictor of mortality in advanced HF patients. Fractalkine improves risk prediction beyond NT-proBNP and might therefore help to identify high risk patients who need special care. Our data indicate the implication of immune modulation in HF pathology.

Topics: Aged; Aged, 80 and over; Biomarkers; Chemokine CX3CL1; Cohort Studies; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors

Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45(+) and CD133/45(+) CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD.

Topics: AC133 Antigen; Aged; Antigens, CD; Antigens, CD34; Bone Marrow Transplantation; Female; Glycoproteins; Heart; Hematopoietic Stem Cell Mobilization; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptides; Point-of-Care Systems; Stem Cells; Stroke Volume; Transplantation, Autologous; Ventricular Function, Left

The aim of the study was to assess clinical and classic echocardiographic data in patients with different cardiac resynchronization therapy (CRT) outcomes.. Sixty consecutive patients (aged 66.3 ± 8.7 years, 57 men) with chronic heart failure (CHF) in New York Heart Association (NYHA) classes III-IV despite optimized pharmacotherapy, with left ventricular end-diastolic diameter (LVEDD) > 55 mm, left ventricular ejection fraction £ 35% and wide QRS complex (≥ 120 ms), including individuals with permanent atrial fibrillation (AF) and single- and dual-chamber pacing, were assessed firstly before, and secondly three months after, biventricular heart stimulator implantation (excluding three patients who died during the follow-up). Patients developing ≥ 10% reduction of left ventricular end-systolic volume (LVESV) were classified as responders to CRT.. The group of responders (n = 34, 59.7%) and the group of non-responders (n = 23, 40.3%) did not differ regarding baseline echocardiographic parameters or in terms of clinical data of age, gender, concomitant diseases, smoking or pharmacological treatment. The differences involved higher rates of ischemic CHF background, prevalence of hypertension and permanent AF, and a higher concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) among the non-responders. In the multivariate logistic regression analysis, NT-proBNP, body mass index (BMI) and the presence of permanent AF correlated negatively with the magnitude of LVESV reduction following CRT introduction.. Classic echocardiographic data did not predict left ventricle reverse remodeling. Higher rates of ischemic CHF aetiology, hypertension, permanent AF and higher NT-proBNP concentration were found in the group without at least 10% LVESV reduction at the three month follow-up. NT-proBNP, BMI and the presence of permanent AF had negative effects on the magnitude of LVESV.

Topics: Aged; Atrial Fibrillation; Cardiac Resynchronization Therapy; Echocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Ventricular Function, Left; Ventricular Remodeling

Among patients with non-ST-segment elevation acute coronary syndromes, recurrent ischemia and ventricular arrhythmias detected on continuous electrocardiographic monitoring remain common events that are associated with worse outcomes. The relative clinical significance of both events together is not well described. We determined the risk associated with ischemia (≥1 mm ST depression lasting ≥1 minutes) and ventricular tachycardia (VT) (≥4 beats) detected on 7-day continuous electrocardiographic monitoring in 6,355 patients with non-ST-segment elevation acute coronary syndromes from the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction (MERLIN-TIMI) 36 trial. The patients were categorized into 4 groups according to the presence or absence of VT and ischemia. Cardiovascular death, sudden cardiac death (SCD), myocardial infarction, and recurrent ischemia were assessed during a median follow-up of 348 days. A total of 60.0% patients had no VT or ischemia, 20.0% had VT alone, 14.7% had ischemia alone, and 5.3% had both. The patients with either VT or ischemia were at increased risk of cardiovascular outcomes. The combination of ischemia and VT identified a particularly high-risk population for cardiovascular death (10.1% vs 3.0%, p <0.001), SCD (7.8% vs 0.9%, p <0.001), and myocardial infarction (15.4% vs 6.2%, p <0.001) compared to patients with neither. The addition of arrhythmia and ischemia significantly improved the clinical model for predicting cardiovascular death or SCD (p <0.001). In patients with both ischemia and VT, 66.6% of SCD occurred within 90 days of the non-ST-segment elevation acute coronary syndromes. In conclusion, in >6,300 patients with non-ST-segment elevation acute coronary syndromes, the presence of myocardial ischemia or VT alone, and particularly in combination, was independently associated with poor cardiovascular outcomes and thus provides incremental improvement in early risk stratification.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Diabetes Mellitus; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Recurrence; Risk Assessment; Sex Factors; Stroke Volume; Tachycardia, Ventricular; Troponin

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial perfusion scintigraphy (MPS). Myocardial ischemia on MPS was present in 140 (50%) patients. These ischemic patients had significantly higher NT-pro-BNP levels compared with patients without ischemia: 183 pg/ml (64-324 pg/ml) vs. 88 pg/ml (34-207 pg/ml), respectively (p<0.001). In addition, NT-pro-BNP ≥180 pg/ml was an independent predictor of the presence of myocardial ischemia (OR 2.36, 95%CI 1.40-3.97, p=0.001). Possible confounding factors such as age and creatinine clearance were of no influence on the predictive value in this specific patient population. These findings strengthen the idea that NT-pro-BNP may be of value in the early detection of diabetic patients with hemodynamic significant coronary artery disease.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Right ventricular (RV) dysfunction adversely affects prognosis in patients with chronic heart failure (CHF) due to left ventricular (LV) dysfunction. However, little evidence exists regarding the prognostic role of RV systolic and diastolic function indexes in combination with plasma B-type natriuretic peptide (BNP) in advanced CHF. Thus, 102 consecutive hospitalized patients with advanced CHF (New York Heart Association classes III to IV) due to LV systolic dysfunction (LV ejection fraction <35%) were studied by 2-dimensional conventional and tissue Doppler imaging (TDI) echocardiography of the left and right ventricles. Plasma BNP was also measured. Patients were followed for 6 months for major cardiovascular events (cardiovascular death and/or CHF-related hospitalization). During follow-up, 13 patients died and 63 patients reached the combined end point of cardiovascular death or CHF-related hospitalization. By univariate analysis, RV TDI systolic velocity, dilated cardiomyopathy, digoxin treatment (all p values <0.01), and female gender (p <0.05) were associated with increased cardiovascular death. Transmitral Doppler to mitral annular TDI early diastolic velocity ratio, RV TDI early diastolic velocity (p <0.05), and ratio of early to late RV diastolic TDI velocities (p <0.01) predicted the combined end point. In multivariate analysis, decreased RV systolic velocity, dilated cardiomyopathy, and female gender (all p values <0.05) were independent predictors of cardiovascular death, whereas increased ratio of early to late RV diastolic TDI velocities (p <0.01) and increased BNP (p <0.05) predicted the combined end point. In conclusion, RV TDI indexes combined with increased plasma BNP additively predict adverse cardiac outcomes in advanced CHF.

Topics: Aged; Biomarkers; Blood Flow Velocity; Cardiomyopathy, Dilated; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Ventricular Dysfunction, Right

The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis.. Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (n=25) rise to peak values ( approximately 3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curve=0.97; P<0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted.. Our results demonstrate for the first time that BNPsp exists as a distinct entity in the human circulation and could serve as a new class of circulating biomarker with the potential to accelerate the clinical diagnosis of cardiac ischemia and myocardial infarction. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: ACTRN12609000040268.

Topics: Acute Coronary Syndrome; Biomarkers; Chest Pain; Electrocardiography; Humans; Immunoassay; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Tandem Mass Spectrometry

Fluorouracil (FU) is a cornerstone of colorectal cancer treatment; however, it has clinical and subclinical influence on the heart. This study aimed to clarify the pathophysiology, risk factors, and long-term effects of FU cardiotoxicity.. The study prospectively accrued colorectal cancer patients (n=106) completely resected and adjuvantly treated with FU and oxaliplatin according to the FOLFOX4 regimen (infusional FU, folinic acid, and oxaliplatin). Serial measurements were made of systolic and diastolic features of the left ventricle by radionuclide ventriculography, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), lactic acid, and ECG before chemotherapy, immediately after a treatment infusion, and at follow-up 2 weeks after cessation of the intended 12 treatment courses and were further evaluated by multivariate regression analysis that included cardiovascular history and its risk factors.. In the entire cohort, NT-proBNP significantly increased from baseline 14.5±3.2 pmol/L (mean±standard error) to 28.3±5.3 pmol/L during FU therapy (P<.001). Nine patients (8.5%) with cardiotoxicity had significantly higher NT-proBNP of 55.3±40.8 pmol/L compared with 25.4±4.1 pmol/L in those without (P<.001). In multivariate analysis, the FU-induced rise of NT-proBNP was significantly higher in females (P<.001). Plasma lactic acid significantly increased from baseline (1.3±0.1 mmol/L to 1.8±0.1 mmol/L) during FU therapy (P<.001). Left ventricular ejection fraction at baseline of 0.66±0.01 remained unchanged at 0.65±0.01 during FU therapy and 0.66±0.01 at follow-up (P=.4).. FU therapy generally induces myocardial neuroendocrine changes with increasing plasma NT-proBNP and lactic acid but without long-term dysfunction of the left ventricle. The usability of NT-proBNP as a predictive marker for FU cardiotoxicity remains to be clarified.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Colorectal Neoplasms; Female; Fluorouracil; Humans; Lactic Acid; Leucovorin; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Organoplatinum Compounds; Prospective Studies; Risk Factors; Ventricular Dysfunction, Left

Functional electrical stimulation (FES) improves exercise capacity and endothelial function in chronic heart failure (CHF) patients. This study evaluates the impact of FES on quality of life and emotional stress in patients with moderate to severe CHF.. Thirty patients with stable CHF (24 men; NYHA class II-III; left ventricular ejection fraction <35%) were randomly assigned (2:1) to a 6-week FES training program (n=20) or placebo (n=10). Questionnaires addressing quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall], and emotional stress [Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)], as well as plasma B-type natriuretic peptide (BNP) and 6-min walking distance test (6MWT) were assessed at baseline and after completion of training protocol.. A significant improvement in KCCQ functional (F=76.666, p<0.001), KCCQ overall (F =41.508, p<0.001), BDI (F =17.768, p<0.001) and Zung SDS (F =27.098, p<0.001) was observed in the FES group compared to placebo. Patients in the FES group had also a significant increase in 6MWT (F =19.413, p<0.001) and a trend towards reduction in plasma BNP (F =4.252, p=0.053) compared to placebo.. FES seems to have a beneficial effect on quality of life, exercise capacity and emotional stress in patients with moderate to severe CHF.

Topics: Analysis of Variance; Cardiomyopathy, Dilated; Chronic Disease; Electric Stimulation Therapy; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Placebos; Quality of Life; Statistics, Nonparametric; Stress, Psychological; Surveys and Questionnaires; Treatment Outcome

Cardiac peptides are increased at rest in heart failure patients representing a useful diagnostic tool for this condition. Recently it has been demonstrated that cardiac peptides increase also during myocardial ischemia. Cardiac peptides increase during exercise in heart failure patients, but it has not been established yet if the increase is the same in ischemic and nonischemic patients.. There were studied 50 heart failure patients, 32 ischemic and 18 nonischemic, 35 males and 15 females aged 61.8 +/- 11.61 after the relief of congestive syndrome, which was submitted to a symptom-limited exercise stress test on a cycloergometer. Blood samples were obtained at rest and at a peak effort and the plasmatic values of NT-proBNP (NV<250 fmoles/mL) and of NT-proANP (NV<1950 fmoles/mL) were determined using the ELISA method.. At rest, both NT-proBNP and NT-proANP were more increased in nonischemic (1104.33 +/- 730; 3275.55 +/- 3424) than in ischemic patients (685.68 +/- 452.01, 2265.0 +/- 2552.32) with significant differences only for NT-proBNP (p=0.016). During exercise NT-proBNP increase from 836.40 +/- 596.34 to 1403.92 +/- 2126.21 and NT-proANP from 2628.80 +/- 2903.41 to 3701.30 +/- 3237.76, the final values being again more increased in nonischemic patients (NT-proBNP-2945.44 +/- 3257.89; NT-proANP-3174 +/- 2905); for NT-proBNP p<0.05. The results suggest that the stretching effect during exercise is more increased at the ventricular level in comparison with the atrial level (67% increase for NT-proBNP and only 40% for NT-proANP). Surprisingly, myocardial ischemia does not increase additionally cardiac peptides either at rest or during exercise. Our data suggest that the intracardiac pressure is more important than ischemia in determining the increase of cardiac peptides in heart failure patients because the left ventricular ejection fraction was lower in nonischemic patients (40.03 +/- 5.5 vs 38.11 +/- 4.07).. Cardiac peptides are increased, both at rest and during exercise, in nonischemic heart failure patients in comparison with ischemic ones, probably in relationship with the lower left ventricular systolic function.

Topics: Atrial Natriuretic Factor; Exercise Test; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index

The aim of the study was to assess the accuracy of N-terminal probrain natriuretic peptide (NT-proBNP) to predict mortality or detect acute ischemia in patients with coronary artery disease (CAD).. This study included 1,552 patients with stable (n = 1,059) or unstable (n = 493) CAD undergoing percutaneous coronary intervention. NT-proBNP was measured before percutaneous coronary intervention. The primary endpoint of the study was mortality. Patients were followed for 3.6 years.. There were 171 deaths (11%) during follow-up. In the entire group of patients, NT-proBNP had the best accuracy to predict mortality (area under receiver operating characteristic curve 0.76, 95% CI 0.72-0.80). In patients without congestive heart failure (n = 760) there were 46 deaths (6%). The area under receiver operating characteristic curve of NT-proBNP was reduced to 0.70 (95% CI 0.63-0.79) which was not better than the area under curve of age (p = 0.981) or C-reactive protein (p = 0.082) regarding mortality. NT-proBNP showed limited power to detect patients with acute ischemia (area under curve 0.63, 95% CI 0.60-0.66) among consecutive patients with stable and unstable CAD.. NT-proBNP has a moderate accuracy to predict mortality and does not assist in the diagnosis of acute myocardial ischemia in patients with CAD.

Topics: Aged; Biomarkers; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests

To determine whether serum B-type natriuretic peptide measured at rest and peak exercise and DeltaBNP contribute to the predictive value and diagnostic accuracy of exercise test in the diagnosis of myocardial ischemia.. Ventricular myocytes release BNP in response to increased wall stress that occurs in acute ischemia. During exercise testing, transient myocardial ischemia could also cause acute myocardial stress and changes in circulating BNP.. BNP was measured before and immediately after exercise testing with radionuclide imaging in 203 consecutive subjects referred for chest pain evaluation. Tested subjects were classified as ischemic and non-ischemic based on exercise results, and no ischemia, mild-moderate, and severe ischemia according to perfusion scan results. A logistic regression model, constructed of an ROC and an AUC (area under the curve), was used.. Ischemic ECG changes (> or =1 mm, horizontal S-T shift) were detected in the treadmill exercise test in 127 subjects (62.6%), and 76 (37.4%) had neither ST segment shift nor chest pain. Baseline BNP was higher in the ischemic group compared to the non-ischemic group (p=0.044); peak BNP was also higher in the ischemic group (p=0.025), as was DeltaBNP (p=0.0126). Of these 127 subjects, 106 (52% of all) had abnormal perfusion scan results. In the ischemic group, the median baseline, peak exercise BNP, and DeltaBNP values from baseline to peak were higher than in the non-ischemic group. In the severe ischemic group these variables were approximately three-fold higher than in the mild-moderate ischemic group (p<0.0001 for baseline; p<0.0001 for peak; and p<0.0001 for DeltaBNP). Rest, peak exercise, and DeltaBNP values were significantly higher in patients with previous myocardial infarction (p<0.001) and in patients treated with beta blockers; peak exercise BNP was higher in hypertensives and diabetics (p<0.05). The ROC convergence model showed that the AUC for peak-exercise BNP was best able to discriminate and predict severe ischemia and no ischemia, while DeltaBNP from rest to peak exercise discriminated best between mild-moderate and severe ischemia.. Peak exercise BNP and DeltaBNP improved the sensitivity, specificity, positive likelihood ratio, predictive value, and diagnostic accuracy of severe ischemia detection during an exercise test. The contribution of BNP determination during exercise was, however, less impressive than previously reported by others.

Topics: Aged; Biomarkers; Exercise Test; Female; Humans; Male; Middle Aged; Models, Statistical; Myocardial Ischemia; Natriuretic Peptide, Brain; Physical Exertion; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Rest; Sensitivity and Specificity; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon

In patients with ischemic cardiomyopathy, mortality rate and quality of life are unsatisfactory. We investigated the effects of the metabolic agent trimetazidine (TMZ) on exercise tolerance and prognostic markers B-type natriuretic peptide (BNP) and cardiac troponin T (cTnT) plasma levels.. Fifty patients with ischemic cardiomyopathy were randomized either to receive TMZ (20 mg, TID) in addition to their conventional treatment (TMZ group, n = 25) or to continue their usual drug therapy (control group, n = 25) for 6 months. Patients were evaluated at baseline, at 1 month, and at 6 months (echocardiography and 6-minute walking test). At enrollment and at the end of follow-up, blood testing was performed for determination of BNP and cTnT plasma levels.. After 6 months, no significant New York Heart Association class changes occurred in all patients (P = NS). In the TMZ group, a significant increase of exercise tolerance (P < .01) was detected, whereas left ventricular ejection fraction was unchanged (28% +/- 4%, 29% +/- 5%, and 32% +/- 5% at baseline, at 1 month, and at 6 months, respectively; P = NS). In the TMZ group, BNP was significantly reduced (6 months, 135 +/- 22 vs 252 +/- 44 pg/mL; P < .001), whereas it was significantly increased in controls (6 months, 288 +/- 46 vs 239 +/- 59 pg/mL; P < .02); cTnT significantly (P < .001) reduced during TMZ treatment, whereas it was unchanged in the control group.. Six-month TMZ treatment improves exercise tolerance and reduces plasma levels of BNP and cTnT in patients with compensated ischemic cardiomyopathy.

Topics: Exercise Tolerance; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Trimetazidine; Troponin T; Vasodilator Agents

To investigate the effects of high thoracic epidural anesthesia (HTEA) on chronic heart failure (CHF) and its safety.. 117 patients with ischemic cardiomyopathy (ICM) of NYHA class II - IV and with the LVEF < or = 45%, 90 males and 27 females, aged 45 - 81, were Randomly divided into 2 groups: control group (n = 54, treated with the routine medication) and HTEA group (n = 63, administrated epidurally with 0.5% lidocaine 3 - 5 ml every two hours from 9 a.m. to 11 p.m. everyday via an epidural catheter for one month in addition to the routine treatment). Echocardiography was performed before and after the treatment to examine the cardiac structure and left ventricular systolic function. The plasma brain natriuretic peptide (BNP) was examined before and after the treatment.. The clinical symptoms and signs of the HTEA group were improved markedly. The total effective rate was 95.2% in the HTEA group, significantly higher than in the control group (85.2%, P < 0.05). Echocardiographic parameters showed that the diameters of ventricles and atrium decreased by 3 - 5 mm in the HTEA group. The left ventricular end diastolic volume (LVEDV) of the HTEA group reduced from (337 +/- 132) ml before treatment to 274 ml +/- 109 ml after treatment, and the left ventricular end systolic volume (LVESV) of the HTEA group reduced from (215 +/- 99) ml before treatment to (147 +/- 73) ml after treatment (both P < or = 0.001). The regurgitation area of mitral valve of the HTEA group reduced from (6.6 +/- 3.7) cm(2) before treatment to (4.3 +/- 2.7) cm(2) after treatment, and the regurgitation area of tricuspid valve of the HTEA group reduced from (5.4 +/- 3.2) cm(2) before treatment to (3.3 +/- 2.3) cm(2) after treatment (both P < 0.01). No changes were observed in the E/A ratio in both groups. The BNP level fell from (678 +/- 521) ng/L to (237 +/- 225) ng/L in the HTEA group (P < or = 0.05). In the HTEA group, one patient died because of deterioration of cardiac function. HTEA was well tolerated and caused lower incidence of adverse events.. HTEA obviously improves the heart function of the patients with CHS secondary to ICM. Consequently, HTEA is effective and safe in CHF patients with favorable tolerance.

Topics: Aged; Aged, 80 and over; Anesthesia, Epidural; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Thorax; Treatment Outcome

Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional CABG using cardiopulmonary bypass. Off-pump technique reduces the complications of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000; Mack et al. 2004a,b). The object of this study was to compare peri- and postoperative time courses of vasoactive peptides - atrial natriuretic poptide (ANP), brain natriuretic poptide (BNP) and endothelin-1 (ET-1) in off-pump versus on-pump CABG. 22 patients, who underwent on-pump (group A, n = 11) or off-pump CABG (group B, n = 11) were studied. The peri- and postoperative time courses of plasma ANP and BNP were similar in both groups. A statistically significant difference between ET-1 plasma level 2 h after surgery in the group A and ET-1 plasma level 2 h after surgery in the group B (2.46 + or - 1.14 pg/ml/Ht versus 0.74 + or - 0.09 pg/ml/Ht, p < 0.0001) was found. Different CABG techniques were not associated with significant changes in peri- and postoperative plasma ANP and BNP. By contrast, plasma ET-1 significantly rose in the group A 2 h after surgery, indicating endothelial damage.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Endothelin-1; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain

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

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

Aspirin has been associated with adverse heart failure outcomes, probably because of a blunting interaction with angiotensin-converting enzyme (ACE) inhibitors. Therefore, we hypothesized that clopidogrel when compared with aspirin would be associated with a slower progression of heart failure as determined by levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP).. In an open-label, randomized, 2-treatment, 2-period crossover study, 18 patients with ischemic heart failure (14 post-myocardial infarction, left ventricular ejection fraction 0.32 +/- 0.08), median age 73, New York Heart Association class II (11 patients) or III (7 patients), all taking ACE inhibitors were included. Patients were randomized to 8 weeks of aspirin 100 mg/day followed by 8 weeks of clopidogrel 75 mg/day, or the reversed sequence. Blood levels of NT-proBNP were measured using sandwich immunoassay. Patients on aspirin experienced an 8-times greater increase in log-transformed values of NT-proBNP compared with patients on clopidogrel (average change 4.757% versus 0.597%; P = .0395 for intervention, P = .4453 for period, P = .4046 for sequence). We observed no change in functional class, 6-minute walking test, creatinine levels, or electrolytes.. Aspirin is associated with a greater increase in natriuretic peptides (log-transformed NT-proBNP levels), implying that aspirin therapy is associated with a more progressive course of heart failure.

Topics: Aged; Aged, 80 and over; Aspirin; Cardiac Output, Low; Clopidogrel; Cross-Over Studies; Disease Progression; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation Inhibitors; Ticlopidine

Short-term infusion of carperitide (atrial natriuretic peptide) has beneficial effects on neurohumoral factors; however, it remains unclear whether the effects are sustained for long-term infusion. To evaluate the effects of long-term infusion of carperitide on neurohumoral factors in patients with chronic congestive heart failure (CHF), we measured neurohumoral factors before and 1 hour after stopping carperitide infusion in 42 CHF patients. Carperitide infusion was continued for more than 2 days until there was symptomatic improvement of CHF. Patients were divided into 2 groups by the median value of infusion duration: group 1 (less than 7 days, n=21) and group 2 (more than 7 days, n=21). In group 1, aldosterone (ALD) and endothelin-1 (ET-1) were significantly increased after stopping carperitide. In contrast, ALD and ET-1 did not change after stopping carperitide in group 2. The molar ratio of cyclic guanosine monophosphate/atrial natriuretic peptide before stopping carperitide was significantly lower in group 2 than in group 1. Suppression of ALD and ET-1 was maintained for 7 days of carperitide infusion, but the beneficial effect on neurohumoral factors was attenuated after more than 7 days, probably through down-regulation of biologic receptors coupled with guanylate cyclase in CHF patients.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Chronic Disease; Cyclic GMP; Endothelin-1; Female; Heart Failure; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Time Factors; Treatment Outcome

Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and the marker of apoptosis, Fas/Apo-1.. In a single-center, prospective, randomized, double-blind, placebo-controlled study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to standard therapy. Clinical assessment, radionuclide ventriculography, echocardiography, and blood analyses were performed at baseline and after 6 months. There were no differences in baseline characteristics between the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment resulted in an improvement in functional class (P<0.005) and an increase in systolic blood pressure (P<0.05) and left ventricular radionuclide ejection fraction (P<0.05) compared with the placebo-treated group. There were reductions in plasma concentrations of CRP, NT-pro BNP, TNF-alpha, and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group.. In patients with heart failure due to ischemic left ventricular dysfunction, the addition of pentoxifylline to standard therapy results in improvements in clinical status and radionuclide ejection fraction, which are accompanied by reductions in plasma markers of inflammation, prognosis, and apoptosis.

Topics: Adjuvants, Immunologic; Blood Pressure; C-Reactive Protein; Double-Blind Method; Exercise Test; fas Receptor; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pentoxifylline; Peptide Fragments; Tumor Necrosis Factor-alpha; Ultrasonography; Ventricular Function, Left

The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion.. Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP).. NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Blood Pressure; Carbazoles; Cardiovascular Agents; Carvedilol; Creatinine; Drug Therapy, Combination; Europe; Female; Heart Failure; Hospitalization; Humans; Life Tables; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Prognosis; Propanolamines; Proportional Hazards Models; Prospective Studies; Stroke Volume; Survival Analysis

B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are elevated in patients with acute coronary syndromes and are closely linked to prognosis. Because there is only a small amount of data available concerning NT-proBNP in patients with stable angina pectoris, we aimed to determine whether NT-proBNP is of additional diagnostic value in these patients.. Ninety-four patients with stable angina pectoris were prospectively included. All patients underwent exercise testing and coronary angiography, and 91 patients received thallium-201 single-photon emission computed tomography myocardial scintigraphy. NT-proBNP was analyzed at rest and after exercise testing. NT-proBNP was elevated in patients with inducible myocardial ischemia shown by single-photon emission computed tomography (396 +/- 80 pg/mL vs 160 +/- 101 pg/mL; P <.01) closely linked to the extent of coronary artery disease (CAD) (no CAD, 148 +/- 29 pg/mL; 1- or 2-vessel disease, 269 +/- 50 pg/mL; 3-vessel disease 624 +/- 186 pg/mL; P <.01). In a multivariate analysis, NT-proBNP was an independent predictor for CAD. The area under the curve of the receiver operating characteristic curve was 0.72 for NT-proBNP to predict CAD. Using an optimized cut off level of 214 pg/mL, CAD can be predicted with high accuracy. The total test efficiency of exercise testing can be improved from 1.46 to 1.52 when combined with NT-proBNP measurement.. NT-proBNP is elevated in patients with stable angina pectoris and has a close correlation to disease severity. Combining the measurement of NT-proBNP with exercise testing, the test accuracy for predicting severe CAD can be improved. Our data show an incremental value of NT-proBNP in the diagnostic process of stable angina pectoris.

Topics: Aged; Angina Pectoris; Biomarkers; Coronary Angiography; Coronary Disease; Exercise Test; Humans; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Severity of Illness Index; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

Elevated baseline levels of B-type natriuretic peptide (BNP) and the N-terminal fragments of its prohormone, N-terminal-pro-BNP (NT-proBNP), have been associated with adverse long-term outcome in patients with acute coronary syndromes, whereas the prognostic implications of serial NT-proBNP measurements have not been investigated to date.. NT-proBNP, troponin T, and C-reactive protein were measured at baseline and at 48 and 72 hours in 1791 patients with non-ST-elevation acute coronary syndromes. Death and myocardial infarction were recorded during 30 days of follow-up. After adjustment for independent predictors of cardiac risk, baseline NT-proBNP levels >250 ng/L were associated with higher event rates (adjusted OR, 3.7; 95% CI, 2.3 to 5.7; P<0.001). In troponin T-negative patients, NT-proBNP identified a subgroup of high-risk patients (OR, 5.9; 95% CI, 2.6 to 13.3; P<0.001). The risk in those patients (7.2%) did not significantly differ from that in troponin T-positive patients (9.8%; P=0.25). Importantly, clinical stabilization without refractory ischemia was associated with a rapid (as soon as 48 hours after onset of symptoms) and significant (48 hours; -24%; 72 hours, -49%; both P<0.001) decline in NT-proBNP levels. In patients with high NT-proBNP baseline levels, lack of a rapid decline in NT-proBNP levels (< or =250 ng/L) was linked to an adverse short-term prognosis (OR, 33.7; 95% CI, 8.2 to 138.8; P<0.001). In patients with low NT-proBNP baseline levels, a rise in NT-proBNP levels over 72 hours to >250 ng/L was also linked to an adverse 30-day prognosis (OR, 24.0; 95% CI, 8.4 to 68.5; P<0.001).. Neurohumoral activation as evidenced by NT-proBNP appears as a unifying feature that is independent of other biochemical markers (myocardial necrosis, inflammation) and is a powerful and independent determinant of the short-term cardiac risk in patients with acute coronary syndromes. Whether serial measurements of NT-proBNP in patients with ACS may be used to more rapidly identify patients suitable for early discharge or more intensive therapy deserves future prospective studies.

Topics: Acute Disease; Anticoagulants; Aspirin; Biomarkers; C-Reactive Protein; Drug Therapy, Combination; Follow-Up Studies; Heparin; Humans; Incidence; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Risk; Risk Assessment; Syndrome; Tirofiban; Troponin T; Tyrosine

Topics: Aged; Arrhythmias, Cardiac; Cardiomyopathies; Cardiotonic Agents; Dobutamine; Female; Heart Failure; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Treatment Outcome; Ventricular Premature Complexes

Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP.. Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage.. Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men.. Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Epinephrine; Exercise; Hematocrit; Hemoglobins; Humans; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Norepinephrine; Reference Values; Retrospective Studies; Risk Factors; Running; Troponin T

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

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

Diabetes mellitus is a global health problem. Cardiovascular events accounts for approximately 50 percent of mortality amongst the diabetics. Diabetics often present with silent myocardial ischaemia, since myocardial ischaemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release, we hypothesized that NT-proBNP might be useful in the early diagnosis. This study also evaluates whether any correlation exits between NT-proBNP levels and myocardial performance index (MPI).. This case control study was done on 30 patients with type 2 diabetes and similar matched group of 30 controls. Investigations like fasting and postprandial sugar level, kidney function test, HBA1c, lipid profile and NT-ProBNP levels were done. TMT was done to diagnose silent MI. Echocardiography was performed to assess MPI. The outcome measures were cut off levels of NT-ProBNP for predicting silent myocardial ischaemia based on TMT. P<0.05 was considered as significant.. NT-proBNP (pg/mL) was significantly increased in Diabetics in comparison to controls (595.33±464.48 vs 110.97 ± 34.81, p <.0001). MPI was significantly higher in diabetics (0.54±0.08 vs 0.33±0.02, p<.0001), and NT-proBNP showed significant positive correlation myocardial performance index (r= 0.726, p<0.0001). Silent MI was seen in 18(60%) patients which was based on TMT testing. Compared to those without silent MI, patients with silent MI had higher NTproBNP levels (795.5 vs 106, p value=0.0001) and higher MPI (0.59 ± 0.06 vs 0.46 ± 0.05, p value<.0001). A cut off of NT-pro BNP(pg/ mL) of >152 predicted silent MI in 93.33% cases with 100% sensitivity, 83.33% specificity, 90% PPV and 100% NPV.. NT-proBNP is a novel marker with positive correlation with MPI. It may be used as an independent predictor for silent MI in diabetics, thereby helping in reduction and treatment of CVD among them. Thus, it is suggested to screen all asymptomatic diabetics for underlying myocardial ischaemia by MPI, preferably, or by NTproBNP levels.

Topics: Biomarkers; Case-Control Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear.. Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples.. We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%.. cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

Topics: Biomarkers; Coronary Artery Disease; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin T

There are many detectable changes in circulating biomarkers in the setting of myocardial ischemia. We hypothesize that there are associated changes in circulating B-type natriuretic peptide (BNP) level after stress-induced myocardial ischemia, which can be used for emergency department (ED) acute coronary syndrome (ACS) risk stratification.. In a prospective study, we enrolled 340 patients over the age of 30 receiving an exercise echocardiography stress test in an ED observational unit for suspected ACS. We collected blood samples at baseline and at 2 and 4 h post-stress test, measuring the relative and absolute changes (stress-delta) in plasma BNP concentrations. In addition, patients were contacted at 90 days and at 1 year posttest for a follow-up. We calculated the diagnostic test characteristics of stress-delta BNP for a composite outcome of ischemic imaging on stress echocardiogram, nonelective percutaneous coronary intervention, coronary artery bypass graft surgery, subsequent acute myocardial infarction, or cardiac death at 1 year via a logistic regression. We analyzed the 2-h BNP concentrations using an ANOVA model to adjust for the baseline BNP level.. Baseline and 2-h post-stress BNP were both higher in the positive outcome group, but the stress-delta BNP was not. Stress-delta BNP had a sensitivity and specificity, respectively, of 53% and 76% at 2 h and 67% and 68% at 4 h. It was noted that patients with the composite outcome had a higher baseline BNP level.. BNP stress-deltas are poor diagnostic means for ACS risk stratification, but resting BNP remains a promising prognostic tool for ED patients with suspected ACS.

Topics: Acute Coronary Syndrome; Coronary Artery Disease; Emergency Service, Hospital; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies

Ischemic heart disease (IHD) is the leading cause of death and disability in many countries. The development of IHD is affected by a number of diseases, including metabolic syndrome (MS). Modern predictors of IHD include stimulating growth factor (ST2) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP).. The aim of the study was to investigate serum ST2 and NT-proBNP levels in patients with IHD and in patients with IHD in the setting of MS.. The concentrations levels of ST2 and NTproBNP were investigated using an enzyme-linked immunoassay in 20 patients with verified IHD. 8 patients had IHD without MS (5 males, 3 females) and 10 patients had MS (9 males and 1 female). The mean age of patients was 55 ± 2 years. The control group included 20 virtually healthy, age- and gender-matched individuals.. Serum concentrations of ST2 in patients with IHD in the setting of MS were 31% above normal (p<0.05). In MS-free patients with IHD, serum levels of ST2 were 16% above those in controls (p<0.05). Serum concentration levels of NT-proBNP in patients with IHD in the setting of metabolic syndrome were 62% above normal (p<0.05), while NT-proBNP levels in MS-free patients with IHD were within normal (p>0.05). It was established strong positive correlations between ST2 and NT-proBNP concentration levels (r = 0.90; p<0.05).. Based on the completed analysis of laboratory data, a conclusion can be made that concentrations of ST2 correlates positively with NT-proBNP values in patients with IHD in the setting of MS, which may suggest the presence of ischemic and metabolic disorders in these patients.

Topics: Biomarkers; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Metabolic Syndrome; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

To investigate the effect of myocardial injury on the prognosis of patients with severe or critical coronavirus disease 2019 (COVID-19).. Between February 10, 2020 and March 31, 2020, data of severe and critical COVID-19 patients were collected and retrospectively analyzed. Admission data included age, heart rates, mean arterial pressure, and myocardial injury markers including creatine kinase isoenzyme-MB (CK-MB), myoglobin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and interleukin-6. The endpoints included mortality, the incidence of malignant arrhythmia, and mechanical ventilation time. Univariate regression analysis, multivariate linear regression analysis, and binary logistic analysis were performed to develop the risk predictors in myocardial injury to the prognosis of severe and critical COVID-19 patients.. Seventy-four COVID-19 patients were included (mean age of 67.2 ± 14.6 years, male of 66.2%), including 42 severe and 32 critical cases. The mortality was 62.2% (n = 46). CK-MB (odds ratio = 5.895, p < .001, 95% confidence interval: 3.097-8.692) and interleukin-6 (odds ratio = 0.379; p = .005; 95% confidence interval: 1.051-1.769) were independent risk factors of increased mechanical ventilation time; myoglobin (odds ratio = 7.710; p = .045; 95% confidence interval: 1.051-56.571) were the independent predictor of incidence of malignant arrhythmia; age (odds ratio = 1.077; p = .009; 95% confidence interval: 1.019-1.139), myoglobin (odds ratio = 9.480; p = .032; 95% confidence interval: 1.211-78.188), and NT-proBNP (odds ratio = 4.852; p = .047; 95% confidence interval: 0.956-24.627) were the independent predictors of mortality.. In severe and critical COVID-19 patients, the obvious myocardial injury was observed. Increases of CK-MB, myoglobin, NT-proBNP, interleukin-6, and age were independently associated with poor prognosis including increased ventilation duration, the incidence of malignant arrhythmia, and mortality.

Topics: Aged; Biomarkers; China; COVID-19; Creatine Kinase, MB Form; Female; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Pandemics; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Risk Factors; ROC Curve; SARS-CoV-2; Troponin I

Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied.. To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age.. "The Study of Men Born in 1943" is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups.. Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model's discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up.. In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population.. The study is registered at Clinical Trials.gov Identifier number: NCT03138122.

Topics: Age Factors; Aged; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Early Diagnosis; Follow-Up Studies; Humans; Incidence; Interleukin-6; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Sex Factors; Sweden; Time Factors; Troponin T

B-type natriuretic peptide (BNP) secretion is stimulated by cardiac dysfunction. However, it is unclear how finely myocardial ischaemia contributes to BNP secretion and whether increases in BNP secretion contribute to coronary vasodilation. This study investigated the direct interaction between plasma BNP levels and cardiac ischaemia using the baseline distal-to-aortic pressure ratio (Pd/Pa). We examined the baseline Pd/Pa and fractional flow reserve (FFR) in 167 patients with intermediate coronary stenosis. The plasma BNP level appeared to be associated with the baseline Pd/Pa in the study population, and this association appeared to become clear only in patients with an FFR ≤ 0.80. To examine the effect of the baseline Pd/Pa on the BNP level in these patients, structural equation modeling (SEM) was performed. The baseline Pd/Pa significantly affected the BNP level (β: -0.37, p = 0.003) and the left ventricular ejection fraction (β: 0.43, p = 0.001). To examine the role of BNP in coronary vasodilation, we proposed another path model using a novel value obtained by dividing the FFR by the baseline Pd/Pa (FFR/baseline Pd/Pa) as an index of the hyperaemic response. The BNP level significantly affected the FFR/baseline Pd/Pa (β: 0.48, p = 0.037). This study demonstrated that BNP finely responded to an exacerbation of cardiac ischaemia and that increases in BNP secretion effectively ameliorated coronary vasoconstriction.

Topics: Aged; Arterial Pressure; Coronary Angiography; Coronary Stenosis; Coronary Vessels; Female; Hemodynamics; Humans; Male; Middle Aged; Models, Cardiovascular; Myocardial Ischemia; Natriuretic Peptide, Brain; Vasodilation

The role of NT-proBNP and hs-cTnT levels in predicting heart failure (HF) and cardiovascular disease (CVD) events in persons with prediabetes (pre-DM) and diabetes mellitus (DM) is not well-established. We examined the individual and combined relations of N-terminal natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels among asymptomatic adults with pre-DM and DM with the development of incident HF and CVD events. 5,584 participants with biomarker measures aged 45 to 84 years were included from the Multi-Ethnic Study of Atherosclerosis, of which 4,090 were normoglycemic, 799 had pre-DM, and 695 had DM at baseline and were followed for 12.4 ± 3.8 years. In those with DM, HF incidence rates per 1,000 person-years ranged from 3.2 to 39.4 across quartiles of NT-proBNP and 0.6 to 18.2 for hs-cTnT, respectively. Corresponding values for CVD incidence per 1,000 person-years ranged from 13.7 to 39.4 for NT-proBNP and 13.2 to 35.4 for hs-cTnT. Multivariate adjusted HRs were highest when both NT-proBNP and hs-cTnT were above versus below the median in those with pre-DM/DM (16.7 for incident HF and 2.1 for CVD events, both p <0.01). In conclusion, the combination of both biomarkers to traditional risk factors in participants who were normoglycemic or with pre-DM or DM improved risk prediction for both incident HF and total CVD events in an ethnically diverse population.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Blood Glucose; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prediabetic State; Risk Assessment; Stroke; Troponin T; United States

Topics: Betacoronavirus; C-Reactive Protein; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Endothelium, Vascular; Humans; Interleukin-1; Macrophage Activation; Multiple Organ Failure; Myocardial Ischemia; Natriuretic Peptide, Brain; Pandemics; Peptide Fragments; Pneumonia, Viral; SARS-CoV-2; Troponin I

This study is aimed at investigating natriuretic peptide B (. The microarray dataset GSE26887, containing 19 postischemic HF patients' peripheral blood samples (7 with T2DM and 12 without T2DM), was examined to detect the genes coexpressed with. In patients with T2DM, a total of 41 biological processes (BP), 20 cellular components (CC), 13 molecular functions (MF), and 41 pathways were identified. Furthermore, a total of 61 BPs, 16 CCs, 13 MFs, and 22 pathways in patients without T2DM were identified. In both groups of patients, 17 BPs, 10 CCs, 6 MFs, and 13 pathways were enriched. We also identified 173 intersectional coexpression genes (63 positively, 106 negatively, and 4 differently coexpressed in patients with and without T2DM, respectively) in both types of patients, which were enriched in 16 BPs, 8 CCs, 3 MFs, and 8 KEGG pathways. Moreover, the PPI network (containing 237 edges and 170 nodes) with the top module significantly enriched in 4 BPs (tricarboxylic acid metabolic process, citrate metabolic process, tricarboxylic acid cycle, and aerobic respiration) and 3 pathways (citrate cycle, malaria parasite metabolic pathway, and AGE-RAGE signaling pathway in diabetic complications) was constructed.. Our findings may elucidate the functions and roles of the

Topics: Databases, Nucleic Acid; Diabetes Mellitus, Type 2; Gene Expression Regulation; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain

Background Patients with stable ischemic heart disease represent a heterogeneous population at variable risk for major adverse cardiac events (MACE). Because MACE typically occurs outside the hospital, we studied whether biometric and psychometric remote patient monitoring are associated with MACE risk biomarkers. Methods and Results In 198 patients with stable ischemic heart disease (mean age 65±11 years, 60% women), we evaluated baseline measures, including biometric (FitBit 2) and psychometric (acquired via smartphone-administered patient-reported outcomes) remote monitoring, in the PRE-MACE (Prediction, Risk, and Evaluation of Major Adverse Cardiac Events) study. In multivariable adjusted regression analyses, we examined the association of these measures with biomarkers of MACE risk, including NT-proBNP (N-terminal pro-b-type natriuretic peptide), u-hs-cTnI (ultra-high sensitivity cardiac-specific troponin I), and hs-CRP (high-sensitivity C-reactive) protein. Both biometric and psychometric measures were associated with NT-proBNP. Specifically, step count, heart rate, physical activity, global health score, and physical function score were all inversely related, whereas physical limitation score was directly related (

Topics: Activities of Daily Living; Aged; Biomarkers; Biometry; C-Reactive Protein; Exercise; Female; Heart Rate; Humans; Male; Middle Aged; Mobile Applications; Monitoring, Ambulatory; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Psychometrics; Risk Factors; Smartphone; Troponin I; Wearable Electronic Devices

To describe the intraindividual changes of heart biomarker levels during and after pregnancy and to evaluate existing cut-off levels for heart failure or myocardial ischaemia in pregnant women.. A total of 196 healthy pregnant women were recruited from maternal outpatient clinics and included in the study. Blood samples were obtained on four occasions: at 10-12 gestational weeks (gw), 20-25 gw, after delivery and 6 months postpartum and analysed for N-terminal pro-brain natriuretic peptide (NTproBNP) and high sensitive cardiac troponin T (hs-cTNT). Echocardiography ruled out existing cardiac disease. Estimated glomerular filtration rate (eGFR) was calculated.. There were significant changes in NTproBNP between the measurements with the highest NTproBNP at 10-12 gw and the lowest value being at 20-25 gw, (with eGFR being the highest). Hs-cTNT was significantly higher at the peripartum measurement compared with the other measurements (p<0.05). Regardless, the 95th percentile for both biomarkers was below cut-off levels of 300 ng/L for NTproBNP and 14 ng/L for hs-cTNT. There was an association between NTproBNP above the upper limit of normal of 125 ng/L and eGFR (p=0.04) and between hs-cTNT >5.0 ng/L and time from delivery to blood sample (p=0.001) at the peripartum measurement. Both were associated with the use of oxytocin.. Existing cut-off values for ruling out heart failure (NTproBNP <300 ng/L) and myocardial ischaemia (hs-cTNT <14 ng/L) are applicable during pregnancy and after delivery. Elevated levels mandate further attention on cardiac symptoms and renal function.

Topics: Adult; Biomarkers; Female; Gestational Age; Healthy Volunteers; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Postpartum Period; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Time Factors; Troponin T

Women with symptoms and signs of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD), often have coronary microvascular dysfunction (CMD), and are at risk of future heart failure with preserved ejection fraction (HFpEF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used to evaluate HF and myocardial ischemia. Relationships between NT-proBNP and CMD are not well defined in this population.. We evaluated resting NT-proBNP levels in 208 women with symptoms and signs of ischemic heart disease, preserved LVEF and no obstructive CAD undergoing clinically indicated invasive coronary flow reserve (CFR) as a measure of CMD-related ischemia and resting left ventricular end-diastolic pressure (LVEDP). Chi-square testing was used for categorical variables and ANOVA or Kruskal-Wallis tests were used for continuous variables.. Overall, 79% had an elevated resting LVEDP, and mean NT-proBNP was 115 ± 158 pg/mL. NT-proBNP levels correlated directly with age (r = 0.28, p = <0.0001), and indirectly with body mass index (r = -0.21, p = 0.0006), but did not independently associate with CFR. When stratified by NT-proBNP thresholds, higher NT-proBNP was initially associated with lower CFR, which did not persist with adjustment for multiple testing (p = 0.01 and 0.36, respectively).. Among women with symptoms and signs of ischemia, preserved LVEF, no obstructive CAD, and undergoing clinically indicated functional coronary angiography (FCA) for suspected CMD, while a majority had elevated resting LVEDP, we failed to find an independent association between CFR and NT-proBNP, although stratified clinical thresholds may relate to lower CFR. Further work is needed to investigate if these findings support the hypothesis that CMD-related ischemia may be a precursor to HFpEF.

Topics: Adult; Aged; Coronary Vessels; Female; Heart Failure; Heart Ventricles; Humans; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume

Cardiac cachexia is a wasting syndrome characterized by chronic inflammation and high mortality. Fibroblast growth factor 21 (FGF-21) and monocyte chemoattractant protein 1 (MCP-1) are associated with cardiovascular disease and systemic inflammation. We investigated FGF-21 and MCP-1 in relations to cardiac function, inflammation, and wasting in patients with heart failure with reduced ejection fraction (HFrEF) and cardiac cachexia.. Plasma FGF-21 and MCP-1 were measured in a cross-sectional study among the three study groups: 19 patients with HFrEF with cardiac cachexia, 19 patients with HFrEF without cachexia, and 19 patients with ischaemic heart disease and preserved ejection fraction. Patients with HFrEF and cardiac cachexia displayed higher FGF-21 levels median (inter quantile range) 381 (232-577) pg/mL than patients with HFrEF without cachexia 224 (179-309) pg/mL and ischaemic heart disease patients 221 (156-308) pg/mL (P = 0.0496). No difference in MCP-1 levels were found among the groups (P = 0.345). In a multivariable regression analysis, FGF-21 (logarithm 2) was independently associated with interleukin 6 (logarithm 2) (P = 0.015) and lower muscle mass (P = 0.043), while no relation with N-terminal pro-hormone brain natriuretic peptide was observed.. Fibroblast growth factor 21 (FGF-21) levels were elevated in patients with HFrEF and cardiac cachexia, which could be mediated by increased inflammation and muscle wasting rather than impaired cardiac function.

Topics: Aged; Aged, 80 and over; Biomarkers; Cachexia; Cardiovascular Diseases; Case-Control Studies; Chemokine CCL2; Chronic Disease; Cross-Sectional Studies; Denmark; Female; Fibroblast Growth Factors; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Muscular Atrophy; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Wasting Syndrome

Topics: Coronary Artery Disease; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Natriuretic Peptide, Brain

Topics: Coronary Artery Disease; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Natriuretic Peptide, Brain

Cardiac disease is the most common cause of sudden death in Western countries. It is known that high-sensitivity troponin I (hs-cTnI), widely used for detection of myocardial injury, is a sensitive biochemical marker. B-type natriuretic peptide (BNP) is a reliable tool for diagnosing heart failure, and for establishing prognosis or disease severity. We aimed to evaluate the diagnostic efficacy of the postmortem determination of BNP in serum alone or in addition to other biomarkers, such as hs-cTnI and MB isoenzyme of creatine kinase (CK-MB), to ascertain whether its determination improves the post-mortem diagnosis of heart failure-associated causes of death. This study involved 133 cadavers with a mean age of 58.2 (± 17.6) years and a mean postmortem interval of 12.8 (±6.6) h. Cases were assigned into two diagnostic groups, according to the cause of death: cardiac deaths (N = 62) and control (N = 71). In the cardiac group, two categories were established according to morphological features of the heart: 'ischemic deaths' (N = 39), and 'congestive heart' (n = 23). Both hs-cTnI and BNP were useful in diagnosing cardiac deaths, whereas CK-MB did not have any diagnostic relevance. hs-cTnI is higher in cases which acute ischemia as the principal pathology, while the presence of high BNP values is significantly related with chronic cardiac situations with significant ventricular overload. Our findings show that postmortem determination of hs-cTnI and BNP provides valuable information; hs-cTnI is useful for diagnosis of cardiac deaths, mainly with ischemic implications, and BNP gave better results for the diagnosis of congestive heart failure.

Topics: Biomarkers; Case-Control Studies; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Discriminant Analysis; Female; Forensic Pathology; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Postmortem Changes; Troponin I

Weaning-induced cardiac pulmonary edema (WiPO) is one of the main mechanisms of weaning failure during mechanical ventilation. We hypothesized that weaning-induced cardiac ischemia (WiCI) may contribute to weaning failure from cardiac origin.. A prospective cohort study of patients mechanically ventilated for at least 24 h who failed a first spontaneous breathing trial (SBT) was conducted in four intensive care units. Patients were explored during a second SBT using multiple tools (echocardiography, continuous 12-lead ST monitoring, biomarkers) to scrutinize the mechanisms of weaning failure. WiPO definition was based on three criteria (echocardiographic signs of increased left atrial pressure, increase in B-type natriuretic peptides, or increase in protein concentration during SBT) according to a conservative definition (at least two criteria) and a liberal definition (at least one criterion). WiCI was diagnosed according to the third universal definition of myocardial infarction proposed by the European Society of Cardiology (ESC) and the American Heart Association (AHA) statement for exercise testing.. Among patients who failed a first SBT, WiPO occurred in 124/208 (59.6%) and 44/208 (21.2%) patients, according to the liberal and conservative definition, respectively. Among patients with ST monitoring, WiCI was diagnosed in 36/177 (20.3%) and 12/177 (6.8%) of them, according to the ESC and AHA definitions, respectively. WiCI was not associated with WiPO and was not associated with weaning outcomes. Only two patients of the cohort were treated for an acute coronary syndrome after the second SBT, and seven other patients required coronary angiography during the weaning period.. This observational study showed the common occurrence of pulmonary edema in mechanically ventilated patients who failed a first SBT, but the association with cardiac ischemia and weaning outcomes was weak.

Topics: Aged; Biomarkers; Cohort Studies; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Respiration, Artificial; Ventilator Weaning

Acute myocardial infarction (AMI) is considered a major cause of death and disability. Myocardial perfusion scintigraphy (MPS) as a non-invasive diagnostic imaging procedure and certain biomarkers associated with myocardial ischemia (ISCH), such as ischemia-modified albumin (IMA), neuropeptide Y (NPY), N-terminal pro b-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) could probably aid in the detection of myocardial infarction.. Between December 2011 and June 2012, we prospectively analyzed patients who underwent a MPS study with the clinical question of myocardial ISCH. An exercise test was performed along with a MPS. Blood was drawn from the patients before exercise and the within 3 minutes from achieving maximum load and was analyzed for the aforementioned biomarkers.. A total of 71 patients (56 men and 15 women) were enrolled with a mean age of 61 ± 12 years. Twenty-six patients (36.6%) showed reduced uptake on stress MPS images that normalized at rest, a finding consistent with ISCH. Between ISCH and non-ISCH groups, only hsTnT levels showed a significant difference with the highest levels pertaining to the former group both before (0.0075 ng/ml vs 0.0050 ng/ml, P = 0.023) and after stress exercise (0.0085 vs 0.0050, P = 0.015). The most prominent differences were seen in higher stages of the Bruce protocol (stress duration > 9.05 minutes - P < 0.017). None of the IMA, NPY, and NP-pro BNP showed significant differences in time between the two groups.. Although IMA, NPY, and NT-pro BNP may not detect minor ischemic myocardial insults, serum hsTnT holds a greater ability of detecting not only myocardial infarction but also less severe ischemia. Further studies with larger cohorts of patients are warranted in order to better define the role of hsTnT as a screening tool for myocardial ischemia.

Topics: Aged; Area Under Curve; Biomarkers; Exercise; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Neuropeptide Y; Peptide Fragments; Probability; Prospective Studies; Sensitivity and Specificity; Serum Albumin, Human; Troponin T

Drugs facilitating the cardioprotective effects of natriuretic peptides are introduced in heart failure treatment. ANP and BNP also stimulate lipolysis and increase circulating concentrations of free fatty acids (FFAs); an aspect, however, thought to be confined to primates. We examined the lipolytic effect of natriuretic peptide infusion in healthy young men and evaluated the effect in a porcine model of myocardial ischemia and reperfusion. Six young healthy normotensive men underwent infusion with ANP, BNP, or CNP for 20 min. Blood samples were collected before, during, and after infusion for measurement of FFAs. In a porcine model of myocardial ischemia and reperfusion, animals were infused for 3 h with either BNP (n = 7) or saline (n = 5). Blood samples were collected throughout the infusion period, and cardiac tissue was obtained after infusion for lipid analysis. In humans, ANP infusion dose-dependently increased the FFA concentration in plasma 2.5-10-fold (baseline vs. 0.05 μg/kg/min P < 0.002) and with BNP 1.6-3.5-fold (P = 0.001, baseline vs. 0.02 μg/kg/min) 30 min after initiation of infusion. Infusion of CNP did not affect plasma FFA. In pigs, BNP infusion induced a 3.5-fold increase in plasma FFA (P < 0.0001), which remained elevated throughout the infusion period. Triglyceride content in porcine right cardiac ventricle tissue increased ∼5.5 fold in animals infused with BNP (P = 0.02). Natriuretic peptide infusion has similar lipolytic activity in human and pig. Our data suggest that short-term infusion increases the cardiac lipid content, and that the pig is a suitable model for studies of long-term effects mediated by natriuretic peptides.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Fatty Acids, Nonesterified; Female; Heart; Humans; Infusions, Intravenous; Lipolysis; Male; Models, Animal; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Sus scrofa; Triglycerides

Anaemia is a risk of worsening heart failure. However, anaemia sometimes remains undetected because the superficial cardiac function does not precisely reflect the adverse impact of anaemia. Plasma B-type natriuretic peptide (BNP) could be helpful in these cases. However, the direct anaemic effects on BNP remain unknown. Herein, we compared the direct effect of anaemia on BNP and left ventricular ejection fraction (LVEF) using an advanced statistical procedure.. A retrospective study.. Secondary care (cardiology), single-centre study.. The study consisted of 3756 inpatients, including 684 without ischaemic heart disease (IHD) and 3072 with IHD.. Relationship between plasma BNP levels and LVEF values.. A path model was constructed to simultaneously examine the adverse impact of anaemia on LVEF and plasma BNP, allowing for renal function. The path model revealed that LVEF increased in response to low haemoglobin (Hb), and the phenomenon was prominent in non-IHD (standardised regression coefficients (St.β): -0.264, p<0.001) rather than in IHD (St.β: 0.015, p=0.531). However, the response of BNP was commonly observed in both groups (non-IHD St.β: -0.238, IHD St.β: -0.398, p<0.001, respectively). Additionally, this study showed a direct link between low estimated glomerular filtration rate and high BNP independently of LVEF. Incrementally, Bayesian structural equation modelling in covariance structure analysis clearly supported this result. The scatter plots and simple regression analysis revealed that an adequate blood supply was approximately Hb 110 g/L and over in the non-IHD patients, whereas blood was not supplied in sufficient quantities even by Hb 130 g/L in patients with IHD.. The current study demonstrated that anaemia was a substantial risk for worsening cardiac overload as estimated by plasma BNP. The anaemic response of LVEF likely changed depending on underlying cardiac disorders (IHD or not). However, the response of BNP was robustly observed.

Topics: Aged; Anemia; Biomarkers; Cardiac Catheterization; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Radionuclide Ventriculography; Retrospective Studies; Stroke Volume

There is still no satisfactory large-animal model of ischemic heart failure (IHF) with ideal survival rate and model time. The aim of this study is to explore a novel chronic IHF model in swine. 23 healthy Ba-Ma miniature pigs were included. Pigs in the experimental group underwent multiple strategic ligations on side branches of the left anterior descending (LAD) and circumflex coronary arteries. One week later, sequential intervention occlusion of the distal end of the LAD trunk was performed. In the experimental groups, LV end-diastolic (LVEDV) and end-systolic volume (LVESV) gradually increased starting at 4 weeks post operation. At 12 WPO, LVEDV increased from 45.0 ± 2.9 ml at baseline to 110.0 ± 9.8 ml and LVESV increased from 17.0 ± 1.4 ml at baseline to 42.0 ± 3.6 ml. Meanwhile, left ventricular ejection fraction significantly decreased from 73.8 ± 4.2 % at baseline to 31.0 ± 2.5%. According to histomorphometric assessment, viable cells were observed in infarction lesions, indicating the model has replicated the structural and functional features of chronic IHF.

Topics: Animals; C-Reactive Protein; Coronary Angiography; Coronary Vessels; Disease Models, Animal; Electrocardiography; Heart Failure; Magnetic Resonance Imaging; Male; Models, Biological; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Care; Swine; Swine, Miniature; Ventricular Function, Left; Ventricular Remodeling

In asymptomatic patients with type 2 diabetes (T2D), the prevalence of silent myocardial infarction on routine electrocardiograms is about 4% while for silent myocardial ischemia it is 20-30%. Some studies showed that silent myocardial infarction is associated with an increased risk of incident heart failure (HF), whereas no prospective study has ever reported such a risk in patients with silent myocardial ischemia. In patients with HF, however, previously unrecognized coronary artery disease (CAD) often seems to be involved. Brain natriuretic peptide (BNP) and N‑terminal pro-BNP (NT-proBNP) levels represent first-line diagnostic tools for patients with suspected HF and might also serve as biomarkers for silent CAD. Echocardiography provides a detailed report of cardiac alterations that includes changes suggestive of ischemia, heart failure, and left ventricular dysfunction in addition to strong prognostic indices. Diabetic patients with silent myocardial infarction or silent myocardial ischemia should be screened for asymptomatic changes in left ventricular function or structure. In patients with silent CAD, all risk factors need to be better controlled and the choice of antihyperglycemic agents adjusted. In patients with congestive HF and no obvious cause of HF, invasive coronary angiography (or noninvasive computed tomography angiography) should be performed to detect CAD, since the finding of CAD may involve revascularization and requires additional treatments including antiplatelet agents and statins. Future research is needed to examine the cost effectiveness of screening for silent myocardial ischemia as part of HF risk assessment, and to identify preventive therapies to lower the risk of HF among patients with silent myocardial infarction.

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Heart Failure; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Frances Conti-Ramsden MBBS Academic Clinical Fellow. To determine whether glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations are elevated in pre-eclampsia and superimposed pre-eclampsia (SPE), demonstrating cardiac ischaemia and strain.. A nested case-control study was performed using samples and clinical data available from a prospective pregnancy cohort. Four groups were selected: healthy pregnant controls (n = 21), pre-eclampsia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20) or with superimposed pre-eclampsia (SPE) (n = 19). Plasma samples were taken at time of disease or the third trimester in controls.. Plasma concentrations of GPBB and BNP.. There was no significant difference in GPBB plasma concentrations between controls and pre-eclampsia (geometric mean (GM) [95% CI]: 4.74 [2.54-8.84]ng/mL vs 5.01 [2.58-9.74]ng/mL, p = 0.90)), or between CHT and/or CKD and SPE (GM [95% CI]: 9.49 [4.93-18.25]ng/mL vs 10.24 [5.27-19.92]ng/mL, p = 0.87). BNP plasma concentrations were significantly raised in women with pre-eclampsia compared to controls (GM [95% CI]: 31.83 [20.18-50.22]pg/mL vs 11.33 [7.34-17.51]pg/mL, p = 0.001). Women with CKD, but not CHT, who developed SPE had elevated BNP concentrations. There were no significant differences in BNP concentration between women with comorbidity (CHT and/or CKD) and controls.. GPBB has a limited role as a biomarker in hypertensive disorders of pregnancy. BNP concentrations were elevated in pre-eclampsia compared to controls. This suggests cardiac strain at the time of pre-eclampsia. Further studies are needed to examine whether BNP can identify women at increased risk of cardiovascular disease.

Topics: Adult; Biomarkers; Case-Control Studies; Female; Glycogen Phosphorylase; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Young Adult

Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated.. Patients had reduced direct flow proportion and direct-flow average KE compared with controls ( P<0.0001). The residual volume proportion and residual volume average KE were increased in patients ( P<0.0001). Importantly, in a multiple linear regression model to predict the patient's 6-minute walk test, the independent predictors were age (β=-0.3015; P=0.019) and direct-flow average KE (β=0.280, P=0.035; R. This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Cardiomyopathy, Dilated; Case-Control Studies; Coronary Circulation; Cross-Sectional Studies; Exercise Tolerance; Female; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Ventricular Function, Left; Ventricular Remodeling; Walk Test

Mental stress-induced myocardial ischemia (MSIMI) is closely associated with adverse cardiac events in patients with coronary artery disease (CAD) and we aimed to determine whether biomarkers and blood pressure could be potential predictors of MSIMI.. This study enrolled 82 patients with documented CAD between June 1, 2017 and November 9, 2017. Patient blood samples were obtained at resting period and at the end of mental arithmetic. Then, patients were assigned to MSIMI positive group and MSIMI negative group. The main statistical methods included linear regression, receiver operating characteristic (ROC) curves, and logistic regression.. Patients with CAD with MSIMI had significantly greater median resting N-terminal pro-brain natriuretic peptide (NT-proBNP, 141.02 [45.85-202.76] pg/mL vs. 57.95 [27.06-117.64] pg/mL; Z = -2.23, P = 0.03) and mean systolic blood pressure (SBP) (145.56 ± 16.87 mmHg vs. 134.92 ± 18.16 mmHg, Z = -2.13, P = 0.04) when compared with those without MSIMI. After 5-min mental stress task, those who developed MSIMI presented higher elevation of median post-stressor high sensitivity cardiac troponin I (hs-cTnI, 0.020 [0.009-0.100] ng/mL vs. 0.009 [0.009-0.010] ng/mL; Z = -2.45, P = 0.01), post-stressor NT-proBNP (138.96 [39.93-201.56] pg/mL vs. 61.55 [25.66-86.50] pg/mL; Z = -2.15, P = 0.03) compared with those without MSIMI. Using the ROC curves, and after the adjustment for basic characteristics, the multiple logistic regression analysis showed that patients presenting a post-stressor hs-cTnI ≥ 0.015 ng/mL had seven-fold increase in the risk of developing MSIMI (odds ratio [OR]: 7.09; 95% confidence interval [CI]: 1.65-30.48; P = 0.009), a rest NT-proBNP ≥ 80.51 pg/mL had nearly eight-fold increase (OR: 7.85; 95% CI: 1.51-40.82; P = 0.014), a post-stressor NT-proBNP ≥ 98.80 pg/mL had 35-fold increase (OR: 34.96; 95% CI: 3.72-328.50; P = 0.002), a rest SBP ≥ 129.50 mmHg had 11-fold increase (OR: 11.42; 95% CI: 1.21-108.17; P = 0.034).. The present study shows that CAD patients with higher hs-cTnI level, and/or greater NT-proBNP and/or SBP are at higher risk of suffering from MSIMI when compared with those without MSIMI, indicating that hs-cTnI, NT-proBNP, SBP might be potential predictors of MSIMI.

Topics: Aged; Anxiety; Biomarkers; Blood Pressure; C-Reactive Protein; Coronary Artery Disease; Depression; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prospective Studies; ROC Curve; Stress, Psychological; Tomography, Emission-Computed, Single-Photon; Troponin I; Troponin T

Analyze the parameters of the interaction between the left ventricle and the arterial system in patients with chronic forms of coronary heart disease and to identify relationships with levels of proadrenomedullin (MR‑proADM) and N‑terminal precursor of the brain natriuretic peptide B (NT‑proBNP).. 240 patients with chronic forms of coronary heart disease (median - 55,9 [43; 63] years) and Q‑forming myocardial infarction in the past were examined. Of these, 110 patients with myocardial infarction and preserved lef ventricular ejection fraction and 130 patients with ischemic cardiomyopathy. All patients were calculated parameters of lef ventricular‑arterial interaction and the determination in blood serum levels of MR‑proADM and NT‑proBNP.. In patients with ischemic cardiomyopathy, an increase in the lef ventricular‑arterial interaction index was detected (2,51 [1,18; 5,00]), which reflects a decrease in the functional abilities and efficiency of the heart. In patients with myocardial infarction and a preserved left ventricular ejection fraction, this indicator was in the range of normal values (0,78 [0,55; 1,07]), which indicates an effective cardiac work. A study of MR‑proADM and NT‑proBNP levels demonstrated an increase in both groups (1,72 [1,56; 1,98] nmol/l and 779,3 [473; 2193] pg/ml in the group of patients with ischemic cardiomyopathy; 0,89 [0,51; 1,35] nmol/l and 246 [118; 430] pg/ml in the group of patients with myocardial infarction and preserved left ventricular ejection fraction), and the correlation analysis with left ventricular‑arterial coupling interaction parameters allowed identify statistically significant connections (in the group of patients with ischemic cardiomyopathy: with the level of MR‑proADM ‑ r=0,67, p=0,006, with the level of NT‑proBNP ‑ r=0,78, p<0,001; in the group of patients with myocardial infarction and preserved left ventricular ejection fraction: with MR‑proADM level ‑ r=‑0,52, p=0,024, with NT‑proBNP level ‑ r =‑0,38, p=0,037).. The findings suggest a pathogenetic association between the biomarkers under study and the parameters of left ventricular‑arterial coupling interaction.

Topics: Adult; Biomarkers; Heart Ventricles; Humans; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

The purpose of this study was to investigate the associations between clinical factors and cardiac function as measured by pressure-volume loops (PVLs) in a pediatric heart transplant cohort.. Patients (age < 20 years) who underwent heart transplantation presenting for a clinically indicated catheterization were enrolled. PVLs were recorded using microconductance catheters (CD Leycom. A total of 18 patients were enrolled. Median age was 8.7 years (IQR 5-14 years). There were ten males and eight females. Six patients had a history of rejection and ten had positive donor-specific antibodies. There was no transplant coronary artery disease. Median BNP was 100 pg/mL (IQR 46-140). Time from transplant to PVL obtained during catheterization procedure was 4.1 years (IQR 1.7-7.8 year). No single clinical characteristic was statistically significant when correlated with PVL data. However, longer ischemic time was associated with worse Beta (r = 0.49, p = 0.05).. Our study found that longer ischemic times are associated with increased left ventricular stiffness. No other single clinical variable is associated with cardiac dysfunction as determined by PVL analysis.

Topics: Adolescent; Biomarkers; Cardiac Catheterization; Child; Child, Preschool; Female; Heart Transplantation; Heart Ventricles; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Primary Graft Dysfunction; Risk Factors; Time Factors; Ventricular Dysfunction; Ventricular Function

Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption - measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points - and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n = 405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT ≥ 19.5 U/L and γ-GT ≥ 55 U/L indicated excessive alcohol consumption in Caucasians and Africans, respectively. Ambulatory 24-h blood pressure and electrocardiograms (ECG), 10-lead ECG left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP), and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile and mean 24-h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol and presented significant increases in NT-proBNP (p < 0.001), QTc prolongation (p = 0.008), and ischemic events (p = 0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events, and SBP, in the African high γ-GT group exclusively. High alcohol consumers presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness, predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.

Topics: Adult; Alcoholism; Black People; Blood Pressure; Coronary Circulation; Cross-Sectional Studies; Electrocardiography; Ethnicity; Female; gamma-Glutamyltransferase; Humans; Hypertrophy, Left Ventricular; Long QT Syndrome; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; South Africa; White People

Plasma concentrations of natriuretic peptides have been shown to predict prognosis in heart failure (HF) patients with left ventricle (LV) dysfunction. It is still unclear if measurements after cardiac surgery are associated with any effect on the outcome. We aimed to prospectively investigate the longitudinal profile of serial evaluations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in ischemic HF patients undergoing Surgical Ventricular Reconstruction (SVR) and how NT-proBNP levels at different time-points are associated with the outcome.. One hundred and forty-three patients (122 men, 64 ± 9 years old) with post-infarction LV remodeling referred to our Center for SVR had an assessment of NT-proBNP levels before surgery and 6, 12 and 18 months after surgery. The analysis was performed using the logarithm of the biomarker and joint modeling of serial measurements through mixed models together with Cox regression to analyze time to event data.. The average level of the biomarker decreased by about 50% during the first year after the operation. Time-varying NT-proBNP levels were associated with the hazard of: 1% increase in NT-proBNP during the follow-up was associated with 1.5% increase of the risk of the composite event (95% CI: 1.0%, 2.6%) and with 4.2% increase of the risk of death (95% CI: 2.2%, 8.2%).. Serial profiles (either in increasing or in decreasing) at different time points are associated with a modulation of the risk of adverse events and, therefore, are important indicators for monitoring the evolution of the disease, even after cardiac surgery.

Topics: Aged; Biomarkers; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Natriuretic Peptide, Brain; Peptide Fragments; Plastic Surgery Procedures; Prospective Studies

To investigate the expression of kir6.2 subunit of the sarcKATP channel in exercise-induced myocardial injury and to elucidate the underlying mechanism of myocardial protection by sarcKATP channels.. Healthy male Sprague Dawley(SD) rats were divided into the Control (C) and the Exhaustive Exercise (EE) group. The one-time exhaustive exercise-induced myocardial injury model was established on a treadmill at a speed of 35 m/min. Alterations in myocardial ischemia and hypoxia were examined by hematoxylin-basic fuchsin-picric acid (HBFP) staining and the concentration of cardiac Troponin I (cTnl), a sensitive and specific marker for myocardial injury, was detected using immunochemiluminescence analysis. The mRNA expression level, localization, and protein expression of sarcKATP channel subunit kir6.2 were determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence, and Western blot analysis, respectively.. When compared to Group C, rats in Group EE demonstrated significantly increased areas of myocardial ischemia and hypoxia. Moreover, increased serum levels of cTnI were detected. Increased kir6.2 expression was found on the surface of cardiomyocytes and kir6.2 protein expression was also significantly increased.. Exercise-induced myocardial injury did not result in noticeable alterations in kir6.2 mRNA expression. However, kir6.2 protein expression was significantly increased and resulted in increased numbers of sarcKATP channel openings in the myocardium, thereby further inhibiting exercise-induced myocardial injury.

Topics: Animals; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Physical Conditioning, Animal; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; RNA, Messenger; Troponin I

Following acute myocardial infarction, clinical studies show alterations in the blood levels of corin, a cardiac-selective activator of the natriuretic peptides pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). However, the temporal changes in circulating and cardiac corin levels and their relationships to the severity of myocardial infarction have not been studied. The main objective of this study was to examine the relationship between cardiac and circulating corin levels and their association with cardiac systolic function and infarct size during the early phase of acute myocardial infarction (<72 h) in a translationally relevant induced coronary ligation mouse model. This acute phase timeline was chosen to correlate with the clinical practice within which blood samples are collected from myocardial infarction patients. Heart and plasma samples were examined at 3, 24, and 72 hours post acute myocardial infarction. Plasma corin levels were examined by enzyme-linked immunosorbent assay, transcripts of cardiac corin, pro-ANP and pro-BNP by quantitative real-time polymerase chain reaction, cardiac corin expression by immunohistology, infarct size by histology and heart function by echocardiography. Plasma corin levels were significantly increased at 3 (P<0.05), 24 (P<0.001), and 72 hours (P<0.01) post-acute myocardial infarction. In contrast, cardiac corin transcript levels dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) and immunoreactive cardiac corin protein levels dropped by 30% (P<0.05), 76% (P<0.001) and 75% (P<0.001), while cardiac pro-ANP and pro-BNP transcript levels showed an opposite pattern. Plasma corin levels were negatively correlated with immunoreactive cardiac corin (P<0.01), ejection fraction (P<0.05) and fractional shortening (P<0.05), but positively correlated with infarct size (P<0.01). In conclusion, acute myocardial infarction induces rapid increases in plasma corin and decreases in cardiac corin levels. In the early phase of acute myocardial infarction, plasma corin levels are inversely correlated with heart function and may reflect the severity of myocardial damage.

Topics: Animals; Atrial Natriuretic Factor; Heart; Male; Mice; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; RNA, Messenger; Serine Endopeptidases; Time Factors

Fibroblast growth factor 23 (FGF-23), a key hormone for the regulation of the phosphorus homeostasis, has also several direct effects on cardiac function. In heart failure (HF), the increase of FGF-23 participates to cardiac hypertrophy and remodeling. Measurement of the intact, biologically active hormone is now available. We determined intact FGF-23 in HF patients with reduced ejection fraction and assess its prognosis value for cardiovascular death over a long-term follow-up. We observed that intact FGF-23 is an independent predictor of cardiovascular death in HF patients and provides added value to the standard of care, natriuretic peptide, for risk estimation.

Topics: Aged; Belgium; Biomarkers; Cardiomyopathy, Dilated; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Follow-Up Studies; Heart; Heart Failure; Humans; Immunoassay; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Prognosis; Risk Assessment; Severity of Illness Index; Stroke Volume

The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP.. In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP.. Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM.

Topics: Adult; Aged; Cardiomyopathy, Hypertrophic; Coronary Circulation; Diastole; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left

Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients.. The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP), and these factors played a causative role in IHD (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP). The intrinsic power of the low reactivity of BNP induced by high BMI on the promotion of IHD was fairly potent.. This study demonstrated that obesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD.

Topics: Aged; Female; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Obesity; Risk Factors

Risk stratification and patient management in heart failure (HF) is difficult due to the unpredictable progression of the disease, necessitating the development of reliable diagnostic biomarkers to facilitate decision-making in clinical practice. Pregnancy-associated plasma protein-A (PAPP-A) is a marker of arteriosclerotic heart disease. PAPP-A is a serum protease, which is involved in the insulin-like growth factor 1 (IGF-1) axis where it is inhibited by the proform of the eosinophil major basic protein (proMBP). In this study, we evaluated serum PAPP-A and proMBP as long-term prognostic biomarkers of all-cause mortality in HF. Serum PAPP-A and proMBP concentrations were determined in 683 patients with NYHA III-IV HF recruited in the EchoCardiography and Heart Study (ECHOS) in Denmark. The mean age of the patients (73% male) was 70 at admission. During 7 years of follow-up, 516 patients died. In univariate analysis, both PAPP-A and proMBP, divided into quartiles, showed significant association with mortality. Using a Cox proportional hazard model, hazard ratios for continuous values of PAPP-A and proMBP were HR = 1.42 (CI = 1.23-1.64, p < 0.0001) and HR = 1.36 (CI = 1.22-1.51, p <0.0001), respectively. However, neither PAPP-A nor proMBP were significant independent predictors when the model included age, gender, brain-type natriuretic peptide, medical history of HF, ischemic heart disease, chronic obstructive pulmonary disease, and diabetes mellitus. In conclusion, high levels of PAPP-A and proMBP are associated with increased risk of death from all causes in HF and are potential prognostic markers of adverse outcomes in HF patients.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Diabetes Mellitus; Echocardiography; Eosinophil Major Basic Protein; Female; Follow-Up Studies; Heart Failure; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Pregnancy-Associated Plasma Protein-A; Prognosis; Proportional Hazards Models; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Factors

Increased N-terminal pro b-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can identify patients with heart failure (HF) who are at increased risk of cardiac events. The relationship of these biomarkers to the extent of hibernating myocardium and scar has not been previously characterized in patients with ischemic left ventricular dysfunction and HF.. Patients with ischemic HF meeting recruitment criteria and undergoing perfusion and fluorodeoxyglucose-positron emission tomography to define myocardial hibernation and scar were included in the study. A total of 39 patients (mean age 67 ± 8 years) with New York Heart Association class II-IV HF and ischemic cardiomyopathy (ejection fraction [EF], 27.9% ± 8.5%) were enrolled in the study.. Serum NT-proBNP and hs-cTnT levels were elevated in patients with ≥ 10% hibernating myocardium compared with those with < 10% (NT-pro-BNP, 7419.10 ± 7169.5 pg/mL vs 2894.6 ± 2967.4 pg/mL; hs-cTnT, 789.3 ± 1835.3 pg/mL vs 44.8 ± 78.9 pg/mL; P < 0.05). The overall receiver operating characteristic under the curve value for NT-proBNP and hs-cTnT to predict hibernating myocardium was 0.76 and 0.78, respectively (P < 0.05). The NT-proBNP (P = 0.02) and hs-cTnT (P < 0.0001) levels also correlated with hibernation, particularly in patients with ≥ 10% scar, independent of EF, age, and estimated glomerular filtration rate. No differences were noted in biomarker levels for patients with vs those without ≥ 10% scar.. NT-proBNP and hs-cTnT levels are elevated in patients with ischemic HF hibernation and are correlated with the degree of hibernation but not with the presence or extent of scar. Taken together, these data support the novel concept that NT-proBNP and hs-cTnT release in patients with ischemic HF reflects the presence and extent of hibernating myocardium.

Topics: Aged; Biomarkers; Coronary Angiography; Female; Heart Failure; Humans; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Positron-Emission Tomography; ROC Curve; Severity of Illness Index; Troponin T

Topics: Biomarkers; Cardiomyopathies; Diagnostic Imaging; Echocardiography, Stress; Humans; Mass Screening; Morbidity; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Positron-Emission Tomography; Troponin T

To investigate the expression and mechanism of plasma microRNA-21 in patients with ischemic cardiomyopathy (ICM).. 56 cases of ICM patients were selected in our hospital from February 2010 to March 2016 as the observation group, and 60 cases of healthy patients were selected as control group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of microRNA-21 in two groups. Then, differences of the total cholesterol (TC), triglycerides (TG), left ventricular ejection fraction (LVEF), high and low density lipoprotein cholesterol (HDL-C, LDL-C), left ventricular end-diastolic volume (LVEDV), N terminal B type brain natriuretic peptide (NT-proBNP) and other clinical indicators of the two groups, were compared. The correlation between the plasma microRNA-21 level and the clinical indices was analyzed, and the value of microRNA-21 in the diagnosis and treatment of ICM was evaluated.. The levels of LDL-C, HDL-C and LVEF in the observation group were lower than those in the control group (p<0.05). Plasma microRNA-21, TG, NT-proBNP and LVEDV were higher than those in the control group; the difference was statistically significant (p<0.05). Logistic regression analysis showed that the plasma microRNA-21 level was positively correlated with NT-proBNP and LVEDV (p<0.05).. The expression of microRNA-21 in plasma of patients with ICM was significantly increased. And the expression of micro RNA-21 in plasma was positively correlated with NT-proBNP and LVEDV. Through the ventricular remodeling in ICM patients, it can be used as a new target for the diagnosis and treatment of ICM and a new biomarker for risk assessment.

Topics: Adult; Area Under Curve; Biomarkers; Blood Pressure; Cardiomyopathies; Case-Control Studies; Cholesterol; Female; Humans; Logistic Models; Male; MicroRNAs; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; ROC Curve; Triglycerides; Ventricular Function, Left; Ventricular Remodeling

To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis.. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA.. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （. In myocardial ischemia condition, the higher expression of proBNP in cardiac muscle cell shows that the detection of NT-proBNP in plasma can be useful to differentially diagnose the degree of coronary atherosclerotic heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease.

Topics: Biomarkers; Blotting, Western; Coronary Disease; Death, Sudden, Cardiac; Heart; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Polymerase Chain Reaction

We investigated a correlation between electromechanical properties of the myocardium and response to CD34+ cell therapy in patients with chronic heart failure.. We enrolled 40 patients with ischemic cardiomyopathy (ICM) and 40 with nonischemic dilated cardiomyopathy (DCM). All patients were in New York Heart Association functional class III and had a left ventricular ejection fraction (LVEF) <40%. CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Electroanatomic mapping was performed to define areas of myocardial scar and hibernation, and CD34+ cells were injected transendocardially in the hibernating areas. Patient were followed for 6 months; responders were defined as patients with LVEF increase of >5%. At baseline, the groups did not differ in sex, LVEF, creatinine, N-terminal pro-B-type natriuretic peptide or electroanatomic parameters (scar area: 53 ± 18% in ICM vs 55 ± 23% in DCM [P = .83]; hibernating area: 23 ± 13% vs 22 ± 12% [P = .56]). At 6 months we found similar rates of responders in both groups (60% in ICM vs 65% in DCM [P = .95]). When compared with nonresponders, responders had less myocardial scar (47 ± 17% vs 58 ± 15% [P = .003]).. In patients with chronic heart failure due to ICM and DCM we observed similar electroanatomic properties of the myocardium. In both groups, lower myocardial scar burden was associated with better clinical response to CD34+ cell therapy.

Topics: Adult; Aged; Analysis of Variance; Antigens, CD34; Cardiomyopathy, Dilated; Cell- and Tissue-Based Therapy; Chronic Disease; Echocardiography; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Imaging, Three-Dimensional; Injections, Intralesional; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Stroke Volume; Survival Rate; Time Factors; Treatment Outcome; Ventricular Remodeling

Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls.. The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated.. NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients.. Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.

Topics: Aged; Aortic Valve Insufficiency; Case-Control Studies; Echocardiography; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Wedge Pressure; Scleroderma, Systemic; Stroke Volume; Tricuspid Valve Insufficiency; Troponin I; Ventricular Dysfunction, Left

N-terminal pro-brain natriuretic peptide (NT-proBNP) is seen to be mostly elevated in patients with acute heart failure (AHF). However, cases of AHF presenting with low NT-proBNP levels have been reported. In this study designed to investigate the factors associated with low NT-proBNP levels in AHF patients, we discovered that etiology and related factors have an influence on NT-proBNP levels.. In this study, 154 AHF patients met the study criteria (117 men, median age 74years; left ventricular ejection fraction [LVEF] 46±13%; New York Heart Association [NYHA] classes II-IV). We analyzed the different clinical variables of patients based on plasma NT-proBNP levels. In addition, we identified the differences in NT-proBNP levels between ischemic and non-ischemic etiologies, as well as the relationships between time from symptom onset to ED visit and NT-proBNP levels.. The group with low NT-proBNP levels showed an ischemic association, higher LVEF, lower NYHA class and shorter time from symptom onset to ED visit. Plasma NT-proBNP levels were lower in the ischemic group than in the non-ischemic group (P<0.01). Meanwhile, NT-proBNP levels were relatively low in patients during early phases of AHF hospitalization and increased with time from symptom onset to ED visit (P<0.01).. We inferred that low NT-proBNP levels may infer the ischemic etiology especially in patients with normal LVEF in the early phases of AHF hospitalization.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume

Topics: Aged; Atrial Fibrillation; Biomarkers; Dizziness; Female; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Tachycardia; Troponin T

Levelfor cardiac troponin I (TrI) and MB-fraction of creatine kinase (CKMB) increases in cardiomyocyte necrosis, and B-type natriuretic peptide (of BNP) increasing reflects ventricular overload.. to study the dynamics of BNP, TRI and CKMV in myocardial revascularisation with cardio-pulmonary bypass and to evaluate the clinical significance of these biomarkers elevated levels and establishing the relationship between BNP and markers of myocardial damage in the perioperative period Materials and methods. The study included 52 patients aged 62.5 (54.75; 70) years. Biomarkers concentrations was determined by immunofluorescence.. The initial value of BNP were 57.9 (38.675;88.5) pg/ml, and then increased (p<0,01): at the end of the operation up to 91.75 (59.6;132.75) pg/ml, at 1st day following surgery - up to 260 (157;407) pg/ml, and at 2nd day - up to 184 (115.25;274.5) pg/ml. TrI and CKMV increased (p<0,01) up to 0.95 (0.4175;1.4525) ng/ml and up to 13.1 (5.575;15.525) U/L at the end of surgery, and up to 1,355 (0.76;3.8) ng/ml and 10.5 (5;18.325) U/L at thr Istpostoperative day. Preoperative BNP level and TrI level at the end of surgery were the predictors (p

Topics: Biomarkers; Cardiopulmonary Bypass; Creatine Kinase, MB Form; Female; Humans; Male; Middle Aged; Monitoring, Intraoperative; Myocardial Ischemia; Myocardial Revascularization; Natriuretic Peptide, Brain; Predictive Value of Tests; Troponin I

Myocardial perfusion scintigraphy (MPS) is a well-established diagnostic tool. The sensitivity and specificity of single photon emission computed tomography (SPECT) MPS to detect significant coronary lesion were 86% and 74%, respectively. The aim of this study was to examine the role of serum copeptin in evaluation of MPS.. Sixty-two consecutive patients underwent both SPECT MPS using 99mTc-sestamibi and transthoracic echocardiography were enrolled prospectively. Age, gender, height, weight, presence of cardiovascular risk factors were recorded. Exercise treadmill test (ETT) with modified Bruce protocol was used to induce coronary ischemia during MPS. While performing MPS, blood samples for serum copeptin level were drawn three times at pre-exercise, at the peak of ETT, and 6 h after ETT, respectively. The patients were enrolled into three groups according to MPS results (normal, equivocal and ischemia).. The study included 62 patients (23 with normal, 20 with equivocal, 19 with ischemia on MPS). Pre-, peak-, and post-exercise B-type natriuretic peptide and troponin I values were similar across the groups (p > 0.05 for all comparisons). Serum copeptin values for pre- and peak-exercise were similar among all groups (p = 0.883 and p = 0.089). Post-exercise copeptin values of the normal and equivocal groups were similar (p = 0.661, z = -0.438) while that of the ischemia group was significantly higher than both the normal (p < 0.001) and equivocal group (p < 0.001).. Serum copeptin was found to be increasing significantly in case of ischemia on MPS. It may be used in differentiation of equivocal results from false positive results.

Topics: Adult; Biomarkers; Case-Control Studies; Echocardiography, Doppler; Exercise Test; Female; Glycopeptides; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Reproducibility of Results; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Troponin I; Up-Regulation

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs.

Topics: Acute Disease; Adult; Angina, Unstable; Endothelial Cells; Endothelin-1; Endothelium; Female; Humans; Immunologic Factors; Inflammation; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD.. Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001).. In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.

Topics: Angina, Stable; Biomarkers; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Echocardiography, Stress; Europe; Female; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Positron-Emission Tomography; Predictive Value of Tests; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Troponin T

In patients treated with implantable cardioverter defibrillator (ICD), prediction of both overall survival and occurrence of shocks is important if improved patient selection is desired. We prospectively studied the predictive value of biomarkers and indexes of cardiac and renal function and spectral microvolt T-wave alternans testing and 24-hour Holter variables in a population who underwent first ICD implantation. Consecutive patients in sinus rhythm with ischemic or dilated cardiomyopathy scheduled for primary or secondary prophylactic ICD implantation were enrolled. Exercise microvolt T-wave alternans and 24-hour Holter for number of ventricular premature contractions (VPCs), deceleration capacity, heart rate variability, and heart rate turbulence were done. Death of any cause and first appropriate ICD shock were defined as end points. Over 33 ± 15 months of follow-up, 36 of 253 patients (14%) received appropriate shocks and 39 of 253 patients (15%) died. Only 3 of 253 patients (1%) died after receiving at least 1 appropriate shock. In univariate analyses, New York Heart Association class, ejection fraction, N-terminal pro brain-type natriuretic peptide (NT-proBNP), renal function, ICD indication, deceleration capacity, heart rate variability, and heart rate turbulence were predictive of all-cause mortality and VPC number and deceleration capacity predicted first appropriate shock. NT-proBNP (≥1,600 pg/ml) was identified as the only independent predictor of all-cause mortality (hazard ratio 3.0, confidence interval 1.3 to 7.3, p = 0.014). In contrast, VPC number predicted appropriate shocks (hazard ratio 2.3, confidence interval 1.0 to 5.5, p = 0.047) as the only independent risk marker. In conclusion, NT-proBNP is a strong independent predictor of mortality in a typical prospective cohort of newly implanted patients with ICD, among many electrocardiographic and clinical variables studied. Number of VPCs was identified as a predictor of appropriate shocks (clinicaltrials.gov: NCT02010515).

Topics: Aged; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Defibrillators, Implantable; Disease-Free Survival; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Although pulse pressure (PP) is a recognized risk factor for various cardiovascular diseases, its association with cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is uncertain.. We enrolled 512 of 951 consecutive HFpEF patients admitted to the Kumamoto University Hospital between 2007 and 2013 and divided them into five groups according to PP quintiles. Blood pressure and pulse wave velocity (PWV) were measured by an ankle-brachial index device. The PP values in HFpEF were significantly and positively correlated with PWV and LV stroke volume index, and were negatively correlated with estimated glomerular filtration rate and haemoglobin levels. Furthermore, plasma B-type natriuretic peptide levels in HFpEF patients with the lowest (<45 mmHg) and highest PP (≥75 mmHg) were significantly higher than those with other PP (45-74 mmHg). The percentage of total cardiovascular and heart failure (HF)-related events by PP category resulted in U- and J-shaped curves. The higher frequency of coronary-related events was nearly linear. In the Kaplan-Meier analysis, HFpEF patients with the lowest and highest PP quintiles had a significantly higher risk of cardiovascular and HF-related events than those with other PPs (45-74 mmHg) (log-rank test, both P < 0.01). Conversely, the frequency of coronary-related events in the highest PP group, but not in the lowest PP group, was significantly higher than in other PP groups.. Pulse pressure lower than 45 mmHg and higher than 75 mmHg was closely associated with HFpEF prognosis, indicating the clinical significance of PP for risk stratification of HFpEF.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Ankle Brachial Index; Blood Pressure; Coronary Restenosis; Echocardiography; Female; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Hospitalization; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Pulse Wave Analysis; Risk Factors; Severity of Illness Index; Stroke Volume

Topics: Aged; Airway Extubation; Biomarkers; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Respiration; Time Factors; Treatment Failure; Troponin; Ventilator Weaning

To evaluate whether biomarkers reflecting pathophysiological pathways and selected single nucleotide polymorphisms differ between patients (pts) with heart failure (HF).. 110 pts with were involved, including HF pts with preserved ejection fraction (HFpEF, n=51) with hypertensive origin, HF pts with reduced ejection fraction (HFrEF) with ischemic aetiology (ICM) (n=32) and HFrEF with dilated cardiomyopathy (DCM) (n=27). We assessed selected HF biomarkers, echocardiographic examinations and functional polymorphisms selected from six candidate genes: CYP27B1, NOS3, IL-6, TGF beta, TNF alpha, and PPAR gamma.. Higher concentrations of TNF alpha were observed in pts with hypertensive HFpEF compared to pts with DCM (p=0.008). Pts with HFpEF had higher concentrations of TGF beta 1 compared to DCM and ICM (p=0.0001 and p=0.0003, respectively). For the NOS3 -786 C/T rs2070744 polymorphism in DCM there were significantly more CT heterozygotes than in ICM and HFpEF. In multivariate analysis TGF beta 1 (p=0.001) and syndecan 4 (p=0.001) were the only factors distinguishing HFrEF pts with DCM vs HFpEF and also TGF beta 1 (p=0.001) and syndecan 4 (p=0.023) were the only factors distinguishing HFrEF pts with ICM vs HFpEF pts.. Inflammation mediated through TNF alpha and TGF beta 1 may represent an important component of an inflammatory response that partially drives the pathophysiology of HFpEF. NOS3 -786 C/T rs2070744 polymorphism in DCM may serve as a marker for more rapid progression of heart failure. The only biomarkers independently distinguishing HFpEF and HFrEF are syndecan 4 and TGF beta 1.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiomyopathy, Dilated; Drug Combinations; Female; Genetic Markers; Genetic Predisposition to Disease; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Polymorphism, Single Nucleotide; Stroke Volume; Syndecan-4; Tetrazoles; Transforming Growth Factor beta1; Valsartan

Natriuretic peptide (NP) levels are routinely employed as useful diagnostic and prognostic tools in the evaluation of patients with heart failure (HF). As hospitalization is the major consumer of healthcare resources, the prognostic power of admission NPs with regard to the duration of hospitalization deserves further investigation.. We assessed retrospectively the association between NP values sampled shortly following unplanned admission and the duration of hospitalization in 2978 patients admitted to a cardiology department. Duration of hospitalization (hours) and survival were determined by interrogation of the electronic medical records system. Associations with peptide levels were estimated using regression models and receiver operating characteristic (ROC) analysis. The results demonstrate a significant positive relationship between NP levels and the duration of hospitalization, after adjusting for age (P < 0.001). The median duration of hospitalization for the lowest BNP and NT-proBNP quintiles were 80 and 97 h, respectively, vs. 224.5 and 236 h for the highest quintiles. Using cut-off levels of 115 pmol/L for BNP and 390 pmol/L for NT-proBNP, the peptides have a positive predictive value of 78% and 85% for a stay >4 days. During follow-up, NP levels were strongly predictive of all-cause mortality.. The results quantify the strong relationship between NP levels taken following an unplanned admission to a cardiology department and the duration of hospitalization. This information permits improved identification of a patient population likely to require a prolonged hospital stay and consume more healthcare resources. Such patients may require a more aggressive diagnostic, treatment, and management strategy.

Topics: Aged; Arrhythmias, Cardiac; Cardiology Service, Hospital; Cardiomyopathies; Female; Heart Failure; Hospitalization; Hospitals, University; Humans; Hypertension; Length of Stay; Linear Models; Male; Middle Aged; Mortality; Myocardial Ischemia; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Proportional Hazards Models; Respiratory Tract Infections; Retrospective Studies; ROC Curve

Low 25-hydroxyvitamin D (25[OH]D) is associated with increased cardiovascular disease risk. Less known is whether 25(OH)D deficiency contributes to subclinical myocardial damage and wall stress (high-sensitivity cardiac troponin T [hs-cTnT] and N-terminal pro-brain natriuretic peptide [NT-proBNP]) or whether associations vary among subgroups.. Overall, 11 311 Atherosclerosis Risk in Communities participants without prevalent cardiovascular disease had 25(OH)D, hs-cTnT, and NT-proBNP measured at baseline (1990-1992), and 8990 had measurements of hs-cTnT and NT-proBNP repeated 6 years later. We examined associations of deficient 25(OH)D (<20 ng/mL) with prevalent elevated hs-cTnT (≥14 ng/L) and NT-proBNP (≥100 pg/mL), change in hs-cTnT and NT-proBNP, and incident elevated hs-cTnT and NT-proBNP. We tested for interactions by age (<56 and ≥56 years), sex, and race. In fully adjusted models, 25(OH)D was not associated with prevalent elevated hs-cTnT and NT-proBNP. Deficient 25(OH)D, however, was associated with increased 6-year change in hs-cTnT (β=0.54 ng/L [95% CI 0.08-1.01]) but not change in NT-proBNP. Deficiency in 25(OH)D was not associated with incident elevated hs-cTnT in the overall cohort but was associated with incident elevated hs-cTnT in younger but not older adults (relative risk 2.18 [95% CI 1.21-3.94] versus 0.78 [95% CI 0.56-1.08], respectively; P=0.01 for interaction by age). Deficient 25(OH)D was also associated with incident elevated NT-proBNP in men but not women (P=0.01 for interaction by sex).. Vitamin D deficiency was associated with increased 6-year change in hs-cTnT levels. Hypothesis-generating differences in associations by age and sex, but not race, were observed. If these associations are causal, further research is needed to understand mechanisms by which low 25(OH)D confers increased risk in these subgroups and whether treating deficient 25(OH)D can prevent myocardial damage and wall stress.

Topics: Cohort Studies; Female; Heart; Heart Failure; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Stress, Mechanical; Troponin T; United States; Vitamin D; Vitamin D Deficiency

Recent studies have suggested that B-type Natriuretic Peptide (BNP) is an important predictor of ischemia and death in patients with suspected acute coronary syndrome. Increased levels of BNP are seen after episodes of myocardial ischemia and may be related to future adverse events.. To determine the prognostic value of BNP for major cardiac events and to evaluate its association with ischemic myocardial perfusion scintigraphy (MPS).. This study included retrospectively 125 patients admitted to the chest pain unit between 2002 and 2006, who had their BNP levels measured on admission and underwent CPM for risk stratification. BNP values were compared with the results of the MPS. The chi-square test was used for qualitative variables and the Student t test, for quantitative variables. Survival curves were adjusted using the Kaplan-Meier method and analyzed by using Cox regression. The significance level was 5%.. The mean age was 63.9 ± 13.8 years, and the male sex represented 51.2% of the sample. Ischemia was found in 44% of the MPS. The mean BNP level was higher in patients with ischemia compared to patients with non-ischemic MPS (188.3 ± 208.7 versus 131.8 ± 88.6; p = 0.003). A BNP level greater than 80 pg/mL was the strongest predictor of ischemia on MPS (sensitivity = 60%, specificity = 70%, accuracy = 66%, PPV = 61%, NPV = 70%), and could predict medium-term mortality (RR = 7.29, 95% CI: 0.90-58.6; p = 0.045) independently of the presence of ischemia.. BNP levels are associated with ischemic MPS findings and adverse prognosis in patients presenting with acute chest pain to the emergency room, thus, providing important prognostic information for an unfavorable clinical outcome.

Topics: Aged; Biomarkers; Chest Pain; Emergency Service, Hospital; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Prognosis; Time Factors

Patients with coronary heart disease (CHD) without classical cardiovascular risk factors (CRFs) are uncommon, and their profile has not been thoroughly studied. In CHD patients, we have assessed the differences in several biomarkers between those with and without CRF.. We studied 704 patients with CHD, analyzing plasma levels of biomarkers related to inflammation, thrombosis, renal damage, and heart failure: high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), galectin-3, N-terminal fragment of brain natriuretic peptide (NT-pro-BNP), calcidiol (vitamin D metabolite), fibroblast growth factor-23 (FGF-23), parathormone, and phosphate.. Twenty patients (2.8%) exhibited no CRFs. Clinical variables were well balanced in both groups, with the logical exceptions of no use of antidiabetic drugs, lower triglyceride and glucose, and higher high-density lipoprotein cholesterol in no-CRF patients. No-CRF patients showed lower hs-CRP (2.574±3.120 vs. 4.554±9.786mg/L; p=0.018), MCP-1 (114.75±36.29 vs. 143.56±65.37pg/ml; p=0.003), and FGF-23 (79.28±40.22 vs. 105.17±156.61RU/ml; p=0.024), and higher calcidiol (23.66±9.12 vs. 19.49±8.18ng/ml; p=0.025) levels. At follow-up, 10.0% vs. 11.0% patients experienced acute ischemic event, heart failure, or death in the non-CRF and CRF groups, respectively (p=0.815, log-rank test). The limited number of non-CRF patients may have influenced this finding. A Cox regression analysis in the whole population showed that high calcidiol, and low MCP-1 and FGF-23 plasma levels are associated with a better prognosis.. CHD patients without CRFs show a favorable biomarker profile in terms of inflammation and mineral metabolism. Further studies are needed to investigate whether this difference translates into a better prognosis.

Topics: Biomarkers; C-Reactive Protein; Calcifediol; Chemokine CCL2; Cholesterol; Coronary Artery Disease; Cross-Sectional Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Galectin 3; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Parathyroid Hormone; Peptide Fragments; Phosphates; Prognosis; Risk Factors; Triglycerides

Monitoring N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful for assessing cardiovascular risk in dialysis patients. However, its biologic variation is unknown, hindering the accurate interpretation of serial concentrations. The aims of this prospective cohort study were to estimate the within- and between-person coefficients of variation of NT-proBNP in stable dialysis patients, and derive the critical difference between measurements needed to exclude biologic and analytic variation.. Fifty-five prevalent hemodialysis and peritoneal dialysis patients attending two hospitals were assessed weekly for 5 weeks and then monthly for 4 months between October 2010 and April 2012. Assessments were conducted at the same time in the dialysis cycle and entailed NT-proBNP testing, clinical review, electrocardiography, and bioimpedance spectroscopy. Patients were excluded if they became unstable.. This study analyzed 136 weekly and 113 monthly NT-proBNP measurements from 40 and 41 stable patients, respectively. Results showed that 22% had ischemic heart disease; 9% and 87% had left ventricular systolic and diastolic dysfunction, respectively. Respective between- and within-person coefficients of variation were 153% and 27% for weekly measurements, and 148% and 35% for monthly measurements. Within-person variation was unaffected by dialysis modality, hydration status, inflammation, or cardiac comorbidity. NT-proBNP concentrations measured at weekly intervals needed to increase by at least 46% or decrease by 84% to exclude change due to biologic and analytic variation alone with 90% certainty, whereas monthly measurements needed to increase by at least 119% or decrease by 54%.. The between-person variation of NT-proBNP was large and markedly greater than within-person variation, indicating that NT-proBNP testing might better be applied in the dialysis population using a relative-change strategy. Serial NT-proBNP concentrations need to double or halve to confidently exclude change due to analytic and biologic variation alone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Australia; Biomarkers; Female; Humans; Kidney Diseases; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Peritoneal Dialysis; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Reproducibility of Results; Risk Factors; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Young Adult

Evidence suggests that troponin (Tn) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may predict an increase in mortality risk. We performed an observational study of 935 patients admitted to hospital for AECOPD from January 2010 to December 2012. Principal clinical and laboratory data were recorded, especially ischemic heart disease (IHD) history, Tn T values and cardiovascular drug prescription. The occurrence of all-cause death, cardiac death (CD), nonfatal myocardial infarction (MI), heart failure and cerebrovascular accident (CVA) was assessed on December 2013. Overall, 694 patients respected inclusion and exclusion criteria. We identified 210 (30%) patients without Tn elevation (negative Tn T group) and 484 (70%) patients with Tn elevation (positive Tn T group). With the exception of CVA, all adverse events were significantly higher in positive Tn T group as compared to negative Tn T group. At multivariable analysis, positive Tn T failed to predict all-cause death. Contrarily, positive Tn T emerged as independent predictors of CD (HR 1.61, 95%CI 1.2-2.2, p = 0.04), nonfatal MI (HR 3.12, 95%CI 1.4-8.1, p = 0.03) and composite endpoint including CD and nonfatal MI (HR 1.73, 95%CI 1.2-2.7, p = 0.03). Of note, positive Tn T stratified prognosis in patients without IHD history, but not in those with IHD history. In conclusion, after hospital admission for AECOPD, we observed a significant increase in the risk of cardiac adverse events in patients with Tn T elevation, especially in those without IHD history.

Topics: Age Factors; Aged; Aged, 80 and over; Aspirin; Cause of Death; Creatinine; Disease Progression; Female; Heart Failure; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation Inhibitors; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Stroke; Troponin T

To evaluate diagnostic and long-term prognostic values of hFABP compared to NT-proBNP and troponin I (TnI) in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF).. 401 patients with acute dyspnea or peripheral edema, 122 suffering from AHF, were prospectively enrolled and followed up to 5 years. hFABP combined with NT-proBNP versus NT-proBNP alone was tested for AHF diagnosis. Prognostic value of hFABP versus TnI was evaluated in models predicting all-cause mortality (ACM) and AHF related rehospitalization (AHF-RH) at 1 and 5 years, including 11 conventional risk factors plus NT-proBNP.. Additional hFABP measurements improved diagnostic specificity and positive predictive value (PPV) of sole NT-proBNP testing at the cutoff <300 ng/l to "rule out" AHF. Highest hFABP levels (4th quartile) were associated with increased ACM (hazard ratios (HR): 2.1-2.5; p = 0.04) and AHF-RH risk at 5 years (HR 2.8-8.3, p = 0.001). ACM was better characterized in prognostic models including TnI, whereas AHF-RH was better characterized in prognostic models including hFABP. Cox analyses revealed a 2 % increase of ACM risk and 3-7 % increase of AHF-RH risk at 5 years by each unit increase of hFABP of 10 ng/ml.. Combining hFABP plus NT-proBNP (<300 ng/l) only improves diagnostic specificity and PPV to rule out AHF. hFABP may improve prognosis for long-term AHF-RH, whereas TnI may improve prognosis for ACM.. ClinicalTrials.gov identifier: NCT00143793 .

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Cohort Studies; Diagnosis, Differential; Dyspnea; Echocardiography; Edema; Emergency Service, Hospital; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Heart Failure; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Prospective Studies; Sensitivity and Specificity; Survival Rate; Troponin I; Young Adult

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep. We tested the hypothesis that nocturnal myocardial ischemia is detectable by ST segment depression and elevation of high sensitive troponin T (hsTrop T) and B-type natriuretic peptide (NT-proBNP) in patients with OSA and coexisting coronary artery disease (CAD). Twenty-one patients with OSA and CAD and 20 patients with OSA alone underwent in-hospital polysomnography. Blood samples for hsTrop T and NT-proBNP measurements were drawn before and after sleep. ST segment depression was measured at the time of maximum oxygen desaturation during sleep. The apnea-hypopnea-index (AHI), oxygen saturation nadir, and time in bed with oxygen saturation of ≤80% were similar in both groups. Levels of hsTrop T and NT-proBNP did not differ significantly before and after sleep but NT-proBNP levels were significantly higher in patients suffering from OSA and CAD compared to patients with OSA alone. No significant ST depression was found at the time of oxygen saturation nadir in either group. Despite the fact that patients with untreated OSA and coexisting CAD experienced severe nocturnal hypoxemia, we were unable to detect myocardial ischemia or myocyte necrosis based on significant ST segment depression or elevation of hsTrop T and NT-proBNP, respectively.

Topics: Aged; Biomarkers; Coronary Artery Disease; Electrocardiography; Female; Germany; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Troponin T

In vitro assays could replace animal experiments in drug screening and disease modeling, but have shortcomings in terms of functional readout. Force-generating engineered heart tissues (EHT) provide simple automated measurements of contractile function. Here we evaluated the response of EHTs to hypoxia/reoxygenation (H/R) and the effect of known cardiocytoprotective molecules. EHTs from neonatal rat heart cells were incubated for 24 h in EHT medium. Then they were subjected to 180 min hypoxia (93% N2, 7% CO2) and 120 min reoxygenation (40% O2, 53% N2, 7% CO2), change of medium and additional follow-up of 48 h. Time-matched controls (40% O2, 53% N2, 7% CO2) were run for comparison. The following conditions were applied during H/R: fresh EHT medium (positive control), the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 10(-7), 10(-6), 10(-5) M) or the guanylate cyclase activator brain type natriuretic peptide (BNP, 10(-9), 10(-8), 10(-7) M). Frequency and force of contraction were repeatedly monitored over the entire experiment, pH, troponin I (cTnI), lactate dehydrogenase (LDH) and glucose concentrations measured in EHT medium. Beating activity of EHTs in 24 h-medium ceased during hypoxia, partially recovered during reoxygenation and reached time-control values during follow-up. H/R was accompanied by a small increase in LDH and non-significant increase in cTnI. In fresh medium, some EHTs continued beating during hypoxia and all EHTs recovered faster during reoxygenation. SNAP and BNP showed small but significant protective effects during reoxygenation. EHTs are applicable to test potential cardioprotective compounds in vitro, monitoring functional and biochemical endpoints, which otherwise could be only measured by using in vivo or ex vivo heart preparations. The sensitivity of the model needs improvement.

Topics: Animals; Glucose; L-Lactate Dehydrogenase; Myocardial Contraction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred Lew; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine; Tissue Engineering; Troponin I

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular complications. OSA and coronary artery disease (CAD) share the same risk factors and coexist in many patients. In previous studies, repeated nocturnal cardiac ischemic events in OSA patients with CAD have been reported.. We hypothesized that OSA may precipitate myocardial ischemia, evidenced by ST-segment depression and elevated N-terminal brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TropT) levels in patients with severe OSA and concomitant CAD. We also aimed to evaluate if the effects could be reversed by continuous positive airway pressure (CPAP) therapy.. Twenty-one patients with severe OSA (apnea-hypopnea index >15/h, nadir oxygen desaturation ≤ 80%), and coexisting CAD underwent in-hospital polysomnography at baseline and under CPAP. Blood samples for hs-TropT and NT-proBNP measurements were drawn prior and immediately after sleep. ST-segment depression was measured at the time of maximum oxygen desaturation during sleep.. CPAP significantly decreased elevated NT-proBNP levels from 475 ± 654 pg/mL before sleep to 353 ± 573 pg/mL after sleep and attenuated ST-segment depression during sleep. hs-TropT was not elevated and did not differ after nocturnal oxygen desaturation at baseline and after CPAP.. CPAP significantly reduced NT-proBNP in patients suffering from severe OSA and coexisting CAD. Repeated nocturnal myocardial ischemia did not cause myocyte necrosis evidenced by elevated hs-TropT or ST-segment depression.

Topics: Aged; Biomarkers; Continuous Positive Airway Pressure; Coronary Artery Disease; Electrocardiography; Female; Germany; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Troponin T

Type 2 diabetes (DMT2) combined with ischemic heart disease (IHD) promotes the occurrence and development of coronary atherosclerosis. We aimed to provide a theoretical basis for improving patient prognosis through analyzing expression of plasma brain natriuretic peptide (BNP), endothelin-1 (ET 1), and matrix metalloproteinase 9 (MMP-9).. Enzyme-linked immunosorbent assay (ELISA) was used to detect BNP, ET-1, and MMP-9 levels in 50 patients with DMT2 only (group A), 47 patients with IHD only (group B), 43 patients with comorbid (both) IHD and DMT2 (group C), and 50 health controls (group D). Group C was further divided into single-branch lesion group, double-branch lesions group, and triple-branch lesion group according to coronary angiography, or cardiac function grade II, III, and IV group according to cardiac function, and their BNP, ET-1, and MMP-9 levels were compared.. Compared with group D, TG, diastolic, and systolic blood pressure were all significantly elevated in groups A, B, and C. Group C exhibited obviously higher glycosylated hemoglobin than group A. Gensini score in group C was markedly higher than in group B. Compared with group D, BNP, ET-1, and MMP-9 levels were all increased in groups A, B, and C. Group C showed higher levels of BNP, ET-1, and MMP-9 than group A and B. BNP, ET-1, and MMP-9 levels in the triple-branch lesions group were higher than in the single-branch lesions group and double-branch lesions group. The cardiac function grade IV group presented higher levels of BNP, ET-1, and MMP-9 than did the grade II and III groups. BNP, ET-1, and MMP-9 showed a positive correlation to each other.. BNP, ET-1, and MMP-9 may participate in the occurrence and development of comorbid DMT2 and IHD. They are important objective indicators for evaluating severity and prognosis of patients with comorbid DMA2 and IHD.

Topics: Adult; Aged; Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Heart Function Tests; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis

A recent pilot study suggested that exercise-induced myocardial ischaemia may lead to a delayed release of cardiac biomarkers, so that later sampling, for example, at 4 h after exercise could be used for diagnostic purpose.. In an observational study, we enrolled 129 consecutive patients referred for evaluation of a suspected coronary artery disease by rest/stress myocardial perfusion single-photon emission computed tomography. The treating cardiologist used all available clinical information to quantify clinical judgment regarding the presence of myocardial ischaemia using a visual analogue scale twice: prior and after stress testing. BNP levels were determined in a blinded fashion at rest, at peak stress and 4 h after peak stress. The presence of myocardial ischaemia was adjudicated based on perfusion single-photon emission computed tomography and coronary angiography findings by an independent cardiologist.. Myocardial ischaemia was detected in 58 patients (45%). Patients with myocardial ischaemia had significantly higher BNP levels at all times, compared to patients without ischaemia: BNP rest (99 vs. 61 pg/mL P = 0·007), BNP stress (125 vs. 77 pg/mL P = 0·02) and BNP 4 h (114 vs. 71 pg/mL P = 0·018). Diagnostic accuracy as quantified by the area under the receiver operating characteristics curve (AUC) was moderate for all time points (AUC 0·64-0·66). The change in BNP between rest and 4 h did not provide added value, neither to the baseline BNP level nor to clinical judgment.. In contrast to our hypothesis, myocardial ischaemia did not lead to a differential delayed release of BNP. Late sampling did not seem clinically useful.

Topics: Aged; Area Under Curve; Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography; Coronary Angiography; Coronary Artery Disease; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; ROC Curve; Time Factors

The intensity of accumulation and release of brain natriuretic peptide (BNP) in right atrial cardiac muscle cells was investigated in rats after 5 and 60 min from the reperfusion start. Total ischemia was simulated by cardiovascular bundle compression according to V. G. Korpachev. Immunocytochemical identification of BNP in atrial myocyte granules was investigated in ultrathin cuts. We applied polyclonal antibodies to BNP. The calculation of granules (A- and B-types) with BNP was carried out in (38 x 38 μm) visual fields in transmission electronic microscope. The results were assessed using Mann-Whitney U-test (p < 0.05). After 5 min from the reperfusion start, the amount of the granules with BNP did not change compared to intact animals rate. On the 60th min of the post-reperfusion period was shown active accumulation and release of BNP; the amount of A-type granules increased by 134%, B-type granules increased by 210 % in comparison with intacy level. The results showed stimulating effect of ischemic and reperfusion factors on the processes of the brain natriuretic peptide synthesis and secretion in the early post-reperfusion period.

Topics: Animals; Biomarkers; Cytoplasmic Granules; Disease Models, Animal; Heart Atria; Male; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats; Reperfusion; Time Factors

The aim of the study - to evaluate the prognostic value of galectin-3 for cumulative survival in patients with controlled non-Hodgkin lymphoma. Eighty two out subjects with full or partial remission of non-Hodgkin lymphoma were enrolled in the study. Observation period was up to 12 months. Blood samples for biomarkers measurements were collected. ELISA method for measurements of circulating level of Gal-3 and NT-pro-brain natriuretic peptide (NT-proBNP) was used. Hemodynamic evaluation was performed by transthoracic echocardiography. Fifty five cumulative clinical events occurred in 21 patients (25.6%) within the follow-up, with their distribution being as follows: 5 cardiovascular deaths, 24 cardiac arrhythmias, 8 cardiac ischemic events, 3 strokes, 9 chronic heart failures and 6 hospital admissions for cardiovascular reasons. Circulating levels of Gal-3 in subjects without and with cardiovascular events were 5.37 ng/ml (95% confidence interval [CI]=2.90-7.85 ng/ml) and 13.97 ng/ml (95% CI=7.82-20.11 ng/ml) (P=0.03) respectively. The results of regression analysis showed directly related circulating Gal-3 with E/Em (r=0.45, P=0.045), T2DM (r=0.38, P=0.01). Multivariate logistic regression revealed independent predictive value of circulating Gal-3 for 12 months cumulative cardiovascular events (odds ratio [OR]=1.11; 95% CI=1.05-1.25; P=0.005). In fact, Gal-3, NT-pro-BNP, GFR, and LVEF remained statistically significant predictors for cumulative cardiovascular events, whereas T2DM, hypertension, obesity did not. Increased circulating Gal-3 associates with increased 12 months cumulative cardiovascular events among patients with documented non-Hodgkin lymphoma.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Biomarkers; Blood Proteins; Cyclophosphamide; Doxorubicin; Echocardiography; Female; Galectin 3; Galectins; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prednisone; Prognosis; Prospective Studies; Remission Induction; Rituximab; Stroke; Survival Analysis; Vincristine

Osteonectin (OSN) plays a pivotal role in cardiac remodeling, but predictive value for OSN in ischemic chronic heart failure (CHF) has not been defined. The aim of the study was to evaluate the prognostic value of OSN for cumulative survival and hospitalization among patients with ischemic-induced CHF.. A total of 154 patients with ischemic symptomatic moderate-to-severe CHF were enrolled in the study at discharge from the hospital. Observation period was up to 3 years (156 weeks). Blood samples for biomarkers measurements were collected at baseline prior to study entry. ELISA methods for measurements of circulating level of OSN were used.. During a median follow-up of 2.18 years, 21 participants died and 106 subjects were re-admitted. Medians of circulating levels of OSN in survival and died patient cohorts were 670.96 ng/mL (95% confidence interval [CI] = 636.53-705.35 ng/mL) and 907.84 ng/mL (95% CI = 878.02-937.60 ng/mL). Receiver operation characteristic curve analysis has shown that cut off point of OSN concentration for cumulative survival function was 845.15 ng/mL. It has been found a significant divergence of Kaplan-Meier survival curves in patients with high (>845.15 ng/mL) and low (<845.15 ng/mL) concentrations of OSN. Circulating OSN independently predicted all-cause mortality (odds ratio [OR] = 1.23; 95% CI = 1.10-1.36; p < 0.001), CHF-related death (OR = 1.46; 95% CI = 1.22-1.80; p < 0.001), and also CHF-related re-admission (OR = 1.92; 95% CI = 1.77-2.45; p < 0.001) within 3 years of observation period.. Increased circulating secreted protein acidic and rich in cysteine family member OSN associates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.

Topics: Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Osteonectin; Peptide Fragments; Prospective Studies

Left ventricular filling pressure (LVFP) is raised by the compromised contraction and impaired ventricular compliance in dilated hearts with systolic dysfunction. Timely recognition and staging of this condition are important for planning of the treatment strategy and making the prognosis. Two-dimensional speckle- tracking echocardiography (2D-STE) has recently enabled the quantification of left atrial (LA) myocardial deformation dynamics. In this study, echocardiographic indicators of increased LVFP and NT-pro-BNP were compared with LA strain measured by 2D-STE.. A total of 49 nonischemic dilated cardiomyopathy (DCMP) patients were included in the study. All patients underwent standard 2D echocardiography. In the 2D-STE analysis of the LA, global longitudinal LA strain during ventricular systole (GLAs-res) and strain during late diastole (GLAs-pump) were obtained. NT-pro-BNP levels were measured. The patients were divided into two groups--normal (group 1) and increased (group 2) LVFP--according to E/A ratio, E velocity, and E/E' ratio.. LAVi-max, LAVi-min, and NT-pro-BNP were higher in group 2, whereas LAtotalEF, LAactiveEF, GLAs-res, and GLAs-pump were lower. In univariate analysis, a good negative correlation was seen between GLAs-res vs. NT-pro-BNP, GLAs-res vs. LAVi-max, and GLAs-res vs. E/E' ratio; a good negative correlation was present between GLAs-pump vs. NT-pro-BNP, GLAs-pump vs. LAVi-max, and GLAs-pump vs. E/E' ratio. LAVi-max, LAactiveEF, NT-pro-BNP, GLas-res, and GLAs-pump were studied by logistic regression analysis. GLAs-res (p = 0.009, OR = 0.593, 95 % CI 0.4-0.877), NT-pro-BNP (p = 0.028, OR = 1.027, 95 % CI 1.003-1.052), and LAactiveEF (p = 0.022, OR = 0.001, 95 % CI 0.001-0.024) were found to be independent predictors of increased LVFP.. 2D-STE-based LA function is impaired in patients with nonischemic DCMP. LA reservoir and pump function parameters together with NT-pro-BNP levels might be useful in estimating LVFP in this patient group.

Topics: Adult; Biomarkers; Cardiomyopathy, Dilated; Echocardiography; Elastic Modulus; Elasticity Imaging Techniques; Female; Heart Atria; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Observer Variation; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Remodeling

Plasma BNP and high-sensitivity cardiac troponin-T (hs-TnT) are elevated by both ischaemia and LV systolic dysfunction (LVSD). As a result, it is unknown whether BNP and/or hs-TnT could be useful biomarkers to identify ischaemia in the presence of LVSD.. Three separate patient populations were studied. Study A (n = 500) involved consecutive patients undergoing clinically indicated myocardial perfusion scintigraphy, study B (n = 100) included patients with vascular disease but no known cardiac disease, and study C (n = 300) recruited primary prevention patients with controlled risk factors. Levels of BNP and hs-TnT were measured prior to the stress testing to detect myocardial ischaemia. The prevalence of myocardial ischaemia was 28.2, 28, and 6.3% in study A, B, and C, respectively. For BNP, area under curve (AUC) values to identify ischaemia in the presence and absence of coincidental LVSD were: 0.73 vs. 0.63 (study A), 0.90 vs. 0.81 (study B), and 0.83 vs. 0.80 (study C). Equivalent figures for hs-TnT were: 0.64 vs. 0.60 (study A), 0.75 vs. 0.68 (study B), and 0.53 vs. 0.68 (study C). BNP and hs-cTnT, when combined together, performed better with an AUC of 0.75 vs. 0.65 (study A), 0.91 vs. 0.92 (study B), and 0.84 vs. 0.83 (study C).. In three separate populations a consistent finding is that BNP is increased further by myocardial ischaemia even in the presence of LVSD. A disproportionately high BNP for the degree of LVSD might be due to (unsuspected) ischaemia, and a disproportionately low BNP could be useful as a 'rule out' test for ischaemia even in the presence of LVSD.

Topics: Aged; Biomarkers; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Systole; Troponin T; Ventricular Dysfunction, Left

The clinical history of heart failure (HF) is usually characterized by frequent hospitalizations for decompensation. Therefore, several markers of subclinical hemodynamic congestion are under investigation for predicting early rehospitalization. In this field, the potential of ultrasound inferior vena cava (IVC) assessment has been recently investigated in HF but not yet assessed in the different aetiological categories.. Forty-eight patients admitted for decompensated HF (n = 25 with ischaemic heart disease [IHD] and n = 23 non-IHD) underwent biochemical examination (including NT-proBNP), echocardiography and IVC assessment by hand-carried ultrasound (HCU). During 60-day follow-up after discharge, the re-hospitalization rate for HF was recorded to investigate the predictive power of NT-proBNP and IVC assessment among the two study groups.. IHD and non-IHD patients with HF were similar except for gender distribution. During follow-up, 16·7% of patients were rehospitalized for decompensated HF, with higher prevalence in IHD group (28% vs. 4·3% P = 0·031). IVC assessment at discharge significantly predicted re-admission in the overall population and in IHD group, whereas NT-proBNP failed to predict rehospitalization in IHD group. In adjusted hazard ratio, only IVC min and the changes of IVC from admission significantly predicted re-admission. ROC analysis confirmed the change in IVC min as the best predictor of rehospitalization in patients with IHD.. This pilot study showed a higher early re-admission rate in patients with HF due to IHD. In addition, the change in IVC min diameter from admission to discharge was the best predictor of re-admission in patients with IHD.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Pilot Projects; Ultrasonography; Vena Cava, Inferior

Myocardial ischemia has been shown to be associated with increased levels of B-type natriuretic peptide (BNP). However, it remains unclear whether and how BNP levels could be used clinically in patients with suspected exercise-induced myocardial ischemia.. We enrolled 274 consecutive patients with suspected exercise-induced myocardial ischemia referred for evaluation by rest/bicycle myocardial perfusion single-photon emission computed tomography (SPECT). All clinical information available to the treating cardiologist was used to quantify the clinical judgment regarding the presence of myocardial ischemia using a visual analogue scale twice: once before and once after bicycle exercise stress testing. BNP measurements were obtained before, immediately after, and 2 hours after stress testing in a blinded manner. The presence of myocardial ischemia was adjudicated on the basis of perfusion SPECT combined with coronary angiography findings.. Exercise-induced myocardial ischemia was adjudicated to be present in 103 patients (38%). BNP levels were significantly higher at all time points in patients with myocardial ischemia compared with those without (P < .01 for all). The accuracy of BNP levels as quantified by the area under the receiver operating characteristic curve (AUC) was similar among the time points evaluated (AUC, 0.677-0.697). Combining clinical judgment before exercise testing with BNP levels at rest increased diagnostic accuracy from AUC 0.708 to 0.754 (P = .018). When combining clinical judgment after exercise testing with BNP levels, AUC increased from 0.741 to 0.771 (P = .055).. Combining clinical judgment with BNP levels increased the diagnostic accuracy regarding the presence of myocardial ischemia.

Topics: Aged; Area Under Curve; Biomarkers; Coronary Artery Disease; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Sex Distribution; Tomography, Emission-Computed, Single-Photon

The non-invasive differentiation of ischemic and non-ischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether plasma B-type natriuretic peptide (BNP) can identify ischemic etiology in patients with stage 4-5 chronic kidney disease (CKD) presenting with AHF.. We prospectively analyzed 61 patients. The diagnosis of ischemic AHF was confirmed by coronary angiography or stress myocardial perfusion imaging. Plasma levels of BNP were measured at admission (BNP1) and 48 h after admission (BNP2).. The mean age of the study patients was 67 years. In these patients, 70.5% had diabetes and 47.5% had dialysis-dependent CKD; 28 of these patients (45.9%) had an ischemic etiology with significantly higher concentrations of BNP1 and BNP2 than did patients without ischemia. The area under the receiver operating characteristic curve was 0.755 (P=0.001) for BNP1 and 0.868 (P<0.001) for BNP2 to detect ischemic etiology of AHF. Plasma BNP1 >2907 ng/L (odds ratio [OR], 10.9; 95% confidence interval [CI] 2.5-48.4; P=0.002) and BNP2 >2322 ng/L (OR 93.1, 95% CI 7.0-1238.7; P=0.001) were independently associated with an ischemic etiology of AHF.. Plasma BNP may represent a clinically useful non-invasive tool for identification of ischemic etiology of AHF in patients with stage 4-5 CKD.

Topics: Aged; Female; Heart Failure; Hospitalization; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Risk Factors; ROC Curve; Ultrasonography

Despite a high potential of endothelial progenitor cells (EPCs) for diagnostic purposes, the EPC role in developing ischemic chronic heart failure (CHF) has not been determined obviously. The objective of this study was to assess the counts of CD45(+)CD34(+), CD45(-)CD34(+), CD14(+)CD309(+), and CD14(+)CD309(+)Tie2(+) phenotyped circulating EPCs of various subpopulations in patients with ischemic CHF.. The study involved 153 patients (86 male), aged 48-62 years, with angiographically proven coronary artery disease (CAD) and 25 healthy volunteers. CHF was diagnosed in 109 patients (71.2%). Mononuclear cell populations were phenotyped by flow cytofluorimetry. Cardiovascular risk factors, such as type 2 diabetes mellitus, hyperlipidemia, arterial hypertension, and adherence to smoking, may have a negative effect on circulating EPC counts in CAD patients regardless of the presence of CHF. The depletion of the CD14(+)CD309(+)- and CD14(+)CD309(+)Tie2(+)-phenotyped circulating EPC counts is associated with the severity of left ventricular dysfunction, whereas the CD45(+)CD34(+)- and CD45(-)CD34(+)-mononuclear cell counts are more representative of the severity of atherosclerotic coronary artery lesions.. The authors found that New York Heart Association functional class of CHF, left ventricular ejection fraction <42%, the N-terminal pro-B-type natriuretic peptide level >554 pg/mL, and Е/Еm ratio >15 U had the highest predictive value for the depletion of the EPC count in CAD patients.

Topics: Biomarkers; C-Reactive Protein; Coronary Angiography; Endothelial Progenitor Cells; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index

Topics: Aged; Exercise; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Endothelial Growth Factor A

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia-reperfusion (I/R) injury. B-type natriuretic peptide (BNP) postconditioning has been reported to reduce myocardial I/R injury. The present study investigated whether postconditioning of BNP could reduce myocardial I/R injury by inhibiting HMGB1 expression and the potential mechanisms in rats. The left anterior descending coronary arteries of rats were occluded to induce ischemia for 30 min and reopened to imitate reperfusion for 4 h. The rats were treated with BNP (0.03 μg/kg min, i.v.) 15 min before reperfusion until the end of the procedure, with or without treatment of LY294002 (an inhibitor of phosphoinositide 3-kinase (PI3K), 0.3 mg/kg, i.v.), which was injected 20 min before reperfusion. Lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and infarct size were measured. Phospho-Akt, total Akt, and HMGB1 expression were assessed by immunoblotting. The results showed that treatment of BNP postconditioning could significantly decrease the infarct size and the levels of LDH and CK after 4-h reperfusion (all p<0.05). BNP postconditioning could also significantly inhibit the increases of TNF-α and IL-6 (both p<0.05). In addition, BNP postconditioning could significantly inhibit HMGB1 expression induced by I/R (p<0.05). Administration of LY294002 abolished the effects of BNP postconditioning on myocardial I/R injury and the expressions of phospho-Akt and HMGB1 (all p<0.05). The present study suggests that postconditioning of BNP could protect against myocardial I/R injury which may be associated with inhibiting HMGB1 expression, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of BNP postconditioning.

Topics: Animals; Anti-Inflammatory Agents; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Natriuretic Peptide, Brain; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease.. In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged.. This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.

Topics: Adiponectin; Adipose Tissue; Aged; Brachial Artery; Coronary Artery Bypass; Coronary Artery Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Organ Culture Techniques; Organ Specificity; Risk Factors; Subcutaneous Fat; Thigh; Thorax; Tumor Necrosis Factor-alpha; Ultrasonography; Vasodilation; Ventricular Dysfunction, Left

The study was undertaken to find out the correlation of elevated B-type Natriuretic Peptide (BNP) levels with the severity of coronary artery disease in patients with unstable angina and NSTEMI. This cross sectional analytical study was carried out in the department of cardiology, National Institute of Cardiovascular Diseases, Dhaka during a period of August 2011 to June 2012. A total of 100 consecutive patients with unstable angina and NSTEMI undergoing coronary angiography were included in the study. BNP assay was done by Architect system, a chemo luminescent microparticle immunoassay (CMIA). CAG was done by conventional method within 14 days of index hospital admission. Study patients were divided into two groups on the basis of BNP levels. In Group I, BNP Levels were ≤80pg/ml and in Group II, BNP levels were elevated >80pg/ml. with 50 patients in each group. Angiographic severity of CAD was assessed by vessel score and Friesinger score. Vessel score showed single vessel was involved in 21(47.7%) patients while multi vessel in 23(52.3%) patients was found in Group I. On the contrary 11(22.4%) single vessel patients and 38(77.6%) multivessel patients were found in Group II. There was significant association between vessel involvement (p=0.01). Friesinger score revealed that less severe CAD was found in 22(44%) patients and significant severe CAD in 28(56.0%) patients in Group I. On the contrary 7(14.0%) less severe CAD patients and 43(86.0%) severe CAD patients were found in Group II. There was significant difference between severity of CAD among the study groups (p=0.01). There was linear correlation between BNP pg/ml and coronary artery disease severity in terms of Vessel score (r=0.38, p=0.01) and Friesinger score (r=0.51, p=0.01). The present study concluded that increased BNP level >80pg/ml was significantly associated with the presence and severity of CAD in patient with UA and NSTEMI.

Topics: Adult; Aged; Angina, Unstable; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Humans; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain

Non-invasive assessment using a pharmacological provocative test is an essential part of the workup of patients admitted to the emergency department with chest pain. Some doubts, however, remain about the safety of dipyridamole stress echocardiography in patients with non-diagnostic troponin and ECG.. Twenty-nine consecutive patients admitted to the emergency department with chest pain and no evidence of acute coronary syndrome were subjected to standard dipyridamole stress echocardiography. Blood samples for measurement of galectin-3, NT-proBNP and high-sensitivity troponin T (HS-TnT) were collected at the baseline and after provocative testing. The provocative test was positive in 7/29 patients. As compared with baseline measurements, no significant differences were observed in 1-h values of HS-TnT (10.7 versus 10.5 ng/L; P = 0.085) and galectin-3 (14.3 versus 13.7 ng/mL; P = 0.128), whereas values of NT-proBNP were slightly higher (126 versus 111 ng/L; P = 0.002). The 1-h delta variation of patients with a positive provocative test was significantly higher than that of patients with negative provocative testing for galectin-3 (1.12 versus 1.00; P < 0.001), but not for HS-TnT (0.98 versus 1.00; P = 0.184) and NT-proBNP (1.10 versus 1.04; P = 0.344). The 1-h delta variation of galectin-3 was > 1 in all patients with a positive provocative test as compared with 50% of patients with a negative provocative test (P = 0.018).. Dipyridamole stress testing did not trigger clinically meaningful injuries to the myocardium. Galectin-3 testing may hence be preliminarily regarded as a complementary means for enhancing the diagnostic value of provocative testing. It is also worthwhile investigating whether patients with abnormal response to a provocative test and increased galectin-3 values may be targeted with specific therapy.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chest Pain; Dipyridamole; Echocardiography, Stress; Emergency Service, Hospital; Female; Galectin 3; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Troponin T; Vasodilator Agents

Topics: Adiponectin; Adipose Tissue; Female; Heart Failure; Humans; Inflammation; Male; Myocardial Ischemia; Natriuretic Peptide, Brain

Asymptomatic systolic dysfunction of the left ventricle (LV) refers to patients without current clinical symptoms of heart failure.. 1. Analysis of echocardiographic parameters in patients with stable angina pectoris without symptoms of heart failure and their changes in two years time 2. Determine the importance of NT-proBNP for early detection of asymptomatic heart dysfunction in patients with stable angina pectoris and its influence on the prognosis in two years 3. Analysis of the relationship between the degree of the left ventricular diastolic dysfunction and co-morbidities and selected echocardiographic parameters 4. Significance of prognostic selected echocardiographic parameters (E/ Vp, E/E', Ar) in patients with stable angina pectoris without any symptoms of heart failure.. The study included 57 patients with stable ischemic heart disease, no history of myocardial infarction: including 35 men (61.4%) aged 35-56 years (mean 51.08 +/- 4.01 years) hospitalized in the Department of Coronary Artery Disease, Institute of Cardiology, Jagiellonian University in Krakow. Analysis after two years involved 56 patients (1 patient died after a year of observation).. Patients were evaluated 2x: before and after 2 years (assessment of clinical status: physical examination, the severity of angina and physical examination, atherosclerotic risk factors, ECG, lipid profile, plasma NT-proBNP). Patients were divided into three groups: Group A, patients with LV normal function (32 patients), Group B - with impaired diastolic function (22), Group C - with impaired systolic and diastolic function (EF < or = 50%, as measured by Simpson; 3 patients).. Subgroups of respondents ABC did not differ significantly with respect to age, sex and risk fac- tors of atherosclerosis. There was a significant correlation between the type of LV dysfunction and indicators of elevated end diastolic pressure in LV: E/Vp (p = 0.0002), E/E' (p = 0.0006), Ar (p = 0.034) and the propagation velocity Vp (0 = 0.001). There was a significant correlation between systolic and diastolic heart dysfunction and the levels of NT-proBNP (p = 0.018). After 2 years, patients with deterioration of heart function in group A noticed a significant correlation between occurrence of diastolic dysfunction and presence of diabetes mellitus type II (p = 0.01). Conclusions: 1. Elevated levels of NT-proBNP indicates the impairment of systolic andlor diastolic asymptomatic patients. NT-proBNP is therefore important for early detection of asymptomatic cardiac dysfunction in patients with stable angina pectoris. 2. In patients with stable angina pectoris without symptoms of heart failure: the value of E/Vp > or = 1.5 and E/E '> or = 8 can be the marker of more advanced coronary atherosclerosis, manifested by three-vessel disease or stenosis of the left main coronary artery.

Topics: Adult; Angina Pectoris; Biomarkers; Diabetes Mellitus, Type 2; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Dysfunction, Left

Although the plasma B-type natriuretic peptide (BNP) level is a marker of heart failure, it is unclear whether BNP per se plays a pivotal role for pathogenic mechanisms underlying the development of ischemic heart disease (IHD). In this study, we retrospectively examined the plasma BNP levels in stable patients with IHD and compared to stable patients with cardiovascular diseases other than IHD.. The study population was 2088 patients (1698 males and 390 females) who were admitted to our hospital due to IHD (n = 1,661) and non-IHD (n = 427) and underwent cardiac catheterization. Measurements of the hemodynamic parameters and blood sampling were performed.. The plasma BNP levels were significantly lower in the IHD group than in the non-IHD group (p<0.001). The multiple regression analysis examining the logBNP values showed that age, a male gender, low left ventricular ejection fraction, low body mass index, serum creatinine, atrial fibrillation and IHD per se were significant explanatory variables. When the total study population was divided according to gender, the plasma BNP levels were found to be significantly lower in the IHD group than in the non-IHD group among males (p<0.001), but not females (p = NS). Furthermore, a multiple logistic regression analysis of IHD showed the logBNP value to be a significant explanatory variable in males (regression coefficient: -0.669, p<0.001), but not females (p = NS).. The plasma BNP levels were relatively low in stable patients with IHD compared with those observed in stable patients with non-IHD; this tendency was evident in males. Perhaps, the low reactivity of BNP is causally associated with IHD in males. We hope that this study will serve as a test of future prospective studies.

Topics: Aged; Biomarkers; Body Mass Index; Cardiac Catheterization; Cardiovascular Diseases; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Regression Analysis; Retrospective Studies; Ventricular Function, Left

In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DNA for transcription factors. Using human LV myocardium, we found that, despite nuclear export of histone deacetylase 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetylation in the promoter regions of these genes. In contrast, di- and trimethylation of lysine 9 of histone 3 (H3K9) and binding of heterochromatin protein 1 (HP1) in the promoter regions of these genes were substantially reduced. In isolated working murine hearts, an acute increase of cardiac preload induced HDAC4 nuclear export, H3K9 demethylation, HP1 dissociation from the promoter region, and activation of the ANP gene. These processes were reversed in hearts with myocyte-specific deletion of Hdac4. We conclude that HDAC4 plays a central role for rapid modifications of histone methylation in response to variations in cardiac load and may represent a target for pharmacological interventions to prevent maladaptive remodeling in patients with heart failure.

Topics: Acetylation; Active Transport, Cell Nucleus; Animals; Atrial Natriuretic Factor; Blood Pressure; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiomyopathy, Dilated; Case-Control Studies; Cells, Cultured; Enzyme Induction; Epigenesis, Genetic; Gene Expression; Heart Failure; Heart Ventricles; Histone Deacetylases; Histones; Humans; In Vitro Techniques; Jumonji Domain-Containing Histone Demethylases; Male; Methylation; Methyltransferases; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Promoter Regions, Genetic; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; Repressor Proteins; Sarcoplasmic Reticulum Calcium-Transporting ATPases

The characteristics, in-hospital management, and outcomes of patients hospitalized with worsening heart failure (HF) have been described by large-scale registries performed mainly in the USA and Europe. However, little information is available in Japan. We thus clarified the characteristics and clinical status as well as in-hospital management and outcomes among patients hospitalized with worsening HF in Japan and compared them with those reported in previous studies.. The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in patients hospitalized with worsening HF. From the total cohort of JCARE-CARD, 1677 patients were randomly selected and their detailed data during acute phase were collected as another registry database in the present study. The characteristics, in-hospital management, and outcomes were analyzed.. The mean age was 70.7 years and 59.4% were male. Etiology was ischemic in 34.0% and mean left ventricular ejection fraction was 42.5%. Carperitide was highly used as in-hospital management in Japan (33.5%) compared to the use of nesiritide in the USA (8-11%). The use of angiotensin-converting enzyme inhibitors was lower and angiotensin II receptor blockers (ARB) were more commonly used in this study compared to other studies in the USA and Europe. In-hospital crude mortality rate was comparable among studies (4-8%), however, length of stay was longer in Japan (15-20 versus 4-9 days).. The characteristics, clinical status, and laboratory data on admission in patients hospitalized with worsening HF were similar between the present study and previous Japanese and western studies. Management was also similar except for higher use of carperitide and ARB. The most striking difference between Japanese registries and those from the USA and Europe was the longer length of stay.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Asian People; Atrial Natriuretic Factor; Cohort Studies; Disease Progression; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Myocardial Ischemia; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Random Allocation; Registries; Treatment Outcome

N terminal-proB-type natriuretic peptide (NT-proBNP) is synthesised and secreted from the ventricular myocardium. This marker is known to be elevated in patients with acute coronary syndromes (ACS). We evaluated NT-proBNP asa significant diagnostic marker and an important independent predictor of short-term mortality (one month) in patients with ACS.. NT-proBNP and cardiac troponin I (cTI) were assessed in 134 consecutive patients (median age 66 years, 73% male)hospitalised for ACS in a cardiological university department. The patients were classified into ST-elevation ACS (STE-ACS, n = 74) and non-ST-elevation ACS (NSTE-ACS, n = 60) groups based on the ECG findings on admission. Patients with Killip class ≥ II were excluded.. The serum level of NT-proBNP on admission was significantly higher (p < 0.0005), while there was no difference in cTI serum level in the NSTE-ACS patients compared to STE-ACS patients. There was a significant positive correlation between NT-proBNP and cTI in the NSTE-ACS (r = 0.338, p = 0.008) and STE-ACS (r = 0.441, p < 0.0005) patients. There was a significant difference in NT-proBNP (p < 0.0005) and cTI (p < 0.0005) serum level between ACS patients who died within 30 days or who survived after one month. The increased NT-proBNP level is the strongest predictor of mortality in ACS patients, also NT-proBNP cut-point level of 1,490 pg/mL is a significant independent predictor of mortality.. We demonstrated the differences and the correlation in the secretion of NT-proBNP and cTI in patients with STE-ACS vs. NSTE-ACS. Our results provide evidence that NT-proBNP is a significant diagnostic marker and an important independent predictor of short-term mortality in patients with ACS.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Coronary Angiography; Female; Humans; Logistic Models; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Necrosis; Peptide Fragments; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; ROC Curve; Stents; Survival Rate; Troponin I

Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.. To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.. We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.. COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 μg/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).. Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

Topics: Aged; Aged, 80 and over; Aorta; Blood Pressure; C-Reactive Protein; Cardiomyopathies; Cardiovascular Diseases; Cohort Studies; Disease Progression; Female; Fibrinogen; Heart Rate; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulse Wave Analysis; Risk Factors; Spirometry; Sputum; Troponin T; Vascular Stiffness

Angina is chest pain induced by ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries. People that suffer from average to severe cases of angina have an increased percentage of death before the age of 55, usually around 60%. Therefore, prevention of major complications, optimizing diagnosis, prognosis and therapeutics are of primary importance. The main objective of this study was to uncover biomarkers by comparing serum protein profiles of patients suffering from stable or unstable angina and controls. We identified by non-targeted proteomic approach and confirmed by the means of independent techniques, the differential expression of several proteins indicating significantly increased vascular inflammation response, disturbance in the lipid metabolism and in atherogenic plaques stability.

Topics: Aged; Aged, 80 and over; Angina, Stable; Angina, Unstable; Biomarkers; Blood Proteins; C-Reactive Protein; Case-Control Studies; Female; Humans; Lipid Metabolism; Lipids; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Plaque, Atherosclerotic; Proteomics; Sensitivity and Specificity; Troponin

The aim of this study was to evaluate the prognostic values of serum tenascin-C in patients with heart failure and ischaemic heart disease.. Serum tenascin-C levels were assessed in 83 patients with heart failure and in 30 healthy subjects. The correlations between serum tenascin-C levels and left ventricular ejection fraction, serum B-type natriuretic peptide and procollagen III were analysed. Patients were followed up for 12 months, and the relations between the serum levels of tenascin-C and cardiac events (re-hospitalisation for worsening heart failure and mortality) were analysed.. Serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (72.24 ± 11.02 vs. 22.78 ± 2.51 μg/L, p<0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in patients with NYHA class II (88.56 ± 3.73 vs. 64.88 ± 3.15 μg/L, p<0.01). The levels of tenascin-C were negatively correlated with the left ventricular ejection fraction (r=-0.636, p<0.01), but were positively correlated with serum B-type natriuretic peptide (r=0.553, p<0.01) or procollagen III levels (r=0.665, p<0.01). An increased level of tenascin-C was an independent predictor for combined re-hospitalisation and mortality (OR 1.22, 95% CI: 0.86-2.14).. Serum tenascin-C levels were elevated in patients with heart failure. The levels of tenascin-C were associated with the severity of left ventricular dysfunction and 12-month major adverse cardiac events.

Topics: Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Collagen Type III; Confidence Intervals; Disease Progression; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Odds Ratio; Patient Readmission; Predictive Value of Tests; Proportional Hazards Models; Severity of Illness Index; Stroke Volume; Tenascin; Ventricular Dysfunction, Left

Serial changes in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and atrial natriuretic peptide (ANP) concentrations are unknown in dogs with myocardial injury. The time-course secretory responses between NT-proBNP and ANP or cardiac troponin-T (cTnT) related to myocardial infarction (MI) were investigated in this study. Six dogs were anaesthetised and the left anterior descending artery was ligated. A transient decrease in cardiac function was detected 1h after MI but returned to baseline levels within 7 days and remained so for 6 months. Echocardiographic examination revealed focal ventricular dyskinesis throughout the study. Six months following MI, the left atrium to aorta ratio increased significantly although the relative wall thickness decreased significantly from baseline. Significantly elevated plasma NT-proBNP and cTnT concentrations were detected 1 day after MI and these gradually decreased over 28 days to baseline levels without left ventricular pressure elevation. Plasma ANP was elevated significantly 6 months after MI. The NT-proBNP assay is a helpful diagnostic indicator for identifying asymptomatic acute and subacute myocardial injury whereas plasma ANP concentration mainly reflects atrial dilation.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Disease Models, Animal; Dog Diseases; Dogs; Female; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index

This study sought to determine pro-B-type natriuretic peptide (proBNP), BNP, N-terminal proBNP (NT-proBNP) and GATA-4 in the same cardiac tissue, the correlation among them, and the influence of ischemic etiology on their levels.. Protein levels were analyzed by Western blot techniques and mRNA expression was quantified by quantitative real-time polymerase chain reaction (RT-PCR) in a total of 33 human samples from ischemic (ICM), and control hearts.. Tissue protein level of proBNP is 1.5- and 12-fold higher than BNP or NT-proBNP respectively (p<0.0001), and BNP protein level was 8-fold higher than that of NT-proBNP (p<0.0001) in ICM hearts. Furthermore, proBNP mRNA expression was also increased in ICM (4-fold) compared to control hearts (p<0.05), but there was not a significant increase in GATA-4 mRNA. Then, tissue NP forms showed a high correlation among them (proBNP vs. BNP r=0.74, p<0.0001; proBNP vs. NT-proBNP r=0.43, p=0.03; and BNP vs. NT-proBNP r=0.61, p=0.001, respectively). Furthermore, GATA-4 with proBNP (r=0.536, p=0.007) and BNP (r=0.610, p=0.001) in ischemic samples. Finally, we found that proBNP, BNP, NT-proBNP and GATA-4 were increased in our ICM hearts (by 14%, p=0.004; 46%, p=0.024, 33%, p=0.002, and 49%, p=0.026, respectively) compared with controls.. This study shows higher protein level of proBNP in human hearts than of BNP and NT-proBNP, increased proBNP mRNA expression in ICM samples, and a good correlation among tissue natriuretic peptide and GATA-4. Finally, ICM shows a high tissue protein level of proBNP, BNP, NT-proBNP and GATA-4.

Topics: Adolescent; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; RNA, Messenger

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Dog Diseases; Female; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Brain natriuretic peptide (BNP) and monocyte chemotactic protein-1 (MCP-1) are biomarkers of heart failure (HF). The aim of the present study was to determine the role of oxidized low-density lipoprotein (Ox-LDL) in the induction of these biomarkers and the signaling pathways involved in vitro. Incubation of HL-1 cardiomyocytes and human myocytes with Ox-LDL induced the expression of BNP and MCP-1 genes, while native LDL had no effect. When peroxides associated with Ox-LDL were reduced to hydroxides, the ability to induce BNP and MCP-1 gene expression was abolished. Furthermore, exposure of HL-1 cells to ischemic conditions alone had no effect on BNP gene expression, while ischemia followed by reperfusion resulted in increased expression of BNP gene. Inhibitors of ERK and JNK inhibited the induction of BNP. Signaling array results suggested that the induction of both MAPK and NF-κB pathways is involved in the induction of BNP by Ox-LDL. These results suggest that Ox-LDL or peroxidized lipids formed in oxidatively stressed myocytes during ischemia-reperfusion injury may play a role in the induction of BNP and MCP-1.

Topics: Cell Line, Tumor; Chemokine CCL2; Gene Expression Regulation; Heart Failure; Humans; Lipoproteins, LDL; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidation-Reduction; Oxidative Stress; Reperfusion Injury; Signal Transduction

The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need.. We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604-1525] pg/mL versus 800 [427-1317] pg/mL; P<0.001). Cardiac troponin T (cTnT) and sensitive cardiac troponin I (s-cTnI) were also significantly higher in ischemic compared with nonischemic AHF patients (0.040 [0.010-0.306] μg/L versus 0.018 [0.010-0.060] μg/L [P<0.001]; 0.024 [0.008-0.106] μg/L versus 0.016 [0.004-0.044 ] μg/L [P=0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54-0.63], 0.61 [95% CI, 0.57-0.66], and 0.59 [95% CI,0.54-0.65], respectively). These findings were confirmed in the validation cohort.. At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Diagnosis, Differential; Emergency Service, Hospital; Female; Heart Failure; Hemodynamics; Humans; Male; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Retrospective Studies; Troponin I; Troponin T

The left ventricular (LV) scar size detected by cardiac magnetic resonance (CMR) imaging in ischemic cardiomyopathy (IC) has been correlated with mortality. However, the associations among myocardial fibrosis, ventricular geometry, and physiologic measures of myocardial performance remain to be defined. A retrospective analysis of patients with stable chronic IC (LV ejection fraction ≤50%) who underwent CMR imaging from 2004 to 2010 and had plasma B-type natriuretic peptide (BNP) measured within 14 days of the CMR study was undertaken. A total of 38 patients met the criteria (mean age 66 ± 10 years; 31 men [82%]). The duration of IC was 67 ± 69 months. The CMR characteristics included LV dilation (LV end-diastolic dimension 62 ± 8 mm) and severe systolic dysfunction (LV ejection fraction 28 ± 11%). The average quantitated myocardial fibrosis was 20 ± 12% of the LV mass. When stratified by fibrotic mass, increased myocardial scar size was associated with increased LV cavity size (p = 0.007), lower LV ejection fraction (p = 0.04), and higher BNP (p = 0.013). In comparison, when stratified by median BNP (475 pg/ml), an elevated BNP level was associated, not only with LV size, function, and degree of fibrosis, but also with increased meridional wall stress (p = 0.002) and worse New York Heart Association functional class (p = 0.006). In conclusion, in chronic IC, quantitated myocardial fibrosis is associated with CMR structural and functional LV abnormalities. Elevated BNP levels are related to high-risk structural and functional CMR abnormalities and wall stress and functional status. Myocardial fibrosis appears to be related to plasma BNP through the processes of ventricular remodeling.

Topics: Aged; Cardiomyopathies; Chronic Disease; Diagnosis, Differential; Disease Progression; Female; Fibrosis; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Severity of Illness Index; Ventricular Remodeling

During implantable cardioverter defibrillator insertion, induced ventricular fibrillation followed by test shocks (defibrillation threshold testing [DFT]) is utilized to confirm effective device function. The effect of DFT on ventricular function is uncertain. Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and hemodynamic stress. We hypothesized that DFT causes increased BNP levels.. BNP, creatine kinase, creatine kinase-MB (CK-MB), and troponin I (cTnI) were measured in 31 patients (mean age 71.4 years; 12 women) at preinsertion (T1), at 2-4 hours (T2), and at 8-12 hours (T3) after DFT. Biomarker levels were compared in patients receiving one shock (Group A) or two shocks (Group B).. After DFT all biomarkers increased above baseline levels but did not reach levels diagnostic for myocardial infarction. From T1 to T2, elevations in CK-MB and cTnI occurred in the highest proportion of patients (CK-MB 90% and cTnI 84%). From T1 to T3, elevation in BNP and cTnI were most prevalent (BNP 83% and cTnI 90%). Significant increases were measured in BNP levels from T1 to T3 (P = 0.0003), CK-MB levels from T1 to T2 (P < 0.0001), and cTnI levels from T1 to T2 (P < 0.0001) and from T1 to T3 (P < 0.0001). CK-MB levels did not increase significantly from T1 to T3 (P = 0.51).. BNP levels rise progressively after DFT accompanied by early CK-MB increases and sustained increases in cTnI. These data suggest that DFT is associated with hemodynamic stress and left ventricular dysfunction, as evidenced by increases in BNP.

Topics: Aged; Biomarkers; Creatine Kinase, MB Form; Defibrillators, Implantable; Electric Countershock; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Tachycardia, Ventricular; Troponin I; Ventricular Dysfunction, Left

In patients with ischaemic heart failure (HF), myocardial dysfunction often progresses. Elevated levels of soluble ST2 (sST2) are associated with a poor prognosis, but an association between sST2 and worsening heart failure per se has not been established. We assessed the association between sST2 and cause-specific outcome in 1449 patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA study).. Soluble ST2 was measured with a highly sensitive immunoassay in 1449 patients ≥60 years of age with left ventricular ejection fraction (LVEF) ≤40% due to ischaemic heart disease. By Cox regression analyses, we found sST2 to be associated with the primary endpoint, i.e. a composite of cadiovascular (CV) death, non-fatal myocardial infarction, or stroke, as well as all pre-defined secondary endpoints in the CORONA study, even after adjustment for baseline clinical variables. After adjustment for N-terminal pro brain natriuretic peptide and C-reactive protein, the association between sST2 and the primary endpoint was attenuated and no longer statistically significant. However, sST2 remained associated with death due to worsening HF, hospitalization due to worsening HF, and hospitalization due to any CV cause, even after full adjustment.. Soluble ST2 is associated with adverse outcomes in older patients with systolic, ischaemic HF. In particular, sST2 is independently associated with worsening HF.

Topics: Aged; Analysis of Variance; Biomarkers; Disease Progression; Female; Heart Failure; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Receptors, Cell Surface; Reference Values; Reproducibility of Results; Risk Assessment; Stroke Volume; Treatment Failure; Ventricular Function, Left

Although brain natriuretic peptide has been shown to be superior to the revised cardiac risk index for risk stratification of vascular surgical patients, it remains unknown whether it is superior to alternative dynamic risk predictors, such as other pre-operative biomarkers (C-reactive protein and troponins) or myocardial ischaemia monitoring. The aim of this prospective observational study was to determine the relative clinical utility of these risk predictors for the prediction of postoperative cardiac events in elective vascular surgical patients. Only pre-operative troponin elevation (OR 56.8, 95% CI 6.5-496.0, p < 0.001) and brain natriuretic peptide above the optimal discriminatory point (OR 6.0, 95% CI 2.7-12.9, p < 0.001) were independently associated with cardiac events. Both brain natriuretic peptide and troponin risk stratification significantly improved overall net reclassification (74.6% (95% CI 51.6%-97.5%) and 38.5% (95% CI 22.4-54.6%, respectively)); however, troponin stratification decreased the correct classification of patients with cardiac complications (-59%, p < 0.001). Pre-operative brain natriuretic peptide evaluation was the only clinically useful predictor of postoperative cardiac complications.

Topics: Biomarkers; C-Reactive Protein; Cohort Studies; Elective Surgical Procedures; Electrocardiography, Ambulatory; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Odds Ratio; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Prospective Studies; Risk Assessment; South Africa; Treatment Outcome; Troponin; Vascular Surgical Procedures

In investigating death due to mechanical asphyxiation and drowning, a cardiac attack is important for discriminating between possible causes of death and as a contributory factor in death processes; however, general pathologies involving visceral congestion are often similar. The present study compared terminal cardiac dysfunction in these fatalities using the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain. Both mechanical asphyxiation (n=27) and drowning (n=23) showed significantly lower ANP and BNP mRNA expressions in bilateral ventricular walls than sudden cardiac deaths (n=36). In addition, right atrial wall BNP mRNA expression was lower in asphyxiation; however, immunostaining did not demonstrate any difference among these fatalities. Differences among the subtypes of asphyxiation or between fresh- and saltwater drowning were insignificant. These observations suggest a difference between primary heart failure in sudden cardiac death and terminal cardiac dysfunction secondary to fatal asphyxiation or drowning.

Topics: Adult; Aged; Aged, 80 and over; Asphyxia; Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Drowning; Female; Forensic Pathology; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To assess the merit of a novel single-epitope sandwich (SES) assay specific to the stable part of BNP in patients with reversible myocardial ischemia as post-translational modifications of BNP may influence assay performance.. We measured BNP concentration by a conventional assay and the SES-BNP assay in 198 patients referred for myocardial perfusion imaging (MPI). BNP concentration was determined before and immediately after exercise stress testing, and 1.5 and 4.5h later. Patients were categorized according to MPI results.. BNP concentration was higher with both assays at all time points in patients with reversible myocardial ischemia (n=19) compared to the other patients (n=179). Measuring BNP after stress testing or calculating the changes in BNP concentration did not improve diagnostic accuracy compared to baseline measurements: SES-BNP: AUC 0.71 (95% CI 0.58-0.84) vs. conventional BNP: 0.71 (0.59-0.83), p=0.96. By linear regression analysis, reversible myocardial ischemia was significantly associated with baseline SES-BNP concentration (p=0.043), but not with measurements by the conventional assay (p=0.089). In multivariate logistic regression models, only baseline measurement with the SES-BNP assay was significantly associated with reversible myocardial ischemia: odds ratio [logarithmical transformed BNP] 2.00 (95% CI 1.16-3.47), p=0.013. The SES-BNP assay, but not the conventional BNP assay, reclassified a significant proportion of the patients towards their correct category on top of the best clinical model of our data set: NRI=0.47, p=0.04.. The SES-BNP assay was significantly associated with reversible myocardial ischemia as assessed by several statistical indices, while a conventional BNP assay was not.

Topics: Aged; Area Under Curve; Biomarkers; Coronary Artery Disease; Epitopes; Exercise Test; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Prospective Studies; ROC Curve

Brain natriuretic peptide (BNP) is a powerful predictor of mortality in patients with left ventricular dysfunction. Since malignant ventricular arrhythmias such as sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) are a major cause of death among those patients, we postulated that BNP levels can predict their long-term occurrence.. To study the association between malignant ventricular arrhythmias and BNP level over a long term follow-up.. We prospectively followed 94 patients with ischemic heart disease and left ventricular dysfunction, all implanted with an implantable cardioverter defibrillator (ICD). BNP level was measured at baseline and ICD interrogation and clinical status were recorded at 6 months intervals for a median of 3.5 years.. Patients with BNP levels in the highest quartile experienced significantly more arrhythmic events than those at the lower three quartiles (OR 2.2, 95% C.I 1.2-4.2). In a multivariate analysis only BNP level predicted arrhythmic events. Among patients implanted for primary prevention of sudden cardiac death, BNP at the lowest quartile significantly predicted low event rate.. While high BNP level is predictive of malignant ventricular arrhythmias, low levels among patients implanted for primary prevention can identify a low risk subgroup for which the ICD might be of borderline therapeutic benefit.

Topics: Aged; Defibrillators, Implantable; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Primary Prevention; Prospective Studies; Risk Factors; Severity of Illness Index; Tachycardia, Ventricular; Time Factors; Ventricular Dysfunction, Left; Ventricular Fibrillation

The present study investigated the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium to evaluate terminal cardiac function in routine forensic casework with particular regard to fatal drug intoxication (n = 18; sedative-hypnotics, n = 10; methamphetamine, n = 8), hypothermia (cold exposure, n = 13), and hyperthermia (heatstroke, n = 10), compared with that in acute ischemic heart disease (AIHD, n = 35) and congestive heart disease (CHD, n = 11) as controls (total n = 87; within 48 h postmortem). Quantitative analyses of myocardial ANP and BNP messenger RNA demonstrated that their expressions in bilateral atrial and ventricular walls were high in methamphetamine intoxication and hypothermia, comparable to those in AIHD and CHD, but were low in sedative-hypnotic intoxication and hyperthermia. In pericardial fluid, both ANP and BNP levels were increased in hypothermia, while CHD cases had an elevated BNP level, and ANP level showed a tendency to increase in hyperthermia; however, immunohistochemistry showed no evident differences in myocardial ANP and BNP among the causes of death. These findings suggest terminal high cardiac strain in methamphetamine intoxication, decreased cardiac strain in sedative-hypnotic intoxication and hyperthermia (heatstroke), and persistent congestion in hypothermia (cold exposure).

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Autopsy; Cause of Death; Female; Gene Expression; Heart Atria; Heart Failure; Heart Ventricles; Heat Stroke; Humans; Hypnotics and Sedatives; Hypothermia; Illicit Drugs; Male; Methamphetamine; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Pathology, Molecular; Pericardial Effusion; Poisoning; Postmortem Changes; Prescription Drug Misuse; RNA-Directed DNA Polymerase; RNA, Messenger

Although brain natriuretic peptide (BNP) concentration has been associated with atherosclerosis and ischemic cardiovascular diseases (CVD) in the general population, less is known about this relationship in pre-dialysis chronic kidney disease (CKD) patients.. We prospectively analyzed 227 pre-dialysis patients with CKD [median estimated glomerular filtration rate (eGFR): 28.82 (11.65-48.20) ml/min/1.73 m(2)]. At enrollment, BNP concentrations, biochemical and echocardiographic parameters were measured, and carotid artery ultrasound was performed. Patients were prospectively followed for a mean 31.8 months (range 0.5-57.0 months). Ischemic CV events and patient outcomes were recorded.. Median BNP concentration at enrollment was significantly higher in the CKD patients than in a control group [53.9 (16.2-181.0) pg/ml vs. 9.4 (7.0-15.3) pg/ml, P<0.01]. BNP concentration was positively related with the carotid intima-media thickness of the common carotid artery (CCA-IMT) and left ventricular mass index (LVMI) and was significantly higher in patients with than without carotid plaques (P<0.01). Logistic regression analysis confirmed that lgBNP concentration was independently correlated with carotid plaques. Thirty-two patients experienced ischemic cardiovascular (ICV) events during follow-up. Kaplan-Meier analysis showed that cumulative survival without new ICV events was better in patients with lower than with higher BNP concentrations (P<0.01). Cox regression analysis showed that BNP was an independent risk factor for ICV events (HR=3.167, 95%CI=1.398-7.171, P<0.01).. Similar to findings in the general population, elevated BNP level is related to atherosclerosis and an increased risk of ICV events in pre-dialytic CKD patients.

Topics: Adult; Aged; Atherosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Plaque, Atherosclerotic; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors

Elevated plasma level of asymmetric dimethylarginine (ADMA) has been reported to be associated with endothelial dysfunction and atherosclerotic risk factors, and may predict adverse cardiovascular events in patients with coronary artery disease. In this study, we aimed to assess the association between plasma ADMA and long-term outcome in patients with angiography-documented ischemic chronic heart failure (HF).. We evaluated 285 patients with ischemic chronic HF and measured their plasma ADMA levels by high performance liquid chromatography. The mean age was 70 ± 12 years and the mean left ventricular ejection fraction was 36 ± 8%. Plasma ADMA levels were positively correlated with NYHA functional class (p < 0.001) and log N-terminal pro-B type natriuretic peptide (NT-proBNP) level (p < 0.001). During the median follow-up period of 2.2 years, we observed 58 major adverse cardiovascular events (MACE) (20.4%) and 95 MACE plus cardiac decompensation (33.3%). Multivariate Cox regression analysis adjusted for age, ejection fraction, renal function and log NT-proBNP level revealed that ADMA might be a significant independent risk factor and the relative risk of MACE and MACE plus cardiac decompensation would increase by 23% and 25% respectively when plasma ADMA level increased by 1 SD of value (p = 0.05 and 0.007).. In patients with ischemic chronic HF, elevated plasma ADMA levels might be associated with higher NYHA functional classes and elevated NT-proBNP level, and appear to be an independent predictor of long-term adverse clinical outcomes.

Topics: Aged; Aged, 80 and over; Arginine; Biomarkers; Chi-Square Distribution; Chromatography, High Pressure Liquid; Coronary Angiography; Disease-Free Survival; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke Volume; Taiwan; Time Factors; Ultrasonography; Up-Regulation; Ventricular Function, Left

Topics: Coronary Artery Disease; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain

Asymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines.. L-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine-ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.57 (0.14) μmol/L vs 0.54 (0.12) μmol/L [P < .001]; SDMA 0.47 (0.27) μmol/L vs 0.37 (0.13) μmol/L [P < .001]; L-arginine 81.8 (39.1) μmol/L vs 92.6 (39.3) μmol/L [P < .01]), but no significant differences were observed between the different etiologies. The L-arginine-ADMA ratio was associated with outcome only in patients with DCM. In multivariate analysis, the mortality risk of DCM patients was significantly lower for those in the highest quartile compared with the lowest quartile during a median observation time of 3.3 years (hazard ratio 0.31, 95% CI 0.11-0.88; P = .028, adjusted for other risk factors).. DCM patients with unfavourable L-arginine-ADMA ratio are at increased risk for death.

Topics: Arginine; Biomarkers; Cardiomyopathies; Cardiomyopathy, Dilated; Chromatography, Liquid; Creatinine; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Tandem Mass Spectrometry

Several peptides, named adipokines, are produced by the adipose tissue. Among those, adiponectin (AD) is the most abundant. AD promotes peripheral insulin sensitivity, inhibits liver gluconeogenesis and displays anti-atherogenic and anti-inflammatory properties. Lower levels of AD are related to a higher risk of myocardial infarction and a worse prognosis in patients with coronary artery disease. However, despite a favorable clinical profile, AD increases in relation to worsening heart failure (HF); in this context, higher adiponectinemia is reliably related to poor prognosis. There is still little knowledge about how certain metabolic conditions, such as diabetes mellitus, modulate the relationship between AD and HF.We evaluated the level of adiponectin in patients with ischemic HF, with and without type 2 diabetes, to elucidate whether the metabolic syndrome was able to influence the relationship between AD and HF.. We demonstrated that AD rises in patients with advanced HF, but to a lesser extent in diabetics than in non-diabetics. Diabetic patients with reduced systolic performance orchestrated a slower rise of AD which began only in face of overt HF. The different behavior of AD in the presence of diabetes was not entirely explained by differences in body mass index. In addition, NT-proBNP, the second strongest predictor of AD, did not differ significantly between diabetic and non-diabetic patients. These data indicate that some other mechanisms are involved in the regulation of AD in patients with type 2 diabetes and coronary artery disease.. AD rises across chronic heart failure stages but this phenomenon is less evident in type 2 diabetic patients. In the presence of diabetes, the progressive increase of AD in relation to the severity of LV dysfunction is hampered and becomes evident only in overt HF.

Topics: Adiponectin; Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Models, Cardiovascular; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Exercise is associated with changes in circulating B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP). However, the biological relevance of this phenomenon is poorly examined. We sought to assess determinants of absolute (Δ) and relative (Δ%) exercise-induced changes in BNP and NT-proBNP.. BNP (n = 418) and NT-proBNP (n = 478) at rest and peak exercise were measured in patients undergoing symptom-limited cycle ergometer tests. Multivariate logistic regression was performed to identify predictors of high ΔBNP/ΔNT-proBNP and high ΔBNP/Δ%NT-proBNP defined as their highest quartiles (Q4).. The median (interquartile range) ΔBNP and ΔNT-proBNP was 12 (0-28) pg/ml and 7 (2-21) pg/ml respectively, and Δ%BNP and Δ%NT-proBNP was 21 (0-46) % and 7 (3-12) % respectively. Higher BNP [odds ratio (OR) 3.92 per ln unit; p < 0.001] or NT-proBNP [OR 4.88 per ln unit; p<0.001] at rest was the strongest predictor of ΔBNP in Q4 (≥ 28 pg/ml) or ΔNT-proBNP in Q4 (≥ 21 pg/ml). In contrast, higher maximal work rate expressed as the percentage of the predicted value (OR 1.015 per %; p = 0.007) was the only independent predictor of Δ%BNP in Q4 (≥ 46%), and lower resting heart rate (OR 0.97 per bpm; p = 0.001) and lower age (OR 0.95 per year; p = 0.001) were the only independent predictors of Δ%NT-proBNP in Q4 (≥ 12%).. Higher ΔBNP and ΔNT-proBNP primarily reflected higher BNP and NT-proBNP plasma levels at rest. In contrast, higher Δ%BNP and Δ%NT-proBNP were associated with several prognostically favorable features, indicating that higher Δ%BNP and Δ%NT-proBNP may be markers of health rather than disease.

Topics: Aged; Biomarkers; Cohort Studies; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

MicroRNAs (miRNAs) are endogenous small RNAs that are 21-25 nucleotides in length. Recently, plasma miRNAs have been reported to be sensitive and specific biomarkers of various tissue injuries and pathological conditions. The goal of this study was to assess plasma miRNA profiles and to identify plasma miRNAs that are differentially expressed in patients with heart failure.. A total of 33 patients with ischemic heart diseases and 17 asymptomatic controls were recruited. In 10 patients with heart failure, miRNAs were assessed at both NYHA IV and III. miRNA array analyses were found to be not appropriate for plasma miRNA profiling. The plasma concentrations of well-characterized miRNAs (miR-126, 122 and 499) were assessed by a real-time reverse transcription-polymerase chain reaction using an artificial small RNA as an internal standard. Plasma concentrations of miR-126 were negatively correlated with age and logBNP. In 10 patients with heart failure, plasma concentrations of miR-126 were up-regulated with improvement of the NYHA class from IV to III.. The plasma concentration of miR-126 was negatively correlated with age and NYHA class, and could be a useful biomarker for heart failure.

Topics: Adult; Aged; Aging; Biomarkers; Computer Systems; Endothelial Cells; Female; Heart Failure; Humans; Male; MicroRNAs; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Polymerase Chain Reaction; RNA Interference

Topics: Acute Coronary Syndrome; Biomarkers; Chest Pain; Humans; Immunoassay; Myocardial Ischemia; Natriuretic Peptide, Brain; Protein Sorting Signals; Sensitivity and Specificity

Topics: Acute Coronary Syndrome; Biomarkers; Humans; Immunoassay; Myocardial Ischemia; Natriuretic Peptide, Brain; Protein Sorting Signals; Sensitivity and Specificity

Elevated plasma N-terminal (NT)-proBNP levels and coronary calcium score (CCS) not only predicts myocardial ischaemia and coronary artery stenosis but also adverse cardiovascular events and mortality in type 2 diabetic patients with an increased urinary albumin excretion rate (UAER), whereas low levels are associated with low frequency of coronary artery disease (CAD) and good prognosis. The underlying causes of poor prognosis in patients with elevated NT-proBNP are not known; thus, we investigated the role of putative asymptomatic CAD in type 2 diabetic patients with UAER >30 mg/24 h and elevated P-NT-proBNP and/or CCS.. We identified 200 type 2 diabetic patients without known CAD and with normal creatinine levels. Patients with P-NT-proBNP >45.2 ng/L (the median P-NT-proBNP value in this cohort and in accordance with our previous findings) and/or CCS ≥ 400 were stratified as high-risk patients for CAD (n = 133) and all other patients as low-risk patients (n = 67). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109) and/or computer tomography angiography (n = 20) and/or coronary angiography (CAG; n = 86).. All patients received intensive mulitifactorial intervention. In 70 of 133 (53%) high-risk patients, significant CAD was demonstrated by MPI and/or CAG, corresponding to 35% (70/200) of the total cohort. Among high-risk patients, CCS but not P-NT-proBNP was paralleled by increased prevalence of significant CAD and in the 86 patients where CAG was performed, a CCS <100 had a negative predictive value for coronary artery stenosis of 94% (P = 0.04).. Our study revealed that >50% of asymptomatic type 2 diabetic patients with UAER >30 mg/24 h had significant CAD based on risk stratification with P-NT-proBNP and CCS. This provides some explanation to the previously reported poor prognosis in these asymptomatic patients. Optimized cardio protective treatment in these patients is warranted.

Topics: Adult; Aged; Albuminuria; Algorithms; Biomarkers; C-Reactive Protein; Calcium; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors; Young Adult

Topics: Aged; Angioplasty; Biomarkers; Coronary Angiography; Coronary Disease; Electrocardiography; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Pulmonary Edema; Stents; Treatment Failure; Troponin; Ventilator Weaning

To assess the prognostic value of the mitogenic, antiapoptotic, angiogenic and antifibrotic hepatocyte growth factor (HGF) in heart failure (HF).. Prospective cohort study.. Assessment of HGF levels at inclusion in 351 patients with advanced HF (median 75 years, interquartile range (IQR) 63-82, 66% male).. All-cause mortality, cardiovascular mortality.. During a median follow-up of 16 months, 26% of patients died. HGF tertiles were associated with an increasing risk for all-cause mortality (p < 0.001) with a hazard ratio (HR) of 3.06 (95% confidence interval (CI) 1.69 to 5.53) for the third compared with the first tertile. This association remained significant after multivariable adjustment for B-type natriuretic peptide (BNP) and other risk factors (p = 0.002). Subgroup analysis revealed that HGF was a strong predictor of the secondary end point cardiovascular mortality in ischaemic HF (p = 0.009) with an adjusted HR of 6.2 (95% CI 1.76 to 21.8) comparing the third with the first tertile but not in non-ischaemic HF (HR = 1.47, 95% CI 0.48 to 4.49, p = 0.5). Patients with high HGF but low BNP had a comparable survival rate to those with elevated BNP but low HGF (p=0.66). Of note, the dose of angiotensin converting enzyme (ACE) inhibitors inversely correlated with HGF concentrations (r = -0.25, p < 0.001).. HGF is a strong and independent predictor of mortality in advanced HF and, in particular, in ischaemic HF. These results indicate that HGF with its multiple effects on myocardial function exerts an overall deleterious effect in advanced HF. HGF may be of special interest for risk prediction and tailoring of HF treatment.

Topics: Aged; Aged, 80 and over; Austria; Biomarkers; Chi-Square Distribution; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Hepatocyte Growth Factor; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Up-Regulation

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Glycopeptides; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume

Fractalkine (FKN) is a newly identified membrane-bound chemokine; its role in myocardial ischaemia and heart failure is largely unknown. We attempted to investigate the role of FKN in myocardial ischaemia and ischaemia or pressure overload-induced ventricular remodelling and heart failure.. FKN-induced changes of heart failure-related genes in cultured rat cardiac cells and the effect of FKN on cultured cardiomyocyte injury during anoxia/reoxygenation (A/R) were examined. The direct influence of FKN neutralization on heart failure and the potential mechanism was also investigated. In mice with failing hearts, myocardial FKN expression was correlated with the lung weight/body weight ratio, left ventricular fractional shortening, and brain natriuretic peptide expression. In cultured rat cells, exposure to FKN increased natriuretic peptide A expression in cardiomyocytes, matrix metalloproteinase-9 expression in fibroblasts, and intercellular adhesion molecule-1 expression in microvascular endothelial cells. FKN also promoted cardiomyocyte damage during A/R and neutralizing FKN antibody treatment improved heart failure induced by myocardial infarction or pressure overload. Neutralizing FKN or its receptor inhibited the activation of mitogen-activated protein kinases (MAPKs) in hypoxic cardiomyocytes or ischaemic myocardium.. FKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.

Topics: Animals; Animals, Newborn; Antibodies, Neutralizing; Atrial Natriuretic Factor; Cells, Cultured; Chemokine CX3CL1; Disease Models, Animal; Endothelial Cells; Enzyme Activation; Fibroblasts; Heart Failure; Intercellular Adhesion Molecule-1; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats; Recombinant Proteins; Severity of Illness Index; Time Factors; Ventricular Remodeling

We studied relation between cystatin C level and risk of unfavorable outcome (unstable angina, fatal and nonfatal myocardial infarction [MI], fatal and nonfatal stroke, and death) in patients stabilized after exacerbation of ischemic heart disease. Patients (n=272) were included on day 10 after onset of acute coronary syndrome. No relationship between studied outcomes and cystatin was found in a group as a whole. In patients with normal of slightly reduced renal function (glomerular filtration rate more or equal 60 ml/min/1.73 m2) unfavorable outcomes were independently associated with history of myocardial infarction and stroke, elevated levels of brain natriuretic peptide and cystatin. In subjects with moderately or severely reduced renal function elevation of cystatin level lost its significance. Risk of development of unfavorable outcomes among these subjects was independently related to history of MI and GFR <60 ml/min/1.73 m2 (OR 2.130, 95% CI 1.010-4,489; =0,047). Our data confirm possibility of use of cystatin C level measured early after ACS in patients with normal or slightly lowered renal function as a parameter characterizing risk of cardiovascular complications and death.

Topics: Aged; Biomarkers; Comorbidity; Cystatin C; Disease Progression; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency, Chronic; Reproducibility of Results; Risk Factors; Time Factors

Cardiomyocyte stretching has been reported to be a major trigger for brain natriuretic peptide (BNP) release; however, an increase in circulating BNP is observed in patients with acute myocardial ischemia in the absence of increased left ventricular wall stress or cardiomyocyte stretching. In the present study, to investigate the direct and independent effects of acute myocardial ischemia on BNP expression and its mechanism, we established an in vitro glucose-free ischemia and hypoxia injured model of cultured rat cardiomyotes and proved hypoxia upregulated expressions of interleukin-6(il-6) and BNP. Further treatment with il-6 elicited dose- and time-dependent increases in BNP mRNA and protein expression as well as an upregulation in transforming growth factor-β1 (TGF-β1)/Smad2 expression, which was partially suppressed by a neutralizing antibody. In conclusion, our study showed that acute myocardial ischemia can directly upregulate BNP expression at the translational and transcriptional levels through the action of il-6, and this process is associated with the upregulation of TGF-β1/Smad2 signal path.

Topics: Animals; Antibodies, Neutralizing; Cell Survival; Cytokines; Gene Expression Regulation; Hypoxia; Inflammation; Inflammation Mediators; Interleukin-6; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Smad2 Protein; Transcription, Genetic; Transforming Growth Factor beta1

The inactive N-terminal fragment of B-type natriuretic peptide is a strong predictor of mortality among patients with acute and chronic heart failure secondary to ischaemic heart disease. Its prognostic utility in patients with non-ischaemic heart disease is not well established. We therefore assessed the relationship of N-terminal proBNP levels and long-term mortality in patients with non-ischaemic cardiomyopathy.. N-terminal proBNP was measured in serum samples of 156 patients who presented to a single academic centre with worsening heart failure secondary to non-ischaemic cardiomyopathy. The rate of death from all causes was determined after a mean follow-up of 8.9 years.. Multivariate analyses, using Cox proportional hazards models, established NT-proBNP and left ventricular diastolic diameter as predictors for cardiac mortality with estimated hazard ratios of 2.76 (95% confidence interval: 1.53, 4.98) and 1.06 (95% confidence interval: 1.02, 1.10), respectively.. This to date longest-term analysis of N-terminal proBNP and mortality in patients with proven non-ischaemic cardiomyopathy confirms this cardiac-specific biomarker as powerful, independent risk predictor. It is a superior prognostic determinant to New York Heart Association functional class and left ventricular ejection fraction.

Topics: Biomarkers; Cardiomyopathies; Comorbidity; Female; Germany; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis; Survival Rate; Ventricular Dysfunction, Left

We conducted a cross-sectional study to investigate which factors have a significant impact on wheezing and QOL in the elderly of a Japanese local community.. In 2008, 527 participants (250 participants aged 45 to 64 years and 277 participants aged 65 to 88 years) responded to the questionnaire regarding wheezing and disease history. QOL was evaluated by the Short Form-8. The participants underwent airway reversibility testing. The plasma levels of IgE were measured. The plasma levels of N-terminal-pro-B-type natriuretic peptide were measured in twenty-one participants with a history of ischemic heart disease and in thirty-five age-matched participants without that history.. Wheezing was reported by 50 (9.5%) participants and was associated with a lower score of QOL. In multivariate analysis, wheezing was associated with sex (OR 3.12, CI 1.10-9.67) and a history of bronchial asthma (OR 22.3, CI 6.50-84.0) among participants aged 45 to 64 years. Among participants aged 65 and over, wheezing was associated with a history of bronchial asthma (OR 4.86, CI 1.39-15.1) and ischemic heart disease (OR 5.12, CI 1.61-15.0). Participants with both a history of ischemic heart disease and wheezing showed higher levels of N-terminal-pro-B-type natriuretic peptide. Airway reversibility was only associated with a history of ischemic heart disease (OR 4.65, CI 1.26-17.6).. It is suggested that bronchial asthma and heart disease are both significant causes of wheezing and affect the QOL in the elderly of a Japanese local community.

Topics: Aged; Aged, 80 and over; Asian People; Asthma; Cross-Sectional Studies; Female; Humans; Immunoglobulin E; Japan; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Respiratory Sounds; Surveys and Questionnaires

It is unknown whether the increased B-type natriuretic peptide (BNP) values found in ischemic heart disease are triggered directly by ischemia or whether they are caused indirectly by ischemia through diastolic contractures or regional wall motion abnormalities. Therefore, we investigated the BNP expression in isolated human muscle strips under conditions of ischemia with and without mechanical stress.. Muscle strips (n=90) were isolated from human right atria (n=46). Contractures were induced by oxygen and glucose withdrawal. In 18 muscle strips contractures were prevented by means of butanedione monoxime (BDM). Sarcomere lengths were measured by electron microscopy (n=12). The gene expression and protein amount of BNP were determined and compared to control muscle strips contracting under physiological conditions.. Hypoxia significantly decreased systolic force and induced diastolic contractures. This mechanical stress could be prevented in the group treated with BDM as evidenced by electron microscopy. Ischemia significantly increased BNP expression in both groups as evidenced by Northern blot analysis and immunohistochemistry. This increase was independent from mechanical stress.. Our results indicate that ischemia is a potent mechanism for the expression of BNP. The increase in BNP expression under ischemic conditions is independent from concomitant mechanical alterations.

Topics: Aged; Atrial Appendage; Diastole; Female; Heart Failure; Humans; Hypoxia; Male; Microscopy, Electron; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Stress, Mechanical; Systole

To assess endothelial progenitor cells (EPC) counts, a novel prognostic marker, in relation to classical adverse outcome predictors - N-terminal pro-B-type natriuretic peptide (NT-proBNP), impaired left ventricular (LV) relaxation and exercise-induced ischemia - in stable coronary artery disease (CAD) with preserved LV systolic function.. We studied 30 non-diabetic men with one-vessel CAD, LV ejection fraction 60% and normal LV diastolic function (n=16) or impaired LV relaxation (by ultrasound including tissue Doppler) (n=14), and 14 non-CAD controls matched for risk profile and medication. CD34+/kinase-insert domain receptor (KDR)+ cells (CD34+/KDR+ cells), a leukocytes subpopulation enriched for EPC, were enumerated by flow cytometry.. CAD patients with abnormal LV relaxation exhibited significantly elevated NT-proBNP and decreased CD34+/KDR+ cells vs. CAD with regular diastolic function and non-CAD controls. An inverse NT-proBNP-CD34+/KDR+ cells relationship was precipitated by the clustering of high resting NT-proBNP and low CD34+/KDR+ cells in the subjects with a lower Duke treadmill score.. Propensity to symptomatic exertional ischemia may underlie the coincidence of moderately elevated NT-proBNP and EPC deficiency in stable angina. Additionally, chronic subclinical ischemia can also be involved in these associations. These might result from BNP overexpression in the ischemic myocardium and a hypothetical exhaustion of the bone marrow capacity to mobilize EPC at multiple ischemic episodes, thus contributing to NT-proBNP prognostic effect irrespective of hemodynamic factors.

Topics: Adult Stem Cells; Aged; Angina Pectoris; Antigens, CD34; Biomarkers; Case-Control Studies; Cell Count; Endothelial Cells; Exercise; Exercise Test; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Vascular Endothelial Growth Factor Receptor-2; Ventricular Function, Left

In the early identification of cardiovascular risk, it is essential to establish a biological marker for cardiac complications that is comparable to albuminuria for nephropathy. We tested the hypothesis that N-terminal pro-brain natriuretic peptide (NT-proBNP) might be a marker for silent myocardial ischaemia in diabetes.. In forty consecutively recruited subjects without evident coronary artery disease, serum NT-proBNP was measured together with multi-slice computed tomography. With patients suspected of having significant coronary artery stenosis by multi-slice computed tomography, coronary angiography was performed. Silent myocardial ischaemia was defined as the presence of significant coronary artery stenosis with more than 50% luminal narrowing by angiography.. Thirteen patients (32.5%) had silent myocardial ischaemia. NT-proBNP levels were significantly higher in these patients (181.1 ± 43.8 versus 55.2 ± 9.7 pg/mL, p < 0.005) but HbA(1c), lipid profiles, and creatinine were similar in the two groups. Moreover, log NT-proBNP was identified as an independent predictor of silent myocardial ischaemia (R(2) = 0.502, p < 0.05) after adjustment for HbA(1c), creatinine, albuminuria, hypertension, hyperlipidaemia, or smoking. After stratifying patients by NT-proBNP, the upper tertile compared to the lowest tertile was significantly associated with silent myocardial ischaemia (odds ratio: 26.7, p < 0.05). Receiver operation characteristics analysis with a cut-off value of 52 pg/mL showed 92% sensitivity and 75% specificity for predicting silent myocardial ischaemia (positive predictive value 64.7%, negative predictive value 94.3%).. The outstandingly high negative predictive value of NT-proBNP enables us to focus on diabetic patients with occult coronary disease, independently of microalbuminuria.

Topics: Aged; Albuminuria; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

Topics: Aged; Angina, Unstable; Biomarkers; Dyspnea; Electrocardiography; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Cardiac fibrosis is common and associated with poor prognosis in patients with heart failure. We investigated the effect of cardiac fibrosis on the left ventricular (LV) diastolic function, functional capacity, LV remodeling, and biochemical parameters in patients with nonischemic dilated cardiomyopathy (NIDC). In addition, we investigated the biochemical and echocardiographic predictors of cardiac fibrosis in this group.. Forty patients with NIDC were enrolled. Cardiac fibrosis was evaluated according to the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Nineteen patients had cardiac fibrosis (Group I) and 21 patients did not have cardiac fibrosis (Group II). LV systolic and diastolic parameters were assessed with conventional and tissue Doppler echocardiography. N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels of each patient were recorded. Patients with cardiac fibrosis had impaired diastolic function, higher functional class and NT-pro BNP levels, and significant LV remodeling than the patients without cardiac fibrosis. A correlation analysis revealed that the cardiac fibrosis severity was associated with functional class, cardiac chamber sizes, NT-pro BNP levels, diastolic parameters such as E/Se. A linear regression analysis demonstrated that NT-pro BNP and E/Se were the independent predictors of cardiac fibrosis.. Cardiac fibrosis correlates with impaired LV diastolic function and functional capacity, elevated NT-proBNP levels, and adverse cardiac remodeling in patients with NIDC. Therefore, the assessment of cardiac fibrosis can be useful in the management of these patients.

Topics: Cardiomyopathy, Dilated; Echocardiography; Endomyocardial Fibrosis; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left; Ventricular Remodeling

There is accumulating evidence that transient exercise-induced ischemia triggers the release of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The aim of this study was to either confirm or refute a previous investigation suggesting that myocardial ischemia can reliably be detected by exercise-induced changes in BNP or NT-proBNP levels in selected patients.. A total of 139 consecutive patients with normal left ventricular function and normal resting BNP and NT-proBNP levels referred for rest/stress myocardial perfusion single-photon emission computed tomography (SPECT) were analyzed. Levels of BNP and NT-proBNP were determined before and immediately after symptom-limited bicycle ergometry.. Inducible myocardial ischemia on perfusion images was detected in 46 patients (33%). Median exercise-induced increases in BNP (DeltaBNP) and NT-proBNP (DeltaNT-proBNP) were similar in patients with and without inducible ischemia (DeltaBNP 12.7 pg/ml vs. 9.4 pg/ml, p=0.109; DeltaNT-proBNP 7 pg/ml vs. 6 pg/ml, p=0.309). The area under the receiver operating characteristic curve for the ability to detect myocardial ischemia was 0.583 (95% CI, 0.479-0.688) for DeltaBNP, and 0.553 (95% CI, 0.450-0.656) for DeltaNT-proBNP.. Exercise-induced changes in BNP and NT-proBNP do not reliably detect myocardial ischemia in selected patients.

Topics: Aged; Biomarkers; Cohort Studies; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Tomography, Emission-Computed, Single-Photon

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

Topics: Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain

This study investigated plasma brain natriuretic peptide (BNP) levels in normotensive and hypertensive patients with suspected coronary artery disease during radionuclide pharmacological stress testing. Twenty-seven normotensive patients (15 males, aged 63.0+/-4.5 years and 12 females, aged 63.0+/-4.1 years) and 38 essential hypertensive patients (25 males, aged 63.3+/-3.3 years and 13 females, aged 64.6+/-2.6 years) with chest pain and exercise stress testing inconclusive for coronary artery disease underwent myocardial perfusion single-photon emission computed tomography (SPECT) using adenosine infusion. SPECT identified patients without (16 normotensive and 22 hypertensive) and patients with (11 normotensive and 16 hypertensive) transient perfusion defects. Basal BNP levels in normotensive patients without transient myocardial ischemia (3.1+/-1.2 fmol/ml) were significantly (P<0.01) lower than those observed in normotensive patients with transient ischemia (8.2+/-1.2 fmol/ml), whereas BNP levels in hypertensive patients without transient ischemia (8.2+/-1.0 fmol/ml) did not significantly differ from those in hypertensive patients with transient ischemia (8.1+/-2.0 fmol/ml). No significant difference was found in BNP levels between males or females either in normotensive or hypertensive patients without or with ischemia. Adenosine infusion did not significantly change BNP levels in any subject group without or with myocardial perfusion defects. Our findings show that increases in BNP allow early detection of myocardial ischemia in normotensive patients, but not in hypertensive patients with suspected coronary artery disease. Adenosine-induced myocardial ischemia does not affect BNP production already activated by coronary artery disease in normotensive patients and by hemodynamic changes in hypertensive patients.

Topics: Adenosine; Aged; Coronary Artery Disease; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Tomography, Emission-Computed, Single-Photon

To evaluate the prognostic role of novel biomarkers for the risk stratification of patients admitted with ischemic-type chest pain, a prospective study of 664 patients presenting to 2 coronary care units with ischemic-type chest pain was conducted over 3 years beginning in 2003. Patients were assessed on admission for clinical characteristics, electrocardiographic findings, renal function, cardiac troponin T (cTnT), markers of myocyte injury (heart fatty acid-binding protein [H-FABP] and glycogen phosphorylase BB), neurohormonal activation (N-terminal-pro-brain natriuretic peptide [NT-pro-BNP]), hemostatic activity (fibrinogen and D-dimer), and vascular inflammation (high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase-9, pregnancy-associated plasma protein-A, and soluble CD40 ligand). A >or=12-hour cTnT sample was also obtained. Myocardial infarction (MI) was defined as peak cTnT >or=0.03 microg/L. Patients were followed for 1 year from the time of admission. The primary end point was death or MI. Elevated fibrinogen, D-dimer, H-FABP, NT-pro-BNP, and peak cTnT were predictive of death or MI within 1 year (unadjusted odds ratios 2.5, 3.1, 5.4, 5.4, and 6.9, respectively). On multivariate analysis, H-FABP and NT-pro-BNP were selected, in addition to age, peak cTnT, and left ventricular hypertrophy on initial electrocardiography, as significant independent predictors of death or MI within 1 year. Patients without elevations of H-FABP, NT-pro-BNP, or peak cTnT formed a very low risk group in terms of death or MI within 1 year. A very high risk group had elevations of all 3 biomarkers. In conclusion, the measurement of H-FABP and NT-pro-BNP at the time of hospital admission for patients with ischemic-type chest pain adds useful prognostic information to that provided by the measurement of baseline and 12-hour cTnT.

Topics: Acute Disease; Aged; Biomarkers; Chest Pain; Electrocardiography; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Risk Factors

The Duke Activity Status Index (DASI) provides an accurate estimate of functional capacity in patients with chronic heart failure (HF). The aim of this study was to evaluate the prognostic value of the DASI against well-established prognostic factors in 130 consecutive patients hospitalized for worsening HF symptoms (mean age 64 +/- 12 years, mean left ventricular ejection fraction 26 +/- 7%), followed for 9 months for major cardiovascular events, defined as death or hospitalization for HF decompensation. During follow-up, 77 of 130 patients (59%) experienced major cardiovascular events after a median time of 60 days (range 5 to 220). Patients with eventful courses were in higher New York Heart Association functional classes (p = 0.001) and had shorter 6-minute walking distances (p = 0.041), lower ejection fractions (p <0.001), higher plasma B-type natriuretic peptide (BNP) levels at hospital admission and discharge (both p <0.001), and lower DASI scores (16 +/- 12 vs 25 +/- 17, p = 0.003). In multivariate Cox regression analysis including all these variables, only BNP level at discharge (p = 0.006) and DASI score (p = 0.047) were independently associated with event-free survival. A BNP cutoff of 697 pg/ml predicted future events with 59% sensitivity and 86% specificity, while a DASI score cutoff of 8 had 76% sensitivity and 25% specificity. The combination of the 2 cutoffs predicted events with 33% sensitivity and 95% specificity. Event-free survival was significantly lower in patients with the 2 markers positive (BNP >697 pg/ml and DASI score <8) compared with those with with 2 markers negative (63 +/- 27 vs 183 +/- 15 days, log-rank p <0.0001). In conclusion, functional status assessment by the DASI bears prognostic value, and its combination with plasma BNP may provide quite specific risk stratification in patients with chronic HF.

Topics: Activities of Daily Living; Cardiomyopathy, Dilated; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Stroke Volume; Ventricular Function, Left

Multiple factors influence brain natriuretic peptide (BNP) release in patients with heart failure. We hypothesized that extensive myocardial scarring could result in an attenuated BNP response. A total of 115 patients with New York Heart Association class III chronic heart failure and ischemic cardiomyopathy were evaluated for ischemia, hibernation, and myocardial scarring by dipyridamole-rubidium-positron emission tomographic scanning with fluorine-18, 2-fluoro-2-deoxyyglucose. Plasma BNP levels were determined within 2 weeks of the study. Left ventricular dimension and function were evaluated by echocardiography. Patients were categorized as having <33% myocardial scar (n=67) or>or=33% myocardial scar (n=48). BNP measurements were correlated with amount of myocardial scarring. Compared with patients with less scar, those with >or=33% scar had lower BNP levels (mean 317+/-364 vs 635+/-852 pg/ml, median 212 vs 357, p=0.016). Using multiple regression analysis, presence of scarring was associated with decreased BNP response (p=0.022). Further, patients with <33% scar in whom a higher BNP level was noted had more ischemia (51% vs 27%, p=0.01) and greater myocardial hibernation (22+/-14% vs 12+/-7%, p=0.02) compared with patients with >or=33% scar. In conclusion, in patients with chronic heart failure, a decreased BNP response indicated extensive myocardial scarring.

Topics: Aged; Chi-Square Distribution; Cicatrix; Echocardiography; Female; Fluorodeoxyglucose F18; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Radiopharmaceuticals; Regression Analysis; Retrospective Studies; Tomography, Emission-Computed; Ventricular Dysfunction, Left

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.

Topics: Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Tomography, Emission-Computed, Single-Photon

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiac Catheterization; Exercise; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Relaxin

B-type natriuretic peptide (BNP) is an important clinical parameter of severity in congestive heart failure (CHF). Recent findings suggest a close relation between lipid and glucose metabolism and the natriuretic peptide axis, even if conflicting data exist on the relationship between natriuretic peptide levels and insulin resistance (IR). Thus, we sought to investigate potential relations between BNP level and IR in 134 patients with severe ischemic myocardial dysfunction [mean+/-SD: age =64.8+/-9.6 yr, male/female =104/30; body mass index (BMI) =25.5+/-4.05 kg/m2, 26.1% diabetics; ejection fraction (EF) = 30.2+/-7.7%]. In univariate analysis, an inverse relationship between BNP levels and EF% was observed (R=-0.43, p=0.0006). Moreover, we found an inverse association between BNP levels and BMI (R=-0.27, p=0.036), and also between BNP and homeostasis model assessment of insulin resistance (HOMA-IR) (R=-0.27, p=0.039). In multivariate analysis, EF% and HOMA-IR were significantly and independently associated with logarithmically transformed BNP levels (beta=-0.40, p=0.019 and beta=-0.26, p=0.042, respectively; R2=0.36). In conclusion, in patients with severe ischemic myocardial dysfunction EF and IR are independently associated with BNP levels explaining about 1/3 of the variability of this parameter. Multiple potential mechanisms may underlie this association, but it seems now clinically important to take into account also metabolic features when interpreting plasma natriuretic peptide concentrations obtained for diagnostic or prognostic purposes.

Topics: Aged; Analysis of Variance; Blood Glucose; Body Mass Index; Constriction, Pathologic; Coronary Angiography; Diabetes Mellitus; Female; Humans; Immunoassay; Insulin; Insulin Resistance; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Selection; Ultrasonography

B-type natriuretic peptide (BNP) is an established first-line therapy for acute decompensated heart failure (HF), but its efficacy in preventing left ventricular (LV) remodeling after myocardial injury is unknown. The goal of this study was to evaluate the effects of BNP therapy on remodeling after ischemic injury in an awake canine model. Dogs were chronically instrumented for hemodynamics. Ischemia was created by daily coronary embolization (Embo; 3.1 x 10(4) beads/day) for 3 wk; 60 min after the first embolization, BNP (100 ng x kg(-1) x min(-1); n = 6) or saline (control; n = 6) was continuously infused via a left atrial catheter for 3 wk. Hemodynamics and echocardiography were performed in an awake state at baseline, 3 wk after Embo + BNP infusion, and 4 wk after stopping Embo + BNP infusion. End-systolic elastance (E(es)) and LV change in pressure over time (dP/dt) were preserved throughout Embo + BNP therapy versus control therapy (E(es): 3.76 +/- 1.01 vs. 1.41 +/- 0.16 mmHg/ml; LV dP/dt: 2,417 +/- 96 vs. 2,068 +/- 95 mmHg/s; both P < 0.05 vs. control). LV end-diastolic dimension was significantly smaller in BNP-treated dogs compared with control dogs (4.29 +/- 0.10 vs. 4.77 +/- 0.17 cm), and ejection fraction was maintained in treated dogs vs. control dogs (53 +/- 1% vs. 46 +/- 2%) (both P < 0.05 vs. control). Cyclooxygenase (COX)-2 expression in terminal LV tissue was significantly reduced after BNP therapy. Treatment with continuous infusion of BNP preserved LV geometry, improved systolic function, and prevented the progression of systolic HF after persistent ischemic injury.

Topics: Animals; Cyclic GMP; Cyclooxygenase 2; Disease Models, Animal; Dogs; Echocardiography; Embolism; Factor VIII; Female; Fibrosis; Heart Failure; Infusion Pumps; Macrophages; Male; Myocardial Ischemia; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Pressure; Ventricular Remodeling

To determine plasmic concentrations of NT-proBNP, TNFalpha and IL-6 in patients with coronary heart disease (CHD) complicated with chronic cardiac failure (CCF); to compare these parameters with hemodynamic and functional ones.. A total of 157 CHD patients (84.1% males, mean age 54.3 +/- 6.8 years) were divided into 3 groups matched by sex and age according to the presence of CCF and left ventricular (LV) or systolic dysfunction.. CCF patients with LV dysfunction or intact LV function had much higher plasmic concentrations of neurohumoral mediators than CHD patients without CCF. A plasmic NT-proBNP level over 1000 fmol/ml was associated with a 5.5-fold increase in the relative risk of LV diastolic dysfunction for CCF patients (rR 5.6; 95% CI 1.4-30.0; p = 0.0065) while an IL-6 level over 6.1 pg/ml was associated with a 9-fold increase in this risk (rR 8.9; 95% CI 2.3-35.4; p = 0.00001). Plasmic NT-proBNP and IL-6 levels went up in correlation with a CCF functional class. A plasmic level of TNFalpha correlated with anginal functional class.. Changes in plasmic levels of the above neuromediators are associated with changes in some LV function and functional parameters of CCF patients.

Topics: Biomarkers; Chronic Disease; Echocardiography; Female; Heart Failure; Hemodynamics; Humans; Interleukin-6; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

B-type natriuretic peptide (BNP) is a peptide hormone of myocardial origin with significant cardioprotective properties. Patients with myocardial ischemia present with high levels of BNP in plasma and elevated expression in the myocardium. However, the molecular mechanisms of BNP induction in the ischemic myocardium are not well understood. The aim of the investigation was to assess whether myocardial hypoxia induces the production of BNP in human ventricular myocytes. To test the hypothesis that reduced oxygen tension can directly stimulate BNP gene expression and release in the absence of hemodynamic or neurohormonal stimuli, we used an in vitro model system of cultured human ventricular myocytes (AC16 cells). Cells were cultured under normoxic (21% O(2)) or hypoxic (5% O(2)) conditions for up to 48 h. The accumulation of BNP, atrial natriuretic peptide (ANP), and vascular endothelial growth factor (VEGF) was then measured. Hypoxia stimulated the protein release of BNP and VEGF but not ANP. In concordance, the increased mRNA levels of BNP and VEGF but not ANP were found on culturing AC16 cells under hypoxic conditions. The analysis of the transcriptional activity of the hypoxia-inducible factor 1 (HIF-1) in nuclear extracts showed that HIF-1 activity was induced under hypoxic conditions. Finally, the treatment of AC16 cells with the HIF-1 inhibitor rotenone in hypoxia inhibited BNP and VEGF release. In conclusion, these data indicate that hypoxia induces the synthesis and secretion of BNP in human ventricular myocytes, likely through HIF-1-enhanced transcriptional activity.

Topics: Atrial Natriuretic Factor; Cell Line; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxygen; RNA, Messenger; Vascular Endothelial Growth Factor A

Although B-type natriuretic peptide (BNP) has emerged as an important predictor for cardiac events, its effect on scintigraphic parameters is unknown.. The Q-PROVE study is a multicenter study to evaluate the prognostic value of ECG-gated SPECT in 175 Japanese elderly patients. In addition, BNP was assessed in 102 patients. Outcome assessment included cardiac events and noncardiac deaths. Twelve elderly patients (12%) had increased BNP >130 pg/ml. The summed stress score (SSS) was greater in patients with increased BNP than in those with normal BNP. Kaplan-Meier survival estimation indicated event-free survival rates at 3 years of 83%, 78%, 88%, 80%, respectively, in patients with BNP >130 pg/ml, SSS >or=7, summed difference score (SDS) >or=2, and dilated end-diastolic volume (EDV), but 98%, 98%, 100%, 94% in those with BNP

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Coronary Artery Disease; Disease-Free Survival; Electrocardiography; Humans; Japan; Kaplan-Meier Estimate; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Tomography, Emission-Computed, Single-Photon; Up-Regulation

B-type natriuretic peptide (BNP) is predictive of inducible ischemia in patients with coronary heart disease (CHD). Whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a comparable strength of association with ischemia is uncertain.. Resting NT-proBNP levels are associated with inducible ischemia in patients with stable CHD.. We performed a cross-sectional study of 901 outpatients with stable CHD. NT-proBNP was measured in all patients prior to exercise treadmill testing and stress echocardiography. In addition, plasma BNP was measured in a subset of 355 participants. Logistic regression was used to examine the association of NT-proBNP and BNP quartiles with inducible ischemia.. Inducible ischemia was found in 216 (24%) patients. The proportion with inducible ischemia ranged from 42% (95/225) in the highest quartile of NT-proBNP levels (>410 pg/ml) to 9% (21/226) in the lowest quartile (0-72 pg/ml). The highest quartile had a 7-fold greater odds of inducible ischemia than the lowest quartile (odds ratio [OR]: 7.1, 95% confidence interval [CI]: 4.2-12; P < 0.0001). This association remained robust after adjustment for traditional cardiovascular risk factors, left ventricular ejection fraction, and diastolic dysfunction (OR: 3.6, 95% CI: 1.4-9.1; P = 0.009). In the subgroup with measurements of both NT-proBNP and BNP, both natriuretic peptides were predictive of ischemia. The multivariable-adjusted c-statistics for inducible ischemia were 0.71 for NT-proBNP and 0.62 for BNP (entered as continuous variables).. Resting NT-proBNP levels are independently associated with inducible ischemia in outpatients with stable CHD. Baseline elevations of natriuretic peptide may indicate subclinical inducible ischemia in high risk patients with CHD.

Topics: Aged; Aged, 80 and over; Biomarkers; Coronary Disease; Cross-Sectional Studies; Echocardiography, Stress; Exercise Test; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Odds Ratio; Outpatients; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; United States; Up-Regulation

The aim of this study was to determine whether there are differences in echocardiographic findings or in the level of a biochemical marker (i.e. N-terminal probrain natriuretic peptide [NT-proBNP]) between controls and type-2 diabetic patients with or without ischemic heart disease. Echocardiography was used to assess left ventricular function and morphology. In addition, the plasma NT-proBNP concentration was measured. The prevalence of diastolic dysfunction was greater in diabetics without ischemic heart disease than in controls (88% vs. 74%, respectively; P< .001) and the NT-proBNP concentration was higher (350.6+/-197.8 vs. 281.7+/-190.4 fmol/mL; P< .001). Diabetics with ischemic heart disease had a higher NT-proBNP concentration than those without (720.4+/-278.1 vs. 350.6+/-197.8 fmol/mL, respectively; P< .001). An NT-proBNP concentration >490 fmol/mL had a sensitivity of 84% and a specificity of 75% for detecting ischemic heart disease in diabetics.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography

We included 63 patients with chronic heart failure of ischemic origin (32 with left ventricular ejection fraction less than 40%) into prospective study with average duration of follow-up 27+/-10 months. Relative risk of lethal outcome was significantly increased in patients with initial endsystolic left ventricular dimension >6.0 m, enddiastolic left ventricular dimension >7.0 m, left atrial dimension >5.0 cm, left ventricular ejection fraction <35%, hemoglobin level <120 g/L, with disturbances of rhythm and conduction, and elevation of plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) >1000 mol/ml and interleukin-6 >20 g/ml. Relative risk of combined endpoint significantly increased at same values of echocardiographical parameters, plasma levels of NT-proBNP >500 mol/ml and interleukin-6 >10 g/ml.

Topics: Biomarkers; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Interleukin-6; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Siberia; Survival Rate; Time Factors; Tumor Necrosis Factor-alpha

This study aims to determine whether a relation exists between ischemia/reperfusion and myocardial B-type natriuretic peptide (BNP) mRNA expression independent of variations in intracavitary diastolic volume and consequently, of cardiomyocyte stretching. Twenty-three rats were subjected to the following conditions: control (C), 15 min of ischemia (I15), or ischemia plus 15 (R15), 30 (R30), or 45 (R45) min of reperfusion in the in situ hearts. Isolated hearts of sixteen additional rats (sham, n = 8; occlusion, n = 8) were perfused for studies in the absence of ventricular distension. All hearts were divided in two segments (ischemic and nonischemic). Ventricular distension was avoided by excluding the atria and mitral valves. In both experiments, BNP mRNA was quantified by real-time polymerase chain reaction in both nonischemic and ischemic regions. In the in situ hearts, myocardial BNP mRNA values at R15 (4.24 +/- 0.75) in the ischemic region were higher than in other groups (C: 1.43 +/- 0.81, P = 0.044; I15: 3.05 +/- 0.62, P = 0.048; R30: 0.76 +/- 0.84, P = 0.001; R45: 1.47 +/- 0.60, P = 0.046, [analysis of variance]). In isolated hearts without ventricular distension, myocardial BNP mRNA (arbitrary units) content at R15 in ischemic regions (4.54 +/- 0.26) was greater than in nonischemic regions in both occlusion (3.51 +/- 0.20, P < 0.001) and sham (3.38 +/- 0.25, P = 0.0001 and 3.47 +/- 0.19, P = 0.0001) groups. The present data show that ischemia/reperfusion is responsible for increased BNP mRNA myocardial content independent of changes of ventricular cavity diastolic volume.

Topics: Animals; Disease Models, Animal; Female; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Up-Regulation

To investigate the changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial ischemic injury.. Thirty-five neonates with HIE (17 cases with concurrent myocardial injury and 18 cases without) were enrolled. Twenty healthy neonates were used as the control group. Plasma NT-proBNP levels were measured using enzyme immunoassay.. The mean plasma NT-proBNP levels in patients with myocardial injury (338.8 + or - 76.2 fmol/mL) were significantly higher than those in patients with non-myocardial injury (137.5 + or - 45.1 fmol/mL) and in the control group (113.7 + or - 53.6 fmol/mL) (p<0.01). The NT-proBNP levels in mild, moderate and severe HIE neonates were 141.3 + or - 41.6, 271.8 + or - 118.1 and 347.2 + or - 85.1 fmol/mL, respectively. Compared with the control group, the NT-proBNP levels in the moderate and the severe HIE groups significantly increased (p<0.01). There were significant differences in the NT-proBNP level among the mild, moderate and severe HIE groups (p<0.05). In patients with myocardial injury, the NT-proBNP levels significantly decreased in the convalescent phase compared with those in the acute phase (225.0 + or - 80.0 fmol/mL vs 338.8 + or - 76.2 fmol/mL (p<0.01).. Plasma NT-proBNP levels increase in neonates with HIE complicated by myocardial ischemic injury in the acute phase. Detection of NT-proBNP levels may be useful in the diagnosis of myocardial ischemic injury and the severity evaluation of HIE.

Topics: Female; Humans; Hypoxia-Ischemia, Brain; Immunoenzyme Techniques; Infant, Newborn; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Clinical biomarkers of cardiac function could also be monitored postmortem. Among the natriuretic peptides, the aminoterminal portion of pro-brain natriuretic peptide (NT-proBNP) appears to be a more reliable postmortem tool than the BNP, owing to its longer half-life and greater stability. In living persons, NT-proBNP is considered to be a marker of heart failure, and its level rises after cardiac ischemia. The goal of this study was first to evaluate the postmortem stability of NT-proBNP, then to measure the NT-proBNP levels in postmortem cases of heart failure related to coronary ischemia. The goal of this study was also to evaluate the correlations between different specimens collected at autopsy (e.g. blood, serum, vitreous humor and pericardial fluid). The study included 96 cases, which were classified into 4 groups according to the autopsy and histological findings. The NT-proBNP levels were significantly higher in individuals who had suffered from chronic cardiac ischemia, with or without acute coronary events, than in either control cases or those who had suffered from acute thromboembolism or acute rupture of a plaque without chronic cardiac ischemia. The highest levels were registered in individuals who had suffered from acute coronary thromboembolism in association with chronic coronary ischemia. Good correlations in the NT-proBNP levels for the different specimens were observed between samples of femoral blood, serum, and pericardial fluid. Our data indicated that postmortem measurements of NT-proBNP are reliable and compatible with clinical findings.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Coronary Artery Disease; Coronary Thrombosis; Embolism; Female; Forensic Pathology; Humans; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Pericardium; Sex Factors; Vitreous Body

Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain.. Sixty-nine per cent of the patients presented with GDF-15 levels above the previously defined upper reference limit (1200 ng/L). The risks of the composite endpoint of death or (recurrent) MI after 6 months were 1.3, 5.1, and 12.6% in patients with normal (<1200 ng/L), moderately elevated (1200-1800 ng/L), or markedly elevated (>1800 ng/L) levels of GDF-15 on admission, respectively (P < 0.001). By multivariable analysis that included clinical characteristics, ECG findings, peak cardiac troponin I levels within 2 h (cTnI(0-2 h)), N-terminal pro-B-type natriuretic peptide, C-reactive protein, and cystatin C, GDF-15 remained an independent predictor of the composite endpoint. The ability of the ECG combined with peak cTnI(0-2 h) to predict the composite endpoint was markedly improved by addition of GDF-15 (c-statistic, 0.74 vs. 0.83; P < 0.001).. GDF-15 improves risk stratification in unselected patients with acute chest pain and provides prognostic information beyond clinical characteristics, the ECG, and cTnI.

Topics: Aged; Biomarkers; C-Reactive Protein; Chest Pain; Cohort Studies; Electrocardiography; Female; Growth Differentiation Factor 15; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Statistics, Nonparametric; Triage; Troponin I

Natriuretic peptides have emerged in the last years as useful diagnostic and prognostic biomarkers in patients with stable CAD. Myocardial ischemia per se might increase NT-proBNP levels.. The aim of the present study was to determine whether NT-proBNP levels in patients with stable CAD and preserved left ventricular function are elevated and second, to compare NT-proBNP in patients with verified ischemia on myocardial perfusion imaging (MPI) to non-ischemic subjects with known CAD.. 117 patients were prospectively included, divided in two groups: group A (26 patients)--with normal MPI and without known CAD and group B (91 patients)--with abnormal MPI or known CAD. Patients from group B were further divided according to the presence of ischemia on MPI in non-ischemic (29 pts) and ischemic (62 pts) subgroup.. Levels of NT-proBNP in group B were significantly higher compared to group A (median 53 vs 21 pg/ ml, p = 0.012). End diastolic and end systolic volumes were higher, and ejection fraction after stress and at rest was lower in group B (63% vs 71%, p = 0.0004 and 69% vs 75%, p = 0.008). No significant difference in NT-pro BNP levels (median 48 vs 62 pg/ml, p = 0.5) and functional parameters between the ischemic and nonischemic subjects was found.. Our data show that patients with stable coronary artery disease and preserved left ventricular function have elevated levels of NT-proBNP. We could not demonstrate that the presence of myocardial ischemia per se was an additional factor leading to increase of the natriuretic propeptide (Tab. 4, Ref. 12).

Topics: Coronary Artery Disease; Coronary Circulation; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Tomography, Emission-Computed, Single-Photon

The application of cardiopulmonary bypass (CPB) using a heart-lung machine in open heart surgery is associated with numerous pathophysiological changes in the vascular system and the neurohormonal environment. In this study our purpose was to investigate whether the hormones brain natriuretic peptide (BNP) and ghrelin are involved in changes in the systemic vascular resistance index (SVRI) after CPB, using data from 20 patients who had undergone coronary artery bypass grafting accompanied by CPB. Hemodynamic measurements were obtained using a thermodilution catheter and included cardiac index and systemic vascular resistance index. Blood samples were taken before CPB, after CPB, and at 0 and 24 h postoperatively. The blood levels of total and acylated ghrelin were quantified by radioimmunoassay. Blood levels of BNP were measured by a fluorescence immunoassay kit. The SVRI was significantly higher at the end of CPB and at 0 h postoperatively than before CPB (end of CPB: 4282 +/- 1035 dyne x s x cm(-5) x m(-2), 0 h postoperatively: 3239 +/- 635 dyne x s x cm(-5) x m(-2) vs. before CPB: 2289 +/- 330 dyne x s x cm(-5) x m(-2), p < 0.05). Total and acylated ghrelin levels decreased until 0 h postoperatively but the change was not statistically significant. However, at 24 h after surgery, they showed a statistically significant increase over the initial ghrelin values (total before CPB: 1413.71 +/- 287.93 pg/ml vs. 24 h postoperatively: 1736.85 +/- 236.89 pg/ml; acylated ghrelin before CPB: 55.85 +/- 25.53 pg/ml vs. 24 h postoperatively: 106.28 +/- 30.86 pg/ml; p <0.05 for both). BNP values were markedly lower after than before CPB (before CPB: 69.07 +/- 48 pg/ml vs. after CPB: 21.96 +/- 13 pg/ml, p < 0.05) and reached a maximum value 24 h postoperatively (before CPB: 56.3 +/- 42 vs. after CPB: 454.7 +/- 229 pg/ml, p < 0.05). There was a weak negative correlation between the changes in SVRI and total and acylated ghrelin levels after the CPB period, but this was not statistically significant. However, there was a statistically significant negative correlation between SVRI and BNP after CPB and at 24 h postoperatively (r:-0.709, p < 0.01 and r:-0.649, p < 0.03, respectively). Taken together, our results show that the observed initial increases in ghrelin and/or BNP in the postoperative period (at 24 h) might be causally related to the decrease in the SVRI in the same period. However, further investigations are needed to clarify the significance of this observati

Topics: Aged; Cardiopulmonary Bypass; Female; Ghrelin; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Postoperative Complications; Systemic Inflammatory Response Syndrome; Vascular Resistance

Recent studies suggest that natriuretic peptides are potential biomarkers for myocardial ischemia. However, little is known about the value of NT-proBNP as a predictor of repeat revascularization (RR) at follow-up angiography in patients with normal LV systolic function.. We collected and analyzed the clinical and angiographic data from 445 consecutive patients (62.5+/-10.1 years; 73% males) who showed normal LV systolic function and no regional wall motion abnormalities on transthoracic echocardiogram performed at baseline and follow-up angiography.. Overall, NT-proBNP level on admission for follow-up angiography was significantly higher in patients with RR (n=55) than those without RR (n=390) [92.4 (47.5-178.5) pg/ml vs. 54.8 (30.6-93.1) pg/ml, P<0.001]. In asymptomatic patients, NT-proBNP did not show significant difference between patients with RR and those without RR (P=0.42). An elevated NT-proBNP level, especially in symptomatic patients (n=77) (>87.5 pg/ml as an optimal cut off value) was a strong independent predictor for RR at follow-up angiography (OR, 12.3; 95% CI, 3.25-46.2; P=0.001). NT-proBNP (>122.9 pg/ml) showed high specificity (85.9%) and negative predictive value (91.0%) for predicting RR in overall patients. However, NT-proBNP (>97.0 pg/ml) showed low sensitivity (49.1%) and positive predictive value (23.5%). The areas under the receiver operator characteristic (ROC) curve in predicting RR in overall patients and symptomatic patients were 0.648 (95% CI; 0.564-0.732, P<0.001) and 0.768 (95% CI; 0.653-0.884, P<0.001), respectively.. Our data show that NT-proBNP level at follow-up is a strong independent predictor for RR especially in symptomatic patients. Although routine measurement may be not useful for predict RR, NT-proBNP may help to identify patients with low risk of repeat revascularization.

Topics: Age Factors; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Biomarkers; Cohort Studies; Coronary Angiography; Coronary Disease; Echocardiography, Transesophageal; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retreatment; Risk Assessment; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Sex Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ventricular Remodeling

BNP (brain-type natriuretic peptide) is a cardiac hormone with systemic haemodynamic effects as well as local cytoprotective and antiproliferative properties. It is induced under a variety of pathophysiological conditions, including decompensated heart failure and myocardial infarction. Since regional hypoxia is a potential common denominator of increased wall stretch and myocardial hypoperfusion, we investigated the direct effects of hypoxia on BNP expression, and the role of the HIF (hypoxia-inducible transcription factor) in BNP regulation. Using an RNase protection assay we found a strong hypoxic induction of BNP mRNA expression in different cell lines and in cultured adult rat cardiomyocytes. Systemic hypoxia and exposure to 0.1% CO induced BNP expression in the rodent myocardium in vivo, although this was at a lower amplitude. BNP promoter-driven luciferase expression increased 10-fold after hypoxic stimulation in transient transfections. Inactivation of four putative HREs (hypoxia-response elements) in the promoter by site-directed mutagenesis revealed that the HRE at -466 nt was responsible for hypoxic promoter activation. A functional CACAG motif was identified upstream of this HRE. The HIF-1 complex bound specifically and inducibly only to the HRE at -466 nt, as shown by EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation). siRNA (small interfering RNA)-mediated knockdown of HIF-1alpha, but not HIF-2alpha, interfered with hypoxic BNP mRNA induction and BNP promoter activation, confirming that BNP is a specific HIF-1alpha target gene. In conclusion, BNP appears to be part of the protective program steered by HIF-1 in response to oxygen deprivation. Induction of BNP may therefore contribute to the potential benefits of pharmacological HIF inducers in the treatment of ischaemic heart disease and heart failure.

Topics: 3T3-L1 Cells; Amino Acid Motifs; Animals; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Rats, Wistar

EPO (erythropoietin) has recently been shown to have protective actions upon the myocardium; however, the direct effects of EPO upon cardiac contractile and secretory functions are unknown and the signalling mechanisms are not well defined. In the present study, we provide the first evidence of direct cardiac contractile actions of EPO. In isolated perfused Sprague-Dawley rat hearts, a 30 min infusion of EPO significantly increased contractility in a dose-dependent fashion (maximal change 18+/-2% with 1 unit/ml EPO; P<0.005 compared with vehicle). Perfusate ET-1 (endothelin-1) increased transiently during EPO infusion, and the ET(A/)ET(B) antagonist bosentan abolished the inotropic response to EPO. BNP (B-type natriuretic peptide) secretion (28+/-8%; P<0.05) and nuclear transcription factor GATA-4 DNA-binding activity (51%; P<0.05) were both significantly increased by EPO and blocked by bosentan. In a model of global ischaemic injury, delivery of 1 unit/ml EPO during reperfusion significantly attenuated creatine kinase release (28+/-12%; P<0.05) and significantly improved contractile recovery (P<0.001), independent of ET(A) blockade. Apoptotic indices [assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)/cleaved caspase-3-positive cells] were significantly decreased (P<0.01) by 1 unit/ml EPO during reperfusion alone, coincident with significantly increased phosphorylation of myocardial JAK2 (Janus kinase 2) and STAT3 (signal transducer and activator of transcription 3). Thus EPO directly enhances cardiac contractility and BNP secretion and alleviates ischemia/reperfusion injury via ET-1-dependent and -independent mechanisms respectively.

Topics: Animals; Apoptosis; Bosentan; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Erythropoietin; Heart; Humans; Janus Kinase 2; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Natriuretic Peptide, Brain; Perfusion; Phosphorylation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; STAT3 Transcription Factor; Stimulation, Chemical; Sulfonamides

The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery.. The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index > or =2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications.. Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations.

Topics: Aged; Aged, 80 and over; Elective Surgical Procedures; Female; Heart Failure; Humans; Intraoperative Complications; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Postoperative Period; Predictive Value of Tests; Preoperative Care; Risk Factors

To study the mRNA expression of BNP and c-fos gene in rat heart after acute myocardial ischemia (AMI) and to provide a marker for its medicolegal diagnosis.. AMI animal model of rat was made by ligating LAD. mRNA expression of BNP and c-fos gene were studied with RT-qPCR and ordinary PCR at 10 min, 30 min, 60 min and 3h after the successful ligation. The H&E staining was also used. Changes of the mRNA expression in different time groups were compared.. There was significant difference in BNP mRNA expression of the 3 h group by RT-qPCR compared with normal control group, 10 min, 30 min, and 60 min groups (P < 0.05). There were dramatic differences in c-fos mRNA expression between every two groups (P < 0.05) except between the normal group and the 10 min group, between the 30 min group and the 3 h group. The peak of c-fos expression was in 60 min group. No difference was shown between groups by the ordinary PCR. Myocardial fiber acidophilia staining and wavy changes could be seen occasionally at 3 h experimental group by H&E staining.. C-fos gene probably be used as an auxiliary test for myocardial ischemia of duration of 30 minutes or longer. RT-qPCR may be suitable for diagnosis of early AMI.

Topics: Animals; Biomarkers; Forensic Medicine; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-fos; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

The aim of this study was to assess the predictive value of electrocardiographic, echocardiographic and neurohumoral parameters for adverse outcomes in non-ischaemic dilated cardiomyopathy patients with sinus rhythm.. Seventy-eight patients with non-ischaemic dilated cardiomyopathy (LVEF < 40%) and sinus rhythm were enrolled. All patients underwent electrocardiographic, echocardiographic examination and coronary angiography. Blood samples for plasma NT pro-BNP levels were obtained at rest, following echocardiographic examination. Patients were followed up for clinical end points of death from worsening heart failure, sudden cardiac death and heart transplantation.. The study population consisted of 24 (30.8%) women and 54 (69.2%) men. Forty-four patients (65.4%) suffered from clinical end points during a mean of 1278 +/- 188 days follow-up; cardiac transplantation was performed in 5 (11%), sudden cardiac death occurred in 10 (23%) and death due to worsening heart failure in 29 (66%) patients. The patients were grouped according to the presence (group 1, 44 patients) or absence (group 2, 34 patients) of clinical end points. The patients in group 1 had lower systolic blood pressures (P = 0.006) and higher NYHA functional classes (P < 0.0001). When echocardiographic parameters and NT pro-BNP values were compared, the patients in group 1 had lower left ventricular ejection fractions (P < 0.0001), higher E/A ratios (P < 0.0001), shorter E wave deceleration times (P = 0.004), pulmonary acceleration times (P < 0.0001) and isovolumetric relaxation times (P = 0.03), increased mitral regurgitant volumes (P = 0.033) and higher plasma NT pro-BNP levels (P < 0.0001). There was no significant difference between the two groups regarding electrocardiographic parameters. In univariate analysis, the prognostic predictors of life expectancy were identified as plasma NT pro-BNP, NYHA functional class, left ventricular ejection fraction, E/A ratio and E wave deceleration time. However, in multivariate analysis by logistic regression only plasma NT pro-BNP was determined as independent predictor of life expectancy (P = 0.04, HR (95% CI) = 1.0003 (1.0000-1.0007), chi2 = 3.9).. Electrocardiographic parameters failed to predict clinical end points in this group of patients. Plasma NT pro-BNP is a useful biochemical marker to define the high-risk group that warrants closer follow-up in dilated cardiomyopathy patients with sinus rhythm.

Topics: Adult; Cardiomyopathy, Dilated; Coronary Angiography; Diagnosis, Differential; Echocardiography, Doppler, Color; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; Severity of Illness Index; Stroke Volume

B-type natriuretic peptide (BNP) is a blood test which detects ventricular wall stretch and is being increasingly used in primary care on limited evidence.. To assess the practical implications and potential clinical benefit of measuring BNP to identify and guide the treatment of undiagnosed or under-treated ventricular dysfunction in at-risk patients.. Screening study with single-arm intervention.. A total of 1918 patients with diabetes mellitus or ischaemic heart disease aged > or =65 years registered with 12 general practices were invited; 76 patients with elevated BNP underwent BNP-guided treatment titration.. Eligible patients were invited to attend for a blood test at their own practice; those with a persistently elevated plasma BNP concentration (>43.3 pmol/l) after repeat measurement were offered initiation or up-titration of treatment guided by remeasurement of BNP with a target concentration of <36 pmol/l.. Seven-hundred and fifty-nine patients (40%) attended for screening; 76 (10% of 759) commenced treatment titration. Of these 76 patients, 64 (84%) were asymptomatic or had only mild breathlessness. Maximum titration effect was achieved by the second visit when 27 (36%) had achieved the BNP target concentration and the mean reduction was 10.8 pmol/l (P<0.001). The most effective therapeutic step was a switch in beta-blocker to carvedilol or bisoprolol (P<0.001).. About 10% of patients with diabetes or cardiovascular disease on GP morbidity registers have a persistently raised plasma BNP concentration. Simple adjustment of their drug treatment may reduce their BNP and associated mortality risk, but further up-titration against BNP is only possible if the within-person biological variability of measurement can be reduced.

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Diabetic Angiopathies; Family Practice; Feasibility Studies; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Risk Factors; Ventricular Dysfunction

Topics: Aged; Biomarkers; Female; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Recovery of Function; Ventricular Dysfunction, Left

Aim of the study was to determine the effect of dobutamine stress echocardiography (DSE)-induced ischemia on circulating levels of N-terminal fragment of B-type natriuretic peptide (NT-pro-BNP).. One hundred and twenty-eight patients underwent DSE for the evaluation of known or suspected coronary artery disease. NT-pro-BNP levels were measured before and 1h after completion of DSE. NT-pro-BNP levels were similar before and after DSE regardless of whether patients had (123+/-101.8 vs. 124.2+/-108.3, p=NS) or did not have inducible ischemia (96.5+/-70.5 vs. 100.5+/-71.1, p=NS). Patients with inducible myocardial ischemia had no different NT-pro-BNP levels compared to patients without inducible ischemia both before (123+/-101.8 vs. 96.5+/-70pg/ml, p=0.37) and after DSE (124.2+/-108.3 vs. 100.5+/-71.1pg/ml, p=0.55). Patients with severe inducible ischemia had significantly higher NT-pro-BNP levels compared to patients with mild or moderate inducible ischemia and patients without inducible ischemia, both before (208.5+/-125.5 vs. 96+/-78.9 vs. 96.5+/-70pg/ml, p=0.017 and p=0.025, respectively) and after DSE (212.5+/-138.1 vs. 94.8+/-81.1 vs. 100.5+/-71.1pg/ml, p=0.015 and p=0.023, respectively). NT-pro-BNP levels before DSE could be independently predicted by age (p<0.0001), presence of diabetes mellitus (p=0.002), and ejection fraction (p=0.005), but not DSE inducible ischemia.. NT-pro-BNP is not affected by DSE-induced ischemia and cannot be used in clinical practice to improve diagnostic accuracy of DSE.

Topics: Acute Disease; Adult; Aged; Biomarkers; Coronary Artery Disease; Echocardiography, Stress; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Function, Left

To assess the long-term prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) after major vascular surgery.. A single-centre prospective cohort study.. 335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery.. Prior to surgery, baseline NT-proBNP level was measured. Patients were also evaluated for cardiac risk factors according to the Revised Cardiac Risk Index. Dobutamine stress echocardiography (DSE) was performed to detect stress-induced myocardial ischaemia.. The prognostic value of NT-proBNP was evaluated for the endpoints all-cause mortality and major adverse cardiac events (MACE) during long-term follow-up.. In this patient cohort (mean age: 62 years, 76% male), median NT-proBNP level was 186 ng/l (interquartile range: 65-444 ng/l). During a mean follow-up of 14 (SD 6) months, 49 patients (15%) died and 50 (15%) experienced a MACE. Using receiver operating characteristic curve analysis for 6-month mortality and MACE, NT-proBNP had the greatest area under the curve compared with cardiac risk score and DSE. In addition, an NT-proBNP level of 319 ng/l was identified as the optimal cut-off value to predict 6-month mortality and MACE. After adjustment for age, cardiac risk score, DSE results and cardioprotective medication, NT-proBNP > or =319 ng/l was associated with a hazard ratio of 4.0 for all-cause mortality (95% CI: 1.8 to 8.9) and with a hazard ratio of 10.9 for MACE (95% CI: 4.1 to 27.9).. Preoperative NT-proBNP level is a strong predictor of long-term mortality and major adverse cardiac events after major non-cardiac vascular surgery.

Topics: Aged; Biomarkers; Cardiotonic Agents; Dobutamine; Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; ROC Curve; Survival Rate; Time Factors

The aim of this study was to evaluate serial measurements of B-type natriuretic peptide (BNP) and NT-proBNP levels in the detection of myocardial ischemia. A total of 62 consecutive male patients referred for stress echocardiography in a tertiary care cardiology center were enrolled. Inducible myocardial ischemia was detected in 15 patients (24%). BNP and NT-proBNP levels were significantly lower in patients with ischemia compared to those without ischemia throughout exercise testing and during recovery (p<0.05 for all comparisons). Major differences in baseline characteristics including age and higher incidence of comorbidities including hypertension and kidney disease in patients without ischemia apparently outweighed myocardial ischemia as trigger for BNP and NT-proBNP secretion. The same factors may have induced a selection bias in the decision to offer direct coronary angiography or initial stress testing. In conclusion, BNP and NT-proBNP are not helpful in the evaluation of male patients with suspected myocardial ischemia in a tertiary care cardiology center with rapid access to coronary angiography.

Topics: Aged; Cohort Studies; Coronary Angiography; Echocardiography, Stress; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

There is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis.. We measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing.. Of the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p<0.05; NT-pro ANP 732.5 (470.0/1220.0) pg/mL vs 1470.0 (694.0/1910.0) pg/mL, p<0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects.. The elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoked ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Dipyridamole; Exercise Test; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Placenta Growth Factor; Predictive Value of Tests; Pregnancy Proteins; Protein Precursors; Radionuclide Imaging; Research Design; Sensitivity and Specificity; Serum Albumin; Severity of Illness Index; Troponin T; Vasodilator Agents

B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) are both increasingly used in the clinical management of patients with suspected coronary artery disease (CAD). Unfortunately, there is very limited data regarding the association between BNP and LVEF.. BNP and LVEF were measured in 260 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT). The correlation between BNP and LVEF was studied using Spearman's correlation test.. Median LVEF was 57% (IQR, 50 to 64), and median BNP level was 53 pg/ml (IQR, 24 to 109). LVEF and BNP levels showed a statistically significant, but overall weak correlation (r=0.274, p<0.001). The correlation seemed to depend on the presence of a myocardial scar, which was detected in 104 patients (40%), including 89 men (49% of men) and 15 women (20% of women). The correlation between BNP and LVEF was moderate in patients with a myocardial scar (r=-0.540, p<0.001), but very weak in patients without a scar (r=0.185, p=0.025). Moreover, the correlation between BNP and LVEF was moderate in men (r=-0.503, p<0.001), but not existent at all in women. In the overall cohort, BNP was not an accurate test to detect left ventricular systolic dysfunction. The area under the ROC curve was 0.643 (95% CI, 0.563-0.723).. The BNP level and LVEF show only a weak correlation in patients with suspected myocardial ischemia. Neurohormonal and morphologic assessments provide different windows to the heart.

Topics: Exercise Test; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; ROC Curve; Severity of Illness Index; Stroke Volume; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Elevated levels of B-type natriuretic peptide (BNP) have been reported in association with exercise-induced ischemia. Data regarding BNP as a marker of ischemia during dobutamine stress echocardiography (DSE) are not conclusive. This study was designed to evaluate changes in BNP during DSE. A total of 74 patients referred to rule out ischemia by DSE were enrolled in the study. All patients had DSE using standard protocol. Of 74 patients enrolled, 6 were excluded because of nondiagnostic tests. Of the remaining 68 patients, 15 had positive DSE and 53 were negative for ischemia. The BNP levels (mean +/- SD) in the patients without ischemia were 42.5 pg/mL (+/-SD 47.6) at baseline and 41.9 pg/mL (+/-SD 48.9) at peak, and the measurements in the patients with ischemia were 90 pg/mL (+/-SD 171.7) at baseline and 88 pg/mL (+/-SD 149.2) at peak. BNP levels do not change during DSE with or without evidence of ischemia.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Coronary Disease; Echocardiography, Stress; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Reference Values; Risk Assessment; Sensitivity and Specificity; Statistics, Nonparametric

In this work we aimed to observe (1) the changes in adrenomedullin (AM) and its receptor system - calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) - in myocardial ischemic injury and (2) the response of injuried myocardia to AM and the phosphorylation of Akt to illustrate the protective mechanism of AM in ischemic myocardia. Male SD rats were subcutaneously injected with isoproterenol (ISO) to induce myocardial ischemia. The mRNA levels of AM, CRLR, RAMP1, RAMP2 and RAMP3 were determined by RT-PCR. Protein levels of Akt, phosphor-Akt, CRLR, RAMP1, RAMP2 and RAMP3 were assayed by Western blot. Results showed that, compared with that of the controls, ISO-treated rats showed lower cardiac function and myocardial injury. The mRNA relative amount of AM, CRLR, RAMP1, RAMP2 and RAMP3 in the myocardia of ISO-treated rats was increased. The elevated mRNA levels of CRLR, RAMP1, RAMP2 and RAMP3 were positively correlated with AM content in injured myocardia. The protein levels of CRLR, RAMP1, RAMP2 and RAMP3 in injured myocardia were increased compared with that of control myocardia. AM-stimulated cAMP generation in myocardia was elevated in the ISO group, and was antagonized by AM(22-52) and CGRP(8-37). Western blot analyses revealed that AM significantly enhanced Akt phosphorylation in injured myocardia, which was blocked by pretreatment with AM(22-52) or CGRP(8-37). Ischemia-injured myocardia hyper-expressed AM and its receptors - CRLR, RAMP1, RAMP2 and RAMP3 - and the response of ischemic myocardia to AM was potentiated, and the level of Akt phosphorylation was also increased, which suggests that changes in cardiac AM/AM receptor might play an important role in the pathogenesis of myocardial ischemic injury.

Topics: Adrenomedullin; Animals; Blotting, Western; Calcitonin Receptor-Like Protein; Cardiotonic Agents; Cyclic AMP; Disease Models, Animal; Gene Expression Regulation; Heart; Intracellular Signaling Peptides and Proteins; Isoproterenol; Lipid Peroxides; Male; Membrane Proteins; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Phosphorylation; Proto-Oncogene Proteins c-akt; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptor Activity-Modifying Proteins; Receptors, Calcitonin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

N-terminal pro-b-type natriuretic peptide (NT pro-BNP) is a neurohormone synthesized predominantly in ventricular myocardium. In patients with symptoms of heart failure, elevation in NT pro-BNP accurately identifies ventricular dysfunction. However, NT pro-BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevation in NT pro-BNP. The study was aimed to determine whether NT pro-BNP elevations are associated with myocardial ischemia.. One hundred and thirty patients (104 males, 26 females, mean age 61+12 years), with ST elevation acute myocardial infarction (STEMI) and preserved left ventricular ejection fraction (>45%) at echocardiography performed at entry, from February 2003 and February 2004 were enrolled. In all patients NT pro-BNP plasma levels were checked at entry and 4-5 days after symptoms onset. In addition, maximal or symptom-limited exercise treadmill test (Bruce protocol), and myocardial perfusion scintigraphy using [(99m)Tc]Tetrofosmin single photon emission computed tomography (SPECT) imaging were performed within 30 days of STEMI. Ischemia was defined as reversible perfusion abnormalities.. Of the 130 participants, 66 (51%) had inducible ischemia. Compared with patients in the lowest tertile, those in the highest tertile of NT pro-BNP had a greater significant risk of residual ischemia (odds ratio: 8.66; 95% CI, 3.90 to 19.24). Nevertheless patients in the highest tertile were older (64.19+/-10.80 years versus 55.90+/-9.67 years, P = 0.0001), had a lower left ventricular ejection fraction (49.70+13.46% versus 59.49+/-6.58%, P = 0.0001) and had a great rate of acute myocardial infarction (anterior acute myocardial infarction = 40.63% versus 25%).. Elevated levels of NT pro-BNP are associated with residual myocardial ischemia among patients with STEMI and preserved left ventricular ejection fraction, as demonstrated by perfusion defect on SPECT imaging, suggesting that these patients may need further evaluation for stratification of the future risk of fatal events. The observed association between NT pro-BNP levels and ischemia may explain because tests for NT pro-BNP are not specific for ventricular dysfunction among patients with coronary artery disease.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Echocardiography, Stress; Electrocardiography; Exercise Test; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Odds Ratio; Organophosphorus Compounds; Organotechnetium Compounds; Peptide Fragments; Predictive Value of Tests; Radiopharmaceuticals; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Peroperative infarction (POI) is a frequent and serious event, which is associated with an increase in morbidity and mortality; the risk is aggravated to varying degrees by the techniques of anaesthesia and surgery used. The preoperative evaluation of risk, which combines clinical and paraclinical criteria is described in the algorithm of the new AHA/ACC guidelines. In order to avert these ischemic episodes, beta-blockers must be continued or introduced during vascular surgery. In other types of surgery, they must be considered. It is difficult to diagnose MI in a per-operative context. The electrocardiogram print out and troponin kinetics will identify patients in the postoperative phase that should be oriented towards cardiovascular evaluation and therapy.

Topics: Adrenergic beta-Antagonists; Anesthesia, General; Electrocardiography; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intraoperative Complications; Intraoperative Period; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Preoperative Care; Risk Factors; Surgical Procedures, Operative; Troponin; Vascular Surgical Procedures

The association between B-type natriuretic peptide (BNP) and coronary artery disease is not fully understood.. To assess whether ischaemia per se is a stimulus for BNP secretion.. University tertiary hospital, Spain (Virgen de la Arrixaca).. Prospective interventional study.. 11 patients (55 (9) years, left ventricular ejection fraction (LVEF) 45% (7%) with a non-complicated anterior myocardial infarction (MI) and isolated stenosis of the left anterior descending (LAD) coronary artery, successfully treated by primary angioplasty.. 11.0 (0.9) days after MI, the LAD was occluded (20 min) for intracoronary infusion of progenitor cells. Blood samples were obtained from the femoral artery (peripheral circulation (PC)) and the coronary sinus (coronary circulation (CC)) immediately before and after coronary occlusion.. BNP (pg/ml) was measured and ischaemia biomarkers were monitored.. During coronary occlusion, all patients experienced transitory chest pain and ST-segment dynamic changes. After coronary occlusion, lactic acid levels rose in CC (1.42 (0.63) -1.78 (0.68) ng/ml, p = 0.003). Myoglobin and cardiac troponin T did not differ in CC or PC at 24 h. No differences were found in LVEF (+0.18% (2.4)%, p = 0.86) and motion score index (-0.02 (0.06), p = 0.37). Before occlusion, BNP levels did not differ significantly in CC versus PC (253 (56) vs 179 (34), p = 0.093). After occlusion, BNP showed a significant increase in CC (vs 332 (61), p = 0.004), but no change occurred in PC (vs 177 (23), p = 0.93), and circulating BNP levels were higher in CC versus PC (p = 0.008).. In response to acute ischaemia, BNP levels immediately increase in coronary sinus but not at the peripheral level. BNP release in the coronary effluent may exert local beneficial effects.

Topics: Acute Disease; Aged; Biomarkers; Coronary Circulation; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume

N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and blood urea nitrogen (BUN) predict outcomes in patients with heart failure (HF). However, it is unknown whether NT-pro-BNP is a better prognostic marker than BUN in patients hospitalized with HF. Chart reviews were performed on 257 consecutively hospitalized patients with HF whose NT-pro-BNP levels were drawn at the time of admission. The ability of NT-pro-BNP and BUN to predict the primary end point (death or readmission <30 days after discharge) was determined. Seventy-three patients (28%) reached the primary end point. Patients who reached the primary end point had significantly higher NT-pro-BNP and BUN levels. On multivariate regression analysis, the predictive values of BUN and NT-pro-BNP were very similar: the hazard ratio for NT-pro-BNP greater than the median was 1.81 (p = 0.044), and the hazard ratio for BUN greater than the median was 1.83 (p = 0.039). Analysis of the associations between NT-pro-BNP, BUN, and 30-day death or readmission as end points showed that BUN is a better predictor of outcomes (hazard ratio 3.15, p = 0.012) than NT-pro-BNP (hazard ratio 1.44, p = 0.399). In conclusion, in patients admitted to hospitals with HF, BUN is at least an equal prognosticator of HF rehospitalization or death as NT-pro-BNP. BUN outperforms NT-pro-BNP in predicting mortality in patients with advanced HF. If admitting physicians are confident that the diagnosis of HF is correct, then admission NT-pro-BNP adds little to clinical management.

Topics: Aged; Biomarkers; Blood Pressure; Blood Urea Nitrogen; Cardiac Output, Low; Creatinine; Female; Follow-Up Studies; Forecasting; Hospitalization; Humans; Length of Stay; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Admission; Patient Readmission; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Stroke Volume; Survival Rate; Time Factors

Congestive heart failure (CHF) is associated with altered energy homeostasis and myocardial inflammation, hypertrophy, and fibrosis. Adiponectin, an insulin-sensitizing adipocytokine, may affect these pathogenic factors, and the circulating adiponectin level may serve as a biological marker of CHF. This study aimed to assess the significance of serum adiponectin as a prognostic marker for Japanese CHF patients.. The serum adiponectin levels were compared between 54 (24 ischemic and 30 non-ischemic) CHF patients with left ventricular systolic dysfunction and 55 age- and gender-matched control subjects. The CHF patients also underwent simultaneous clinical assessment and measurements for brain natriuretic peptide (BNP) and parameters of lipid or glucose metabolism. Compared with the controls, the CHF patients showed significantly increased serum adiponectin levels [6.7 (4.9-12.6) vs 14.6 (9.7-25.4) microg/ml, p<0.0001]. In the CHF patients, the log-transformed values of the serum adiponectin levels positively correlated with the log-transformed values of the plasma BNP levels (p=0.0003, r=0.48) and inversely correlated with the body mass index (p=0.0006, r=-0.46). Furthermore, an increase in the serum adiponectin level was associated with higher mortality (p<0.05), particularly in the ischemic CHF patients (p<0.005).. An increase in the circulating adiponectin level was associated with higher mortality in the ischemic CHF patients. Adiponectin may be an informative risk marker for Japanese CHF patients.

Topics: Adiponectin; Aged; Aged, 80 and over; Asian People; Biomarkers; Body Mass Index; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Ventricular Dysfunction, Left

In dialysis patients, cardiac troponin T (cTNT) is often elevated despite the absence of acute myocardial ischaemia, and amino-terminal pro-B-natriuretic peptide (NT-proBNP) is markedly higher compared to non-haemodialysis patients. In a longitudinal observation, we evaluated the association of cTNT and NT-proBNP on cardiovascular morbidity and mortality in haemodialysis patients with and without fluid overload.. Plasma cTNT levels of 134 haemodialysis patients were measured before and after a dialysis session by 3rd generation electro-chemoluminiscence immunoassay. NT-proBNP was determined using a polyclonal antibody recognizing the N-terminal fragment of BNP (Elecsys autoanalyzer 2010, Roche Diagnostics, Mannheim, Germany). Volume status was determined by a clinical score system. Cardiovascular morbidity and mortality were assessed over a follow-up period of 36 months.. Plasma cTNT > 0.03 ng mL(-1) was found in 39.6% of all patients. Patients with hypervolaemia had significantly higher cTNT levels compared to euvolaemic patients (median 0.054 ng mL(-1), interquartile range 0.019-0.153 vs. 0.005 ng mL(-1), < 0.001-0.034; P < 0.001). All haemodialysis patients had excessively high levels of NT-proBNP (median 4524; interquartile range 2000-10 250 pg mL(-1)), and NT-proBNP was significantly higher in hypervolaemic haemodialysis patients (11 988, 5307-19 242) compared to euvolaemic haemodialysis patients (3247, 1619-5574); P < 0.001. Receiver operator curves showed a threshold of cTNT > 0.026 ng mL(-1) and NT-proBNP > 5300 pg mL(-1) as predictors of hypervolaemia. Asymptomatic chronic haemodialysis patients with cTNT > 0.026 ng mL(-1) and NT-proBNP > 5300 pg mL(-1) were more likely to die due to cardiac events in the follow-up period. Multivariate analysis documented that elevated cTNT and NT-proBNP levels were highly predictive for cardiovascular events.. Plasma levels of cTNT are elevated in approximately 40% and NT-proBNP levels in 100% of asymptomatic chronic haemodialysis patients. Both parameters depend on volume status. Increased NT-proBNP and cTNT are strongly associated with adverse outcome in end-stage renal disease patients undergoing haemodialysis, and are a useful tool for risk stratification in chronic haemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Female; Heart Failure; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Mortality; Myocardial Ischemia; Natriuretic Peptide, Brain; Renal Dialysis; Risk Factors; Troponin T

Ischemic (ISCM) and idiopathic dilated (IDCM) cardiomyopathies have different responses to therapy and outcomes. Both may demonstrate elevations in troponin and B-type natriuretic peptides, but biomarker levels have not been reported to differ as a function of the etiology of heart failure (HF). Accordingly, we compared these biomarkers in patients with chronic HF.. Biomarker levels of troponin T, troponin I, B-type natriuretic peptide (BNP), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) are quantitatively different between ischemic and idiopathic dilated etiologies of chronic HF.. Forty patients (27 male, 68 +/- 2 years; LVEF 25 +/- 1%; NYHA Class III-IV) admitted to hospital for acute HF were studied. Biomarkers were drawn at admission prior to treatment intervention.. Of the 40 patients, 27 had ISCM and 13 IDCM. Baseline clinical characteristics were similar with the exception of GFR. cTnT, cTnI, and BNP levels were higher in ISCM patients (cTnT: 0.373 +/- 0.145 vs. 0.064 +/- 0.016 ng/mL, p < 0.05; cTnI: 2.02 +/- 0.76 vs. 0.21 +/- 0.11 ng/mL, p < 0.05; BNP: 776 +/- 91 vs. 532 +/- 85 pg/mL, p < 0.05). Cardiovascular mortality during follow up (10 +/- 1 months) was 48% in patients with ISCM and 23% with IDCM (p < 0.05).. Patients with acutely decompensated chronic HF have elevations in troponin and BNP. These elevations, as well as mortality are significantly higher in patients with ISCM compared to IDCM. The differential levels in biomarkers may be due to differences in disease pathogenesis, and fit with the adverse prognosis in these patients.

Topics: Aged; Biomarkers; Cardiomyopathy, Dilated; Female; Heart Failure; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin I; Troponin T

The percentage of CD4(+) T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4(+) T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-gamma-positive CD4(+) T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4(+) T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-gamma-positive CD4(+) T cells was higher in patients with HF (28.96 +/- 12.90%) than in controls (18.12 +/- 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4(+) T cells between the 2 groups. The proportion of interferon-gamma-positive CD4(+) T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-gamma-positive CD4(+) T cells in the IC group (33.88 +/- 13.33%) was higher than in the IDC group (22.33 +/- 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC.

Topics: Aged; C-Reactive Protein; Cardiomyopathy, Dilated; CD4-Positive T-Lymphocytes; Female; Flow Cytometry; Heart Failure; Heart Rate; Humans; Interferon-gamma; Interleukin-4; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Biomarkers; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity

The pharmacologic properties of Brain natriuretic peptide make it a favourable substance to use after cardiac operations. The goal of this study was to evaluate the effect of BNP following cardio-pulmonary bypass (CPB).. Nineteen pigs were operated on using CPB. One group received BNP and the control group received placebo. A 30-minute ischemic episode was simulated. Following declamping, BNP was administered by an IV bolus, followed by an infusion for 60 minutes. Hemodynamic and clinical chemistry parameters were documented, as well as the amount of catecholamines.. The Cardiac output and Cardiac Index in the BNP group were significantly higher 60 minutes after ending CPB. Seven of ten animals in the control group needed catecholamines at the end of the experiment, whereas none of the animals in the BNP group did at this juncture. Creatine kinase and Lactate were significantly lower.. BNP is a well-tolerated agent that could present a new treatment option for heart failure following cardiac surgery. Hemodynamics are greatly improved with almost no need for pharmacological support.

Topics: Animals; Cardiopulmonary Bypass; Catecholamines; Creatine Kinase; Female; Heart Failure; Hemodynamics; Lactic Acid; Male; Myocardial Ischemia; Natriuretic Agents; Natriuretic Peptide, Brain; Postoperative Period; Swine; Time Factors

Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single-center study. In 113 patients with impaired left ventricular function (ejection fraction <50%; nonischemic cardiomyopathy, n=52; ischemic cardiomyopathy, n=61), MPO plasma levels were elevated (24.5 [IR:15.8-54.0] vs 15.5 [IR:8.9-39.2] ng/ml in controls, P<0.01) as was elastase (111.5 [IR:63.8-233.3] vs 70.5 [IR:45.0-129.0] ng/ml, P<0.01) and NT-proBNP plasma levels (747.4 [IR:216.3-1958.3] vs 264.1 [IR:82.5-671.8] ng/L, P<0.01). Elevation of circulating MPO was irrespective of the etiology of heart failure and independent of traditional confounding variables. No association was observed between MPO -463 promoter polymorphism genotype and LV dysfunction. MPO plasma levels correlated with ejection fraction (P<0.01) and left ventricular end-diastolic diameter (P<0.01), respectively. Myeloperoxidase mRNA expression levels obtained from circulating leukocytes were significantly increased in patients with LV dysfunction. Systemic leukocyte activation with increased transcription of MPO mRNA and augmented release of MPO appears to represent a so far underrecognized characteristic in LV dysfunction, which was revealed to be irrespective of the underlying pathology. Given its potent proinflammatory properties, MPO may represent an important mechanistic link to LV dysfunction and deserves to be evaluated as both marker and therapeutic target in this disease.

Topics: Aged; Cardiomyopathies; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Neutrophils; Pancreatic Elastase; Peroxidase; Polymorphism, Genetic; Predictive Value of Tests; Prospective Studies; RNA, Messenger; Ultrasonography; Ventricular Dysfunction, Left

Topics: Biomarkers; Critical Illness; Humans; Intraoperative Complications; Kidney Failure, Chronic; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Surgical Procedures, Operative; Troponin

Plasma brain natriutetic peptide (BNP) concentrations in type 2 diabetic patients were measured by newly developed enzyme immunoassay, and their clinical application was evaluated. Precision of the measurement system was satisfactory for clinical use, and the value obtained by this system had good correlation to that by radioimmunoassay. Tubes containing NaF in addition to EDTA, usually used for measurement of plasma glucose and HbA1c in diabetic patients, could be used for the collection of plasma sample. In 133 type 2 diabetic patients who had no symptom for heart failure, plasma BNP was elevated in those with ischemic heart disease and it was also significantly elevated even in the patients who had no ischemic change on double Master two-step exercise testing than that in control subjects. In 52 patients receiving the examination by cardiosonography, plasma BNP levels significantly correlated to the left ventricular mass index, and also had a significant correlation to peak flow velocity in early diastole/peak flow velocity in late diastole (E/A) ratio, one of a simple index for an asymptomatic diastolic heart failure. Multiple logistic regression analysis revealed that age and coronary heart disease were extracted as a significant valuable for plasma BNP level in type 2 diabetic patients. These results suggest that measurement of plasma BNP in type 2 diabetic patients was useful as a screening method for evaluating the latent deterioration of heart function such as asymptomatic ischemic heart disease.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain

N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the diagnosis of heart failure (HF). LV two-dimensional cavity area from end-diastole (LVEDA) and end-systole (LVESA), and LV fractional area change (LVFAC) reflect changes in LV morphology and function without using geometric assumptions. In a multicenter study, we correlated LVEDA, LVESA and LVFAC with NT-proBNP, comparing patients with dilated and ischemic cardiomyopathy.. We studied 106 HF patients. In the dilated group, NT-proBNP correlated with LVEDAI (r=0.6), LVESAI (r=0.7) and LVFAC (r=-0.6), all significant at p<0.001. In patients with ischemic cardiomyopathy we found LVESAI (r=0.3, p<0.05) and LVFAC (r=-0.4, p<0.01). After adjustment for age and BMI, LVFAC and LVESAI were associated in a multiple linear regression analysis with peptide levels (adjusted r(2)=0.5, p<0.001).. In this study we found a good correlation of NT-proBNP with LV cavity areas and LVFAC. Multiple regression analysis showed that when adjusted for age and BMI, LVFAC and LVESAI are independent predictors of NT-proBNP levels in both dilated and ischemic etiologies. Patients with dilated cardiomyopathy showed better results than those with ischemic cardiomyopathy. We think LV areas are a useful and reproducible parameter, do not need geometric assumptions and reflect NT-proBNP plasma levels.

Topics: Aged; Biomarkers; Cardiomyopathy, Dilated; Echocardiography, Doppler; Female; Heart Failure; Heart Ventricles; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Research Design; Spain; Stroke Volume; Ventricular Function, Left

To test the hypothesis that B-type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction.. 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP.. In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r = -0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score - rest score; Spearman's r = 0.28, two tailed p = 0.049). In the cohort who did not have left ventricular systolic dysfunction (n = 44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p = 0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman's r = 0.37 and -0.38, respectively).. BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death.

Topics: Aged; Biomarkers; Cohort Studies; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Radionuclide Imaging; Stroke

Bone marrow cells implantation (BMI) has been reported to efficiently improve ischemic heart disease. However, BMI strategies are generally invasive. To establish a BMI strategy for ischemic heart disease, we performed implantation of autologous cryopreserved mononuclear cells (MNCs) from bone marrow (BM) retrogradely into the myocardium via the coronary vein in pigs with acute myocardial infarction (AMI) and old myocardial infarction (OMI).. BM cells were harvested from the pigs' fumurs. MNCs were collected by centrifugation and were cryopreserved. Anterior myocardial infarction was induced by occlusion of the midportion of the left anterior descending coronary artery without surgical intervention. Frozen BM cells were quickly thawed and injected retrogradely via the coronary vein into the myocardium through a single balloon infusion catheter 6 h and 2 weeks after the induction of infarction. Four weeks after implantation, coronary arteriograms were obtained, cardiac function was analyzed with the use of a conductance catheter, and histopathologic analysis was performed with a confocal laser microscope. Plasma levels of natriuretic peptides and angiogenic growth factors were measured after BMI.. Flow cytometric analysis revealed that 90% of cryopreserved BM cells were viable in vitro. Labeled BM cells were entirely distributed around in the infarcted area of maycardium in pigs. BMI increased collateral neovascuralization in infarcted hearts. BMI significantly improved cardiac function in AMI with BMI and OMI with BMI groups. BMI also increased the formation of microcapillary arteries in infarcted hearts. Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI. Confocal laser microscopy revealed the presence of proliferative and activated myocardial cells in infarcted hearts after BMI.. The retrograde infusion of cryopreserved BM cells into myocardium efficiently induced angiogenesis and improved cardiac function in pigs with AMI or OMI. These results suggest that the present strategy of BMI will be safe and feasible as an angiogenic cell therapy for ischemic heart disease.

Topics: Animals; Atrial Natriuretic Factor; Bone Marrow Cells; Bone Marrow Transplantation; Coronary Vessels; Cryopreservation; Fibroblast Growth Factor 2; Injections; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Swine; Vascular Endothelial Growth Factor A

To find out whether B-type natriuretic peptide (BNP) detects silent myocardial ischaemia in patients with type 2 diabetes, since many of these patients have silent ischaemia leading to unexpected cardiac deaths.. Prospective cross-sectional study with consecutive recruitment of patients.. Outpatient, single centre.. 219 patients with type 2 diabetes. Patients were excluded if they had a history or evidence of cardiac failure.. BNP, echocardiography and exercise tolerance test (ETT). BNP was compared with the ETT result in all patients and specifically in those who had no apparent ischaemic heart disease (IHD).. 121 patients had no history of IHD or cardiac failure and of these patients 85 had a clearly abnormal or normal ETT result. BNP was higher in patients with an abnormal than with a normal ETT (mean 58.2 (SD 46.3) v 24.4 (SD 15.7) pg/ml, p < 0.001). In univariate analysis BNP was an independent predictor of an abnormal ETT (p < 0.001). In multivariate analysis BNP remained an independent predictor of the ETT result. BNP concentration over 20 pg/ml predicted an abnormal ETT result with a sensitivity of 87% and specificity of 37%, and BNP over 40 pg/ml had a sensitivity of 63% and a specificity of 81%.. BNP is of value in predicting silent ischaemia on exercise testing in asymptomatic patients with type 2 diabetes.

Topics: Area Under Curve; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves; BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD.. The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance.. Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain.. In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded; BNP and NTproBNP were measured by radioimmunoassay.. Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves.. In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.

Topics: Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Creatinine; Disease-Free Survival; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Radionuclide Ventriculography; ROC Curve; Stroke Volume; Ventricular Function, Left

The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n=27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5+/-0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370+/-191%) and 120 min (+221+/-112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128+/-39%). Hipoxia-inducible factor 1alpha and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327+/-195%; RV, +311+/-122%), but only in the RV at 30 min (+256+/-88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59+/-18%; LV, +567+/-192%) and 120 min (RV, +69+/-33%; LV, +120+/-24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77+/-25%). Ca2+-handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53+/-7%; phospholamban, +31+/-4%; Na+-Ca2+ exchanger, 31+/-6%), while Na+-H+ exchanger was altered only in the RV (-79+/-5%, 30 min; +155+/-70%, 120 min). Tumour necrosis factor-alpha and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure.

Topics: Animals; Coronary Vessels; Disease Models, Animal; Gene Expression Regulation; Heart Ventricles; Hypoxia-Inducible Factor 1, alpha Subunit; Ligation; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; RNA, Messenger; Time Factors

Cardiovascular disease is the leading cause of mortality and morbidity in Western countries. Despite its remarkable medical and social consequences, the prevalence of peripheral arterial disease (PAD) is often underestimated among atherosclerotic disorders. So far, little is known about the behavior of traditional and emerging markers of ischemic heart disease that should allow the reliable identification of PAD patients at increased risk of developing myocardial ischemia and heart failure or dysfunction. To investigate this topic, we measured cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and NT-prohormone-brain natriuretic peptide (NT-proBNP) in 35 consecutive patients with clinically ascertained PAD (stage 2-4, according to Lériche-Fontaine) asymptomatic for chest pain and current heart failure, and 20 controls displaying moderate to high cardiovascular risk factors (hypertension, diabetes, hyperlipidemia), but with no clinical evidence of PAD. Although the concentrations of cTnT and IMA were not statistically increased in PAD patients, NT-pro-BNP values were substantially higher in PAD patients than in controls (62.6 vs. 7.4 pmol/L, p<0.0001). The percentage of subjects displaying values exceeding the specific NT-proBNP diagnostic threshold (>14.8 pmol/L) was also significantly different between PAD patients and controls (74% vs. 10%, p<0.001). After excluding PAD patients exceeding the 0.01 ng/mL cTnT cutoff value indicative of current ischemic cardiac involvement, the median concentration of NT-proBNP remained statistically increased (28.0 vs. 5.8 pmol/L, p<0.0001). Taken together, these results indicate that NT-proBNP, but not IMA, is substantially increased in PAD patients. This finding suggests that such patients, even though asymptomatic, might develop myocardial dysfunction, and thus warrant further investigation.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases; Serum Albumin

Aminoterminal B-type pro-natriuretic peptide (NT-proBNP) is a reliable indicator of heart failure severity. Levels of NT-proBNP are markedly increased in patients with coronary artery disease (CAD) and severely impaired left ventricular (LV) function. The aim of our study was to assess the impact of NT-proBNP levels after high-risk coronary artery bypass grafting (CABG) with regard to recovery potential.. Between 1998 and 2004, 121 patients with CAD and severely impaired LV function, who were undergoing CABG, were investigated. Their mean age was 64 +/- 11 years. All patients were in New York Heart Association (NYHA) Class III/IV status; LV ejection fraction (EF) was 20 +/- 6%. All survivors underwent follow-up (59 +/- 34 months) spiroergometric, electrocardiographic (ECG) and echocardiographic assessment and were tested for routine blood controls and NT-proBNP levels (Roche, Mannheim, Germany).. The survival rate after 8 years was 70%. All survivors received follow-up assessment. Among survivors the median NT-proBNP level at follow-up was 896 (521 to 1,687) pg/ml. The maximum oxygen uptake was 14.6 +/- 4.9 ml/min/kg, and EF increased to 42% at follow-up among all survivors. On dichotomizing survivors into two groups with NT-proBNP levels above and below the median, the post-operative body mass index was significantly higher in the high NT-proBNP group (p = 0.036). EF (p = 0.028) and NYHA classification (p < 0.05) improved significantly in both groups, with a tendency toward higher EF in the low NT-proBNP group.. Patients undergoing a high-risk CABG procedure have a survival rate comparable to heart transplantation patients and show a potential for clinical and myocardial recovery. NT-proBNP use a useful marker for recovery after a high-risk CABG procedure, with significant correlation with clinical parameters.

Topics: Aged; Biomarkers; Comorbidity; Coronary Artery Bypass; Exercise Test; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Recovery of Function; Spirometry; Survival Analysis; Ventricular Dysfunction, Left

To determine the relationship between baseline plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and the presence and extent of myocardial ischemia during dobutamine stress echocardiography (DSE).. NT-proBNP was measured in 170 consecutive patients prior to DSE. Rest wall motion abnormalities (RWMAs) and new wall motion abnormalities (NWMAs) were scored using a 5-point, 17-segment model. Kruskal-Wallis tests were applied to study differences in NT-proBNP levels between patients with normal DSE, RWMAs but no NWMAs, and NWMAs, and (in patients with NWMAs) between those with 1-2, 3-4 and >4 ischemic segments. Univariate and multivariate regression analyses were used to determine the value of NT-proBNP in predicting NWMAs.. The median NT-proBNP level was 110 ng/l (interquartile range: 42-389 ng/l). Median NT-proBNP was 59, 321 and 440 ng/l in patients with normal DSE, with RWMAs but no NWMAs, and with NWMAs, respectively (P<0001). Among patients with NWMAs, median NT-proBNP was associated with the number of ischemic segments: 364, 710 and 2376 ng/l in patients with 1-2, 3-4 and >4 ischemic segments, respectively (P<0.001). Elevated NT-proBNP levels were significantly associated with NWMAs (odds ratio per 100 ng/l increase: 1.14, 95% confidence interval: 1.1-1.2) in a multivariate analysis of clinical baseline variables and RWMAs.. Elevated baseline levels of NT-proBNP are associated with the presence and extent of myocardial ischemia during DSE, independent of the presence of RWMAs.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Coronary Artery Disease; Echocardiography, Stress; Female; Heart Rate; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sensitivity and Specificity

In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis.. We studied the effects of BNP on preload-dependent myocardial sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) expression. In rabbit isolated muscle strips stretched to high preload and shortening isotonically over 6 hours, the SERCA/glyceraldehyde phosphate dehydrogenase mRNA ratio was enhanced by 168% (n=8) compared with unloaded preparations (n=8; P<0.001). Recombinant human BNP at a concentration typically found in end-stage HF patients (350 pg/mL) abolished SERCA upregulation by stretch (n=9; P<0.0001 versus BNP free). Inhibition of cyclic guanosine 3',5' monophosphate (cGMP)-phosphodiesterase-5 mimicked this effect, whereas inhibition of cGMP-dependent protein kinase restored preload-dependent SERCA upregulation in the presence of recombinant human BNP. Furthermore, in myocardium from human end-stage HF patients undergoing cardiac transplantation (n=15), BNP expression was inversely correlated with SERCA levels. Moreover, among 23 patients treated with left ventricular assist devices, significant SERCA2a recovery occurred in those downregulating BNP.. Our data indicate that preload stimulates SERCA expression. BNP antagonizes this mechanism via guanylyl cyclase-A, cGMP, and cGMP-dependent protein kinase. This novel action of BNP to uncouple preload-dependent SERCA expression may adversely affect contractility in patients with HF.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Animals; Calcineurin; Calcium Signaling; Calcium-Transporting ATPases; Cardiomyopathy, Dilated; Cohort Studies; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Enzyme Induction; Female; Guanylate Cyclase; Heart Failure; Heart-Assist Devices; Humans; In Vitro Techniques; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; NFATC Transcription Factors; Receptors, Atrial Natriuretic Factor; Recombinant Fusion Proteins; RNA, Messenger; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stress, Mechanical

Exercise electrocardiography (ECG) has high specificity but limited sensitivity for the detection of myocardial ischemia. The aim of this study was to determine whether measurement of B-type natriuretic peptide (BNP) can improve the diagnostic accuracy of exercise ECG.. A total of 256 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography were enrolled. Levels of BNP were determined before and 1 minute after maximal exercise.. Inducible myocardial ischemia on perfusion images was detected in 127 patients (49.6%). Median BNP levels at rest and after peak exercise were higher in patients with than without inducible ischemia (71 pg/mL vs 38 pg/mL, P < .001; and 88 vs 52 pg/mL, P < .001, respectively). Compared with patients in the lowest peak exercise BNP quartile, those in the highest quartile of peak exercise BNP had more than 3 times the risk of inducible ischemia (adjusted relative risk 3.3, 95% CI 1.3-8.6, P = .015). Using 110 pg/mL as a cutoff, the combination of exercise ECG and peak exercise BNP level distinguished between ischemic and nonischemic patients more accurately than the exercise ECG alone (67% vs 60%, P = .024). Although the increase in accuracy was similar for the combination of exercise ECG with baseline BNP or DeltaBNP, overall, peak exercise BNP seemed to be the preferred measurement.. B-type natriuretic peptide levels are associated with inducible myocardial ischemia. The use of BNP levels improves the diagnostic accuracy of exercise ECG.

Topics: Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Reproducibility of Results

Topics: Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Selection; Tachycardia

Recent studies have indicated that stem cell implantation increases cardiac function by repairing damaged myocardium. We investigated whether intracoronary transplantation of autologous bone marrow-derived mononuclear cells (BMMCs) confers beneficial effects in patients with refractory chronic heart failure. Twenty-eight patients received standard heart failure medication and BMMC transplantation (BMMC treatment) or standard medication only (controls). BMMCs were harvested from each patient. Clinical manifestations, biochemical assays, rhythm studies, echocardiograms, and positron emission tomograms were recorded. Fourteen patients with cell grafting had symptomatic relief of heart failure within 3 days. Left ventricular ejection fraction increased by 9.2% and 10.5% at 1 week and 3 months after the procedure, respectively, versus baseline (p < 0.01 for the 2 comparisons). Left ventricular end-systolic volume decreased by 30.7% after 3 months (p < 0.01). Brain natriuretic peptide levels at days 3 and 7 after cell infusion significantly decreased by 69.2% and 70.4%, respectively, whereas atrial natriuretic peptide levels increased by 30.1% at day 7. Positron emission tomographic analysis showed a significant increase in cell viability of 10.3% in the infarcted zone. No patient died in the BMMC-treated group at 6-month follow-up. In contrast, heart failure did not improve in any control patient. Left ventricular ejection fraction decreased by 7.2% after 3 months. Two control patients died from heart failure within 6 months. In conclusion, this is the first demonstration in humans that intracoronary BMMC transplantation is a feasible and safe therapeutic strategy to decrease symptoms, increase cardiac function, and possibly prolong life in patients with end-stage heart failure refractory to standard medical therapy.

Topics: Aged; Bone Marrow Transplantation; Coronary Vessels; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Injections, Intra-Arterial; Male; Middle Aged; Monocytes; Myocardial Ischemia; Natriuretic Peptide, Brain; Positron-Emission Tomography; Stroke Volume; Transplantation, Autologous; Treatment Outcome

Raised N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with a poor cardiac outcome in non-diabetic populations. Elevated NT-proBNP predicts excess morbidity and mortality in diabetic patients with an elevated urinary albumin excretion rate. This study investigated the prognostic value of NT-proBNP in a cohort of type 2 diabetic patients.. In a prospective observational follow-up study, 315 type 2 diabetic patients with normoalbuminuria (n=188), microalbuminuria (n=80) and macroalbuminuria (n=47) at baseline were followed for a median (range) of 15.5 (0.2-17.0) years. Plasma NT-proBNP concentrations were determined by immunoassay at baseline. Endpoints were overall and cardiovascular mortality.. Of the patients, 162 died (51%), 119 of them (74%) due to cardiovascular causes. All-cause mortality was increased in patients with NT-proBNP in the second and third tertiles (hazard ratios [95% CI] compared with the first tertile, 1.70 [1.08-2.67] and 5.19 [3.43-7.88], p<0.001). These associations persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate and conventional cardiovascular risk factors (covariate adjusted hazard ratios 1.46 [0.91-2.33] and 2.54 [1.56-4.14], p<0.001). This increased mortality was attributable to more cardiovascular deaths in the second and third NT-proBNP tertile (unadjusted hazard ratios 1.63 [0.96-2.77] and 4.88 [3.01-7.91], p<0.001; covariate adjusted 1.37 [0.79-2.37] and 2.26 [1.27-4.02], p=0.01). When patients with normo-, micro- and macroalbuminuria were analysed separately, NT-proBNP levels above the median (62 ng/l) were consistently associated with increased overall and cardiovascular mortality in all three groups (p<0.001).. In patients with type 2 diabetes, elevated circulating NT-proBNP is a strong predictor of the excess overall and cardiovascular mortality, this predictor status being independent of urinary albumin excretion rate and conventional cardiovascular risk factors.

Topics: Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Survival Analysis; Time Factors

Ligation of the left anterior descending coronary artery (LAD) is used to induce experimental myocardial infarction (MI). Most previous studies have focused on the early postoperative period, while data on mid-term follow-up are scanty. This study examined the mid-term effects of LAD ligation in 95 MI rats and 28 controls. The following parameters were evaluated: systemic blood pressure (SBP), heart rate (HR), and plasma brain natriuretic peptide (BNP) level. In addition, M-mode and B-mode echocardiography, histologic examinations, and cardiac hydroxyproline assays were performed. Forty-seven perioperative and 5 late deaths were recorded. Left ventricular dilation, observed 1 mo after MI, did not progress with time. Septal thickening was similar in the 2 groups, while wall thickening was lower in the MI rats at 1 mo only. Stroke volume was diminished in MI rats, while cardiac output was depressed only at 1 and 2 mo, due to increased heart rate. SBP was unchanged and plasma BNP level was similar in the 2 groups. The infarcted area (mean +/- SD) was 35 +/- 10%. The ventricles in MI rats were heavier and had increased hydroxyproline content. In conclusion, these data show that LAD ligation is not only a model of acute MI, but at mid-term it provides a model of chronic ischemic dilated cardiomyopathy.

Topics: Animals; Blood Pressure; Cardiac Output; Cardiomyopathy, Dilated; Echocardiography, Doppler; Heart Rate; Histocytochemistry; Hydroxyproline; Ligation; Male; Models, Animal; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Ventricular Remodeling

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in patients with acute coronary syndrome (ACS), and is a powerful predictor of long-term mortality. Differences in the clinical utility and pathophysiological implication of NT-proBNP and conventional cardiac markers in patients with ST elevation (STE) vs non-STE (NSTE) ACS were investigated in the present study.. Ninety consecutive patients admitted with acute chest pain and a diagnosis of unstable angina or acute myocardial infarction were analyzed. Patients with >or=Killip class II were excluded to focus on the effect of myocardial ischemia on the release of cardiac markers. The markers were measured on admission and analyzed according to the time from onset. Conventional cytosolic marker (creatine kinase-MB) and myofibril marker (troponin T: TnT) were both significantly higher in STE-ACS patients compared with NSTE-ACS patients. Conversely, NT-proBNP was significantly higher in NSTE-ACS patients than STE-ACS especially within 3 h of onset, suggesting a larger ischemic insult despite the smaller extent of myocardial necrosis compared with STE-ACS patients. There was no significant correlation between NT-proBNP level and left ventricular ejection fraction (LVEF) obtained at acute-phase echocardiography in either NSTE-ACS patients (LVEF 57.7+/-11.2%) or STE-ACS patients (LVEF 55.1+/-12.7%). Comparison between NT-proBNP and TnT levels revealed a marked difference of elevations, with significantly augmented elevation of NT-proBNP (p<0.001) in NSTE-ACS patients as compared with prominent elevation of TnT in STE-ACS patients.. NT-proBNP is an early sensitive marker of myocardial ischemia that rises much higher in the earlier phase as compared with conventional markers of myocardial damage, especially in NSTE-ACS patients.

Topics: Aged; Angina, Unstable; Biomarkers; Coronary Thrombosis; Creatine Kinase, MB Form; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Necrosis; Peptide Fragments; Syndrome; Tachycardia, Sinus; Troponin T; Ventricular Dysfunction, Left

Cardiac biomarkers, including high-sensitivity C-reactive protein (hs-CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (Tn-I), have been associated with an adverse outcome in patients with acute coronary syndrome (ACS). Thus, in the present study the incremental prognostic value of these cardiac biomarkers was evaluated for risk stratification of ACS.. The baseline levels of hs-CRP, NT-proBNP and Tn-I were measured in 215 patients (140 males; 65+/-46 years) with ACS: ST-elevation myocardial infarction (STEMI): 56; non-ST-elevation myocardial infarction (NSTEMI): 98; unstable angina (UA): 61. The patients were retrospectively followed up for a mean of 246 days. There were 24 cardiac events: STEMI: 1, NSTEMI: 6, UA: 6, chronic heart failure: 1, death: 10. The baseline levels of hs-CRP and NT-proBNP were significantly higher in the patients with cardiac events than in those without events. After adjustment for major clinical prognostic factors, hs-CRP and NT-proBNP remained significantly independent predictors for cardiac events. Patients with hs-CRP level >3.5 mg/L and NT-proBNP level >500 pg/ml had an 11-fold higher risk for cardiac events than those with hs-CRP level

Topics: Aged; Angina, Unstable; C-Reactive Protein; Coronary Thrombosis; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Syndrome; Tachycardia, Sinus; Troponin I

Coronary heart disease is associated with increased B-type natriuretic peptides (BNPs), and, although controversial, may cause exaggerated exercise-induced BNP secretion. We investigated BNP in relation to reversible myocardial ischaemia.. Serum N-terminal proBNP (NT-proBNP) was measured before and after an exercise electrocardiogram test (ETT) in 14 patients with and 45 patients without exercise-induced myocardial ischaemia. Statistical analysis was carried out on logarithmically transformed data. Results, however, are pre-transformed data.. NT-proBNP increased with exercise both in ETT-positive patients (mean (SD) 71.4 (41.2) v 76.8 (44.0) ng/l; p<0.001) and ETT-negative patients (54.0 (61.2) v 60.1 (69.0) ng/l; p<0.001). Pre-exercise and post-exercise NT-proBNP were higher (p<0.05) in ETT-positive than in ETT-negative patients. Incremental NT-proBNP was similar in ETT-positive (4.7 (4.2) ng/l) and ETT-negative (6.2 (8.6) ng/l) patients.. Serum NT-proBNP concentrations are higher in patients with exercise-induced myocardial ischaemia than in those without. Exercise-induced electrocardiographic myocardial ischaemia, however, is not associated with exaggerated BNP secretion.

Topics: Adult; Aged; Electrocardiography; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain

Topics: Angina, Unstable; Biomarkers; Creatine Kinase; Data Interpretation, Statistical; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Pregnancy-Associated Plasma Protein-A; Sensitivity and Specificity; Serum Albumin; Troponin

Dynamics of fatty acid binding protein (FABP) and pro-brain natriuretic peptide (pro-BNP) levels was studied in patients with ischemic heart disease at rest, during transitory myocardial ischemia, and before and after balloon angioplasty. Forty patients were included: 25 patients with stable angina comprised the study group and 15 patients with acute myocardial infarction (AMI) comprised control group. No significant elevation of FABP was revealed after myocardial revascularization, a tendency was noted to elevation of FABP after transitory ischemia. At the background of stress test pro-BNP level significantly rose. Comparison of FABP levels during first 24 hours of AMI and in patients with IHD both at rest and after veloergometry showed that FABP level in AMI was significantly higher. On day 21 of AMI FABP level became lower and did not differ significantly from this parameter in patients with IHD. Data of this work confirm that search of markers of myocardial ischemia in peripheral blood of patients with IHD is justified, and investigation of their role can allow not only to elevate diagnostic value of stress test, but to assess prognosis and to supplement algorithm of examination of patients with suspected IHD.

Topics: Angioplasty, Balloon, Coronary; Exercise Test; Fatty Acid-Binding Proteins; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain

Preliminary data indicate that B type natriuretic peptides' levels may rise in exercise induced myocardial ischemia in patients with stable coronary artery disease. Such findings hint at a potential broader application of these markers reaching beyond its present use in chronic heart failure and acute coronary syndromes. Ischemia modified albumin (IMA) is a novel diagnostic marker in acute coronary syndromes as its value increases in states of myocardial ischemia and necrosis. The role of this marker in the assessment of exercise induced myocardial ischemia in stable coronary artery disease has not been extensively investigated and remains unknown.. To examine changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and ischemia modified albumin (IMA) during an ECG stress test in patients with stable coronary artery disease and to assess the potential of these markers to detect exercise induced myocardial ischemia.. Patients with angiographically confirmed coronary atherosclerosis were included into the study. In all of them prognostic ECG stress test according to Bruce protocol was performed. The test was considered true positive (ischemia present) in case of significant ST-segment depression in the presence of significant coronary stenosis. The test was considered true negative (ischemia absent) when no significant ST depression was noted in the absence of significant coronary stenosis. In all patients echocardiography was performed and blood was drawn for NT-proBNP, IMA, serum albumin and creatinine before and within the first five minutes after exercise.. 41 patients with unequivocal stress test result corresponding to coronary angiogram were included in the final analysis (out of 51 examined patients). 21 patients demonstrated ischemia during exercise, 20 did not. NT-proBNP concentration was significantly higher after the stress test than before in the whole group: 127.9 (10.7-994.2) pg/ml and 110 (10.5-990.2) pg/ml respectively; p < 0.0001. NT-proBNP increase was higher in the ischemic than in the non-ischemic group; however, the difference was not statistically significant: deltaNT-proBNP 12.3 (1.0-172.3) pg/ml and 4.2 (1.0-77.1) pg/ml respectively; p = 0.09. This manifested itself in poor sensitivity and specificity of NT-proBNP in detecting exercise induced myocardial ischemia: 62 and 55% respectively (AUC 0.589). In the whole group the increase of NT-proBNP depended on baseline NT-proBNP concentration (r = 0.54; p = 0.0003), the magnitude of ST-segment depression (r = 0.38; p = 0.01), creatinine concentration (r = 0.34; p= 0.03) and history of myocardial infarcion: log deltaNT-proBNP in post-MI patients and in patients without prior MI 1.19 ( +/- 0.54) i 0.61 ( +/- 0.57) respectively; p = 0.004. In multiple regression analysis the only factor independently determining NT-proBNP increase during exercise was the history of myocardial infarction (beta = 0.342; p = 0.01) but not left ventricle ejection fraction. IMA decreased during exercise in all patients significantly--the mean value before and after exercise was 88.20 (7.72) and 78.05 (8.33) U/ml respectively; p = 0.0001. Decrease in IMA correlated only with increase in albumin concentration measured before and after exercise (r = -0.6; p < 0.0001).. Exercise induced myocardial ischemia has little influence on NT-proBNP increase. The test measuring it has therefore insufficient ability to detect exercise induced ischemia in stable coronary artery disease. In patients with stable coronary artery disease without severe impairment of left ventricular function the history of myocardial infarction is the main factor determining NT-proBNP increase during exercise. Changes in serum albumin concentration during exercise seem to exclude the use of IMA in the assessment of exercise induced myocardial ischemia.

Topics: Adult; Aged; Biomarkers; Coronary Artery Disease; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Serum Albumin

This study was undertaken to determine the diagnostic value of admission B-type natriuretic peptide (BNP) for acute myocardial infarction (AMI) in patients with acute chest pain and no ST-segment elevation.. A prospective study with 631 consecutive patients was conducted in the emergency department. Non-ST elevation AMI was present in 72 patients and their median admission BNP level was significantly higher than in unstable angina and non-acute coronary syndrome patients. Sensitivity of admission BNP for AMI (cut-off value of 100 pg/mL) was significantly higher than creatine kinase-MB (CKMB) and troponin-I on admission (70.8 vs. 45.8 vs. 50.7%, respectively, P<0.0001) and specificity was 68.9%. Simultaneous use of these markers significantly improved sensitivity to 87.3% and the negative predictive value to 97.3%. In multiple logistic regression analysis, admission BNP was a significant independent predictor of AMI, even when CKMB and troponin-I were present in the model.. BNP is a useful adjunct to standard cardiac markers in patients presenting to the emergency department with chest pain and no ST-segment elevation, particularly if initial CKMB and/or troponin-I are non-diagnostic.

Topics: Aged; Angina, Unstable; Biomarkers; Chest Pain; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Troponin I

The effects of exercise, a therapeutic tool in ischemic heart disease (IHD), may differ in ischemic and infarcted hearts.. To assess this, we created coronary stenosis (CS), which reduced coronary flow reserve (CFR), or coronary occlusion to induce myocardial infarction (MI) in rats, and subjected them to treadmill exercise for either 5 (5-min Ex) or 15 min/day (15-min Ex) for 12 weeks. Left ventricular (LV) diameters were increased and ejection fractions decreased by echocardiography, and myocardial nitric oxide (NO) activity, measured by the in vitro MVO2 method, was reduced in both CS and MI rats compared with the sham. In CS rats, myocardial wall thickening fractions were not affected at 5 min of exercise, whereas they were reduced at 15 min of exercise, suggesting exercise-induced ischemia. Despite no changes in CS severity, the 5-min Ex increased CFR, ameliorated myocardial NO activity, attenuated left ventricular (LV) dysfunction and remodeling, reduced serum brain natriuretic peptide (BNP) levels, and improved survival, whereas the 15-min Ex aggravated LV dysfunction and remodeling. In contrast, neither of the exercise protocols improved these parameters in MI rats.. Therapeutic responses to exercise differed in ischemic and infarcted hearts, partly via circulatory modulation downstream of the epicardial CS in relation to exercise-induced ischemia. When employing exercise for IHD, the causes of IHD, as well as the exercise protocols, need to be considered to achieve optimal effects.

Topics: Animals; Coronary Stenosis; Echocardiography; Exercise Therapy; Male; Models, Animal; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide; Rats; Rats, Sprague-Dawley; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Biomarkers; Coronary Restenosis; Coronary Stenosis; Half-Life; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Outpatients; Protein Precursors; Systole; Ventricular Function, Left

Cardiac natriuretic peptides and echo-Doppler indexes are important as prognostic indicators of congestive heart failure (CHF). However, differences between etiologies have not been fully investigated. This study aimed to assess the prognostic value of transmitral flow (TMF) and B-type natriuretic peptide (BNP) on admission or predischarge in patients with acutely decompensated CHF of ischemic and nonischemic etiologies.. We studied 52 patients with chronic CHF, 31 with old myocardial infarction (OMI), and 21 with idiopathic dilated cardiomyopathy (DCM), admitted for emergency acute decompensation. Patients underwent echo-Doppler study and measurement of plasma BNP on admission and predischarge. The combined index of BNP with echo-Doppler indexes were calculated. Pulmonary capillary wedge pressure (PCWP) and cardiac index were measured on admission. All were followed for 1 year, and those rehospitalized (R group) were compared with those with a stable clinical course (S group). TMF and BNP on admission were similar between DCM and OMI groups. During follow up, 9 with OMI and 10 with DCM were rehospitalized. There were no statistical differences in TMF or BNP levels on admission between the R and S groups. However, the predischarge BNP level was significantly higher in the R group than in the S. Kaplan-Meier curves revealed the influence of predischarge BNP on prognosis.. Predischarge BNP, not BNP on admission, levels are considered predictive of rehospitalization for decompensation within a year. There were no differences between BNP and echo-Doppler indexes with regard to the CHF etiology.

Topics: Aged; Echocardiography, Doppler; Echocardiography, Doppler, Pulsed; Heart Failure; Humans; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Survival Analysis

It has been suggested that plasma B-type natriuretic peptide (BNP) level may be used as a noninvasive biomarker of the adequacy of long-term heart failure therapy. The effect of contemporary therapy on the relation between BNP measured using modern commercially available assays and cardiac filling pressures has not been studied in detail, because most of the original studies predate these developments. The investigators sought to assess the diagnostic accuracy of BNP to identify significantly elevated pulmonary capillary wedge pressure (PCWP) in a group of patients with severe chronic heart failure on treatment. BNP correlated well with PCWP (r = 0.50, p <0.001), but the diagnostic accuracy of the test to identify patients with PCWP >15 mm Hg was only 74%, largely because of poor sensitivity or a large number of false-negative test results. Maximizing medical therapy irrespective of plasma BNP results remains the best approach to managing chronic heart failure.

Topics: Adult; Aged; Cardiomyopathy, Dilated; Heart Failure; Humans; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Ventricular Dysfunction, Left

The objective of the present study was to assess the cardioprotective effect of dual NEP-ACE inhibition in relation to endogenous cardiac bradykinin (BK), its active metabolite des-Arg9-BK, endogenous brain natriuretic peptides (BNP), and cGMP. Rats were treated with the dual metallopeptidase inhibitor, omapatrilat, or the ACE inhibitor, ramipril, for 7 d (1 mg.kg(-1).d(-1)). Hearts were then isolated and subjected to a zero-flow ischemia and reperfusion (except controls), in the absence or presence of either a B2-receptor antagonist (Hoe-140), a B1-receptor antagonist (Lys-Leu8-des-Arg9-BK), or the GC-A/GC-B-receptor antagonist (HS-142-1). Chronic omapatrilat and ramipril increased the amount of endogenous BK collected upon reperfusion, but only ramipril increased that of des-Arg9-BK. Only omapatrilat increased both peak BNP and peak cGMP upon reperfusion, those increases being blocked by Hoe-140. Chronic omapatrilat (but not ramipril) decreased the total noradrenaline and lactate dehydrogenase release during the reperfusion period. Importantly, only omapatrilat improved the functional recovery of the ischemic reperfused heart, with a reduced left ventricular end-diastolic pressure, and improved developed left ventricular pressure. All cardio protective effects of omapatrilat were blocked by Hoe-140 and by HS-142-1, but not by the B1-receptor antagonist. In conclusion, a chronic treatment with a dual metallopeptidase inhibitor demonstrated a cardioprotective action not observed with an ACE inhibitor in a context of severe ischemia in rat isolated hearts, which was mediated by both endogenous BK and BNP.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin B1 Receptor Antagonists; Bradykinin B2 Receptor Antagonists; Hemodynamics; In Vitro Techniques; Kinins; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Neprilysin; Pyridines; Ramipril; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; Thiazepines

Plasma brain natriuretic peptide levels increase during acute ischemic events. In this study we tested the diagnostic performance of brain natriuretic peptide measurements in the detection of acute myocardial ischemia.. Blood brain natriuretic peptide was measured in 101 patients with ongoing chest pain but no heart failure or an ST-segment elevation myocardial infarction on arrival at the emergency department (baseline) and at 2 and 6 h later. After diagnostic testing and 1-month follow-up for ischemia, patients were classified as either ischemic or non-ischemic.. In the ischemic group median (25th, 75th percentiles) brain natriuretic peptide values (pg/ml) were 122 (20, 349) at baseline, 116 (36, 347) at 2 h, increasing to 148 (52, 428) at 6 h (p<0.001 vs. baseline). Non-ischemic patients had 12 (5, 32) at baseline, 9 (6, 30) at 2 h, and 13 (5, 29) at 6 h (p<0.001 vs. corresponding values of the ischemic group). Receiver operator characteristic curves were constructed for brain natriuretic peptide values at baseline 2 and 6 h and for the increase of peptide levels from baseline to 6 h. All areas under curve indicated a significant diagnostic ability for the detection of ischemia. The 6-h measurement had better diagnostic performance than baseline and 2-h measurements. The subgroup of ischemic patients without myocardial necrosis also had higher brain natriuretic peptide values and could thus be discriminated from non-ischemic subjects.. Brain natriuretic peptide values may detect acute myocardial ischemia in patients with ongoing chest pain but without ST-segment elevation, and distinguish ischemic patients from those with pain of non-ischemic origin.

Topics: Acute Disease; Adult; Aged; Angina Pectoris; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Time Factors

Topics: Adult; Heart Ventricles; Heart-Assist Devices; Humans; Male; Mitral Valve; Myocardial Ischemia; Natriuretic Peptide, Brain; Prostheses and Implants; Shock, Cardiogenic; Ultrasonography; Ventricular Function, Left

The effects of patient-activated atrial defibrillation on subclinical myocardial injury are unknown. Using biochemical markers, this study assessed the effect of a single internal atrial shock delivered by the implantable atrial defibrillator on myocardial damage, neurohormonal activation and inflammation.. Twelve patients were implanted with a dual chamber defibrillator for the sole indication of drug refractory symptomatic persistent atrial fibrillation (AF). All had maximum defibrillation energy programmed to maximise the first shock success rate. Creatine kinase isoenzyme, troponin T, cortisol, catecholamines, C-reactive protein and brain natriuretic peptide were measured (i) during sinus rhythm, (ii) 8 h after onset of spontaneously occurring AF (before cardioversion) and (iii) 8 h following successful patient activated cardioversion.. There was no change in creatine kinase, troponin T, cortisol or C-reactive protein during AF or following internal cardioversion. Brain natriuretic peptide levels rose from a median value of 56 pg/ml during sinus rhythm (inter-quartile range 14-92 pg/ml) to 133 pg/ml during AF (30-262 pg/ml), p=0.002. There was a decrease 8 h after cardioversion to baseline (52 and 40-189 pg/ml), p=0.01. There were increases in serum adrenaline and noradrenaline levels during AF from 0.43 (0.12-0.61) to 0.58 pg/ml (0.39-0.80 pg/ml), p=0.002 and from 2.06 (1.61-2.59) to 2.83 nmol/l (2.43-3.46 nmol/l), p=0.02, respectively. These figures reverted to baseline levels 8 h post-cardioversion.. Internal atrial defibrillation does not result in myocardial injury. The onset of AF results in sympathetic activation and increased brain natriuretic peptide levels, which resolve following restoration of sinus rhythm.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Catecholamines; Chromatography, High Pressure Liquid; Creatine Kinase; Electric Countershock; Female; Follow-Up Studies; Humans; Hydrocortisone; Immunoassay; Inflammation; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Severity of Illness Index; Troponin T

N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in the diagnosis of heart failure and ventricular dysfunction. Obesity is an independent cardiovascular risk factor. The purpose of this study was to measure NT-proBNP plasma levels in obese and non-obese subjects with heart failure and to compare levels in subjects with ischaemic and dilated aetiology. In this study, obese subjects had 63% lower NT-proBNP plasma levels than non-obese subjects (p < 0.01). In multivariate analysis, BMI was inversely associated with NT-proBNP plasma levels (p < 0.05) and a 17% decrease in natriuretic peptide levels was attributed to obesity (p < 0.036). When we analyzed data according to the aetiology of heart failure, we found that both groups (ischaemic and dilated) had a 65% decrease in NT-proBNP plasma levels in obese subjects compared to non-obese subjects.

Topics: Aged; Biomarkers; Cardiomyopathy, Dilated; Female; Heart Failure; Humans; Immunoassay; Male; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Risk Factors; Severity of Illness Index

Angina represents the earliest stage of symptomatic atherothrombotic disease and is part of the continuum that ultimately results in myocardial infarction. Development of plaque is related to conventional risk factors. The progression to active disease occurs as a result of plaque destabilisation and rupture. This is a continuous process with clinically apparent disease occurring when there are multiple episodes of plaque rupture. Elevation of inflammatory markers including C reactive protein is predictive of the risk of development of cardiac events. However, it appears that B type natriuretic peptide is single most powerful predictor of cardiovascular mortality. This probably reflects its role as the integrator of the cardiac neuroendocrine system and marker of global cardiac performance. Progression of disease to occlusion will initially produce myocardial ischaemia, which may then progress to infarction. Ischaemia modified albumin is currently the most promising of the markers for early detection of ischaemia at first presentation.

Topics: Angina Pectoris; Biomarkers; C-Reactive Protein; Humans; Lipoproteins, LDL; Myocardial Ischemia; Natriuretic Peptide, Brain

Acute heart failure syndromes (AHFS) are related to several diseases affecting not only the heart but also the kidneys and blood vessels. Emerging evidence indicates that myocardial injury may also play a role in the pathophysiology of AHFS, as suggested by increased levels of markers of injury, such as cardiac troponin (cTn). Although cTn is a known prognostic marker, the release of cTn during hospitalization has not been evaluated prospectively with serial measures. We prospectively evaluated patterns of cTn release by conducting serial measures of cTnI and cTnT in patients hospitalized for AHFS. This study enrolled 51 patients with AHFS who were admitted with worsening heart failure (HF) and a history of coronary artery disease (CAD) in whom an acute coronary event was not suspected. Levels of cTnI and cTnT were measured at 8, 32, 56, and 80 hours after study entry. At baseline, 73.9% of patients had detectable cTnI, and 43.5% had detectable cTnT levels. The median concentrations of cTnI and cTnT were unchanged from 0 to 32 hours, increased from 32 to 56 hours, then either plateaued (cTnT) or decreased to baseline (cTnI). Of the 26 patients who had no detectable cTn levels at baseline, 2 (7.7%) developed detectable cTnT and 5 (41.7%) developed detectable cTnI release during hospitalization. Detectable levels of cTn at baseline were related to short-term clinical events. In this study of patients with CAD in whom an acute coronary event was not suspected, most had detectable levels of cTn present at admission, and some patients developed cTn release during hospitalization. Because cTn release may be a marker for myocardial injury, this study raises the possibility that injury occurred in most patients admitted with AHFS. Therefore, the goal of therapy for AHFS should be not only to improve symptoms and hemodynamics but also to salvage myocardium. Accordingly, therapies for AHFS that are aimed at improving hemodynamics may affect long-term prognosis by either injuring or salvaging myocardium.

Topics: Adrenergic beta-Agonists; Aged; Biomarkers; Dobutamine; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Agents; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Troponin I; Troponin T

Myocardial ischemia leads to changes in regional wall stress. Induction of ischemia during a treadmill exercise, although brief, may lead to transient elevation in the plasma level of B-type natriuretic peptide (BNP) from baseline levels, which could serve as a biochemical marker of myocardial ischemia.. Sixty subjects (mean age 57, 41 men) undergoing myocardial single-photon emission computed tomography (SPECT) in conjunction with Bruce protocol treadmill exercise for evaluation of chest pain or screening for ischemia had their BNPs measured (Triage Biosite Test) at baseline, immediately postexercise, and 10 to 15 minutes after exercise.. Of the 60 patients, 10 had ischemic perfusion defects by SPECT (mean 14%, range 5%-37%). In patients with no evidence of ischemia, median BNP level at baseline was 15.05 pg/mL (interquartile range 7-37.7), increased significantly immediately postexercise median level (34.7 pg/mL [14.9-67.6]), and decreased toward baseline levels within 10 to 15 minutes postexercise (20.3 pg/mL [8.6-48.5], analysis of variance P < .001). This transient rise in BNP level during exercise was also observed in patients with ischemia but was more pronounced. Percent change in BNP level from baseline for each minute of exercise was significantly higher in patients with evidence of ischemia compared with those without (14% +/- SEM 2.3 vs 7% +/- SEM 1.2, P = .014). Patients with and without ischemia did not differ in age, exercise time, peak systolic or diastolic blood pressure, peak heart rate, or other baseline characteristics. A > 10% change in BNP level from rest per minute of exercise had a sensitivity of 80%, a specificity of 71%, and a negative predictive value of 92% to detect reversible ischemia by SPECT.. Transient elevation in BNP occurs during treadmill exercise and is more pronounced in patients with ischemia. B-type natriuretic peptides may therefore be used in combination with treadmill exercise for the evaluation of coronary artery disease.

Topics: Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies

To evaluate the utility of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels to detect myocardial ischemia.. We conducted a prospective observational study in 260 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography. Levels of NT-proBNP were determined before and immediately after symptom-limited bicycle ergometry.. Inducible myocardial ischemia on perfusion images was detected in 129 patients (49.6%). Baseline NT-proBNP and exercise induced increase in NT-proBNP (DeltaNT-proBNP) were significantly higher in patients with myocardial ischemia (median baseline NT-proBNP 155 pg/mL vs 91 pg/mL, P <.001; DeltaNT-proBNP 15 pg/mL vs 7 pg/mL, P = .002). Compared with patients in the lowest DeltaNT-proBNP quartile, those in the highest quartile of DeltaNT-proBNP had three times the risk of inducible ischemia (relative risk, 2.9; 95% confidence interval, 1.4 to 6.0; P = .003). Overall, the accuracy of baseline NT-proBNP and DeltaNT-proBNP in the detection of myocardial ischemia were similar to that of the exercise electrocardiogram (ECG). Combining exercise ECG and baseline NT-proBNP or DeltaNT-proBNP slightly increased the accuracy of exercise ECG only.. The NT-proBNP level at rest as well as DeltaNT-proBNP during exercise stress testing is associated with inducible myocardial ischemia. NT-proBNP levels may have incremental value in the diagnosis of myocardial ischemia.

Topics: Aged; Biomarkers; Cardiovascular Agents; Comorbidity; Electrocardiography; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Factors; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Plasma brain natriuretic peptide (BNP) levels have been associated with left ventricular dysfunction and acute myocardial infarction. Although natriuretic peptide responses have been linked to exercise-induced myocardial ischemia, it is not known whether BNP levels predict dobutamine-induced myocardial ischemia. The aim of this study was to determine whether elevations in BNP levels immediately before or after dobutamine-induced stress are associated with echocardiographic myocardial ischemia. Plasma BNP was measured before and after stress during dobutamine-stress echocardiography in 317 patients (aged 68 +/- 11 years; 46% women) who had creatinine <1.5 mg/dl and did not have valvular disease. Ischemia, as assessed by blinded echocardiographic interpretation, was noted in 31 patients (10%). In univariable analyses, prestress BNP was predictive of echocardiographic ischemia (rates of ischemia according to tertiles of BNP 4%, 9%, and 16%, chi-square for trend = 8, p = 0.0059). The change in BNP levels with dobutamine stress was not associated with ischemia. In multivariable analyses, after adjusting for age, gender, and left ventricular ejection fraction, BNP before and after stress remained predictive of ischemia (1 SD increase in the log of resting BNP adjusted odds ratio 2.0, 95% confidence interval 1.3 to 3.0, p = 0.002). In this pilot study, resting BNP was predictive of dobutamine-induced ischemia. Future work is needed to confirm these findings.

Topics: Aged; Biomarkers; Cardiotonic Agents; Dobutamine; Double-Blind Method; Echocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Severity of Illness Index

To obtain region- and disease-specific transcription profiles of human myocardial tissue, we explored mRNA expression from all four chambers of eight explanted failing [idiopathic dilated cardiomyopathy (DCM), n=5; ischemic cardiomyopathy (ICM), n=3], and five non-failing hearts using high-density oligonucleotide arrays (Affymetrix U95Av2). We performed pair-wise comparisons of gene expression in the categories (1) atria versus ventricles, (2) disease-regulated genes in atria and (3) disease-regulated genes in ventricles. In the 51 heart samples examined, 549 genes showed divergent distribution between atria and ventricles (272 genes with higher expression in atria, 277 genes with higher expression in ventricles). Two hundred and eighty-eight genes were differentially expressed in failing myocardium compared to non-failing hearts (19 genes regulated in atria and ventricles, 172 regulated in atria only, 97 genes regulated in ventricles only). For disease-regulated genes, down-regulation was 4.5-times more common than up-regulation. Functional classification according to Gene Ontology identified specific biological patterns for differentially expressed genes. Eleven genes were validated by RT-PCR showing a good correlation with the microarray data. Our goal was to determine a gene expression fingerprint of the heart, accounting for region- and disease-specific aspects. Recognizing common gene expression patterns in heart failure will significantly contribute to the understanding of heart failure and may eventually lead to the development of pathway-specific therapies.

Topics: Adult; Cardiac Output, Low; Cardiomyopathy, Dilated; Down-Regulation; Female; Gene Expression Profiling; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Peptide Fragments; Transcription, Genetic; Up-Regulation

Since B-type natriuretic peptide (BNP) concentration has been shown by recent studies to be elevated in patients presenting acute coronary syndrome (ACS) even in the absence of overt heart failure, other mechanisms for elevating plasma BNP (p-BNP) concentrations may be suggested to exist. We have studied the correlation between p-BNP level and the extent of myocardial ischemia (EMI) in non-ST elevation (NSTE) ACS and evaluated the BNP level as an objective marker of EMI. In 204 patients with NSTE ACS, we estimated the EMI by the echocardiographic wall motion score index (WMSI) and the coronary angiographic Gensini score. As the positive control group, 44 patients with stable angina were enrolled into the study. We compared their initial p-BNP levels with WMSI and the Gensini score. Additionally, peak troponin-T level was compared with p-BNP level in NSTE myocardial infarction (MI) patients. Using the multiple regression analysis, adjustments for age, left ventricle (LV) wall stress, LV mass amount and ejection fraction (EF) were made. Patients with LVEF < 45% or age > 75 years or underlying diseases that could elevate BNP levels were excluded from the study. P-BNP level was increased in NSTE ACS patients compared with stable angina patients (133.9 +/- 87.4 vs. 12.2 +/- 9.2 pg/ml, p < 0.05). P-BNP levels were found to correlate with WMSI and the Gensini score in unstable angina (r=0.519, p < 0.01; r=0.680, p < 0.01) and NSTEMI (r=0.716, p < 0.01; r=0.684, p < 0.01) patients, respectively. Additionally, p-BNP levels correlated with the peak troponin-T level in patients with NSTEMI (r=0.700, p < 0.01). P-BNP level might be a useful marker in the assessment of EMI.

Topics: Acute Disease; Aged; Biomarkers; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Severity of Illness Index

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Dilated; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Severity of Illness Index

Topics: Angiotensin II; Biomarkers; Cardiac Surgical Procedures; Cardiomyopathies; Heart Failure; Heart Ventricles; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Renin; Stroke Volume; Ventricular Function, Left

Activation of the neuroendocrine axis in congestive heart failure is of prognostic significance, and neurohumoral blocking therapy prolongs survival. The hypothesis that surgical reduction of left ventricular size and function decreases neuroendocrine activation is less established. We evaluated the neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy.. Norepinephrine, plasma renin activity, and angiotensin II were measured in 10 patients before and 12 months after left ventricular reconstruction. In an additional 5 patients, brain natriuretric peptide was measured before and 3 months postoperatively. Three-dimensional cardiovascular imaging was used to assess ejection fraction and left ventricular end-diastolic volume index.. Concurrent with improvements of New York Heart Association functional class (2.9 +/- 0.5 preoperatively vs 2.0 +/- 0.4 postoperatively, P <.001), ejection fraction (23.9% +/- 6.6% vs 36.2% +/- 6.2%, P <.01), and left ventricular end-diastolic volume index (140.8 +/- 33.8 mL/m(2) vs 90.6 +/- 18.3 mL/m(2), P <.01), considerable reductions were observed for median plasma profiles of norepinephrine (562.0 pg/mL vs 319.0 pg/mL, P <.05), plasma renin activity (5.75 microg/L/h vs 3.45 microg/L/h, P <.05), angiotensin II (41.0 ng/mL vs 23.0 ng/mL, P =.051), and brain natriuretric peptide (771.0 pg/mL vs 266.0 pg/mL, P <.05). The more plasma renin activity or angiotensin II decreased after left ventricular reconstruction, the higher was the increase in ejection fraction (R = -.745, P <.05 [plasma renin activity]; R = -.808, P <.05 [angiotensin II]).. Surgical improvements of ejection fraction and left ventricular end-diastolic volume index by left ventricular reconstruction were accompanied by improvement of both the neuroendocrine activity and the functional status in patients with congestive heart failure. Whether this favorable neurohormonal response is predictive of an improved survival requires further evaluation.

Topics: Aged; Angiotensin II; Biomarkers; Cardiac Surgical Procedures; Cardiomyopathies; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Renin; Statistics as Topic; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Topics: Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Risk Assessment; Risk Factors

Angiogenic gene therapy in angina pectoris has been disappointing so far. Reasons might be that the administered genes already are overexpressed in ischemic myocardium, or that atrial and brain natriuretic peptides (ANP and BNP) are overexpressed, as they have anti-angiogenic effects. Five stable angina pectoris patients without heart failure were studied. Left ventricular biopsies were taken during coronary by-pass surgery from a region with stress-inducible ischemia and from a normal region. Both ANP and BNP but not vascular endothelial growth factor (VEGF) and VEGF-receptor 1 and 2 were overexpressed in ischemic regions compared to non-ischemic regions as measured by real-time PCR. The expression of 15 other angiogenic genes measured by oligonucleotide arrays was not consistently increased in ischemic regions. The overexpression of ANP and BNP suggests an anti-angiogenic effect in ischemic heart disease. The lack of overexpression of angiogenic genes supports the concept of therapeutic overexpression of these genes.

Topics: Aged; Angina Pectoris; Atrial Natriuretic Factor; Female; Gene Expression Regulation; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Oligonucleotide Array Sequence Analysis; Tissue Distribution; Vascular Endothelial Growth Factor A

Topics: AIDS Serodiagnosis; Bacterial Infections; Blood Glucose; Heart Failure; Hematologic Tests; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Point-of-Care Systems; Reagent Kits, Diagnostic

Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated.. Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group.. Intravenous administration of ANP had beneficial effects on LV remodeling, function, and fibrosis after LVR. ANP could be a useful intravenous infusion drug for postoperative management after LV repair surgery.

Topics: Animals; Atrial Natriuretic Factor; Calcium-Transporting ATPases; Drug Evaluation, Preclinical; Fibrosis; Gene Expression Profiling; Heart Aneurysm; Humans; Hypertrophy, Left Ventricular; Infusion Pumps, Implantable; Infusions, Intravenous; Ligation; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Renin-Angiotensin System; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Single-Blind Method; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ventricular Remodeling

Brain natriuretic peptide (BNP) levels were measured in 100 patients with coronary heart disease (CHD) who underwent myocardial stress thallium-201 single-photon emission computed tomography (30 with stable angina without basal electrocardiographic ischemia and no perfusion defects, 31 with angina with electrocardiographic ischemia and reversible perfusion defects, and 39 with myocardial infarction and irreversible defects) and in 42 controls. BNP levels progressively increased in patients with CHD and were significantly greater in patients with ischemia (p <0.01) and infarction (p <0.001) compared with controls and subjects with angina. BNP concentration was correlated positively (r = 0.923, p <0.001) with perfusion defect extent and inversely (r = -0.690, p <0.001) with the left ventricle ejection fraction (not different in the subjects examined).

Topics: Analysis of Variance; Angina Pectoris; Electrocardiography; Female; Humans; Linear Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Sensitivity and Specificity; Statistics, Nonparametric; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

Inflammation has a pathogenetic role in acute myocardial infarction (MI). Pentraxin-3 (PTX3), a long pentraxin produced in response to inflammatory stimuli and highly expressed in the heart, was shown to peak in plasma approximately 7 hours after MI. The aim of this study was to assess the prognostic value of PTX3 in MI compared with the best-known and clinically relevant biological markers.. In 724 patients with MI and ST elevation, PTX3, C-reactive protein (CRP), creatine kinase (CK), troponin T (TnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assayed at entry, a median of 3 hours, and the following morning, a median of 22 hours from symptom onset. With respect to outcome events occurring over 3 months after the index event, median PTX3 values were 7.08 ng/mL in event-free patients, 16.12 ng/mL in patients who died, 9.12 ng/mL in patients with nonfatal heart failure, and 6.88 ng/mL in patients with nonfatal residual ischemia (overall P<0.0001). Multivariate analysis including CRP, CK, TnT, and NT-proBNP showed that only age > or =70 years (OR, 2.11; 95% CI, 1.04 to 4.31), Killip class >1 at entry (OR, 2.20; 95% CI, 1.14 to 4.25), and PTX3 (>10.73 ng/mL) (OR, 3.55; 95% CI, 1.43 to 8.83) independently predicted 3-month mortality. Biomarkers predicting the combined end point of death and heart failure in survivors were the highest tertile of PTX3 and of NT-proBNP and a CK ratio >6.. In a representative contemporary sample of patients with MI with ST elevation, the acute-phase protein PTX3 but not the liver-derived short pentraxin CRP or other cardiac biomarkers (NT-proBNP, TnT, CK) predicted 3-month mortality after adjustment for major risk factors and other acute-phase prognostic markers.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Creatine Kinase; Electrocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Prospective Studies; Protein Isoforms; Serum Amyloid P-Component; Treatment Outcome; Troponin T

The purpose of this study was to examine the effect of exercise-induced ischemia on levels of B-type natriuretic peptide (BNP) and its inactive N-terminal fragment (NT-pro-BNP)and to determine whether measurement of these peptides can improve the diagnostic accuracy of exercise testing.. The ability of exercise testing to detect coronary artery disease (CAD) is limited by modest sensitivity and specificity. B-type natriuretic peptides (NT-pro-BNP and BNP) are released by ventricular myocytes in response to wall stress. We hypothesized that exercise-induced ischemia results in increased wall stress and triggers release of NT-pro-BNP and BNP.. A total of 74 patients with known CAD, normal left ventricular function, and normal resting levels of NT-pro-BNP and BNP who were referred for exercise testing with radionuclide imaging, and 21 healthy volunteers, were enrolled. Blood was drawn before and after maximal exercise and analyzed for NT-pro-BNP and BNP.. Of the patients with CAD, 40 had ischemia on perfusion images and 34 did not. Median post-exercise increases in NT-pro-BNP and BNP (DeltaNT-pro-BNP and DeltaBNP) were approximately four-fold higher in the ischemic group than in the nonischemic group (DeltaNT-pro-BNP 14.5 vs. 4 pg/ml, p < 0.0001; DeltaBNP 36.5 vs. 7.5 pg/ml, p < 0.0001). In volunteers, median DeltaNT-pro-BNP was almost identical to that of the nonischemic patient group. At equal specificity to the electrocardiogram (ECG) (58.8%), the sensitivities of DeltaNT-pro-BNP and DeltaBNP for detecting ischemia were 90% and 80%, respectively; in contrast, the sensitivity of the exercise ECG was 37.5%.. Measurement of exercise-induced increases in BNPs more than doubles the sensitivity of the exercise test for detecting ischemia with no loss of specificity.

Topics: Adult; Case-Control Studies; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Radionuclide Imaging; ROC Curve; Sensitivity and Specificity

The aim of this study was to determine the effect of transient myocardial ischemia on circulating natriuretic peptide levels.. Natriuretic peptides are released by the heart in response to wall stress. We hypothesized that transient myocardial ischemia would cause acute changes in circulating natriuretic peptide levels.. B-type natriuretic peptide (BNP), N-terminal fragment of BNP pro-hormone (NT-pro-BNP), and N-terminal fragment of atrial natriuretic peptide pro-hormone (NT-pro-ANP) levels were measured in 112 patients before, immediately after, and 4 h after exercise testing with nuclear perfusion imaging.. Baseline levels of BNP were associated with the subsequent severity of provoked ischemia, with median levels of 43, 62, and 101 pg/ml in patients with none, mild-to-moderate, and severe inducible ischemia, respectively (p = 0.03). Immediately after exercise, the median increase in BNP was 14.2 pg/ml in patients with mild-to-moderate ischemia (p = 0.0005) and 23.7 pg/ml in those with severe ischemia (p = 0.017). In contrast, BNP levels only rose by 2.3 pg/ml in those who did not develop ischemia (p = 0.31). A similar relationship was seen between baseline NT-pro-BNP levels and inducible ischemia, but the changes in response to ischemia were less pronounced. NT-pro-ANP levels rose with exercise in both ischemic and non-ischemic patients. When added to traditional clinical predictors of ischemia, a post-stress test BNP >or=80 pg/ml remained a strong and independent predictor of inducible myocardial ischemia (odds ratio 3.0, p = 0.025).. Transient myocardial ischemia was associated with an immediate rise in circulating BNP levels, and the magnitude of rise was proportional to the severity of ischemia. These findings demonstrate an important link between the severity of an acute ischemic insult and the circulating levels of BNP.

Topics: Atrial Natriuretic Factor; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Natriuretic Peptides; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Radionuclide Imaging; Sensitivity and Specificity; Severity of Illness Index

Congestive heart failure is accompanied by increased cardiac brain natriuretic peptide (BNP) gene expression with elevated plasma concentrations of BNP and its precursor, proBNP. We investigated if myocardial ischemia in the absence of overt heart failure may be another mechanism for increased myocardial BNP expression. The BNP expression was examined in hypoxic myocardium of patients undergoing coronary bypass grafting surgery, in patients with coronary artery disease and normal left ventricular function undergoing percutaneous transluminal intervention therapy, and in heart failure patients without coronary artery disease. BNP mRNA was quantified by real-time PCR, and plasma BNP and proBNP concentrations were measured with radioimmunoassays. Quantitative analysis of BNP mRNA in atrial and ventricular biopsies from coronary bypass grafting patients revealed close associations of plasma BNP and proBNP concentrations to ventricular, but not atrial, BNP mRNA levels. Plasma BNP and proBNP concentrations were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. These results are compatible with the notion that myocardial ischemia, even in the absence of left ventricular dysfunction, augments cardiac BNP gene expression and increases plasma BNP and proBNP concentrations. Thus, elevated BNP and proBNP concentrations do not necessarily reflect heart failure but may also result from cardiac ischemia.

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Artery Disease; Gene Expression Regulation; Heart Atria; Heart Ventricles; Humans; Models, Cardiovascular; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; RNA, Messenger

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Ventricular Remodeling

Topics: Acute Disease; Aged; Aged, 80 and over; C-Reactive Protein; E-Selectin; Endothelin-1; Female; Heart Failure; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; P-Selectin; Pulmonary Edema; Sympathomimetics; Tumor Necrosis Factor-alpha

In the general population, plasma concentrations of cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptides (NT-proBNP) are useful as markers of cardiac ischemia and heart failure respectively. Whether these cardiac markers have similar diagnostic potential in chronic dialysis patients are not known. The authors studied the diagnostic value of cTnT and NT-proBNP correlated with the clinical status of 63 chronic renal failure (CRF) patients with chronic dialysis (30 males and 33 females), aged 26 to 77 years (mean +/- SD, 55.9 +/- 12.6 years). Plasma cTnT and NT-proBNP were determined by using Elecsys 2010 (Roche, Switzerland). The authors found that 23.8 per cent of the chronic dialysis patients had cTnT concentrations more than the cut-off (> or = 0.1 ng/ml) and 100 per cent of these patients had NT-proBNP concentrations over the cut-off (> 334 pg/ml). The authors could not demonstrate the statistical difference between males and females for NT-proBNP concentrations as reported in the general population. But cTnT concentrations in females were significantly less than males. The authors also found a weak correlation between the two markers, when the circulating cTnT was correlated with NT-proBNP. These results suggested that plasma cTnT in chronic dialysis patients should be a prognostic marker for cardiac ischemia by using the same cut-off as the normal population. However, plasma NT-proBNP concentrations could not be used as a heart failure marker in this group of patients and needed another cut-off value for specific use in chronic dialysis patients. Moreover, the combination of cTnT and NT-proBNP concentrations in these patients may be another choice for detection of both cardiac ischemia and heart failure in the same situation. These combination markers should improve mortality in chronic dialysis patients.

Topics: Adult; Aged; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Dialysis; Troponin T

The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.. We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction < or =40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.. Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormalities had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.. Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

Topics: Aged; Aged, 80 and over; Cardiomegaly; Diastole; Echocardiography, Doppler; Edema; Family Practice; Female; Heart Failure; Humans; Kidney; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Protein Precursors; Radiography; ROC Curve; Systole; Ventricular Dysfunction

Physical training in cardiac patients can increase exercise capacity and reduce plasma brain natriuretic peptide(BNP) concentration, but these effects may depend on the etiology of cardiac disease. The change in exercise capacity and BNP during the training period were investigated in patients with different cardiac diseases.. Ninety-one patients after coronary artery bypass grafting(CABG) and 78 patients after valve replacement (VR) underwent a symptom-limited incremental cardiopulmonary exercise test before (1 month) and 6 months after physical training. Anaerobic threshold and peak oxygen uptake(peak-Vo2) were measured during the cardiopulmonary exercise test. Before each cardiopulmonary exercise test, a blood sample was obtained in the resting condition for measuring BNP.. Anaerobic threshold and peak-Vo2 were increased significantly from 1 month to 6 months in both groups. BNP in the CABG group indicated a tendency to decrease (194.6 +/- 155.3-->144.2 +/- 232.2 pg/ml, p < 0.1) from 1 month to 6 months. BNP in VR group was significantly decreased (159. 9 +/- 115.5-->112.8 +/- 131.7 pg/ml, p < 0.05) during the training period. The CABG group showed a significant negative correlation between peak-Vo2 and BNP at 1 month(r = -0.28, p < 0.01) and at 6 months(r = -0.39, p = 0.001). The VR group showed a significant negative correlation between peak-Vo2 and BNP at 6 months(r = -0.32, p < 0.01), but not at 1 month.. Six months of physical training in patients after cardiac surgery may improve exercise capacity and reduce BNP. BNP concentration in the VR group before physical training did not reflect functional capacity.

Topics: Aged; Cardiac Surgical Procedures; Coronary Artery Bypass; Exercise Tolerance; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Postoperative Period

There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.

Topics: Angiotensin II; Atrial Natriuretic Factor; Endothelin-1; Growth Substances; Humans; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Pericardial Effusion; Prognosis; Receptors, Tumor Necrosis Factor

This study noninvasively examined total creatine (CR) of the myocardium in dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) using proton magnetic resonance spectroscopy ((1)H-MRS).. Abnormalities in CR metabolism in failing hearts have been reported. A biochemical study suggested that myocardial metabolic changes are very similar in DCM and HCM despite the different heart failure (HF) mechanisms.. Using cardiac-gated (1)H-MRS with magnetic resonance image (MRI)-guided point-resolved spectroscopy (PRESS) localization, we quantitatively measured septal CR. Patients with either DCM (n = 11) or HCM (n = 7) and age-matched normal subjects (n = 14) were examined.. Myocardial CR was significantly lower in DCM patients (16.1 +/- 4.5 micromol/g wet weight [range 10.2 to 22.9], p < 0.05) than that in subjects with normal hearts (27.6 +/- 4.1 micromol/g [range 21.4 to 36.2]). Myocardial CR in HCM patients (22.6 +/- 8.1 micromol/g [range 12.2 to 34.5]) was significantly lower than that in subjects with normal hearts (p < 0.05) but was significantly higher than that in DCM patients (p < 0.05). In 18 patients with either DCM or HCM, myocardial CR correlated positively with left ventricular ejection fraction (LVEF) (y = 0.22x + 9.8, r = 0.73, p = 0.0006) but correlated negatively with plasma B-type natriuretic peptide (BNP) levels (y = -0.012x + 22.4, r = -0.54, p = 0.022).. This study showed that (1)H-MRS can noninvasively detect CR depletion associated with the severity of HF in cardiomyopathy.

Topics: Adult; Cardiomyopathy, Dilated; Creatine; Disease Progression; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Protons; Stroke Volume; Ventricular Function, Left

In patients with symptoms of heart failure, elevations in B-type natriuretic peptide (BNP) accurately identify ventricular dysfunction. However, BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevations in BNP.. To determine whether BNP elevations are associated with myocardial ischemia, we measured plasma BNP levels before performing exercise treadmill testing with stress echocardiography in outpatients with stable coronary disease. Of the 355 participants, 113 (32%) had inducible ischemia. Compared with participants in the lowest BNP quartile (0 to 16.4 pg/mL), those in the highest quartile of BNP (> or =105 pg/mL) had double the risk of inducible ischemia (adjusted relative risk, 2.0; 95% CI, 1.2 to 2.6; P=0.008). The relation between elevated BNP levels and inducible ischemia was especially evident in the 206 participants who had a history of myocardial infarction (adjusted relative risk, 2.6; 95% CI, 1.5 to 3.7, P=0.002) and was absent in those without a history of myocardial infarction (adjusted relative risk, 1.0; 95% CI, 0.3 to 2.2; P=0.9). This association between BNP levels and inducible ischemia remained strong after adjustment for measures of systolic and diastolic dysfunction.. Elevated levels of BNP are independently associated with inducible ischemia among outpatients with stable coronary disease, particularly among those with a history of myocardial infarction. The observed association between BNP levels and ischemia may explain why tests for BNP are not specific for ventricular dysfunction among patients with coronary disease.

Topics: Aged; Cohort Studies; Coronary Disease; Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies

Natriuretic peptides can be used as markers of heart failure, its severity and also in the differential diagnosis of dyspnea. Moreover, the dynamics of natriuretic peptides in physical standardized exercise may be used in the assessment of latent heart failure.. Can determination of NT-proBNP be used in the diagnosis of exercise-induced ischemia or latent heart failure? 18 probands (10 men, 8 women) under study were risk persons with unspecified ECG, without signs of manifest heart failure. They were subjected to ergometric bike exercises up to the subjective maximum, SPECT myocardium with estimated ejection fraction of the left ventricle at peak ergometric exercise. The following parameters were followed-up: a) before ergometric exercise: NT-proBNP, CRP, TNF-alpha, Hb, Htc, lactate b) at subjective maximum: NT-proBNP, Hb, Htc, lactate c) 30 min after stopping the exercise: NT-proBNP d) 60 min after stopping the exercise: NT-proBNP. The volume blood changes were taken into account (estimation from the dynamics of Htc, Hb with calculation of metabolic changes of NT-proBNP). To evaluate the dynamics of NT-proBNP, the group was divided into subgroups according to the results obtained in ergometric exercises.. initial values of NT-proBNP within normal limits (< 59 pmol/l, 500 ng/l) in 94%, the submaximal pulse rate was reached in 94%, ischemic changes in ECG were observed in 59%, typical clinical signs of heart ischemia were recorded in 35%. Signs of heart dysfunction according to SPECT were found in 47% and ischemic symptoms were observed in 43%. In general, the plasmatic volume decreased by 24% at maximal exercise. Lactate concentration in the plasma increased in all cases. Conversion of NT-proBNP into volume blood changes revealed that increased NT-proBNP occurred only in 22%. Differences between NT-proBNP before exercises and at maximal exercise prior and after correction into volume blood changes were statistically insignificant. 30 and 60 min after the exercise, no significant differences were found in NT-proBNP concentrations. Dividing into subgroups according to the results of ergometric exercises, showed no significant differences in NT-proBNP concentrations. Dynamics of NT-proBNP changes during and after ergometric exercises cannot be used for the diagnosis of exercise-induced heart failure. The high stability of NT-proBNP related to physical activity was confirmed.

Topics: Biomarkers; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Tomography, Emission-Computed, Single-Photon

To determine the contributors to elevating plasma brain natriuretic peptide (BNP) concentrations in older people with normal systolic function. To investigate the relationship between cyclic guanosine monophosphate (cGMP) and BNP in older people with and without ischemic heart disease (IHD).. Observational study.. Hospitalized patients in Nagoya University Hospital from November 1997 to May 2000.. Younger patients (<65) without IHD (n = 31), older patients (> or=65) without IHD (n = 37), and older patients with stable IHD (n = 32). All participants showed 45% or greater of their left ventricular ejection fraction (LVEF).. LVEF, peak atrial velocity/peak early velocity (A/E) ratio at the mitral valve, and left ventricular mass volume were measured using transthoracic echocardiogram. Plasma BNP level, cGMP, and serum creatinine (Scr) were measured. Creatinine clearance (CLcr) was calculated based on 24-hour urine collection.. Plasma BNP levels in older people with and without IHD were significantly greater than in younger patients (mean +/- standard deviation = 76.4 +/- 96.0 (P <.001), 165.2 +/- 200.6 (P <.001), and 8.1 +/- 7.0, respectively). By simple regression analysis, in the groups without IHD, the logarithm of plasma BNP (Log BNP) concentrations had a significant positive relationship with age (R = 0.657, P <.001), Scr (R = 0.449, P <.001), and A/E ratio (R = 0.326, P =.003) and a significant negative relationship with CLcr (R = -0.663, P <.001). A stepwise multiple regression analysis with Log BNP level as the dependent variable and age, Scr, CLcr, and A/E ratio as independent variables showed that CLcr was a significant independent contributor in groups without IHD (R = -0.766, P <.001). In this analysis, the regression coefficient of the intercept was 2.006, and that of CLcr was -0.010. The cGMP/BNP ratio in older subjects with stable IHD tended to be lower than in those without IHD (P =.063).. Elevated BNP levels in older patients with normal systolic function may be in part due to latent renal dysfunction, despite normal Scr levels. In healthy older people, it is important to exclude the effects of latent renal function in assessing cardiac function according to BNP level. In older subjects with stable IHD, the cGMP/BNP ratio tended to be lower than in those without IHD. This may be a reflection of a poor response of cGMP to BNP.

Topics: Aged; Creatinine; Cyclic GMP; Female; Humans; Kidney Diseases; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume

Atrial natriuretic peptide (ANP) release is increased in patients with ischaemic left ventricular dysfunction. A beneficial effect of naloxone on recovery from myocardial stunning was shown previously. The aim of this study was to investigate the effects of naloxone on ANP release during regional myocardial ischaemia and stunning in awake dogs.. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure (LVP), LV dP x dtmax/min(-1), and myocardial wall-thickening fraction. An occluder around the left anterior descending artery (LAD) allowed induction of reversible ischaemia in the LAD-perfused myocardium. Each dog underwent two ischaemic episodes (randomized crossover fashion; separate days): 10 min of LAD occlusion (1) after application of naloxone (63 microg kg(-1)), and (2) without naloxone. ANP levels were measured at baseline (BL) and at predetermined time points until complete recovery of myocardial stunning occurred.. LAD ischaemia-induced release of ANP (peak level: 182 (30) vs 27 (7) pg ml(-1) BL) only in the control group without naloxone. Between 1 and 180 min of reperfusion, ANP levels were significantly higher only in the control group (P<0.05).. Pre-ischaemic application of naloxone prevents this ischaemia-induced ANP-release in conscious dogs.

Topics: Animals; Atrial Natriuretic Factor; Blood Flow Velocity; Cross-Over Studies; Dogs; Female; Hemodynamics; Male; Myocardial Ischemia; Myocardial Stunning; Naloxone; Narcotic Antagonists; Natriuretic Peptide, Brain

We measured plasma atrial/brain natriuretic peptide (ANP/BNP) levels at rest and during exercise and correlated the results with various clinical findings, particularly with myocardial ischemia, in asymptomatic hypertrophic cardiomyopathy (HCM).. In patients with HCM, ANP and BNP levels are elevated and exercise-induced myocardial ischemia is common. However, it has not yet been elucidated how these levels at rest and their change with dynamic exercise are related to ischemia.. Levels of ANP and BNP were measured at rest and at peak exercise during (99m)Tc-tetrofosmin scintigraphy in 31 asymptomatic patients with non-obstructive HCM and in 10 control subjects.. Levels of ANP and BNP at rest and the change of ANP and BNP levels (PG/ML) from rest to exercise were significantly greater in HCM than in control subjects (ANP: rest, 53.2 +/- 31.8 vs. 11.6 +/- 6.1; exercise, 114.5 +/- 74.8 vs. 28.3 +/- 23.4. BNP: rest, 156.7 +/- 104.1 vs. 9.8 +/- 9.6; exercise, 201.6 +/- 131.5 vs. 13.2 +/- 14.5). Septal perforator compression (SPC) and exercise-induced ischemia were observed, respectively, in 20 (64.5%) and in 19 (61.3%) patients with HCM. The increment of ANP during exercise was similar between HCM subgroups with or without inducible ischemia. However, BNP levels at rest and BNP increments during exercise were significantly greater in the HCM subgroup with inducible ischemia than in the subgroup without (rest, 190.5 +/- 116.2 vs. 103.1 +/- 48.3; exercise, 250.5 +/- 142.2 vs. 124.2 +/- 58.6). Multiple logistic regression analysis revealed that SPC and BNP levels at rest were independently associated with exercise-induced ischemia.. Measurement of plasma BNP levels at rest may be useful in predicting silent myocardial ischemia in HCM.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Reference Values

Experimental studies have demonstrated that adrenomedullin (AM) has a positive inotropic action and exerts inhibitory effects against ventricular remodelling as an autocrine and paracrine factor. However, there is no clinical evidence for AM acting as a local regulator in the human heart. We measured the levels of various molecular forms of AM, i.e. an active form of mature AM (AM-m), an intermediate inactive form of glycine-extended AM (AM-Gly) and total AM (AM-T=AM-m+AM-Gly), in plasma and pericardial fluid using our newly developed immunoradiometric assay in consecutive 67 patients undergoing coronary artery bypass graft surgery. Pericardial fluid and plasma cAMP, atrial natriuretic peptide and brain natriuretic peptide levels were also measured. The relationships between pericardial fluid AM levels and ventricular functions and other hormone levels were analysed. The level of each molecular form of AM in pericardial fluid was closely correlated with that of the other molecular forms of AM in the fluid. However, levels were not correlated with those in plasma. AM-T levels were slightly higher in pericardial fluid than in plasma (+72%; P<0.05), whereas AM-m levels and AM-m/AM-T ratios were markedly higher in pericardial fluid than in plasma (AM-m, +994%; AM-m/AM-T ratio, +443%; both P<0.01). AM-m, AM-Gly and AM-T levels in pericardial fluid were correlated with indices of left ventricular function, and with atrial natriuretic peptide and brain natriuretic peptide levels. Interestingly, AM and cAMP levels were positively correlated in plasma, but negatively correlated in pericardial fluid. In addition, AM-m, AM-Gly and AM-T levels in pericardial fluid were higher in patients with acute coronary syndrome than in those with stable ischaemic heart disease (AM-m, +80%; AM-Gly, +96%; AM-T, +83%; all P<0.01). These results suggest that AM in pericardial fluid reflects cardiac synthesis, and that enhanced cardiac secretion of AM is associated with left ventricular dysfunction, ventricular overload and myocardial ischaemia. Considering that AM has positive inotropic, coronary vasodilatory and anti-remodelling actions, increased cardiac AM may play a compensatory role in the ischaemic and failing myocardium.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Cyclic AMP; Female; Humans; Immunoradiometric Assay; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptides; Pericardial Effusion; Ventricular Function, Left

Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-kappaB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.

Topics: Animals; Atrial Natriuretic Factor; Binding Sites, Antibody; Blotting, Western; Evans Blue; Guanylate Cyclase; Heart Ventricles; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Natriuretic Peptide, Brain; Neutrophils; NF-kappa B; P-Selectin; Peroxidase; Polysaccharides; Receptors, Atrial Natriuretic Factor; Signal Transduction; Time Factors; Up-Regulation

Long term effects of left ventricle (LV) repair surgery (LVR) for ischemic cardiomyopathy are not well understood.. Sixty-nine rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after the left anterior descending artery was ligated. In a second surgery 4 weeks later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group), and 36 underwent rethoracotomy alone (sham group). No medication was used in either group. All rats survived the second surgery. LV end-diastolic dimension as measured by echocardiography, LV fractional shortening, and the maximal end-systolic pressure-volume relationship (E(max)) as calculated from the data by catheter-tipped manometer and echocardiography improved in the LVR group after the second surgery, but LV end-diastolic dimension and E(max) gradually deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks postoperatively.. Initial improvement in LV function and neurohormonal status after LVR did not last for 4 weeks in this rat model when untreated medically. The mechanism of deterioration should be elucidated to improve long-term results of LVR.

Topics: Animals; Cardiac Surgical Procedures; Cardiomyopathies; Disease Models, Animal; Disease Progression; Echocardiography; Heart Ventricles; Hemodynamics; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stroke Volume; Time; Treatment Failure; Ventricular Dysfunction, Left

Brain (B-type) natriuretic peptide (BNP) is known to be secreted predominantly from the myocardium. Brain natriuretic peptide plasma concentrations have been shown to be markedly increased in patients with acute myocardial infarction; however, plasma BNP response during episodes of myocardial ischemia has not been established.. This study was designed to examine plasma BNP in patients with transient myocardial ischemia induced by inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon.. Thirty consecutive patients (26 men and 4 women; mean age 61 years) who underwent PTCA, and another 49 patients (39 men and 10 women; mean age 63 years) who underwent diagnostic coronary angiography were enrolled in this study. Serum BNP concentrations were assayed in all patients.. Plasma BNP was increased significantly with a peak concentration of 66.1 +/- 65.2 pg/ml 24 h after PTCA. Coronary angiography did not cause plasma BNP increase (immediately before 30.4 +/- 29.0 pg/ml, 24 h after 33.7 +/- 30.6 pg/ml). No significant differences were present in hemodynamic parameters measured immediately before and 24 h after PTCA.. Plasma BNP is increased by transient myocardial ischemia induced by PTCA.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Angiography; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Time Factors

The cardiac ATP-sensitive potassium (K(ATP)) channel is potentially composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the cardiac type of sulfonylurea receptor (SUR2A). We reported that cardiac Kir6.1 mRNA and protein are specifically upregulated in the non-ischemic as well as the ischemic regions in rats with myocardial ischemia, suggesting that humoral and/or hemodynamic factors are responsible for this regulation. In the present study, pretreatment with TCV-116, an angiotensin (Ang) II type 1 receptor antagonist, completely inhibited the upregulation of Kir6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 min of coronary artery occlusion followed by 24 h of reperfusion; whereas pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, partly inhibited this upregulation. Except for rats pretreated with TCV-116, Kir6.1 mRNA levels were positively correlated with those for brain natriuretic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not elevated in rats with control myocardial ischemia compared with sham rats. Thus, the stress-related induction of cardiac Kir6.1 mRNA and protein expression under myocardial ischemia is inhibited by pretreatment with an AT1 antagonist, but also in part by an ACE inhibitor, suggesting that activation of local renin-angiotensin system may play a role.

Topics: Angiotensin I; Angiotensin II; Animals; Benzimidazoles; Biphenyl Compounds; Blotting, Northern; Blotting, Western; DNA, Complementary; Lisinopril; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Potassium Channels; Potassium Channels, Inwardly Rectifying; Random Allocation; Rats; Rats, Wistar; Renin-Angiotensin System; RNA; RNA, Messenger; Tetrazoles; Time Factors; Up-Regulation

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Cromakalim; Dogs; Embolization, Therapeutic; Female; Hemodynamics; Hormones; Male; Microspheres; Myocardial Ischemia; Natriuretic Peptide, Brain; Nicorandil; Nitroglycerin; Potassium Channels; Renin; Vasodilator Agents

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

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

Newly discovered circulating peptides, N-terminal pro-brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction.. The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes.. Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Cyclic GMP; Epinephrine; Female; Heart; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norepinephrine; Peptides; Predictive Value of Tests; Prognosis; Radionuclide Imaging; Regression Analysis; Sensitivity and Specificity; Survival Rate; Ventricular Function, Left

In a model of acute ischaemic left ventricular failure in pigs, we compared the plasma levels and cardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N-terminal proatrial natriuretic factor (N-terminal proANF) and brain natriuretic peptide (BNP). Acute ischaemic left ventricular failure was induced by embolization of the left coronary artery with plastic microspheres. Thereafter, treatment was given by an intravenous injection of the angiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatment were documented by measurement of haemodynamic parameters and plasma concentrations of catecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricular failure was accompanied by significant increases in cardiac secretion and plasma levels of all three atrial peptides, which was considerably more pronounced for ANF and N-terminal proANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANF and N-terminal proANF, whereas BNP did not change. These findings indicate that ANF and N-terminal proANF may be better suited than BNP as markers of cardiac preload during the development and treatment of acute heart failure.

Topics: Acute Disease; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Animals; Atrial Natriuretic Factor; Biomarkers; Disease Models, Animal; Embolism; Female; Heart; Heart Failure; Losartan; Male; Microspheres; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Protein Precursors; Swine

The aim of the study was to investigate the release of natriuretic peptides during myocardial ischaemia and reperfusion associated with cardioplegic cardiac arrest. Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in paired arterial, central venous and coronary sinus blood samples in 19 patients undergoing elective coronary artery bypass grafting before aortic crossclamping and 1, 5, 10 and 20 min after aortic declamping. Peak myocardial BNP release after aortic declamping was significantly higher than baseline values before aortic crossclamping. Both peak and cumulative BNP release during reperfusion correlated significantly with the severity of ischaemia, as assessed by myocardial lactate production. In 3 patients with perioperative myocardial ischaemia, cumulative and peak myocardial BNP release after aortic unclamping was markedly higher than in the remaining 16 uneventful patients. Myocardial ANP release during reperfusion was not significantly different from baseline values before aortic crossclamping. In conclusion, our data demonstrate a significantly enhanced myocardial BNP release early during reperfusion of the human heart after global ischaemia associated with cardioplegic cardiac arrest.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Coronary Artery Bypass; Extracorporeal Circulation; Female; Heart Arrest, Induced; Humans; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Troponin; Troponin T

In order to clarify the different secretion profiles of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in response to acute hemodynamic change by volume expansion, we measured plasma ANP and BNP levels after intravenous isotonic saline infusion for 3 min at a rate of 3 ml/kg body weight/min in 15 patients with ischemic heart disease. Plasma ANP and BNP levels before the volume loading were 30.7 +/- 16.7 and 19.4 +/- 24.6 pg/ml, respectively. Five and 10 minutes after infusion, plasma ANP levels rose significantly to 43.5 +/- 20.7 and to 46.0 +/- 22.5 pg/ml, respectively (p < 0.01), and plasma BNP levels rose significantly to 27.3 +/- 30.8 and 24.8 +/- 23.2 pg/ ml, respectively (p < 0.01). The BNP/ANP ratio was not affected by volume loading. The maximum increments of plasma ANP level correlated significantly with those of the mean pulmonary capillary wedge pressure (mPCWP, r = 0.78, p < 0.01) or left ventricular end-diastolic pressure (LVEDP, r = 0.86, p < 0.01). However, there were no significant correlations between the maximum increments of plasma BNP levels and those of mPCWP or LVEDP. Plasma ANP level can be a useful parameter for atrial pressure even if the hemodynamic state change rapidly. However, in an early phase of ventricular overload BNP secretion is not increased sufficiently despite the raised LVEDP, and plasma BNP level may not always reflect ventricular hemodynamics.

Topics: Atrial Natriuretic Factor; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Sodium Chloride

This study was designed to examine the plasma levels of B-type or brain natriuretic peptide (BNP), as well as A-type or atrial natriuretic peptide (ANP) in patients with unstable angina as compared with those in patients with stable exertional angina and control subjects. We measured the plasma levels of BNP and ANP in 33 patients with unstable angina, 20 patients with stable exertional angina, and 20 control subjects. The plasma levels of BNP were significantly increased in patients with unstable angina compared with those in patients with stable exertional angina and control subjects, respectively (39.5 +/- 29.4 pg/ml vs 15.1 +/- 8.0 pg/ml; p < 0.01 and 39.5 +/- 29.4 pg/ml vs 10.3 +/- 6.4 pg/ml; p < 0.01, respectively). On the other hand, there was no significant difference in the plasma levels of ANP among the three groups. Furthermore, in patients with unstable angina, the plasma levels of BNP decreased significantly after the medical treatment (from 39.5 +/- 29.4 pg/ml to 15.8 +/- 11.0 pg/ ml; p < 0.01), whereas the plasma levels of ANP did not change. We conclude that the plasma levels of BNP are increased in the majority of patients with unstable angina and that the increased levels decrease toward normal after treatment.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Atrial Natriuretic Factor; Cardiovascular Agents; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Physical Exertion

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Diastole; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Ventricular Function, Left