natriuretic-peptide--brain and Embolism

Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis.. We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index.. From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up.. Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification.

Topics: Aged; Aged, 80 and over; Electrocardiography; Embolism; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke

Topics: Aged; Angioplasty, Balloon; Arteriosclerosis; Biomarkers; Diagnostic Imaging; Embolism; Female; Heart Diseases; Humans; Hypertension, Renovascular; Male; Mass Screening; Meta-Analysis as Topic; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Pulmonary Edema; Randomized Controlled Trials as Topic; Recurrence; Renal Artery Obstruction; Stents; Treatment Outcome

B-type natriuretic peptide (BNP) is a risk factor for stroke and cardiac death in patients with atrial fibrillation. We hypothesized the prognostic outcomes of very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment would vary according to BNP stratification.. In this subanalysis of the ELDERCARE-AF trial, patients were stratified by BNP levels at enrollment, and clinical outcomes compared among BNP subgroups. Hazard ratios were adjusted for age, atrial fibrillation type, body mass index, creatine clearance, congestive heart failure, and D-dimer. BNP levels were measured using chemiluminescence enzyme immunoassays.. In total, 984 patients (average age: 86.6 years) not considered eligible for oral anticoagulant therapy at approved doses for stroke prevention were included. The BNP levels at enrollment were <200 (low), 200 to <400 (moderate), and ≥400 (high) pg/mL in 428, 300, and 256 patients, respectively. The number (%) of patients with stroke or systemic embolism (SSE) was 7 (1.2%), 24 (5.9%), and 28 (8.6%) in the low, moderate, and high BNP subgroups, respectively (adjusted hazard ratio 3.82, P = .0025 for low vs moderate BNP and 4.76, P = .0007 for low vs high BNP). There was no significant difference in major bleeding incidence between the BNP subgroups. Edoxaban 15 mg was associated with a consistent reduction in SSE vs placebo in all BNP subgroups.. Stratification by BNP level was associated with the incidence of SSE for very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment, and the effect of edoxaban 15 mg was consistent across BNP levels.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Humans; Natriuretic Peptide, Brain; Prognosis; Stroke

Cardiac troponin T (cTnT) and I (cTnI) concentrations provide strong prognostic information in anticoagulated patients with atrial fibrillation (AF). Whether the associations between cardiac troponin concentrations and mortality and morbidity differ by sex is not known.. To assess whether men and women have different concentrations and prognostic value of cTnT and cTnI measurements in anticoagulated patients with AF.. cTnT and cTnI concentrations were measured with high-sensitivity (hs) assays in EDTA plasma samples obtained from the multicentre ARISTOTLE trial, which randomized patients with AF and at least one risk factor for stroke or systemic embolic event to warfarin or apixaban. Patients were stratified according to sex and the associations between hs-troponin concentrations, and all-cause death, cardiac death, myocardial infarction, stroke or systemic embolic event and major bleeding were assessed in multivariable regression models.. We found higher cardiac troponin concentrations in men (n = 9649) compared to women (n = 5331), both for hs-cTnT (median 11.8 [Q1-3 8.1-18.0] vs. 9.6 [6.7-14.3] ng L. Men have higher hs-troponin concentrations than women in AF. Regardless of sex, hs-troponin concentrations remain similarly associated with adverse clinical outcomes in anticoagulated patients with AF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Embolism; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Sex Factors; Stroke; Troponin I; Troponin T

Background To explore the pathophysiological features of ischemic stroke in patients with atrial fibrillation (AF), we evaluated the association between 268 plasma proteins and subsequent ischemic stroke in 2 large AF cohorts receiving oral anticoagulation. Methods and Results A case-cohort sample of patients with AF from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, including 282 cases with ischemic stroke or systemic embolism and a random sample of 4124 without these events, during 1.9 years of follow-up was used for identification. Validation was provided by a similar case-cohort sample of patients with AF from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, including 149 cases with ischemic stroke/systemic embolism and a random sample of 1062 without these events. In plasma obtained before randomization, 268 unique biomarkers were measured with OLINK proximity extension assay panels (CVD II, CVD III, and Inflammation) and conventional immunoassays. The association between biomarkers and outcomes was evaluated by random survival forest and adjusted Cox regression. According to random survival forest or Cox regression analyses, the biomarkers most strongly and consistently associated with ischemic stroke/systemic embolism were matrix metalloproteinase-9, NT-proBNP (N-terminal pro-B-type natriuretic peptide), osteopontin, sortilin, soluble suppression of tumorigenesis 2, and trefoil factor-3. The corresponding hazard ratios (95% CIs) for an interquartile difference were as follows: 1.18 (1.00-1.38), 1.55 (1.28-1.88), 1.28 (1.07-1.53), 1.19 (1.02-1.39), 1.23 (1.05-1.45), and 1.19 (0.97-1.45), respectively. Conclusions In patients with AF, of 268 unique biomarkers, the 6 biomarkers most strongly associated with subsequent ischemic stroke/systemic embolism represent fibrosis/remodeling (matrix metalloproteinase-9 and soluble suppression of tumorigenesis 2), cardiac dysfunction (NT-proBNP), vascular calcification (osteopontin), metabolism (sortilin), and mucosal integrity/ischemia (trefoil factor-3). Registration URL: https://www.clinicaltrials.gov. Unique Identifiers: NCT00412984 and NCT00262600.

Topics: Adaptor Proteins, Vesicular Transport; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Embolism; Factor Xa Inhibitors; Female; Humans; Interleukin-1 Receptor-Like 1 Protein; Ischemic Stroke; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Osteopontin; Patient Outcome Assessment; Peptide Fragments; Pyrazoles; Pyridones; Stroke; Thromboembolism; Trefoil Factor-3

Atrial fibrillation (AF) is the most prevalent clinical arrhythmia and a major risk factor for ischaemic stroke. Treatment with oral anticoagulants (OACs) reduces the risk of stroke by two thirds in AF patients with risk factors. Due to its often paroxysmal and asymptomatic presentation, AF is sometimes challenging to diagnose. So far, AF screening studies have applied opportunistic or systematic screening, most often using a single 12-lead electrocardiogram (ECG) recording or ambulatory ECG. We hypothesise that the biomarker N-terminal pro b-type natriuretic peptide (NT-proBNP) is a valuable adjunct in population based AF screening.. We are conducting a randomized population-based study on AF screening using ambulatory ECG recording where the decision to use prolonged intermittent ECG recording is directed by NT-proBNP levels, the STROKESTOP II trial. The entire population of inhabitants 75 or 76 years of age (n = 28 712) in the capital region of Sweden will be randomized 1:1 to intervention or control group. In the intervention group NT-proBNP will be analysed in all without previously known AF. Those with NT-proBNP ≤ 125 pg/L will make a single one lead ECG recording, participants with NTproBNP ≥ 125 np/L will be instructed to record ECG for 30 s at least twice daily for 2 weeks with a handheld ambulatory ECG recorder. Participants with newly diagnosed or undertreated AF will be referred to a cardiologist and offered OAC treatment. Primary endpoint is incidence of stroke or systemic embolus, during a 5 year follow-up period in the control group vs the group invited to screening.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Clinical Protocols; Electrocardiography, Ambulatory; Embolism; Female; Heart Rate; Humans; Male; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Predictive Value of Tests; Research Design; Stroke; Sweden; Treatment Outcome

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984).

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Embolism; Female; Fibrinolytic Agents; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Assessment; Stroke; Warfarin

We investigated whether patients with atrial fibrillation (AF) demonstrate detectable changes in biomarkers including high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of stroke or systemic embolic events (S/SEE) and bleeding.. ENGAGE AF-TIMI 48 was a randomized trial of the oral factor Xa inhibitor edoxaban in patients with AF and a CHADS2 score of ≥2. We performed a nested prospective biomarker study in 6308 patients, analysing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/mL change), GDF-15 in 45.6% (≥300 pg/mL change) during 12 months. In a Cox regression model, upward changes in log2-transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE [adjusted hazard ratio (adj-HR) 1.74; 95% confidence interval (CI) 1.36-2.23 and adj-HR 1.27; 95% CI 1.07-1.50, respectively] and log2-transformed GDF-15 with bleeding (adj-HR 1.40; 95% CI 1.02-1.92). Reassessment of ABC-stroke (age, prior stroke/transient ischaemic attack, hsTnT, and NT-proBNP) and ABC-bleeding (age, prior bleeding, haemoglobin, hsTnT, and GDF-15) risk scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk [net reclassification improvement (NRI) 0.50; 95% CI 0.36-0.65; NRI 0.42; 95% CI 0.33-0.51, respectively].. Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed that a substantial proportion of patients with AF had dynamic values. Greater increases in these biomarkers measured over 1 year are associated with important clinical outcomes in anticoagulated patients with AF.

Topics: Atrial Fibrillation; Biomarkers; Embolism; Humans; Infant; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Assessment; Risk Factors; Stroke

Topics: Aged, 80 and over; Anti-Bacterial Agents; Aortic Valve Stenosis; Ceftriaxone; Computed Tomography Angiography; Embolectomy; Embolism; Endocarditis; Fatal Outcome; Gentamicins; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Streptococcus salivarius; Thrombosis; Transcatheter Aortic Valve Replacement; Ultrasonography, Doppler

The ability of cardiovascular biomarkers to predict the incidence of stroke subtypes remains ill-defined in the general population.Methods and Results:The blood levels of B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) and urinary albumin corrected by urinary creatinine (UACR) were determined in a general population (n=13,575). The ability to predict the incidence of ischemic stroke subtypes (lacunar, atherothrombotic, cardioembolic) for each biomarker was assessed based on the area under the receiver-operating characteristic curve (AUC-ROC) and using Cox proportional hazard modeling. The predictive abilities of UACR and hs-CRP for any subtype of ischemic event were found to be suboptimal. However, the ability of BNP to predict the incidence of cardioembolic stroke was excellent (AUC-ROC=0.81). When BNP was added to established stroke risk factors, the ability to predict cardioembolic stroke in terms of the AUC-ROC significantly improved (4-year follow-up, P=0.018; 8-year follow-up, P=0.009). Furthermore, when BNP was added to the JPHC score, the ability to predict cardioembolic stroke was significantly improved (net reclassification improvement=0.968, P<0.0001: integrated discrimination improvement=0.039, P<0.05).. In the general population, plasma BNP was an excellent biomarker for predicting the incidence of cardioembolic stroke when used alone or in combination with established stroke risk factors.

Topics: Aged; Albumins; Albuminuria; Area Under Curve; Biomarkers; C-Reactive Protein; Embolism; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; ROC Curve; Stroke

Topics: Biomarkers; Brain Ischemia; Embolism; Heart Diseases; Humans; Natriuretic Peptide, Brain; Stroke

Clinical characteristics are important for determining the etiologies of embolic stroke, including patent foramen ovale and complex aortic plaques demonstrated on transesophageal echocardiography (TEE). This study sought to analyze the clinical signs of cryptogenic stroke (CS) without such embolic etiologies and to examine the association between CS and brain natriuretic peptide (BNP), which is currently unknown.. Patients with CS after routine examinations who underwent TEE were included in this single-center observational study. Patients were classified into the potential embolic sources (PES) group (patients having PES on TEE) and the no potential embolic source (NPES) group. Patients were also categorized according to the tertile of BNP.. A total of 158 patients (age, 64.0 ± 13.9 years; 119 males) with CS were enrolled. The PES group had 108 (68%) patients, and the NPES group had 50 (32%). Hypertension was more common, and glucose, D-dimer, and BNP were higher in the NPES than in the PES group (p<0.05). NPES was independently associated with high-BNP tertile (OR: 5.61; 95% CI: 1.91 to 16.44; p=0.002).. BNP, an indicator of cardioembolism, was closely associated with NPES. Cardiogenic mechanisms may be implicated in the etiology of CS without potential embolic etiologies on TEE.

Topics: Aged; Echocardiography, Transesophageal; Embolism; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Statistics, Nonparametric; Stroke

There has been debate regarding whether natriuretic peptides can be used as a marker to distinguish cardioembolic (CE) origin of ischemic stroke from other subtypes. Therefore, the aim of this study was to study the value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in differentiating CE from other subtypes of stroke in patients with acute ischemic stroke.. All 125 consecutive patients with acute ischemic stroke in a 1-year period were included. Admission blood samples of all patients were analyzed for the serum level of NT-proBNP. Patients were evaluated for etiology of stroke by imaging modalities and classified based on Trial of Org 10172 in Acute Stroke Treatment criteria. Medical history and risk factors for vascular diseases were also obtained. Receiver operating characteristic (ROC) analysis was used for estimating the diagnostic performance of NT-proBNP levels.. Patients were a mean of 67.5 ± 12.6 years of age, and 60 (48%) were men. The most frequent subtype of stroke (57 patients) was CE (45.6%). Levels of NT-proBNP at admission were significantly higher in the CE group (P = .001). After omitting confounding variables, NT-proBNP levels and age were independent predictors of CE stroke subtype. ROC analysis revealed that the diagnostic performance of NT-proBNP levels (area under the curve), optimum cutoff point and its sensitivity and specificity were 0.882 ± 0.031pg/mL, 342 pg/mL, 93%, and 75%, respectively.. NT-proBNP has an acceptable diagnostic value in distinguishing CE ischemic stroke from other subtypes. It can be used to differentiate the stroke subtype and facilitate the treatment process in these patients.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Brain Ischemia; Chi-Square Distribution; Diagnosis, Differential; Embolism; Female; Heart Diseases; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; ROC Curve; Stroke

The risk of recurrent stroke is likely related to etiology. Therefore it is important to identify which patients are at highest early risk. We evaluated whether selected blood biomarkers may aid in the diagnosis of stroke etiology. We studied consecutive non-lacunar stroke patients between November 2006 and January 2007, and selected undetermined origin strokes. Blood samples were drawn at arrival to test brain natriuretic peptide (BNP), D-dimer, CK-MB, myoglobin, and troponin. Second harmonic transthoracic echocardiography (SHTTE) and ECG-24 h monitoring were also performed within the first 24 h. We evaluated 294 patients with ischemic stroke; 89 had an initial undetermined origin. After a cardiological work-up, 49 were diagnosed as embolic including atrial fibrillation (4), severe aortic arch atheromatosis (24), severe wall abnormalities (12), valve disease (3), dilated cardiomyopathy (1), and patent foramen (5). Higher levels of CK-MB, BNP, and myoglobin were found in patients with embolic source in SHTTE, but only CK-MB >1.5 ng/ml and BNP >64 pg/ml remained as independent predictors: BNP (OR 8.86; CI 95 % 2.79-28.09), CK-MB (OR 6.28; CI 95 % 1.66-23.69). BNP showed specificity of 75 %, sensitivity of 63.4 %, and positive predictive value (PPV) of 75.6 %. CK-MB had specificity of 85 %, sensitivity of 47.9 %, and PPV of 79.3 %. Measuring both biomarkers improves the finding of embolic source, increasing specificity to 95 % and PPV to 88.2 %. High-level CK-MB and BNP during the acute phase of ischemic stroke are associated with an embolic source. Measurement of both biomarkers may improve the diagnosis, guiding the need to perform a heart exploration.

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Creatine Kinase, MB Form; Echocardiography; Embolism; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Stroke

Although serum cardiac troponin I (cTnI) and plasma brain natriuretic peptide (BNP) have become clinically important tools as diagnostic and prognostic markers for ischemic heart disease and heart failure, the usefulness of these biomarkers for risk stratification of hypertrophic cardiomyopathy (HCM) is not clear.. We studied 167 patients with HCM, and cTnI and BNP were measured. During follow-up (38.5 months), 20 patients suffered from cardiovascular events: HCM-related deaths in 6, hospitalization for heart failure in 8, embolic stroke in 5 and 1 patient with spontaneous sustained ventricular tachycardia. Patients with high cTnI values (≥0.04 ng/ml) had more frequent cardiovascular events than did those with low cTnI values (P=0.008). Similarly, there were more frequent adverse events in the high BNP group (≥200 pg/ml) than in the low BNP group (P=0.002). When groups were allocated according to both cTnI and BNP measurements, serum cTnI used in conjunction with BNP further improved the prognostic value; patients with both high cTnI and BNP values had an 11.7-fold increased risk of cardiovascular events compared with those with both low cTnI and BNP values.. CTnI and BNP are useful parameters for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in HCM.

Topics: Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Embolism; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Stroke; Tachycardia, Ventricular; Troponin I

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

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

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