Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels.
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PMID:Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. 1922 57

We wanted to evaluate if brain natriuretic peptide (BNP) is cleared during continuous veno-venous hemofiltration (CVVH) sessions in children with congenital heart disease. A prospective observational single-center study was conducted in a post-cardiac surgery intensive care unit of the city children's hospital. Ten children requiring CVVH for acute kidney injury following cardiac surgery were enrolled. Seven of them were undergoing postoperative extracorporeal membrane oxygenation. BNP clearance was evaluated by the difference between pre-filter and post-filter BNP blood amount indexed to pre-filter BNP concentration. All CVVH treatments were performed with 0.6 m2 polyacrylonitrile filter, in predilution setting, at a dose of 80 ml/kg/h. Troponin I and myoglobin levels were also measured and CVVH clearances of these markers calculated for comparison with BNP. A significant decrease in post-filter compared with pre-filter levels of BNP was shown in all 10 cases (P<0.01). Median BNP clearance was 35.6 (29-39.3) ml/min. Troponin I and myoglobin levels did not show any significant drop between pre- and post-filter values (P>0.05) and their clearance was significantly lower than BNP (P: 0.0004). A daily analysis of BNP levels showed a significant decrease of its blood concentration. BNP levels were significantly reduced after three and four days from CVVH start (P<0.05). During 80 ml/kg/h CVVH, utilizing polyacrylonitrile membranes, BNP is efficiently cleared from blood in a small cohort of pediatric post-cardiosurgical patients. In this situation, BNP absolute blood levels may be unpredictable.
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PMID:Brain natriuretic peptide is removed by continuous veno-venous hemofiltration in pediatric patients. 1954 92

Blood cystatin C has increasingly been used as an endogenous marker for estimating glomerular filtration rate (GFR) and evaluating prognosis in patients with acute or chronic heart failure. The goal of the study was to investigate the impact of heart failure on the determination of renal function based on cystatin C or creatinine in nonacute cardiac patients. A total of 880 consecutive and clinically stable patients with heart disease were prospectively evaluated. Serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) showed a stronger correlation with cystatin C (r = 0.60, p <0.001) compared with creatinine (r = 0.46, p <0.001). Multivariate analysis identified estimated GFR according to the MDRD Study formula (p <0.001), serum NT-pro-BNP (p <0.001), use of immunosuppressive agents (p <0.001), and allopurinol treatment (p <0.001) as the strongest independent predictors of serum cystatin C. Parallel measurement of creatinine clearance using timed urine collection in a subgroup of 160 patients showed that estimated GFR according to cystatin C was almost identical to measured creatinine clearance independent of NT-proBNP. Conversely, creatinine-based calculation using the MDRD Study formula underestimated GFR in patients from the low (12 to 238 pg/ml) and medium (241 to 990 pg/ml) NT-pro-BNP tertiles. In conclusion, in patients without severe heart failure, indicated by low serum NT-pro-BNP, estimation of GFR using creatinine-based formulas underestimated renal function. The known prognostic impact of cystatin C in cardiac patients might result from a strong correlation with NT-pro-BNP, as well as its superior ability to predict renal function in patients with and without heart failure.
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PMID:Role of N-terminal pro-brain natriuretic peptide and cystatin C to estimate renal function in patients with and without heart failure. 1936 1

There have been few reports describing the use of carvedilol in children or patients with congenital heart disease. Therefore, its optimal regimen, efficacy, and safety in these patients have not been adequately investigated. Subjects were 27 patients with two functioning ventricles, for whom carvedilol was initiated (from December 2001 to December 2005) to treat heart failure. All patients had failed to respond to conventional cardiac medication. They consisted of 12 males and 15 females, aged 23 days to 47 years (median age: 2 years). Heart failure due to ischemia (myocardial infarction, intraoperative ischemic event) or due to myocardial disease (cardiomyopathy, myocarditis), and heart failure with atrial or ventricular tachyarrhythmia represented 70% of all cases. Carvedilol was initiated at a dose of 0.02-0.05 mg/kg/day, which was increased by 0.05-0.1 mg/kg/day after 2 days, 0.1 mg/kg/day after 5 days, and 0.05-0.1 mg/kg/day every month thereafter with a target dose of 0.8 mg/kg/day. This study retrospectively assessed the efficacy and adverse reactions based on changes of symptoms, cardiothoracic ratio (CTR), left ventricular ejection fraction (LVEF), and human atrial natriuretic peptide (hANP)/b-type natriuretic peptide (BNP) blood levels. The mean follow-up period was 10.2 months (range: 1-46 months). Twenty-six (96.3%) patients showed improvement in symptoms and were discharged from the hospital. However, the remaining one patient failed to respond and died. Significant cardiovascular adverse reaction was seen in none of the patients. The mean CTR decreased from 61.8% +/- 5.3% before treatment to 57.6% +/- 7.4% after treatment (P < 0.05, n = 25), and the mean LVEF improved from 41.4% +/- 23.1% to 61.1% +/- 10.1% (P < 0.05, n = 10), respectively. Mean hANP and BNP levels showed a decrease from 239.1 pg/ml to 118.3 pg/ml and a significant decrease from 437.9 pg/ml to 120.5 pg/ml, respectively (P < 0.05, n = 10). Improvements in these data were also demonstrated when analyzed individually among the pediatric group (aged younger than 18) and the congenital heart disease group. Initiation of carvedilol at a lower dose with more gradual dose escalation, compared with previously reported regimens, might have efficacy with low incidence of adverse effects in pediatric patients and patients with congenital heart disease. Carvedilol may be effective in treating heart failure in children due to ischemia, myocardial disease, and complicated by tachyarrhythmia.
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PMID:Efficacy and safety of carvedilol for heart failure in children and patients with congenital heart disease. 1946 19

In adults without congenital heart disease, B-type natriuretic peptide (BNP) has been shown to be a very sensitive and specific marker of heart failure. The utility of BNP as a marker of clinical heart failure in children with a ventricular septal defect (VSD) has yet to be determined. A prospective, observational study evaluated BNP levels and other measures of heart failure. Eligible patients were <2 years old, scheduled to undergo surgical repair of a VSD, and without other significant structural heart disease. Data collected before and after surgical repair included echocardiographic measurements, electrocardiographic (ECG) findings, Ross score, BNP measurements, and weight gain. A total of 21 patients were enrolled and 14 patients had complete postoperative follow-up data. For patients with complete data, mean BNP decreased by 94 pg/ml (118 pre vs. 24 post; paired t-test, p = 0.041), mean left ventricular end-diastolic dimension z-score decreased by 1.75 (+0.86 vs. -0.89; paired t-test, p = 0.013), mean weight z-score change per month increased by 0.35 (-0.25 vs. +0.10; Wilcoxon test, p = 0.013), and the incidence of biventricular hypertrophy on ECG decreased (46% vs. 0%; McNemar test, p = 0.031). The change in BNP showed a trend toward a negative correlation with weight z-score change per month (r = -0.531, p = 0.075). In conclusion, BNP, along with other measures of heart failure, decreased following VSD repair, and the change in BNP was most closely correlated with improved weight gain.
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PMID:B-type natriuretic peptide and heart failure in patients with ventricular septal defect: a pilot study. 1963 81

Plasma atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have been used for the diagnosis of heart disease. The aim of the study was to investigate differences in secretory responses of plasma ANP and N-terminal proBNP (NT-proBNP) concentrations related to acute changes in preload. Six dogs were anaesthetised and infused intravenously with Ringer's solution (90-100mL/kg/h) for 60 min. Thereafter, furosemide was administered and dogs were monitored for 60 min. Plasma ANP and NT-proBNP concentrations were determined by chemiluminescence enzyme immunoassay and enzyme immunoassay, respectively. Volume overload significantly increased plasma ANP and NT-proBNP concentrations (P<0.001); however, preload reduction significantly reduced plasma ANP concentrations (P<0.05) without concurrent changes in plasma NT-proBNP. Mean pulmonary capillary wedge pressures were strongly correlated with plasma ANP concentrations (r=0.53, P<0.001), but not plasma NT-proBNP. Thus, plasma ANP is a useful, non-invasive parameter for measuring rapid haemodynamic changes.
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PMID:Acute cardiac volume load-related changes in plasma atrial natriuretic peptide and N-terminal pro-B-type natriuretic peptide concentrations in healthy dogs. 1970 13

The growing knowledge about genetic influence on cardiovascular diseases (CVD) combined with the recently generated amounts of genomic data hold promise to the identification of new markers for atherosclerotic CVD. Cardiovascular pharmacogenomics and pharmacogenetics have now the potential for leading to identification of genetic contributors and therefore to the development of predictive genetic tests that could optimize drugs efficacy and minimize toxicity. Clinical studies have shown that genetic variations within cytochromes P450 (CYPs), 3-Hydroxyl-3-Methylglutaryl Coenzyme A Reductase (HMGCR) and apolipoprotein E (APOE) genes influence individual's response to lipid lowering statins. Furthermore, development of antagonists or inhibitors of molecules such as peroxisome proliferator-activated receptors (PPARs), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), angiotensin-converting enzyme (ACE), angiotensin receptors and tumor necrosis factor (TNF)-alpha could be another alternative to prevent atherosclerosis. In addition, novel molecules under the name of biologics including family of peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), urocortin, apelin and antimicrobial peptides (AMPs) could be considered as new targets for the prevention and treatment of CVD. In this article, we will focus mainly on recent genomic advances in the development of new markers and therapeutic agents for CVD. We present an array of molecules that could have pharmacological benefit for the treatment of heart disease. We also discuss in details new strategies including biologics, which are actually the focus of companies for clinical development of therapeutic drugs. All these efforts provide optimism and attractive promise to cure CVD.
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PMID:Genomics and the prospects of existing and emerging therapeutics for cardiovascular diseases. 1975 91

Children with single ventricle physiology have increased ventricular work and are at greater risk of developing heart failure than other children with congenital heart disease. However, the diagnosis of heart failure is difficult because few objective measures have been validated for this cohort. Plasma proteins have been identified as biomarkers of heart failure in adults with structurally normal hearts. However, whether these correlate similarly with heart failure in children with single ventricle physiology is unknown, because the etiology of adult heart failure is typically ischemic heart disease, but heart failure in these children is presumed to be due to primary myocardial dysfunction. We conducted a single-site, cross-sectional observational study of young, single-ventricle patients. Clinical heart failure was defined as a Ross score >2. The association of several candidate biomarkers with heart failure was assessed using logistic regression analysis and receiver operating characteristic curves. Of the 29 included children, 9 (31%) were in clinical heart failure. A doubling of plasma B-type natriuretic peptide was associated with an odds ratio for heart failure of 2.17. The area under the receiver operating characteristic curve was 80.3%. A threshold value of > or =30 pg/ml showed both sensitivity and specificity for heart failure. Three other candidate biomarkers were not associated with clinical heart failure in this sample. In conclusion, plasma B-type natriuretic peptide is a sensitive biomarker for clinical heart failure in young children with single-ventricle heart disease. The use of this plasma biomarker might facilitate detection of heart failure in these complex patients.
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PMID:Usefulness of various plasma biomarkers for diagnosis of heart failure in children with single ventricle physiology. 1984 May 77

Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well characterized. An ongoing characterization of the molecular heterogeneity will help appreciate the biosynthetic capacity of the endocrine heart and could introduce new diagnostic possibilities. Notably, different biosynthetic products may not be equal markers of the same pathophysiological processes. An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology.
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PMID:Biosynthesis of cardiac natriuretic peptides. 1985 77

A 3-year-old girl was diagnosed with restrictive cardiomyopathy (RCM) after showing symptoms of heart failure, and a 6-year-old boy was found to have RCM after abnormal electrocardiographic findings were seen during school-based heart disease screening. Both had typical clinical features of the disease. Plasma levels of brain natriuretic peptide increased significantly in both patients, allowing us to distinguish this disease from constrictive pericarditis which has similar clinical and hemodynamic features. The early diastolic mitral annular velocity recorded by tissue Doppler echocardiography was also useful to discriminate RCM from constrictive pericarditis. The former case successfully received heart transplantation, but the latter case died suddenly prior to receiving a heart transplant. The plasma level of brain natriuretic peptide and tissue Doppler echocardiography helped us to diagnose this disease earlier and follow it more carefully, which has important implications in optimal treatment and improved prognosis of RCM in children.
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PMID:Two cases of restrictive cardiomyopathy in children. 2003 98


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