How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review

Objective To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure. Design Systematic review of studies assessing BNP for prognosis m patients with heart failure or asymptomatic patients. Data sources Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies. Study selection and data extraction We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data. Data synthesis 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance-that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk. Conclusion Although systematic reviews of prognostic studies have inherent difficulties, including die possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients mid for patients with heart failure at all stages of disease.

Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development

Establishment of the left-right axis is a fundamental process of vertebrate embryogenesis. Failure to develop left-right asymmetry leads to incorrect positioning and morphogenesis of numerous internal organs, and is proposed to underlie the etiology of several common cardiac malformations. The transcriptional modulator Cited2 is essential for embryonic development: Cited2-null embryos die during gestation with profound developmental abnormalities, including cardiac malformations, exencephaly and adrenal agenesis. Cited2 is also required for normal establishment of the left-right axis; we demonstrate that abnormal heart looping and right atrial and pulmonary isomerism are consistent features of the left-right-patterning defect. We show by gene expression analysis that Cited2 acts upstream of Nodal, Lefty2 and Pitx2 in the lateral mesoderm, and of Lefty1 in the presumptive floor plate. Although abnormal left-right patterning has a major impact on the cardiac phenotype in Cited2-null embryos, laterality defects are only observed in a proportion of these embryos. We have therefore used a combination of high-resolution imaging and three-dimensional (3D) modeling to systematically document the full spectrum of Cited2-associated cardiac defects. Previous studies have focused on the role of Cited2 in cardiac neural crest cell development, as Cited2 can bind the transcription factor Tfap2, and thus affect the expression of Erbb3 in neural crest cells. However, we have identified Cited2-associated cardiac defects that cannot be explained by laterality or neural crest abnormalities. In particular, muscular ventricular septal defects and reduced cell density in the atrioventricular (AV) endocardial cushions are evident in Cited2-null embryos. As we found that Cited2 expression tightly correlated with these sites, we believe that Cited2 plays a direct role in development of the AV canal and cardiac septa. We therefore propose that, in addition to the previously described reduction of cardiac neural crest cells, two other distinct mechanisms contribute to the spectrum of complex cardiac defects in Cited2-null mice; disruption of normal left-right patterning and direct loss of Cited2 expression in cardiac tissues.

Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development

MeCP2 plays a critical role in interpreting epigenetic signatures that command chromatin conformation and regulation of gene transcription. In spite of MeCP2`s ubiquitous expression, its functions have always been considered in the context of brain physiology. In this study, we demonstrate that alterations of the normal pattern of expression of MeCP2 in cardiac and skeletal tissues are detrimental for normal development. Overexpression of MeCP2 in the mouse heart leads to embryonic lethality with cardiac septum hypertrophy and dysregulated expression of MeCP2 in skeletal tissue produces severe malformations. We further show that MeCP2`s expression in the heart is developmentally regulated; further suggesting that it plays a key role in regulating transcriptional programs in non-neural tissues.

Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial

Background. It is not known if the adjustment of antihypertensive therapy based on home blood pressure monitoring (HBPM) can improve blood pressure (BP) control among haemodialysis patients. Methods. This is an open randomized clinical trial. Hypertensive patients on haemodialysis were randomized to have the antihypertensive therapy adjusted based on predialysis BP measurements or HBPM. Before and after 6 months of follow-up, patients were submitted to ambulatory blood pressure monitoring (ABPM) for 24 h, HBPM during 1 week and echocardiogram. Results. A total of 34 and 31 patients completed the study in the HBPM and predialysis BP groups, respectively. At the end of study, the systolic (SBP) and diastolic (DBP) blood pressure during the interdialytic period measured by ABPM were significantly lower in the HBPM group in relation to the predialysis BP group (mean 24-h BP: 135 +/- 12 mmHg/76 +/- 7 mmHg versus 147 +/- 15 mmHg/79 +/- 8 mmHg; P < 0.05). In the HBPM analysis, the HBPM group showed a significant reduction only in SBP compared to the predialysis BP group (weekly mean: 144 +/- 21 mmHg versus 154 +/- 22 mmHg; P < 0.05). There were no differences between the HBPM and predialysis BP groups in relation to the left ventricular mass index at the end of the study (108 +/- 35 g/m(2) versus 110 +/- 33 g/m(2); P > 0.05). Conclusions. Decision making based on HBPM among haemodialysis patients has led to a better BP control during the interdialytic period in comparison with predialysis BP measurements. HBPM may be a useful adjuvant instrument for blood pressure control among haemodialysis patients.

Transfer of Cholesterol and Other Lipids From a Lipid Nanoemulsion to High-density Lipoprotein in Heart Transplant Patients

Background: Beyond the first year after a heart transplant (HT) procedure, patients often develop dyslipidemias, which may be implicated in the genesis of transplant coronary heart disease. High-density lipoprotein (HDL) has a several anti-atherogenic properties, but the status of HDL in HT patients is still controversial. Nonetheless, determination of HDL cholesterol concentration is not sufficient for evaluation of the overall HDL protective role. In this study, a fundamental functional property of HDL, the ability to simultaneously receive the major lipid classes, was tested in HT patients. Methods: Twenty HT patients and 20 healthy normolipidemic subjects paired for gender, age and body mass index were studied. Blood samples were collected after 12-hour fasting for determination of plasma lipids, glucose, paraxonase I (PON 1) activity, HDL diameter and transfer of labeled lipids from an artificial nanoemulsion to HDL. Results: Plasma triglycerides (159 +/- 63 vs 94 +/- 35 mg/dl) and glucose (104 +/- 20 vs 86 +/- 10 mg/dl) were greater in HT patients than in control subjects. HDL cholesterol was lower and HDL diameter was smaller in the HT group (HDL cholesterol: 44 +/- 11 vs 55 +/- 15 mg/dl; HDL diameter: 8.8 +/- 0.6 vs 9.0 +/- 1.2 nm). PON 1 activity did not differ (87 +/- 47 vs 75 +/- 37 nmol/min/ml). The transfer rates of free cholesterol and cholesteryl esters were diminished in HT patients (HT: 8.4 +/- 1.2% and 3.8 +/- 0.6%; controls: 9.7 +/- 1.9% and 4.7 +/- 1.2%, respectively). Conclusions: The transfer of free cholesterol and cholesteryl esters to HDL is diminished in HT patients; disturbance in the ability of HDL to receive lipids may affect the anti-atherogenic properties of the lipoprotein. J Heart Lung Transplant 2009;28:1075-80. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.

Endomyocardial Biopsy as Risk Factor in the Development of Tricuspid Insufficiency After Heart Transplantation

Objective. Endomyocardial biopsy (EMB), which is used to monitor for rejection, may cause tricuspid regurgitation (TR) after orthotopic heart transplantation (OHT). The purpose of this investigation was to examine the occurrence of tricuspid valve tissue in myocardial specimens obtained by routine EMB performed after OHT. Patients and Methods. From January 2000 to July 2008, 125 of the patients who underwent OHT survived more than I month. Their follow-up varied from I month to 8.5 years (mean, 5.1 +/- 3.7 years). EMB was the gold standard examination and myocardial scintigraphy with gallium served as a screen to routinely monitor rejection. Results. Each of 428 EMB including 4 to 7 fragments, totaling 1715 fragments, were reviewed for this study. The number of EMB per patient varied from 3 to 8 (mean, 4.6 +/- 3.5). Histopathological analysis of these fragments showed tricuspid tissue in 4 patients (3.2%), among whom only I showed aggravation of TR. Conclusions. EMB remains the standard method to diagnose rejection after OLT. It can be performed with low risk. Reducing the number of EMB using gallium myocardial scintigraphy or other alternative methods as well as adoption of special care during the biopsy can significantly minimize trauma to the tricuspid valve.