Three-dimensional alignment of the aggregated myocytes in the normal and hypertrophic murine heart.

Several observations suggest that the transmission of myocardial forces is influenced in part by the spatial arrangement of the myocytes aggregated together within ventricular mass. Our aim was to assess, using diffusion tensor magnetic resonance imaging (DT-MRI), any differences in the three-dimensional arrangement of these myocytes in the normal heart compared with the hypertrophic murine myocardium. We induced ventricular hypertrophy in seven mice by infusion of angiotensin II through a subcutaneous pump, with seven other mice serving as controls. DT-MRI of explanted hearts was performed at 3.0 Tesla. We used the primary eigenvector in each voxel to determine the three-dimensional orientation of aggregated myocytes in respect to their helical angles and their transmural courses (intruding angles). Compared with controls, the hypertrophic hearts showed significant increases in myocardial mass and the outer radius of the left ventricular chamber (P < 0.05). In both groups, a significant change was noted from positive intruding angles at the base to negative angles at the ventricular apex (P < 0.01). Compared with controls, the hypertrophied hearts had significantly larger intruding angles of the aggregated myocytes, notably in the apical and basal slices (P < 0.001). In both groups, the helical angles were greatest in midventricular sections, albeit with significantly smaller angles in the mice with hypertrophied myocardium (P < 0.01). The use of DT-MRI revealed significant differences in helix and intruding angles of the myocytes in the mice with hypertrophied myocardium.

Effect of Carvedilol on QT Duration in Paediatric Patients with Congestive Heart Failure.

OBJECTIVE: To investigate the effect of carvedilol on electrocardiographic parameters in children with congestive heart failure. PATIENTS AND METHODS: 18 children with heart failure (aged 2 months-17 years) were treated with carvedilol (initially 0.09 mg/kg/day, slowly increased up to 0.7 mg/kg/day) in addition to conventional therapy with digoxin, ACE inhibitors and diuretics. Twelve-lead rest electrocardiograms (ECGs) and echocardiography were performed in 16 patients with sinus rhythm at baseline and after 1, 2, 4 (n = 14) and 6 months (n = 14) of therapy. ECGs were analysed for heart rate, QT duration and QT dispersion. Echocardiography was performed for analysis of ejection fraction. RESULTS: After 6 months of therapy the mean ejection fraction increased from 37% to 55% (p < 0.05) and mean heart rate decreased by 14% (p < 0.05). Mean QT duration calculated by Bazett's formula (QT(B)) and Fridericia's formula (QT(F)) decreased from 428 msec (372-507 msec) to 387 msec (323-440 msec [QT(B)]; p < 0.05) and from 381 msec (315-466 msec) to 355 msec (309-435 msec [QT(F)]; p < 0.05) following therapy with carvedilol. In contrast, mean QT dispersion did not change significantly (18 msec; 10-40 msec before to 12 msec; 5-20 msec; p > 0.05). CONCLUSION: In conclusion, carvedilol treatment reduced QT duration but not QT dispersion in paediatric patients with heart failure. The decrease in QT duration reflects stabilisation of the action potential, and this may contribute to the improved prognosis in these patients.

NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies.

In cardiology, B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP) are important biomarkers. The importance of these peptides as markers for heart disease in pediatric cardiology is reviewed. The peptide levels are dependent on age, assay, and possibly gender. The normal value range and upper limits for infants and children are needed. To determine reference values, data were combined from four studies that measured NT-proBNP levels in normal infants and children using the same electrochemiluminescence assay. The age intervals for the upper limits of normal were chosen for intervals in which no age-dependent change was observed. Statistical analysis was performed on log-transformed data. A total of 690 subjects (47% males) ages birth to 18 years were included in the review. The levels of NT-proBNP were highest in the first days of life, then showed a marked decline in the first week or weeks. The peptide levels continued to decline gradually with age (r = 0.43; p < 0.001). Male and female levels differed only for children ages 10 to 14 years. However, the upper limit of normal did not differ between the boys and girls in any age group. The findings lead to the conclusion that B-type natriuretic peptide (BNP) and NT-proBNP are important markers for heart disease in pediatric cardiology. The levels of NT-proBNP are highest in the first days of life and decrease drastically thereafter. A mild gradual decline occurs with age throughout childhood. Girls have somewhat higher levels of NT-proBNP during puberty.

Integrated assessment of diastolic and systolic ventricular function using diagnostic cardiac magnetic resonance catheterization: validation in pigs and application in a clinical pilot study.

OBJECTIVES: This study sought to develop and validate a method for the integrated analysis of systolic and diastolic ventricular function. BACKGROUND: An integrated approach to assess ventricular pump function, myocontractility (end-systolic pressure-volume relationship [ESPVR]), and diastolic compliance (end-diastolic pressure-volume relation [EDPVR]) is of high clinical value. Cardiac magnetic resonance (CMR) is well established for measuring global pump function, and catheterization-combined CMR was previously shown to accurately measure ESPVR, but not yet the EDPVR. METHODS: In 8 pigs, the CMR technique was compared with conductance catheter methods (gold standard) for measuring the EDPVR in the left and right ventricle. Measurements were performed at rest and during dobutamine administration. For CMR, the ESPVR was estimated with a single-beat approach by synchronizing invasive ventricular pressures with cine CMR-derived ventricular volumes. The EDPVR was determined during pre-load reduction from additional volume data that were obtained from real-time velocity-encoded CMR pulmonary/aortic blood flow measurements. Pre-load reduction was achieved by transient balloon occlusion of the inferior vena cava. The stiffness coefficient beta was calculated by an exponential fit from the EDPVR. After validation in the animal experiments, the EDPVR was assessed in a pilot study of 3 patients with a single ventricle using identical CMR and conductance catheter techniques. RESULTS: Bland-Altman tests showed good agreement between conductance catheter-derived and CMR-derived EDPVR. In both ventricles of the pigs, dobutamine enhanced myocontractility (p < 0.01), increased stroke volume (p < 0.01), and improved diastolic function. The latter was evidenced by shorter early relaxation (p < 0.05), a downward shift of the EDPVR, and a decreased stiffness coefficient beta (p < 0.05). In contrast, in the patients, early relaxation was inconspicuous but the EDPVR shifted left-upward and the stiffness constant remained unchanged. The observed changes in diastolic function were not significantly different when measured with conductance catheter and CMR. CONCLUSIONS: This novel CMR method provides differential information about diastolic function in conjunction with parameters of systolic contractility and global pump function.

Levels of brain natriuretic peptide in children with right ventricular overload due to congenital cardiac disease.

OBJECTIVE: To evaluate the role of the concentration of brain natriuretic peptide in the plasma, and its correlation with haemodynamic right ventricular parameters, in children with overload of the right ventricle due to congenital cardiac disease. METHODS: We studied 31 children, with a mean age of 4.8 years, with volume or pressure overload of the right ventricle caused by congenital cardiac disease. Of the patients, 19 had undergone surgical biventricular correction of tetralogy of Fallot, 11 with pulmonary stenosis and 8 with pulmonary atresia, and 12 patients were studied prior to operations, 7 with atrial septal defects and 5 with anomalous pulmonary venous connections. We measured brain natriuretic peptide using Triage(R), from Biosite, United States of America. We determined end-diastolic pressures of the right ventricle, and the peak ratio of right to left ventricular pressures, by cardiac catheterization and correlated them with concentrations of brain natriuretic peptide in the plasma. RESULTS: The mean concentrations of brain natriuretic peptide were 87.7, with a range from 5 to 316, picograms per millilitre. Mean end-diastolic pressure in the right ventricle was 5.6, with a range from 2 to 10, millimetres of mercury, and the mean ratio of right to left ventricular pressure was 0.56, with a range from 0.24 to 1.03. There was a positive correlation between the concentrations of brain natriuretic peptide and the ratio of right to left ventricular pressure (r equal to 0.7844, p less than 0.0001) in all patients. These positive correlations remained when the children with tetralogy of Fallot, and those with atrial septal defects or anomalous pulmonary venous connection, were analysed as separate groups. We also found a weak correlation was shown between end-diastolic right ventricular pressure and concentrations of brain natriuretic peptide in the plasma (r equal to 0.5947, p equal to 0.0004). CONCLUSION: There is a significant correlation between right ventricular haemodynamic parameters and concentrations of brain natriuretic peptide in the plasma of children with right ventricular overload due to different types of congenital cardiac disease. The monitoring of brain natriuretic peptide may provide a non-invasive and safe quantitative follow up of the right ventricular pressure and volume overload in these patients.