atrial-natriuretic-factor and Tetralogy-of-Fallot

The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot.. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] <50%) but without severe valvular dysfunction were eligible. Patients were randomly assigned between losartan (150 mg daily) and placebo with target treatment duration between 18 and 24 months. The primary outcome was RV EF change, determined by cardiovascular MRI in intention-to-treat analysis.. Losartan had no significant effect on RV dysfunction or secondary outcome parameters in repaired tetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Double-Blind Method; Drug Administration Schedule; Female; Humans; Losartan; Male; Middle Aged; Placebo Effect; Prospective Studies; Protein Precursors; Tetralogy of Fallot; Treatment Outcome; Ventricular Dysfunction, Right

Objective To investigate the influence of surgical correction on biomarkers of endothelial dysfunction in children with congenital heart disease and to evaluate anthropometric data. Methods Children with pulmonary hypertension (PH) or Tetralogy of Fallot (TOF) who were scheduled for corrective surgery were enrolled in this prospective study. Age-matched healthy children were included as controls. Demographic, haemodynamic and cardiac ultrasonography data were collected. Blood samples were taken pre-surgery, 24-48 hours post-surgery and again 3-6 months later. Several biomarkers (protein C, soluble platelet selectin [CD62P], soluble endothelium selectin [CD62E], soluble leukocyte selectin [CD62L], plasma von Willebrand Factor [vWF] atrial natriuretic peptide [ANP], brain natriuretic peptide[(BNP] and insulin-like growth factor-1 [IGF-1]) were measured. Results Sixty-three children (32 with PH, 15 with TOF, and 16 controls) were enrolled. No significant differences between the PH and TOF groups were observed in the expression of biomarkers pre- and post-surgery. IGF-1 levels were closely related to anthropometric data, particularly those children with PH. Expression of IGF-1 and weight/height normalized after corrective surgery. Conclusions No significant endothelial dysfunction was observed in children with PH or TOF before or after corrective surgery. Significant retardation of growth, particularly weight, was found before surgery and may be related to IGF-1 suppression.

Topics: Anthropometry; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; E-Selectin; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Insulin-Like Growth Factor I; L-Selectin; Male; Natriuretic Peptide, Brain; P-Selectin; Prospective Studies; Protein C; Tetralogy of Fallot; Ultrasonography; von Willebrand Factor

To examine whether preoperative heart failure and cardiac surgery influence nitric oxide production and atrial natriuretic peptide (ANP) biological activity in infants and whether nitric oxide and ANP participate in the control of postoperative pulmonary vascular tone.. Prospective, clinical study.. Tertiary pediatric cardiac intensive care unit in a referral cardiosurgical center.. Nineteen infants (median age 4 months) undergoing cardiac surgery: 13 infants with ventricular or atrioventricular septal defect associated with heart failure and pulmonary hypertension (group 1); and six infants with tetralogy of Fallot, without heart failure (group 2).. Blood samples obtained from indwelling catheters or bypass circuit outlets.. Nitrite and nitrate blood concentrations (as a marker for nitric oxide synthesis) and the molar ratio of cyclic guanosine 3',5'-monophosphate (cGMP) to ANP (as a marker for ANP biological activity) were determined before, during, and up to 24 hrs after cardiopulmonary bypass (CPB). In group 1 patients, these biological parameters were related to postoperative pulmonary arterial pressure. Preoperative nitrite and nitrate concentrations were higher in group 1 patients than in group 2 patients (p < .02), and this difference persisted during CPB. Nitrite and nitrate concentrations 24 hrs postoperatively were lower than preoperative values in group 1 patients (p < .05) and were unchanged in group 2 patients. An inverse correlation was observed postoperatively between nitrite and nitrate concentrations and systolic pulmonary arterial pressure (r2 = 0.4, p < .05). Group 1 patients had a lower preoperative cGMP/ANP ratio than group 2 patients (p < .05), despite higher ANP levels (p < .005). The cGMP/ANP ratio decreased during CPB in both groups (p < .0001), and in group 2 patients, cGMP and ANP values remained below preoperative values < or = 24 hrs postoperatively. A correlation was observed between ANP levels and systolic pulmonary arterial pressure 2 and 4 hrs postoperatively (r2 = .4, p < .05, respectively), but no correlation was observed between ANP biological activity and postoperative pulmonary arterial pressure.. Infants with heart failure and pulmonary hypertension have increased nitric oxide synthesis and decreased ANP biological activity; both phenomena may be involved in the pathophysiology of this clinical condition. CPB has no detectable effect on nitric oxide production but does decrease ANP biological activity. In patients with preoperative heart failure and pulmonary hypertension, endogenous nitric oxide appears to play a role in the control of postoperative pulmonary vascular tone.

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiopulmonary Bypass; Cyclic GMP; Heart Failure; Heart Septal Defects; Humans; Hypertension, Pulmonary; Infant; Nitrates; Nitric Oxide; Nitrites; Prospective Studies; Pulmonary Circulation; Tetralogy of Fallot

To investigate the alpha-atrial natriuretic factor in congenital cardiac malformations, three groups of children, aged 7 months to 16 years, with different hemodynamic situations were studied during routine cardiac catheterization. Twenty-one (group I) had tetralogy of Fallot, 24 (group II) had a left to right shunt with pulmonary hypertension and 12 (control group) had a minor cardiac lesion. Alpha-atrial natriuretic factor levels were determined by a radioimmunoassay on blood samples from the inferior vena cava, right atrium, pulmonary artery, left atrium and aorta. To evaluate the effect of an acute volume load, measurements of hormone and pressures were repeated after right ventriculography. Alpha-atrial natriuretic factor levels varied over a wide range in all groups and in all chambers investigated. Nevertheless, children with pulmonary hypertension had significantly higher levels of the hormone (p less than 0.01) and were well separated from the control group, but less well from those with tetralogy of Fallot. A 50% increase of alpha-atrial natriuretic factor from the inferior vena cava to the right atrium occurred in patients with shunt lesions with pulmonary hypertension and in patients with tetralogy of Fallot (p less than 0.001) and a further 30% increase from the right atrium to the pulmonary artery (p less than 0.05). After right ventriculography, a 100% to 200% increase of alpha-atrial natriuretic factor was observed in the total sample (p less than 0.001). A positive correlation was observed between right atrial mean pressure and right atrial alpha-atrial natriuretic factor (r = 0.63) and between pulmonary artery mean pressure and pulmonary artery alpha-atrial natriuretic factor (r = 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Child; Child, Preschool; Heart Defects, Congenital; Heart Ventricles; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Pulmonary Artery; Radiography; Regression Analysis; Tetralogy of Fallot

The plasma level of human alpha-atrial natriuretic peptide was measured in healthy children and patients, 1 month to 15 years of age, with congenital heart diseases. Significant increases were found in patients with a ventricular septal defect, tricuspid valve atresia, patent ductus arteriosus, and atrial septal defect but not in those with pulmonary valve stenosis or tetralogy of Fallot. The levels were significantly higher in children with ventricular septal defects (221 +/- 123 pg/mL) or patent ductus arteriosus (124 +/- 38 pg/mL) than in those with atrial septal defects (65 +/- 42 pg/mL) (P less than .01). The increased levels appeared to be correlated with enlargement of the left atrium (r = .85, P less than .01) but not with the right atrial size or the mean right atrial pressure. They were higher in younger than in older healthy infants, but this age difference did not affect the results. These findings indicate that human alpha-atrial natriuretic peptide is released into the circulation in response to chronic atrial expansion in patients with congenital heart disease and may have an important role in volume homeostasis.

Topics: Adolescent; Atrial Natriuretic Factor; Child; Child, Preschool; Ductus Arteriosus, Patent; Female; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Infant; Male; Pulmonary Valve Stenosis; Tetralogy of Fallot; Tricuspid Valve