ABSTRACT
OBJECTIVE: Noninvasive diagnostics for pulmonary arterial hypertension (PAH) have traditionally sought to predict main pulmonary artery pressure from qualitative or direct quantitative measures of the flow velocity pattern obtained from spectral Doppler ultrasound examination of the main pulmonary artery. A more detailed quantification of flow velocity patterns in the systemic circuit has been obtained by parameterizing the flow trace with a simple dynamic system model. Here, we investigate such a model's utility as a noninvasive predictor of total right heart afterload and right heart function. DESIGN: Flow velocity and pressure was measured within the main pulmonary artery during right heart catheterization of patients with normal hemodynamics (19 subjects, 20 conditions) and those with PAH undergoing reactivity evaluation (34 patients, 69 conditions). Our model parameters were obtained by least-squares fitting the model velocity to the measured flow velocity. RESULTS: Five parameter means displayed significant (P < .05) differences between normotensive and hypertensive groups. The model stiffness parameter correlated to actual pulmonary vascular resistance (r = 0.4924), pulmonary vascular stiffness (r = 0.6811), pulmonary flow (r = 0.6963), and stroke work (r = 0.7017), while the model initial displacement parameter had good correlation to stiffness (r = 0.6943) and flow (r = 0.6958). CONCLUSIONS: As predictors of total right heart afterload (resistance and stiffness) and right ventricle work, the model parameters of stiffness and initial displacement offer more comprehensive measures of the disease state than previous noninvasive methods and may be useful in routine diagnostic monitoring of patients with PAH.
Subject(s)
Blood Pressure Determination/methods , Blood Pressure Determination/standards , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/physiopathology , Pulmonary Artery/physiopathology , Adolescent , Cardiac Catheterization , Child , Child, Preschool , Female , Humans , Infant , Male , Models, Cardiovascular , Pilot Projects , Pulmonary Artery/diagnostic imaging , Reference Standards , Reproducibility of Results , Ultrasonography, Doppler , Vascular ResistanceABSTRACT
Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP>20 mmHg for at least 1h during the 48h following surgery measured by an indwelling pulmonary artery catheter. Multiple dimensionality reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N=41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR=0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p<0.001). This two-variable model correctly predicted 73% of the outcomes from the validation cohort. A five-variable model that added race, gender and Down's syndrome was not significantly better than the two-variable model. In conclusion, the CPSI T1405N genotype appears to be an important new factor in predicting susceptibility to increased PAP following surgical repair of congenital cardiac defects in children.
Subject(s)
Carbamoyl-Phosphate Synthase (Ammonia)/genetics , Genetic Variation , Heart Defects, Congenital/surgery , Hypertension, Pulmonary/epidemiology , Postoperative Complications/physiopathology , Cohort Studies , DNA/blood , DNA/genetics , DNA Primers , Down Syndrome/epidemiology , Female , Humans , Infant , Male , Polymerase Chain Reaction , Polymorphism, Genetic , Reproducibility of ResultsABSTRACT
BACKGROUND: The myocardial performance index (MPI) correlates with clinical status in adults with idiopathic pulmonary arterial (PA) hypertension (IPAH). This pediatric study used MPI to assess response to bosentan therapy. METHODS: The study included 12 children with IPAH and 12 healthy control subjects. MPI was correlated with catheterization data at initiation of bosentan and at a median follow-up of 9 months. Therapy responders were defined by a greater than 20% decrease in mean PA pressure. RESULTS: Right ventricular MPI for patients with IPAH was 0.64 +/- 0.30 versus 0.28 +/- 0.03 in control subjects (P < .01). It had a strong correlation with mean PA pressure (R = 0.94; P < .001). Right ventricular MPI decreased significantly in responders (range 20%-44%, mean 25%) with a 5% increase in nonresponders. CONCLUSIONS: Right ventricular MPI in pediatric IPAH correlates with mean PA pressure and response to therapy. This study suggests that this noninvasive Doppler index may be useful to follow up children with IPAH, particularly when tricuspid regurgitation data are insufficient.
