Validation of the Proximal Isovelocity Surface Area Method for Assessing Mitral Regurgitation in Children

The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2π×~ r ²×~ V (r= maximal radius, V= aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2π×~ MSR ×~ V×~ T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area–length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSV_D: RSV_D= TSV − FSV) and regurgitant fraction (RF: RF = RSV_D/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSV_D (X) (MFR = 4.2X + 54.0, r= 0.84. RSVpisa = 1.0X + 9.8, r= 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m²) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 ×~ X/(1 − X) + 16.8, r= 0.85. MFR/BSA = 121.8 ×~ X/(1 − X) + 92.2, r= 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.     

Oxygen consumption in infants and children during heart catheterization

Oxygen consumption was measured in infants, children, and adolescents during diagnostic heart catheterizations. A total of 825 measurements of oxygen consumption (VO₂) was performed in 504 subjects using a semiopen hood system and a paramagnetic oxygen analyzer. In 256 subjects under 3 years of age, body dimensions and heart rate were found to be significant factors for oxygen consumption. The regression equation for both sexes was: VO₂/BSA (ml/min · m²) = 3.42 · height (cm) − 7.83 · weight (kg) + 0.38 · HR − 54.1 (r ²= 0.39, SD = 38.7), where BSA is body surface area and HR is heart rate. VO₂/BSA was significantly lower in infants less than 3 months of age (133 ± 33 ml/min · m²) compared with infants of 3–12 months (171 ± 37 ml/min · m²; p < 0.01). In 272 children aged 3 years and older and adolescents, gender was a significant factor in oxygen consumption together with BSA and HR. The regression line equation for males was VO₂/BSA (ml/min · m²) = 0.79 · HR − 7.4 · BSA(m²) + 108.1 (r ²= 0.45, SD = 34.2). The regression line equation for females is VO₂/BSA (ml/min · m²) = 0.77 · HR − 5.2 · BSA(m²) + 106.8 (r ²= 0.43, SD = 34.4). Hematocrit, systemic oxygen saturation, and blood pressure were not significant factors. The predictive value of nomograms for oxygen consumption is limited because of the large interindividual variations not explained by differences in gender, body size, or simple hemodynamic variables. Preferably, oxygen consumption is measured; but if nomograms for oxygen consumption are used for hemodynamic assessment, the wide confidence intervals should be considered.     

A Direct Comparison of Right and Left Ventricular Performance in the Isolated Neonatal Pig Heart

A comparison is presented between the performance of the right ventricle (RV) and the left ventricle (LV) in neonatal hearts studied under conditions of volume loading and tachycardia. Isolated, atrially paced (150 or 300 bpm), isovolumically beating pig hearts (1–3 days of age) underwent retrograde aortic perfusion with a nonrecirculating, crystalloid solution. Ventricular pressure was assessed with saline-filled balloon catheters, which allowed separate loading of the RV or LV. Both ventricles showed an initial increase followed by a leveling off, but no decline, in peak systolic pressure (PSP) and +dP/dt _max with volume loading up to an end-diastolic pressure (EDP) of 18 mmHg. The LV generated a higher PSP and +dP/dt _max compared to the RV at equivalent pressure or volume preloads. However, the maximal systolic elastance (E _max) was comparable for both ventricles. Although the RV demonstrated a greater compliance than the LV, the myocardial relaxation time constant (τ) was similar for both chambers at equivalent volume preloads (sarcomere stretch). Positive dP/dt _max correlated closely and in the same linear fashion with −dP/dt _max for both ventricles, indicating that the RV and LV exhibited similar contraction–relaxation coupling. Increasing the heart rate to 300 bpm decreased PSP, +dP/dt _max, and −dP/dt _max and increased EDP for both ventricles, whereas E _max and τ were not significantly altered. Thus, although there are differences between the functional properties of the neonatal RV and LV, there are also important similarities, especially with regard to myocardial relaxation.     

Effects of Doxorubicin on Diastolic Function, Contractile Reserve, and Ventricular–Vascular Coupling in Piglets

The use of doxorubicin as an anticancer drug is limited by its cardiac toxicity. To examine the adverse effects of doxorubicin on cardiac function and ventricular–vascular coupling in piglets, eight piglets received five doses of intravenous doxorubicin, 1.5 mg/kg/dose, every 4–7 days starting at 3 weeks of age. A control group consisted of eight normal piglets. Using conductance and manometric catheters, indices of cardiac function, including end systolic elastance (E _es), preload-recruitable stroke work, dP/dt _max, τ, dP/dt _min, dV/dt _max, and end systolic stiffness, were calculated from volume and pressure measurements at rest and during infusion of isoproterenol. Ventricular–vascular coupling was examined by measuring arterial elastance (E _a) and E _a/E _es. Significant differences in relaxation were found between groups. Indices of diastolic stiffness and of contractile function were not different between groups. Baseline contractile efficiency was increased in the doxorubicin group. E _a and E _a/E _es were lower in the doxorubicin group. E _a/E _es was near 1 at baseline in the doxorubicin group, indicating that conditions were optimized for performance of external stroke work. Therefore, the reserve to increase external cardiac work was diminished. The finding of altered diastolic function suggests the importance of screening of diastolic indices to detect the earliest disturbances in cardiac function caused by doxorubicin.     

Phase-Velocity Cine Magnetic Resonance Imaging Measurement of Pulsatile Blood Flow in Children and Young Adults: In Vitro and In Vivo Validation

Quantification of blood flow in vessels provides valuable information that aids management decisions in a variety of cardiac conditions. Current flow measurement techniques are often limited by accuracy, time resolution, convenience, or anatomic localization. This study examined the accuracy of a commercially available phase-velocity cine magnetic resonance imaging (PVC MRI) technique to quantify flow rate in a pulsatile flow phantom. In addition, the equivalence of PVC MRI measurements of pulmonary and systemic flow was evaluated in children and adults without any pathologic shunt. Using a pulsatile flow phantom, volume flow rates measured by PVC MRI were compared to those by a transit-time ultrasound flowmeter over a range of flow rates (1.25–3.5 L/min, 13 trials). Close agreement was found between these techniques (y= 1.02x− 0.02, r= 0.99, Bland–Altman bias =−0.045 L/min, 95% limits of agreement =−0.19–0.10 L/min). Twenty subjects (median age 12.8 years, range 0.7–49 years) with no pathologic shunt underwent PVC MRI measurement of blood flow in the main pulmonary artery (Q _p) and the ascending aorta (Q _s). Data processing time for each location was 20 minutes. The Q _p/Q _s ratio closely approximated unity (mean = 0.99, SD = 0.10, range 0.85–1.19). Interobserver agreement was excellent (Bland–Altman bias = 0.09 L/min, 95% limits of agreement = 0.15–0.33 L/min). PVC MRI is an accurate technique to quantify pulsatile blood flow at a specific location. It can be used to noninvasively calculate Q _p and Q _s under normal flow conditions.     

Regression of Right Ventricular Pressure in Ventricular Septal Defect in Infancy: A Longitudinal Color-Flow Doppler Echocardiographic Study

To determine the course of right ventricular pressure (RVP) in patients with isolated ventricular septal defect (VSD) and factors influencing it, unselected 148 infants were followed-up longitudinally with color-Doppler echocardiography from a median age of 1 month for 201 patient-years. The patients were divided into three groups by absolute echographic size of VSD: group I, ≤4.0 mm; group II, >4 to ≤7 mm; group III, >7 mm. Sixty percent belonged to group I. Muscular defects dominated in group I, perimembranous defects dominated in group II, and those with outlet extensions dominated in group III. Peak systolic RVP was obtained by Doppler-estimated difference between systolic brachial artery and peak gradient across the VSD. Initial RVP ranged between 15 and 95 mmHg and increased in parallel to the size of defect. According to the regression equations RVP decreased in general by 0.17 mmHg per month. This correlated significantly with the size of the defect. In group I, the rate of decrease was very fast and is best expressed by a log function of time (r=−0.67, r ²= 0.45). In groups II and III the rate of decrease was less steep and had a greater variability. RVP normalized in 100% in those of group I and in 90% of group II, at median ages of 0.17 and 0.33 years, respectively. Median Q _p:Q _s values were 1.5, 2.2, and 3.0 in groups I–III, respectively. The outcome depended on the size of VSD. Spontaneous closure was observed in 51% of group I, 10% of group II, and none of group III. The rate was higher in muscular defects. Congestive heart failure was present in 53% and 100% in groups II and III, respectively. Death rate was 2.03%, all in patients with large defects. It is concluded that the temporal course of RVP with time can be estimated fairly well by the regression equation presented in relation to the initial size of the VSD.     

Radioangioscintigraphy and Doppler Echocardiography in the Quantification of Left-to-Right Shunt

The magnitude of left-to-right shunt in 55 children with isolated congenital heart disease [atrial septal defect (ASD) or ventricular septal defect (VSD) (muscular and perimembranous)] was estimated by two methods: radionuclide quantification and Doppler echocardiography [flow (L/min) = mean velocity × area × ejection time × heart rate]. We found little difference between the magnitude of left-to-right shunt obtained with Doppler echocardiography and that with radioangioscintigraphy for a whole group of patients (N= 55, −11.42% to 12.04%) and for subgroups of ASD (n= 24, −12.49% to 12.19%) and VSD (n= 31, −10.69% to 12.23%). These results indicate that Doppler echocardiography, in comparision with radioangioscintigraphy, is sufficiently accurate for clinical estimation of the Q _p/Q _s ratio in isolated congenital heart disease with left-to-right shunt.     

The Use of High-Resolution Computed Tomography in the Evaluation of Pulmonary Hemodynamics in Patients with Congenital Heart Disease: In Pulmonary Vessels Larger Than 1 mm in Diameter

High-resolution computed tomography (HRCT) was carried out in 36 patients with congenital left-to-right shunt disease and 10 normal control subjects to assess the feasibility of CT in the evaluation of pulmonary hemodynamics. The patients had a left-to-right or a bidirectional shunt and the hemodynamic data obtained by cardiac catheterization in these patients were compared to the information obtained by CT imaging. The pulmonary/systemic blood flow (Q _p/Q _s) ratio and pulmonic/systemic resistance (R _p/R _s) ratio had a significant correlation with the pulmonary artery/bronchus (PA/Br) ratio (r= 0.54 and r=−0.37, respectively) and pulmonary vein/bronchus (PV/Br) ratio (r= 0.66 and r=−0.66, respectively), and the R _p/R _s and mean PA pressure also showed a significant correlation with the PA/PV ratio (r= 0.53 and r=−0.61, respectively) in the mid-lung field when accompanying bronchi were 4.0–5.9 mm in diameter. There was no correlation between the hemodynamic data and the size of the central and hilar PA or with the rate of PA tapering. With HRCT, it is possible to evaluate pulmonary hemodynamics in patients with congenital heart disease with a left-to-right or bidirectional shunt, particularly R _p/R _s and mean PA pressure, which have been very difficult to obtain noninvasively. The small-sized pulmonary vessel/Br ratio or the small-sized PA/PV ratio could offer very useful information, but the dimension of the central PA provided the least useful information.     

Age Dependency of Stiffness of the Abdominal Aorta and the Mechanical Properties of the Aorta in Kawasaki Disease in Children

Measuring aortic distensibility has been shown to be useful in adults as a noninvasive method in the early detection of atherosclerosis. This study had two purposes: to assess the stiffness of the abdominal aorta by using two-dimensional echocardiography (2DE) in healthy neonates, children, and adults and to assess aortic distensibility in children with Kawasaki disease in acute and subacute phases. The study comprised 168 healthy subjects and 40 patients with Kawasaki disease. We recorded systolic (P _s) and diastolic (P _d) blood pressure and measured aortic diameter (D _d) at both minimum diastolic pressure and maximum systolic expansion (D _s) by 2DE. These measurements were used to determine (1) aortic strain (S) = (D _s−D _d)/D _d, (2) pressure strain elastic modulus (E _p) = (P _s−P _d)/S, and (3) normalized E _p (E _p*) =E _p/P _d. Significant correlations were found between S and age, E _p and age, and E _p* and age. In Kawasaki disease, E _p and E _p* showed negative correlations to day after onset. The aorta was less distensible in infants, became soft in 12- to 16-year-olds, and then stiffened with increasing age among normal subjects. In Kawasaki disease, aortic stiffness was high at the acute phase and normal at the subacute phase. These tendencies may be related to the biological characteristics of smooth muscle cells.     

Assessment of Progressive Changes in Exercise Performance in Patients with a Systemic Right Ventricle Following the Atrial Switch Repair

There is a high prevalence of right ventricular dysfunction and reduced exercise performance in survivors of atrial switch repair for transposition of the great arteries. However, it is not known whether the impairment in exercise performance is progressive. We performed paired comparison of exercise performance in 28 patients who underwent two serial incremental exercise tests at an interval of 5.0 ± 1.4 years between the two tests (age 11.5 ± 3.7 years at first test, 16.4 ± 3.6 years at second test). There was no change in the chronotropic response between the two tests. However, there was a reduction in both the peak VO₂ (32.5 ± 8.3 vs 29.6 ± 5.7 ml/kg/min, p= 0.05) and anerobic threshold (22.1 ± 5.1 vs 18.3 ± 4.2 ml/kg/min, p < 0.01) with time. Furthermore, there was a decline in the O₂ pulse (oxygen uptake/beat) at anaerobic threshold (% predicted value 95 ± 23% vs 82 ± 23%, p= .02), O₂ pulse at a heart rate of 140 (% predicted value 100 ± 30% vs 85 ± 19%, p= 0.02), and the maximum O₂ pulse (z value −0.27 ± 1.31 vs −1.27 ± 1.16, p < 0.01) when compared to growth-related normal values. We conclude that there is a progressive reduction in aerobic response to exercise in patients with a systemic right ventricle. The maintenance of chronotropic response suggests that the stroke volume response of the systemic right ventricle during exercise does not increase commensurate with somatic growth.     

Time Course of Myocardial Amiodarone Uptake in the Piglet Heart Using a Chronic Animal Model

This investigation sought to study single dose pharmacokinetics of amiodarone in a chronic animal model. We developed a new chronic animal model that allows serial direct access to the heart of the immature piglet via an implanted acrylic thoracic window. Following instrumentation and 72-hour recovery, amiodarone (5 mg/kg) was administered as a single intravenous bolus in immature piglets. Timed paired serum samples and myocardial biopsies for amiodarone level were obtained prior to, and up to 72 hours following, amiodarone administration. Peak concentrations of amiodarone in both serum (3.60 ± 1.02 μg/ml) and tissue (84.2 ± 6.50 ng/mg) occurred within 5 minutes of drug administration. As reported by others, this study demonstrated that the volume of distribution (V_D) of amiodarone was large (33.31 ± 35.21 L/kg), and the clearance (Cl) was low (13.6 ± 4.4 ml/min/kg). Marked prolongation of both the serum t _1/2 (29.98 ± 29.26 hours) and the myocardial t _1/2 (29.20 ± 29.49 hours) were noted as well. The early, rapid myocardial peak of amiodarone in the immature myocardium corresponds with recent clinical observations of onset of antiarrhythmic efficacy 5 to 10 minutes following intravenous amiodarone administration in young children.     

Neurophysiological Effects of Pediatric Balloon Dilatation Procedures

Balloon dilatation of valvar and vascular stenoses has become routine therapy in pediatric cardiology. Repeated balloon inflations cause many episodes of low cerebral oxygen delivery. This study is a prospective study to assess the effects of balloon dilatation on cerebral perfusion and oxygenation. The study included 11 patients scheduled for elective catheterization and balloon dilatation at a university pediatric hospital. Blood flow velocity in the middle cerebral artery (V _mca) and regional cerebral oxygen saturation (rSO₂) were monitored by means of transcranial Doppler sonography and near infrared spectroscopy, respectively. In group 1, consisting of 6 patients without an intracardiac shunt, inflation of the balloon resulted in a decrease in V _mca followed by a minor decrease in rSO₂. In group 2, consisting of 5 patients with an interatrial communication, inflation resulted in an increase in right-to-left shunt fraction, arterial desaturation, and a major decrease in rSO₂ with minor changes in V _mca. Balloon dilatation causes an important decrease in cerebral oxygen delivery by different mechanisms. This may lead to serious morbidity and even mortality. Neuromonitoring is a useful tool in assessing the cerebral effects of balloon dilatation and brain recovery.     

Prostacyclin Treatment for Persistent Pulmonary Hypertension of the Newborn

To study the effect of prostacyclin treatment on pulmonary arterial pressure (PAP), systolic pressure (BP), and systemic oxygenation, eight infants with persistent pulmonary hypertension of the newborn (PPHN) born between 34 and 42 weeks' gestation and having a birth weight of 2540–4130 g were studied using Doppler echocardiography. At a mean age of 19 hours (range 3–32 hours), despite maximal ventilator therapy and an FiO₂ of 1.0, the mean PaO₂/PAO₂ was 0.07 (range 0.04–0.09) and the AaDO₂ was 616 mmHg (range 521–654 mmHg). After volume correction and during inotropic medication with dopamine and dobutamine, the mean PAP by echocardiography was 68.6 ± 6.5 mmHg and the mean BP 59.8 ± 4.8 mmHg. Prostacyclin infusion was then started at a dose of 20 ng/kg/min and increased stepwise to a mean dose of 60 ng/kg/min (range 30–120 ng/kg/min) over 4–12 hours, at which time PAP decreased to 49.2 ± 3.5 mmHg (p= 0.0005) and BP to 53.2 ± 9.1 mmHg (p= 0.17); the PAP thereafter remained below the BP. After 72 hours of prostacyclin infusion, PAP was 49.6 ± 18 mmHg, BP 66.1 ± 5.4 mmHg, PaO₂/PAO₂ 0.14 ± 0.12, and AaDO₂ 428 ± 189 mmHg at FiO₂ 0.65. The median duration of prostacyclin infusion was 3.6 days and of respirator treatment 7.0 days. All patients survived without extracorporeal membrane oxygenation. At 6–12 months, none of the patients had severe central nervous system complications, but two had bronchopulmonary dysplasia. These findings indicate that prostacyclin is able to reverse the right-to-left shunt in PPHN by decreasing PAP, and that systemic hypotension can be prevented with adequate volume correction and inotropic medication.     

Branch Pulmonary Artery Growth After Blalock–Taussig Shunts in Tetralogy of Fallot and Pulmonary Atresia with Ventricular Septal Defect: A Retrospective, Echocardiographic Study

We performed a retrospective echocardiographic study in tetralogy of Fallot (TOF) or pulmonay atresia with ventricular septal defect (PA&VSD) to evaluate the effects of Blalock–Taussig shunt on branch pulmonary artery growth. There were 35 patients with TOF and 11 with PA&VSD. We measured the right and left pulmonary artery area index and also the combined pulmonary artery area index, both before and after shunt operation. The mean ± SD of these three variables before the shunt operation in the TOF group were 63.5 ± 22.5, 57.8 ± 24.9, and 121.4 ± 42.8 mm²/m²; after shunt operation they were 98.5 ± 33.6, 85.9 ± 31.9, and 184.0 ± 59.8 mm²/m², respectively (p values <0.0001, <0.0002, and <0.0001, respectively). In the PA&VSD group the comparable values before shunt operation were 66.5 ± 16.0, 55.4 ± 10.6, and 120.9 ± 26.9 mm²/m² and after shunt operation were 90.5 ± 22.9, 77.2 ± 24.1, and 166.6 ± 44.4 mm²/m², respectively (p values <0.0006, <0.014, and <0.002, respectively). We also examined the effect of distensibility of pulmonary arteries by comparing the percentage change in size of the combined pulmonary artery area index in the first 4 months after shunt with those after this time (p < 0.023). There were no significant differences between left- and right-sided shunts, origin and distal pulmonary artery growth, and the TOF and PA&VSD groups.     

Inhalation of Low-Dose Nitric Oxide to Evaluate Pulmonary Vascular Reactivity in Children with Congenital Heart Disease

The objective of this study was to investigate the efficacy of low-dose nitric oxide (NO). The study used fifteen consecutive Japanese preoperative patients (7 males and 8 females) with congenital heart disease and pulmonary hyptertension (mean pulmonary arterial pressure >30 mmHg), 6 of these patients had Down's syndrome. Hemodynamic measurements were taken in room air, 100% oxygen, 5 and 40 parts per million NO (NO5 and NO40) by inhalation. The differences between two observations within the same group were determined by the two-tailed paired t-test. A pulmonary vascular resistance (R _p) regression curve was constructed by using linear regression analysis. The percentage change in pulmonary arterial pressure per systemic arterial pressure (P _p/P _s) with NO40 (P _p/P _s-40) exceeded that of P _p/P _s-5 (p < 0.0001). The percentage change for the R _p with NO40 (Rp-40) was larger than that for the R _p-5 (p= 0.0003). The percentage change of P _p/P _s-5 and that with oxygen were similar (p= 0.266). The relationship between R _p-5 and R _p-40 was linear. In conclusion, the effects of NO5 were equivalent to 100% oxygen but less than NO40. NO5 should initially be used to test pulmonary reactivity. If there is no response, patients should still be given NO40.     

Magnetic resonance imaging demonstration of “Remodeling” of the aorta following balloon angioplasty of discrete native coarctation

Assessment of the hemodynamic and anatomic results following balloon angioplasty of discrete native coarctation of the aorta, with particular attention to ``remodeling,' has required repeat cardiac catheterization and angiography, which is invasive and has limited resolution. Eight patients with hypertension and discrete native coarctation with an otherwise normally developed aortic arch underwent angioplasty at 5.0 ± 6.8 years of age. Angiographic cross-sectional areas of the aorta indexed to body surface area at the isthmus (I), coarctation site (C), and 1 cm distal to the coarctation site (Cd) pre- and postangioplasty were compared with MRI-indexed cross-sectional areas 18 ± 10 months (MRI-1) and 35 ± 11 months (MRI-2) postangioplasty. From preangioplasty to MRI-2, the isthmus was smaller (149 ± 22 versus 127 ± 27 mm<sup>2</sup>/m<sup>2</sup>; p < 0.05). The coarctation site was larger postangioplasty (25 ± 9 versus 116 ± 40 mm<sup>2</sup>/m<sup>2</sup>; p < 0.001) with continued growth at latest follow-up (116 ± 40 versus 164 ± 36 mm<sup>2</sup>/m<sup>2</sup>; p < 0.01). The segment 1 cm distal to the coarctation site continued to decrease in area at latest follow-up (267 ± 78 versus 163 ± 38 mm<sup>2</sup>/m<sup>2</sup>; p < 0.001). I versus C versus Cd at MRI-2 were similar, whereas postangioplasty and MRI-1 cross-sectional area measurements were significantly different. Following angioplasty of discrete native coarctation, the aorta becomes more uniform or undergoes ``remodeling.' Noninvasive MRI is an effective means of evaluating the anatomic result following balloon angioplasty, obviating the need for repeated invasive cardiac catheterizations.     

{V}_{\text{O}_{2}}@RER1.0: A Novel Submaximal Cardiopulmonary Exercise Index

Maximal oxygen consumption ( [(V)\dot]_\textO2\textmax \dot{V}_{\text{O}_{2}}\text{max}) is the “gold standard” by which to assess functional capacity; however, it is effort dependent. \textV_\textO2\text{V}_{\text{O}_{2}}@RER_1.0 is defined when \textV_\textO2=V_\textCO2\text{V}_{\text{O}_{2}}={V}_{\text{CO}_{2}}. Between December 22, 1997 and November 9, 2004, 305 pediatric subjects underwent cycle ergometer cardiopulmonary exercise testing, exercised to exhaustion, and reached a peak respiratory exchange ratio ≥1.10. Group 1 subjects achieved a peak \textV_\textO2 3 80%\text{V}_{\text{O}_{2}} \ge 80\% of predicted [(V)\dot]_\textO2\textmax \dot{V}_{\text{O}_{2}}\text{max}; group 2 subjects achieved a peak \textV_\textO2 ￡ 60% \text{V}_{\text{O}_{2}} \le 60\% of predicted [(V)\dot]_\textO2\textmax \dot{V}_{\text{O}_{2}}\text{max}; and group 3 subjects achieved a peak \textV_\textO2\text{V}_{\text{O}_{2}} between 61 and 79% of predicted [(V)\dot]_\textO2\textmax \dot{V}_{\text{O}_{2}}\text{max}. Linear regression analysis was performed for \textV_\textO2\text{V}_{\text{O}_{2}}@RER_1.0 as a function of predicted [(V)\dot]_\textO2\textmax \dot{V}_{\text{O}_{2}}\text{max} for group 1 subjects. A −2 SD regression line and equation was created. \textV_\textO2 \text{V}_{\text{O}_{2}}@RER_1.0 data from groups 2 and 3 were plotted onto the normative graph. Contingency table and relative-risk analysis showed that an abnormal \textV_\textO2 \text{V}_{\text{O}_{2}}@RER_1.0 predicted an abnormal peak \textV_\textO2\text{V}_{\text{O}_{2}}(positive-predictive value 83%, negative-predictive value 85%, sensitivity 84%, and specificity 84%). \textV_\textO2 \text{V}_{\text{O}_{2}}@RER_1.0 is a highly sensitive, specific, and predictive submaximal index of functional capacity. This submaximal index is easy to identify without subjectivity. This index may aid in the evaluation of subjects who cannot exercise to maximal parameters.     

Generation of Reactive O2 Species in the Myocardium of Newborn Lambs Following Intrauterine Increase in Right Ventricular Pressure

Fetuses with pulmonary stenosis and constriction of the ductus arteriosus or the recipient twin in the context of a twin-to-twin transfusion syndrome may present with severe right ventricular myocardial dysfunction. Free O₂ radicals are known to be increased in hypertrophied adult myocardium secondary to an increase in endocavitary pressure. This study investigates whether products of reactive O₂ species generation are abnormally elevated in the myocardium of fetuses with increased right ventricular pressure. Banding of the main pulmonary artery was performed in five fetal lambs at 90 to 100 days of gestation. Three other animals had a sham intervention and were used as controls. Postoperative observation lasted on average 42 days (range 33–49 days). The levels of hydroperoxides were found to be significantly higher in the right ventricle of the stenosed lambs (6.6 ± 3.5 nmol/mg protein) compared to the left ventricle of the same lambs (0.7 ± 0.7 nmol/mg protein), and compared to the right (0.12 ± 0.1 nmol/mg protein) and the left (0.5 ± 0.8 nmol/mg protein) ventricles of the controls. It is concluded that during fetal life, an increase in right ventricular pressure is associated with a marked accumulation of products of reactive O₂ species generation in the right ventricular myocardium.     

Responses of Plasma Norepinephrine and Heart Rate During Exercise in Patients After Fontan Operation and Patients with Residual Right Ventricular Outflow Tract Obstruction After Definitive Reconstruction

To determine the exercise responses of patients with congenital heart disease, 20 patients—5 who had undergone a right ventricular outflow tract reconstruction (group R; age, 15 ± 2 years), eight who had undergone a Fontan operation (group F; age, 13 ± 2 years), and seven who had a history of Kawasaki disease (group C; age, 15 ± 1 years)—performed a treadmill exercise test. Patients of group R had a significant residual right ventricular outflow obstruction. Oxygen uptake (VO₂), heart rate (HR), and plasma norepinephrine (NE) concentrations were measured at rest, during warm-up, at ventilatory threshold (VT), and at peak exercise. Exercise capacity was determined as a percentage of the predicted normal peak VO₂ (%pVO₂). The %pVO₂ for groups R and F was 65 ± 10 and 56 ± 11, respectively. Peak HR for groups R and F was 171 ± 4 and 155 ± 5, which were lower than the HR for group C (p < 0.001). Although NE concentrations at rest, during warm-up, and at VT were significantly greater in groups R and F (p < 0.05), there were no significant differences in the NE concentrations at peak exercise. Peak HR correlated with %pVO₂ (p < 0.001). The ratio of the increase in HR to NE from rest to VT was significantly lower in groups R and F than in group C (p < 0.001) and correlated with %pVO₂ (r= 0.80; p < 0.001). These data suggest that sympathetic nervous activity in groups R and F is increased at rest and during mild to moderate exercises, and reduced sinus node sensitivity to NE may be partly responsible for the abnormal HR response during exercise of patients with uncorrected congenital heart disease.     

Left Ventricular Diastolic Filling Patterns Associated with Progressive Anthracycline-Induced Myocardial Damage: A Prospective Study

The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m² (median 270 mg/m²). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m² of anthracycline. Six patients developed cardiac failure. After 1–100 mg/m² of anthracyclines, the EA ratio decreased (mean 1.54–1.40, p= 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p= 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.