The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

AIMS/HYPOTHESIS: We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. METHODS: Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. RESULTS: Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). CONCLUSIONS/INTERPRETATION: Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice.

Retinoids play a critical role in cardiac morphogenesis. To examine the effects of excessive retinoid signaling on myocardial development, transgenic mice that overexpress a constitutively active retinoic acid receptor (RAR) controlled by either the alpha- or beta-myosin heavy chain (MyHC) promoter were generated. Animals carrying the alpha-MyHC-RAR transgene expressed RARs in embryonic atria and in adult atria and ventricles, but developed no signs of either malformations or disease. In contrast, beta-MyHC-RAR animals, where expression was activated in fetal ventricles, developed a dilated cardiomyopathy that varied in severity with transgene copy number. Characteristic postmortem lesions included biventricular chamber dilation and left atrial thrombosis; the incidence and severity of these lesions increased with increasing copy number. Transcript analyses showed that molecular markers of hypertrophy, alpha-skeletal actin, atrial natriuretic factor and beta-MyHC, were upregulated. Cardiac performance of transgenic hearts was evaluated using the isolated perfused working heart model as well as in vivo, by transthoracic M-mode echocardiography. Both analyses showed moderate to severe impairment of left ventricular function and reduced cardiac contractility. Thus, expression of a constitutively active RAR in developing atria and/ or in postnatal ventricles is relatively benign, while ventricular expression during gestation can lead to significant cardiac dysfunction.

Fibroblast growth factor-2 mediates pressure-induced hypertrophic response.

In vitro, fibroblast growth factor-2 (FGF2) has been implicated in cardiomyocyte growth and reexpression of fetal contractile genes, both markers of hypertrophy. However, its in vivo role in cardiac hypertrophy during pressure overload is not well characterized. Mice with or without FGF2 (Fgf2(+/+) and Fgf2(-/-), respectively) were subjected to transverse aortic coarctation (AC). Left ventricular (LV) mass and wall thickness were assessed by echocardiography preoperatively and once a week postoperatively for 10 weeks. In vivo LV function during dobutamine stimulation, cardiomyocyte cross-sectional area, and recapitulation of fetal cardiac genes were also measured. AC Fgf2(-/-) mice develop significantly less hypertrophy (4-24% increase) compared with AC Fgf2(+/+) mice (41-52% increase). Cardiomyocyte cross-sectional area is significantly reduced in AC Fgf2(-/-) mice. Noncoarcted (NC) and AC Fgf2(-/-) mice have similar beta-adrenergic responses, but those of AC Fgf2(+/+) mice are blunted. A lack of mitotic growth in both AC Fgf2(+/+) and Fgf2(-/-) hearts indicates a hypertrophic response of cardiomyocytes. Consequently, FGF2 plays a major role in cardiac hypertrophy. Comparison of alpha- and beta-cardiac myosin heavy chain mRNA and protein levels in NC and AC Fgf2(+/+) and Fgf2(-/-) mice indicates that myosin heavy chain composition depends on hemodynamic stress rather than on FGF2 or hypertrophy, and that isoform switching is transcriptionally, not posttranscriptionally, regulated.

Myofibril degeneration caused by tropomodulin overexpression leads to dilated cardiomyopathy in juvenile mice.

Loss of myofibril organization is a common feature of chronic dilated and progressive cardiomyopathy. To study how the heart compensates for myofibril degeneration, transgenic mice were created that undergo progressive loss of myofibrils after birth. Myofibril degeneration was induced by overexpression of tropomodulin, a component of the thin filament complex which determines and maintains sarcomeric actin filament length. The tropomodulin cDNA was placed under control of the alpha-myosin heavy chain gene promoter to overexpress tropomodulin specifically in the myocardium. Offspring with the most severe phenotype showed cardiomyopathic changes between 2 and 4 wk after birth. Hearts from these mice present characteristics consistent with dilated cardiomyopathy and a failed hypertrophic response. Histological analysis showed widespread loss of myofibril organization. Confocal microscopy of isolated cardiomyocytes revealed intense tropomodulin immunoreactivity in transgenic mice together with abnormal coincidence of tropomodulin and alpha-actinin reactivity at Z discs. Contractile function was compromised severely as determined by echocardiographic analyses and isolated Langendorff heart preparations. This novel experimentally induced cardiomyopathy will be useful for understanding dilated cardiomyopathy and the effect of thin filament-based myofibril degeneration upon cardiac structure and function.

Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis.

Apolipoprotein J/clusterin (apoJ/clusterin), an intriguing protein with unknown function, is induced in myocarditis and numerous other inflammatory injuries. To test its ability to modify myosin-induced autoimmune myocarditis, we generated apoJ-deficient mice. ApoJ-deficient and wild-type mice exhibited similar initial onset of myocarditis, as evidenced by the induction of two early markers of the T cell-mediated immune response, MHC-II and TNF receptor p55. Furthermore, autoantibodies against the primary antigen cardiac myosin were induced to the same extent. Although the same proportion of challenged animals exhibited some degree of inflammatory infiltrate, inflammation was more severe in apoJ-deficient animals. Inflammatory lesions were more diffuse and extensive in apoJ-deficient mice, particularly in females. In marked contrast to wild-type animals, the development of a strong generalized secondary response against cardiac antigens in apoJ-deficient mice was predictive of severe myocarditis. Wild-type mice with a strong Ab response to secondary antigens appeared to be protected from severe inflammation. After resolution of inflammation, apoJ-deficient, but not wild-type, mice exhibited cardiac function impairment and severe myocardial scarring. These results suggest that apoJ limits progression of autoimmune myocarditis and protects the heart from postinflammatory tissue destruction.

The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo.

Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators of cell growth, proliferation, and stress responsiveness. A family of dual-specificity MAP kinase phosphatases (MKPs) act as critical counteracting factors that directly regulate the magnitude and duration of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. Here we show that constitutive expression of MKP-1 in cultured primary cardiomyocytes using adenovirus-mediated gene transfer blocked the activation of p38, JNK1/2, and ERK1/2 and prevented agonist-induced hypertrophy. Transgenic mice expressing physiological levels of MKP-1 in the heart showed (1) no activation of p38, JNK1/2, or ERK1/2; (2) diminished developmental myocardial growth; and (3) attenuated hypertrophy in response to aortic banding and catecholamine infusion. These results provide further evidence implicating MAPK signaling factors as obligate regulators of cardiac growth and hypertrophy and demonstrate the importance of dual-specificity phosphatases as counterbalancing regulatory factors in the heart.

Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein.

The advent of conditional and tissue-specific recombination systems in gene-targeted or transgenic mice has permitted an assessment of single gene function in a temporally regulated and cell-specific manner. Here we generated transgenic mice expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer) under the control of the alpha-myosin heavy chain promoter. These transgenic mice were crossed with the ROSA26 lacZ-flox-targeted mice to examine Cre recombinase activity and the fidelity of the system. The data demonstrate essentially no Cre-mediated recombination in the embryonic, neonatal, or adult heart in the absence of inducing agent but >80% recombination after only four tamoxifen injections. Expression of the MerCreMer fusion protein within the adult heart did not affect cardiac performance, cellular architecture, or expression of hypertrophic marker genes, demonstrating that the transgene-encoded protein is relatively innocuous. In summary, MerCreMer transgenic mice represent a tool for temporally regulated inactivation of any loxP-targeted gene within the developing and adult heart or for specifically directing recombination and expression of a loxP-inactivated cardiac transgene in the heart.

Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy.

BACKGROUND: Vascular hypertension resulting in increased cardiac load is associated with left ventricular hypertrophy and is a leading predicator for progressive heart disease. The molecular signaling pathways that respond to increases in cardiac load are poorly understood. One potential regulator of the hypertrophic response is the calcium-sensitive phosphatase calcineurin. METHODS AND RESULTS: We showed that calcineurin enzymatic activity is increased 3. 2-fold in the heart in response to pressure-overload hypertrophy induced by abdominal aortic banding in the rat. Western blot analysis further demonstrates that calcineurin A (catalytic subunit) protein content and association with calmodulin are increased in response to pressure-overload hypertrophy. This increase in calcineurin protein content was prevented by administration of the calcineurin inhibitor cyclosporine A (CsA). CsA administration attenuated load-induced cardiac hypertrophy in a dose-dependent manner over a 14-day treatment protocol. CsA administration also partially reversed pressure-overload hypertrophy in aortic-banded rats after 14 days. CsA also attenuated the histological and molecular indexes of pressure-overload hypertrophy. CONCLUSIONS: These data suggest that calcineurin is an important upstream regulator of load-induced hypertrophy.

Relation of left ventricular mass, preload, afterload and contractility in pediatric patients with essential hypertension.

OBJECTIVES: The aim of this study was to determine if left ventricular preload, afterload or contractility is a correlate of left ventricular mass index in hypertensive pediatric patients. BACKGROUND: It is believed that decreased contractility and increased preload are associated with left ventricular hypertrophy in adult hypertensive patients. METHODS: Ninety pediatric hypertensive patients underwent echocardiography to assess left ventricular mass, preload (diastolic dimension and volume) and afterload (end-systolic wall stress, vascular resistance and blood pressure). Contractility was assessed by 1) the end-systolic stress/volume ratio, and 2) the difference between measured and predicted velocity of circumferential fiber shortening. Univariate and multivariate analyses were performed. RESULTS: Univariate analysis showed significant correlations between left ventricular mass and 1) body mass (r = 0.33, p < 0.001), 2) black race (r = 0.37, p < 0.0003), 3) diastolic dimension (r = 0.26, p < 0.01), 4) diastolic volume (r = 0.20, p < 0.05), and 5) stress/volume ratio (r = -0.53, p < 0.0001) but not the difference between measured and predicted velocity of circumferential fiber shortening. A multivariate model included body mass, age at diagnosis, diastolic dimension, wall stress and vascular resistance but not the difference between measured and predicted velocity of circumferential fiber shortening. CONCLUSIONS: Contractility is not significantly related to left ventricular mass. The positive correlation between mass and stress/volume may be due to the dependence of the latter variable on loading conditions. We speculate that both elevated preload and systemic vascular resistance may have a role in the development of hypertrophy in hypertensive pediatric patients.

Persistent hyperdynamic cardiovascular state at rest and during exercise in children after successful repair of coarctation of the aorta.

OBJECTIVES: The purposes of this study were to evaluate left ventricular performance and contractility at rest and during exercise to determine mechanisms and correlates for alterations in performance and blood pressure in pediatric patients after successful repair of coarctation of the aorta. BACKGROUND: Blood pressure and left ventricular function are elevated in children despite successful repair. The mechanisms for these changes are not understood. METHODS: Thirty asymptomatic pediatric patients with successful coarctation repair (mean age [+/- SD] 12.5 +/- 4 years) underwent echocardiographic determination of left ventricular mass, performance (shortening fraction), preload (indexed diastolic dimension), afterload (end-systolic wall stress), contractility (velocity of circumferential fiber shortening/wall stress relation) and Doppler gradient at rest and during exercise. Data were compared with those of 24 control subjects (mean age 21.0 +- 4 years). Because of the age discrepancy between groups, age-dependent echocardiographic data were indexed by body surface area. RESULTS: The mean age at operation was 5 +/- 4 years, and the average follow-up period was 7.5 +/- 3 years. The average blood pressure gradient between upper and lower limbs was 4 mm Hg. Left ventricular mass was higher in the postoperative group than in the control group (1.58 vs. 1.31 g/ht2.7, p = 0.04), as were values at rest for performance (44% vs. 31%, p = 0.0001), preload (3.9 vs. 3.7 cm/body surface area0.5), indexes systolic blood pressure (1.05 vs. 0.91, p = 0.0001) and contractility (0.23 vs. -0.05 circumferences/s, p= 0.001). Afterload was lower at rest (36 vs. 52 g/cm2, p = 0.0004). These differences between groups persisted during and after exercise. Contractility underwent an exaggerated increase after exercise in the postoperative group. CONCLUSIONS: Left ventricular performance in children after coarctation repair is higher at rest and during exercise than in control subjects as a result of higher preload and contractility and lower afterload. These changes may be due to associated hypertrophy. Persistent postoperative hypertension may be due to a hyperdynamic, hypercontractile state caused by residual gradients manifested only during exertion.

Effect of ligation of patent ductus arteriosus on left ventricular performance and its determinants in premature neonates.

OBJECTIVES: The purpose of this study was to determine in preterm newborn infants the effects of ductal ligation on ventricular performance and its determinants: preload, afterload and contractility. BACKGROUND: Neonatal ventricular performance is highly sensitive to afterload. Therefore, the increase in systemic vascular resistance associated with ligation of a patent ductus arteriosus might worsen ventricular performance in the preterm infant. METHODS: All 14 premature infants undergoing patent ductus arteriosus ligation in a 1-year period at our institution underwent echocardiography at three times: before, immediately after and 24 h after ligation. Indexes studied included ventricular performance (fractional area change), preload (left ventricular end-diastolic dimension), afterload (end-systolic wall stress) and contractility (the difference between the measured and predicted velocity of circumferential fiber shortening). Blood pressure was measured; systemic resistance was calculated. These data were compared with those of 14 preterm infants without patent ductus arteriosus. RESULTS: The infants with patent ductus arteriosus had higher values for ventricular performance (mean +/- SD fractional area change 60 +/- 9% vs. 52 +/- 11%, p < 0.05) and lower values for wall stress (22 +/- 6 vs. 44 +/- 17 g/cm2, p < 0.05) before ligation than did the control group. At 24 h after ligation, ventricular performance was not significantly changed (fractional area change 60 +/- 9% to 57 +/- 12%). There were significant increases in blood pressure and systemic vascular resistance but no changes in wall stress or contractility. CONCLUSIONS: Ventricular performance is higher in premature infants with than in those without patent ductus arteriosus because afterload is lower in the former group. Although ductal ligation increases blood pressure and systemic resistance, wall stress and ventricular performance are maintained. Our results suggest that the premature newborn maintains ventricular performance during stress, at least in part, by manipulating afterload.

Effect of veno-venous ultrafiltration on myocardial performance immediately after cardiac surgery in children. A prospective randomized study.

OBJECTIVES: This study sought to evaluate the effects of veno-venous ultrafiltration on myocardial contractility in children undergoing cardiopulmonary bypass (CPB) for repair of congenital heart defects. BACKGROUND: Ultrafiltration (UF) is currently used to diminish postoperative fluid accumulation following CPB in children. Previous reports indicate improvement in hemodynamics immediately after UF, but the mechanism of its action is unknown. METHODS: Twenty-three patients (ages 2 months to 9.1 years; 13 males, 10 females) underwent UF for 10 min after CPB. Twelve patients underwent UF immediately after CPB (Group A). They were studied: (1) before and (2) after CPB, (3) after UF, and (4) 10 min after UF. Eleven patients underwent UF 10 min after CPB (Group B). They were studied: (1) before and (2) after CPB, (3) after a 10-min delay before UF, and (4) after UF. Contractility was determined by the difference in the observed and predicted velocity of circumferential fiber shortening for the measured wall stress, using transesophageal echocardiography. Left ventricular wall thickness was also measured. RESULTS: There was significant improvement in contractility after UF in both groups (mean+/-SD, Group A: -0.28+/-0.13 to -0.01+/-0.21 circ/s, p < 0.05; Group B: -0.26+/-0.16 to -0.11+/-0.17 circ/s, p < 0.05). Myocardial thickness to cavity dimension decreased in both groups following UF (Group A: 0.19+/-0.04 to 0.14+/-0.03, p < 0.05; Group B: 0.18+/-0.04 to 0.14+/-0.03, p < 0.05). CONCLUSIONS: UF improves hemodynamics by improving contractility and possibly by reducing myocardial edema in children following cardiac surgery. Enhanced patient outcome after ultrafiltration may in part be due to these changes.

Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice.

OBJECTIVE: Dilation and hypertrophy often occur concurrently in cardiomyopathy, yet the interaction between these two functionally distinct conditions remains unknown. METHODS: Combinatorial effects of hypertrophy and dilation were investigated by cross-breeding of two cardiomyopathic transgenic mouse lines which develop either hypertrophy (calcineurin-mediated) or dilation (tropomodulin-mediated). RESULTS: Altering the intensity of signals driving hypertrophy and dilation in cross-bred litters resulted in novel disease phenotypes different from either parental line. Augmenting the calcineurin-dependent hypertrophic stimulus in tropomodulin overexpressing transgenics elevated heart:body weight ratios, increased ventricular wall thickness, and significantly accelerated mortality. These effects were evident in calcineurin cross-breeding to tropomodulin backgrounds of transgene homozygosity (severe dilation) or heterozygosity (mild dilation to asymptomatic). Molecular analyses indicated that tropomodulin and calcineurin signaling events in the first week after birth were critical for determination of disease outcome, substantiated by demonstration that temporary neonatal inhibition of tropomodulin expression prevents dilation. CONCLUSIONS: This study shows that postnatal timing of altered signaling in cardiomyopathic transgenic mouse models is a pivotal part of determining outcome. In addition, intensifying hypertrophic stimulation exacerbates dilated cardiomyopathy, supporting the concept of shared molecular signaling between hypertrophy and dilation.

Correlates of the hemodynamic determinants of blood pressure.

The purpose of this study was to investigate the association of sex, race, lean body mass, and fat mass with the hemodynamic determinants of blood pressure, including stroke volume, heart rate, and total peripheral vascular resistance. The study included 201 subjects aged 6 to 17 years, 105 of whom were male and 98 of whom were black. Lean body mass and fat mass were both significant (P < .05) independent determinants of stroke volume, cardiac output, and total peripheral vascular resistance. However, the direction of the effect of lean body mass was opposite for stroke volume and cardiac output compared with that of total peripheral vascular resistance. The direct relationship of lean body mass with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (regression coefficients, 0.55 +/- 0.05 for SBP and 0.47 +/- 0.05 for DBP) indicates that the effect of lean body mass on cardiac output may predominate. Lean body mass explained substantially more of the variance of the hemodynamic variables than did fat mass. After control for the effects of body size, male subjects had higher heart rate and cardiac output, and female subjects had higher vascular resistance. White subjects had higher stroke volume and cardiac output, and black subjects had higher peripheral vascular resistance. This study demonstrates that lean body mass is a more important correlate of the hemodynamic determinants of blood pressure than is fat mass and that sex and race have significant independent relationships with the hemodynamic determinants of blood pressure in children and adolescents.

Age-related changes in total arterial capacitance from birth to maturity in a normotensive population.

We evaluated the effect of body growth and aging on the ratio of echocardiographic (Teichholz) stroke volume to pulse pressure (SV/PP ratio) in 373 normal-weight, normotensive children to adolescents (1 day to 17 years old; 166 girls, 87 nonwhite) and 393 normal adults (17 to 85 years old; 164 women, 112 nonwhite). Stroke volume increased with age in children (r = .64, P < .0001) and was stable in adults; pulse pressure decreased slightly with age in children (r = -.10, P = .06) and increased in adults (r = .29, P < .0001). As a consequence, SV/PP ratio increased with age in children (r = .51, P < .0001) and decreased in adults (r = -.18, P = .0004). To control for changes in body size that influence the size of the arterial tree, we used ANCOVA to adjust SV/PP for body size. Body size-adjusted SV/PP ratio was no longer related to age in children, whereas the negative relation with aging in adults remained statistically significant (r = -.19, P < .0002). Heart rate was negatively related to SV/PP ratio in both children and adolescents and adults, but this relation did not influence the relation with age. In multivariate analysis, high SV/PP ratio was predicted by greater height (P < .002) and weight (P < .04) and nonwhite race (P < .001) in children and adolescents and by younger age (P < .0001), greater weight (P < .0001), and low heart rate (P < .001) in adults. Sex did not enter the regression models. Thus, (1) SV/PP ratio is a measure of increasing capacity of the arterial tree during growth, whereas it depends on arterial compliance during adulthood through old age; (2) arterial compliance decreases progressively with aging; (3) the apparent difference between males and females might be due to their different body sizes.

Interaction between body size and cardiac workload: influence on left ventricular mass during body growth and adulthood.

The development of the left ventricle parallels body growth. During infancy, the relation between body size and left ventricular (LV) mass is very close. With advancing age, variability of LV mass in relation to body size markedly increases. To test the hypothesis that the age-related increase in variability of LV mass is due to the progressive impact of hemodynamic stimuli on LV growth, quantitative M-mode echocardiograms were obtained in 766 normal-weight, normotensive individuals over a range of ages from 1 day to 85 years (330 female subjects, 373 subjects younger than 18 years). LV mass was linearly related to height2.7 (r2=.69). Prediction of values of LV mass by body size was more accurate at birth and progressively less precise with increasing age. Stroke work (stroke volume times systolic pressure) was closely related to LV mass (r2=.74). The explained variance of LV mass increased from 69% in the univariate regression with height2.7 to 82% in a multivariate model including height2.7, stroke work, and gender. In children and adolescents (younger than 18 years), height2.7 was the main determinant of LV mass, whereas during adulthood stroke work and gender were more important predictors of LV mass than height2.7. Thus (1) the influence of body growth on development of LV mass decreases after early infancy because of both the variability of hemodynamic load and the increasing effect of gender; (2) after adolescence, during adulthood, in normotensive, normal-weight individuals, the impact of hemodynamic load and male gender on LV mass is greater than the one of body size; and (3) an appreciable proportion of variability of LV mass remains unexplained with the studied models. This might be due to genotypic variations and/or measurement error.

Design and baseline characteristics for the ACE Inhibitor After Anthracycline (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors.

PURPOSE: The ACE Inhibitor After Anthracycline (AAA) study is a randomized, double-blind, controlled clinical trial comparing enalapril with placebo to determine whether treatment can slow the progression of cardiac decline in patients who screen positive for anthracycline cardiotoxicity. METHODS: The primary outcome measure is the rate of decline, over time, in maximal cardiac index (in liters per minute per meters squared) at peak exercise; the secondary outcome measure is the rate of increase in left ventricular end systolic wall stress (in grams per centimeters squared). Patients >2 years off therapy and <4 years from diagnosis, aged 8 years and older, were eligible if they had received anthracyclines and had at least one cardiac abnormality identified at any time after anthracycline exposure. RESULTS: A total of 135 patients were randomized to enalapril or placebo. Baseline characteristics were similar across treatment groups. CONCLUSIONS: The AAA study will provide important information concerning the efficacy of using angiotensin-converting enzyme inhibitors to offset the effects of late anthracycline cardiotoxicity.

Age-related variation in contractility estimate in patients less than or equal to 20 years of age.

The relation between velocity of circumferential fiber shortening (VCF) and wall stress (WS) is being used to estimate contractile state in a variety of disease states and patient ages more frequently. However, its relation to age has not been established. To determine reproducibility and age and sex dependence of this relation, 204 normal children (113 boys, 91 girls) underwent echographic determination of VCF and WS. The children were enrolled in 3 groups: group 1 less than 6 months old (n = 27); group 2 greater than 6 months and less than 3 years old (n = 38); and group 3 greater than 3 and less than 20 years old (n = 139). Twenty-five children also underwent serial echocardiography (n = 44) to determine reproducibility of the relation. Only 1 of the 44 repeat data pairs of VCF and WS was outside the 95% confidence limits of that relation. In all 3 groups, VCF was significantly inversely and linearly related to WS (p less than 0.001). The regression equation in the oldest group was very similar to previous reports (VCF = -0.0031 [WS] + 1.21). The regression lines in the 2 younger groups were significantly steeper and had a significantly higher y-intercept (p less than 0.01). Group 1 had the steepest slope and highest y-intercept. There was no difference in the regression lines of different sexes in any of the patient groups. It is concluded that the relation of VCF to WS is reproducible over time. It is age-dependent but has no relation to gender. VCF in patients less than 6 months old is more highly dependent on WS.(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine stress echocardiography in the assessment of suspected myocardial ischemia in children and young adults.

In 67 studies in 43 children with suspected coronary artery disease, dobutamine stress echocardiography was safe and accurate in diagnosing coronary insufficiency. The efficacy and safety of dobutamine echocardiography make it the ideal test for diagnosing myocardial ischemia in children.