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Biomedical subjects

Sandra A Witt

Publications and source records attributed to Sandra A Witt.

17 recordsLinked to original sources
PubMed2006

Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study.

OBJECTIVE: To determine the prevalence and incidence of left ventricular hypertrophy (LVH) and LV geometry and identify variables associated with LV mass (LVM) growth and development of LVH in children and adolescents with chronic kidney disease (CKD). STUDY DESIGN: A 2-year longitudinal study of children with CKD (glomerular filtration rate [GFR] 15-89 mL/minute/1.73 m2). Thirty-one subjects had baseline and repeated echocardiography. RESULTS: Six (19%) of 31 children had LVH at baseline; the prevalence of LVH increased to 39% at 2-year follow-up. Eccentric LVH was the most common geometric pattern throughout the study. Among 25 children with initially normal LVM index, 8 (32%) developed new LVH. Children with incident LVH had significantly higher mean parathyroid hormone (iPTH), lower hemoglobin and calcium levels at baseline, and significantly larger increase in iPTH during a follow-up than children with normal LVM index. Stepwise regression analysis showed that lower initial LVM index and hemoglobin level and interval increase in iPTH and nighttime systolic blood pressure (SBP) load during a follow-up independently predicted interval increase in LVM index. CONCLUSIONS: LVH progresses in children during early stages of CKD. More aggressive control of anemia, BP, and hyperparathyroidism might be important in preventing the development of LVH in these patients.

Adolescent↗
PubMed2005

Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism.

In children, cardiac abnormalities such as increased left ventricular mass (LVM) and diastolic dysfunction develop at the time of mild to moderate chronic renal insufficiency (CRI) and progress as renal function deteriorates. It was hypothesized that in this age group, vascular abnormalities develop early in the course of chronic kidney disease (CKD) in parallel with cardiac abnormalities and become more severe as end-stage disease is reached. Echocardiography and ultrasound of the carotid artery were performed on 44 patients with CKD stages 2 to 4 (CRI group), 16 patients who were on maintenance dialysis, and 35 healthy individuals. Carotid artery intima-media thickness (cIMT) was measured and distensibility and stiffness were calculated to assess carotid artery structure and function. Both the CRI and dialysis groups had greater cIMT, higher LVM index, and poorer diastolic function than the control subjects (P < 0.0001). Children who were on dialysis had greater cIMT and higher LVM index than those with CRI (P < 0.001) and greater arterial stiffness than both CRI patients and control subjects (P < 0.001). Arterial compliance was similar in CRI and control subjects. In all patients with CKD (CRI and dialysis), increased calcium-phosphorus product predicted increased cIMT. Increased serum phosphorus and intact parathyroid hormone predicted increased arterial stiffness. Elevated intact parathyroid hormone was a predictor of increased LVM index and poor diastolic function. In dialysis patients, the cumulative dose of phosphate binders and calcitriol predicted abnormal vascular structure and function. It is concluded that vascular abnormalities are already present in children and adolescents during early stages of CKD; they are more severe in children who are on maintenance dialysis and are related to abnormal calcium-phosphorus metabolism.

Adaptation, Physiological↗
PubMed2005

Left ventricular function in children with sleep-disordered breathing.

Severe obstructive sleep apnea in children leads to congestive heart failure. We studied the early changes in left ventricular function across a range of severity of the disorder. A dose-dependent decrease in diastolic function with increased severity of obstructive apnea was demonstrated.

Adolescent↗
PubMed2004

Structural cardiac changes as a predictor of respiratory complications after adenotonsillectomy for obstructive breathing during sleep in children.

BACKGROUND AND PURPOSE: To determine the association between structural cardiac changes and postoperative respiratory complications after adenotonsillectomy for obstructive breathing during sleep. PATIENTS AND METHODS: Forty-eight children, ages 2-18 years, undergoing adenotonsillectomy for obstructive breathing during sleep were recruited for this case control study. The case group consisted of 24 children with postoperative respiratory complications after adenotonsillectomy who also had an echocardiogram. An equal number of children without postoperative respiratory complications after adenotonsillectomy were recruited as controls. Left ventricular mass (LVM) was calculated from 2D guided M mode echocardiographic measurements of the left ventricle. Left ventricular mass index (LVMI) was calculated as left ventricular mass/height(2.7). Left ventricular hypertrophy (LVH) was defined as LVMI index greater than the 95th percentile for age. The two groups were compared for demographic variables and cardiac structure. RESULTS: The two groups did not significantly differ by age, height, gender or racial distribution. LVH and right ventricular (RV) dimension greater than the 95th percentile for age remained significantly associated with the occurrence of postoperative respiratory complications after controlling for body mass index (BMI) Z score, age, gender, race, systolic and diastolic blood pressure. CONCLUSIONS: The increased prevalence of structural cardiac changes in the group with complications (P<0.01) suggests an underlying cardiac origin for postoperative respiratory complications in this group of children.

Adenoidectomy↗
PubMed2004

Abnormal carotid artery structure and function in children and adolescents with successful renal transplantation.

BACKGROUND: Abnormal carotid artery compliance and increased intima-media thickness (IMT), markers of early atherosclerosis, are prevalent in adults with chronic kidney failure. However, little is known about the extent of these abnormalities in children after transplantation. METHODS AND RESULTS: Thirty-one children (age, 14.5+/-4.1 years) with renal transplant (estimated glomerular filtration rate, 78.1+/-24.5 mL/min per 1.73 m2; range, 44 to 128 mL/min per 1.73 m2) and 33 age- and sex-matched control subjects had ultrasound of the carotid artery, echocardiography, and ambulatory blood pressure monitoring (transplant patients only). IMT was measured, and distensibility and stiffness parameter (beta) were calculated to assess carotid artery structure and function. The results were correlated with demographic, clinical, and biochemical variables. Compared with control subjects, children with transplant had higher IMT (P=0.03) and beta (P<0.0001) and lower distensibility (P<0.001). In multiple regression analysis, increased IMT in children who had received transplants was associated with higher mean office systolic blood pressure taken within 1 year before the study (R2=0.19, P=0.024) and receipt of >1 transplant (R2=0.16, P=0.02). Worse distensibility and beta were significantly associated with higher daytime systolic blood pressure load calculated from ambulatory blood pressure and receipt of cadaveric kidney. When number of antihypertensives was added to the models, only higher number of blood pressure medications independently predicted abnormal distensibility (R2=0.38, P=0.002) and beta (R2=0.25, P=0.016). CONCLUSIONS: Carotid arteriopathy is present in children with successful renal transplant and is associated with hypertension. The results suggest that these children might be at risk for accelerated atherosclerosis and premature cardiovascular disease.

Adolescent↗
PubMed2004

Right ventricular strain rate and strain analysis in patients with repaired tetralogy of Fallot: possible interventricular septal compensation.

BACKGROUND: Indices such as strain rate (SR) and strain (epsilon) are free of geometric assumptions and, thus, may provide new insights into right ventricular (RV) function and compensatory mechanisms in repaired tetralogy of Fallot (TOF). METHODS: All those with postoperative (>1 year) TOF had echocardiography evaluation of SR and epsilon indices along the RV lateral free wall (RVFW) and the interventricular septum (IVS) in the apical 4-chamber view. Pulmonary regurgitation, pulmonary stenosis, QRS duration, RV ejection fraction, and RV dimension were also measured and compared with control subjects. RESULTS: There were 15 patients with TOF (7 +/- 4 years old) 6 +/- 3 years remote from surgical repair and 25 control subjects (10 +/- 5 years old). In the patients with TOF, systolic and diastolic SR and epsilon in the RVFW were significantly reduced but were normal in the IVS. In the RVFW, reduced systolic SR and epsilon correlated with reduced RV ejection fraction (r = -0.7 [P <.01] and -0.6 [P <.03], respectively), and poorer early diastolic SR correlated with poorer RV ejection fraction (r = 0.7, P <.01). CONCLUSIONS: In patients with postoperative TOF, systolic and diastolic RV SR and epsilon were impaired in the RVFW but preserved in the IVS. We speculate that IVS myocardial function is preserved as a compensatory mechanism for impaired RVFW function.

Adolescent↗
PubMed2004

Abnormal cardiac function in children after renal transplantation.

BACKGROUND: Cardiac hypertrophy frequently is found in children with a renal transplant. In adults with a transplant, left ventricular (LV) mass (LVM) is associated with cardiac dysfunction. However, in children with a transplant, the relationship between LVM and LV function has not been evaluated. METHODS: Twenty-nine children who underwent transplantation and 33 controls had echocardiographic evaluations during rest and peak exercise. LV contractility was determined based on the relation between heart rate-corrected velocity of circumferential fiber shortening and end-systolic wall stress. Contractile reserve was assessed by the difference between contractility at rest and peak exercise. Early diastole was assessed using indices of LV relaxation derived from transmitral and tissue Doppler and reported as maximal early (E wave) and late (A wave) wave ratio (E-A ratio) and septal mitral annular velocities (Em). Late diastole was determined using an index of LV compliance (E-Em ratio). RESULTS: Compared with controls, children with a transplant had a significantly greater LVM index (P < 0.001) and high prevalence of LV hypertrophy (LVH; 55%). Transplant recipients had increased LV contractility (P < 0.001). Contractile reserve was similar to that of controls. Patients with a transplant had a lower E-A ratio and Em (P < 0.01 for both variables) and higher E-Em ratio (P < 0.001) than controls. In children with a transplant, LVM index was a significant independent predictor for both abnormal LV relaxation (Em; P = 0.03) and abnormal LV compliance (E-Em ratio; P = 0.02). CONCLUSION: Results show impaired cardiac structure and diastolic function in pediatric renal allograft recipients. This suggests that LVH may be a risk factor for diastolic dysfunction in these children.

Adolescent↗
PubMed2004

Impaired left ventricular diastolic function in children with chronic renal failure.

BACKGROUND: Diastolic dysfunction is frequent in adults with renal failure. However, in children with mild-to-moderate chronic renal insufficiency (CRI), it has not been evaluated. We compared diastolic function and assessed risk factors associated with diastolic dysfunction in children with CRI with those on dialysis. METHODS: Thirty-three children with CRI, 17 on chronic dialysis, and 33 control patients, had echocardiography performed. Early diastole was assessed using indices of left ventricular (LV) relaxation derived from transmitral and tissue Doppler, and reported as the peak E/A wave ratio, and septal mitral annular velocities (Em). Late diastole was determined using an index of LV compliance (E/Em ratio). Left atrial (LA) dimension was also determined. RESULTS: Children with CRI had worse diastolic function (lower Em, and higher E/Em ratio than control patients, P < 0.001). Dialysis patients had worse diastolic function (lower E/A ratio and Em, and higher E/Em ratio, P < 0.001) than CRI children. LA dimension was higher in renal patients when compared with control patients (P < 0.001). In children on dialysis, LV relaxation (Em) was significantly related to left ventricular mass (LVM) index (r=-0.58, P= 0.04), and LV compliance (E/Em) was significantly associated with LA index (r= 0.67, P= 0.01), LVM index (r= 0.75, P < 0.01), hemoglobin level (r=-0.65, P= 0.02), serum phosphorus (r= 0.56, P= 0.05), and calcium-phosphorus ion product (r= 0.59, P= 0.04). CONCLUSION: Our results indicate that diastolic dysfunction is already present in children with mild-to-moderate CRI. Worse diastolic function in dialysis patients might be related to LV hypertrophy. The results suggest that children with advanced renal failure and diastolic dysfunction may be at risk for ultimate worsening of cardiac function over time.

Adolescent↗
PubMed2003

Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity.

We recently developed a mouse model with a single functional allele of Serca2 (Serca2+/-) that shows impaired cardiac contractility and relaxation without overt heart disease. The goal of this study was to test the hypothesis that chronic reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2 levels in combination with an increased hemodynamic load will result in an accelerated pathway to heart failure. Age-matched wild-type and Serca2+/- mice were subjected to 10 wk of pressure overload via transverse aortic coarctation surgery. Cardiac hypertrophy and heart failure were assessed by echocardiography, gravimetry/histology, hemodynamics, and Western blotting analyses. Our results showed that approximately 64% of coarcted Serca2+/- mice were in heart failure compared with 0% of coarcted wild-type mice (P < 0.05). Overall, morbidity and mortality were greatly increased in Serca2+/- mice under pressure overload. Echocardiography assessment revealed a significant increase in left ventricular (LV) mass, and LV hypertrophy in coarcted Serca2+/- mice converted from a concentric to an eccentric pattern, similar to that seen in human heart failure. Coarcted Serca2+/- mice had decreased contractile/systolic and relaxation/diastolic performance and/or function compared with coarcted wild-type mice (P < 0.05), despite a similar duration and degree of pressure overload. SERCA2a protein levels were significantly reduced (>50%) in coarcted Serca2+/- mice compared with noncoarcted and coarcted wild-type mice. Our findings suggest that reduction in SERCA2 levels in combination with an increased hemodynamic load results in an accelerated pathway to heart failure.

Animals↗
PubMed2003

Left ventricular mass and systolic performance in pediatric patients with chronic renal failure.

BACKGROUND: Children with chronic renal disease have a high prevalence of left ventricular hypertrophy (LVH), which is thought to be adaptive to improve contractility and lower wall stress in the face of increased afterload and preload. The aim of this study was to determine the association between LV mass, LV performance, and LV contractility in children with chronic renal insufficiency (CRI) and children undergoing chronic dialysis. METHODS AND RESULTS: Twenty-five children with CRI, 12 undergoing chronic dialysis, and 24 controls had echocardiographic evaluation during rest and peak exercise. LV performance was assessed by calculation of shortening fraction and heart rate-corrected velocity of circumferential fiber shortening (VCF). Contractility (VCF difference) was determined based on the relation between VCF and end-systolic wall stress. Contractile reserve was assessed by the difference between contractility at rest and peak exercise. The dialysis group had higher LVM index than the group with CRI (42.9+/-10.3 versus 29.9+/-9.4 g/m(2.7), P<0.001). Both groups had higher LVM index compared with controls (22.2+/-6.1 g/m(2.7), P<0.001). At rest, the CRI and dialysis groups had significantly higher VCF(c) (P<0.001) and VCF difference (P<0.05) and significantly lower wall stress (P<0.01) compared with the control group. Dialysis patients had significantly lower contractile reserve compared with the control group (P<0.03). CONCLUSIONS: These results indicate that children with CRI and undergoing chronic dialysis have increased LVM, LV performance, and contractility at rest. However, dialysis patients have diminished contractile reserve during exercise, which might be an indicator for the development of more severe systolic dysfunction over time.

Adolescent↗
PubMed2003

Color M-mode and Doppler tissue evaluation of diastolic function in children: simultaneous correlation with invasive indices.

OBJECTIVE: The purpose of this study was to explore the validity of diastolic indices derived from color M-mode Doppler and Doppler tissue imaging in a heterogeneous group of pediatric patients by comparing them with simultaneously obtained invasive indices of diastolic function. METHODS: A total of 20 children undergoing left heart catheterization had echocardiographic images recorded simultaneously with high-fidelity left ventricular (LV) pressure tracings. Transmitral Doppler, pulmonary vein Doppler, Doppler tissue imaging, and color M-mode Doppler flow propagation velocity were recorded. LV peak negative dP/dt, the time constant of isovolumic relaxation, and LV end-diastolic pressure were compared with the echocardiographic indices. RESULTS: The ratio of peak E-wave mitral velocity/propagation velocity correlated significantly with LV end-diastolic pressure (r = 0.71; P <.001). Propagation velocity correlated with the time constant of isovolumic relaxation (r = -0.56; P =.01) and peak negative dP/dt (r = 0.50; P <.03). Septal mitral annular myocardial velocity correlated significantly with the time constant of isovolumic relaxation (r = -0.58, P =.01). CONCLUSION: The newer diastolic indices derived from color M-mode Doppler and Doppler tissue imaging appear to be a helpful adjunct in the noninvasive assessment of diastolic function in children.

Adolescent↗
PubMed2003

Moderate-dose dobutamine maximizes left ventricular contractile response during dobutamine stress echocardiography in children.

BACKGROUND: Assessment of ventricular contractile reserve by dobutamine stress echocardiography (DSE) may be a powerful tool for detection of subclinical ventricular dysfunction, however, the hemodynamic dose-response relationship during DSE in children has not been established. METHODS: To characterize changes in hemodynamics and ventricular contractility during DSE in children, 26 participants (age 8.3 +/- 4.8 years; 17 male/9 female) with normal resting left-ventricular function underwent DSE. Participants with abnormal wall motion at rest or during DSE, or rejection were excluded. Left ventricular M-mode echocardiography and carotid pulse tracings were obtained at each stage for calculation of shortening fraction, velocity of circumferential fiber shortening (VCFc), and end-systolic wall stress (WS). Contractility was expressed as the difference between actual and predicted VCFc for measured WS. Dose-response curves for shortening fraction, VCFc, WS, and contractility (the difference between actual and predicted VCFc for measured WS) were obtained. RESULTS: Stepwise changes in contractility, systolic blood pressure, WS, and left ventricular shortening fraction were observed at doses up to, but not beyond, 20 microg/kg/min. Increases in double product were observed at doses up to 30 microg/kg/min. CONCLUSIONS: DSE at a dobutamine dose of 20 microg/kg/min is optimal to fully assess contractile reserve in children. Lesser doses may provide insufficient stress, whereas higher doses may incur unnecessary increases in myocardial oxygen consumption and side effects.

Adolescent↗
PubMed2003

Is there a role for intravenous transpulmonary contrast imaging in pediatric stress echocardiography?

OBJECTIVE: Intravenous transpulmonary contrast echocardiography plays a significant role in the enhancement of endocardial border delineation during stress echocardiography in the adult population. The current study was conducted to evaluate the feasibility of intravenous transpulmonary contrast in pediatric patients and to compare the quality of endocardial visualization by harmonic 2-dimensional (2D) imaging alone with harmonic 2D echocardiography with contrast imaging. METHODS: Twenty-two children, age 9.3 +/- 3.9 underwent dobutamine (19 patients) or exercise (3 patients) stress echocardiography. None had intracardiac shunting. Each patient underwent both harmonic 2D imaging alone and harmonic 2D imaging with contrast administration at peak stress. Oxygen saturation, heart rate, and blood pressure were monitored. Endocardial delineation was evaluated by qualitative grading of 22 endomyocardial regional segments in each patient. Contrast images were graded by an echocardiographer who was blinded to the scores previously assigned to harmonic 2D echocardiography images. RESULTS: There were no changes in saturation, heart rate, or blood pressure during or after contrast administration. Use of contrast significantly improved endocardial visualization in 11 of 22 segments (P <.05), particularly lateral, apical, and anterior left ventricular wall segments. CONCLUSION: Intravenous intrapulmonary administration is feasible and has no obvious adverse effects in a small pediatric patient group. Contrast echocardiography improves endocardial border delineation over harmonic imaging in pediatric stress echocardiography.

Adolescent↗
PubMed2002

Left ventricular hypertrophy and abnormal ventricular geometry in children and adolescents with obstructive sleep apnea.

Obstructive sleep apnea (OSA) has been shown to be an independent risk factor for cardiovascular disease in adults. However, there are severe limitations in the extent to which the cardiovascular consequences of OSA are being studied in children. To investigate the echocardiographic changes in children with OSA, right and left ventricular (RV, LV) dimensions and LV mass index and geometry were measured in 28 children with OSA and 19 children with primary snoring (PS). The study showed that LV mass index and relative wall thickness were greater in the OSA group compared with those with PS (p = 0.012 and p < 0.0001, respectively). An apnea-hypopnea index of more than 10 per hour was significantly associated with RV dimension above the 95th percentile (odds ratios, 6.7; 95% confidence interval, 1.4-32) and LV mass index above the 95th percentile (odds ratios, 11.2; confidence interval, 1.9-64). Abnormality of LV geometry was present in 15% of children with PS compared with 39% of children with OSA. We conclude that OSA in children is associated with increased LV mass.

Adolescent↗
PubMed2002

Left atrial size in children with hypertension: the influence of obesity, blood pressure, and left ventricular mass.

OBJECTIVE: To evaluate the prevalence of left atrial enlargement and the correlates of left atrial size in children and adolescents with essential hypertension. BACKGROUND: Left atrial enlargement has been associated with increased risk of cardiovascular disease, including stroke in adults. Risk factors for left atrial size in adults with hypertension include age, race, and obesity. METHODS AND RESULTS: Patients (n =112; average age, 14.2 years) with essential hypertension were studied with echocardiography. The average left atrial dimension was 2.8 (+/- 0.5) cm; 51% patients had left atrial dimension >95% upper confidence limit. The patients with left atrial enlargement had greater body mass index (P <.05) than those without left atrial enlargement. In multiple regression analysis, height, body mass index, systolic blood pressure, and left ventricular geometry were significant independent correlates of left atrial size. Children with eccentric left ventricular hypertrophy were more likely to have a larger left atrial dimension. CONCLUSIONS: Left atrial enlargement is prevalent in children and adolescents with essential hypertension. This may indicate an increased risk of cardiovascular disease morbidity and mortality. Control of obesity and blood pressure elevation offer two approaches for treatment that may prevent left atrial enlargement.

Adolescent↗
PubMed2002

TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II.

Angiotensin II (Ang II), a potent hypertrophic stimulus, causes significant increases in TGFb1 gene expression. However, it is not known whether there is a causal relationship between increased levels of TGF-beta1 and cardiac hypertrophy. Echocardiographic analysis revealed that TGF-beta1-deficient mice subjected to chronic subpressor doses of Ang II had no significant change in left ventricular (LV) mass and percent fractional shortening during Ang II treatment. In contrast, Ang II-treated wild-type mice showed a >20% increase in LV mass and impaired cardiac function. Cardiomyocyte cross-sectional area was also markedly increased in Ang II-treated wild-type mice but unchanged in Ang II-treated TGF-beta1-deficient mice. No significant levels of fibrosis, mitotic growth, or cytokine infiltration were detected in Ang II-treated mice. Atrial natriuretic factor expression was approximately 6-fold elevated in Ang II-treated wild-type, but not TGF-beta1-deficient mice. However, the alpha- to beta-myosin heavy chain switch did not occur in Ang II-treated mice, indicating that isoform switching is not obligatorily coupled with hypertrophy or TGF-beta1. The Ang II effect on hypertrophy was shown not to result from stimulation of the endogenous renin-angiotensis system. These results indicate that TGF-beta1 is an important mediator of the hypertrophic growth response of the heart to Ang II.

Angiotensin II↗