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2.
J Pediatr ; 153(4): 565-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18534216

ABSTRACT

OBJECTIVES: Midwall shortening (mwSF) is thought to be a more accurate measure of myocardial performance in the presence of left ventricular hypertrophy (LVH). We examined mwSF in pediatric patients with varying degrees of chronic kidney disease (CKD). STUDY DESIGN: Fifty-seven children with CKD stages 2 to 4, 25 who were undergoing hemodialysis and 49 who were transplant recipients, were compared with 35 healthy control subjects. Left ventricular (LV) geometry and indices of LV function were assessed echocardiographically. RESULTS: There were no significant differences in LV contractility or endocardial shortening fraction between patients and control subjects. Yet, patients undergoing hemodialysis had significantly lower mwSF compared with control subjects (P < .01) and patients with stage 2 to 4 CKD (P < .01). Renal transplant patients had lower mwSF compared with control subjects (P < .01). The prevalence of abnormal mwSF (ie, <16) was significantly higher in patients undergoing hemodialysis (40%) compared with patients who were renal transplant recipeints (12%) and patients with CKD stages 2 to 4 (9%; P = .03). With stepwise regression, mwSF was demonstrated to be predicted by using relative wall thickness (P < .0001), dialysis group (P = .005), and endocardial shortening fraction (P = .001; model R(2) = 0.86). CONCLUSIONS: Children undergoing maintenance hemodialysis and children with concentric LVH have subclinical systolic dysfunction, which might be an indicator for the development of more severe cardiac disease.


Subject(s)
Heart/physiopathology , Hypertrophy, Left Ventricular/complications , Kidney Diseases/complications , Adolescent , Child , Chronic Disease , Echocardiography, Doppler , Female , Glomerular Filtration Rate , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Kidney Transplantation/physiology , Male , Renal Dialysis , Systole/physiology
3.
Pediatr Nephrol ; 23(8): 1297-302, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18458956

ABSTRACT

We sought to determine flow-mediated vasodilatation (FMD) of the brachial artery and to assess the relationship of FMD with multiple demographic, clinical and biochemical parameters and cardiac and vascular structure and function in children with chronic kidney disease (CKD) stages 2-4. Forty-three patients, aged 6-20 years, with CKD [mean glomerular filtration rate (GFR) 47 +/- 21 ml/min per 1.73 m2 body surface area, range 16-89 ml/min per 1.73 m2] and 34 healthy age-matched controls were included and studied cross-sectionally between 2001 and 2005. The peak FMD was similar in the CKD and control subjects (mean 6.3% vs 6.7%, P = 0.85). However, abnormally low FMD (< 1.1%) was found in ten (23%) children with CKD. Among children with CKD, those with low FMD were younger, shorter, lighter, and had lower body mass index (BMI) than children with normal FMD, but the difference reached statistical significance only for weight and BMI. Serum triglyceride levels were significantly lower in those with low FMD; otherwise, the two groups were similar with respect to multiple clinical and biochemical parameters. Cardiac and vascular structure was similar in children with normal and low FMD. In conclusion, children with CKD stage 2-4 appear to have increased prevalence of decreased FMD of the brachial artery. However, our study identified few significant factors associated with low FMD in children with CKD.


Subject(s)
Brachial Artery/physiology , Endothelium, Vascular/physiology , Regional Blood Flow/physiology , Renal Insufficiency, Chronic/physiopathology , Vasodilation/physiology , Adolescent , Body Mass Index , Child , Cohort Studies , Cross-Sectional Studies , Female , Glomerular Filtration Rate/physiology , Humans , Male , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Triglycerides/blood
4.
J Am Coll Cardiol ; 51(14): 1342-8, 2008 Apr 08.
Article in English | MEDLINE | ID: mdl-18387434

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate changes in cardiac geometry, systolic and diastolic function before and after weight loss in morbidly obese adolescents. BACKGROUND: Cardiac abnormalities are present in morbidly obese adolescents; however, it is unclear if they are reversible with weight loss. METHODS: Data from 38 adolescents (13 to 19 years; 29 females, 9 males, 33 Caucasians, 5 African Americans) were evaluated before and after bariatric surgery. Left ventricular mass (LVM), left ventricular (LV) geometry, systolic and diastolic function were assessed by echocardiography. Mean follow up was 10 +/- 3 months. RESULTS: Weight and body mass index decreased post-operatively (mean weight loss 59 +/- 15 kg, pre-operative body mass index 60 +/- 9 kg/m(2) vs. follow-up 40 +/- 8 kg/m(2), p < 0.0001). Change in LVM index (54 +/- 13 g/m(2.7) to 42 +/- 10 g/m(2.7), p < 0.0001) correlated with weight loss (r = 0.41, p = 0.01). Prevalence of concentric left ventricular hypertrophy (LVH) improved from 28% at pre-operative to only 3% at follow up (p = 0.007), and normal LV geometry improved from 36% to 79% at follow up (p = 0.009). Diastolic function also improved (mitral E/Ea lateral 7.7 +/- 2.3 at pre-operative vs. 6.3 +/- 1.6 at post-operative, p = 0.003). In addition, rate-pressure product improved suggesting decreased cardiac workload (p < 0.001). CONCLUSIONS: Elevated LVM index, concentric LVH, altered diastolic function, and cardiac workload significantly improve following surgically induced weight loss in morbidly obese adolescents. Large weight loss due to bariatric surgery improves predictors of future cardiovascular morbidity in these young people.


Subject(s)
Bariatric Surgery , Heart Diseases/etiology , Heart Diseases/prevention & control , Heart/physiopathology , Obesity, Morbid/complications , Weight Loss , Adolescent , Adult , Body Mass Index , Diastole , Disease Progression , Female , Heart Diseases/physiopathology , Humans , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/physiopathology , Male , Obesity, Morbid/physiopathology , Obesity, Morbid/surgery , Prevalence , Systole
5.
Am J Physiol Heart Circ Physiol ; 294(6): H2480-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18390820

ABSTRACT

The purpose of this study is to provide standard echocardiographic and morphometric data for normal mouse valve structure and function from late fetal to aged adult stages. Cross-sectional, two-dimensional and Doppler transthoracic echocardiography was performed in C57BL6 mice anesthetized with 1% to 2% isoflurane at embryonic day 18.5 (late fetal), 10 days (neonate), 1 mo (juvenile), 2 mo (young adult), 9 mo (old adult), and 16 mo (aged adult). Normal annulus dimensions indexed to age or weight, and selected flow velocities, were established by echocardiography. After echocardiographic imaging, hearts were harvested and histological and morphometric analyses were performed. Morphometric analysis demonstrated a progressive valve thinning and elongation during the fetal and juvenile stages that plateaued during adult stages (ANOVA, P < 0.01); however, there was increased thickening of the hinge of the aortic valve with advanced age, reminiscent of human aortic valve sclerosis. There was no age-related calcification. The results of this study provide comprehensive echocardiographic and morphometric data for normal mouse valve structure and function from late fetal to aged adult stages and should prove useful as a reference standard for future studies using mouse models of progressive valve disease.


Subject(s)
Aging , Echocardiography, Doppler , Heart Valves/embryology , Heart Valves/growth & development , Age Factors , Animals , Animals, Newborn , Body Weight , Female , Gestational Age , Heart Valves/diagnostic imaging , Hemodynamics , Male , Mice , Mice, Inbred C57BL , Myocardial Contraction , Organ Size , Reference Values , Ventricular Function
6.
J Pediatr ; 150(5): 503-9, 2007 May.
Article in English | MEDLINE | ID: mdl-17452225

ABSTRACT

OBJECTIVE: To evaluate whether essential hypertension impacts diastolic function in children. STUDY DESIGN: In this cross-sectional study, patients with essential hypertension (n = 50) were compared with a normotensive group (n = 53). Echocardiographic assessment of diastolic function included measures derived from transmitral, color M-mode, and tissue Doppler interrogation. Cardiac dimensions, wall thickness, geometry, and systolic function were also assessed. Multiple linear regression analysis was performed to identify predictors of altered diastolic function. RESULTS: Diastolic filling abnormalities were found in 36% of the children with blood pressure elevation. Those subjects with concentric hypertrophy were more significantly affected. Abnormalities in indices reflective of left ventricular (LV) relaxation occurred more commonly (39%) than those of LV compliance (33%). Elevated indexed LV mass was found to be the most significant independent predictor of diastolic filling abnormalities. CONCLUSIONS: LV diastolic filling abnormalities were found in one-third of the pediatric subjects with essential hypertension. Whether these changes represent an adaptive or maladaptive response requires further study.


Subject(s)
Diastole , Hypertension/physiopathology , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male
7.
J Pediatr ; 149(5): 671-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17095341

ABSTRACT

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.


Subject(s)
Hypertrophy, Left Ventricular/physiopathology , Kidney Failure, Chronic/physiopathology , Adolescent , Adult , Atrial Function , Biomarkers/blood , Blood Pressure , Child , Circadian Rhythm , Disease Progression , Echocardiography , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/epidemiology , Incidence , Kidney Failure, Chronic/diagnostic imaging , Kidney Failure, Chronic/epidemiology , Male , Predictive Value of Tests , Prevalence , Prospective Studies , Severity of Illness Index , Stroke Volume , Time Factors , Ventricular Function, Left
8.
J Am Soc Nephrol ; 16(9): 2796-803, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16049067

ABSTRACT

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.


Subject(s)
Calcium/metabolism , Kidney Failure, Chronic/metabolism , Phosphorus/metabolism , Adaptation, Physiological , Adolescent , Adult , Blood Vessels/physiopathology , Carotid Arteries/pathology , Carotid Arteries/physiopathology , Case-Control Studies , Child , Child, Preschool , Female , Heart/physiopathology , Humans , Hypertrophy, Left Ventricular/etiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/physiopathology , Male , Renal Dialysis , Ventricular Dysfunction, Left/etiology
9.
Sleep Med ; 6(3): 241-5, 2005 May.
Article in English | MEDLINE | ID: mdl-15854854

ABSTRACT

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.


Subject(s)
Adenoidectomy , Adenoids/surgery , Blood Pressure , Hypertrophy, Left Ventricular/etiology , Postoperative Complications , Respiration Disorders/diagnosis , Respiration Disorders/etiology , Sleep Apnea, Obstructive/etiology , Tonsillectomy , Tonsillitis/complications , Tonsillitis/surgery , Body Mass Index , Child , Female , Humans , Hypertrophy, Left Ventricular/diagnosis , Male , Severity of Illness Index
11.
Circulation ; 110(1): 97-101, 2004 Jul 06.
Article in English | MEDLINE | ID: mdl-15210594

ABSTRACT

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.


Subject(s)
Arteriosclerosis/pathology , Arteriosclerosis/physiopathology , Carotid Arteries/pathology , Carotid Arteries/physiopathology , Kidney Transplantation , Adolescent , Adult , Blood Pressure , Child , Compliance , Female , Humans , Male
12.
Kidney Int ; 65(4): 1461-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15086489

ABSTRACT

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.


Subject(s)
Kidney Failure, Chronic/complications , Ventricular Dysfunction, Left/etiology , Adolescent , Adult , Case-Control Studies , Child , Diastole , Echocardiography , Female , Humans , Hypertrophy, Left Ventricular/etiology , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , Male , Renal Dialysis , Severity of Illness Index , Ventricular Dysfunction, Left/diagnostic imaging
13.
Am J Kidney Dis ; 43(4): 721-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15042550

ABSTRACT

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.


Subject(s)
Hypertrophy, Left Ventricular , Kidney Transplantation , Ventricular Dysfunction, Left/epidemiology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Heart Failure/epidemiology , Heart Function Tests , Humans , Hypertrophy, Left Ventricular/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Male , Risk Factors , Ventricular Function, Left
14.
J Am Soc Echocardiogr ; 17(4): 338-44, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15044867

ABSTRACT

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.


Subject(s)
Cardiac Surgical Procedures , Tetralogy of Fallot/physiopathology , Tetralogy of Fallot/surgery , Ventricular Function, Right/physiology , Adolescent , Child , Child Welfare , Child, Preschool , Diastole/physiology , Female , Heart Septum/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Observer Variation , Ohio , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Pulmonary Valve Insufficiency/epidemiology , Pulmonary Valve Insufficiency/etiology , Pulmonary Valve Insufficiency/physiopathology , Pulmonary Valve Stenosis/epidemiology , Pulmonary Valve Stenosis/etiology , Pulmonary Valve Stenosis/physiopathology , Statistics as Topic , Stroke Volume/physiology , Systole/physiology , Tetralogy of Fallot/epidemiology , Treatment Outcome
15.
Am J Physiol Heart Circ Physiol ; 286(3): H1146-53, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14630633

ABSTRACT

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.


Subject(s)
Calcium-Transporting ATPases/genetics , Calcium-Transporting ATPases/metabolism , Heart Failure/metabolism , Heart Failure/physiopathology , Animals , Calcium/metabolism , Cardiac Catheterization , Diastole , Echocardiography , Female , Heart Failure/diagnostic imaging , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/metabolism , Hypertrophy, Left Ventricular/physiopathology , Male , Mice , Mice, Knockout , Phenotype , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Systole
16.
J Am Soc Echocardiogr ; 16(9): 988-94, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12931112

ABSTRACT

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.


Subject(s)
Echocardiography , Stroke Volume/physiology , Adolescent , Adult , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Cardiac Catheterization , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/physiopathology , Child , Child Welfare , Child, Preschool , Diastole/physiology , Echocardiography, Doppler, Color , Echocardiography, Doppler, Pulsed , Female , Heart Atria/abnormalities , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/physiopathology , Heart Rate/physiology , Heart Ventricles/abnormalities , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Infant , Infant Welfare , Infant, Newborn , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/physiopathology , Observer Variation , Ohio , Pulmonary Veins/abnormalities , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/physiopathology , Reproducibility of Results , Statistics as Topic
17.
J Am Soc Echocardiogr ; 16(2): 140-6, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12574740

ABSTRACT

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.


Subject(s)
Cardiotonic Agents/administration & dosage , Dobutamine/administration & dosage , Echocardiography, Stress , Myocardial Contraction , Ventricular Function, Left/physiology , Adolescent , Child , Child, Preschool , Female , Hemodynamics/drug effects , Humans , Infant , Male
18.
Circulation ; 107(6): 864-8, 2003 Feb 18.
Article in English | MEDLINE | ID: mdl-12591757

ABSTRACT

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.


Subject(s)
Kidney Failure, Chronic/physiopathology , Organ Size , Systole , Ventricular Function, Left , Adolescent , Adult , Antihypertensive Agents/therapeutic use , Child , Chronic Disease , Echocardiography , Exercise Test , Female , Hemodynamics , Humans , Kidney Failure, Chronic/therapy , Male , Myocardial Contraction/physiology , Reference Values , Renal Dialysis , Systole/physiology , Ventricular Function, Left/physiology
19.
J Am Soc Echocardiogr ; 16(1): 9-14, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12514629

ABSTRACT

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.


Subject(s)
Contrast Media/administration & dosage , Echocardiography, Stress , Image Enhancement , Adolescent , Adult , Blood Pressure/drug effects , Body Mass Index , Child , Child Welfare , Child, Preschool , Coronary Circulation/drug effects , Coronary Circulation/physiology , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/physiopathology , Heart Rate/drug effects , Humans , Infant , Infant Welfare , Infusions, Intravenous , Oxygen/blood
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