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Thomas R Kimball

Publications and source records attributed to Thomas R Kimball.

At least 37 records · Page 2Linked to original sources
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

Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy.

Calcineurin (PP2B) is a calcium/calmodulin-activated, serine-threonine phosphatase that transmits signals to the nucleus through the dephosphorylation and translocation of nuclear factor of activated T cell (NFAT) transcription factors. Whereas calcineurin-NFAT signaling has been implicated in regulating the hypertrophic growth of the myocardium, considerable controversy persists as to its role in maintaining versus initiating hypertrophy, its role in pathological versus physiological hypertrophy, and its role in heart failure. To address these issues, NFAT-luciferase reporter transgenic mice were generated and characterized. These mice showed robust and calcineurin-specific activation in the heart that was inhibited with cyclosporin A. In the adult heart, NFAT-luciferase activity was upregulated in a delayed, but sustained manner throughout eight weeks of pathological cardiac hypertrophy induced by pressure-overload, or more dramatically following myocardial infarction-induced heart failure. In contrast, physiological hypertrophy as produced in two separate models of exercise training failed to show significant calcineurin-NFAT coupling in the heart at multiple time points, despite measurable increases in heart to body weight ratios. Moreover, stimulation of hypertrophy with growth hormone-insulin-like growth factor-1 (GH-IGF-1) failed to activate calcineurin-NFAT signaling in the heart or in culture, despite hypertrophy, activation of Akt, and activation of p70 S6K. Calcineurin Abeta gene-targeted mice also showed a normal hypertrophic response after GH-IGF-1 infusion. Lastly, exercise- or GH-IGF-1-induced cardiac growth failed to show induction of hypertrophic marker gene expression compared with pressure-overloaded animals. Although a direct cause-and-effect relationship between NFAT-luciferase activity and pathological hypertrophy was not proven here, our results support the hypothesis that separable signaling pathways regulate pathological versus physiological hypertrophic growth of the myocardium, with calcineurin-NFAT potentially serving a regulatory role that is more specialized for maladaptive hypertrophy and heart failure.

Animals↗
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

Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction.

Cardiovascular disease is the leading cause of mortality and morbidity within the industrialized nations of the world, with coronary heart disease (CHD) accounting for as much as 66% of these deaths. Acute myocardial infarction is a typical sequelae associated with long-standing coronary heart disease resulting in large scale loss of ventricular myocardium through both apoptotic and necrotic cell death. In this study, we investigated the role that the calcium calmodulin-activated protein phosphatase calcineurin (PP2B) plays in modulating cardiac apoptosis after acute ischemia-reperfusion injury to the heart. Calcineurin Abeta gene-targeted mice showed a greater loss of viable myocardium, enhanced DNA laddering and TUNEL, and a greater loss in functional performance compared with strain-matched wild-type control mice after ischemia-reperfusion injury. RNA expression profiling was performed to uncover potential mechanisms associated with this loss of cardioprotection. Interestingly, calcineurin Abeta-/- hearts were characterized by a generalized downregulation in gene expression representing approximately 6% of all genes surveyed. Consistent with this observation, nuclear factor of activated T cells (NFAT)-luciferase reporter transgenic mice showed reduced expression in calcineurin Abeta-/- hearts at baseline and after ischemia-reperfusion injury. Finally, expression of an activated NFAT mutant protected cardiac myocytes from apoptotic stimuli, whereas directed inhibition of NFAT augmented cell death. These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart.

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

Normal values of left ventricular systolic and diastolic function derived from signal-averaged acoustic quantification waveforms: a multicenter study.

Automated border-detection techniques such as acoustic quantification have proven accurate and useful for quantifying left ventricular (LV) function. We acquired LV acoustic quantification waveforms from the parasternal short-axis window in 140 healthy patients in the age range of 16 to 78 years. Signal-averaged waveforms were analyzed for parameters of systolic and diastolic performance. The average fractional area change was 54 +/- 12%, and there were no significant changes in LV systolic function in the age range studied. There were significant changes in diastolic parameters with aging. The percentage of contribution to total LV filling occurring during atrial filling nearly tripled during the 6 decades studied, from 13% in the youngest cohort to 36% in the eighth decade of life. This study provides normal reference values for systolic and diastolic parameters of LV function determined from signal-averaged acoustic quantification waveforms acquired from the parasternal short-axis view in adult and adolescent patients over a wide age range.

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↗
PubMed2003

Does assessment of pretest probability of disease improve the utility of echocardiography in suspected endocarditis in children?

OBJECTIVE: To compare the yield rate (YR) of echocardiography when evaluating children with suspected infectious endocarditis (IE) in both the actual clinical setting and in the hypothetic setting where strict clinical criteria are applied. Study design Medical records of 101 children undergoing echocardiography for suspected IE were reviewed. Echocardiograms with positive findings were identified and the actual diagnostic YR was calculated. With the use of clinical criteria proposed by von Reyn (VR), the probability of IE was retrospectively classified as (1) rejected, (2) possible, or (3) probable. Theoretic YR of echocardiography was calculated for each classification. RESULTS: The actual YR of echocardiography was 12% (12/101). The YR of echocardiography by VR class was 0% in rejected, 20% in possible, and 80% in probable cases (chi(2) = 55.1, P <.0001). Echocardiography did not change the probability of IE in any patient classified as rejected, but allowed reassignment of disease probability in a significant proportion of patients with possible or probable IE. CONCLUSIONS: The YR of echocardiography was significant when clinical probability of IE was intermediate-to-high, and low, with marginal clinical utility, when clinical probability was low. Strict pretest assessment of disease probability may lead to more effective utilization of echocardiography in this population.

Bacteria↗
PubMed2003

Cardiovascular physiology during supine cycle ergometry and dobutamine stress.

PURPOSE: This study compared cardiac hemodynamics during supine cycle ergometry and dobutamine stress. METHODS: Thirty-two healthy volunteers (19 female, 13 male, 23.5 +/- 3.5 yr old) completed respective tests on separate days and in random order. Heart rate, blood pressure, and cardiac output were recorded at baseline and peak stress. Echocardiographic measures included left ventricular end-diastolic dimension, fractional shortening, heart rate corrected velocity of circumferential fiber shortening, end-systolic wall stress, and the difference between measured and predicted fiber shortening for measured wall stress. RESULTS: Compared with peak exercise, dobutamine infusion resulted in lower cardiac output (12 +/- 2 vs 16 +/- 4 l x min(-1), P < 0.0001), heart rates (163 +/- 7 vs 175 +/- 12 beats x min(-1), P < 0.0001), and systolic blood pressure (160 +/- 22 vs 185 +/- 20 mm Hg, P < or = 0.0001). Echocardiography demonstrated smaller left ventricular end-diastolic dimension (4.2 +/- 0.7 vs 4.5 +/- 0.7 cm, P = 0.013), higher fractional shortening (0.55 +/- 0.07 vs 0.50 +/- 0.06%, P < 0.001), higher VCFc (2.07 +/- 0.36 vs 1.54 +/- 0.20 circs x s(-1), P < 0.001) higher VCFdiff (0.94 +/- 0.35 vs 0.48 +/- 0.20 circs x s(-1), P < 0.001), and lower end-systolic wall stress (25 +/- 11 vs 42 +/- 16 g x cm(-2), P < 0.001). The stress-velocity relationship during dobutamine demonstrated higher y-intercept and steeper slope, indicating greater load-independent contractility. CONCLUSION: The cardiovascular adaptation to exercise and dobutamine stress differ significantly. Cardiac output during peak exercise is greater than during peak dobutamine secondary to increased heart rate and stroke volume. Despite a greater increase in contractility and decrease in afterload, a smaller increase in cardiac output during dobutamine stress may be secondary to limited ventricular preload.

Adaptation, Physiological↗
PubMed2002

Office and ambulatory blood pressure elevation in children with chronic renal failure.

Hypertension is a frequent complication in patients with chronic renal insufficiency (CRI) and is associated with target organ damage, including left ventricular hypertrophy (LVH). To better assess hypertension in pediatric patients with CRI, we performed 24-h ambulatory blood pressure monitoring (ABPM) and evaluated the relationship between ABPM parameters and LVH in 29 children, mean age 12.4+/-3.8 years. There was no significant difference in the frequency of hypertension comparing casual systolic blood pressure (SBP) (21%) with the mean 24-h (21%) or daytime mean SBP (21%). However, diastolic hypertension was detected more frequently using ABPM: 24% for 24-h diastolic blood pressure (DBP), 14% for daytime DBP, and 7% for casual DBP. Nighttime systolic hypertension as well as diastolic hypertension was detected in 12 (41%) children. Seventeen (59%) patients had attenuated dipping for SBP and 9 (31%) had abnormal DBP dipping. Lower SBP dipping was associated with lower glomerular filtration rate (r=0.44, P<0.05). LVH was found in 6 (21%) patients. LVM index was significantly correlated with 24-h SBP (r=0.43, P<0.05). Multiple regression analysis confirmed that higher 24-h SBP was the only independent predictor for increased LVM index (P=0.001). No significant relationship was found between LVM index and office blood pressure. These results confirm a high prevalence of blood pressure abnormalities using ABPM criteria in children with CRI and suggest that ABP may better predict end-organ damage in these patients than casual BP.

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

Conversion to digital technology improves efficiency in the pediatric echocardiography laboratory.

BACKGROUND: Although the videotape method (VTM) is commonly used to record and intrepret ecocardiographic images, many pediatric echocardiographers are considering acquiring to, interpreting from, and storing their images to digital disk using the single-beat digital acquisition method (SBM). The paucity of image redundancy using SBM should translate into improved laboratory efficiency compared with VTM, but hard data are lacking. The purpose of this study was to test the hypothesis that the time to acquire images to videotape using VTM and to disk using SBM would be the same for normal hearts and corresponding congenital heart diseases, but interpretation times would be shorter using SBM. METHODS: We measured the times to acquire and interpret 403 echocardiograms using standard VTM from Children's Hospital in Cincinnati, Ohio, and 352 echocardiograms acquired using SBM from Children's Hospital in San Diego, Calif. Diagnostic categories at each site included: (1) normal, (2) simple shunt or isolated valve disease, and (3) multiple-lesion disease. RESULTS: As a group, SBM echocardiograms included more hemodynamic measurements and took more time to acquire (P <.037), but less time to read (P <.001) than corresponding images acquired using VTM. Using SBM, it took more time to acquire normals and isolated valve or shunt lesions, whereas the average time to acquire multiple-lesion disease was the same using both VTM and SBM. With SBM, in contrast, interpretation times were significantly less for all corresponding diagnoses. CONCLUSION: SBM studies took longer to acquire because more hemodynamic measurements were acquired, but they were read in less time than corresponding VTM studies even though all videotapes were replayed in search fast-forward mode. Pediatric echocardiographers can increase their laboratory efficiency by converting from VTM to SBM.

Analog-Digital Conversion↗