Normal values of regional left ventricular endocardial motion: multicenter color kinesis study. Am J Physiol Heart Circ Physiol 279: H2464– H2476

. Normal values of regional left ventricular endocardial motion: multicenter color kinesis study. Am J Physiol Heart Circ Physiol 279: H2464-H2476, 2000.-Our goal was to establish normal values for quantitative color kinesis indexes of left ventricular (LV) wall motion over a wide range of ages, which are required for objective diagnosis of regional systolic and diastolic dysfunction. Color-encoded images were obtained in 194 normal subjects (95 males, 99 females, age 2 mo to 79 yr) in four standard views. Quantitative indexes of magnitude and timing of systolic and diastolic function were studied for age-and genderrelated differences. Normal limits of all ejection and filling indexes were in a narrow range (Յ25% of the mean), with no major gender-related differences. Despite invariable ejection fractions, both peak filling and ejection rates decreased with age (30 and 20%, correspondingly) with a concomitant increase in mean filling and ejection times, resulting in fiveand twofold increases in the late to early filling and ejection ratios, correspondingly. Diastolic asynchrony increased with age (from 4.7 Ϯ 2.0 to 6.4 Ϯ 3.2 from the 2nd to 7th decade). The normal values of color kinesis indexes should allow objective detection of regional LV systolic and diastolic dysfunction. echocardiography; ultrasound imaging; ventricular function; wall motion COLOR KINESIS IS AN EMERGING echocardiographic technique based on acoustic quantification, which uses color-encoding to depict left ventricular (LV) systolic and diastolic endocardial motion However, a new technique, which detects abnormalities by comparing individual patient's data with normal values, relies on having these normal values established in a large sample of the normal population. Accordingly, normal values of different indexes of magnitude and timing of global and regional LV function derived from color kinesis images need to be established to allow objective detection of abnormalities with a high level of confidence. We also hypothesized that these indexes may be age and gender dependent, in which case normal values would need to be established for different demographic groups. Accordingly, the purpose of this collaborative multicenter effort was to establish normal values for magnitude and timing indexes of wall motion by acquiring and analyzing systolic and diastolic color kinesis images in a large group of normal subjects of both sexes over a wide range of ages. METHODS Study population. The protocol for this study was approved by the Institutional Review Board of the University of Chicago (protocol #9171). This protocol was initially designed to include eight age groups (8 decades between 0 and 80 yr) with a minimum of 20 normal subjects each (50% males and 50% Address for reprint requests and othe

Impaired left ventricular diastolic function in children with chronic renal failure

Impaired left ventricular diastolic function in children with chronic renal failure.BackgroundDiastolic 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.MethodsThirty-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.ResultsChildren 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).ConclusionOur 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

Targeted Disruption of NFATc3, but Not NFATc4, Reveals an Intrinsic Defect in Calcineurin-Mediated Cardiac Hypertrophic Growth

A calcineurin-nuclear factor of activated T cells (NFAT) regulatory pathway has been implicated in the control of cardiac hypertrophy, suggesting one mechanism whereby alterations in intracellular calcium handling are linked to the expression of hypertrophy-associated genes. Although recent studies have demonstrated a necessary role for calcineurin as a mediator of cardiac hypertrophy, the potential involvement of NFAT transcription factors as downstream effectors of calcineurin signaling has not been evaluated. Accordingly, mice with targeted disruptions in NFATc3 and NFATc4 genes were characterized. Whereas the loss of NFATc4 did not compromise the ability of the myocardium to undergo hypertrophic growth, NFATc3-null mice demonstrated a significant reduction in calcineurin transgene-induced cardiac hypertrophy at 19 days, 26 days, 6 weeks, 8 weeks, and 10 weeks of age. NFATc3-null mice also demonstrated attenuated pressure overload- and angiotensin II-induced cardiac hypertrophy. These results provide genetic evidence that calcineurin-regulated responses require NFAT effectors in vivo

TGF-β1 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-β1 and cardiac hypertrophy. Echocardiographic analysis revealed that TGF-β1–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 IItreatment. 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-β1–deficient mice. No significant levels of fibrosis, mitotic growth, or cytokine infiltration were detected in Ang II–treated mice. Atrial natriuretic factor expression was ∼6-fold elevated in Ang II–treated wild-type, but not TGF-β1–deficient mice. However, the α- to β-myosin heavy chain switch did not occur in Ang II–treated mice, indicating that isoform switching is not obligatorily coupled with hypertrophy or TGF-β1. The Ang IIeffect on hypertrophy was shown not to result from stimulation of the endogenous renin-angiotensis system. These results indicate that TGF-β1 is an important mediator of the hypertrophic growth response of the heart to Ang II