Gian Francesco Mureddu

Interaction Between Body Size and Cardiac Workload: Influence on Left Ventricular Mass During Body Growth and Adulthood

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

Estimation of left ventricular chamber and stroke volume by limited M-mode echocardiography and validation by two-dimensional and Doppler echocardiography.

This study has been designed to improve estimation of stroke volume from linear left ventricular (LV) dimensions measured by M-mode echocardiography, in symmetrically contracting ventricles. In experimental studies, the ratio of LV epicardial long/short axes Z is about 1.3. We measured systolic and diastolic epicardial long and short axes by 2-dimensional echocardiography in 115 adults with widely varying LV short-axis dimensions (LV end-diastolic dimension = 3.95 to 8.3 cm). In a learning series of 23 normotensive and 27 hypertensive subjects, Z(diastole) was 1.3 +/- 0.1 and Z(systole) = 1.2 +/- 0.1, similar to findings in experimental animals. Regression equations were developed by comparing LV volumes by M-mode and 2-dimensional echocardiography. In a test series (65 subjects), LV volumes were calculated using separate regression equations for end-diastolic volume ([LV end-diastolic dimension] 4.765 - 0.288 x posterior wall thickness]) and for end-systolic volume ([LV end-systolic dimension] [4.136 - 0.288 x posterior wall thickness]). Because the term 0.288 x wall thickness was only about 8% of the first term between brackets, the average wall thickness in the learning series was substituted in the Z-volume formulas applied to the test series: end-diastolic volume = (4.5 x [LV end-diastolic dimensions]2) and end-systolic volume = (3.72 x [LV end-diastolic dimension]2). The mean relative error produced with this simplified method was 0.9%. in diastole and 1.4% in systole. Compared with Teichholz M-mode volume method, Z-derived end-diastolic volume in the test series was equally well related to 2-dimensional volumes (both r = 0.88), with a better intercept (1.5 vs -23 ml, p <0.001) and a slope closer to the identity line (1.1 vs 1.4). Similar results were found for systolic volumes. In a second test series of 1,721 American Indian participants in the Strong Heart Study without mitral regurgitation or segmental LV wall motion abnormalities, Doppler-derived LV stroke volume (70 +/- 14 ml/beat) was similarly predicted by the Z-derived method (r = 0.65, 70 +/- 11 ml/beat) and Teichholz formulas (r = 0.64, 72 +/- 13 ml/beat), but Z-derived volumes had a regression line significantly closer to the identity line (p <0.005). Thus, LV chamber and stroke volumes can be determined from M-mode LV diameters over a wide range of LV sizes and in epidemiologic as well as clinical populations. The performance of this new method appears better than that obtained using the Teichholz formula, with a formula that is easy to handle and makes calculation of LV volumes by pocket calculator possible, even from limited echocardiographic studies.

Left ventricular filling pattern in uncomplicated obesity

To determine if uncomplicated obesity is associated with systolic dysfunction or impairment of left ventricular (LV) filling, 40 normotensive, white, asymptomatic, obese subjects (16 men and 24 women, mean +/- SD age 35 +/- 13 years; body mass index 36 +/- 6 kg/m2) and 40 normotensive, normal-weight, white volunteers matched for age and sex distribution, were studied by Doppler echocardiography. Endocardial and midwall shortening did not show differences between groups (obese = 33 +/- 4% and 17 +/- 2%; normal weight = 33 +/- 3% and 18 +/- 2%, respectively). LV mass index was higher in obese than in normal-weight subjects (p <0.0001). Obese persons had prolonged isovolumic relaxation time (p <0.0001), lower transmitral peak early diastolic filling wave (E) velocity (p <0.02), higher E velocity deceleration time (p <0.002) and lower E/atrial diastolic filling wave (A) flow velocity ratio (p <0.01) than did normal-weight subjects, even after controlling for age and blood pressure. Between-group differences in E and E velocity deceleration time disappeared when controlling for LV mass index, whereas prolonged isovolumic relaxation time in obesity was independent of LV mass, chamber dimension, and end-systolic stress. LV filling variables were not statistically related to endocardial or midwall shortening, both as absolute value or as a percentage of that predicted from wall stress. We conclude that uncomplicated obesity is associated with primary impairment of LV isovolumic relaxation; abnormalities of early passive filling flow in obesity are associated with increased LV mass.

Left ventricular filling in arterial hypertension influence of obesity and hemodynamic and structural confounders

We assessed the relations of left ventricular filling to load and geometry by Doppler echocardiography in 80 normotensive subjects (40 normal-weight [36 +/- 12 years, 24 women] and 40 obese [35 +/- 13 years, 24 women]) and 61 hypertensive subjects without silent coronary heart disease (29 normal-weight [43 +/- 13 years, 15 women] and 32 obese [42 +/- 13 years, 19 women]) and comparable left ventricular midwall performance. Left ventricular mass divided by height to the 2.7 power was higher in all groups than in normotensive normal-weight subjects (all P < .0001) and in hypertensive than normotensive obese subjects (P < .001). After controlling for age, sex, blood pressure, and heart rate, isovolumic relaxation time was prolonged in hypertensive subjects and normotensive obese subjects compared with normotensive normal-weight subjects (all P < .0001). Body mass index, left ventricular dimension and mass, and circumferential end-systolic stress did not influence these differences. In pooled groups, prolonged isovolumic relaxation time was predicted by high mean blood pressure (beta = 0.52, P < .001), low end-systolic stress (beta = -0.33, P < .001), increased left ventricular mass (beta = 0.24, P < .004), and high body mass index (beta = 0.14, P < .05, multiple R = .72, SEE = 16.5 milliseconds, P < .0001). Between-group differences in peak early transmitral flow velocity, the deceleration time of early filling velocity, and the ratio of early to late left ventricular filling disappeared after controlling for left ventricular mass. Thus, (1) isovolumic relaxation time is prolonged in both arterial hypertension and obesity; (2) the presence of obesity does not significantly increase isovolumic relaxation time in hypertension; and (3) abnormalities of left ventricular filling in arterial hypertension are offset after controlling for left ventricular mass.

Appropriate or inappropriate left ventricular mass in the presence or absence of prognostically adverse left ventricular hypertrophy.

Objectives To evaluate whether assessment of appropriateness of left ventricular mass (LVM) adds to the traditional definition of left ventricular hypertrophy (LVH). Design Cross-sectional, relational. Methods Echocardiographic LVH and appropriateness of LVM were studied in 562 subjects (231 normotensive controls, aged 35 ± 11 years, 142 women; 331 hypertensive patients, aged 47 ± 11 years, 135 women) classified on the basis of either the presence or the absence of both LVH (LVM index ⩾ 51 g/m2.7) and inappropriate LVM (LVM > 128% of the value predicted by an equation including age, sex and stroke work). Results Body mass index was comparable in hypertensive patients and controls. Hypertensive patients without LVH but with inappropriate LVM (n = 21) had higher relative wall thickness and total peripheral resistance than all other groups, whereas cardiac output was lower (all P < 0.001). Midwall mechanics was normal with appropriate LVM, independently of presence of LVH, whereas it was depressed in inappropriate LVM, either with or without LVH (both P < 0.0001). There was no substantial difference in ejection fraction among controls and hypertensive groups. Stress-corrected midwall shortening was more closely related to deviation of LVM from the value appropriate for stroke work, body size and gender (r =− 0.56, P < 0.0001) than to LVM index (r =− 0.26). Conclusions Inappropriate LVM is associated with concentric geometry, high peripheral resistance and depressed wall mechanics. The deviation of LVM from the value appropriate for stroke work, body size and sex correlates with measures of myocardial function better than LVM.

Influence of Obesity on Left Ventricular Midwall Mechanics in Arterial Hypertension

The evaluation of the effect of obesity on left ventricular systolic performance may differ in relation to the method used to measure left ventricular function and to the type of study population. Whether obesity worsens left ventricular midwall mechanics in arterial hypertension has never been investigated. Accordingly, we assessed echocardiographic left ventricular midwall shortening-circumferential end-systolic stress relations in 156 normotensive and normal-weight (reference) adults, 94 normotensive and overweight (1985 National Institutes of Health partition values) to obese (body mass index > 30 kg/m2) adults, 263 hypertensive and normal-weight adults, and 224 hypertensive and overweight-to-obese adults. There was an inverse relation of midwall shortening to circumferential end-systolic stress in all groups (all P < .005). Left ventricular performance as a ratio of observed to predicted midwall shortening fell below the fifth percentile in 4 of 94 (4%) of overweight-to-obese normotensive individuals. Eighty-eight of 487 hypertensive subjects (18.1%) exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects. Sixty-one normotensive and 131 hypertensive subjects were frankly obese. After adjustment for sex and age, midwall shortening, as either absolute values or a percentage of predicted, was not statistically different among obese, overweight, and normal-weight subjects in both normotensive and hypertensive groups. For each quartile of observed-to-predicted midwall shortening ratio, obese subjects had greater left ventricular end-diastolic volume than normal-weight subjects among both normotensive and, more evidently, hypertensive subjects. A predicted midwall shortening was generated from both wall stress and left ventricular volume with the use of multiple regression analysis. High body mass index, mean blood pressure, aging, and male sex independently predicted low afterload and left ventricular volume-independent midwall left ventricular performance (multiple R = .31, P < .0001). Thus, (1) midwall left ventricular systolic performance in asymptomatic overweight or frankly obese individuals is comparable to that in normal-weight individuals in both the presence and absence of arterial hypertension; (2) however, maintenance of normal life ventricular performance in obese individuals is associated with the use of Starling reserve; and (3) this compensatory mechanism is especially evident when arterial hypertension and obesity coexist.

Inappropriate left ventricular mass in normotensive and hypertensive patients.

We evaluated cardiovascular features of normotensive and hypertensive adults with left ventricular (LV) mass values exceeding levels predicted for given stroke work, gender, and height, termed inappropriate LV mass. Inappropriate LV mass is associated with overweight, concentric LV geometry, and low myocardial systolic function not only in hypertensive subjects, but also in normotensive subjects.

Blood pressure and cardiac morphology in young children of hypertensive subjects.

Our aim was to assess echocardiographic parameters and the effort blood pressure of 50 children of hypertensives with respect to 50 children of normotensives. Systolic and diastolic blood pressures at rest were comparable between the two groups. Left ventricular mass index (LVMI), interventricular septum and posterior wall thicknesses were higher in children of hypertensives (P < 0.01). Systolic blood pressure was higher in children of hypertensives at maximal effort until 5 min of recovery (P < 0.01). Similarly, diastolic blood pressure was higher at 1 and 2 min of recovery (P < 0.01). Direct correlations of mean diastolic wall thickness (r = 0.39, P < 0.01) and LVMI (r = 0.33, P < 0.05) with percentage effort systolic blood pressure increases were found in children of hypertensives but not in children of normotensives. In conclusion, we confirmed early cardiac alterations and a tendency for effort hypertension in children of hypertensives. The relationship between these data could be explained, either by effort systolic overload or by a common response to an increased adrenergic stimulus.

Relations of Left Ventricular Geometry and Function to Body Composition in Children With High Casual Blood Pressure

To determine whether abnormal casual blood pressure (BP) is associated with left ventricular (LV) abnormalities in children, 190 6- to 11-year-old children (77 girls, 113 boys) were studied at a school site in Naples, Italy, by limited echocardiography and bioelectric impedance to calculate fat-free body mass (FFM). Single-visit BP measurements (defined as casual BP) were high (based on the Italian tables of BP) in 34 children (18%; 9 girls, 25 boys; 133+/-8/81+/-10 mm Hg) and obesity was present in 44 (23%; 15 girls, 29 boys). Sex- and age-independent risk of high casual BP value was 2.9-fold (odds ratio) greater in obese than in normal-weight children (95% confidence interval, 1.3 to 6.5; P<.01). LV mass (as both absolute value and normalized for height or FFM) was higher and relative wall thickness increased in children with high casual BP (all P<.01). Prevalence of LV hypertrophy was 21% among children with high casual BP (P<.004 versus 4.3% in normal group). Risk of LV hypertrophy was 5.5-fold higher in the presence of high casual BP (P<.004), whereas obesity, age, and sex did not have independent effects. Endocardial shortening was slightly higher in children with high casual BP (36.8+/-8.2%) than in children with normal BP (34.3+/-4.8%, P<.02), whereas midwall shortening was identical in the two groups (20%). Both endocardial shortening and midwall shortening were negatively related to end-systolic stress (r=-.62, SEE=3.8% and r=-.32, SEE=2.4% in normal children). Shortening as a percentage of predicted from wall stress was increased in children with high casual BP at the endocardial level (P<.001), whereas it was normal at the midwall. Therefore, (1) casual detection of high BP in school children is associated with LV geometric abnormalities similar to those found in adults with sustained hypertension (LV hypertrophy, concentric pattern); (2) similar to in adult hypertension, endocardial chamber function in children is supranormal; and (3) in contrast to findings in adults, midwall shortening is normal in children with high casual BP.

Relations of pulse pressure and other components of blood pressure to preclinical echocardiographic abnormalities

Objective To evaluate the extent to which pulse pressure (PP) is associated with echocardiographic abnormalities, and in particular to whether PP is related to LV hypertrophy taking into account other blood pressure (BP) components. Design Cross-sectional. Setting University hospital, hypertension outpatient unit. Participants A total of 275 adults (mean age 47 years, range 19–69, 3% aged ⩾ 65) with essential hypertension. Overt coronary artery disease, valvular disease and secondary hypertension were exclusion criteria. Subjects were divided in two groups with PP ⩽ 50 or PP > 50 mmHg. Outcome measures Left ventricular (LV) mass, hypertrophy, LV systolic dysfunction. Results Prevalence of LV hypertrophy was higher in subjects with clinic PP > 50 mmHg. Subjects with PP > 50 mmHg had higher clinic and ambulatory systolic than subjects with PP ⩽ 50 mmHg while diastolic BP did not differ between groups. PP and systolic BP, either clinic or ambulatory, showed similar correlation to LV hypertrophy in separate logistic multivariate models. Using different methodologies, PP was not related to LV mass index or hypertrophy when the effect of its component systolic BP was taken into account. In separate analyses, PP was not significantly related to ejection fraction or midwall mechanics. Conclusion Middle-aged clinically healthy hypertensives with PP > 50 mmHg had two-fold higher prevalence of LV hypertrophy than those with PP ⩽ 50 mmHg, which may contribute to the higher cardiovascular risk in subjects with higher PP. However, in our sample, PP was not related to LV hypertrophy independently of systolic BP, suggesting that systolic BP is the explanatory link of the relation between PP and LV hypertrophy.