A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart.

We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell isoforms, upregulated in this skeletal muscle. We have now studied dystrophin transcription and expression in the heart of one member of this family. In contrast to the skeletal muscle, dystrophin transcription and expression were absent in the heart, with the exception of the distal Dp71 dystrophin isoform, normally present in the heart. The 43- and 50-kD dystrophin-associated proteins were severely reduced in the heart, despite the presence of Dp71, but not in skeletal muscle. The absence of dystrophin and the down-regulation of the dystrophin-associated proteins in the heart accounted for the severe cardiomyopathy in this family. The mutation present in these males selectively affects dystrophin expression in the heart; this could be secondary to the removal of cardiac-specific regulatory sequences. This family may represent the first example of a mutation specifically affecting the cardiac expression of a gene, present physiologically in both the skeletal and cardiac muscles.

Relation of arterial pressure waveform to left ventricular and carotid anatomy in normotensive subjects.

OBJECTIVES: The purpose of this study was to examine the relation of the central arterial pressure waveform to left ventricular and carotid structure. BACKGROUND: The pressure waveform in the central arteries is affected by reflection of the pressure wave from the periphery. When reflected waves merge with the incident wave during systole, a late systolic peak and increment in systolic blood pressure are observed. The consequent increase in hemodynamic load may stimulate left ventricular and vascular adaptive changes. METHODS: Sixty-seven normotensive adults were studied by noninvasive techniques. Anatomy and function of the left ventricle and carotid artery were investigated by ultrasonography. Pressure waveforms were recorded by an external tonometer applied to the carotid artery, and waveform shape was expressed by the augmentation index, calculated from the difference between the maximal systolic pressure and that at the inflection between early and late systolic pressure peaks divided by the pulse pressure. Subjects were assigned to groups with a dominant early (group 1, augmentation index < or = 0) or dominant late systolic peak (group 2, augmentation index > 0). RESULTS: Left ventricular mass index was significantly higher in group 2 than in group 1, a difference that persisted after controlling for the confounding effects of gender, age and blood pressure. Carotid wall thickness and regional arterial stiffness were significantly increased in group 2, but differences disappeared in the analysis of covariance for age. CONCLUSIONS: Left ventricular and carotid artery structure are related to the shape of the central pressure waveform. Although the increase in left ventricular mass seen in subjects with a dominant late systolic peak pressure appears to be directly related to the shape of the pressure waveform, changes in the structural and physical properties of the carotid artery appear to be more closely related to the aging process.

Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension.

The spectrum of left ventricular geometric adaptation to hypertension was investigated in 165 patients with untreated essential hypertension and 125 age- and gender-matched normal adults studied by two-dimensional and M-mode echocardiography. Among hypertensive patients, left ventricular mass index and relative wall thickness were normal in 52%, whereas 13% had increased relative wall thickness with normal ventricular mass ("concentric remodeling"), 27% had increased mass with normal relative wall thickness (eccentric hypertrophy) and only 8% had "typical" hypertensive concentric hypertrophy (increase in both variables). Systemic hemodynamics paralleled ventricular geometry, with the highest peripheral resistance in the groups with concentric remodeling and hypertrophy, whereas cardiac index was super-normal in those with eccentric hypertrophy and low normal in patients with concentric remodeling. The left ventricular short-axis/long-axis ratio was positively related to stroke volume (r = 0.45, p less than 0.001), with cavity shape most elliptic in patients with concentric remodeling and most spheric in those with eccentric hypertrophy. Normality of left ventricular mass in concentric remodeling appeared to reflect offsetting by volume "underload" of the effects of pressure overload, whereas eccentric hypertrophy was associated with concomitant pressure and volume overload. Thus, arterial hypertension is associated with a spectrum of cardiac geometric adaptation matched to systemic hemodynamics and ventricular load. Concentric left ventricular remodeling and eccentric hypertrophy are more common than the typical pattern of concentric hypertrophy in untreated hypertensive patients.

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics.

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (greater than 25 fmol/ml) were significantly (p less than 0.01) older and had greater atrial and ventricular size and higher systolic pressure and function than normal subjects or patients with normal natriuretic factor levels. Plasma atrial natriuretic factor was inversely related to peak diastolic filling rate in normal subjects (r = -0.59; p less than 0.001), whereas it was positively related to the proportional contribution of atrial systole to left ventricular filling in hypertensive patients (r = 0.77; p less than 0.001). These findings suggest that in normal subjects, impairment of ventricular relaxation with age may contribute to atrial natriuretic factor secretion by increasing left atrial afterload; the correlation with left ventricular size may reflect physiologic fluctuations in plasma volume. In patients with uncomplicated hypertension, left atrial enlargement and consequent stronger atrial contraction contributed to increased atrial natriuretic factor release, whereas no independent relation existed with left ventricular hypertrophy or systolic function. Because ventricular relaxation was normal and ventricular size and systolic performance were increased in hypertensive patients with high atrial natriuretic factor levels, the observed increase in left atrial size and atrial contribution to ventricular filling might reflect a primary increase in venous return in this subset of hypertensive patients.

Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension.

OBJECTIVES: This study examined left ventricular performance in relatively unselected hypertensive patients by use of physiologically appropriate midwall shortening/end-systolic stress relations. BACKGROUND: Supranormal left ventricular function has been reported in hypertensive patients, possibly due to an artifact of mismatching endocardial rather than midwall fractional shortening to mean left ventricular end-systolic stress. METHODS: Samples of 474 hypertensive patients (150 women, 324 men) and 140 normal subjects (68 women, 72 men) were drawn from a large urban employed population. The inverse relations (p < 0.0001) of both echocardiographic endocardial and midwall fractional shortening to end-systolic stress in normal subjects were used to calculate the ratios of observed to predicted endocardial and midwall fractional shortening in hypertensive patients. Midwall shortening was calculated from an elliptic model, taking into account the epicardial migration of the midwall during systole. RESULTS: Use of midwall fractional shortening in hypertensive patients reduced the proportion of patients with function above the 95th percentile of normal from 22% to 4% (p < 0.0001) and fractional shortening as a percent of predicted from 107% (p < 0.001 vs. 100% in normotensive control subjects) to 95% (p < 0.0001; p < 0.001 vs. 101% in normotensive control subjects). Midwall shortening was below the 5th percentile of normal in 16% of hypertensive patients instead of 2% with endocardial shortening (p < 0.0001): They tended to be older than other hypertensive patients and had concentric left ventricular hypertrophy. Among hypertensive patients, those with concentric left ventricular hypertrophy or remodeling had reduced midwall shortening as a percent of predicted from end-systolic stress (p < 0.0001). CONCLUSIONS: Use of the physiologically more appropriate midwall shortening/end-systolic stress relation 1) markedly reduces the proportion of hypertensive subjects identified as having high endocardial left ventricular function; and 2) identifies a substantial subgroup of patients with reduced left ventricular function who have concentric geometry of the left ventricle, a pattern associated with high cardiovascular risk.

Cardiac and arterial hypertrophy and atherosclerosis in hypertension.

Clinical evaluation of the hypertensive patient has traditionally relied on physician measurement of blood pressure and assessment of target-organ involvement by simple laboratory tests. However, this approach is limited in its ability to identify individual patients at high or low risk of complications. In recent years, noninvasive methods have been developed to identify pathological transformations of the heart and arteries that collectively comprise "preclinical hypertensive disease." Measurements by echocardiogram or other methods of left ventricular mass and relative wall thickness identify a spectrum of cardiac adaptations to hypertension, including concentric and eccentric hypertrophy, the recently described pattern of "concentric left ventricular remodeling" (normal mass but increased relative wall thickness), and normal ventricular geometry. In clinical studies, each anatomic pattern is associated with a distinct profile of resting hemodynamics, ambulatory blood pressure, myocardial contractility, and risk of adverse outcomes. Ultrasonic imaging of the carotid or other arteries makes it possible to detect increased arterial wall thickness and discrete atheromas noninvasively. Carotid wall thickness and lumen diameter parallel similar ventricular dimensions in normotensive and hypertensive humans, indicating the presence of integrated patterns of cardiac and vascular adaptation to hypertension. Furthermore, peripheral atherosclerosis is associated with higher ventricular mass and a more adverse 24-hour blood pressure profile. In summary, noninvasive visualization of the heart and blood vessels reveals a spectrum of patterns of anatomic and functional adaptations that are related to the pathophysiology and prognosis of hypertension.

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.

Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension.

Ratio of stroke volume (SV, M-mode echocardiography) to pulse pressure (PP) has been proposed as an estimate of total arterial compliance and has been shown to be related to body size, age, and heart rate in normal adults. SV/PP was estimated in 294 hypertensive patients (98 women) as a raw value by use of SV/body surface area (SVi) and by the ratio of SV/PP to the value predicted by a previously developed equation (%SV/PP). At baseline, the 50 patients who had cardiovascular events over the following 10 years exhibited higher PP and lower SV/PP, SVi/PP, and %SV/PP (all P<0.008) than patients without events. Crude risk of follow-up total and fatal cardiovascular events increased with increasing level of PP and decreasing SV/PP, SVi/PP, and %SV/PP (all P<0.002). In multivariate logistic regression models with continuous covariates, the risk of total cardiovascular events was independently related to increasing age (P<0.0001) and left ventricular (LV) mass index (P<0.003) and decreasing values of %SV/PP (P<0.006) but not to increasing systolic, pulse, or mean blood pressure or gender. Similar although less strong results were obtained with the use of SVi/PP (P<0.02), whereas SV/PP did not enter the model as an independent predictor. Risk of cardiovascular death was only predicted by age and LV mass index. The %SV/PP was also an independent predictor of total cardiovascular events in Cox proportional hazards analysis (exp[b]: 2.49, P<0.001) independent of age (exp[b]: 1.05, P<0.003) and LV mass index (exp[b]: 1.02, P<0.0003), whereas no effect was detected for height. Thus, in patients with arterial hypertension, a reduced ratio of M-mode echocardiographic SV/PP as a percentage of the value predicted by demographic variables is a predictor of cardiovascular morbid events independent of age and LV mass index.

Relation of left ventricular longitudinal and circumferential shortening to ejection fraction in the presence or in the absence of mild hypertension.

OBJECTIVES: To study left ventricular longitudinal shortening in arterial hypertension and the relative contribution of longitudinal and circumferential fiber shortening to ventricular ejection. METHODS: Two-dimensional and M-mode echocardiograms were obtained for 50 normotensive subjects (aged 49 +/- 12 years) and 50 never-treated mild hypertensive patients (aged 49 +/- 11 years), to measure the minor-axis endocardial and midwall shortening, long-axis shortening and ejection fraction. RESULTS: The midwall shortening was lower in hypertensive than it was in normotensive subjects (P < 0.001) and was related inversely to the circumferential wall stress for both groups (P < 0.04 and 0.0001, respectively). The long-axis shortening in hypertensive patients (22.2 +/- 4.2%) and in normotensives (23.6 +/- 5.4%) was not statistically different, and was not related either to the meridional or to the circumferential wall stress. The ejection fraction was also similar for the two groups (68.2 +/- 6.3 versus 68.6 +/- 5.6%). Both for normotensive and for hypertensive subjects, the ejection fraction was influenced mainly by the midwall shortening (61 and 40% of the variance for normal and hypertensive individuals, respectively), with a minor contribution from the long-axis shortening, which was 7% for normotensive subjects and 18% for hypertensive patients, a statistically significant difference (P < 0.001). The combined effect of midwall and longitudinal shortenings on the ejection fraction was regulated by the relative wall thickness, and was maximal for hypertensive patients with an ejection fraction greater than that predicted by the midwall shortening. CONCLUSIONS: Left ventricular ejection is produced principally by circumferential shortening and is related independently to the relative wall thickness. In the presence of arterial hypertension and an altered cardiac load, longitudinal shortening becomes an important mechanism by which to augment ejection, thereby offsetting the reduction in midwall shortening.

Ageing induces left ventricular concentric remodelling in normotensive subjects.

OBJECTIVE: To assess whether age affects left ventricular anatomy independently of age-related hypertension or concomitant heart diseases. DESIGN AND METHODS: In 430 consecutive normotensive and clinically healthy subjects aged 16-85 years we obtained echocardiographic measurements of left ventricular posterior wall thickness, internal diameter, relative wall thickness, Penn mass index and systemic haemodynamics. The pulse pressure : stroke volume ratio was calculated as an estimate of systemic arterial stiffness. The subjects were divided into three age groups: < or = 40 (group 1, n = 137), 41-64 (group 2, n = 261) and > or = 65 years (group 3, n = 32). RESULTS: Systolic blood pressure increased from group 1 to group 3, as did the pulse pressure : stroke volume ratio and posterior wall thickness, whereas the left ventricular internal diameter was less in group 3 than in groups 1 and 2. The relative wall thickness increased from group 1 to groups 2 and 3, whereas the left ventricular mass index did not differ among age groups. Age was related positively to the systolic blood pressure, pulse pressure : stroke volume ratio, posterior wall thickness index and relative wall thickness, and negatively to the left ventricular internal diameter but not to the left ventricular mass index. CONCLUSIONS: In healthy adults, relative wall thickness increases with age whereas left ventricular mass does not change. The concentric remodelling of left ventricular geometry parallels age-related stiffening of the arterial tree, elevation of systolic blood pressure and decrease in left ventricular volume. Thus partition values of relative wall thickness should be adjusted for age.

Impact of arterial elastance as a measure of vascular load on left ventricular geometry in hypertension.

OBJECTIVE: Effective arterial elastance (Ea), integrating the pulsatile component of left ventricular (LV) afterload, is an estimate of aortic input impedance. We evaluated relationships of Ea with left ventricular anatomy and function in essential hypertension. DESIGN: A cross-sectional analysis in 81 normotensive and 174 untreated hypertensive individuals enrolled in a referral hypertension centre. METHODS: Using echocardiography we determined left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume (SV), endocardial (FSe) and midwall (FSm) fractional shortening and total peripheral resistance (TPR). Carotid pressure waveforms were obtained by arterial tonometry, and end-systolic pressure (Pes) was measured at the dicrotic notch. Ea index (EaI) was calculated as Pes/(SV index); LV elastance (Ees) was estimated as Pes/LV end-systolic volume, and ventriculo-arterial coupling was evaluated by the Ea/Ees ratio. RESULTS: EaI was higher in hypertensives than in normotensives (3.02 +/- 0.63 versus 2.40 +/- 0.52 mmHg/l per m2; P< 0.0001). Using the 95% upper confidence limit in normotensives, hypertensives were divided in two groups with normal or elevated EaI. The 38 hypertensives with elevated EaI had higher RWT (0.41 +/- 0.06 versus 0.37 +/- 0.05), lower LVMI (87.5 +/- 18.5 versus 96.8 +/- 19.3 g/m2), higher TPR (2247 +/- 408 versus 1658 +/- 371 dynes/cm s(-5)) and lower FSe and FSm (35 +/- 5 versus 39 +/- 5 and 16 +/- 2 versus 18 +/- 2%; all P< 0.05) than patients with normal EaI. Ea/Ees ratio was increased and cardiac output was reduced in hypertensives with elevated EaI. CONCLUSIONS: High values of EaI identify a minority of hypertensive patients characterized by elevated TPR, left ventricular concentric remodelling, depressed left ventricular systolic function and impaired ventriculo-arterial coupling.

Relationship of effective arterial elastance to demographic and arterial characteristics in normotensive and hypertensive adults.

OBJECTIVE: To evaluate demographic and vascular correlates of the effective arterial elastance noninvasively in normotensive and hypertensive adults. METHODS: In 202 subjects carotid ultrasonography and external arterial tonometry were simultaneously performed; carotid cross-sectional area, absolute and relative wall thicknesses, Peterson's and Young's elastic moduli and beta', a pressure-dependent index of arterial stiffness, were calculated. The impact of reflected waves on central pressure waveforms was evaluated by the 'augmentation index' (the relative increment in systolic pressure caused by the late-systolic peak). Left ventricular mass and relative wall thickness were assessed echocardiographically. The effective arterial elastance was estimated by dividing the pressure at the dicrotic notch by the Doppler-determined stroke index. RESULTS: The effective arterial elastance was higher in women among normotensives but similar between sexes among hypertensive subjects. It was correlated to age, mean blood pressure, body mass index and measures of arterial function, including Peterson's and Young's elastic moduli and beta', and to the augmentation index. It was also related to absolute and relative carotid wall thicknesses, lumen diameter and indexed cross-sectional area. Age, beta' and carotid cross-sectional area independently predicted effective arterial elastance in multiple regression analysis. CONCLUSIONS: Effective arterial elastance is related to demographic and arterial structural and functional characteristics. Increases in effective arterial elastance resulting from altered arterial structure and function may play a role in inducing left ventricular adaptative modifications.

Reliability and limitations of echocardiographic measurement of left ventricular mass for risk stratification and follow-up in single patients: the RES trial. Working Group on Heart and Hypertension of the Italian Society of Hypertension. Reliability of M-mode Echocardiographic Studies.

OBJECTIVE: To investigate the clinical reliability of repeated measurements of left ventricular mass in a single patient. DESIGN: We used test-retest reliability analysis, within-class correlation and interval of agreement measures. METHODS: Two M-mode tracings (three consecutive cycles) were recorded in the same session and 3-10 days apart (5+/-2 days; mean +/- SD) in 261 participants (age 45+/-13 years, body mass index 24.7+/-3.6 kg/m2; 131 hypertensive and 130 normotensive; 50% of each group women) in 16 centres in Italy. The two tracings were read by two observers in each centre, after classification by a three-order quality score (1 = poor, 2 = sufficient, 3 = optimal). RESULTS: The average quality score was 2.11+/-0.71 (21% poor, 50% sufficient, 29% optimal). Left ventricular mass values ranged from 56 to 419 g (170+/-61 g). On the same day, within-observer 90% interval of agreement between tracing 1 and tracing 2 was -28 to +22 g (-17 to +11% of tracing 1). For day-to-day test-retest within-observer variability (average three cycles), the 90% interval of agreement was -30 to +35 g (-18 to +18%). This variability decreased to -13 to +12% at the 80% interval of agreement and -12 to +11% at the 75% interval of agreement. The 90% interval of agreement of test- retest between-observer variability was -26 to 30 g (-19 to +15%). A negligible regression toward the mean was identified. Categorical consistency of retest in the identification of hypertensive patients with left ventricular hypertrophy, classified in the first study, was 87% (k = 0.87). CONCLUSIONS: Measurement of left ventricular mass in single patients allows reliable risk stratification on the basis of the presence of left ventricular hypertrophy. The probability of a true change in left ventricular mass over time is maximized for a single-reader difference greater than 18% of the initial value, although differences of 10-13% might also have clinical relevance.

Assessment of left ventricular function by meridional and circumferential end-systolic stress/minor-axis shortening relations in dilated cardiomyopathy.

Echocardiographic meridional wall stress-endocardial shortening relations provide estimates of left ventricular (LV) contractility that do not uniformly detect myocardial dysfunction despite severe symptoms in dilated cardiomyopathy. To improve detection of myocardial dysfunction in patients with congestive heart failure (CHF) due to dilated cardiomyopathy, echocardiographic meridional and circumferential end-systolic stress were related to endocardial and midwall shortening in 42 patients (95% dead within a mean of 22 months) with dilated cardiomyopathy and 140 normal subjects. A method to estimate LV long-axis dimension from M-mode minor-axis epicardial measurements was developed in a separate series of 115 subjects. Endocardial shortening to meridional wall stress relation identified 31 of 42 CHF patients falling below the 95% normal confidence interval of the reference population; use of midwall shortening decreased this number to 26 (p = NS). The use of circumferential wall stress identified 39 of 42 patients with subnormal endocardial LV shortening and 41 of 42 patients with depressed midwall performance (p < 0.01 vs use of meridional stress). The circumferential/meridional wall stress ratio was 2.6 +/- 0.5 in normal subjects and 1.3 +/- 0.2 in CHF patients (p < 0.0001). Thus, use of circumferential end-systolic stress as the measure of afterload improves the detection of myocardial dysfunction by stress/shortening relations in patients with CHF. The ratio between the 2 stresses decreases with more spherical LV shape. Midwall and endocardial shortening measurements are equivalent in the setting of thin LV walls as occurs in dilated cardiomyopathy.

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.

Gender differences in left ventricular anatomy, blood viscosity and volume regulatory hormones in normal adults.

Gender differences in left ventricular (LV) anatomy, whole blood and plasma viscosity, and blood volume regulatory hormones were studied in 110 normotensive employed adults (28 black and 34 white men [mean age 51 +/- 12 years], 20 black and 28 white women [mean age 53 +/- 12 years]). LV mass and wall thicknesses were positively related to whole blood viscosity, primarily because of higher values of both variables in men. LV chamber size was inversely related to hematocrit and to blood viscosity (p less than 0.002) in women but not in men. Whole blood viscosity increased with age in men (p less than 0.01), but tended to decrease in women; older women also had better LV function, larger LV chambers, and a trend toward increasing LV mass. Atrial natriuretic factor increased with age in women but not in men (r = 0.60, p less than 0.001), and plasma renin activity decreased (r = -0.35, p less than 0.02). Thus, in women, increase in LV chamber size with age and associated changes in LV systolic function, atrial natriuretic factor levels and plasma renin activity suggest plasma volume expansion related to the aging process. These findings also suggest that an increase in LV volume load with age may contribute to previously reported increases in LV mass in older women.

Relation of age to left ventricular function in clinically normal adults.

The extent to which age, independent of cardiovascular diseases, influences left ventricular (LV) function in adults is uncertain. Echocardiograms and simultaneous arterial pressure in 464 clinically normal adults aged 16 to 88 years were used to measure LV dimensions, endocardial and midwall LV fractional shortening, stroke volume, cardiac output, and circumferential end-systolic stress. The ratios of observed endocardial and midwall shortening to values predicted for observed end-systolic stress were used as measures of chamber and myocardial function. LV endocardial shortening increased slightly with age, as did an index of LV chamber performance, the end-systolic stress/volume index ratio (r = 0.11, p = 0.019, and r = 0.20, p <0.001). However, when age-related increases in LV wall thickness and blood pressure were controlled for by examining afterload-corrected endocardial shortening, no age relation was detected. Weak age-related declines were observed in midwall shortening (r = -0.09, p = 0.043) and afterload-corrected midwall shortening (r = -0.12, p <0.01). Cardiac index decreased slightly with advancing age (r = -0.14, mean -6.7 ml/min/m2/ year, p = 0.003). Total peripheral resistance and the pulse pressure/stroke volume ratio, a measure of arterial stiffness, increased more strongly with age (r = 0.27 and 0.38, both p <0.001). Thus, LV pump performance at rest measured by cardiac index is slightly lower in older than in younger clinically normal adults. Endocardial fractional shortening was slightly higher in older subjects, but the physiologically more appropriate midwall measures of myocardial function decreased slightly. The observed change in LV pump performance was related to smaller LV chamber size and higher total peripheral resistance in older subjects.

Familial insulinoma: description of two cases.

We describe cases of isolated functioning insulinoma occurring in two members of the same family (father and daughter). The father had a first encapsulated insulinoma diagnosed at 14 years of age and at the age of 33 years he was operated on for a second insulinoma infiltrating the exocrine pancreas with lymph node metastases. The daughter was operated on for an encapsulated insulinoma in the tail of the pancreas when she was 6 years old. No clinical and laboratory signs of other endocrine disturbances have so far been detected in either care or in any other members of the family. Our report suggests the possibility of multiple familial insulinoma, although this is an extremely rare condition. Our data also indicate that insulinomas, even if well controlled by medical treatment, should always be removed by surgery because malignancy cannot be excluded with certainty. Moreover, patients should be closely followed up, as recurrence may develop up to 15 years after surgery.

The response of the ageing heart to regular physical exercise. An echo and Doppler study.

In upper middle age healthy subjects the functional cardiac reserve is known to be decreased (Port et al., 1980; Aubert et al., 1994). On the other hand regular physical exercise improves the cardiovascular function (Nishimura et al., 1980). The aim of this study was to establish whether regular physical exercise is associated with a significant change in the ageing process of the cardiovascular system.

[Echo-flowmetric control 6 years after percutaneous treatment of varicocele]. / Controllo eco-flussimetrico a 6 anni di distanza dal trattamento percutaneo del varicocele.

Several Authors have discussed the long term efficacy of sclerotherapy; somebody supposes that percutaneous angiographic treatment of spermatic vein is not sure at all because the occlusion due to the sclerosing agents is not retained as long lasting. Studies have been done by other Authors about comparison of recurrent varicocele anatomy following surgery and percutaneous balloon occlusion: it is concluded that venous collaterals are identified easily by renal venography, and knowledge of these collaterals is helpful in planning further radiological treatment. Since 1980 we have always treated left varicocele by means of percutaneous sclerotherapy of the spermatic veins following renal phlebography: the treatment is done on an outpatient basis, in local anaesthesia. Sclerosing agents we usually adopt are: sodium-tetradecyl sulphate and alcohol. At our knowledge long-term results of this treatment have never been published; this is the reason for which long-term follow-up of 27 patients that 6 years ago underwent percutaneous sclerotherapy was done. Only 16 of them have accepted to repeat: a) physical examination; b) Doppler flowmetry; c) scrotal ultrasound. The presence of a varicocele was demonstrated in 2 out of 16 patients (12.5% of the case). These data confirms that percutaneous treatment performed following the procedures we adopted in 1986 has a long term efficacy in 87.5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)