Left Ventricular End-diastolic Wall Thickness Research Articles

Reliability of echocardiographic measurements of left cardiac structures in healthy children

Echocardiographic measurements are widely used as outcomes of different studies. The aim of this study was to assess intraobserver and interobserver reliability of echocardiographic measurements in healthy children. We studied 28 children, with a median age of 7.5 years, and inter-quartile range from 3 to 11 years. Intraobserver and interobserver reliability were assessed by repeated measurements of the diameters of the aortic root, the left atrium, and left ventricular end-diastolic structure. We also measured the ventricular end-diastolic septal thickness and the end-diastolic thickness of the left ventricular posterior wall. We calculated intraclass correlation coefficients, with corresponding 95% confidence intervals, and computed Bland and Altman plots, permitting us to derive limits of agreement plus or minus 2 standard deviations for the mean differences in cardiac measurements. We found high intraobserver and interobserver intraclass correlation coefficient, ranging from 0.91 for ventricular septal thickness, with 95% confidence intervals from 0.78 to 0.96, to 0.99 for the diameter of the aortic root, 95% confidence interval from 0.97 to 1.00. Limits of agreement in the Bland and Altman plots ranged from zero millimetres for left ventricular end-diastolic posterior wall thickness to 1.60 millimeters (6.3%) for left atrial diameter. Our study demonstrated good repeatability and reproducibility for ultrasonic measurements of left cardiac structures in children, showing that values obtained for measurement of these structures in both clinical and epidemiological research projects can be confidently accepted.

Cross-sectional relations of multiple biomarkers representing distinct biological pathways to plasma markers of collagen metabolism in the community

Hyperhomocysteinemia, neurohormonal activation, inflammation and altered fibrinolysis have been linked to atherothrombosis as well as to myocardial fibrosis and heart failure. Hence, we related a panel of biomarkers representing these pathways to plasma markers of collagen metabolism in a large community-based sample. We related nine biomarkers representing select biologic pathways (independent variables: C-reactive protein, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and homocysteine) to three plasma markers of collagen turnover [dependent variables, separate models for each: aminoterminal propeptide of type III collagen, tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-9 (present versus absent)] in 921 Framingham Heart study participants (mean age 57 years; 58% women). Participants were separated a priori into those with left ventricular end-diastolic dimensions and wall thickness below sex-specific median values (referent group) and either measure at least 90th sex-specific percentile ('remodeled' group). We used stepwise multivariable regression analysis adjusting for cardiovascular risk factors to relate the panel of systemic biomarkers to the three biomarkers of collagen metabolism. Plasma homocysteine was positively related to all three markers of collagen metabolism in the remodeled group and to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in the referent group. Plasminogen activator inhibitor-1 was positively related to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in both groups, whereas the natriuretic peptides were associated positively with these collagen markers in the referent group. In our large community-based sample, plasma homocysteine and plasminogen activator inhibitor-1 were positively related to circulating collagen biomarkers, consistent with experimental studies implicating these pathways in cardiovascular collagen turnover.

Chronic Left Ventricular Pacing Preserves Left Ventricular Function in Children

Chronic right ventricular (RV) pacing can induce structural and functional cardiac deterioration. Because animal studies showed a benefit of left ventricular (LV) over RV pacing, this study compared the effects of chronic RV and LV pacing in children. Retrospectively, echocardiographic data were evaluated from 18 healthy children (control subjects) and from children undergoing chronic epicardial RV pacing (7 RVP) or LV pacing (7 LVP). Assessment included LV end-diastolic wall thickness (LVEDWT) and end-systolic wall thickness (LVESWT) as well as LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD). The shortening fraction and eccentricity index (LV diameter/2xLV wall thickness) were calculated as measures of LV function and eccentricity, respectively. Duration of QRS and septal posterior wall motion delay (SPWMD) were used as measures of electrical and mechanical dyssynchrony, respectively. A p value less than 0.05 determined significance. As the findings showed, LVEDD, LVESD, LVEDWT, and LVESWT were not significantly different between the groups. The shortening fraction was significantly lower in the RVP (21.7%+/-6.0%) than in the LVP (32.2%+/-5.2%) or control (29.3%+/-4.3%) children. The systolic LV eccentricity index was significantly larger in the RVP (1.8+/-0.2) than in the LVP (1.4+/-0.1) or control (1.4+/-0.2) children. The SPWMD was significantly larger in the RVP (338+/-20 ms) than in the LVP (-16+/-14 ms) or control (-5+/-35 ms) group, whereas QRS duration was similarly longer in the RVP (157+/-10 ms) and LVP (158+/-22 ms) groups compared than in the control group (69+/-7 ms). The authors conclude that LV function in children is preserved by chronic pacing at the LV lateral wall.

Effects of ivabradine on allograft function and exercise performance in heart transplant recipients with permanent sinus tachycardia

Aim of this retrospective analysis was to evaluate the effects of ivabradine given primarily as a heart rate-lowering agent on allograft function and cardiopulmonary performance in heart transplant recipients with permanent sinus tachycardia. Starting May 2006, 26 heart transplant recipients with permanent sinus tachycardia received ivabradine (5 mg bid). It was discontinued early in 3 patients (11.5%) due to adverse events. In the remaining 23 patients, resting heart rate (HR) was significantly lowered from 106.3 +/- 9.1 to 82.2 +/- 6.3 bpm after 3 weeks of treatment. The effect remained constant during the remaining treatment period, whereas resting blood pressure was not affected. After 12 weeks of ivabradine treatment, the corrected QT interval was significantly reduced into the range seen in normal individuals. Left ventricular (LV) end-diastolic posterior wall thickness, LV mass and LV mass index were also found to have decreased significantly. There was a trend to improvement of cardiopulmonary performance and LV ejection fraction, both of which did not reach statistical significance, however. It may be concluded that ivabradine successfully reduced the resting HR of heart transplant recipients with sinus tachycardia without negatively influencing the blood pressure. The definitive impact of ivabradine on LV mass regression and cardiopulmonary performance require further prospective, randomized and controlled trials.

Tolerance development during a 1-week course of dobutamine treatment

Eleven patients with chronic heart failure (NYHA stage III or IV) were given dobutamine infusions over 7 days, mean dose 6.2 +/- 2.2 micrograms/kg X min. The patients were pretreated with digitalis, diuretics, and vasodilators. Haemodynamic parameters were measured prior to infusion, 30 minutes and 7 days thereafter as well as 24 hours after the end of therapy. Before and after the 7-day therapy a two-dimensional echocardiogram was taken. In four patients, the protocol had to be discontinued prematurely for technical or medical reasons. Arterial blood pressure, body weight, fractional shortening and end-diastolic diameter of the left ventricle were not changed significantly. Cardiac index rose acutely and returned to initial values after 7 days. Total peripheral resistance, which was initially significantly reduced, again rose after infusion over 7 days. Permanent reduction in pulmonary artery wedge pressure, even one day after the end of therapy, was observed in three patients showing a left-ventricular end-diastolic wall thickness greater than 7 mm. However, in patients whose wall thickness was less than 7 mm, there was a rise in pulmonary artery wedge pressure accompanied by a fall in cardiac index even below initial values.

Abstract 3431: Pulse Pressure Is Inversely Related to Aortic Root Diameter: Implications for the Pathogenesis of Systolic Hypertension

Background: The age-associated increase in central arterial stiffness manifests as a rise in pulse pressure, which leads to a marked increase in the prevalence of systolic hypertension among older individuals. Aortic root diameter (AoD) also increases with advancing age. According to the prevailing views, hypertension contributes to a further increase in AoD. Conversely, it has been suggested that the age-associated increase in AoD may partially compensate for the increased arterial stiffness. We tested the hypothesis that AoD is inversely associated with pulse pressure. Methods: The study population comprised 1256 individuals, aged 30 –79 years (48% women, 48% hypertensive), none of whom were on antihypertensive medications. Brachial pulse pressure (bPP) was calculated as the difference between sphygmomanometric systolic and diastolic blood pressures. Central pulse pressure (cPP) was derived from calibrated carotid artery pressure waveforms. AoD was measured by echocardiography at the level of the Sinuses of Valsalva. The relationships of AoD with bPP and cPP were evaluated with multiple regression analyses. Results: bPP was 54 ± 18 mmHg in women and 50 ± 14 mmHg in men, and AoD was 28.9 ± 3.5 mm in women and 31.9 ± 3.5 mm in men. After adjusting for age, age 2 , height, weight, and mean arterial pressure, bPP was inversely associated with AoD in both sexes. This inverse association persisted even after adjusting for aortic pulse wave velocity, carotid intima-media thickness, reflected waves, and left ventricular end-diastolic diameter and wall thickness. In the fully adjusted models predicting bPP, the regression coefficients for AoD were −0.48 in men (p = 0.0003, model R 2 =0.51) and −0.40 in women (p = 0.01, model R 2 = 0.61). Similarly, cPP was inversely associated with AoD in both men (coefficient = −0.45, p = 0.0007, model R 2 =0.50) and women (coefficient = −0.40, p = 0.01 model R 2 = 0.61). Thus, each 1 mm increase in AoD was associated with a 0.4 – 0.5 mmHg decrease in bPP and cPP in both sexes. Conclusions: Contrary to the prevailing views, AoD is independently and inversely associated with both bPP and cPP. These findings suggest that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility.

Changes in morphometric parameters and function of left ventricle in child and adolescent athletes

The aim of the study was to assess the impact of physical load on left ventricular morphometric parameters and function in child and adolescent athletes. A total of 143 trained athletes aged 7-17 years and 54 healthy nonathletic children and adolescents aged 8-17 years were involved in this study. The participants were divided into four groups according to the duration of physical activity (training hours per week). Two-dimensional, M-mode, and Doppler echocardiography were used to evaluate cardiac dimensions and function. Absolute parameters and parameters corrected for body surface area were calculated. Left ventricular fractional shortening was calculated as an index of systolic function, and E/A ratio was calculated for evaluation of left ventricular diastolic function. In 69.9% of athletes, septal and posterior wall thickness, end-diastolic diameter, left ventricular mass, and mass index were statistically significantly higher than in controls. There were no differences in left ventricular end-diastolic diameter and posterior wall thickness corrected for body surface area as well as diastolic E/A ratio between the groups. The fractional shortening in athletes was significantly higher (P<0.01). Interventricular septum thickness, end-diastolic diameter, and left ventricular mass were significantly higher in athletes whose training exceeded 8 hours per week compared to the controls. Left ventricular fractional shortening was significantly higher in athletes training more than 10 hours per week than in controls. Diastolic function index--E/A ratio--did not differ between the groups. Our study demonstrated that echocardiographic parameters of child and adolescent athletes statistically significantly exceeded the parameters of untrained controls. These parameters were dependent on the anthropometric data and physical activity (the duration of training expressed in hours per week).

Do mechanical markers of myocardial ischaemia predict the transmural extent of myocardial infarction in man?

The present study aimed to explore the relationship between the transmural extent of myocardial necrosis and mechanical markers of myocardial ischaemia in man. A group of 40 patients with previous Q-wave myocardial infarction and a left ventricular ejection fraction (LVEF) of 27 +/- 11% was studied by cine and contrast-enhanced magnetic resonance imaging. Necrotic areas of delayed contrast enhancement were present in every patient and involved 20 +/- 8% of left ventricular myocardium. In involved segments, the transmural extent of contrast enhancement varied from 5% to 100%, being on average 38 +/- 25% of the wall thickness. End-diastolic left ventricular wall thickness and systolic wall thickening were lower in contrast-enhanced segments than in the other segments (P < 0.001). Furthermore, although left ventricular wall thickness and systolic wall thickening decreased as the transmural extent of contrast enhancement increased, the correlations were weak (r = -0.382 and -0.45, respectively). Finally, a delayed contrast enhancement was present in 89% of akinetic and in 94% of dyskinetic segments; however, contrast enhancement was also present in 18% of the segments with normal wall motion and in 56% of hypokinetic segments. Although mechanical markers of myocardial ischaemia substantially reflect the transmural extent of myocardial infarction, none of them can be considered as a substitute for the direct observation of necrotic tissue and its transmural extent, as provided by contrast-enhanced magnetic resonance imaging.

Factors Affecting Accuracy of Ventricular Volume and Ejection Fraction Measured by Gated Tl-201 Myocardial Perfusion Single Photon Emission Computed Tomography

The electrocardiogram-gated single photon emission computed tomography (SPECT) measurement of left ventricular end-diastolic volume, end-systolic volume and ejection fraction may contain substantial errors. We evaluated whether patient-related factors affect the accuracy of left ventricular volume and ejection fraction measured by gated Tl-201 SPECT. A total of 518 patients without perfusion defects on Tl-201 SPECT or coronary artery disease were studied. Left ventricular volume and ejection fraction were measured from echocardiography and adenosine stress/redistribution gated Tl-201 SPECT using commercially available software packages (QGS and 4D-MSPECT). We identified factors affecting the accuracy of gated SPECT via multiple linear regression analysis of the differences between echocardiography and gated SPECT. Gated SPECT analyzed with QGS underestimated end-diastolic and end-systolic volume, and overestimated ejection fraction, but 4D-MSPECT overestimated all those values (P<0.001). Independent variables associated with increasing the difference in end-diastolic volume between echocardiography and gated SPECT were decreasing left ventricular end-diastolic wall thickness, decreasing body surface area, female sex and increasing end-diastolic volume (P<0.001). Those for end-systolic volume were decreasing left ventricular end-systolic wall thickness, female sex, and decreasing end-systolic volume (P<0.001). Increasing end-systolic wall thickness, male sex and decreasing age were independent determinants associated with an increased difference in ejection fraction (P<0.001). Adenosine stress SPECT showed significantly higher end-diastolic and end-systolic volume values and a lower ejection fraction than did redistribution SPECT (P<0.001). Patient-related factors affect the accuracy of left ventricular volume and ejection fraction measured by gated Tl-201 SPECT. Modification of gated SPECT measurements by taking account of these factors would lead to reduce systemic errors.

Hypertrophic cardiomyopathy in Noonan Syndrome closely mimics familial hypertrophic cardiomyopathy due to sarcomeric mutations

A 27 year old female with Noonan syndrome and hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. These images showed asymmetrical septal hypertrophy with maximal left ventricular end-diastolic wall thickness of 25 mm. Following administration of gadolinium, areas of hyperenhancement were seen in the anterior, anteroseptal and lateral walls. This is the first report of focal gadolinium hyperenhancement in hypertrophic cardiomyopathy due to Noonan syndrome and suggests that myocardial fibrosis can be imaged by MR hyperenhancement as seen previously in sarcomeric hypertrophic cardiomyopathy.

Angiotensin deficiency in mice leads to dilated cardiomyopathy

To explore the role of angiotensin II, we assessed hemodynamics and cardiac function in angiotensinogen-deficient mice in comparison to wild-type animals. Left ventricular end-diastolic diameter and wall thickness were evaluated by echocardiography and systolic and diastolic left ventricular function by pressure–volume relations using a micro-conductance catheter. Compared to wild-type animals, the angiotensinogen-deficient mice were hypotensive and showed impaired systolic function. The hearts were dilated, demonstrated by echocardiography and by a right-ward shift of the pressure–volume loops, but end-diastolic pressure, isovolumic relaxation ( τ) and diastolic stiffness were unchanged. Afterload, however, was reduced leading to maintained cardiac output. Although a blockade of the renin-angiotensin system via angiotensin converting enzyme inhibitors or angiotensin AT 1 receptor antagonist is beneficial after cardiac failure, the absence of angiotensin peptides during the ontogenesis leads to dilated cardiomyopathy.

Left ventricular remodeling with age in normal men versus women: Novel insights using three-dimensional magnetic resonance imaging

Echocardiographic left ventricular (LV) wall thickness increases with age, suggesting LV hypertrophy. However, autopsy studies have shown no change, or even a decrease, in LV mass with age. With many pathologies, LV remodeling results in changes in ventricular shape. Age-associated LV shape change might explain this discrepancy, although this has not been studied. Magnetic resonance imaging (MRI) was used in 336 healthy, normotensive adults (mean age 56 ± 18 years; 200 women, 136 men) to measure LV mass, end-diastolic LV wall thickness, length, diameter, and shape. Echocardiographic LV mass was measured in a subset of 86 subjects by a standard algorithm. In women, LV wall thickness increased by 14% (r = 0.19, p <0.02), whereas LV length decreased by 9% (r = −0.26, p = 0.0006); LV diameter was unchanged. Thus, LV mass did not vary with age (r −0.04, p = 0.06) and the sphericity index decreased (r = −0.165, p <0.05). In men, LV wall thickness and diameter were unrelated to age, but there was an 11% decrease in LV length (r = −0.29, p = 0.003); therefore, there was an 11% decrease in LV mass (r = −0.20, p = 0.019) and a decrease in the sphericity index (r = −0.218, p <0.04). No change occurred in echocardiographic LV mass with age in either gender, although echocardiographic LV wall thickness increased in both. The left ventricle becomes more spherical with age in normal adults due to reduced LV length. In women, increased LV wall thickness offsets the decreasing LV length, whereas in men, LV wall thickness fails to compensate, resulting in decreased LV mass with age.

Heart rate decline after exercise in patients with hypertrophic cardiomyopathy

To evaluate the heart rate recovery, submaximal exercise, echocardiographic examination, and Holter monitoring were performed on 30 patients with hypertrophic cardiomyopathy and 11 controls. The time constant of heart rate decline after exercise was calculated. Spectral analysis was performed on Holter recordings. The time constant did not correlate with heart rate, left ventricular end-diastolic pressure, ejection fraction, or wall thickness. There was no correlation between the time constant and any mean spectral indices over 24 hours in patients. However, the time constant correlated with high frequency component in the night. Nocturnal high frequency component in patients with short time constant was significantly less than in those with long time constant, but did not significantly differ from that in controls. In conclusion, the heart rate decline after exercise does not primarily reflect the severity of hypertrophy or hemodynamic impairment but is associated with nocturnal parasympathetic modulation in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy in a newborn infant

the feet was appreciated. Bilateral hydroceles were noted. Results of neurologic examination were normal. A chest x-ray film showed marked cardiomegaly and normal pulmonary vascularity. Sinus tachycardia was apparent from the electrocardiogram with a heart rate of 160/min, QRS axis 120°. The PR interval was shortened to 0.08 seconds; there was severe biventricular hypertrophy with ST-T wave changes. The echocardiogram revealed severe left and right ventricular hypertrophy with compressed ventricular cavities (Fig 1). The left ventricular end-diastolic dimension was 18 mm (normal, 20 mm), and the end-systolic dimension was 6 mm (normal 13 mm). The left ventricular end-diastolic wall thickness was 12 mm (normal, 3.5 mm). The left ventricular shortening fraction was increased to 50%. There was anterior motion of the mitral valve during systole, and Doppler study showed mild subaortic obstruction. There was no aortic valve stenosis or coarctation of the aorta. Results of a skeletal survey were normal. Initial laboratory evaluation revealed: creatine kinase, 17.10 microkatal (μkat)/L (normal, 0.50 to 3.67 μkat/L [1026 U/L; normal, 30 to 220 /U/L]); serum total carnitine, 11 nmol/mL (normal, 17 to 46 nmol/mL); free carnitine, 8 nmol/mL (normal, 10 to 29 nmol/mL); urine catecholamines, 8 μg/24 h (normal, <540 μg/24 h). Results of urine hexuronic acid analysis (26 mg/g) were normal. Leukocyte lysosomal enzyme panel (including α-glucosidase CASE PRESENTATION Dr Chen

Effect of Digoxin on Ventricular Remodeling and Responsiveness of beta-Adrenoceptors in Chronic Volume Overload.

BACKGROUND: Digoxin improves baroreflex function and reduces neurohumoral activation in severe heart failure, but it is uncertain how digoxin affects ventricular remodeling and progression to left ventricular dysfunction. In addition, the effect of digoxin in in vitro beta-adrenoceptor density and function, and contractile reserve in vivo is not well understood. METHODS AND RESULTS: To study this, we compared digoxin with placebo treatment in rats with chronic volume overload induced by aortocaval fistula and in sham-operated control animals. Left ventricular end-diastolic cavity dimensions (LVDd) and wall thickness were measured weekly by in vivo transthoracic echocardiography, and left ventricular mass (LVM) and percent fractional shortening (%FS) were calculated. Six weeks after fistula creation, simultaneous echocardiographic and invasive hemodynamic evaluation at rest and in response to incremental dobutamine (1-10 µg/kg/min intravenously) were measured. Myocardial plasma membrane beta-adrenoceptor density and maximal adenylate cyclase responses (V(max)) to isoproterenol, 5'-guanylylimi dodiphosphate, and forskolin were measured in vitro. Volume overload induced progressive increases in LVDd and LVM over the 6-week study period. Percent fractional shortening at rest, and the change in %FS in response to dobutamine stress were dramatically reduced 6 weeks after fistula creation. Although 6-week fistula animals had unchanged beta-adrenoceptor density (B(max)) and binding affinity (K(d)) as compared with controls, maximal adenylate cyclase responses to stimulation in vitro (V(max)) were markedly reduced. Digoxin treatment prevented this loss of responsiveness of adenylate cyclase but did not affect beta-adrenoceptor density or affinity in vitro. Digoxin had no effect on LVDd, LVM, %FS, or the response to dobutamine infusion in vivo. CONCLUSIONS: Although digoxin prevented beta-adrenoceptor desensitization and improved in vitro myocardial adenylate cyclase response, the cardiac response to adrenergic stimulation in vivo was not significantly improved. These results suggest that the role of beta-adrenoceptor desensitization in the progression from volume overload hypertrophy to left ventricular dysfunction and heart failure may be less important than previously thought. Furthermore, although digoxin treatment did produce modest hemodynamic benefits, it did not prevent progressive remodeling in this model.

Changes in patterns of left ventricular diastolic filling revealed by Doppler echocardiography in infants with ventricular septal defect.

To evaluate left ventricular diastolic filling in infants with ventricular septal defect, which has yet to be documented, we measured various Doppler echocardiographic indexes from transmitral flow in the following groups: 10 infants with ventricular septal defect without pulmonary hypertension; 10 infants with ventricular septal defect with pulmonary hypertension; and 9 normal infants to serve as controls. The peak A, total velocity time integral, E area, and A area in patients without pulmonary hypertension were all significantly larger than those in controls. The peak ratio E/A, and 1/3 filling fraction, in patients without pulmonary hypertension were significantly lower than in controls. The peak A, A area, and deceleration time in patients with pulmonary hypertension were significantly larger than in patients without pulmonary hypertension and controls. The peak E/A, area E/A, and 1/3 filling fraction in patients with pulmonary hypertension were significantly lower than in those without pulmonary hypertension and controls. The index of left ventricular mass, as well as the index of end-diastolic left ventricular wall thickness, correlated strongly with peak A, A area, and deceleration time. The ratio between the systolic pulmonary and systemic pressures correlated strongly with peak A, A area, peak E/A, area E/A, and 1/3 filling fraction. These results demonstrated that the patterns of left ventricular filling in infants with ventricular septal defect were different from those in normal infants, and suggested that the abnormal patterns may indicate the insufficiency of adaptation of left ventricle (increase of left ventricular compliance) for volume overload in the presence of a ventricular septal defect.

Development of heart failure following isoproterenol administration in the rat: role of the renin-angiotensin system.

High dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin-angiotensin system using ramipril. Following the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol + ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins. In rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin-angiotensin system.

Regional myocardial effects of intracoronary bradykinin in conscious dogs

This study examined in conscious dogs, the coronary and regional myocardial effects of bradykinin (BK) administered by intracoronary route and their modulation by an angiotensin-converting enzyme inhibitor. Eleven dogs were chronically instrumented with a left ventricular (LV) micromanometer, a circumflex coronary catheter, a flow probe, and ultrasonic crystals in the LV posterior wall. In the absence of systemic hemodynamic changes, BK (0.1-10 ng/kg i.c.) produced dose-dependent increases in coronary blood flow velocity (CBFV) and in LV posterior end-diastolic wall thickness (EDWT) but produced no change in LV regional myocardial function as assessed by LV posterior systolic wall thickening. The increases in LV EDWT and CBFV were linearly correlated. The BK B2 antagonist (HOE 140) abolished the effects of BK. Intracoronary enalaprilat (0.75 mg) extended the duration of the effect of BK on CBFV without modification of peak responses and induced a further increase in LV posterior EDWT but no change in LV regional myocardial function. Thus, in conscious dogs, the vasodilator effect of intracoronary BK alone or modulated by enalaprilat is not associated with changes in LV regional myocardial function.

Athlete's Heart in Women

<h3>Objectives</h3> —To define the expression of "athlete's heart" in women by determining the alterations in cardiac dimensions associated with long-term intense conditioning in elite female athletes. <h3>Design</h3> —Prospective cardiovascular assessment conducted from 1986 through 1993. Subjects were evaluated using 2-dimensional, M-mode, and Doppler echocardiographic studies. <h3>Setting</h3> —Institute of Sports Science, Italian National Olympic Committee, Rome, Italy. <h3>Participants</h3> —A total of 600 elite female athletes (mean age, 21 years; range, 12-49 years) who had participated in vigorous training (mean duration, 9 years; range, 2-32 years) and had competed in 27 sports, including 211 athletes at the international level and 389 at the national level. A control group consisted of 65 sedentary volunteer women (mean age, 23.7 years; range, 14-41 years) who were free of cardiovascular disease and who did not participate in regular athletic training. <h3>Main Outcome Measures</h3> —Left ventricular end-diastolic cavity dimension and wall thickness. <h3>Results</h3> —Athletes demonstrated larger left ventricular end-diastolic cavity dimension (mean±SD)(49±4 mm) and greater maximal wall thickness (8.2±0.9 mm) than controls (46±3 mm and 7.2±0.6 mm;<i>P</i>&lt;.001). These dimensions were 6% and 14% larger in athletes. Among athletes, left ventricular cavity dimension was 40 mm to 66 mm, exceeded normal limits (&gt;54 mm) in 47 women (8%), and was within the range consistent with primary dilated cardiomyopathy (≥60 mm) in 4 athletes (1%). Training for endurance sports, such as cycling, cross-country skiing, and rowing had the greatest effect on cavity dimension. Left ventricular wall thickness was 6 mm to 12 mm in athletes and did not exceed normal limits or extend into the borderline gray zone with hypertrophic cardiomyopathy in any subject. Compared with data from 738 previously studied male athletes, female athletes showed significantly smaller left ventricular cavity dimension (11% less; P&lt;.001) and wall thickness (23% less;<i>P</i>&lt;.001). <h3>Conclusions</h3> —Highly trained women athletes frequently demonstrate cardiac dimensional changes as an adaptation to physical training, although absolute left ventricular cavity size exceeding normal limits was evident in a minority (8%) of women athletes and was rarely (1% of athletes) within the range of dilated cardiomyopathy. Athletic training was not a stimulus for substantial increases in absolute left ventricular wall thickness, which was within normal limits for all women athletes. These findings suggest that the clinical differentiation of athlete's heart and hypertrophic cardiomyopathy appears to be a diagnostic dilemma that is limited to male athletes.

Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease.

In the present work, we studied clinical and haemodynamic correlates of impaired cardiac high-energy phosphate metabolism in patients with heart failure due to dilated cardiomyopathy (DCM). Myocardial 31P-magnetic resonance (MR) spectra were obtained at 1.5 T in 14 volunteers and 23 patients with DCM (mean ejection fraction 34%) in order to quantify the creatine phosphate (CP)/ATP ratio. In addition, patients underwent cardiac catheterization and echocardiography. Compared to volunteers (2.02 +/- 0.11), CP/ATP ratios were significantly reduced in DCM patients (1.54 +/- 0.10; P < 0.05), indicating impaired high-energy phosphate metabolism. CP/ATP ratios correlated with the clinical severity of heart failure estimated from the NYHA class (r = 0.47, P < 0.01); also, CP/ATP correlated with left ventricular ejection fraction (r = 0.54, P < 0.01) and left ventricular end-diastolic wall thickness (r = 0.51, P < 0.01). Thus, 31P-MR spectroscopy can detect abnormal cardiac high-energy phosphate metabolism in patients with heart failure due to DCM. These abnormalities correlate with clinical and haemodynamic parameters. Future studies will have to determine whether 31P-MR spectroscopy can contribute to the routine clinical evaluation of patients with heart failure.