Increase In Left Ventricular End-diastolic Dimension Research Articles

Abstract 9493: Differences in Prognostic Implications of Changes in Echocardiography in Asymptomatic Severe Aortic Stenosis Managed Conservatively

Background: No previous study has explored the association between the changes in echocardiographic parameters during follow-up and clinical outcomes in patients with asymptomatic severe aortic stenosis (AS) and who were managed conservatively. Objective: This study aimed to investigate the prognostic impact of the changes in echocardiographic parameter at 1-year follow-up in asymptomatic severe AS patients managed conservatively. Methods: Among 3815 patients with severe AS enrolled in the multicenter CURRENT AS registry in Japan, we analyzed conservatively managed 555 patients who underwent echocardiography at 1-year follow-up and remained asymptomatic. The primary outcome measure was a composite of AS-related deaths and hospitalization due to heart failure. A decline in left ventricular ejection fraction (LVEF), an increase in left ventricular end-diastolic dimension (LVEDD), and an increase in aortic valve pressure gradient (PG) were defined as above 10%, 5mm, and 30mmHg, respectively, based on the clinically relevant values. Results: There were 61 patients (11.0 %) with >10% decline in LVEF and 494 patients (89.0%) without decline. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the decline in LVEF group than in no decline in LVEF group. After adjusting for confounders, the excess risk of the decline in LVEF relative to no decline in LVEF for the primary outcome measure remained significant (hazard ratio; 2.76, 95% confidence interval 1.66-4.45). The cumulative 3-year incidence of the primary outcome measure was significantly higher in the increase in LVEDD group than in no increase in LVEDD group. In contrast, there were no difference in cumulative 3-year incidence of the primary outcome measure between the increase in aortic valve PG and no increase group. Conclusions: Severe asymptomatic AS patients with a >10% LVEF decline or >5mm increase in LVEDD at 1-year after diagnosis had worse AS-related clinical outcome than those without under conservative management, whereas there were no differences in the outcomes stratified by changes in aortic valve PG. This indicated the importance in the LV morphology and function during follow-up in asymptomatic severe AS patients when managed conservatively.

Sphingosine-1-phosphate induces myocyte autophagy after myocardial infarction through mTOR inhibition

Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague–Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 μg/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI.

Xanthine oxidase inhibition preserves left ventricular systolic but not diastolic function in cardiac volume overload

Xanthine oxidase (XO) is increased in human and rat left ventricular (LV) myocytes with volume overload (VO) of mitral regurgitation and aortocaval fistula (ACF). In the setting of increased ATP demand, XO-mediated ROS can decrease mitochondrial respiration and contractile function. Thus, we tested the hypothesis that XO inhibition improves cardiomyocyte bioenergetics and LV function in chronic ACF in the rat. Sprague-Dawley rats were randomized to either sham or ACF ± allopurinol (100 mg·kg(-1)·day(-1), n ≥7 rats/group). Echocardiography at 8 wk demonstrated a similar 37% increase in LV end-diastolic dimension (P < 0.001), a twofold increase in LV end-diastolic pressure/wall stress (P < 0.05), and a twofold increase in lung weight (P < 0.05) in treated and untreated ACF groups versus the sham group. LV ejection fraction, velocity of circumferential shortening, maximal systolic elastance, and contractile efficiency were significantly depressed in ACF and significantly improved in ACF + allopurinol rats, all of which occurred in the absence of changes in the maximum O2 consumption rate measured in isolated cardiomyocytes using the extracellular flux analyzer. However, the improvement in contractile function is not paralleled by any attenuation in LV dilatation, LV end-diastolic pressure/wall stress, and lung weight. In conclusion, allopurinol improves LV contractile function and efficiency possibly by diminishing the known XO-mediated ROS effects on myofilament Ca(2+) sensitivity. However, LV remodeling and diastolic properties are not improved, which may explain the failure of XO inhibition to improve symptoms and hospitalizations in patients with severe heart failure.

Effects of ACE2 Inhibition in the Post-Myocardial Infarction Heart

Background There is evidence that angiotensin-converting enzyme 2 (ACE2) is cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a selective ACE2 inhibitor, after permanent coronary artery ligation or sham operation. Methods and Results Coronary artery ligation resulting in MI between 25% to 50% of the left ventricular (LV) circumference caused substantial cardiac remodeling. Daily C16 administration from postoperative days 2 to 28 at a dose that inhibited myocardial ACE2 activity was associated with a significant increase in MI size and reduction in LV % fractional shortening. Treatment with C16 did not significantly affect post-MI increases in LV end-diastolic dimension but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On postoperative day 7, C16 had no significant effect on the increased level of apoptosis in the infarct and border zones nor did it significantly affect capillary density surrounding the MI. It did, however, significantly reduce the number of c-kit + cells in the border region. Conclusions These findings support the notion that ACE2 exerts cardioprotective effects by preserving jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and fibrosis with C16, however, suggests that ACE2 activity has diverse effects on post-MI remodeling.

Abstract 3816: Injection of GSK-3β Overexpressing Bone Marrow Derived Mesenchymal Stem Cells Attenuates Cardiac Dysfunction after Myocardial Infarction

Glycogen synthase kinase 3β (GSK-3β) induces expression of cardiac markers in mesenchymal stem cells (MSCs). We examined whether injection of ex vivo -modified GSK-3β overexpressing MSCs improves cardiac dysfunction after myocardial infarction (MI). Mouse MSCs were transduced with adenovirus harboring LacZ or GSK-3β (LacZ-MSC or GSK-MSC). MI was induced by coronary ligation and thirty μL of saline alone or MSCs (1.5 x 10 5 cells) were injected into the MI border zone just after coronary ligation. In saline injected MI mice, a progressive increase in left ventricular end diastolic dimension (LVEDD) and a progressive decrease in LV ejection fraction (LVEF) and LV fractional shortening (%FS) were observed compared with sham (Table ). LacZ-MSC or GSK-MSC attenuated increases in LVEDD at 2 and 12 weeks. However, LVEF and %FS were significantly greater in GSK-MSC than in LacZ-MSC group at 2 and 12 weeks (Table ). Heart weight/body weight (HW/BW) in GSK-MSC (4.4±0.1) group was significantly smaller than that in LacZ-MSC (5.1±0.2) and saline (5.0±0.2) groups and not significantly different from that in sham group (4.1±0.0), suggesting that cardiac remodeling was attenuated by GSK-MSC. To further confirm the effect of GSK-3β, MSCs acquired from inducible GSK-3β (tet-OFF) mice were injected into the MI mice fed with or without doxycycline (Dox), where expression of GSK-3β transgene was abrogated by Dox treatment in situ . After two weeks of MI, both LVEF (61.5±2.2, 37.4±7.1, p&lt;0.01) and %FS (27.6±1.4, 15.4±3.2, p&lt;0.001) were significantly greater in Dox (−) (n=13) than in Dox (+) mice (n=9). These results suggest that ex vivo introduction of GSK-3β improves the effect of MSC injection, thereby attenuating LV dysfunction after MI. Furthermore, in situ Dox-regulatable expression of GSK-3β also facilitated the therapeutic effect of MSCs injection. Echocardiography on 2 Weeks and 12 Weeks

Predictors of Left Ventricular Dilatation in Young Adults (from the Bogalusa Heart Study)

Left ventricular (LV) dilatation may be an early sign of cardiac decompensation progressing to LV dysfunction. Determinants of LV dilatation in young asymptomatic adults are unknown. Five hundred six asymptomatic subjects (mean age 32 +/- 3 years) enrolled in the Bogalusa Heart Study underwent echocardiographic examination. LV dilatation (LV end-diastolic diameter >5.5 cm) as measured by M-mode echocardiography was found in 31 subjects (6%). Subjects with LV dilatation had greater body mass indexes (32 +/- 9 vs 27 +/- 6 kg/m2, p <0.0001), systolic (119 +/- 15 vs 112 +/- 12 mm Hg, p = 0.007) and diastolic (79 +/- 12 vs 75 +/- 9 mm Hg, p = 0.04) blood pressures, and LV mass (230 +/- 50 vs 123 +/- 39 g, p <0.0001). Age, gender, race, and metabolic parameters (glucose, insulin, and lipoprotein levels) did not differ significantly between the subjects with and without LV dilatation. After correction for age, gender, and race differences, adulthood obesity (body mass index >30 kg/m2) was associated with a threefold odds ratio (2.9, 95% confidence interval 1.4 to 6.1), and hypertension (defined as per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) was also associated with a threefold odds ratio (3.0, 95% confidence interval 1.2 to 7.1) for an increased incidence of LV dilatation. There was an incremental increase in LV end-diastolic dimension depending on the presence of hypertension or obesity, and subjects with obesity and hypertension in adulthood had the greatest degree of LV end-diastolic dimensions. In multiple regression analyses, body mass index in childhood was the only significant predictor of LV dilatation in adulthood (odds ratio 1.47, 95% confidence interval 1.03 to 2.09). In conclusion, obesity beginning in childhood and obesity and hypertension in young adulthood are predictors of LV dilatation in an otherwise healthy young adult population.

Predictors of left ventricular remodeling in patients with acute myocardial infarction participating in cardiac rehabilitation.

This study was designed to determine the factors influencing the development of left ventricular (LV) remodeling in patients participating in a comprehensive cardiac rehabilitation (CR) program after acute myocardial infarction (AMI), with special reference to exercise intensity and frequency. A total of 72 patients with AMI participated in CR consisting of exercise training of moderate intensity (heart rate reserve 40-60%) and education for 12 weeks. Plasma concentration of brain natriuretic peptide (BNP) was measured at the beginning and the end of CR. Echocardiography was performed before and 1 year after CR. An increase in LV end-diastolic dimension (delta-LVDd) from baseline was used as an index of remodeling. Delta-LVDd was significantly greater in patients with an anterior AMI than with other infarct locations (p<0.05) and correlated significantly with baseline BNP concentration (p<0.05). Delta-LVDd >5 mm occurred exclusively in patients with baseline BNP >150 pg/ml. Variables representing the intensity and frequency of exercise training did not correlate with delta-LVDd. In patients with AMI participating in CR, those having both anterior infarction and baseline BNP concentration >150 pg/ml are at high risk for subsequent LV remodeling, whereas neither exercise intensity nor participation frequency in CR appears to be associated with LV remodeling.

Unusual left ventricular dilatation without functional or biochemical impairment in normotensive extremely overweight japanese professional sumo wrestlers

To explore the physiologic limit of left ventricular (LV) enlargement, we performed echocardiography and air displacement plethysmography to respectively assess LV dimension and function and the body composition of Japanese professional sumo wrestlers. After excluding subjects with cardiovascular disease, hypertension, plasma brain natriuretic peptide (BNP) ≥17.9 pg/ml, diabetes mellitus, or asthma, 331 subjects (mean ± SD age, 21.6 ± 3.7 years; height 179.2 ± 5.3 cm; weight 1,17.9 ± 21.5 kg; percent fat, 29.6 ± 6.6%) were analyzed. LV end-diastolic dimension averaged 58.4 ± 3.7 mm and was within the generally regarded normal limit (≤54 mm) in 14.5% of subjects, but was ≥60 mm in 41.1% of subjects. LV septal and posterior wall thicknesses were 10.3 ± 0.9 and 10.2 ± 0.9 mm, respectively. Peak E- and A-wave velocities, E/A ratio, LV fractional shortening, and BNP were 96 ± 16 and 51 ± 13 cm/s, 2.0 ± 0.7, 33.5 ± 4.5%, and 3.1 ± 3.7 pg/ml, respectively. LV end-diastolic dimension was not correlated with these indexes of LV function or with plasma BNP levels, but was significantly correlated with height, weight, body surface area, fat-free mass, and fat mass. These results show that among very large, highly trained, professional athletes, LV end-diastolic dimension frequently exceeds the traditionally accepted upper limit of normal for the general population. This increase in LV end-diastolic dimension may thus represent an extreme example of the physiologic adaptation of the athlete’s heart.

Longitudinal observations of left ventricular end-diastolic dimension in children using echocardiography.

Previous studies have evaluated left ventricular dimensions in children using two-dimensional echocardiography, but there is little information on gender differences and on the longitudinal development of the dimensions of the left ventricle. Our objective was to assess, by two-dimensional echocardiography, the normal size of the left ventricular end-diastolic dimension (LVDd) in children, its differences by sex, and the rate of its development using height, weight, and body surface area as indices. The study group consisted of 437 patients (264 males, 173 females) with a history of Kawasaki disease but with no coronary artery lesions, as determined by repeated echocardiographic and other examinations. A total of 1595 examinations were done over an average of 6.7 years. The increase in LVDd was significantly more rapid in (1) children below 2 years of age than in older children of either sex and (2) in males who were 11 and 12 years old than in males who were 10 years old. Significant gender differences were observed in the increase in LVDd by all indices (p < 0.001).

Noninvasive evaluation of cardiovascular hemodynamics during multiple follicular stimulation, late luteal phase and early pregnancy

A noninvasive hemodynamic study in three moments of the gamete intrafallopian transfer (GIFT) cycle was carried out on 25 patients: before beginning multiple follicular stimulation (MFS) (study I); after rapid increase of serum estradiol (E2) (study II); and 12 days after GIFT (study III). In the 25 patients, the rapid increase in E2 proved to be combined with a significant increase in the left ventricular end diastolic dimension (LVEDD), the left ventricular end systolic dimension, the heart rate (HR), the systolic index, the cardiac index, and a significant reduction in the mean arterial pressure, in the systolic arterial pressure and in the systemic vascular resistence index. In the 14 pregnant patients in study III, all of the hemodynamic parameters studied proved to be significantly modified with respect to study I. In the 11 nonpregnant patients between Studies I and III were no significant cardiovascular modifications except for a significant increase in LVEDD in Study III. It is concluded that, during MFS, the rapid increase in E2 is combined with hemodynamic modifications and that, in pregnancy, the cardiovascular adaptation modifications occur in the very early stages.

Relation of mitral valve prolapse to left ventricular size in Marfan's syndrome

Sporadic recent reports suggest that mitral valve prolapse (MVP) disappears with progressive left ventricular (LV) dilatation. To test this hypothesis, we sought to determine if an inverse relation exists between MVP and LV cavity size on M-mode echocardiograms in 83 patients with Marfan's syndrome. LV end-diastolic dimensions and presence or absence of MVP were determined. Forty-six patients had MVP. Of patients with an LV end-diastolic dimension ≤ 5 cm, 90% had MVP; only 19% of the 32 patients with abnormally large (>5.8 cm) end-diastolic dimension had MVP. The prevalence of MVP in patients with an LV end-diastolic dimension of 5.1 to 5.8 cm was 69%. Thus, the prevalence of MVP was inversely related to LV cavity size. To determine whether appearance or disappearance of MVP was associated with decrease or increase in LV cavity size, serial echocardiograms from 67 patients (mean follow-up 42 months, range 3 to 99) were examined. These patients were separated into 3 groups based on changes in the LV end-diastolic dimension of >1 cm over time. Group 1 consisted of 9 patients, all of whom had MVP and normal LV cavity size on their initial study. With subsequent increase in LV end-diastolic dimension (mean 1.42 ± 0.3), MVP disappeared in 6 of the 9. Conversely, group 2 consisted of 4 patients, all of whom had dilated left ventricles on their initial echocardiogram and no evidence of MVP. After aortic valve replacement, the LV cavity size decreased (mean 2.3 ± 0.7) and MVP appeared on follow-up studies. Group 3 consisted of 54 patients with little or no change in LV end-diastolic dimension (≤ 1 cm, mean 0.4 ± 0.2 cm). In this group, MVP status remained unchanged throughout the follow-up period. Thus, in patients with Marfan's syndrome, serial increase or decrease in LV size is associated, respectively, with disappearance or appearance of MVP.

Chronic verapamil therapy in pediatrie and young adult patients with hypertrophic cardiomyopathy

Oral verapamil, 5.2 ± 1.1 mg/kg/day (range 2.8 to 7), was administered to 13 pediatric patients with hypertrophic Cardiomyopathy for 13 ± 6 months (range 2 to 20). The patients had significant symptomatic improvement on verapamil therapy. Murmur intensity diminished in 6 patients during therapy and left ventricular (LV) electromotive forces on the electrocardiogram diminished in 4, increased in 5 and did not change in 4. Exercise endurance increased from 8.4 ± 3.9 to 10.9 ± 2.8 minutes (p < 0.01). Seven patients had ST-segment depression (0.38 ± 0.28 mV) before verapamil therapy, which improved after verapamil therapy in 5 (0.24 ± 0.17 mV, p < 0.02). Of 4 patients with exercise-induced ventricular ectopic activity, 3 had diminution or abolishment of ectopy following verapamil. By echocardiography, the patients had an increase in LV end-diastolic dimension from 3.4 ± 0.7 to 3.9 ± 0.8 cm (p < 0.01), with no significant change in shortening fraction (46.1 ± 8.0% vs 44.6 ± 8.0%). When adjusted for body size and age there was a significant decrease in LV septal thickness (from 106 ± 70 to 45 ± 52% of predicted normal values, p < 0.05) and LV posterior wall thickness (from 40 ± 45 to 5 ± 26% of predicted normal values p = 0.05) after verapamil. Isovolumic relaxation time decreased from 69 ± 26 to 42 ± 19 ms after verapamil (p < 0.01). Systolic anterior motion of the anterior mitral leaflet disappeared in 5 of 8 patients and midsystolic closure of the aortic valve was no longer present in 4 of 8. Chronic oral verapamil appears to be an effective form of therapy for pediatric patients with hypertrophic Cardiomyopathy.

The hemodynamics and hemodynamic effects of indenolol in mild hypertension.

For clarifying the onset mechanism of essential hypertension, the hemodynamics in 9 mildly hypertensive men, mean age of 39.8 +/- 10.7 (mean +/- SD), was compared with 7 normotensive men, mean age of 39.8 +/- 10.7, by means of exercise echocardiography, and the effects of indenolol (administered 30 mg/day for 7 days orally to both groups) were studied. The interventricular septum and the left ventricular posterior wall were thickened in the mild hypertensives. No significant differences between the both groups were shown in the cardiac performance at rest and the cardiac index during exercise. The total peripheral vascular resistance was higher in the mild hypertensives than the normotensives during exercise. However, during exercise, the normotensives showed significant increases in the left ventricular end-diastolic dimension (LVDd) and the stroke index (SI); these changes were not significant in the mild hypertensives. After administration of indenolol, the significant increases in LVDd and SI during exercise were observed in the mild hypertensives. This study suggests that mild hypertensives with cardiac hypertrophy display a diminished Frank-Starling effect during exercise which may be attributed to the decreased left ventricular compliance due to cardiac hypertrophy and elevated afterload. Indenolol improved the Frank-Starling effect, which decreased in the mild hypertensives.

Age-associated decrease in ventricular response to haemodynamic stress during beta-adrenergic blockade.

measurementsofleft ventricular end-diastolic dimension, left ventricular end-systolic dimension, andvelocity ofcircumferential fibre shortening weremadeatrestandduring 30mmHgincreases insystolic blood pressure induced byhandgrip exercise orphenylephrine infusion. Atrestthere was no agedifference inheart rate,left ventricular end-diastolic dimension, left ventricular end-systolic dimension, orcircumferential fibre shortening. Bothhandgrip andphenylephrine induced significant changes inthese indices inboth agegroupsbutno agedifference intheresponsescould beelicited. Inorder toeliminate theinfluence ofbeta-adrenergic drive, themeasurements wererepeated during propranolol block. Whilethere was no agedifference inventricular responseduring beta-blockade atrest,phenylephrine infusion during beta-blockade induced greater increase inleft ventricular end-diastolic dimension intheelderly group (2.3 i 0-6mm)compared with the younggroup(0.1 ± 05mm, P< 0.01). Thisincrease intheelderly groupoccurred despite a significantly smaller decrease inheart ratethanintheyounggroup.The normal agedhumanheart performs aswell asayoungheart atrestandduring beta-blockade buthasa greater reliance onbeta-adrenergic drive during haemodynamic stress. Previous studies haveshowntheusefulness of M-modeechocardiography inassessing left ventricular function during handgrip exercise (Stefadouros etal., 1974) andphenylephrine infusion (Redwood etal., 1974; Hirshleifer etal., 1975) innormal and diseased hearts. Earlier studies fromthis andother laboratories (Sj6gren, 1971;Gardin etal., 1977; Gerstenblith etal., 1977)havealsoshownthe feasibility ofusingthistechnique todetect age changes inventricular function anddimensions. Therefore, itappeared that echocardiography could beusedasanoninvasive methodofdetermining the effects ofaging ontheability oftheleft ventricle to respond tohaemodynamic stress. Previous studies suggest thattheoldheart functions aswellastheyoungheart undernormal conditions butmay havea diminished response

110 ECHOCARDIOGRAPHIC LEFT VENTRICULAR SIZE IN GROWING MALE AND FEMALE CHILDREN

Left ventricular end-diastolic dimension (LVD) in the echocardiogram (E) is widely used to assess the LV size. There is no study available where difference in male (M) and female (F) growing children were examined. Therefore, we studied 110 M and 90 F normal school children, 5-14 years of age and with body surface area (BSA) varying from 0.7 to 1.59. Strip chart E recordings of the LV at its midcavity sector containing mitral echos were obtained by means of a 2.25 M Hz transducer in the standard fashion. Internal LVD was measured in millimeters at the onset of the Q wave of the EKG for several cardiac cycles and averaged. Our results for the mean and 1 standard deviation in M and F children with the different BSA were as follows: This study shows increase in LVD with larger BSA as in other studies in both M and F children. However, there was no statistically significant difference in LVD between M and F growing children at any BSA.